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24500507 | To evaluate weight retention 12 months postpartum and factors associated among women who had received prenatal care at Health Care Centers in Porto Alegre, southern Brazil.
Pregnant women in the last trimester were identified at 20 Health Care Centers. Socioeconomic, demographic and anthropometrics data were obtained. Six and 12 months after delivery, the women received home visits for anthropometric measures. The gestational weight gain was defined by pre-pregnancy Body Mass Index (BMI). Weight retention was defined as the difference between pre-gestational weight and weight at postpartum. Data were analyzed using McNemar's Test, ANOVA with Bonferroni correction and multiple linear regression.
Of the 715 pregnant women recruited, 545 were assessed 12 months after delivery. Women were more likely to be overweight 12 months postpartum compared to the pre-pregnancy period (52.9 versus 36.7%) and weight retention during the 12 months postpartum was more than 10 kg in 30.7% of the women. Weight retention in the postpartum period was higher among women who were overweight (9.9 ± 7.7 kg) compared to those who were of normal weight during the pre-pregnancy period (7.6 ± 6.2 kg). Pre-pregnancy BMI, gestational weight gain, and maternal age were associated with gestational weight retention 12 months postpartum (p<0.001). | Is [ Excessive gestational weight gain risk factor for overweight among women ]? | No. Adequate prenatal care is necessary to minimize the adverse effects of excessive weight gain during pregnancy on women's health. | FAIL | pubmedQA | 0 |
26635207 | Female sexual interest and arousal disorder is personally distressing for women. To better understand the mechanism of the candidate therapeutic, flibanserin, we determined its effects on an index of brain glucose metabolism.
We hypothesized that chronic treatment with flibanserin would alter metabolism in brain regions associated with serotonergic function and female sexual behavior.
In a crossover design, eight adult female common marmosets (Calithrix jacchus) received daily flibanserin or vehicle. After 7-12 weeks of treatment, the glucose metabolism radiotracer [(18) F]fluorodeoxyglucose (FDG) was administered to each female immediately prior to 30 minutes of interaction with her male pairmate, after which females were anesthetized and imaged by positron emission tomography. Whole-brain normalized images were analyzed with anatomically defined regions of interest. Whole-brain voxelwise mapping was used to explore treatment effects. Correlations were examined between alterations in metabolism and pairmate social grooming.
Changes in metabolism associated with flibanserin were determined for dorsal raphe, medial prefrontal cortex (mPFC), medial preoptic area of hypothalamus (mPOA), ventromedial nucleus of hypothalamus, and field cornu ammonis 1 (CA1) of the hippocampus.
In response to chronic flibanserin, metabolism in mPOA declined, and this reduction correlated with increases in pairmate grooming. A cluster of voxels in frontal cortico-limbic regions exhibited reduced metabolism in response to flibanserin and overlapped with a voxel cluster in which reductions in metabolism correlated with increases in pairmate grooming. Finally, reductions in mPOA metabolism correlated with increases in metabolism in a cluster of voxels in somatosensory cortex. | Does flibanserin-Stimulated Partner Grooming reflect Brain Metabolism Changes in Female Marmosets? | Yes. Taken together, these results suggest that flibanserin-induced reductions in female mPFC neural activity increase intimate affiliative behavior with male pairmates. | FAIL | pubmedQA | 0 |
25463823 | Moderately and late preterm infants represent a considerable and increasing proportion of infants cared for in neonatal departments worldwide. Parents of preterm infants are at risk of postpartal depression (PPD) and posttraumatic stress disorder (PTSD), and preterm infants are at risk of developmental impairment.
This study aimed to assess (1) the incidence of parental PPD and PTSD in moderate to late preterm infants in comparison to full-term infants and (2) the influence of infants' motor repertoire assessed by Prechtl's general movements and illness severity on parental PPD and PTSD.
We studied 60 mothers and 56 fathers of 69 preterm infants (born at 32 to 37 weeks of gestation) and 32 mothers and 29 fathers of 34 full-term infants.
We assessed the incidence of parental PPD, PTSD and perceived social support as well as infants' illness severity and motor repertoire at birth, term and 3 months corrected age.
Preterm mothers and fathers had significant higher depression scores after birth compared to full-term parents (p=0.033 and 0.021). Preterm fathers also had higher traumatization scores compared to full-term fathers (p=0.007). Probable or possible PPD/PTSD was not associated with infant's illness severity or quality of motor repertoire. No differences in motor development were found between preterm and full-term infants. | Is increased rate of parental postpartum depression and traumatization in moderate and late preterm infants independent of the infant 's motor repertoire? | No. Moderate to late preterm infants' parents are at increased risk for PPD only if the infants have poor motor repertoire or severe illness. | FAIL | pubmedQA | 0 |
11081684 | To elucidate whether the duration of previous use of combined oral contraceptives (COC) is associated with disabling back or pelvic pain during pregnancy and pain persisting eight months after delivery.
Questionnaires were distributed to a group of women at 36 weeks of pregnancy and eight months after their delivery. There were no exclusion criteria. Disabling pain was defined as moderate or severe pain restricting physical activity. Multiple logistic regression analysis of disabling pain during pregnancy and persistent pain after delivery comprised the duration of COC use adjusted for age, pain in a previous pregnancy and a history of back pain when not pregnant.
The study comprised 161 women. Pain during pregnancy was classified as disabling in 57 of the women (35%), pain in a previous pregnancy being a risk factor, odds ratio (OR) 5.0 (95% CI 2.1; 12.1), whereas no association was found with the duration of COC use. Persistent pain eight months after delivery was reported by 41 women (26%), risk factors being a history of back pain when not pregnant; OR 7.5 (2.8; 19.5), disabling pain in the recent pregnancy; OR 5.0 (1.9; 13.4), and short use of COC; 0-<1 year; OR 4.2 (1.3; 12.9), 1-<5 years; OR 4.6 (1.5; 14.4) (reference=>10 years). | Do combined oral contraceptives increase the risk of back and pelvic pain during pregnancy or after delivery? | Yes. The results indicate that non- or short term users of COC have an increased risk of persistent pain after delivery compared to long term users. An association was found between the duration of COC use and back or pelvic pain during pregnancy. | FAIL | pubmedQA | 0 |
19353375 | Chronic increases in blood flow induce remodeling associated with increases in diameter and endothelium-mediated dilation. Remodeling requires cell growth and migration, which may involve reactive oxygen species (ROS). Nevertheless, the role of ROS in flow-mediated remodeling in resistance arteries is not known.
Rat mesenteric resistance arteries (MRAs) were exposed to high flow (HF) by sequentially ligating second-order MRAs in vivo. After three weeks, arteries were collected for structural, pharmacological, and biochemical analysis.
In HF arteries, luminal diameter (431+/-12 to 553+/-14 microm; n=10), endothelium (acetylcholine)-mediated vasodilatation (61+/-6 to 77+/-6% relaxation) and NAD(P)H subunit (gp91phox and p67phox) expression levels, and ROS (dihydroethydine microphotography) and peroxynitrite (3-nitro-tyrosine) production were higher than in normal flow arteries. Acute ROS scavenging with tempol improved acetylcholine-dependent relaxation (92+/-4% relaxation), confirming that ROS are produced in HF arteries. Chronic treatment with tempol prevented the increase in diameter, reduced ROS and peroxynitrite production, and improved endothelium-mediated relaxation in HF arteries. Thus, ROS and NO were involved in HF-induced diameter enlargement, possibly through the formation of peroxynitrite, while ROS reduced the increase in endothelium-dependent relaxation. | Are reactive oxygen species necessary for high flow ( shear stress ) -induced diameter enlargement of rat resistance arteries? | No. ROS production is not necessary for flow-mediated diameter enlargement of resistance arteries. However, ROS counteract, in part, the associated improvement in endothelium-mediated relaxation. | FAIL | pubmedQA | 0 |
23585997 | To determine whether switching within or between antidepressant therapy (ADT) classes prior to the use of adjunctive antipsychotic treatment is associated with different outcomes in major depressive disorder (MDD).
This was a post hoc analysis of pooled data from 3 similar, multicenter, randomized, double-blind, placebo-controlled registrational studies of aripiprazole adjunctive to ADT conducted between September 2004 and April 2008. The trials comprised the following 3 phases: a 7- to 28-day screening phase, an 8-week single-blind prospective treatment phase, and a 6-week double-blind, randomized phase. Patients were aged 18-65 years and met DSM-IV-TR criteria for MDD. Patients with an inadequate response to ADT during the screening phase entered the prospective treatment phase, during which they were switched to another ADT medication of either the same or a different class. Those patients with an inadequate response were then randomized to double-blind adjunctive aripiprazole or adjunctive placebo and followed for 6 weeks.
Mean improvement in Montgomery-Asberg Depression Rating Scale total score was significantly greater with adjunctive aripiprazole versus adjunctive placebo for both between-class (-9.2 vs -6.2, P < .001) and within-class (-9.8 vs -6.6, P < .001) switch groups. Relative risks for response were 1.6 (95% CI = 1.3-2.1) for those who switched between classes and 1.7 (95% CI = 1.2-2.2) for those who switched within class. | Are beneficial effects of adjunctive aripiprazole in major depressive disorder dependent on antidepressant therapy history : a post hoc analysis of 3 randomized , double-blind , placebo-controlled trials? | Yes. Augmentation with aripiprazole, after either a between-class or within-class switch following initial ADT failure, is not an effective option for patients with nonresponsive MDD. In contrast to current strategies employed in clinical practice, these results suggest that adjunctive aripiprazole is not a logical strategy in patients unresponsive to ADT. | FAIL | pubmedQA | 0 |
11159875 | Prucalopride (PRU) is a selective benzofuran 5-hydroxytryptamine(4)-receptor agonist with gastrointestinal and colonic prokinetic activities. We evaluated the effects of PRU on gastrointestinal and colonic transit in patients with constipation.
Gastrointestinal and colonic transit were measured over 48 hours in 40 patients who fulfilled modified Rome I criteria for functional constipation. Patients had no evidence of a rectal evacuation disorder. Subjects were randomized to receive a daily dose of 2 or 4 mg PRU or placebo in a double-blind, parallel-group design. Each treatment lasted 7 days. The transit test was performed over the last 48 hours of the study. Effects on gastric emptying, small bowel transit, and colonic transit were analyzed using Kruskal-Wallis and Wilcoxon rank sum tests.
Of 61 patients screened, 40 were eligible and randomized. Two patients withdrew because of adverse events. PRU accelerated overall gastric emptying and small bowel transit. PRU tended to accelerate overall colonic transit with significantly faster overall colonic transit and ascending colon emptying with the 4-mg dose. | Does prucalopride accelerate gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder? | Yes. PRU accelerates transit through the stomach, small bowel, and colon in patients with constipation associated with a rectal evacuation disorder. | FAIL | pubmedQA | 0 |
20976104 | Ecological succession drives large-scale changes in ecosystem composition over time, but the mechanisms whereby climatic change might alter succession remain unresolved. Here, we asked if the effects of atmospheric and climatic change would alter tree seedling emergence and establishment in an old-field ecosystem, recognizing that small shifts in rates of seedling emergence and establishment of different species may have long-term repercussions on the transition of fields to forests in the future.
We introduced seeds from three early successional tree species into constructed old-field plant communities that had been subjected for 4 years to altered temperature, precipitation, and atmospheric CO(2) regimes in an experimental facility. Our experiment revealed that different combinations of atmospheric CO(2) concentration, air temperature, and soil moisture altered seedling emergence and establishment. Treatments directly and indirectly affected soil moisture, which was the best predictor of seedling establishment, though treatment effects differed among species. | Does climate change alter seedling emergence and establishment in an old-field ecosystem? | No. The observed impacts, coupled with variations in the timing of seed arrival, are not demonstrated as predictors of seedling emergence and establishment in ecosystems under global change. | FAIL | pubmedQA | 0 |
25899394 | Stem cell factor (SCF) is essential in the haematopoietic stem cells (HSCs) niche, and is therefore used extensively in haematopoietic stem and progenitor cells (HSPCs) ex vivo expansion. However, in the literature, dose and schedule of SCF feeding varies widely. We previously proposed a novel SCF feeding regimen with proven effectiveness for HSPCs expansion; however, physiological function of expanded cells with this SCF feeding regimen required further research.
CD34(+) cells were cultured with or without SCF supplementation in serum-free medium for 10 days. Expanded cells were transplanted into sublethally irradiated non-obese diabetic/severe combined immune-deficient (NOD/SCID) mice. Engraftment and multilineage reconstitution of transplanted cells were determined. Also, clonogenic potential of engrafted cells was analysed.
Cells, both cultured with and without SCF supplementation, successfully engrafted and reconstituted blood cell lineages in NOD/SCID mice. However, level of engraftment and multilineage reconstitution reduced when cells were expanded without SCF supplementation. Meanwhile, frequencies of colony-forming cells (CFCs) amongst bone marrow cells were higher in mice transplanted with CD34(+) cells expanded with SCF supplementation. | Is stem cell factor essential for preserving NOD/SCID reconstitution capacity of ex vivo expanded cord blood CD34 ( + ) cells? | No. Reconstitution capacity was not affected when CD34(+) cells were expanded without SCF supplementation, though this feeding regimen did not have any effect on cell expansion. This finding suggested that SCF was not essential for preserving NOD/SCID reconstitution capacity of ex vivo expanded CD34(+) cells. | FAIL | pubmedQA | 0 |
11321874 | Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) are frequently used in cancer patients to overcome the granulocytopenic effects of chemotherapy, and also to mobilize the stem cells. The mobilized stem cells are collected from the peripheral blood and used for transplantation following high doses of chemotherapy. However, the molecular mechanism by which these colony stimulating factors (CSFs) bring about proliferation of myeloid precursor cells is not clearly known. Dihydrofolate reductase (DHFR), which has an established role in DNA synthesis, could be a link between administration of CSF and stem cell proliferation. The purpose of this study was to investigate whether CSFs induce white cell proliferation by producing multiple forms of DHFR.
Twelve patients with non-haematological malignancies were treated with either G-CSF or GM-CSF to mobilize stem cells. Nine healthy subjects were treated with placebo as controls. Blood samples were obtained before and after stimulation with CSFs or placebo. White blood cells were separated and concentrations of both active DHFR and immunoreactive nonfunctional form of DHFR were determined in their cytoplasm using methotrexate-binding assay and enzyme-linked immunosorbent assay, respectively. Total leucocytes count (TLC) was also monitored before and after stimulation with CSFs or placebo.
There was a significant (P < 0.05) increase in concentration of immunoreactive nonfunctional form of DHFR and TLC following stimulation with CSFs. There was an increase in concentration of active DHFR as well, however, this did not reach statistical significance. In the placebo-treated subjects, no significant increase in active DHFR, immunoreactive nonfunctional form of enzyme or TLC was observed. However, it was noticed that the base-line values of active DHFR and immunoreactive nonfunctional form of enzyme in leucocytes of cancer patients were higher than the base-line values in leukocytes of normal healthy subjects. | Is induction of white cell proliferation due to haematopoietic growth factors associated with an increase in multiple forms of dihydrofolate reductase in non-neutropenic cancer patients? | No. Our data suggest that colony stimulating factors do not induce white cell proliferation by increasing levels of multiple forms of DHFR. | FAIL | pubmedQA | 0 |
23214337 | Anesthesia management is characterized by salary limiting and pressure for decreasing anesthetics and other drug budget. The aim of this paper is to determine the possibility of reducing the direct costs in anesthesia.
This paper is a part ofa five-year (2005-2009), academic, pharmaco-economic retrospective- prospective study (phase IV). The study was done according to European Union Directive for Clinical Research. We retrospectively calculated and analyzed all anesthesia direct costs (personnel costs, anesthetics and other drug costs, materials, laboratory analyses, and machines) at the Institute For Ane- sthesia and Reanimation, Clinical Center of Serbia in relation to the costs refunded by National Health Insurance in all patients who underwent anesthesia in 2006.
Out of 70 195 anesthesia services rendered to 32 267 patients in one-year period, 47% were general anesthesia, 23% were local anesthesia, and 30% were anesthetic procedures. Our results of highly significant association between personnel costs (r = 0.980, p = 0.000) and consumption of anesthetics and drugs (r = 0.885, p = 0.000) with the direct costs do not provide an opportunity for further cost reduction due to disassociation of direct costs and the "unit price" of National Health Insurance issued in terms of the restricted maximum budget for health. | Is [ Reductions in anesthesia direct costs the right way for racionalization of anesthesia costs ]? | Yes. There is significant space for direct cost reduction in anesthesia. | FAIL | pubmedQA | 0 |
19710048 | The pathogenesis of cerebral small-vessel disease (SVD) is incompletely understood. Endothelial dysfunction has been implicated and may result in increased blood-brain barrier (BBB) permeability with leakage of blood constituents into the vessel wall and white matter. We used contrast-enhanced MRI to determine whether there was any evidence for BBB permeability in the white matter of patients with SVD, and whether this was present not only in areas of leucoaraiosis (white-matter lesions) but also in normal-appearing white matter (NAWM).
Subjects underwent T1 volumetric MRI before and after bolus injection of contrast. Scanning was continued for 30 min postinjection to determine the contrast-enhancement time course. The mean signal intensity change was plotted against time to calculate the area under the curve values, a parameter related to BBB permeability. Automated brain segmentation and regions of interest analysis were performed to determine 'permeability' in different brain compartments.
Compared with controls (n=15), the SVD patient group (n=24) had signal changes consistent with increased BBB permeability in NAWM (p=0.033). Multivariate regression analyses identified leucoaraiosis grade as an independent predictor of these permeability related signal changes in NAWM after adjustment for age, gender, weight, brain volume, area under the curve in the internal carotid arteries and cardiovascular risk factors. | Is blood-brain barrier permeability increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis? | No. This study provides evidence against increased BBB permeability in SVD, and this is particularly seen in SVD with leucoaraiosis. Its absence in NAWM would be consistent with it not playing a causal role in disease pathophysiology. | FAIL | pubmedQA | 0 |
23863954 | Dominant mutations in cellular junction proteins are the major cause of arrhythmogenic cardiomyopathy, whereas recessive mutations in those proteins cause cardiocutaneous syndromes such as Naxos and Carvajal syndrome. The Hutterites are distinct genetic isolates who settled in North America in 1874. Descended from <100 founders, they trace their origins to 16th-century Europe.
