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25189483 | Non-small cell lung cancers (NSCLC) that express EGF receptor with activating mutations frequently develop resistance to EGFR kinase inhibitors. The mucin 1 (MUC1) heterodimeric protein is aberrantly overexpressed in NSCLC cells and confers a poor prognosis; however, the functional involvement of MUC1 in mutant EGFR signaling is not known.
Targeting the oncogenic MUC1 C-terminal subunit (MUC1-C) in NSCLC cells harboring mutant EGFR was studied for effects on signaling, growth, clonogenic survival, and tumorigenicity.
Stable silencing of MUC1-C in H1975/EGFR(L858R/T790M) cells resulted in downregulation of AKT signaling and inhibition of growth, colony formation, and tumorigenicity. Similar findings were obtained when MUC1-C was silenced in gefitinib-resistant PC9GR cells expressing EGFR(delE746_A750/T790M). The results further show that expression of a MUC1-C(CQC → AQA) mutant, which blocks MUC1-C homodimerization, suppresses EGFR(T790M), AKT and MEK → ERK activation, colony formation, and tumorigenicity. In concert with these results, treatment of H1975 and PC9GR cells with GO-203, a cell-penetrating peptide that blocks MUC1-C homodimerization, resulted in inhibition of EGFR, AKT, and MEK → ERK signaling and in loss of survival. Combination studies of GO-203 and afatinib, an irreversible inhibitor of EGFR, further demonstrate that these agents are synergistic in inhibiting growth of NSCLC cells harboring the activating EGFR(T790M) or EGFR(delE746-A750) mutants. | Does targeting the oncogenic MUC1-C protein inhibit mutant EGFR-mediated signaling and survival in non-small cell lung cancer cells? | Yes. These findings indicate that targeting MUC1-C inhibits mutant EGFR signaling and survival, and thus represents a potential approach alone and in combination for the treatment of NSCLCs resistant to EGFR kinase inhibitors. | PASS | pubmedQA | 1 |
22269009 | Hyperbaric oxygen therapy is known to reduce fasting blood glucose in individuals with Type 2 diabetes. However, the mechanisms of this effect are not clear. The aim of this study was to determine whether peripheral insulin sensitivity by hyperinsulinaemic euglycaemic clamp is increased in patients presenting for hyperbaric oxygen therapy.
Participants were non-obese individuals without Type 2 diabetes (n=5) or obese patients with Type 2 diabetes (n=5). Patients were given 100% oxygen at 2.0 absolute atmospheres for 2 h, six sessions per week for 5 weeks.
Peripheral insulin sensitivity was increased in the whole cohort (P=0.04). Subsequent analysis revealed that this was significant at both treatment 3 (+37.3 ± 12.7%, P=0.02) and treatment 30 (+40.6 ± 12.6%, P=0.009). HbA(1c) was significantly reduced in subjects without diabetes only (P<0.05). | Does hyperbaric oxygen therapy improve peripheral insulin sensitivity in humans? | Yes. Insulin sensitivity increased within 3 days of hyperbaric oxygen treatment and this was maintained for 30 sessions. This increase in insulin sensitivity is equivalent to that observed following moderate weight loss. The mechanisms underlying the insulin-sensitizing effect of hyperbaric oxygen require further elucidation. | PASS | pubmedQA | 1 |
25990448 | Comprehensive gene-expression analysis is very useful for classifying specific cancers into subgroups on the basis of their biological characteristics; it is used both prognostically and predictively. The purpose of this study was to classify unresectable advanced or recurrent colorectal cancer (CRC) by gene-expression profiling of formalin-fixed paraffin-embedded tissues and to correlate CRC subgroups with clinicopathological and molecular features and clinical outcomes.
One hundred patients with advanced or recurrent CRC were enrolled. RNA extracted from FFPE tissues was subjected to gene-expression microarray analysis.
The patients were stratified into four subgroups (subtypes A1, A2, B1, and B2) by unsupervised hierarchical clustering. By use of principle-components analysis (PCA), the patients were divided into subtypes A and B on the basis of component 1 and into subtypes 1 and 2 on the basis of component 2. Subtype A was significantly enriched among patients without the KRAS mutation and with an earlier clinical stage at diagnosis. With regard to anti-EGFR therapy, progression-free survival (PFS) was better for patients in subtype A without the KRAS mutation than for those with the KRAS mutation (P = 0.047). PFS for patients without the KRAS mutation in subtype B was comparable with that for patients with the KRAS mutation (P = 0.55). Similar results were observed in a validation set. | Do gene-expression profiles correlate with the efficacy of anti-EGFR therapy and chemotherapy for colorectal cancer? | Yes. We found that gene-expression profiles enabled stratification of CRC patients into four subgroups. The efficacy of anti-EGFR therapy was correlated with component 1 from PCA. This comprehensive study may explain the heterogeneity of unresectable advanced or recurrent CRC and could be useful for identifying novel biomarkers for CRC treatment. | PASS | pubmedQA | 1 |
25963323 | Pregnant women are at increased risk of gallbladder (GB) stasis, an important risk factor for gallstones (GS). In non-pregnant women, Vitamin-D deficiency (VDD) is associated with GB stasis, which improves on supplementation. Relationship of VDD with GB stasis among pregnant women is not known.
This is a prospective study in tertiary care centre. Consecutive healthy pregnant women (12-16 weeks gestation) were enrolled. Serum 25(OH) vitamin-D was estimated, and levels <20 ng ml(-1) were considered as VDD. Risk factors and clinical features of VDD were assessed. Gallbladder ejection fraction (GBEF) was assessed by ultrasound after a standard fatty meal, and <40 % was defined as stasis. Statistical analysis was performed to assess relationship of GB stasis and vitamin-D levels and identify factors associated with VDD.
Median serum vitamin-D in 304 women was 7.9 ng ml(-1) (IQR 5.7, 12). VDD afflicted 92 % of them. Women with VDD more often had GB stasis (20 % vs 0 %; p = 0.015) and had lower GBEF [53.7 ± 17 % vs 59 ± 10 %; p = 0.026] compared to those with normal vitamin-D. GBEF showed positive correlation with vitamin-D levels (r = 0.117; p = 0.042). Risk factors for low vitamin-D levels were urban residence (p = 0.001), lower sun-exposure time (p = 0.005), limited skin exposure (p < 0.001), higher BMI (p = 0.05) and higher socioeconomic status (p = 0.02). Vitamin-D deficiency was associated with low serum calcium (ρ = 0.457; p < 0.001). | Does vitamin-D Deficiency be Associated with Gallbladder Stasis Among Pregnant Women? | Yes. Vitamin D deficiency is highly prevalent among pregnant Indian women. It is associated with GB stasis and lower GBEF. The risk factors for VDD were reduced sun exposure, inadequate dietary intake and urban lifestyle. | PASS | pubmedQA | 1 |
11683916 | DNA replication-related element binding factor (DREF) has been suggested to be involved in regulation of DNA replication- and proliferation-related genes in Drosophila. While the effects on the mutation in the DNA replication-related element (DRE) in cultured cells have been studied extensively, the consequences of elevating wild-type DREF activity in developing tissues have hitherto remained unclear.
We over-expressed DREF in the wing imaginal disc using a GAL4-UAS targeted expression system in Drosophila. Over-expression of DREF induced a notching wing phenotype, which was associated with ectopic apoptosis. A half reduction of the reaper, head involution defective and grim gene dose suppressed this DREF-induced notching wing phenotype. Furthermore, this was also the case with co-expression of baculovirus P35, a caspase inhibitor. In addition, over-expression of the 32 kDa boundary element-associated factor (BEAF-32), thought to compete against DREF for common binding sites in genomic regions, rescued the DREF-induced notching wing phenotype, while a half reduction of the genomic region, including the BEAF-32 gene, exerted enhancing effects. To our knowledge, this is the first evidence for a genetic interaction between DREF and BEAF-32. | Does over-expression of DREF in the Drosophila wing imaginal disc induce apoptosis and a notching wing phenotype? | Yes. The DREF-induced notching wing phenotype is caused by induction of apoptosis in the Drosophila wing imaginal disc. | PASS | pubmedQA | 1 |
25472866 | Olive cultivation blends with the history of the Mediterranean countries since ancient times. Even today, activities around the olive tree constitute major engagements of several people in the countryside of both sides of the Mediterranean basin. The olive fly is, beyond doubt, the most destructive pest of cultivated olives. The female fly leaves its eggs in the olive fruit. Upon emergence, the larvae feed on the olive sap, thus destroying the fruit. If untreated, practically all olives get infected. The use of chemical insecticides constitutes the principal olive fly control approach. The Sterile Insect Technique (SIT), an environmentally friendly alternative control method, had been tried in pilot field applications in the 1970's, albeit with no practical success. This was mainly attributed to the low, non-antagonistic quality of the mixed-sex released insects. Many years of experience from successful SIT applications in related species, primarily the Mediterranean fruit fly, Ceratitis capitata, demonstrated that efficient SIT protocols require the availability of fundamental genetic and molecular information.
Among the primary systems whose understanding can contribute towards novel SIT approaches (or its recently developed alternative RIDL: Release of Insects carrying a Dominant Lethal) is the reproductive, since the ability to manipulate the reproductive system would directly affect the insect's fertility. In addition, the analysis of early embryonic promoters and apoptotic genes would provide tools that confer dominant early-embryonic lethality during mass-rearing. Here we report the identification of several genes involved in these systems through whole transcriptome analysis of female accessory glands (FAGs) and spermathecae, as well as male testes. Indeed, analysis of differentially expressed genes in these tissues revealed higher metabolic activity in testes than in FAGs/spermathecae. Furthermore, at least five olfactory-related genes were shown to be differentially expressed in the female and male reproductive systems analyzed. Finally, the expression profile of the embryonic serendipity-α locus and the pre-apoptotic head involution defective gene were analyzed during embryonic developmental stages. | Does the molecular biology of the olive fly come of age? | Yes. Several years of molecular studies on the olive fly can now be combined with new information from whole transcriptome analyses and lead to a deep understanding of the biology of this notorious insect pest. This is a prerequisite for the development of novel embryonic lethality female sexing strains for successful SIT efforts which, combined with improved mass-reared conditions, give new hope for efficient SIT applications for the olive fly. | PASS | pubmedQA | 1 |
27379395 | Previously, a strong positive association between background parenchymal enhancement (BPE) at magnetic resonance imaging (MRI) and breast cancer was reported in high-risk populations. We sought to determine, whether this was also true for non-high-risk patients.
540 consecutive patients underwent breast MRI for assessment of breast findings (BI-RADS 0-5, non-high-risk screening (no familial history of breast cancer, no known genetic mutation, no prior chest irradiation, or previous breast cancer diagnosis)) and subsequent histological work-up. For this IRB-approved study, BPE and fibroglandular tissue FGT were retrospectively assessed by two experienced radiologists according to the BI-RADS lexicon. Pearson correlation coefficients were calculated to explore associations between BPE, FGT, age and final diagnosis of breast cancer. Subsequently, multivariate logistic regression analysis, considering covariate colinearities, was performed, using final diagnosis as the target variable and BPE, FGT and age as covariates.
Age showed a moderate negative correlation with FGT (r = -0.43, p<0.001) and a weak negative correlation with BPE (r = -0.28, p<0.001). FGT and BPE correlated moderately (r = 0.35, p<0.001). Final diagnosis of breast cancer displayed very weak negative correlations with FGT (r = -0.09, p = 0.046) and BPE (r = -0.156, p<0.001) and weak positive correlation with age (r = 0.353, p<0.001). On multivariate logistic regression analysis, the only independent covariate for prediction of breast cancer was age (OR 1.032, p<0.001). | Is mRI Background Parenchymal Enhancement Associated with Breast Cancer? | No. Based on our data, neither BPE nor FGT independently correlate with breast cancer risk in non-high-risk patients at MRI. Our model retained only age as an independent risk factor for breast cancer in this setting. | PASS | pubmedQA | 1 |
22373776 | Clinicians occasionally face the challenge of moving a tooth through the maxillary sinus. The objective of this study was to evaluate tissue remodeling during tooth movement into the maxillary sinus, more specifically as regards to bone formation.
The maxillary first molar of 20 male mice was moved toward the palatal side by a nickel-titanium super elastic wire for 1 to 14 days, and the bone remodeling around the root was evaluated using histomorphometry and immunodetection of bone-restricted Ifitm-like (Bril) protein, a novel marker of active bone formation.
When mechanical stress was applied to the tooth, the periodontal ligament on the palatal side was immediately compressed to approximately half of its original width by the tipping movement of the tooth. At the same time, osteoblasts deposited new bone on the wall of the maxillary sinus prior to bone resorption by osteoclasts on the periodontal side, as evidenced by the high level of expression of Bril at this site. As a result of these sequential processes, bone on the sinus side maintained a consistent thickness during the entire observation period. No root resorption was observed. | Does mechanical stress induce bone formation in the maxillary sinus in a short-term mouse model? | Yes. Bone formation on the surface of the maxillary sinus was evoked by mechanotransduction of mechanical stress applied to a tooth over a 2-week period, and was induced ahead of bone resorption on the periodontal ligament side. | PASS | pubmedQA | 1 |
18257131 | Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore (MPTP) opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP.
Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer (CTRL group) or buffer containing 20 micromol/L atractyloside (ATR group), 3% (v/v) sevoflurane (SPC group), 50 micromol/L propofol (PPC group), or the combination of atractyloside with respective anesthetics (SPC+ATR and PPC+ATR groups). Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area (percent necrotic area).
Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size (SPC vs CTRL: (17.48+/-2.70)% vs (48.47+/-6.03)%, P<0.05; PPC vs CTRL: (35.60+/-2.10)% vs (48.47+/-6.03)%, P<0.05). SPC group had less infarct size than PPC group (SPC vs PPC: (17.48+/-2.70)% vs (35.60+/-2.10)%, P<0.05). Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol. | Is postconditioning of sevoflurane and propofol associated with mitochondrial permeability transition pore? | Yes. Postconditioning of sevoflurane and propofol has cardioprotective effect against ischemia-reperfusion injury of heart, which is associated with inhibition of MPTP opening. Compared to propofol, sevoflurane provides superior protection of functional recovery and infarct size. | PASS | pubmedQA | 1 |
19354171 | The purpose of this paper is to evidence the advantages of artificial Acrysof Toric IOL implantation in patients with cataract and corneal astigmatism.
Prospective clinical study on 30 patients with cataract operated on with phacoemulsification and implantation of Acrysof Toric IOL on 32 eyes, between September 2007- March 2008.
The predictability between estimated and obtained astigmatism is 96.87%. In most of the cases the IOL was well centered in the capsular bag and stable on the predetermined axis, in 1 eye the IOL was rotated with about 30 degrees. The astigmatism evaluated in all patients at 6 months postoperatively being corrected in 78.13% of cases and reduced in 21.87% of cases. The UCVA between 2/3-5/5 was in 65.63% of cases and BCVA was in 34.37% of cases. To mention that 63.63% of patients with BCVA wanted to remain with myopia. | Does [ Toric intraocular lens implantation in cataract patients -- 6 months result ]? | Yes. Phacoemulsification and Acrysof Toric IOL implantation are an attractive alternative for patients with cataract and corneal astigmatism. The Acrysof Toric IOL eliminates or reduces preoperatively astigmatism, providing many patients a clear distance vision without glasses. | PASS | pubmedQA | 1 |
26464363 | During recent years, microRNAs (Greek: micros = small; miRNA) have become more important. miRNAs are highly conserved, noncoding, single-stranded RNA molecules 17–28 nucleotide in length. Secreted by tumor cells, miRNAs regulate many biological processes and are also involved in chemoresistance. Classical forms of cancer treatment lead to miRNA release. Which miRNAs are correlated to head and neck squamous cell carcinomas (HNSCC) and their chemoresistance to paclitaxel remains unknown.
Identification of miRNAs expressed in HNSCC and elucidation of those involved in conferring chemoresistance to paclitaxel.
To identify changes in gene expression, HNSCC cell lines were treated with 10 μM paclitaxel for 48 h and analyzed by microarray analysis. Thereafter, changed in expression of single miRNAs (miR221*, miR222 and miR222*) following paclitaxel treatment were analyzed using a quantitative real-time polymerase chain reaction (qRT-PCR).
Under treatment with paclitaxel, miRNAs were released. The dominant change is upregulation of MIR222 gene expression. Regulation of miR222* expression under paclitaxel treatment seems to be different in human papillomavirus (HPV)-negative and HPV-positive HNSCC cell lines. | Does [ Chemotherapy with paclitaxel lead to microRNA release ]? | Yes. Expression of mirR221/222 is correlated to cell cycle regulation, carcinogenesis, and chemoresistance. Detailed knowledge of the molecular mechanisms and effects ofmiRNAs is important for identifying miRNAs as cancermarkers, as well as for increasing the efficiency of cancer therapeutics. | PASS | pubmedQA | 1 |
26463477 | The aim of this study was to explore the efficacy and define mechanisms of action of PRIMA-1(MET) as a TP53 targeted therapy in soft-tissue sarcoma (STS) cells.
We investigated effects of PRIMA-1(MET) on apoptosis, cell cycle, and induction of oxidative stress and autophagy in a panel of 6 STS cell lines with different TP53 status.
Cell viability reduction by PRIMA-1(MET) was significantly observed in 5 out of 6 STS cell lines. We found that PRIMA-1(MET) was capable to induce cell death not only in STS cells harboring mutated TP53 but also in TP53-null STS cells demonstrating that PRIMA-1(MET) can induce cell death independently of TP53 in STS cells. We identified an important role of reactive oxygen species (ROS), involved in PRIMA-1(MET) toxicity in STS cells leading to a caspase-independent cell death. ROS toxicity was associated with autophagy induction or JNK pathway activation which represented potential mechanisms of cell death induced by PRIMA-1(MET) in STS. | Does pRIMA-1 ( MET ) induce death in soft-tissue sarcomas cell independent of p53? | Yes. PRIMA-1(MET) anti-tumor activity in STS partly results from off-target effects involving ROS toxicity and do not deserve further development as a TP53-targeted therapy in this setting. | PASS | pubmedQA | 1 |
10570427 | E2F-1 is a transcription factor that stimulates cellular proliferation and cell cycle progression from G(1) to S-phase. Somewhat paradoxically, E2F-1 also has the properties of a tumor suppressor. Overexpression of E2F-1 has been shown to induce apoptosis in some cancer cells. In the current study, the effect of adenovirus-mediated E2F-1 gene transfer on human melanoma cell growth was investigated.
Two human melanoma cell lines, SK-MEL-28 (wild-type p53) and SK-MEL-2 (mutant p53), were treated by mock infection, infection with a control vector expressing the beta-galactosidase gene (Ad5CMV-LacZ), or infection with a vector expressing E2F-1 (Ad5CMV-E2F-1) at a multiplicity of infection of 100. Cell proliferation and viability were determined by WST-1 assay and trypan blue exclusion, respectively. Apoptosis was assessed by cell flow cytometry and confirmed by cell morphology, in situ terminal deoxynucleotidyl nick end labeling assay, and poly(ADP-ribose) polymerase cleavage assay.
