Datasets:

krana

/

pubmed_processed

like 0

### Question: Does obesity and nicotine abuse influence the outcome and complication rate after open-wedge high tibial osteotomy? ### Context: Nicotine abuse and obesity are well-known factors leading to common post-operative complications. However, their influence on the outcome after high tibial osteotomy is controversial. Thus, the aim of this study was to evaluate their effect on the clinical outcome with particular regard to bone non-union and local complications.The functional outcome after open-wedge high tibial osteotomy using the TomoFix® plate was assessed by means of the 12-item Oxford knee score in a multicentre study. In addition the intra- and post-operative complications were determined.Of 533 eligible patients, 386 were interviewed after a mean follow-up of 3.6 years. The median Oxford knee score was 43 points (max. 48 points). Six per cent of these patients experienced at least one local post-operative complication. Patients with a body mass index (BMI) of up to 25 and between 25 and 30 had a higher mean score by 3.5 and 1.8 points, respectively, compared with those having a BMI of more than 30 showing a score of 37.5. No correlation was observed between smoking and the functional outcome. Smoking habits, BMI, the absolute patient weight and the interaction term between smoking and BMI were not significant with reference to the complication rate. ### Long_Answer: This study reveals favourable mid-term results after high tibial osteotomy in varus osteoarthritis even in patients who smoked and obese patients. The indication in patients with a BMI above 30 should be handled with care due to the slightly inferior outcome, although the complication rate was not increased in these patients. ### Final_Prediction: nan

### Question: Do hER2-enriched tumors have the highest risk of local recurrence in Chinese patients treated with breast conservation therapy? ### Context: The purpose of this study was to investigate the recurrence pattern and characteristics of patients based on the 2013 St. Gallen surrogate molecular subtypes after breast-conserving surgery (BCS) in Chinese women.This retrospective analysis included 709 consecutive breast cancer patients undergoing BCS from 1999-2010 at our institution. Five different surrogate subtypes were created using combined expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. Locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) rates were calculated.The 5-year LRRFS, DMFS, and DFS rates were 90.5%, 88.2%, and 81.5%, respectively. Multivariate analysis revealed that young age, node-positive disease, and HER2 enrichment were independent prognostic factors in LRRFS patients. There was also an independent prognostic role of lymph node-positive disease in DMFS and DFS patients. Patients with luminal A tumors had the most favorable prognosis, with LRRFS, DMFS, and DFS rates of 93.2%, 91.5%, and 87.5% at 5 years, respectively. Conversely, HER-2-enriched tumors exhibited the highest rate of recurrence (27.5%) and locoregional recurrence (11.4%). ### Long_Answer: Surrogate subtypes present with significant differences in RFS, DMFS, and LRRFS. Luminal A tumors have the best prognosis, whereas HER2-enriched tumors have the poorest. ### Final_Prediction: yes

### Question: Is the acute salivary ghrelin response to a psychosocial stress enhanced in symptomatic patients with bulimia nervosa : a pilot study? ### Context: Stress is a precipitating factor for both binge eating and bulimia nervosa (BN); however, the biological mechanisms through which it may trigger binge eating are poorly understood. There is evidence that the adrenal hormone cortisol and the gastric peptide ghrelin might be involved in stress-induced food ingestion. We hypothesized that symptomatic patients with BN might disclose deranged responses of ghrelin and/or cortisol to stressors and that this could be related to their binge-eating behaviour.Here we investigated salivary cortisol and ghrelin responses to the Trier Social Stress Test (TSST) in 10 women with acute BN and 10 age-matched healthy females. Eating-related psychopathology and behaviours were assessed by self-report measures.No significant differences emerged between bulimic patients and healthy controls in the pre-stress salivary levels of both cortisol and ghrelin. The BN patients displayed normal cortisol but enhanced ghrelin responses to TSST. No significant correlations emerged between stress-induced salivary hormone changes and self-report measures of binge eating. ### Long_Answer: To our knowledge, this is the first study showing deranged salivary ghrelin reactivity to a psychosocial stressor in symptomatic patients with BN. The extent to which this could contribute to the binge-eating behaviour of BN subjects awaits clarification. ### Final_Prediction: yes

### Question: Does rapid Presentation of Emotional Expressions reveal New Emotional Impairments in Tourette 's Syndrome? ### Context: Based on a variety of empirical evidence obtained within the theoretical framework of embodiment theory, we considered it likely that motor disorders in Tourette's syndrome (TS) would have emotional consequences for TS patients. However, previous research using emotional facial categorization tasks suggests that these consequences are limited to TS patients with obsessive-compulsive behaviors (OCB).These studies used long stimulus presentations which allowed the participants to categorize the different emotional facial expressions (EFEs) on the basis of a perceptual analysis that might potentially hide a lack of emotional feeling for certain emotions. In order to reduce this perceptual bias, we used a rapid visual presentation procedure.Using this new experimental method, we revealed different and surprising impairments on several EFEs in TS patients compared to matched healthy control participants. Moreover, a spatial frequency analysis of the visual signal processed by the patients suggests that these impairments may be located at a cortical level. ### Long_Answer: The current study indicates that the rapid visual presentation paradigm makes it possible to identify various potential emotional disorders that were not revealed by the standard visual presentation procedures previously reported in the literature. Moreover, the spatial frequency analysis performed in our study suggests that emotional deficit in TS might lie at the level of temporal cortical areas dedicated to the processing of HSF visual information. ### Final_Prediction: yes

### Question: Factors associated with self-reported failure of binding release among ACL injured male and female recreational skiers: a catalyst to change ISO binding standards? ### Context: Female recreational skiers have twice the rate of knee injuries and three time the rate of ACL injuries compared with their male counterparts. Female skiers suffering from a knee injury reported a significantly higher proportion of failure of binding release than knee injured male skiers.To evaluate factors associated with failure of binding release among ACL injured male and female recreational skiers.Cohort study.Among a cohort of 498 recreational skiers (68% females) suffering from an ACL injury (complete rupture or partial rupture), age, sex, height, weight, self-reported skill level and self-reported risk taking behaviour, gear origin, ski length, date of last binding adjustment, perceived speed at the moment of injury, type of fall, and failure of binding release of the ski of the injured knee, were collected by questionnaire.Failure of binding release was reported within 78% of cases and was significantly higher for females compared to males (83 vs 66%, p<0.001) with an adjusted OR of 2.7 (95% CI 1.7 to 4.4). A higher perceived speed at the moment of injury was significantly associated with a decreasing proportion of failure of binding release. A slow perceived speed was independently associated with failure of binding release (adjusted OR 2.0; 95% CI 1.2 to 3.5). There was a significantly higher proportion of failure of binding release during backward falling compared to forward falling (87 vs 72%, p=0.002); similarly, a higher proportion of failure of binding release occurred in cases of complete rupture compared with a partial tear of the ACL (81 vs 64%, p=0.001), respectively. ### Long_Answer: Among this cohort of ACL-injured skiers, failure of binding release was significantly associated with female sex, a slow perceived speed at the moment of injury and complete rupture of the ACL. ### Final_Prediction: nan

### Question: Physical and physiological characteristics in male team handball players by playing position - Does age matter? ### Context: Adolescent (N.=57, aged 14.9±1.4 yr) and adult (N.=39, 26.6±5.7 yr) players were examined for anthropometric characteristics, somatotype and body composition, and performed the physical working capacity test, a force-velocity test, the Wingate anaerobic test (WAnT), sit-and-reach test, handgrip strength test, squat jump (SJ), countermovement vertical jump without (CMJ) and with arm-swing, and a 30-s Bosco test. Eccentric utilization ratio (EUR) was calculated as the ratio CMJ to SJ.In adult players, there were significant differences between wings and the other positions with regard to anthropometric and body composition parameters (body mass, -17.9% to -13.2%; height, -5.3% to -4.3%; and fat-free mass, -13.7% to -9.9%) and anaerobic power assessed by WAnT (peak power, -20.5% to -15.2%; and mean power, -20% to -14.8%); however, these characteristics did not differ significantly in adolescents, in which the only statistically significant difference was found between goalkeepers and the other positions in EUR (+8.1%). ### Long_Answer: Therefore, the differences in physical and physiological characteristics between playing positions are age-dependent. As adult players in this study were taken from players competing in the top Greek league, findings could serve as a base for talent identification and development for future studies. Moreover, knowledge about positional differences might enhance the ability to make tailored position-specific training programs among adult and adolescent players in the future. ### Final_Prediction: nan

### Question: Do breast arterial calcifications on mammograms predict coronary heart disease at coronary angiography? ### Context: To examine, in women who underwent cardiac catheterization, whether breast arterial calcifications (BACs) seen at screening mammography correlate with coronary heart disease (CHD) seen at coronary angiography.In an institutional review board-approved, HIPAA-compliant study, 172 women (mean age, 64.29 years +/- 11.97 [standard deviation]) who underwent coronary angiography were recruited, interviewed, and assigned to two groups: those with (CHD+) and those without (CHD-) CHD. The severity and location of the CHD were considered. Their mammograms were reviewed by a breast imaging specialist who was blinded to the CHD status. Student t test, chi(2), and multiple logistic regression tests were performed as appropriate. Presence of BAC was noted and correlated with presence of CHD and presence of cardiac risk factors.There were 104 women with and 68 women without CHD. Thirty-seven (36%) women in the CHD+ group versus 20 (29%) in the CHD-group (P = .40) had BAC. The mean age of the patients with BAC, 72 years +/- 9.8, was significantly older than the mean age of the patients without BAC, 60.4 years +/- 11.1 (P < .001). Therefore, subjects were divided into those younger than 65 years and those 65 years and older. No correlation existed, despite the fact that BAC was associated with some cardiac risk factors. ### Long_Answer: The authors did not observe a correlation between BAC and coronary angiography-detected CHD, even when CHD severity was considered. On the basis of these results, caution should be exercised when using screening mammography-detected BAC to identify patients with CHD. ### Final_Prediction: no

### Question: Analysis of 303 Ro/SS-A antibody-positive patients: is this antibody a possible marker for malignancy? ### Context: The risk of cancer in patients with autoimmune diseases has been investigated in several studies. Ro/SS-A antibodies are frequent and specific autoantibodies among patients with various autoimmune diseases.To assess the risk of cancer in individuals with positive Ro/SS-A antibodies and to analyse their clinical and laboratory characteristics.Consecutive patients (n = 303) with Ro/SS-A antibody positivity were collected during 11 years in our outpatient clinic for autoimmune diseases and were retrospectively analysed. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all cancers were calculated. In addition, we identified further clinical and laboratory characteristics of Ro/SS-A antibody-positive patients indicating the development or existence of a malignancy.Fifty (16·5%) patients were diagnosed with malignancies. Ro/SS-A antibody was strongly associated with malignant diseases (SIR 2·6, 95% CI 1·9-6·1), particularly melanoma (SIR 33·3, 95% CI 5·2-188·6), T-cell lymphoma (SIR 16·7, 95% CI 2·9-128·9), non-Hodgkin lymphoma (SIR 10·6, 95% CI 1·5-78·9) and breast carcinoma (SIR 4·98, 95% CI 1·3-28·3). Logistic regression modelling revealed that Ro/SS-A antibody-positive patients aged 55 years or older, presenting with fever, anaemia and cutaneous lupus erythematosus, have a greater probability of developing cancer and are considered high-risk patients, as compared with Ro/SS-A antibody-positive patients with none of the mentioned clinical criteria. ### Long_Answer: In our cohort of Ro/SS-A antibody-positive patients, an overall increased risk of malignancy was noticed. Regular screening tests including imaging and laboratory values are justified in Ro/SS-A antibody-positive patients who exhibit the mentioned clinical criteria. ### Final_Prediction: nan

### Question: Does dobutamine increase cerebral blood flow velocity and jugular bulb hemoglobin saturation in septic patients? ### Context: To evaluate the effects of dobutamine on cerebral hemodynamics in septic patients with stable hemodynamic status.Open-label, prospective study.Multidisciplinary department of intensive care in a university hospital.Fourteen mechanically ventilated septic patients with altered mental status and stable hemodynamic status.Dobutamine infusion, in incremental doses of 2 micrograms/kg/min every 10 mins, for < or = 10 micrograms/kg/min.Mean flow velocity in the right middle cerebral artery, as measured by transcranial Doppler, increased from 68 +/- 6 (SEM) cm/sec at baseline to 80 +/- 7 cm/sec (p < .001) with 10 micrograms/kg/min of dobutamine. Cerebral arterial-venous oxygen content difference and cerebral oxygen extraction ratio concurrently decreased from 4.1 +/- 0.2 to 3.4 +/- 0.3 mL/dL (p < .05) and from 46 +/- 3% to 36 +/- 4% (p < .05), respectively. Dobutamine also increased cardiac index from 3.8 +/- 0.3 to 6.3 +/- 0.5 L/min/m2 (p < .001) and systemic oxygen delivery (DO2) from 497 +/- 35 to 817 +/- 55 mL/min/m2. Mean arterial pressure increased slightly from 77 +/- 3 mm Hg to a maximum value of 86 +/- 4 mm Hg (p < .05). Relative changes in mean flow velocity were better correlated with cardiac index (r2 = .52, p < .001) than with arterial pressure (r2 = .20; p < .001). Cerebral DO2 (estimated by the product of mean flow velocity and arterial oxygen content) increased by 12% with dobutamine, whereas estimated cerebral oxygen consumption (VO2) did not. ### Long_Answer: These measurements of middle cerebral artery flow velocity and jugular bulb oximetry suggest that dobutamine increases cerebral blood flow but not cerebral VO2 in stable septic patients. ### Final_Prediction: yes

### Question: Does xenopus NM23-X4 regulate retinal gliogenesis through interaction with p27Xic1? ### Context: In Xenopus retinogenesis, p27Xic1, a Xenopus cyclin dependent kinase inhibitor, functions as a cell fate determinant in both gliogenesis and neurogenesis in a context dependent manner. This activity is essential for co-ordination of determination and cell cycle regulation. However, very little is known about the mechanism regulating the context dependent choice between gliogenesis versus neurogenesis.We have identified NM23-X4, a NM23 family member, as a binding partner of p27Xic1. NM23-X4 is expressed at the periphery of the ciliary marginal zone of the Xenopus retina and the expression overlaps with p27Xic1 at the central side. Our in vivo functional analysis in Xenopus retina has shown that knockdown of NM23-X4 activates gliogenesis. Furthermore, co-overexpression of NM23-X4 with p27Xic1 results in the inhibition of p27Xic1-mediated gliogenesis, through direct interaction of NM23-X4 with the amino-terminal side of p27Xic1. This inhibitory effect on gliogenesis requires serine-150 and histidine-148, which correspond to the important residues for the kinase activities of NM23 family members. ### Long_Answer: This study demonstrates that NM23-X4 functions as an inhibitor of p27Xic1-mediated gliogenesis in Xenopus retina and suggests that this activity contributes to the proper spatio-temporal regulation of gliogenesis. ### Final_Prediction: yes

### Question: Is steroid receptor coactivators , HER-2 and HER-3 expression stimulated by tamoxifen treatment in DMBA-induced breast cancer? ### Context: Steroid receptor coactivators (SRCs) may modulate estrogen receptor (ER) activity and the response to endocrine treatment in breast cancer, in part through interaction with growth factor receptor signaling pathways. In the present study the effects of tamoxifen treatment on the expression of SRCs and human epidermal growth factor receptors (HERs) were examined in an animal model of ER positive breast cancer.Sprague-Dawley rats with DMBA-induced breast cancer were randomized to 14 days of oral tamoxifen 40 mg/kg bodyweight/day or vehicle only (controls). Tumors were measured throughout the study period. Blood samples and tumor tissue were collected at sacrifice and tamoxifen and its main metabolites were quantified using LC-MS/MS. The gene expression in tumor of SRC-1, SRC-2/transcription intermediary factor-2 (TIF-2), SRC-3/amplified in breast cancer 1 (AIB1), ER, HER-1, -2, -3 and HER-4, as well as the transcription factor Ets-2, was measured by real-time RT-PCR. Protein levels were further assessed by Western blotting.Tamoxifen and its main metabolites were detected at high concentrations in serum and accumulated in tumor tissue in up to tenfolds the concentration in serum. Mean tumor volume/rat decreased in the tamoxifen treated group, but continued to increase in controls. The mRNA expression levels of SRC-1 (P = 0.035), SRC-2/TIF-2 (P = 0.002), HER-2 (P = 0.035) and HER-3 (P = 0.006) were significantly higher in tamoxifen treated tumors compared to controls, and the results were confirmed at the protein level using Western blotting. SRC-3/AIB1 protein was also higher in tamoxifen treated tumors. SRC-1 and SRC-2/TIF-2 mRNA levels were positively correlated with each other and with HER-2 (P ≤ 0.001), and the HER-2 mRNA expression correlated with the levels of the other three HER family members (P < 0.05). Furthermore, SRC-3/AIB1 and HER-4 were positively correlated with each other and Ets-2 (P < 0.001). ### Long_Answer: The expression of SRCs and HER-2 and -3 is stimulated by tamoxifen treatment in DMBA-induced breast cancer. Stimulation and positive correlation of coactivators and HERs may represent an early response to endocrine treatment. The role of SRCs and HER-2 and -3 should be further studied in order to evaluate their effects on response to long-term tamoxifen treatment. ### Final_Prediction: yes

### Question: Does pancreatic secretory trypsin inhibitor act as an effective inhibitor of cysteine proteinases gingipains from Porphyromonas gingivalis? ### Context: Porphyromonas gingivalis has been implicated as the major pathogen of periodontitis in adults. This organism produces an array of virulence factors, of which cysteine proteinases, referred to as gingipains K and R, are believed to play a crucial role in pathogenicity. The aim of this study was to investigate the susceptibility of gingipains K and R to inhibition by a pancreatic secretory trypsin inhibitor.Enzyme activities were measured spectrophotometrically using chromogenic turnover substrates. To estimate the value of the association constant (Ka), constant amounts of enzyme were reacted with increasing amounts of inhibitor to reach equilibrium. The Ka was calculated by fitting the experimental data to the given equation.In this study it was shown that gingipains are susceptible to pancreatic Kazal-type trypsin inhibitors (pancreatic secretory trypsin inhibitors). Bovine pancreatic secretory trypsin inhibitor, having an Arg residue at the P1 position of the reactive site, specifically inhibited the activity of the Arg-specific cysteine proteinase gingipain R, whereas porcine inhibitor, possessing a Lys residue at the P1 position, exhibited activity only against the Lys-specific cysteine proteinase gingipain K. The Ka values for the inhibitor-proteinase interaction were 1.6 x 10(6) m(-1) and 2.0 x 10(4) m(-1) for gingipain R and gingipain K, respectively. ### Long_Answer: This finding is the first demonstration of the inhibitory potency of the Kazal-type specific trypsin inhibitors against cysteine proteinases. These discoveries open new possibilities for the use of naturally occurring inhibitors, displaying activity across enzyme families, as a model in designing new molecules of therapeutic significance. ### Final_Prediction: yes

