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18258429 | The maintenance of the body's Mg(2+) balance is of great importance because of its involvement in numerous enzymatic systems and its intervention in neuromuscular excitability, protein synthesis, and nucleic acid stability. Recently, the transient receptor potential melastatin 6 (TRPM6) was identified as the gatekeeper of active Mg(2+) transport and therefore plays a crucial role in the regulation of Mg(2+) homeostasis. Remarkably, TRPM6 combines a Mg(2+) channel with an alpha-kinase domain whose function remains elusive.
Here, we identify the receptor for activated C-kinase 1 (RACK1) as the first regulatory protein of TRPM6 that associates with the alpha-kinase domain. RACK1 and TRPM6 are both present in renal Mg(2+)-transporting distal convoluted tubules. We demonstrate that RACK1 inhibits channel activity in an alpha-kinase activity-dependent manner, whereas small interference (si) RNA-mediated knockdown of RACK1 increases the current. Moreover, threonine(1851) in the alpha-kinase domain was identified as an autophosphorylation site of which the phosphorylation state is essential for the inhibitory effect of RACK1. Importantly, threonine(1851) was crucial for the Mg(2+) sensitivity of TRPM6 autophosphorylation and channel activity. TRPM6 channel activity was less sensitive to Mg(2+) when RACK1 was knocked down by siRNA. Finally, activation of protein kinase C by phorbol 12-myristate 13-acetate-PMA prohibited the inhibitory effect of RACK1 on TRPM6 channel activity. | Does rACK1 inhibit TRPM6 activity via phosphorylation of the fused alpha-kinase domain? | Yes. We propose a unique mode of TRPM6 regulation in which the Mg(2+) influx is controlled by RACK1 through its interaction with the alpha-kinase and the phosphorylation state of the serine(1851) residue. | FAIL | pubmedQA | 0 |
19898899 | KRAB-associated protein 1 (KAP1) is a universal corepressor for Kruppel-associated box zinc finger proteins. Here we demonstrate the biological function and clinical significance of KAP1 expression in gastric cancer.
Knockdown of the KAP1 gene by siRNA transfection was performed to evaluate KAP1 function in gastric cancer cells. Real-time polymerase chain reaction was performed in 91 samples obtained from gastric cancer patients.
The proliferation rate was impaired and resistance to anoikis was decreased after knockdown of KAP1 in the gastric cancer cell lines AZ521 and KATO III. Expression of the KAP1 gene was significantly higher in cancerous tissues than in noncancerous tissues (P < .05). Patients with high KAP1 expression showed a higher incidence of peritoneal carcinomatosis (P < .05) and significantly poorer overall survival compared to patients with low KAP1 expression (5-year overall survival rates, 35.4% and 50.5%, respectively; P < .05). Multivariate analysis revealed that high KAP1 expression was an independent prognostic factor (risk ratio, 1.44; 95% confidence interval, 1.03-1.99; P < .05). Intriguingly, high KAP1 expression was also an independent factor for peritoneal carcinomatosis (odds ratio, 4.53; 95% confidence interval, 1.27-18.5; P < .05). | Is kAP1 associated with peritoneal carcinomatosis in gastric cancer? | No. KAP1 does not provide a survival advantage to gastric cancer cells and is not an independent factor for peritoneal dissemination in patients with gastric cancer. These results suggest that KAP1 does not play an important role in progression to peritoneal carcinomatosis in gastric cancer patients. | FAIL | pubmedQA | 0 |
26230759 | Polymorphisms in the genes encoding C3 and C5 are associated with several immune-mediated diseases. However, the association of C3 and C5 SNPs with acute anterior uveitis (AAU) has not yet been investigated and was the purpose of the study described.
Genotyping was performed for six SNPs in C3 and four SNPs in C5 in 395 AAU patients with ankylosing spondylitis (AS), 397 AAU patients without AS, and 597 healthy controls by PCR-restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP assay. The mRNA expression was detected by real-time PCR. Cytokine production and total C5 serum concentrations were measured by ELISA.
The frequency of the GG genotype of rs2269067 in C5 was increased in AAU patients with or without AS compared to controls (Pc = 4.0 × 10(-5), odds ratio [OR] = 1.94 and Pc = 9.4 × 10(-5), OR = 1.89, respectively). The mRNA and serum concentrations of C5 were significantly increased in rs2269067 GG cases as compared to that in CG or CC cases (P = 0.012, P = 0.002; P = 0.021, P = 0.006, respectively). An increased production of interleukin-17 was observed in rs2269067 GG cases compared to CG or CC cases (P = 5.1 × 10(-4), P = 1.4 × 10(-4), respectively). | Does complement C5 Gene confer Risk for Acute Anterior Uveitis? | Yes. The C5 rs2269067 CC genotype confers risk for AAU in a Chinese population and is associated with an elevated C5 serum concentration and an increased IL-17 production. | FAIL | pubmedQA | 0 |
22382749 | This study compares success rates and hard and periimplant soft tissue responses, between placement and nonplacement of the following five different types of grafts: autogenous bone (A); deproteinized bovine bone mineral (H); demineralized freeze-dried bone allograft (D); A + H; A + D in horizontal gaps between implant surfaces and the buccal bone wall, in immediate placed and immediate nonfunctional loaded implants in maxillary arch.
Forty-one patients with a mean age of 42.5 years were enrolled in this retrospective comparative study. Outcome assessments included clinical and radiographic evaluation.
Patients were followed up on average for 32 months with a 100% implant survival rate. No significant difference was found between the two groups. | Do comparison between graft and no-graft in an immediate placed and immediate nonfunctional loaded implant? | Yes. Results of this study suggest that immediate placed and immediate restored single implants are valuable therapeutic options in the maxillary arch. The types of grafts placement: A, H, D, A + H, and A + D in horizontal gaps have shown significant benefits in promoting better clinical outcomes given that a thick gingival biotype is present. | FAIL | pubmedQA | 0 |
10456409 | The intra-operative assessment of the quality of anastomosis in minimally invasive coronary artery bypass surgery (CABG) is critical. Recent investigations demonstrated that flow probes used intra-operatively to assess anastomotic errors may give the surgeon a false sense of confidence as only severely stenotic anastomoses (>90%) could be reliably detected. We developed a neural network system using graft flow data and assessed its potential to improve anastomotic error detection.
Mammary to LAD grafts (n = 46) were constructed in mongrel dogs off-pump. Continuous beat-to-beat graft flow was recorded using transit-time flow probes. Various degrees of anastomotic stenoses (0-100%) were created by an additional suture. The degree of anastomotic stenosis was confirmed by postoperative angiography. A learning vector quantization neural network was created using heart rate, mean aortic pressure, mean systolic, maximum systolic, minimum systolic, mean diastolic, maximum diastolic, minimum diastolic, and mean graft flows. In addition, a spectral analysis of the flow waveforms was performed and the magnitude and phase of the first five harmonics were used to further develop the neural network.
The neural network pattern recognition system was 94% accurate in detecting any stenosis >50%. To validate the model, a testing set was used with 20% of the data values, and the accuracy remained at 100% above chance alone. | Does neural network pattern recognition analysis of graft flow characteristics improve intra-operative anastomotic error detection in minimally invasive CABG? | No. Pattern recognition of transit-time flow probe tracings using neural network systems does not significantly improve anastomotic error detection compared to the surgeon's visual assessment in minimally invasive CABG. | FAIL | pubmedQA | 0 |
24309268 | Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders that share significant clinical, pathological and genetic overlap and are considered to represent different ends of a common disease spectrum. Mutations in Profilin1 have recently been described as a rare cause of familial ALS. The PFN1 E117G missense variant has been described in familial and sporadic cases, and also found in controls, casting doubt on its pathogenicity. Interpretation of such variants represents a significant clinical-genetics challenge.
Here, we combine a screen of a new cohort of 383 ALS patients with multiple-sequence datasets to refine estimates of the ALS and FTD risk associated with PFN1 E117G. Together, our cohorts add up to 5118 ALS and FTD cases and 13 089 controls. We estimate a frequency of E117G of 0.11% in controls and 0.25% in cases. Estimated odds after population stratification is 2.44 (95% CI 1.048 to ∞, Mantel-Haenszel test p=0.036). | Is profilin1 E117G a moderate risk factor for amyotrophic lateral sclerosis? | No. Our results show no association between E117G and ALS. | FAIL | pubmedQA | 0 |
24485498 | Metabolic syndrome (MetS) and depression are considered important risk factors for diabetes and cardiovascular disease. Recent evidence suggests that depression can be an important predictor of MetS. Data on the association between anxiety and MetS remain mixed. In a large primary care based community sample we investigated an association of depressive and anxiety disorders and symptoms with MetS.
A total of 1115 (51% men, mean age 62.0 ± 9.6 years) randomly selected individuals of 45 years and older were evaluated for: (i) MetS using the World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) and International Diabetes Federation (IDF) criteria; (ii) current major depressive episode (MDE) and current generalized anxiety disorder (GAD), the Mini International Neuropsychiatric interview; (iii) lifetime MDE; and (iv) symptoms of depression and anxiety, the Hospital Anxiety and Depression scale (HADS). Socio-demographic characteristics (education, residence, marital status and social status) and medical histories (physical activity, smoking status, alcohol consumption and histories of myocardial infarction and stroke) were also evaluated.
After adjusting for socio-demographic status, medical histories and current GAD, current MDE and lifetime MDE were associated with greater prevalence of MetS according to the WHO criteria (OR=1.7, 95%CI [1.1-2.7] and OR=3.7, 95%CI [2.4-5.7], respectively, p ≤ 0.001). Lifetime MDE was also associated with MetS according to the IDF and NCEP/ATP III criteria. On the other hand, current GAD was not associated with MetS in multivariate regression models when adjusted for current MDE. Similar results were obtained when evaluating an association between depression/anxiety symptoms and MetS, since elevated depressive, but not anxiety, symptoms were independently associated with MetS. | Is depression but not anxiety associated with metabolic syndrome in primary care based community sample? | Yes. Depressive and anxiety disorders and symptoms are associated with greater prevalence rate of MetS. Assessment and management of MetS risk factors should be considered in both depressed and anxious individuals. | FAIL | pubmedQA | 0 |
23028600 | Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzed the association of the B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival of untreated node-negative breast cancer patients.
IGKC expression was evaluated by immunostaining in a cohort of 335 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of IGKC for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 and human epidermal growth factor receptor 2 (HER-2) status.
160 patients (47.7%) showed strong expression of IGKC. Univariate analysis showed that IGKC was significantly associated with DFS (P = 0.017, hazard ratio [HR] = 0.570, 95% confidence interval [CI] = 0.360-0.903) and OS (P = 0.011, HR = 0.438, 95% CI = 0.233-0.822) in the entire cohort. The significance of IGKC was especially strong in ER negative and in luminal B carcinomas. In multivariate analysis IGKC retained its significance independent of established clinical factors for DFS (P = 0.004, HR = 0.504, 95% CI = 0.315-0.804) as well as for OS (P = 0.002, HR = 0.371, 95% CI = 0.196-0.705). | Does immunoglobulin kappa C predict overall survival in node-negative breast cancer? | No. Expression of IGKC does not have an independent protective impact on DFS and OS in node-negative breast cancer. | FAIL | pubmedQA | 0 |
19439502 | SSc is characterized by microvascular abnormalities and leucocyte infiltration. Previous studies have suggested a proadhesive phenotype in SSc skin, but the functional consequences of this phenotype are not fully understood. Molecules known to mediate leucocyte adhesion include those present at intracellular junctions, such as junctional adhesion molecule-B (JAM-B), JAM-C and CD99, as well as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). The aim of this study was to examine adhesive interactions in SSc skin.
The expression of JAM-B, JAM-C, CD99, ICAM-1 and VCAM-1 in SSc skin was determined by immunohistology and cell surface ELISA. Myeloid U937 cell-SSc dermal fibroblast adhesion assays or in situ adhesion assays to SSc skin were performed.
JAM-C and CD99 expression on endothelial cells (ECs) in SSc skin was decreased compared with expression on normal ECs. CD99 was overexpressed on mononuclear cells in SSc skin and on SSc dermal fibroblasts. Neutralizing ICAM-1 inhibited the binding of U937 cells to SSc dermal fibroblasts. In addition, blocking both ICAM-1 and VCAM-1 inhibited U937 cell adhesion to either proximal (less involved) or distal (more involved) SSc skin. | Does the proadhesive phenotype of systemic sclerosis skin promote myeloid cell adhesion via ICAM-1 and VCAM-1? | Yes. These studies show that JAM-C and CD99 are aberrantly expressed in SSc skin. However, these adhesion molecules mediate myeloid cell-SSc skin adhesion. In contrast, we demonstrate an important role for ICAM-1 and VCAM-1 in the retention of myeloid cells in SSc skin, suggesting that targeting these molecules may be useful SSc therapies. | FAIL | pubmedQA | 0 |
12000371 | It is well known from clinical practice that repeated treatment with dithranol leads to the development of tolerance.
To investigate the characteristics and mechanism of such dithranol tolerance.
The mouse ear was pretreated with a low dose of dithranol or croton oil or, in previously sensitized animals, with dinitrofluorobenzene (DNFB). Twenty-four hours later irritant dermatitis was elicited by painting the mouse ear with a high dose of dithranol, croton oil or DNFB, and the dermatitis was characterized by measurement of ear thickness.
Low-dose dithranol significantly suppressed dithranol-induced oedema, whereas it had no effect on croton oil- or DNFB-induced dermatitis, suggesting that dithranol-induced tolerance is specific. Tolerance to dithranol could not be induced by pretreatment of the mouse ear with a low dose of croton oil or DNFB. Mild tape stripping of the mouse ear also inhibited the inflammatory effect of dithranol applied 24 h later. Superoxide dismutase treatment abolished the tolerance-inducing effect of low-dose dithranol or stripping. | Do low-dose dithranol treatment and tape stripping induce tolerance to dithranol in a mouse ear oedema model? | Yes. These results suggest that superoxide anion radicals are involved only in the inflammatory effect of dithranol, but not in the induction of tolerance. | FAIL | pubmedQA | 0 |
9767530 | Tamm-Horsfall glycoprotein (THP) is a unique protein that is produced exclusively by cells of the thick ascending limb of Henle's loop (TALH). This study examined whether dietary salt altered renal THP production.
Male Sprague-Dawley rats were examined on days 1, 4, and 15 following placement in metabolic cages on diet that contained 0.3%, 1.0% or 8.0% NaCl. THP expression was quantified using Northern hybridization and Western blotting analysis.
An increase in dietary salt produced sustained increases in relative steady-state mRNA and protein levels of THP in the kidney. Addition of furosemide, but not chlorothiazide, to animals on the 8.0% NaCl diet further augmented steady-state mRNA levels of THP. | Does dietary salt regulate expression of Tamm-Horsfall glycoprotein in rats? | Yes. A decrease in dietary salt and the loop diuretic, furosemide, increased expression of THP in the rat. The data support the involvement of this unique protein in the function of the TALH during changes in dietary salt. These findings also suggest that restriction of dietary salt may be beneficial in cast nephropathy in multiple myeloma and recurrent nephrolithiasis, two diseases in which THP can play an important pathogenetic role. | FAIL | pubmedQA | 0 |
25799128 | We conducted a cross-sectional study of primary total joint replacement (TJR) patients to determine predictors for prolonged length of stay (LOS) in hospital to identify patient characteristics that may inform resource allocation, accounting for patient complexity.
Preoperative demographics, medical comorbidities and acute hospital LOS from a consecutive series of primary TJR patients from an academic arthroplasty centre were abstracted. We categorized patients as LOS of 3 or fewer days, 4 days, or 5 or more days to align results with varying LOS benchmarks. To identify predictors for LOS, we used a generalized logistic regression model fitted on an LOS ternary outcome, using LOS of 3 or fewer days as a reference category.
The sample included 1459 patients: 61.7% total knee and 38.3% total hip. Male sex was predictive of an LOS of 3 or fewer days (4 d: odds ratio [OR] 0.48, 95% confidence interval [CI] 0.364-0.631; ≥ 5 d: OR 0.57, 95% CI 0.435-0.758), as was current smoking status (4 d: OR 0.425, 95% CI 0.274-0.659; ≥ 5 d: OR 0.489, 95% CI 0.314-0.762). Strong predictors of prolonged LOS included total hip versus total knee arthroplasty, age 75 years or older, American Society of Anesthesiologists classification of 3 and 4 and number of cardiovascular comorbidities. | Are not all total joint replacement patients created equal : preoperative factors and length of stay in hospital? | Yes. Not all patients undergoing TJR are equal. The goal should be individual patient-focused care rather than a predetermined LOS that is not achievable for all patients. Hospital resource planning must account for patient complexity when planning future bed management. Male sex and current smoking status are strong predictors of prolonged LOS. | FAIL | pubmedQA | 0 |
26909317 | The ventromedial nucleus of the hypothalamus (VMH) controls energy and glucose homeostasis through direct connections to a distributed network of nuclei in the hypothalamus, midbrain, and hindbrain. Structural changes in VMH circuit morphology have the potential to alter VMH function throughout life, however, molecular signals responsible for specifying its neural connections are not fully defined. The VMH contains a high density of neurons that express brain-derived neurotrophic factor (BDNF), a potent neurodevelopmental effector known to regulate neuronal survival, growth, differentiation, and connectivity in a number of neural systems. In the current study, we examined whether BDNF impacts the afferent and efferent connections of the VMH, as well as energy homeostatic function.
To determine if BDNF is required for VMH circuit formation, a transgenic mouse model was used to conditionally delete Bdnf from steroidogenic factor 1 (SF1) expressing neurons of the VMH prior to the onset of establishing neural connections with other regions. Projections of SF1 expressing neurons were visualized with a genetically targeted fluorescent label and immunofluorescence was used to measure the density of afferents to SF1 neurons in the absence of BDNF. Physiological changes in body weight and circulating blood glucose were also evaluated in the mutant mice.
Our findings suggest that BDNF is required to establish normal densities of GABAergic afferents onto SF1 neurons located in the ventrolateral part of the VMH. Furthermore, loss of BDNF from VMH SF1 neurons results in impaired physiological responses to insulin-induced hypoglycemia. | Is ventromedial hypothalamic expression of Bdnf required to establish normal patterns of afferent GABAergic connectivity and responses to hypoglycemia? | No. The results of this study indicate that BDNF is not required for formation and/or maintenance of inhibitory inputs to SF1 neurons, with enduring effects on glycemic control. | FAIL | pubmedQA | 0 |
9861306 | Recent reports indicate that endothelin (ET) plays an important pathophysiological role in congestive heart failure (CHF). However, existing data on local cardiopulmonary ET production are few. No studies have hitherto examined the specific anatomic localization of cardiopulmonary ET synthesis in CHF. Thus, the aims of the present study were to examine whether cardiopulmonary preproET-1 mRNA synthesis is upregulated in CHF and to determine the anatomic localization of preproET-1 mRNA and the mature peptide.
CHF was induced in rats by occluding the left coronary artery. Only animals with a left ventricular end-diastolic pressure above 15 mmHg after one week were included (n = 28). Sham-operated animals served as controls (n = 24). Hearts and lungs were examined by mRNA slot blot analyses, in situ hybridization (ISH) and immunohistochemistry (IHC).
