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### Question: Does transfection of human HGF plasmid DNA improve limb salvage in Buerger 's disease patients with critical limb ischemia? ### Context: Hepatocyte growth factor is a potent angiogenic agent. This study investigated the efficacy and safety of intramuscular injection of naked plasmid DNA encoding the human hepatocyte growth factor gene in Japanese patients with Buerger's disease and critical limb ischemia.An open-label clinical study was performed at eight hospitals in Japan from May 2004 to April 2008. Ten patients were enrolled. They had Buerger's disease with ischemic ulcers, were not candidates for revascularization, and were unresponsive to conventional drug therapy. Treatment consisted of 8 injections (total dose: 4 mg) of hepatocyte growth factor plasmid, which were administered into the calf muscles and/or distal thigh muscles of the ischemic limbs under ultrasound guidance. Administration was done twice at an interval of 4 weeks. If there was no improvement after 2 doses, a 3rd dose could be administered. The response to treatment was evaluated from the reduction of ischemic ulcer size.The size of ischemic ulcers showed a decrease in 6/9 (66.7%) patients and the ulcers healed completely in 5/9 (55.6%) patients after gene therapy. Major amputation was not required. There were no deaths and no major safety concerns. ### Long_Answer: Hepatocyte growth factor gene therapy is safe and effective for critical limb ischemia in patients with Buerger's disease. ### Final_Prediction: yes

### Question: Does gelam honey potentiate ex vivo corneal keratocytes proliferation with desirable phenotype expression? ### Context: This study aimed to evaluate the effects of Gelam honey on corneal keratocytes proliferative capacity and phenotypic characterization via MTT assay, gene expression and immunocytochemistry.Corneal keratocytes from New Zealand white rabbits were cultured in basal medium (BM) and serum enriched medium (BMS). Serial dilutions of Gelam honey (GH) were added to both media and cells were cultured until passage 1. MTT assay was performed on corneal keratocytes in both media to ascertain the optimal dose of GH that produced maximum proliferation.Gelam honey at the concentration of 0.0015% in both media showed the highest proliferative capacity with no morphological changes compared to their respective controls. The gene expression of aldehyde dehydrogenase (ALDH), a marker for quiescent keratocytes and vimentin, a marker for fibroblast, were higher in the GH enriched groups. The alpha smooth muscle actin (α-SMA) expression, marker for myofibroblast, was lower in GH treated groups compared to the controls. Immunocytochemistry results were in accordance to the gene expression analyses. ### Long_Answer: Gelam honey at a concentration of 0.0015% promotes ex vivo corneal keratocytes proliferation while retaining desirable phenotype expression. The results serve as a basis for the development of Gelam honey as a potential natural product in promoting corneal wound healing. ### Final_Prediction: yes

### Question: Complex sleep apnea syndrome: is it a unique clinical syndrome? ### Context: Some patients with apparent obstructive sleep apnea hypopnea syndrome (OSAHS) have elimination of obstructive events but emergence of problematic central apneas or Cheyne-Stokes breathing pattern. Patients with this sleep-disordered breathing problem, which for the sake of study we call the "complex sleep apnea syndrome," are not well characterized. We sought to determine the prevalence of complex sleep apnea syndrome and hypothesized that the clinical characteristics of patients with complex sleep apnea syndrome would more nearly resemble those of patients with central sleep apnea syndrome (CSA) than with those of patients with OSAHS.Retrospective reviewSleep disorders center.Two hundred twenty-three adults consecutively referred over 1 month plus 20 consecutive patients diagnosed with CSA.NA.Prevalence of complex sleep apnea syndrome, OSAHS, and CSA in the 1-month sample was 15%, 84%, and 0.4%, respectively. Patients with complex sleep apnea syndrome differed in gender from patients with OSAHS (81% vs 60% men, p<.05) but were otherwise similar in sleep and cardiovascular history. Patients with complex sleep apnea syndrome had fewer maintenance-insomnia complaints (32% vs 79%; p<.05) than patients with CSA but were otherwise not significantly different clinically. Diagnostic apnea-hypopnea index for patients with complex sleep apnea syndrome, OSAHS, and CSA was 32.3 +/- 26.8, 20.6 +/- 23.7, and 38.3 +/- 36.2, respectively (p = .005). Continuous positive airway pressure suppressed obstructive breathing, but residual apnea-hypopnea index, mostly from central apneas, remained high in patients with complex sleep apnea syndrome and CSA (21.7 +/- 18.6 in complex sleep apnea syndrome, 32.9 +/- 30.8 in CSA vs 2.14 +/- 3.14 in OSAHS; p<.001). ### Long_Answer: Patients with complex sleep apnea syndrome are mostly similar to those with OSAHS until one applies continuous positive airway pressure. They are left with very disrupted breathing and sleep on continuous positive airway pressure. Clinical risk factors don't predict the emergence of complex sleep apnea syndrome, and best treatment is not known. ### Final_Prediction: nan

### Question: Outpatient cardiac rehabilitation: are the potential benefits being realised? ### Context: to give a comprehensive description of the practice of outpatient cardiac rehabilitation in Scotland.an identifying survey of 1,270 individuals in hospital, general practice and community sources nationally, followed by computer-assisted telephone interviews about programme characteristics with key personnel from identified cardiac rehabilitation schemes.patient provision, referral criteria and programme features.65 programmes provided outpatient cardiac rehabilitation for 4,980 patients in one year, representing 17% of the 29,180 patients who survived admission to hospital with coronary heart disease. Cardiac rehabilitation practice varied widely: 53 (82%) programmes included exercise, although only 19 (29%) at the most beneficial level; 40 (62%) included relaxation training, although only three (5%) at a level shown to give benefit; 47 (72%) included education, although only 16 (25%) in a manner with reported benefits in randomised trials. ### Long_Answer: outpatient cardiac rehabilitation was provided to a minority of patients with coronary heart disease. Programmes varied widely, and were often more limited than those reporting mortality and morbidity benefits in randomised trials. There is a substantial gap between current provision and practice of cardiac rehabilitation and that advocated in published guidelines. ### Final_Prediction: nan

### Question: Is adriamycin disruption of the Shh-Gli pathway associated with abnormalities of foregut development? ### Context: The hedgehog signalling pathway appears to have a crucial role in the embryogenesis of the foregut in vertebrates. Sonic hedgehog (Shh) protein and gene are involved in the differentiation of many organ systems such as notochord, floor plate, and limbs; development of the left-right axis in vertebrates; and differentiation of trachea and esophagus from the primitive foregut.The prenatal exposure of Sprague-Dawley fetal rats to Adriamycin between days 6 and 9 of gestation was used to induce esophageal atresia and tracheoesophageal fistula. Embryos were harvested by cesarean section on gestational days 11 to 15. Embryos were examined by microscopy, dissection, and serial histology. In situ hybridization was used to study Shh gene expression in the rat embryos.In situ hybridization showed that the pattern and level of Shh gene expression are affected by Adriamycin. Adriamycin-treated rats have deformed notochord and undivided foregut, and some of the embryos had a lack of the dorso-ventral patterning of Shh expression seen in control embryos. ### Long_Answer: These results are consistent with the hypothesis that Adriamycin influences the Shh signalling pathway, resulting in disruption of normal development of the foregut. ### Final_Prediction: yes

### Question: Are antegrade colonic enemas and intestinal diversion highly effective in the management of children with intractable constipation? ### Context: Intractable constipation in children is an uncommon but debilitating condition. When medical therapy fails, surgery is warranted; but the optimal surgical approach has not been clearly defined. We reviewed our experience with operative management of intractable constipation to identify predictors of success and to compare outcomes after 3 surgical approaches: antegrade continence enema (ACE), enteral diversion, and primary resection.A retrospective review of pediatric patients undergoing ACE, diversion, or resection for intractable, idiopathic constipation from 1994 to 2007 was performed. Satisfactory outcome was defined as minimal fecal soiling and passage of stool at least every other day (ACE, resection) or functional enterostomy without abdominal distension (diversion).Forty-four patients (range = 1-26 years, mean = 9 years) were included. Sixteen patients underwent ACE, 19 underwent primary diversion (5 ileostomy, 14 colostomy), and 9 had primary colonic resections. Satisfactory outcomes were achieved in 63%, 95%, and 22%, respectively. Of the 19 patients diverted, 14 had intestinal continuity reestablished at a mean of 27 months postdiversion, with all of these having a satisfactory outcome at an average follow-up of 56 months. Five patients underwent closure of the enterostomy without resection, whereas the remainder underwent resection of dysmotile colon based on preoperative colonic manometry studies. Of those undergoing ACE procedures, age younger than 12 years was a predictor of success, whereas preoperative colonic manometry was not predictive of outcome. Second manometry 1 year post-ACE showed improvement in all patients tested. On retrospective review, patient noncompliance contributed to ACE failure. ### Long_Answer: Antegrade continence enema and enteral diversion are very effective initial procedures in the management of intractable constipation. Greater than 90% of diverted patients have an excellent outcome after the eventual restoration of intestinal continuity. Colon resection should not be offered as initial therapy, as it is associated with nearly 80% failure rate and the frequent need for additional surgery. ### Final_Prediction: yes

### Question: Highly well differentiated hepatocellular carcinoma and benign hepatocellular lesions. Can they be distinguished on fine needle aspiration biopsy? ### Context: To determine whether highly well differentiated hepatocellular carcinoma can be distinguished from benign hepatocellular lesions on fine needle aspiration biopsy (FNAB).Ninety-five FNABs from 88 patients with hepatic masses/diffuse conditions were reviewed according to new cytologic criteria established by Takenaka et al. They were classified into well-, moderately and poorly differentiated hepatocellular carcinomas (W-, M- and P-HCC) and benign aspirates and histologically verified.There were 21 W-HCC, 39 M-HCC, 10 P-HCC, 3 problematic and 22 benign aspirates. The most useful criteria for diagnosing highly W-HCC were architectural features on the smears/cell block sections, including hypercellularity; arborescent, cohesive clusters; broad trabeculae; transgressing and peripheral endothelium; and cytologic details of small, monotonous hepatocytes with nuclear crowding, decreased cytoplasm, increased nuclear/cytoplasmic ratio, atypical naked nuclei and tumor giant cells. Well-defined cytoplasmic borders, abundant thick and monotonous cytoplasm, eccentric nuclei, thick nuclear membranes, irregular nuclear contours, increased chromatin density, irregular chromatin distribution and macronucleoli were not always detectable in highly W-HCC. In fact, some of them were seen in dysplastic hepatocytes. Deficient reticulin patterns and diffuse sinusoidal CD34 reactivity were helpful. ### Long_Answer: Experience, attention to architectural and cytologic details in smears/cell blocks and clinicopathologic correlation should reduce the number of indeterminate reports. However, there will always remain some cytohistologically challenging cases. ### Final_Prediction: nan

### Question: Does continuous oral administration of atorvastatin ameliorate brain damage after transient focal ischemia in rats? ### Context: Pre-treatment with statins is known to ameliorate ischemic brain damage after experimental stroke, and is independent of cholesterol levels. We undertook pre- vs post-ischemic treatment with atorvastatin after focal cerebral ischemia in rats.Male Sprague-Dawley rats underwent transient 90-min middle cerebral artery occlusion (MCAO). Atorvastatin (20mg/kg/day) or vehicle was administered orally. Rats were divided into vehicle-treated, atorvastatin pre-treatment, atorvastatin post-treatment, and atorvastatin continuous-treatment groups. In the pre-treatment, rats were given atorvastatin or vehicle for 7 days before MCAO. In the post-treatment, rats received atorvastatin or vehicle for 7 days after MCAO. Measurement of infarct volume, as well as neurological and immunohistochemical assessments, were done 24h and 7 days after reperfusion.Each atorvastatin-treated group demonstrated significant reductions in infarct and edema volumes compared with the vehicle-treated group 24h after reperfusion. Seven days after reperfusion, infarct volumes in the post-treatment group and continuous-treatment group (but not the pre-treatment group) were significantly smaller than in the vehicle-treated group. Only the continuous-treatment group had significantly improved neurological scores 7 days after reperfusion compared with the vehicle group. Post-treatment and continuous-treatment groups had significantly decreased lipid peroxidation, oxidative DNA damage, microglial activation, expression of tumor necrosis factor-alpha, and neuronal damage in the cortical ischemic boundary area after 7 days of reperfusion. ### Long_Answer: These results suggest that continuous oral administration (avoiding withdrawal) with statins after stroke may reduce the extent of post-ischemic brain damage and improve neurological outcome by inhibiting oxidative stress and inflammatory responses. ### Final_Prediction: yes

### Question: Does factor structure of the Mood and Anxiety Symptom Questionnaire generalize to an anxious/depressed sample? ### Context: The tripartite model of anxiety and depression has been proposed as a representation of the structure of anxiety and depression symptoms. The Mood and Anxiety Symptom Questionnaire (MASQ) has been put forwards as a valid measure of the tripartite model of anxiety and depression symptoms. This research set out to examine the factor structure of anxiety and depression symptoms in a clinical sample to assess the MASQ's validity for use in this population.The present study uses confirmatory factor analytic methods to examine the psychometric properties of the MASQ in 470 outpatients with anxiety and mood disorder.The results showed that none of the previously reported two-factor, three-factor or five-factor models adequately fit the data, irrespective of whether items or subscales were used as the unit of analysis. ### Long_Answer: It was concluded that the factor structure of the MASQ in a mixed anxiety/depression clinical sample does not support a structure consistent with the tripartite model. This suggests that researchers using the MASQ with anxious/depressed individuals should be mindful of the instrument's psychometric limitations. ### Final_Prediction: no

### Question: Do validation of the Japanese Society for Surgery of the Hand version of the Carpal Tunnel Syndrome Instrument? ### Context: The Carpal Tunnel Syndrome Instrument (CTSI) is a disease-specific, self-administered questionnaire that consists of a symptom severity scale (SS) and a functional status scale (FS). The CTSI was cross-culturally adapted and developed by the Impairment Evaluation Committee, Japanese Society for Surgery of the Hand (JSSH). The purpose of this study was to test the reliability, validity, and responsiveness of the Japanese version of the CTSI (CTSI-JSSH).A consecutive series of 87 patients with carpal tunnel syndrome completed the CTSI-JSSH, the JSSH version of the Disability of the Arm, Shoulder, and Hand questionnaire (DASH-JSSH), and the 36-Item Short-Form Health Survey (SF-36). Seventy-two of the patients were reassessed for test-retest reliability 1 or 2 weeks later. Reliability was investigated by the reproducibility and the internal consistency. To analyze the validity, a factor analysis (principal axis factoring) of the CTSI-JSSH and the correlation coefficients between the CTSI-JSSH and DASH-JSSH were obtained. The responsiveness was examined by calculating the standardized response mean (SRM; mean change/SD) and effect size (mean change/SD of baseline value) after carpal tunnel release in 42 patients.Cronbach's alpha coefficients for the CTSI-JSSH-SS and the CTSI-JSSH-FS were 0.84 and 0.90, respectively, and the intraclass correlation coefficients were 0.82 and 0.83, respectively. The unidimensionality of the CTSI-JSSH-SS was barely confirmed; the unidimensionality of the CTSI-JSSH-FS was confirmed. The correlation coefficients between the CTSI-JSSH-FS and the CTSI-JSSH-SS or DASH-JSSH were 0.58 and 0.80, respectively. The correlation coefficient between the CTSI-JSSH-SS and DASH-JSSH was 0.54. The correlation coefficients between the subscales of SF-36 and the CTSI-JSSH-SS or the CTSI-JSSH-FS ranged from -0.23 to -0.66 and from -0.19 to -0.63, respectively. The SRMs/effect sizes of the CTSI-JSSH-SS and the CTSI-JSSH-FS were -0.85/-0.99 and -0.70/-0.61, which indicated that they were more than moderately sensitive. ### Long_Answer: The CTSI-JSSH has sufficient reliability, validity, and responsiveness to assess the health status in carpal tunnel syndrome. ### Final_Prediction: yes

### Question: Chest pain in general practice or in the hospital emergency department: is it the same? ### Context: The aim of the present study was to provide a description of the impact of setting on the diagnostic case mix that is identified in consecutive patients presenting with chest pain.A cross-sectional study was carried out of patients presenting with chest pain according to setting: general practice, self-referred, referred or arriving by ambulance at the hospital emergency department (ED). GPs from 25 general practices situated in the Flemish part of Belgium were recruited, and the hospital involved was a major teaching hospital in the same area. A total of 320 patients in general practice and 580 patients in the hospital ED were studied. The difference in prevalence rates for the major diagnostic categories was the main outcome measure.Gastrointestinal disorders, musculoskeletal problems and psychopathology are identified more frequently in general practice; and serious lung diseases and cardiovascular diseases in the hospital ED. Within the hospital, there is a strong trend towards increasing frequency of serious cardiovascular diseases including unstable angina (P = 0.01) from self-referred to referred patients and those rushed in by ambulance. The opposite trend was identified for respiratory (P = 0.02) and musculoskeletal (P = 0.07) diseases. The diagnostic case mix in self-referred patients tends to be more similar to the other groups of hospital patients than to patients in general practice. ### Long_Answer: There is a large difference between the diagnostic case mix presented in general practice compared with the ED and among referral-related subgroups within the hospital emergency department. ### Final_Prediction: nan

### Question: Can ophthalmic requests for neuroimaging be improved? ### Context: Patients referred for diagnostic neuroimaging were identified from the radiology database over a 1-year period. A case note review was undertaken. The clinical indication for and results of neuroimaging performed were ascertained. The justification for neuroimaging was determined.Of the total 31,411 patients that were seen in the eye department, 103 (0.32%) had diagnostic neuroradiological imaging performed. The indications for imaging were: suspected compressive lesion of the anterior visual pathway in 57 patients (55.3%), acquired ocular motility disturbance in 20 patients (19.4%), suspected orbital pathology in 11 patients (10.6%), cerebrovascular accident in nine patients (8.7%), and six patients (5.8%) were imaged for either headache or sinusitis. Radiological lesion detection rate was highest for cerebrovascular accident (88.8%) and lowest acquired for ocular motility disturbance (4.9%). ### Long_Answer: Ophthalmic requests for diagnostic neuroimaging were found to be unnecessary in only 9% of patients. Guidelines for the referral of ophthalmic patients for neuroimaging are discussed. ### Final_Prediction: nan

### Question: Do human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation? ### Context: Antibodies directed against alloantigens are implicated in the pathogenesis of several immune reactions complicating transplantation, including humoral rejection after solid organ transplantation. Mesenchymal stem cells (MSCs) have immunomodulatory capacity, since in vivo they may prolong skin graft survival in the animal model and can rescue patients with life-threatening graft-versus-host disease.To investigate whether MSCs exert an inhibitory effect on antibody production during allostimulation, we stimulated peripheral blood mononuclear cells, obtained from healthy controls or sensitized patients undergoing dialysis for end-stage renal failure, in mixed lymphocyte culture (MLC), and evaluated immunoglobulin production either in the absence or in the presence of third-party allogeneic MSCs. We also evaluated the effect of MSCs on B-cell allostimulation performed adding to MLC a polyclonal stimulus delivered by an agonist anti-CD40 monoclonal antibody.We found that the addition of MSCs at the beginning of MLC considerably inhibited immunoglobulin production in standard MLC, irrespective of the MSC dose employed. Conversely, immunoglobulin secretion induced by direct CD40-CD40L binding was not significantly inhibited. Furthermore, we demonstrated, in one sensitized patient, that secretion of donor-specific anti-HLA class I antibodies detected both in baseline serum and in the supernatant of control MLC was inhibited by the addition of MSCs. Mechanistically, the addition of MSCs induced a striking decrease of IL-5 production in the cultures. ### Long_Answer: Our findings suggest that third-party MSC are able to suppress allo-specific antibody production in vitro, and may therefore help overcome a positive cross-match in sensitized transplant recipients. ### Final_Prediction: yes