Marked overexpression of E2F-1 was evident in both cell lines 24 hours after infection with Ad5CMVE2F-1 by Western blot analysis. E2F-1 overexpression resulted in growth inhibition and rapid loss of cell viability. Overexpression of E2F-1 also resulted in premature S-phase entry and G(2) arrest at 24 hours followed by apoptotic cell death at 48 hours. After Ad5CMVE2F-1 infection, expression of Bax and Bak was unchanged, whereas Mcl-1 levels decreased markedly. In SK-MEL-28 cells, Bcl-XL levels also declined after E2F-1 expression. Bcl-2 was undetectable in SK-MEL-28 cells but was increased in SK-MEL-2 cells in response to E2F-1 overexpression. | Does adenovirus-mediated E2F-1 gene transfer efficiently induce apoptosis in melanoma cells? | Yes. Adenovirus-mediated E2F-1 gene transfer efficiently induces widespread apoptosis in human melanoma cells. E2F-1 overexpression induced apoptosis in cell lines containing wild-type and mutant p53, suggesting that this effect does not require wild-type p53 function. Anti-apoptotic proteins of the Bcl-2 family, notably Mcl-1 and Bcl-XL, may be involved in mediating the response to E2F-1. These data suggest that adenovirus-mediated E2F-1 gene therapy may be effective in the treatment of melanoma. | PASS | pubmedQA | 1 |
21381010 | TRAIL (tumor necrosis factor related apoptosis-inducing ligand) is involved in tumor immune surveillance and, thus, may be a potential cancer therapy. TRAIL expression in the tumor microenvironment has been shown to impact cancer survival in multiple tumor types, including ovarian cancer. We studied TRAIL expression and outcomes in patients with prostate cancer.
A tissue microarray (TMA) of 200 prostate cancer patients and benign prostate tissue controls was used to assess the epithelial and stromal protein expression of TRAIL, death receptors (DR4 and DR5), decoy receptors (DcR1 and DcR2), and the FLICE inhibitory protein (FLIP(L) ). We correlated these expression patterns with clinicopathological parameters and determined its impact on recurrence-free survival.
Nearly all (99.5%) prostate cancer tissues examined displayed either decreased expression of pro-apoptotic TRAIL receptors, increased FLIP(L) expression, or both. We observed elevated death receptor, decoy receptor, FLIP(L) , and epithelial TRAIL expression in prostate cancer epithelium. TRAIL expression in the stromal tumor microenvironment surrounding the prostate cancer was markedly lower. Elevated TRAIL expression in the tumor microenvironment was also significantly associated with increased recurrence-free survival (P = .014), after controlling for other prognostic markers. In contrast, epithelial expression of TRAIL did not have an effect on overall survival. | Is recurrence-free survival in prostate cancer related to increased stromal TRAIL expression? | Yes. Expression of the components of the pro-apoptotic TRAIL pathway is altered in prostate cancer. Moreover, TRAIL expression in the tumor microenvironment may affect recurrence-free survival rate of prostate cancer patients. Consequently, these results may be useful in devising future therapeutic strategies targeting the TRAIL pathway in prostate cancer. | PASS | pubmedQA | 1 |
19468252 | Recovery from stroke is dependent on the survival of neurons in the dynamic peri-infarcted region. Although several markers of neuronal injury and apoptotic cell death have been described, administration of neuroprotective drugs directed at specific molecules has had limited success. A complete understanding of deregulated genes associated with neuronal death would be beneficial. Our previous microarray studies identified increased expression of a novel protein, the B-cell translocation gene 2 (BTG2), in infarcted regions.
We have used immunohistochemistry and Western blotting to examine the expression and localization of BTG2 in stroked brain tissue and immunofluorescent staining of human fetal brain neurons to determine if oxygen-glucose deprivation affected its expression.
We show that BTG2 is strongly expressed in peri-infarcted and infarcted regions of brain tissue, localizing in neuronal nuclei and cytoplasm, whilst being absent or very weakly expressed in normal looking contralateral tissue. Exposure of human fetal brain neurons to oxygen-glucose deprivation also induced BTG2 expression in the cytoplasm and perinuclear regions of cells staining positive for propidium iodide (a marker of nuclear damage). | Is b-cell translocation gene 2 over-expressed in peri-infarct neurons after ischaemic stroke? | Yes. BTG2 may be a modulator of cell survival and differentiation and could help to protect against cell death by inhibition of necrosis and/or apoptotic signalling pathways. | PASS | pubmedQA | 1 |
20164810 | Limited information is currently available regarding muscle synergistic patterns and triggered reflex responses during dynamic weight-bearing activities in the presence of muscle fatigue.
The purpose of this study was to examine the effects of quadriceps muscle fatigue on patterns of muscle activation and performance in response to sudden, unexpected perturbations during a weight-bearing task.
Motion of the knee was measured as subjects were asked to track a visual target as accurately as possible while performing a resisted single leg squat task. Random perturbations were delivered in 20% of the trials by unexpectedly releasing the resistance during the flexion phase of the exercise. Absolute and constant errors were calculated to evaluate target tracking performance. Quadriceps and hamstring muscle activity was recorded during both perturbed and unperturbed trials. Twelve healthy women were tested before and after completing a repetitive submaximal eccentric quadriceps fatigue protocol. A second group of 12 women served as controls. Unexpected perturbations elicited long-latency responses characterized by facilitation of the quadriceps and inhibition of the hamstrings.
Muscle fatigue increased the amplitude of the long-latency response in vastus lateralis by 4.3% maximum voluntary isometric contraction (P = 0.004). Changes in tracking error occurred in response to perturbations after fatigue in spite of significantly increased quadriceps muscle activity, especially during the extension phase of the exercise. | Does quadriceps fatigue alter human muscle performance during a novel weight bearing task? | Yes. Quadriceps muscle fatigue alters the patterns of coordinated muscle activity and may render subjects less able to cope with unexpected perturbations during weight-bearing tasks. | PASS | pubmedQA | 1 |
19127288 | Injection of CD8 T cells primed against immunodominant minor histocompatibility antigens (MiHA) such as H7(a) can eradicate leukemia and solid tumors. To understand why MiHA-targeted T cells have such a potent antitumor effect it is essential to evaluate their in vivo behavior. In the present work, we therefore addressed two specific questions: what is the proliferative dynamics of H7(a)-specifc T cells in tumors, and do H7(a)-specific T cells persist long-term after adoptive transfer?
By day 3 after adoptive transfer, we observed a selective infiltration of melanomas by anti-H7(a) T cells. Over the next five days, anti-H7(a) T cells expanded massively in the tumor but not in the spleen. Thus, by day 8 after injection, anti-H7(a) T cells in the tumor had undergone more cell divisions than those in the spleen. These data strongly suggest that anti-H7(a) T cells proliferate preferentially and extensively in the tumors. We also found that two host factors regulated long-term persistence of anti-H7(a) memory T cells: thymic function and expression of H7(a) by host cells. On day 100, anti-H7(a) memory T cells were abundant in euthymic H7(a)-negative (B10.H7(b)) mice, present in low numbers in thymectomized H7(a)-positive (B10) hosts, and undetectable in euthymic H7(a)-positive recipients. | Do two host factors regulate persistence of H7-specific T cells injected in tumor-bearing mice? | Yes. Although in general the tumor environment is not propitious to T-cell invasion and expansion, the present work shows that this limitation may be overcome by adoptive transfer of primed CD8 T cells targeted to an immunodominant MiHA (here H7(a)). At least in some cases, prolonged persistence of adoptively transferred T cells may be valuable for prevention of late cancer relapse in adoptive hosts. Our findings therefore suggest that it may be advantageous to target MiHAs with a restricted tissue distribution in order to promote persistence of memory T cells and thereby minimize the risk of cancer recurrence. | PASS | pubmedQA | 1 |
26852107 | The critical issue related to breast-conserving therapy (BCT) is that cosmetic outcomes deteriorate with long-term follow-up. There is little research for breast density as a predictor of cosmetic outcomes at the late stage after BCT. To improve the long-term quality of life after BCT of breast cancer patients, the correlation of volumetric breast density (VBD) and cosmetic outcome at the late stage after BCT was evaluated.
Breast volume, fibroglandular tissue volume, adipose tissue volume, and VBD were calculated on mammography using image analysis software (Volpara(®)) in 151 patients with BCT. Furthermore, the correlation of breast density and the change of breast volume over time was analyzed on mammography in 99 patients who were followed-up long-term after BCT.
On multivariate analysis, VBD was a predictor of cosmetic outcome after BCT with percent breast volume excised (PBVE). Decreased adipose tissue volume and increased fibrosis were more common in patients with VBD < 15%. Furthermore, remnant breast volume continued to decrease over time in low breast density patients during long-term follow-up. 93% of patients with VBD ≥ 15% and PBVE < 10% had a better cosmetic outcome, while 60% of patients with VBD < 15% and PBVE ≥ 10% had a worse cosmetic outcome after BCT. | Is volumetric breast density essential for predicting cosmetic outcome at the late stage after breast-conserving surgery? | Yes. While PBVE was involved in cosmetic outcome at the early stage after BCT, VBD was associated with cosmetic outcome at the late stage after BCT. Thus, a combination of VBD and PBVE could predict cosmetic outcome after BCT and contribute to the selection for the appropriate BCT. | PASS | pubmedQA | 1 |
9758028 | This study evaluated the ability of partial liquid ventilation (PLV, gas ventilation of the perfluorocarbon-filled lungs) to reduce the amount of lung albumin leak present in the setting of acute lung injury.
An experimental controlled, randomized design was used. All studies were performed in the liquid ventilation laboratories at the University of Michigan Medical Center. Twenty-five Sprague-Dawley male rats 500+/-50 g were divided into five experimental groups: (1) CVF only (n=5), animals were cobra venom factor (CVF) lung injured; (2) PLV-CVF (n=5) animals received perflubron and PLV before CVF lung injury; (3) CVF-PLV (n=5) animals received PLV after CVF lung injury; (4) PLV only (n=5) animals underwent partial liquid ventilation without lung injury; and (5) Gas only (n=5) animals underwent gas ventilation without lung injury. In all groups iodinated bovine serum albumin (125I-BSA) was delivered by intravenous injection along with CVF or a saline placebo.
When the CVF animals were compared with all other groups, a decrease in albumin leak was observed for all groups when compared with the CVF only controls (P < .001 by ANOVA; CVF only=1.22+/-0.12 versus PLV-CVF=0.46+/-0.08, P < .001; CVF-PLV=0.70+/-0.25, P < .001; PLV only=0.22+/-0.01, P < .001; Gas only=0.17+/-0.02, P < .001). | Does partial liquid ventilation decrease albumin leak in the setting of acute lung injury? | Yes. These data suggest that intratracheal instillation of perfluorocarbon before or after induction of lung injury results in a reduction in pulmonary albumin leak. | PASS | pubmedQA | 1 |
11189197 | To determine the expression of PGH synthase-1 and the sensitivity of vascular smooth muscle to PGH2 in the aorta from the SHR at an age when no endothelium-dependent contractions to acetylcholine are observed under control conditions.
All experiments were performed in parallel on aortas from 20-wk-old SHR and Wistar-Kyoto normotensive rats (WKY). Rings, with or without endothelium, were suspended in conventional organ chambers for the recording of changes in isometric force. The expression of PGH synthase-1 was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis.
Under control conditions acetylcholine did not cause contractions of rings with or without endothelium. However, in the presence of nitro-L-arginine (NLA, an inhibitor of nitric-oxide synthase), it evoked endothelium-dependent contraction in the SHR but not in the WKY aortas. The expression of PGH synthase-1 was comparable in the aortas of both strains (with and without endothelium). PGH2 caused greater contractions in rings without endothelium from the SHR than those from WKY, while U46,619 evoked a comparable response, in aortas from both strains. | Does increased response to prostaglandin H2 precede changes in PGH synthase-1 expression in the SHR aorta? | Yes. In the aorta of 20-wk-old SHR, endothelium-dependent contractions to acetylcholine are observed only when the production of nitric oxide is prevented. They are associated with an augmented sensitivity of the smooth muscle to PGH2, but not with an increased expression of PGH synthase-1. | PASS | pubmedQA | 1 |
17577119 | Recent accumulating evidence indicates that lysophosphatidic acid (LPA) is a lipid mediator, abundantly present in blood, with a wide range of biologic actions including the regulation of proliferation and contraction in liver cells. Although it is speculated that LPA might play a role in pathophysiologic processes in vivo, not only its role but also even a possible alteration in its blood concentration under specific diseases is essentially unknown. Autotaxin (ATX), originally purified as an autocrine motility factor for melanoma cells, was revealed to be a key enzyme in LPA synthesis. We determined LPA and ATX levels in the blood of patients with liver disease.
ATX activity was measured by determining choline with the substrate of lysophosphatidylcholine, and the LPA level by an enzymatic cycling method in 41 patients with chronic hepatitis C.
The serum ATX activity and plasma LPA level were significantly increased in patients, and were correlated positively with serum hyaluronic acid, and negatively with platelets, albumin, and prothrombin time. The plasma LPA level was strongly correlated with serum ATX activity. There were significant correlations between the histologic stage of fibrosis and both the serum ATX activity and plasma LPA level. | Are both plasma lysophosphatidic acid and serum autotaxin levels increased in chronic hepatitis C? | Yes. The serum ATX activity and plasma LPA level are increased in chronic hepatitis C in association with liver fibrosis. Our study may provide the first evidence showing a significant increase of both ATX and LPA in the blood under a specific disease. | PASS | pubmedQA | 1 |
21740135 | Cyanide is a component of smoke in residential and industrial fires, and accidental exposure to cyanide occurs in a variety of industries. Moreover, cyanide has the potential to be used by terrorists, particularly in a closed space such as an airport or train station. Current therapies for cyanide poisoning must be given by intravenous administration, limiting their use in treating mass casualties.
We are developing two new cyanide antidotes--cobinamide, a vitamin B(12) analog, and sulfanegen, a 3-mercaptopyruvate prodrug. Both drugs can be given by intramuscular administration, and therefore could be used to treat a large number of people quickly. We now asked if the two drugs would have an augmented effect when combined.
We used a non-lethal and two different lethal models of cyanide poisoning in mice. The non-lethal model assesses neurologic recovery by quantitatively evaluating the innate righting reflex time of a mouse. The two lethal models are a cyanide injection and a cyanide inhalation model.
We found that the two drugs are at least additive when used together in both the non-lethal and lethal models: at doses where all animals died with either drug alone, the combination yielded 80 and 40% survival in the injection and inhalation models, respectively. Similarly, drug doses that yielded 40% survival with either drug alone, yielded 80 and 100% survival in the injection and inhalation models, respectively. As part of the inhalation model, we developed a new paradigm in which animals are exposed to cyanide gas, injected intramuscularly with an antidote, and then re-exposed to cyanide gas. This simulates cyanide exposure of a large number of people in a closed space, because people would remain exposed to cyanide, even after receiving an antidote. | Is the combination of cobinamide and sulfanegen highly effective in mouse models of cyanide poisoning? | Yes. The combination of cobinamide and sulfanegen shows great promise as a new approach to treating cyanide poisoning. | PASS | pubmedQA | 1 |
22491550 | Traumatic hemorrhagic shock and subsequent resuscitation may promote bacteria translocation and cause endotoxemia, a two-hit process that will induce severe lung injury. The pathogenesis involves oxidative stress, neutrophil infiltration, and inflammatory response. Platonin, a potent antioxidant, possesses potent anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury in a two-hit model of traumatic hemorrhage/resuscitation and subsequent endotoxemia.
Adult male rats were randomized to receive traumatic hemorrhage/resuscitation plus lipopolysaccharide (HS/L) alone or HS/L plus platonin (200 μg/kg; n = 12 in each group). Sham groups were used simultaneously. At 6 hours after resuscitation, rats were killed and the levels of lung injury were assayed.
Rats treated with HS/L alone had severe lung injury as evidenced by significant alterations in lung function (i.e., arterial blood gas and alveolar-arterial oxygen difference) and histology. Significant increases in polymorphonuclear leukocytes/alveoli ratio (neutrophil infiltration index) and significant increases in the concentrations of inflammatory molecules (including chemokine, cytokine, and prostaglandin E2) and malondialdehyde (lipid peroxidation index) revealed that HS/L caused significant oxidative stress, neutrophil infiltration, and inflammatory response in rat lungs. Moreover, our data revealed that the levels of functional and histologic alteration as well as polymorphonuclear leukocytes/alveoli ratio and the concentrations of inflammatory molecules and malondialdehyde in rats treated with HS/L plus platonin (200 μg/kg) were significantly lower than those treated with HR/L alone. | Does platonin mitigate lung injury in a two-hit model of hemorrhage/resuscitation and endotoxemia in rats? | Yes. Platonin mitigates lung injury in a two-hit model of traumatic hemorrhage/resuscitation and endotoxemia in rats. | PASS | pubmedQA | 1 |
15234290 | To classify and describe clinically meaningful classes of color vision defects using pretreatment Farnsworth-Munsell 100-hue results from the Early Treatment Diabetic Retinopathy Study (ETDRS) patients using standard statistical techniques.
The ETDRS was a randomized trial investigating retinal photocoagulation and oral aspirin in diabetic retinopathy.
Farnsworth-Munsell (FM) 100-hue test was successfully administered before initiation of study treatment in each eye of 2701 of the 3711 ETDRS patients. Test results were converted into a Fourier series, classified by cluster analysis in the deferred-treatment group of eyes, and verified in the immediate-treatment group of eyes as separate samples.
Cluster analysis uncovered thirteen distinct patterns. Pattern A (51% or 1366 of the eyes) showed unimpaired hue discrimination and was comprised of younger patients with no or little macular edema. Pattern B eyes (10% or 262) showed generalized impairment of hue discrimination with no main axis defect. Patterns C (C1, C2, C3), comprising 26% (or 698) of the eyes, showed increasing severity of the yellow-blue diabetic retinopathy defect, associated with increasing mean age and increasing macular edema severity. Patterns D (D1, D2), comprising 6% (or 164) of the eyes, were similar to the C patterns but showed a stronger yellow-blue defect. Patterns E (E1, E2, E3), or approximately 2% (or 38) of the eyes and predominantly male, exhibited the expected pattern for congenital protan defect. Patterns F, G, and H, approximately 6% (or 153) of the eyes, showed distinct patterns of one-sided axes. The nomenclature is arbitrary. | Does classification of Farnsworth-Munsell 100-hue test result in the early treatment diabetic retinopathy study? | Yes. Cluster analysis of FM 100-hue test results has found 13 patterns of impaired hue discrimination, helpful in understanding color vision defects in diabetes mellitus. | PASS | pubmedQA | 1 |
25113270 | Total serum transforming growth factor-beta 1 (tsTGF-β1) is increased in patients with Marfan syndrome (MFS), but it has not been assessed in thoracic aortic aneurysm and dissection (TAAD), Loeys-Dietz syndrome (LDS), and bicuspid aortic valve disease (BAVD).
tsTGF-β1 is increased in genetic aortic syndromes including TAAD, LDS, MFS, and BAVD.
We measured tsTGF-β1 and performed sequencing of the genes FBN1, TGFBR1, and TGFBR2 in 317 consecutive patients with suspected or known genetic aortic syndrome (167 men, 150 women; mean age 43 ± 14 years). TAAD was diagnosed in 20, LDS in 20, MFS in 128, and BAVD in 30 patients, and genetic aortic syndrome was excluded in 119 patients.
Elevated tsTGF-β1 levels were associated with causative gene mutations (P = 0.008), genetic aortic syndrome (P = 0.009), and sporadic occurrence of genetic aortic syndrome (P = 0.048), whereas only genetic aortic syndrome qualified as an independent predictor of tsTGF-β1 (P = 0.001). The tsTGF-β1 levels were elevated in FBN1 and NOTCH1 mutations vs patients without mutations (both P = 0.004), and in NOTCH1 mutations vs ACTA2/MYH11 mutations (P = 0.015). Similarly, tsTGF-β1 levels were elevated in MFS (P = 0.003) and in BAVD (P = 0.006) vs patients without genetic aortic syndrome. In contrast to specific clinical features of MFS, FBN1 in-frame mutations (P = 0.019) were associated with increased tsTGF-β1 levels. | Is total serum transforming growth factor-β1 elevated in the entire spectrum of genetic aortic syndromes? | Yes. tsTGF-β1 is elevated in the entire spectrum of genetic aortic syndromes. However, gradual differences in the increases of tsTGF-β1 levels may mirror different degrees of alteration of tsTGF-β1 signaling in different genetic aortic syndromes. | PASS | pubmedQA | 1 |
15510613 | Aberrations in folate metabolism contribute to the risk of cancer via effects on the synthesis, methylation and repair of DNA. Functional genetic variants in the methylene tetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) genes may be risk factors for breast cancer because of their central roles in cellular folate metabolism.
