Datasets:

krana

/

pubmed_processed

like 0

### Question: Sudden reversible vitritis after keratoprosthesis: an immune phenomenon? ### Context: To report our experience with late vitritis associated with keratoprosthesis (KPro).Between 1990 and 2003, 218 patients underwent an all-polymethylmethacrylate, collar button-shaped KPro surgery. Eight patients developed a total of 12 episodes of sudden, massive vitritis. Five of these patients had an Ahmed shunt implant, 3 had anterior vitrectomy during surgery, and 4 had a soft contact lens in place. Preoperative diagnoses were multiple graft failures, chemical burn, Stevens-Johnson syndrome, or ocular cicatricial pemphigoid. All patients were maintained on prophylactic topical ofloxacin 0.3% or polymyxin-B/trimethoprim, as well as prednisolone acetate 1% (in 2 cases, medroxyprogesterone 1%), at least twice daily. Vancomycin (14 mg/mL) was also given twice daily in 2 patients.Vitritis occurred in 8 patients (12 episodes), 2 to 23 months postoperatively. All patients presented with sudden, very marked decrease in vision, with little or no pain, tenderness, conjunctival redness, or discharge. Eight of the 12 events were subjected to vitreous tap and injection of antibiotics and steroids on the day of presentation. Cultures grew Staphylococcus epidermidis, only in liquid (broth) media, in 3 cases; the other 5 showed no growth. The vitritis episodes resolved after 2 to 9 weeks. Full recovery to pre-episode status of a quiet eye with clear vitreous was seen in all patients. Visual acuity recovered almost completely or completely (mental debilitation in one patient made accurate assessment uncertain). ### Long_Answer: This phenomenon of sudden vitritis after KPro, with few other symptoms and with complete recovery, would be uncharacteristic of a bacterial endophthalmitis. It may represent a uveitic immune phenomenon. ### Final_Prediction: nan

### Question: Is prolactin gene polymorphism ( -1149 G/T ) associated with hyperprolactinemia in patients with schizophrenia treated with antipsychotics? ### Context: Antipsychotic drugs can cause hyperprolactinemia. However, hyperprolactinemia was also observed in treatment-naive patients with a first schizophrenic episode. This phenomenon might be related to the role of prolactin as a cytokine in autoimmune diseases. Extrapituitary prolactin production is regulated by an alternative promoter, which contains the functional single nucleotide polymorphism -1149 G/T (rs1341239). We examined whether this polymorphism was associated with hyperprolactinemia in patients with schizophrenia.We recruited 443 patients with schizophrenia and 126 healthy controls. The functional polymorphism -1149 G/T (rs1341239) in the prolactin gene was genotyped with multiplexed primer extension, combined with MALDI-TOF mass spectrometry. Genotype and allele frequencies were compared between groups with the χThe frequency of genotypes and alleles in patients with schizophrenia did not differ from those in control subjects. A comparison between patients with schizophrenia with and without hyperprolactinemia revealed significantly higher frequency of the G allele in patients with hyperprolactinemia than in patients without it (χ ### Long_Answer: This study revealed a significant association between the polymorphic variant rs1341239 and the development of hyperprolactinemia in patients with schizophrenia. The serum prolactin concentration in patients with schizophrenia treated with antipsychotics may provide an indication of the activity of the gene that regulates extrapituitary prolactin production which is believed to play a role in the immune system. ### Final_Prediction: yes

### Question: Kaiy as traditional therapy for pain: is it helpful or a myth? ### Context: Two cases of traditional kaiy (Arabic for cauterisation) therapy for pain are reported. This technique is unknown in western countries and should be banned following a review of the topic.Many patients in developing countries use alternative, complementary or traditional therapies before seeking medical advice. This may be due to social or religious beliefs. Kaiy is one such traditional therapy which should be discouraged. Two cases are reported, the first with aural pain and the second with thyroid pain (with malignancy later diagnosed). ### Long_Answer: In these days of modern health care, the practice of kaiy is not science-based and is associated with considerable health risks. Health authorities in the relevant societies should move towards banning this undesirable practice; they should also use multi-media health education to advise of its dangerous outcomes, and enlist the help of community religious leaders to change public opinion and belief. ### Final_Prediction: nan

### Question: Is platelet-to-lymphocyte ratio a marker of poor prognosis in patients with diabetes mellitus and ST-elevation myocardial infarction? ### Context: Platelet-to-lymphocyte ratio (PLR) has emerged as a strong marker of worse outcomes. We determined the association between PLR and clinical outcomes in patients with diabetes mellitus and ST-elevation myocardial infarction.Five hundred and twenty three patients were enrolled. Low PLR (group 1, n = 349) was defined as ≤ 124 and high PLR (group 2, n = 174) as >124.In-hospital and 1-year mortality was higher in group 2. Receiver operating characteristic analysis revealed moderate diagnostic value in predicting in-hospital (PLR cut-off >155) and long-term (PLR cut-off >146) death. PLR remained an independent risk factor of early and late mortality. ### Long_Answer: PLR proved to have good prognostic value for in-hospital and late mortality. PLR cut-off value for predicting in-hospital mortality was higher to that predicting late mortality. PLR remained an independent risk factor early and late mortality. ### Final_Prediction: yes

### Question: Are serum levels of S100B , S100A1B and S100BB all related to outcome after severe traumatic brain injury? ### Context: S100B is an established marker of brain damage. Used in the context as a biochemical marker, S100B denotes a measurement of all S100 proteins, including at least one S100B monomer, i.e. the sum of the two dimers S100A1B and S100BB. Almost all published studies are based on this "sum concentration". However, the brain specificity of S100B has been questioned and increased serum levels have also been reported after trauma without head injury. Since the S100B monomer dominates in the brain, we hypothesised that the S100BB dimer should be better related to outcome after severe traumatic brain injury than S100A1B or the "sum concentration".Daily serum samples were collected from 59 patients with severe traumatic brain injury. Three different ELISA methods were used for measurements of S100B, S100A1B and S100BB respectively. Outcome was assessed after one year and categorised according to the Glasgow Outcome Scale.Serum levels of S100B, S100A1B and S100BB followed the same temporal course, with early maximum and rapidly decreasing values over the first days after the trauma. Maximum serum concentrations of each of the parameters were increased in the patient group with an unfavourable outcome compared with those with a favourable outcome (p = 0.01, 0.006 and 0.004, respectively). ### Long_Answer: Both S100A1B and S100BB were related to outcome after severe traumatic brain injury. Even though this study is small, it seems unlikely that separate analyses of the dimers are of any advantage compared with measuring S100B alone. ### Final_Prediction: yes

### Question: Does spinal anesthesia affect cerebral oxygenation during transurethral prostatectomy? ### Context: Transurethral resection of the prostate (TURP) is associated with the unique complication of transurethral resection of prostate syndrome (TURS), which is attributed to the absorption of irrigating fluid. This study was initiated to investigate the effects of spinal anesthesia and TURP on cerebral oxygen balance.Thirty patients scheduled for TURP were included. Jugular bulb oxygen saturation (SjbO2) was measured via retrograde cannulation of jugular venous bulb. Spinal anesthesia was initiated by 3 mL hyperbaric 0.5% bupivacaine injected at L3-L4 in the sitting position, producing a block to the T10 dermatome. Hemodynamic measurements and arterial and jugular bulb blood gasometry were performed before and after spinal anesthesia, throughout surgery, and during the postoperative period.A significant decrease of cerebral perfusion pressure after spinal anesthesia was accompanied by a significant decrease of SjbO2 below a preoperative value of 61% +/- 1. Eight patients developed yawning, irritability, restlessness, and nausea toward the end of surgery, and these were considered to be early signs of TURS. These patients demonstrated SjbO2 below 55% and 50% in 63% and 42% of respective data set points. ### Long_Answer: The neurologic symptoms in patients undergoing TURP during spinal anesthesia might not only be caused by absorption of irrigating fluid but also by impairment of cerebral oxygenation. ### Final_Prediction: nan

### Question: Detection of significant residual stenosis of the infarct-related artery after thrombolysis by high-dose dipyridamole echocardiography test: is it detected often enough? ### Context: It has been reported that high-dose dipyridamole echocardiography test (DET) can be successfully used for the detection of critical residual stenosis of the infarct-related artery (IRA). However, we have recently noticed low sensitivity of DET for the detection of residual IRA stenosis in patients with single-vessel disease. This study sought to determine the value of DET for the detection of significant residual stenosis of the IRA after thrombolysis.Dipyridamole echocardiography test was performed in 55 consecutive patients after a first acute myocardial infarction before hospital discharge. All patients underwent coronary angiography 23 +/- 6 days after infarction.Nine of 19 patients with positive DET revealed new adjacent asynergy and all of the patients had patient and significantly stenotic IRA. Sensitivity and specificity of DET in identifying significant residual stenosis of the IRA were 24 and 100%, respectively. Among 49 patients with significantly stenotic of occluded IRA, 40 patients without adjacent asynergy during DET had higher baseline wall motion score index (WMSI) compared with 9 patients who revealed adjacent asynergy during DET (1.45 +/- 0.30 vs. 1.24 +/- 0.18; p<0.05). When all patients with positive DET (adjacent or remote asynergy) were compared with those with negative DET, no difference in baseline WMSI was found (1.37 +/- 0.24 vs. 1.44 +/- 0.24; p>0.05). ### Long_Answer: Our data indicate that sensitivity of DET in detecting significant residual stenosis of the IRA after thrombolysis is low. It seems that the extent of myocardial infarction affects the ability of DET to detect adjacent, but not remote asynergy. ### Final_Prediction: nan