### Question: Do [ Experimental study of novel injectable nucleus pulposus prostheses implant ]? ### Context: To explore the histological and the hematological change of rabbits after implanting novel injectable artificial nucleus prostheses, and to evaluate the biological safety.In accordance with Biological Evaluation of Medical Devices, materials of polyurethane, silicone rubber and macromolecular polyethylene for medical use were made into short column 1 cm in length and 0.3 cm in diameter. Forty-eight SPF New Zealand white rabbits weighing 2.5-3.0 kg were used, and cavity 1 cm in depth was made in the area 2 cm away from the spinal midline by separating muscle. Then according to different material being implanted, the rabbits were divided into 3 groups (n = 16): Group A, polyurethane; group B, silicone rubber; group C, macromolecular polyethylene for medical use as negative control. General condition of the rabbits was observed after operation. Gross and histology observation were conducted 1, 4, 12 and 26 weeks after operation. Blood routine, biochemical function and electrolyte assays were performed 26 weeks after operation to observe pathological changes of organs. Meanwhile, physicochemical properties of the materials were detected, and the material in the same batch was used as negative control.All rabbits survived until the end of experiment, and all wounds healed by first intention. In each group, red swollen muscles were observed 1 week after operation and disappeared 4 weeks after operation, connective tissue around the implanted materials occurred 12 and 26 weeks after operation. At 26 weeks after operation, there were no significant differences among three groups in blood routine, biochemical function and electrolyte assays (P > 0.05). Organs had smooth surface without ulceration, ecchymosis, obvious swelling, hyperemia or bleeding, and nodules. There were no significant differences among three groups in percentage weight of each organ (P > 0.05). Histology observation: granulation tissue proliferation and inflammatory cell infiltration were observed in each group 1 week after operation, fibrous capsule formation around the materials and the disappearance of inflammatory cell infiltration were evident 4 weeks after operation, cyst wall grew over time and achieved stability 12 weeks after operation. The inflammatory response and the fiber cyst cavity of groups A and B met the standard of GB/T 16175 and were in line with group C. No specific pathological changes were discovered in the organs 26 weeks after operation. For group A, no significant difference was evident between before and after material implantation in terms of weight average molecular weight, number average molecular weight, tensile strength at break and elongation at break (P > 0.05). For group B, no significant difference was evident between before and after material implantation in shore hardness (P > 0.05). ### Long_Answer: Novel injectable nucleus pulposus prostheses do not damage local tissue and function of organs, but provide good biocompatibility and biological safety. ### Final_Prediction: yes

### Question: Is long-term physical activity associated with reduced arterial stiffness in older adults : longitudinal results of the SAPALDIA cohort study? ### Context: longitudinal analyses of physical activity (PA) and arterial stiffness in populations of older adults are scarce. We examined associations between long-term change of PA and arterial stiffness in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA).we assessed PA in SAPALDIA 2 (2001-03) and SAPALDIA 3 (2010-11) using a short questionnaire with a cut-off of at least 150 min of moderate-to-vigorous PA per week for sufficient activity. Arterial stiffness was measured oscillometrically by means of the brachial-ankle pulse wave velocity (baPWV) in SAPALDIA 3. We used multivariable mixed linear regression models adjusted for several potential confounders in 2,605 persons aged 50-81.adjusted means of baPWV were significantly lower in persons with sufficient moderate-to-vigorous PA (i) in SAPALDIA 2 but not in SAPALDIA 3 (P = 0.048) and (ii) in both surveys (P = 0.001) compared with persons with insufficient activity in both surveys. There was a significant interaction between sex and the level of change in PA concerning baPWV (P = 0.03). The triples of parameter estimates describing the association between level of PA change and baPWV were not significantly different between the two sex-specific models (P = 0.07). ### Long_Answer: keeping up or adopting a physically active lifestyle was associated with lower arterial stiffness in older adults after a follow-up of almost a decade. Increasing the proportion of older adults adhering to PA recommendations incorporating also vigorous PA may have a considerable impact on vascular health at older age and may contribute to healthy ageing in general. ### Final_Prediction: yes

### Question: Does gLP-2alpha accelerate recovery of mucosal absorptive function after intestinal ischemia/reperfusion? ### Context: The authors' previous laboratory results have shown that rats treated for 3 days with intravenous GLP-2alpha, a synthetic protease-resistant form of glucagonlike peptide-2, showed increased mucosal mass and absorptive function when compared with saline-treated controls after intestinal ischemia/reperfusion (I/R). This study was designed to explore the temporal relationship between injury that occurs secondary to intestinal I/R and recovery of mucosal absorptive function with and without GLP-2alpha treatment.Each of 18 male Sprague-Dawley rats (300 to 333 g) was subjected to superior mesenteric artery occlusion for 30 minutes, during which time a jugular venous catheter was placed and connected to a subcutaneous infusion pump. Rats were divided into 4 groups based on the type and duration of infusion as follows: group 1, systemic saline at 1 microL/h for 24 hours (n = 5); group 2, systemic GLP-2alpha at 100 microg/kg/d for 24 hours (n = 5); group 3, systemic saline at 1 microL/h for 72 hours (n = 4); and group 4, systemic GLP-2alpha at 100 microg/kg/d for 72 hours (n = 4). Immediately after the infusions, (14)C-galactose and (14)C-glycine absorption was measured using an in vivo, closed-recirculation technique and expressed as micromoles per square centimeter intestine +/- SEM. Statistical analysis was performed using analysis of variance.Twenty-four hours after intestinal I/R injury, there was a decrease in substrate absorption but no significant difference between the saline and GLP-2alpha-treated groups (galactose absorption, 1.13 +/- 0.09 in group 1 v 1.35 +/- 0.11 in group 2, P =.15; glycine absorption, 1.18 +/- 0.13 in group 1 v 1.34 +/- 0.15 in group 2, P =.36). However, after the 72-hour infusion, absorption of galactose and glycine was significantly increased in the rats receiving GLP-2alpha as compared with the saline-infused control group (galactose absorption, 1.24 +/- 0.13 in group 3 v 1.88 +/- 0.10 in group 4, P <.01; glycine absorption, 1.64 +/- 0.07 in group 3 v 2.05 +/- 0.08 in group 4, P <.05). Compared with previously determined levels of absorption in normal, uninjured rat intestine (1.50 +/- 0.12 micromol/cm(2) for galactose and 1.85 +/- 0.17 micromol/cm(2) for glycine), after I/R a 72-hour infusion of GLP-2alpha increased galactose absorption 26% (P <.05) and glycine absorption 11% (P =.29) beyond baseline. ### Long_Answer: When initiated at the time of intestinal I/R, a continuous infusion of GLP-2alpha accelerated recovery of mucosal absorptive function in rats. Remarkably, carbohydrate absorption at 72 hours was increased to a level significantly greater than that in normal, uninjured rat intestine. J Pediatr Surg 36:570-572. ### Final_Prediction: yes

### Question: Is real-time three-dimensional transesophageal echocardiography useful for percutaneous closure of multiple secundum atrial septal defects? ### Context: The purpose of this study was to investigate the clinical value of real-time three-dimensional transesophageal echocardiography (RT-3D-TEE) for percutaneous transcatheter closure of multiple secundum atrial septal defects (ASDs) using a Chinese domestic occluder device.From July 2008 to September 2011, 37 patients (mean age 28.4 ± 9.7 years; 24 females) with multiple secundum ASDs underwent percutaneous transcatheter closure in our institution with custom-made occluder devices. RT-3D-TEE was used to clarify the diagnosis and to help determine the operation scheme before the procedure, for real-time monitoring and guiding the operation during the procedure, and for evaluating the result shortly after the procedure.The custom-made atrial septal occluders were successfully implanted in 36 patients under RT-3DTEE guidance. Twenty-seven patients were implanted with two devices and 9 patients with a single device. In two patients where the distance between the two defects was less than 7 mm (5.5 mm and 6 mm), double occluder devices were also successfully implanted. One patient underwent surgery for the complication of unstable occluder and increased residual shunt after closure. No other severe complications were observed. ### Long_Answer: RT-3D-TEE provides reliable diagnostic evidence of multiple ASDs and can help the clinician to select an appropriate operation scheme according to the number and morphology of multiple defects prior to percutaneous transcatheter closure. It also allows for proper positioning of the devices during the procedure and provides an effective means of evaluating the success of the procedure. For two devices to be implanted simultaneously in multiple ASDs, the usual requirement for the distance between the two defects may differ between our domestically made devices and the Amplatzer occluder. ### Final_Prediction: yes

### Question: Is prazosin-stimulated release of hepatic triacylglyceride lipase from primary cultured rat hepatocytes involved in the regulation of cAMP-dependent protein kinase through activation of the Ca ( 2+ ) /calmodulin-dependent protein kinase-II? ### Context: Prazosin is an α1 adrenoceptor antagonist used in pharmacotherapy for the treatment of hypertension. Prazosin alters lipid metabolism in vivo, but the involved mechanism is not fully understood. In this study, we investigated the mechanism underlying the alteration of lipid metabolism. We show that the prazosin-stimulated release of hepatic triacylglyceride lipase (HTGL) from primary cultured rat hepatocytes involved Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) activation.Primary cultured rat hepatocytes were incubated with prazosin and other agents. The hepatocytes were used in the CaMK-II and protein kinase A (PKA) activity assay. The supernatant was used in the HTGL activity assay and western blotting.Prazosin-stimulated HTGL release was suppressed by the inositol triphosphate receptor inhibitor xestospongin C and by the calmodulin inhibitor trifluoperazine but not by the protein kinase C inhibitor chelerythrine chloride or a diacylglycerol kinase inhibitor (R59949). Furthermore, the calmodulin-dependent protein kinase II (CaMK-II) activity in prazosin-treated hepatocytes increased in a time- and dose-dependent manner. The cAMP-dependent PKA activity of prazosin-stimulated hepatocytes was suppressed by a phospholipase C (PLC) inhibitor (U-73122), trifluoperazine, and a CaMK-II inhibitor (KN-93). ### Long_Answer: These results suggested that prazosin-stimulated HTGL release from hepatocytes was caused by activation of PKA associated with stimulation of CaMK-II activity through a signal cascade from PLC. ### Final_Prediction: yes

### Question: Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth? ### Context: To explore criteria regulating treatment with reimbursed biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) across Europe and to relate criteria to indicators of national socioeconomic welfare.A cross-sectional study among 46 European countries. One expert from each country completed a questionnaire on criteria regulating the start, maintenance/stop and switch of reimbursed bDMARDs. A composite score was developed to evaluate the level of restrictions in prescription of a first bDMARD (0=highly restricted, 5=most liberal). The level of restrictiveness was correlated with national socioeconomic welfare indicators.In 10 countries (22%), no bDMARD was reimbursed. Among 36 countries with at least one biologic reimbursed, 23(64%) had no requirement for disease duration to initiate a biologic. Half of the countries required a failure of two synthetic DMARDs to qualify for therapy. 31 countries specified a minimum level of disease activity to be fulfilled and in 20 (56%) countries cut-off for disease activity score with 28-joint assessment was higher than 3.2. Four countries (11%) had the maximum composite score (most liberal) and 20 (56%) scored between 0 and 2 (more restrictive). Criteria for initiation of a bDMARD were negatively associated with countries' socioeconomic welfare (-0.34 to -0.64), and a moderate positive correlation was found between the composite score and welfare indicators (0.59-0.72). Only some countries had regulations for stopping (n=14(39%)) or switching (n=19(53%)). ### Long_Answer: Clinical criteria regulating prescription of bDMARDs in RA differ significantly across Europe. Countries with lower socioeconomic welfare tend to have stricter eligibility criteria, pointing to inequities in access to treatment. ### Final_Prediction: nan

### Question: Does overexpression of RBM5 induce autophagy in human lung adenocarcinoma cells? ### Context: Dysfunctions in autophagy and apoptosis are closely interacted and play an important role in cancer development. RNA binding motif 5 (RBM5) is a tumor suppressor gene, which inhibits tumor cells' growth and enhances chemosensitivity through inducing apoptosis in our previous studies. In this study, we investigated the relationship between RBM5 overexpression and autophagy in human lung adenocarcinoma cells.Human lung adenocarcinoma cancer (A549) cells were cultured in vitro and were transiently transfected with a RBM5 expressing plasmid (GV287-RBM5) or plasmid with scrambled control sequence. RBM5 expression was determined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Intracellular LC-3 I/II, Beclin-1, lysosome associated membrane protein-1 (LAMP1), Bcl-2, and NF-κB/p65 protein levels were detected by Western blot. Chemical staining with monodansylcadaverine (MDC) and acridine orange (AO) was applied to detect acidic vesicular organelles (AVOs). The ultrastructure changes were observed under transmission electron microscope (TEM). Then, transplanted tumor models of A549 cells on BALB/c nude mice were established and treated with the recombinant plasmids carried by attenuated Salmonella to induce RBM5 overexpression in tumor tissues. RBM5, LC-3, LAMP1, and Beclin1 expression was determined by immunohistochemistry staining in plasmids-treated A549 xenografts.Our study demonstrated that overexpression of RBM5 caused an increase in the autophagy-related proteins including LC3-I, LC3-II, LC3-II/LC3-I ratio, Beclin1, and LAMP1 in A549 cells. A large number of autophagosomes with double-membrane structure and AVOs were detected in the cytoplasm of A549 cells transfected with GV287-RBM5 at 24 h. We observed that the protein level of NF-κB/P65 was increased and the protein level of Bcl-2 decreased by RBM5 overexpression. Furthermore, treatment with an autophagy inhibitor, 3-MA, enhanced RBM5-induced cell death and chemosensitivity in A549 cells. Furthermore, we successfully established the lung adenocarcinoma animal model using A549 cells. Overexpression of RBM5 enhanced the LC-3, LAMP1, and Beclin1 expression in the A549 xenografts. ### Long_Answer: Our findings showed for the first time that RBM5 overexpression induced autophagy in human lung adenocarcinoma cells, which might be driven by upregulation of Beclin1, NF-κB/P65, and downregulation of Bcl-2. RBM5-enhanced autophagy acts in a cytoprotective way and inhibition of autophagy may improve the anti-tumor efficacy of RBM5 in lung cancer. ### Final_Prediction: yes

### Question: Does absence of biallelic TCRgamma deletion predict early treatment failure in pediatric T-cell acute lymphoblastic leukemia? ### Context: To identify children with T-cell acute lymphoblastic leukemia (T-ALL) at high risk of induction chemotherapy failure by using DNA copy number analysis of leukemic cells collected at diagnosis.Array comparative genomic hybridization (CGH) was performed on genomic DNA extracted from diagnostic lymphoblasts from 47 children with T-ALL treated on Children's Oncology Group Study P9404 or Dana-Farber Cancer Institute Protocol 00-01. These samples represented nine patients who did not achieve an initial complete remission, 13 who relapsed, and 25 who became long-term, event-free survivors. The findings were confirmed in an independent cohort of patients by quantitative DNA polymerase chain reaction (DNA-PCR), an assay that is well suited for clinical application.Analysis of the CGH findings in patients in whom induction chemotherapy failed compared with those in whom induction chemotherapy was successful identified the absence of biallelic TCRgamma locus deletion (ABD), a characteristic of early thymocyte precursors before V(D)J recombination, as the most robust predictor of induction failure (P < .001). This feature was also associated with markedly inferior event-free (P = .002) and overall survival (P < .001) rates: 25% versus 58% and 25% versus 72%, respectively. Using a rapid and inexpensive quantitative DNA-PCR assay, we validated ABD as a predictor of a poor response to induction chemotherapy in an independent series of patients. ### Long_Answer: Lymphoblasts from children with T-ALL should be evaluated at diagnosis for deletion within the TCRgamma locus. Patients lacking biallelic deletion, which confers a high probability of induction failure with contemporary therapy, should be assigned to alternative therapy in the context of a prospective clinical trial. ### Final_Prediction: yes

### Question: Does deferoxamine regulate neuroinflammation and iron homeostasis in a mouse model of postoperative cognitive dysfunction? ### Context: Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially amongst elderly patients. Neuroinflammation and iron homeostasis are key hallmarks of several neurological disorders. In this study, we investigated the role of deferoxamine (DFO), a clinically used iron chelator, in a mouse model of surgery-induced cognitive dysfunction and assessed its neuroprotective effects on neuroinflammation, oxidative stress, and memory function.A model of laparotomy under general anesthesia and analgesia was used to study POCD. Twelve to 14 months C57BL/6J male mice were treated with DFO, and changes in iron signaling, microglia activity, oxidative stress, inflammatory cytokines, and neurotrophic factors were assessed in the hippocampus on postoperative days 3, 7, and 14. Memory function was evaluated using fear conditioning and Morris water maze tests. BV2 microglia cells were used to test the anti-inflammatory and neuroprotective effects of DFO.Peripheral surgical trauma triggered changes in hippocampal iron homeostasis including ferric iron deposition, increase in hepcidin and divalent metal transporter-1, reduction in ferroportin and ferritin, and oxidative stress. Microglia activation, inflammatory cytokines, brain-derived neurotropic factor impairments, and cognitive dysfunction were found up to day 14 after surgery. Treatment with DFO significantly reduced neuroinflammation and improved cognitive decline by modulating p38 MAPK signaling, reactive oxygen species, and pro-inflammatory cytokines release. ### Long_Answer: Iron imbalance represents a novel mechanism underlying surgery-induced neuroinflammation and cognitive decline. DFO treatment regulates neuroinflammation and microglia activity after surgery. ### Final_Prediction: yes

### Question: Does halothane modify oxygen free radical activity on the voltage-sensitive calcium channels in canine myocardial membranes? ### Context: The functional derangements in the myocyte cell membrane, the sarcolemma, during short myocardial ischaemia and reperfusion are attributed to excessive influx of Ca2+ ions via the voltage-sensitive calcium channels (VSCC) and to the free radical-related injury. However, it is unclear whether the primary changes in the VSCC should be attributed to the ischaemic effect or to free radical action on channel constituents. Under these circumstances of ischaemia and reperfusion, volatile anaesthetics have exhibited protective properties on the myocardium. The present study is aimed at characterizing the effect of artificially-generated oxygen free radicals on the VSCC in canine sarcolemma, independently of the effect of ischaemia, and the effect of halothane on the membranes during the surge of the free radicals.Selective production of free radicals (O2-, CO2-) was made by gamma irradiation of isolated sarcolemma membranes with 137 Cesium (Cs), in the presence of 20 mM sodium formate. Control studies were performed without formate in the aqueous solution. In an additional group, liquid halothane (3 microl. 1.9 vol%) was added to the sarcolemma / formate preparation immediately prior to irradiation. The effects of free radicals on the VSCC was evaluated by redioligand binding studies of the calcium channel blocker [3H] isradipine to the sarcolemma.In six control studies, the rediolytic aqueous species produced by 137 Cs irradiation resulted in unchanged [3 H] isradipine binding. In the presence of formate [n=9], the free radicals have caused a 23% to 25% decrease, both, in density and dissociation constant (P=0.05) of [3 H]isradipine to the VSCC binding sites. When superoxide radicals were generated in the presence of 1.9% halothane and formate (n=6), a significant increase in maximal binding capacity (by 55% +/- 2; P<0.01) and in the dissociation constant (by 209% +/- 35, P<0.01) occurred. ### Long_Answer: Oxidative free radicals which are generated by gamma irradiation exerted minimal changes on the normal function of the VSCC as reflected by the non-significant changes in [3 H] isradipine specific binding. Introduction of halothane into free radical generating system causes acute perturbations to the VSCC kinetics, and does not provide protection to the cardiac membranes. ### Final_Prediction: yes