The MTHFR C677T and TS tandem repeat polymorphisms were investigated in a case-control study of 339 women with breast cancer for possible associations with the risk of this disease, tumor phenotype and patient survival.
The MTHFR and TS polymorphisms were not associated with a significantly increased risk of breast cancer. No associations were observed with any pathological or molecular feature and neither polymorphism was associated with survival from this disease. | Are methylenetetrahydrofolate reductase and thymidylate synthase polymorphisms associated with breast cancer risk or phenotype? | No. The common MTHFR C677T and TS enhancer region polymorphisms were not risk factors for breast cancer in this patient cohort nor were they associated with phenotypic features or with prognosis. | PASS | pubmedQA | 1 |
9175815 | Allograft survival can be prolonged by the administration of alloantigen(s) before transplantation. Blood transfusion is the commonest form of alloantigen pretreatment currently used in clinical practice. However, for recipients of organs from cadaver donors, it is not possible to predict the identity of the organ donor in advance. Therefore, it is highly unlikely that all the alloantigens expressed by a cadaver organ donor will be represented in the alloantigen pretreatment inoculum. We have previously shown that it is not necessary to expose the recipient to the full complement of donor alloantigens to induce long-term survival of a subsequent cardiac allograft. Here, we investigated the in vivo mechanism responsible for this phenomena.
Unresponsiveness to the mouse MHC class I molecule Kb was induced in CBA.Ca (H2k) recipients by administration of bone marrow cells from transgenic CBA mice, CBK (H2k + Kb) before transplantation of fully allogeneic and F1 vascularized cardiac allografts.
Pretreatment with CBK bone marrow cells resulted in the long-term survival of all cardiac allografts expressing H2-Kb. For example, C57BL/10 (H2b) and (CBKxBALB/c) F1 (H2k,d + Kb) cardiac allografts were accepted by recipients treated with CBK bone marrow cells before transplantation. In contrast, allografts that did not express Kb, such as BALB/c (H2d) or (CBAxBALB/c) F1 (H2k,d), were rejected acutely, with a median survival time (MST) of 7 and 6 days, respectively, in recipients treated with CBK bone marrow cells. Furthermore, when recipients pretreated with CBK bone marrow cells were grafted with a BALB/c heart and a CBK heart simultaneously, the BALB/c hearts were rejected (MST=10 days), whereas the CBK hearts were accepted. By contrast, in the maintenance phase (i.e., after transplantation), recipients with long-term surviving (CBKxBALB/c) F1 hearts (> 100 days) were found to accept BALB/c hearts indefinitely, whereas fourth-party B10.S (H2s) grafts were rejected (MST=7.5 days). This indicated that the allografts bearing Kb could tolerize recipients to other alloantigens expressed by the transplanted heart. | Is pretransplant administration of a single donor class I major histocompatibility complex molecule sufficient for the indefinite survival of fully allogeneic cardiac allografts : evidence for linked epitope suppression? | Yes. These data provide clear evidence for linked epitope suppression in the induction of operational tolerance in vivo. | PASS | pubmedQA | 1 |
16962471 | Collagens are important components of the extracellular matrix (ECM). Alterations in collagen structure and composition can lead to end-stage heart failure. Left ventricular assist devices (LVADs) are frequently used as a bridge to heart transplantation (HTx). In this study, we analyzed changes in composition of the collagens as well as the synthesis or degradation of these collagens after prolonged LVAD support.
The ECM volume was quantified after Picro-Sirius red staining. With immunohistochemistry (IHC), Type I and Type III collagen proteins were analyzed and, using quantitative polymerase chain reaction (PCR), collagen mRNA expression was analyzed. Collagen synthesis and degradation was studied by measuring N-terminal pro-peptide for Type I collagen (PINP), N-terminal pro-peptide for Type III collagen (PIIINP) and carboxyterminal telopeptide for Type I collagen (ICTP) in plasma. Collagen composition was measured using the hydroxyproline/Sircol assay.
The ECM volume increased in the first 200 days after LVAD implantation. At between 200 and 400 days the ECM volume decreased, but remained higher than pre-LVAD. After 400 days the ECM volume was smaller than the pre-LVAD volume. IHC did not show a significant difference pre- and post-LVAD for collagen composition. Collagen mRNA expression did not change but an augmented synthesis of collagen during the first month after LVAD support was detected upon measurement of plasma PINP and PIIINP levels. In addition, the quality of the collagen network improved. | Does reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follow a biphasic pattern? | Yes. Reverse remodeling during LVAD support follows a biphasic pattern. Initially, an increase in Type I and Type III collagen turnover occurs, which is paralleled by a volume increase of the ECM. Subsequently, this turnover decreases as ECM volume decreases, which results in a restoration of the collagen network. | PASS | pubmedQA | 1 |
20065626 | Although the cardioprotective effects of supplemental doses of vitamin E have been investigated in several conditions, its role in gonadectomy- induced fatty lesion formation is unclear. The present study was designed to examine the efficacy of vitamin E in a dose-dependent manner on indices of oxidative stress and in preventing the formation of aortic fatty lesions in orchidectomized (Orx) aged rats.
Forty 12-month old male Sprague-Dawley rats were either sham-operated (Sham) or Orx and fed a semi-purified control diet for 120 days. Thereafter, rats were assigned to four treatment groups (n=10): Sham and one Orx group received 75 IU vitamin E and served as controls, and the other two Orx groups received either 250 or 500 IU vitamin E per kg diet for 90 days.
Vitamin E at the highest dose (500 IU) was able to lower serum total cholesterol by 16% and significantly increase superoxide dismutase by 9% compared to Orx controls. Similarly, this dose was able to significantly reduce the development of atherosclerotic lesion formation and aortic fatty streak area by 93% compared to Orx controls. | Does vitamin E dose-dependently reduce aortic fatty lesion formation in orchidectomized aged rats? | Yes. The findings of this study suggest that dietary vitamin E supplementation in Orx aged rats provide anti-atherogenic effects, in part, due to vitamin E's antioxidative properties. Clinical studies are needed to confirm whether supplemental doses of vitamin E can prevent the development of atherosclerosis in older men particularly with low testosterone level. | PASS | pubmedQA | 1 |
23434818 | Prenatal exposure to environmental levels of organochlorines (OCs) has been demonstrated to have immunotoxic effects in humans. We investigated the relationship between prenatal exposure to OCs and the occurrence of otitis media (OM) among Inuit children in Greenland.
We estimated the concentration of 14 PCB congeners and 11 pesticides in maternal and cord blood samples and in breast milk in a population-based cohort of 400 mother-child pairs. At follow-up, we examined the children's ears and used their medical records to assess the OM occurrence and severity. Multivariate regression analyses were used with adjustments for passive smoking, crowding, dietary habits, parent's educational level, breast feeding and the use of child-care.
The children were 4-10 years of age at follow-up and 223 (85%) participated. We found no association between prenatal OC exposure and the development of OM. Factors associated with the child's hazard of OM during the first 4 years of life were: mother's history of OM (HR 1.70, 95% CI 1.11-2.59, p=0.01); mother's smoking habits: current (HR 2.47, 95% CI 1.45-4.21, p<0.01) and previous (HR 2.00, 95% CI 1.19-3.36, p<0.01); number of smokers in the home (HR 1.17, 95% CI 1.05-1.31, p<0.01). After adjustment mothers' smoking habits remained significant. | Does tobacco smoke increase the risk of otitis media among Greenlandic Inuit children while exposure to organochlorines remain insignificant? | Yes. We found no relationship between high levels of prenatal exposure of OCs and occurrence of OM. Passive smoking was found as the strongest environmental risk factor for the development of OM. Interventions to reduce passive smoke in children's environment are needed. | PASS | pubmedQA | 1 |
23544041 | In Parkinson's disease (PD), commonly reported risk factors for malnutrition in other populations commonly occur. Few studies have explored which of these factors are of particular importance in malnutrition in PD. The aim was to identify the determinants of nutritional status in people with Parkinson's disease (PWP).
Community-dwelling PWP (>18 years) were recruited (n = 125; 73M/52F; Mdn 70 years). Self-report assessments included Beck's Depression Inventory (BDI), Spielberger Trait Anxiety Inventory (STAI), Scales for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT), Modified Constipation Assessment Scale (MCAS) and Freezing of Gait Questionnaire (FOG-Q). Information about age, PD duration, medications, co-morbid conditions and living situation was obtained. Addenbrooke's Cognitive Examination (ACE-R), Unified Parkinson's Disease Rating Scale (UPDRS) II and UPDRS III were performed. Nutritional status was assessed using the Subjective Global Assessment (SGA) as part of the scored Patient-Generated Subjective Global Assessment (PG-SGA).
Nineteen (15%) were malnourished (SGA-B). Median PG-SGA score was 3. More of the malnourished were elderly (84% vs. 71%) and had more severe disease (H&Y: 21% vs. 5%). UPDRS II and UPDRS III scores and levodopa equivalent daily dose (LEDD)/body weight (mg/kg) were significantly higher in the malnourished (Mdn 18 vs. 15; 20 vs. 15; 10.1 vs. 7.6 respectively). Regression analyses revealed older age at diagnosis, higher LEDD/body weight (mg/kg), greater UPDRS III score, lower STAI score and higher BDI score as significant predictors of malnutrition (SGA-B). Living alone and higher BDI and UPDRS III scores were significant predictors of a higher log-adjusted PG-SGA score. | Are markers of disease severity associated with malnutrition in Parkinson 's disease? | Yes. In this sample of PWP, the rate of malnutrition was higher than that previously reported in the general community. Nutrition screening should occur regularly in those with more severe disease and depression. Community support should be provided to PWP living alone. Dopaminergic medication should be reviewed with body weight changes. | PASS | pubmedQA | 1 |
19053924 | Recent studies have reported an association between poor dental health and acute coronary syndrome (ACS). The purpose of this study was to correlate the presence of periodontitis with serum endotoxin/lipopolysaccharides (LPS), lipid profiles, troponin, and immunoglobulin G (IgG) antibody to Porphyromonas gingivalis in control patients or patients with ACS or angina at the time of hospital admission.
Blood samples from 194 subjects presenting with ACS, angina, or non-cardiac chest pain were analyzed for endotoxin/LPS (Limulus amebocyte lysate assay), lipid profile, troponin, and IgG antibody to P. gingivalis. Data were collected from hospital charts and dental records, and health questionnaire responses.
Subjects with ACS or angina were more likely to have poor oral care, fewer remaining teeth, and increased alveolar radiographic bone loss compared to subjects with chest pain. In all subjects, endotoxin/LPS and IgG antibody to P. gingivalis tended to increase in association with increased radiographic bone loss. Endotoxin/LPS increased directly with triglyceride and troponin levels (P = 0.04 and P = 0.006, respectively) and inversely with high-density lipoprotein (HDL) levels (P = 0.002). IgG antibody to P. gingivalis levels was directly correlated with very low-density lipoprotein (P = 0.03) and triglycerides (P = 0.06) and inversely with low-density lipoprotein (P = 0.01). | Are endotoxin levels associated with high-density lipoprotein , triglycerides , and troponin in patients with acute coronary syndrome and angina : possible contributions from periodontal sources? | Yes. Results showed more alveolar bone loss in patients with cardiac disease than in patients without cardiac disease, but there was no difference between the groups in the serum levels of endotoxin/LPS or IgG antibody to P. gingivalis. However, there were associations between endotoxin/LPS and levels of serum triglycerides, troponin, and HDL. | PASS | pubmedQA | 1 |
16186269 | Stressful life events have been shown to constitute a risk factor for type 1 diabetes during childhood. Our aim was to investigate in the general child population (i.e., irrespective of genetic risk for type 1 diabetes) whether mothers' experiences of serious life events, such as divorce and violence, were associated with diabetes-related autoimmunity in their children at age 2.5 years.
The study cohort was comprised of the first 5,986 consecutive children and their families from the prospective population-based All Babies in Southeast Sweden project for whom 2.5-year study data were available. Data were drawn from parental questionnaires that included questions about experiences of serious life events and the blood samples taken from the children when the children were age 2.5 years. The blood samples were analyzed for diabetes-related autoantibodies against tyrosine phosphatase and GAD.
Mothers' experiences of divorce (odds ratio 3.6, 95% CI 1.4-9.6, P < 0.05) and violence (2.9, 1.0-7.8, P < 0.05) were associated with diabetes-related autoimmunity in the children, independent of a family history of type 1 diabetes. | Do mothers ' experiences of serious life events increase the risk of diabetes-related autoimmunity in their children? | Yes. The results support the beta-cell stress hypothesis and suggest that maternal experiences of serious life events such as divorce and violence seem to be involved in the induction or progression of diabetes-related autoimmunity in children at age 2.5 years, independent of family history of type 1 diabetes. | PASS | pubmedQA | 1 |
21185397 | The fecal immunochemical test (FIT) is superior to the guaiac-based fecal occult blood test in detecting neoplasia. There are not much data on the optimal number of FITs to perform. We conducted a population-based trial to determine attendance and diagnostic yield of 1- and 2-sample FIT screening.
The study included 2 randomly selected groups of subjects aged 50-74 years (1-sample FIT, n=5007; 2-sample FIT, n=3197). The 2-sample group was instructed to collect fecal samples on 2 consecutive days. Subjects were referred for colonoscopy when at least 1 sample tested positive (≥50 ng hemoglobin/mL).
Attendance was 61.5% in the 1-sample group (2979 of 4845; 95% confidence interval, 60.1%-62.9%) and 61.3% in the 2-sample group (1875 of 3061; 95% confidence interval, 59.6%-63.0%; P=.84). In the 1-sample group 8.1% tested positive, and in the 2-sample group 12.8% had at least 1 positive test outcome and 5.0% had 2 positive test outcomes (P<.05). When the mean from both test results in the 2-sample group was used, 10.1% had a positive test outcome (P<.05). The detection rates for advanced neoplasia were 3.1% in the 1-sample group, 4.1% in the 2-sample group with at least 1 positive test outcome, 2.5% when both test results were positive, and 3.7% among subjects with the mean from both test results being positive. | Does diagnostic yield improve with collection of 2 samples in fecal immunochemical test screening without affecting attendance? | Yes. There is no difference in attendance for subjects offered 1- or 2-sample FIT screening. The results allow for the development of efficient FIT screening strategies that can be adapted for local colonoscopy capacities, rather than varying the cut-off value in a 1-sample strategy. | PASS | pubmedQA | 1 |
25520328 | Variability in the duration of attempted in‐hospital cardiopulmonary resuscitation (CPR) is high, but the factors influencing termination of CPR efforts are unknown.
We examined the association between patient and hospital characteristics and CPR duration in 45 500 victims of in‐hospital cardiac arrest who did not experience return of spontaneous circulation (ROSC) and who were enrolled in the Get With the Guidelines registry between 2001 and 2010. In a secondary analysis, we performed analyses in 46 168 victims of in‐hospital cardiac arrest who experienced ROSC. We used ordered logistic regression to identify factors associated with CPR duration. Analyses were conducted by tertile of CPR duration (tertiles: ROSC group: 2 to 7, 8 to 17, and 18 to 120 minutes; no‐ROSC group: 2 to 16, 17 to 26, 27 to 120 minutes). In those without ROSC, younger age (aged 18 to 40 versus >65 years; odds ratio [OR] 1.81; 95% CI 1.69 to 1.95; P<0.001), female sex (OR 1.05; 95% CI 1.02 to 1.09; P=0.005), ventricular tachycardia or fibrillation (OR 1.50; 95% CI 1.42 to 1.58; P<0.001), and the need to place an invasive airway (OR 2.59; 95% CI 2.46 to 2.72; P<0.001) were associated with longer CPR duration. In those with ROSC, ventricular tachycardia or fibrillation (OR 0.89; 95% CI 0.85 to 0.93; P<0.001) and witnessed events (OR 0.87; 95% CI 0.82 to 0.91; P<0.001) were associated with shorter duration. | Are age , sex , and hospital factors associated with the duration of cardiopulmonary resuscitation in hospitalized patients who do not experience sustained return of spontaneous circulation? | Yes. Age and sex were associated with attempted CPR duration in patients who do not experience ROSC after in‐hospital cardiac arrest but not in those who experience ROSC. Understanding the mechanism of these interactions may help explain variability in outcomes for in‐hospital cardiac arrest. | PASS | pubmedQA | 1 |
27821059 | Transposable elements (TEs) are mobile pieces of genetic information with high mutagenic potential for the host genome. Transposition is often neutral or deleterious but may also generate potentially adaptive genetic variation. This additional source of variation could be especially relevant in non-recombining species reproducing asexually. However, evidence is lacking to determine the relevance of TEs in plant asexual genome evolution and their associated effects. Here, we characterize the repetitive fraction of the genome of the common dandelion, Taraxacum officinale and compare it between five accessions from the same apomictic lineage. The main objective of this study is to evaluate the extent of within-lineage divergence attributed to TE content and activity. We examined the repetitive genomic contribution, diversity, transcription and methylation changes to characterize accession-specific TEs.
Using low-coverage genomic sequencing, we report a highly heterogeneous TE compartment in the triploid apomict T. officinale representing up to 38.6 % of the homoploid genome. The repetitive compartment is dominated by LTR retrotransposon families accompanied by few non-LTR retrotransposons and DNA transposons. Up to half of the repeat clusters are biased towards very high read identity, indicating recent and potentially ongoing activity of these TE families. Interestingly, the five accessions are divided into two main clades based on their TE composition. Clade 2 is more dynamic than clade 1 with higher abundance of Gypsy Chromovirus sequences and transposons. Furthermore, a few low-abundant genomic TE clusters exhibit high level of transcription in two of the accessions analysed. Using reduced representation bisulfite sequencing, we detected 18.9 % of loci differentially methylated, of which 25.4 and 40.7 % are annotated as TEs or functional genes, respectively. Additionally, we show clear evidence for accession-specific TE families that are differentially transcribed and differentially methylated within the apomictic lineage, including one Copia Ale II LTR element and a PIF-Harbinger DNA transposon. | Do recent and dynamic transposable elements contribute to genomic divergence under asexuality? | Yes. We report here a very young and dynamic repetitive compartment that enhances divergence within one asexual lineage of T. officinale. We speculate that accession-specific TE families that are both transcriptionally and epigenetically variable are more prone to trigger changes in expression on nearby coding sequences. These findings emphasize the potential of TE-induced mutations on functional genes during asexual genome evolution. | PASS | pubmedQA | 1 |
20657867 | The purpose of this study was to determine whether osseous tissues engineered in three-dimensional (3D) environments preserved their mineralizing capacity and retained biologic characteristics when cultured on dental implant surfaces.
Human preosteoblast cells were cultured in both 3D rotary wall vessels and on 2D tissue culture plastic plates for 3 days. Aggregates from the 3D chambers and cells from the 2D plates were collected and transferred to commercially pure titanium disks with either 600-grit polished or sandblasted surfaces. These were cultured for an additional 7 days. The aggregates and cells from the disks were collected and prepared for scanning electron microscopy for microscopic evaluation and atomic adsorption assays for mineral content analysis. Additionally, staining with Alizarin red S was performed to compare the mineralization amount and pattern in each group. Polymerase chain reaction analysis was performed to evaluate expression of osteogenic genes, including Runx2, FAK, bone morphogenetic protein 2, and osteocalcin.