### Question: Are thoracic aortic aneurysm frequency and dissection associated with fibrillin-1 fragment concentrations in circulation? ### Context: Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA.Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection.Plasma samples were obtained from 1265 patients with aortic aneurysm or dissection and from 125 control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were measured with novel immunoassays. One hundred and seventy-four patients (13%) had aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and 1091 (86%) had TAA. Of those with TAA, 300 patients (27%) had chronic dissection and 109 (10%) had acute or subacute dissection. Associations of fragment concentrations with TAA (versus abdominal aortic aneurysm) or with dissection (versus no dissection) were estimated with odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, sex, and smoking. Compared with controls, significantly higher percentages of aneurysm patients had detectable levels of fibrillin fragments. TAA was significantly more common (than abdominal aortic aneurysm) in the highest compared with lowest quartile of fibrillin-1 concentration (OR=2.9; 95% CI, 1.6-5.0). Relative to TAA without dissection, acute or subacute dissection (OR=2.9; 95% CI, 1.6-5.3), but not chronic dissection, was more frequent in the highest compared with lowest quartile of fibrillin-1 concentration. Neither TAA nor dissection was associated with fibrillin-2 or fibulin-4. ### Long_Answer: Circulating fibrillin-1 fragments represent a new potential biomarker for TAA and acute aortic dissection. ### Final_Prediction: yes

### Question: Does genetic variation in caveolin-1 affect survival after lung transplantation? ### Context: Caveolin-1 (CAV-1), a structural protein of the cell membrane, is involved in tissue homeostasis, inflammation, oxidative stress, microbial clearance, and fibrosis.We investigated a genetic predisposition of the CAV-1 gene on survival, acute and chronic rejection, lymphocytic bronchiolitis (LB), and respiratory infection after lung transplantation (LTx).In 503 of 568 patients, the CAV-1 (rs3807989) polymorphism was successfully determined; 92 had the AA, 234 the AG, and 177 the GG genotype. Patients with the GG genotype had a decreased mortality with a adjusted hazard ratio of 0.72 (CI=0.53-0.98; P=0.034), but no association was found with chronic rejection, LB, acute rejection, or respiratory infections, although significantly less patients with the GG genotype died of infections (P=0.029). Airway neutrophilia (P=0.047) and systemic C-reactive protein (CRP, P=0.034) were decreased over time in the GG carriers compared to carriers of the A allele. ### Long_Answer: We conclude that the GG genotype of CAV-1 is protective, associated with a decreased overall mortality but not with acute or chronic rejection, LB, and respiratory infections after LTx. The decreased mortality was linked with less infections of any kind and also lower systemic CRP, and airway neutrophils were observed, suggesting an overall decreased susceptibility for infectious complications in carriers of the GG genotype. ### Final_Prediction: yes

### Question: Do patients with breast cancer participating in clinical trials receive better nursing care? ### Context: To examine differences in nursing care received by patients with breast cancer enrolled in clinical trials and those not enrolled in clinical trials.Retrospective review of clinic charts.Oncology outpatient department of a tertiary-care hospital.90 women with early stage breast cancer. The mean age of the women was 53 years. More than half of the women (51 of 90) were treated in a clinical trial.Retrospective chart review of all the nurse-patient clinic encounters for a six-month period from date of cancer diagnosis. The content of each encounter was coded using a modified version of the Nursing Action Classification System.Nursing interventions (i.e., assessment, medical scheduling, psychosocial scheduling, reassurance, and teaching) and phone calls.Women enrolled in clinical trials had more phone interactions with nursing staff (p = 0.003) and received teaching (p<0.001) and reassurance (p = 0.005) from nursing staff more often than women not enrolled in clinical trials. Controlling for age and stage of disease, teaching (p<0.001), and reassurance (p = 0.10) were the primary differences in nursing care between the patients enrolled in clinical trials and those not enrolled. ### Long_Answer: Differences in nursing care received exist between patients with breast cancer enrolled in clinical trials and those not enrolled. ### Final_Prediction: nan

### Question: Is serum level of adiponectin a surrogate independent biomarker of radiographic disease progression in early rheumatoid arthritis : results from the ESPOIR cohort? ### Context: Adipokines such as adiponectin, leptin, and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed to determine whether serum adipokine levels independently predicted early radiographic disease progression in early RA.In total, 791 patients were included from the prospective Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA (n = 632) or had undifferentiated arthritis (UA) (n = 159). Enzyme-linked immunosorbent assay (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and visfatin/NAMPT. In the RA group, we tested the association of serum adipokine levels and (a) baseline radiographic damage and (b) radiographic disease progression, defined as a change >0 or ≥ 5 in total Sharp-van der Heijde Score (∆SHS) between inclusion and 1 year (∆SHS ≥1 or rapid radiographic progression: ∆SHS ≥5), adjusting for confounders (age, sex, body-mass index, insulin resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health Assessment Questionnaire score, autoantibody status, steroid use, and radiographic evidence of RA damage at inclusion).Adiponectin level was independently associated with baseline total SHS (adjusted β = 0.12; P = 0.006). It was also associated with ∆SHS ≥1 (adjusted odds ratio (aOR) = 1.84 (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR = 1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin level predicted ∆SHS ≥5 (aOR = 2.0 (1.14 to 3.52)). Serum leptin level was independently associated only with ∆SHS >0 (aOR = 1.59 (1.05 to 2.42)). Conversely, serum visfatin/NAMPT level and radiographic disease progression were unrelated. Considering the receiver-operated characteristic curves, the best adiponectin cut-offs were 4.14 μg/ml for ∆SHS ≥1 and 6.04 μg/ml for ∆SHS ≥5, with a good specificity (58% and 75% for ∆SHS ≥1 and ∆SHS ≥5, respectively) and high negative predictive values (75% and 92% for ∆SHS ≥1 or ∆SHS ≥5, respectively). ### Long_Answer: Serum adiponectin level is a simple useful biomarker associated with early radiographic disease progression in early RA, independent of RA-confounding factors and metabolic status. ### Final_Prediction: yes

### Question: Is anxiety contagious-symptoms of anxiety in the terminally ill child affect long-term psychological well-being in bereaved parents? ### Context: We studied the relation between unrelieved symptoms in terminally ill children and the psychological well-being in the bereaved parents 4-9 years after their loss.We contacted parents in Sweden who had lost a child to a malignancy 1992-1997. The parents were asked to assess symptoms affecting their child's well-being during his or her last month of life, and their own current psychological well-being.Altogether 449/561 (80%) eligible parents supplied information on 19 specific symptoms that may occur in children with a malignancy and how each of these symptoms had affected their child's well-being during his or her last month of life (not applicable, none, low, moderate, or severe). These results were linked to questions concerning the parents' self-assessed mental health. Parents of children who were affected by disturbed sleep also had increased risk to develop these symptoms; RR 2.0 [1.4-2.9] for depression, 1.8 [1.3-2.5] for anxiety, 1.5 [1.2-1.8] for decreased psychological well-being, and 1.5 [1.3-1.9] for decreased quality of life. ### Long_Answer: Bereaved parents whose children were affected by anxiety or disturbed sleep due to anxiety or pain had an increased risk of long-term psychological morbidity. Reducing psychological complications in seriously ill children may also improve the psychological well-being in bereaved parents. ### Final_Prediction: yes

### Question: Is tissue microarray a reliable method for immunohistochemical analysis of pleomorphic adenoma? ### Context: To determine the most adequate number and size of tissue microarray (TMA) cores for pleomorphic adenoma immunohistochemical studies.Eighty-two pleomorphic adenoma cases were distributed in 3 TMA blocks assembled in triplicate containing 1.0-, 2.0-, and 3.0-mm cores. Immunohistochemical analysis against cytokeratin 7, Ki67, p63, and CD34 were performed and subsequently evaluated with PixelCount, nuclear, and microvessel software applications.The 1.0-mm TMA presented lower results than 2.0- and 3.0-mm TMAs versus conventional whole section slides. Possibly because of an increased amount of stromal tissue, 3.0-mm cores presented a higher microvessel density. Comparing the results obtained with one, two, and three 2.0-mm cores, there was no difference between triplicate or duplicate TMAs and a single-core TMA. ### Long_Answer: Considering the possible loss of cylinders during immunohistochemical reactions, 2.0-mm TMAs in duplicate are a more reliable approach for pleomorphic adenoma immunohistochemical study. ### Final_Prediction: yes