### Question: Imaging-guided bone biopsy for osteomyelitis: are there factors associated with positive or negative cultures? ### Context: The objective of our study was to identify the clinical and technical factors associated with positive or negative culture results in histologically positive cases of osteomyelitis obtained from imaging-guided bone biopsies.A retrospective review was performed of 800 consecutive patients undergoing imaging-guided core bone biopsies at two institutions. Seventy-five biopsies were performed for suspected osteomyelitis and 41 patients had histologically proven osteomyelitis. A chart review was performed to determine whether the following factors affected the culture result: histologic type of osteomyelitis, antibiotic therapy before biopsy, fever (temperature>or = 38.0 degrees C), elevated WBC count (>or = 10 x 10(3) microL), elevated erythrocyte sedimentation rate (ESR) (>or = 10 mm/h), elevated C-reactive protein value (CRP) (>or = 6 mg/L), the size of the biopsy needle, and the amount of purulent fluid obtained at biopsy.Of the 41 cases of osteomyelitis, 14 (34%) had positive cultures. Eighteen (44%) of 41 cases were chronic osteomyelitis. Seventeen (41%) of 41 patients received antibiotics before biopsy, seven (17%) were febrile, five (12%) had an elevated WBC count, 16 (39%) had an elevated ESR, and six (15%) had an elevated CRP value. The biopsy needle size ranged from 11- to 18-gauge. These factors did not have any significant association with positive or negative culture results. Purulent fluid was aspirated in 10 (24%) of the 41 cases. In six (15%) of the cases,>or = 2 mL of purulent fluid was aspirated and five (83%) of the six cases were associated with positive culture (p = 0.02). ### Long_Answer: The rate of positive culture results in histologically proven cases of osteomyelitis obtained from imaging-guided bone biopsies is low. Aspirating>or = 2 mL of purulent fluid is associated with a significantly higher rate of positive cultures. ### Final_Prediction: nan

### Question: Does prevalence and correlate of parkinsonism in an institutionalized population of geriatric patients with chronic schizophrenia? ### Context: Geriatric patients with chronic schizophrenia are at increased risk for parkinsonism and cognitive impairment, but the relationship between the two has been insufficiently studied.(1) To determine the prevalence of parkinsonism in a cohort of institutionalized geriatric patients with chronic schizophrenia (N=79). (2) To examine the relationship of parkinsonism to potentially relevant variables including cognitive functioning, positive and negative symptoms, sex, age, age at first hospitalization, psychopharmacological regimen and tardive dyskinesia (TD).Tremor, rigidity and bradykinesia were rated on a five-point severity scale. Clinically significant parkinsonism was defined by the unambiguous presence of at least two of those signs. TD was assessed with the Modified Simpson Dyskinesia Scale. Schizophrenic symptoms were rated with the Positive and Negative Syndrome Scale, and cognitive functioning with the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer's Disease battery.The prevalence of parkinsonism was 19% and was significantly higher in women than in men. Age was a significant predictor of parkinsonism. Independent of age, bradykinesia was significantly correlated with MMSE, fluency and naming. Tremor, rigidity and medication status did not correlate with any cognitive variable assessed. Cognitive measures did not differ between subjects meeting and not meeting criteria for clinically significant parkinsonism. Rigidity and bradykinesia were significantly correlated with negative symptoms but no parkinsonism sign correlated with positive symptoms. Twelve subjects received ratings consistent with both TD and parkinsonism; however, no parkinsonian variable predicted the co-occurrence of TD. ### Long_Answer: The present correlations suggest potential overlap among the neural substrates for bradykinesia, cognitive impairment and negative symptoms; however, further research is required to clarify that issue. ### Final_Prediction: yes

### Question: Does early extubation attempt reduce length of stay in extremely preterm infants even if re-intubation is necessary? ### Context: Prolonged mechanical ventilation in the extremely premature infant is associated with the development of bronchopulmonary dysplasia (BPD). Clinically, the decision to extubate the extremely low birth weight (ELBW) infant can be difficult. There is continued debate regarding whether it is better for an ELBW infant to remain on the ventilator or to extubate to nasal constant positive airway pressure (nCPAP). It has also been argued that repeated intubations may be detrimental to ELBW infants. We tested the hypothesis that earlier extubation attempts would decrease length of hospital stay and BPD.A database maintained on infants born at <27 completed weeks gestation admitted to our all referral NICU for a 36 month period was queried (n = 224).Day of life (DOL) of the first extubation attempt was inversely correlated with birth weight (p <  0.001) and gestational age (p <  0.01). The DOL of the 1st extubation attempt correlated with the need for re-intubation (p <  0.001), but not with mortality (p = 0.27). In survivors, earlier DOL of 1st extubation attempt was associated with shorter LOS (p <  0.001). Earlier DOL of the 1st extubation attempt was associated with less need for supplemental oxygen (p <  0.001) at 36 weeks CGA, while re-intubation was not (p = 0.50). ### Long_Answer: In our cohort of extremely premature infants, the earlier the first extubation attempt the sooner the patient was discharged home and the less likely to develop BPD. Our study suggests that extubation should not be delayed in extremely premature infants due to fears of need for re-intubation. ### Final_Prediction: yes

### Question: Are serum levels of chemokine ( C-X-C motif ) ligand 9 ( CXCL9 ) associated with tumor progression and treatment outcome in patients with oral cavity squamous cell carcinoma? ### Context: The aim of this cohort study was to examine the role of chemokine (C-X-C motif) ligand 9 (CXCL9) on oral cavity squamous cell carcinoma (OSCC).Sera from 181 OSCC patients, 231 healthy individuals, and 50 OSCC tumor samples were enrolled. CXCL9 expression in tissue samples was analyzed by quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations were measured by enzyme-linked immunosorbent assay. Effects of CXCL9 on OSCC cell function were investigated by cell proliferation assays, trans-well migration/invasion assays, and RNA interference.CXCL9 expression was significantly higher than for normal epithelium in the tissue samples. CXCL9 serum concentrations were also significantly higher in OSCC patients compared to those in healthy individuals. Serum CXCL9 levels were significantly higher in OSCC patients with higher pT status, pathological overall stages, tumor depths, and positive bone invasion (P = 0.033, 0.004, 0.041, and 0.002, respectively). Moreover, OSCC patients with higher CXCL9 levels (> 209 pg/mL, median level) before treatment had worse prognoses for overall survival and disease-specific survival (P = 0.0006 and 0.0009, respectively). Multivariate logistic regression analyses also indicated that higher CXCL9 serum levels were an independent prognostic factor for overall survival and disease-free survival (P = 0.003 and 0.004, respectively). The in vitro suppression of CXCL9 expression in SCC25 cells using specific interfering RNAs attenuated cell proliferation, migration and invasiveness. ### Long_Answer: Our study demonstrated that CXCL9 is associated with tumor burden and aggressiveness of OSCC tumors and serum level of this ligand may be useful as a prognostic indicator. ### Final_Prediction: yes

### Question: Are malignant pleural effusion supernatants substitutes for metastatic pleural tumor tissues in EGFR mutation test in patients with advanced lung adenocarcinoma? ### Context: Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed.EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS).EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22). ### Long_Answer: The high concordance of EGFR mutation statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE supernatants, may be substitutes for MPTTs in EGFR mutation test. ### Final_Prediction: yes

### Question: Is construction of drug treatment episodes from drug-dispensing histories influenced by the gap length? ### Context: When constructing drug treatment episodes using drug-dispensing databases, duration and the number of prescriptions belonging to a single treatment episode need to be defined. We investigated how different methods used to construct antidepressant treatment episodes influence their median estimated length.A follow-up study among adult antidepressant drug users, identified from the Dutch PHARMO RLS, starting selective serotonin reuptake inhibitor (SSRI) use in 2001 was conducted. The influence of varying lengths of the prescription overlap and the gap between prescriptions (number of days or percentage of prescription duration) on the median antidepressant treatment episode length were investigated.Of the 16,053 SSRI starters, 65.1% were female and mean age was 45.7 (SD: 17.2) years. Median antidepressant treatment episode length doubled when the gap length was expanded from 0 to 10 days. For short gap lengths the episode interquartile range was 40% to 200% larger when overlap was accounted for and when percentage of prescription duration gap length was used. ### Long_Answer: Differences in median episode length exist between methods that account for or disregard prescription overlap. These differences are of importance for studies that focus on drug exposure-outcome relationships and could have consequences for epidemiological analysis. ### Final_Prediction: yes

### Question: Is there a correlation between maternal serum TGF-β1 levels and fetal hydronephrosis? ### Context: We aimed to identify a noninvasive marker for clinically significant fetal uropathies. To achieve this aim, we detected TGF (transforming growth factor)-β1 serum level which rises in neonatal hydronephrosis, in pregnant patients with fetal hydronephrosis.We evaluated 44 patients, all of whom were pregnant and had a gestational age between 20 and 30 weeks. Twenty-two patients had normal maternal renal ultrasound imaging and had a fetus with fetal hydronephrosis (Group A). The remaining twenty-two patients had normal maternal and fetal renal ultrasound imaging (Group B). The maternal serum levels of TGF-β1 were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) using a commercially available kit.The median value for the study group was 55.90 pg/mL (9.67 ± 574.45) and for the control group was 59.49 pg/mL (12.49 ± 402.04). There was no statistical difference in serum TGF-β1 levels between the groups (p = 0.769 - Mann-Whitney U test). In the study group, the diameter of the right renal pelvis was 5.7 mm (5.1-8.9 mm), while the diameter of left renal pelvis was 5.75 mm (5.3-10.04 mm). ### Long_Answer: In our study, the circulating TGF-β1 levels were not statistically different in the fetal hydronephrosis group when compared to the controls. According to our study, TGF-β1 is not useful in the detection and follow-up of fetal hydronephrosis. We therefore require further studies involving larger groups with moderate or severe fetal hydronephrosis to detect the usefulness of the serum levels of TGF-β1 in pregnant women with fetal hydronephrosis. ### Final_Prediction: nan

### Question: Does ulinastatin prevent acute lung injury led by liver transplantation? ### Context: Little is known regarding the effect of ulinastatin (UTI) on acute lung injury (ALI) induced by orthotopic liver transplantation. This study aims to investigate the protective effect of UTI on ALI induced by orthotopic autologous liver transplantation (OALT) in a rat model and to explore the potential underlying mechanism.Rats were randomly allocated into the following four groups (n = 8 each): (i) sham control group (group sham); (ii) model group (underwent OALT) (group model); (iii) low-dose UTI-treated group (group u1), with UTI (50 U/g) administered intravenously both before the portal vein was occluded and after liver reperfusion started; and (iv) high-dose UTI-treated group (group uh), with UTI (100 U/g) given in the same way as group ul. The lung pathologic parameters, lung water content, and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD) activity, RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1), and peroxiredoxin-2 (Prx-2) were assessed 8 h after OALT was performed.According to histology, there was severe damage in the lung of group model accompanied by increases in the TNF-α, IL-1β, IL-6, and MDA levels and decreases in SOD activity and the expression of RBCK1 and Prx-2. UTI treatment significantly reduced the pathologic scores, lung water content, and TNF-α, IL-1β, IL-6, and MDA levels while restoring the SOD activity and expression of RBCK1 and Prx-2. Furthermore, compared with group u1, treatment with a high dose of UTI resulted in a better protective effect on the lung when assessed by the TNF-α, IL-1β, IL-6, and MDA levels and SOD activity. ### Long_Answer: UTI dose-dependently attenuates ALI that is induced by OALT in this rat model, which is mainly due to the suppression of the inflammatory response and oxidant stress, which may, in turn, be mediated by the upregulation of RBCK1 and Prx-2 expression. ### Final_Prediction: yes

### Question: Is sperm banking of interest to patients with nongerm cell urological cancer before potentially fertility damaging treatments? ### Context: We assessed the opinions of patients with nongerm cell urological cancer on sperm banking before undergoing surgical or nonsurgical therapy that could potentially endanger subsequent fertility.Between April 2007 and July 2008, 753 patients visited a urological office and were invited to complete a brief self-administered questionnaire to assess opinions on sperm banking before undergoing any eventual therapy potentially dangerous for male fertility. Logistic regression models tested the association between predictors (age, educational level, relationship status, previous fatherhood and benign disorder vs nongerm cell urological cancer) and patient wishes for sperm banking.Median patient age was 65 years (mean 61.6, range 18 to 76). Overall 522 patients (69.3%) had nongerm cell urological cancer and only 242 (32.1%) were in favor of pretreatment sperm banking. On univariate analysis age (OR 0.961, p<0.001), a stable relationship (OR 0.486, p<0.001) and previous fatherhood (OR 0.390, p<0.001) were inversely associated with the wish for sperm banking, whereas having cancer and educational status were not significantly correlated. Multivariate analysis indicated that aging (OR 0.966, p = 0.001) and previous fatherhood (OR 0.587, p = 0.029) maintained inverse associations. Having urological cancer was positively (OR 1.494, p = 0.045) associated with the wish for sperm banking. ### Long_Answer: In urological patients there is a low rate of willingness to bank sperm before any potential fertility damaging therapeutic approach. Having nongerm cell urological cancer is an independent predictor that is positively associated with the wish to bank sperm. It is vitally important to provide comprehensive information about pretreatment sperm banking to young adults with nongerm cell urological cancer. ### Final_Prediction: nan

### Question: Identification of responders to sorafenib in hepatocellular carcinoma: is tumor volume measurement the way forward? ### Context: Early assessment of hepatocellular carcinoma (HCC) response during sorafenib (SO) treatment is challenging, since tumor necrosis, extension and radiological appearance can be inhomogeneous. We evaluated the predictive value of different imaging criteria - such as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), tumor density and volume variations - in the early follow-up of SO treatment.The study included 22 patients. CT images from baseline and 2 months were reviewed to assess response according to RECIST 1.1, mRECIST, EASL, Choi's criteria (decreased tumor density by ≥15%) and arterial-enhancing tumor volume ratio; α-fetoprotein (AFP) variations were expressed as AFP ratio.The response criteria and volume measurements were reproducible (k>0.80). The overall disease control rate was 40.9% by EASL and mRECIST, and 27.3% by RECIST 1.1; a ≥15% decrease in tumor density was observed in 9 patients (40.9%). The mean volume ratio was 1.73 ± 2.12, the mean AFP ratio 14 ± 37. The 1-year survival rate was 65.9%. Volume ratio was the only predictive factor for survival, with 1-year cumulative survival rates of 90% for volume ratios ≤1.1 and of 45.4% for volume ratios>1.1 (p = 0.04). ### Long_Answer: Tumor volume measurements are reproducible and might provide an early predictive marker of response in HCC patients treated with SO. ### Final_Prediction: nan

### Question: Is the oocyte spindle preserved by 1,2-propanediol during slow freezing? ### Context: To investigate the specific changes in oocyte spindle subjected to severe challenges of low temperature, as well as to examine the effect of cryoprotectants in preserving oocyte spindle during cryopreservation.In vitro experimental study.Academic research laboratory.B6D2F1 (C57BL/6 X DBA/2) mice.Mouse oocytes were cryopreserved using a slow freezing method in a sodium-depleted medium with 1.5 mol/l 1,2-propanediol (PROH) and 0.3 M sucrose. To examine the spindle, oocytes were fixed before, during, and after cryopreservation, and oocytes were analyzed by immunocytochemistry and confocal microscopy.The MII spindle was preserved during the slow freezing, because the cryoprotectant PROH was found to support the organization of MII spindle in resisting the subzero temperature. In contrast, the MII spindle was disassembled gradually during the thawing process with or without PROH. Most of the oocytes were able to recover the MII spindle after thawing, but a portion of thawed oocytes could not sustain the meiotic spindle because of parthenogenetic activation. ### Long_Answer: 1,2-Propanediol can support the organization of MII spindle to defy the subphysiologic temperature; however, the PROH cannot sustain oocyte spindle structure after the subsequent thawing process. ### Final_Prediction: yes

### Question: Is normoxic accumulation of HIF1α associated with glutaminolysis? ### Context: The stabilization of the transcription factor and prognostic tumor marker hypoxia-inducible factor 1α (HIF1α) is considered to be crucial for cellular metabolic adaptations to hypoxia. However, HIF1α has also been shown to accumulate under normoxic conditions, although this phenomenon is poorly understood.We investigated the conditions for normoxic HIF1α stabilization in different tumor cell lines (e.g., two mammary carcinoma cell lines and three oral squamous cell carcinoma cell lines) via Western blot analysis or immunohistochemical staining. The transcriptional activity of HIF1 was demonstrated by analyzing the messenger RNA (mRNA) expression of the HIF1 target carbonic anhydrase 9 (CA9) via PCR.Our data demonstrate that the combined incubation of tumor cells with glutamine and growth factors (e.g., EGF, insulin, and serum) mediates the normoxic accumulation of HIF1α in vitro. Consequently, the inhibition of glutaminolysis by a glutaminase inhibitor blocked the normoxic accumulation of HIF1α. Additionally, the normoxic HIF1α protein displayed nuclear translocation and transcriptional activity, which was confirmed by the induction of CA9 mRNA expression. Furthermore, the normoxic accumulation of HIF1α was associated with impaired proliferation of tumor cells. Finally, ammonia, the toxic waste product of glutaminolysis, induced a normoxic accumulation of HIF1α to the same extent as glutamine. ### Long_Answer: Our study suggests that HIF1α is involved in the regulation of glutamine metabolism and the cellular levels of the toxic metabolic waste product ammonia under normoxia. Hence, our results, together with data presented in the literature, support the hypothesis that HIF1α and its target genes play a crucial role in metabolic pathways, such as glutaminolysis and glycolysis, under both hypoxic and normoxic conditions. ### Final_Prediction: yes

### Question: Iodine removal in intravenous dual-energy CT-cholangiography: is virtual non-enhanced imaging effective to replace true non-enhanced imaging? ### Context: To evaluate whether virtual non-enhanced imaging (VNI) is effective to replace true non-enhanced imaging (TNI) applying iodine removal in intravenous dual-energy CT-cholangiography.From April 2009 until February 2010, fifteen potential donors for living-related liver transplantation (mean age 37.6±10.8 years) were included. Potential donors underwent a two-phase CT-examination of the liver. The first phase consisted of a single-energy non-enhanced CT-acquisition that provided TNI. After administration of hepatobiliary contrast agent, the second phase was performed as a dual-energy cholangiographic CT-acquisition. This provided VNI. Objective image quality (attenuation values [bile ducts and liver parenchyma] and contrast-to-noise ratio) and subjective overall image quality (1 - excellent; 5 - non diagnostic) were evaluated. Effective radiation dose was compared.For TNI and VNI, attenuation values for bile ducts were 16.8±11.2HU and 5.5±17.0HU (p<0.05) and for liver parenchyma 55.3±8.4HU and 58.1±10.6HU (n.s.). For TNI and VNI, contrast-to-noise ratio was 2.6±0.6HU and 6.9±2.1HU (p<0.001). For VNI, subjective overall image quality was 1 in ten datasets, 2 in four datasets and 3 in one dataset. Effective radiation dose for the dual-energy cholangiographic CT-acquisition was 3.6±0.9mSv and for two-phase single-energy CT-cholangiography 5.1±1.3mSv (p<0.001). ### Long_Answer: In this study on iodine removal in intravenous dual-energy CT-cholangiography, subjective image quality is equivalent, contrast-to-noise ratio is improved and effective radiation dose is reduced when VNI is performed. The differences between TNI and VNI with respect to attenuation values seem to have limited clinical relevance and therefore we consider VNI as effective to replace TNI. ### Final_Prediction: nan