Cells from 3D rotary wall vessel cultures attached to implant surfaces and presented cell attachment and growth patterns similar to those of standard 2D cultured cells, showing evidence of radial and random growth, yet they formed multiple focal niches on implant surfaces out of which cells proliferated. The 3D cultured cells and osseous tissues retained higher amounts of mineral formed during the initial culture and showed a higher tendency toward mineralization on implant surfaces compared to standard cultured cells. The 3D cultured cells and osseous tissues on implant surfaces at 1 week showed higher key gene protein expression. RNA expression at 1 week was equivalent to that of standard cultured cells. | Do analysis of the attachment and differentiation of three-dimensional rotary wall vessel cultured human preosteoblasts on dental implant surfaces? | Yes. Culture of human osteogenic cells and tissues in 3D rotary wall vessels may expedite the osseointegration process on dental implant surfaces, thus reducing the overall treatment time. | PASS | pubmedQA | 1 |
15749040 | AAA repair is associated with a systemic inflammatory response, mediated in part by neutrophils. The aim of this study was to determine where neutrophil activation occurs.
Blood was sampled from the femoral vein, portal vein and radial artery of 10 patients undergoing elective AAA repair at four time-points [induction of anaesthesia (systemic sample only), pre-aortic clamp application, pre-clamp removal and after 30min of reperfusion]. Whole blood was analysed for the white cell count, neutrophil count, and for neutrophil CD11b expression.
The white cell count and neutrophil counts increased after aortic clamp release. Neutrophil expression of CD11b was significantly higher in the femoral vein than the portal vein and systemic circulation during ischaemia [P=0.001 (FV vs. PV), P=0.017 (FV vs. systemic)] and reperfusion [P=0.001 (FV vs. PV), P=0.013 (FV vs. systemic)]. There were no significant differences in neutrophil CD11b expression between the systemic and portal vein samples at any time. | Does neutrophil activation occur in the lower-limbs of patients undergoing elective repair of abdominal aortic aneurysm? | Yes. Ischaemia and reperfusion during abdominal aortic aneurysm repair are associated with a global increase in the white cell count and neutrophil count, but with increased neutrophil CD11b expression only in the femoral vein. This suggests the lower-limbs are sensitive to aortic clamp-related reperfusion injury and may fuel the inflammatory response. | PASS | pubmedQA | 1 |
15958363 | To investigate cytokine gene expression in patients with aortic valve stenosis (AS) and with idiopathic dilated cardiomyopathy (DCM), and to correlate wall stress with myocardial proinflammatory cytokine gene expression.
Human left ventricular (LV) myocardial biopsies were obtained for subsequent reverse transcription polymerase chain reaction of tumour necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6 mRNA. The study population consisted of 24 patients with AS and 10 patients with idiopathic DCM.
Patients with AS had a larger ejection fraction (56 (5) v 37 (4)%, p < 0.01), smaller LV end diastolic volumes (146 (11) v 267 (21) ml, p < 0.01), and lower end systolic wall stress (44 (7) v 112 (11) kdyn/cm2, p < 0.001). Upregulation of TNFalpha, IL-1beta, and IL-6 gene expression was detected in both groups. However, TNFalpha gene expression was significantly higher in AS than in DCM (p = 0.009). No correlation was found between haemodynamic parameters and TNFalpha gene expression. In patients with AS there was a strong inverse relation between circulating TNFalpha and TNFalpha gene expression (r = -0.685, p = 0.014), between circulating TNFalpha and IL-1beta gene expression (r = -0.664, p = 0.018), and between soluble TNF receptor 2 and TNFalpha gene expression (r = -0.685, p = 0.020). Myocardial gene expression of TNFalpha was significantly higher in patients with well compensated AS than in patients with decompensated AS (p = 0.017). Similarly, patients with decompensated DCM were characterised by significantly lower TNFalpha gene expression than were patients with well compensated DCM (p = 0.011). | Is myocardial cytokine gene expression higher in aortic stenosis than in idiopathic dilated cardiomyopathy? | Yes. TNFalpha gene expression is significantly higher in patients with pressure overload than in normal hearts, in patients with idiopathic DCM, and in patients with compensated versus decompensated heart failure. Secondly, in patients with AS proinflammatory cytokine gene expression did not affect systolic performance. The higher TNFalpha gene expression in patients with compensated heart failure suggests that cytokine gene expression has an adaptive role in the early phase of LV remodelling. | PASS | pubmedQA | 1 |
25806553 | To estimate the economic consequences of the current Brazilian government policy for attention-deficit/hyperactivity disorder (ADHD) treatment and how much the country would save if treatment with immediate-release methylphenidate (MPH-IR), as suggested by the World Health Organization (WHO), was offered to patients with ADHD.
Based on conservative previous analyses, we assumed that 257,662 patients aged 5 to 19 years are not receiving ADHD treatment in Brazil. We estimated the direct costs and savings of treating and not treating ADHD on the basis of the following data: a) spending on ADHD patients directly attributable to grade retention and emergency department visits; and b) savings due to impact of ADHD treatment on these outcomes.
Considering outcomes for which data on the impact of MPH-IR treatment are available, Brazil is probably wasting approximately R$ 1.841 billion/year on the direct consequences of not treating ADHD in this age range alone. On the other hand, treating ADHD in accordance with WHO recommendations would save approximately R$ 1.163 billion/year. | Is the Brazilian policy of withholding treatment for ADHD probably increasing health and social costs? | Yes. By increasing investments on MPH-IR treatment for ADHD to around R$ 377 million/year, the country would save approximately 3.1 times more than is currently spent on the consequences of not treating ADHD in patients aged 5 to 19 years. | PASS | pubmedQA | 1 |
20950982 | Angioembolization is an effective adjunct to the management of retroperitoneal hemorrhage in pelvic fractures. Most patients with stable-type pelvic fracture are treated conservatively. However, in some stable pelvic fracture cases, patients should receive angioembolization for hemostasis upon incidental finding of contrast extravasation on computed tomography (CT). In this study, we attempted to define the characteristics of patients with stable pelvic fracture requiring angioembolization.
We retrospectively reviewed the charts of patients with pelvic fractures between January 2005 and November 2009. We focused on stable pelvic fracture patients with contrast extravasation on CT who then received angioembolization. The demographics, Injury Severity Score (ISS), Abbreviated Injury Scale score, and the blood glucose levels on admission were analyzed.
In total, 334 patients were enrolled. Patients with higher blood glucose level on admission with stable pelvic fracture had a higher rate of angioembolization. Furthermore, these patients presented with a higher Abbreviated Injury Scale score and ISS. | Is higher glucose on admission associated with need for angioembolization in stable pelvic fracture? | Yes. In patients with stable pelvic fracture, higher blood glucose level on admission was associated with a higher likelihood of needing angioembolization. Blood glucose level should be checked during the initial survey of a pelvic fracture, and greater attention should be given to patients with higher blood glucose level or with an ISS of 25 or greater, even when the imaging study only reveals a stable pelvic fracture. | PASS | pubmedQA | 1 |
24112871 | In orthopaedic surgery, accumulation of agents such as anti-infectives in the bone as target tissue is difficult. The use of magnetic nanoparticles (MNPs) as carriers principally enables their accumulation via an externally applied magnetic field. Magnetizable implants are principally able to increase the strength of an externally applied magnetic field to reach also deep-seated parts in the body. Therefore, the integration of bone-addressed therapeutics in MNPs and their accumulation at a magnetic orthopaedic implant could improve the treatment of implant related infections. In this study a martensitic steel platelet as implant placeholder was used to examine its accumulation and retention capacity of MNPs in an in vitro experimental set up considering different experimental frame conditions as magnet quantity and distance to each other, implant thickness and flow velocity.
The magnetic field strength increased to approximately 112% when a martensitic stainless steel platelet was located between the magnet poles. Therewith a significantly higher amount of magnetic nanoparticles could be accumulated in the area of the platelet compared to the sole magnetic field. During flushing of the tube system mimicking the in vivo blood flow, the magnetized platelet was able to retain a higher amount of MNPs without an external magnetic field compared to the set up with no mounted platelet during flushing of the system. Generally, a higher flow velocity led to lower amounts of accumulated MNPs. A higher quantity of magnets and a lower distance between magnets led to a higher magnetic field strength. Albeit not significantly the magnetic field strength tended to increase with thicker platelets. | Do increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications? | Yes. A martensitic steel platelet significantly improved the attachment of magnetic nanoparticles in an in vitro flow system and therewith indicates the potential of magnetic implant materials in orthopaedic surgery. The use of a remanent magnetic implant material could improve the efficiency of capturing MNPs especially when the external magnetic field is turned off thus facilitating and prolonging the effect. In this way higher drug levels in the target area might be attained resulting in lower inconveniences for the patient. | PASS | pubmedQA | 1 |
24162840 | Isolated limb infusion (ILI) is a limb-preserving treatment for in-transit extremity melanoma. The benefit of resecting residual disease after ILI is unclear.
A multi-institutional experience was analyzed comparing patients who underwent ILI plus resection of residual disease (ILI + RES) versus ILI-alone.
A total of 176 patients were included, 154 with ILI-alone and 22 with ILI + RES. There were no differences between the groups with respect to gender, age, extremity affected, or time from diagnosis to ILI. All surgical resections were performed as an outpatient procedure, separate from the ILI. Within the ILI + RES group, 15 (68%) had a partial response (PR), 2 (9%) stable disease (SD), and 5 (23%) progressive disease (PD). The ILI-alone group had 52 (34%) CR, 30 (19%) PR, 15 (10%) SD, and 46 (30%) PD. Eleven (7%) ILI-alone patients did not have 3-month response available for review. Evaluating overall survival (OS) from date of ILI, the ILI-alone group had a median OS of 30.9 months, whereas the ILI + RES group had not reached median OS, p = 0.304. Although the ILI + RES group had a slightly longer disease-free survival (DFS) compared to those with a CR after ILI-alone (12.4 vs. 9.6), this was not statistically significant, p = 0.978. Within the ILI + RES group, those with an initial PR after ILI had improved DFS versus those with SD or PD after ILI, p < 0.0001. | Is resection of residual disease after isolated limb infusion ( ILI ) equivalent to a complete response after ILI-alone in advanced extremity melanoma? | Yes. Resection of residual disease after ILI offers a DFS and OS similar to those who have a CR after ILI-alone. It may offer a treatment strategy that benefits patients undergoing ILI. | PASS | pubmedQA | 1 |
19285667 | To investigate the relationship between interleukin-8 (IL-8) in the human ovarian follicle and follicular size, patient age, and fertility factors in IVF cycles.
Prospective study.
University hospital research laboratory and infertility clinic.
Women undergoing IVF with oocyte retrieval.
Follicular fluid (FF) aspiration, oocyte isolation, FF storage, and experimental studies.
Quantization of IL-8 by ELISAs and protein microarray; high-performance liquid chromatography (HPLC) followed by ELISA and Western blotting to evaluate alpha(2)-macroglobulin (alpha(2)M) bound IL-8; association of IL -8 to follicular size, patient age, and IVF outcomes.
Samples of FF from 63 patients contained an average of 629.59 pg/mL of IL-8 with 50%-70% bound to alpha(2)M. Large follicles contained higher levels of IL-8 than small follicles (937.34 vs. 86.97 pg/mL). The IL-8 concentration in the large follicles of women of young age was higher than that of older reproductive age women (1,373.61 vs. 673.29 pg/mL). There were no statistically significant associations found between IL-8 concentration and other IVF cycle factors or pregnancy outcome. | Is the human ovarian follicular fluid level of interleukin-8 associated with follicular size and patient age? | Yes. Our findings indicate that IL-8 is present in FF, both in its free and alpha(2)M-bound state, and its concentration is correlated with follicular size and patient age. | PASS | pubmedQA | 1 |
23940858 | Trauma systems use prehospital evaluation of anatomic and physiologic criteria and mechanism of injury (MOI) to determine trauma center need (TCN). MOI criteria are established nationally in a collaborative effort between the Centers for Disease Control and Prevention and the American College of Surgeons' Committee on Trauma and have been revised several times, most recently in 2011. Controversy exists as to which MOI criteria truly predict TCN. We review our single-center experience with past and present National Trauma Triage Criteria to determine which MOI predict TCN.
The trauma registry of an urban Level I trauma center was reviewed from 2001 to 2011 for all patients meeting only MOI criteria. Patients meeting any anatomic and physiologic criteria were excluded. TCN was defined as death, Injury Severity Score (ISS) of greater than 15, emergency department transfusion, intensive care unit admission, need for laparotomy/thoracotomy/vascular surgery within 24 hours of arrival, pelvic fracture, 2 or more proximal long bone fractures, or neurosurgical intervention during admission. Logistic regression analysis was used to identify which MOI predict TCN.
A total of 3,569 patients were transported to our trauma center who met only MOI criteria and had the MOI recorded in the registry; 821 MOI patients (23%) were identified who met our definition of TCN. Significant predictors of TCN included death in the same passenger compartment, ejection from vehicle, extrication time of more than 20 minutes, fall from more than 20 feet, and pedestrian thrown/runover. Criteria not meeting TCN include vehicle intrusion, rollover motor vehicle collision, speed of more than 40 mph, injury from autopedestrian/autobicycle of more than 5 mph, and both of the motorcycle crash (MCC) criteria. | Are not all mechanisms created equal : a single-center experience with the national guidelines for field triage of injured patients? | Yes. With the exception of vehicle intrusion and MCC, the new National Trauma Triage Criteria accurately predicts TCN. In addition, extrication time of more than 20 minutes was a positive predictor of TCN in our system. Elimination of the vehicle intrusion and MCC criteria and reevaluation of extrication time merits further study. | PASS | pubmedQA | 1 |
24859614 | This study evaluated the efficacy of oropharyngeal exercises in children with symptoms of obstructive sleep apnea syndrome (OSA) after adenotonsillectomy.
Polysomnographic recordings were performed before adenotonsillectomy and 6 months after surgery. Patients with residual OSA (apnea-Hypopnea Index, AHI > 1 and persistence of respiratory symptoms) after adenotonsillectomy were randomized either to a group treated with oropharyngeal exercises (group 1) or to a control group (group 2). A morphofunctional evaluation with Glatzel and Rosenthal tests was performed before and after 2 months of exercises. All the subjects were re-evaluated after exercise through polysomnography and clinical evaluation. The improvement in OSA was defined by ΔAHI: (AHI at T1 - AHI at T2)/AHI at T1 × 100.
Group 1 was composed of 14 subjects (mean age, 6.01 ± 1.55) while group 2 was composed of 13 subjects (mean age, 5.76 ± 0.82). The AHI was 16.79 ± 9.34 before adenotonsillectomy and 4.72 ± 3.04 after surgery (p < 0.001). The ΔAHI was significantly higher in group 1 (58.01 %; range from 40.51 to 75.51 %) than in group 2 (6.96 %; range from -23.04 to 36.96 %). Morphofunctional evaluation demonstrated a reduction in oral breathing (p = 0.002), positive Glatzel test (p < 0.05), positive Rosenthal test (p < 0.05), and increased labial seal (p < 0.001), and lip tone (p < 0.05). | Does oropharyngeal exercise to reduce symptoms of OSA after AT? | Yes. Oropharyngeal exercises may be considered as complementary therapy to adenotonsillectomy to effectively treat pediatric OSA. | PASS | pubmedQA | 1 |
20670777 | Although secondary lymphedema is a common complication after surgical and radiation therapy for cancer, the treatment options for lymphedema remain limited and largely ineffective. We thus studied the effect of extracorporeal shock wave therapy on promoting lymphangiogenesis and improving secondary lymphedema.
A rabbit ear model of lymphedema was created by disruption of lymphatic vessels. Two weeks after surgery, the lymphedematous ear was treated with or without low-energy shock waves (0.09 mJ/mm(2), 200 shots), three times per week for 4 weeks.
Western blot analysis showed that the expression of vascular endothelial growth factor (VEGF)-C (1.23-fold, P < .05) and VEGF receptor 3 (VEGFR3; 1.53-fold, P < .05) was significantly increased in the ears treated with shock wave than in the untreated lymphedematous ears. Compared with the control group, shock wave treatment led to a significant decrease in the thickness of lymphedematous ears (3.80 +/- 0.25 mm vs 4.54 +/- 0.18 mm, P < .05). Immunohistochemistry for VEGFR3 showed the density of lymphatic vessels was significantly increased by shock wave treatment (P < .05). | Does extracorporeal shock wave therapy ameliorate secondary lymphedema by promoting lymphangiogenesis? | Yes. Extracorporeal shock wave therapy promotes lymphangiogenesis and ameliorates secondary lymphedema, suggesting that extracorporeal shock wave therapy may be a novel, feasible, effective, and noninvasive treatment for lymphedema. | PASS | pubmedQA | 1 |
18355778 | The objective of this study was to develop a rodent model of Porphyromonas gingivalis infection during pregnancy.
Sprague Dawley rats were infected intravenously with 10(5), 10(7), or 10(9) CFU per dam of P gingivalis strain W83, ATCC 33277, or A7436 at gestational day 14 and necropsied at gestational day 18. Maternal organs were cultured to assess the spread of the infection. Six fetal units (placenta, amniotic fluid, membranes, and fetus) per dam were cultured; additional fetal units were examined by histopathology. Polymerase chain reaction was performed on placentas.
Colonization rates were dependent on the strain of P gingivalis used and the infection dose. At an infection dose of 10(9) CFU/dam, P gingivalis W83, ATCC 33277, or A7436 was detected in 33%, 83%, or 100% of placentas, respectively. Epithelial hyperplasia, cellular necrosis, and inflammatory infiltrate were observed in infected placental tissues. | Is colonization of maternal and fetal tissues by Porphyromonas gingivalis strain-dependent in a rodent animal model? | Yes. This study demonstrated that P gingivalis can invade both maternal and fetal tissues, resulting in chorioamnionitis and placentitis. | PASS | pubmedQA | 1 |
25645291 | The epithelial-mesenchymal transition (EMT) is crucial for the invasion and metastasis of breast cancer. However, how Notch signaling regulates the EMT process and invasion in breast cancer remains largely unknown.
The impact of Notch1 silencing by specific shRNAs on the EMT and invasion of human breast cancer MCF-7 and MDA-MB-231 cells as well as xenografts was tested by western blot, real-time polymerase chain reaction (RT-PCR), immunofluorescence, transwell, and immunohistochemistry assays. The effect of Slug silencing or upregulation on the EMT and invasion of breast cancer cells was analyzed, and the effect of Notch1 signaling on Slug expression was determined by the luciferase reporter assay.
The Notch1 intracellular domain (N1ICD) and Jagged1 were expressed in breast cancer cells. Notch1 silencing reversed the spontaneous EMT process and inhibited the migration and invasion of breast cancer cells and the growth of xenograft breast cancers. The expression of N1ICD was upregulated significantly by Jagged1-mediated Notch signaling activation. Moreover, Jagged1-mediated Notch signaling promoted the EMT process, migration, and invasion of breast cancer cells, which were abrogated by Notch silencing. Furthermore, the N1ICD positively regulated the Slug expression by inducing Slug promoter activation. Importantly, the knockdown of Slug weakened the invasion ability of breast cancer cells and reversed the Jagged1-induced EMT process with significantly decreased expression of vimentin and increased expression of E-cadherin. In addition, Slug overexpression restored the Notch1 knockdown-suppressed EMT process. | Does notch1 signaling regulate the epithelial-mesenchymal transition and invasion of breast cancer in a Slug-dependent manner? | Yes. Our novel data indicate that Notch signaling positively regulates the EMT, invasion, and growth of breast cancer cells by inducing Slug expression. The Notch1-Slug signaling axis may represent a potential therapeutic target for breast cancer therapy. | PASS | pubmedQA | 1 |
21876856 | To determine the generalizability of the predictions for 90-day mortality generated by Model for End-stage Liver Disease (MELD) and the serum sodium augmented MELD (MELDNa) to Atlantic Canadian adults with end-stage liver disease awaiting liver transplantation (LT).