### Question: Do tendon proper- and peritenon-derived progenitor cells have unique tenogenic properties? ### Context: Multipotent progenitor populations exist within the tendon proper and peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials.Isolated progenitors were seeded within fibrinogen/thrombin gel-based constructs with or without supplementation with recombinant growth/differentiation factor-5 (GDF5). Early and late in culture, gene expression of differentiation markers and matrix assembly genes was analyzed. Tendon construct ultrastructure was also compared after 45 days. Moreover, conditioned media from tendon proper-derived progenitors, peritenon-derived progenitors, or tenocytes was applied to each of the three cell types to determine paracrine stimulatory effects of the factors secreted from each of the respective cell types.The cell orientation, extracellular domain and fibril organization of constructs were comparable to embryonic tendon. The tendon proper-derived progenitors produced a more tendon-like construct than the peritenon-derived progenitors. Seeded tendon proper-derived progenitors expressed greater levels of tenogenic markers and matrix assembly genes, relative to peritenon-derived progenitors. However, GDF5 supplementation improved expression of matrix assembly genes in peritenon progenitors and structurally led to increased mean fibril diameters. It also was found that peritenon-derived progenitors secrete factor(s) stimulatory to tenocytes and tendon proper progenitors. ### Long_Answer: Data demonstrate that, relative to peritenon-derived progenitors, tendon proper progenitors have greater potential for forming functional tendon-like tissue. Furthermore, factors secreted by peritenon-derived progenitors suggest a trophic role for this cell type as well. Thus, these findings highlight the synergistic potential of including these progenitor populations in restorative tendon engineering strategies. ### Final_Prediction: yes

### Question: Do electrocardiographic markers predict left ventricular wall motion improvement in patients with acute myocardial infarction receiving thrombolysis? ### Context: In patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolysis, prediction of early left ventricular wall motion changes is important for prognosis.In 106 patients with STEMI treated with thrombolysis, we analyzed the degrees of total and maximal ST-segment resolution at 3 hours and changes in sums of T-wave amplitudes in leads with ST elevation 3 and 48 hours after thrombolysis as the predictors of the echocardiographic left ventricular wall motion score index (WMSI) improvement.Wall motion score index improvement was best predicted by total ST-segment resolution of more than 44% in anterior infarctions (sensitivity, 81%; specificity, 62%) and more than 59% in nonanterior infarctions (sensitivity, 100%; specificity, 42%) and by difference in sums of T-wave amplitudes between electrocardiograms at 48 hours and baseline less than -28 mm (sensitivity, 68%; specificity, 76%). ### Long_Answer: In STEMI, the total ST-segment resolution 3 hours and T-wave changes at 48 hours after thrombolysis are the reliable predictors of the left ventricular WMSI improvement. ### Final_Prediction: yes

### Question: Are biochemicals associated with pain and inflammation elevated in sites near to and remote from active myofascial trigger points? ### Context: To investigate the biochemical milieu of the upper trapezius muscle in subjects with active, latent, or absent myofascial trigger points (MTPs) and to contrast this with that of the noninvolved gastrocnemius muscle.We used a microanalytic technique, including needle insertions at standardized locations in subjects identified as active (having neck pain and MTP), latent (no neck pain but with MTP), or normal (no neck pain, no MTP). We followed a predetermined sampling schedule; first in the trapezius muscle and then in normal gastrocnemius muscle, to measure pH, bradykinin, substance P, calcitonin gene-related peptide, tumor necrosis factor alpha, interleukin 1beta (IL-1beta), IL-6, IL-8, serotonin, and norepinephrine, using immunocapillary electrophoresis and capillary electrochromatography. Pressure algometry was obtained. We compared analyte concentrations among groups with 2-way repeated-measures analysis of variance.A biomedical research facility.Nine healthy volunteer subjects.Not applicable.Preselected analyte concentrations.Within the trapezius muscle, concentrations for all analytes were higher in active subjects than in latent or normal subjects (P<.002); pH was lower (P<.03). At needle insertion, analyte concentrations in the trapezius for the active group were always higher (pH not different) than concentrations in the gastrocnemius muscle. At all times within the gastrocnemius, the active group had higher concentrations of all analytes than did subjects in the latent and normal groups (P<.05); pH was lower (P<.01). ### Long_Answer: We have shown the feasibility of continuous, in vivo recovery of small molecules from soft tissue without harmful effects. Subjects with active MTPs in the trapezius muscle have a biochemical milieu of selected inflammatory mediators, neuropeptides, cytokines, and catecholamines different from subjects with latent or absent MTPs in their trapezius. These concentrations also differ quantitatively from a remote, uninvolved site in the gastrocnemius muscle. The milieu of the gastrocnemius in subjects with active MTPs in the trapezius differs from subjects without active MTPs. ### Final_Prediction: yes

### Question: Does cXCR2 blockade impair angiotensin II-induced CC chemokine synthesis and mononuclear leukocyte infiltration? ### Context: Angiotensin II (Ang-II) and mononuclear leukocytes are involved in atherosclerosis. This study reports the inhibition of Ang-II-induced mononuclear cell recruitment by CXCR2 antagonism and the mechanisms involved.Ang-II (1 nmol/L, i.p. in rats) induced CXC and CC chemokines, followed by neutrophil and mononuclear cell recruitment. Administration of the CXCR2 antagonist, SB-517785-M, inhibited the infiltration of both neutrophils (98%) and mononuclear cells (60%). SB-517785-M had no effect on the increase in CXC chemokine levels but reduced MCP-1, RANTES, and MIP-1alpha release by 66%, 63%, and 80%, respectively. Intravital microscopy showed that pretreatment with SB-517785-M inhibited Ang-II-induced arteriolar mononuclear leukocyte adhesion. Stimulation of human umbilical arterial endothelial cells (HUAECs) or whole blood with 1 micromol/L Ang-II induced the synthesis of chemokines. Ang-II increased HUAEC CXCR2 expression, and its blockade caused a significant reduction of MCP-1, -3, and RANTES release, as well as mononuclear cell arrest. Ang-II-induced MIP-1alpha release from blood cells was also inhibited. ### Long_Answer: Mononuclear leukocyte recruitment induced by Ang-II is, surprisingly, largely mediated by the CXC chemokines which appear to induce the release of CC chemokines. Therefore, CXC chemokine receptor antagonists may help to prevent mononuclear cell infiltration and the progression of the atherogenic process. ### Final_Prediction: yes

### Question: Are beliefs about medicines strongly associated with medicine-use patterns among the general population? ### Context: To investigate self-reported beliefs and perceived sensitivity to medicines and their effects in relation to self-reported use of medicines and herbal remedies.A survey sent to 13,931 randomly selected Swedish adults included the Beliefs about Medicines Questionnaire-General (BMQ-General) Questionnaire and the Perceived Sensitivity to Medicines Scale (PSM). The survey also asked about individuals' use of prescribed and over-the-counter (OTC) medicines and herbal remedies in the past month. We examined all associations between scores on the BMQ-General subscales and PSM in relation to the use of medicines and herbal remedies, using analysis of covariance adjusted for potential confounders.Among 7099 respondents, those using herbal remedies exclusively believed strongly that prescription and OTC medicines are harmful and overprescribed. Respondents using prescription and OTC medicines reported more positive beliefs [coefficient 0.67 (95% CI 0.47-0.87) and 0.70 (95% CI 0.51-0.90)] on the benefits of medicines compared with those using herbal remedies [-0.18 (95% CI -0.57-0.20)]. Perceived sensitivity to medicines was higher among those using herbal remedies only [1.25 (95% CI 0.46-2.03)] compared with those using no medicines (reference 0) or prescription [-0.44 (95% CI -0.84 to -0.05)] or OTC [-0.27 (95% CI -0.66-0.12)] medicines alone. ### Long_Answer: Respondents using prescription and/or OTC medicines reported stronger positive beliefs about the benefits of medicines in general, supporting the hypothesis that beliefs influence medicine use. Therefore, addressing beliefs and concerns about medicines during patient counselling may influence medicine use, particularly regarding unintentional non-adherence. ### Final_Prediction: yes