### Question: Do multiple sclerosis risk genotypes correlate with an elevated cerebrospinal fluid level of the suggested prognostic marker CXCL13? ### Context: The mechanisms of multiple sclerosis (MS) pathogenesis are still largely unknown. The heterogeneity of disease manifestations make the prediction of prognosis and choice of appropriate treatment protocols challenging. Recently, increased cerebrospinal fluid (CSF) levels of the B-cell chemokine CXCL13 was proposed as a possible marker for a more severe disease course and conversion from clinically isolated syndrome (CIS) to relapsing-remitting MS (RRMS).To investigate whether there are genetic susceptibility variants in MS that correlate with the levels of CXCL13 present in the CSF of MS patients.We genotyped the human leukocyte antigens HLA-DRB1 and HLA-A, plus a panel of single nucleotide polymorphisms (SNPs) that have been associated with susceptibility to MS and then correlated the genotypes with the levels of CXCL13, as measured with ELISA in the CSF of a total of 663 patients with MS, CIS, other neurological diseases (OND) or OND with an inflammatory component (iOND).Presence of the HLA-DRB1*15 and the MS risk genotypes for SNPs in the RGS1, IRF5 and OLIG3/TNFAIP3 gene regions correlated significantly with increased levels of CXCL13. ### Long_Answer: Our results pointed towards a genetic predisposition for increased CXCL13 levels, which in MS patients correlates with the severity of the disease course. These findings encourage further investigation and replication, in an independent patient cohort. ### Final_Prediction: yes

### Question: Do specific miRNA expression profiles of non-tumor liver tissue predict a risk for recurrence of hepatocellular carcinoma? ### Context: It is reasonable to investigate non-tumor liver tissues to predict a risk for development of hepatocellular carcinoma (HCC). A molecular analysis of chronically damaged liver tissues may identify specific miRNA expression profiles associated with a risk for multicentric (MC) HCC.Twenty HCC patients, who underwent a curative hepatectomy were classified into two groups: a non-MC group (no MC recurrence in more than 3 years, n = 10) and an MC group (MC recurrence within 3 years after hepatectomy, n = 10). An miRNA microarray (955 probes) was used to compare the miRNA expression patterns of the non-cancerous liver tissues between the two groups. This study identified the differentially expressed miRNA related to MC recurrence in the liver remnant.No differences were observed between the two groups in the liver function tests and pathological variables including both tumor factors and non-tumor liver tissues. The investigation selected 20 differentially expressed miRNA related to MC recurrence. Eighteen miRNA were downregulated, while two miRNA were upregulated in the MC group. A hierarchical clustering analysis identified a cluster that may be associated with risk of the MC recurrence of HCC. The MC recurrence-related miRNA included let-7d*, miR-328 and miR18a*, which potentially regulate K-ras gene expression. A significant inverse correlation between the miR-18a* expression and the K-ras mRNA expression was confirmed by quantitative reverse transcription polymerase chain reaction. ### Long_Answer: Specific miRNA expression signatures in non-cancerous liver tissue may help to predict the risk for de novo development of HCC. ### Final_Prediction: yes

### Question: Does voice activity and participation profile presenting coordinate for readjustment of preventive action of educators? ### Context: To investigate the perception of voice impairment in professional and social contexts, to correlate these data with existing data in the literature, and to explore the perception of voice problems and the adherence to vocal health programs.502 Brazilian educators working in municipal public schools responded to the Voice Activity and Participation Profile (VAPP) questionnaire. Then a correlation was made with previous results in the literature dealing with a dysphonic and a nondysphonic group.The VAPP data showed that self-perception of voice problems had a higher vocal impact on daily communication and lower scores for activity limitation and participation restriction. The educators' scores were closer to those of the nondysphonic group with regard to daily and social communication, and emotional and activity limitation, but perception of the voice problem was closest to that of the dysphonic group. Nevertheless, the opposite was the case for participation restriction. ### Long_Answer: The educators perceive vocal problems but do not perceive participation restriction to the same extent. This may explain the decreasing participation in the Vocal Health Program. It probably occurs because adults voluntarily apply for training when they feel that their work performance needs to improve so that they can carry out their job properly. ### Final_Prediction: yes

### Question: Is the greater omentum the primary site of neutrophil exudation in peritonitis? ### Context: Peritonitis remains a major infectious problem. Neutrophil influx into the peritoneal cavity is one of the most important host defense mechanisms. However, no studies have focused on the site of neutrophil exudation. This study examined the primary anatomic site of neutrophil exudation in bacterial peritonitis.Fifty-five rats were injected intraperitoneally with saline solution (control group) or 10(7) Escherichia coli (peritonitis group). In experiment 1, 1 x 10(6) fluorescein-labeled neutrophils were infused 3 hours after the challenge. Then, peritoneal-lavaged fluids and peritoneal tissues (the greater omentum, mesentery, parietal peritoneum, colon, and ileum) were obtained. Subpopulations of peritoneal exudative cells and numbers of labeled neutrophils in tissues were counted. In experiment 2, labeled neutrophils were infused at 10 minutes and at 1 and 5 hours after the challenge. Peritoneal tissues were also harvested. The number of labeled neutrophils in each tissue was determined.In experiment 1, numbers of labeled peritoneal neutrophils and exudative neutrophils were higher in the peritonitis group than in the control group. Numbers of exudative neutrophils showed a positive correlation with numbers of labeled peritoneal neutrophil. In experiment 2, at 1 and 5 hours after the challenge, the number of labeled neutrophils was higher in the peritonitis group than in the control group. The number of neutrophils in the omentum was higher than the number in other peritoneal tissues. ### Long_Answer: Our fluorescence microscopic method is useful for detecting neutrophil adhesion. Neutrophil exudation into the peritoneal cavity was most marked in the omentum. The greater omentum may play an important role in host defense as a source of exudative neutrophils. ### Final_Prediction: yes

### Question: Rating improvements in urinary incontinence: do patients and their physicians agree? ### Context: to determine whether patients' perceptions of improvement following behavioural interventions for urinary incontinence (UI) correspond with physicians' global ratings of change, and to compare both these ratings with more objective UI outcome measures.consecutive new female patients aged 65 years and older recruited from outpatient UI clinics in Quebec received a behavioural management protocol for UI. At 3-month follow-up, patients and physicians were independently asked for their global impression of change in UI status. Patients completed 3-day voiding diaries and a UI-specific quality-of-life index before and after treatment.108 patients (mean age 73 +/- 5 years, range 65-86 years) with stress, urge and mixed UI participated. There was concordance between patients' and physicians' ratings of change in 57% of cases. Among the remaining cases, patients were 1.6 times as likely to report significant improvements compared to physicians. Patients' ratings correlated more strongly with improvements in UI episodes in the voiding diary (r = 0.4, P = 0.002 versus r = 0.3, P = 0.004 for physicians) and on the quality-of-life index (r = -0.5, P<0.0001 versus r = -0.4, P<0.0001 for physicians). ### Long_Answer: physicians underestimate clinically meaningful changes in UI in older women following behavioural interventions. ### Final_Prediction: nan

### Question: Is quality of life before intensive care unit admission a predictor of survival? ### Context: Predicting whether a critically ill patient will survive intensive care treatment remains difficult. The advantages of a validated strategy to identify those patients who will not benefit from intensive care unit (ICU) treatment are evident. Providing critical care treatment to patients who will ultimately die in the ICU is accompanied by an enormous emotional and physical burden for both patients and their relatives. The purpose of the present study was to examine whether health-related quality of life (HRQOL) before admission to the ICU can be used as a predictor of mortality.We conducted a prospective cohort study in a university-affiliated teaching hospital. Patients admitted to the ICU for longer than 48 hours were included. Close relatives completed the Short-form 36 (SF-36) within the first 48 hours of admission to assess pre-admission HRQOL of the patient. Mortality was evaluated from ICU admittance until 6 months after ICU discharge. Logistic regression and receiver operating characteristic analyses were used to assess the predictive value for mortality using five models: the first question of the SF-36 on general health (model A); HRQOL measured using the physical component score (PCS) and mental component score (MCS) of the SF-36 (model B); the Acute Physiology and Chronic Health Evaluation (APACHE) II score (an accepted mortality prediction model in ICU patients; model C); general health and APACHE II score (model D); and PCS, MCS and APACHE II score (model E). Classification tables were used to assess the sensitivity, specificity, positive and negative predictive values, and likelihood ratios.A total of 451 patients were included within 48 hours of admission to the ICU. At 6 months of follow up, 159 patients had died and 40 patients were lost to follow up. When the general health item was used as an estimate of HRQOL, area under the curve for model A (0.719) was comparable to that of model C (0.721) and slightly better than that of model D (0.760). When PCS and MCS were used, the area under the curve for model B (0.736) was comparable to that of model C (0.721) and slightly better than that of model E (0.768). When using the general health item, the sensitivity and specificity in model D (sensitivity 0.52 and specificity 0.81) were similar to those in model A (0.45 and 0.80). Similar results were found when using the MCS and PCS. ### Long_Answer: This study shows that the pre-admission HRQOL measured with either the one-item general health question or the complete SF-36 is as good at predicting survival/mortality in ICU patients as the APACHE II score. The value of these measures in clinical practice is limited, although it seems sensible to incorporate assessment of HRQOL into the many variables considered when deciding whether a patient should be admitted to the ICU. ### Final_Prediction: yes

### Question: Does chronic estrogen treatment increase levels of endothelial nitric oxide synthase protein in rat cerebral microvessels? ### Context: A number of studies indicate that the female gonadal hormone, estrogen, confers protection against cerebrovascular disorders such as stroke. One postulated mechanism for these effects of estrogen is an action on the enzyme endothelial nitric oxide synthase (eNOS), which produces the vasodilatory molecule NO. We have investigated the hypothesis that estrogen increases expression of eNOS in cerebral microvessels of male and female rats.We measured levels of eNOS protein by Western blot in cerebral microvessels isolated from 7 groups of animals: females, ovariectomized females, ovariectomized females treated with estrogen, males, castrated males, castrated males treated with estrogen, and castrated males treated with testosterone.Ovariectomized female rats treated with estrogen had 17. 4-fold greater levels of eNOS protein in cerebral microvessels than ovariectomized females, and intact females had 16.6-fold greater levels than ovariectomized females (P<0.01). In intact females, cerebral microvessel eNOS protein levels were 9.2-fold higher than those of intact males (P<0.05). Levels of eNOS protein in castrated males, castrated males treated with testosterone, and males were not different from each other. Estrogen treatment of castrated animals resulted in an 18.8-fold increase in cerebral microvessel eNOS protein (P<0.05). ### Long_Answer: Chronic estrogen treatment increases levels of eNOS protein in cerebral microvessels of male and female rats. This increase in eNOS protein correlates with our previous functional findings indicating that estrogen exposure increases NO modulation of cerebrovascular reactivity in both male and female animals. Upregulation of eNOS expression may contribute to the neuroprotective effect of estrogen. ### Final_Prediction: yes

### Question: Is orientation week a gateway to persistent alcohol use in university students? ### Context: Orientation Week is common at many universities throughout the world and is a way to introduce students to their new environment. Despite some benefits, Orientation Week is often typified by heavy alcohol use. Although typically viewed as a "one-time" event, the higher levels of drinking that students engage in during Orientation Week may persist into the academic year. We investigated this possibility in the present study.Freshman-year students (n = 143; 41% male) residing in a dormitory were surveyed about their alcohol intake before university. During Orientation Week, students were sent a daily text message asking about the number of drinks they consumed the previous night. Then, during the academic year, students were sent one text message each month to record their weekend drinking.Participants consumed a higher number of standard drinks during Orientation Week (M = 26.0, SD = 28.6) than they did either before entering university (M = 13.1, SD = 13.6) or during the academic year (M = 6.4, SD = 8.5). For male students, but not female students, higher Orientation Week drinking uniquely contributed to higher rates of drinking during the academic year when controlling for pre-university drinking (b = 0.122, p<.001). Students who drank at low levels before entering university were particularly susceptible to the negative effects of Orientation Week drinking. ### Long_Answer: Orientation Week may act as a gateway for male students, as drinking during Orientation Week predicted their subsequent drinking throughout the academic year. Based on these findings, Orientation Week could be a prime period for interventions aimed at curbing academic-year drinking. ### Final_Prediction: nan

### Question: Does insulin resistance determine phagocytic nicotinamide adenine dinucleotide phosphate oxidase overactivation in metabolic syndrome patients? ### Context: Metabolic syndrome (MetS) is associated with insulin resistance and increases the cardiovascular risk. Oxidative stress constitutes a potential mechanism that links insulin resistance and cardiovascular disease. The aim of this study was to analyze the relationship of NADPH oxidase activation with insulin resistance, and the effect of this interaction on the cardiovascular risk in MetS patients.NADPH oxidase-dependent superoxide production and expression was evaluated by luminescence and western blot, respectively, in peripheral blood mononuclear cells obtained from 125 patients with MetS. Insulin resistance was defined by the homeostasis model assessment index. Matrix metalloproteinase-9 was quantified by enzyme-linked immunosorbent assay in plasma samples. To ascertain the mechanisms involved in vivo, we performed in-vitro experiments in cultured macrophages.Fifty-six percent of patients with MetS showed insulin resistance. Plasma matrix metalloproteinase-9 levels were higher (P < 0.05) in insulin-resistant patients than in patients with insulin sensitivity. NADPH oxidase-dependent superoxide production was augmented (P < 0.05) in insulin-resistant patients with respect to insulin-sensitive patients. The interaction between insulin resistance and abnormally high NADPH oxidase-mediated superoxide production was associated with the highest matrix metalloproteinase-9 values. Increased NADPH oxidase-dependent superoxide production was significantly associated with higher NADPH oxidase p22phox expression in insulin-resistant than in insulin-sensitive patients. Interestingly, insulin upregulated p22phox in peripheral blood mononuclear cells and in murine macrophages. ### Long_Answer: Insulin resistance is associated with phagocytic NADPH oxidase activation. This association results in the highest cardiovascular risk in MetS patients. ### Final_Prediction: yes

### Question: Does the great saphenous vein stripping improve arterial leg blood flow during exercise? ### Context: It has been shown that the leg muscle pump increases arterial leg blood flow during upright exercise in healthy subjects, and that this effect is reduced in patients with incompetence of the great saphenous vein (GSV). In this study, patients with GSV reflux causing varicose veins were investigated after GSV stripping, to see whether the muscle pump effect on arterial leg blood flow is improved.Prospective case study.Nine patients with GSV incompetence resulting in symptomatic varicose veins, but without peripheral artery disease were included in this study. Patients exercised in the supine and 30° head up tilted positions by rhythmically pressing down a pedal with one foot. Blood flow was measured in the femoral artery using Doppler ultrasound. The Exercise-induced rise in femoral artery blood flow was compared in the supine and 30° head up tilted positions. Patients were investigated both before and after undergoing saphenofemoral ligation and GSV stripping as a treatment for their varicose veins. The arterial blood flow response to exercise was compared between the pre and postoperative observations.Prior to GSV stripping the immediate rise in femoral flow was 0.25 l min(-1) above rest in both supine and tilted positions. After GSV stripping however, the rise in flow was 30% larger in the tilted position than in the supine position (0.26 vs. 0.20 l min(-1), P<0.05). ### Long_Answer: GSV stripping modestly improves arterial leg blood flow at the onset of exercise in patients with GSV insufficiency, because of an improved effect of the leg muscle pump. ### Final_Prediction: nan

### Question: Do a phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer? ### Context: A phase I study was conducted to assess the safety of adoptive immunotherapy using gene-modified autologous T cells for the treatment of metastatic ovarian cancer.T cells with reactivity against the ovarian cancer-associated antigen alpha-folate receptor (FR) were generated by genetic modification of autologous T cells with a chimeric gene incorporating an anti-FR single-chain antibody linked to the signaling domain of the Fc receptor gamma chain. Patients were assigned to one of two cohorts in the study. Eight patients in cohort 1 received a dose escalation of T cells in combination with high-dose interleukin-2, and six patients in cohort 2 received dual-specific T cells (reactive with both FR and allogeneic cells) followed by immunization with allogeneic peripheral blood mononuclear cells.Five patients in cohort 1 experienced some grade 3 to 4 treatment-related toxicity that was probably due to interleukin-2 administration, which could be managed using standard measures. Patients in cohort 2 experienced relatively mild side effects with grade 1 to 2 symptoms. No reduction in tumor burden was seen in any patient. Tracking 111In-labeled adoptively transferred T cells in cohort 1 revealed a lack of specific localization of T cells to tumor except in one patient where some signal was detected in a peritoneal deposit. PCR analysis showed that gene-modified T cells were present in the circulation in large numbers for the first 2 days after transfer, but these quickly declined to be barely detectable 1 month later in most patients. An inhibitory factor developed in the serum of three of six patients tested over the period of treatment, which significantly reduced the ability of gene-modified T cells to respond against FR+ tumor cells. ### Long_Answer: Large numbers of gene-modified tumor-reactive T cells can be safely given to patients, but these cells do not persist in large numbers long term. Future studies need to employ strategies to extend T cell persistence. This report is the first to document the use of genetically redirected T cells for the treatment of ovarian cancer. ### Final_Prediction: yes

### Question: Interactive nutrition education via a touchscreen: is this technology well received by low-income Spanish-speaking parents? ### Context: To evaluate the usability of touchscreen mediated nutrition and feeding educational modules among low-income Latino immigrant parents.A cross-sectional study was performed March-August, 2010 in an outpatient pediatric setting among low-income Spanish-speaking parents of children<3 years. Culturally-targeted educational modules focused on infant/toddler nutrition and feeding were delivered via touchscreen to participants in Spanish using a multimedia format including text, audio and pictures. Viewing of all modules lasted 25 minutes. Demographic and computer use data was collected. The outcomes assessed were perceived ease of use of the touchsreen and usefulness of the educational modules.The majority of the eighty participants reported rarely/never using a computer (64%; n=51) and 46% reported ≤ 8th grade education. 92% of participants found the touchscreen 'easy'/'very easy' to use. Nearly all users found the modules 'useful' (95%) and 'easy' to understand (96%). Higher educated individuals were more likely to find the touchscreen 'very easy' versus 'easy' to use (Odds Ratio=3.67, 95% CI:1.18-11.43) and the modules 'very easy' to understand (OR=3.99, 95% CI:1.37-11.62). ### Long_Answer: Despite low computer experience levels, participants perceived touchscreens and the content presented as highly usable. Ongoing evaluation of providing targeted health education via touchscreens in this population is indicated. ### Final_Prediction: nan