We clinically and genetically evaluated 2 large families of the Alberta Hutterite population with a history of sudden death and found several individuals with severe forms of biventricular cardiomyopathy characterized by mainly left-sided localized aneurysms, regions of wall thinning with segmental akinesis, in addition to typical electric and histological features known for arrhythmogenic right ventricular cardiomyopathy. We identified a homozygous truncation mutation, c.1660C>T (p.Q554X) in desmocollin-2 (DSC2), in affected individuals and determined a carrier frequency of this mutation of 9.4% (1 in 10.6) among 1535 Schmiedeleut Hutterites, suggesting a common founder in that subgroup. Immunohistochemistry of endomyocardial biopsy samples revealed altered expression of the truncated DSC2 protein at the intercalated discs but only minor changes in immunoreactivity of other desmosomal proteins. Recombinant expressed mutant DSC2 protein in cells confirmed a stable, partially processed truncated protein with cytoplasmic and membrane localization. | Does homozygous founder mutation in desmocollin-2 ( DSC2 ) cause arrhythmogenic cardiomyopathy in the Hutterite population? | Yes. A homozygous truncation mutation in DSC2 leads to a cardiac-restricted phenotype of an early onset right ventricular arrhythmogenic cardiomyopathy. The truncated protein remains partially stable and localized at the intercalated discs. These data suggest that the processed DSC2 protein plays a role in maintaining desmosome integrity and function. | FAIL | pubmedQA | 0 |
21327489 | Lead failure is a common complication of pacemaker placement in the pediatric population and is often due to insulation breaks or lead fracture. Usually these leads are replaced with new leads. This study describes the surgical technique of lead repair and investigates the longevity of such repairs.
Retrospective review of lead repairs performed in the pediatric population (<21 years old) between December 1995 and December 2008. Operative records, pre-operative interrogation data, and most recent follow-up data were reviewed.
Twenty-one lead repairs were performed on 17 patients. Sixteen were ventricular leads and five were atrial leads. There were 14 insulation defect repairs, six new lead tip splicings, and one lead extender splicing. The repaired leads were followed for a mean time of 3.6 ± 3.0 years (range, 0.3-10.6 years). The freedom from repaired lead failure by Kaplan-Meier survival analysis was 89% at 5 years and 22% at 10 years. One atrial lead and two ventricular leads have been replaced since the repairs. One atrial lead has had a repeat insulation break repair since the initial repair. One of the five atrial leads had an elevated threshold at follow-up. Five of 16 ventricular leads had elevated thresholds at follow-up. All leads had normal impedance at follow-up. | Does durability of repaired pacemaker lead in the pediatric population? | No. The option of pacemaker lead repair, if surgically feasible, does not offer an alternative to lead replacement in the pediatric population and does not extend the longevity of pacemaker leads in this population. | FAIL | pubmedQA | 0 |
10971319 | Ceramides produced by sphingomyelin hydrolysis activate a cycle that is followed by three different major cellular responses: downregulation of cell proliferation, induction of cell differentiation and apoptosis. In the skin, the generation of intracellular ceramide may also provide a link between an extracellular signal and the induction of the apoptosis programme for the elimination of damaged cells.
We investigated the effect of ceramides capable of entering cells on cultured keratinocytes.
Human keratinocytes from neonatal skin were cultured in serum-free medium with or without increasing concentrations of ceramide 2 (CER-2; N-acetyl sphingosine) (5, 10, 20 and 40 micromol L-1). Proliferative effects were studied either by cell counts or by 3H-thymidine incorporation and flow cytometric analysis. Apoptosis was studied by TUNEL staining and Western blot analysis of Bcl-2 protein.
Cell counts and DNA synthesis were reduced in a dose-dependent manner following CER-2 treatment. TUNEL staining showed CER-2-induced apoptosis at 48, 72 and 96 h. Western blot analysis showed that CER-2 induces downregulation of Bcl-2 at 24-96 h. | Is ceramide 2 ( N-acetyl sphingosine ) associated with reduction in Bcl-2 protein levels by Western blotting and with apoptosis in cultured human keratinocytes? | Yes. These results demonstrate that CER-2 inhibits cell proliferation and induces apoptosis, possibly via a Bcl-2-independent mechanism. | FAIL | pubmedQA | 0 |
26489743 | We hypothesized that an elevated preoperative alkaline phosphatase (AP) predicted worse outcomes for patients undergoing transarterial chemoembolization (TACE) for neuroendocrine tumor (NET) liver metastases.
We reviewed all patients who underwent TACE for metastatic NET between 2009 and 2013. Survival was evaluated using preprocedure variables.
One hundred and nine patients underwent 210 TACE procedures. The average age was 57.7 years (range 20-78). Primary sites included pancreas (N = 20), other gastrointestinal (N = 52), lung (N = 9), and unknown (N = 28). The tumor was grade 1 in 68 (62 %), grade 2 in 21 (19 %), and grade 3 in 3 (3 %). Extrahepatic disease was present in 54 (50 %) and greater than 50 % hepatic tumor burden by imaging in 63 (58 %). Elevated bilirubin occurred in 8 (7 %), elevated AP in 22 (20 %), elevated ALT in 21 (19 %), and elevated AST in 41 (38 %). Univariate predictors included tumor grade (43 vs 27 vs 21 months, p = 0.015), hepatic tumor burden (59 vs 37 months, p = 0.009), and elevated AP (59 vs 23 months, p < 0.001). On multivariate analysis, only elevated AP (p = 0.001) predicted worse survival. | Does elevated Alkaline Phosphatase Prior to Transarterial Chemoembolization for Neuroendocrine Tumors predict Worse Outcomes? | No. Elevated AP prior to TACE for metastatic NET does not predict worse survival outcomes compared to tumor grade or extent of hepatic disease. | FAIL | pubmedQA | 0 |
25966742 | Treatments targeting cancer stem cells (CSCs) are most effective cancer therapy, whereas determination of CSCs is challenging. We have recently reported that Lgr5-positive cells are cancer stem cells (CSCs) in human skin squamous cell carcinoma (SCC). Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancers, whereas its effects on the SCC have not been examined.
Here, we transduced human SCC cells with lentivirus carrying GFP reporter under Lgr5 promoter. The transduced SCC cells were treated with different doses of GRh2, and then analyzed cell viability by CCK-8 assay and MTT assay. The effects of GRh2 on Lgr5-positive CSCs were determined by fow cytometry and by tumor sphere formation. Autophagy-associated protein and β-catenin were measured by Western blot. Expression of short hairpin small interfering RNA (shRNA) for Atg7 and β-catenin were used to inhibit autophagy and β-catenin signaling pathway, respectively, as loss-of-function experiments.
We found that GRh2 dose-dependently reduced SCC viability, possibly through reduced the number of Lgr5-positive CSCs. GRh2 increased autophagy and reduced β-catenin signaling in SCC cells. Inhibition of autophagy abolished the effects of GRh2 on β-catenin and cell viability, while increasing β-catenin abolished the effects of GRh2 on autophagy and cell viability. | Does ginsenoside rh2 inhibit cancer stem-like cells in skin squamous cell carcinoma? | Yes. Taken together, our data suggest that GRh2 inhibited SCC growth, possibly through increased the number of Lgr5-positive CSCs. This may be conducted through an interaction between autophagy and β-catenin signaling. | FAIL | pubmedQA | 0 |
23280001 | The goal of the present study was to investigate whether the antioxidants vitamin E, vitamin C and vitamin B1 can reduce the transforming growth factor-beta2 (TGF-β2)-induced gene expressions in cultured human optic nerve head (ONH) astrocytes.
Cultured human ONH astrocytes were pretreated with different concentrations of vitamin E, vitamin C and vitamin B1 and then exposed to 1.0 ng/ml TGF-β2 for 24 hr. Expression of the heat shock proteins Hsp27 and αB-crystallin, the extracellular matrix (ECM) component fibronectin and the ECM-modulating protein connective tissue growth factor (CTGF) was detected by immunohistochemistry or real-time PCR analysis.
TGF-β2 increased the expression of Hsp27, αB-crystallin, fibronectin and CTGF in human ONH astrocytes. Pretreatment with different concentrations of vitamin E, vitamin C and vitamin B1 reduced the TGF-β2-stimulated gene expressions. | Do antioxidants reduce TGF-beta2-induced gene expressions in human optic nerve head astrocytes? | Yes. In cultured human ONH astrocytes, the TGF-β2-stimulated gene expressions could be reduced by pretreatment with vitamin E, vitamin C and vitamin D. Therefore, the use of antioxidants in glaucomatous optic neuropathy might be a promising approach to prevent TGF-β2-induced cellular changes in ONH astrocytes. | FAIL | pubmedQA | 0 |
22492380 | Maternal calcium intake and vitamin D status may affect fetal bone development.
This study was designed to examine relations between maternal calcium intake, 25-hydroxyvitamin D [25(OH)D] status, and fetal bone growth across pregnancy.
This was a prospective longitudinal design. Maternal 25(OH)D, parathyroid hormone, and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were determined at midgestation (∼26 wk) and at delivery in 171 adolescents (≤ 18 y). Dietary recalls and fetal sonograms were performed up to 3 times across gestation, and fetal femur and humerus z scores were generated.
Fetal femur and humerus z scores and neonatal birth length were significantly greater (P < 0.03) in adolescents consuming ≥ 1050 mg than in those consuming <1050 mg Ca/d. Maternal 25(OH)D > 50 nmol/L was significantly positively associated with fetal femur and humerus z scores (P < 0.01). When maternal smoking, height, race, weight gain, and gestational age were controlled for, these relations remained significant. Interactions between calcium intake and 25(OH)D were evident. Calcium intake was associated with fetal femur z scores and birth length only when maternal 25(OH)D was ≤ 50 nmol/L (P < 0.05). Similarly, maternal 25(OH)D was associated with fetal femur and humerus z scores only when maternal calcium intake was <1050 mg/d (P < 0.03). | Do maternal vitamin D status and calcium intake interact to affect fetal skeletal growth in utero in pregnant adolescents? | Yes. Optimal calcium intake and adequate maternal vitamin D status are both needed to maximize fetal bone growth. Interactions between these nutrients were evident when either calcium or vitamin D status was limited. Improving maternal calcium intake and/or vitamin D status during pregnancy may have a positive effect on fetal skeletal development in pregnant adolescents, especially when maternal 25(OH)D is > 50 nmol/L. | FAIL | pubmedQA | 0 |
26696530 | While the prevalence of obesity in IBD patients is rapidly increasing, it is unclear if obesity impacts surgical outcomes in this population. We aim to investigate the effects of BMI on perioperative and postoperative outcomes in IBD patients by stratifying patients into BMI groups and comparing outcomes between these groups.
This is a retrospective cohort study where IBD patients who underwent intestinal surgeries between the years of 2000 to 2014 were identified. The patients were divided into groups based on BMI: underweight (BMI <18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), and obese (BMI ≥30). Preoperative patient demographics, operative variables, and postoperative complications were collected and compared between BMI groups.
A total of 391 surgeries were reviewed (34 underweight, 187 normal weight, 105 overweight, and 65 obese) from 325 patients. No differences were observed in preoperative patient demographics, type of IBD, preoperative steroid or biologic mediator use, or mean laboratory values. No differences were observed in percent operative procedures with anastomosis, surgeries converted to open, estimated blood loss, intraoperative complications, and median operative time. Thirty-day postoperative complication rates including total complications, wound infection, or anastomotic leak were similar between groups. There was a statistically significant increased postoperative bleeding risk (p = 0.029) in underweight patients. The relative percent for increased postoperative bleeding risk between BMI groups was as follows: 2.9% in underweight, zero in normal weight, 2.9% in overweight, and zero in obese. | Does obesity Impact Perioperative or Postoperative Outcomes in Patients with Inflammatory Bowel Disease? | Yes. Obesity appears to impact intraoperative variables and worsens postoperative complication rates in IBD patients. | FAIL | pubmedQA | 0 |
22682966 | Serum concentration of anti-Mullerian hormone (AMH) is used as a biomarker in clinical practice. Therefore, it is important to elucidate the mechanism by which AMH is regulated in granulosa cells (GC). An important first step in understanding AMH regulation is to determine which factors up-regulate AMH expression.
Human GC, obtained from 28 women undergoing oocyte retrieval for in vitro fertilization, were stimulated with various intraovarian cytokines including bone morphogenetic protein (BMP)-2, -6, -7 -15, activin-A and growth differentiation factor (GDF)-9 (100 ng/ml). The expression of AMH mRNA was evaluated with reverse transcription and quantitative real-time polymerase chain reaction (PCR), and AMH protein in cultured supernatant was measured with EIA kit.
BMP-2, -6, -7 and -15, but not activin-A and GDF-9, significantly induced AMH expression in GC at mRNA and protein level, while all stimuli increased FSH receptor mRNA and decreased steroidogenic acute regulatory protein (StAR) mRNA level. | Is anti-Mullerian hormone ( AMH ) induced by bone morphogenetic protein ( BMP ) cytokines in human granulosa cells? | Yes. Among the transforming growth factor (TGF)-β superfamily, BMP-2, -6, -7 and -9 significantly induced AMH expression in human GC. | FAIL | pubmedQA | 0 |
26241525 | Accuracy of biopsy scheme depends on different parameters. Prostate-specific antigen (PSA) level and digital rectal examination (DRE) influenced the detection rate and suggested the biopsy scheme to approach each patient. Another parameter is the prostate volume. Sampling accuracy tends to decrease progressively with an increasing prostate volume. We prospectively observed detection cancer rate in suspicious prostate cancer (PCa) and improved by applying a protocol biopsy according to prostate volume (PV).
Clinical data and pathological features of these 1356 patients were analysed and included in this study. This protocol is a combined scheme that includes transrectal (TR) 12-core PBx (TR12PBx) for PV ≤ 30 cc, TR 14-core PBx (TR14PBx) for PV > 30 cc but < 60 cc, TR 18-core PBx (TR18PBx) for PV ≥ 60 cc.
Out of a total of 1356 patients, in 111 (8.2%) PCa was identified through TR12PBx scheme, in 198 (14.6%) through TR14PBx scheme and in 253 (18.6%) through TR18PBx scheme. The PCa detection rate was increased by 44% by adding two TZ cores (TR14PBx scheme). The TR18PBx scheme increased this rate by 21.7% vs. TR14PBx scheme. The diagnostic yield offered by TR18PBx was statistically significant compared to the detection rate offered by the TR14PBx scheme (p < 0.003). The biopsy Gleason score and the percentage of core involvement were comparable between PCa detected by the TR14PBx scheme diagnostic yield and those detected by the TR18PBx scheme (p = 0.362). | Is the best prostate biopsy scheme dictated by the gland volume : a monocentric study? | No. The only PV parameter, in our opinion, cannot be significant in choosing the best biopsy scheme to approach in a first setting of biopsies increasing PCa detection rate. | FAIL | pubmedQA | 0 |
20829328 | Brain metastases of breast cancer appear to be increasing in incidence, confer significant morbidity, and threaten to compromise gains made in systemic chemotherapy. The blood-tumor barrier (BTB) is compromised in many brain metastases; however, the extent to which this influences chemotherapeutic delivery and efficacy is unknown. Herein, we answer this question by measuring BTB passive integrity, chemotherapeutic drug uptake, and anticancer efficacy in vivo in two breast cancer models that metastasize preferentially to brain.
Experimental brain metastasis drug uptake and BTB permeability were simultaneously measured using novel fluorescent and phosphorescent imaging techniques in immune-compromised mice. Drug-induced apoptosis and vascular characteristics were assessed using immunofluorescent microscopy.
Analysis of over 2,000 brain metastases from two models (human 231-BR-Her2 and murine 4T1-BR5) showed partial BTB permeability compromise in greater than 89% of lesions, varying in magnitude within and between metastases. Brain metastasis uptake of ¹⁴C-paclitaxel and ¹⁴C-doxorubicin was generally greater than normal brain but less than 15% of that of other tissues or peripheral metastases, and only reached cytotoxic concentrations in a small subset (∼10%) of the most permeable metastases. Neither drug significantly decreased the experimental brain metastatic ability of 231-BR-Her2 tumor cells. BTB permeability was associated with vascular remodeling and correlated with overexpression of the pericyte protein desmin. | Does heterogeneous blood-tumor barrier permeability determine drug efficacy in experimental brain metastases of breast cancer? | Yes. This work shows that the BTB is not a significant impediment to standard chemotherapeutic delivery and efficacy in experimental brain metastases of breast cancer. New brain permeable drugs will not be needed. Evidence is presented for vascular remodeling in BTB permeability alterations. | FAIL | pubmedQA | 0 |
15282995 | Although sleep deprivation often occurs during stressful or threatening situations, the effects of sleep loss on defensive and coping behaviors are not well known. The purpose of the present study was to measure the effects of selective rapid eye movement (REM) sleep deprivation (RSD) on responses elicited by threatening situations and to assess the extent to which RSD-induced changes are reversed by amphetamine.
Animals were divided into 3 groups; home-cage control, apparatus control, and REM sleep-deprived groups. The flowerpot method was used to produce RSD for up to 5 days. One set of rats was tested in the elevated plus maze, open field, shock-induced freezing, and analgesia tests. A second set of rats was evaluated for locomotor activity. A third set of animals was assessed in the defensive burying test. For the amphetamine studies, groups of home-cage control and REM sleep-deprived rats received an intraperitoneal injection of amphetamine prior to administration of the shock-induced freezing test or the defensive burying test.
Sleep Research Laboratory at UW-Madison.
186 male Long-Evans rats approximately 3 months old.
RSD increased the proportion of time spent in open arms of the elevated plus maze and center of the open field, decreased freezing time, and reduced defensive burying. Amphetamine did not reverse RSD-induced changes in freezing or burying responses. | Does rEM sleep deprivation induce changes in coping responses that are not reversed by amphetamine? | Yes. RSD causes widespread abnormalities in coping and defensive responses in threatening situations; these deficits are reversed by amphetamine. | FAIL | pubmedQA | 0 |
26350299 | Prehypertension (blood pressure (BP) of 120-139 mm Hg systolic and/or 80-89 mm Hg diastolic) is highly prevalent and is associated with increased cardiovascular risk. Our goal was to investigate the extent to which prehypertension is associated with end-organ alterations in cardiac structure and function in a large biracial cohort of older men and women.
We studied 4,871 participants of the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5 (2011-2013) and underwent two-dimensional echocardiography while free of prevalent coronary heart disease or heart failure. We categorized participants into 3 groups: optimal BP (BP <120 mm Hg and <80 mm Hg) (n = 402), prehypertension (n = 537), and hypertension (n = 3,932).