### Question: Is soluble galectin-3 a strong , colonic epithelial-cell-derived , lamina propria fibroblast-stimulating factor? ### Context: Colonic lamina propria fibroblasts (CLPFs) play an important role in the pathogenesis of fibrosis and strictures in Crohn's disease.To identify colonic epithelial cell (CEC)-derived factors that activate CLPFs.Primary human CECs and CLPFs were isolated from control mucosa and interleukin 8 (IL8) of CLPF cultures was quantified by ELISA. Activation of nuclear factor kappaB (NF-kappaB) was shown, and translocation of NF-kappaB was inhibited by a dominant-negative IkappaB-expressing adenovirus. The major CLPF-activating and IL8 inducing protein was purified using fast-performance liquid chromatography (HiPrep 16/60 Sephacryl S-200 High Resolution Column) and sodium dodecyl sulphate gel electrophoresis.A considerable increase in IL8 secretion by CLPFs cultured in CEC-conditioned media compared with that in unconditioned media (155.00 (10.00) pg/microg v 1.434 (0.695) pg/microg) was found. The effect of CEC-conditioned media on CLPF IL8 secretion was NF-kappaB dependent. A protein or DNA array confirmed the involvement of NF-kappaB and activator protein-1. Purification of a candidate band isolated with the use of sodium dodecyl sulphate-polyacrylamide gel electrophoresis and subsequent sequencing showed soluble galectin-3 to be a strong CLPF-activating factor. Depletion of galectin-3 from conditioned media by immunoprecipitation abolished the CLPF stimulatory effect. ### Long_Answer: Using a classical biochemical approach, soluble galectin-3 was identified as a strong activator of CLPFs produced by CEC. Galectin-3 induced NF-kappaB activation and IL8 secretion in these cells and may be a target for future therapeutic approaches to reduce or avoid stricture formation. ### Final_Prediction: yes

### Question: Does [ Impaired non-viral specific immune function of dendritic cell interfere with clearance and cytotoxic T lymphocyte response to HBV or HCV ]? ### Context: To investigate the correlation between impaired non-viral specific immune function of dendritic cell (DC) and viral clearance and cytotoxic T lymphocyte (CTL) response to HBV or HCV in patients with HBV and HCV coinfection.Twenty-five patients with HBV and HCV coinfection were investigated in this study. In 1994 and 2002, biochemical and virological markers and quantitative serum HBV DNA and HCV RNA levels were detected in these patients. According to the virus clearance status, these patients were divided into 4 groups: 14 patients with both HBV and HCV clearance (Group A), 6 patients with HCV clearance only (Group B), 3 patients with HBV clearance only (Group C), and 2 patients with persistent infection of HBV and HCV (Group D). Phenotypes and immune functions of monocyte-derived DCs were compared between these groups. 51Cr release assay were used to measure CTL response to epitopes derived from HBV, HCV or influenza virus (as positive control) in HLA-A2+ patients.Impaired non-viral specific immune functions of DCs were observed in group B, C and D compared with group A and normal donors (Group N). These impaired functions included CD86 decreasing expression and lower capacity to stimulating allogenic T cells and uptaking antigen. The specific CTL response to HBV- and HCV-derived peptides could be induced in group A (12/12). The specific CTL response to HBV-derived peptides or to HCV-derived peptides could be induced in group C (3/3) or B (5/5), respectively. But the specific CTL response to both of two HBV-derived peptides or two HCV-derived peptides could not be induced in group C (0/3) or B (0/5), respectively. And no CTL response to HBV or HCV-derived peptides could be induced in groups D (0/1) and N (0/4). ### Long_Answer: 1. The results suggest that specific CTL response to HBV or HCV play a vital role in the viral clearance. 2. The DCs with impaired non-viral specific immune functions exist in chronic patients with HBV and/or HCV infection, but do not interfere with clearance and CTL response to HBV or HCV. It is reasonable to speculate that impaired functions of DCs result from viral infection. ### Final_Prediction: no

### Question: Is high bone morphogenetic protein-15 level in follicular fluid associated with high quality oocyte and subsequent embryonic development? ### Context: Bone morphogenetic protein-15 (BMP-15) has been shown to influence oocyte maturation and quality. However, no relationship has been established between BMP-15 and oocyte quality/embryonic development in humans. The aim of this study is to investigate BMP-15 level in human follicular fluid (FF) and its possible role in determining oocyte quality and developmental potential.A total of 79 oocytes and their corresponding FF from 79 women undergoing ICSI were examined. Individual oocytes were inseminated and subsequently assessed on the basis of their fertilization, cleavage and preimplantation development. BMP-15, FSH, estradiol (E(2)) and progesterone levels of FF were also analysed via the techniques of western blot or radioimmunoassay.Higher FF BMP-15 levels were observed in the fertilized and cleaved groups versus the unfertilized and uncleaved groups, respectively (P < 0.05). The best (Grade I) embryo morphology was associated with higher FF BMP-15 levels than Grade II or III embryos (P < 0.01). A significant positive correlation was found between BMP-15 and E(2) levels in the same follicle. ### Long_Answer: The present study demonstrates that the BMP-15 level in FF appears to be a potential factor in predicting oocyte quality and subsequent embryo development, and is correlated with E(2) level, which may additionally be a valuable predictor of oocyte fertilization. ### Final_Prediction: yes

### Question: Does estrogen-dependent regulation of human uterine natural killer cells promote vascular remodelling via secretion of CCL2? ### Context: Does intrauterine biosynthesis of estrogen play an important role in early pregnancy by altering the function of uterine natural killer (uNK) cells? ### Long_Answer: Estrogens directly regulate the function of human uNK cells by increasing uNK cell migration and secretion of uNK cell-derived chemokine (C-C motif) ligand 2 (CCL2) that critically facilitates uNK-mediated angiogenesis. ### Final_Prediction: yes

### Question: Is portal hypertension associated with increased mRNA levels of vasopressor G-protein-coupled receptors in human hepatic arteries? ### Context: The contractile response of human splanchnic vessels to different vasoconstrictors is attenuated in cirrhosis. Functional studies indicate a cellular signalling defect upstream of the G-protein level. The aim of the present study was to analyze expression and mRNA levels of the following most relevant vasopressor receptors in the smooth musculature of human hepatic arteries: alpha1 adrenoceptor (AR) subtypes a, b and d, angiotensin II type 1 receptor (AT1), arginine vasopressin receptor type 1a (V1a), endothelin receptor type A (ETA) and B (ETB).Hepatic arteries were collected from 10 donors (noncirrhotic) and 14 recipients (cirrhotic) at liver transplantations. Real-time-PCR was performed to quantify steady-state levels of receptor mRNAs.alpha 1aAR mRNA levels showed no significant difference between the cirrhotic arteries and the controls while the mRNA levels of the other vasoactive receptors were significantly higher in the cirrhotic hepatic arteries (alpha 1bAR: 4-fold, P = 0.013; AT1: 16-fold, P = 0.024; V1a: 23-fold, P = 0.001; ETA: 4-fold, P = 0.02; ETB: 8-fold, P = 0.008). No mRNA for the alpha 1dAR was detected either in the donor or recipient hepatic arteries. ### Long_Answer: We conclude that vascular hyporeactivity to the most relevant endogenous vasoconstrictors of cirrhotic hepatic arteries is not caused by a receptor down-regulation at mRNA levels. In contrast they were up-regulated. ### Final_Prediction: yes

### Question: Body-image dissatisfaction in gay versus heterosexual men: is there really a difference? ### Context: Gay men are thought to experience body-image concerns or disorders more frequently than heterosexual men. It is unclear, however, whether these putative concerns are due to unrealistic body ideals (aspiring to a body shape that is difficult or impossible to attain), body-image distortion (misperceiving the actual shape of one's body), or both.We administered a well-established computerized body-image test, the "somatomorphic matrix," to 37 gay men recruited from the community in April 1999 and compared the results with previous data from 49 community-recruited heterosexual comparison men and 24 clinic-recruited heterosexual men with eating disorders.Gay men were indistinguishable from the community-recruited heterosexual comparison men on measures of both body ideals and body-image distortion. By contrast, eating-disordered men were significantly distinguishable from both other groups on body-image distortion. The lack of differences between community gay and heterosexual men on body-image indices seems unlikely to represent a type II error, since the somatomorphic matrix showed ample power to detect abnormalities in the eating-disordered men, despite the smaller sample size of the latter group. ### Long_Answer: Contrary to our hypotheses, gay men did not differ significantly from heterosexual men on measures of body image. These unexpected findings cast doubt on the widespread belief that gay men experience greater body-image dissatisfaction than heterosexual men. If our findings are valid, it follows that some previous studies of body image in gay men may possibly have been influenced by selection bias. ### Final_Prediction: nan

### Question: Improving the diagnostic yield of single-operator cholangioscopy-guided biopsy of indeterminate biliary strictures: ROSE to the rescue? ### Context: Tissue diagnosis, regardless of technique or endoscope used, can be challenging in patients with indeterminate biliary strictures (IDBSs). This exploratory study evaluated the utility and role of rapid onsite evaluation of touch imprint cytology (ROSE-TIC) when single-operator cholangioscopy (SOC)-guided biopsies of IDBSs are performed.Patients with IDBSs were evaluated by intraprocedural ROSE-TIC during SOC-guided biopsy procedures. Final diagnosis was established by long-term patient follow-up in conjunction with off-site findings or surgical histology. The main outcome measure was to evaluate the utility of ROSE-TIC by determination of its operating characteristics and comparison with off-site histologic assessment.Of 31 patients with IDBSs, tissue diagnosis was indeterminate at prior ERCP-guided brush and/or biopsy in 14, prior EUS-guided FNA (EUS-FNA) in 6, and a mass could not be identified at EUS in 11. The mean number of biopsies performed was 3.3 (range 1-8), and diagnostic interpretation by ROSE-TIC was diagnostic and/or suspicious for carcinoma in 15, benign in 13, atypical-reactive in 2, and bile duct intraductal papillary mucinous neoplasm in 1. Final diagnosis by surgical histology (n = 4), death by disease (n = 10), and patient follow-up (n = 17) showed that the overall sensitivity of ROSE-TIC for diagnosing malignancy was 100%, specificity 88.9%, positive predictive value 86.7%, negative predictive value 100%, and diagnostic accuracy 93.5%. ### Long_Answer: Preliminary data suggest that the diagnostic outcomes of SOC-guided biopsies in IDBSs can be significantly improved by using ROSE-TIC. This technique also may benefit centers that rely mainly on fluoroscopy-guided intraductal biopsies. ### Final_Prediction: nan