### Question: Is mechanism for muscarinic inhibition of I ( Ca ( L ) ) determined by the path for elevating cyclic AMP in cardiac myocytes? ### Context: Does carbachol (CCh) require NO/cGMP for inhibition of L-type calcium current (I(Ca(L))) when either adenylyl cyclase activation or phosphodiesterase suppression is used to raise cAMP?The effects of the NO donor SIN-1 (3-morpholino-sydnonimine), CCh and atrial natriuretic peptide (ANP) were evaluated when I(Ca(L)) had been stimulated by isoproterenol (ISO) or 3-isobutyl-1-methylxanthine (IBMX) in guinea pig isolated ventricular myocytes (35 degrees C).Carbachol, SIN-1 or ANP did not affect basal I(Ca(L)); each inhibited IBMX-stimulated I(Ca(L)). Dialyzed (30-100 microM) ODQ (1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one), a soluble guanylyl cyclase (sGC) inactivator, blocked inhibition of IBMX-stimulated I(Ca(L)) by SIN-1 (10 microM) but not by CCh (1-100 microM) or ANP (100 nM). Dialysis with 3 microM LY83583 (6-anilino-5,8-quinolinedione), a particulate (pGC) and sGC inactivator, opposed muscarinic-, ANP- and SIN-1-induced inhibition of IBMX-stimulated I(Ca(L)). Thus CCh can increase cGMP synthesis via pGC. Even with 100 microM [LY83583](pip), CCh inhibited ISO-stimulated I(Ca(L)), an effect referable to suppression of adenylyl cyclase activity. However, 3 microM [LY83583](pip) prevented inhibition of ISO-stimulated I(Ca(L)) by ANP. [LY83583](pip) did not affect inhibition by 8 bromo-cGMP (100 microM) of ISO- or IBMX-stimulated I(Ca(L)). The observations indicate that: (1) myocytes have ODQ-sensitive sGC activated by NO and LY8353-sensitive pGC activated by ANP, (2) CCh does not inhibit I(Ca(L)) via NO, (3) the mechanism for muscarinic inhibition depends upon the cAMP-elevating agent and (4) LY83583 distinguishes between two pathways for muscarinic inhibition. ### Long_Answer: The nature of the stimulant pathway that increases cAMP determines intracellular transduction of muscarinic inhibition. This hypothesis accords with distinct cyclic nucleotide compartments for the differential expression of muscarinic inhibition of I(Ca(L)). ### Final_Prediction: yes

### Question: Women and myocardial infarction: agism rather than sexism? ### Context: To determine whether women with myocardial infarction are treated differently from men of the same age and to assess the effect of changes in the coronary care unit admission policy.Clinical audit.The coronary care unit and general medical wards of a teaching hospital. In 1990 the age limit for admission to coronary care was 65 years. This age limit was removed in 1991.539 female and 977 male patients admitted with myocardial infarction between 1990 and 1992.Admission to the coronary care unit, administration of thrombolysis, and in-hospital mortality.409 men and 254 women were admitted with myocardial infarction in 1990 and 568 men and 285 women in 1992. Removal of the age limit for admission to the coronary care unit resulted in an increase in the numbers of both sexes admitted with myocardial infarction. In both years, however, proportionately more men with infarction were admitted to coronary care: 226 men (55%) and 96 women (38%) (P<0.01) (95% CI 7 to 28) in 1990 and 459 men (81%) and 200 women (70%) (P<0.01) (%CI 2 to 19) in 1992. Some 246 men (60%) and 133 women (52%) with infarction (P<0.01) received thrombolytic treatment in 1990 compared with 319 men (56%) and 130 women (46%) (P<0.01) in 1992. The mean age of women sustaining a myocardial infarction was significantly greater in both years studied. In 1992 a total of 78 men (7%) and 34 women (4%) (P<0.05) admitted with chest pain underwent cardiac catheterisation before discharge from hospital. ### Long_Answer: Differences in admission rates to the coronary care unit and the rate of thrombolysis between the sexes can be explained by the older age of women sustaining infarction. The application of age limits for admission to coronary care or administration of thrombolysis places elderly patients at a disadvantage. As women sustain myocardial infarctions at an older age they are placed at a greater disadvantage. ### Final_Prediction: nan

### Question: Does continuous interscalene brachial plexus nerve block prolong unilateral diaphragmatic dysfunction? ### Context: Single interscalene blocks (ISB) impair pulmonary function (<24h). We hypothesized that continuous ISBs would prolong pulmonary dysfunction until h48 compared with a single ISB. We compared the time course of spirometric and diaphragmatic dysfunction following single or continuous ISBs.We prospectively included consecutive adult patients scheduled to undergo shoulder surgery under standard general anaesthesia with single (n=30) or continuous (n=31) ISB. Before ISB (baseline), spirometric tests were recorded and the diaphragm course was evaluated with a B-mode ultrasound technique every 12h until h48. ISBs were performed with 15mL 0.5% ropivacaine using an ultrasound technique approach. The continuous group received the same bolus followed by 0.2% ropivacaine 5mL·hPatient characteristics were similar in both groups. Thirty minutes after blocks in the PACU, all patients demonstrated a similar and significant unilateral diaphragm paralysis (< 25% from baseline). For the primary end point (FVC), no significant difference was observed between groups over the study period. A difference between single and continuous groups was observed at h24 for: FVC (-25%, P=0.038), FEV1s (-24%, P=0.036), diaphragmatic course (-26%, P=0.02), while no differences for other time points (h0-h48) were noted. Clinical respiratory evaluations (respiratory rate, SpO ### Long_Answer: Over infusion, continuous ISB did not significantly prolong unilateral phrenic paresis and demonstrated a limited pulmonary impact. ### Final_Prediction: yes

### Question: Does over 500 obturator nerve block in the lithotomy position during transurethral resection of bladder tumor? ### Context: Spinal anesthesia for transurethral resection of bladder tumor (TURB) does not prevent unintended stimulation of the obturator nerve when electroresection is performed on the lateral wall of the bladder. It results in muscle contraction of the adductor muscles of the thigh, which may lead to perforation of bladder wall with the resectoscope loop. The aim of the study was to assess the efficacy and safety of obturator nerve block (ONB).This prospective study was conducted between 01/01/1999 and 12/31/2010 in the Department of General, Oncologic and Functional Urology, Medical University of Warsaw. In 431 patients undergoing TURB adductor spasms were observed. In these cases nerve stimulation and ONB with 2% lidocaine using thigh interadductor approach in the lithotomy position were performed.The efficacy of 542 ONB was 94%. In 31 cases general anesthesia was necessary. There were two cases of urinary bladder perforation, but only one resulted from an insufficient nerve block. Both were managed conservatively. Neither hematomas nor neurological adverse events were observed. ### Long_Answer: The described method offers a high rate of efficacy and ensures optimal and safe conditions for the resection of a tumor located on the inferolateral wall of the urinary bladder. The risk of complication is low. ### Final_Prediction: yes

### Question: Is pI3K/AKT/mTOR signaling-mediated neuropeptide VGF in the hippocampus of mice involved in the rapid onset antidepressant-like effects of GLYX-13? ### Context: VGF (nonacryonimic) and phosphatidylinositol 3-kinase (PI3K)/AKT (also known as protein kinase B, PKB)/mammalian target of rapamycin (mTOR) signaling play pivotal roles in depression. However, whether phosphatidylinositol 3-kinase/AKT/mTOR signaling-mediated VGF participates in rapid-acting antidepressant-like actions of GLYX-13 is unclear.Herein, we evaluated the effects of acute treatment of GLYX-13 (0.5, 5, and 10mg/kg, i.p.) in the forced swim test. In addition, we assessed whether the acute treatment with GLYX-13 reverses the depressive-like behaviors induced by chronic unpredictable mild stress. Furthermore, we determined whether the Vgf knockdown in hippocampus of mice blocks the effects of GLYX-13. Moreover, we also demonstrated the effects of intra-hippocampus infusion of LY294002 (10 nmol/side), a specific phosphatidylinositol 3-kinase inhibitor prior to the treatment of GLYX-13 in the forced swim test. Lastly, whether alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mTOR activation involves in the antidepressant-like effects of GLYX-13 was examined.Our results shown that GLYX-13 dose-dependently reversed the depressive-like behaviors in forced swim test. Additionally, GLYX-13 significantly reversed the downregulation of phosphorylation of AKT, mTOR, and eukaryotic elongation factor 2 as well as VGF induced by chronic unpredictable mild stress in hippocampus. Further, Vgf knockdown in hippocampus of mice significantly blocked the rapid-acting antidepressant-like effects and upregulation on phosphatidylinositol 3-kinase/AKT/mTOR/VGF signaling of GLYX-13. Moreover, intra-hippocampus infusion of LY294002 significantly abolished the antidepressant-like effects and upregulation on phosphatidylinositol 3-kinase/AKT/mTOR/VGF signaling of GLYX-13. Finally, antidepressant-like effects of GLYX-13 required AMPA receptor and mTOR activation, as evidenced by the ability of NBQX and rapamycin to block the effects of GLYX-13, respectively. ### Long_Answer: Our results suggest that phosphatidylinositol 3-kinase/AKT/mTOR signaling-mediated VGF in hippocampus may be involved in the antidepressant-like effects of GLYX-13. ### Final_Prediction: yes

### Question: Are psychological resources associated with reduced incidence of coronary heart disease . An 8-year follow-up of a community-based Swedish sample? ### Context: A large number of studies have provided clear evidence for a link between the risk of coronary heart disease and psychological risk factors. Much less attention has been given to the potential protective effect of psychological resources.The major aim of this study was to investigate the independent association between psychological resources and incidence of coronary heart disease (CHD) in an 8-year follow-up study of a Swedish community-based cohort.The cohort consisted of 484 men and 497 women, aged 45-69 years at baseline. The incidence of first-time major event of CHD was analysed in relation to baseline levels of psychological resources, including mastery, self-esteem, and sense of coherence as well as psychological risk factors including cynicism and hostile affect, vital exhaustion, hopelessness, and depressive symptoms. In Cox proportional hazard models, adjustments were made for age, sex, eight traditional cardiovascular risk factors, and depressive symptoms.A total of 56 CHD events had occurred after the 8-year follow-up. After adjustment for age, sex, and eight traditional risk factors, a significantly decreased risk of CHD was found for mastery (HR 0.62 per SD, p = 0.003), self-esteem (HR 0.64, p = 0.004), and sense of coherence (HR 0.70, p = 0.031). An increased risk of CHD was found for vital exhaustion (HR 1.46, p = 0.014), hopelessness (HR 1.59, p = 0.003), and depressive symptoms (HR 1.45, p = 0.009). After further adjustment for depressive symptoms, significant associations remained for mastery (HR 0.67, p = 0.034), self-esteem (HR 0.69, p = 0.048), and hopelessness (HR 1.48, p = 0.023). ### Long_Answer: The psychological resources, mastery and self-esteem, showed robust protective effects on CHD, also after adjustment for established risk factors as well as depressive symptoms. In parallel, hopelessness was an independent risk factor for CHD. The results may have implications for novel approaches in preventive efforts. ### Final_Prediction: yes

### Question: Is protein kinase C/zeta ( PRKCZ ) gene associated with type 2 diabetes in Han population of North China and analysis of its haplotypes? ### Context: To identify the susceptible gene (s) for type 2 diabetes in the previously mapped region, 1p36.33-p36.23, in Han population of North China using single nucleotide polymorphisms (SNPs) and to analyze the haplotypes of the gene (s) related to type 2 diabetes.Twenty three SNPs located in 10 candidate genes in the mapped region were chosen from public SNP domains with bioinformatic methods, and the single base extension (SBE) method was used to genotype the loci for 192 sporadic type 2 diabetes patients and 172 normal individuals, all with Han ethical origin, to perform this case-control study. The haplotypes with significant difference in the gene (s) were further analyzed.Among the 23 SNPs, 8 were found to be common in Chinese Han population. Allele frequency of one SNP, rs436045 in the protein kinase C/zetagene (PRKCZ) was statistically different between the case and control groups(P<0.05). Furthermore, haplotypes at five SNP sites of PRKCZ gene were identified. ### Long_Answer: PRKCZ gene may be associated with type 2 diabetes in Han population in North China. The haplotypes at five SNP sites in this gene may be responsible for this association. ### Final_Prediction: yes

### Question: Increasing the reach of quitlines through active telephone recruitment: do cold-called smokers differ from quitline callers? ### Context: Only 1%-7% of smokers use quitlines annually. Active telephone recruitment ("cold calling") can enroll about 50% of community smokers to quitline services. However, whether cold-called smokers' characteristics differ from traditional quitline clients is unknown. To assess whether active telephone recruitment reaches new groups of smokers, New South Wales (NSW) Quitline callers were compared with cold-called smokers who received telephone counseling as part of a randomized controlled trial.Data were extracted from the NSW Quitline database from September 13, 2005, to April 10, 2007, to coincide with the trial's recruitment period. Records (n = 18,584) of first-time quitline callers, who smoked daily, resided in NSW, Australia, and received telephone counseling were included. Cold-called participants who received telephone counseling (n = 695) were recruited by telephone from the electronic NSW telephone directory. Eligibility requirements were daily tobacco use, aged 18 or older, NSW resident, and English speaking. Smokers were eligible regardless of their quitting intention.Male smokers, older age groups, those living in nonmetropolitan areas, smokers who took longer to smoke their first cigarette after waking, consumed fewer cigarettes per day, and were less motivated to quit had greater odds of being referred to the quitline through cold calling. ### Long_Answer: Active telephone recruitment enrolls new groups of smokers to quitlines. The reach of quitlines could be improved if quitlines incorporated cold calling into their recruitment strategies. ### Final_Prediction: nan

### Question: Is marginal vitamin C status associated with reduced fat oxidation during submaximal exercise in young adults? ### Context: Vitamin C is a cofactor in the biosynthesis of carnitine, a molecule required for the oxidation of fatty acids. A reduction in the ability to oxidize fat may contribute to the reported inverse relationship between vitamin C status and adiposity. To examine this possibility, we conducted a preliminary trial to evaluate the impact of vitamin C status on fat oxidation during submaximal exercise.Fat energy expenditure was determined in individuals with marginal (n = 15) or adequate (n = 7) vitamin C status during a submaximal, 60-minute treadmill test. Subsequently, eight of the subjects with marginal vitamin C status completed an 8-week double-blind, placebo-controlled, depletion-repletion trial with submaximal exercise testing.Individuals with marginal vitamin C status oxidized 25% less fat per kg body weight during the treadmill test as compared to individuals with adequate vitamin C status. Fat oxidation during exercise was inversely related to fatigue (r = -0.611, p = 0.009). Vitamin C repletion of vitamin C depleted subjects (500 mg vitamin C/d) raised fat energy expenditure during exercise 4-fold as compared to depleted control subjects (p = 0.011). ### Long_Answer: These preliminary results show that low vitamin C status is associated with reduced fat oxidation during submaximal exercise. Low vitamin C status may partially explain the inverse relationship between vitamin C status and adiposity and why some individuals are unsuccessful in their weight loss attempts. ### Final_Prediction: yes

### Question: Do toll-like receptor 3 ligands induce CD80 expression in human podocytes via an NF-κB-dependent pathway? ### Context: Recent studies suggest that CD80 (also known as B7.1) is expressed on podocytes in minimal-change disease (MCD) and may have a role in mediating proteinuria. CD80 expression is known to be induced by Toll-like receptor (TLR) ligands in dendritic cells. We therefore evaluated the ability of TLR to induce CD80 in human cultured podocytes.Conditionally immortalized human podocytes were evaluated for TLR expression. Based on high expression of TLR3, we evaluated the effect of polyinosinic-polycytidylic acid (polyIC), a TLR3 ligand, to induce CD80 expression in vitro.TLR1-6 and 9 messenger RNA (mRNA) were expressed in podocytes. Among TLR ligands 1-9, CD80 mRNA expression was significantly induced by polyIC and lipopolysaccharide (TLR4 ligand) with the greatest stimulation by polyIC (6.8 ± 0.7 times at 6 h, P < 0.001 versus control). PolyIC induced increased expression of Cathepsin L, decreased synaptopodin expression and resulted in actin reorganization which suggested a similar injury pattern as observed with lipopolyssaccharide. PolyIC induced type I and type II interferon signaling, nuclear factor kappa B (NF-κB) activation and the induction of CD80 expression. Knockdown of CD80 protected against actin reorganization and reduced synaptopodin expression in response to polyIC. Dexamethasone, a corticosteroid commonly used to treat MCD, also blocked both basal and polyIC-stimulated CD80 expression, as did inhibition of NF-κB. ### Long_Answer: Activation of TLR3 on cultured human podocytes induces CD80 expression and phenotypic change via an NF-κB-dependent mechanism and is partially blocked by dexamethasone. These studies provide a mechanism by which viral infections may cause proteinuria. ### Final_Prediction: yes

### Question: Do metabolic factors and microinflammatory state promote kidney injury in type 2 diabetes mellitus patients? ### Context: This study examined the associations among the factors of metabolic syndrome, microinflammatory state, and kidney injury in type 2 diabetes mellitus patients.A retrospective study was conducted on 914 type 2 diabetes mellitus patients from January 2007 to May 2008. We observed the prevalence of chronic kidney disease in different groups of type 2 diabetes mellitus patients, and analyzed the association between metabolic syndrome and chronic kidney disease. We chose 84 cases randomly from this cohort to test their inflammatory biomarkers including tumor necrosis factor alpha, interleukin-6, and C-reactive protein to study the relationship to chronic kidney disease.The prevalence of chronic kidney disease was 39.17% (358 patients), and patients with metabolic factors had a significantly higher prevalence of chronic kidney disease than without metabolic factors (40.90% vs. 17.65%, p < 0.01). The metabolic factors and microinflammatory biomarkers were significantly higher in patients with chronic kidney disease. Patients who had more abnormal metabolic factors also had higher levels of microinflammatory biomarkers, as well as higher risk of chronic kidney disease. Multiple logistic regression analyses revealed that systolic blood pressure, serum triglyceride, low density lipoprotein, age, and duration of diabetes were independent risk factors of chronic kidney disease in type 2 diabetes mellitus patients. ### Long_Answer: The abnormality of metabolic factors in type 2 diabetes mellitus had a close relationship to the microinflammatory state and chronic kidney disease. Hypertension and hyperlipidemia were independent factors of chronic kidney disease in type 2 diabetes mellitus. ### Final_Prediction: yes