Individuals with prehypertension (75±5 years) had higher left ventricular (LV) mass index and wall thickness, and higher prevalence of abnormal LV geometry than those with optimal BP (74±5 years), but lower than those with frank hypertension (76±5 years). In addition, participants with prehypertension had impairment of diastolic parameters (E/A, E' and E/E'), and had higher prevalence of mild and moderate-severe diastolic dysfunction compared to those with optimal BP, but no differences in systolic parameters. These differences in cardiac structure and function remained significant after adjusting for important clinical covariates. | Is prehypertension Associated With Abnormalities of Cardiac Structure and Function in the Atherosclerosis Risk in Communities Study? | Yes. In the ARIC cohort at visit 5, prehypertension was associated with increased LV remodeling and impaired systolic function, but not diastolic function, suggesting that even mildly elevated BP within the normal range is associated with cardiac end-organ damage. | FAIL | pubmedQA | 0 |
27064133 | High levels of ferritin in patients with non-alcoholic fatty liver disease (NAFLD) are associated with significant fibrosis and higher NAFLD activity score (NAS). It is unclear if this association has an impact on mortality. We investigated if high levels of ferritin, with or without iron overload, were associated with an increased mortality in NAFLD.
We included 222 patients between 1979 and 2009 with biopsy-proven NAFLD and available serum ferritin concentrations. The cohort was divided into 'high' (n = 89) and 'normal' (n = 133) ferritin values, using a cut-point of 350 μg/L in males, and 150 μg/L in females, and stratified upon iron overload status. Data on mortality were obtained from a national, population-based register. Poisson regression was used to estimate hazard ratios for mortality. The estimates were adjusted for age at biopsy, sex, smoking, BMI, diabetes, hypertension, cardiovascular disease and fibrosis stage at the time of biopsy.
The median follow-up time was 15.6 years (range: 0.5-34.2). Patients with high ferritin had more advanced fibrosis and higher NAS than patients with normal ferritin (P < 0.05). Fifteen years after diagnosis, and after adjusting for confounders, the high-ferritin group showed an increasingly higher mortality that was statistically significant (Hazard ratio = 1.10 per year, 95% Confidence interval 1.01-1.21, P < 0.05). There was no difference in mortality between patients with different iron overload patterns. | Is elevated serum ferritin associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up? | No. High levels of ferritin are not associated with a long-term increased risk of death. | FAIL | pubmedQA | 0 |
18592788 | To assess the clinical use of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the post-therapy surveillance of uterine sarcoma.
Eight whole-body FDG-PET studies were performed in seven women with previously treated uterine sarcoma. Conventional image studies (computed tomography) and physical examinations were performed for follow-up. All FDG-PET studies were indicated to localize suspected recurrences noted by conventional methods.
The per case sensitivity of the FDG-PET studies and CT scans was 85.7% (6/7) and 100% (7/7), respectively (p = 0.174). FDG-PET was able to detect seven extrapelvic metastastic sites below the diaphragm (7/7, sensitivity: 100%), including the liver, spleen, paraaortic lymph node, spine and paracolic gutter, as well as pulmonary lesions in five patients, while the CT scan detected only three lesions (3/7, sensitivity: 42.9%; p = 0.070). FDG-PET detected only four recurrent pelvic lesions (4/6) and CT scan detected six (6/6) recurrent pelvic lesions (66.7% vs 100%, p = 0.455). | Is whole-body positron emission tomography with 18F-fluorodeoxyglucose an effective method to detect extra-pelvic recurrence in uterine sarcomas? | Yes. The FDG-PET showed a better detection rate than the abdominal CT scan for extrapelvic metastatic lesions and a similar detection rate as well as abdominal CT scan. FDG-PET can serve as a useful detection tool for patients with uterine sarcomas because nearly 60% of recurrence involve an extrapelvic site. | FAIL | pubmedQA | 0 |
15126161 | To report a novel test that uses computerized kinetic perimetry to detect tubular visual fields in patients with functional visual loss.
Observational case series.
Ten patients who demonstrated generalized visual field constriction on prior examinations underwent testing combining computerized kinetic perimetry with a reversed Galilean telescope, used for optical visual field expansion.
Six patients with physiologic visual field constriction demonstrated expansion of their visual fields with the use of the reversed telescope. Four patients with functional visual loss responded to the reversed telescope by demonstrating tubular visual fields, with responses equal to or smaller than their demonstrated visual fields delineated without the telescope. | Does computerized kinetic perimetry detect tubular visual fields in patients with functional visual loss? | No. This test uses a computerized kinetic examination to reduce the subjective nature of tangent screen testing for tubular visual fields and to provide a computerized recording of visual fields. This method is a novel and easy-to-use technique to demonstrate functional visual loss. | FAIL | pubmedQA | 0 |
23410633 | In the acute coronary syndrome setting, the interaction between epicardial coronary artery stenosis and microcirculation subtended by the culprit vessel is poorly understood. The purpose of the present study was to assess the immediate impact of percutaneous coronary intervention (PCI) on microvascular resistance (MR) in patients with non-ST-elevation myocardial infarction (NSTEMI).
Thirty-eight patients undergoing PCI for NSTEMI were recruited consecutively. Culprit lesions were stented over a Doppler and pressure-sensor-equipped guidewire. In the presence of epicardial stenosis, MR was calculated by taking collateral flow, as measured by the coronary wedge pressure, into consideration. After removal of epicardial stenosis, MR was calculated simply as distal coronary pressure divided by average peak velocity. When collateral flow was incorporated into the calculation, MR increased significantly from 1.70 ± 0.76 to 2.05 ± 0.72 (p=0.001) after PCI in the whole population. Periprocedural changes (Δ) in absolute values of MR and troponin T correlated significantly (r=0.629, p=0.0001). In patients who developed periprocedural myocardial infarction, MR increased significantly after PCI (1.48 ± 0.73 versus 2.28 ± 0.71, p<0.001). Nevertheless, removal of the epicardial lesion did not change MR in patients without periprocedural MI (1.91±0.73 versus 1.81±0.67, p=0.1). | Does percutaneous coronary intervention increase microvascular resistance in patients with non-ST-elevation acute coronary syndrome? | No. When collateral flow is accounted for, removal of epicardial stenosis does not increase MR in patients with NSTEMI undergoing PCI. | FAIL | pubmedQA | 0 |
22428533 | Recently, many studies reported that high carbohydrate and simple sugar intake increase a risk of obesity and metabolic syndrome significantly.
To investigate the effect of carbohydrate on aminotransferase levels in Korea, where the proportion of carbohydrate in meals is extremely high but fat is low.
We used the data of Korean National Health and Nutrition Examination Surveys (KNHANES). A total of 19 749 people were included. Amounts and types of consumed foods were examined by the 24 h recall method.
Mean carbohydrate and fat proportions in total energy intake were 67.7% and 17.4%, respectively. Aminotransferase activity increased according to the rise of the proportion of carbohydrate in the energy intake. A high carbohydrate intake (>70% of energy) was associated with abnormal aminotransferase activity and metabolic syndrome. After adjusting for covariates, such as age, energy intake and body mass index, abnormal aminotransferase activity was significantly associated with carbohydrate proportion. There was a negative correlation between fat proportion in the total energy intake and aminotransferase activity (P < 0.01). The relation between aminotransferase activity and carbohydrate composition showed a J-shaped curve. The lowest point (the J point) was located at 50-60% carbohydrate. | Is carbohydrate but not fat associated with elevated aminotransferases? | Yes. The proportion of fat in energy intake but not carbohydrate is positively correlated with abnormal aminotransferase activity in Koreans. This finding may be useful in planning a strategy of nutrition education for NAFLD in countries where the proportion of fat in most meals is extremely high. | FAIL | pubmedQA | 0 |
27644591 | To identify a screening strategy for dry eye patients with a high likelihood of having Sjogren syndrome (SS) through the evaluation of the association of ocular surface tests with the extraocular signs used for the diagnosis of SS.
Multicenter cross-sectional study.
The Sjogren's International Clinical Collaborative Alliance (SICCA) registry enrolled 3514 participants with SS or possible SS from 9 international academic sites. Ocular surface evaluation included Schirmer I testing, tear breakup time (TBUT), and staining of the cornea (0-6 points) and conjunctiva (0-6 points). Multivariate logistic regression analysis was performed to identify predictive factors for (1) histopathologic changes on labial salivary gland (LSG) biopsies (positive = focus score of ≥1 focus/4 mm
The adjusted odds of having a positive LSG biopsy were significantly higher among those with an abnormal Schirmer I test (adjusted OR = 1.26, 95% CI 1.05-1.51, P = .014) and positive conjunctival staining (for each additional unit of staining 1.46; 95% CI 1.39-1.53, P < .001) or corneal staining (for each additional unit of staining 1.14; 95% CI 1.08-1.21, P < .001). The odds of having a positive serology were significantly higher among those with an abnormal Schirmer I test (adjusted OR = 1.3; 95% CI 1.09-1.54, P = .004) and conjunctival staining (adjusted OR = 1.51; 95% CI 1.43-1.58, P < .001). | Does association of Dry Eye test With Extraocular Signs Among 3514 Participants in the Sjögren 's Syndrome International Registry? | Yes. In addition to corneal staining, which was associated with a higher likelihood of having a positive LSG biopsy, tear breakup time (TBUT) and abnormal Schirmer I testing are of critical importance to include when screening dry eye patients for possible SS, as they were associated with a higher likelihood of having a positive LSG biopsy and serology. | FAIL | pubmedQA | 0 |
16775432 | The prognostic role of tumor biological markers (biomarkers) in predicting recurrence of hepatocellular carcinoma (HCC) was investigated in this study, the results of which may help to select appropriate candidates for liver transplantation (LT).
Tissue samples from 82 HCC patients with cirrhosis who had undergone LT were immunohistochemically stained with antibodies of anti-CD147, anti-matrix metalloproteinases-2 (MMP-2), MMP-9 and anti-vascular endothelial growth factor (VEGF). Tumor microvessel density (MVD) was evaluated by using CD34. Multivariate Cox regression analysis was performed to identify the relevant prognostic factors.
A significant correlation was found between the expression of CD147, VEGF, MMP-2, MMP-9 and MVD-CD34 in HCC. Tumor CD147 expression (P < 0.0001), tumor MVD-CD34 (P < 0.0001), MMP-9 in stromal compartment (P = 0.0257) and tumor VEGF expression (P = 0.0335) were significantly associated with the recurrence in HCC patients after LT. Univariate analysis showed that strong CD147 expression and high MVD-CD34 were significantly associated with poor tumor recurrence-free survival after LT (P < 0.0001). Multivariate analysis indicated that CD147 (P = 0.0001), MVD-CD34 (P = 0.0118), MMP-2 (P = 0.0312) and MMP-9 (P = 0.0280) in stromal compartment were all significant predictors in predicting HCC recurrence, while VEGF, MMP-2 and MMP-9 in tumor compartment were not significantly associated with poor prognosis. | Are cD147 , MMP-2 , MMP-9 and MVD-CD34 significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients? | Yes. The tumor biomarkers CD147 and MVD-CD34 are more feasible markers for rational selection of LT candidates with HCC. MMP-9 and MMP-2 expression in tumor compartment, combined with pTNM tumor grade, may be helpful in predicting poor prognosis in HCC patients after LT. | FAIL | pubmedQA | 0 |
22818364 | Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases.
Elastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11).
The sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p < 0.001) and 124% higher in IPF patients (p < 0.0001) compared with controls. ELN-441 had better diagnostic value in COPD patients (AUC 97%, p = 0.001) than in IPF patients (AUC 90%, p = 0.0001). The odds ratios for differentiating controls from COPD or IPF were 24 [2.06-280] for COPD and 50 [2.64-934] for IPF. | Does measurement of MMP-9 and -12 degraded elastin ( ELM ) provide unique information on lung tissue degradation? | Yes. MMP-9 and -12 time-dependently released the ELN-441 epitope from elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in smaller clinical settings. | FAIL | pubmedQA | 0 |
24132375 | This study evaluated longitudinal CSF biomarker measures collected when participants were cognitively normal to determine the magnitude and time course of biomarker changes before the onset of clinical symptoms in subjects with mild cognitive impairment (MCI).
Longitudinal CSF collection and cognitive assessments were performed on a cohort of 265 participants who were cognitively normal at their baseline assessment and subsequently developed MCI or dementia. CSF β-amyloid 1-42 (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) were determined longitudinally. Consensus diagnoses were completed annually. Cox regression analyses were performed, with baseline CSF values and time-dependent rate of change in CSF values as covariates (adjusted by baseline age, race, and education), in relation to time to onset of mild cognitive symptoms.
The mean time from baseline to onset of mild cognitive symptoms was 5.41 years. Increased risk of progressing from normal cognition to onset of clinical symptoms was associated with baseline values of Aβ1-42, p-tau, and the ratios of p-tau/Aβ1-42 and t-tau/Aβ1-42 (p < 0.002). Additionally, the rate of change in the ratios of t-tau/Aβ1-42 (p < 0.004) and p-tau/Aβ1-42 (p < 0.02) was greater among participants who were subsequently diagnosed with MCI. | Do cSF biomarker changes precede symptom onset of mild cognitive impairment? | No. Baseline differences in CSF values were not predictive of clinical symptoms that were a harbinger of a diagnosis of MCI more than 5 years before symptom onset, and do not show longitudinal changes as cognitive symptoms develop, demonstrating that baseline and longitudinal changes in CSF biomarkers are not evident during the preclinical phase of Alzheimer disease. | FAIL | pubmedQA | 0 |
21804442 | Epithelium regeneration and revascularization of tracheal implants are challenging issues to be solved in tracheal transplantation research. Bone marrow-derived mesenchymal stem cells (BMSCs) can migrate to the damaged tissue and promote functional restoration. Here, we applied intravenous transplantation of BMSCs combined with a cryopreserved allograft to investigate the role of BMSCs in enhancing implant survival, tracheal epithelium regeneration and revascularization.
After transplantation with cryopreserved allografts, PKH-26 labeled 3 to 5 passage BMSCs were injected into recipient rats through the tail vein. Rats in the control groups were injected with a comparable amount of phosphate-buffered saline. We observed the histology of the tracheal allograft and measured vascular endothelial growth factor (VEGF) protein levels in the epithelium to evaluate the effect of BMSCs on epithelium regeneration and revascularization.
Histologic observation of the rats from the BMSCs injection groups showed that the tracheal lumen was covered by pseudostriated ciliated columnar epithelium. The cartilage structure was intact. There were no signs of denaturation or necrosis. PKH-26 labeled BMSCs migrated to the implant site and exhibited red fluorescence, with the brightest red fluorescence at the anastomotic site. VEGF protein levels in the allograft epithelium of the BMSCs injection group were higher than the levels in the phosphate-buffered saline injection group. | Do bone marrow-derived mesenchymal stem cells enhance cryopreserved trachea allograft epithelium regeneration and vascular endothelial growth factor expression? | No. Our results indicate that given systemic administration, BMSCs do not enhance epithelium regeneration and revascularization by upregulating VEGF expression. | FAIL | pubmedQA | 0 |
22095988 | MicroRNAs are a class of small ribonucleotides regulating gene/protein targets by transcript degradation or translational inhibition. Transforming growth factor-β (TGF-β) is involved in cardiac fibrosis partly by stimulation of endothelial-to-mesenchymal transition (EndMT). Here, we investigated whether microRNA (miR)-21, a microRNA enriched in fibroblasts and involved in general fibrosis, has a role in cardiac EndMT.
TGF-β treatment of endothelial cells significantly increased miR-21 expression and induced EndMT characterized by suppression of endothelial and increase of fibroblast markers. Overexpression of miR-21 alone also stimulated EndMT. Importantly, miR-21 blockade by transfection of specific microRNA inhibitors partly prevented TGF-β-induced EndMT. Mechanistically, miR-21 silenced phosphatase and tensin homolog in endothelial cells, resulting in activation of the Akt-pathway. Akt inhibition partly restored TGF-β-mediated loss of endothelial markers during EndMT. In vivo, pressure overload of the left ventricle led to increased expression of miR-21 in sorted cardiac endothelial cells, which displayed molecular and phenotypic signs of EndMT. This was attenuated by treatment of mice subjected to left ventricular pressure overload with an antagomir against miR-21. | Is transforming growth factor-β-induced endothelial-to-mesenchymal transition partly mediated by microRNA-21? | Yes. TGF-β-mediated EndMT is regulated at least in part by miR-21 via the Smad pathway. In vivo, antifibrotic effects of miR-21 antagonism are partly mediated by blocking EndMT under stress conditions. | FAIL | pubmedQA | 0 |
27480415 | Apoptotic protease activating factor-1 (APAF-1) is a key regulator in the mitochondrial apoptotic pathway and an important diagnostic and therapeutic biomarker. Loss of APAF-1 expression has been observed in various tumors including colorectal cancer. The aim of our study was to evaluate the relationship between loss of APAF-1 expression and early recurrence of stage I-III colorectal cancer.
We investigated 165 out of 492 patients who had undergone curative resection for colorectal cancer between 1991 and 2001. Sixty-one patients (37.0 %) had early recurrence within 1 year after surgery. Tissue microarrays were used for immunohistochemical detection of APAF-1.
The mean age of patients with recurrence was 58 years (range, 24-85); 88 (53.3 %, 88/165) were male. APAF-1 was expressed in 32 (19.4 %, 32/165) cases and was not expressed in 133 (80.6 %, 133/165). In univariate analysis, early recurrence significantly correlated with loss of APAF-1 expression (p = 0.017), tumor stage (p = 0.005), N category (p = 0.001), and lymphatic invasion (p = 0.008). In a logistic regression model, loss of APAF-1 expression (p = 0.015, 95 % CI = 1.280-10.063) and N category (p = 0.001, 95 % CI = 0.004-0.739) proved to be independent risk factors associated with early recurrence. In patients with lymph node metastasis, early recurrence was more frequent in the APAF-1-negative group than in the APAF-1-positive group (46.2 % (54/117) vs. 22.2 % (6/27), p = 0.023). | Is loss of APAF-1 expression associated with early recurrence in stage I , II , and III colorectal cancer? | No. Loss of APAF-1 expression is not associated with early recurrence in stage I-III colorectal cancer, suggesting that APAF-1 may not have clinical value as a predictive marker of early recurrence. | FAIL | pubmedQA | 0 |
23294880 | Tumor-associated lymphatic networks are the primary routes for tumor cell dissemination and metastasis. Behind the background of possible lymphangiogenesis-associated therapies, the clinical impact of lymphangiogenesis (measured by lymphatic microvessel density [LMVD]) and specific lymphovascular invasion (LVI) in esophageal cancer remains unclear. The aim of this study was to evaluate the clinical role of lymphangiogenesis and LVI in a large cohort of esophageal cancer.