### Question: Does the association of bulbar conjunctival fold with other clinical findings in normal and moderate dry eye subjects? ### Context: Conjunctival folds have been reported as incidental findings in routine biomicroscopic examination, especially related to patients with dry eye disease. We compared the number of lower temporal lid-parallel conjunctival folds (LIPCOF) in normal and moderate dry-eyed patients with specific biomicroscopic findings (corneal staining, limbal injection, and bulbar conjunctival injection) and tear osmolality.Fourteen moderate dry eye subjects (12 female, 2 male; mean age, 43.4 years--range, 23 to 71 years) and eight normal subjects (3 female, 5 male; mean age, 37.25 years--range, 20 to 55 years) participated in this study. Bulbar conjunctival folds were quantified in the temporal aspect of each eye following fluorescein instillation. Tear osmolality was measured with a vapor pressure osmometer.There was a slight difference in the number of bulbar conjunctival folds between the moderate dry eye group and the normal controls (2.07 +/- 2.16 vs. 2.25 +/- 0.70, p = 0.676). Conjunctival folds were not correlated with any of the above parameters nor were they associated with the age of the subject. However, the study did reveal that tear osmolality (p = 0.005), corneal staining (p = 0.019), and conjunctival bulbar injection (p = 0.016) were significantly higher in the moderate dry eye group of subjects (Mann Whitney U Test). A significant correlation (Spearmans rho) was found between limbal injection (r2 = 0.535, p = 0.01) and comeal staining. Age was only found to be correlated with tear osmolality (r2 = 0.520, p = 0.013). ### Long_Answer: Although there was a small difference in the number of conjunctival folds between normal and moderate dry eye subjects, they do not appear to be as discriminating as other variables measured in the study. Additionally, age does not affect the number of conjunctival folds. ### Final_Prediction: yes

### Question: Is microRNA-21 a unique signature associated with coronary plaque instability in humans by regulating matrix metalloproteinase-9 via reversion-inducing cysteine-rich protein with Kazal motifs? ### Context: Coronary atherosclerotic unstable plaque is one of the leading causes of cardiovascular death. Macrophage-derived matrix metalloproteinase (MMP) 9 is considered for degrading extracellular matrix and collagen, thereby thinning the fibrous cap in plaques. miR-21 is implicated to play an important role in the progression of atherosclerosis. Nevertheless, miR-21 as the biomarker for coronary atherosclerotic unstable plaque remains unknown. We aimed to investigate the prediction role of miR-21 for unstable plaque by pathway study of miR-21 on MMPs and its inhibitor RECK in macrophages.Expression of miR-21 in macrophages and serum miR-21 as well as MMP-9 was measured in patients with coronary non-calcified plaque, calcified plaque and controls. In vitro experiment was done in human macrophages by over-expressing miR-21 or down-regulating RECK. The regulation of RECK and MMP-9 by miR-21 was evaluated by western blotting and siRNA strategy.Patients with non-calcified coronary artery lesions had significantly higher miR-21 in macrophages and lower miR-21 serum levels compared to the control and calcified plaque patients. At the same time, the serum levels of MMP-9 were significantly elevated in non-calcified patients. Experiments in vitro indicated that over-expressing miR-21 could induce the expression and secretion of pro-MMP-9 and active-MMP-9 in human macrophages via targeting gene RECK, and knocking down RECK expression by specific siRNA can resemble that of miR-21 over-expression. ### Long_Answer: miR-21 might be a biomarker for plaque instability by suppressing target gene RECK to promote the expression and secretion of MMP-9 in macrophages. ### Final_Prediction: yes

### Question: Does insulin-like growth factor binding protein-5 influence pancreatic cancer cell growth? ### Context: To investigate the functional significance of insulin-like growth factor binding protein-5 (IGFBP-5) overexpression in pancreatic cancer (PaC).The effects of IGFBP-5 on cell growth were assessed by stable transfection of BxPC-3 and PANC-1 cell lines and measuring cell number and DNA synthesis. Alterations in the cell cycle were assessed by flow cytometry and immunoblot analyses. Changes in cell survival and signal transduction were evaluated after mitogen activated protein kinase and phosphatidylinositol 3-kinase (PI3K) inhibitor treatment.After serum deprivation, IGFBP-5 expression increased both cell number and DNA synthesis in BxPC-3 cells, but reduced cell number in PANC-1 cells. Consistent with this observation, cell cycle analysis of IGFBP-5-expressing cells revealed accelerated cell cycle progression in BxPC-3 and G2/M arrest of PANC-1 cells. Signal transduction analysis revealed that Akt activation was increased in BxPC-3, but reduced in PANC-1 cells that express IGFBP-5. Inhibition of PI3K with LY294002 suppressed extracellular signal-regulated kinase-1 and -2 (ERK1/2) activation in BxPC-3, but enhanced ERK1/2 activation in PANC-1 cells that express IGFBP-5. When MEK1/2 was blocked, Akt activation remained elevated in IGFBP-5 expressing PaC cells; however, inhibition of PI3K or MEK1/2 abrogated IGFBP-5-mediated cell survival. ### Long_Answer: These results indicate that IGFBP-5 expression affects the cell cycle and survival signal pathways and thus it may be an important mediator of PaC cell growth. ### Final_Prediction: yes

### Question: Does fasting insulin modify the relation between age and renal function? ### Context: The worldwide increase in end-stage renal disease has been alleged to be associated with insulin resistance-related conditions. Insulin resistance and the concomitant compensatory hyperinsulinaemia may accelerate age-related decline in renal function through inducing glomerular hyperfiltration, even in non-diabetic subjects. This population-based study is the first to investigate whether fasting insulin concentrations modify the relationship between age and renal function in a general non-diabetic population.Fasting insulin was measured in 3432 subjects, representing the general population. Cross-sectional analyses of the association between age, renal function and its modification by insulin were performed by means of linear regression. Renal function was assessed as 24-h creatinine clearance (CrCl) and 24-h urinary albumine excretion (UAE).Age was 48 +/- 12 (range: 28-75) years, 44% were male, CrCl was 100 +/- 26 ml/min and UAE was 7.0 (5.4-10.7)] mg/24 h. The results confirmed a parabolic relation between age and renal function. Fasting insulin modified these parabolic relationships of age with CrCl and UAE (P < 0.001 for both interaction terms), in such a way that hyperinsulinaemia is associated with a stronger inverse parabolic relation between age and CrCl, and stronger positive parabolic relation between age and UAE at an older age than lower insulin concentrations. ### Long_Answer: Our results are consistent with the hypothesis that insulin accelerates the age-related decline of renal function in the general non-diabetic population. This indicates that insulin resistance, and the concomitant compensatory hyperinsulinaemia could contribute to the increased incidence in end-stage renal disease. ### Final_Prediction: yes

### Question: Does maternal hypomagnesemia cause placental abnormalities and fetal and postnatal mortality? ### Context: Magnesium (Mg(2+)) is essential for cellular growth and the maintenance of normal cellular processes. However, little is known about how maternal hypomagnesemia during pregnancy affects fetal growth and development. This study investigated the effects of maternal hypomagnesemia on the late gestation placenta and fetus, and postnatal outcomes until weaning.Female CD1 mice consumed a control (0.2% w/w Mg(2+)), moderately Mg(2+) deficient (MMD; 0.02% w/w Mg(2+)) or severely Mg(2+) deficient (SMD; 0.005% w/w Mg(2+)) diet for 4 weeks prior to mating and throughout pregnancy. Dams were killed at E18.5 for embryonic studies or allowed to litter naturally and the offspring studied up to postnatal day 21.At E18.5, both Mg(2+) deficient diets decreased maternal plasma and bone Mg(2+) but only the SMD diet decreased fetal plasma Mg(2+). Maternal hypomagnesemia led to fetal loss and fetal growth restriction. Maternal Mg(2+) deficiency increased placental glycogen cell area and decreased spongiotrophoblast cell area while upregulating mRNA expression of the MagT1 Mg(2+) transporter in spongiotrophoblast cells. The SMD animals also displayed instances of gross placental abnormalities. After birth, pups in the SMD group had increased early postnatal mortality and failed to thrive. Pups in the MMD group underwent catch-up growth but remained shorter than controls at PN21 and were hypomagnesemic and hypoglycemic. ### Long_Answer: These changes suggest that maternal Mg(2+) deficiency during pregnancy impairs placental development and fetal growth, which may have long-term health consequences for offspring. Collectively, these results have important implications for women who are Mg(2+) deficient during pregnancy. ### Final_Prediction: yes