The predictive accuracy of the MELD and the MELDNa was evaluated by measurement of the discrimination and calibration of the respective models' estimates for the occurrence of 90-day mortality in a consecutive cohort of LT candidates accrued over a five-year period. Accuracy of discrimination was measured by the area under the ROC curves. Calibration accuracy was evaluated by comparing the observed and model-estimated incidences of 90-day wait-list failure for the total cohort and within quantiles of risk.
The area under the ROC curve for the MELD was 0.887 (95% CI 0.705 to 0.978) - consistent with very good accuracy of discrimination. The area under the ROC curve for the MELDNa was 0.848 (95% CI 0.681 to 0.965). The observed incidence of 90-day wait-list mortality in the validation cohort was 7.9%, which was not significantly different from the MELD estimate of 6.6% (95% CI 4.9% to 8.4%; P=0.177) or the MELDNa estimate of 5.8% (95% CI 3.5% to 8.0%; P=0.065). Global goodness-of-fit testing found no evidence of significant lack of fit for either model (Hosmer-Lemeshow c2 [df=3] for MELD 2.941, P=0.401; for MELDNa 2.895, P=0.414). | Does the Model for End-stage Liver Disease accurately predict 90-day liver transplant wait-list mortality in Atlantic Canada? | Yes. Both the MELD and the MELDNa accurately predicted the occurrence of 90-day wait-list mortality in the study cohort and, therefore, are generalizable to Atlantic Canadians with end-stage liver disease awaiting LT. | PASS | pubmedQA | 1 |
25882475 | There are two leading theories on the origin of motion sickness. One, the sensory conflict theory, states that sensory information provided by one sensory channel does not match the expected input from another channel; commonly, these two inputs originate in the vestibular system and the eyes. The second theory - the postural instability theory - states that motion sickness comes about not through sensory conflict, but through an inability to control one's posture.
Given that people with a motor-complete spinal cord injury cannot control their muscles below the level of the spinal lesion, we predicted that susceptibility to motion sickness would be higher in individuals who have suffered a spinal cord injury.
Twenty-one people living with chronic spinal cord injury (9 quadriplegics, 12 paraplegics) completed the Motion Sickness Susceptibility Questionnaire (MSSQ), via an online survey, to compare susceptibility to motion sickness before and after injury.
Spinal cord injury, regardless of level, did not produce an increase in susceptibility to motion sickness. | Is susceptibility to motion sickness increased following spinal cord injury? | No. We have tested the general validity of the postural-instability theory by assessing susceptibility to motion sickness in individuals with spinal cord injury. Despite the loss of postural control, there was no increase in motion sickness susceptibility. | PASS | pubmedQA | 1 |
11350093 | Abnormal coronary vasomotion plays a role in the clinical expression of coronary artery disease. We hypothesized that the functional C825T polymorphism located in the ubiquitous G-protein beta3 subunit, implicated in the cellular signal transduction of many receptors, could modify artery coronary vasomotion. We assessed the potential association of the pertussis toxin-sensitive G protein beta3 subunit (GNB3) gene C825T polymorphism on coronary vasomotion in humans.
We examined the response of angiographically normal human coronary arteries (n=131) after intravenous injection of methylergonovine maleate, a vasoconstrictor, followed by injection of isosorbide dinitrate, a vasodilator, according to GNB3 genotypes. Coronary vasomotion was assessed with quantitative coronary angiography. Subjects bearing at least one T allele had greater susceptibility to vasoconstriction in response to methylergonovine maleate than CC subjects, whereas vasodilation in response to isosorbide dinitrate did not differ among the different genotypes. | Is the human G-protein beta3 subunit C825T polymorphism associated with coronary artery vasoconstriction? | Yes. The C825T polymorphism of the G-protein beta3 subunit may be a genetic determinant of coronary artery vasomotion in humans. | PASS | pubmedQA | 1 |
24118071 | To compare the oncological outcome between extravesical excision and transurethral excision for bladder cuff management in patients undergoing nephroureterectomy with upper urinary tract urothelial cancer.
From January 2005 to December 2010, 396 patients were enrolled in the present retrospective study. Nephroureterectomy was carried out either by endoscopic or extravesical bladder cuff excision. The oncological outcome between these two procedures was analyzed in patients with different tumor locations.
The average age of the patients was 66.41 ± 10.52 years, and the median follow-up duration was 40.65 ± 23.84 months. For upper urinary tract urothelial cancer management, extravesical bladder cuff excision was carried out in 240 patients, whereas the endoscopic method was carried out in 156 patients. Previous bladder cancer is still the most independent predictor for bladder recurrence (P < 0.001). In addition, endoscopic bladder cuff management for low ureteral tumor was also independently associated with more bladder tumor recurrence (P = 0.017). Non-organ confined pathological stage still independently predicted metastasis (P < 0.001) and cancer-specific death (P < 0.001). | Does oncological impact of endoscopic bladder cuff management during nephroureterectomy vary according to upper urinary tract tumor location? | Yes. There are similar oncological outcomes after nephroureterectomy combined with extravesical or endoscopic bladder cuff management for patients with upper urinary tract urothelial cancer above the low ureter. However, there is a higher incidence of bladder tumor recurrence for the low ureteral tumor after nephroureterectomy with endoscopic bladder cuff excision. | PASS | pubmedQA | 1 |
19270741 | Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD). Impairment of the mitochondrial electron transport chain (ETC) and an increased frequency in deletions of mitochondrial DNA (mtDNA), which encodes some of the subunits of the ETC, have been reported in the substantia nigra of PD brains. The identification of mutations in the PINK1 gene, which cause an autosomal recessive form of PD, has supported mitochondrial involvement in PD. The PINK1 protein is a serine/threonine kinase localized in mitochondria and the cytosol. Its precise function is unknown, but it is involved in neuroprotection against a variety of stress signalling pathways.
In this report we have investigated the effect of silencing PINK1 expression in human dopaminergic SH-SY5Y cells by siRNA on mtDNA synthesis and ETC function. Loss of PINK1 expression resulted in a decrease in mtDNA levels and mtDNA synthesis. We also report a concomitant loss of mitochondrial membrane potential and decreased mitochondrial ATP synthesis, with the activity of complex IV of the ETC most affected. This mitochondrial dysfunction resulted in increased markers of oxidative stress under basal conditions and increased cell death following treatment with the free radical generator paraquat. | Does silencing of PINK1 expression affect mitochondrial DNA and oxidative phosphorylation in dopaminergic cells? | Yes. This report highlights a novel function of PINK1 in mitochondrial biogenesis and a role in maintaining mitochondrial ETC activity. Dysfunction of both has been implicated in sporadic forms of PD suggesting that these may be key pathways in the development of the disease. | PASS | pubmedQA | 1 |
22647483 | Endothelial dysfunction (ED) participates to atherogenesis associated to rheumatoid arthritis. We recently reported increased arginase activity/expression in vessels from adjuvant-induced arthritis (AIA) rats. In the present study, we investigated the effects of a curative treatment with the arginase inhibitor Nw-hydroxy-nor-L-arginine (nor-NOHA) on vascular dysfunction in AIA rats.
AIA rats were treated with nor-NOHA (40 mg/kg/d, ip) for 21 days after the onset of arthritis. A group of untreated AIA rats and a group of healthy rats served as controls. ED was assessed by the vasodilatory effect of acetylcholine (Ach) on aortic rings. The role of superoxide anions, prostanoids, endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide synthase (NOS) pathway was studied. Plasma levels of IL-6 and vascular endothelial growth factor (VEGF) were determined by ELISA kits. Arthritis severity was estimated by a clinical, radiological and histological analysis.
Nor-NOHA treatment fully restored the aortic response to Ach to that of healthy controls. The results showed that this beneficial effect is mediated by an increase in NOS activity and EDHF and reduced superoxide anion production as well as a decrease in the activity of cyclooxygenase (COX)-2, thromboxane and prostacyclins synthases. In addition, nor-NOHA decreased IL-6 and VEGF plasma levels in AIA rats. By contrast, the treatment did not modify arthritis severity in AIA rats. | Does treatment with the arginase inhibitor Nw-hydroxy-nor-L-arginine restore endothelial function in rat adjuvant-induced arthritis? | Yes. The treatment with an arginase inhibitor has a potent effect on ED in AIA independently of the severity of the disease. Our results suggest that this new pharmacological approach has the potential as a novel add-on therapy in the treatment of RA. | PASS | pubmedQA | 1 |
19357361 | Identifying the cues required for the survival and development of photoreceptors is essential for treating retinal neurodegeneration. The authors previously established that glial-derived neurotrophic factor (GDNF) stimulates proliferation and that docosahexaenoic acid (DHA) promotes photoreceptor survival and differentiation. Later findings that ceramide triggers photoreceptor apoptosis suggested sphingolipids might also control photoreceptor development. The present study investigated whether sphingosine-1-phophate (S1P), which promotes survival and differentiation in several cell types, regulates photoreceptor proliferation and differentiation and whether it is a mediator in GDNF and DHA effects.
Rat retina neuronal cultures were supplemented at day 0 or 1 with S1P, GDNF, or DHA and were treated with DL-threo-dihydrosphingosine to inhibit S1P synthesis or with brefeldin A (BFA) to block intracellular trafficking. Proliferation was quantified to determine bromodeoxyuridine uptake and number of mitotic figures. Opsin, peripherin, and sphingosine kinase (SphK), the enzyme required for S1P synthesis, were quantified by immunocytochemistry and Western blot analysis.
S1P increased the proliferation of photoreceptor progenitors. It also stimulated the formation of apical processes, enhanced opsin and peripherin expression, and promoted their localization in these processes; DHA had similar effects. BFA prevented S1P and DHA enhancement of apical process formation without affecting opsin expression. GDNF and DHA enhanced SphK expression in photoreceptors, while inhibiting S1P synthesis blocked GDNF mitogenic effects and DHA effects on differentiation. | Is sphingosine-1-phosphate a key regulator of proliferation and differentiation in retina photoreceptors? | Yes. The authors propose S1P as a key regulator in photoreceptor development. GDNF and DHA might upregulate SphK levels to promote S1P synthesis, which would initially promote proliferation and then advance photoreceptor differentiation. | PASS | pubmedQA | 1 |
16460692 | Prenatal stress constitutes a developmental risk factor for later psychopathology. The behavioral disorders are sustained by neurobiological alterations including long-term reduction of hippocampal neurogenesis; its deregulation has been involved in cognitive impairments, mood disorders and addiction. A major goal is to define periods in development and strategies for intervening to prevent the effects of early stressful events. We investigated the ability of a postnatal infantile stimulation to prevent prenatal stress-induced alteration in hippocampal neurogenesis.
The influence of postnatal handling on prenatal stress-induced changes in hippocampal neurogenesis was examined in 4 and 26 month-old male rats. Three distinct phases of the neurogenesis were studied: proliferation, survival and neuronal differentiation.
Prenatal stress reduced hippocampal cell proliferation all throughout life. Furthermore, the survival rate of newborn cells, the number of immature neurons and the number of differentiated new neurons were reduced in young and old prenatally-stressed rats. All those deleterious effects were counteracted by neonatal handling. | Does postnatal stimulation of the pups counteract prenatal stress-induced deficits in hippocampal neurogenesis? | Yes. These data show that finer aspects of brain shaping can be rewired by environmental influences occurring at sensitive phase of development. They also suggest that infantile stimulation may reverse the appearance of behavioral disorders induced by early life stress. | PASS | pubmedQA | 1 |
19564661 | Walking is usually undertaken at a speed that coincides with the lowest metabolic cost. Aging however, alters the speed-cost relationship, as preferred walking speeds decrease and energy costs increase. It is unclear to what extent this relationship is affected when older women undertake walking as an exercise modality. The aim of this study was to compare the energetic cost of walking at a self-selected exercise pace for a 30 minute period in older and younger women.
The energetic cost of walking was assessed using the energy equivalent of oxygen consumption measured in 18 young (age 25 to 49 years) and 20 older (age 50 to 79 years) women who were asked to walk at their 'normal' exercise pace on a motorized treadmill for 30 minutes duration.
The mass-specific net cost of walking (Cw) was 15% higher and self-selected walking speed was 23% lower in the older women than in the younger group. When speed was held constant, the Cw was 0.30 (J.kg-1.m-1) higher in the older women. | Is walking speed at self-selected exercise pace lower but energy cost higher in older versus younger women? | Yes. Preferred exercise pace incurs a higher metabolic cost in older women and needs be taken into consideration when recommending walking as an exercise modality. | PASS | pubmedQA | 1 |
27749735 | While many women undergo menopausal transition while they are in paid employment, the effect of poor working conditions on women's experience of the menopause has received scant empirical attention. We examined associations between employment conditions, work-related stressors, and menopausal symptom reporting among perimenopausal and postmenopausal working women.
Data were drawn from an online survey conducted between 2013 and 2014 involving 476 perimenopausal and postmenopausal women working in the higher education sector in Australia. Survey questions assessed demographics; health-related variables; menopausal symptom reporting; employment status; presence of flexible working hours; presence of temperature control; job autonomy; and supervisor support.
A forced entry multivariable regression analysis revealed that high supervisor support (β = -0.10, P = 0.04), being employed on a full-time basis (β = -0.11, P = 0.02), and having control over workplace temperature (β = -0.11, P = 0.02) were independently associated with lower menopausal symptom reporting. | Are employment conditions and work-related stressors associated with menopausal symptom reporting among perimenopausal and postmenopausal women? | Yes. These findings may help inform the development of tailored occupational health policies and programs that cater for the needs of older women as they transition through menopause in the workplace. | PASS | pubmedQA | 1 |
25161822 | Poly(ADP-ribose) polymerase 1 (PARP1) is a chromatin-associated enzyme that participates in processes such as transcription and DNA repair through the regulation of chromatin structure. Accumulating evidence suggests an important role for PARP1 enzymatic activity in promoting CNS inflammation by facilitating the expression of inflammatory cytokines in glial cells. However, the molecular mechanisms by which PARP1 enzymatic activity mediates this process are not well understood. In this report we sought to determine the molecular mechanisms by which PARP1 enzymatic activity facilitates the expression of Il1β and TNF in LPS-stimulated BV2 cells.
PARP1 enzymatic activity and histone ADP-ribosylation were measured in LPS-stimulated BV2 cells by radioactive labelling with (32)P-NAD(+). To assess the effect of histone ADP-ribosylation on nucleosome structure, in vitro nucleosome remodeling, nuclease accessibility and binding assays were performed. These studies were complemented by chromatin immunoprecipitation assays in resting and LPS-stimulated BV2 cells in order to determine the occupancy of PARP1, nucleosomes and the RelA subunit of NF-κB, as well as ADP-ribosylation, at the Il1β and Tnf promoters. Finally, we determined the effect of pharmacological inhibition of PARP1 enzymatic activity on the LPS stimulation-dependent induction of Il1β and Tnf mRNA.
Our results indicate that LPS stimulation induces PARP1 enzymatic activity and histone ADP-ribosylation in the chromatin compartment of BV2 cells. In vitro studies show that nucleosome-bound PARP1 disrupts nucleosome structure histone ADP-ribosylation, increasing the accessibility of nucleosomal DNA. Consistent with this PARP1 is constitutively associated with at the Il1β and Tnf promoters in resting BV2 cells. Upon stimulation with LPS, ADP-ribosylation is observed at these promoters, and this is correlated with increased recruitment of the transcription factor NF-κB, resulting in robust transcription of these inflammatory cytokines. Accordingly, pharmacological inhibition of PARP1 enzymatic activity reduces NF-κB recruitment, and Il1β and Tnf expression in LPS-stimulated microglia. | Does pARP1 enhance inflammatory cytokine expression by alteration of promoter chromatin structure in microglia? | Yes. Collectively, our data suggest that PARP1 facilitates inflammatory cytokine expression in microglia by increasing the accessibility of promoter DNA via histone ADP-riboyslation. | PASS | pubmedQA | 1 |
22040499 | Recently, we reported the identification of a previously uncharacterized and evolutionarily conserved gene, fragile-site associated tumor suppressor (FATS), at a frequently deleted region in irradiation (IR)-induced tumors. However, the role of FATS in breast cancer development and its clinical significance has not been defined. The aim of this study was to determine the role of FATS in breast cancer development and to evaluate its clinical significance in breast cancer.
The expression level of FATS mRNA was determined in 106 breast carcinomas and 23 paired normal breast tissues using quantitative real time reverse transcription-polymerase chain reaction (RT-PCR). The relationship between FATS expression and clinicopathological parameters were also analyzed.
The mRNA level of FATS was down-regulated in breast cancer compared with paired normal tissues. Low expression of FATS was correlated with high nuclear grade. There was a tendency to a favorable outcome for patients with high expression of FATS (P = 0.346). However, low expression of FATS was associated with poor outcome of breast cancer patients with node positive (P = 0.011). Furthermore, the mRNA level of FATS showed an independent value in predicting the outcome of breast cancer patients with positive lymph nodes. | Is expression level of novel tumor suppressor gene FATS associated with the outcome of node positive breast cancer? | Yes. FATS is involved in the carcinogenesis and development of breast cancer and could be a potential biomarker and prognostic factor for breast cancer therapy. | PASS | pubmedQA | 1 |
18503057 | There are growing data suggesting a clinical relevance of residual platelet aggregation (RPA) in patients undergoing PCI. Drug-drug interaction of statins and clopidogrel has been controversially discussed in ex vivo studies and clinical trials. The aim of the present study was to investigate the effects of peri-procedural statin medication on the metabolization of aspirin and clopidogrel with regard to platelet aggregation and clinical outcome in patients undergoing coronary intervention.
Patients with coronary stenting for symptomatic coronary artery disease are routinely evaluated by platelet function analysis in a monocentre registry, and for the present study, a consecutive cohort of 1155 patients were analysed. About 87.7% of the patients were treated with statins at the time of platelet function analysis. Residual platelet activity assessed by adenosine diphosphate (20 micromol/L)-induced platelet aggregation was not significantly influenced by statin treatment. Nor the significant effects of CYP3A4-metabolization pathway on post-treatment aggregation were recorded, although there was even a trend to lower RPA values in patients treated with CYP3A4-metabolized statins. Further, in an inter-individual analysis comparing patients treated with CYP3A4- and non-CYP3A4-metabolized statins, no time-dependent difference of clopidogreĺs anti-aggregatory effects was observed. Clinical follow-up of major adverse events (myocardial infarction, ischaemic stroke, death) in 991 patients within 3 months revealed no significant adverse effects of statin treatment on clinical outcome. Instead, statin treatment was independently associated with lower incidence of composite events (HR 0.44, 95% confidence interval 0.23-0.83, P = 0.01). | Do statins adversely affect post-interventional residual platelet aggregation and outcomes in patients undergoing coronary stenting treated by dual antiplatelet therapy? | No. Peri-procedural co-administration of statins does not increase the post-interventional RPA in cardiovascular patients treated with dual antiplatelet therapy and does not worsen the clinical prognosis of these patients. | PASS | pubmedQA | 1 |
12509559 | Response to intravenous immunoglobulin (IVIG) has been shown to predict response to splenectomy in adults with immune thrombocytopenic purpura (ITP). However, reports in children have been inconsistent. We sought to determine whether response to IVIG is predictive of response to splenectomy in children.
Thirty-two assessable children were identified by a retrospective chart review. Response was graded according to previously published criteria as follows: "excellent" (platelets >150 000 within 1 week), "good" (platelets between 50 000 and 150 000), and "poor" (platelets <50 000). "Response" refers to both splenectomy and IVIG, and response to splenectomy was counted only when it was durable.