In CHF-rats, slot blot analyses revealed a 3.5 +/- 1.1-fold and a 6.4 +/- 0.8-fold upregulation of preproET-1 mRNA in the noninfarcted and the infarcted area of the left ventricles, respectively (p < 0.05 for both). ISH revealed that the preproET-1 mRNA was localized predominantly over the granulation tissue in the infarcted region. The ET peptide was predominantly localized to inflammatory cells and remaining cardiomyocytes in the infarcted region as determined by IHC. Lungs from CHF-rats showed a 1.5 +/- 0.1-fold upregulation of preproET-1 mRNA (p = 0.01). The most abundant preproET-1 mRNA and ET-1-like-immunoreactivity (ET-1-ir) was seen over inflammatory cells and over airway epithelial cells. Some ET-1-ir was also located to bronchial and vascular smooth muscle cells. | Are pulmonary and cardiac expression of preproendothelin-1 mRNA increased in heart failure after myocardial infarction in rats . Localization of preproendothelin-1 mRNA and endothelin peptide? | No. Cardiopulmonary ET synthesis is not significantly altered in CHF. | FAIL | pubmedQA | 0 |
26342849 | Accurate, standardized information on childhood immunization is not available in Japan. We investigated current practices in perinatal childhood immunization education in the community and the needs and interest for such education among Japanese mothers.
This cross-sectional, descriptive study evaluated pregnant and postnatal women at four institutions in Niigata, Japan from May through July 2014. Data were collected using questionnaires inquiring about demographics, immunization education received, intent to receive childhood vaccines, and needs regarding information on childhood immunization.
Questionnaires were distributed to 300 women, and 116 (38.6%) were returned; 70 (59.6%) of the respondents were pregnant women and 46 (40.3%) were postnatal women. Fourteen (20%) of the 70 pregnant women reported receiving some form of immunization education; in contrast, 34 (73.9%) of 46 postnatal women had received such education within 1 month of delivery. The rates of respondents who felt that the information was insufficient were high: 78.6% among pregnant women and 52.9% among postnatal women. Pregnant women reported that the most important information was general concepts of immunization; in contrast, postnatal women desired more-detailed information, e.g., on immunization scheduling. | Does current practices and need regarding perinatal childhood immunization education for Japanese mothers? | Yes. Japanese women receive sufficient perinatal immunization education. The information needed during the prenatal and postnatal periods differs. Thus, educational approaches may need to provide carefully targeted information. | FAIL | pubmedQA | 0 |
22809888 | Pravastatin can reduce atherosclerotic progression in patients after coronary artery bypass graft. However, it is unknown whether pravastatin has a direct effect on intimal hyperplasia of grafted vessels in vivo or what the underlying mechanisms may be. In this study, a murine vein graft model was applied to deal with these issues.
Vein grafting was performed between C57BL/6J mice. Immediately after operation, pravastatin (30 μM) or phosphate-buffered saline in 50 μL 20% pluronic F-127 gel was delivered to the adventitia of grafted vessels.
Compared with the vehicle, pravastatin significantly reduced intimal hyperplasia 4 weeks after the surgical procedure. Immunohistochemical studies revealed that vascular smooth muscle cells (VSMCs) are a major component of the neointima. The percentage of cells positive for proliferating cell nuclear antigen and Mac-3-positive immunostaining intensity within the intima of vein grafts was significantly lower in the pravastatin-treated group than in the control group. We separated VSMCs from mouse inferior vena cava and collected peritoneal macrophage from mice injected intraperitoneally with 4% thioglycollate. Pravastatin significantly decreased VSMC proliferation and platelet-derived growth factor-induced VSMC migration and, in a dose-dependent manner, inhibited macrophage migration induced by monocyte chemotactic protein-1. | Does local delivery of pravastatin inhibit intimal formation in a mouse vein graft model? | Yes. Local delivery of pravastatin at the time of vein-graft surgery directly suppresses subsequent neointimal formation of grafted vessels in a vein graft model of hypercholesterolemic mice. These beneficial effects are associated with inhibitory actions on VSMC and macrophage functions. | FAIL | pubmedQA | 0 |
24423354 | In most ethnicities at least a quarter of all cases with diabetes is assumed to be undiagnosed. Screening for diabetes using saliva has been suggested as an effective approach to identify affected individuals.
The objective of the study was to identify a noninvasive metabolic marker of type 2 diabetes in saliva.
In a case-control study of type 2 diabetes, we used a clinical metabolomics discovery study to screen for diabetes-relevant metabolic readouts in saliva, using blood and urine as a reference. With a combination of three metabolomics platforms based on nontargeted mass spectrometry, we examined 2178 metabolites in saliva, blood plasma, and urine samples from 188 subjects with type 2 diabetes and 181 controls of Arab and Asian ethnicities.
We found a strong association of type 2 diabetes with 1,5-anhydroglucitol (1,5-AG) in saliva (P = 3.6 × 10(-13)). Levels of 1,5-AG in saliva highly correlated with 1,5-AG levels in blood and inversely correlated with blood glucose and glycosylated hemoglobin levels. These findings were robust across three different non-Caucasian ethnicities (Arabs, South Asians, and Filipinos), irrespective of body mass index, age, and gender. | Is 1,5-Anhydroglucitol in saliva a noninvasive marker of short-term glycemic control? | No. Clinical studies have already established 1,5-AG in blood as a reliable marker of short-term glycemic control. Our study suggests that 1,5-AG in saliva cannot be used in national screening programs for undiagnosed diabetes, which are of particular interest for Middle Eastern countries with young populations and exceptionally high diabetes rates. | FAIL | pubmedQA | 0 |
23633127 | To elucidate disease associations and possible etiology of lichen sclerosus (LS), we identified comorbidities present in men with LS. LS is a chronic inflammatory disease of unknown etiology affecting genitals and urethra of men commonly resulting in strictures.
Men with LS of the urethra, penis, prepuce and scrotum were identified. A control population was generated from men seen in the Department of Urology matched by age and race in a 5:1 ratio. A case-control study was performed and comorbidities identified by ICD9, CPT codes and medication use via systematic electronic medical record review. Subgroup analysis of men with urethral strictures was performed based on their LS status.
Men with LS had a significantly higher mean body mass index [31.0 (range 18.9-52.6)] compared to controls [28.1 (16.8-64.1), p = 0.001], significantly increased rate of coronary artery disease (CAD) (15.3 vs. 8.9%, p = 0.05) as well as a twofold higher rate of diabetes mellitus (15.5 vs. 8.3%, p = 0.02). Of men with LS and stricture disease, 11/19 (58%) were current or former smokers, compared to 28% of men with strictures without LS (p = 0.006). No association of LS with other morbidities like hyperlipidemia, hypertension, cerebrovascular disease, peripheral vascular disease or dermatologic disorders was found. | Is lichen sclerosus in men associated with elevated body mass index , diabetes mellitus , coronary artery disease and smoking? | Yes. Men suffering from LS have a decreased BMI and a higher prevalence of concomitant CAD, diabetes mellitus and tobacco use. Development and chronicity of LS may not be a purely dermatologic condition, but be associated or confounded by systemic or vascular compromise from disorders of CAD, DM and smoking. | FAIL | pubmedQA | 0 |
21458864 | We comparative effects of mitomycin-c and heparin which have different mechanism of action in a minimal invasive corrosive esophagitis model which was formed by NaOH 40%.
The study was performed on forty female Wistar albino rats; were divided into four equal groups each including ten animals. Group C (n=10); control, the group that esophagus was washed with normal saline, group I (n=10); injury group; alkali esophagus burn, not treated, group M (n=10); alkali esophagus burn, mitomycin-c treatment group, group H (n=10); alkali esophagus burn, heparin treatment group. The study was performed on a minimal invasive model which did not require general anesthesia and abdominal operation. In 28 day, all subjects were killed and their esophagus's were removed by thoraco-abdominal cut. Total esophagi from oropharynx to stomach were removed and they were examined macroscopically and microscopically and evaluated for esophageal tissue collagen deposition and histopathologic damage score.
When group C is compared with each of the other groups, statistically significant weight losses were detected; [(p<0.005, p<0.05, p<0.005), respectively]. Significant inflammation increase was detected in groups I, M and H in comparison to group C [(p<0.001, p<0, 0001, p<0.005)]. When granulation scores of groups were compared; statistically significant granulation increases were detected in groups I, M, and H [(p<0.05, p<0.05, p<0.05) compared to group C]. Significant collagen increase was detected in all 3 layers in groups; I, M and H according to group C [(p<0.05, p<0.05, p<0.05)]. Collagen increase in every 3 layers in groups M and H were significantly less according to group I [(p<0.05, p<0.05, p<0.05)]. Collagen increase in every 3 layers was less in group M than group H (p<0.05). | Does comparison of mitomycin-c and heparin affect in experimental corrosive esophagitis on rats? | Yes. In corrosive esophagitis due to NaOH, mitomycin-c treatment is more effective in inflammation and granulation formation, heparin treatment is more effective in preventing the collagen accumulation step. Mitomycin-c decreases the tissue damage by preventing the inflammation and granulation formation; and prevents collagen accumulation and stricture development. As completing the effect of mitomycin-c; heparin prevents fibroblastic activity inhibition with direct collagen accumulation and stricture development strongly. | FAIL | pubmedQA | 0 |
21979885 | Mitral valve prolapse (MVP) is a common diagnosis in patients with primary spontaneous pneumothorax (PSP). This description assumes that MVP and PSP might be manifestations of a systemic connective tissue abnormality. The purpose of this study was to determine the prevalence of MVP in PSP patients of Croatian origin and evaluate their relationship with connective tissue disorders. We also examined the prevalence of PSP in patients with primary MVP.
Thirty-two patients with PSP and without underlying pulmonary disease or connective tissue disease underwent two-dimensional transthoracic echocardiography performed by a certified cardiologist. Echocardiography and demographic features were analyzed using descriptive statistics. We also examined the medical records of 60 patients with primary MVP.
MVP was found in none of the 32 patients suffering from PSP. The age, sex, smoking status, body mass index, side, rate, and family history were similar to previous investigations. Likewise, none of the 60 patients with primary MVP ever had PSP. | Are primary spontaneous pneumothorax and mitral valve prolapse associated? | Yes. By applying an updated definition of MVP, we found several MVP cases among PSP patients of Croatian origin. We also found PSP in the primary MVP group. Ethnicity may influence the occurrence of MVP in PSP patients, and PSP in primary MVP patients. | FAIL | pubmedQA | 0 |
26741117 | Physical inactivity is associated with increased risk for morbidity and mortality and contributes to health care costs. Although data supporting the secondary preventive benefits of being physically active continues to grow, there is limited data on the prevalence of sufficient volume of leisure-time physical activity among individuals diagnosed with chronic disease.
To describe the association between select chronic diseases and the prevalence of sufficient volume of aerobic leisure-time physical activity to achieve substantial health benefits (i.e., ≥150 min·wk) among adults in the United States.
Self-reported leisure-time physical activity (LTPA) and history of select chronic diseases were obtained from a nationally representative sample of noninstitutionalized civilian adults 18 yr or older in the United States who participated in the 2014 National Health Interview Survey (n = 36,697).
Among all adults, the prevalence of sufficient volume of aerobic LTPA was 50.1% ± 0.5% (mean ± standard error). This prevalence was inversely related to age and was lower in women (47.1% ± 0.6%) compared with men (53.4% ± 0.6%; P < 0.001). Prevalence of sufficient volume of aerobic LTPA was lower for each chronic disease (prevalence range = 26.1%-48.6%) compared with apparently healthy adults (53.6% ± 0.7%). Relative to no chronic disease, each additional chronic disease was associated with an odds ratio of 0.83 (95% confidence interval, 0.81-0.85; P < 0.001) for sufficient volume of aerobic LTPA. | Does prevalence of Physical Activity be Lower among Individuals with Chronic Disease? | Yes. The prevalence of sufficient volume of aerobic LTPA to achieve substantial health benefits is inversely related to age and is higher among women and individuals with a chronic disease. Systems to regularly assess physical activity are needed as well as programs to help individuals be more active. | FAIL | pubmedQA | 0 |
9415571 | Use of the murine CD3 monoclonal antibody OKT3 is limited by first-dose side effects, which are thought to be caused by the release of inflammatory mediators. Because these processes might be influenced by the speed of administration, we compared a 2-hr OKT3 infusion with the bolus infusion usually applied nowadays.
Eighteen renal allograft recipients were prophylactically treated with OKT3 and randomized to receive the first dose either as a 2-hr infusion or as an intravenous bolus infusion. Clinical side effects score and the occurrence of complement activation, cytokine release, and activation of neutrophils were determined.
Two-hour infusion of OKT3 completely prevented the occurrence of dyspnea, reduced the incidence of other side effects, and attenuated complement activation. Cytokine release and depletion of peripheral blood lymphocytes were similar in both groups. | Does administration of OKT3 as a two-hour infusion attenuate first-dose side effects? | No. Thus, complement activation seems to play an additional role in the development of side effects after the first OKT3 dose. | FAIL | pubmedQA | 0 |
22223149 | Although C-reactive protein (CRP) is significantly increased in patients with diabetic nephropathy, whether CRP exerts direct proinflammatory effects on human renal tubular epithelial cells (HK-2 cells) is still unclear.
HK-2 cells were incubated with purified CRP at clinically relevant concentrations (0, 5, 10, 20 and 40 μg/ml). The protein and transcript levels of thrombospondin-1 (TSP-1) and interleukin-6 (IL-6) were determined by ELISA and RT-PCR. Phosphorylation of p38MAPK was investigated through Western blot analysis in HK-2 cells induced by CRP. The activation of nuclear factor-kappa B (NF-κB) was studied via EMSA. A specific p38MAPK inhibitor (SB203580) and an NF-κB inhibitor (PDTC; pyrrolidine dithiocarbamate) were used to analyze the signal transduction in CRP induction. To explore the direct or indirect role of CRP in HK-2 cells, IL-6 or TSP-1 antibodies were used. The expression of IL-6, TSP-1 and transforming growth factor-β(1 )(TGF-β(1)) were determined through Western blot analysis in HK-2 cells.
In HK-2 cells, purified CRP significantly induced protein release and mRNA expression of IL-6 and TSP-1 in a dose- and time-dependent manner. TGF-β(1) protein was overexpressed in HK-2 cells induced by CRP, which cannot be inhibited by IL-6 or TSP-1 antibodies. CRP triggered phosphorylation of p38MAPK and activation of NF-κB-mediated signal transduction. SB203580 (5 μM) and PDTC (50 μM) efficiently suppressed those effects of CRP in HK-2 cells. | Does c-reactive protein induce interleukin-6 and thrombospondin-1 protein and mRNA expression through activation of nuclear factor-ĸB in HK-2 cells? | Yes. CRP induces IL-6 and TSP-1 protein release and mRNA expression from HK-2 cells via activation of the JNK and NF-κB signaling pathways and TGF-β(1) was highly expressed in HK-2 cells, suggesting that CRP plays an important role in the propagation and prolongation of inflammation in renal fibrosis. | FAIL | pubmedQA | 0 |
26637877 | Altered expression of circadian clock genes has been linked to various types of cancer. This study aimed to investigate whether these genes are also altered in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL).
The expression profiles of nine circadian clock genes of peripheral blood (PB) leukocytes from patients with newly-diagnosed AML (n=41), ALL (n=23) and healthy individuals (n=51) were investigated.
In AML, the expression of period 1 (PER1), period 2 (PER2), period 3 (PER3), cryptochrome 1 (CRY1), cryptochrome 2 (CRY2), brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like 1 (BMAL1), and timeless (TIM) was significantly down-regulated, while that of CK1ε was significantly up-regulated. In ALL, the expression of PER3 and CRY1 was significantly down-regulated, whereas those of CK1ε and TIM were significantly up-regulated. Recovery of PER3 expression was observed in both patients with AML and those with ALL who achieved remission but not in patients who relapsed after treatment. | Does up-regulation of PER3 Expression be Correlated with Better Clinical Outcome in Acute Leukemia? | No. Circadian clock genes are altered in patients with acute leukemia and up-regulation of PER3 is correlated with a worse clinical outcome. | FAIL | pubmedQA | 0 |
26179622 | Recombinant Saccharomyces cerevisiae expressing exogenous carotenogenic genes can synthesize carotenoids. NADPH is a key cofactor for carotenoid biosynthesis, while glucose-6-phosphate dehydrogenase (Zwf1) and an NADH kinase (Pos5) are the two main NADPH-supplying sources in S. cerevisiae. Here, the effect of ZWF1 and POS5 overexpression on carotenoid yield in recombinant S. cerevisiae was explored. The initial carotenogenic strain Sc-EYBIH+I which expressed crtE, crtYB, crtI, cHMG1 and another copy of crtI could synthesize 1·35 ± 0·13 mg l(-1) of lycopene and 0·32 ± 0·02 mg l(-1) of β-carotene. When ZWF1 was overexpressed (Sc-EYBIZH+I), glucose-6-phosphate dehydrogenase activity increased by 103-fold, the transcription level of crtE and crtI increased significantly, the lycopene and β-carotene yield increased to 2·29 ± 0·06 and 0·38 ± 0·02 mg l(-1) respectively. When POS5 was overexpressed (Sc-EYBIPH+I), NAD kinase activity increased by 5·5-fold, the transcription level of crtE, crtYB and crtI increased obviously, the lycopene and β-carotene yield increased to 2·50 ± 0·11 and 0·53 ± 0·03 mg l(-1) respectively. Therefore, improvement of NADPH supply contributed to carotenoids biosynthesis in S. cerevisiae and overexpression of POS5 was more effective than overexpression of ZWF1. This study provides a new strategy for enhancing carotenoid biosynthesis. | Does overexpression of ZWF1 and POS5 improve carotenoid biosynthesis in recombinant Saccharomyces cerevisiae? | Yes. NADPH is a key cofactor for carotenoid biosynthesis. Glucose-6-phosphate dehydrogenase (Zwf1) and an NADH kinase (Pos5) are effective NADPH-supplying sources in Saccharomyces cerevisiae. When ZWF1 and POS5 were overexpressed in a carotenoid-producing S. cerevisiae strain individually, the total yield of lycopene and β-carotene increased by 59·9% and 81·4%, respectively, and the final product β-carotene yield increased by 18·8% and 65·6% respectively. This suggests the improvement of NADPH supply as a useful strategy for carotenoids biosynthesis, with overexpression of ZWF1 being more effective than overexpression of POS5. | FAIL | pubmedQA | 0 |
17389923 | When brief stimuli contact the skin in rapid succession at two or more locations, perception strikingly shrinks the intervening distance, and expands the elapsed time, between consecutive events. The origins of these perceptual space-time distortions are unknown.
Here I show that these illusory effects, which I term perceptual length contraction and time dilation, are emergent properties of a Bayesian observer model that incorporates prior expectation for speed. Rapidly moving stimuli violate expectation, provoking perceptual length contraction and time dilation. The Bayesian observer replicates the cutaneous rabbit illusion, the tau effect, the kappa effect, and other spatiotemporal illusions. Additionally, it shows realistic tactile temporal order judgment and spatial attention effects. | Does a Bayesian perceptual model replicate the cutaneous rabbit and other tactile spatiotemporal illusions? | Yes. The remarkable explanatory power of this simple model supports the hypothesis, first proposed by Helmholtz, that the brain biases perception in favor of expectation. Specifically, the results suggest that the brain automatically incorporates prior expectation for distance in order to overcome spatial and temporal imprecision inherent in the sensorineural signal. | FAIL | pubmedQA | 0 |
16519628 | Rho GTPases regulate a wide range of cellular functions affecting both cell proliferation and cytoskeletal dynamics. They cycle between inactive GDP- and active GTP-bound states. This cycle is tightly regulated by GEFs (guanine nucleotide-exchange factors) and GAPs (GTPase-activating proteins). Mouse CdGAP (mCdc42 GTPase-activating protein) has been previously identified and characterized as a specific GAP for Rac1 and Cdc42, but not for RhoA. It consists of an N-terminal RhoGAP domain and a C-terminal proline-rich region. In addition, CdGAP-related genes are present in both vertebrates and invertebrates. We have recently reported that two predominant isoforms of CdGAP (250 and 90 kDa) exist in specific mouse tissues.