For the specific assessment of LMVD and LVI, 393 tissue samples from a prospective tissue databank of esophageal adenocarcinomas, squamous cell carcinomas, and their precursor lesions were included into this study. LMVD and LVI were assessed by immunostaining for podoplanin, a selective marker of lymphatic endothelium. In addition the peritumoral inflammatory stroma reaction (ISR) was assessed.
Patients with high LMVD had a significant increased risk to develop LVI (P = .00123; coefficient of regression [CR] 0.27) and lymph node metastasis (P = .00233), independent of the tumor's histology. During a follow-up of 52 months, patients with high LMVD had a significantly reduced overall survival (OS; P < .001; 5-year OS 30% vs 54%) and disease-free survival (DFS; P < .001; 5-year DFS 28% vs 48%). OS (P < .001; 5-year OS 14% vs 60%) and DFS (P < .001; 5-year DFS 14% vs 49%) were significantly reduced in patients with present LVI. In invasive cancer, LMVD was significantly increased compared with precursor lesions (P = .008). The amount of ISR correlated significantly with LMVD. | Does lymphangiogenesis and lymphovascular invasion diminish prognosis in esophageal cancer? | No. Our data provide evidence that lymphangiogenesis does not play a significant role in esophageal cancer. Patients with high lymphangiogenic tumor activity do not represent candidates for lymphangiogenesis-associated therapies. | FAIL | pubmedQA | 0 |
26231928 | COPD and heart failure occur with a considerable coincidence. Beside well-known mechanisms of increased right heart load in COPD, dedicated changes of the left ventricle (LV) are ill-defined and the question remains, whether specific interactions exist beyond common shared risk factors.
LV wall stress was calculated based on cardiac magnetic resonance imaging in 28 patients with COPD (GOLD I to III) and coexistent heart failure (LVEF 42 ± 19%) due to non-ischaemic and ischaemic cardiomyopathy.
LV enddiastolic (p = 0.048) and endsystolic wall stress (p = 0.034) increased from GOLD stage I to III. Reduced FEV1 was correlated with increased enddiastolic (p = 0.0210) and endsystolic LV volume (p = 0.0413) and with increased enddiastolic (p = 0.0161) and endsystolic LV wall stress (p = 0.0315), respectively. Increased wall stress was associated with a decreased FEV1/FVC ratio. | Is airflow limitation in COPD associated with increased left ventricular wall stress in coincident heart failure? | No. The severity of airflow limitation in COPD was not correlated with increased LV wall stress. It is suggested that respiration in pulmonary obstruction is not associated with an increased negative intrathoracic pressure when compared with normal lung function, which is transmitted to the heart and does not increase the transmural pressure gradient and thereby distending forces on the heart. Increased ventricular wall stress is not known to be associated with a broad variety of unfavourable consequences, which should be taken into account to contribute to a worse prognosis in COPD. | FAIL | pubmedQA | 0 |
24747581 | Oxylipins, including eicosanoids, are highly bioactive molecules endogenously produced from polyunsaturated fatty acids. Oxylipins play a key role in chronic disease progression. It is possible, but unknown, if oxylipin concentrations change with the consumption of functional foods or differ with subject age.
Therefore, in a parallel comparator trial, 20 healthy individuals were recruited into a younger (19-28years) or older (45-64years) age group (n=10/group). Participants ingested one muffin/day containing 30g of milled flaxseed (6g alpha-linolenic acid) for 4weeks. Plasma oxylipins were isolated through solid phase extraction, analyzed with HPLC-MS/MS targeted lipidomics, and quantified with the stable isotope dilution method.
At baseline, the older group exhibited 13 oxylipins ≥2-fold the concentration of the younger group. Specifically, pro-inflammatory oxylipins 5-hydroxyeicosatetraenoic acid, 9,10,13-trihydroxyoctadecenoic acid, and 9,12,13-trihydroxyoctadecenoic acid were significantly greater in the older (1.1±0.23nM, 5.6±0.84nM, and 4.5±0.58nM, respectively) versus the younger group (0.34±0.12nM, 3.5±0.33nM, and 3.0±0.24nM, respectively) (p<0.05). After 4weeks of flaxseed consumption the number of oxylipins that were ≥2-fold higher in the older versus the younger group was reduced to 3. 5-Hydroxyeicosatetraenoic acid, 9,10,13-trihydroxyoctadecenoic acid, and 9,12,13-trihydroxyoctadecenoic acid decreased in the older group to concentrations equivalent to the younger group after flaxseed consumption. | Are elevated levels of pro-inflammatory oxylipins in older subjects normalized by flaxseed consumption? | No. These data suggest that nutritional interventions like flaxseed do not have a significant impact on the biological changes associated with inflammation and aging. | FAIL | pubmedQA | 0 |
23625381 | Neuromuscular electrical stimulation (NMES) is used to improve quadriceps mass after anterior cruciate ligament (ACL) injury. We studied the effect of NMES on mRNA levels of atrophy genes in the quadriceps muscle of rats after ACL transection.
mRNA levels of atrogin-1, MuRF-1, and myostatin were assessed by quantitative PCR and the polyubiquitinated proteins by Western blot at 1, 2, 3, 7, and 15 days postinjury.
NMES minimized the accumulation of atrogenes and myostatin according to time period. NMES also prevented reduction in muscle mass in all muscles of the ACLES group at 3 days. | Does neuromuscular electrical stimulation alter gene expression and delays quadriceps muscle atrophy of rats after anterior cruciate ligament transection? | Yes. Use of NMES decreased the accumulation of atrogenes and myostatin mRNA in the quadriceps muscles, inhibiting early atrophy at 7 days, although it did not prevent atrophy at 3 and 15 days after ACL transection. This study highlights the importance of therapeutic NMES interventions in the acute phase after ACL transection. | FAIL | pubmedQA | 0 |
17849098 | Cocaine increases endoplasmic reticulum (ER) stress protein expression via glutamate and dopamine receptor activation in the dorsal striatum.
The present study was performed to investigate ER stress response in the dorsal striatum in response to acute or repeated cocaine stimulation. It was hypothesized that cocaine upregulates the ER stress protein immunoglobulin heavy chain binding protein (BiP) and the ER stress-associated protein caspase-12 via N-methyl-D-aspartate (NMDA) and D1 dopamine receptor activation.
Western immunoblot and immunohistochemical analyses were mainly performed to test this hypothesis in the rat dorsal striatum.
The results showed that BiP and caspase-12 immunoreactivities were significantly increased at 30, 60, and 120 min after acute or repeated intraperitoneal (i.p.) injections of three doses (10, 20, 40 mg/kg) of cocaine for seven consecutive days. Intrastriatal (i.s.) infusion of the selective NMDA antagonist MK801 (2 nmol) or AP5 (2 nmol) significantly attenuated the increase in the immunoreactivity of caspase-12 in the dorsal striatum induced by repeated, but not acute, cocaine (20 mg/kg) administration. However, i.p. injection of the selective D1 antagonist SCH23390 (0.1 mg/kg) significantly attenuated the increase in the immunoreactivity of caspase-12 in the dorsal striatum induced by both acute and repeated cocaine (20 mg/kg) stimulation. | Does cocaine increase immunoglobulin heavy chain binding protein and caspase-12 expression in the rat dorsal striatum? | Yes. These findings suggest that acute or repeated cocaine administration can cause ER stress response in the dorsal striatum in which NMDA and D2 dopamine receptors participate in the mediation of the process. | FAIL | pubmedQA | 0 |
25069864 | It is known that enhancement of sympathetic nerve activity based on a decrease in parasympathetic nerve activity is associated with fatigue induced by mental tasks lasting more than 30 min. However, to measure autonomic nerve function and assess fatigue levels in both clinical and industrial settings, shorter experimental durations and more sensitive measurement methods are needed. The aim of the present study was to establish an improved method for inducing fatigue and evaluating the association between it and autonomic nerve activity.
Twenty-eight healthy female college students participated in the study. We used a kana pick-out test (KPT) as a brief verbal cognitive task and recorded electrocardiography (ECG) to measure autonomic nerve activity. The experimental design consisted of a 16-min period of ECG: A pre-task resting state with eyes open for 3 min and eyes closed for 3 min, the 4-min KPT, and a post-task resting state with eyes open for 3 min and eyes closed for 3 min.
Baseline fatigue sensation, measured by a visual analogue scale before the experiment, was associated with the decrease in parasympathetic sinus modulation, as indicated the by ratio of low-frequency component power (LF) to high-frequency component power (HF), during the KPT. The LF/HF ratio during the post-KPT rest with eyes open tended to be greater than the ratio during the KPT and correlated with fatigue sensation. Fatigue sensation was correlated negatively with log-transformed HF, which is an index of parasympathetic sinus modulation, during the post-KPT rest with eyes open. | Does fatigue correlate with the decrease in parasympathetic sinus modulation induced by a cognitive challenge? | No. The methods described here are not useful for assessing the association between fatigue sensation and autonomic nerve activity using a brief cognitive test in healthy females. | FAIL | pubmedQA | 0 |
12168811 | Simian virus 40 (SV40), a contaminant of polio vaccines used in the United States and Europe between 1955 and 1963, has been detected with high frequency in human malignant mesotheliomas (MM). In Sweden, from 1958, due to production in Javanese macaque kidney cells and SV40 testing from 1961, only polio vaccine claimed to be free of SV40 has been used. Hence, we aimed to screen Swedish MM patients for the presence of SV40.
Forty-one paraffin-embedded pleural MM samples, obtained from patients born from 1893-1958, were examined for amplifiable DNA. Testable samples were thereafter evaluated for the presence of SV40 DNA by two types of polymerase chain reactions (PCR) followed by sequencing.
SV40 could be confirmed by sequencing in only 3 of the 30 MM samples containing DNA that could be amplified by PCR. | Is presence of simian virus 40 ( SV40 ) frequent in Swedish malignant mesotheliomas? | Yes. The presence of SV40 is frequent in Swedish MM patients. | FAIL | pubmedQA | 0 |
12571168 | The study aim was to compare the relationship between serum anti-Müllerian hormone (AMH) levels and other markers of ovarian function with early antral follicle count on day 3.
A total of 75 infertile women was studied prospectively. On cycle day 3, serum levels of AMH, inhibin B, estradiol (E(2)), FSH and LH levels were measured, and the number of early antral follicles (2-10 mm in diameter) estimated at ultrasound scanning to compare the strengths of hormonal-follicular correlations.
Median (range) serum levels of AMH, inhibin B, E(2), FSH and LH were 1.39 ng/ml (0.24-6.40), 90 (16-182) pg/ml, 31 (15-111) pg/ml, 7.0 (2.9-19.3) mIU/ml and 4.7 (1.2-11.7) mIU/ml respectively, and follicular count was 12 (1-35). Serum AMH levels were more strongly correlated (P < 0.001) with follicular count (r = 0.74, P < 0.0001) than were serum levels of inhibin B (r = 0.29, P < 0.001), E(2) (r = -0.08, P = NS), FSH (r = -0.29, P < 0.001) and LH (r = 0.05, P = NS). | Is serum anti-Müllerian hormone more strongly related to ovarian follicular status than serum inhibin B , estradiol , FSH and LH on day 3? | No. Serum AMH levels were less robustly correlated with the number of early antral follicles than inhibin B, E(2), FSH and LH on cycle day 3. This suggests that AMH may not reflect ovarian follicular status as well as the usual hormone markers. | FAIL | pubmedQA | 0 |
20708005 | Little data are available from genome-wide association studies (GWASs) of liver histology in patients with nonalcoholic fatty liver disease (NAFLD). We conducted a pilot GWAS in patients with NAFLD, characterized by histology, who were enrolled in the NASH Clinical Research Network (CRN) Database Study.
We studied clinical, laboratory, and histologic data from 236 non-Hispanic white women with NAFLD. We analyzed 324,623 single nucleotide polymorphisms (SNPs) from the 22 autosomal chromosomes. Multivariate-adjusted logistic regression analyses were conducted for binary outcomes, and linear regression analysis was applied for quantitative traits. A P value < 1 × 10(-6) was considered to be significant.
In multivariate models adjusted for age, body mass index, diabetes, waist/hip ratios, and levels of glycated hemoglobin, the NAFLD activity score was associated with the SNP rs2645424 on chromosome 8 in farnesyl diphosphate farnesyl transferase 1 (FDFT1) (P = 6.8 × 10(-7)). The degree of fibrosis was associated with the SNP rs343062 on chromosome 7 (P = 2.7 × 10(-8)). SNPs associated with lobular inflammation included SNP rs1227756 on chromosome 10 in COL13A1 (P = 2.0 × 10(-7)), rs6591182 on chromosome 11 (P = 8.6 × 10(-7)), and rs887304 on chromosome 12 in EFCAB4B (P = 7.7 × 10(-7)). SNPs associated with serum levels of alanine aminotransferase included rs2499604 on chromosome 1 (P = 2.2 × 10(-6)), rs6487679 on chromosome 12 in PZP (P = 1.3 × 10(-6)), rs1421201 on chromosome 18 (P = 1.0 × 10(-5)), and rs2710833 on chromosome 4 (P = 6.3 × 10(-7)). No significant associations were observed between genotypes and steatosis, ballooning degeneration, portal inflammation, or other features of NAFLD. | Does genome-wide association study identify variants associated with histologic features of nonalcoholic Fatty liver disease? | No. A GWAS did not significantly associate genetic variants with features of hepatic histology in patients with NAFLD. These findings should be validated in larger and more diverse cohorts. | FAIL | pubmedQA | 0 |
15730649 | To explore the molecular mechanism of apoptosis of the human umbilical vein endothelial cells (HUVECs) induced by burn serum and subeschar tissue fluid.
In vitro cultured HUVECs were randomly divided into A (treated by normal serum, n = 6), B (treated by burn serum, n = 6) and C (treated by subeschar tissue fluid, n = 6) groups. The change in cellular nuclear morphology was determined by Hochst 33258 fluorescent staining, and the apoptotic rate was calculated at 24th and 36th post treatment hours (PTHs). The DNA ladder strips were observed with agarose electrophoresis at 12th and 24th PTH. The activity of caspase-3, 8, 9 was assayed by caspase colorimetric assay kit at 12 PTH.
It was found that nuclei appeared to be condensed and highly fluorescent granular in form in B and C groups. The nucleic apoptotic rate in B and C groups was (38.9 +/- 7.3)% and (49.5 +/- 6.5)%, respectively, which was evidently higher than that in A group (P < 0.01). The DNA ladder strips could be found by agarose electrophoresis in B and C groups. The activity of caspase-3, 8, 9 in B and C groups was significantly higher than that in A group after 12 PTHs (P < 0.01). | Do [ Experimental study on the induction of endothelial apoptosis by burn serum and subeschar tissue fluid ]? | Yes. Burn serum and subeschar tissue fluid might induce apoptosis of HUVEC by means of the activation of death receptor pathways exclusively. | FAIL | pubmedQA | 0 |
25916817 | Abdominal aortic aneurysm (AAA) is often asymptomatic until rupture occurs. Although ultrasound screening has significantly improved the early diagnosis of AAA, the timely biomarker-based diagnosis of AAA remains a major clinical challenge. In this study, we aimed to assess plasma microRNAs (miRNAs) as promising novel biomarkers in patients with AAA.
Pooled plasma samples from 10 AAA and 10 healthy controls were profiled by microarray. The differentially expressed miRNAs were evaluated in a separate cohort of 120 subjects, including 60 AAA patients and 60 normal controls.
The initial profiling study identified 151 miRNAs that showed more than two-fold change. Among them, three miRNAs, miR-191-3p, miR-455-3p and miR-1281 exhibited the largest increase in the patient group (fold change>5). A subsequent validation study confirmed the elevation of these three miRNAs. Receiver operator characteristic curve analysis using the expression ratio of miR-191-3p, miR-455-3p and miR-1281 showed an area under the curve of 0.9700, 0.9825 and 0.9206, respectively. | Do plasma microRNAs serve as potential biomarkers for abdominal aortic aneurysm? | Yes. Our results suggest that plasma miR-191-3p, miR-455-3p and miR-1281 may be used as potential prognosis biomarkers for AAA. | FAIL | pubmedQA | 0 |
26921215 | Immunological characterization of mycobacterial peptides may help not only in the preparation of a vaccine for leprosy but also in developing in vitro T-cell assays that could perhaps be used as an in vitro correlate for treatment outcome. The main goal of this study was to evaluate the use of Mycobacterium bovis recombinant 32-kDa protein (r32-kDa) antigen-stimulated T-cell assay as a surrogate marker for treatment outcome and monitor vitamin D receptor (VDR)-mediated anti-microbial responses during multidrug therapy (MDT) in leprosy.
Newly diagnosed tuberculoid and lepromatous leprosy patients were enrolled and followed up during their course of MDT at 6 and 12 months. IFN-γ, IL-10, IL-17 and IL-23 levels in culture supernatants and expression of VDR, TLR2, LL37 and DEFB in r32-kDa-stimulated PBMCs were measured. Controls comprised household contacts (HHCs) and healthy endemic subjects (HCs).
Significant differences were observed in the levels of IFN-γ, IL-17, IL-23, VDR and anti-microbial peptides LL37 and DEFB after treatment and when compared with that of HHCs and HCs, respectively. | Do mycobacterial r32-kDa antigen-specific T-cell responses correlate with successful treatment and a heightened anti-microbial response in human leprosy patients? | No. These findings suggest that responses to r32-kDa antigen do not reflect an improved immunological and anti-microbial response in leprosy patients during therapy, thereby indicating its potential use as an immune correlate in the treatment of leprosy patients. | FAIL | pubmedQA | 0 |
21802023 | Asthma is a chronic airway inflammatory disease that is associated with a large influx of inflammatory cells. Several chemokines and chemokine receptors play critical roles in the development of allergic airway inflammation.
Because polarized human T(H)2 cells express a functional CXCR3 chemokine receptor, we evaluated the effects of a selective CXCR3 inhibitor in a mouse model of allergic airway disease.
Ovalbumin-specific CD8(+) T effector cells were generated from OT-1 mice in the presence of interleukin 2. The activity of a CXCR3 inhibitor was examined in vitro by monitoring Ca(2+) influx after receptor ligation. In vivo, the activity was assessed in sensitized and challenged mice by monitoring airway function, inflammatory parameters, including cellular infiltrates and cytokines in the bronchoalveolar lavage fluid.