### Question: Does microRNA-483-3p inhibit Extracellular Matrix Production by Targeting Smad4 in Human Trabecular Meshwork Cells? ### Context: This study investigated the effects of microRNA-483-3p (miR-483-3p) on extracellular matrix (ECM) production, and clarified the regulatory mechanism of microRNA-483-3p in human trabecular meshwork cells (HTMCs) under oxidative stress.The expression levels of ECM (fibronectin, laminin, collagen I) in HTMCs under oxidative stress were measured by Western blot. Changes of miR-483-3p expression in HTMCs were evaluated by quantitative polymerase chain reaction (qPCR). After using lentivirus stably expressing pri-miR-483, the effects of miR-483-3p on the ECM were assessed by qPCR and Western blot. Smad4, the potential target of miR-483-3p according to mRNA target-predicting algorithms, was confirmed by luciferase assay and Western blot. Furthermore, the effects of Smad4 knockdown on ECM expression were investigated by qPCR and Western blot.The mRNA and protein levels of ECM (fibronectin, laminin, collagen I) were upregulated in HTMCs induced by oxidative stress. The expression level of miR-483-3p decreased in HTMCs under oxidative stress, and the ectopic expression of miR-483-3p decreased the levels of ECM. In addition, miR-483-3p targeted Smad4 through two binding sites, resulting in a decrease of Smad4 expression. Furthermore, knockdown of Smad4 reduced the levels of ECM in HTMCs. ### Long_Answer: MicroRNA-483-3p has an inhibitory effect on ECM production in HTMCs through downregulating Smad4, which indicates that miR-483-3p may serve as a potential therapeutic target in glaucoma. ### Final_Prediction: yes

### Question: Do extracellular dextran and DNA affect the formation of Enterococcus faecalis biofilms and their susceptibility to 2 % chlorhexidine? ### Context: Enterococcus faecalis is frequently recovered from root-filled teeth with refractory apical periodontitis. The ability of E. faecalis to form a matrix-encased biofilm contributes to its pathogenicity; however, the role of extracellular dextran and DNA in biofilm formation and its effect on the susceptibility of the biofilm to chlorhexidine remains poorly understood.E. faecalis biofilms were incubated on dentin blocks. The effect of a dextran-degrading enzyme (dextranase) and DNase I on the adhesion of E. faecalis to dentin was measured using the colony-forming unit (CFU) counting method. CFU assays and confocal laser scanning microscopy were used to investigate the influence of dextranase and DNase I on the antimicrobial activity of 2% chlorhexidine.The CFU count assays indicated that the formation of biofilms by E. faecalis was reduced in cells treated with dextranase or DNase I compared with that in untreated cells (P < .05). In addition, we found that treating E. faecalis biofilms with dextranase or DNase I effectively sensitized the biofilms to 2% chlorhexidine (P < .05). ### Long_Answer: Both dextranase and DNase I decrease the adhesion of E. faecalis to dentin and sensitized E. faecalis biofilms to 2% chlorhexidine. ### Final_Prediction: yes

### Question: Is realtime PCR more sensitive than multiplex PCR for diagnosis and serotyping in children with culture negative pneumococcal invasive disease? ### Context: Pneumococcal serotyping is usually performed by Quellung reaction, considered the gold standard test. However the method cannot be used on culture-negative samples. Molecular methods can be a useful alternative. The aim of the study was to evaluate the use of Multiplex-sequential-PCR (MS-PCR) or Realtime-PCR on blood samples for diagnosis and serotyping of invasive pneumococcal disease (IPD) in a pediatric clinical setting.Sensitivity and specificity of MS-PCR and Realtime-PCR have been evaluated both on 46 well characterized pneumococcal isolates and on 67 clinical samples from children with culture-negative IPD. No difference in sensitivity and specificity between MS-PCR and Realtime PCR was found when the methods were used on isolates: both methods could type 100% isolates and the results were always consistent with culture-based methods. On the contrary, when used on clinical samples 43/67 (64.2%) were typeable by MS-PCR and 61/67 (91.0%) by Realtime-PCR (p = 0.0004,K Cohen 0.3, McNemar's p<0.001). Non-typeability by MS-PCR was associated in 18/20 cases (90.0%) with low bacterial load. The difference between the two methods was present both when they were used on normally sterile fluids (respectively 31/33 (93.9%) typeable samples for Realtime-PCR and 24/33 (72.7%) for MS-PCR, p = 0.047, 95%CL 0.03-0.98; K Cohen 0.3; McNemar's p = 0.0016) and when they were used on nasopharyngeal swabs (respectively 30/34 (88.2%) typeable samples for Realtime-PCR and 19/34 (55.9%) for MS-PCR, p = 0.007, 95%CL 0.04-0.66); the presence of multiple pneumococcal serotypes in nasopharyngeal swabs was found more frequently by Realtime PCR (19/30; 63.3%) than by Multiplex-sequential PCR (3/19; 15.8%; p = 0.003;95%CL 1.87-39.97). ### Long_Answer: In conclusion, both MS-PCR and Realtime PCR can be used for pneumococcal serotyping of most serotypes/serogroups directly on clinical samples from culture-negative patients but Realtime-PCR appears more sensitive. ### Final_Prediction: yes

### Question: Does sRPK1 inhibition modulate VEGF splicing to reduce pathological neovascularization in a rat model of retinopathy of prematurity? ### Context: We tested the hypothesis that recombinant human VEGF-A165b and the serine arginine protein kinase (SRPK) inhibitor, SRPIN340, which controls splicing of the VEGF-A pre-mRNA, prevent neovascularization in a rodent model of retinopathy of prematurity (ROP).In the 50/10 oxygen-induced retinopathy (50/10 OIR) model that exposes newborn rats to repeated cycles of 24 hours of 50% oxygen alternating with 24 hours of 10% oxygen, pups received intraocular injections of SRPIN340, vehicle, VEGF165b, anti-VEGF antibody, or saline. Whole mounts of retinas were prepared for isolectin immunohistochemistry, and preretinal or intravitreal neovascularization (PRNV) determined by clock hour analysis.The anti-VEGF antibody (P < 0.04), rhVEGF165b (P < 0.001), and SRPIN340 (P < 0.05) significantly reduced PRNV compared with control eyes. SRPIN340 reduced the expression of proangiogenic VEGF165 without affecting VEGF165b expression. ### Long_Answer: These results suggest that splicing regulation through selective downregulation of proangiogenic VEGF isoforms (via SRPK1 inhibition) or competitive inhibition of VEGF signaling by rhVEGF165b has the potential to be an effective alternative to potential cyto- and neurotoxic anti-VEGF agents in the treatment of pathological neovascularization in the eye. ### Final_Prediction: yes

### Question: Does passive leg raising performed before a spontaneous breathing trial predict weaning-induced cardiac dysfunction? ### Context: Weaning-induced cardiac dysfunction is more likely to occur if the heart does not tolerate the changes in loading conditions induced by spontaneous breathing trial (SBT). We hypothesized that the presence of cardiac preload independence before an SBT is associated with weaning failure related to cardiac dysfunction.We included 30 patients after a first failed 1-h T-tube SBT who had a transpulmonary thermodilution already in place. Preload independence [no increase in the pulse contour analysis-derived cardiac index ≥10 % during passive leg raising (PLR)] was assessed before the second SBT. Failure of the SBT related to cardiac dysfunction was defined by an increase in pulmonary artery occlusion pressure above 18 mmHg at the end of the SBT associated with clinical intolerance.Fifty-seven SBTs were analyzed. The SBT failed in 46 cases. Overall, 31 failed SBTs were associated with weaning-induced cardiac dysfunction. During PLR, the cardiac index did not change in cases of failed SBTs with cardiac dysfunction, whereas it significantly increased in the other cases: 4 % (interquartile range, IQR 0-5) vs. 12 % (IQR 11-15), respectively. If PLR did not increase the cardiac index by more than 10 % before the SBT, the occurrence of SBT failure related to cardiac dysfunction was predicted with a sensitivity of 97 % [95 % confidence interval (CI) 83-100], specificity of 81 % (95 % CI 61-93) and area under the receiver-operating characteristic curve of 0.88 (95 % CI 0.78-0.98). ### Long_Answer: Preload independence assessed by a negative PLR test performed before an SBT predicts weaning failure related to cardiac dysfunction. ### Final_Prediction: yes

### Question: Is automaticity of walking regained after stroke? ### Context: The aim of this study was to determine whether people who have completed rehabilitation after stroke have regained a level of automaticity of walking comparable to healthy people of similar age.Twenty stroke subjects, 20 healthy elderly controls and 20 healthy young controls were tested. To quantify the automaticity of walking, subjects were required to walk simultaneously while performing an additional task(s). Subjects walked under four counterbalanced conditions: a single walking task, a dual-cognitive task, a dual-manual task and a triple-task. Walking velocity, cadence, stride length and step length were analysed.Stroke subjects walked slower (p = 0.001), took shorter strides (p = 0.002) and fewer steps/min (p = 0.04) than elderly controls. Velocity declined significantly across conditions from the single to the dual-cognitive to the dual-manual and finally to the triple-task (p<0.001). Both stroke and elderly groups showed similar deterioration in walking velocity across conditions (p = 0.99), while the deterioration in the young subjects was significantly less than for healthy elderly subjects (p = 0.04) and the stroke subjects (p = 0.02). ### Long_Answer: Community dwelling stroke subjects display the same level of automaticity of walking as elderly controls, but both elderly controls and stroke subjects are less automated than young controls. ### Final_Prediction: nan

### Question: Is bMI the main determinant of the circulating leptin in women after vertical banded gastroplasty? ### Context: To assess the main determinant of serum leptin concentration changes in morbidly obese patients treated by banded vertical gastroplasty.Serum leptin and insulin concentrations, insulin resistance, BMI, body weight, and body fat mass in 18 obese women and 8 obese men treated by vertical banded gastroplasty were studied. Lean women and men subjects were used as controls.Before surgery, serum leptin and insulin concentrations and insulin resistance index were significantly higher in morbidly obese patients than in control subjects. BMI, body fat mass, and serum triacylglycerol concentrations were also significantly higher in obese than in lean subjects. All of these parameters gradually decreased during 50 weeks after surgery. Univariate regression analysis displayed significant correlations between the following: serum leptin concentration and BMI (and body fat mass), serum leptin concentration and serum insulin concentration, and serum leptin concentration and insulin resistance index. Multivariate regression analysis indicated that only BMI was independently correlated with the decrease in serum leptin concentration. ### Long_Answer: Obtained data suggest the following: 1) vertical banded gastroplasty causes reduction of body weight, serum leptin and insulin concentration, insulin resistance, and serum triacylglycerol concentration; and 2) BMI is the main determinant of the circulating leptin concentration in morbidly obese women after anti-obesity surgery. ### Final_Prediction: yes

### Question: Is substance use a risk factor for violent behavior in male patients with bipolar disorder? ### Context: To determine the factors involved in violent behavior in patients with bipolar disorder (BD) and to investigate the relationship between violence and substance use disorder (SUD).A sample of 100 male inpatients diagnosed with BD type I who were experiencing a current mood episode participated in the study. Violent behavior was defined as physical aggression against others. All patients were evaluated using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Positive and Negative Syndrome Scale-positive subscale (PANSS-p), Barratt Impulsivity Scale-11 (BIS-11), Buss-Perry Aggression Questionnaire (BPAQ) and Overt Aggression Scale (OAS). Lifetime SUD and current use of substances were evaluated. Logistic regression analysis was conducted to predict violent behavior.Current substance use (CSU) rather than lifetime SUD was found to be related to violent behavior in patients with BD, and CSU was associated with a threefold increase in the risk of violence. The rate of lifetime SUD in our sample was 59%, and the rate of CSU was 39%. The most commonly abused substances were cannabis and alcohol, followed by synthetic cannabinoids, in both groups of patients with lifetime SUD and CSU. Individuals abusing any substance were more likely to have a criminal record and history of incarceration than other patients. One of the most significant risk factors for violence was a previous history of violent behavior. ### Long_Answer: The sample was limited to male patients. Data on some participants' recent substance use from standard urine analysis was not obtained. The data on the use of synthetic cannabinoids was obtained from patients and their families owing to the lack of equipment for detecting synthetic cannabinoids using laboratory analysis. ### Final_Prediction: yes

### Question: Do transcranial high-frequency repetitive electrical stimulation for recording myogenic motor evoked potentials with the patient under general anesthesia? ### Context: To demonstrate the feasibility of transcranial high-frequency electrical stimulation with the patient under general anesthesia with propofol and alfentanil. This method may be a useful tool for intraoperative monitoring of the motor pathways during cerebral and spinal operations.A short train from one to eight monopolar anodal electrical pulses was applied transcranially to the motor cortex with a frequency from 100 to 500 Hz in 10 patients. Myogenic motor evoked potentials (MEPs) were recorded from forearm flexor muscles, thenar, and hypothenar. Amplitude and latency of MEPs were evaluated after different stimulation parameters. This combination of anesthetic and transcranial stimulation technique allows recording of myogenic MEPs during general anesthesia, which was found not to be possible with single pulse transcranial stimulation.To elicit myogenic MEPs from the target muscles, stimulation had to be applied within the following parameters: minimum threshold intensity was 60 mA for forearm flexor and thenar and 80 mA for hypothenar; minimum number of pulses was two for forearm flexor muscles and thenar and three for hypothenar; minimum stimulation frequency was 200 Hz for thenar and hypothenar and 100 Hz for forearm flexor muscles. ### Long_Answer: Transcranial high-frequency repetitive electrical stimulation seems to be a new method for monitoring the motor tract. With this method, it is possible to monitor the motor function without interfering with the surgical team or with the surgical treatment of infratentorial and spinal lesions. Monitoring of relaxation is necessary to compare the amplitude of MEPs. ### Final_Prediction: yes

### Question: Is circulating monocyte oxidative activity increased in patients with type 2 diabetes and erectile dysfunction? ### Context: We investigated the relationship between oxidative stress and diabetic erectile dysfunction.A total of 23 patients with a mean +/- SD age of 56.7 +/- 5.6 years, a history of type 2 diabetes for 10.0 +/- 8.3 years and erectile dysfunction, as tested by the International Index of Erectile Function questionnaire, but without vascular and neurological complications, and 15 age matched patients with diabetes without erectile dysfunction were recruited. Circulating monocyte oxidative activity by cytofluorometry, and endothelin-1, intercellular adhesion molecule-1, plasminogen activator inhibitor-1 by enzyme linked immunosorbent assay were evaluated in all patients in the study.Monocyte free radical production, and total and low density lipoprotein cholesterol were higher in patients with than in those without erectile dysfunction (p <0.03, <0.02 and <0.05, respectively). In all patients the International Index of Erectile Function score inversely correlated with low density lipoprotein (p <0.05), while in patients with erectile dysfunction it negatively correlated with age (p <0.03), body mass index (p <0.02), endothelin-1 (p <0.02) and intercellular adhesion molecule-1 (p <0.05). Endothelin-1, intercellular adhesion molecule-1 and plasminogen activator inhibitor-1 were not different in patients with diabetes with and without erectile dysfunction. ### Long_Answer: In men with type 2 diabetes who have erectile dysfunction but are asymptomatic for cardiovascular disease oxidative activation of monocytes is increased and it is related to other risk factors of endothelial dysfunction. ### Final_Prediction: yes

### Question: Does inhibition of Hepatocellular Carcinoma by Total Alkaloids of Rubus alceifolius Poir involve Suppression of Hedgehog Signaling? ### Context: We evaluated the effects of total alkaloids of Rubus alceifolius Poir (TARAP) on the migration and invasion of hepatocellular carcinoma (HCC) and furthermore investigated the possible molecular mechanisms mediating its anticancer activity.We implanted nude mice with human HCC HepG2 cells and fed them with vehicle (physiological saline) or 3 g/kg/day dose of TARAP 5 days per week for 21 days. We determined the in vitro effect of TARAP on the migration and invasion of HepG2 cells by transwell assay. We evaluated SHH signaling components' (SHH, PTCH, SMO, and Gli1) expression levels by reverse transcriptase-polymerase chain reaction and immunohistochemistry. Activity of the matrix metalloproteinases (MMPs) in supernatants was analyzed by zymography. The expression of the MMPs and their specific tissue inhibitor (tissue inhibitor of matrix metalloproteinases, TIMP-1, 2) in HCC tissues was detected by immunohistochemistry.We discovered that TARAP inhibited hepatocellular migration and invasion in a dose-dependent manner in vitro. In addition, TARAP decreased the expression of SHH, PTCH, SMO, and Gli1 in HCC mouse tumors at both transcriptional and translational levels. Moreover, TARAP inhibited the activity of MMP2 and MMP9. We found that TARAP reduced the expression of MMP2 and MMP9, as well as the tissue inhibitor of MMPs. ### Long_Answer: Our study showed that TARAP inhibits HCC migration and invasion likely through suppression of the hedgehog pathway. This may, in part, explain its anticancer properties. These results suggest that total alkaloids in Rubus alceifolius may have potential as a novel antimetastasis drug in the treatment of HCC. ### Final_Prediction: yes

### Question: Do inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells? ### Context: Several diseases have been related to asbestos exposure, including the pleural tumor mesothelioma. The mechanism of pleural injury by asbestos fibers is not yet fully understood. The inflammatory response with release of mediators leading to a dysregulation of apoptosis may play a pivotal role in the pathophysiology of asbestos-induced pleural disease.To determine whether pro-inflammatory cytokines produced by asbestos-exposed pleural mesothelial cells modify the injury induced by the asbestos.Mouse pleural mesothelial cells (PMC) were exposed to crocidolite or chrysotile asbestos fibers (3.0 μg/cm(2)) for 4, 24, or 48 h and assessed for viability, necrosis and apoptosis, and the production of cytokines IL-1β, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1β, anti-IL-6, anti- IL-1β+anti-IL-6 or anti-MIP-2 or their irrelevant isotypes, and assessed for apoptosis and necrosis. Non-exposed cells and cells treated with wollastonite, an inert particle, were used as controls.Mesothelial cells exposed to either crocidolite or chrysotile underwent both apoptosis and necrosis and released cytokines IL-1β, IL-6 and MIP-2. In the crocidolite group, apoptosis and the levels of all cytokines were higher than in the chrysotile group, at comparable concentrations. Neutralization of IL-1β andIL-6, but not MIP-2, inhibited apoptosis and necrosis, especially in the cells exposed to crocidolite fibers. ### Long_Answer: Both crocidolite and chrysotile asbestos fibers induced apoptosis and produced an acute inflammatory response characterized by elevated levels of IL-1β, IL-6 and MIP-2 in cultured mouse PMC. IL-1β and IL-6, but not MIP-2, were shown to contribute to asbestos-induced injury, especially in the crocidolite group. ### Final_Prediction: yes

### Question: Is early-onset atopy associated with enhanced lymphocyte cytokine responses in 11-year-old children? ### Context: Early age at onset of atopy is associated with more severe asthma and increased airway responsiveness (AR); the underlying mechanism is unclear but may involve T cell responses.To test the hypothesis that enhanced T cell responses may be associated with early-onset atopy.In a longitudinal study, atopy was determined in infancy and at 6 and 11 years of age. Individuals were categorized as persistent infant-onset atopy (PIOA), early childhood-onset atopy (ECOA) and later childhood-onset atopy (LCOA). At 11 years of age, peripheral blood T cell cytokine responses, AR, exhaled nitric oxide (FE(NO)) and forced expiratory volume in 1 s were determined.The age at onset of atopy was determined for 60 children, of whom 15 had PIOA, 24 had ECOA and 21 had LCOA. An additional 76 children who were never atopic were also included. T cell responses to house dust mite, including interleukin-5, -9, -10 and tumour necrosis factor alpha, were higher among children with PIA and ECOA, and lower in children with LCOA, P<0.05. In contrast, those children with LCOA or who were not atopic had the highest IL-10 response to PHA (P=0.014). Children with PIOA and ECOA, but not LCOA, had higher AR and FE(NO) compared with non-atopic children (P<0.05). The group with PIOA were more likely among the atopic children to be admitted to hospital for asthma (P<0.05) and also had lower %FEV(1) compared with non-atopic children (P=0.023). ### Long_Answer: Early age at sensitization is associated with enhanced T cell cytokine responses and indices of adverse asthma outcome. T cell cytokine responses might be programmed at the time of initial atopic sensitization. ### Final_Prediction: yes