Twenty-one of 23 patients who had a good or excellent response to IVIG also had an excellent response to splenectomy. Six of 9 patients who had a poor response to IVIG also had a poor response to splenectomy. Response to IVIG was a sensitive predictor of response to splenectomy in 88% of patients. Response to IVIG had a specificity of 75%, a positive predictive value of 91%, and a negative predictive value of 67%. Response to prednisone and length of time to splenectomy were not correlated with splenectomy response. | Does response to intravenous immunoglobulin predict splenectomy response in children with immune thrombocytopenic purpura? | Yes. These results suggest that response to IVIG is predictive of response to splenectomy in children with chronic ITP. This correlation may be of value in deciding whether a splenectomy should be performed in children with chronic ITP. | PASS | pubmedQA | 1 |
25268673 | We investigated whether annexin A8 (A-A8), a Ca-binding protein overexpressed in pancreatic cancer, plays a role in cell growth and migration and investigated its association with pancreatic cancer prognosis.
Clinicopathological features and associations between increased A-A8 expression (determined by immunohistochemistry) and histologic grade were studied in a tissue microarray of 90 patients with resected stage I/II pancreatic cancer. We investigated A-A8's effect on cell migration, proliferation, and colony formation in 2 pancreatic cancer cells (BXPC-3 and Panc-1). Statistical analyses included Fisher exact test, t test, analysis of variance, and survival analysis.
Western blot showed increased A-A8 expression in human pancreatic cancer cells, with A-A8 knockdown in BXPC-3 and Panc-1 cells demonstrating decreased cell viability (P = 0.017 and P = 0.001), migration (2.5 vs 0.9 mm and 1.6 vs 1 mm at 96 hours; P = 0.048 and P = 0.004), and colony formation (approximately 75% and 40% from scramble; P ≤ 0.01), respectively. In our tissue microarray, A-A8 expression increased 5.9-fold (r = 0.31; P = 0.019) from low- to high-grade tumors, correlating with tumor grade (r = 0.23; P = 0.027). In addition, high A-A8 expression was associated with a decreased 5-year survival (P = 0.042). | Does annexin A8 be a Prognostic Marker and Potential Therapeutic Target for Pancreatic Cancer? | Yes. Our study is the first showing that increased A-A8 expression is associated with poor prognosis in early-stage pancreatic cancer, thus supporting its further investigation as a future therapeutic target and prognostic marker. | PASS | pubmedQA | 1 |
16497990 | Increased level of plasma advanced oxidation protein products (AOPPs) has been found in patients with uremia and nonuremic subjects with coronary artery disease. This study was conducted to test the hypothesis that AOPPs play a causal role in atherosclerosis.
Hypercholesterolemic (0.5% wt/wt diet) or normal rabbits received either repeated intravenous injections of AOPPs modified rabbit serum albumin (AOPPs-RSA) or unmodified RSA for 8 weeks. Compared with RSA- or vehicle-treated hypercholesterolemic rabbits, AOPPs-RSA-treated animals displayed increased atherosclerotic plaque area oxidized low-density lipoprotein (oxLDL) deposition, macrophage infiltration, and smooth muscle cell proliferation. Aortic sections from AOPPs-RSA-treated normal rabbits showed significant focal intima proliferation and mild Oil-Red-O staining lipid deposition in the affected areas, a phenomenon not observed in the RSA- or vehicle-treated controls. Plasma AOPPs levels in AOPPs-treated groups significantly increased in both hypercholesterolemic and normal rabbits compared with their relevant controls. Close correlations were found between plasma levels of AOPPs and the parameters of oxidative stress, eg, oxLDL and thiobarbituric acid reactive substances levels, or glutathione peroxidase activity. A highly significant correlation was also observed between plasma AOPPs and tumor necrosis factor (TNF)-alpha levels. | Do advanced oxidation protein products accelerate atherosclerosis through promoting oxidative stress and inflammation? | Yes. This study provides in vivo evidence for a causal relationship between chronic AOPPs accumulation and atherosclerosis. | PASS | pubmedQA | 1 |
9427283 | Rad51 and Dmc1 are Saccharomyces cerevisiae homologues of the Escherichia coli recombination protein RecA. Mutant analysis has shown that both proteins are required for normal meiotic recombination, for timely and efficient formation of synaptonemal complex and for normal progression out from meiotic prophase.
We have further characterized rad51 and dmc1 single mutants. A dmc1 mutation confers more severe defects in double strand break (DSB) resolution, crossover recombination and meiotic progression than does a rad51 mutant; in contrast, during return to growth, a rad51 mutation confers more severe defects in viability and intrachromosomal recombination than does a dmc1 mutation. Analysis of a rad51 dmc1 double mutant, in parallel with single mutants, shows that the double mutant is more defective with respect to the formation of crossovers during meiosis and, especially strikingly, with respect to interhomologue and intrachromosomal recombination during return to growth. Consistent with the observation of DMC1-dependent recombination in a rad51 mutant, subnuclear complexes of Dmc1 protein were detected for the first time in this mutant. In contrast to the effects on recombination, the effect of the double mutant on meiotic progression was similar to that of the rad51 single mutant. | Do saccharomyces cerevisiae recA homologues RAD51 and DMC1 have both distinct and overlapping roles in meiotic recombination? | Yes. Rad51 and Dmc1 each make unique contributions to meiotic recombination. However, the two proteins are capable of substituting for one another under some circumstances, implying that they most likely share at least one recombination function. Recombination and cell cycle phenotypes are all consistent with the possibility that a dmc1 mutation causes an arrest of the post-DSB recombination complexes at a later, more stable stage than does a rad51 mutation. | PASS | pubmedQA | 1 |
25069832 | In breast cancer, distinct expression profiles of microRNAs (miRNAs) have been associated with molecular subgroups and clinicopathological characteristics, implicating a diagnostic and prognostic role of miRNAs. However, the biological functions of deregulated miRNAs in tumor progression are not yet completely defined. In this study, we investigated the function of miR-18a in regulating breast cancer metastasis through the hypoxia-inducible factor 1α (HIF1A)-dependent hypoxic response.
An orthotopic metastatic breast cancer xenograft model (MDA-MB-231 cells) was used to identify miRNAs associated with spontaneous lung metastasis. The function of miR-18a in regulating HIF1A expression, as well as cellular responses to hypoxia and metastasis, were then studied in vitro and in vivo by assessing ectopic miR-18a expression or miR-18a inhibition. miRNA-mRNA interactions (AGO2 immunoprecipitation and 3' untranslated region Luciferase reporter assays), gene expression (quantitative PCR and microarray), cell migration and invasion, and cell growth were assessed under normoxic or hypoxic conditions, complemented by orthotopic xenograft of tumor cells to the mammary fat pad to investigate the effect of modulating miR-18a expression on primary tumor growth and lung metastasis. Last, clinically relevant correlations between miR-18a, HIF1A, hypoxia-responsive gene expression and distant metastasis-free survival (DMFS) were assessed using published expression array breast tumors data sets.
miRNAs encoded by the MIR17HG gene were downregulated in lung metastases compared to primary tumors. Ectopic expression of miR-18a, a MIR17HG family member, in a metastatic variant of MDA-MB-231 cells reduced primary tumor growth and lung metastasis, whereas miR-18a inhibition in the parental cells promoted tumor growth and lung metastasis. We identified HIF1A as a direct target of miR-18a. Modulating miR-18a expression significantly affected hypoxic gene expression, cell invasiveness and sensitivity to anoikis and hypoxia in vitro in a HIF1A-dependent manner. Analysis of previously published data revealed that higher expression of HIF1A and a panel of hypoxic genes is associated with shorter DMFS interval in patients with basal-like breast tumors, and that, within this subtype, miR-18a expression is inversely correlated with hypoxic gene expression. Together, these data support a role of miR-18a in repressing distant metastasis through a HIF1A-dependent pathway. | Does microRNA-18a inhibit hypoxia-inducible factor 1α activity and lung metastasis in basal breast cancers? | Yes. The results of this study reveal a novel role for miR-18a in targeting HIF1A and repressing metastasis of basal-like breast tumors. | PASS | pubmedQA | 1 |
15838661 | Under certain circumstances, fyn may serve to negatively regulate the differentiation of naïve helper T (Th) cells into Th2 cells. This study aimed to investigate whether fyn negatively regulates the development of experimental immune-mediated blepharoconjunctivitis (EC), in which Th2 cells play an important role in C57BL/6 mice.
C57BL/6 background wild-type (WT) or fyn knockout (fyn-/-) mice were subcutaneously immunized with ragweed (RW) adsorbed in aluminum hydroxide. Ten days later the mice were challenged with RW in eye drops, and 24 h after challenge, eyes, blood and spleens were harvested for histology, measurement of serum IgE, and proliferation or cytokine assays, respectively. RW-primed splenocytes from WT and fyn-/- mice were cultured in the presence of RW. Seventy-two hours later, either whole splenocytes or isolated CD4+T cells were transferred into syngeneic WT mice. Four days after the transfer, the recipient mice were challenged with RW and evaluated as described above.
Infiltration of eosinophils into the conjunctiva induced by active immunization was significantly increased in fyn-/- mice relative to WT mice. Total serum IgE was also significantly higher in fyn-/- mice than in WT mice. In parallel, a higher level of IL-4 production from splenocytes was induced by concanavalin A stimulation in fyn-/- mice than in WT mice. In contrast to active immunization, transfer of whole splenocytes or separated CD4+T cells derived from WT or fyn-/- mice induced similar levels of eosinophilic infiltration in WT mice. | Does fyn regulate eosinophil infiltration into the conjunctiva by downregulating the Th2 response? | Yes. Fyn regulates infiltration of eosinophils into the conjunctiva through downregulation of Th2 responses. This negative regulation is exerted only during the induction phase of EC. | PASS | pubmedQA | 1 |
11839632 | Mammalian platelets contain small, cationic, staphylocidal peptides, termed thrombin-induced platelet-microbicidal proteins (tPMPs). Evidence suggests that tPMPs play a key role in host defense against endovascular infections, such as infective endocarditis (IE). In the present study, we evaluated the influence of differences in staphylococcal tPMP-susceptibility profiles in vitro on disease severity in experimental IE.
Experimental IE was induced in rabbits with either a tPMP-susceptible or an isogenic tPMP-resistant Staphylococcus aureus strain. Vegetation size, left ventricular fractional shortening, and onset of aortic valvular regurgitation were serially assessed by echocardiography over an 11-day postinfection period. In addition, blood cultures were performed daily. Parameters delineated at autopsy included vegetation weights; bacterial densities in vegetations, myocardium, and kidneys; extent of valvular and perivalvular tissue damage; and renal embolization. The following significant differences were observed in animals infected with the tPMP-susceptible versus the tPMP-resistant S aureus strain: substantially lower bacteremia rates (P=0.02); reduced vegetation growth (P<0.001) and weight (P<0.001); a later onset of aortic valvular regurgitation (P=0.0039); increased preservation of left ventricular function (P<0.001); reduced valvular tissue damage (P=0.01) and perivalvular inflammation (P=0.015); and reduced bacterial densities in vegetations (P<0.001) and kidneys (P<0.01). | Is in vitro susceptibility to thrombin-induced platelet microbicidal protein associated with reduced disease progression and complication rates in experimental Staphylococcus aureus endocarditis : microbiological , histopathologic , and echocardiographic analyses? | Yes. The in vitro tPMP-susceptibility profile in S aureus substantially affects a number of well-defined cardiac and microbiological parameters related to disease severity and prognosis in IE. These findings underscore the likelihood that platelets mitigate the pathogenesis of endovascular infections via local secretion of antimicrobial peptides. | PASS | pubmedQA | 1 |
16151723 | To compare the causative pathogens of early-onset and late-onset ventilator-associated pneumonia (VAP) diagnosed by bronchoalveolar lavage quantitative cultures. Most previous reports have been based on endotracheal aspirate cultures and gave uncertain findings.
Prospective evaluation of consecutive patients with clinical suspicion for VAP.
Multidisciplinary intensive care unit of a university hospital.
During a 3-year period 473 patients with clinical suspicion of VAP entered the study. Diagnosis of VAP was confirmed by cultures of bronchoalveolar lavage (> 10(4) cfu/ml) specimens in 408 patients.
Protected bronchoalveolar lavage samples were taken. Initial antibiotic therapy was modified upon bronchoalveolar lavage culture results.
Among 408 patients 191 had early-onset (< 7 days mechanical ventilation) and 217 late-onset (> or = 7 days) VAP. Potentially multiresistant bacteria, mainly Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), were the most commonly isolated pathogens in both types of VAP. No difference was noted in the contribution of potentially multiresistant pathogens (79% vs. 85%), P. aeruginosa (42% vs. 47%), or MRSA (33% vs. 30%) between early-onset and late-onset VAP. Initial antibiotic therapy was modified in 58% of early-onset VAP episodes and in 36% of late-onset VAP episodes. No difference in mortality was found between the two types of VAP. | Are both early-onset and late-onset ventilator-associated pneumonia caused mainly by potentially multiresistant bacteria? | Yes. Both early-onset and late-onset VAP were mainly caused by potentially multiresistant bacteria, most commonly P. aeruginosa and MRSA. Antimicrobial agents against these pathogens should be prescribed empirically, at least in our institution. | PASS | pubmedQA | 1 |
24852606 | The host species composition in a household and their relative availability affect the host-feeding choices of blood-sucking insects and parasite transmission risks. We investigated four hypotheses regarding factors that affect blood-feeding rates, proportion of human-fed bugs (human blood index), and daily human-feeding rates of Triatoma infestans, the main vector of Chagas disease.
A cross-sectional survey collected triatomines in human sleeping quarters (domiciles) of 49 of 270 rural houses in northwestern Argentina. We developed an improved way of estimating the human-feeding rate of domestic T. infestans populations. We fitted generalized linear mixed-effects models to a global model with six explanatory variables (chicken blood index, dog blood index, bug stage, numbers of human residents, bug abundance, and maximum temperature during the night preceding bug catch) and three response variables (daily blood-feeding rate, human blood index, and daily human-feeding rate). Coefficients were estimated via multimodel inference with model averaging.
Median blood-feeding intervals per late-stage bug were 4.1 days, with large variations among households. The main bloodmeal sources were humans (68%), chickens (22%), and dogs (9%). Blood-feeding rates decreased with increases in the chicken blood index. Both the human blood index and daily human-feeding rate decreased substantially with increasing proportions of chicken- or dog-fed bugs, or the presence of chickens indoors. Improved calculations estimated the mean daily human-feeding rate per late-stage bug at 0.231 (95% confidence interval, 0.157-0.305). | Do domestic animal hosts strongly influence human-feeding rates of the Chagas disease vector Triatoma infestans in Argentina? | Yes. Based on the changing availability of chickens in domiciles during spring-summer and the much larger infectivity of dogs compared with humans, we infer that the net effects of chickens in the presence of transmission-competent hosts may be more adequately described by zoopotentiation than by zooprophylaxis. Domestic animals in domiciles profoundly affect the host-feeding choices, human-vector contact rates and parasite transmission predicted by a model based on these estimates. | PASS | pubmedQA | 1 |
10226343 | Determination of the reliability of ultrasonography as a diagnostic tool for rupture of the quadriceps tendon and for follow-up after surgical repair.
11 patients (12 tendons) with a clinical suspicion of quadriceps tendon rupture were studied with ultrasonography in two planes.
In 9 cases we were able to confirm the results of the clinical examination using ultrasonography. In 2 cases we did not find a rupture of the quadriceps tendons ultrasonographically. Within the postoperative follow-up, the homogeneity and echogeneity normalised after the sixth week. | Do [ Ultrasonography as a diagnostic tool in cases of quadriceps tendon rupture ]? | Yes. Using ultrasonography we are able to clearly diagnose ruptures of the quadriceps tendon and objectively assess the postoperative follow-up. | PASS | pubmedQA | 1 |
20941651 | Increasing evidence show that Type D personality is a risk factor for morbidity, mortality, and quality of life of patients with coronary vascular disease. Few studies examined coping as a potential behavioral mechanism to explain the harmful effect of Type D personality.
This study examined the association between Type D personality, coping, and perceived health among Chinese patients with coronary heart disease (CHD).
One hundred seventeen CHD patients completed the assessments on Type D personality, coping, perceived severity of CHD, and morale.
There was no difference on severity of coronary artery stenosis between Type D and non-Type D patients. Compared to the non-Type D patients, the Type D patients perceived higher severity of CHD (5.31 ± 2.41 versus 4.45 ± 2.17, p < 0.05) and lower morale (12.67 ± 4.71 versus 15.00 ± 4.43, p < 0.05), and used less confrontation (16.90 ± 5.39 versus 20.88 ± 4.95, p < 0.001) and more acceptance-resignation coping (10.16 ± 3.50 versus 8.35 ± 3.48, p < 0.05). Mediation analyses showed that confrontation coping mediated the association between Type D personality and perceived severity of disease, and acceptance-resignation coping mediated the association between Type D personality and morale after controlling for age, gender, and clinical variables. | Does coping mediate the association between Type D personality and perceived health in Chinese patients with coronary heart disease? | Yes. The Type D patients used maladaptive coping in response to disease. These coping strategies fully mediated the association between Type D personality and perceived health. Implications for integrating coping training into the intervention for patients with a Type D personality are discussed. | PASS | pubmedQA | 1 |
18942762 | Healthy colonic mucosa uses butyrate as the major energy source. In ulcerative colitis (UC) butyrate oxidation has been shown to be disturbed, but it remains unclear whether this is a primary defect. The aim of this study was to measure mucosal butyrate oxidation in UC (involved and noninvolved colon) and in pouchitis and to study the relationship with endoscopic as well as histological disease activity.
Butyrate oxidation was measured in 73 UC patients, 22 pouchitis patients, and 112 controls (95 colon, 17 ileum) by incubating biopsies with 1 mM 14C-labeled Na-butyrate and measuring the released 14CO2.
Compared with that in normal colon, butyrate oxidation was significantly impaired in endoscopically active but not in quiescent disease or uninvolved colon segments. The severity of the metabolic defect was related to histological disease activity and decreased epithelial cell height. In active pouchitis, butyrate oxidation was significantly decreased compared with that in normal ileum and excluded pouches without inflammation. The histological pouchitis score correlated significantly with butyrate oxidation. | Is pouchitis , similar to active ulcerative colitis , associated with impaired butyrate oxidation by intestinal mucosa? | Yes. Active UC and pouchitis show the same inflammation-related metabolic defect. Our data suggest that the defect is a consequence of inflammation and that pouchitis is metabolically similar to active UC. | PASS | pubmedQA | 1 |
19250763 | To study the effect of 16 Gy radiotherapy (RT) vs. 20 Gy RT on Leydig cell function in men treated with radiotherapy against carcinoma in situ (CIS) of the testis.
Fifty-one men who were treated between 1985 and 2005 were included. Fourteen men had been treated with 20 Gy and 37 with 16 Gy RT. Measurements of sex hormone-binding globulin and basic and stimulated testosterone, as well as luteinizing hormone levels were performed.
The follow-up periods for the patients treated without additional chemotherapy were for the 20 Gy and 16 Gy group mean/median/min-max: 9.0/10.0/1.0-20.3 years and 4.0/3.1/0.4-14.1 years, respectively. During the follow-up period, men treated with 16 Gy RT had stable testosterone levels (-1.1%/year, p = 0.4), whereas men treated with 20 Gy had an annual decrease of 2.4% (p = 0.008). For the latter group, the testosterone decrease was most pronounced in the first 5 years, leveling off during the following 5 years. Additionally, more men treated with 20 Gy needed androgen substitution treatment. Our study showed an increased luteinizing hormone level for the men treated with 16 Gy, although this was not significant (p = 0.5). We anticipated a similar increase in the patients treated with 20 Gy but instead observed a decrease (-3.1%, p = 0.01). | Is testosterone production better preserved after 16 than 20 Gray irradiation treatment against testicular carcinoma in situ cells? | Yes. RT at 16 and 20 Gy seem to affect Leydig cell function differently, with 16 Gy RT better preserving testosterone levels and thus being preferred from an endocrinological point of view. | PASS | pubmedQA | 1 |
17244356 | According to the traditional two-stage model of face processing, the face-specific N170 event-related potential (ERP) is linked to structural encoding of face stimuli, whereas later ERP components are thought to reflect processing of facial affect. This view has recently been challenged by reports of N170 modulations by emotional facial expression. This study examines the time-course and topography of the influence of emotional expression on the N170 response to faces.