In the present study, we have identified and characterized human CdGAP (KIAA1204) which shares 76% sequence identity to the long isoform of mCdGAP (mCdGAP-l). Similar to mCdGAP, it is active in vitro and in vivo on both Cdc42 and Rac1, but not RhoA, and is phosphorylated in vivo on serine and threonine residues. In contrast with mCdGAP-l, human CdGAP interacts with ERK1/2 (extracellular-signal-regulated kinase 1/2) through a region that does not involve a DEF (docking site for ERK Phe-Xaa-Phe-Pro) domain. Also, the tissue distribution of CdGAP proteins appears to be different between human and mouse species. Interestingly, we found that CdGAP proteins cause membrane blebbing in COS-7 cells. | Is the human orthologue of CdGAP a phosphoprotein and a GTPase-activating protein for Cdc42 and Rac1 but not RhoA? | Yes. Our results suggest that CdGAP properties are well conserved between human and mouse species, and that CdGAP may play an unexpected role in cell proliferation. | FAIL | pubmedQA | 0 |
9146771 | Helicobacter pylori eradication reduces the recurrence of duodenal ulcers. It is unclear why duodenal ulcers rarely recur in the absence of reinfection with H. pylori or NSAID treatment.
Basal, gastrin-releasing peptide- and pentagastrin-stimulated peak acid outputs in patients with ulcer relapse after H. pylori eradication were measured, and compared with patients without ulcer relapse after H. pylori eradication.
Pentagastrin-stimulated peak acid output was significantly higher in H. pylori-positive patients with duodenal ulcers than in H. pylori-negative controls, and fell significantly after H. pylori eradication. In H. pylori-negative patients with recurrent duodenal ulcers, pentagastrin-stimulated peak acid output was significantly higher than in controls and similar to H. pylori-positive patients with duodenal ulcers. | Is recurrence of duodenal ulcer after Helicobacter pylori eradication related to high acid output? | No. These findings suggest that duodenal ulcer relapse after eradication of H. pylori is not related to high pentagastrin-stimulated peak acid output. In this subset of patients with duodenal ulcers, maintenance anti-secretory treatment may not be necessary to prevent relapse. | FAIL | pubmedQA | 0 |
27789555 | Calcific aortic valve disease is characterized by an abnormal mineralization of the aortic valve. Osteogenic activity in the aortic valve is under the control of NOTCH1, which regulates the expression of key pro-osteogenic genes such as RUNX2 and BMP2. Long noncoding RNAs (lncRNAs) may reprogram cells by altering the gene expression pattern.
Multidimensional genomic profiling was performed in human aortic valves to document the expression of lncRNAs and the DNA methylation pattern in calcific aortic valve disease. In-depth functional assays were carried out to document the impact of lncRNA on the mineralization of the aortic valve.
We documented that lncRNA H19 (H19) was increased in calcific aortic valve disease. Hypomethylation of the promoter region was observed in mineralized aortic valves and was inversely associated with H19 expression. Knockdown and overexpression experiments showed that H19 induces a strong osteogenic phenotype by altering the NOTCH1 pathway. Gene promoter analyses showed that H19 silenced NOTCH1 by preventing the recruitment of p53 to its promoter. A knockdown of H19 in valve interstitial cells (VICs) increased the expression of NOTCH1 and decreased the level of RUNX2 and BMP2, 2 downstream targets repressed by NOTCH1. In rescue experiments, the transfection of a vector encoding for the active Notch intracellular domain prevented H19-induced mineralization of valve interstitial cells. | Does altered DNA Methylation of Long Noncoding RNA H19 in Calcific Aortic Valve Disease promote Mineralization by Silencing NOTCH1? | Yes. These findings indicate that a dysregulation of DNA methylation in the promoter of H19 during calcific aortic valve disease is associated with a lower expression of this lncRNA, which promotes an osteogenic program by interfering with the expression of NOTCH1. | FAIL | pubmedQA | 0 |
22570703 | Environmental alternations leading to fetal programming of cardiovascular diseases in later life have been attributed to maternal factors. However, animal studies showed that paternal obesity may program cardio-metabolic diseases in the offspring. In the current study we tested the hypothesis that paternal BMI may be associated with fetal growth.
We analyzed the relationship between paternal body mass index (BMI) and birth weight, ultrasound parameters describing the newborn's body shape as well as parameters describing the newborns endocrine system such as cortisol, aldosterone, renin activity and fetal glycated serum protein in a birth cohort of 899 father/mother/child triplets. Since fetal programming is an offspring sex specific process, male and female offspring were analyzed separately. Multivariable regression analyses considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal total glycated serum protein, parity and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding showed that paternal BMI is associated with growth of the male but not female offspring. Paternal BMI correlated with birth parameters of male offspring only: birth weight; biparietal diameter, head circumference; abdominal diameter, abdominal circumference; and pectoral diameter. Cortisol was likewise significantly correlated with paternal BMI in male newborns only. | Is paternal body mass index ( BMI ) associated with offspring intrauterine growth in a gender dependent manner? | Yes. Paternal BMI affects growth of the female but not male offspring. Paternal BMI may thus represent a risk factor for cardiovascular diseases of female offspring in later life. It remains to be demonstrated whether this is linked to an offspring sex specific paternal programming of cortisol secretion. | FAIL | pubmedQA | 0 |
8426215 | A retrospective analysis was performed to evaluate the role of surgery in the management of patients with solitary and multiple brain metastases.
Between 1980 and 1990, 46 patients underwent surgical resection of brain metastases at the University of Colorado Health Sciences Center. All but two patients received postoperative whole-brain radiotherapy to a median total dose of 30 Gy (range, 11.4 Gy to 50.0 Gy). Lung was the most common (56%) primary site and adenocarcinoma was the most common (46%) tumor histology. Twenty-eight of 46 patients (61%) had solitary metastases, while the remaining 18 patients had two or more foci.
The median survival of all 46 patients was 11 months, and the 1- and 2-year survival rates were 40% and 12%, respectively. Moderately severe to severe neurologic impairment at the time of diagnosis and the presence of multiple brain metastases were associated with a significantly poorer survival. In patients with solitary metastasis, gross total resection and adenocarcinoma tumor histology significantly prolonged survival, whereas primary tumor site, the presence of active extracranial disease, and radiation dose had no significant effect on survival. | Are multiple brain metastases associated with poor survival in patients treated with surgery and radiotherapy? | Yes. These results are consistent with a recent randomized study supporting the role of surgery and whole-brain radiation therapy in the management of patients with multiple brain metastases. We would caution against the generalization of this concept to patients with solitary brain metastases. | FAIL | pubmedQA | 0 |
14697293 | Local recurrences after cryoablation of liver tumors have been reported at rates from 5% to 44% and can be caused by inadequate coverage of the tumor by the frozen region. Hepatic vascular inflow occlusion may facilitate ablation by enlarging the size of the frozen region and the tissue necrosis induced by freezing. Few studies have documented these effects of inflow occlusion during liver cryoablation.
Two cryolesions were induced in the liver of 12 pigs in a standardized set-up. Vascular inflow occlusion was used in six pigs during freezing. Two freeze cycles were performed at each location. Ice-ball volume was estimated by intraoperative magnetic resonance imaging. Cryolesion volume was estimated from histopathologic examination of the lesions 4 days after ablation.
The median volume of ice-balls produced during inflow occlusion was 107% larger than for ice-balls produced without occlusion (P < 0.001). The median volume of cryolesions made during inflow occlusion was 195% larger than for cryolesions induced without occlusion (P < 0.001). The geometry of the ice-balls was more regular if produced during inflow occlusion than if not. The ice-balls produced during the second freeze cycle were 17% and 20% larger than the ice-ball produced during the first freeze for lesions made with (P = 0.01) and without (P = 0.03) inflow occlusion. | Does hepatic vascular inflow occlusion enhance tissue destruction during cryoablation of porcine liver? | No. Hepatic vascular inflow occlusion does not enhance freezing of larger volumes of liver tissue nor increase the volume of tissue necrosis induced during cryoablation of porcine liver. | FAIL | pubmedQA | 0 |
27406942 | Children with short bowel syndrome (SBS) can vary significantly in their growth trajectory. Recent data have shown that children with SBS possess a unique gut microbiota signature compared with healthy controls. We hypothesized that children with SBS and poor growth would exhibit more severe gut microbiota dysbiosis compared with those with SBS who are growing adequately, despite similar intestinal anatomy.
Stool samples were collected from children with SBS (n = 8) and healthy controls (n = 3) over 3 months. Gut microbiota populations (16S ribosomal RNA sequencing and metagenomic shotgun sequencing) were compared, including a more in-depth analysis of SBS children exhibiting poor and good growth. Statistical analysis was performed using Mann-Whitney, Kruskal-Wallis, and χ
Children with SBS had a significant deficiency of the commensal Firmicutes order Clostridiales (P = .025, Kruskal-Wallis) compared with healthy children. Furthermore, children with SBS and poor growth were deficient in beneficial bacteria known to produce short-chain fatty acids and had expansion of proinflammatory Enterobacteriaceae (P = .038, Kruskal-Wallis) compared with children with SBS who were growing adequately. Using metabolic function analyses, SBS/poor growth microbiomes were deficient in genes needed for gluconeogenesis but enriched in branched and aromatic amino acid synthesis and citrate cycle pathway genes. | Does severe Gut Microbiota Dysbiosis be Associated With Poor Growth in Patients With Short Bowel Syndrome? | No. Patients with SBS, particularly those with suboptimal growth, do not have a marked gut dysbiosis and have a similar composition of gut microbiota as healthy children. | FAIL | pubmedQA | 0 |
21068611 | Hemorrhage and coagulopathy are major contributors to death after trauma. The contribution of red blood cells (RBCs) in correcting coagulopathy is poorly understood. Current methods of measuring coagulopathy may fail to accurately characterize in vivo clotting. We aimed to determine the effect of RBCs on clotting parameters by comparing resuscitation regimens containing RBCs and plasma with those containing plasma alone.
Thirty-two Yorkshire swine were anesthetized, subjected to a complex model of polytrauma and hemorrhagic shock, and resuscitated with either fresh frozen plasma, lyophilized plasma (LP), or 1:1 ratios of fresh frozen plasma:packed RBC (PRBC) or LP:PRBC. Activated clotting time, prothrombin time, partial thromboplastin time, and thrombelastography (TEG) were performed at 1 hour, 2 hours, 3 hours, and 4 hours after resuscitation.
Animals treated with 1:1 LP:PRBC had less blood loss than the other groups (p < 0.05). The activated clotting time was shorter in the 1:1 groups when compared with the pure plasma groups at all time points (p < 0.05). The 1:1 groups had shorter TEG R times (time to onset of clotting) at 1 hour, 3 hours, and 4 hours compared with pure plasma groups (p < 0.05). Other TEG parameters did not differ between groups. Partial thromboplastin time was shorter in the pure plasma groups than the 1:1 groups at all time points (p < 0.05). | Do red blood cells accelerate the onset of clot formation in polytrauma and hemorrhagic shock? | No. Whole blood assays reveal that RBCs do not accelerate the onset of clot formation. Coagulation assays using spun plasma accurately characterize clot formation and the effect of RBCs on clotting. | FAIL | pubmedQA | 0 |
19884690 | Tuberculosis (TB) is an important cause of mortality and morbidity in human immunodeficiency virus (HIV) infection in Africa. The interaction between TB and HIV infections is reviewed.
Literature on TB, HIV and their co-infection, especially in sub-Saharan Africa, including Nigeria, is reviewed.
Burden of TB is fueled by the HIV epidemic, and clinical presentation of TB may be atypical with co-infection. Recommendations on drugs and timing of antiretroviral therapy (ART) initiation are discussed. Use of cotrimoxazole prophylaxis (CPT) in co-infected patients reduces morbidity and mortality, while the principles of TB prevention in HIV infection can be summarized with the three I's: intensive TB case finding and surveillance, isoniazid preventive therapy (IPT) and infection-control measures; to these can be added a fourth 'I,' viz., instituting ART. Clinical complications like drug resistance, toxicity and drug interactions; and immune reconstitution inflammatory syndrome (IRIS) with CPT, IPT and ART are highlighted. Emergence of drug-resistant- and nosocomial- TB in HIV infection poses serious challenges and potential consequences in Africa, and appropriate measures are recommended. | Do a clinical and epidemiologic update on the interaction between tuberculosis and human immunodeficiency virus infection in adults? | Yes. Many barriers exist for optimizing the care of the two diseases, but the aim should be strengthening capacities, collaborations, linkages and eventually integrating the services. Interventions for TB prevention in HIV infection should be limited to high-risk populations. | FAIL | pubmedQA | 0 |
23221421 | We have shown that indomethacin has the potential to activate Ca2+/ calmodulin-dependent protein kinase II (CaMKII), regardless of cyclooxygenase (COX) inhibition. To understand the underlying mechanism, the present study investigated the effect of indomethacin on protein phosphatases such as protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A), and protein tyrosine phosphatase 1B (PTP1B).
Activity of CaMKII was assayed in cultured rat hippocampal neurons and under the cell-free conditions. Activities of protein phosphatases were monitored under the cell-free conditions. Indomethacin binding assay was carried out using a fluorescein-conjugated indomethacin.
Indomethacin enhanced CaMKII activity in cultured rat hippocampal neurons, that is abolished the CaMKII inhibitor KN-93. In the cell-free assay, no CaMKII activation was obtained with indomethacin, but indomethacin otherwise inhibited PP1 in a concentration (10 µM-1 mM)-dependent manner, the maximum reaching 70% of basal levels. This indicates that indomethacin indirectly activates CaMKII due to PP1 inhibition. Likewise, indomethacin still inhibited PP2A and PTP1B in a concentration (10 µM-1 mM)-dependent manner, reaching 80 and 10% of basal levels at 1 mM, respectively. In the indomethacin binding assay, indomethacin bound to all the investigated protein phosphatases. | Does indomethacin serve as a potential inhibitor of protein phosphatases? | Yes. The results of the present study indicate that indomethacin inhibits PP1, PP2A, and PTP1B, possibly through its direct binding and that the inhibitory effect of indomethacin on PP1 could cause indirect CaMKII inhibition. This may represent the novel indomethacin action. | FAIL | pubmedQA | 0 |
19344532 | Plastids arose from a free-living cyanobacterial endosymbiont and multiply by binary division as do cyanobacteria. Plastid division involves nucleus-encoded homologs of cyanobacterial division proteins such as FtsZ, MinD, MinE, and ARC6. However, homologs of many other cyanobacterial division genes are missing in plant genomes and proteins of host eukaryotic origin, such as a dynamin-related protein, PDV1 and PDV2 are involved in the division process. Recent identification of plastid division proteins has started to elucidate the similarities and differences between plastid division and cyanobacterial cell division. To further identify new proteins that are required for plastid division, we characterized previously and newly isolated plastid division mutants of Arabidopsis thaliana.
Leaf cells of two mutants, br04 and arc2, contain fewer, larger chloroplasts than those of wild type. We found that ARC2 and BR04 are identical to nuclear genes encoding the plastid chaperonin 60 alpha (ptCpn60alpha) and chaperonin 60 beta (ptCpn60beta) proteins, respectively. In both mutants, plastid division FtsZ ring formation was partially perturbed though the level of FtsZ2-1 protein in plastids of ptcpn60beta mutants was similar to that in wild type. Phylogenetic analyses showed that both ptCpn60 proteins are derived from ancestral cyanobacterial proteins. The A. thaliana genome encodes two members of ptCpn60alpha family and four members of ptCpn60beta family respectively. We found that a null mutation in ptCpn60alpha abolished greening of plastids and resulted in an albino phenotype while a weaker mutation impairs plastid division and reduced chlorophyll levels. The functions of at least two ptCpn60beta proteins are redundant and the appearance of chloroplast division defects is dependent on the number of mutant alleles. | Are plastid chaperonin proteins Cpn60 alpha and Cpn60 beta required for plastid division in Arabidopsis thaliana? | No. Our results suggest that neither ptCpn60alpha nor ptCpn60beta are required for the formation of a normal plastid division apparatus, as the prokaryotic counterparts are not required for assembly of the cell division apparatus. Since moderate reduction of ptCpn60 levels did not impair normal FtsZ ring formation but did affect import of FtsZ into plastids, it is suggested that the proper levels of ptCpn60 are not required for folding of stromal plastid division proteins and/or regulation of FtsZ polymer dynamics. | FAIL | pubmedQA | 0 |
19228708 | Following injury, fibroblasts transform into myofibroblasts and produce extracellular matrix (ECM). Excess production of ECM associated with cardiac fibrosis severely inhibits cardiac function. Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, regulates the function of numerous cell types. In this study, we determined the role of S1P in promoting pro-fibrotic actions of cardiac fibroblasts (CFs).
S1P-mediated effects on myofibroblast transformation, collagen production, and cross-talk with transforming growth factor-beta (TGF-beta) using mouse CF were examined. S1P increased alpha-smooth muscle actin (a myofibroblast marker) and collagen expression in a S1P2 receptor- and Rho kinase-dependent manner. TGF-beta increased sphingosine kinase 1 (SphK1; the enzyme responsible for S1P production) expression and activity. TGF-beta-stimulated collagen production was inhibited by SphK1 or S1P2 siRNA, a SphK inhibitor, and an anti-S1P monoclonal antibody. | Are sphingosine-1-phosphate and sphingosine kinase critical for transforming growth factor-beta-stimulated collagen production by cardiac fibroblasts? | No. These findings suggest that TGF-beta-stimulated collagen production in CF does not involve 'inside-out' S1P signalling and that S1P produced intracellularly by SphK1 is not released to act in an autocrine/paracrine fashion to activate S1P2 and increase collagen production. | FAIL | pubmedQA | 0 |
21295874 | To compare CT-, MR- and PET-CT based tumor length measurements in rectal cancer with pathology.
Twenty-six rectal cancer patients underwent both MR and PET-CT imaging followed by short-course radiotherapy (RT 5×5 Gy) and surgery within 3 days after RT. Tumor length was measured manually and independently by 2 observers on CT, MR and PET. PET-based tumor length measurements were also generated automatically using the signal-to-background-ratio (SBR) method. All measurements were correlated with the tumor length on the pathological specimen.
CT-based measurements did not show a valuable correlation with pathology. MR-based measurements correlated only weakly, but still significantly (Pearson correlation=0.55 resp. 0.57; p<0.001). Manual PET measurements reached a good correlation with pathology, but less strong (Pearson correlation 0.72 and 0.76 for the two different observers) than automatic PET-CT based measurements, which provided the best correlation with pathology (Pearson correlation of 0.91 (p<0.001)). Bland-Altman analysis demonstrated in general an overestimation of the tumor diameter using manual measurements, while the agreement of automatic contours and pathology was within acceptable ranges. A direct comparison of the different modalities revealed a significant better precision for PET-based auto-contours as compared to all other measurements. | Does fDG-PET provide the best correlation with the tumor specimen compared to MRI and CT in rectal cancer? | No. Automatically generated PET-CT based contours do not show the best correlation with the surgical specimen and thus do not provide a useful and powerful tool to accurately determine the largest tumor dimension in rectal cancer. This could not be used as a quick and reliable tool for target delineation in radiotherapy. However, a 3D volume analysis is needed to confirm these results. | FAIL | pubmedQA | 0 |
21429569 | Asymmetric dimethylarginine (ADMA) is a potent endogenous inhibitor of nitric oxide (NO) synthase. An increased synthesis and/or a reduced catabolism of ADMA might contribute to the onset and progression of thrombosis. The present study was designed to evaluate the effect of ADMA on fibrinolytic factors in endothelial cells, and to investigate the cellular mechanisms.
Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of ADMA for various periods; Then HUVECs were preincubated with NO precursor (L-arginine), MAPK inhibitors, or NF-κB inhibitor (PDTC) before ADMA treatment to repeat the experiment. Protein levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), and NF-κB activity were measured by ELISA; mRNA levels of tPA and PAI-1 were assayed by qRT-PCR; The activation of MAPK was characterized by western blot analysis.