### Question: Trends in use of barium enema examination, colonoscopy, and sigmoidoscopy: is use commensurate with risk of disease? ### Context: To assess replacement of barium enema examination with colonoscopy in relation to age- and sex-related risk factors, place of service, physician specialty, and cost.Between 1985 and 1992, 894,777 insurance claims for barium enema examination and lower gastrointestinal endoscopy were retrospectively examined. Changes in use were investigated. Use of proctosigmoidoscopy and flexible sigmoidoscopy, two office-based endoscopic procedures, was also examined.Use of diagnostic colonoscopy increased from 191 to 406 services per 100,000 persons; colonoscopy with biopsy, from 77 to 183 services; and colonoscopy with lesion removal, from 77 to 202 services. Barium enema examination use declined from 929 to 511 services per 100,000 persons; diagnostic proctosigmoidoscopy, from 854 to 193 services; and diagnostic flexible sigmoidoscopy, from 656 to 620 services. Increases in use of colonoscopy in patients aged younger than 40 years were greater than overall increases. ### Long_Answer: Colonoscopy has been replacing barium enema examination as the initial colorectal examination since 1985. Increased use of colonoscopy in patients with lower risk of neoplasia suggests that indications have become overly broad. ### Final_Prediction: nan

### Question: Do bovine pericardium buttress reinforces colorectal anastomoses in a canine model? ### Context: The consequences of an anastomotic leak or disruption can be devastating, particularly in the colorectal surgery population. The purpose of this study was to evaluate and compare colon anastomoses with or without a collagen matrix buttress derived from bovine pericardium.A circular stapler was used to create colon-colon anastomoses in a canine model. Twenty animals underwent two anastomoses each: one buttressed with bovine pericardium, and one without any reinforcement. Staple lines were evaluated at Days 0, 3, 7, 14, 42, and 84. Three animals were killed at each time interval, and evaluation included bursting pressure, bursting location, and histology.Colon segments with nonbuttressed anastomoses were more likely to burst at the staple line (63 percent), whereas buttressed anastomoses were more likely to burst at the adjacent intestine (74 percent; P=0.048). The burst pressure of nonbuttressed staple lines tended to be consistently, although not significantly, higher than the burst pressure of buttressed staple lines (P=0.651). At histologic analysis, the bovine pericardium buttress demonstrated an ability to allow cellular ingrowth at Day 3 and neovascularization at Day 7. There was no evidence of stenosis or infection. ### Long_Answer: The use of a collagen matrix buttress in colorectal anastomoses was safe in a canine model. Our study indicates that true burst strength of the majority of buttressed anastomoses was greater than the adjacent intestine. ### Final_Prediction: yes

### Question: Do sedative and hypnotic effect of freeze-dried paeoniflorin and sini san freeze-dried powder in pentobarbital sodium-induced mice? ### Context: To investigate the sedative and hypnotic activity of paeoniflorin and freeze-dried Sini San powder on mice and provide a reliable method for determining the pharmacodynamic material basis of Sini San.Male adult mice weighing 20-22 g were used in this study. Three experiments were carried out. Synergism with pentobarbital was used as an index for hypnotic effect. Loss of the righting reflex was used to determine the start of sleep. Sleep latency and sleeping time were recorded in each experiment.The coefficient of variation of the suprathreshold dose (55 mg/kg) was significantly lower than that of the threshold dose. The sleep latency of mice was significantly decreased, and the sleeping time of mice was significantly prolonged. The effects of paeoniflorin and Sini San on prolonging the sleeping time of mice induced by pentobarbital sodium were significantly stronger than those in the control group. ### Long_Answer: Paeoniflorin produces significant sedative and hypnotic effects, and there is an obvious dose-effect relationship. ### Final_Prediction: yes

### Question: Does an active lifestyle induce positive antioxidant enzyme modulation in peripheral blood mononuclear cells of overweight/obese postmenopausal women? ### Context: The aim of this study was to investigate the effects of an active lifestyle on mitochondrial functioning, viability, bioenergetics, and redox status markers in peripheral blood mononuclear cells (PBMC) of overweight/ obese postmenopausal women.We performed a cross-sectional study with postmenopausal women aged 45–64 years and body mass index N 25 kg/m2, divided into physically active (n = 23) and sedentary (n = 12) groups. Mitochondria functioning and viability, bioenergetics and redox status parameters were assessed in PBMC with spectrophotometric and fluorometric assays.No differences were found in the enzyme activity of complexes I and II of the electron transport chain (ETC), mitochondrial superoxide dismutase (MnSOD) activity, methyl-tetrazolium reduction levels and reduced glutathione and oxidized glutathione levels between the groups. However, the physically active group presented higher levels of reactive oxygen species (ROS) (P= 0.04) and increased catalase (CAT) (P= 0.029), total (P= 0.011) and cytosolic SOD (CuZnSOD) (P= 0.009) activities. ### Long_Answer: An active lifestyle that includes aerobic exercise for at least 30 min, three times per week may improve antioxidant enzyme activities in PBMC in overweight/obese postmenopausal women, without changes in the activity of the ETC enzymes. However, this low intensity physical activity is not able to induce relevant mitochondrial adaptations. ### Final_Prediction: yes

### Question: Are single nucleotide polymorphisms in new candidate genes associated with bone mineral density and fracture risk? ### Context: Osteoporosis (OP) is a multifactorial disease with high heritability but its exact genetic background is still poorly understood. We examined the effect of 24 single nucleotide polymorphisms (SNPs) located in five genes--alkaline phosphatase, matrix metalloproteinase-2, tissue inhibitor of metalloproteases-2 (TIMP2), fibroblast growth factor receptor-1 (FGFR1), and fatty acid-binding protein-3 (FABP3)--previously not associated with OP.We performed a genotype-phenotype association study at a university hospital.A total of 360 Hungarian postmenopausal women were involved in the study. Bone mineral density (BMD) was determined at spine, hip, and distal radius. Genomic DNA was extracted from venous blood samples and a high-throughput genotyping method based on single-based primer extension was applied for allelic discrimination. Robust statistical tools were utilized for multiplex data analysis.SNP rs6996321 in FGFR1 was significantly related to spine BMD (P=0.002) and rs10914367 in FABP3 was associated with hip BMD (P=0.028). Non-vertebral fracture risk was significantly increased in carriers of 'A' allele of rs9900972 in TIMP2 (odds ratio=2.06, P=0.0187). We could also identify validated gene-gene interactions significantly affecting BMD and fracture risk. ### Long_Answer: We identified two previously unreported SNPs in FGFR1 and FABP3 associated with BMD and a third SNP in TIMP2 related to risk for non-vertebral osteoporotic fractures. This is the first report about the association between these allelic variants and the phenotypes of postmenopausal OP. Further studies need to clarify the role of these genes and their polymorphisms in the process of bone loss. ### Final_Prediction: yes

### Question: Does a high-fat diet decrease GABA concentration in the frontal cortex and hippocampus of rats? ### Context: It has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats.The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats. ### Long_Answer: HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior. ### Final_Prediction: yes

### Question: Is expression of caveolin-1 associated with poor prognosis of patients with squamous cell carcinoma of the lung? ### Context: Caveolin-1, as a major component of caveolae, is involved in the regulation of cell cycle by impacting various signaling pathways. Previous studies of caveolin-1 in cancer showed two contrary results. In most in vitro studies, caveolin-1 played a role as a tumor suppressor. On the other hand, the elevated expression of caveolin-1 was often reported to be associated with poor clinical outcome in human studies. These results indicate differential biological functions of caveolin-1 depending on the development and progression stage of cancer in vivo.To clarify the correlation between the clinicopathologic profiles of pulmonary squamous cell carcinomas and the expression of caveolin-1, 107 cases of formalin-fixed and paraffin-embedded tissues of pulmonary squamous cell carcinomas were immunohistochemically evaluated for the expression of caveolin-1 by the tissue-array method.Caveolin-1 was expressed in 34 cases (31.7%) among 107 cases of pulmonary squamous cell carcinoma. The expression of caveolin-1 was statistically correlated with pathologic stage (stage I and II vs. III; P<0.001), pT (T1 and T2 vs. T3 and T4; P=0.001), and pN (N1 vs. N2 and N3; P=0.0143). The patients with caveolin-1 expression in pulmonary squamous cell carcinomas showed a poorer prognosis than those in caveolin-1-negative group (P=0.0345). ### Long_Answer: The expression of caveolin-1 is significantly correlated with advanced pathologic stage and poor prognosis in pulmonary squamous cell carcinoma. The results of current study suggest that the expression level of caveolin-1 may be a candidate factor for predicting prognosis in patients with pulmonary squamous cell carcinoma. ### Final_Prediction: yes