### Question: Is the risk for behavioural deficits determined by the maternal immune response to prenatal immune challenge in a neurodevelopmental model? ### Context: Schizophrenia is a highly disabling psychiatric disorder with a proposed neurodevelopmental basis. One mechanism through which genetic and environmental risk factors might act is by triggering persistent brain inflammation, as evidenced by long-lasting neuro-immunological disturbances in patients. Our goal was to investigate whether microglia activation is a neurobiological correlate to the altered behaviour in the maternal immune activation (MIA) model, a well-validated animal model with relevance to schizophrenia. A recent observation in the MIA model is the differential maternal body weight response to the immune stimulus, correlated with a different behavioural outcome in the offspring. Although it is generally assumed that the differences in maternal weight response reflect differences in cytokine response, this has not been investigated so far. Our aim was to investigate whether (i) the maternal weight response to MIA reflects differences in the maternal cytokine response, (ii) the differential behavioural phenotype of the offspring extends to depressive symptoms such as anhedonia and (iii) there are changes in chronic microglia activation dependent on the behavioural phenotype.Based on a dose-response study, MIA was induced in pregnant rats by injecting 4mg/kg Poly I:C at gestational day 15. Serum samples were collected to assess the amount of TNF-α in the maternal blood following MIA. MIA offspring were divided into weight loss (WL; n=14) and weight gain (WG; n=10) groups, depending on the maternal body weight response to Poly I:C. Adult offspring were behaviourally phenotyped for prepulse inhibition, locomotor activity with and without amphetamine and MK-801 challenge, and sucrose preference. Finally, microglia activation was scored on CD11b- and Iba1-immunohistochemically stained sections.Pregnant dams that lost weight following MIA showed increased levels of TNF-α compared to controls, unlike dams that gained weight following MIA. Poly I:C WL offspring showed the most severe behavioural outcome. Poly I:C WG offspring, on the other hand, did not show clear behavioural deficits. Most interestingly a reduced sucrose preference indicative of anhedonia was found in Poly I:C WL but not Poly I:C WG offspring compared to controls. Finally, there were no significant differences in microglia activation scores between any of the investigated groups. ### Long_Answer: The individual maternal immune response to MIA is an important determinant of the behavioural outcome in offspring, including negative symptoms such as anhedonia. We failed to find any significant difference in the level of microglia activation between Poly I:C WL, Poly I:C WG and control offspring. ### Final_Prediction: yes

### Question: Is acidic α-galactosidase the most abundant nectarin in floral nectar of common tobacco ( Nicotiana tabacum )? ### Context: To date, most floral nectarins (nectar proteins) are reported to function in nectar defence, particularly for insect-pollinated outcrossing species. We compared nectarin composition and abundance in selfing common tobacco (Nicotiana tobaccum) with outcrossing ornamental tobacco plants to elucidate the functional difference of nectarins in different reproductive systems.Common tobacco (CT) nectarins were separated by SDS-PAGE and the N terminus of the most abundant nectarin was sequenced via Edman degradation. The full-length nectarin gene was amplified and cloned from genomic DNA and mRNA with hiTail-PCR and RACE (rapid amplification of cDNA ends), and expression patterns were then investigated in different tissues using semi-quantitative reverse transcriptase PCR. Additionally, high-performance liquid chromatography and enzymatic analyses of nectar sugar composition, and other biochemical traits and functions of the novel nectarin were studied.The most abundant nectarin in CT nectar is an acidic α-galactosidase, here designated NTα-Gal. This compound has a molecular mass of 40 013 Da and a theoretical pI of 5·33. NTα-Gal has a conserved α-Gal characteristic signature, encodes a mature protein of 364 amino acids and is expressed in different organs. Compared with 27 other melliferous plant species from different families, CT floral nectar demonstrated the highest α-Gal activity, which is inhibited by d-galactose. Raffinose family oligosaccharides were not detected in CT nectar, indicating that NTα-Gal does not function in post-secretory hydrolysis. Moreover, tobacco plant fruits did not develop intact skin with galactose inhibition of NTα-Gal activity in nectar, suggesting that NTα-Gal induces cell-wall surface restructuring during the initial stages of fruit development. ### Long_Answer: α-Gal was the most abundant nectarin in selfing CT plants, but was not detected in the nectar of strictly outcrossing sister tobacco species. No function was demonstrated in antimicrobial defence. Therefore, floral nectarins in selfing species maintain their functional significance in reproductive organ development. ### Final_Prediction: yes

### Question: Is the MAP2K5-linked SNP rs2241423 associated with BMI and obesity in two cohorts of Swedish and Greek children? ### Context: Recent genome-wide association studies have identified a single nucleotide polymorphism within the last intron of MAP2K5 associated with a higher body mass index (BMI) in adults. MAP2K5 is a component of the MAPK-family intracellular signaling pathways, responding to extracellular growth factors such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In this study, we examined the association of this variant in two cohorts of children from Sweden and Greece.We examine the association of rs2241423 to BMI in a cohort of 474 Swedish children admitted for treatment of childhood obesity and 519 children matched for gender, ethnicity and socioeconomic background from the Stockholm area, as well as a cross-sectional cohort of 2308 Greek school children (Healthy Growth Study). Children were genotyped using a predesigned TaqMan polymorphism assay. Logistic regression was used to test for an association of rs2241423 to obesity in the cohort of Swedish children. Linear regression was used to test for an association of rs2241423 to BMI z-score and phenotypic measurements of body adiposity in the cohort of Greek children. Models were adjusted for age and gender. In the cohort of Greek children the model was also adjusted for stage of pubertal development.The minor allele of rs2241423, allele A, was associated with a protective effect against obesity in the cohort of Swedish children (p = 0.029, OR = 0.79 (95% CI: 0.64-0.98)), and with a lower BMI z-score in the cohort of Greek children (p = 0.028, β = -0.092). No association to phenotypic measurements of body fat distribution could be observed in our study. ### Long_Answer: rs2241423 was associated with BMI and obesity in two independent European cohorts suggesting a role for MAP2K5 in early weight regulation. ### Final_Prediction: yes

### Question: Does hedyotis diffusa Willd extract inhibit the growth of human glioblastoma cells by inducing mitochondrial apoptosis via AKT/ERK pathways? ### Context: Hedyotis diffusa Willd (Rubiaceae) (HDW) has been widely applied for the treatment of tumors, inflammation and toxication in traditional Chinese medicine. The antitumor effect of HDW on glioblastoma has been rarely reported. We aim to evaluate the activity of this extract and explore the underlying mechanism in U87 human glioblastoma cell line.Cytotoxicity of HDW extract on U87 cells was measured by MTT assay. Apoptosis, cell cycle arrest and mitochondrial membrane potential (MMP) collapse induced by HDW extract were determined by flow cytometry. Caspase activity was analyzed based on colorimetric assay with a microplate spectrophotometer. Protein expression was examined by Western blot.HDW extract suppressed U87 cells growth in a dose- and time-dependent manner. Flow cytometry showed that HDW extract induced significant apoptosis, S/G2-M phase arrest and MMP collapse in U87 cells. Furthermore, dose-dependent activation of caspase-3, Bcl-2, Bax and ERK was observed with HDW extract treatment. Decreased Bcl-2/Bax ratio and Akt suppression were readily found as well. ### Long_Answer: Induction of mitochondria-mediated apoptosis played an essential role in antitumor activity of HDW extract in U87 cells, in which ERKs and Akt signaling proteins were also involved. These findings contributed to the feasibility of using HDW extract in glioblastoma treatment and the understanding of the molecular mechanism. ### Final_Prediction: yes

### Question: Does ischemia-reperfusion injury after lung transplantation increase risk of late bronchiolitis obliterans syndrome? ### Context: Bronchiolitis obliterans syndrome (BOS) is the most common cause of long-term morbidity and mortality after lung transplantation. Our hypothesis was that early ischemia-reperfusion injury after lung transplantation increases the risk of BOS.Data on 134 patients who had lung transplantation between January 1, 1990 and January 1, 2000, was used for univariate and multivariate logistic regression analysis.After lung transplantation, 115 patients (115 of 134, 86%) survived more than 3 months. In that group, 41 patients developed BOS, of which 23 had progressive disease. Univariate analysis revealed that ischemia-reperfusion injury (p = 0.017) and two or more acute rejection episodes (p = 0.032) were predictors of BOS onset, whereas ischemia-reperfusion injury (p = 0.011) and cytomegalovirus infection (p = 0.009) predicted progressive BOS. Multivariate logistic regression analysis showed that ischemia-reperfusion injury was an independent predictor for both BOS development and BOS progression. Two or more acute rejection episodes were also an independent predictor of BOS development, whereas cytomegalovirus infection was an independent predictor of progressive BOS. ### Long_Answer: Ischemia-reperfusion injury increases the risk of BOS after lung transplantation. ### Final_Prediction: yes

### Question: Is pAI-1 4G/5G polymorphism associated with brain vessel reocclusion after successful fibrinolytic therapy in ischemic stroke patients? ### Context: Despite t-PA proven benefits related to vessel reopening, up to 13% of stroke patients suffer reocclusions after t-PA. We aimed to analyze whether a functional polymorphism in a fibrinolysis inhibitor gene [plasminogen activator inhibitor-1 (PAI-1)] might be associated with reocclusion rates after stroke thrombolytic therapy.165 patients with ischemic stroke who received t-PA < 3 h were studied. Reocclusion and recanalization was diagnosed by transcranial Doppler. PAI-1 4G/5G polymorphism determination was performed by sequencing. PAI-1 mRNA was studied by real-time PCR analysis. National institutes of health stroke scale (NIHSS) was serially measured since patients arrival to assess the neurological outcome, and modified ranking scale (mRS) at 3rd month was used to evaluate functional outcome following stroke.PAI-1 4G/4G patients had higher reocclusion rates (4G/4G = 12.5% versus other genotypes = 2.7%, p = 0.025). . In a logistic regression, the 4G/4G genotype was the only factor associated with reocclusion (OR = 15.16 95%, CI = 1.4-163.4, p = 0.025). 4G/4G genotype was also associated with poor functional outcome at 3rd month (4G/4G = 4 versus others genotypes = 3, p = 0.017) and with mRNA levels at 12 h post stroke symptoms onset (4G/4G patients = 2.01% versus other genotypes = 0.68%, p = 0.034). ### Long_Answer: PAI-1 4G/4G genotype is associated with reocclusion rates and poor functional outcome among stroke patients treated with t-PA. ### Final_Prediction: yes

### Question: Cardiovascular risk in a rural adult West African population: is resting heart rate also relevant? ### Context: Elevated resting heart rate (RHR) is a neglected marker in cardiovascular risk factor studies of sub-Saharan African populations. This study aimed to determine the prevalence of elevated RHR and other risk factors for cardiovascular disease (CVD) and to investigate any associations between RHR and these risk factors in a rural population in Ghana.Cross-sectional analysis.A total of 574 adults aged between 18-65 years were randomly sampled from a population register. Data collected included those on sociodemographic variables and anthropometric, blood pressure (BP), and RHR measurements. Within-person variability in RHR was calculated using data from repeat measurements taken 2 weeks apart.Of study participants, 36% were male. Prevalence of casual high BP was 19%. In the population, 10% were current cigarette smokers and habitual alcohol use was high at 56%. As measured by body mass index, 2% were obese and 14% had abdominal obesity. RHR was elevated (>90 bpm) in 19%. Overall, 79% of study participants were found to have at least one CVD risk factor. RHR was significantly associated with age, waist circumference, and BP. Individuals with an elevated RHR had a higher risk (OR 1.94, 95% CI 1.15-3.26%, p = 0.013) of casual high BP compared with participants with normal RHR independently of several established CVD risk factors. The regression dilution ratio of RHR was 0.75 (95% CI 0.62-0.89). ### Long_Answer: Significant associations were observed between RHR and several established cardiovascular risk factors. Prospective studies are needed in sub-Saharan African populations to establish the potential value of RHR in cardiovascular risk assessment. ### Final_Prediction: yes

### Question: Does habitual Myofibrillar Protein Synthesis be Normal in Patients with Upper GI Cancer Cachexia? ### Context: Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity, and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in patients with cancer compared with healthy controls.An oral heavy water (87.5 g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine, and alanine in the myofibrillar component of muscle using gas chromatography-pyrolysis-isotope ratio mass spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown.Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (≥5% weight loss) patients undergoing surgery for upper gastrointestinal cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight-stable, and weight-losing patients, respectively. Weight-losing patients had higher synthetic rates than controls (P = 0.03). ### Long_Answer: Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting. ### Final_Prediction: yes

### Question: Does a combination of physical training, specific exercises and pain education improve health-related quality of life in patients with chronic neck pain? ### Context: A multicentre randomised controlled trial of 200 neck pain patients receiving pain education. The exercise group received additional exercises for neck/shoulder, balance and oculomotor function, plus graded physical activity training. Patient-reported outcome measures (Short Form-36 Physical and Mental component summary scores, EuroQol-5D, Beck Depression Inventory-II, Neck Disability Index, Pain Bothersomeness, Patient-Specific Functioning Scale, Tampa Scale of Kinesiophobia, Global Perceived Effect) and clinical tests (Aastrand Physical Fitness, cervical Range of Motion, Pressure Pain Threshold at infraspinatus, tibialis anterior and cervical spine, Cranio-cervical Flexion, Cervical Extension muscle function, and oculomotion) were recorded at baseline and after 4 months.The exercise group showed statistically significant improvement in physical HR-QoL, mental HR-QoL, depression, cervical pressure pain threshold, cervical extension movement, muscle function, and oculomotion. Per protocol analyses confirmed these results with additional significant improvements in the exercise group compared with controls. ### Long_Answer: This multimodal intervention may be an effective intervention for chronic neck pain patients. ### Final_Prediction: nan

### Question: Can the feeling scale be used to regulate exercise intensity? ### Context: It is important that individuals experience a positive affective response during exercise to encourage future behavior. Exercise intensity is a determinant of the affective response. Current research protocols have failed to find the intensity at which all individuals will experience this positive affective response. Consequently, the purpose of this study was to evaluate whether sedentary women could self-regulate their exercise intensity during exercise using the Hardy and Rejeski Feeling Scale (FS) to experience a specific positive affective state and to examine the specific intensities chosen and their consistency over exercise bouts.Seventeen sedentary women completed eight 30-min laboratory-based treadmill exercise sessions (two sessions were completed each week). In four consecutive sessions, participants exercised at an intensity they perceived corresponded to an FS value of 1 (fairly good) and the other four sessions at an intensity corresponding to an FS value of 3 (good). Measures of exercise intensity were recorded.Participants exercised at a lower intensity to achieve an affective state of good (FS 3) compared with fairly good (FS 1). Both these intensities lay close to the individual's ventilatory threshold. The selected intensity was consistent across trials with intensity increasing across time to maintain the required affective state. ### Long_Answer: Sedentary women can regulate intensity using the FS to experience a pleasant affective state, and the intensities chosen are physiologically beneficial for health and fitness. ### Final_Prediction: nan

### Question: Is food preparation by young adults associated with better diet quality? ### Context: To describe food-preparation behaviors, cooking skills, resources for preparing food, and associations with diet quality among young adults.Cross-sectional analyses were performed in a sample of young adults who responded to the second wave of a population-based longitudinal study. Measures pertaining to food preparation were self-reported and dietary intake was assessed by a food frequency questionnaire, both by a mailed survey.Males (n = 764) and females (n = 946) ages 18 to 23 years.Cross-tabulations and chi2 tests were used to examine associations between food preparation, skills/resources for preparing foods, and characteristics of young adults. Mixed regression models were used to generate expected probabilities of meeting the Healthy People 2010 dietary objectives according to reported behaviors and skills/resources.Food-preparation behaviors were not performed by the majority of young adults even weekly. Sex (male), race (African American), and living situation (campus housing) were significantly related to less frequent food preparation. Lower perceived adequacy of skills and resources for food preparation was related to reported race (African American or Hispanic) and student status (part-time or not in school). The most common barrier to food preparation was lack of time, reported by 36% of young adults. Young adults who reported frequent food preparation reported less frequent fast-food use and were more likely to meet dietary objectives for fat (P < 0.001), calcium (P < 0.001), fruit (P < 0.001), vegetable (P < 0.001), and whole-grain (P = 0.003) consumption. ### Long_Answer: To improve dietary intake, interventions among young adults should teach skills for preparing quick and healthful meals. ### Final_Prediction: yes

### Question: Does waist circumference lead to prolonged microvascular reactive hyperemia response in young overweight/obese women? ### Context: Previous data in our laboratory have shown microvascular dysfunction in normoglycaemic subjects with metabolic syndrome (MS). In a step further, we have investigated which clinical parameters related or not to MS would elicit microvascular dysfunction and the need of diagnosing MS for the establishment of microcirculatory impairment in overweight/obese women.Nineteen lean [23.6±3.1years, body mass index (BMI) 21.9±1.8kg/m(2)] and 59 overweight/obese [24.6±3.7years; BMI 34.4±5.9kg/m(2)] sedentary non-smoking women, divided in overweight/obese without (MS negative, n=36) and obese with MS (MS positive, n=23) were evaluated. Blood biochemistry, HOMA-IR index and anthropometric variables were determined. Morphological (capillary diameters) and functional [functional capillary density, red blood cell velocity (RBCV) at baseline and peak and time (TRBCV(max)) to reach it during post-occlusive reactive hyperemia after 1min ischemia] microcirculatory variables were examined by nailfold videocapillaroscopy.Compared to controls, overweight/obese MS negative and obese MS positive presented longer TRBCV(max); the presence of two MS components was sufficient to prolong it and the MS diagnosis did not add any significant impairment to the microcirculation. Among clinical parameters investigated, a direct relationship between TRBCV(max) and waist circumference and insulin concentrations was found. ### Long_Answer: Our results have shown that microvascular dysfunction is independent of metabolic syndrome diagnosis and could be predicted by the waist circumference on young overweight/obese women, reinforcing the relationship between obesity-related microvascular/metabolic disturbances. ### Final_Prediction: yes

### Question: Do trends in the use and role of biomarkers in phase I oncology trials? ### Context: There has been interest in using biomarkers that aid the evaluation of new anticancer agents. We evaluated trends in the use of biomarkers and their contribution to the main goals of phase I trials.We did a systematic review of abstracts submitted to the American Society of Clinical Oncology annual meeting from 1991 to 2002 and the publications related to these abstracts. We analyzed the use of biomarkers and their contribution to published phase I trials.Twenty percent of American Society of Clinical Oncology phase I abstracts (503 of 2458) from 1991 to 2002 included biomarkers. This proportion increased over time (14% in 1991 compared with 26% in 2002; P < 0.02). Independent predictors of the use of biomarkers included National Cancer Institute sponsorship, submission in the time period of 1999 to 2002, adult population, and drug family (biological agents). Biomarkers supported dose selection for phase II studies in 11 of 87 of the trials (13%) emanating from these abstracts. However, the primary determinants of phase II dose and schedule were toxicity and/or efficacy in all but one of these 87 trials (1%). Biomarker studies provided evidence supporting the proposed mechanism of action in 34 of 87 of the published trials (39%). ### Long_Answer: The use of biomarkers in phase I trials has increased over the period from 1991 to 2002. To date, biomarker utilization has made a limited and primarily supportive contribution to dose selection, the primary end point of phase I studies. Additional studies are needed to determine what type of biomarker information is most valuable to evaluate in phase I trials. ### Final_Prediction: yes