Dense-array ERPs were recorded in response to a set (n = 16) of fear and neutral faces. Stimuli were normalized on dimensions of shape, size and luminance contrast distribution. To minimize task effects related to facial or emotional processing, facial stimuli were irrelevant to a primary task of learning associative pairings between a subsequently presented visual character and a spoken word.
N170 to faces showed a strong modulation by emotional facial expression. A split half analysis demonstrates that this effect was significant both early and late in the experiment and was therefore not associated with only the initial exposures of these stimuli, demonstrating a form of robustness against habituation. The effect of emotional modulation of the N170 to faces did not show significant interaction with the gender of the face stimulus, or hemisphere of recording sites. Subtracting the fear versus neutral topography provided a topography that itself was highly similar to the face N170. | Is the face-specific N170 component modulated by emotional facial expression? | Yes. The face N170 response can be influenced by emotional expressions contained within facial stimuli. The topography of this effect is consistent with the notion that fear stimuli exaggerates the N170 response itself. This finding stands in contrast to previous models suggesting that N170 processes linked to structural analysis of faces precede analysis of emotional expression, and instead may reflect early top-down modulation from neural systems involved in rapid emotional processing. | PASS | pubmedQA | 1 |
12407146 | To examine the mechanism underlying transcript heterogeneity in the gene for the retinitis pigmentosa GTPase regulator (RPGR).
Transcript heterogeneity was analyzed by reverse transcription-polymerase chain reactions (RT-PCR), rapid amplification of cDNA ends (RACE), and transient expression of minigene constructs. Protein variants were identified by immunoblot analysis and by immunocytochemistry.
RPGR transcripts terminated either uniformly at the end of exon 19, producing the constitutive transcript with few variants, or at variable sites downstream from exon 15. The latter transcripts resembled the previously described open reading frame (ORF)14/15 variant, but the ORF14/15 exon was not found in full length. Instead, various portions of a purine-rich region were removed as introns. Numerous splice site combinations were used, giving rise to innumerable variants. Analysis of the purine-rich region found multiple exonic splicing enhancers (ESEs) known to promote splicing through interaction with serine-arginine repeat (SR) proteins. Antibodies targeting different regions of RPGR detected a multitude of RPGR proteins in photoreceptors, concentrated in the connecting cilium. Predominant ORF14/15-encoded RPGR polypeptides migrated at approximately 200 kDa and were photoreceptor specific. | Does complex expression pattern of RPGR reveal a role for purine-rich exonic splicing enhancers? | Yes. The exceptional heterogeneity in RPGR transcript processing results primarily from a novel form of alternative RNA splicing mediated by multiple exonic splicing enhancers. RPGR is composed of a population of proteins with a constant N-terminal core encompassing the RCC1 homology domain followed by a C-terminal portion of variable lengths and sequences. | PASS | pubmedQA | 1 |
20332759 | To analyze antitumor efficacy of experimental cancer vaccine therapy combined with introduction of vitamin D3 (VD3) for treatment of Lewis lung carcinoma (3LL).
Cancer vaccines composed from recombinant murine beta-defensin-2 (mBD-2) and 3LL cell lysate, or DNA, coding for mBD-2-Muc1 fusion construct cloned in pcDNA3+ vector, were prepared and used for intradermal vaccination. Experimental cancer vaccines introduced i. d. at therapeutic and prophylactic regimens to 3LL-bearing C57Bl mice, were applied alone or in combination with VD3 (administered per os) and/or low-dose cyclophosphamide (CP, administered intraperitoneal). Efficacy of treatments was analyzed by primary tumor growth dynamics indexes and by metastasis rate in vaccinated animals.
As it has been shown, administration of the protein-based vaccine composed from mBD-2 and 3LL cell lysate in combination with VD3 and CP, but not in VD3 free setting, led to significant suppression of primary tumor growth (p < 0.005) and had significant antimetastatic effect. Introduction of VD3 with or without CP in the scheme of treatment with mBD- 2-Muc1-DNA vaccine at therapeutic regimen has led to significant suppression of primary tumor (p < 0.05) and metastasis volumes (p < 0.005), while in the groups of animals treated with DNA-vaccine + VD3 with or without CP at prophylactic regimen, significant antimetastatic effect (p < 0.05) and elevation of average life-span (p < 0.05) have been registered. | Does administration of vitamin D3 improve antimetastatic efficacy of cancer vaccine therapy of Lewis lung carcinoma? | Yes. The results of this pilot study have shown promising clinical effects of VD3 administration in combination with cancer vaccinotherapy in vivo. | PASS | pubmedQA | 1 |
27059776 | This study aims to determine if the integrity of the sperm plasma membrane and acrosome vesicle could be limiting factors in sheep intracytoplasmic sperm injection (ICSI).
Prior to in vitro fertilization (IVF) or ICSI, the oocytes were subjected to in vitro maturation (IVM) for 24 h. First, to evaluate the need of artificial activation for ovine ICSI, 226 oocytes were injected with intact spermatozoa (IS), from which 125 were activated by incubation in ionomycin and 101 were cultured without activation. Next, spermatozoa were mechanically (by piezo-electrical pulses) and/or chemically (by ionomycin/Triton X-100) treated to break membranes and acrosomes and were injected into oocytes, grouped as follows: (i) piezo-pulsed spermatozoa (PPS), (ii) PPS pre-treated with ionomycin (PPS-I), (iii) PPS pre-treated with Triton X-100 (PPS-T), and (iv) intact and untreated spermatozoa as a control (CTR-IS).
No differences were observed in the zygote/cleavage/blastocyst rate between chemically activated and non-activated oocytes (50 vs. 45 %, 11.6 vs. 10.1 %; 1.8 vs. 1.1 %, respectively), after ICSI with CTR-IS. Injection of PPS compared to CTR-IS increased the proportion of zygotes and blastocysts (84.6 vs. 45 %, p < 0.01; 15.5 vs. 1.1 %, p < 0.0001, respectively). Moreover, the percentage of PPS-derived blastocysts was not significantly different from that obtained by conventional IVF (15.5 vs. 20.2 %). The ICSI blastocysts' development was also improved with PPS pre-treated with ionomycin (15.6 %), but was completely impeded with PPS pre-treated with Triton X-100 (0 %). | Is plasma membrane and acrosome loss before ICSI required for sheep embryonic development? | Yes. Our findings confirm that ICSI with spermatozoa whose plasma membrane and acrosome have been mechanically damaged substantially improves embryonic development until the blastocyst stage. | PASS | pubmedQA | 1 |
26898427 | Sulforaphane (SFN), an isothiocyanate isolated from broccoli, has been reported to have chemopreventive activity. However, the effects of SFN on lung cancer have not been investigated. In this study, we investigate the chemopreventive role of SFN through the inhibition of histone deacetylase (HDAC) in two different lung cancer cells by in vitro and in vivo mouse models.
A549 and H1299 lung cancer cells were treated with SFN for 48h. The HDAC activity, expression of acetylated histones H3 and H4, apoptosis and cell cycles were analyzed by western blot, qRT-PCR and flow cytometry. A549 cells were implanted into the immunocompromised mice for xenografts.
The results showed that SFN inhibited HDAC activity and increased the levels of acetylated histones H3 and H4 in all two lung cancer cells. Further, SFN induced apoptosis, increased the accumulation of cells at G0/G1 and G2/M and arrest cells at S phase. We also found that a concomitant increase of apoptosis related proteins by SFN administration. More interestingly, SFN suppressed the lung cancer growth in xenograft mouse model. | Does sulforaphane suppress in vitro and in vivo lung tumorigenesis through downregulation of HDAC activity? | Yes. In conclusion, the chemopreventive effect of SFN is associated with inhibition of HDAC activity, thereby attenuating lung cancer growth. Therefore, these findings suggest that SFN may be a therapeutic agent for lung cancer through the inhibition of HDAC. | PASS | pubmedQA | 1 |
21573120 | Inflammation is associated with perinatal brain injury but the underlying mechanisms are not completely characterized. Stimulation of Toll-like receptors (TLRs) through specific agonists induces inflammatory responses that trigger both innate and adaptive immune responses. The impact of engagement of TLR2 signaling pathways on the neonatal brain is still unclear. The aim of this study was to investigate the potential effect of a TLR2 agonist on neonatal brain development.
Mice were injected intraperitoneally (i.p.) once a day from postnatal day (PND) 3 to PND11 with endotoxin-free saline, a TLR2 agonist Pam(3)CSK(4) (5 mg/kg) or Lipopolysaccharide (LPS, 0.3 mg/kg). Pups were sacrificed at PND12 or PND53 and brain, spleen and liver were collected and weighed. Brain sections were stained for brain injury markers. Long-term effects on memory function were assessed using the Trace Fear Conditioning test at PND50. After 9 days of Pam(3)CSK(4) administration, we found a decreased volume of cerebral gray matter, white matter in the forebrain and cerebellar molecular layer that was accompanied by an increase in spleen and liver weight at PND12. Such effects were not observed in Pam3CSK4-treated TLR 2-deficient mice. Pam3CSK4-treated mice also displayed decreased hippocampus neuronal density, and increased cerebral microglia density, while there was no effect on caspase-3 or general cell proliferation at PND12. Significantly elevated levels of IL-1β, IL-6, KC, and MCP-1 were detected after the first Pam3CSK4 injection in brain homogenates of PND3 mice. Pam(3)CSK(4) administration did not affect long-term memory function nor the volume of gray or white matter. | Does systemic stimulation of TLR2 impair neonatal mouse brain development? | Yes. Repeated systemic exposure to the TLR2 agonist Pam(3)CSK(4) can have a short-term negative impact on the neonatal mouse brain. | PASS | pubmedQA | 1 |
26936519 | To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR.
We conducted a post hoc analysis of data pooled from two phase III clinical trials in hypertensive patients with type 2 diabetes (T2DM) on stable angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, randomly assigned to dapagliflozin 10 mg/day or matched placebo. This analysis included only patients with microalbuminuria or macroalbuminuria at baseline.
Patients were randomized to receive dapagliflozin 10 mg (n = 167) or placebo (n = 189). Dapagliflozin resulted in greater 12-week reductions in albuminuria compared with placebo: -33.2% [95% confidence interval (CI) -45.4, -18.2]. The reduction in albuminuria was also present after adjusting for age, sex and changes in HbA1c, SBP, body weight and eGFR: -23.5% (95% CI -37.6, -6.3). There was a decrease in eGFR with dapagliflozin versus placebo that was readily reversed 1 week after last dose. No serious renal-related adverse events were observed in any group. | Does dapagliflozin reduce albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers? | Yes. Dapagliflozin was effective in lowering albuminuria in patients with T2DM and hypertension using renin-angiotensin system blockade therapy. Reductions in albuminuria were still present after adjusting for changes in HbA1c, SBP, body weight and eGFR. Dapagliflozin-induced improvements in glycaemic control and reductions in SBP, coupled with other potentially beneficial renal effects, may lead to a reduced long-term renal and cardiovascular risk. | PASS | pubmedQA | 1 |
22394272 | To investigate the cell viability of Bifidobacterium longum 5(1A) in fermented milks and to study its immunostimulating and protective capacity against Salmonella enterica ssp. enterica serovar Typhimurium infection in mice.
Bifidobacterium longum 5(1A) was added to milk fermented with different yoghurt starter cultures, before or after fermentation, and viability was monitored during storage (5°C, 28 days). Resistance to simulated gastric acid digestion was assessed. Fermented milks were orally administered to mice for 10 days followed by oral infection with Salmonella Typhimurium. The number of IgA+ cells in the small and large intestine was determined before infection. Survival to infection was monitored for 20 days. Bifidobacterium longum 5(1A) lost viability during storage, but the product containing it was effective for the induction of IgA+ cells proliferation in the gut and for the protection of mice against Salm. Typhimurium infection. | Are cell viability and immunostimulating and protective capacities of Bifidobacterium longum 51A differentially affected by technological variables in fermented milks? | Yes. Cell viability of Bif. longum 5(1A) in fermented milks along storage did not condition the capacity of the strain to enhance the number of IgA+ cells in the gut and to protect mice against Salmonella infection. | PASS | pubmedQA | 1 |
12196435 | The purpose of this study was to assess the effect of glimepiride on insulin sensitivity and secretion in subjects with type 2 diabetes.
After a 2-week washout from prior sulfonylurea therapy, 11 obese subjects with type 2 diabetes underwent euglycemic and hyperglycemic clamp studies before and during glimepiride therapy.
Glimepiride resulted in a 2.4-mmol/l decrease in fasting plasma glucose (P = 0.04) that was correlated with reductions in postabsorptive endogenous glucose production (EGP) (16.4 +/- 0.6 vs. 13.5 +/- 0.5 micro mol. kg(-1). min(-1), P = 0.01) (r = 0.21, P = 0.01). Postabsorptive EGP on glimepiride was similar to that of control subjects (12.8 +/- 0.9 micro mol. kg(-1). min(-1), NS). Fasting plasma insulin (66 +/- 18 vs. 84 +/- 48 pmol/l, P = 0.05), and first-phase (19 +/- 8 vs. 32 +/- 11 pmol/l, P = 0.04) and second-phase incremental insulin responses to glucose (48 +/- 23 vs. 72 +/- 32 pmol/l, P = 0.02) improved with glimepiride therapy. Insulin sensitivity did not change with treatment (4.6 +/- 0.7 vs. 4.3 +/- 0.7 micro mol. kg(-1). min(-1). pmol(-1)) and remained below that of control subjects (8.1 +/- 1.8 micro mol. kg(-1). min(-1). pmol(-1), P = 0.04). | Does glimepiride improve both first and second phases of insulin secretion in type 2 diabetes? | Yes. The current study demonstrates that glimepiride improves both first and second phases of insulin secretion, but not insulin sensitivity, in individuals with type 2 diabetes. | PASS | pubmedQA | 1 |
23339127 | Plasmacytoid dendritic cells (pDC) are antigen-presenting cells specialized in antiviral response. The measles virus vaccine is proposed as an antitumor agent to target and specifically kill tumor cells without infecting healthy cells.
Here, we investigated, in vitro, the effects of measles virus vaccine-infected tumor cells on the phenotype and functions of human pDC. We studied maturation and tumor antigen cross-presentation by pDC, exposed either to the virus alone, or to measles virus vaccine-infected or UV-irradiated tumor cells.
We found that only measles virus vaccine-infected cells induced pDC maturation with a strong production of IFN-α, whereas UV-irradiated tumor cells were unable to activate pDC. This IFN-α production was triggered by the interaction of measles virus vaccine single-stranded RNA (ssRNA) with TLR7. We observed that measles virus vaccine-infected tumor cells were phagocytosed by pDC. Interestingly, we showed cross-presentation of the tumor antigen NYESO-1 to a specific CD8(+) T-cell clone when pDC were cocultured with measles virus vaccine-infected tumor cells, whereas pDC were unable to cross-present NYESO-1 after coculture with UV-irradiated tumor cells. | Do measles virus vaccine-infected tumor cells induce tumor antigen cross-presentation by human plasmacytoid dendritic cells? | Yes. Altogether, our results suggest that the use of measles virus vaccine in antitumor virotherapy induces immunogenic tumor cell death, allowing pDC to mature, produce high amounts of IFN-α, and cross-present tumor antigen, thus representing a mode of recruiting these antigen-presenting cells in the immune response. Clin Cancer Res; 19(5); 1147-58. ©2012 AACR. | PASS | pubmedQA | 1 |
24029364 | NON-ISCHEMIC MITRAL REGURGITATION (MR) IS PRIMARILY CAUSED BY MYXOMATOUS MITRAL VALVE (MV) DISEASE LEADING TO ADAPTIVE REMODELING, ENLARGEMENT, AND DYSFUNCTION OF THE LEFT VENTRICLE. THE AIM OF THIS STUDY WAS TO EXAMINE THE REGULATION OF PLASMA MARKERS AND SEVERAL CARDIAC KEY GENES IN A NOVEL PORCINE MODEL OF NON-ISCHEMIC MR.
Twenty-eight production pigs (Sus scrofa) were randomized to experimental MR or sham surgery controls. MR was induced by external suture(s) through the posterior MV leaflet and quantified using echocardiography. The experimental group was subdivided into mild MR (mMR, MR=20-50%, n=10) and moderate/severe MR (sMR, MR >50%, n=6) and compared with controls (CON, MR ≤10%, n=12). Eight weeks postoperatively, follow-up examinations were performed followed by killing. Circulating concentrations of pro-atrial natriuretic peptide (proANP), l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine (SDMA) were measured. MV, anterior papillary muscle, and left ventricular free wall tissues were collected to quantify mRNA expression of eNOS (NOS3), iNOS (NOS2), MMP9, MMP14, ANP (NPPA), BNP (NPPB), and TGFB1, 2, and 3 and five microRNAs by quantitative real-time PCR. Pigs with sMR displayed markedly increased plasma proANP and SDMA concentrations compared with both controls and mMR (P<0.05). The expression of all genes examined differed significantly between the three localizations in the heart. miR-21 and miR-133a were differently expressed among the experimental groups (P<0.05). | Are plasma proANP and SDMA and microRNAs associated with chronic mitral regurgitation in a pig model? | Yes. Plasma proANP and SDMA levels and tissue expression of miR-21 and miR-133a are associated with severity of chronic MR in an experimental porcine model. | PASS | pubmedQA | 1 |
18264613 | Chronic otorrhoea occurs commonly in HIV-infected children. However, there are few data on incidence and severity.
To document the prevalence of otorrhoea in the clinic attendees.
A retrospective chart review was done of all HIVI infected children seen at the Family Clinic for HIV from 1 February 1997 to 31 December 2001, a period preceding widespread availability of antiretrovirals. Otorrhoea was classified into two groups, viz. group 1 (mild): an episode lasting less than 1 month, and group 2 (severe): an episode lasting more than 1 month or more than 1 episode of otorrhoea. The clinical and immune stages of the children were noted.
Of 326 children seen during the study period, 104 (32%) had otorrhoea. Forty-five (13.8%) had mild and 59 (18.1%) severe otorrhoea. Two hundred and eighty-eight (88.6%) had either Centers for Disease Control stage B or C disease. The median CD4 percentage in children with otorrhoea was 17.5% (8.3-23%) versus 21% (14-28%) in those without otorrhoea (p=0.004). The odds ratio (OR) of children in stage B or C not having severe otorrhoea was 0.1 (0.01 - 0.72, p = 0.013). The OR for immune class 2 or 3 without severe otorrhoea was 0.39 (0.18 - 0.85, p = 0.021). | Is otorrhoea a marker for symptomatic disease in HIV-infected children? | Yes. Otorrhoea contributes to the morbidity of HIV infection in children. It is a marker for symptomatic disease and CD4 depletion and should be included in clinical classifications. | PASS | pubmedQA | 1 |
17934148 | The purpose of this study was to determine whether type 2 diabetic patients have more liver fat than age-, sex-, and BMI-matched nondiabetic subjects and whether liver enzymes (serum alanine aminotransferase [S-ALT] and serum aspartate aminotransferase) are similarly related to liver fat in type 2 diabetic patients and normal subjects.