### Question: Does rimonabant block the expression but not the development of locomotor sensitization to nicotine in rats? ### Context: Cannabinoid, especially CB(1,) receptors have been implicated in the development and expression of a variety of behaviors produced by addictive drugs.The intent was to determine if coadministration of the selective CB(1) receptor antagonist, rimonabant (SR141716A), would block the development or expression of locomotor sensitization to repeated injections of nicotine.Male Long-Evans rats were injected with either 2 mg/kg rimonabant or its vehicle 30 min before an injection of 0.4 mg/kg nicotine or saline and immediately placed in activity chambers for 1 h on each of six sessions on alternating days. Before the two subsequent challenge sessions, all rats were injected with the vehicle and 0.4 mg/kg nicotine combination and then with the 2 mg/kg rimonabant and 0.4 mg/kg nicotine combination, respectively.Repeated injections of nicotine produced a progressive increase in locomotion that was blocked by coadministration of rimonabant. However, the subsequent nicotine challenge increased locomotion in both nicotine-pretreated groups equally more than in the saline-pretreated groups. Coadministration of rimonabant along with nicotine on the second challenge decreased the locomotion of the nicotine-pretreated rats to equal that of the saline-pretreated rats. Rimonabant had no effect on the saline-pretreated rats. ### Long_Answer: These data suggest that rimonabant blocks the expression but not the development of locomotor sensitization to nicotine. ### Final_Prediction: yes

### Question: Can augmentation index be used as an accurate tool in the diagnosis of peripheral obstructive arterial disease? ### Context: The use of radial augmentation index (rAI) as an indicator of vascular disease was investigated in the vascular imaging laboratory in a regional hospital.The aim of this study was to investigate whether a correlation exists between ankle-brachial pressure index (ABPI) and rAI in normal subjects, patients with peripheral obstructive arterial disease, and diabetic patients.A group of 46 patients and 14 controls had ABPI and rAI measured and factors affecting AI were assessed.rAI was found to have a negative correlation with ABPI (Spearman's ρ = -0.513, p<0.01). There was significant increase in the rAI scores of diabetic patients compared to normal patients (normal median was 64% lower than diabetic median, p<0.01) and in peripheral obstructive vascular disease patients compared to normal (normal median 69% lower, p<0.001). Of the various affecting factors, age stood out with rAI having a positive correlation to age (Spearman's ρ = 0.68, p<0.01). ### Long_Answer: The augmentation index appears be a significant indicator of cardiovascular disease and may be a useful tool in the diagnosis of vascular pathology. ### Final_Prediction: nan

### Question: Does administration of microRNA-210 promote spinal cord regeneration in mice? ### Context: Experimental animal study of treatment of spinal cord injury (SCI).To investigate the therapeutic effects of administering microRNA-210 (miR-210) to promote angiogenesis in a mouse SCI model.Despite many previous studies regarding SCI, there is no established treatment in clinical practice. miRNAs have attracted immense attention because of their crucial role in human disease, and they have been proposed as potential new therapeutic targets for SCI.At specific times after administration, mice were analyzed by several methods to examine the distribution of miR-210, histological angiogenesis and neurogenesis, functional recovery from SCI, and the expression levels of target genes of miR-210.After injection of miR-210 into the lesion of the injured spinal cord, expression of endogenous miR-210 increased until 6 days after injection. The administration of miR-210 promoted angiogenesis and astrogliosis, and improved functional recovery after SCI compared with the noninjected controls. Furthermore, the area made up of axons and myelin in the spinal cord tissues caudal to the injury site was larger in mice injected with miR-210 than those of the controls. Apoptotic cell death was lower in mice administered miR-210. After administration of miR-210, the expressions of protein-tyrosine phosphate 1B and ephrin-A3, both gene targets of miR-210, were downregulated at the protein level and protein-tyrosine phosphate 1B expression was also downregulated at the transcriptional level. ### Long_Answer: MiR-210 might contribute to spinal cord repair by promoting angiogenesis via the inhibition of protein-tyrosine phosphate 1B and ephrin-A3. ### Final_Prediction: yes

### Question: Do challenges in the peer review of systematic reviews and meta-analyses? ### Context: To assess the role of the referees in assisting the peer review process of systematic reviews and meta-analyses.A one-page questionnaire was mailed to 1391 referees of two journals, the American Journal of Obstetrics and Gynecology and Obstetrics and Gynecology. The referees were asked how often they verified by their own independent analysis 11 key items related to the methodology and statistical analysis of systematic reviews and meta-analyses. Response categories included "always", "frequently" (>50% of the time), "infrequently" (≤ 50% of the time) and "never". A second and a third mailing was sent to the non-respondents.42 mailings were returned because of change of address. Of the remaining 1349 referees, 272 responded (response rate 20%). Of the 272 respondents, 159 (58%) had previously reviewed articles dealing with systematic reviews or meta-analyses. The responses varied according to the key items in the questions but the referees used their own independent analyses "always" in only 2%-17% of the time. The rates of "infrequently" or "never" responses combined together ranged from 51% to 86% for the various key items. ### Long_Answer: The overwhelming majority of the referees do not verify, by their own independent analysis, key items related to methodology and statistical analysis of submitted systematic reviews and meta-analyses. ### Final_Prediction: yes

### Question: Do α ( 2 ) Adrenergic and imidazoline receptor agonists prevent cue-induced cocaine seeking? ### Context: Drug-associated cues can elicit stress-like responses in addicted individuals, indicating that cue- and stress-induced drug relapse may share some neural mechanisms. It is unknown whether α(2) adrenergic receptor agonists, which are known to attenuate stress-induced reinstatement of drug seeking in rats, also reduce cue-induced reinstatement.Rats were tested for reinstatement of drug seeking following cocaine self-administration and extinction. We first evaluated the effects of clonidine, an agonist at α(2) and imidazoline-1 (I(1)) receptors, on relapse to cocaine seeking. To explore possible mechanisms of clonidine's effects, we then tested more specific α(2) or I(1) agonists, postsynaptic adrenergic receptor (α(1) and β) antagonists, and corticotropin-releasing factor receptor-1 antagonists.We found that clonidine, and the more selective α(2) agonists UK-14,304 and guanfacine, decreased cue-induced reinstatement of cocaine seeking. The specific I(1) receptor agonist moxonidine reduced cue-induced as well as cocaine-induced reinstatement. Clonidine or moxonidine effects on cue-induced reinstatement were reversed by the selective α(2) receptor antagonist RS-79948, indicating a role for α(2) receptors. Prazosin and propranolol, antagonists at the α(1) and β receptor, respectively, reduced cue-induced reinstatement only when administered in combination. Finally, the corticotropin-releasing factor receptor-1 antagonist CP-154,526 reduced cue-induced reinstatement, as previously observed for stress-induced reinstatement, indicating possible overlap between stress and cue mechanisms. ### Long_Answer: These results indicate that α(2) and I(1) receptor agonists are novel therapeutic options for prevention of cue-induced cocaine relapse. Given that α(2) receptor stimulation is associated with sedation in humans, the I(1) agonist moxonidine seems to have substantial potential for treating addictive disorders. ### Final_Prediction: yes

### Question: Does the method of radiologic surveillance affect survival after resection of stage I non-small cell lung cancer? ### Context: Controversy persists regarding appropriate radiographic surveillance strategies after lung cancer resection. We compared the impact of surveillance computed tomography scan versus chest radiography in patients who underwent resection for stage I lung cancer.A retrospective analysis was performed of all patients undergoing resection for pathologic stage I lung cancer from January 2000 to April 2013. After resection, follow-up included routine history and physical examination in conjunction with chest radiography or computed tomography at the discretion of the treating physician. Identification of successive lung malignancy (ie, recurrence at any new site or new primary) and survival were recorded.There were 554 evaluable patients, with 232 receiving routine postoperative computed tomography and 322 receiving routine chest radiography. Postoperative 5-year survival was 67.8% in the computed tomography group versus 74.8% in the chest radiography group (P = .603). Successive lung malignancy was found in 27% (63/232) of patients receiving computed tomography versus 22% (72/322) receiving chest radiography (P = .19). The mean time from surgery to diagnosis of successive malignancy was 1.93 years for computed tomography versus 2.56 years for chest radiography (P = .046). For the computed tomography group, 41% (26/63) of successive malignancies were treated with curative intent versus 40% (29/72) in the chest radiography group (P = .639). Cox proportional hazard analysis indicated imaging modality (computed tomography vs chest radiography) was not associated with survival (P = .958). ### Long_Answer: Surveillance computed tomography may result in earlier diagnosis of successive malignancy versus chest radiography in stage I lung cancer, although no difference in survival was demonstrated. A randomized trial would help determine the impact of postoperative surveillance strategies on survival. ### Final_Prediction: nan