### Question: Atypical femoral fractures and bisphosphonates treatment: is it a risk factor? ### Context: Bisphosphonates are effective in preventing osteoporotic fracture, however atypical femoral fractures with a well-defined radiological pattern have been described in association with prolonged treatment with bisphosphonates. Our objectives in this study were to characterize patients ≥ 65 years old with femoral fractures (subtrochanteric/diaphyseal) considered typical and atypical and the relationship between the occurrence of atypical fractures and bisphosphonate use.We conducted a case-control study with patients admitted in our hospital with subtrochanteric or diaphyseal femur fracture in a period of five and a half years. After applying the exclusion criteria, the 92 fractures (91 patients) were classified as typical or atypical. The determination of prior bisphosphonate treatment was obtained through consultation of the individual medical history.We found 11 atypical fractures (10 patients) and 81 typical fractures (81 patients). The median age of both groups was statistically different (72 years - atypical vs. 80 years - typical, p&lt; 0.01). The reason for the use of bisphosphonates was 0.60 in atypical fractures and 0.01 in typical, and an odds ratio of 101.1 was obtained (p&lt; 0.01).Our results are supported and are in agreement with published studies relating to the occurrence of atypical femoral fractures associated with treatment with bisphosphonates. ### Long_Answer: Despite the small number of cases it was possible to demonstrate a statistically significant relation between atypical femoral fractures and treatment with bisphosphonates. One should note that these atypical fractures occurred in patients significantly younger than patients with typical fractures. ### Final_Prediction: nan

### Question: Can long-term antibiotic treatment prevent progression of peripheral arterial occlusive disease? ### Context: The purpose was to investigate in a large, randomized, double-blinded, placebo-controlled trial, whether antibiotic treatment can prevent progression of peripheral arterial disease (PAD).Five hundred and seven patients were included; all patients had an established diagnosis of PAD. Their mean age was 66 years (36-85), and 59% were males. Patients were randomized to Roxithromycin 300 mg daily for 28 days. Baseline investigations were ankle blood pressure, ankle-brachial blood pressure index (ABPI), walking distance, C. pneumoniae serology, cholesterol and medical history. Follow-up was performed every 6 months. Primary events were defined as death, peripheral revascularization and major lower limb amputation. Secondary events were thrombosis, stroke, transient cerebral ischaemic attack and myocardial infarction. Change in ABPI was also investigated. Data were analyzed mainly by Cox regression and linear regression.Included patients with PAD were randomized. Two patients withdrew. Of the remaining, 248 received roxithromycin and 257 placebo. In the treatment group 55% were seropositive and 53% in the placebo group. Mean follow-up was 2.1 years (range 0.06-5.1 years). In the placebo group, 26 died and 80 primary events occurred in total. In the treatment group, 28 died and 74 primary events were observed. The hazard ratio of death was 1.13 (95% CI: 0.68; 1.90), and of primary events 0.92 (95% CI: 0.67; 1.26). Also on secondary events and ABPI changes, no significant differences were found. ### Long_Answer: Long-term treatment with roxithromycin is ineffective in preventing death, amputation, peripheral revascularization, myocardial infarction, stroke, transient cerebral ischaemic attack, thrombosis and decline in ABPI in patients with an established diagnosis of PAD. ### Final_Prediction: nan

### Question: Hepatitis B and C infection: is it a problem in Polish healthcare workers? ### Context: Hepatitis B (HBV) and C viruses (HCV) are among the most frequent blood borne pathogens. According to WHO, 5% of healthcare workers (in central Europe), are exposed to at least one sharps injury contaminated with HBV per year, 1,7% - contaminated with HCV.The aims of the study were to determine prevalence of HCV and HBV infections, vaccination efficacy against hepatitis B and usefulness of alanine aminotransferase (ALT) testing in prophylactic examinations in healthcare workers (HCWs).In a group of 520 healthcare workers, a survey, laboratory and serologic tests such as ALT, HBsAg, anti-HBs, anti-HBcT and anti-HCV were carried out.The study revealed a low rate of workers with presence of HBsAg and anti-HCV (1,2% and 0,8% respectively). Anti-HBcT was found in 99 subjects (19%) without a significant association with experiencing an occupational percutaneous injury. Being vaccinated against HBV was declared by 90% of the subjects. There was no relationship between ALT level rise and positive HBsAg, anti-HCV and anti-HBcT tests. ### Long_Answer: A seroprevalence of HBV and HCV markers in HCWs found in the study is low and similar to the one found in general population. Current or past hepatitis B infections were independent of needle stick injuries. Vaccination against HBV coverage, although found to be high, should improve to 100%. Occupational prophylactic medical examinations found performing ALT test (obligatory in Poland for HCWs) not helpful. It seems that determination of anti-HBcT and anti-HCV status would be essential in pre-employment medical examinations. ### Final_Prediction: nan

### Question: Do post-translational modifications influence IgE reactivity to the major allergen Phl p 1 of timothy grass pollen? ### Context: Grass group I consists of very potent allergenic components which are found in the pollen of all temperate grasses. Several post-translational modifications are predicted from the cDNA data.The aim of this study was to identify sequential IgE-binding sites on the allergen Phl p 1 and to determine their influence on IgE reactivity.Based on cDNA data and microsequencing results we synthesized overlapping decapeptides covering the complete Phl p 1 molecule and tested them for immunological reactivity by means of the PEPSCAN technique. In a dot test we determined the frequency of IgE reactivities to post-translationally modified structures (hydroxylated proline residues, carbohydrate structure, and disulphide formations).Screening by overlapping peptides demonstrated an IgE binding site on the 10 N-terminal amino acids. Comprehensive studies showed that the two hydroxyproline residues of the native Phl p 1 allergen (at positions 5 and 8) and the N-glycan (at position 9) can result in an increased IgE reactivity; 3.3% of the sera exclusively bound to the hydroxyproline bearing peptide, while only 0.4% bound to the proline containing peptide. With regard to glycosylation, we estimated that 20% of sera recognized protein and carbohydrate epitopes, while one serum exclusively bound to the glycan. The formation of disulphide bonds has no detectable effect on the IgE reactivity to Phl p 1. ### Long_Answer: Our results indicate that the post-translational modifications, the carbohydrate structure and the hydroxylation of proline residues, can enhance the IgE reactivity of Phl p 1. ### Final_Prediction: yes

### Question: Can visual inspection with acetic acid under magnification substitute colposcopy in detecting cervical intraepithelial neoplasia in low-resource settings? ### Context: To compare the sensitivity, specificity, positive and negative predictive values and accuracy of visual inspection with acetic acid under magnification (VIAM) and colposcopy for detecting cervical intraepithelial neoplasia (CIN) to determine if VIAM can substitute colposcopy in identifying the biopsy site in screen-positive cases.A prospective cross-sectional study was carried out on 408 symptomatic multiparous women in the reproductive age group (15-49 years) at a tertiary care teaching hospital. VIAM and colposcopy were used to screen for cervical precancerous lesions. Screen-positive women underwent guided biopsy and endocervical curettage. The site of biopsy was recorded as VIAM guided or colposcopy guided. Histopathology was taken as the gold standard.The mean age was 32.3 ± 6.8 years (range 15-49), whilst the mean parity was 2.9 ± 1.2 (range 1-9). A total of 113 women screened positive. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of VIAM and colposcopy were 95, 78, 19, 99 and 79%, and 86, 79, 18, 99 and 79%, respectively for high-grade lesions. ### Long_Answer: VIAM can be a useful alternative to colposcopy when the latter is not available, as it has better sensitivity and equivalent specificity for detecting high-grade CIN. ### Final_Prediction: nan

### Question: Brachial artery injuries in a rural catchment trauma center: are the upper and lower extremity the same? ### Context: The predictors of amputation for patients with lower extremity vascular trauma are well described in the literature, but the predictors of amputation in the upper extremity are not so well defined. We hypothesize that the predictors of amputation in the lower extremity are much different when compared with the upper extremity.Retrospective chart review of all brachial artery traumatic injuries presenting to a rural-state university trauma center.In a 6-year period, 41 patients presented with brachial artery injuries. Operative management was performed in 38 (93%) patients which included 23 reversed saphenous vein grafts, 13 primary repairs, and 2 synthetic grafts. There were four deaths (9.8%) and four (9.8%) amputations. Comparing the amputation and limb salvage groups, the Injury Severity Score (ISS) was 32 versus 12, whereas the Mangled Extremity Severity Score (MESS) was 7 versus 4.3. Five patients had a MESS score greater than 7; four of whom had an amputation or died. Amputation was performed in only 4 of 23 patients with neurologic deficits. Limb salvage was successful in 24 of 28 patients without a palpable pulse on arrival. ### Long_Answer: Predictors of amputation in brachial artery injuries differ from lower extremity vascular injuries. Delayed presentation greater than 6 hours, MESS, open fracture, nerve deficits, and diminished capillary refill were not predictive of amputation for patients with brachial artery injuries. These data suggest that the vast majority of upper extremity injuries should have attempted salvage regardless of the severity scoring systems. ### Final_Prediction: nan

### Question: Does non-responder bias have a significant effect on the results in a postal questionnaire study? ### Context: In epidemiological questionnaire studies results can be influenced by non-responder bias. However, in respiratory epidemiology this has been analysed in very few recently published papers. The aim of our paper is to assess if the results found in our previous postal questionnaire study in an adult population in Northern Finland were biased by non-response.A random sample of 385 persons from the 1,284 non-responders in a previous postal questionnaire study was examined. The same questionnaire as in the original study was again mailed to these persons, and those still not answering were contacted by phone.Totally 183 complete answers (48%) were collected. Lack of interest (56%) and forgetting to mail the response letter (22%) were the most common reasons to non-response. Typical non-responders were young men and current smokers who less frequently reported respiratory symptoms in exercise and asthma than the responders in the original study. Answers collected by phone gave for some questions higher prevalence rates than postal answers. ### Long_Answer: Firstly, in this population the response rate (83.6%) in the original study was high enough to provide reliable results for respiratory symptoms and diseases, only the prevalence of current smoking was biased by non-response. Secondly, the methods used for collecting responses in a non-response study may influence the results. ### Final_Prediction: nan

### Question: Do nK cells control HIV-1 infection of macrophages through soluble factors and cellular contacts in the human decidua? ### Context: During the first trimester of pregnancy, HIV-1 in utero transmission is rare despite the permissivity of the placenta and the decidua (the uterine mucosa during pregnancy) to infection. In the decidua from the first trimester of pregnancy, macrophages (dMs) are the HIV-1 main target cells. Decidual natural killer (dNK) cells account for 70 % of decidual leukocytes. They display distinct phenotype and functions compared to peripheral NK cells. At the periphery, NK cells are involved in the control of HIV-1 infection. In this study, we investigate whether human decidual natural killer (dNK) cells control dM HIV-1 infection.Autologous cocultures of infected dMs with dNK cells reveal that dNK cells strongly inhibit dM HIV-1 infection. The addition of dNK cells to dMs at different times after infection suggests that the control occurs before the complete establishment of the infection. Double chamber cocultures show that cellular contacts are necessary for an optimal control of infection. Nevertheless, soluble factors secreted by dMs and dNK cells in double chamber cocultures partially inhibit dM HIV-1 infection, indicating that soluble factors have also a role in the control of infection. IFN-γ secretion is increased in infected and uninfected cocultures. We show that IFN-γ is involved in the control of dM HIV-1 infection by dNK cells. ### Long_Answer: These results demonstrate that human dNK cells inhibit efficiently HIV-1 infection in dMs in vitro, and highlight the role of innate immune determinants in the control of HIV-1 transmission. ### Final_Prediction: yes

### Question: Is cruciate-retaining TKA an option in patients with prior patellectomy? ### Context: The recommendation for using posterior-stabilized (PS) implants in patellectomy patients undergoing total knee arthroplasty (TKA) is based on older case series with heterogeneous patient populations. The use of cruciate-retaining implants in these patients has not been evaluated with more contemporary implant designs.The purpose of this study was to evaluate the survivorship and functional outcomes (Knee Society score, presence of an extensor lag, and range of motion) of cruciate-retaining (CR) TKA in patients with prior patellectomy.Between 1986 and 2012, we performed 27 CR TKAs in 25 patients after patellectomy. Of those, 23 CR TKAs in 21 patients were available for followup at a minimum of 2 years (mean, 11.2 years; range, 2.3-25.1 years). In this retrospective study, we queried a prospectively maintained database to assess functional outcomes and survivorship.Aseptic loosening-free survival was 100% at 5 and 10 years, and survival with revision for any reason as the outcome was 96% at 5 years (95% confidence interval [CI], 87.7%-100%) and 84% at 10 years (95% CI, 69.5%-100%). One patient was revised for aseptic loosening at 10.2 years postoperatively. Mean Knee Society scores improved from 36±13 preoperatively to 92±9.6 at followup. Extensor lag was present in seven patients preoperatively and only three at followup. Average knee flexion at followup was 112°±12.5°. ### Long_Answer: In this study we found good long-term survivorship and functional outcomes with a CR implant design in patients following patellectomy. Earlier studies have favored PS over CR implants for patients with patellectomies. We believe this series suggests that CR TKA is indeed an option in patients with patellectomy. ### Final_Prediction: yes

### Question: Is secretory leukocyte protease inhibitor , an inhibitor of neutrophil activation , elevated in serum in human sepsis and experimental endotoxemia? ### Context: To document changes in serum secretory leukocyte protease inhibitor (SLPI) in human sepsis and in experimental endotoxemia in vivo. To compare changes in serum SLPI in human sepsis with changes in interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha. To determine whether or not changes in SLPI correlate with the severity of multiple organ dysfunction syndrome as measured by the maximal multiple organ dysfunction score. Finally, because neutrophils have been implicated in tissue injury associated with organ dysfunction, to determine whether recombinant human SLPI blocks activation of isolated human neutrophils.Case-control study and ex-vivo cellular assay.Surgical intensive care unit and clinical research center of university hospitals; laboratory of a medical school.None.There was a significant dose-dependent elevation (50.2+/-4.0 ng/mL, p = .01) in plasma SLPI 12 hrs after administration of lipopolysaccharide to seven healthy adults (36.4+/-2.3 ng/mL). Further, serum concentrations of SLPI (132+/-15 ng/mL) were elevated in septic surgical patients compared with healthy controls (43+/-2 ng/mL, p < .01) and nonseptic surgical controls (69+/-10 ng/mL, p = .01). Serum SLPI concentrations correlated (r2 = .71, p < .01) better with organ dysfunction as measured by maximal multiple organ dysfunction score than did serum IL-6 (r2 = .49, p < .01), IL-10 (r2 = .05, p = .22), or TNF-alpha (r2 = .02, p = .44). We found that recombinant human SLPI in vitro inhibits TNF-alpha-induced hydrogen peroxide production by human neutrophils (ID50 = 1-2 microg/mL). ### Long_Answer: Serum SLPI is elevated in human sepsis and experimental endotoxemia. Maximal concentrations of serum SLPI correlate significantly with maximal multiple organ dysfunction scores in patients with sepsis. Secretory leukocyte protease inhibitor may function to limit ongoing neutrophil-mediated tissue injury associated with organ dysfunction. ### Final_Prediction: yes

### Question: Stressful life events, education, and metabolic syndrome in women: are they related? ### Context: Some reports show that the prevalence of metabolic syndrome is higher in poorly educated women. In our opinion, one probable reason for this is that these women experience more stressful events in their lives. We investigated the association between major stressful life events and the prevalence of metabolic syndrome and the effect of education on this relationship in women.This cross-sectional study included 35- to 55-year-old women who were first-degree relatives of type 2 diabetics. They were questioned about stressful events in their lives, their physical activities, and basic characteristics. In addition waist circumference, blood pressure, fasting blood sugar, triglyceride, total and high-density lipoprotein cholesterol (HDL-C) were measured. Metabolic syndrome was defined according to Adult Treatment Panel III (ATP III) criteria, and the number of stresses was compared between two groups of participants with and without metabolic syndrome.Among the 351 study participants, the prevalence of metabolic syndrome was 28.9%. The mean number of stresses in the metabolic syndrome group was higher than in the nonmetabolic syndrome group at 3.82 ± 2.67 and 3.14 ± 2.35, respectively (P = 0.036). The prevalence of metabolic syndrome in subjects with eight or more stressful life events (46%) was greater compared to those who had experienced less than eight stresses (23.4%; P = 0.017). The relationship between stressful life events and the prevalence of metabolic syndrome was independent of the low level of education, but the prevalence of poorly educated women was associated with the number of stresses. ### Long_Answer: Considering the probable association between stress and prevalence of metabolic syndrome, which itself increases the risk of cardiovascular diseases, educating high-risk people to cope with stresses may be beneficial in reducing the incidence of cardiovascular diseases and preventing the onset of metabolic syndrome. ### Final_Prediction: nan

### Question: Does thyrotropin increase hepatic triglyceride content through upregulation of SREBP-1c activity? ### Context: Hallmarks of non-alcoholic fatty liver disease (NAFLD) are increased triglyceride accumulation within hepatocytes. The prevalence of NAFLD increases steadily with increasing thyrotropin (TSH) levels. However, the underlying mechanisms are largely unknown. Here, we focused on exploring the effect and mechanism of TSH on the hepatic triglyceride content.As the function of TSH is mediated through the TSH receptor (TSHR), Tshr(-/-) mice (supplemented with thyroxine) were used. Liver steatosis and triglyceride content were analysed in Tshr(-/-) and Tshr(+/+) mice fed a high-fat or normal chow diet, as well as in Srebp-1c(-/-) and Tshr(-/-)Srebp-1c(-/-) mice. The expression levels of proteins and genes involved in liver triglyceride metabolism was measured.Compared with control littermates, the high-fat diet induced a relatively low degree of liver steatosis in Tshr(-/-) mice. Even under chow diet, hepatic triglyceride content was decreased in Tshr(-/-) mice. TSH caused concentration- and time-dependent effects on intracellular triglyceride contents in hepatocytes in vitro. The activity of SREBP-1c, a key regulator involved in triglyceride metabolism and in the pathogenesis of NAFLD, was significantly lower in Tshr(-/-) mice. In Tshr(-/-)Srebp-1c(-/-) mice, the liver triglyceride content showed no significant difference compared with Tshr(+/+)Srebp-1c(-/-) mice. When mice were injected with forskolin (cAMP activator), H89 (inhibitor of PKA) or AICAR (AMPK activator), or HeG2 cells received MK886 (PPARα inhibitor), triglyceride contents presented in a manner dependent on SREBP-1c activity. The mechanism, underlying TSH-induced liver triglyceride accumulation, involved that TSH, through its receptor TSHR, triggered hepatic SREBP-1c activity via the cAMP/PKA/PPARα pathway associated with decreased AMPK, which further increased the expression of genes associated with lipogenesis. ### Long_Answer: TSH increased the hepatic triglyceride content, indicating an essential role for TSH in the pathogenesis of NAFLD. ### Final_Prediction: yes

### Question: Does dexmedetomidine modify uterine contractions in pregnancy terms of rats? ### Context: The present study was aimed at determining the effective doses of Dexmedetomidine (Dex) involved in amplitude of contraction-force and frequency of uterine rings in pregnancy terms of rats. All experiments involving animal subjects were carried out with the approval of animal care and use Ethical Committee of Cukurova University. Experiments were performed on female Albino-Wistar rats (200-260 g; n = 40).Uterine rings from pregnant rats were placed in organ bath with Krebs and calcium ion (Ca(2+))-free solutions to record and exposed to serially increasing log10 concentrations of Dex.In Krebs solution, while Dex caused an increase in the spontaneous contraction-forces in all pregnancy terms of rats in a significant dose-dependent manner, it led to a decrease in contraction-frequency in late-pregnancy term of rats. In Ca(2+)-free, the spontaneous contraction-force decreased in late-pregnancy term and increased in early and middle-pregnancy terms. In addition, while Dex increased the contraction-frequency in early and middle-pregnancy terms, it decreased in late-pregnancy term in a dose-dependent manner.The data were subjected to one-way analysis of variance. Repeated measures were employed for comparison of several group means through the Tukey post-hoc test (SPSS 10.00 Inc., Chicago, Ill, USA). P < 0.05 was considered statistically significant. ### Long_Answer: This study suggested that Dex might differently alter the spontaneous contraction-forces and contraction-frequencies of uterine rings in all pregnancy terms of rats in Krebs and Ca(2+)-free solutions. ### Final_Prediction: yes