(1) ADMA decreased tPA antigen levels in time- and concentration-dependent manners, with the maximum effect of 30 μmol/L ADMA for 48h (control 109.01 ± 4.15 ng/ml vs ADMA 86.76 ± 5.95 ng/ml, p<0.01); (2) 30 μmol/L ADMA elevated antigen levels of PAI-1 in a time-dependent manner, with the maximum effect of 30 μmol/L ADMA for 48 h (control 2721.12 ± 278.02 ng/ml vs. ADMA 3435.78 ± 22.33ng/ml, p<0.05); (3) ADMA reduced tPA mRNA levels and increased PAI-1 mRNA levels; (4) L-arginine, SB203580 (p38 MAPK inhibitor) and PDTC attenuated the effects of ADMA on tPA and PAI-1 significantly. (5) ADMA induced a rapid phosphorylation of p38 MAPK, and stimulated NF-κB activity greatly. | Does asymmetric dimethylarginine impair fibrinolytic activity in human umbilical vein endothelial cells via p38 MAPK and NF-κB pathways? | Yes. ADMA may accelerate thrombosis development by impairing fibrinolytic activity in vascular via inhibiting nitric oxide production and then activating its downstream ERK1/2 and NF-κB pathways. | FAIL | pubmedQA | 0 |
25829783 | Bacopa monnieri (L.) Pennell, commonly known as Brahmi is an important medicinal plant traditionally used as memory enhancer and antiepileptic agent.
The present study investigated antioxidant and stress resistance potentials of B. monnieri aqueous extract (BMW) using Caenorhabditis elegans animal model system.
The antioxidant activity of the BMW was measured using in vitro (DPPH, reducing power and total polyphenol content) and in vivo (DCF-DA assay) assays. The antistress potential of BMW (0.1, 0.01, and 0.001 mg/ml) was evaluated through thermal stress (37°C) and oxidative stress (10 mM paraquat) using C. elegans. Quantification of the HSP-16.2 level was done using CL2070 transgenic worms.
Present study reveals that BMW possess in vitro and in vivo antioxidant activities. BMW significantly enhanced stress tolerance and increased the mean lifespan of worms during thermal and oxidative stress, although it did not extend lifespan at 20°C and attenuated age dependent decline in physiological behaviors. Moreover, it was shown that BMW was able to up-regulate expression of stress associated gene hsp-16.2, which significantly (P < 0.001) extends the mean lifespan of worms under stress conditions. | Does bacopa monnieri promote longevity in Caenorhabditis elegans under stress conditions? | Yes. The study strongly suggests that BMW acts as an antistressor and potent reactive oxygen species scavenger which enhances the survival of the worms in normal conditions. | FAIL | pubmedQA | 0 |
25708760 | Stool-based colonoscopy is the preferred strategy for colorectal cancer (CRC) screening. The Asia-Pacific Colorectal Screening System (APCS) score also is helpful in stratifying the risk for advanced neoplasia in the asymptomatic population. The combination of the fecal immunochemical test (FIT) result and clinical risk stratification may be more helpful in stratifying the risk.
To evaluate the value of the combination of FIT and APCS scores in stratifying asymptomatic participants for colonoscopy.
Cross-sectional study.
University hospital.
A total of 948 asymptomatic participants eligible for screening colonoscopy.
FIT, APCS score evaluation, screening colonoscopy.
The prevalence of colorectal neoplasia in 4 different groups of participants according to FIT and APCS score evaluations.
The prevalence of non-advanced and advanced neoplasia in the 4 groups (high risk with positive FIT result, high risk with negative FIT result, moderate risk with positive FIT result, and moderate risk with negative FIT result) was 44% versus 36.9%, 30.1% versus 11.6%, 27.1% versus 12%, and 22.6% versus 6.4%, respectively (P < .001). Participants with both high-risk scores and positive FIT results had a significantly higher detection rate of advanced neoplasia (6.15-fold, 95% confidence interval, 3.72-10.17) compared with the other 3 groups. Seven cancers were discovered; 4 were in the high-risk with positive FIT result group. | Does a combination of clinical risk stratification and fecal immunochemical test result to prioritize colonoscopy screening in asymptomatic participants? | No. Hospital-based study. | FAIL | pubmedQA | 0 |
18795901 | Carbon monoxide (CO) produced by haem-oxygenase isoforms (HO-1 & HO-2) is involved in the regulation of systemic vascular tone. We aimed to elucidate the vasoregulatory role of CO in the microcirculation in normal and thioacetamide cirrhotic rat livers.
Haem-oxygenase expression was examined by Western blot. Total HO enzymatic activity was measured spectrophotometrically. Sensitivity of hepatic stellate cells (HSCs) to CO-mediated relaxation was studied by a stress-relaxed-collagen-lattice model. To define the relative role of CO, the CO-releasing molecule CORM-2, the HO-inhibitor zinc protoporphyrin-IX and the HO-1 inducer hemin were added to an in situ liver perfusion set-up. The topography of vasoactive CO production was evaluated by applying different CO- and nitric oxide-trapping reagents in the liver perfusion set-up and by immunohistochemistry.
Western blot showed decreased expression of both HO isoenzymes (P<0.036 for HO-1; P<0.001 for HO-2) in cirrhotic vs normal rat livers, confirmed by the HO-activity assay (P=0.004). HSCs relaxed on exposure to CORM-2 (P=0.013). The increased intrahepatic vascular resistance (IHVR) of cirrhotic rats was attenuated by perfusion with CORM-2 (P=0.016) and pretreatment with hemin (P<0.001). Inhibition of HO caused a dose-related increase in IHVR in normal and cirrhotic liver. In normal liver, the haemodynamically relevant CO production occurred extrasinusoidally, while intrasinusoidally HO-1 predominantly regulated the microcirculation in cirrhotic livers. | Does carbon monoxide produced by intrasinusoidally located haem-oxygenase-1 regulate the vascular tone in cirrhotic rat liver? | No. We demonstrate that CO and HO do not play a role in the regulation of normal and cirrhotic microcirculation. These findings are of importance in the pathophysiology of portal hypertension and establish CO/HO as irrelevant treatment targets. | FAIL | pubmedQA | 0 |
17225881 | Liver transplantation (LT) offers a possible cure for patients with hepatocellular carcinoma (HCC) and cirrhosis. However, tumour progression while on the waiting list and tumour recurrence after LT are common. The prognostic significance of various pre- and postoperative variables were investigated in regard to tumour recurrence, with an emphasis on the slope of preoperative serum alpha-fetoprotein (AFP) levels. patients and
Data from 48 patients who had HCC diagnosed preoperatively and underwent LT at the McGill University Health Centre (Montreal, Quebec) were reviewed retrospectively, and possible risk factors for tumour recurrence were examined.
Univariate analysis revealed a positive correlation between the preoperative AFP slope and vascular invasion (P = 0.045), total tumour diameter at explant (P = 0.040), Cancer of the Liver Italian Program score (P = 0.017) and recurrence-free survival (P = 0.028). Of the preoperative variables examined, only the preoperative AFP slope was identified as an independent predictor of tumour recurrence by multivariate analysis. Receiver operating characteristic analysis showed that the best discriminant cut-off value, calculated as the value of the maximized likelihood ratio, was preoperative AFP slope greater than 50 microg/L per month. At this cut-off, sensitivity was 36%, and specificity was 97%. Patients with a preoperative AFP slope greater than 50 microg/L per month had a much worse one-year recurrence-free survival rate than those with a preoperative AFP slope 50 microg/L per month or less (40% versus 90%, P < 0.001). | Is preoperative alpha-fetoprotein slope predictive of hepatocellular carcinoma recurrence after liver transplantation? | No. These results suggest that the preoperative AFP slope is not an important predictor of HCC recurrence after LT and should not be examined in future studies of patients receiving LT for HCC. | FAIL | pubmedQA | 0 |
24503192 | The aim of this study was to measure the capacity of glucose- and weight-related parameters to predict pregnancy-induced hypertensive disorders in women with gestational diabetes.
An observational study was conducted involving 2037 women with gestational diabetes. The associations of glycaemic and weight-related parameters with pregnancy-induced hypertensive disorders were obtained by univariate and adjusted multivariate analyses. Also, model predictability and attributable predictor risk percentages were calculated, and collinearity and factor interactions examined.
Multivariate analyses revealed that hypertensive disorders were mainly predicted by average third-trimester glycated haemoglobin (HbA(1c)) levels ≥ 5.9%, by being overweight or obese before pregnancy and by excess gestational weight gain after adjusting for age, tobacco use, chronic hypertension, parity, urinary tract infections and gestational age at delivery. Prepregnancy body weight (overweight and obesity) had the strongest impact on pregnancy-related hypertensive disorders (attributable risk percentages were 51.5% and 88.8%, respectively). The effect of being overweight or obese on hypertensive disorders was enhanced by HbA(1c) levels and gestational weight gain, with elevated HbA(1c) levels multiplying the effect of being overweight before pregnancy. | Are body weight , weight gain and hyperglycaemia associated with hypertensive disorders of pregnancy in women with gestational diabetes? | Yes. The average third-trimester HbA1c level is a novel risk factor for pregnancy-induced hypertensive disorders in women with gestational diabetes. HbA(1c) levels ≥ 5.9%, prepregnancy underweight and excess gestational weight gain are all independent risk factors of pregnancy-related hypertensive disorders in such women. In treated gestational diabetes patients, the strongest influence on hypertensive disorders is prepregnancy underweight. | FAIL | pubmedQA | 0 |
17239166 | Sepsis is a life-threatening disorder resulting from systemic inflammatory and coagulatory responses to infection. High-mobility group box 1 protein (HMGB1), an abundant intranuclear protein, was recently identified as a potent lethal mediator of sepsis. However, the precise mechanisms by which HMGB1 exerts its lethal effects in sepsis have yet to be confirmed. We recently reported that plasma HMGB1 levels correlated with disseminated intravascular coagulation (DIC) score, indicating that HMGB1 might play an important role in the pathogenesis of DIC.
To investigate the mechanisms responsible for the lethal effects of HMGB1, and more specifically, to explore the effects of HMGB1 on the coagulation system.
Rats were exposed to thrombin with or without HMGB1, and a survival analysis, pathologic analyses and blood tests were conducted. The effects of HMGB1 on the coagulation cascade, anticoagulant pathways and surface expression of procoagulant or anticoagulant molecules were examined in vitro.
Compared to thrombin alone, combined administration of thrombin and HMGB1 resulted in excessive fibrin deposition in glomeruli, prolonged plasma clotting times, and increased mortality. In vitro, HMGB1 did not affect clotting times, but inhibited the anticoagulant protein C pathway mediated by the thrombin-thrombomodulin complex, and stimulated tissue factor expression on monocytes. | Does high-mobility group box 1 protein promote development of microvascular thrombosis in rats? | No. These findings demonstrate that HMGB1 does not play a significant role in the development of DIC during sepsis. | FAIL | pubmedQA | 0 |
23035925 | Directional preferences during center-out horizontal shoulder-elbow movements were previously established for both the dominant and non-dominant arm with the use of a free-stroke drawing task that required random selection of movement directions. While the preferred directions were mirror-symmetrical in both arms, they were attributed to a tendency specific for the dominant arm to simplify control of interaction torque by actively accelerating one joint and producing largely passive motion at the other joint. No conclusive evidence has been obtained in support of muscle effort minimization as a contributing factor to the directional preferences. Here, we tested whether distal load changes directional preferences, making the influence of muscle effort minimization on the selection of movement direction more apparent.
The free-stroke drawing task was performed by the dominant and non-dominant arm with no load and with 0.454 kg load at the wrist. Motion of each arm was limited to rotation of the shoulder and elbow in the horizontal plane. Directional histograms of strokes produced by the fingertip were calculated to assess directional preferences in each arm and load condition. Possible causes for directional preferences were further investigated by studying optimization across directions of a number of cost functions.
Preferences in both arms to move in the diagonal directions were revealed. The previously suggested tendency to actively accelerate one joint and produce passive motion at the other joint was supported in both arms and load conditions. However, the load increased the tendency to produce strokes in the transverse diagonal directions (perpendicular to the forearm orientation) in both arms. Increases in required muscle effort caused by the load suggested that the higher frequency of movements in the transverse directions represented increased influence of muscle effort minimization on the selection of movement direction. This interpretation was supported by cost function optimization results. | Does load emphasize muscle effort minimization during selection of arm movement direction? | Yes. While without load, the contribution of muscle effort minimization was minor, and therefore, not apparent, the load revealed this contribution by diminishing it. Unlike control of interaction torque, the revealed tendency to minimize muscle effort was independent of arm dominance. | FAIL | pubmedQA | 0 |
24589771 | Traumatic brain injury (TBI) is a worldwide health problem with oxidative stress recognized as a major pathogenetic factor. The present experimental study was designed to explore the neuroprotective effect of NADPH oxidase (NOX) inhibitor, apocynin, on mouse TBI.
Moderately severe weight-drop impact head injury was induced in adult male mice, randomly divided into four groups: sham, TBI, TBI+vehicle and TBI+apocynin treatment. Apocynin (50 mg/kg) was injected intraperitoneally 30 min before TBI. The expression of NOX2 protein was investigated using immunoblotting techniques 1 and 24h after TBI. Neurological score was evaluated 24h after TBI. Blood-brain barrier disruption was detected by Evans blue extravasation and cortical apoptosis was analyzed by TUNEL assay. Additionally, we assessed tissue levels of malondialdehyde (MDA).
NOX2 expression increased rapidly following TBI in male mice, with an early peak at 1h, followed by a second peak at 24h. Pre-treatment with the NOX inhibitor, apocynin markedly inhibited NOX2 expression. Apocynin also attenuated MDA levels and TBI-induced blood-brain barrier dysfunction. In addition apocynin significantly attenuated TBI-induced neurological deficits and cortical apoptosis. | Does nADPH oxidase inhibition improve neurological outcome in experimental traumatic brain injury? | No. Pre-treatment with apocynin does not effectively attenuate markers of cerebral oxidative stress after TBI, thus not supporting the hypothesis that apocynin is a potential neuroprotectant and adjunct therapy for TBI patients. | FAIL | pubmedQA | 0 |
10378546 | To investigate whether the localization of multiple sclerosis (MS), the duration of the disease, and the level of neurologic functioning in patients with MS predispose them to disturbed breathing control.
Case-control study.
Outpatient pneumology department of a university hospital.
Twenty-three MS patients and 51 healthy control subjects.
Resting mouth occlusion pressure at 0.1 s after onset of inspiratory effort (P0.1) was measured during the hypercapnic response (HCR) and the hypoxic response (HR) in all subjects. The Kurtzke expanded disability status scale and the functional system score were used to describe the level of neurologic functioning of the MS patients. Predictors of HCR and HR were assessed by multiple regression analysis. Low maximal inspiratory pressure (MIP) values correlated with low resting P0.1 values (r = 0.44; p = 0.05), although in neuromuscular diseases, high resting P0.1 values are usually found to compensate for low MIPs. Detrusor-sphincter dyssynergia (DSD) was the only predictor for lower ventilatory HCR (p = 0.006; r2 = 0.52), lower P0.1 HCR (p = 0.004; r2 = 0.47), lower ventilatory HR (p = 0.04; r2 = 0.28), and lower P0.1 HR (p = 0.04; r2 = 0.10); low MIPs and pyramidal tract involvement had no role. | Are micturitional disturbances associated with impaired breathing control in multiple sclerosis? | Yes. (1) Impaired control of breathing in some MS patients is related mainly to peripheral defects. (2) DSD is the most important predictor of disturbed ventilatory control, presumably because the micturition and pneumotaxic center are closely related and located in the rostral pons. (3) No relationship with the duration of the MS disease could be demonstrated, which can be explained by the variable course of MS itself. | FAIL | pubmedQA | 0 |
27863926 | The oncogenic PI3K/Akt/mTOR pathway is frequently activated in hepatocellular carcinoma (HCC). The aim of this study is to investigate the anti-HCC effect of combination of temsirolimus, an mTOR inhibitor, and adriamycin, a routinely used drug for treating HCC.
Proliferation of HCC cells exposure to temsirolimus, adriamycin, and their combination was determined using MTT assay in vitro as well as in a nude mice model in vivo. Cell apoptosis was examined using flow cytometry. Expressions of apoptosis-related proteins including caspase-9, -3, PARP, Bax, and Bcl-2 were determined using Western blotting.
Temsirolimus plus adriamycin showed an enhanced inhibitory effect on cell proliferation compared to temsirolimus or adriamycin in HCC cells PLC/PRF/5, BEL7402, and HuH7 in vitro. The drug combination solicited a higher percentage of apoptosis cells and induced higher levels of cleaved caspase-9, -3, and PARP than temsirolimus or adriamycin used alone. The ratio of Bax/Bcl-2 was increased in cells exposed to the combination treatment. The enhanced anti-tumor effect of this drug combination was verified in a nude mice model. We also observed that half doses of temsirolimus and adriamycin used in combination achieved a comparable tumor growth inhibitor rate with full dose of temsirolimus or adriamycin used alone. | Does combination of temsirolimus and adriamycin exhibit an enhanced antitumor effect in hepatocellular carcinoma? | No. Temsirolimus plus adriamycin did not exhibit an enhanced antitumor effect in HCC and this drug combination might not have a potential value in treatment of HCC. Studies are warranted to comprehensively evaluate the efficacy and safety of this regimen in the future. | FAIL | pubmedQA | 0 |
25062768 | Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension which is often difficult to manage, and a significant cause of morbidity and mortality. In this study, we have used a rabbit model of CDH to evaluate the effects of BAY 60-2770 on the in vitro reactivity of left pulmonary artery.
CDH was performed in New Zealand rabbit fetuses (n = 10 per group) and compared to controls. Measurements of body, total and left lung weights (BW, TLW, LLW) were done. Pulmonary artery rings were pre-contracted with phenylephrine (10 μM), after which cumulative concentration-response curves to glyceryl trinitrate (GTN; NO donor), tadalafil (PDE5 inhibitor) and BAY 60-2770 (sGC activator) were obtained as well as the levels of NO (NO3/NO2).
LLW, TLW and LBR were decreased in CDH (p < 0.05). In left pulmonary artery, the potency (pEC50) for GTN was markedly lower in CDH (8.25 ± 0.02 versus 9.27 ± 0.03; p < 0.01). In contrast, the potency for BAY 60-2770 was markedly greater in CDH (11.7 ± 0.03 versus 10.5 ± 0.06; p < 0.01). The NO2/NO3 levels were 62 % higher in CDH (p < 0.05). | Does the soluble guanylyl cyclase activator BAY 60-2770 potently relax the pulmonary artery on congenital diaphragmatic hernia rabbit model? | No. BAY 60-2770 does not exhibit a greater potency to relax the pulmonary artery in CDH, indicating it may not be useful for pulmonary hypertension in this disease. | FAIL | pubmedQA | 0 |
7553392 | TGF-beta 1-coated beta-TCP pellets were grafted in experimental defects of rat calvariae to study the effects on new bone formation.
The grafted sites were evaluated by light microscopy using hematoxylin-eosin (H-E) staining for histology and detection of alkaline phosphatase (ALPase) and tartrate-resistant acid phosphatase (TRACPase) activities to demonstrate osteoblastic and osteoclastic cells. Confocal laser scanning microscopy (CLSM) was performed for morphometry of newly formed bone.