Approximately 40% of CD8(+) T effector cells expressed the CXCR3 receptor. In vitro, CXCR3 antagonism reduced Ca(2+) influx after receptor engagement. In contrast, the CXCR3 antagonist had little to no effect on airway function or inflammatory parameters despite adequate exposure levels. | Does targeting CXCR3 reduce ligand-induced T-cell activation but not development of lung allergic responses? | Yes. CXCR3 antagonism prevented allergen-induced airway hyperresponsiveness and airway inflammation in a mouse allergy model despite having activity in in vitro functional assays. | FAIL | pubmedQA | 0 |
26787368 | To describe the effects of internal and external femoral rotation on radiographic measurements of the anatomical lateral distal femoral angle (a-LDFA) using two methods for defining the anatomical proximal femoral axis (a-PFA).
Digital radiographs were obtained of 14 right femora at five degree intervals from 10° external rotation to 10° internal rotation. Using freely available software, a-LDFA measurements were made using two different a-PFA by a single observer on one occasion.
Mean a-LDFA was significantly greater at 10° external rotation than at any other rotation. The response of individual femora to rotation was unpredictable, although fairly stable within ±5° of zero rotation. Mean a-LDFA for the two a-PFA methods differed by 1.5°, but were otherwise similarly affected by femoral rotation. | Does femoral rotation unpredictably affect radiographic anatomical lateral distal femoral angle measurements? | Yes. If zero femoral elevation can be achieved for radiography, a-LDFA measurements do not vary much with mild femoral rotation (±10°). Outside of this range, a-LDFA varies unpredictably with femoral rotation. | FAIL | pubmedQA | 0 |
26941538 | To investigate the in vitro cytotoxic effect and to isolate and characterize a chemopreventive secondary metabolite from Sphaeranthus amaranthoides Burm F (sivakaranthai).
In vitro cytotoxic effect was carried out by 3 (4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide assay. Different concentrations of the extracts were tested on three different cell lines namely A549, HT29, and MCF7. The chloroform extract was subjected to column chromatography, and the isolated compound was characterized by various spectral methods and by single crystal X-ray crystallography.
The concentration that cause 50% growth inhibition value of chloroform extract was found to be 0.9 and 19 μg/mL against MCF7 and A549 cell lines, respectively. Chloroform extract was subjected to column chromatography for the isolation of phytoconstituent. The structure of the isolated compound was identified by spectroscopic techniques such as infrared, nuclear magnetic resonance, XRD, and mass spectroscopy. On comparison of complete spectral detail of the compound, the proposed structure was identified as chrysosplenol D (a flavonoid). Chrysosplenol D was isolated for the first time from this plant. | Do isolation and Characterization of Chemopreventive Agent from Sphaeranthus amaranthoides Burm F? | Yes. The chloroform extract had higher cytotoxic effect, and the isolated chrysosplenol D may be responsible for the anti-inflammatory effect of the plant. | FAIL | pubmedQA | 0 |
18222259 | The generation of thrombin and its procoagulant activity are upregulated during cardiopulmonary bypass (CPB). Thrombophilia associates with increased basal thrombin generation and might therefore propagate thrombin generation during CPB. The objective of this study was to test whether preoperative thrombophilic variables associate with increased generation of thrombin or its procoagulant activity during and after CPB.
Comprehensive thrombophilia screening was performed in patients (n = 100) before elective coronary artery bypass grafting (CABG) with CPB. Markers of thrombin generation (prothrombin fragment F1+2), its procoagulant activity (soluble fibrin complexes), and a marker of fibrin degradation (D-dimer) were measured serially at eight time points before, during, and after CABG.
Abnormal thrombophilia screening was common (44%). While patients with thrombophilic variables had higher preoperative prothrombin fragment F1+2 than others (median [interquartile range] 0.55 [0.34] vs 0.45 (0.21) nmol/L, p = 0.009) they did not have higher F1+2, D-dimer, or soluble fibrin complex levels during CPB or postoperatively than patients without thrombophilic variables. | Do thrombophilic variables increase the generation or procoagulant activity of thrombin during cardiopulmonary bypass? | Yes. Preoperative thrombophilic variables associate with perioperative thrombin generation and its procoagulant activity in patients undergoing CABG. Our results support routine thrombophilia screening before CABG. | FAIL | pubmedQA | 0 |
19592469 | Osteoprotegerin (OPG) is a tumor necrosis factor receptor-related cytokine, initially found to inhibit osteoclastogenesis. In the present study we investigated the effect of OPG treatment on atherosclerosis.
Hypercholesterolemic apoe(-/-) mice were treated with recombinant 15 mg/kg OPG or vehicle injections twice a week for 10 consecutive weeks. Mice treated with OPG showed increased amounts of smooth muscle cells and collagen within the atherosclerotic lesions. OPG treatment did not affect atherosclerotic lesion size (8.2% versus 7.6%) or total vessel area but led to a 250% increase in lesion collagen, formation of mature collagen fibers in subendothelial fibrous caps, and upregulated mRNA for lysyl oxidase that promotes collagen crosslinking. In cell culture studies, OPG promoted cell proliferation in rat aortic smooth muscle cells. In contrast, OPG treatment did not affect markers of vascular or systemic inflammation. | Does osteoprotegerin promote fibrous cap formation in atherosclerotic lesions of ApoE-deficient mice -- brief report? | Yes. OPG treatment promotes smooth muscle accumulation, collagen fiber formation, and development of fibrous caps and also reduces inflammatory properties of atherosclerotic lesions. Its effects may contribute to plaque stabilization. | FAIL | pubmedQA | 0 |
20571440 | We assessed the correlation between intima-media thickness (IMT) and stiffness and test whether they are independent risk factors for atherosclerotic diseases.
We enrolled 2333 participants from the general population. Among the study subjects, 197 subjects had a history of stroke or myocardial infarction (MI) and were treated as patients, and the rest were the control subjects. Intima-media thickness was measured at the common carotid artery (CCA), bifurcation, and internal carotid artery. Three parameters (arterial stiffness [beta], elastic modulus, and pulse wave velocity) were measured for carotid stiffness. Correlation between IMT and stiffness was first calculated. Multivariate regression model was used to evaluate whether inclusion of both IMT and stiffness can increase the prediction of cardiovascular events.
Only CCA and bifurcation IMTs were significantly and positively correlated with stiffness. After adjusting for age and sex, the correlations were substantially attenuated. Common carotid artery IMT was most significantly associated with stroke and MI (P = 2.6 x 10) followed by bifurcation IMT (P = 5.5 x 10), and internal carotid artery IMT was least significant (P = 0.02). For stiffness, beta was most significant (P = 3.6 x 10) for stroke and MI, followed by elastic modulus (P = 1.1 x 10) and pulse wave velocity (P = 6.8 x 10). The best model for the combined effect was from beta (P < 0.03) and CCA (P = 0.056) or bifurcation IMT (P = 0.057). | Are carotid intima-media thickness and stiffness independent risk factors for atherosclerotic diseases? | No. Carotid IMT and stiffness represent the same properties of atherosclerotic vessel wall. Measuring both traits does not provide a better characterization of atherosclerosis. | FAIL | pubmedQA | 0 |
21836070 | The anti-inflammatory properties of the female sex hormone estrogen have been linked to a reduced incidence of cardiovascular disease. In the present study, we addressed whether estrogen could activate vasculoprotective mechanisms via annexin A1 (AnxA1) mobilization in human polymorphonuclear cells (PMNs).
Using whole-blood flow cytometry, we demonstrated that premenopausal women expressed higher levels of surface AnxA1 on circulating PMNs compared with males. This correlated with high plasma estrogen during the menstrual cycle. The addition of estrogen in vitro to male PMNs induced rapid mobilization of AnxA1, optimal at 5 ng/mL and a 30-minute incubation period; this effect was abolished in the presence of the estrogen receptor antagonist ICI182780. Estrogen addition to human PMNs induced a distinct AnxA1(hi) CD62L(lo) CD11b(lo) phenotype, and this was associated with lower cell activation as measured by microparticle formation. Treatment of human PMNs with E(2) inhibited cell adhesion to an endothelial cell monolayer under shear, which was absent when endogenous AnxA1 was neutralized. Of interest, addition of estrogen to PMNs flowed over the endothelial monolayer amplified its upregulation of AnxA1 localization on the cell surface. Finally, in a model of intravital microscopy, estrogen inhibition of white blood cell adhesion to the postcapillary venule was absent in mice nullified for AnxA1. | Does activation of the annexin A1 pathway underlie the protective effects exerted by estrogen in polymorphonuclear leukocytes? | No. We unveil a novel AnxA1-independent mechanism behind the inhibitory properties of estrogen on PMN activation, describing a novel phenotype with a conceivable impact on the vasculoprotective effects of this hormone. | FAIL | pubmedQA | 0 |
23360583 | Bullous pemphigoid is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies directed mainly to the hemidesmosomal component collagen XVII. While recapitulating the main immunopathological features of the human disease, frank skin blistering does not develop in the absence of skin rubbing in experimental pemphigoid models that have been established in neonatal mice. Moreover, due to their experimental design they only allow for short-term disease observation. In the present study we aimed to establish a model that reproduces the frank skin blistering seen in patients and allows for longer observation times.
Rabbit and sheep antibodies specific to several fragments of collagen XVII were generated and the purified antibodies were passively transferred into adult mice.
Collagen XVII-specific IgG bound to the basal membrane of the skin and mucous membranes activating murine complement in vivo. Mice injected with collagen XVII-specific antibodies, in contrast to mice receiving control antibodies, developed frank skin blistering disease, reproducing human bullous pemphigoid at the clinical, histological and immunopathological levels. Titres of circulating IgG in the serum of mice correlated with the extent of the clinical disease. Mice receiving sheep antibodies specific to murine collagen XVII showed an early onset and a more active disease when compared to litter mates receiving specific rabbit antibodies. | Does passive transfer of collagen XVII-specific antibodies induce sustained blistering disease in adult mice? | No. This novel animal model for bullous pemphigoid should facilitate further investigations of the pathogenesis of bullous pemphigoid and the development of innovative therapies for this disease. | FAIL | pubmedQA | 0 |
18240302 | Three common mutations in the NOD2/CARD15 gene are strongly associated with Crohn's disease (CD). NOD2 is an intracellular receptor of muramyl dipeptide (MDP), a component of peptidoglycan present in the cell wall of gram-positive (G+) and gram-negative (G-) bacteria.
We generated monocyte-derived dendritic cells (MoDCs) from CD patients mutated or not for CARD15 (n = 53) or from healthy donors (n = 12) and analyzed their activation in response to live Salmonella typhimurium as a model of pathogenic G- bacteria.
MoDCs carrying the L1007fs mutation, although phenotypically activated by bacteria, produced a significantly reduced amount of tested cytokines. MoDCs carrying R702W or compound G908R/R702W NOD2 mutations displayed an increased basal level of IL-8 release. After a bacterial encounter, these cells were phenotypically activated and produced levels of cytokines similar to healthy controls. Interestingly, although L1007fs/WT mutations conferred reduced production of cytokines, including IL-12, these cells were perfectly capable of inducing T-cell polarization toward the Th1 phenotype. | Do monocyte-derived dendritic cells from Crohn patients show differential NOD2/CARD15-dependent immune responses to bacteria? | Yes. NOD2 mutations affect the basal characteristics of MoDCs and their response to G+ bacteria differently. MoDCs could be involved in CD onset because they have defects in releasing inflammatory cytokines and in polarizing T-cell responses. | FAIL | pubmedQA | 0 |
23362302 | Therapeutic management of asymptomatic patients with a Wolff-Parkinson-White (WPW) pattern is controversial. We compared the risk:benefit ratios between prophylactic radiofrequency ablation and no treatment in asymptomatic patients with WPW.
Decision analysis software was used to construct a risk-benefit decision tree. The target population consisted of 20- to 40-year-old asymptomatic patients with WPW without structural fatal heart disease or a family history of sudden cardiac death. Baseline estimates of sudden death and radiofrequency ablation complication rates were obtained from the literature, an empirical data survey, and expert opinion. The outcome measure was death within 10 years. Sensitivity analyses determined the variables that significantly impacted the decision to ablate or not. Threshold analyses evaluated the effects of key variables and the optimum policy. At baseline, the decision to ablate resulted in a reduction of mortality risk of 8.8 patients for 1000 patients compared with abstention. It is necessary to treat 112 asymptomatic patients with WPW to save one life over 10 years. Sensitivity analysis showed that 3 variables significantly impacted the decision to ablate: (1) complication of radiofrequency ablation, (2) success of radiofrequency ablation, and (3) sudden death in asymptomatic patients with WPW. | Is prophylactic radiofrequency ablation in asymptomatic patients with Wolff-Parkinson-White yet a good strategy : a decision analysis? | Yes. This study provides a decision aid for treating asymptomatic patients with the WPW ECG pattern. Using the model and the population we tested, prophylactic catheter ablation is ready for widespread clinical use. | FAIL | pubmedQA | 0 |
23385100 | Cardiovascular dysfunction occurs in the majority of asphyxiated neonates and has been suggested to be a major cause of neonatal morbidity and mortality. We previously demonstrated that cyclosporine A treatment during resuscitation can significantly improve cardiovascular performance in asphyxiated newborn piglets. However, the mechanisms through which cyclosporine elicits its protective effect in neonates have not yet been fully characterized. We hypothesized that cyclosporine A treatment would attenuate myocardial and cardiac mitochondrial injury during the resuscitation of asphyxiated newborn piglets.
After acute instrumentation, piglets received normocapnic alveolar hypoxia (10% to 15% oxygen) for 2 hours followed by reoxygenation with 100% oxygen (0.5 hr) and then 21% oxygen (3.5 hr). At 4 hours of reoxygenation, plasma troponin level, left ventricle myocardial levels of lipid hydroperoxides, cytochrome-c, and mitochondrial aconitase activity were determined.
Neonatal asphyxia and reoxygenation.
Twenty-four newborn (1-4 days old) piglets.
Piglets were randomized to receive an IV bolus of cyclosporine A (10 mg/kg) or normal saline (placebo, control) at 5 minutes of reoxygenation (n=8/group). Sham-operated piglets (n=8) underwent no asphyxia-reoxygenation.
Asphyxiated piglets treated with cyclosporine had lower plasma troponin and myocardial lipid hydroperoxides levels (vs. controls, both p<0.05, analysis of variance). Cyclosporine treatment also improved mitochondrial aconitase activity and attenuated the rise in cytosol cytochrome-c level (vs. controls, all p<0.05). The improved mitochondrial function significantly correlated with cardiac output (p<0.05, Spearman rank-correlation test). | Does postresuscitation cyclosporine treatment attenuate myocardial and cardiac mitochondrial injury in newborn piglets with asphyxia-reoxygenation? | No. We demonstrate that the postresuscitation administration of cyclosporine does not attenuate myocardial and cardiac mitochondrial injury in asphyxiated newborn piglets following resuscitation. | FAIL | pubmedQA | 0 |
12615675 | Atherosclerosis is considered to be a chronic inflammatory disease and many cytokines participate in the development of atherosclerosis. We focused on the role of interleukin-1beta (IL-1beta), one of the proinflammatory cytokines secreted by monocytes/macrophages, in the progression of atherosclerosis.
We generated mice lacking both apoE and IL-1beta. The sizes of atherosclerotic lesions at the aortic sinus in apoE-/-/IL-1beta-/-mice at 12 and 24 weeks of age showed a significant decrease of approximately 30% compared with apoE-/-/IL-1beta+/+ mice, and the percentage of the atherosclerotic area to total area of apoE-/-/IL-1beta-/- at 24 weeks of age also showed a significant decrease of about 30% compared with apoE-/-/IL-1beta+/+. The mRNA levels of vascular cell adhesion molecule (VCAM)-1 and monocyte chemotactic protein-1 in the apoE-/-/IL-1beta-/- aorta were significantly reduced compared with the apoE-/-/IL-1beta+/+. Furthermore, VCAM-1 was also reduced at the protein level in apoE-/-/IL-1beta-/- aorta compared with apoE-/-/IL-1beta+/+. | Does lack of interleukin-1beta decrease the severity of atherosclerosis in ApoE-deficient mice? | Yes. The lack of IL-1beta decreases the severity of atherosclerosis in apoE deficient mice, possibly through decreased expressions of VCAM-1 and monocyte chemotactic protein-1 in the aorta. | FAIL | pubmedQA | 0 |
23140663 | Tauopathies, including Alzheimer's disease and frontotemporal dementia, are diseases characterized by the formation of pathological tau protein aggregates in the brain and progressive neurodegeneration. Presently no effective disease-modifying treatments exist for tauopathies.
To identify drugs targeting tau neurotoxicity, we have used a Caenorhabditis elegans model of tauopathy to screen a drug library containing 1120 compounds approved for human use for the ability to suppress tau-induced behavioral effects.
One compound, the typical antipsychotic azaperone, improved the motility of tau transgenic worms, reduced levels of insoluble tau, and was protective against neurodegeneration. We found that azaperone reduces insoluble tau in a human cell culture model of tau aggregation and that other antipsychotic drugs (flupenthixol, perphenazine, and zotepine) also ameliorate the effects of tau expression in both models. | Does dopamine D2 receptor antagonism suppress tau aggregation and neurotoxicity? | No. Reduction of dopamine signaling through the dopamine D2 receptor with the use of gene knockouts in Caenorhabditis elegans or RNA interference knockdown in human cell culture does not have protective effects against tau toxicity. These results suggest dopamine D2 receptor antagonism does not hold promise as a potential neuroprotective strategy for targeting tau aggregation and neurotoxicity. | FAIL | pubmedQA | 0 |
21555162 | Prior studies highlighted cyclin D1 as a key biomarker of response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. This study builds on prior work by examining the roles of cyclin D1, cyclin D3, and cyclin E in mediating erlotinib sensitivity or resistance.
Expression plasmids for G1 cyclins were independently transfected into NIH 3T3 cells and effects on erlotinib sensitivity were examined. The expression profiles of G1 cyclins were compared in erlotinib-sensitive and erlotinib-resistant lung cancer cell lines. A549 and H358 cells were treated with erlotinib and changes in cyclin protein expression were assessed. Cyclin D3 immunohistochemical staining was measured in biopsy tissues obtained from patients before and after treatment with erlotinib. Erlotinib-sensitive lung cancer cells were transfected with cyclin D3 and changes in erlotinib sensitivity were examined.