### Question: Does cell array-based intracellular localization screening reveal novel functional features of human chromosome 21 proteins? ### Context: Trisomy of human chromosome 21 (Chr21) results in Down's syndrome, a complex developmental and neurodegenerative disease. Molecular analysis of Down's syndrome, however, poses a particular challenge, because the aneuploid region of Chr21 contains many genes of unknown function. Subcellular localization of human Chr21 proteins may contribute to further understanding of the functions and regulatory mechanisms of the genes that code for these proteins. Following this idea, we used a transfected-cell array technique to perform a rapid and cost-effective analysis of the intracellular distribution of Chr 21 proteins.We chose 89 genes that were distributed over the majority of 21q, ranging from RBM11 (14.5 Mb) to MCM3AP (46.6 Mb), with part of them expressed aberrantly in the Down's syndrome mouse model. Open reading frames of these genes were cloned into a mammalian expression vector with an amino-terminal His6 tag. All of the constructs were arrayed on glass slides and reverse transfected into HEK293T cells for protein expression. Co-localization detection using a set of organelle markers was carried out for each Chr21 protein. Here, we report the subcellular localization properties of 52 proteins. For 34 of these proteins, their localization is described for the first time. Furthermore, the alteration in cell morphology and growth as a result of protein over-expression for claudin-8 and claudin-14 genes has been characterized. ### Long_Answer: The cell array-based protein expression and detection approach is a cost-effective platform for large-scale functional analyses, including protein subcellular localization and cell phenotype screening. The results from this study reveal novel functional features of human Chr21 proteins, which should contribute to further understanding of the molecular pathology of Down's syndrome. ### Final_Prediction: yes

### Question: Do distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation? ### Context: The liver X receptors (LXRs, NR1H2 and NR1H3) and peroxisome proliferator-activated receptor gamma (PPARG, NR1C3) nuclear receptor transcription factors (TFs) are master regulators of energy homeostasis. Intriguingly, recent studies suggest that these metabolic regulators also impact tumor cell proliferation. However, a comprehensive temporal molecular characterization of the LXR and PPARG gene regulatory responses in tumor cells is still lacking.To better define the underlying molecular processes governing the genetic control of cellular growth in response to extracellular metabolic signals, we performed a comprehensive, genome-wide characterization of the temporal regulatory cascades mediated by LXR and PPARG signaling in HT29 colorectal cancer cells. For this analysis, we applied a multi-tiered approach that incorporated cellular phenotypic assays, gene expression profiles, chromatin state dynamics, and nuclear receptor binding patterns.Our results illustrate that the activation of both nuclear receptors inhibited cell proliferation and further decreased glutathione levels, consistent with increased cellular oxidative stress. Despite a common metabolic reprogramming, the gene regulatory network programs initiated by these nuclear receptors were widely distinct. PPARG generated a rapid and short-term response while maintaining a gene activator role. By contrast, LXR signaling was prolonged, with initial, predominantly activating functions that transitioned to repressive gene regulatory activities at late time points. ### Long_Answer: Through the use of a multi-tiered strategy that integrated various genomic datasets, our data illustrate that distinct gene regulatory programs elicit common phenotypic effects, highlighting the complexity of the genome. These results further provide a detailed molecular map of metabolic reprogramming in cancer cells through LXR and PPARG activation. As ligand-inducible TFs, these nuclear receptors can potentially serve as attractive therapeutic targets for the treatment of various cancers. ### Final_Prediction: yes

### Question: Is upregulation of hepatic bile acid synthesis via fibroblast growth factor 19 defective in gallstone disease but functional in overweight individuals? ### Context: Fibroblast growth factor 19 (FGF19) is an enteric hormone regulating bile acid de novo synthesis by sensing ileal bile acid flux. However, the role of FGF19 in cholelithiasis has not yet been elucidated and therefore is investigated in the present study.Total mRNA and protein were isolated from ileal biopsies and used for tissue expression analysis. FGF19, 7α-hydroxycholesterol (7α-OH-Chol), 27-hydroxycholesterol (27-OH-Chol), and different bile acids were determined in the blood samples.FGF19 serum levels did not differ between gallstone carriers and controls but were significantly decreased in the overweight individuals (-32%, p = 0.0002), irrespective of gallstone status (normalweight to overweight controls -29%, p = 0.0017; normalweight to overweight gallstone carriers -44%, p = 0.0338), and correlated inversely with bodyweight (p < 0.0001, ρ = -0.3317). Compared to non-overweight controls, apical sodium-dependent bile acid transporter expression was significantly diminished in the non-overweight gallstone carriers (-42%, P mRNA = 0.0393; -52%, p protein = 0.0169) as well as in the overweight controls (-24%, P mRNA = 0.0148; -43%, p protein = 0.0017). FGF19 expression varied widely and was similar in all groups. A significant negative correlation was noted between 7α-OH-Chol, 27-OH-Chol, and FGF19 serum levels (p < 0.01; ρ7α-OH-Chol = -0.2155; ρ27-OH-Chol = -0.2144) in obesity. ### Long_Answer: Upregulation of hepatic bile acid synthesis via FGF 19 is defective in gallstone disease but functional in overweight individuals. ### Final_Prediction: yes

### Question: Does laminin and fibronectin treatment lead to generation of dendritic cells with superior endocytic capacity? ### Context: Sampling the microenvironment at sites of microbial exposure by dendritic cells (DC) and their subsequent interaction with T cells in the paracortical area of lymph nodes are key events for initiating immune responses. Most of our knowledge of such events in human is based on in vitro studies performed in the absence of extracellular matrix (ECM) proteins. ECM in basement membranes and interstitial spaces of different tissues, including lymphoid organs, plays an important role in controlling specific cellular functions such as migration, intracellular signalling and differentiation. The aim of this study was, therefore, to investigate the impact of two abundant ECM components, fibronectin and laminin, on the phenotypical and functional properties of DC and how that might influence DC induced T-cell differentiation.Human monocyte derived DC were treated with laminin and fibronectin for up to 48 hours and their morphology and phenotype was analyzed using scanning electron microscopy, flow cytometry and real time PCR. The endocytic ability of DC was determined using flow cytometry. Furthermore, co-culture of DC and T cells were established and T cell proliferation and cytokine profile was measured using H(3)-thymidine incorporation and ELISA respectively. Finally, we assessed formation of DC-T cell conjugates using different cell trackers and flow cytometry. Our data show that in the presence of ECM, DC maintain a 'more immature' phenotype and express higher levels of key endocytic receptors, and as a result become significantly better endocytic cells, but still fully able to mature in response to stimulation as evidenced by their superior ability to induce antigen-specific T cell differentiation. ### Long_Answer: These studies underline the importance of including ECM components in in vitro studies investigating DC biology and DC-T cell interaction. Within the context of antigen specific DC induced T cell proliferation, inclusion of ECM proteins could lead to development of more sensitive assays. ### Final_Prediction: yes

### Question: Does interleukin-22 ameliorate acute severe pancreatitis-associated lung injury in mice? ### Context: To investigate the potential protective effect of exogenous recombinant interleukin-22 (rIL-22) on L-arginine-induced acute severe pancreatitis (SAP)-associated lung injury and the possible signaling pathway involved.Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase (MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin (HE) staining. Expression of B cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL and IL-22RA1 mRNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot.Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group (P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-xL mRNAs in the SAP group was decreased markedly, while the IL-22RA1 mRNA expression was increased significantly relative to the normal control group (P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-xL or IL-22RA1 mRNA (P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the rIL-22 group were significantly lower than those in the SAP group (P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, rIL-22 stimulated the expression of Bcl-2, Bcl-xL and IL-22RA1 mRNAs in the lung (P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the rIL-22 group was significantly higher than that in the PBS group (P < 0.05). ### Long_Answer: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway. ### Final_Prediction: yes

### Question: Does arterial health affect VO2peak and muscle oxygenation in a sedentary cohort? ### Context: An association between arterial health and peak oxygen consumption (VO2peak) has been demonstrated; however, little is known about how arterial health influences muscular oxygenation during exercise. The aim of this study was to gain insight into the relations between arterial health, VO2peak, and muscle oxygenation in a middle-age sedentary population.Radial augmentation index (AIx) (via pulse wave analysis) of 21 sedentary middle-age participants (15 females and six males; age, 54.7 ± 5.4; body mass index, 29.0 ± 4.7 kg·m; mean ± SD) was assessed, and on another day (<7 d), participants completed a modified Bruce protocol (MBP). Using near-infrared spectroscopy, total oxygenation index (TOI) of the left flexor carpi ulnaris and the left vastus lateralis were monitored throughout the MBP. Independent and average (arm + leg) percentage decrease in TOI between stage 1 of the MBP and maximal exertion (TOIdiff) during MBP was calculated. Changes between dependent variables were correlated using Pearson product-moment correlations and were interpreted as follows: r>0.5, strong; 0.5>r>0.3, moderate; and r<0.3, weak.We observed moderate negative correlation between AIx and VO2peak (r = -0.34, -0.63 to -0.03; Pearson correlation, 90% confidence limits) and strong negative correlation between AIx and average TOIdiff (r = -0.58, -0.78 to -0.27). The VO2peak and average TOIdiff were strongly correlated (r = 0.55, 0.23-0.77). ### Long_Answer: Arterial health seems to be an important determinant of muscle oxygenation during exercise. In turn, muscle oxygenation during exercise is strongly related to VO2peak. Developing training modalities to prioritize arterial health outcomes may be a useful way of improving VO2peak in this population. ### Final_Prediction: nan

### Question: Does lovastatin raise serum osteoprotegerin level in people with type 2 diabetic nephropathy? ### Context: Osteoprotegerin (OPG), a glycoprotein, is a member of the tumor necrotizing factor alpha receptor super-family. By considering the possible role of OPG in cardiovascular disease (CVD), higher incidence of CVD in people with type 2 diabetic nephropathy (T2DN), and anti-atherosclerotic effects of statins, the present study aimed to investigate the effects of lovastatin on serum levels of OPG and soluble receptor activator of nuclear factor-κB ligand (sRANKL) in people with T2DN.Thirty patients completed the study course, out of 38 adult male patients with T2DN who were initially enrolled. Lovastatin, 20mg/d, was administered for 90 days. Afterwards, lovastatin was withdrawn for the next 30 days. Serum levels of OPG and sRANKL were measured using commercial ELISA kits at baseline, after 90 days of intervention, and after 30 days of withdrawal of lovastatin.Serum level of OPG was significantly increased (10.76 ± 16.44) and decreased (-7.38 ± 11.98) during 90 days of intervention and 30 days of withdrawal periods, respectively, while, sRANKL level was significantly decreased (-1192.08 ± 578.20) and increased (4418.67 ± 2124.66) during the same periods, respectively. ### Long_Answer: Lovastatin therapy increased serum OPG level and decreased sRANKL level in people with T2DN. The withdrawal of lovastatin decreased serum OPG level, while sRANKL level was extensively increased. ### Final_Prediction: yes

### Question: Do prognostic value of initial elevation in cardiac troponin I level in critically ill patients without acute coronary syndrome? ### Context: Cardiac troponin I levels are often obtained to help rule out acute coronary syndrome.To determine if elevation of troponin level within 24 hours for patients without acute coronary syndrome admitted to the intensive care unit provides important prognostic information.Patients without acute coronary syndrome admitted to the intensive care unit were prospectively divided into 2 groups according to highest serum level of cardiac troponin I within 24 hours of admission (elevated > 0.049 ng/mL; control ≤ 0.049 ng/mL). Hospital mortality, incidence of intubation, and other parameters were compared between the 2 groups.Patients with elevated troponin level (n = 40) had higher mortality than did control patients (n = 50) (35% vs 12%; P= .01). Compared with control patients, patients with elevated levels were more likely to be intubated (41% vs 17%; P= .02). ### Long_Answer: Critically ill patients without acute coronary syndrome with elevated levels of cardiac troponin I at admission had higher mortality and more intubations than did control patients. ### Final_Prediction: yes

### Question: Is 3alpha-androstenol pheromone related to menstrual synchrony? ### Context: The ovarian cycles of females living and interacting together may synchronise due to pheromones released from axillary secretary glands, the highest concentration of which is produced in the mid-follicular phase, prior to ovulation. The objective of this study was to find evidence for menstrual synchrony in a group of female students living together and to obtain a correlation between the ability to smell the putative pheromone, 5alpha-androst-16-en-3alpha-ol (3alpha-androstenol), found in apocrine secretions and menstrual synchrony. This cross-sectional study involved 88 students who completed a standard questionnaire and whose sense of smell was measured using ten varying thresholds. The menstrual history, friendship scale and menstrual hygiene score was determined for the participants.A total of 59.1% of the subjects studied were found to have menstrual synchrony. There was no significant association between menstrual synchrony and smelling threshold. However, a significant correlation was found between menstrual synchrony and personal hygiene score (p<0.01). ### Long_Answer: The phenomenon of menstrual synchrony may be related to various factors. The results failed to demonstrate any significant difference between synchronised and non-synchronised subjects in detecting the steroid by sense of smell. However, the odours associated with menstrual blood or vaginal discharge might have an affect on menstrual synchrony. ### Final_Prediction: nan

### Question: Is cytokine gene variation associated with depressive symptom trajectories in oncology patients and family caregivers? ### Context: Depressive symptoms are common in cancer patients and their family caregivers (FCs). While these symptoms are characterized by substantial interindividual variability, the factors that predict this variability remain largely unknown. This study sought to confirm latent classes of oncology patients and FCs with distinct depressive symptom trajectories and to examine differences in phenotypic and genotypic characteristics among these classes.Among 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their FCs, growth mixture modeling (GMM) was used to identify latent classes of individuals based on Center for Epidemiological Studies-Depression (CES-D) scores obtained prior to, during, and for four months following completion of radiation therapy. One hundred four single nucleotide polymorphisms (SNPs) and haplotypes in 15 candidate cytokine genes were interrogated for differences between the two largest latent classes. Multivariate logistic regression analyses assessed effects of phenotypic and genotypic characteristics on class membership.Four latent classes were confirmed: Resilient (56.3%), Subsyndromal (32.5%), Delayed (5.2%), and Peak (6.0%). Participants who were younger, female, non-white, and who reported higher baseline trait and state anxiety were more likely to be in the Subsyndromal, Delayed, or Peak groups. Variation in three cytokine genes (i.e., interleukin 1 receptor 2 [IL1R2], IL10, tumor necrosis factor alpha [TNFA]), age, and performance status predicted membership in the Resilient versus Subsyndromal classes. ### Long_Answer: Findings confirm the four latent classes of depressive symptom trajectories previously identified in a sample of breast cancer patients. Variations in cytokine genes may influence variability in depressive symptom trajectories. ### Final_Prediction: yes

### Question: Do unused sterile instruments for closure prevent wound surgical site infection after pancreatic surgery? ### Context: The incidence of incisional surgical site infection (SSI) after pancreatic surgery remains high. The aim of this study was to assess the effectiveness of the unused sterile instruments that were not used throughout the course of surgery and were opened exactly at the moment of wound closure to prevent incisional SSI after open pancreatic surgery.We retrospectively evaluated the incidence of incisional SSI and the clinical course in 203 patients who underwent pancreatic resection in our institution between April 2012 and October 2015.Twenty-one patients were excluded because they underwent laparoscopic pancreatic surgery; therefore, data from 182 patients were analyzed. Of these, 93 underwent abdominal closure with unused sterile forceps and drape, and 89 did not. The intervention group included 53 pancreaticoduodenectomies, 20 distal pancreatectomies, and 20 underwent other procedures. The control group included 55 pancreaticoduodenectomies, 26 distal pancreatectomies, and eight underwent other procedures. The incidence of incisional SSI in the intervention group (two cases, 2/93, 2.2%) was significantly lower (P = 0.017) compared with that of the control group (11 cases, 11/89, 12.4%). All incisional SSIs in the control group occurred after pancreaticoduodenectomy (11 cases, 11/89, 20.0%). However, none of the pancreaticoduodenectomy patients in the intervention group experienced incisional SSI (P = 0.002). ### Long_Answer: Unused sterile forceps and drapes during abdominal closure reduced the incidence of incisional SSI after pancreatic surgery, especially pancreaticoduodenectomy. ### Final_Prediction: yes

### Question: Colorectal cancer in young patients in Israel: a distinct clinicopathological entity? ### Context: This study was designed to characterize the entity of colorectal cancer (CRC) in young patients and to evaluate whether it has any unique epidemiological or clinicopathological features.The study population consisted of all consecutive young (≤50 years old at diagnosis) patients with CRC who were diagnosed during the years 1997-2007 and were treated at our institution, and a matching group of patients (>50 years at diagnosis). The medical files of these patients were reviewed, and the epidemiological, clinical, and pathological features of both groups were compared.There were 406 patients: 203 in each group. The features of the older group were typical for patients with CRC, but the younger group showed female predominance, different ethnic composition, prevalence of family history of cancer and hereditary CRC syndromes, and lower incidence of polyps. The incidence of left-sided tumors and advanced stages (III-IV) at diagnosis was higher in the younger patients. Mucinous/signet ring histology, grade, stage, lymphatic and vascular invasion were all predictive of survival, whereas age was not. ### Long_Answer: Colorectal cancer in young patients was found to display a cluster of unique characteristics but fewer than previously reported and young age by itself was not found to impact patient outcome. ### Final_Prediction: nan

### Question: Does a member of the Plasmodium falciparum PHIST family bound to the erythrocyte cytoskeleton component band 4.1? ### Context: Plasmodium falciparum parasites export more than 400 proteins into the cytosol of their host erythrocytes. These exported proteins catalyse the formation of knobs on the erythrocyte plasma membrane and an overall increase in erythrocyte rigidity, presumably by modulating the endogenous erythrocyte cytoskeleton. In uninfected erythrocytes, Band 4.1 (4.1R) plays a key role in regulating erythrocyte shape by interacting with multiple proteins through the three lobes of its cloverleaf-shaped N-terminal domain. In P. falciparum-infected erythrocytes, the C-lobe of 4.1R interacts with the P. falciparum protein mature parasite-infected erythrocyte surface antigen (MESA), but it is not currently known whether other P. falciparum proteins bind to other lobes of the 4.1R N-terminal domain.In order to identify novel 4.1R interacting proteins, a yeast two-hybrid screen was performed with a fragment of 4.1R containing both the N- and α-lobes. Positive interactions were confirmed and investigated using site-directed mutagenesis, and antibodies were raised against the interacting partner to characterise it's expression and distribution in P. falciparum infected erythrocytes.Yeast two-hybrid screening identified a positive interaction between the 4.1R N- and α-lobes and PF3D7_0402000. PF3D7_0402000 is a member of a large family of exported proteins that share a domain of unknown function, the PHIST domain. Domain mapping and site-directed mutagenesis established that it is the PHIST domain of PF3D7_0402000 that interacts with 4.1R. Native PF3D7_0402000 is localized at the parasitophorous vacuole membrane (PVM), and colocalizes with a subpopulation of 4.1R. ### Long_Answer: The function of the majority of P. falciparum exported proteins, including most members of the PHIST family, is unknown, and in only a handful of cases has a direct interaction between P. falciparum-exported proteins and components of the erythrocyte cytoskeleton been established. The interaction between 4.1R and PF3D7_0402000, and localization of PF3D7_0402000 with a sub-population of 4.1R at the PVM could indicate a role in modulating PVM structure. Further investigation into the mechanisms for 4.1R recruitment is needed. ### Final_Prediction: yes