H-E sections showed more new bone formation in sites grafted with TGF-beta 1-coated beta-TCP pellets (experimental sites) than those with beta-TCP pellets only (control sites). TRACPase-positive and ALPase-positive cells at experimental sites were more frequent than at control sites. The bone formation rate calculated by computerized CLSM pixel image analysis showed more new bone formation at the experimental sites than at control sites (3.4 +/- 0.8% vs 9.3 +/- 1.7% on week 2 and 11.8 +/- 2.1% vs 39.8 +/- 10.9% on week 4). | Do transforming growth factor-beta 1 coated beta-tricalcium phosphate pellets stimulate healing of experimental bone defects of rat calvariae? | No. TGF-beta 1-coated beta-TCP pellets do not promote new bone formation and may not be a useful modality in synthetic bone grafting. | FAIL | pubmedQA | 0 |
23133486 | Single-nucleotide polymorphism (SNP) markers within LIN28B have been reported to be related to the timing of pubertal growth. However, no study has investigated the frequency of genetic markers in girls with precocious puberty (PP) or early puberty (EP). This study aimed to determine the frequency of putative genetic markers in girls with PP or EP.
Genomic DNAs were obtained from 77 and 109 girls that fulfilled the criteria for PP and EP, respectively. The controls in this study were 144 healthy volunteers between 20 and 30 years of age. The haplotypes were reconstructed using 11 SNPs of LIN28B, and haplotype association analysis was performed. The haplotype frequencies were compared. Differences in the clinical and laboratory parameters were analyzed according to the haplotype dosage.
Eleven SNPs in LIN28B were all located in a block that was in linkage disequilibrium. The haplotype could be reconstructed using 2 representative SNPs, rs4946651 and rs369065. The AC haplotype was less frequently observed in the PP group than in the controls (0.069 vs. 0.144, P=0.010). The trend that girls with non-AC haplotypes tended to have earlier puberty onset (P=0.037) was illustrated even in the EP+PP patient group by Kaplan-Meier analysis. | Are lIN28B polymorphisms associated with central precocious puberty and early puberty in girls? | No. The results of the present study showed that non-AC haplotypes of LIN28B had no significant association with PP in girls. | FAIL | pubmedQA | 0 |
18751465 | A growing body of data indicates an independent association between serum gamma-glutamyltransferase (GGT) activity, a marker of increased oxidative stress, and cardiovascular diseases. The process of calcific aortic valve disease has been shown to present characteristics of atherosclerosis. The study aim was to evaluate the possible role of serum GGT in patients with calcific aortic valve disease.
The results of patients' echocardiography studies from 2005 for the presence of calcific aortic valve disease in the forms of aortic stenosis (AS) and aortic valve calcification (AVC) without significant valve stenosis, were retrospectively evaluated. Age-and gender-matched patients with normal aortic valve morphology were selected at random as a control group. A total of 383 patients was enrolled into the study (126 with AS, 133 with AVC, 124 controls). Serum GGT activity, along with other liver enzyme analyses and laboratory results, were determined and compared among the groups.
Age, gender and clinical and laboratory results were similar among the three groups. Median serum GGT levels in the AS, AVC and control groups were 23.0 U/1 (mean 31.5 +/- 24.9 U/1), 22.0 U/1 (mean 27.6 +/- 18.6 U/) and 18.0 U/l (mean 22.4 +/- 16.4 U/l), respectively. Compared to controls, AS patients had significantly higher serum GGT and C-reactive protein levels, while the differences between AVC patients and controls for these parameters were not significant. | Is serum gamma-glutamyltransferase activity increased in patients with calcific aortic valve stenosis? | Yes. The study results suggest that serum GGT activity is increased in patients with calcific AS. These increases seem to occur in both advanced and milder forms of calcific aortic valve disease. | FAIL | pubmedQA | 0 |
22011061 | To report the results from a nationwide survey on glaucoma management in Sweden, performed as a part of an Open Angle Glaucoma project conducted by the Swedish Council on Health Technology Assessment 2004-2008.
In 2005, a survey was distributed to all providers of glaucoma care in Sweden: public eye departments, public outpatient departments and private practices. The questionnaire included questions on number of examined patients, types of examinations during one defined week, internal organization and access to diagnostic equipment. The questionnaire was endorsed by the Swedish Ophthalmological Society. Reminders were sent out to nonresponders.
Response rate was high; 97% (33/34) of eye departments, 85% (39/46) of outpatient departments and 55% (69/125) of private practices. Out of 29 282 visits in ophthalmic care during the study week, 7737 (26%) were related to glaucoma. Diagnostic equipment was generally available; all public eye facilities and 92% of private practices had at least one computerized perimeter, while equipment for fundus photography/imaging was available at 100% of eye departments, 82% of outpatient departments and 62% of private practices. The number of visual field tests and fundus images was rather low. Survey results indicate that patients on the average underwent bilateral field testing every 2nd year and fundus imaging every 8th year. | Does glaucoma management in Sweden -- result from a nationwide survey? | Yes. Glaucoma care generated about a quarter of all patient visits in Swedish ophthalmic care. Access to diagnostic facilities was good. To meet modern standards of glaucoma care, glaucoma damage must be measured and followed more frequently than at the time of the survey, with patients undergoing bilateral field testing every year and fundus imaging every 4 years. | FAIL | pubmedQA | 0 |
18504409 | Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a key rate-limiting enzyme in the mevalonate pathway. Accumulating data suggest that statins exhibit anti-inflammatory effects on a number of experimental models including experimental autoimmune encephalomyelitis and antigen-induced allergic airway inflammation. However, the mechanism underlying the anti-inflammatory effect of statins is still largely unknown. In this study, we examined the effect of a representative statin, simvastatin, on proinflammatory cytokine production from murine mast cells.
Bone marrow-derived mast cells (BMMCs) were stimulated with lipopolysaccharide (LPS) in the presence or absence of simvastatin, and TNF-alpha and IL-6 production from BMMCs was evaluated at mRNA and protein levels. The effect of simvastatin on the expression of tristetraprolin, an RNA-binding protein that promotes decay of TNF-alpha mRNA, was evaluated.
Incubation of BMMCs with simvastatin resulted in the inhibition of LPS-induced TNF-alpha production at both mRNA and protein levels. Simvastatin also inhibited IL-6 production from LPS-stimulated BMMCs. However, simvastatin did not enhance the expression of tristetraprolin. | Does hMG-CoA reductase inhibitor simvastatin inhibit proinflammatory cytokine production from murine mast cells? | Yes. Simvastatin inhibits the production of TNF-alpha and IL-6 from activated mast cells by enhancing the expression of tristetraprolin, an RNA-binding protein that promotes decay of TNF-alpha mRNA, and the inhibition may account for the anti-inflammatory effect of simvastatin. | FAIL | pubmedQA | 0 |
10973847 | Nicotine is a main constituent of cigarette smoke and smokeless tobacco, known to increase the risk of sudden cardiac death. This study aimed at establishing ionic mechanisms underlying potential electrophysiological effects of nicotine.
Effects of nicotine on Kv4.3 and Kv4.2 channels expressed in Xenopus oocytes were studied at the whole-cell and single-channel levels. The effects of nicotine on the transient outward K(+) current (I:(to)) were studied by use of whole-cell patch-clamp techniques in canine ventricular myocytes. Nicotine potently inhibited Kv4 current. The concentration for half-maximal inhibition (IC(50)) was 40+/-4 nmol/L, and the current was abolished by 100 micromol/L nicotine. The IC(50) for block of native I:(to) was 270+/-43 nmol/L. The steady-state activation properties of Kv4.3 and I:(to) were unaltered by nicotine, whereas positive shifts of the inactivation curves were observed. Of the total inhibition of Kv4.3 and I:(to) by nicotine, 40% was due to tonic block and 60% was attributable to use-dependent block. Activation, inactivation, and reactivation kinetics were not significantly changed by nicotine. Nicotine reduced single-channel conductance, open probability, and open time but increased the closed time of Kv4.3. The effects of nicotine were not altered by antagonists to various neurotransmitter receptors, indicating direct effects on I:(to) channels. | Is nicotine a potent blocker of the cardiac A-type K ( + ) channels . Effects on cloned Kv4.3 channels and native transient outward current? | No. Nicotine is not a potent inhibitor of cardiac A-type K(+) channels, and its effects on cardiac electrophysiology are minimal. | FAIL | pubmedQA | 0 |
18676242 | To observe the effect of neural stem cell (NSC) transplantation and nerve growth factor (NGF) on neurological function recovery in rats with ischemic stroke induced by transient middle cerebral artery occlusion (MCAO).
Cultured hippocampal NSCs isolated from neonate rats were labeled with BrdU. Sixty-four rats subjected to transient MCAO were randomized equally into 4 groups, namely group A (MCAO model group), group B (model group with NGF treatment, group C (model group with NSC transplantation), and group D (model group with both NGF and NSC transplantation). The neurological deficits of the rats were evaluated with neurological severity score (NSS) after the treatment, and the brain tissues were examined with immunohistochemical and immunofluorescent staining for BrdU and nestin expression.
The NSS of rats in group D 2 and 4 weeks after transplantation was significantly lower than that in the other 3 groups (P<0.05), and the scores in groups B and C were significantly lower than those in group A (P<0.05). The number of BrdU- and nestin-positive cells was significantly greater in group B than in group A (P<0.05), and BrdU-positive cells were markedly more numerous in group D than in group C (P<0.05). | Do [ Neural stem cell transplantation and nerve growth factor promote neurological recovery in rats with ischemic stroke ]? | Yes. Both NSC transplantation and NGF treatment can obviously improve the neurological function of rats after MCAO, but their combined use shows weaker effects. NGF can promote autologous NSC activation and proliferation, with also stimulatory effect on the proliferation of transplanted NSCs. | FAIL | pubmedQA | 0 |
8736558 | Human thioredoxin (hTRX) is a 12 kDa cellular redox protein that has been shown to play an important role in the activation of a number of transcriptional and translational regulators via a thiol-redox mechanism. This activity may be direct or indirect via another redox protein known as Ref-1. The structure of a complex of hTRX with a peptide comprising its target from the transcription factor NF kappa B has previously been solved. To further extend our knowledge of the recognition by and interaction of hTRX with its various targets, we have studied a complex between hTRX and a Ref-1 peptide. This complex represents a kinetically stable mixed disulfide intermediate along the reaction pathway.
Using multidimensional heteronuclear edited and filtered NMR spectroscopy, we have solved the solution structure of a complex between hTRX and a 13-residue peptide comprising residues 59-71 of Ref-1. The Ref-1 peptide is located in a crescent-shaped groove on the surface of hTRX, the groove being formed by residues in the active-site loop (residues 32-36), helix 3, beta strands 3 and 5, and the loop between beta strands 3 and 4. The complex is stabilized by numerous hydrogen-bonding and hydrophobic interactions that involve residues 61-69 of the peptide and confer substrate specificity. | Does the solution structure of human thioredoxin complexed with its target from Ref-1 reveal peptide chain reversal? | Yes. The orientation of the Ref-1 peptide in the hTRX-Ref-1 complex is the same as that found in the previously solved complex of hTRX with the target peptide from the transcription factor NF kappa B. Orientation is determined by three discriminating interactions involving the nature of the residues at the P-2' P-4 and P-5 binding positions. (P0 defines the active cysteine of the peptide, Cys65 for Ref-1 and Cys62 for NF kappa B. Positive and negative numbers indicate residues N-terminal and C-terminal to this residue, respectively, and vice versa for NF kappa B as it binds in the same orientation.) The environment surrounding the reactive Cys32 of hTRX, as well as the packing of the P+3 to P-4 residues are essentially the same in the two complexes, despite the same orientation of the peptide chains. This versatility in substrate recognition permits hTRX to act as a wide-ranging redox regulator for the cell. | FAIL | pubmedQA | 0 |
27863293 | This study sought to explore the efficacy of the conical stent implantation in the coronary artery by comparing the effects of cylindrical and conical stents on wall shear stress (WSS) and velocity of flow and fractional flow reserve (FFR).
The traditional cylindrical stent currently used in the percutaneous coronary intervention (PCI) has a consistent diameter, which does not match the physiological change of the coronary artery. On the contrary, as a new patent, the conical stent with tapering lumen is consistent with the physiological change of vascular diameter. However, the effect of the conical stent implantation on the coronary hemodynamics remains unclear.
The coronary artery, artery stenosis and two stent models were established by Solidworks software. All models were imported into the computational fluid dynamics (CFD) software ANSYS ICEM-CFD to establish the fluid model. After the boundary conditions were set, CFD analysis was proceeded to compare the effects of two stent implantation on the change of WSS, velocity of flow and FFR.
Hemodynamic indexes including FFR, blood flow velocity distribution (BVD) and WSS were improved by either the cylindrical or the conical stent implantation. However, after the conical stent implantation, the change of FFR seemed to be slower and more homogenous; the blood flow velocity was more appropriate without any obvious blood stagnation and direction changes; the WSS after the conical stent implantation was uniform from the proximal to distal side of the stent. | Does the conical stent in coronary artery improve hemodynamics compared with the traditional cylindrical stent? | No. Compared with the cylindrical stent, the conical stent implantation in the coronary artery does not make the changes of vascular hemodynamic closer to the physiological condition, which does not reduce the incidence of intra-stent restenosis and thrombosis, thus making it less suitable for PCI therapy. | FAIL | pubmedQA | 0 |
17375706 | To determine whether serum CA-125 levels, in addition to tumor size and ultrasonographic findings can help in differentiating benign ovarian cysts from malignant disease.
All postmenopausal women who had undergone explorative laporatomy for a preoperative diagnosis of an adnexal cyst between January 1999 and February 2006 were included if serum CA-125 levels were below 50 IU/ml.
Ninety-three patients with ovarian cysts and serum CA-125 levels lower than 50 IU/ml were included. Seventy-five (80%) of the patients (53 unilocular, 22 multilocular) had ovarian cysts < 13 cm. Of 18 patients with ovarian cysts > 13 cm, seven had unilocular and 11 had multilocular cysts. All the patients (n = 77) with a serum CA-125 level < 35 IU/ml had benign histopathology regardless of the tumor size or ultrasonic features. Among 16 patients with CA-125 levels between 35 and 50 IU/ml, two with unilocular cysts > 13 cm and nine with multilocular cysts (3 < 13 cm, 6 > 13 cm) had borderline histopathology. | Is serum CA-125 a good predictor of benign disease in patients with postmenopausal ovarian cysts? | Yes. We concluded that when unilocular ovarian cyst size is < 13 cm and serum CA-125 levels are below 50 IU/ml in a postmenopausal woman, the possibility of a benign etiology is most likely. | FAIL | pubmedQA | 0 |
20521332 | Among people with arthritis, the need for work transitions may signal a risk for more adverse work outcomes in the future, such as permanent work loss. Our aim was to evaluate the ability of the Work Instability Scale for Rheumatoid Arthritis (RA-WIS) to predict arthritis-related work transitions within a 12-month period.
Workers with osteoarthritis or rheumatoid arthritis (n = 250) from 3 clinical sites participated in self-administered surveys that assessed the impact of health on employment at multiple time points over 12 months. Multivariable logistic regressions were conducted to assess the ability of the RA-WIS (range 0-23, where 23 = highest work instability) to predict 4 types of work transition: reductions in work hours, disability leaves of absence, changes in job/occupation, or temporary unemployment, assembled as a composite outcome. Covariates assessed include age, sex, education, marital status, income, pain intensity, disease duration, and the Health Assessment Questionnaire. Areas under the receiver operating characteristic curves (AUROCCs) were also assessed to further examine the predictive ability of the RA-WIS and to determine optimal cut points for predicting specific work transitions.
After 12 months, 21.7% (n = 50 of 230) of the participants had indicated at least one arthritis-related work transition. Higher baseline RA-WIS was predictive of such an outcome (relative risk [RR] 1.05 [95% confidence interval (95% CI) 1.00-1.11]), particularly at >17 (RR 2.30 [95% CI 1.11-4.77]). The RA-WIS cut point of >13 was found to be most accurate for prediction (AUROCC 0.68 [95% CI 0.58-0.78]). | Does the Work Instability Scale for rheumatoid arthritis predict arthritis-related work transitions within 12 months? | No. The RA-WIS did not demonstrate the ability to predict arthritis-related work transitions within a short timeframe, and is not a promising measurement candidate for risk prognostication where work disability outcomes are of concern. | FAIL | pubmedQA | 0 |
9710002 | To quantify the rate of cognitive decline on the Mini-Mental State Examination (MMSE) in autopsy-diagnosed Lewy body variant (LBV) of Alzheimer's disease (AD) cases. We hypothesized that LBV patients would have a faster cognitive decline and shorter survival compared with patients with pure AD.
Prior reports have shown extrapyramidal signs to be associated with a poorer prognosis in AD. It has been suggested that LBV is often characterized by a rapidly progressive course. Few data are available regarding the rate of cognitive decline in autopsy-confirmed LBV dementia cases.
We searched the databases of the University of California-San Diego Alzheimer's Disease Research Center and the Consortium to Establish a Registry in Alzheimer's Disease (CERAD) for dementia cases with 1) an autopsy diagnosis of definite or probable AD (CERAD criteria) with concomitant Lewy bodies and 2) longitudinal MMSE assessments. This resulted in a series of 40 LBV cases and 148 AD cases without Lewy bodies, with comparable baseline MMSE scores, age, and education. The rate of cognitive decline was calculated as the baseline MMSE -- final MMSE. Methods were devised to reduce floor effects on the MMSE.
The average rate of cognitive decline was -5.8 +/- 4.5 points/y in LBV and -4.1 +/- 3.0 points/y in AD (t-test, p < 0.01). The LBV group declined a similar amount on the MMSE (means, -10.0 versus -9.6 points) over a significantly shorter time interval (1.9 versus 2.7 years; p = 0.005) than did AD patients. At baseline, the mean MMSE scores were nearly identical (18.2 in LBV; 17.8 in AD), but on follow-up examinations approximately 1, 2, and 3 years later, there were intergroup mean differences of 1.8 points (two-tailed p = 0.19), 4.2 points (p = 0.04), and 5.6 points (p = 0.03), respectively. The LBV cases had shorter survival time from the onset of cognitive symptoms (7.7 +/- 3.0 years versus 9.3 +/- 3.5 years; p = 0.007) and a shorter mean survival after entry/baseline, which was of marginal significance (3.6 versus 4.1 years; p = 0.11). | Is cognitive decline faster in Lewy body variant than in Alzheimer 's disease? | No. This study demonstrates that LBV is characterized by a slower cognitive decline and decelerated mortality compared with AD. | FAIL | pubmedQA | 0 |
12097847 | In patients with carotid artery occlusion (CAO), collateral flow may reduce the risk of ischemic stroke. Collateral flow via the ophthalmic artery (OphthA) and flow via leptomeningeal vessels have been considered secondary collaterals, which are recruited only if the primary collateral circulation via the circle of Willis is insufficient. The aim of this study was to investigate whether patients with symptomatic CAO who have secondary in addition to primary collaterals have a worse flow state of the brain than those without secondary collaterals, as measured by vascular reactivity testing.
We studied 70 patients with symptomatic CAO who were independent for their daily activities. In all patients, collateral circulation through the circle of Willis was present. Vascular reactivity, measured by means of transcranial Doppler sonography with carbogen inhalation, was compared between patients with and without secondary collaterals.
CO2 reactivity was lower in 64 patients with (mean +/- standard deviation 8 +/- 14%) than in 6 patients without secondary collaterals (33 +/- 18%) resulting in a mean difference of 24% (95% confidence interval 12-37%; p < 0.01). | Is collateral circulation via the ophthalmic artery or leptomeningeal vessels associated with impaired cerebral vasoreactivity in patients with symptomatic carotid artery occlusion? | No. Patients with symptomatic CAO with collateral circulation through the OphthA or through leptomeningeal vessels in addition to collaterals via the circle of Willis have a better hemodynamic status of the brain than those with Willisian collaterals only. Therefore the presence of these collaterals may indicate sufficiency of collateral blood flow via the circle of Willis. | FAIL | pubmedQA | 0 |
21715105 | Benzodiazepine (BZD) misuse in opioid-maintained patients is widespread and has been related to poorer treatment success. Associated factors, in particular, traumatic childhood experiences, have not been investigated extensively.