Seventy type 2 diabetic patients and 70 nondiabetic subjects matched for BMI, age, and sex were studied. Liver fat ((1)H-magnetic resonance spectroscopy), body composition (magnetic resonance imaging), and biochemical markers of insulin resistance were measured.
The type 2 diabetic patients had, on average, 80% more liver fat and 16% more intra-abdominal fat than the nondiabetic subjects. The difference in liver fat between the two groups remained statistically significant when adjusted for intra-abdominal fat (P < 0.05). At any given BMI or waist circumference, the type 2 diabetic patients had more liver fat than the nondiabetic subjects. The difference in liver fat between the groups rose as a function of BMI and waist circumference. Fasting serum insulin (r = 0.55, P < 0.0001), fasting plasma glucose (r = 0.29, P = 0.0006), A1C (r = 0.34, P < 0.0001), fasting serum triglycerides (r = 0.36, P < 0.0001), and fasting serum HDL cholesterol (r = -0.31, P = 0.0002) correlated with liver fat similarly in both groups. The slopes of the relationships between S-ALT and liver fat were significantly different (P = 0.004). Liver fat content did not differ between the groups at low S-ALT concentrations (10-20 units/l) but was 70-200% higher in type 2 diabetic patients compared with control subjects at S-ALT concentrations of 50-200 units/l. | Is liver fat increased in type 2 diabetic patients and underestimated by serum alanine aminotransferase compared with equally obese nondiabetic subjects? | Yes. Type 2 diabetic patients have 80% more liver fat than age-, weight-, and sex-matched nondiabetic subjects. S-ALT underestimates liver fat in type 2 diabetic patients. | PASS | pubmedQA | 1 |
18174488 | Previous studies have reported a low, approximately 1% to 3%, rate of detection of occult atrial fibrillation (AF) with Holter monitor in patients with acute stroke. Furthermore, at least one study has reported that Holter monitoring could not always corroborate initial electrocardiographic (ECG) detection of AF suggesting underestimation of AF by Holter. We compare the detection of new-onset AF by serial ECG assessments and Holter after acute ischemic stroke.
One hundred forty-four patients with ischemic stroke admitted to a stroke unit were studied. The number of ECGs conducted within the first 3 days up to the detection of AF as well as the time interval for Holter "hookup" and subsequent reporting of AF was documented.
ECGs were performed in 143 patients with a baseline of 10 (7%) patients having a history of AF. Serial ECGs detected 15 new AF cases in <2 days of admission, thereby increasing the total number of known AF cases to 25 (17.5%), a 2.6-fold increased realization of AF (P=0.011). Holter was also completed in 12 of 15 new cases of AF but surprisingly identified AF in only 50% (6 of 12). Holter monitoring was performed in 126 cases and in this subgroup, there was no statistically significant difference in the rate of AF detection with ECG or Holter. | Do serial electrocardiographic assessments significantly improve detection of atrial fibrillation 2.6-fold in patients with acute stroke? | Yes. Serial ECG assessments within the first 72 hours of an acute stroke significantly improve detection of AF. The discordance regarding the corroboration of AF by Holter in ECG-positive patients with AF supports previous observations and suggests a high incidence of paroxysmal AF as a cause of ischemic stroke. | PASS | pubmedQA | 1 |
8996501 | There is a clinical imperative for noninvasive tests for carotid disease that have high sensitivity. Previous studies have shown that transcranial Doppler ultrasound (TCD) can identify intracranial collateral flow patterns and other hemodynamic consequences of carotid occlusion. We hypothesized that a battery of such TCD findings would have a greater sensitivity than any one TCD finding alone and would have clinical utility in identifying carotid disease.
We determined the prevalence of seven TCD findings in patients with various degrees of carotid stenosis as measured by a blinded observer on 138 cerebral angiograms. We further determined the sensitivity and specificity of any one finding or any single abnormality in the TCD battery (the combination of all seven findings) for identifying severe (> or = 70%) carotid stenosis by angiography.
The following four individual TCD findings were associated (P < .001) with > or = 70% carotid stenosis on cerebral angiography: ophthalmic and anterior cerebral artery flow reversal and low middle cerebral artery flow acceleration and pulsatility. The presence of any single abnormality in the TCD battery had a similar association (P < .001) with > or = 70% carotid stenosis. The individual TCD findings had sensitivities of 3% to 83% and specificities of 60% to 100% for identifying > or = 70% carotid stenosis. The TCD battery had a sensitivity of 95% and specificity of 42% for identifying > or = 70% carotid stenosis. | Does transcranial Doppler ultrasound battery reliably identify severe internal carotid artery stenosis? | Yes. A battery of TCD findings that can be routinely measured reliably identified patients with > or = 70% angiographic internal carotid artery stenosis with high sensitivity. | PASS | pubmedQA | 1 |
17912373 | The discovery of genetic code alterations and expansions in both prokaryotes and eukaryotes abolished the hypothesis of a frozen and universal genetic code and exposed unanticipated flexibility in codon and amino acid assignments. It is now clear that codon identity alterations involve sense and non-sense codons and can occur in organisms with complex genomes and proteomes. However, the biological functions, the molecular mechanisms of evolution and the diversity of genetic code alterations remain largely unknown. In various species of the genus Candida, the leucine CUG codon is decoded as serine by a unique serine tRNA that contains a leucine 5'-CAG-3'anticodon (tRNA(CAG)(Ser)). We are using this codon identity redefinition as a model system to elucidate the evolution of genetic code alterations.
We have reconstructed the early stages of the Candida genetic code alteration by engineering tRNAs that partially reverted the identity of serine CUG codons back to their standard leucine meaning. Such genetic code manipulation had profound cellular consequences as it exposed important morphological variation, altered gene expression, re-arranged the karyotype, increased cell-cell adhesion and secretion of hydrolytic enzymes. | Is a genetic code alteration a phenotype diversity generator in the human pathogen Candida albicans? | Yes. Our study provides the first experimental evidence for an important role of genetic code alterations as generators of phenotypic diversity of high selective potential and supports the hypothesis that they speed up evolution of new phenotypes. | PASS | pubmedQA | 1 |
25331010 | The MISAGO ILIAC study is a prospective, non--randomized, multi-center, bi--national, monitored trial, conducted at 3 hospitals in Belgium and 2 hospitals in Germany. This manuscript reports the findings up to 12--month follow-up time for the total cohort. The primary endpoint of the study is primary potency, defined as a target lesion without a hemodynamically significant stenosis on duplex ultrasound (>50%, peak systolic velocity ratio no greater than 2.0) and without target lesion revascularization (TLR), within 12 months.
Between September 2011 and April 2012, 120 patients with TASC II Class A or TASC II Class B aortoiliac lesions were included. The cumulative lesion length in the overall population was 45.49 mm with a maximum stenosis pre--treatment of 83.76%. The demographic data were compatible for the TASC II Class A and TASC II Class B cohort. One patient with a TASC II class C was included as a protocol deviation.
The primary patency rate for the total patient population was 97.4%. The primary patency rates at 12 months for the TASC II Class A and TASC II Class B(C) lesions were respectively 98.3% and 96.6%. No statistical significant difference was shown when comparing these 2 groups (p=0.6407). | Is primary stenting nowadays the golden standard treatment for TASC II A & B iliac lesions : The definitive MISAGO 1-year results? | Yes. Our findings confirm that nowadays primary stenting with modern generation stents replaced the more invasive surgery as the golden standard treatment for patients with TASC II Class A and B aortoiliac lesions. | PASS | pubmedQA | 1 |
20549164 | Repetitive training of simple upper limb movements is effective in stroke rehabilitation. For the repetitive training of complex movements, however, results are inconsistent. The aim of this study was to determine whether repetitive training of complex upper limb movements, focussing on strength and velocity as shaping elements, is effective in stroke rehabilitation.
Longitudinal study, A-B-A design.
Fifteen first-ever stroke patients.
Phases (A): "house-typical" therapy and repetitive training of: (i) grasping and transport movements; and (ii) sawing movements of the affected arm with shaping elements and focussing on velocity over 10 min each, twice daily, 5 days per week. Phase B: "house-typical" occupational and physiotherapy. Each phase lasted 3 weeks.
Patients experienced continuous functional improvement. Voluntary forces improved significantly during the first training phase. Sawing movement improved significantly only during phases A. The grasping and transport movement improved considerably during phase A with a trend of further improvement during the other phases. The transported weight clearly increases only during phases A. | Is repetitive training of complex hand and arm movements with shaping beneficial for motor improvement in patients after stroke? | Yes. Repetitive training of complex movements results in motor improvement in stroke patients without relevant transfer to functional improvement if strength and velocity are to be enhanced as shaping elements. | PASS | pubmedQA | 1 |
25512478 | Syndecan-1 (SDC-1) is a major constituent of the endothelial glycocalyx, which plays a role in maintaining vascular homeostasis and functions as a glomerular filtration barrier. SDC-1 is readily shed into the blood under various conditions, but the clinical implication of circulating SDC-1 in patients with systemic lupus erythematosus (SLE) remains unclear. We aimed to investigate the association of serum SDC-1 level with certain clinical manifestations of SLE.
We measured serum SDC-1 levels by ELISA in 111 patients with SLE, 18 with rheumatoid arthritis (RA), and 20 healthy subjects, and investigated its association with clinical manifestations and laboratory variables.
Serum SDC-1 levels were higher in patients with SLE than in those with RA and healthy controls (both p < 0.001) and were positively correlated with SLE Disease Activity Index (SLEDAI; r = 0.367, p < 0.001) and anti-dsDNA antibody level (r = 0.259, p = 0.007), but inversely correlated with serum C3 and CH50 levels (r = -0.305, p = 0.001 and r = -0.244, p = 0.012). Patients with active nephritis had higher serum SDC-1 levels than patients with inactive nephritis and those without nephritis (both p < 0.001). In addition, serum SDC-1 levels were correlated with renal SLEDAI score (r = 0.540, p < 0.001) and excretion of proteinuria as measured by spot urine protein/creatinine ratio (r = 0.538, p < 0.001). In 14 patients with lupus nephritis (LN) whose serum samples were obtained at the time of renal biopsy, there was a positive correlation between serum SDC-1 levels and activity index (r = 0.632, p = 0.015). | Are elevated serum levels of syndecan-1 associated with renal involvement in patients with systemic lupus erythematosus? | Yes. Serum SDC-1 levels are increased in SLE patients with nephritis, indicating that SDC-1 might be a useful serum biomarker for active LN. | PASS | pubmedQA | 1 |
25157773 | This study compared survival after initial treatment with esophagectomy as primary therapy to induction therapy followed by esophagectomy for patients with clinical T2N0 (cT2N0) esophageal cancer in the National Cancer Database (NCDB).
Predictors of therapy selection for patients with cT2N0 esophageal cancer in the NCDB from 1998 to 2011 were identified with multivariable logistic regression. Survival was evaluated using Kaplan-Meier and Cox proportional hazards methods.
Surgery was used in 42.9% (2057 of 4799) of cT2N0 patients. Of 1599 esophagectomy patients for whom treatment timing was recorded, induction therapy was used in 44.1% (688). Pretreatment staging was proven accurate in only 26.7% of patients (210 of 786) who underwent initial surgery without induction treatment and had complete pathologic data available: 41.6% (n = 327) were upstaged and 31.7% (n = 249) were downstaged. Adjuvant therapy (chemotherapy or radiation therapy) was given to 50.2% of patients treated initially with surgery who were found after resection to have nodal disease. There was no significant difference in long-term survival between strategies of primary surgery and induction therapy followed by surgery (median 41.1 versus 41.9 months, p = 0.51). In multivariable analysis, induction therapy was not independently associated with risk of death (hazard ratio [HR], 1.16, p = 0.32). | Does induction therapy improve survival for clinical stage T2N0 esophageal cancer? | No. Current clinical staging for early-stage esophageal cancer is highly inaccurate, with only a quarter of surgically resected cT2N0 patients found to have had accurate pretreatment staging. Induction therapy for patients with cT2N0 esophageal cancer in the NCDB is not associated with improved survival. | PASS | pubmedQA | 1 |
17904063 | To investigate the significance of N-terminal proBrain natriuretic peptide (NT-proBNP) in predicting the outcome of acute stroke in relation to other cardiovascular variables and stroke severity.
Prospective study of previously independent acute ischemic and hemorrhagic stroke patients admitted to the acute stroke ward.
Measurements of NT-proBNP in acute phase in addition to standard assessment of cardiovascular and neurological details.
Concentrations and significance of NT-proBNP in patients who were dead versus alive at 120 days after acute stroke and Cox regression analysis with stroke severity measured as Scandinavian Stroke Scale (SSS) and other cardiovascular disease to predict mortality.
One hundred fourteen patients were recruited, median age 74 years. At 120 days, 13 patients had died. Deceased patients had a significantly higher concentration of NT-proBNP as compared to alive patients (P < .001). All patients who had died had NT-proBNP concentration above the median for the whole group. Cox regression analysis revealed that NT-proBNP was the most significant independent variable predicting mortality (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.35 to 4.41, P = .003) followed by the SSS (OR 0.95, 95% CI 0.90 to 0.98, P = .005). Higher NT-proBNP and lower SSS predicted mortality. There was a significant negative correlation of NT-proBNP with SSS score (r = -0.24, P = .02). There were no significant difference in NT-proBNP concentrations between ischemic and hemorrhagic strokes (P < .346). At 6 weeks, the dependent patients had higher concentrations of NT-proBNP than independent patients. | Do n-terminal proBrain natriuretic peptide levels predict short-term poststroke survival? | Yes. NT-proBNP, an index of cardiac impairment, has an independent prognostic value in acute stroke patients over other cardiovascular variables and stroke severity. This may provide a channel for interventional therapy in acute stroke. | PASS | pubmedQA | 1 |
27330686 | Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are antihyperlipidemic drugs with an established efficacy in stabilizing atherosclerotic plaques and preventing atherogenesis and reducing cardiovascular events. The purpose of this study was to determine the effect of simvastatin on serum Vitamin D status in dyslipidemic patients as Vitamin D status has an impact on monocyte/macrophage function and may also contribute to cardiovascular risk.
Selected individuals (n = 102) were treated with simvastatin (40 mg/day), or matching placebo in a randomized, double-blind, placebo-controlled, crossover trial. Each treatment period (with simvastatin or placebo) lasted for 30 days and was separated by a 2-week washout phase. Serum Vitamin D concentration was assessed pre- and post-treatment.
Seventy-seven completed the trial, noncompliance with the study protocol and drug intolerance or relocation were the causes for drop-out. No significant carry-over effect was observed for the assessed parameters. There was a reduction in the serum levels of low-density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), and triglycerides (P < 0.05). Nevertheless, simvastatin therapy did not significantly affect serum level of high-density lipoprotein cholesterol and Vitamin D level (P > 0.05). | Does simvastatin Treatment Affect Serum Vitamin D Concentrations in Patients with Dyslipidemia : A Randomized Double-blind Placebo-controlled Cross-over Trial? | No. Short-term treatment with simvastatin (40 mg/day) does not have a significant affect on serum levels of Vitamin D. | PASS | pubmedQA | 1 |
12438463 | Patients with intractable epilepsy may benefit from epilepsy surgery especially if they have a radiologically demonstrable cerebral lesion. Dedicated magnetic resonance imaging (MRI) protocols as performed at epilepsy surgery centres can detect epileptogenic abnormalities with great sensitivity and specificity. However, many patients with epilepsy are investigated with standard MRI sequences by radiologist outside epilepsy centres ("non-experts"). This study was undertaken to compare standard MRI and epilepsy specific MRI findings in patients with focal epilepsy.
Comparison of results of standard MRI reported by "non-expert" radiologists, standard MRI evaluated by epilepsy "expert" radiologists, and epilepsy specific MRI read by "expert" radiologists in 123 consecutive patients undergoing epilepsy surgery evaluation between 1996 and 1999. Validation of radiological findings by correlation with postoperative histological examination.
Sensitivity of "non-expert" reports of standard MRI reports for focal lesions was 39%, of "expert" reports of standard MRI 50%, and of epilepsy dedicated MRI 91%. Dedicated MRI showed focal lesions in 85% of patients with "non-lesional" standard MRI. The technical quality of standard MRI improved during the study period, but "non-expert" reporting did not. In particular, hippocampal sclerosis was missed in 86% of cases. Neuropathological diagnoses (n=90) were predicted correctly in 22% of "non-expert" standard MRI reports but by 89% of dedicated MRI reports. | Is standard magnetic resonance imaging inadequate for patients with refractory focal epilepsy? | Yes. Standard MRI failed to detect 57% of focal epileptogenic lesions. Patients without MRI lesion are less likely to be considered candidates for epilepsy surgery. Patients with refractory epilepsy should be referred to an MRI unit with epileptological experience at an early point. | PASS | pubmedQA | 1 |
23396543 | To determine whether indication-based computer order entry alerts intercept wrong-patient medication errors.
At an academic medical center serving inpatients and outpatients, we developed and implemented a clinical decision support system to prompt clinicians for indications when certain medications were ordered without an appropriately coded indication on the problem list. Among all the alerts that fired, we identified every instance when a medication order was started but not completed and, within a fixed time interval, the same prescriber placed an order for the same medication for a different patient. We closely reviewed each of these instances to determine whether they were likely to have been intercepted errors.
Over a 6-year period 127 320 alerts fired, which resulted in 32 intercepted wrong-patient errors, an interception rate of 0.25 per 1000 alerts. Neither the location of the prescriber nor the type of prescriber affected the interception rate. No intercepted errors were for patients with the same last name, but in 59% of the intercepted errors the prescriber had both patients' charts open when the first order was initiated. | Does indication-based prescribing prevent wrong-patient medication errors in computerized provider order entry ( CPOE )? | Yes. Indication alerts linked to the problem list have previously been shown to improve problem list completion. This analysis demonstrates another benefit, the interception of wrong-patient medication errors. | PASS | pubmedQA | 1 |
26446484 | Dietary supplement use is widespread in the United States. Although it has been suggested in both in vitro and small in vivo human studies that chromium has potentially beneficial effects in type 2 diabetes (T2D), chromium supplementation in diabetes has not been investigated at the population level.
The objective of this study was to examine the use and potential benefits of chromium supplementation in T2D by examining NHANES data.
An individual was defined as having diabetes if he or she had a glycated hemoglobin (HbA1c) value of ≥6.5%, or reported having been diagnosed with diabetes. Data on all consumed dietary supplements from the NHANES database were analyzed, with the OR of having diabetes as the main outcome of interest based on chromium supplement use.
The NHANES for the years 1999-2010 included information on 62,160 individuals. After filtering the database for the required covariates (gender, ethnicity, socioeconomic status, body mass index, diabetes diagnosis, supplement usage, and laboratory HbA1c values), and when restricted to adults, the study cohort included 28,539 people. A total of 58.3% of people reported consuming a dietary supplement in the previous 30 d, 28.8% reported consuming a dietary supplement that contained chromium, and 0.7% consumed supplements that had "chromium" in the title. Compared with nonusers, the odds of having T2D (HbA1c ≥6.5%) were lower in persons who consumed chromium-containing supplements within the previous 30 d than in those who did not (OR: 0.73; 95% CI: 0.62, 0.86; P = 0.001). Supplement use alone (without chromium) did not influence the odds of having T2D (OR: 0.89; 95% CI: 0.77, 1.03; P = 0.11). | Does risk of Type 2 Diabetes be Lower in US Adults Taking Chromium-Containing Supplements? | Yes. Over one-half the adult US population consumes nutritional supplements, and over one-quarter consumes supplemental chromium. The odds of having T2D were lower in those who, in the previous 30 d, had consumed supplements containing chromium. Given the magnitude of exposure, studies on safety and efficacy are warranted. | PASS | pubmedQA | 1 |