### Question: Are patient assessed symptoms poor predictors of objective findings . Results from a cross sectional study in patients treated with radiotherapy for pharyngeal cancer? ### Context: The aim of the study was to assess the value of the EORTC questionnaires C30 and H&N35, as an instrument for the study of side effects.We invited all recurrence free patients, treated with radical radiotherapy for pharyngeal cancer between 1998 and 2002 at our institution, to participate in the study. Data was retrieved using questionnaires, functional endoscopic evaluation of swallowing, dental examination with orthopantomography and saliva flow measurements. Thirty-five (55% of invited) participated.Side effects were omnipresent and often severe. The value of patient assessed symptom scores to predict equivalent objective changes was varied: We found a sensitivity of 0.59-0.93, specificity of 0.40-0.81, positive predictive value of 0.28-0.81 and a negative predictive value of 0.46-0.94. ### Long_Answer: The questionnaire should be used to retrieve information on subjective side effects and objective examination should be used for objective changes. One cannot conclude from one to the other. ### Final_Prediction: yes

### Question: Do membrane complement regulators protect against the development of type II collagen-induced arthritis in rats? ### Context: To investigate changes in the distribution patterns of membrane complement regulators (MCRs) during the development of type II collagen-induced arthritis (CIA) and to examine the protective effects of these molecules against the augmentation of CIA in the knee joint.Immunohistochemistry was used to examine the distribution of the MCRs Crry, DAF, and CD59 in the synovium of knee joints before and 2, 4, and 10 weeks after induction of CIA by immunization with type II collagen. In addition, at 2 or 10 weeks after induction of CIA, rats were injected intraarticularly with anti-Crry and/or anti-CD59 as the F(ab')2 fraction of monoclonal antibodies (mAb). Knee joint swelling and histologic changes in the synovium were examined 2 weeks after mAb injection.Synovial expression of Crry, DAF, and CD59 decreased in parallel with increased inflammation. When Crry and CD59 were functionally blocked at 2 weeks after the induction of CIA, swelling of the knee joints was markedly increased. Blocking of either regulator alone had no effect on swelling. Thickening of the synovial surface and proliferation of subsynovial tissue were all increased after blocking Crry and CD59, whereas blocking of either MCR alone had no effect. When both Crry and CD59 were blocked, deposits of membrane attack complex were found in the synovium. ### Long_Answer: Our findings indicate that in rats with CIA and severely inflamed synovium, local expression of MCR is reduced. The MCRs Crry and CD59 appear to suppress the development of CIA. ### Final_Prediction: yes

### Question: Are late biliary complications in human alveolar echinococcosis associated with high mortality? ### Context: To evaluate the incidence of late biliary complications in non-resectable alveolar echinococcosis (AE) under long-term chemotherapy with benzimidazoles.Retrospective analysis of AE patients with biliary complications occurring more than three years after the diagnosis of AE. We compared characteristics of patients with and without biliary complications, analyzed potential risk factor for biliary complications and performed survival analyses.Ninety four of 148 patients with AE in Zurich had non-resectable AE requiring long-term benzimidazole chemotherapy, of which 26 (28%) patients developed late biliary complications. These patients had a median age of 55.5 (35.5-65) years at diagnosis of AE and developed biliary complications after 15 (8.25-19) years of chemotherapy. The most common biliary complications during long-term chemotherapy were late-onset cholangitis (n = 14), sclerosing cholangitis-like lesions (n = 8), hepatolithiasis (n = 5), affection of the common bile duct (n = 7) and secondary biliary cirrhosis (n = 7). Thirteen of the 26 patients had undergone surgery (including 12 resections) before chemotherapy. Previous surgery was a risk factor for late biliary complications in linear regression analysis (P = 0.012). ### Long_Answer: Late biliary complications can be observed in nearly one third of patients with non-resectable AE, with previous surgery being a potential risk factor. After the occurrence of late biliary complications, the median survival is only 3 years, suggesting that late biliary complications indicate a poor prognostic outcome. ### Final_Prediction: yes

### Question: Does deep sequencing-based transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus reveal insight into the immune-relevant genes in marine fish? ### Context: Systematic research on fish immunogenetics is indispensable in understanding the origin and evolution of immune systems. This has long been a challenging task because of the limited number of deep sequencing technologies and genome backgrounds of non-model fish available. The newly developed Solexa/Illumina RNA-seq and Digital gene expression (DGE) are high-throughput sequencing approaches and are powerful tools for genomic studies at the transcriptome level. This study reports the transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus using RNA-seq and DGE in an attempt to gain insights into the immunogenetics of marine fish.RNA-seq analysis generated 169,950 non-redundant consensus sequences, among which 48,987 functional transcripts with complete or various length encoding regions were identified. More than 52% of these transcripts are possibly involved in approximately 219 known metabolic or signalling pathways, while 2,673 transcripts were associated with immune-relevant genes. In addition, approximately 8% of the transcripts appeared to be fish-specific genes that have never been described before. DGE analysis revealed that the host transcriptome profile of Vibrio harveyi-challenged L. japonicus is considerably altered, as indicated by the significant up- or down-regulation of 1,224 strong infection-responsive transcripts. Results indicated an overall conservation of the components and transcriptome alterations underlying innate and adaptive immunity in fish and other vertebrate models. Analysis suggested the acquisition of numerous fish-specific immune system components during early vertebrate evolution. ### Long_Answer: This study provided a global survey of host defence gene activities against bacterial challenge in a non-model marine fish. Results can contribute to the in-depth study of candidate genes in marine fish immunity, and help improve current understanding of host-pathogen interactions and evolutionary history of immunogenetics from fish to mammals. ### Final_Prediction: yes

### Question: Reducing an already low dental diagnostic X-ray dose: does it make sense? ### Context: To find a method that is suitable for providing an objective assessment of the cost effectiveness of a dose-reducing measure used for diagnostic dental X-ray exposures.Three cost-utility analysis (CUA) methods were evaluated by comparing their assessments of two dose-reduction measures, a rectangular collimator and the combination of two devices that reduce the radiation dose received during orthodontic lateral cephalography. The following CUA methods were used: (1) the alpha value (AV), a monetary valuation of dose reduction used in the nuclear industry; (2) the value of a statistical life for valuation of the reduction in stochastic adverse effects; and (3) the time-for-time method, based on the postulate that risk reduction is effective when the number of years of life gained is more than the years that an average worker must work to earn the costs of the risk-reducing measure. The CUA methods were used to determine the minimum number of uses that was required for the dose-reducing device to be cost effective. The methods were assessed for coherence (are comparable results achieved for comparable countries?) and adaptability (can the method be adjusted for age and gender of specific patient groups?).The performance of the time-for-time method was superior to the other methods. Both types of dose-reduction devices tested were assessed as cost effective after a realistic number of uses with all three methods except low AVs. ### Long_Answer: CUA for the methods of X-ray dose reduction can be performed to determine if investment in low dose reduction is cost effective. The time-for-time method proved to be a coherent and versatile method for performing CUA. ### Final_Prediction: nan

### Question: Is bilateral ureterorenoscopy the first choice for the treatment of bilateral ureteral stones? ### Context: We analyze our recent results and discuss the advantages and disadvantages of bilateral single-session ureterorenoscopy (URS) for bilateral ureteral stones.55 patients underwent URS with pneumatic lithotripsy (PL) for bilateral stones. 61 (55.5%), 28 (25.4%) and 21 (19.1%) stones were located in the lower, middle and upper ureter, respectively.Of the 110 stones, 99 (90.0%) were fragmented in a single procedure. The stone clearance rate was 94.5% after the second session. The stone clearance rates with regard to stone location were 71.4, 89.3 and 96.7% for the upper, middle and lower ureter, respectively. An analysis of the clearance rates based on location demonstrated that lower ureteric stones were more successfully removed than upper ureteric stones (96.7 vs.71.4%, p = 0.003). ### Long_Answer: Bilateral single-session URS with PL is a highly effective treatment modality for bilateral ureteral stones. The success rate of PL is affected by stone size and location. ### Final_Prediction: nan

### Question: Does peroxisome proliferator-activated receptor-γ in capillary endothelia promote fatty acid uptake by heart during long-term fasting? ### Context: Endothelium is a crucial blood-tissue interface controlling energy supply according to organ needs. We investigated whether peroxisome proliferator-activated receptor-γ (PPARγ) induces expression of fatty acid-binding protein 4 (FABP4) and fatty acid translocase (FAT)/CD36 in capillary endothelial cells (ECs) to promote FA transport into the heart.Expression of FABP4 and CD36 was induced by the PPARγ agonist pioglitazone in human cardiac microvessel ECs (HCMECs), but not in human umbilical vein ECs. Real-time PCR and immunohistochemistry of the heart tissue of control (Pparg(fl/null)) mice showed an increase in expression of FABP4 and CD36 in capillary ECs by either pioglitazone treatment or 48 hours of fasting, and these effects were not found in mice deficient in endothelial PPARγ (Pparg(▵)(EC)(/null)). Luciferase reporter constructs of the Fabp4 and CD36 promoters were markedly activated by pioglitazone in HCMECs through canonical PPAR-responsive elements. Activation of PPARγ facilitated FA uptake by HCMECs, which was partially inhibited by knockdown of either FABP4 or CD36. Uptake of an FA analogue, (125)I-BMIPP, was significantly reduced in heart, red skeletal muscle, and adipose tissue in Pparg(▵)(EC)(/null) mice as compared with Pparg(fl/null) mice after olive oil loading, whereas those values were comparable between Pparg(fl/null) and Pparg(▵)(EC)(/null) null mice on standard chow and a high-fat diet. Furthermore, Pparg(▵)(EC)(/null) mice displayed slower triglyceride clearance after olive oil loading. ### Long_Answer: These findings identified a novel role for capillary endothelial PPARγ as a regulator of FA handing in FA-metabolizing organs including the heart in the postprandial state after long-term fasting. ### Final_Prediction: yes

### Question: Is remnant preservation helpful to obtain good clinical results in posterior cruciate ligament reconstruction : comparison of clinical results of three techniques? ### Context: The purpose of the present study was to compare the clinical results of 3 posterior cruciate ligament reconstruction techniques according to the time from injury to surgery and remnant PCL status and to evaluate the efficiency of each technique.The records of 89 patients who underwent primary PCL reconstructions with a posterolateral corner sling were analyzed retrospectively. Thirty-four patients were treated by anterolateral bundle (ALB) reconstruction with preservation of the remnant PCL using a transtibial tunnel technique in the acute and subacute stages of injury (group 1). Forty patients were treated with remnant PCL tensioning and an ALB reconstruction using the modified inlay technique in the chronic stage (group 2), and fifteen patients were treated with double-bundle reconstruction using the modified inlay technique (group 3). The double-bundle reconstruction was performed if there was a very weak or no PCL remnant.The mean side-to-side differences in posterior tibial translation on the stress radiographs were reduced from 10.1 ± 2.5 mm in group 1, 10.6 ± 2.4 mm in group 2, and 12.8 ± 3.2 mm in group 3 preoperatively to 2.3 ± 1.4 mm in group 1, 2.3 ± 1.5 mm in group 2, and 4.0 ± 2.5 mm in group 3 at the last follow-up (p < 0.001, p < 0.001, and p < 0.001, respectively). Statistical analyses revealed that group 1 and group 2 were similar in terms of side-to-side difference changes in posterior tibial translation on the stress radiographs; however, group 3 was inferior to group 1 and group 2 at the last follow-up (p = 0.022). The clinical results were not significantly different among the three groups. ### Long_Answer: Excellent posterior stability and good clinical results were achieved with ALB reconstruction preserving the injured remnant PCL in the acute and subacute stages and remnant PCL tensioning with ALB reconstruction in the chronic stage. The PCL injuries could be surgically corrected with different techniques depending on both the remnant PCL status and the interval between the knee trauma and operation. ### Final_Prediction: yes

### Question: Is epithelial-mesenchymal transition in primary human bronchial epithelial cells Smad-dependent and enhanced by fibronectin and TNF-alpha? ### Context: Defective epithelial repair, excess fibroblasts and myofibroblasts, collagen overproduction and fibrosis occur in a number of respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Pathological conversion of epithelial cells into fibroblasts (epithelial-mesenchymal transition, EMT) has been proposed as a mechanism for the increased fibroblast numbers and has been demonstrated to occur in lung alveolar epithelial cells. Whether other airway cell types also have the capability to undergo EMT has been less explored so far. A better understanding of the full extent of EMT in airways, and the underlying mechanisms, can provide important insights into airway disease pathology and enable the development of new therapies. The main aim of this study was to test whether primary human bronchial epithelial cells are able to undergo EMT in vitro and to investigate the effect of various profibrotic factors in the process.Our data demonstrate that primary human bronchial epithelial cells (HBECs) are able to undergo EMT in response to transforming growth factor-beta 1 (TGF-beta1), as revealed by typical morphological alterations and EMT marker progression at the RNA level by real-time quantitative polymerase chain reaction and, at the protein level, by western blot. By using pharmacological inhibitors we show that this is a Smad-dependent mechanism and is independent of extracellular signal-related kinase pathway activation. Additional cytokines and growth factors such as tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL1beta) and connective tissue growth factor (CTGF) were also tested, alone or in combination with TGF-beta1. TNF-alpha markedly enhances the effect of TGF-beta1 on EMT, whereas IL1beta shows only a very weak effect and CTGF has no significant effect. We have also found that cell-matrix contact, in particular to fibronectin, an ECM component upregulated in fibrotic lesions, potentiates EMT in both human alveolar epithelial cells and HBECs. Furthermore, we also show that the collagen discoidin domain receptor 1 (DDR1), generally expressed in epithelial cells, is downregulated during the EMT of bronchial epithelium whereas DDR2 is unaffected. Our results also suggest that bone morphogenetic protein-4 is likely to have a context dependent effect during the EMT of HBECs, being able to induce the expression of EMT markers and, at the same time, to inhibit TGF-beta induced epithelial transdifferentiation. ### Long_Answer: The results presented in this study provide additional insights into EMT, a potentially very important mechanism in fibrogenesis. We show that, in addition to alveolar epithelial type II cells, primary HBECs are also able to undergo EMT in vitro upon TGF-beta1 stimulation via a primarily Smad 2/3 dependent mechanism. The effect of TGF-beta1 is potentiated on fibronectin matrix and in the presence of TNF-alpha, representing a millieu reminiscent of fibrotic lesions. Our results can contribute to a better understanding of lung fibrosis and to the development of new therapeutic approaches. ### Final_Prediction: yes

### Question: Is repair of the injury to respiratory epithelial cells characteristic of asthma stimulated by Allomyrina dichotoma agglutinin specific serum glycoproteins? ### Context: The airway epithelium acts as a protective barrier, separating the external environment from the underlying tissue. Daily challenges result in damage to the epithelium that, in normal individuals, is quickly and effectively repaired. In respiratory diseases, such as asthma, this repair is compromised. Following injury to the epithelium, plasma leaks into the airway lumen acting as a protective protein cap. Carbohydrates are mediators of epithelial repair, however, the associated regulatory proteins remain unknown.To identify mediators of epithelial repair based on their carbohydrate moieties using an in vitro wound repair culture model of human airway epithelial cells (1HAEo(-)).Using the lectin Allomyrina dichotoma agglutinin (AlloA) as a tool, ligands essential in the repair of damaged epithelium were characterized. AlloA was subsequently used to purify and identify a glycoprotein associated with epithelial repair.The addition of AlloA to the media of mechanically wounded monolayers inhibited repair. Fetuin, a highly glycosylated serum protein, was identified as a glycoprotein bound by AlloA. The addition of fetuin to serum starved monolayers stimulated wound closure. ### Long_Answer: These results indicate that following mechanical injury to the epithelium, serum glycoproteins, not only provide a protective barrier, but also are involved in the initiation of wound closure. ### Final_Prediction: yes

### Question: Is meconium-stained liquor during labor associated with raised neonatal cord blood 8-iso-prostaglandin F2alpha concentration? ### Context: The purpose of this study was to compare the umbilical arterial 8-iso-prostaglandin F2alpha, concentrations between pregnancies that were complicated by moderate or thick meconium-stained liquor and those with clear liquor.Umbilical cord arterial blood samples were collected from 247 singleton pregnancies with either moderate or thick meconium-stained liquor at any stage of labor or clear liquor at all stages of labor for the determination of the total 8-iso-prostaglandins F2alpha concentration.The median total 8-iso-prostaglandins F2alpha concentration of the meconium-stained liquor group was significantly higher than that of the control group (719.2 vs 115.8 pg/mL). Among the meconium-stained liquor group, those who had a change from "clear liquor" at early labor to "moderate/ thick meconium-stained liquor" at late first stage or at delivery (late meconium-stained liquor group) had higher 8-iso-prostaglandins F2alpha concentration, compared with those who had moderate/ thick meconium-stained liquor since early labor (early meconium-stained liquor group; 959.8 vs 499.9 pg/mL). With the use of multiple regression analysis, meconium-stained liquor, duration of second stage of labor, and abnormal fetal heart tracings were independent determinants of cord blood 8-iso-prostaglandins F2alpha concentration. ### Long_Answer: Moderate or thick meconium-stained liquor is an independent factor for increased oxidative stress in pregnancy. ### Final_Prediction: yes

### Question: Does concordance facilitate access in diabetes care -- service provider perspectives of service improvement and cultural competency? ### Context: Inequalities between different ethnic groups in diabetes care and outcomes are well documented in the UK. This research sought to explore and understand how national and local policy interventions impacted upon access and the development of culturally competent diabetes services from the care provider perspective.This paper describes the care provider perspective of access to diabetes care in ethnically mixed populations from a thematic analysis of 14 semi-structured interviews conducted with professionals, at three study sites, with different roles in the diabetes care pathway.National policy level initiatives to improve quality have led to quality improvements at a practical level. These achievements, however, have been unable to address all aspects of care that service providers identified as important in facilitating access for all patient groups. Concordance emerged as a key process in improving access to care within local systems and barriers to this exist at different levels and are greater for some groups of patients compared with others. ### Long_Answer: Concordance is a key concept that underpins access and cultural competency in diabetes service improvement. A focus on concordance at different levels within local systems may improve access to quality diabetes care for ethnic minority groups. ### Final_Prediction: yes

### Question: Can small changes in cardiovascular risk factors predict large future reductions in coronary heart disease mortality in Ireland? ### Context: A previously validated model was used, which integrates information on all cardiology treatments, and trends in all the major cardiovascular risk factors, stratified by age and sex to estimate the reduction in coronary deaths by 2010. The model was extended from 2000 (the base year) to 2010 for two contrasting scenarios: If recent risk factor trends simply continued to 2010, or if greater reductions in risk factors were achieved.If recent risk factor trends simply continued, approximately 635 fewer coronary deaths in 2010 compared with an observed 6,589 coronary deaths in 2000; approximately 1,055 fewer deaths attributable to improvements in total cholesterol, blood pressure, smoking and physical activity, offset by 420 additional deaths attributable to adverse trends in obesity and diabetes. Additional reductions in the six cardiovascular risk factors by 2010, already achieved elsewhere, could potentially achieve 3,100 fewer deaths (minimum 1,815, maximum 4,535). Approximately 2,065 fewer deaths were from reducing total mean cholesterol levels alone. These results remained stable in a rigorous analysis of extremes sensitivity analysis. ### Long_Answer: If recent trends in the major cardiovascular risk factors simply continued to 2010, the national targets for CHD death rates are less likely to be achieved in Ireland. However, additional reductions in the major cardiovascular risk factors through tobacco control and healthier diet policies could halve the current coronary deaths by 2010. ### Final_Prediction: nan