### Question: Is serum 25-hydroxyvitamin D3 related to physical activity and ethnicity but not obesity in a multicultural workforce? ### Context: Recent research suggests that body vitamin D levels are decreased in coronary heart disease and diabetes, but it is unclear which cardiovascular risk factors are related to vitamin D status.To examine the relation between vitamin D status and major cardiovascular risk factors.Serum 25-hydroxyvitamin D3, a marker of recent sun exposure and vitamin D status, was measured in 390 New Zealand residents (95 Pacific Islanders, 74 Maori and 221 others mostly of European descent), who were part of a larger cross-sectional survey of a workforce (n = 5677) aged 40-64 years.Serum 25-hydroxyvitamin D3 levels were significantly lower in Pacific Islanders (mean (SE) = 56 (3) nmol/L; p = 0.0001) and Maoris (68 (3) nmol/L; p = 0.036) compared with Europeans (75 (2) nmol/L) after adjusting for age, sex and time of year. Also adjusting for ethnic group, 25-hydroxyvitamin D3 was higher in people doing vigorous (aerobic) leisure physical activities (71 (2) nmol/L; p = 0.0066) and moderate (non-aerobic) activities (68 (3) nmol/L; p = 0.12) compared with those who were inactive (63 (2) nmol/L). However, 25-hydroxyvitamin D3 was unrelated to body mass index, serum lipids, blood pressure or cigarette smoking. ### Long_Answer: People with increased skin pigmentation, such as Polynesians, and people who are inactive, have decreased body levels of vitamin D; this might partly explain their increased risk of cardiovascular disease. ### Final_Prediction: yes

### Question: Do microvascular dysfunction and pulse wave reflection characterize different vascular pathologies in patients at cardiovascular risk? ### Context: Endothelial function and arterial pulse wave reflections play a crucial role in the pathogenesis of atherosclerosis. While the endothelium-dependent reactive hyperemia index (RHI) of the digital arteries is considered as a marker of microvascular function, an increased augmentation index (AI) may indicate beginning macrovascular damage. In this study we assessed the interrelationships among these noninvasive measures of vascular function.In 178 all-comer patients with documented cardiovascular risk factors (22 % female; 65 % coronary artery disease, CAD), we measured radial AI (rAI) by radial applanation tonometry and digital AI (dAI) as well as RHI by using fingertip peripheral arterial tonometry. A modified SMART risk score was calculated in all participants based on cardiovascular risk factors and preexisting vascular disease.dAI and rAI demonstrated a significant and robust overall correlation (Pearson rank coefficient r = 0.63, p < 0.01), which was not affected by age, sex, diabetes mellitus and CAD. In contrast, both parameters demonstrated at most a weak correlation (dAI: r = 0.26, p < 0.01 and rAI: r = 0.12, p = 0.10) with microvascular function (RHI). While dAI and rAI were significantly correlated to female sex, age, low body height, low heart rate and the presence of CAD, RHI was associated with the presence of diabetes mellitus and nicotine use. Finally, only microvascular function was associated with the modified SMART risk score, but not augmentation indices. ### Long_Answer: RHI and increased pulse wave reflection appear to represent two distinct vascular pathologies in patients with cardiovascular risk. In contrast, RHI might be useful to identify patients at highest cardiovascular risk once atherosclerotic disease has been diagnosed. ### Final_Prediction: yes

### Question: Does the relationship of clinical laboratory parameters and patient attribute to the quality of life of patients on hemodialysis? ### Context: With advances in medicine, the subjective assessment of patients on hemodialysis regarding their quality of life (QOL) is gaining importance. Clinicians cannot rely solely on objective markers, such as the rates of complications and mortality, when evaluating responses to dialysis. In clinical settings, laboratory values are used as measures of patients' health. However, the relationship between clinical laboratory values and QOL has not been elucidated yet. Therefore, the present study aimed to define the relationship of laboratory values and patient attributes to the QOL of outpatients on hemodialysis in order to obtain basic data for reevaluating nursing support for patients on hemodialysis in the future.The participants were 44 outpatients receiving hemodialysis at Hospital B. The QOL was surveyed using a self-administered questionnaire, the Kidney Disease Quality of Life Short Form. The following patient attributes and laboratory values were taken from the medical records: age; sex; primary disease; number of years on hemodialysis; complications; number of hours of hemodialysis per session; percentage weight gain; cardiothoracic ratio; blood pressure; hematocrit; and the serum levels of albumin, potassium, phosphorus, and calcium.The serum potassium level significantly affected mental health, social functioning, symptoms, and the effect of kidney disease, with the 3.5-5.0 mEq/L target range group scoring higher than the > or =5.1 mEq/L group. ### Long_Answer: The serum potassium level significantly affected not only physical health, but also QOL, a measure of psychosocial health. This suggests that providing nursing support to patients, guided by the serum potassium target range of 3.5-5.0 mEq/L, might improve and maintain QOL. ### Final_Prediction: yes

### Question: Do fourier and wavelet analyses of dental radiographs detect trabecular changes in osteoporosis? ### Context: Osteoporosis results in loss of bone mass and microarchitectural deterioration. Dental radiographs potentially offer a means of screening for osteoporosis as they are commonly made on adults. Spatial frequency analyses are well suited to detect subtle changes in image patterns. We hypothesize that individuals with osteoporosis exhibit an altered radiographic trabecular pattern that can be detected by spatial frequency and strut analysis.Maxillary and mandibular periapical radiographs of 26 women with osteoporosis and 23 controls were examined using one-dimensional discrete Fourier and wavelet analyses in both jaws to measure the spatial frequency distributions of trabecular structures. A strut analysis was also performed.Individuals with osteoporosis revealed an altered trabecular pattern compared to controls. Using Fourier and strut variables allows classification of subjects with 92% sensitivity, 96% specificity, and a 22% cross-validation error rate. Wavelet analysis was also useful but did not perform better than Fourier analysis for subject classification. ### Long_Answer: Spatial frequency analysis of digitized dental radiographs, especially Fourier analysis, and strut analysis provide value for identifying individuals with osteoporosis. ### Final_Prediction: yes

### Question: Should cervical ultrasonography be a routine staging investigation for lung cancer patients with impalpable cervical lymph nodes? ### Context: Detection of cervical N3 lymph nodes is currently not a routine preoperative investigation for lung cancer patients. We designed a study to assess if the frequency and accuracy of detection of metastatic cervical lymph nodes using cervical ultrasonography (US) and fine needle aspiration (FNA) justify their routine use in all lung cancer patients with impalpable cervical lymph nodes.Fifty patients with suspected and potentially operable non-small cell lung cancer were enrolled. Patients with palpable cervical lymph nodes were excluded. In addition to routine preoperative investigations, all patients received cervical US to determine the presence of cervical lymph nodes. Nodes suspicious of harboring malignancy according to a specific set of sonographic criteria (which include shape, echogenicity, nodal architecture, and vascular patterns) were subjected to biopsy by ultrasound-guided FNA.Normal cervical lymph nodes were detected by cervical US in 30 patients (60%). Cervical lymph nodes suspicious of harboring malignancy were detected in 10 patients (20%). FNA confirmed cervical nodal metastasis in four of these patients (8%). The TNM staging of two patients (4%) was revised up to stage IIIb as a result, excluding them from further surgery. Cost analysis suggests this technique to be cost-effective when used as a routine preoperative investigation to exclude patients from unnecessary surgical intervention. No mortality or complications were encountered in all patients. ### Long_Answer: Cervical US and FNA is a safe and cost-effective method of evaluating the status of impalpable cervical lymph nodes in lung cancer patients. Further study is warranted to establish the role of cervical US and FNA in lung cancer staging algorithms. ### Final_Prediction: nan

### Question: Is major mite allergen Der f 1 concentration reduced in buildings with improved energy performance? ### Context: Environmental conditions play a crucial role in mite growth, and optimal environmental control is key in the prevention of airway inflammation in chronic allergic rhinoconjunctivitis or asthma.To evaluate the relationship between building energy performance and indoor mite allergen concentration in a cross-sectional study.Major allergen concentration (Der f 1, Der p 1, mite group 2, Fel d 1 and Bla g 2) was determined by quantitative dot blot analysis from mattress and carpet dust samples in five buildings designed for low energy use (LEB) and in six control buildings (CB). Inhabitants had received 4 weeks prior to mite measurement a personal validated questionnaire related to the perceived state of health and comfort of living.Cumulative mite allergen concentration (with Der f 1 as the major contributor) was significantly lower in LEB as compared with CB both in mattresses and in carpets. In contrast, the two categories of buildings did not differ in Bla g 2 and Fel d 1 concentration, in the amount of dust and airborne mould collected. Whereas temperature was higher in LEB, relative humidity was significantly lower than in CB. Perceived overall comfort was better in LEB. ### Long_Answer: Major mite allergen Der f 1 preferentially accumulates in buildings not specifically designed for low energy use, reaching levels at risk for sensitization. We hypothesize that controlled mechanical ventilation present in all audited LEB may favour lower air humidity and hence lower mite growth and allergen concentration, while preserving optimal perceived comfort. ### Final_Prediction: yes

### Question: Do methionine derivatives diminish sulphide damage to colonocytes -- implications for ulcerative colitis? ### Context: Bacterial production of anionic sulphide is increased in the colon of ulcerative colitis and sulphides can cause metabolic damage to colonocytes.To assess the reversal of the damaging effect of sulphide to isolated colonocytes by methionine and methionine derivatives.Isolated colonocytes were prepared from rat colons and 12 human colectomy specimens. In cell suspensions 14CO2/acetoacetate generation was measured from [1-14C]-butyrate (5.0 mmol/l) in the presence of 0-2.0 mmol/l sodium hydrogen sulphide. The effect of 5.0 mmol/l L-methionine, S-adenosylmethionine 1,4 butane disulphonate and DL-methionine-S-methylsulphonium chloride on sulphide inhibited oxidation was observed.In rat colonocytes sodium hydrogen sulphide dose dependently reduced oxidative metabolite formation from n-butyrate, an action reversed in order of efficacy by S-adenosylmethionine 1,4 butane disulphonate > DLmethionine-S-methyl-sulphonium chloride > L-methionine. In human colonocytes S-adenosylmethionine 1,4 butane disulphonate most significantly improved 14CO2 production (p = < 0.005) suppressed by sodium hydrogen sulphide. ### Long_Answer: Sulphide toxicity in colonocytes is reversible by methyl donors. The efficiency of sulphide detoxification may be an important factor in the pathogenesis and treatment of ulcerative colitis for which S-adenosylmethionine 1,4 butane disulphonate may be of therapeutic value. ### Final_Prediction: yes

### Question: Can restrictions on reimbursement for anti-ulcer drugs decrease Medicaid pharmacy costs without increasing hospitalizations? ### Context: To examine the impact of a policy restricting reimbursement for Medicaid anti-ulcer drugs on anti-ulcer drug use and peptic-related hospitalizations.DATA SOURCES/In addition to U.S. Census Bureau data, all of the following from Florida: Medicaid anti-ulcer drug claims data, 1989-1993; Medicaid eligibility data, 1989-1993; and acute care nonfederal hospital discharge abstract data (Medicaid and non-Medicaid), 1989-1993.In this observational study, a Poisson multiple regression model was used to compare changes, after policy implementation, in Medicaid reimbursement for prescription anti-ulcer drugs as well as hospitalization rates between pre- and post-implementation periods in Medicaid versus non-Medicaid patients hospitalized with peptic ulcer disease.Following policy implementation, the rate of Medicaid reimbursement for anti-ulcer drugs decreased 33 percent (p<.001). No associated increase occurred in the rate of Medicaid peptic-related hospitalizations. ### Long_Answer: Florida's policy restricting Medicaid reimbursement for anti-ulcer drugs was associated with a substantial reduction in outpatient anti-ulcer drug utilization without any significant increase in the rate of hospitalization for peptic-related conditions. ### Final_Prediction: nan

### Question: Does programmed cell death 4 ( PDCD4 ) suppress metastastic potential of human hepatocellular carcinoma cells? ### Context: Hepatocellular carcinoma (HCC) is a lethal malignancy with high rate of metastasis and poor prognosis. There are no effective managements to block metastasis of HCC. Programmed cell death 4 (PDCD4) is found to be a tumor transformation suppressor. Among investigations on effects of PDCD4, little is about the metastatic potentials of HCC cells. This study was to investigate the role of PDCD4 on metastatic potential of human HCC cells.We examined the expression of PDCD4 in three HCC cell lines with different metastatic potentials, MHCC-97H (high metastatic potential), MHCC-97L (low metastatic potential) and Hep3B (no metastatic potential). A plasmid encoding PDCD4 gene was constructed and then transfected into HCC cells with the lowest PDCD4 expression level. Effects of PDCD4 on cell proliferation, cell apoptosis, gene expression of metastasis tumor antigen 1 (MTA1) and in vitro migration and invasion capacity were assessed after transfection.Our results showed that the expression level of PDCD4 was inversely correlated to the metastatic potential of HCC cells. After transfection with the PDCD4 gene, HCC cell proliferation rate was significantly decreased, cell apoptosis rate was significantly increased, the expression of MTA1 gene, HCC cell migration and Matrigel invasion were also remarkably inhibited. ### Long_Answer: PDCD4 expression is inversely correlated to the metastatic potential of HCC cells. PDCD4 can effectively suppress the metastatic potential of HCC cells. ### Final_Prediction: yes

### Question: Is nicotinic receptor-evoked hippocampal norepinephrine release highly sensitive to inhibition by isoflurane? ### Context: Inhaled anaesthetics (IAs) produce multiple dose-dependent behavioural effects including amnesia, hypnosis, and immobility in response to painful stimuli that are mediated by distinct anatomical, cellular, and molecular mechanisms. Amnesia is produced at lower anaesthetic concentrations compared with hypnosis or immobility. Nicotinic acetylcholine receptors (nAChRs) modulate hippocampal neural network correlates of memory and are highly sensitive to IAs. Activation of hippocampal nAChRs stimulates the release of norepinephrine (NE), a neurotransmitter implicated in modulating hippocampal synaptic plasticity. We tested the hypothesis that IAs disrupt hippocampal synaptic mechanisms critical to memory by determining the effects of isoflurane on NE release from hippocampal nerve terminals.Isolated nerve terminals prepared from adult male Sprague-Dawley rat hippocampus were radiolabelled with [(3)H]NE and either [(14)C]GABA or [(14)C]glutamate and superfused at 37 degrees C. Release evoked by a 2 min pulse of 100 microM nicotine or 5 microM 4-aminopyridine was evaluated in the presence or absence of isoflurane and/or selective antagonists.Nicotine-evoked NE release from rat hippocampal nerve terminals was nAChR- and Ca(2+)-dependent, involved both alpha7 and non-alpha7 subunit-containing nAChRs, and was partially dependent on voltage-gated Na(+) channel activation based on sensitivities to various antagonists. Isoflurane inhibited nicotine-evoked NE release (IC(50)=0.18 mM) more potently than depolarization-evoked NE release (IC(50)=0.27 mM, P=0.014), consistent with distinct presynaptic mechanisms of IA action. ### Long_Answer: Inhibition of hippocampal nAChR-dependent NE release by subanaesthetic concentrations of isoflurane supports a role in IA-induced amnesia. ### Final_Prediction: yes

### Question: Are transient ischemic attack patients with fluctuations at highest risk for early stroke? ### Context: The management and risk of early stroke are unclear in patients with fluctuating neurological symptoms. We aimed to evaluate the clinical course of these patients presenting within 24 h after onset of acute cerebral ischemia symptoms.All patients with transient ischemic signs/symptoms consecutively admitted to our Emergency Stroke Unit were recruited. Patients were neurologically examined and underwent prompt CCT plus MRI imaging for visualization of early signs of ischemia.Among 122 patients, 84 (69%) had single symptoms, 33 (27%) showed rapidly relapsing and remitting symptoms - in 5 cases (4%) symptom duration could not reliably be assessed. 11/122 (9%) suffered a stroke during hospitalization. ABCD(2) scores did not predict early strokes: 2/11 (18.2%) were in the 'lower risk', 7/11 (63.6%) in the 'moderate risk' and only 2/11 (18.2%) in the 'high risk' group (p = 0.103). 3/11 patients (27.3%) revealed lesions in neuroimaging, but surprisingly 8/11 (72.7%, p = 0.132) did not. However, patients with fluctuations in neurological status were significantly more likely to suffer a stroke: 9/122 versus 2/122 with stable symptoms (p < 0.05). Patients with small vessel disease were common in all (53/ 122; 43.4%) and within those who suffered an early stroke (6/11; 54.5%). ### Long_Answer: Patients with unstable transient ischemic attacks immediately after onset of clinical symptoms are at high risk for subsequent stroke - they may benefit from Stroke Unit management and potential early thrombolysis once they develop strokes. ### Final_Prediction: yes

### Question: Are in adults with Prader-Willi syndrome , elevated ghrelin levels more consistent with hyperphagia than high PYY and GLP-1 levels? ### Context: Prader-Willi syndrome (PWS) is a leading genetic cause of obesity, characterized by hyperphagia, endocrine and developmental disorders. It is suggested that the intense hyperphagia could stem, in part, from impaired gut hormone signaling. Previous studies produced conflicting results, being confounded by differences in body composition between PWS and control subjects.Fasting and postprandial gut hormone responses were investigated in a cross-sectional cohort study including 10 adult PWS, 12 obese subjects matched for percentage body fat and central abdominal fat, and 10 healthy normal weight subjects.PYY[total], PYY[3-36], GLP-1[active] and ghrelin[total] were measured by ELISA or radioimmunoassay. Body composition was assessed by dual energy X-ray absorptiometry. Visual analog scales were used to assess hunger and satiety.In contrast to lean subjects (p<0.05), PWS and obese subjects were similarly insulin resistant and had similar insulin levels. Ghrelin[total] levels were significantly higher in PWS compared to obese subjects before and during the meal (p<0.05). PYY[3-36] meal responses were higher in PWS than in lean subjects (p=0.01), but not significantly different to obese (p=0.08), with an additional non-significant trend in PYY[total] levels. There were no significant differences in self-reported satiety between groups, however PWS subjects reported more hunger throughout (p=0.003), and exhibited a markedly reduced meal-induced suppression of hunger (p=0.01) compared to lean or obese subjects. ### Long_Answer: Compared to adiposity-matched control subjects, hyperphagia in PWS is not related to a lower postprandial GLP-1 or PYY response. Elevated ghrelin levels in PWS are consistent with increased hunger and are unrelated to insulin levels. ### Final_Prediction: yes