Cross-sectional survey including the childhood trauma questionnaire (CTQ) and clinical data among 193 patients prescribed oral opioids or injectable diacetylmorphine for opioid dependence.
BZD use was prevalent (61%) and the burden of childhood traumatic experiences was high with 67% reporting at least one trauma subscore of moderate-to-severe level. In univariate analysis, CTQ-subcategories "emotional abuse" (p<0.05), "emotional neglect" (p<0.01) and "physical neglect" (p<0.001) were significantly associated with prolonged BZD use. In multivariate analysis, prolonged BZD use was associated with categorized overall CTQ-scores (OR 1.5), HCV-seropositivity (OR 4.0), psychiatric family history (OR 2.3), and opioid dose (mg methadone equivalents, OR 1.010). | Is prolonged use of benzodiazepines associated with childhood trauma in opioid-maintained patients? | No. Childhood traumatic experiences are not associated with prolonged BZD use in opioid-maintained patients and do not pose an important starting-point for prevention. | FAIL | pubmedQA | 0 |
11029153 | Cellular debris, an indicator of cell death, appears in limb buds of gestational day 12 rabbit embryos 4 hr after either a subcutaneous injection of hydroxyurea to pregnant rabbits or an injection of hydroxyurea into the exocoelomic cavities of the embryos. This episode of early cell death appears to be central to the teratogenic action of hydroxyurea. Several chemicals that are structurally related to hydroxyurea, and that possess a terminal hydroxylamine moiety (-NHOH), also produce limb abnormalities.
To investigate whether the hydroxylamine moiety is responsible for early cell death and, therefore, is likely to be associated with teratogenesis, five structurally related hydroxylamine-bearing chemicals (hydroxylamine hydrochloride, N-methylhydroxylamine hydrochloride, hydroxyurea, acetohydroxamic acid, and hydroxyurethane) were administered at equimolar doses to rabbits either by subcutaneous (8.55 mmol/kg) or intracoelomic (2.66 micromol/embryo) injection on gestational day 12. Five additional chemicals, structurally similar to the hydroxylamine-bearing compounds, but possessing a terminal amino group (-NH(2)) (ammonium hydroxide, methylamine, urea, acetamide, and urethane), were tested at equimolar or higher doses by an identical protocol. In a subsequent experiment, the antioxidant propyl gallate (3.0 mmol/kg or 1.30 micromol/embryo) was co-administered with the hydroxylamine-bearing compounds to determine its effect on early cell death. Embryos were harvested 4 or 8 hr after treatment and analyzed by light microscopy.
Cellular debris was obvious in forelimb buds from embryos treated with the hydroxylamine-bearing compounds; however, none of the amino compounds produced an early episode of embryonic cell death. In all cases, the antioxidant propyl gallate prevented or delayed the early episode of cell death observed after treatment with the hydroxylamine-bearing compounds. | Is hydroxylamine moiety of developmental toxicants associated with early cell death : a structure-activity analysis? | Yes. These results are consistent with the concept that the rapidly occurring embryonic cytotoxicity induced by hydroxylamine-bearing compounds involves a free radical mechanism that requires the presence of a terminal amino group for initiation. | FAIL | pubmedQA | 0 |
22843878 | Recently we reported that amplification of the Zinc Finger Protein 217 (ZNF217) gene adversely affects survival of patients with ovarian clear cell carcinoma. This study sought to determine the mechanism by which ZNF217 amplification affects patient survival.
Fluorescence in situ hybridization (FISH) was used to detect ZNF217 gene amplification status and ZNF217-specific siRNA was used to inactivate ZNF217 for in vitro biological analyses.
We found ZNF217 gene amplification to be significantly correlated with lymph node metastasis (p<0.05) in ovarian clear cell carcinoma. Profound inhibition of cell migration and invasion was observed in siRNA-treated cells with ZNF217 amplification, compared to cells without amplification. | Does gene amplification of ZNF217 located at chr20q13.2 is associate with lymph node metastasis in ovarian clear cell carcinoma? | No. These findings provide new insight into the biological role of ZNF217 gene amplification in ovarian clear cell carcinoma. Additionally, our observations have an important therapeutic implication for patients with ovarian clear cell carcinomas with ZNF217 amplification, as these patients may potentially benefit from ZNF217 targeted-therapy. | FAIL | pubmedQA | 0 |
27399532 | The efficacy of radiotherapy in many tumor types is limited by normal tissue toxicity and by intrinsic or acquired radioresistance.
An unbiased functional microRNA screen identified 4 miRNAs (miR1, miR125a, miR150, and miR425) that induced glioblastoma radioresistance. We employed gain and loss of function approaches to validate the critical importance of these miRNAs as determinants of glioblastoma radiation resistance.
Overexpression of miR1, miR125a, miR150, and/or miR425 in glioblastoma promotes radioresistance through upregulation of the cell-cycle checkpoint response. Conversely, antagonizing with antagomiRs sensitizes glioblastoma cells to irradiation, suggesting their potential as targets for inhibiting therapeutic resistance. Analysis of glioblastoma data sets from The Cancer Genome Atlas (TCGA) revealed that these miRNAs are expressed in glioblastoma patient specimens and correlate with transforming growth factor β (TGFβ) signaling. Finally, it is demonstrated that expression of miR1 and miR125a can be induced by TGFβ and antagonized by a TGFβ receptor inhibitor. Together, these results identify and characterize a new role for miR425, miR1, miR125, and miR150 in promoting radioresistance in glioblastomas and provide insight into the therapeutic application of TGFβ inhibitors in radiotherapy. | Does 334 A Functional Screen identify miRNAs that Induce Radioresistance in Glioblastomas? | Yes. Systematic identification of miRs that cause radiosensitivity in gliomas is important for uncovering predictive markers for radiotherapy or targets for overcoming radiosensitivity. | FAIL | pubmedQA | 0 |
17302028 | To study the effect of different concentrations of the extract of acanthopanacis senticosus on human sperm motility in vitro and to investigate its possible mechanism.
By computer-assisted sperm analysis (CASA) system, we observed the effect of different concentrations of the extract of acanthopanacis senticosus on human sperm motility in vitro. The sperm obtained by masturbation and prepared by swim-up technique from 35 men with asthenospermia was incubated in different concentrations of the extract of acanthopanacis senticosus, and all the specimens were measured at 30, 60, 120 and 180 min respectively.
Different concentrations of the extract of acanthopanacis senticosus obviously improved the sperm motility of asthenospermia patients. The extract at the concentrations of 5 and 10 g/L increased the rate of motility (MOT), the percentage of progressive mobile sperm, the curvilinear velocity (VCL), the straight line velocity (VSL) and the average path velocity (VAP). Compared with the control group, the difference was significant (P < 0.05). | Does [ Extract of acanthopanacis senticosus improve sperm motility of asthenospermia patients in vitro ]? | Yes. The extract of acanthopanacis senticosus can improve the sperm motility of asthenospermia patients in vitro and its optimal concentration is 5 g/L. The study may provide a new drug therapy for asthenospermia. | FAIL | pubmedQA | 0 |
11089753 | To determine whether a) pre-operative measurement of gastric intramucosal pHi is predictive for mortality and morbidity in high-risk surgical patients and b) peri-operative improvement of global oxygen delivery (DO2) with fluids and dopexamine leads to increased gastric pHi and c) either improved global perfusion or improved splanchnic perfusion is related to the prevention of multiple organ failure (MOF).
Retrospective analysis of a double-blind, placebo-controlled, randomised study.
General intensive care units from 14 hospitals.
Two hundred eighty-six high-risk surgical patients.
Swan-Ganz and tonometer catheter placement; patients were stabilised pre-operatively using fluids, blood and/or oxygen to preset goals before receiving placebo or two doses of dopexamine (0.5 or 2.0 microg.kg.min) peri-operatively.
Haemodynamic assessment (including DO2 and oxygen consumption (VO2)) was performed together with measurement of gastric mucosal pHi pre-operatively and directly, 2, 6, 12, 24 and 36 h post-operatively. Retrospectively, patients were divided pre-operatively into two sub-groups based on the optimal cut-off value for mortality of the first pHi measurement after induction of anaesthesia as calculated by a receiver operator characteristic (ROC) curve analysis --low pHi group (< 7.35) and normal pHi (> or =7.35). Mortality in the low pHi, was higher than in the normal pHi, group (16.8 vs 2.3%; p = 0.0001). In the normal pHi group dopexamine, which was given prior to the first pHi measurement, had no effect on pHi, while DO2 increased significantly. In this group MOF score and number of patients with MOF remained similar for the treatment sub-groups. In the low pHi group gastric pHi increased significantly during dopexamine infusion (p = 0.008), despite the lack of an increase in DO2 and VO2. In this group the MOF score and the number of patients developing MOF decreased significantly with the use of dopexamine (p = 0.04). In both groups bicarbonate levels remained similar for the treatment subgroups. | Is pre-operative tonometry predictive for mortality and morbidity in high-risk surgical patients? | Yes. In high-risk surgical patients pre-operative measurement of pHi was predictive for morbidity. The peri-operative response of pHi to dopexamine seemed to be dependent on pre-operative gastric pHi. | FAIL | pubmedQA | 0 |
10200703 | The aim of this investigation was to clarify the mechanism of alkalization induced by carbachol in HSG cells.
Cells of the HSG cell line derived from a human submandibular gland adenocarcinoma and those of the A-431 human epidermoid carcinoma cell line were loaded with a fluorescent pH indicator, BCECF/AM, and the change in the intracellular pH of adherent cells and suspended ones were measured following stimulation with various concentrations (10(-7) M to 10(-2) M) of neurotransmitters (carbachol, noradrenaline, and isoproterenol).
Isoproterenol did not cause alkalization of either cell type, whereas, noradrenaline and carbachol alkalized both types over the concentration ranges of 10(-6) M to 3 x 10(-3) M (HSG cell by noradrenaline), 10(-7) M to 2 x 10(-4) M (A-431 cell by noradrenaline), and 7 x 10(-5) M to 10(-4) M (A-431 cell by carbachol). On the other hand, alkalization induced by carbachol in the HSG cells was recognized at concentrations higher than 6 x 10(-5) M, and it showed no upper limit in terms of carbachol concentration. This high-dose carbachol alkalization was not eliminated by preincubation with nifedipine (100 microM), a Ca2+ channel blocker, or with thapsigargin (100 microM), a microsomal Ca(2+)-ATPase inhibitor. | Is alkalization produced by high-dose carbachol in HSG cell line independent of Ca2+? | No. The alkalization system induced by carbachol in the HSG cell was quite different from that in the A-431 cell, and that induced by high-dose carbachol in HSG cells appeared to be dependent on intracellular Ca2+. These findings will be useful to clarify the mechanism of salivary secretion stimulated by neurotransmitters. | FAIL | pubmedQA | 0 |
23826518 | To investigate the effects of Msx2 on lens epithelium cell cycle, and evaluate the changes of the proliferation, apoptosis of lens epithelium cells.
Mice lens epithelium cells were cultured and transfected with pEGFP-Msx2 and control. Msx2-deficient mice (Msx2(-/-) ) lens tissue were isolated. Lens tissue and transfected cells were prepared for mRNA extraction using Trizol reagent. CyclinD1 and Prox1 expression were evaluated by real-time RT-PCR. BrdU incorporation and apoptosis rate were investigated by immunofluorescence and flow cytometry analysis.
After transfected with pEGFP-Msx2, lens epithelium cells failed to incorporate BrdU and anti-phospho-histone-3 immunofluorescence failed to detect cell nuclei which GFP were positive. Msx2 over expression resulted in increasing apoptosis rate in lens epithelium cells. CyclinD1 and Prox1 expression increased significantly in Msx2 knockout mice by real-time RT-PCR quantization and CyclinD1 expression decreased significantly in Msx2 overexpressed cell. | Does msx2 play a critical role in lens epithelium cell cycle control? | Yes. Msx2 has the effect of promoting proliferation and differentiation, reducing apoptosis on mice lens epithelium cells. | FAIL | pubmedQA | 0 |
27542917 | Surgical excision is currently recommended after pathologic radial scar is found on breast core needle biopsy because surgical upgrade to carcinoma is not uncommon. The goal of our study was to identify the true pathologic upgrade rate for a "pure" radial scar, those without associated proliferative lesion, based on indication for biopsy, biopsy type, and needle size.
The pathology database of Continuum Health Partners was searched for the terms radial scar and radial sclerosing lesion, from January 2007 to December 2015. From review of 1,513 pathology reports, 292 cases of core biopsies without malignancy were identified. Age, indication for biopsy, type of biopsy, and excisional pathology were obtained. Data were then analyzed using SPSS.
Two hundred nineteen (75%) of the 292 core biopsies showed pure radial scar without associated proliferative lesion, and 161 (74%) of these patients had surgical excision. Only 1 of these patients had disease that was upgraded to ductal carcinoma in situ-a 2-mm focus located 5 mm away from the radial scar biopsy cavity. This patient also had residual calcifications on mammography after the stereotactic biopsy. Six additional malignant upgrades were found in patients who had radial scar associated with atypical ductal hyperplasia (n = 5) or lobular neoplasia (n = 1) on needle biopsy. | Does radial Scar at Percutaneous Breast Biopsy That Require Surgery? | No. Surgical excision is unnecessary when radial scar is found at percutaneous needle biopsy without an associated proliferative lesion. Surgical excision is still indicated when radial scar is associated with ductal carcinoma in situ or lobular neoplasia. | FAIL | pubmedQA | 0 |
24161319 | The purpose of this paper was to determine whether microRNAs (miRNAs) involved in myocardial remodeling were differentially expressed in the blood of hypertrophic cardiomyopathy (HCM) patients, and whether circulating miRNAs correlated with the degree of left ventricular hypertrophy and fibrosis.
miRNAs-small, noncoding ribonucleic acids (RNAs) that regulate gene expression by inhibiting RNA translation-modulate cellular function. Myocardial miRNAs modulate processes such as cardiomyocyte (CM) hypertrophy, excitation-contraction coupling, and apoptosis; non-CM-specific miRNAs regulate myocardial vascularization and fibrosis. Recently, the possibility that circulating miRNAs may be biomarkers of cardiovascular disease has been raised.
Forty-one HCM patients were characterized with conventional transthoracic echocardiography and cardiac magnetic resonance. Peripheral plasma levels of 21 miRNAs were assessed by quantitative real-time polymerase chain reaction and were compared with levels in a control group of 41 age- and sex-matched blood donors.
Twelve miRNAs (miR-27a, -199a-5p, -26a, -145, -133a, -143, -199a-3p, -126-3p, -29a, -155, -30a, and -21) were significantly increased in HCM plasma. However, only 3 miRNAs (miR-199a-5p, -27a, and -29a) correlated with hypertrophy; more importantly, only miR-29a correlated also with fibrosis. | Is circulating miR-29a , among other up-regulated microRNAs , the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy? | Yes. Our data suggest that cardiac remodeling associated with HCM determines a significant release of miRNAs into the bloodstream: the circulating levels of both cardiac- and non-cardiac-specific miRNAs are significantly increased in the plasma of HCM patients. However, correlation with left ventricular hypertrophy parameters holds true for only a few miRNAs (i.e., miR-199a-5p, -27a, and -29a), whereas only miR-199a-5p is significantly associated with both hypertrophy and fibrosis, identifying it as a potential biomarker for myocardial remodeling assessment in HCM. | FAIL | pubmedQA | 0 |
24366371 | High fructose corn syrup (HFCS) is the most commonly used sweetener in the United States. Some studies show that HFCS consumption correlates with obesity and insulin resistance, while other studies are in disagreement. Owing to conflicting and insufficient scientific evidence, the safety of HFCS consumption remains controversial.
We investigated the metabolic consequences of mice fed a (a) regular diet, (b) 'Western' high-fat diet or (c) regular diet supplemented with 8% HFCS in drinking water (to mimic soft drinks) for 10 months. Adipose tissue macrophages (ATMs) have emerged as a major pathogenic factor for obesity and insulin resistance. ATMs consist of proinflammatory F4/80(+)CD11c(+) macrophages and anti-inflammatory F4/80(+)CD11c(-) macrophages. In this study, we assessed the effects of HFCS on ATMs in intra-abdominal fat.
We found that HFCS feeding in mice induced more severe adipose inflammation and insulin resistance than even the higher-calorie-containing 'Western' high-fat diet, and these HFCS-induced deleterious effects were independent of calorie intake or body fat content. We showed that similar to 'Western' high-fat diet, HFCS triggered a robust increase of both proinflammatory ATMs and anti-inflammatory ATMs in intra-abdominal fat. Remarkably, however, the anti-inflammatory ATMs were much less abundant in HFCS-fed mice than in high-fat-fed mice. Furthermore, we showed that deletion of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) ameliorates HFCS-induced adipose inflammation and insulin resistance. HFCS-fed GHS-R-null mice exhibit decreased proinflammatory ATMs in intra-abdominal fat, reduced adipose inflammation and attenuated liver steatosis. | Does ghrelin receptor regulate HFCS-induced adipose inflammation and insulin resistance? | No. Our studies demonstrate that HFCS has detrimental effects on metabolism, suggesting that dietary guidelines on HFCS consumption for Americans may need to be revisited. GHS-R deletion does not mitigate the effects of HFCS on adipose inflammation and insulin resistance, suggesting that GHS-R antagonists may not represent a novel therapy for insulin resistance. | FAIL | pubmedQA | 0 |
23241383 | Lineage specific differentiation of human embryonic stem cells (hESCs) is largely mediated by specific growth factors and extracellular matrix molecules. Growth factors initiate a cascade of signals which control gene transcription and cell fate specification. There is a lot of interest in inducing hESCs to an endoderm fate which serves as a pathway towards more functional cell types like the pancreatic cells. Research over the past decade has established several robust pathways for deriving endoderm from hESCs, with the capability of further maturation. However, in our experience, the functional maturity of these endoderm derivatives, specifically to pancreatic lineage, largely depends on specific pathway of endoderm induction. Hence it will be of interest to understand the underlying mechanism mediating such induction and how it is translated to further maturation. In this work we analyze the regulatory interactions mediating different pathways of endoderm induction by identifying co-regulated transcription factors.
hESCs were induced towards endoderm using activin A and 4 different growth factors (FGF2 (F), BMP4 (B), PI3KI (P), and WNT3A (W)) and their combinations thereof, resulting in 15 total experimental conditions. At the end of differentiation each condition was analyzed by qRT-PCR for 12 relevant endoderm related transcription factors (TFs). As a first approach, we used hierarchical clustering to identify which growth factor combinations favor up-regulation of different genes. In the next step we identified sets of co-regulated transcription factors using a biclustering algorithm. The high variability of experimental data was addressed by integrating the biclustering formulation with bootstrap re-sampling to identify robust networks of co-regulated transcription factors. Our results show that the transition from early to late endoderm is favored by FGF2 as well as WNT3A treatments under high activin. However, induction of late endoderm markers is relatively favored by WNT3A under high activin. | Does analysis of alternative signaling pathways of endoderm induction of human embryonic stem cells identify context specific differences? | Yes. Use of FGF2, WNT3A or PI3K inhibition with high activin A may serve well in definitive endoderm induction followed by BMP4 specific signaling to direct the definitive endoderm into late endodermal lineages. Other combinations, though still feasible for endoderm induction, appear less promising for pancreatic endoderm specification in our experiments. | FAIL | pubmedQA | 0 |
23702238 | Many patients who develop atrial fibrillation (AF) will experience a worsening of their arrhythmia over time. The optimal time to proceed with catheter ablation during the disease course is unknown. Further, whether delays in treatment will negatively influence outcomes is unknown.