### Question: Pediatric intravenous insertion in the emergency department: bevel up or bevel down? ### Context: Intravenous catheters are usually inserted with the bevel facing up. Bevel down may be superior in small and/or dehydrated children. We seek to determine whether there is a difference in the success rate of intravenous insertion using these 2 methods.We recruited children requiring an intravenous catheter in the emergency department where there was time to obtain consent. Patients were randomized to have the first attempt bevel up or bevel down. If the first attempt was unsuccessful, the alternate technique was used on second attempt. Attempts beyond 2 were not tracked.We recruited 428 patients. Data are available from 396 (201 bevel-up and 195 bevel-down techniques). At least 63 different nurses participated. The nurses participated in the study a median number of 2 times (maximum, 36). Four nurses used the bevel-down technique more than 10 times. The success rate on first attempt was 75.6% (95% confidence interval [CI], 69.8-81.4) for bevel up and 60% (95% CI, 53.2-66.8) for bevel down. The success rate on second attempt was 56.8% (95% CI, 45.3-68.2) for bevel up and 42.9% (95% CI, 30.3-55.5) for bevel down. In the subgroup of infants weighing less than 5 kg, there was no difference between the 2 techniques on the first attempt, with bevel up having a success of 33% (95% CI, 8.4-57.6) and bevel down 30% (95% CI, 4.1-55.9). ### Long_Answer: The bevel-up technique performed superior to bevel-down technique in this study. The bevel-down technique might be useful in small infants. ### Final_Prediction: nan

### Question: Does a single dose of ursodiol affect cyclosporine absorption in liver transplant patients? ### Context: To study the possible influence of ursodiol (ursodeoxycholic acid), a hydrophilic bile acid, on cyclosporine (CsA) bioavailability.Seven adult liver transplant recipients participated in a randomised cross-over pharmacokinetic study comparing ursodiol (600 mg) with placebo in single doses. Blood concentrations of CsA were measured by HPLC.There was no significant effect of ursodiol on CsA absorption: AUC was 5011 vs 5486 ng.h.ml-1, Cmax was 832 vs 871 ng.ml-1 and tmax was 2 vs 2 h, after ursodiol and placebo, respectively. ### Long_Answer: Although a significant period effect was observed, we conclude that a single dose of ursodiol has little effect on CsA absorption in liver transplant patients and that an interaction in the intestinal lumen between these two drugs is unlikely. ### Final_Prediction: no

### Question: Does the antioxidant EPC-K1 attenuate renal ischemia-reperfusion injury in a rat model? ### Context: Acute kidney injury (AKI) occurs frequently in the intensive care unit. A primary cause is renal ischemia/reperfusion (I/R) injury, during which excess reactive oxygen species (ROS) are produced. ROS subsequently damage renal cells, leading to the development of AKI. Here, we investigated whether renal I/R injury could be attenuated by the antioxidant EPC-K1.We divided male Wistar rats into the following three groups: (1) a renal I/R group, (2) an EPC-K1 + renal I/R group and (3) a control group. Rats were sacrificed 24 h after treatment (I/R or sham). To measure oxidative stress in renal tissue, histological examinations were performed and serum levels of blood urea nitrogen (BUN) and creatinine were measured. The antioxidant action of EPC-K1 was also evaluated in RAW264.7 cells stimulated with antimycin A.Serum BUN and creatinine levels were elevated in the I/R group; however, this increase was significantly attenuated by EPC-K1 in the EPC-K1 + I/R group. Renal tissue injury was also significantly lower in the EPC-K1 + I/R group compared with the I/R group. In vitro experiments showed that EPC-K1 significantly attenuated the generation of ROS induced by antimycin A. ### Long_Answer: In our study, EPC-K1 was able to attenuate AKI due to renal I/R by reducing oxidative stress. These results suggest that EPC-K1 may be effective against various types of I/R injury. ### Final_Prediction: yes

### Question: Does granulocyte-macrophage colony-stimulating factor inhibit HIV-1 replication in monocyte-derived macrophages? ### Context: Previous studies of the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on HIV-1 replication in macrophages have had inconsistent results, variously reporting no effect, augmentation or inhibition of viral replication.To investigate the regulation of HIV-1 in monocyte-derived macrophages (MDM) by GM-CSF in vitro.The role of GM-CSF on HIV-1 replication was assessed as supernatant and intracellular p24 antigen concentrations and by HIV-1 DNA and mRNA production under different culture conditions. Expression of CD4 and CCR5 receptors was examined. The effect of GM-CSF with an E21R mutation, which binds only to the alpha-chain of GM-CSF receptor, was used as an additional control.GM-CSF consistently suppressed HIV-1 replication in human MDM in vitro, as assessed by supernatant and intracellular p24 antigen concentrations and HIV-1 gag mRNA expression. The inhibitory effect of GM-CSF on HIV-1 replication was observed regardless of HIV-1 strain, source of GM-CSF, stage of MDM maturation or timing of GM-CSF exposure in relation to HIV-1 infection. The effect was dose dependent and reversed by addition of a neutralizing monoclonal antibody (4D4). Flow cytometric analysis of surface expression of CD4 and CCR5 indicates that GM-CSF does not affect HIV-1 entry into MDM. Analysis of intracellular HIV-1 DNA and mRNA suggests that HIV-1 replication is inhibited at or before transcription. E21R GM-CSF had no effect on HIV-1 replication in MDM. ### Long_Answer: GM-CSF regulates HIV-1 replication in MDM, inhibiting HIV-1 replication through binding to the beta-chain of the GM-CSF receptor. ### Final_Prediction: yes

### Question: Does modulation of serotonin transporter function during fetal development cause dilated heart cardiomyopathy and lifelong behavioral abnormalities? ### Context: Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI.In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. ### Long_Answer: These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy and a higher vulnerability to affective disorders in a dose-dependent manner. ### Final_Prediction: yes

### Question: Do forest structure and roe deer abundance predict tick-borne encephalitis risk in Italy? ### Context: The Western Tick-borne encephalitis (TBE) virus often causes devastating or lethal disease. In Europe, the number of human TBE cases has increased dramatically over the last decade, risk areas are expanding and new foci are being discovered every year. The early localisation of new TBE foci and the identification of the main risk factors associated with disease emergence represent a priority for the public health community. Although a number of socio-economic parameters have been suggested to explain TBE upsurges in eastern Europe, the principal driving factors in relatively stable western European countries have not been identified.In this paper, we analyse the correlation between the upsurge of TBE in 17 alpine provinces in northern Italy from 1992 to 2006 with climatic variables, forest structure (as a proxy for small mammal reservoir host abundance), and abundance of the principal large vertebrate tick host (roe deer), using datasets available for the last 40 years. No significant differences between the pattern of changes in climatic variables in provinces where TBE has emerged compared to provinces were no clinical TBE cases have been observed to date. Instead, the best model for explaining the increase in TBE incidence in humans in this area include changes in forest structure, in particular the ratio of coppice to high stand forest, and the density of roe deer. ### Long_Answer: Substantial changes in vegetation structure that improve habitat suitability for the main TBE reservoir hosts (small mammals), as well as an increase in roe deer abundance due to changes in land and wildlife management practices, are likely to be among the most crucial factors affecting the circulation potential of Western TBE virus and, consequently, the risk of TBE emergence in humans in western Europe. We believe our approach will be useful in predicting TBE risk on a wider scale. ### Final_Prediction: yes

### Question: Is metastasis of prostate cancer and melanoma cells in a preclinical in vivo mouse model enhanced by L-plastin expression and phosphorylation? ### Context: Tumor cell migration and metastasis require dynamic rearrangements of the actin cytoskeleton. Interestingly, the F-actin cross-linking and stabilizing protein L-plastin, originally described as a leukocyte specific protein, is aberrantly expressed in several non-hematopoietic malignant tumors. Therefore, it has been discussed as a tumor marker. However, systematic in vivo analyses of the functional relevance of L-plastin for tumor cell metastasis were so far lacking.We investigated the relevance of L-plastin expression and phosphorylation by ectopical expression of L-plastin in human melanoma cells (MV3) and knock-down of endogenous L-plastin in prostate cancer (PC3M). The growth and metastatic potential of tumor cells expressing no L-plastin, phosphorylatable or non-phosphorylatable L-plastin was analyzed in a preclinical mouse model after subcutaneous and intracardial injection of the tumor cells.Knock-down of endogenous L-plastin in human prostate carcinoma cells led to reduced tumor cell growth and metastasis. Vice versa, and in line with these findings, ectopic expression of L-plastin in L-plastin negative melanoma cells significantly increased the number of metastases. Strikingly, the metastasis promoting effect of L-plastin was not observed if a non-phosphorylatable L-plastin mutant was expressed. ### Long_Answer: Our data provide the first in vivo evidence that expression of L-plastin promotes tumor metastasis and, importantly, that this effect depends on an additionally required phosphorylation of L-plastin. In conclusion, these findings imply that for determining the importance of tumor-associated proteins like L-plastin a characterization of posttranslational modifications is indispensable. ### Final_Prediction: yes

### Question: Do myocardial T1 maps reflect histological findings in acute and chronic stages of myocarditis in a rat model? ### Context: Cardiovascular magnetic resonance offers both diagnostic and prognostic information in myocarditis. Using an established animal model of myocarditis, the aim of this study was to measure myocardial T1 before the onset, in the acute and in the chronic phases of the disease and to compare its course with histological and immunohistochemistry findings.Male young Lewis rats were immunized with 0.25 mg porcine myocardial myosin into the rear footpads on day 0. Native and contrast-enhanced ECG-triggered cardiac MRI examinations were performed before immunization on day 0 and on days 14, 21 and 35. Left ventricular function, pre- and post- contrast T1 parameters and LGE images were assessed using Small animal look-locker inversion recovery (SALLI). For each of the indicated time points a minimum of 4 rats were randomly sacrificed for pathological investigations including conventional histology (HE and Sirius-Red staining) and immunohistochemistry (CD 68) investigations.All immunized rats developed myocarditis (morbidity 100%). Histologically we observed increased wall thickness with biventricular macrophage-rich mixed inflammatory infiltrates. All rats with a histologically severe myocarditis showed increased native T1 and decreased post-contrast T1 of the myocardium. ### Long_Answer: The assessment of native T1 and post-contrast T1 allows accurate differentiation between healthy myocardium and myocardium with inflammation and also between the acute and chronic phases of the disease. ### Final_Prediction: yes

### Question: Correlation between maternal hepatitis B surface antigen carrier status with social, medical and family factors in an endemic area: have we overlooked something? ### Context: Hepatitis B virus (HBV) infection is endemic in many countries, but the risk factors for HBV carriage in the obstetric population are unclear.A survey on 1,580 women attending the antenatal clinic in an endemic region was conducted in order to examine the prevalence of and factors associated with maternal HBV carriage, including socio-demographic, medical, and previous obstetrical and family history, by means of a questionnaire.The prevalence of maternal HBV carriage was 9.1%, and 4.8% of women with a history of hepatitis B vaccination were found to be HBV carriers. Factors associated with maternal HBV carriage were residency status (adjusted odds ratio [aOR] 3.65 for immigrants; aOR 7.62 for non-residents), positive family history (aOR 3.72 for infected mother; aOR 5.36 for other family members), no previous vaccination (aOR 4.39) and having previous HBsAg testing (aOR 2.26). ### Long_Answer: The findings suggest that there was probably an overlooked role of horizontal transmission within the family setting in addition to perinatal transmission in determining the likelihood of HBV infection in our obstetric population. Reconfirmation of hepatitis B status might be necessary among individuals with a history of vaccination to ensure the effectiveness of their immunoprotection. ### Final_Prediction: nan

### Question: Do caries risk indicators in children with type 1 diabetes mellitus in relation to metabolic control? ### Context: The purpose of this study was to investigate the interaction of caries risk indicators and metabolic control in children with type 1 diabetes mellitus.The study included 50 children with type 1 DM and 50 healthy controls, all 6 to 9 years old. Diabetic children were classified into 3 groups: well, fairly, and poorly controlled based on glycosilated hemoglobin level. Personal, family data, medical and dental history were collected. Children were examined for caries experience, plaque, and gingival condition. Saliva samples were obtained for culturing mutans streptococci, lactobacilli, and Candida, and colony forming units were counted.No significant differences existed between all groups regarding caries experience or mean log count of micro-organisms. Diabetic children differed significantly from healthy children in parental occupation and education, dental visits, oral hygiene, and plaque and gingival indices, whereas no differences were observed among children with different levels of metabolic control regarding these factors. Regression analysis identified mutans streptococci as a significant variable affecting caries experience in diabetic children. ### Long_Answer: Regarding the interaction of caries risk indicators and metabolic control on caries experience in diabetic children, the only variable that showed a significant effect was mutans streptococci. ### Final_Prediction: yes

### Question: Is the human G147D-protein phosphatase 1 inhibitor-1 polymorphism associated with altered clinical characteristics in heart failure? ### Context: A human protein phosphatase inhibitor-1 polymorphism, G147D (c.440G>A, p.147G>D), has been previously demonstrated to blunt the contractile responses of cardiomyocytes to beta-adrenergic agonists. The present study sought to examine whether the G147D inhibitor-1 polymorphism may be associated with specific clinical characteristics of heart failure carriers.Clinical information of 963 heart failure patients was analyzed according to race, inhibitor-1 genotype, treatment with beta-blockers and mortality patterns.The G147D inhibitor-1 genetic variant was found almost exclusively in black subjects and its frequency was similar between normals and heart failure patients, indicating that it was not a primary risk factor for developing heart failure. Comparison of the major cardiac functional parameters and transplant-free survival patterns between carrier and noncarrier patients did not reveal any significant differences. Furthermore, echocardiographic evaluation showed similar outcomes of beta-blocker treatment between G147D carriers and noncarriers. ### Long_Answer: The present findings indicate that the human inhibitor-1 G147D polymorphism, found almost exclusively in blacks, may act as a modifier rather than risk factor in heart failure development. ### Final_Prediction: no

### Question: Does fiberoptic microneedle device facilitate volumetric infusate dispersion during convection-enhanced delivery in the brain? ### Context: A fiberoptic microneedle device (FMD) was designed and fabricated for the purpose of enhancing the volumetric dispersal of macromolecules delivered to the brain through convection-enhanced delivery (CED) by concurrent delivery of sub-lethal photothermal hyperthermia. This study's objective was to demonstrate enhanced dispersal of fluid tracer molecules through co-delivery of 1,064  nm laser energy in an in vivo rodent model.FMDs capable of co-delivering fluids and laser energy through a single light-guiding capillary tube were fabricated. FMDs were stereotactically inserted symmetrically into both cerebral hemispheres of 16 anesthetized rats to a depth of 1.5  mm. Laser irradiation (1,064 nm) at 0 (control), 100, and 200 mW was administered concurrently with CED infusions of liposomal rhodamine (LR) or gadolinium-Evans blue-serum albumin conjugated complex (Gd-EBA) at a flow rate of 0.1 µl/min for 1 hour. Line pressures were monitored during the infusions. Rodents were sacrificed immediately following infusion and their brains were harvested, frozen, and serially cryosectioned for histopathologic and volumetric analyses.Analysis by ANOVA methods demonstrated that co-delivery enhanced volumetric dispersal significantly, with measured volumes of 15.8  ±  0.6 mm(3) for 100 mW compared to 10.0  ±  0.4 mm(3) for its fluid only control and 18.0  ±  0.3 mm(3) for 200 mW compared to 10.3  ±  0.7 mm(3) for its fluid only control. Brains treated with 200 mW co-delivery exhibited thermal lesions, while 100 mW co-deliveries were associated with preservation of brain cytoarchitecture. ### Long_Answer: Both lethal and sub-lethal photothermal hyperthermia substantially increase the rate of volumetric dispersal in a 1 hour CED infusion. This suggests that the FMD co-delivery method could reduce infusion times and the number of catheter insertions into the brain during CED procedures. ### Final_Prediction: yes

### Question: Does estimated 10-year cardiovascular mortality seriously underestimate overall cardiovascular risk? ### Context: The European Society of Cardiology's prevention guideline suggests that the risk of total (fatal plus non-fatal) cardiovascular disease (CVD) may be calculated from the risk of CVD mortality using a fixed multiplier (3×). However, the proposed multiplier has not been validated. We investigated the ratio of total CVD to CVD mortality in a large population-based cohort.CVD mortality and total CVD (fatal plus non-fatal CVD requiring hospitalisation) were analysed using Kaplan-Meier estimates among 24 014 men and women aged 39-79 years without baseline CVD or diabetes mellitus in the prospective population-based European Prospective Investigation of Cancer and Nutrition-Norfolk cohort. CVD outcomes included death and hospitalisations for ischaemic heart disease, heart failure, cerebrovascular disease, peripheral artery disease or aortic aneurysm. The main study outcome was the ratio of 10-year total CVD to 10-year CVD mortality stratified by age and sex.Ten year CVD mortality was 3.9% (900 CVD deaths, 95% CI 3.6% to 4.1%); the rate of total CVD outcomes was 21.2% (4978 fatal or non-fatal CVD outcomes, 95% CI 20.7% to 21.8%). The overall ratio of total CVD to CVD mortality was 5.4. However, we found major differences in this ratio when stratified by gender and age. In young women (39-50 years), the ratio of total CVD to CVD mortality was 28.5, in young men (39-50 years) 11.7. In the oldest age group, these ratios were considerably lower (3.2 in women and 2.4 in men aged 75-79 years). ### Long_Answer: The relationship between 10-year total CVD and CVD mortality is dependent on age and sex, and cannot be estimated using a fixed multiplier. Using CVD mortality to estimate total CVD risk leads to serious underestimation of risk, particularly in younger age groups, and particularly in women. ### Final_Prediction: yes

### Question: Is valdecoxib as efficacious as diclofenac in the treatment of acute low back pain? ### Context: To compare the efficacy of valdecoxib 40 mg q.d. (with a second dose on day 1) with diclofenac 75 mg b.i.d. in the treatment of acute low back pain.This was a multicenter, randomized, double-blind study. Patients with acute low back pain, class 1a or 2a (Quebec Task Force), with a visual analog scale score >/=50 mm (on a 100-mm scale) and moderate to severe pain on a categorical scale, were randomized to valdecoxib 40 mg q.d. (with a second dose on day 1) or diclofenac 75 mg b.i.d. for 7 days (170 patients per group). The primary efficacy end point was change in pain intensity (visual analog scale, mm) from baseline to day 3 for the per-protocol population.Least squares mean reductions in pain intensity from baseline to day 3 were similar for valdecoxib (-42.02 mm) and diclofenac (-41.43 mm). Valdecoxib was comparable to diclofenac as the lower limit of the 95% confidence interval of the estimated difference (0.59 mm; 95% confidence interval, -3.40 to 4.59 mm) was within the prespecified noninferiority margin of -10 mm. The overall incidence of adverse events was similar for valdecoxib (28%) and diclofenac (26%). No statistically different moderate or severe upper gastrointestinal adverse events were reported, although they were numerically greater for diclofenac (8) than for valdecoxib (3). ### Long_Answer: Valdecoxib 40 mg q.d. (with a second dose on day 1) provides effective relief for acute low back pain, and was at least as efficacious as diclofenac 75 mg b.i.d., with a nonsignificant but numerically lower incidence of gastrointestinal adverse events. ### Final_Prediction: yes