### Question: Are free fatty acids associated with obesity , insulin resistance , and atherosclerosis in renal transplant recipients? ### Context: Insulin resistance (IR) may be implicated in the pathogenesis of atherosclerosis in renal transplant recipients (RTRs) and be contributed to, in part, by free fatty acids (FFAs), produced in excess in centrally obese individuals. The aim of this study was to determine the prevalence of IR and the relationships between FFAs, central obesity, and atherosclerosis in a cohort of prevalent RTRs.Observational data were collected on 85 RTRs (mean age 54 years; 49% male, 87% Caucasian). Fasting serum was analyzed for FFAs, glucose, and insulin; IR was calculated using the homeostasis model assessment (HOMA-IR) score. Vascular structure was assessed by carotid intima-media thickness (IMT) measurement. Linear regression analyses were performed to determine the factors associated with IR and atherosclerosis.IR occurred in 75% of RTRs, and FFA levels were independently associated with its occurrence (beta: -0.55, 95% CI: -1.02 to -0.07, P = 0.02). Other variables independently associated with IR were male sex, body mass index, central obesity, diabetes, systolic blood pressure and corticosteroid use. There was a significant correlation between FFA levels and IMT (r = 0.3, P=0.01). On multivariate analysis, IMT correlated with elevated FFA (beta: 0.07, 95% CI: 0.02-0.12, P = 0.007), diabetes mellitus (P = 0.05), older age (P < 0.002), and a body mass index >25 kg/m (P = 0.002). ### Long_Answer: FFAs are associated with the development of IR and may be involved in the pathogenesis of atherosclerosis in RTRs. Additional studies are required to explore these associations further before considering whether an interventional trial aimed at lowering FFA would be a worthwhile undertaking. ### Final_Prediction: yes

### Question: Does connective Tissue Growth Factor ( CTGF/CCN2 ) enhance lactogenic differentiation of mammary epithelial cells via integrin-mediated cell adhesion? ### Context: Connective Tissue Growth Factor (CTGF/CCN2), a known matrix-associated protein, is required for the lactogenic differentiation of mouse mammary epithelial cells. An HC11 mammary epithelial cell line expressing CTGF/CCN2 was constructed to dissect the cellular responses to CTGF/CCN2 that contribute to this differentiation program.Tetracycline-regulated expression of CTGF/CCN2 in HC11 cells enhanced multiple markers of lactogenic differentiation including beta-casein transcription and mammosphere formation. In a separate measure of mammary differentiation the addition of CTGF/CCN2 to cultures of MCF10A cells increased the development of acini in vitro. In HC11 cells the elevated levels of CTGF/CCN2 diminished the requirement for extracellular matrix proteins in the activation of beta-casein transcription, indicating that CTGF/CCN2 contributed to lactogenic differentiation through the regulation of matrix dependent cell adhesion. CTGF/CCN2 expression in HC11 cells increased expression of extracellular matrix proteins and integrins, enhanced the formation of focal adhesion complexes, and increased survival signaling. In addition, HC11 cells adhered to immobilized CTGF/CCN2 and this was inhibited by function-blocking antibodies to the integrins alpha6 and beta1, and to a lesser degree by antibody to beta3 integrin. ### Long_Answer: CTGF/CCN2 expression in HC11 cells led to an increase in multiple markers of lactogenic differentiation. The mechanisms by which CTGF/CCN2 contributed to lactogenic differentiation include direct binding of CTGF/CCN2 to integrin complexes and CTGF/CCN2-induced matrix protein expression resulting in elevated integrin functionality. ### Final_Prediction: yes

### Question: Does normal carcinoembryonic antigen indicate benefit from perioperative chemotherapy to gastric carcinoma patients? ### Context: To evaluate pretreatment serum carcinoembryonic antigen (CEA) as a predictor of survival for patients with locally advanced gastric cancer receiving perioperative chemotherapy.We retrospectively studied a cohort of 228 gastric cancer patients who underwent D2 gastrectomy combined with chemotherapy at the Sun Yat-sen University Cancer Center between January 2005 and December 2009. Among them, 168 patients received 6-12 cycles of oxaliplatin-based adjuvant (post-operative) chemotherapy, while 60 received perioperative chemotherapy (2 cycles of FOLFOX6 or XELOX before surgery and 4-10 cycles after surgery). Serum CEA was measured using an enzyme immunoassay. The follow-up lasted until December 2010.In the group that had elevated serum CEA, the difference in survival time between patients receiving perioperative chemotherapy and those receiving adjuvant chemotherapy had no statistical significance (P > 0.05). However, in the group that had normal serum CEA, patients receiving perioperative chemotherapy had a longer survival time. In multivariate analysis, T staging and lymph node metastatic rate were independent prognostic factors for the patients. Perioperative chemotherapy improved the overall survival of patients who had a normal pretreatment CEA level (P = 0.070). ### Long_Answer: Normal pretreatment serum CEA is a predictor of survival for patients receiving perioperative chemotherapy. ### Final_Prediction: yes

### Question: Does disease severity adversely affect delivery of dialysis in acute renal failure? ### Context: Methods of intermittent hemodialysis (IHD) dose quantification in acute renal failure (ARF) are not well defined. This observational study was designed to evaluate the impact of disease activity on delivered single pool Kt/V(urea) in ARF patients.100 patients with severe ARF (acute intrinsic renal disease in 18 patients, nephrotoxic acute tubular necrosis in 38 patients, and septic ARF in 44 patients) were analyzed during four consecutive sessions of IHD, performed for 3.5-5 h every other day or daily. Target IHD dose was a single pool Kt/V(urea) of 1.2 or more per dialysis session for all patients. Prescribed Kt/V(urea) was calculated from desired dialyzer clearance (K), desired treatment time (t) and anthropometric estimates for urea distribution volume (V). The desired clearance (K) was estimated from prescribed blood flow rate and manufacturer's charts of in vivo data obtained in maintenance dialysis patients. Delivered single pool Kt/V(urea) was calculated using the Daugirdas equation.None of the patients had prescription failure of the target dose. The delivered IHD doses were substantially lower than the prescribed Kt/V values, particularly in ARF patients with sepsis/septic shock. Stratification according to disease severity revealed that all patients with isolated ARF, but none with 3 or more organ failures and none who needed vasopressive support received the target dose. ### Long_Answer: Prescription of target IHD dose by single pool Kt/V(urea) resulted in suboptimal dialysis dose delivery in critically ill patients. Numerous patient-related and treatment-immanent factors acting in concert reduced the delivered dose. ### Final_Prediction: yes

### Question: Is tissue inhibitor of matrix metalloproteinase-1 prognostic in head and neck squamous cell carcinoma : comparison of the circulating and tissue immunoreactive protein? ### Context: Tissue inhibitors of metalloproteinases (TIMP) are capable of inhibiting the matrix metalloproteinases, but they also possess other biological functions. Little is known about the role of TIMP-1 in the progression and spreading of cancer cells among patients with head and neck squamous cell carcinoma (HNSCC). In this study, the pretreatment serum levels of TIMP-1 or the overexpression of TIMP-1 immunoreactive protein in the primary tumor was correlated to the clinical course in patients with HNSCC.The TIMP-1 immunoreactive protein was studied in 74 cases representing HNSCC. The tissue immunoreactive protein was evaluated from paraffin-embedded tumor sections in 68 cases using immunohistologic staining with a specific antibody, and in 68 cases the pretreatment serum levels of TIMP-1 were quantitatively measured by ELISA assay. The results were compared with the clinicopathologic factors of the disease and the patients' outcome.A positive correlation was found between the size of the primary tumor (T) and the circulating TIMP-1 level (P = 0.021) or the positive immunoreaction of TIMP-1 in tumor (P = 0.039). The 5-year cause-specific survival was significantly lower in patients presenting with a high serum TIMP-1 level than in those with a low level of TIMP-1 (38% versus 64%, P = 0.034). They also had an unfavorable 5-year relapse-free survival rate (37% versus 56%, respectively). Similarly, the expression of TIMP-1 in tumor was prognostic for shortened survival, the 5-year cumulative relapse-free survival being 42% in patients with a TIMP-1-positive tumor versus 75% in cases with a negative tumor (P = 0.035). Tissue TIMP-1 positivity also seemed associated to the cause-specific survival (P = 0.075) and to be connected with later lymph node or hematogenic relapses. ### Long_Answer: This study shows for the first time that both circulating and tissue TIMP-1 immunoreactive protein predicts the clinical course and dissemination in HNSCC, suggesting that TIMP-1 might be related to both tumor growth and metastasis in HNSCC. ### Final_Prediction: yes

### Question: Does the chemokine CXCL1/growth related oncogene increase sodium currents and neuronal excitability in small diameter sensory neurons? ### Context: Altered Na+ channel expression, enhanced excitability, and spontaneous activity occur in nerve-injury and inflammatory models of pathological pain, through poorly understood mechanisms. The cytokine GRO/KC (growth related oncogene; CXCL1) shows strong, rapid upregulation in dorsal root ganglion in both nerve injury and inflammatory models. Neurons and glia express its receptor (CXCR2). CXCL1 has well-known effects on immune cells, but little is known about its direct effects on neurons.We report that GRO/KC incubation (1.5 nM, overnight) caused marked upregulation of Na+ currents in acutely isolated small diameter rat (adult) sensory neurons in vitro. In both IB4-positive and IB4-negative sensory neurons, TTX-resistant and TTX-sensitive currents increased 2- to 4 fold, without altered voltage dependence or kinetic changes. These effects required long exposures, and were completely blocked by co-incubation with protein synthesis inhibitor cycloheximide. Amplification of cDNA from the neuronal cultures showed that 3 Na channel isoforms were predominant both before and after GRO/KC treatment (Nav 1.1, 1.7, and 1.8). TTX-sensitive isoforms 1.1 and 1.7 significantly increased 2 - 3 fold after GRO/KC incubation, while 1.8 showed a trend towards increased expression. Current clamp experiments showed that GRO/KC caused a marked increase in excitability, including resting potential depolarization, decreased rheobase, and lower action potential threshold. Neurons acquired a striking ability to fire repetitively; IB4-positive cells also showed marked broadening of action potentials. Immunohistochemical labelling confirmed that the CXCR2 receptor was present in most neurons both in dissociated cells and in DRG sections, as previously shown for neurons in the CNS. ### Long_Answer: Many studies on the role of chemokines in pain conditions have focused on their rapid and indirect effects on neurons, via release of inflammatory mediators from immune and glial cells. Our study suggests that GRO/KC may also have important pro-nociceptive effects via its direct actions on sensory neurons, and may induce long-term changes that involve protein synthesis. ### Final_Prediction: yes

### Question: Prevalence of thyroid dysfunction in women in early pregnancy: does it increase with maternal age? ### Context: Recent studies report high rates of thyroid disorders in pregnant women. However, the need for universal thyroid screening remains controversial. Our aim was to estimate the prevalence of thyroid dysfunction (TD) during pregnancy and to analyse the association with maternal age.We conducted a cross-sectional study in a referral centre in collaboration with the primary care units from April 2010 to March 2011. The study included 2509 consecutive pregnant women resident in an iodine-sufficient area, mean age 32 years (range 16-47) who were universally screened for TD in their first trimester (median gestation 8 weeks, range 4-13 weeks). Thyroid-stimulating hormone (TSH) and free T4 (FT4) were analysed during the first antenatal visit. We applied first trimester-specific population-based TSH and FT4 reference ranges.We identified 416 women with positive TD screening [16·6%, 95% confidence interval (95% CI) 15·1-18·0]. Of these, 47 had overt hypothyroidism (1·9%), 90 subclinical hypothyroidism (3·6%), 23 overt hyperthyroidism (0·9%), 20 subclinical hyperthyroidism (0·8%) and 236 had isolated hypothyroxinaemia (9·4%). Applying a logistic regression model, age ≥30 years was not associated with a higher risk of TD [odds ratio (OR) 0·85, 95% CI 0·67-1·08]or hypothyroidism (OR 0·72, 95% CI 0·50-1·06). ### Long_Answer: TD affects one in six pregnant women in an iodine-sufficient population. Maternal age ≥30 years do not increase the risk of TD. ### Final_Prediction: nan

### Question: Does epidermal growth factor receptor ( EGFR ) mutation correlate with platinum resistance in ovarian carcinoma . Results of a prospective pilot study? ### Context: Different studies have demonstrated epidermal growth factor receptor (EGFR) status as an independent prognostic factor for ovarian cancer (OC). Recent studies in non-small cell lung cancer suggest that the presence of a clinical response to tyrosine kinase inhibitors correlates with somatic mutations in the kinase domain of EGFR, exons 18-21. For patients with OC, data are not available on EGFR gene mutation.Shock-frozen samples from 32 patients with OC were screened for L858R deletion mutations of EGFR within exon 21 of the kinase domain and 15 bp deletion in exon 19. Additionally, nine commercially available OC cell lines and 32 established OC lines were analysed.In cell lines, as well as in tumor samples, stratified to platinum-free therapy interval, no mutation of the EGFR gene was observed. ### Long_Answer: Mutations in the kinase domain of the EGFR, exons 19 and 21, are absent or very infrequent in patients with OC. ### Final_Prediction: no

### Question: Does control of the intracellular redox state by glucose participate in the insulin secretion mechanism? ### Context: Production of reactive oxygen species (ROS) due to chronic exposure to glucose has been associated with impaired beta cell function and diabetes. However, physiologically, beta cells are well equipped to deal with episodic glucose loads, to which they respond with a fine tuned glucose-stimulated insulin secretion (GSIS). In the present study, a systematic investigation in rat pancreatic islets about the changes in the redox environment induced by acute exposure to glucose was carried out.Short term incubations were performed in isolated rat pancreatic islets. Glucose dose- and time-dependently reduced the intracellular ROS content in pancreatic islets as assayed by fluorescence in a confocal microscope. This decrease was due to activation of pentose-phosphate pathway (PPP). Inhibition of PPP blunted the redox control as well as GSIS in a dose-dependent manner. The addition of low doses of ROS scavengers at high glucose concentration acutely improved beta cell function. The ROS scavenger N-acetyl-L-cysteine increased the intracellular calcium response to glucose that was associated with a small decrease in ROS content. Additionally, the presence of the hydrogen peroxide-specific scavenger catalase, in its membrane-permeable form, nearly doubled glucose metabolism. Interestingly, though an increase in GSIS was also observed, this did not match the effect on glucose metabolism. ### Long_Answer: The control of ROS content via PPP activation by glucose importantly contributes to the mechanisms that couple the glucose stimulus to insulin secretion. Moreover, we identified intracellular hydrogen peroxide as an inhibitor of glucose metabolism intrinsic to rat pancreatic islets. These findings suggest that the intracellular adjustment of the redox environment by glucose plays an important role in the mechanism of GSIS. ### Final_Prediction: yes

### Question: Is cartilage thickness different in young subjects with and without patellofemoral pain? ### Context: To determine the differences in load-bearing patellofemoral joint cartilage thickness between genders. To determine the differences in load-bearing cartilage thickness between pain-free controls and individuals with patellofemoral pain.The articular cartilage thickness of the patella and anterior femur was estimated from magnetic resonance images in 16 young, pain-free control subjects (eight males, eight females) and 34 young individuals with patellofemoral pain (12 males, 22 females). The average age of all subjects was 28+/-4 years. The cartilage surfaces were divided into regions approximating the location of patellofemoral joint contact during knee flexion. The mean and peak cartilage thicknesses of each region were computed and compared using a repeated-measures Analysis of Variance.On average, males had 22% and 23% thicker cartilage than females in the patella (P<0.01) and femur (P<0.05), respectively. Male control subjects had 18% greater peak patellar cartilage thickness than males with patellofemoral pain (P<0.05); however, we did not detect differences in patellar cartilage thickness between female control subjects and females with patellofemoral pain (P = 0.45). We detected no significant differences in femoral cartilage thickness between the control and pain groups. ### Long_Answer: Thin cartilage at the patella may be one mechanism of patellofemoral pain in male subjects, but is unlikely to be a dominant factor in the development of pain in the female population. ### Final_Prediction: nan

### Question: Does plasma profiling reveal three proteins associated to amyotrophic lateral sclerosis? ### Context: Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease leading to muscular paralysis and death within 3-5 years from onset. Currently, there are no reliable and sensitive markers able to substantially shorten the diagnosis delay. The objective of the study was to analyze a large number of proteins in plasma from patients with various clinical phenotypes of ALS in search for novel proteins or protein profiles that could serve as potential indicators of disease.Affinity proteomics in the form of antibody suspension bead arrays were applied to profile plasma samples from 367 ALS patients and 101 controls. The plasma protein content was directly labeled and protein profiles obtained using 352 antibodies from the Human Protein Atlas targeting 278 proteins. A focused bead array was then built to further profile eight selected protein targets in all available samples.Disease-associated significant differences were observed and replicated for profiles from antibodies targeting the proteins: neurofilament medium polypeptide (NEFM), solute carrier family 25 (SLC25A20), and regulator of G-protein signaling 18 (RGS18). ### Long_Answer: Upon further validation in several independent cohorts with inclusion of a broad range of other neurological disorders as controls, the alterations of these three protein profiles in plasma could potentially provide new molecular markers of disease that contribute to the quest of understanding ALS pathology. ### Final_Prediction: yes

### Question: Are advanced glycation end products direct modulators of β-cell function? ### Context: Excess accumulation of advanced glycation end products (AGEs) contributes to aging and chronic diseases. We aimed to obtain evidence that exposure to AGEs plays a role in the development of type 1 diabetes (T1D).The effect of AGEs was examined on insulin secretion by MIN6N8 cells and mouse islets and in vivo in three separate rodent models: AGE-injected or high AGE-fed Sprague-Dawley rats and nonobese diabetic (NODLt) mice. Rodents were also treated with the AGE-lowering agent alagebrium.β-Cells exposed to AGEs displayed acute glucose-stimulated insulin secretory defects, mitochondrial abnormalities including excess superoxide generation, a decline in ATP content, loss of MnSOD activity, reduced calcium flux, and increased glucose uptake, all of which were improved with alagebrium treatment or with MnSOD adenoviral overexpression. Isolated mouse islets exposed to AGEs had decreased glucose-stimulated insulin secretion, increased mitochondrial superoxide production, and depletion of ATP content, which were improved with alagebrium or with MnTBAP, an SOD mimetic. In rats, transient or chronic exposure to AGEs caused progressive insulin secretory defects, superoxide generation, and β-cell death, ameliorated with alagebrium. NODLt mice had increased circulating AGEs in association with an increase in islet mitochondrial superoxide generation, which was prevented by alagebrium, which also reduced the incidence of autoimmune diabetes. Finally, at-risk children who progressed to T1D had higher AGE concentrations than matched nonprogressors. ### Long_Answer: These findings demonstrate that AGEs directly cause insulin secretory defects, most likely by impairing mitochondrial function, which may contribute to the development of T1D. ### Final_Prediction: yes