The purpose of this study was to examine the impact of delay in treatment after the first clinical diagnosis of AF on ablation-related outcomes.
A total of 4535 consecutive patients who underwent an AF ablation procedure that had long-term established care within an integrated health care system were evaluated. Recursive partitioning was used to determine categories associated with changes in risk from the time of first AF diagnosis to first AF ablation: 1: 30-180 (n = 1152), 2: 181-545 (n = 856), 3: 546-1825 (n = 1326), and 4: >1825 (n = 1201) days. Outcomes evaluated include 1-year AF recurrence, stroke, heart failure hospitalization, and death.
With increasing time to treatment, surprisingly patients were older (1: 63.7 ± 11.1, 2: 62.6 ± 11.8, 3: 66.4 ± 10.2, 4: 67.6 ± 9.7; P <.0001) and had more hypertension (1: 53.0%, 2: 59.0%, 3: 53.8%, 4: 39.0%; P <.0001). For each strata of time increase, there was a direct increase of 1-year AF recurrence (1: 19.4%, 2: 23.4%, 3: 24.9%, 4: 24.0%: P trend = .02). After adjustment, clinically significant differences in risk of recurrent AF were found when compared to the 30-180 day time category: 181-545: odds ratio (OR) = 1.23, P = .08; 546-1825: OR = 1.27, P = .02; and >1825: OR = 1.25, P = .05. No differences were observed for 1-year stroke among the groups. Death (1: 2.1%, 2: 3.9%, 3: 5.7%, 4: 4.4%: P trend = .001) and heart failure hospitalization (1: 2.6%, 2: 4.1%, 3: 5.4%, 4: 4.4%; P trend = .009) rates at 1 year were higher in the most delayed groups. | Does increasing time between first diagnosis of atrial fibrillation and catheter ablation adversely affect long-term outcomes? | No. Delays in treatment with catheter ablation do not impact procedural success rates independent of temporal changes to the AF subtype at ablation. | FAIL | pubmedQA | 0 |
23046676 | Acetaminophen (AAP) overdose is the most frequent cause of drug-induced liver failure. c-Jun N-terminal kinase (JNK) is thought to play a central role in AAP-induced hepatocellular necrosis. The apoptosis repressor with caspase recruitment domain (ARC) is a death repressor that inhibits death receptor and mitochondrial apoptotic signaling. Here, we investigated ARC's therapeutic effect and molecular mechanisms on AAP-induced hepatocellular necrosis.
We tested the in vivo and in vitro effects of ARC fused with the transduction domain of HIV-1 (TAT-ARC) on murine AAP hepatotoxicity.
Treatment with TAT-ARC protein completely abrogated otherwise lethal liver failure induced by AAP overdose in C57BL/6 mice. AAP triggered caspase-independent necrosis, as evidenced by liver histology, elevated serum transaminases, and secreted HMGB1 that was inhibited by ARC. ARC-mediated hepatoprotection was not caused by an alteration of AAP metabolism, but resulted in reduced oxidative stress. AAP overdose led to induction of RIP-dependent signaling with subsequent JNK activation. Ectopic ARC inhibited JNK activation by specific interactions between ARC and JNK1 and JNK2. Importantly, survival of mice was even preserved when ARC therapy was initiated in a delayed manner after AAP administration. | Is aRC a novel therapeutic approach against acetaminophen-induced hepatocellular necrosis? | Yes. This work identifies for the first time ARC-JNK-binding with subsequent inhibition of JNK signaling as a specific mechanism of ARC to interfere with AAP-dependent necrosis. Our data suggests that AAP-mediated induction of RIP signaling serves as a critical switch for hepatocellular necrosis. The efficacy of TAT-ARC protein transduction in murine AAP hepatotoxicity suggests its therapeutic potential for preventing AAP intoxication also in humans. | FAIL | pubmedQA | 0 |
12113542 | Postoperative ileus limits early hospital discharge for patients who have undergone laparoscopic procedures. Sham feeding has been reported to enhance bowel motility. Here, the effect of gum chewing is evaluated as a convenient method to enhance postoperative recovery from ileus after laparoscopic colectomy.
A total of 19 patients who underwent elective laparoscopic colectomy for colorectal cancer participated in the study. Each patient was randomly assigned to one of two groups: a gum-chewing group (n = 10, mean age 58.6 years, range 50 to 71 years) or a control group (n = 9, mean age 60.6 years, range 45 to 80 years). The patients in the gum-chewing group chewed gum three times a day from the first postoperative AM until oral intake. The times of the first passage of flatus and defecation were recorded precisely.
The first passage of flatus was seen, on average, on postoperative day 2.1 in the gum-chewing group and on day 3.2 in the control group (p < 0.01). The first defecation was 2.7 days sooner in the gum-chewing group (postoperative day 3.1) than in the control group (5.8 days; p< 0.01). All patients tolerated gum chewing on the first operative AM. The postoperative hospital stays for the gum-chewing and control groups were 13.5+/-3.0 days and 14.5+/-6.1 days, respectively. | Does gum chewing enhance early recovery from postoperative ileus after laparoscopic colectomy? | No. Gum chewing does not aid early recovery from postoperative ileus and is not an effective method for stimulating bowel motility. Gum chewing should not be added as an adjunct treatment in postoperative care because it does not contribute to shorter hospital stays. | FAIL | pubmedQA | 0 |
23023371 | Inflammatory responses are the driving force of atherosclerosis development. IκB kinase β (IKKβ), a central coordinator in inflammation through regulation of nuclear factor-κB, has been implicated in the pathogenesis of atherosclerosis. Macrophages play an essential role in the initiation and progression of atherosclerosis, yet the role of macrophage IKKβ in atherosclerosis remains elusive and controversial. This study aims to investigate the impact of IKKβ expression on macrophage functions and to assess the effect of myeloid-specific IKKβ deletion on atherosclerosis development.
To explore the issue of macrophage IKKβ involvement of atherogenesis, we generated myeloid-specific IKKβ-deficient low-density lipoprotein receptor-deficient mice (IKKβ(ΔMye)LDLR(-/-)). Deficiency of IKKβ in myeloid cells did not affect plasma lipid levels but significantly decreased diet-induced atherosclerotic lesion areas in the aortic root, brachiocephalic artery, and aortic arch of low-density lipoprotein receptor-deficient mice. Ablation of myeloid IKKβ attenuated macrophage inflammatory responses and decreased atherosclerotic lesional inflammation. Furthermore, deficiency of IKKβ decreased adhesion, migration, and lipid uptake in macrophages. | Does myeloid-specific IκB kinase β deficiency decrease atherosclerosis in low-density lipoprotein receptor-deficient mice? | No. The present study demonstrates that myeloid IKKβ expression does not play a significant role in atherosclerosis by modulating macrophage functions involved in atherogenesis. These results suggest that inhibiting nuclear factor-κB activation in macrophages may not represent a feasible approach to combat atherosclerosis. | FAIL | pubmedQA | 0 |
15475453 | A reliable method for diagnosing parathyroid carcinoma has remained elusive over the years, resulting in its under-recognition and suboptimal therapy. Obtaining an accurate diagnosis has become an even more pressing matter with recent evidence that germline HRPT2 gene mutations are found in patients with apparently sporadic parathyroid carcinoma. There is a high prevalence of HRPT2 gene mutations and biallelic inactivation in parathyroid carcinoma. We hypothesize that loss of parafibromin, the protein product of the HRPT2 gene, would distinguish carcinoma from benign tissue.
We generated a novel antiparafibromin monoclonal antibody and performed immunostaining on 52 definite carcinoma specimens, 6 equivocal carcinoma specimens, 88 benign specimens, and 9 hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from patients with primary hyperparathyroidism from nine worldwide centers and one national database.
We report that the loss of parafibromin nuclear immunoreactivity has 96% sensitivity [95% confidence interval (CI), 85-99%] and 99% specificity (95% CI, 92-100%) in diagnosing definite carcinoma. Inter-observer agreement for evaluation of parafibromin loss was excellent, with unweighted kappa of 0.89 (95% CI, 0.79-0.98). Two equivocal carcinomas misclassified as adenomas were highlighted by parafibromin immunostaining. One of these tumors has since recurred, satisfying criteria for a definite carcinoma. Similarly, eight of nine HPT-JT syndrome-related adenomas showed absent nuclear immunoreactivity. | Is loss of parafibromin immunoreactivity a distinguishing feature of parathyroid carcinoma? | No. Parafibromin is not a reliable molecular marker for diagnosing parathyroid carcinoma. The similar loss of parafibromin immunoreactivity in HPT-JT syndrome-related adenomas suggests that this is not a pivotal step in parathyroid tumorigenesis. | FAIL | pubmedQA | 0 |
23240045 | Shiga toxin (Stx) are cardinal virulence factors of enterohemorrhagic E. coli O157:H7 (EHEC O157). The gene content and genomic insertion sites of Stx-associated bacteriophages differentiate clinical genotypes of EHEC O157 (CG, typical of clinical isolates) from bovine-biased genotypes (BBG, rarely identified among clinical isolates). This project was designed to identify bacteriophage-mediated differences that may affect the virulence of CG and BBG.
Stx-associated bacteriophage differences were identified by whole genome optical scans and characterized among >400 EHEC O157 clinical and cattle isolates by PCR.
Optical restriction maps of BBG strains consistently differed from those of CG strains only in the chromosomal insertion sites of Stx2-associated bacteriophages. Multiplex PCRs (stx1, stx2a, and stx2c as well as Stx-associated bacteriophage-chromosomal insertion site junctions) revealed four CG and three BBG that accounted for >90% of isolates. All BBG contained stx2c and Stx2c-associated bacteriophage-sbcB junctions. All CG contained stx2a and Stx2a-associated bacteriophage junctions in wrbA or argW. | Does carriage of stx2a differentiate clinical and bovine-biased strains of Escherichia coli O157? | No. Presence or absence of stx2a (or another product encoded by the Stx2a-associated bacteriophage) is not a parsimonious explanation for differential virulence of BBG and CG, as reflected in the distributions of these genotypes in humans and in the cattle reservoir. | FAIL | pubmedQA | 0 |
23652269 | Stroke survivors often have permanent deficits that are only partially addressed by physical therapy. This study evaluated the effects of dalfampridine, a potassium channel blocker, on persistent sensorimotor deficits in rats with treatment initiated 4 or 8 weeks after stroke.
Rats underwent permanent middle cerebral artery occlusion. Sensorimotor function was measured using limb-placing and body-swing symmetry tests, which normally show a partial recovery from initial deficits that plateaus ≈4 weeks after permanent middle cerebral artery occlusion. Dalfampridine was administered starting at 4 or 8 weeks after permanent middle cerebral artery occlusion in 2 blinded, vehicle-controlled studies. Plasma samples were collected and brain tissue was processed for histologic assessment.
Dalfampridine treatment (0.5-2.0 mg/kg) improved forelimb- and hindlimb-placing responses and body-swing symmetry in a reversible and dose-dependent manner. Plasma dalfampridine concentrations correlated with dose. Brain infarct volumes showed no differences between treatment groups. | Does dalfampridine improve sensorimotor function in rats with chronic deficits after middle cerebral artery occlusion? | No. Dalfampridine does not improve sensorimotor function in the rat permanent middle cerebral artery occlusion model. Dalfampridine extended-release tablets (prolonged release fampridine outside the United States) are used to improve walking in patients with multiple sclerosis, but these preclinical data do not support the potential of dalfampridine to treat chronic stable deficits in stroke patients. | FAIL | pubmedQA | 0 |
26728088 | White-handed gibbons (Hylobates lar) are small Asian apes known for living in stable territories and producing loud, elaborate vocalizations (songs), often in well-coordinated male/female duets. The female great call, the most conspicuous phrase of the repertoire, has been hypothesized to function in intra-sexual territorial defense. We therefore predicted that characteristics of the great call would correlate with a caller's physical condition, and thus might honestly reflect resource holding potential (RHP). Because measurement of RHP is virtually impossible for wild animals, we used age as a proxy, hypothesizing that great call climaxes are difficult to produce and maintain over time, and that older adults will therefore perform lower quality great calls than young adults. To test this we analyzed the great call climaxes of 15 wild lar gibbon females at Khao Yai National Park, Thailand and 2 captive females at Leo Conservation Center, Greenwich, CT.
Findings show that call climaxes correlate with female age, as young animals (n = 8, mean age: 12.9 years) produced climaxes with a higher frequency range (delta F0), maximum F0 frequency and duty cycle than old animals (n = 9, mean age: 29.6 years). A permuted discriminant function analysis also correctly classified calls by age group. During long song bouts the maximum F0 frequency of great call climaxes' also decreased. Additional data support the hypothesis that short high notes, associated with rapid inhalation as an individual catches its breath, reflect increased caller effort. Older females produced more high notes than younger females, but the difference only approached statistical significance, suggesting that calling effort may be similar across different ages. Finally, for the first time in this species, we measured peak intensity of calls in captive females. They were capable of producing climaxes in excess of 100 dB at close range (2.7 m). | Does age related decline in female lar gibbon great call performance suggest that call features correlate with physical condition? | No. Age and within-bout differences in the lar gibbon great call climax suggest that call features do not correlate with physical condition and thus the call may not have evolved as an honest signal in the context of intra-sexual territorial defense and possibly also in male mate choice via sexual selection, although further testing of these hypotheses is necessary. | FAIL | pubmedQA | 0 |
24511665 | The Myelin and lymphocyte-associated protein gene (MAL), which is located on the long arm of chromosome 2, assigned to the region cen-q13 in humans, has been reported as tumor suppressor in several cancers. The aim of this study was to clarify the clinical significance of MAL gene in gastric cancer.
The expression levels of MAL mRNA was examined using 50 resected gastric cancer specimens used by laser microdissected to determine the clinicopathological significance. MAL expression was then examined by real-time quantitative PCR assay, and we analyzed the correlation between MAL expression and clinicopathological factors.
In clinicopathologic analysis, the low MAL expression group showed significantly higher incidence of lymph node metastasis than the high expression group (79% and 46%, respectively, p < 0.05). Furthermore, the low MAL expression group had a significantly poorer prognosis than the high expression group (p < 0.05). | Does suppression of MAL gene expression in gastric cancer correlate with metastasis and mortality? | No. The MAL gene repression is not related to lymph node metastasis and poor prognosis in gastric cancer, suggesting that the MAL may not be a candidate node metastasis-suppressor gene for gastric cancer. | FAIL | pubmedQA | 0 |
21896931 | Angiotensin (ANG) II interacts with insulin-signaling pathways to regulate insulin sensitivity. The type 1 (AT(1)R) and type 2 (AT(2)R) receptors reciprocally regulate basal perfusion of muscle microvasculature. Unopposed AT(2)R activity increases muscle microvascular blood volume (MBV) and glucose extraction, whereas unopposed AT(1)R activity decreases both. The current study examined whether ANG II receptors modulate muscle insulin delivery and sensitivity.
Overnight-fasted rats were studied. In protocol 1, rats received a 2-h infusion of saline, insulin (3 mU/kg/min), insulin plus PD123319 (AT(2)R blocker), or insulin plus losartan (AT(1)R blocker, intravenously). Muscle MBV, microvascular flow velocity, and microvascular blood flow (MBF) were determined. In protocol 2, rats received (125)I-insulin with or without PD123319, and muscle insulin uptake was determined.
Insulin significantly increased muscle MBV and MBF. AT(2)R blockade abolished insulin-mediated increases in muscle MBV and MBF and decreased insulin-stimulated glucose disposal by ~30%. In contrast, losartan plus insulin increased muscle MBV by two- to threefold without further increasing insulin-stimulated glucose disposal. Plasma nitric oxide increased by >50% with insulin and insulin plus losartan but not with insulin plus PD123319. PD123319 markedly decreased muscle insulin uptake and insulin-stimulated Akt phosphorylation. | Do angiotensin II receptors modulate muscle microvascular and metabolic responses to insulin in vivo? | Yes. We conclude that both AT(1)Rs and AT(2)Rs regulate insulin's microvascular and metabolic action in muscle. Although AT(1)R activity enhances muscle metabolic responses to insulin via increased microvascular recruitment and insulin delivery, AT(2)R activity is required for normal microvascular responses to insulin. Thus, pharmacologic manipulation aimed at increasing the AT(2)R-to-AT(1)R activity ratio may afford the potential to improve muscle insulin sensitivity and glucose metabolism. | FAIL | pubmedQA | 0 |
16239591 | HIV combination therapy using protease inhibitors is associated with elevated plasma levels of atherogenic lipoproteins and increased risk for atherosclerosis. We investigated whether the HIV entry inhibitor TAK-779 affects lipoprotein levels and atherogenesis in low-density lipoprotein receptor-deficient mice. TAK-779 is an antagonist for the chemokine receptors CCR5 and CXCR3, which are expressed on leukocytes, especially T-helper 1 cells, and these receptors may be involved in recruitment of these cells to atherosclerotic plaques.
TAK-779 treatment of low-density lipoprotein receptor-deficient mice did not elevate the levels of atherogenic lipoproteins, whereas it dramatically reduced atherosclerosis in the aortic root and in the carotid arteries. The number of T cells in the plaque was reduced by 95%, concurrently with a 98% reduction in the relative IFN-gamma area. TAK-779-treated animals showed a decreased percentage of CD4+ and CD8+ T cells in peripheral blood and in mediastinal lymph nodes compared with control-treated animals. | Does hIV entry inhibitor TAK-779 attenuate atherogenesis in low-density lipoprotein receptor-deficient mice? | Yes. TAK-779 not only suppresses HIV entry via blockade of CCR5 but also attenuates atherosclerotic lesion formation by blocking the influx of T-helper 2 cells into the plaque. TAK-779 treatment may be especially beneficial for young HIV patients as they face lifelong treatment, and this drug impairs atherogenesis. | FAIL | pubmedQA | 0 |
15820263 | The purpose of the present study is to examine whether sonoporation with doxorubicin enhances suppression of intimal hyperplasia (IH) in a vein graft model.
After the administration of 1.5 mg/kg doxorubicin intravenously, the right external jugular vein of six rabbits was exposed at 2 W/cm2 and 1 MHz of ultrasound for 2 min (Sonoporation group). Tissue doxorubicin concentration was measured. In 48 rabbits, the right common carotid artery was ligated after performing a vein graft bypass. The animals were divided into the following four groups: the C0 group (surgical procedure only); the C0S (sonoporation without doxorubicin); the C1 (doxorubicin administration only); the C1S (sonoporation with doxorubicin). Twenty-four grafts were subjected to Elastic van Gieson staining for morphometric analysis 4 weeks after the operation; others were subjected to TdT-mediated X-dUTP nick end-labeling for detection of apoptic cells and to staining with a monoclonal antibody against the proliferating cell nuclear antigen for assessment of cell proliferation 1 week after.
The tissue doxorubicin concentration was significantly higher in the Sonoporation group than in the Control group. Compared with the C0 group, IH was not suppressed in the C1 group but was significantly suppressed in the C1S group. Sonoporation with doxorubicin administration suppressed IH significantly (C1 group versusC1S group: P < 0.05). Cell apoptosis was induced and cell proliferation was suppressed significantly in the C1S group. | Does sonoporation with doxorubicin enhance suppression of intimal hyperplasia in a vein graft model? | No. Sonoporation with doxorubicin did not suppress IH of the vein graft. Sonoporation may not be effective in coronary or peripheral revascularization using vein grafts. | FAIL | pubmedQA | 0 |
22035075 | Many previous studies have evaluated the impact of mitral valve (MV) deformity scores on the percutaneous transvenous mitral commissurotomy (PTMC) outcome in patients with mitral stenosis; however, the relationship between mitral annulus calcification (MAC) and the PTMC result has not yet been established. The current study aimed to investigate whether MAC could independently influence the immediate result of PTMC.