### Question: Do patients who take part in stroke research differ from non-participants? ### Context: Stroke is one of the most disabling neurological conditions. Clinical research is vital for expanding knowledge of treatment effectiveness among stroke patients. However, evidence begins to accumulate that stroke patients who take part in research represent only a small proportion of all stroke patients. Research participants may also differ from the broader patient population in ways that could potentially distort treatment effects reported in therapeutic trials. The aims of this study were to estimate the proportion of stroke patients who take part in clinical research studies and to compare demographic and clinical profiles of research participants and non-participants.5,235 consecutive patients admitted to the Stroke Care Unit of the Royal Melbourne Hospital, Melbourne, Australia, for stroke or transient ischaemic attack between January 2004 and December 2011 were studied. The study used cross-sectional design. Information was collected on patients' demographic and socio-economic characteristics, risk factors, and comorbidities. Associations between research participation and patient characteristics were initially assessed using χ(2) or Mann-Whitney tests, followed by a multivariable logistic regression analysis. The logistic regression analysis was carried out using generalised estimating equations approach, to account for patient readmissions during the study period.558 Stroke Care Unit patients (10.7%) took part in at least one of the 33 clinical research studies during the study period. Transfer from another hospital (OR = 0.35, 95% CI 0.22-0.55), worse premorbid function (OR = 0.61, 95% CI 0.54-0.70), being single (OR = 0.61, 95% CI 0.44-0.84) or widowed (OR = 0.77, 95% CI 0.60-0.99), non-English language (OR = 0.67, 95% CI 0.53-0.85), high socio-economic status (OR = 0.74, 95% CI 0.59-0.93), residence outside Melbourne (OR = 0.75, 95% CI 0.60-0.95), weekend admission (OR = 0.78, 95% CI 0.64-0.94), and a history of atrial fibrillation (OR = 0.79, 95% CI 0.63-0.99) were associated with lower odds of research participation. A history of hypertension (OR = 1.50, 95% CI 1.08-2.07) and current smoking (OR = 1.23, 95% CI 1.01-1.50) on the other hand were associated with higher odds of research participation. ### Long_Answer: The results of this study indicate that stroke patients who take part in clinical research do not represent 'typical' patient admitted to a stroke unit. The imbalance of prognostic factors between stroke participants and non-participants has serious implications for interpretation of research findings reported in stroke literature. This study provides insights into clinical, demographic, and socio-economic characteristics of stroke patients that could potentially be targeted to enhance generalizability of stroke research studies. Given the imbalance of prognostic factors between research participants and non-participants, future studies need to examine differences in stroke outcomes of these groups of patients. ### Final_Prediction: nan

### Question: Is iMPACT a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans? ### Context: The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2.Here, we tested whether IMPACT down-regulation mimics the effects of DR in C. elegans. Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2-dependent manner. Impt-1 knockdown exacerbated DR-induced longevity and required several DR-activated transcription factors to extend lifespan, among them SKN-1 and DAF-16, which were induced during larval development and adulthood, respectively, in response to impt-1 RNAi. ### Long_Answer: IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR. ### Final_Prediction: yes

### Question: Do enhancers reside in a unique epigenetic environment during early zebrafish development? ### Context: Enhancers, not promoters, are the most dynamic in their DNA methylation status throughout development and differentiation. Generally speaking, enhancers that are primed to or actually drive gene expression are characterized by relatively low levels of DNA methylation (hypo-methylation), while inactive enhancers display hyper-methylation of the underlying DNA. The direct functional significance of the DNA methylation state of enhancers is, however, unclear for most loci.In contrast to conventional epigenetic interactions at enhancers, we find that DNA methylation status and enhancer activity during early zebrafish development display very unusual correlation characteristics: hypo-methylation is a unique feature of primed enhancers whereas active enhancers are generally hyper-methylated. The hypo-methylated enhancers that we identify (hypo-enhancers) are enriched close to important transcription factors that act later in development. Interestingly, hypo-enhancers are de-methylated shortly before the midblastula transition and reside in a unique epigenetic environment. Finally, we demonstrate that hypo-enhancers do become active at later developmental stages and that they are physically associated with the transcriptional start site of target genes, irrespective of target gene activity. ### Long_Answer: We demonstrate that early development in zebrafish embodies a time window characterized by non-canonical DNA methylation-enhancer relationships, including global DNA hypo-methylation of inactive enhancers and DNA hyper-methylation of active enhancers. ### Final_Prediction: yes

### Question: Is apoptosis in skeletal myocytes of patients with chronic heart failure associated with exercise intolerance? ### Context: The purpose of the study was to investigate if apoptosis occurs in skeletal muscle myocytes and its relation to exercise intolerance in patients with chronic heart failure (CHF).Intrinsic abnormalities of skeletal muscle frequently limit exercise tolerance in CHF patients. Recently, apoptosis has been detected in cardiac myocytes of patients with CHF, suggesting that apoptosis may contribute to the reduced contractile force. The presence and regulation of apoptosis in skeletal myocytes of patients with CHF remains to be defined.Skeletal muscle biopsies (m. vastus lateralis) of 34 CHF patients (New York Heart Association functional class II-III) and eight age-matched healthy control subjects were analyzed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling for the presence of apoptosis, and by immunohistochemistry and videodensitometrical quantification for inducible nitric oxide synthase (iNOS) and Bcl-2 expression. Maximal oxygen consumption (VO2max) was determined by ergospirometry.Apoptosis was detected in 16/34 (47%) patients with CHF and in none of the healthy subjects. Patients with apoptosis-positive skeletal muscle myocytes exhibited a significantly lower VO2max (12.0 +/- 3.7 vs. 18.2 +/- 4.4 ml/kg/min; p = 0.0005), a higher iNOS expression (6.8 +/- 3.6 vs. 3.7 +/- 2.6% iNOS-positive stained tissue area; p = 0.015) and a lower Bcl-2 expression (1.0 +/- 0.3 vs. 1.4 +/- 0.4% Bcl-2-positive tissue area; p = 0.03) as compared with patients with apoptosis-negative biopsies. ### Long_Answer: These results indicate that apoptosis is frequently found in skeletal muscle obtained from CHF patients, which is associated with significant impairment of functional work capacity. In skeletal muscle of these patients, iNOS and Bcl-2 are possibly involved in the regulation of apoptosis. ### Final_Prediction: yes

### Question: Is there a better way to predict death using heart rate recovery? ### Context: Heart rate recovery (HRR) during exercise testing is an independent predictor of prognosis. The relative predictive power of computational analysis of HRR as a function of resting and maximum heart rate (HR) compared with direct measurement of the drop in HR has not been determined.We aimed to improve on the prognostic value of HRR by the use of mathematical representations of HRR kinetics.In all, 2,193 patients who underwent exercise testing, coronary angiography, and clinical evaluation were followed up for 10.2 +/- 3.6 years. Mathematical functions were used to model HRR as a function of resting (HR(Rest)), maximum HR (HR(Peak)) and time (t): (a) HRR= HR(Rest) + (HR(peak) - HR(Rest)) X e(-kt) and (b) HRR= HR(Rest) + (HR(peak) - HR(Rest)) e(-kt2)Equation (b) provided the best fit of the recovery HR curve. An abnormal HRR at 2 min was a better predictor of mortality than HRR at 1, 3, or 5 min. At 2 min, HRR also predicted mortality better than computational models of HRR, relating HRR as a function of maximum and resting HRs. After adjusting for univariately significant predictors of mortality, HRR, age, exercise capacity, and maximum HR were chosen in order as the best predictors of mortality. ### Long_Answer: Even though the computational models of HRR and the determination of HRR at different time intervals were significant predictors of mortality, the simple discrete measure of HRR at 2 min was the best predictor of mortality. At 2 min, HRR outperformed age, METs, and maximum exercise HR in predicting all-cause mortality. ### Final_Prediction: nan

### Question: Is adjustment for reporting heterogeneity necessary in sleep disorders? ### Context: Anchoring vignettes are brief texts describing a hypothetical character who illustrates a certain fixed level of a trait under evaluation. This research uses vignettes to elucidate factors associated with sleep disorders in adult Japanese before and after adjustment for reporting heterogeneity in self-reports. This study also evaluates the need for adjusting for reporting heterogeneity in the management of sleep and energy related problems in Japan.We investigated a dataset of 1002 respondents aged 18 years and over from the Japanese World Health Survey, which collected information through face-to-face interview from 2002 to 2003. The ordered probit model and the Compound Hierarchical Ordered Probit (CHOPIT) model, which incorporated anchoring vignettes, were employed to estimate and compare associations of sleep and energy with socio-demographic and life-style factors before and after adjustment for differences in response category cut-points for each individual.The prevalence of self-reported problems with sleep and energy was 53 %. Without correction of cut-point shifts, age, sex, and the number of comorbidities were significantly associated with a greater severity of sleep-related problems. After correction, age, the number of comorbidities, and regular exercise were significantly associated with a greater severity of sleep-related problems; sex was no longer a significant factor. Compared to the ordered probit model, the CHOPIT model provided two changes with a subtle difference in the magnitude of regression coefficients after correction for reporting heterogeneity. ### Long_Answer: Sleep disorders are common in the general adult population of Japan. Correction for reporting heterogeneity using anchoring vignettes is not a necessary tool for proper management of sleep and energy related problems among Japanese adults. Older age, gender differences in communicating sleep-related problems, the presence of multiple morbidities, and regular exercise should be the focus of policies and clinical practice to improve sleep and energy management in Japan. ### Final_Prediction: no

### Question: Is nT-proBNP elevated in patients with obstructive sleep apnoea? ### Context: N-terminal pro-brain natriuretic peptide (NT-ProBNP) has emerged as an important marker of cardiac stress and may reflect the severity of underlying cardiac dysfunction, which is thought to be associated with obstructive sleep apnoea syndrome (OSAS).This study evaluated the plasma concentration of NT-ProBNP in 60 consecutive patients (median age 55.7 years, median body mass index (BMI) 31.8) who were referred to a sleep laboratory with a suspicion of OSAS. Each subject underwent measurement of morning NT-ProBNP plasma levels, polysomnography and echocardiography. Patients were treated with nasal continuous or bilevel positive airway pressure ventilation (nCPAP/BIPAP) or without mechanical respiratory support, depending on clinical symptoms and results of polysomnography. Three months after treatment of OSAS 28 of the patients were reassessed for re-evaluation of NT-ProBNP and polysomnography.Low or high levels of NT-proBNP were not associated with AHI and other sleep related indices (p>0.3). There was no correlation between NT-proBNP and AHI or other sleep related indices. In multiple regression analysis, NT-proBNP was significantly correlated with left ventricular ejection fraction, creatinine clearance and the presence of systemic arterial hypertension but not with AHI. ### Long_Answer: Our results show by a robust multiple regression analysis, that NT-pro BNP is not associated with OSAS and NT-pro BNP cannot be used as a sensitive marker for underlying cardiovascular abnormalities in patients with OSAS. ### Final_Prediction: no

### Question: Is a single nucleotide polymorphism in the p27 ( Kip1 ) gene associated with primary patency of lower extremity vein bypass grafts? ### Context: Factors responsible for the variability in outcomes after lower extremity vein bypass grafting (LEVBG) are poorly understood. Recent evidence has suggested that a single nucleotide polymorphism (SNP) in the promoter region of the p27(Kip1) gene, a cell-cycle regulator, is associated with coronary in-stent restenosis. We hypothesized an association with vein graft patency.This was a retrospective genetic association study nested within a prospective cohort of 204 patients from three referral centers undergoing LEVBG for claudication or critical ischemia. The main outcome measure was primary vein graft patency.All patients were followed up for a minimum of 1 year with duplex graft surveillance (median follow-up, 893 days; interquartile range, 539-1315). Genomic DNA was isolated and SNP analysis for the p27(Kip1)-838C>A variants was performed. Allele frequencies were correlated with graft outcome using survival analysis and Cox proportional hazards modeling. The p27(Kip1)-838C>A allele frequencies observed were CA, 53%; CC, 30%; and AA, 17%, satisfying Hardy-Weinberg equilibrium. Race (P = .025) and history of coronary artery disease (P = .027) were different across the genotypes; all other baseline variables were similar. Primary graft patency was greater among patients with the -838AA genotype (75% AA vs 55% CA/CC at 3 years; P = .029). In a Cox proportional hazards model including age, sex, race, diabetes, critical limb ischemia, redo (vs primary) bypass, vein type, and baseline C-reactive protein level, the p27(Kip1)-838AA genotype was significantly associated with higher graft patency (hazard ratio for failure, 0.4; 95% confidence interval, 0.17-0.93). Genotype was also associated with early (0-1 month) changes in graft lumen diameter by ultrasound imaging. ### Long_Answer: These data suggest that the p27(Kip1)-838C>A SNP is associated with LEVBG patency and, together with previous reports, underscore a central role for p27(Kip1) in the generic response to vascular injury. ### Final_Prediction: yes

### Question: Do the sap from Euphorbia peplus is effective against human nonmelanoma skin cancers? ### Context: The sap from Euphorbia peplus, commonly known as petty spurge in the U.K. or radium weed in Australia, has been used as a traditional treatment for a number of cancers.To determine the effectiveness of E. peplus sap in a phase I/II clinical study for the topical treatment of basal cell carcinomas (BCC), squamous cell carcinomas (SCC) and intraepidermal carcinomas (IEC).Thirty-six patients, who had refused, failed or were unsuitable for conventional treatment, were enrolled in a phase I/II clinical study. A total of 48 skin cancer lesions were treated topically with 100-300 μL of E. peplus sap once daily for 3 days.The complete clinical response rates at 1 month were 82% (n = 28) for BCC, 94% (n = 16) for IEC and 75% (n = 4) for SCC. After a mean follow-up of 15 months these rates were 57%, 75% and 50%, respectively. For superficial lesions < 16 mm, the response rates after follow-up were 100% for IEC (n = 10) and 78% for BCC (n = 9). ### Long_Answer: The clinical responses for these relatively unfavourable lesions (43% had failed previous treatments, 35% were situated in the head and neck region and 30% were > 2 cm in diameter), are comparable with existing nonsurgical treatments. An active ingredient of E. peplus sap has been identified as ingenol mebutate (PEP005). This clinical study affirms community experience with E. peplus sap, and supports further clinical development of PEP005 for the treatment of BCC, SCC and IEC. ### Final_Prediction: yes

### Question: Does thorax irradiation trigger a local and systemic accumulation of immunosuppressive CD4+ FoxP3+ regulatory T cells? ### Context: Lymphocyte infiltration is a common feature of radiation-induced pneumonitis and fibrosis, but their contribution to the pathogenic processes is still unclear. Here, we addressed the impact of thorax irradiation on the T cell compartment with a focus on immunosuppressive regulatory T cells (Treg).C57BL/6 wild type mice (WT) received anesthesia only (sham controls, 0 Gy) or were exposed to a single dose of whole thorax irradiation (15 Gy). Immune cells from lung tissue, spleen, and cervical lymph nodes were collected 10 to 84 days post-irradiation and phenotypically characterized by flow cytometry.Whole thorax irradiation provoked an increased influx of CD3+ T cells at 42 and 84 days post-irradiation. In contrast, local irradiation caused a sustained reduction in CD3+ T cells in peripheral lymphoid tissues. Interestingly, we observed a significant local and systemic increase in the fraction of CD4+ T cells expressing the transcription factor forkhead box P3 (FoxP3), the phenotypic marker for murine Treg, at day 21 post-irradiation. The accumulation of Treg was associated with increased levels of T cells expressing surface proteins characteristic for recruitment and immunosuppressive activity, e.g. CD103, CTLA-4 and CD73. Importantly, Treg isolated at this time point were able to suppress CD4+ effector T cells to a similar extent as Treg isolated from control mice. ### Long_Answer: The response of the adaptive immune system to whole thorax irradiation is characterized by local immunoactivation and systemic immunosuppression. The transient accumulation of immunosuppressive CD4+ FoxP3+ Treg may be required to protect the lung against excessive inflammation-induced tissue damage. Further investigations shall define the mechanisms underlying the accumulation of Treg and their role for the pathogenesis of radiation-induced lung disease. ### Final_Prediction: yes

### Question: Is bclI polymorphism of the glucocorticoid receptor gene associated with decreased bone mineral density in patients with endogenous hypercortisolism? ### Context: The hypothalamic-pituitary-adrenal axis setpoint and the glucocorticoid sensitivity of various tissues are at least partially genetically determined. We investigated the impact of glucocorticoid receptor (GR) gene polymorphisms, including the BclI, N363S, ER22/23EK and A3669G variants on bone turnover and/or mineral density (BMD) in patients with endogenous glucocorticoid excess.Sixty patients including 35 patients with ACTH producing pituitary adenoma (CD) and 25 patients with adrenal Cushing's syndrome (ACS) as well as 129 healthy subjects were genotyped. Analysis of the GR gene polymorphisms were determined using allele specific PCR, PCR-RFLP and Taqman allelic discrimination assays. Hormonal evaluation, BMD and bone marker measurements were carried out.No significant differences were found in allelic frequencies of the four polymorphisms between patients with ACS, CD and healthy controls. Patients with endogenous hypercortisolism carrying the BclI polymorphism in a homozygous form had reduced BMD at femoral subregions compared to patients with the wild-type variant; femoral neck Z-score (-1.44 +/- 0.73 vs. -0.39 +/- 0.91; P < 0.05), trochanteric Z-score (-1.89 +/- 0.47 vs.-0.54 +/- 0.98; P < 0.05). Patients with homozygous BclI polymorphism had significantly higher beta-CrossLaps Z-scores compared to those with the heterozygous and wild-type variants (+4.42 +/- 2.37 vs. +0.79 +/- 1.67 and +0.11 +/- 1.47; P < 0.01). ### Long_Answer: The BclI, N363S, ER22/23EK and A3669G polymorphisms of the GR gene probably do not modify the risk for the development of CD or ACS. Contrary to healthy subjects, however, the BclI polymorphism may modify the skeletal sensitivity to glucocorticoids in patients with endogenous glucocorticoid excess. ### Final_Prediction: yes

### Question: Are pediatric melanoma : recent advances in the management of adult melanoma relevant to the pediatric population? ### Context: Although melanoma in childhood is a rare condition, there is evidence that it is increasing in frequency. As advances are being made in the understanding and therapy of adult melanoma, we need to consider the relevance of these advances to the pediatric population.We have reviewed our experience at the University of Colorado Health Sciences Center with the clinical parameters, therapy, and outcomes of melanoma in 27 patients age 16 years or younger and contrasted these to the adult experience.Most cases were diagnosed early with the median thickness of the primary melanoma being 0.75 mm. Six of seven patients who had lymph node metastases develop remain alive at a median follow-up of 62 months. Durable complete responses to a variety of therapies were seen in three of five patients with advanced disease outside the central nervous system. Our experience with sentinel node biopsy, adjuvant interferon, and new therapies for metastatic melanoma were also reviewed and appear to be relevant for younger patients. ### Long_Answer: The behavior of melanoma in the pediatric population at our center is similar to that seen in adults. The integration of recent advances in the staging and therapy of melanoma in adults would be of benefit to children with this condition. ### Final_Prediction: yes