### Question: Do pre-admission clinical factors affect length of stay in the epilepsy monitoring unit? ### Context: Video-EEG monitoring in the epilepsy monitoring unit (EMU) is a limited clinical resource. Knowledge of the predicting factors for length of stay (LOS) in the EMU may allow providers to more efficiently utilize EMU bed space.The records for all consecutive admissions to the EMU at the University of Colorado Hospital between December 1, 2010 and May 31, 2011 (n = 142) were retrospectively reviewed.Univariate analyses focusing on variables known prior to admission showed that EMU LOS (in hours) was not significantly correlated with patient age, number of event types, or number of antiepileptic drugs at admission. Patients who were admitted to the EMU for event characterization had statistically significantly shorter average LOS than patients who had been admitted as a part of a presurgical evaluation. Patients who reported < = 1 seizure per week had a statistically significantly higher average LOS than patients who reported >= 1 seizure per day. These variables were also significantly predictive of total LOS (p < 0.0001 and p = 0.03, respectively) in multivariate analysis. ### Long_Answer: Pre-admission clinical variables may predict EMU LOS. These factors could be used at the administrative level for maximum EMU resource utilization. ### Final_Prediction: yes

### Question: Does eosinopenia in Children following Traumatic Intracranial Hemorrhage be Associated with Poor Prognosis and Prolonged Hospital Admission? ### Context: Neutrophilia is associated with brain injury and is frequently accompanied by eosinopenia. Although eosinopenia is a poor prognostic indicator for various diseases, its significance in intracranial events has not been investigated.We retrospectively included 22 pediatric patients (≤18 years old) who experienced traumatic intracranial hemorrhage between 2002 and 2015. Patients were divided into two groups based on the presence or absence of eosinopenia on admission, i.e. the proportion of eosinophils to total white blood cells <1.0%.The mean Glasgow Coma Scale score was marginally lower in the eosinopenia group (14.1 vs. 12.0, p = 0.06). The mean Glasgow Outcome Scale-Extended (GOSE) score was significantly lower in the eosinopenia group (7.5 vs. 5.7, p = 0.02), and the mean length of hospital stay tended to be longer in patients with eosinopenia (7.8 vs. 28.4, p = 0.10). In our multivariate logistic regression analysis, eosinopenia was the only significant risk factor for poor outcome (GOSE score 1-7, OR 29.7, p = 0.03) and prolonged hospital stay (>2 weeks, OR 7.1, p = 0.047). ### Long_Answer: These results demonstrate the significance of eosinopenia as a novel prognostic factor in traumatic intracranial hemorrhage in children. ### Final_Prediction: yes

### Question: Does attention bias away from threat during life threatening danger predict PTSD symptoms at one-year follow-up? ### Context: Recent studies find a correlation between attentional threat avoidance under stress and posttraumatic stress symptoms. In this study, we assessed this association longitudinally in exposed and unexposed individuals. The degree of threat avoidance during exposure was expected to predict levels of posttraumatic stress symptoms 1 year later.Thirty-two participants were recruited and followed for 12 months, including 18 subjects exposed to rocket attacks and 14 nonexposed subjects. At 1-year follow-up, participants completed self-reports and an attention dot-probe task assessing threat-related bias.State anxiety decreased at follow-up in exposed participants, though posttraumatic stress disorder (PTSD) and depression symptoms remained higher in exposed than in the nonexposed group. Attentional threat avoidance during imminent danger in the exposed group changed to threat attendance a year later, such that both the exposed and the nonexposed group exhibited similar threat bias patterns. As hypothesized, in the exposed group, stronger attentional threat avoidance during stress exposure predicted higher levels of PTSD symptoms 1 year later. ### Long_Answer: Attention bias away from threat during acute stress may relate to risk for PTSD. This suggests that neurocognitive measures may index risk for PTSD. ### Final_Prediction: yes

### Question: Is esophageal dilation for endosonographic evaluation of malignant esophageal strictures safe and effective? ### Context: Endoscopic ultrasound (EUS) is accepted as the most accurate modality for T- and N-staging of esophageal cancer, but some malignant strictures prevent passage of the echoendoscope beyond the level of the tumor. This incomplete evaluation may decrease staging accuracy. Previous studies have yielded conflicting results regarding the safety and efficacy of esophageal dilation for EUS.We prospectively evaluated 267 consecutive patients undergoing EUS for esophageal carcinoma staging at our institution over a 66-month period to determine the number of patients requiring dilation for EUS examination, the success of dilation, safety of dilation, and clinical importance.Among 267 endosonographic examinations of the esophagus, 81 (30.3%) required dilation to advance the echoendoscope beyond the level of the stricture. After dilation was performed, the echoendoscope could be passed through the stricture in 69 patients (85.2%), and in 63 of 67 of the patients dilated to > or = 14 mm (94.0%). No complications have occurred secondary to the dilations performed to permit completion of the endosonographic examination. Tumor staging by EUS after dilation was T2 (14.8%), T3 (56.8%), and T4 (21.0%), nodal staging N0 (14.6%) and N1 (75.3%); and M1 (9.9%). ### Long_Answer: We conclude that incremental, stepwise dilation of malignant strictures to 14 mm is safe and effective in permitting echoendoscope passage beyond the stenosis. The presence of a malignant stricture does not seem to diminish the utility of EUS staging of esophageal cancer. ### Final_Prediction: yes

### Question: Does dietary bile acid supplementation improve intestinal integrity and survival in a murine model? ### Context: In vitro supplementation of the bile salt, taurodeoxycholic acid (TDCA), has been shown to stimulate proliferation and prevent intestinal apoptosis in IEC-6 cells. We hypothesize that addition of TDCA to a rodent liquid diet will be protective against induced intestinal injury.C57Bl6 mice were fed a liquid diet with or without 50-mg/(kg d) TDCA supplementation. After 6 days, the mice were injected with lipopolysaccharide (LPS) (10 mg/kg) to induce intestinal injury. Specimens were obtained 24 hours later and evaluated for intestinal apoptosis, crypt proliferation, and villus length. A separate cohort of animals was injected with LPS (25 mg/kg) and followed 7 days for survival.Mice whose diet was supplemented with TDCA had significantly increased survival. After LPS-induced injury, mice supplemented with TDCA showed decreased intestinal apoptosis by both H&E and caspase-3. They also had increased intestinal proliferation by 5-bromo-2'deoxyuridine staining and increased villus length. ### Long_Answer: Dietary TDCA supplementation alleviates mucosal damage and improves survival after LPS-induced intestinal injury. Taurodeoxycholic acid is protective of the intestinal mucosa by increasing resistance to injury-induced apoptosis, stimulating enterocyte proliferation, and increasing villus length. Taurodeoxycholic acid supplementation also results in an increased survival benefit. Therefore, bile acid supplementation may potentially protect the intestine from injury or infection. ### Final_Prediction: yes

### Question: Does recurrent Clostridium difficile infection associate with distinct bile acid and microbiome profiles? ### Context: The healthy microbiome protects against the development of Clostridium difficile infection (CDI), which typically develops following antibiotics. The microbiome metabolises primary to secondary bile acids, a process if disrupted by antibiotics, may be critical for the initiation of CDI.To assess the levels of primary and secondary bile acids associated with CDI and associated microbial changes.Stool and serum were collected from patients with (i) first CDI (fCDI), (ii) recurrent CDI (rCDI) and (iii) healthy controls. 16S rRNA sequencing and bile salt metabolomics were performed. Random forest regression models were constructed to predict disease status. PICRUSt analyses were used to test for associations between predicted bacterial bile salt hydrolase (BSH) gene abundances and bile acid levels.Sixty patients (20 fCDI, 19 rCDI and 21 controls) were enrolled. Secondary bile acids in stool were significantly elevated in controls compared to rCDI and fCDI (P < 0.0001 and P = 0.0007 respectively). Primary bile acids in stool were significantly elevated in rCDI compared to controls (P < 0.0001) and in rCDI compared to fCDI (P = 0.02). Using random forest regression, we distinguished rCDI and fCDI patients 84.2% of the time using bile acid ratios. Stool deoxycholate to glycoursodeoxycholate ratio was the single best predictor. PICRUSt analyses found significant differences in predicted abundances of bacterial BSH genes in stool samples across the groups. ### Long_Answer: Primary and secondary bile acid composition in stool was different in those with rCDI, fCDI and controls. The ratio of stool deoxycholate to glycoursodeoxycholate was the single best predictor of disease state and may be a potential biomarker for recurrence. ### Final_Prediction: yes

### Question: Does apolipoprotein E deficiency worsen outcome from global cerebral ischemia in the mouse? ### Context: Apolipoprotein E (apoE) has been found relevant in a variety of central nervous system disorders. This experiment examined the effect of endogenous murine apoE on selective neuronal necrosis resulting from a transient forebrain ischemia insult.ApoE deficient (n=16) and wild type (n=17) halothane-anesthetized mice were subjected to severe forebrain ischemia (10 minutes of bilateral carotid occlusion and systemic hypotension). After 3 days' recovery, brain injury was determined histologically. In other apoE-deficient and wild-type mice, regional cerebral blood flow (CBF) was determined by 14C-iodoantipyrine autoradiography 10 minutes before, 5 minutes after onset of, and 30 minutes after reperfusion from 10 minutes of forebrain ischemia.The percentage of dead hippocampal CA1 neurons (mean+/-SD) was greater in the apoE-deficient group (apoE deficient=67+/-30%; wild type=37+/-33%; P=0.011). A similar pattern was observed in the caudoputamen (P=0.002) and neocortex (P=0.014). Cerebral blood flow was similar between groups at each measurement interval. Marked hypoperfusion persisted in both groups at 30 minutes after ischemia. ### Long_Answer: ApoE deficiency worsens ischemic outcome. This is not attributable to effects on CBF. A role of apoE in the cerebral response to global ischemia is consistent with prior reports that murine apoE deficiency increases infarct size resulting from focal cerebral ischemia. ### Final_Prediction: yes

### Question: Do an update on palonosetron hydrochloride for the treatment of radio/chemotherapy-induced nausea and vomiting? ### Context: Nausea and vomiting are well recognized in different clinical situations, suggesting that no single mechanism is likely to be responsible for their production. Chemotherapy-induced nausea and vomiting (CINV) can have a negative impact on quality of life and this may lead to a refusal of curative therapy or to a decline in palliative benefits offered by cytotoxic treatment. Palonosetron is a new agent in the class of 5-HT3 receptor antagonists (5-HT3RAs), and differs from the other agents by its higher receptor-binding affinity and longer half-life. These pharmacological properties have resulted in improved antiemetic activity in clinical trials, particularly in the treatment of delayed CINV following moderate emetogenic chemotherapy (MEC).A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library and meeting materials from ASCO and MASCC were all searched. ### Long_Answer: Palonosetron was the only serotonin receptor antagonist approved for prevention of delayed CINV caused by MEC and its use was incorporated in guideline recommendations. To date, several treatment settings such as multiple day chemotherapy require further studies to improve emesis related to therapy. ### Final_Prediction: yes

### Question: Is physical behavior affected in fatigued persons with multiple sclerosis? ### Context: To study physical behavior in detail in fatigued persons with multiple sclerosis (MS).Case-control explorative study.Outpatient rehabilitation department and participants' daily environment.Fatigued persons with MS (n=23) were selected from a randomized controlled trial. Cases were matched by age and sex to healthy, nonfatigued controls (n=23). Eligible persons with MS were severely fatigued (Checklist Individual Strength fatigue domain mean score, 43.2±6.6) and ambulatory (Expanded Disability Status Scale mean score, 2.5±1.5).Not applicable.Measurements were performed using an accelerometer over 7 days. Outcomes included the following: amount of physical activity expressed in counts per day, counts per minute (CPM), and counts per day period (morning, afternoon, evening); duration of activity intensity categories (sedentary, light physical activity, moderate-to-vigorous physical activity [MVPA]); and distribution of MVPA and sedentary periods over the day.Persons with MS had fewer counts per day (mean difference, -156×10(3); 95% confidence interval [CI], -273×10(3) to -39×10(3); P=.010), had fewer CPM (mean difference, -135; 95% CI, -256 to -14; P=.030), and were less physically active in the morning (mean difference, -200; 95% CI, -389 to -11; P=.039) and evening (mean difference, -175; 95% CI, -336 to -14; P=.034) than controls. Persons with MS spent a higher percentage of their time sedentary (mean difference, 5.6; 95% CI, .1-11.1; P=.045) and spent less time at the higher MVPA intensity (mean difference, -2.4; 95% CI, -4.7 to -0.09; P=.042). They had fewer MVPA periods (mean difference, 29; 95% CI, -56.2 to -2.6; P=.032) and a different distribution of sedentary (mean difference, .033; 95% CI, .002 to .064; P=.039) and MVPA periods (mean difference, -.08; 95% CI, -.15 to -.01; P=.023). ### Long_Answer: Detailed analyses of physical behavior showed that ambulatory fatigued persons with MS do differ from healthy controls not only in physical activity level, but also in other physical behavior dimensions (eg, day patterns, intensity, distribution). ### Final_Prediction: nan

### Question: Is interleukin-6 and interleukin-1 alpha production associated with antigen-induced late nasal response? ### Context: Cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-6 and granulocyte macrophage-colony stimulating factor (GM-CSF) are able to potentiate allergic inflammation and seem to be implicated in the development of the late allergic reaction.To study the time course of cytokine production, sequential lavages were performed after nasal allergen challenge. Thirteen patients with allergic rhinitis and four healthy subjects were exposed to grass pollen (n = 6 and n = 2, respectively) or dust mite allergen (n = 7 and n = 2, respectively).Among the patients with allergic rhinitis, a single early response (single responders) developed in four, eight exhibited a dual response (dual responders) and one patient as well as the four healthy subjects did not respond. In addition to the measurement of IL-1 alpha, IL-6, TNF-alpha and GM-CSF concentrations by ELISA, the release of histamine, tryptase, and eosinophil cationic protein was also evaluated by radioimmunoassay performed on nasal lavage fluids. Concerning mediator levels in nasal lavage fluid, neither histamine release nor cytokine elevation were noted in healthy subjects. As previously described, histamine, tryptase and eosinophil cationic protein were released in single and dual responders. Concerning cytokines, TNF-alpha was undetectable in the majority of nasal lavages and an increase in GM-CSF concentration was occasionally observed whatever the type of response. In contrast, an increase in IL-1 alpha and IL-6 levels was observed for dual responders during the early period (12.6 +/- 3 and 9.2 +/- 2 pg/ml, respectively; p < 0.01 in both cases) and at a higher level during the late period (14.5 +/- 4, p not significant and 16.7 +/- 8 pg/ml, respectively; p < 0.01) when compared with baseline values (7.2 +/- 2.2 and 2 +/- 0.7 pg/ml, respectively). For single responders IL-1 alpha and IL-6 secretion was detected mainly during the early period. ### Long_Answer: These data suggest a role for IL-1 alpha in the induction and perennisation of the inflammatory reaction in allergic rhinitis, whereas the role of IL-6 remains to be investigated. ### Final_Prediction: yes

### Question: Does barriers and challenges in research by Iranian students of medical universities? ### Context: Health sciences research (HSR) is an essential part of improving health care which plays a critical role in the field of medicine and clinical practice. The aim of the current study was to assess barriers to the research by students of medical sciences as well as to find out effective strategies for management of student researches in Iranian universities.This study utilized a hybrid design with quantitative and qualitative analytical approaches conducted on 627 students in six schools of medical sciences in two universities in Central Province in Iran from April to December, 2012. Questionnaires were distributed among researcher and non-researcher students to find barriers to the research. These barriers were approved and validated by similar studies and strategies using the Delphi technique on 36 students.The most important barriers among researcher students were institutional barriers (3.3 ± 1.3), but in non-researcher students they were individual barriers (3.6 ± 1.7). The majority of barriers to involvement in the research among researcher students appeared to be time, lack of access to electronic resources and prolongation of the process of buying equipment. In addition, the greatest barriers among non-researcher students included the lack of time, scientific writing skills, and access to trained assistants. ### Long_Answer: The results showed the issue of attitudes towards compulsory research as a component of critical scholarship in the curriculum of medical courses. Moreover, employment of the research experts can be helpful for research training in schools of medical sciences. ### Final_Prediction: yes

### Question: Dietary intakes and eating habits of college athletes: are female college athletes following the current sports nutrition standards? ### Context: The objective of this study was to assess dietary intakes and eating habits of female college athletes and compared them with the minimum sports nutrition standards.Data were obtained from 52 female college athletes from a National Collegiate Athletic Association (NCAA) Division I university between January 2009 and May 2010.Participants completed anthropometric measurements and dietary assessment using a 3-day food record, a 24-hour recall, and a nutrition questionnaire.t tests indicated the energy and carbohydrate intakes were below the minimum recommended amount (p<.001), with only 9% of the participants meeting their energy needs. Seventy-five percent of the participants failed to consume the minimum amount of carbohydrates that is required to support training. The majority of the participants reported no regular breakfast, 36% consumed<5 meals/day, and only 16% monitored their hydration status. ### Long_Answer: Effective nutrition interventions are needed to improve dietary intakes and eating habits of female college athletes. ### Final_Prediction: nan

### Question: Is symptom-oriented follow-up of early breast cancer inferior to conventional control . Results of a prospective multicentre study? ### Context: The homogeneity of the schemes for follow-up care after curative surgical treatment of early breast cancer is still a matter of debate in Germany. We investigated whether symptom-oriented follow-up is equivalent in terms of survival rates to conventional surveillance based on scheduled tests.In a prospective, non-randomised, multicentre cohort study carried out between 1995 and 2000, 244 patients underwent a conventional follow-up (scheduled laboratory tests including CEA and CA 15-3, chest X-rays and liver ultrasound). 426 patients were monitored in a symptom-oriented manner (additional tests only in the case of symptoms indicating possible recurrence). Mammography, structured histories and physical examinations were done regularly in both branches. 1,108 patients did not participate in the project. They represent 'real world patients', unaffected by the implications of a study.The symptom-oriented follow- up group produced results not inferior to those of the intensive one (p < 0.05) in terms of overall and relapse-free survival. Furthermore, no difference was indicated in terms of overall survival between study participants and the 'real world patients' (p = 0.316). ### Long_Answer: The results confirm that regular imaging and laboratory tests have no relevant effect on overall survival of patients after curative primary therapy of early breast cancer and support the implementation of a symptom-oriented routine follow-up. ### Final_Prediction: no

### Question: Is alcohol a risk factor for liver cirrhosis in HBsAg and anti-HCV negative subjects? ### Context: In order to evaluate the association between alcohol intake and the risk of liver cirrhosis in the absence of B and C hepatitis viruses, we analyzed data from three hospital-based case-control studies performed in various Italian areas.From the case and control series we excluded HBsAg and/or anti-HCV positive patients. Cases were 221 cirrhotic patients admitted for the first time to hospital for liver decompensation. Controls were 614 patients admitted to the same hospitals during the same period as the cases for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI).We found a dose-effect relationship between LDAI and the risk of liver cirrhosis (LC). Considering the extreme LDAI categories (LDAI = 0 g: lifetime teetotallers and LDAI>or = 100 g), the LC odds ratio (OR) increased from 1.0 (reference category) to 44.7 (95% confidence interval: 95% CI: 20.0-99.9). An increased risk of LC associated with the female gender independent of alcohol consumption was also observed (OR = 2.9; 95% CI: 1.8-4.6). ### Long_Answer: Alcohol intake acts as a risk factor for symptomatic liver cirrhosis also in the absence of HBV and/or HCV infection. Besides alcohol and viruses, some unknown gender-related factors might be involved in the occurrence of the disease. ### Final_Prediction: nan