Individual transfection of cyclin D1, cyclin D3, and cyclin E expression plasmids each significantly reduced erlotinib sensitivity in NIH-3T3 cells. The erlotinib-resistant A549 cell line expressed high basal levels of cyclin D3 mRNA and protein. Comparison of tumor biopsies obtained from patients before and after treatment with erlotinib indicated an increase in the percentage of cancer cells expressing cyclin D3 following treatment with erlotinib (P=.02). Transfection of cyclin D3 into an erlotinib-sensitive lung cancer cell line inhibited erlotinib-induced signaling changes and reduced the growth-suppressive effects of erlotinib. | Does high cyclin D3 expression confer erlotinib resistance in aerodigestive tract cancer? | No. High expression of cyclin D3 does not confer resistance to erlotinib in vitro and in vivo. Cyclin D3 immunohistochemical staining does not warrant investigation as a biomarker for predicting erlotinib resistance. | FAIL | pubmedQA | 0 |
26847947 | Few trials have explored the effect of nutrition support on quality of life (QoL). This study examined the effects of oral nutritional supplements (ONS) vs dietary advice on QoL in malnourished care home residents.
104 malnourished, care home residents (medium + high risk), identified using the Malnutrition Universal Screening Tool ('MUST'), (mean age 88.5 ± 7.9y) were randomised to receive either oral nutritional supplements (ONS) (n = 53) or dietary advice (n = 51) for 12 weeks. Dietary intake was measured using 24 h dietary recall, and QoL assessed using EuroQol (EQ-5D), including time trade off (TTO) (range -0.59 to 1) and visual analogue scale (VAS) (score 0 to 100) for self-perceived health.
QoL (adjusted for baseline QOL, malnutrition risk, type of care received (nursing or residential)) was significantly higher in the ONS than the dietary advice group (intention to treat analysis at week 12; n = 104 ). EQ-5D TTO scores (mean ± SE) were 0.50 ± 0.04 vs 0.36 ± 0.05 (P = 0.005), VAS rescaled scores were 0.54 + 0.03 vs 0.046 + 0.03 (P = 0.006) and VAS scores were 61.3 ± 4.5 vs 54.6 ± 6.3 (P = 0.533) for ONS vs dietary advice respectively. Total energy, protein and the majority of micronutrient intakes were significantly greater in the ONS group, with energy intake being 423 kcal greater in the ONS than the dietary advice group at week 12. | Are oral nutritional supplements in a randomised trial more effective than dietary advice at improving quality of life in malnourished care home residents? | No. This study in malnourished care home residents indicates that dietary advice can improve QoL and nutritional intake more effectively than ONS alone. | FAIL | pubmedQA | 0 |
19023201 | We have shown that compared with silybin, 2,3-dehydrosilybin (DHS) exhibits more potent in vitro anticancer activities alone or in combination with tumor necrosis factor (TNF)-alpha. Since TNF-alpha sensitization is related to DNA topoisomerase (topo) inhibition, DHS may be a potent topo inhibitor.
Under significant apoptosis induction by DHS, we measured specific topo I activity in nuclear extracts or purified enzyme.
Treatment of more transformed FIB cells with 30 microM DHS for 24 h caused significant decreases in topo I activity in nuclear extracts while silybin did not have any effects. Less transformed EPI cells were more resistant against DHS-induced topo I inhibition. Inhibitory effects of topo I activity by DHS were also found in cell-free assays using purified topo I, whereas silybin again did not have any effects. | Is 2,3-dehydrosilybin a better DNA topoisomerase I inhibitor than its parental silybin? | No. DHS is not a potent topo I inhibitor and does not sensitize TNF-alpha for enhanced cytotoxicity. | FAIL | pubmedQA | 0 |
17182877 | To evaluate cochlear implant users' understanding of telephone speech.
Telephone speech was simulated by band-limiting broadband speech stimuli. Multitalker vowel, consonant, and sentence recognition was measured for both simulated telephone speech and broadband speech in 10 postlingually deafened adult cochlear implant users. The study was approved by the St. Vincent's Hospital institutional review board, and signed, informed consent was obtained from all participants.
There was no significant difference in vowel recognition scores between broadband and telephone speech. However, mean consonant and sentence recognition scores were significantly poorer with telephone speech. | Do recognition of simulated telephone speech by cochlear implant users? | No. The limited telephone bandwidth did not significantly reduce cochlear implant users' understanding of telephone speech. The effect of band-limited speech was minimal, suggesting that the contribution of high-frequency information to speech recognition was not significant among the cochlear implant users. | FAIL | pubmedQA | 0 |
17137506 | Androgen-independent prostate adenocarcinomas are responsible for about 6% of overall cancer deaths in men.
We used DNA microarrays to identify genes related to the transition between androgen-dependent and androgen-independent stages in the LuCaP 23.1 xenograft model of prostate adenocarcinoma. The expression of the proteins encoded by these genes was then assessed by immunohistochemistry on tissue microarrays (TMA) including human prostate carcinoma samples issued from 85 patients who had undergone radical prostatectomy.
FGFR1, TACC1 and WT1 gene expression levels were associated with the androgen-independent stage in xenografts and human prostate carcinoma samples. MART1 protein expression was correlated with pT2 tumor stages. | Are fGFR1 and WT1 markers of human prostate cancer progression? | No. Our results suggest that each of these four genes may not play a role, or at least do not reflect a stage of prostate carcinoma growth/development/progression. | FAIL | pubmedQA | 0 |
25790249 | The purpose of this project was to implement clinic system changes that support evidence-based guidelines for childhood obesity prevention. Adherence rates for prevention and screening of children in a rural Midwest primary care setting were used to measure the success of the program.
Retrospective chart reviews reflected gaps in current practice and documentation. An evidence-based toolkit for childhood obesity prevention was used to implement clinic system changes for the identified gaps. | Does translation of clinical practice guidelines for childhood obesity prevention in primary care mobilize a rural Midwest community? | No. The quality improvement approach did not prove to be effective in translating knowledge of obesity prevention guidelines into rural clinic practices, with no significant improvements in documentation of prevention measures that may positively impact the childhood obesity epidemic. | FAIL | pubmedQA | 0 |
1797497 | To determine factors influencing recall of examination results after 4 yr.
At two examinations that were 4 yr apart, a diabetic population was asked, "Have you been told that your diabetes has affected the back of your eyes, that is the retina?" Participants were informed by letter whether they had retinopathy. Subjects in this study included younger-onset (n = 311) and older-onset (n = 279) diabetic subjects who had retinopathy at baseline and did not know it.
Forty-two percent of younger-onset and 29% of older-onset subjects recalled at follow-up that they had been told their diabetes had affected their eyes. People in both groups were more likely to recall they had retinopathy if they had more severe retinopathy, had more symptoms of neuropathy and peripheral vascular disease, had seen an ophthalmologist within 2 yr, or monitored their blood glucose more often. In addition, younger-onset diabetic subjects with poorer visual acuity or who were on a combination insulin regimen and older-onset people taking insulin, having more education, or who were younger were more likely to recall they had retinopathy. Factors not associated with recall in either group included sex, duration of diabetes, proteinuria, glycosylated hemoglobin, and family income. | Does factors determining recall of examination result in diabetic population? | Yes. These results underscore the need to develop better methods to deliver health-care information to people who have diabetes, especially those with longer duration of diabetes. | FAIL | pubmedQA | 0 |
18952922 | To study how central visual motion integration and segmentation processes are influenced by the congruence or incongruence of peripheral contextual moving surrounds and to determine their clinical relevance.
Nine subjects participated in experiments 1 and 2 (12-second blocks containing 2-second static fixation and 10-second surface plaid movement) and 15 in experiment 3 (72-second blocks, with 12-second fixation, and 60-second motion). Observers reported whether they perceived nontransparent (corresponding to visual integration of motion cues into one surface) or transparent (segmentation of two surfaces from motion cues) plaid motion within a 5 degrees central circular region. Surround stimuli were 20 degrees transparent or nontransparent moving plaids.
Contextual effects required the presence of both local and global ambiguity. If central local motion became unambiguous, then surrounds became ineffective. Under local and global ambiguity, transparent surrounds invariably induced central congruence while also strongly suppressing incongruent percepts. Nontransparent surrounds produced similar but less consistent congruent bias, especially for longer viewing times. In the latter case, however, suppression of incongruent central interpretations became barely detectable compared to the observed significant facilitation of congruent percepts. | Are peripheral influences on motion integration in foveal vision modulated by central local ambiguity and center-surround congruence? | Yes. Local ambiguity is critical in contextual modulation, and the peripheral enhancement or suppression of central motion integration depends both on transparency bias and center-surround congruence. The importance of local ambiguity in contextual modulation is clinically relevant, because it implies that contextual effects will be weaker in disorders with impaired central vision, such as macular degeneration. Moreover, the increased efficacy of global context under conditions of increased local ambiguity may be useful in future rehabilitation approaches. | FAIL | pubmedQA | 0 |
17900679 | IL-31 is a novel cytokine that, when overexpressed in transgenic mice, induces severe itching dermatitis resembling human eczema.
We aimed to evaluate the importance of polymorphisms in the human IL-31 gene (IL31) in the genetic susceptibility to eczema.
We sequenced the entire IL-31 gene, including the promoter region, and determined the haplotype structure. Single nucleotide polymorphisms tagging the main haplotypes were genotyped in 3 independent European populations comprising 690 affected families. An association analysis of IL31 gene variants with atopic and nonatopic eczema was performed.
We found significant association of a common IL31 haplotype with the nonatopic type of eczema in all 3 study populations (combined P = 4.5 x 10(-5)). Analysis of PBMCs in healthy individuals revealed a strong induction IL31 mRNA expression on stimulation with anti-CD3 and anti-CD28 that was 3.8-fold higher in individuals homozygous for the risk haplotype (AA) in contrast to non-A haplotype carriers, suggesting that altered regulation of IL-31 gene expression is the disease-causing factor. | Is a common haplotype of the IL-31 gene influencing gene expression associated with nonatopic eczema? | No. Our results do not support a role of IL-31 in the pathogenesis of nonatopic eczema. | FAIL | pubmedQA | 0 |
27157121 | We aimed to evaluate malignancy rate and to determine false negativity of fine needle aspiration biopsy (FNAB) in thyroid nodules ≥4.0 cm.
The medical records of patients who underwent thyroidectomy between January 2007 and December 2014 were reviewed. Demographic and clinical data as well as preoperative ultrasonography findings were analyzed. The nodules in these patients were grouped as ≥4.0 cm and <4.0 cm according to ultrasonography measurements. Nodules <4.0 cm were further divided into 1.0-3.9 cm and <1.0 cm. Histopathologically malignant nodules with preoperative benign cytology were defined as having false-negative FNAB.
There were 1,008 nodules that measured ≥4.0 cm, 4,013 nodules that measured 1.0-3.9 cm, and 540 that measured nodules <1.0 cm. Based on histopathologic findings, 8.5%, 10.2%, and 25.6% of nodules ≥4.0 cm, 1.0-3.9 cm, and <1.0 cm were malignant, respectively (P < .001). There was no significant difference between 1.0-3.9-cm and ≥4.0-cm nodules with respect to malignancy (P = .108). False-negativity rates were 4.7% in nodules ≥4.0 cm, 2.2% in nodules measuring 1.0-3.9 cm, and 4.8% in <1.0-cm nodules. Nodules measuring <1.0 cm and ≥4.0 cm had similar false-negativity rates (P = .93), while 1.0-3.9-cm nodules had statistically lower false-negativity rates than those found in the other two groups (P = .03 and P < .001, respectively). | Do malignancy risk and false-negative rate of fine needle aspiration cytology in thyroid nodules ≥4.0 cm? | Yes. Of the nodules that were operatively excised, nodules ≥4.0 cm had a higher risk of malignancy compared to nodules 1.0-3.9 cm. The rate of false-negative FNAB in nodules ≥4.0 cm was twice as high as in nodules 1.0-3.9 cm; however, we do not think it is high enough to recommend a routine operation when cytology results are benign. | FAIL | pubmedQA | 0 |
20502455 | Lung cancer is known as the top cancer killer in most developed countries. However, there is currently no promising diagnostic or prognostic biomarker for lung cancer. This study aims to discover non-invasive differential markers in the serum of lung cancer patients, to determine the protein identity of the candidate biomarker(s), and to investigate any clinical implication of the biomarker(s) concerned.
Blood specimens were collected from 154 pre-operative patients with lung cancer and 35 healthy blood donors with no evidence of lung cancer. Fractionated serum samples were processed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (MS). Candidate biomarker was identified using sodium dodecyl sulphate polyacrylamide gel electrophoresis and tryptic digestion followed by tandem MS fragmentation analysis, which was subsequently validated with immunoassay.
A differential protein with m/z 11.6 kDa was detected and identified as an isoform of human serum amyloid A (SAA). It was significantly increased by 1822% in lung cancer patients when compared with the healthy controls, which gave an area under the receiver operator characteristic curve of 0.88. In addition, the protein was also significantly elevated by 77% in lung cancer patients with survival <5 years when compared with patients with survival > or =5 years. | Is serum amyloid A elevated in the serum of lung cancer patients with poor prognosis? | No. There are several functions of the SAA protein, described in the context of inflammation, that are compatible with the mechanism of tumour invasion and metastasis. Our study not only detected decreased SAA level in the serum of lung cancer patients but also identified that decreased SAA level may be a non-invasive biomarker useful for the prediction of lung cancer prognosis. | FAIL | pubmedQA | 0 |
10364743 | In the past, the rabbit model of repeated airway lavage has been extensively used to induce a decrease in lung volume accompanied by impairment in lung mechanics and gas exchange.
The rationale of our study was to investigate the influence of different end-expiratory pressure (EEP) levels (0.4-4.2 cm H2O) on changes in functional residual capacity (FRC) and the efficacy of lavages administered.
Forty-five rabbits were subjected to 2-8 lavages with 20 ml/kg warm normal saline until arterial/alveolar oxygen tension (a/A ratio) had decreased to </=0. 12.
FRC and dynamic compliance of the respiratory system (Crs) decreased significantly (both p < 0.001; from 19.1 +/- 4.2 to 10.5 +/- 5.6 ml/kg and from 1.17 +/- 0.27 to 0.47 +/- 0.10 ml/cm H2O, respectively, means +/- SD). The decrease in FRC was significantly influenced by EEP (-28.6 +/- 15.8% at EEP = 1 cm H2O vs. -58.7 +/- 12.9% at EEP = 3 cm H2O, p < 0.0001). There was a significant correlation between the number of lavages and EEP (p < 0.01), indicating that successive lavages at higher EEP became ineffective in lowering FRC compared to those at lower EEP. | Does decrease in lung volume depend on end-expiratory pressure in a rabbit model of airway lavage? | No. We conclude that the EEP levels used in this model are not of critical importance for the prediction of a decrease in lung volume (FRC) and the efficacy of lavages. | FAIL | pubmedQA | 0 |
24824797 | MicroRNAs (miRNAs) are small non-coding RNAs that regulate complex transcriptional networks underpin immune responses. However, little is known about the specific miRNA networks that control differentiation of specific leukocyte subsets. In this study, we profiled miRNA expression during differentiation of eosinophils from bone marrow (BM) progenitors (bmEos), and correlated expression with potential mRNA targets involved in crucial regulatory functions. Profiling was performed on whole BM cultures to document the dynamic changes in miRNA expression in the BM microenvironment over the differentiation period. miRNA for network analysis were identified in BM cultures enriched in differentiating eosinophils, and chosen for their potential ability to target mRNA of factors that are known to play critical roles in eosinophil differentiation pathways or cell identify.
We identified 68 miRNAs with expression patterns that were up- or down- regulated 5-fold or more during bmEos differentiation. By employing TargetScan and MeSH databases, we identified 348 transcripts involved in 30 canonical pathways as potentially regulated by these miRNAs. Furthermore, by applying miRanda and Ingenuity Pathways Analysis (IPA), we identified 13 specific miRNAs that are temporally associated with the expression of IL-5Rα and CCR3 and 14 miRNAs associated with the transcription factors GATA-1/2, PU.1 and C/EBPε. We have also identified 17 miRNAs that may regulate the expression of TLRs 4 and 13 during eosinophil differentiation, although we could identify no miRNAs targeting the prominent secretory effector, eosinophil major basic protein. | Does expression profiling of differentiating eosinophils in bone marrow cultures predict functional links between microRNAs and their target mRNAs? | Yes. This is the first study to map changes in miRNA expression in whole BM cultures during the differentiation of eosinophils, and to predict functional links between miRNAs and their target mRNAs for the regulation of eosinophilopoiesis. Our findings provide an important resource that will promote the platform for further understanding of the role of these non-coding RNAs in the regulation of eosinophil differentiation and function. We identified 17 miRNAs that may regulate the expression of eosinophil major basic protein during eosinophil differentiation. | FAIL | pubmedQA | 0 |
20607217 | In this longitudinal study of 4,160 postmenopausal women (3,947 without and 213 with self-reported diabetes), smoking was strongly related to fracture risk in those with diabetes.
Smoking is related to low bone mass and increased risk of fracture risk in postmenopausal women of the general population. The aim of the present longitudinal population-based study was to examine the effect of smoking on the risk of non-vertebral fractures in women ≥ 55 years of age, with specific focus on its relationship with diabetes.
A total of 4,160 women (3,947 without and 213 with self-reported diabetes) from the municipality of Tromsø, Norway, were followed for a mean of 7.6 years. Measurements of height and weight and questionnaire information concerning smoking and alcohol consumption habits, physical activity, prevalent diseases, and use of medication were collected before the start of follow-up. Non-vertebral fractures were registered during follow-up.
A total of 1,015 without and 66 with diabetes sustained a new non-vertebral fracture. Smoking status (never, past, and current) was significantly associated with an increased risk of fracture both in women with and without diabetes (p values for trend 0.02 and <0.001, respectively, after adjustments for age), but in women without diabetes, the relationship was no longer significant after multiple adjustments. There was a strong interaction between smoking status and diabetes on fracture risk (p= 0.004). Women with diabetes who were current smokers had a 3.47 (95% CI 1.82-6.62) higher risk of non-vertebral fractures than diabetic women who were never smokers (p value for linear trend = 0.001, after multiple adjustments). | Is smoking a strong risk factor for non-vertebral fractures in women with diabetes : the Tromsø Study? | No. We conclude that smoking is not related to fracture risk in postmenopausal women with self-reported diabetes. | FAIL | pubmedQA | 0 |
20831751 | KCNJ10 encodes subunits of inward rectifying potassium (Kir) channel Kir4.1 found predominantly in glial cells within the brain. Genetic inactivation of these channels in glia impairs extracellular K(+) and glutamate clearance and produces a seizure phenotype. In both mice and humans, polymorphisms and mutations in the KCNJ10 gene have been associated with seizure susceptibility. The purpose of the present study was to determine whether there are differences in Kir channel activity and potassium- and glutamate-buffering capabilities between astrocytes from seizure resistant C57BL/6 (B6) and seizure susceptible DBA/2 (D2) mice that are consistent with an altered K(+) channel activity as a result of genetic polymorphism of KCNJ10.