Of all patients undergoing PTMC in our institution between April 2005 and November 2009, we included 87 patients (28.7%male, mean ± SD age = 42.8 ± 12.6 years) with rheumatic mitral stenosis who had additional data on the echocardiographic evaluation of MAC along with MV leaflets morphology. Echocardiographic assessments were repeated up to six weeks after PTMC to evaluate the immediate PTMC outcome. The frequency of the optimal PTMC result (secondary MV area > = 1.5 cm(2) with > = 25% increase and without final mitral regurgitation grade > 2) was compared between two groups of patients with MAC (n = 17) and those without MAC (n = 70).
The optimal result was obtained in 55 (63.2%) patients, whereas the result was suboptimal in 32 (36.8%) patients due to insufficient MV area increase in 31(96.9%) subjects and post-procedure mitral regurgitation grade > 2 in 1(3.1%). The rate of optimal PTMC results was less in patients with MAC in comparison to those without MAC (29.4% vs.71.4%). After adjustments for possible confounders such as age and leaflets morphological subcomponents (thickening, mobility, calcification, and subvalvular thickening), MAC remained a significant negative predictor of a suboptimal PTMC result (odds ratio = 0.154; 95%CI = 0.038-0.626, p value = 0.009) together with leaflet thickening (odds ratio = 0.214; 95%CI = 0.060-0.770, p value = 0.018). | Does mitral annular calcification predict immediate results of percutaneous transvenous mitral commissurotomy? | No. MAC does not independently influence the immediate result of PTMC; therefore, mitral annulus evaluation may not be necessary in the echocardiographic assessment of the mitral apparatus prior to PTMC. | FAIL | pubmedQA | 0 |
25608526 | Methyl donor deficiency (MDD) aggravates experimental colitis in rats and increases endoplasmic reticulum (ER) stress through decreased sirtuin 1 (SIRT1) in neuronal cells and myocardium. ER stress plays a key role in IBD pathogenesis.
We investigated whether the influence of MDD on colitis resulted from an ER stress response triggered by decreased SIRT1 expression.
The unfolded protein response (UPR), chaperones proteins, heat shock factor protein 1 (HSF1) and SIRT1 were examined in rats with MDD and dextran sulfate sodium (DSS)-induced colitis in a Caco-2 cell model with stable expression of transcobalamin-oleosin (TO) chimera, which impairs cellular availability of vitamin B12, and in IBD. The effects of SIRT1 activation were studied both in vitro and in vivo.
MDD aggravated DSS-induced colitis clinically, endoscopically and histologically. MDD activated ER stress pathways, with increased phosphorylate-PKR-like ER kinase, P-eiF-2α, P-IRE-1α, activating transcription factor (ATF)6, XBP1-S protein and ATF4 mRNA expression levels in rats. This was accompanied by reduced SIRT1 expression level and greater acetylation of HSF1, in relation with a dramatic decrease of chaperones (binding immunoglobulin protein (BIP), heat shock protein (HSP)27 and HSP90). Adding either vitamin B12, S-adenosylmethionine or an SIRT1 activator (SRT1720) reduced the UPR in vitro. In rats, SIRT1 activation by SRT1720 prevented colitis by reducing HSF1 acetylation and increasing expression of BIP, HSP27 and HSP90. Immunohistochemistry showed impaired expression of SIRT1 in the colonic epithelium of patients with IBD. | Does methyl-deficient diet promote colitis and SIRT1-mediated endoplasmic reticulum stress? | No. SIRT1 is not involved in ER stress and severity of experimental colitis in case of MDD. It does not deserve further interest as a therapeutic target of IBD. | FAIL | pubmedQA | 0 |
25735324 | Prostate cancer is one of the main causes of cancer death, and drug resistance is the leading reason for therapy failure. However, how this occurs is largely unknown. We therrfore aimed to study the response of DU145 cells to cisplatin.
Du145 prostate cancer cells were treated with a low dose of cisplatin for 24 h and cell viability and number were determined by MTT assay and trypan blue exclusion assay, respectively. The real time polymerase chain reaction (PCR) was used to assess responses to cisplatin treatment.
After 24h 2 μg/ml treatment did not result in significant reduction in cell viability or number. However, it led to enhanced cancer cell invasiveness. E-cadherin mRNA was reduced, and vimentin, Snail, Slug, metalloproteinase 9 (MMP9) mRNA expression increased significantly, a feature of epithelial-mesenchymal transition (EMT). | Does short low concentration cisplatin treatment lead to an epithelial mesenchymal transition-like response in DU145 prostate cancer cells? | No. Short time low concentration cisplatin treatment does not lead to elevated invasiveness of DU145 cancer cells and this is not due to EMT. | FAIL | pubmedQA | 0 |
9306941 | Breast tumours with a DNA content higher than 4N (hypertetraploidy) are not well characterised. The aim of this study was to evaluate the clinical and biological characteristics of 51 hypertetraploid breast carcinomas selected from a series of 860 consecutive cases analysed by flow cytometry.
The clinicopathological characteristics of the hypertetraploid group were compared with those of a control group of 138 non-hypertetraploid breast carcinomas. Breast tumours from patients submitted to surgery as primary therapeutic approach (15 hypertetraploid and the 138 non-hypertetraploid) were TNM staged and classified according to the histological type and grade. The remaining 36 patients had advanced neoplastic disease at presentation and were classified by cytological criteria only. DNA flow cytometric analysis was performed on fresh-frozen samples stained with propidium iodide. Hormone receptors were analysed by immunocytochemistry.
The incidence of hypertetraploid breast tumours was 5.9% (51 of 860). All the patients were women and the mean age at diagnosis was 65 years. There was a family history of breast cancer in 21.6% of cases. In the group of operated patients, 33.3% had pT3 tumours and 53.3% had axillary lymph node metastases. All but one tumour were invasive ductal carcinomas; the remaining was an invasive papillary carcinoma. Ten (66.7%) tumours were classified as poorly differentiated carcinomas. Oestrogen and progesterone receptors were negative in 33 (64.7%) and 38 (74.5%) tumours, respectively. At last follow up, 35 (72.9%) patients were alive, while 13 (27.1%) died of disease within three years of diagnosis. Statistical comparison of the clinicopathological features of hypertetraploid v non-hypertetraploid breast carcinomas yielded a significant difference in tumour size (p < 0.001), histological grade (p < 0.001), hormone receptor status (p < 0.001), and overall survival (p < 0.001) between the two groups. | Is flow cytometric DNA hypertetraploidy associated with unfavourable prognostic features in breast cancer? | No. Flow cytometric DNA hypertetraploidy is not related to clinicopathological features of breast cancer usually associated with unfavourable prognosis. | FAIL | pubmedQA | 0 |
20432339 | To assess potential cognitive deficits under the influence of static magnetic fields at various field strengths some studies already exist. These studies were not focused on attention as the most vulnerable cognitive function. Additionally, mostly no magnetic resonance imaging (MRI) sequences were performed.
In all, 25 right-handed men were enrolled in this study. All subjects underwent one MRI examination of 63 minutes at 1.5 T and one at 7 T within an interval of 10 to 30 days. The order of the examinations was randomized. Subjects were referred to six standardized neuropsychological tests strictly focused on attention immediately before and after each MRI examination. Differences in neuropsychological variables between the timepoints before and after each MRI examination were assessed and P-values were calculated
Only six subtests revealed significant differences between pre- and post-MRI. In these tests the subjects achieved better results in post-MRI testing than in pre-MRI testing (P = 0.013-0.032). The other tests revealed no significant results. | Does exposure to high-field MRI affect cognitive function? | Yes. The improvement in post-MRI testing is only explicable as a result of learning effects. MRI examinations, even in ultrahigh-field scanners, seem to have a persisting influence on the attention networks of human cognition immediately after exposure. | FAIL | pubmedQA | 0 |
23217394 | The role of tumor-infiltrating lymphocytes (TILs) in the immunopathogenesis of individual cancer is not clear and is a challenge for anti-tumor immunotherapy. This study aimed to investigate the effects of interleukin (IL)-18 and -12 on cytotoxic functions of TILs.
TILs from postoperative gastric cancer patients were costimulated with IL-18 and IL-12. SGC-7901 tumor cells were pre-incubated with TILs and subcutaneously injected into BALB/C SCID mice. The function of TILs was evaluated by measuring tumor sizes in tumor-bearing mice, T helper (Th)1 (tumor necrosis factor (TNF)-α, interferon (IFN)-γ) and Th2 cytokine levels (IL-10 and IL-4) in serum and cytotoxicity of mouse natural killer (NK) and CD8(+) T cells.
IL-18 and IL-12 synergistically inhibited the growth of SGC-7901 cells in vivo and significantly extended the survival rate of SGC-7901-bearing mice (66.7% vs. 13.7%, P < 0.01). Moreover, TILs could promote the secretion of TNF-α and IFN-γ ((130.34 ± 7.65) vs. (210.63 ± 12.31) pg/ml, P < 0.01; (14.23 ± 1.97) vs. (30.52 ± 2.12) pg/ml, P < 0.01), and downregulate IL-10 and IL-4 secretion ((103.72 ± 11.21) vs. (61.36 ± 5.41) pg/ml, P = 0.021; (49.36 ± 4.67) vs. (28.48 ± 3.86) pg/ml, P = 0.024). | Do interleukin-18 and -12 synergistically enhance cytotoxic functions of tumor-infiltrating lymphocytes? | Yes. IL-18 and IL-12 can synergistically enhance cytotoxic functions of TILs from human lung cancer. | FAIL | pubmedQA | 0 |
10379739 | The limitation of current urinary tumor markers is the low specificity and positive predictive value, which clinically manifests as a high false-positive rate. We analyzed the false-positive data of 2 urinary tumor markers, NMP22 and the BTA stat tests. We examined the clinical categories of the false-positive results, established relative exclusion criteria, and recalculated the specificity and positive predictive value after using the exclusion criteria.
A total of 278 symptomatic patients who presented to a urology clinic were asked to submit a single voided urine sample. Each sample was divided into 3 aliquots of which 1 was stabilized with the NMP22 test kit stabilizer and assayed for NMP22, 1 was tested for BTA stat and 1 was sent for cytological examination. All patients subsequently underwent office cystoscopy and bladder biopsy if indicated.
Of the 278 symptomatic patients 112 presented with microscopic hematuria, 77 gross hematuria and 89 chronic symptoms of urinary frequency or dysuria. Of 34 cases (12%) of histologically confirmed bladder cancer NMP22 detected 28 (82.4%), BTA stat 23 (67.7%) and cytology only 10 (29.4%). When atypical cytologies were considered positive, cytology then detected 19 cases (55.9%). Elevated NMP22 values were positive in 28 cases and false-positive in 44 for a specificity of 82% and a positive predictive value of 38.9%. Similarly, BTA stat test was positive in 23 cases and false-positive in 43 for a specificity of 82.4% and a positive predictive value of 34.9%. When atypical cytologies were considered positive, the specificity and positive predictive value were 93% and 55.9%. Greater than 80% of the false-positive results were clinically categorized as benign inflammatory or infectious conditions, renal or bladder calculi, recent history of a foreign body in the urinary tract, bowel interposition segment, another genitourinary cancer or an instrumented urinary sample. A category of "no known pathology" was included in analysis as a control. History of ureteral stents or any bowel interposition segment had a 100% false-positive rate. Exclusion of all 6 clinical categories improved the specificity and positive predictive value of NMP22 (95.6%, 87.5%) and BTA stat (91.5%, 69.7%), and was similar to urinary cytology. | Do exclusion criteria enhance the specificity and positive predictive value of NMP22 and BTA stat? | Yes. Awareness and exclusion of the categories of false-positive results can increase the specificity and enhance the clinical usefulness of NMP22 and BTA stat tests. Similarly, treating an atypical cytology as negative can enhance the sensitivity and usefulness of urinary cytology. | FAIL | pubmedQA | 0 |
25401746 | Abnormalities of vascular smooth muscle cells (VSMCs) contribute to development of vascular disease. Atrial natriuretic peptide (ANP) exerts important effects on VSMCs. A common ANP molecular variant (T2238C/αANP) has recently emerged as a novel vascular risk factor.
We aimed at identifying effects of CC2238/αANP on viability, migration and motility in coronary artery SMCs, and the underlying signaling pathways.
Cells were exposed to either TT2238/αANP or CC2238/αANP. At the end of treatment, cell viability, migration and motility were evaluated, along with changes in oxidative stress pathway (ROS levels, NADPH and eNOS expression), on Akt phosphorylation and miR21 expression levels. CC2238/αANP reduced cell vitality, increased apoptosis and necrosis, increased oxidative stress levels, suppressed miR21 expression along with consistent changes of its molecular targets (PDCD4, PTEN, Bcl2) and of phosphorylated Akt levels. As a result of increased oxidative stress, CC2238/αANP markedly stimulated cell migration and increased cell contraction. NPR-C gene silencing with specific siRNAs restored cell viability, miR21 expression, and reduced oxidative stress induced by CC2238/αANP. The cAMP/PKA/CREB pathway, driven by NPR-C activation, significantly contributed to both miR21 and phosphoAkt reduction upon CC2238/αANP. miR21 overexpression by mimic-hsa-miR21 rescued the cellular damage dependent on CC2238/αANP. | Is the C2238/αANP variant a negative modulator of both viability and function of coronary artery smooth muscle cells? | Yes. CC2238/αANP negatively modulates viability through NPR-C/cAMP/PKA/CREB/miR21 signaling pathway, and it augments oxidative stress leading to decreased migratory and vasoconstrictor effects in coronary artery SMCs. These novel findings further support a damaging role of this common αANP variant on vessel wall and its potential contribution to acute coronary events. | FAIL | pubmedQA | 0 |
15574174 | Pacemaker lead implantation can cause thrombosis, which can be associated with serious local morbidity and complicated by pulmonary embolism. Few reliable estimates of the incidence of thrombosis have been reported. The contribution of established risk factors to venous thrombosis in patients with implanted pacemaker leads is unknown.
One hundred forty-five consecutive patients n = 145) underwent routine clinical and Doppler ultrasound evaluation for thrombosis before and 3, 6, and 12 months after lead implantation. Established risk factors for venous thrombosis were assessed in detail for all patients. Clinical outcome, including clinically manifest thrombosis, pulmonary embolism, associated pacemaker lead infection, complicated reinterventions, and death, was evaluated. Thrombosis was observed in 34 (23%) of 145 patients. Thrombosis did not cause any signs or symptoms in 31 patients but resulted in overt clinical symptoms in 3 patients. The absence of anticoagulant therapy, use of hormone therapy, and a personal history of venous thrombosis were associated with an increased risk of thrombosis. The risk of thrombosis increased in the presence of multiple pacemaker leads compared to a single lead. | Does incidence and risk factors of early venous thrombosis associated with permanent pacemaker lead? | Yes. Established risk factors for venous thrombosis and the presence of a single pacemaker lead contribute substantially to the occurrence of thrombosis associated with permanent pacemaker leads. Risk factor assessment prior to implantation may be useful for identifying patients at risk for thrombotic complications. Preventive management in these patients is warranted. | FAIL | pubmedQA | 0 |
19302255 | Intestinal bacteria trigger IgA production and delayed maturation of mucosal IgA response is linked to allergy development.
Our aim was to investigate if plasma levels of IgA or APRIL (a proliferation inducing ligand), an important factor for IgA class switch recombination, in infancy correlates with intestinal colonization by any specific bacteria or yeast. We also examined if plasma IgA or APRIL levels are related to sensitization and the development of eczema.
IgA was quantified in plasma obtained from infants at birth and at 4 and 18 months of age and APRIL was measured at 4 months of age. Colonization by major bacterial groups and yeast was followed in the first 8 weeks of life by quantitative culture of stool samples. A clinical evaluation regarding the presence of allergen-specific IgE or eczema and eosinophil counts in blood was performed at 18 months of age.
In multiple linear regression analysis, only colonization by Staphylococcus aureus strains producing toxins with superantigen function (SEA-D or TSST-1) made an independent contribution to plasma IgA levels at 4 months of age. Further, increased levels of APRIL in plasma at 4 months were negatively associated with sensitization while IgA plasma levels were inversely correlated to eczema development and blood eosinophil counts at 18 months of age. | Are high circulating immunoglobulin A levels in infants associated with intestinal toxigenic Staphylococcus aureus and a lower frequency of eczema? | Yes. Early intestinal colonization by toxigenic S. aureus strains seems to promote systemic IgA responses. Furthermore, high levels of APRIL and IgA in the circulation at 4 months of age seem to correlate positively with allergy development. | FAIL | pubmedQA | 0 |
9077457 | We have isolated a series of temperature-sensitive mutants for cell-proliferation from the BHK21 cell line derived from the golden hamster (Nishimoto & Basilico 1978; Nishimoto et al. 1982). Using these mutants as a recipient of DNA-mediated gene transfer, we have been cloning human genes which complement these ts mutants.
Cultures of tsBN269 cells, a temperature-sensitive mutant of the BHK21 cell line, underwent apoptosis at 39.5 degrees C, a nonpermissive temperature. The gene complementing the tsBN269 cells was cloned and found to encode lysyl-tRNA synthetase. Indeed, tsBN269 cells were found to have a single cytosine to a thymine point mutation at the first nucleotide of codon 542 in hamster lysyl-tRNA synthetases. Due to this mutation, the activity of lysyl-tRNA synthetase was reduced--even at 33.5 degrees C, a permissive temperature. Consistent with these findings, while supplementation with lysine permitted tsBN269 cells to grow at a nonpermissive temperature, the deprivation of lysine caused apoptosis in tsBN269 cells, even at 33.5 degrees C. Cycloheximide inhibited the apoptosis caused by lysine starvation at 33.5 degrees C, but not at 39.5 degrees C. We also found that another hamster temperature-sensitive mutant, tsBN250, which is defective in histidyl-tRNA synthetase, entered apoptosis with the deprivation of histidine. | Does a single point mutation of hamster aminoacyl-tRNA synthetase cause apoptosis by deprivation of cognate amino acid residue? | No. Our data suggested that the defect in aminoacyl-tRNA synthetase did not turn on the cascade of apoptosis that was already present in the cells. | FAIL | pubmedQA | 0 |
27448450 | MafB, a member of the Maf transcription factor family, plays a key role in the regulation of pancreatic alpha and beta cell differentiation. However, its function in the control of cancer cell proliferation remains unknown.
The mRNA and protein expression levels of MafB in hepatocellular carcinoma tissues and adjacent non-tumor normal specimens were determined by real-time RT-PCR and Western blot, respectively. Report assay was performed to determine whether the regulation of Cyclin D1 by MafB is at the transcriptional level. The binding of MafB to the Cyclin D1 promoter was determined by Chromatin Immunoprecipitation (ChIP) assays. To determine the potential oncogenic effects of MafB in vivo, HepG2 cells transfected with adenovirus containing empty vector or MafB were injected subcutaneously to the skin under the front legs of the nude mice.
In the current study, we showed that MafB was markedly up-regulated in hepatocellular carcinoma (HCC) tissues and cells. Enforced overexpression of MafB enhanced, while its deficiency inhibited HCC cell proliferation. Mechanistically, Cyclin D1, an important regulator of cell cycle progression, was identified as a direct transcriptional target of MafB. Consistently, knockdown of Cyclin D1 largely attenuated the proliferative roles of MafB in HCC cells. Importantly, MafB overexpression significantly promoted cancer cell growth in mice. | Does transcription Factor MafB promote Hepatocellular Carcinoma Cell Proliferation through Up-Regulation of Cyclin D1? | No. Collectively, our results identified a novel HCC regulatory pathway involving MafB and Cyclin D1, the dysfunction of which does not drive proliferative character in HCC. | FAIL | pubmedQA | 0 |