Using cultured astrocytes and hippocampal brain slices together with whole-cell patch-clamp, we determined the electrophysiologic properties, particularly K(+) conductances, of B6 and D2 mouse astrocytes. Using a colorimetric assay, we determined glutamate clearance capacity by B6 and D2 astrocytes.
Barium-sensitive Kir currents elicited from B6 astrocytes are substantially larger than those elicited from D2 astrocytes. In addition, potassium and glutamate buffering by D2 cortical astrocytes is impaired, relative to buffering by B6 astrocytes. | Are potassium channel activity and glutamate uptake impaired in astrocytes of seizure-susceptible DBA/2 mice? | Yes. In summary, the activity of Kir4.1 channels is similar between seizure-susceptible D2 and seizure-resistant B6 mice. Reduced activity of Kir4.1 channels in astrocytes of D2 mice is associated with deficits in potassium and glutamate buffering. These deficits may, in part, explain the relatively low seizure threshold of D2 mice. | FAIL | pubmedQA | 0 |
16492437 | To evaluate the impact of duration of untreated symptoms in children with juvenile dermatomyositis (JDM) on clinical and laboratory status at diagnosis.
We examined physical and laboratory data from the first physician visit for 166 untreated children with JDM. Disease activity scores (DASs) assessed skin and muscle involvement. Height and weight were compared with the National Health and Nutrition Examination Survey III dataset. Duration of untreated illness was designated as the time from first sign of rash or weakness to diagnostic visit.
Boys and girls with untreated JDM were shorter and lighter than national norms (P > .0005 for both), and nonwhite children were weaker than white children (P > .0005). Older children had more dysphagia (P = .017) and arthritis (P > .001). Duration of untreated JDM was negatively associated with DAS weakness (P > .0005), unrelated to DAS skin, and positively associated with pathological calcifications (P = .006). With untreated disease > or = 4.7 months, serum levels of 4 muscle enzymes (aldolase, lactic dehydrogenase, creatine kinase, serum glutamic-oxaloacetic transaminase/aspartate aminotransferase) tended toward normal (P > .01 for each). | Is duration of illness an important variable for untreated children with juvenile dermatomyositis? | No. Duration of untreated symptoms is not an important variable and should not be included in decisions concerning both diagnostic criteria and intensity of therapy for children with JDM. | FAIL | pubmedQA | 0 |
12198220 | Hypertension (HT) is common in patients on continuous ambulatory peritoneal dialysis (CAPD) and is responsible for increased cardiovascular morbidity and mortality. In this study, we aimed to determine the prevalence of 'uncontrolled HT' during background therapy in CAPD patients by using office measurements and ambulatory blood pressure monitoring (ABPM). We further determined whether intravascular volume status, assessed by inferior vena cava diameter (IVCD) index, contributes to higher blood pressure (BP) and increased left ventricular mass index (LVMI).
Seventy-four CAPD patients were included in the final analysis. All patients underwent echocardiographic examination and received ABPM. Patients undergoing CAPD were categorized into two groups: 'uncontrolled HT' (Group A) and 'normotensive and controlled HT' (Group B). Intravascular volume status was determined using the IVCD index and collapsibility index (CI) on the same day as ABPM.
The prevalence of HT was 84% when using office measurements and 82% when using daytime ABPM. Daytime BP was 147/92 mm Hg by office measurements and 145/91 mm Hg by ABPM (P>0.05). The prevalence of 'uncontrolled HT' measured by ABPM was 73% (n=54). Patients with uncontrolled HT (Group A) were taking more antihypertensive medications than patients with 'normotension and controlled HT' (Group B, n=20; 1.0+/-0.8 vs 0.5+/-0.7, P=0.008). The IVCD index was higher in Group A than in Group B (9.2+/-2.1 vs 7.7+/-1.9 mm/m(2), P=0.007). There was no correlation between IVCD index and office BP, ABPM measurements or LVMI. The LVMI was also higher in Group A than in Group B (145+/-39 vs 118+/-34 g/m(2), P<0.01). Stepwise multiple regression analysis revealed that 24 h diastolic BP and haemoglobin were independent determinants of LVMI. | Does uncontrolled hypertension due to volume overload contribute to higher left ventricular mass index in CAPD patients? | No. Uncontrolled HT on background therapy is not prevalent among volume overloaded CAPD patients. Further long-term prospective studies examining effects of salt restriction and ultrafiltration on BP control and left ventricle wall thickness are warranted. | FAIL | pubmedQA | 0 |
11917178 | To determine the effect of topical therapy with several corticosteroids with limited potency on viral clearance in the adenovirus type 5 (Ad5) rabbit ocular model.
Sixty rabbits were inoculated in both eyes with Ad5. On the first day, the rabbits were equally divided into four topical treatment groups: 0.12% prednisolone acetate (PA), 0.1% fluorometholone (FM), 1% rimexolone (RMX), and control. Treatment was administered four times daily, in both eyes, for 3 days. All eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, 14, 16, 18, and 21.
Compared with the control group, treatment with PA, FM, and RMX significantly increased the number of Ad5 positive eye cultures from days 7-21. Fluorometholone and RMX prolonged the duration of Ad5 shedding, and FM increased the mean combined Ad5 titer from days 1-5 and 7-21. | Do topical corticosteroids of limited potency promote adenovirus replication in the Ad5/NZW rabbit ocular model? | No. Treatment of an experimental ocular adenovirus infection with PA, FM, and RMX for 3 days did not significantly enhance adenovirus replication compared with the control group. Short-term treatment of EKC with several commercially available topical corticosteroids with limited potency may offer symptomatic relief without delaying viral clearance or promoting office and community epidemics. | FAIL | pubmedQA | 0 |
27541280 | No study so far has evaluated the relationship between insulin secretion (ISEC) and insulin sensitivity (ISEN) in pediatric nonalcoholic fatty liver disease (NAFLD). We evaluated the relationship between ISEC and ISEN in young obese patients with and without NAFLD.
We matched 401 NAFLD
The NAFLD·ISEN interaction was not significant in any regression model, implying commons slopes for NAFLD | Is nonalcoholic Fatty Liver Associated with the Relationship between Insulin Secretion and Insulin Sensitivity in Obese Children : Matched Case-Control Study? | Yes. NAFLD is associated with the relationship between ISEN and ISEC in young obese children strictly matched for sex, age, pubertal status, and BMI. | FAIL | pubmedQA | 0 |
21548917 | Subclinical inflammation is a common phenomenon in patients on either continuous ambulatory peritoneal dialysis (CAPD) or maintenance hemodialysis (MHD). We hypothesized that vitamin C had anti-inflammation effect because of its electron offering ability. The current study was designed to test the relationship of plasma vitamin C level and some inflammatory markers.
In this cross-sectional study, 284 dialysis patients were recruited, including 117 MHD and 167 CAPD patients. The demographics were recorded. Plasma vitamin C was measured by high-performance liquid chromatography. And we also measured body mass index (BMI, calculated as weight/height(2)), Kt/V, serum albumin, serum prealbumin, high-sensitivity C-reactive protein (hsCRP), ferritin, hemoglobin. The relationships between vitamin C and albumin, pre-albumin and hsCRP levels were tested by Spearman correlation analysis and multiple regression analysis. Patients were classified into three subgroups by vitamin C level according to previous recommendation 12 in MHD and CAPD patients respectively: group A: < 2 ug/ml (< 11.4 umol/l, deficiency), group B: 2-4 ug/ml (11.4-22.8 umol/l, insufficiency) and group C: > 4 ug/ml (> 22.8 umol/l, normal and above).
Patients showed a widely distribution of plasma vitamin C levels in the total 284 dialysis patients. Vitamin C deficiency (< 2 ug/ml) was present in 95(33.45%) and insufficiency (2-4 ug/ml) in 88(30.99%). 73(25.70%) patients had plasma vitamin C levels within normal range (4-14 ug/ml) and 28(9.86%) at higher than normal levels (> 14 ug/ml). The similar proportion of different vitamin C levels was found in both MHD and CAPD groups. Plasma vitamin C level was inversely associated with hsCRP concentration (Spearman r = -0.201, P = 0.001) and positively associated with prealbumin (Spearman r = 0.268, P < 0.001), albumin levels (Spearman r = 0.161, P = 0.007). In multiple linear regression analysis, plasma vitamin C level was inversely associated with log(10)hsCRP (P = 0.048) and positively with prealbumin levels (P = 0.002) adjusted for gender, age, diabetes, modality of dialysis and some other confounding effects. | Is low levels of vitamin C in dialysis patients associated with decreased prealbumin and increased C-reactive protein? | Yes. The investigation indicates that vitamin C deficiency is common in both MHD patients and CAPD patients. Plasma vitamin C level is negatively associated with serum prealbumin level and positively associated with hsCRP level in both groups. Vitamin C deficiency may play an important role in the increased inflammatory status in dialysis patients. Further studies are needed to determine whether inflammatory status in dialysis patients can be improved by using vitamin C supplements. | FAIL | pubmedQA | 0 |
21378253 | Diet may play an important role in the management of patients with short bowel syndrome who have colon in continuity. However, macronutrient absorption has not been well characterized, and the most appropriate dietary constituents have not been well defined.
To define carbohydrate absorption characteristics in patients with short bowel syndrome and determine the potential role of pectin as a dietary substrate.
The authors studied the effect of a custom pectin-based supplement in 6 subjects (3 male/3 female) aged 29-67 years with jejunocolonic anastomosis, 4 of whom required long-term parental nutrition. Small intestinal absorption capacity, macronutrient and fluid balance, gastrointestinal transit time, and energy consumption were measured.
Data showed that 53% nitrogen, 50% fat, and 32% total energy were malabsorbed. In contrast, the majority (92%) of total carbohydrate was utilized. Fecal short-chain fatty acids (SCFAs) were increased, an indication of increased fermentation. Although only 4% of starch was recovered in stool, it is indicative of considerable starch malabsorption, thus providing the main carbohydrate substrate, for colonic bacterial fermentation. In contrast, nonstarch polysaccharide was a relatively minor fermentation substrate with only 49% utilized. Eighty percent of the pectin was fermented. Supplementation was associated with increased total SCFAs, acetate, and propionate excretion. There was a trend observed toward greater fluid absorption (-5.9% ± 54.4% to 26.9% ± 25.2%) following pectin supplementation. Nonsignificant increases in gastric emptying time and orocolonic transit time were observed. | Is macronutrient absorption characteristics in humans with short bowel syndrome and jejunocolonic anastomosis : starch the most important carbohydrate substrate , although pectin supplementation may modestly enhance short chain fatty acid production and fluid absorption? | Yes. Despite malabsorption, starch is the primary carbohydrate substrate for colonic bacterial fermentation in patients with short bowel syndrome, although insoluble fiber intake also enhances colonic SCFA production. | FAIL | pubmedQA | 0 |
21600601 | We investigated the importance of EPLIN, a cytoskeletal associated protein implicated in cancer, in clinical prostate cancer and its role in the PC-3 prostate cancer cell line (ATCC™).
Full-length human EPLIN cDNA was cloned into a pEF6 expression vector and used to transfect the PC-3 human prostate cancer cell line. Cells over expressing EPLIN were termed PC-3(EPLIN EXP) while wild-type and empty pEF6 vector control cells were designated PC-3(WT) and PC-3(pEF6), respectively. The in vitro and in vivo impact of EPLIN on PC-3 cells was examined using a number of model assays.
EPLIN over expression in PC-3 cells resulted in a decrease in the growth rate of this cell line (mean ± SD 0.6 ± 0.17 for PC-3(pEF6) cells vs 0.33 ± 0.01 for PC-3(EPLIN EXP) cells, p <0.01). PC-3(EPLIN EXP) cells were significantly less able to adhere to extracellular matrix than control cells (mean 61.0 ± 12.4 vs 102.8 ± 20.7, p = 0.028). Immunofluorescence staining showed an increased staining profile for paxillin in PC-3(EPLIN EXP) cells compared to wild-type cells. | Is ePLIN a negative regulator of prostate cancer growth and invasion? | No. EPLIN over expression in the PC-3 cell line resulted in increased in vivo and in vitro growth potential together with increased cell invasiveness and ability to adhere to extracellular matrix, and enhanced paxillin staining. This further highlights the importance of EPLIN in regulating prostate cancer cell growth and aggressiveness, and suggests a possible connection between EPLIN and paxillin. | FAIL | pubmedQA | 0 |
17714825 | Liver transplantation (LTX) is the only curative treatment for end-stage liver disease caused by hepatitis C (HCV). Hepatocellular carcinoma (HCC) is common in patients with HCV cirrhosis.
Two hundred and eighty-two HCV patients listed for LTX in the Nordic countries in a 17-year period were included. For comparison a group of patients with non-viral chronic liver disease (n=1552) was used.
Two hundred and fifty-three (90%) patients received a first liver allograft. HCC was found in 38% of the explanted livers. Survival at 1, 3 and 5years was 82%, 69% and 61% vs. 85%, 80% and 76% for the comparison group (p<0.0001), this survival difference was also evident when excluding patients with HCC (p=0.007). HCV patients with HCC had 1, 3 and 5year survival of 73%, 52% and 46% compared with 88%, 80% and 71% for the HCV patients without HCC (p=0.0005). In an intention-to-treat analysis (from time of acceptance to the waiting list) HCV was also associated with an impaired survival. | Does hepatitis C impair survival following liver transplantation irrespective of concomitant hepatocellular carcinoma? | No. HCV cirrhosis, which is now also an important indication for LTX in the Nordic countries, does not significantly impair survival following LTX. Concomitant HCC and donor age are the two most important factors contributing to an impaired survival. | FAIL | pubmedQA | 0 |
24969960 | After years of disuse of chloroquine (CQ) as first-line anti-malarial drug in Ghana, reports from molecular studies conducted in parts of the country indicate varying prevalence of T76 mutation in the pfcrt gene. This situation has several health implications, one being that mutations that confer resistance to CQ have been reported to show substantial cross-resistance to other anti-malarial drugs. It is important to identify some of the factors contributing to the continuous presence of CQ resistance markers in the country. This study determined the prevalence of T76 mutation in pfcrt gene of Plasmodium falciparum isolates collected from selected areas of the Central region of Ghana and correlated with the level of CQ use in these areas.
Plasmodium falciparum DNA was extracted from collected blood-blot filter paper samples in the study sites. The prevalence of T76 point mutation in pfcrt gene was assessed using nested PCR followed by RFLP. CQ from pharmacy and chemical shops was obtained using mystery buying method. The extent of CQ use by the participants was determined by measuring the level of the drug in their urine samples using the Saker-Solomon method.
Of the 214 P. falciparum isolates analysed, 71.9% were found to have T76 mutation of pfcrt gene. The study revealed that 14.49% of community pharmacies and chemical shops had stocks of CQ for sale while 16.9% of the participants had CQ in their urine samples. There is five times more risks of becoming infected with CQ resistant strain for staying in an area where CQ is stocked for sale [RR = 0.20, p < 0.0001] and thirteen times more risks of having CQ-resistant mutant from those who still use CQ than non-users [OR = 0.08, p < 0.0001]. | Is use of proscribed chloroquine associated with an increased risk of pfcrt T76 mutation in some parts of Ghana? | No. This study has shown that there is no significant association between the prevalence of T76 mutations of P. falciparum and the level of CQ stocking and usage within study area. | FAIL | pubmedQA | 0 |
11330538 | Graft pancreatitis is thought to be induced by ischemia/reperfusion. Animal experiments have suggested that an impaired microcirculation is crucial in this process. We have therefore studied the relevance of microcirculation in clinical pancreas transplantation.
In 17 patients undergoing pancreas transplantation, tissue pO2 was monitored continuously by an electrode implanted into the pancreatic tail. A catheter was inserted in the distal part of the splenic vein of the pancreas graft. After reperfusion blood samples were taken from this catheter and blood flow was measured by the venous outflow method. The degree of graft pancreatitis was assessed by peak-C-reactive protein (CRP) defined as highest CRP within 3 days after transplantation.
Tissue pO2 increased within 5 min after reperfusion. Thereafter, in most patients a transient decrease was noted, indicating impairment of nutritive perfusion. During this period there was an increasing negative correlation between peak-CRP and tissue pO2 which was highly significant at 60 min after reperfusion (r=-0.70, P<0.002). Also donor age correlated significantly with peak-CRP (r=0.64, P<0.005) and to a somewhat lesser extend with tissue pO2 60 min after reperfusion (r= -0.55, P<0.03). | Does impairment of microcirculation in the early reperfusion period predict the degree of graft pancreatitis in clinical pancreas transplantation? | No. These data show that the degree of organ damage in clinical pancreas transplantation is not related to an impairment of microcirculation in the early reperfusion period. These data also support the idea that grafts from older donors have a lower probability to develop graft pancreatitis and that this might be due to a decreased incidence of microcirculatory disturbances in these organs. | FAIL | pubmedQA | 0 |
26991240 | Essentials Information about the formation of the demarcation membrane system (DMS) is still lacking. We investigated the role of the cytoskeleton in DMS structuration in megakaryocytes. Cdc42/Pak-dependent F-actin remodeling regulates DMS organization for proper megakaryopoiesis. These data highlight the mandatory role of F-actin in platelet biogenesis. | Do cdc42-dependent F-actin dynamics drive structuration of the demarcation membrane system in megakaryocytes? | No. Background Blood platelet biogenesis results from the maturation of megakaryocytes (MKs), which involves the development of a complex demarcation membrane system (DMS). Therefore, MK differentiation is an attractive model for studying membrane remodeling. Objectives We sought to investigate the mechanism of DMS structuration in relationship to the cytoskeleton. Results Using three-dimensional (3D) confocal imaging, we have identified consecutive stages of DMS organization that rely on microtubule dynamics to polarize membranes and nuclei territories. Interestingly, F-actin is not involved in this process. We found that the mechanism underlying microtubule-dependent DMS formation required the activation of the guanosine triphosphate hydrolase Cdc42 and its p21-activated kinase effectors (Pak1/2/3). Förster resonance energy transfer demonstrated that active Cdc42 was associated with endomembrane dynamics throughout terminal maturation. Inhibition of Cdc42 or Pak1/2/3 severely destructured the DMS and blocked proplatelet formation. Even though this process does not require containment within the hematopoietic niche, because DMS structuration was observed upon thrombopoietin-treatment in suspension, integrin outside-in signaling was required for Pak activation and probably resulted from secretion of extracellular matrix by MKs. Conclusions These data indicate a functional link, mandatory for MK differentiation, between microtubule dynamics, regulated by Cdc42/Pak1/2/3, and DMS maturation. | FAIL | pubmedQA | 0 |
26611144 | Neurological impairments following stroke impact the ability of individuals to perform daily activities, although the relative impact of individual impairments is not always clear. Recovery of sensorimotor function following stroke can vary widely, from complete recovery to modest or minimal improvements, across individuals. An important question is whether one can predict the amount of recovery based on initial examination of the individual. Robotic technologies are now being used to quantify a range of behavioral capabilities of individuals post-stroke, providing a rich set of biomarkers of sensory and motor dysfunction. The objective of the present study is to use mathematical models to identify which biomarkers best predict the ability of subjects with stroke to perform daily activities before and after rehabilitation.
The Functional Independence Measure (FIM) was quantified approximately 2 weeks and three months post-stroke in 61 ischemic and 24 hemorrhagic subjects with stroke. At 2 weeks post-stroke, subjects also completed clinical assessments and robotic assessments of sensory and motor function. A computational search algorithm, known as Fast Orthogonal Search, was used to identify the robotic and clinical biomarkers that best estimated Functional Independence Measures.
Clinical and robot-based biomarkers were statistically similar at predicting FIM scores at 2 weeks (r = 0.817 vs. 0.774, respectively) and 3 months (r = 0.643 vs. 0.685, respectively). Importantly, robot-based biomarkers highlighted that parameters related to proprioception were influential for predicting FIM scores at 2 weeks, whereas biomarkers related to bimanual motor function were influential for predicting FIM scores at 3 months. | Does robot-based assessment of motor and proprioceptive function identify biomarkers for prediction of functional independence measures? | No. The present study does not provide a proof of principle on the use of robot-based biomarkers of sensory and motor dysfunction to estimate present and future FIM scores. The addition of other behavioral tasks will likely not increase the accuracy of these predictions, and potentially help guide rehabilitation strategies to maximize functional recovery. | FAIL | pubmedQA | 0 |
24855377 | Macrophage chemotaxis followed by blood-brain barrier transendothelial migration is believed to be associated with inflammation in the central nervous system. Antineuroinflammatory strategies have identified the dietary-derived epigallocatechin-3-gallate (EGCG) as an efficient agent to prevent neuroinflammation-associated neurodegenerative diseases by targeting proinflammatory mediator signaling.
Given that high levels of sphingosine kinase and its product, sphingosine-1-phosphate (S1P), are present in brain tumors, we used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunoblotting to test whether EGCG may impact on S1P receptor gene expression and prevent S1P response in undifferentiated and in terminally differentiated macrophages.
Promyelomonocytic human leukemia (HL)-60 cells were differentiated into macrophages, and S1P triggered phosphorylation in extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 mitogen-activated protein kinase (MAPK) intracellular signaling, as shown by Western blot analysis. Pretreatment of cells with EGCG prior to differentiation inhibited the response to S1P in all three pathways, while EGCG abrogated P38 MAPK phosphorylation when present only during differentiation. Terminally-differentiated macrophages were, however, insensitive to EGCG treatment. Using qRT-PCR, gene expression of the S1P receptors S1P1, S1P2, and S1P5 was predominantly induced in terminally-differentiated macrophages, while the S1P2 was decreased by EGCG treatment. | Does transcriptional targeting of sphingosine-1-phosphate receptor S1P2 by epigallocatechin-3-gallate prevent sphingosine-1-phosphate-mediated signaling in macrophage-differentiated HL-60 promyelomonocytic leukemia cells? | Yes. Our data suggest that diet-derived EGCG achieves efficient effects as a preventive agent, targeting signaling pathways after cell terminal differentiation. Such properties could impact on cell chemotaxis through the blood-brain barrier and prevent cancer-related neuroinflammation. | FAIL | pubmedQA | 0 |
8566603 | Nitric oxide is associated with hyperdynamic circulation and development of collaterals in portal hypertension. The aim of this study was to investigate whether NO synthase is activated in the portal-hypertensive esophagus.
In esophageal specimens after portal ligation or sham operation, the expression of constitutive and inducible NO synthase messenger RNA was assessed by reverse transcription-polymerase chain reactions. NO synthase protein at 14 postoperative days was visualized with immunofluorescence staining with specific antibodies against constitutive and inducible NO synthase.
The esophageal muscularis mucosae and epithelium overlying large submucosal veins in portal-hypertensive rats were significantly thinner than in controls (muscularis mucosae, 24.3% thinner, P < 0.01; epithelium, 23.0% thinner, P < 0.05). Expression of NO synthase proteins in endothelia of submucosal veins was significantly higher in portal-hypertensive rats than in controls (constitutive NO synthase, 17.6%; inducible NO synthase, 18.0% increased over controls, respectively; P < 0.01). Expression of both constitutive and inducible NO synthase messenger RNA in portal-hypertensive rats was significantly increased (constitutive NO synthase, 10-fold; inducible NO synthase, 20-fold at 14 days vs. controls; P < 0.01). | Does portal hypertension activate the nitric oxide synthase genes in the esophageal mucosa of rats? | Yes. Portal hypertension triggers overexpression of NO synthase messenger RNA and protein in the rat esophageal submucosa. This phenomenon, combined with the thinness of muscularis mucosae and epithelium, may facilitate development and rupture of esophageal varices. | FAIL | pubmedQA | 0 |
17007862 | We tested the ability of optical coherence tomography (OCT) to identify very early stages of atherosclerosis in vivo.
Twelve New Zealand white male rabbits (weight 3.5-4.0 kg) underwent perivascular electrical injury of the common carotid arteries, and were then fed a cholesterol-rich diet. At 43+/-16 (range 27-63) days after injury, arteries were imaged by OCT, then rabbits were euthanized and vessels processed for histology.
A total of 14 carotid arteries were imaged by OCT and histology; 22 atherosclerotic lesions were identified, 16 (73%) occurring at the site of the electrical injury. At histology, 4 lesions were defined as Stary type I (isolated macrophages), 8 as type II (intracellular lipid accumulations), and 10 as type III (small extracellular lipid pools). No advanced (> or =type IV) lesions were documented. OCT failed to detect any type I lesions, but correctly defined a minority (2/8, 25%) of type II lesions and the majority (8/10, 80%) of type III lesions. For type III lesions, sensitivity, specificity and diagnostic accuracy of OCT were 80%, 95%, and 95%, respectively. | Does optical coherence tomography accurately identify intermediate atherosclerotic lesions -- an in vivo evaluation in the rabbit carotid artery? | Yes. OCT can accurately detect intermediate (type-III) atherosclerotic lesions in vivo, and it also successfully identifies earlier stages of atherosclerosis. | FAIL | pubmedQA | 0 |
15090794 | Heterosexual transmission of HIV-1 is the major route of infection worldwide. HLA-G molecules are involved in the inhibition of cell-mediated immune responses and could permit or even promote the propagation of infection in the female reproductive tract.
To examine whether HLA-G genetic variants are associated with the risk of heterosexual HIV-1 infection.
HLA-G polymorphism in DNA samples from 431 (228 HIV-positive and 203 HIV-negative) Zimbabwean women was determined by amplified-restriction fragment length polymorphism and DNA sequencing analyses.
Six HLA-G alleles were identified in the study population. HLA-G*0105N, which does not encode functional HLA-G1 proteins, was significantly associated with protection from HIV-1 infection [odds ratio (OR), 0.51; 95% confidence interval (CI), 0.31-0.85; P = 0.0083). The HLA-G*010108 allele was associated with a 2.5-fold increased risk of HIV-1 infection (OR, 2.47; 95% CI, 1.32-4.64; P = 0.0038). In addition, two HLA-G*010108-containing genotypes were associated with elevated risk of HIV-1 infection: HLA-G*010108/010401 (OR, 23.6; 95% CI, 1.39-401.7; P = 0.0009) and G*010101/010108 (OR, 5.6; 95% CI, 1.24-25.3; P = 0.012). | Are functionally active HLA-G polymorphisms associated with the risk of heterosexual HIV-1 infection in African women? | No. This study demonstrates that functionally active HLA-G polymorphisms are not associated with altered risk of HIV-1 infection in African women. This provides evidence to support the hypothesis that modulation of HLA-G expression by HIV-1 does not contribute to the risk of infection. Targeted interventions to reduce or block HLA-G expression in genital tissues would not lead to novel strategies for the prevention of heterosexual HIV-1 transmission. | FAIL | pubmedQA | 0 |
27631774 | To evaluate the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values, and the presence of invasive carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN).
NLR and (PLR) are inflammatory markers that have been associated with overall survival in patients with invasive malignancies, including pancreatic cancer.
We retrospectively reviewed 272 patients who underwent surgical resection for histologically confirmed IPMN from January 1997 to July 2015. NLR and PLR were calculated and coevaluated with additional demographic, clinical, and imaging data for possible correlation with IPMN-associated carcinoma in the form of a predictive nomogram.
NLR and PLR were significantly elevated in patients with IPMN-associated invasive carcinoma (P < 0.001). In the multivariate analysis, NLR value higher than 4 (P < 0.001), IPMN cyst of size more than 3 cm (P < 0.001), presence of enhanced solid component (P = 0.014), main pancreatic duct dilatation of more than 5 mm (P < 0.001), and jaundice (P < 0.001) were statistically significant variables. The developed statistical model has a c-index of 0.895. Implementation of the statistically significant variables in a predictive nomogram provided a reliable point system for estimating the presence of IPMN-associated invasive carcinoma. | Is neutrophil-to-lymphocyte Ratio a Predictive Marker for Invasive Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas? | No. NLR is not an independent predictive marker for the presence of IPMN-associated invasive carcinoma. Further prospective studies are needed to assess the predictive ability of NLR and how it can be applied in the clinical setting. | FAIL | pubmedQA | 0 |
15569418 | To investigate the mechanism of peplomycin (PEP)-induced apoptosis in liver carcinoma cell line (Bel-7402).
Growth inhibition by PEP was analyzed using 3- 4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptotic cells were detected using Hoechest 33258 staining, and confirmed by flow cytometric analysis and DNA fragmentation analysis. The expression of cyclin A and B1 were determined by flow cytometry and Western blot. Annexin V assay was measured by flow cytometric analysis.
PEP induced apoptosis and then inhibited cell proliferation in liver carcinoma cell line Bel-7402. Cells treated with PEP 50 mumol/L for 15 h were arrested in G2-phase with dramatical expression of cyclin A and a little change in cyclin B1. Almost all the apoptosis occurred in cells undergoing the G1-phase after treatment for 24 h. | Does peplomycin induce G1-phase specific apoptosis in liver carcinoma cell line Bel-7402 involving G2-phase arrest? | Yes. Peplomycin induced G2-phase specific apoptosis in Bel-7402 involving G1-phase arrest. | FAIL | pubmedQA | 0 |
17724290 | Treatment with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors ("statins") has been associated in some epidemiologic studies with reduced risk of Alzheimer disease (AD). However, direct evidence of statin effects on neuropathologic markers of AD is lacking. We investigated whether antecedent statin exposure is associated with neuritic plaque (NP) or neurofibrillary tangle (NFT) burden in a population-based sample of human subjects.
Brain autopsies were performed on 110 subjects, ages 65 to 79 years, who were cognitively normal at enrollment into the Adult Changes in Thought Study. Neuropathologic findings were compared between statin users with > or =3 prescriptions of > or =15 pills of simvastatin, pravastatin, lovastatin, or atorvastatin vs nonusers, based on pharmacy dispensing records.
After controlling for age at death, gender, cognitive function at study entry, brain weight, and presence of cerebral microvascular lesions, the odds ratio (OR) for each unit increase in Braak NFT stage in statin users vs nonusers was 0.44 (95% CI: 0.20 to 0.95). The OR for each unit increase in Consortium to Establish a Registry for Alzheimer's Disease (CERAD) staging of NPs did not deviate significantly from unity (OR 0.69; 95% CI: 0.32 to 1.52). However, the risk for typical AD pathology (Braak stage > or = IV and CERAD rating > or = moderate) was reduced in statin users (OR 0.20; 95% CI: 0.05 to 0.86). | Is statin therapy associated with reduced neuropathologic changes of Alzheimer disease? | Yes. These findings demonstrate an association between antecedent statin use and neuritic plaque burden at autopsy. Additional study is needed to examine whether statin use may be causally related to decreased development of Alzheimer disease-related neuropathologic changes. | FAIL | pubmedQA | 0 |
23127585 | To evaluate whether eliciting repetitive cortical and autonomic arousals during sleep is able to induce the occurrence of periodic leg movements during sleep (PLMS).
Fifteen normal subjects underwent one night of uninterrupted and two sequential nights of experimental sleep fragmentation achieved by auditory and mechanical stimuli eliciting frequent EEG arousals. Sleep was polygraphically recorded and subsequently used to determine the frequency of arousals and occurrence of leg movement (LM) activity during the first (baseline) and the second fragmentation night. Also, heart rate variability parameters were obtained to assess the autonomic changes induced by the stimulation.
Sleep fragmentation was associated with an increase in the arousal index, percentage of sleep stage 1, and frequency of stage shifts. In addition, there was a decrease in sleep latency and in percentage of slow-wave sleep. Moreover, a significant increase in heart rate variability and especially of its sympathetic component, was also found. In contrast, parameters of the leg movement activity showed no significant change following experimental sleep fragmentation. The lack of an increase in leg movement activity was also observed in one subject who demonstrated PLMS at baseline. | Do experimentally induced arousals elicit periodic leg motor activity during sleep in normal subjects? | Yes. Experimental sleep fragmentation is associated with an increase in PLMS in normal young adults. | FAIL | pubmedQA | 0 |
22691188 | The finite replicative lifespan of cells, termed cellular senescence, has been proposed as a protective mechanism against the proliferation of oncogenically damaged cells, that fuel cancer. This concept is further supported by the induction of premature senescence, a process which is activated when an oncogene is expressed in normal primary cells as well as following intense genotoxic stresses. Thus, deregulation of genes that control this process, like the tumor suppressor p53, may contribute to promoting cancer by allowing cells to bypass senescence. A better understanding of the genes that contribute to the establishment of senescence is therefore warranted. Necdin interacts with p53 and is also a p53 target gene, although the importance of Necdin in the p53 response is not clearly understood.
In this study, we first investigated Necdin protein expression during replicative senescence and premature senescence induced by gamma irradiation and by the overexpression of oncogenic RasV12. Gain and loss of function experiments were used to evaluate the contribution of Necdin during the senescence process.
Necdin expression declined during replicative aging of IMR90 primary human fibroblasts or following induction of premature senescence. Decrease in Necdin expression seemed to be a consequence of the establishment of senescence since the depletion of Necdin in human cells did not induce a senescence-like growth arrest nor a flat morphology or SA-β-galactosidase activity normally associated with senescence. Similarly, overexpression of Necdin did not affect the life span of IMR90 cells. However, we demonstrate that in normal human cells, Necdin expression mimicked the effect of p53 inactivation by increasing radioresistance. | Does necdin modulate proliferative cell survival of human cells in response to radiation-induced genotoxic stress? | No. This result suggests that Necdin does not attenuate p53 signaling in response to genotoxic stress in human cells and supports similar results describing a non-inhibitory function of Necdin over p53-dependent growth arrest in mice. | FAIL | pubmedQA | 0 |
26404652 | Studies both in vitro and ex vivo of rodent skeletal muscle have highlighted the potential involvement of neuregulin 1 (NRG1) in glucose metabolism regulation, yet nothing is known of the role of NRG1 in systemic glucose homoeostasis. For this reason, it was hypothesized that systemic delivery of NRG1 might improve glucose tolerance and that the effect might be age-dependent.
Glucose tolerance tests were performed in 6-month-old (adult) and 22-month-old (old) male Wistar rats 15min after a single injection of either NRG1 (50μg/kg) or saline (controls). Skeletal muscle and liver samples were also collected 30min after the acute NRG1 or saline treatment, while the phosphorylation status of ErbB receptors and AKT was assessed by Western blotting.
Acute NRG1 treatment decreased the glycaemic response to an oral glucose load in both adult and old rats. NRG1 injection did not activate ErbB receptors in skeletal muscle, whereas phosphorylation of ErbB3 and AKT was markedly increased in the liver of NRG1-treated adult and old rats compared with controls. | Does neuregulin 1 improve glucose tolerance in adult and old rats? | Yes. This study shows that NRG1 has a possible glucose-lowering effect in the liver and via an ErbB3/AKT signaling pathway. This NRG1 effect is also maintained in adult rats, but not in old rats, suggesting that the NRG1/ErbB signaling pathway might represent a promising therapeutic target in insulin resistance states. | FAIL | pubmedQA | 0 |
9127645 | To evaluate the independent ability of midtrimester amniotic fluid tumor necrosis factor-alpha (TNF-alpha) in the prediction of small-for-gestational-age (SGA) infants.
In this case-control study, patients delivering a SGA infant were matched with controls based on GA at delivery, maternal age, race, and parity. Patients with immune disease, chronic hypertension, diabetes, asthma, congenital hearts disease, multiple gestation, and fetal anomalies were excluded. Amniotic fluid samples were immunoassayed for TNF-alpha. Potential confounding variables evaluated were maternal serum alpha-fetoprotein level, smoking history, pregnancy induced hypertension, and neonatal gender. Statistical analysis included Fisher's exact test and ANOVA after log transformation with P < 0.05 considered significant.
Eighteen patients delivered SGA neonates and were matched with 41 controls. No significant differences were identified in the confounding variables between patients with SGA neonates and controls. Amniotic fluid TNF-alpha levels were not significantly different between patients subsequently delivering SGA neonates and controls [median 7.63 (range 0.25-16.1) pg/mL versus 9.39 (0.25-66.9) pg/mL, P = 0.8]. | Does midtrimester amniotic fluid tumor necrosis factor-alpha predict small-for-gestational-age infants? | Yes. Midtrimester amniotic fluid TNF-alpha levels are predictive of SGA neonates when compared with controls matched for gestational age at delivery. | FAIL | pubmedQA | 0 |