### Question: Is hand-held dynamometry useful for the measurement of quadriceps strength in older people? ### Context: The lower limb muscle strength is an important determinant of physical function in older people. However, measurement in clinical and epidemiological settings has been limited because of the requirement for large-scale equipment. A protocol using a novel, versatile hand-held dynamometer (HHD) has been developed to measure the quadriceps strength in a supine position.The objective of this study was to assess the validity of this new methodology for measuring the lower limb muscle strength compared to the gold standard Biodex dynamometer.The supine quadriceps strength was measured twice with each of the Biodex and the HHD in 20 men and women, aged 61-81 years, on their non-dominant leg. The agreement between the peak torques obtained by Biodex and HHD was analyzed.The mean peak Biodex and HHD results were 83.4 +/- (SD) 28.0 Nm and 68.9 +/- 19.6 Nm, respectively. The HHD undermeasured the quadriceps strength by an average of 14.5 Nm (95% CI 8.5, 20.6) compared to the Biodex, and this effect was most marked in the strongest participants. Nevertheless, there was a good correlation between the measures (r = 0.91, p<0.0001). Classification of individuals into tertiles of muscle strength showed good agreement between the two methods (Kappa = 0.69, p<0.0001). ### Long_Answer: Our findings suggest that the HHD using a supine positioning offers a feasible, inexpensive, and portable test of quadriceps muscle strength for use in healthy older people. It underestimates the absolute quadriceps strength compared to the Biodex particularly in stronger people, but is a useful tool for ranking muscle strength of older people in epidemiological studies. It may also be of value for quick and objective assessment of physical function in the clinical setting. ### Final_Prediction: nan

### Question: Does a pyruvate-buffered dialysis fluid induce less peritoneal angiogenesis and fibrosis than a conventional solution? ### Context: Conventional lactate-buffered peritoneal dialysis (PD) fluids containing glucose and glucose degradation products are believed to contribute to the development of fibrosis and angiogenesis in the dialyzed peritoneum. To reduce potential negative effects of lactate, pyruvate was substituted as a buffer and its effects on peritoneal pathological alterations were studied in a chronic peritoneal exposure model in the rat.20 Wistar rats were infused intraperitoneally with pyruvate-buffered (n = 9) or lactate-buffered PD fluid. After 20 weeks of daily infusion, peritoneal function was assessed. In omental peritoneal tissue, the number of blood vessels was analyzed following alpha-smooth muscle actin staining. The degree of fibrosis was quantitated in Picro Sirius Red-stained sections and by assessment of the hydroxyproline content. Plasma lactate/pyruvate and betahydroxybutyrate/acetoacetate (BBA/AA) ratios were determined. Plasma and dialysate vascular endothelial growth factor (VEGF) levels were quantitated by ELISA.The mass transfer area coefficient of creatinine was higher and the dialysate-to-plasma ratio of sodium was lower in pyruvate-treated animals compared to the lactate-treated group (0.11 vs 0.05 mL/min, p < 0.05, and 78% vs 89%, p < 0.05). The BBA/AA ratio tended to be lower in the pyruvate animals (p = 0.07). The number of blood vessels was lower in pyruvate-treated animals (16 vs 37 per field, p < 0.001). Total surface area, luminal area, and wall/total area of the vessels were larger in the pyruvate group. The degree of fibrosis was lower in intersegmental and perivascular areas of pyruvate-exposed animals. Effluent VEGF was higher in the pyruvate group. ### Long_Answer: Replacement of lactate by pyruvate resulted in changes in peritoneal solute transport, accompanied by a reduction in both peritoneal membrane angiogenesis and fibrosis, suggesting potentially novel mechanisms to reduce glucose-driven alterations to the peritoneal membrane in PD patients. ### Final_Prediction: yes

### Question: Is self-efficacy for managing pain associated with disability , depression , and pain coping among retirement community residents with chronic pain? ### Context: Little is known about cognitive and behavioral factors that influence older adults' adjustment to chronic pain. The objective of this study was to investigate the relationship of self-efficacy for managing pain to reports of pain intensity, pain-related disability, depressive symptoms, and pain coping strategy use among 140 retirement community residents (88% female; age mean = 81.7, range 66-99 years) with chronic pain. The 8-item Arthritis Self-Efficacy Scale, modified to specify pain rather than arthritis, demonstrated good psychometric characteristics (Cronbach alpha = .89, minimal floor and ceiling effects, and validity) in this sample. Controlling for age, gender, and pain intensity, self-efficacy was associated significantly and negatively with pain-related disability and depressive symptoms (P values < .001), and positively with use of pain coping strategies previously found to be associated with better outcomes (task persistence, exercise/stretch, coping self-statements, activity pacing; P values < .05). Self-efficacy for managing pain appears to be important in the adjustment of older adults with pain. Research is needed to determine whether interventions designed to increase self-efficacy improve quality of life and prevent functional declines in this population. ### Long_Answer: Among retirement community residents (mean age of 82 years) with chronic pain, higher self-efficacy for managing pain is associated with less disability and depression and with the use of pain coping strategies related to better adjustment. This suggests the potential value of interventions to increase self-efficacy in this population. ### Final_Prediction: yes

### Question: Adding-on Phenomenon After Surgery in Lenke Type 1, 2 Adolescent Idiopathic Scoliosis: Is it Predictable? ### Context: A retrospective study.The aim of this study was to detect risk factors for Adding-on after posterior correction surgery in patients with Lenke 1 or 2 AIS, and to explore whether Adding-on Index could be used to predict Adding-on effectively.Adding-on phenomenon is a common complication in Lenke 1 or 2 AIS patients after correction surgery. However, whether it can be predicted after surgery remains unknown.Lenke 1 or 2 AIS patients receiving correction surgery in our center from January 2009 to July 2013 were analyzed. Antero-posterior and lateral films were evaluated before surgery, at 2 weeks' and 2 years' follow-up. Patients were divided into 2 groups according to whether Adding-on occurred at the 2 years' follow-up. Risk factors of Adding-on were analyzed, and Adding-on Index was proposed and verified.Sixteen patients (16.3%) suffered from distal Adding-on at 2-year follow-up. Several parameters were found to be significantly different between 2 groups, including Risser's sign, postoperative Cobb angle of main thoracic, postoperative Cobb angle of main thoracic curve at 2-year follow-up, preoperative and postoperative Cobb angle of lumbar curve, postoperative Cobb angle of lumbar curve at 2-year follow-up, LIV-EV, LIV-SV, LIV-CSVL, LAV-CSVL, LAV-LIV, DnfS, and postoperative TJK. No significant differences in SRS-22 scores were observed. Binary logistic regression analysis showed that DnfS and postoperative residual Cobb angle of lumbar curve were primary factors for occurrence of Adding-on. According to the regression equation, Adding-on Index was defined as 4 × DnfS-postoperative lumbar curves Cobb angle. On the basis of ROC curve, if Adding-on Index was more than 12, the occurrence rate of Adding-on was 88%. On the contrary, the rate of no Adding-on phenomenon was 80%. ### Long_Answer: DnfS and posterior Cobb angle of lumbar curve were 2 important factors for Adding-on in Lenke 1, 2 AIS patients. Adding-on Index can be used to predict the occurrence of Adding-on effectively. ### Final_Prediction: nan

### Question: Is adherence to the ERAS protocol Associated with 5-Year Survival After Colorectal Cancer Surgery : A Retrospective Cohort Study? ### Context: Surgical stress can influence oncological outcome and survival. The enhanced recovery after surgery (ERAS) protocol is designed to reduce perioperative stress and has been shown to reduce postoperative morbidity. We studied if adherence to ERAS is associated with increased long-term survival.Between the years 2002 and 2007, 911 consecutive patients, operated with major colorectal cancer surgery at Ersta Hospital, Stockholm, Sweden were analyzed. The histopathological reports of the resected specimen, date, and cause of death of the patients as well as postoperative CRP levels were obtained. The relation between the rate of adherence to the ERAS protocol at the time of surgery, and the short-term outcomes in relation to 5-year overall and colorectal cancer-specific survival was determined in this retrospective cohort study.In patients with ≥70 % adherence to ERAS interventions (N = 273,), the risk of 5-year cancer-specific death was lowered by 42 %, HR 0.58 (0.39-0.88, cox regression) compared to all other patients (<70 % adherence). Significant independent perioperative predictors of increased 5-year survival were avoiding overload of intravenous fluids, HR 0.53 (0.32-0.86); oral intake on the day of operation, HR 0.55 (0.34-0.78); and low CRP levels on postoperative day 1. ### Long_Answer: High adherence to the ERAS protocol may be associated with improved 5-year cancer-specific survival after colorectal cancer surgery. ### Final_Prediction: yes

### Question: Is bispectral index a topographically dependent variable in patients receiving propofol anaesthesia? ### Context: As very strong agreement has been reported between bispectral index (BIS) values measured from the occipital and frontal skull areas, we compared BIS values measured from central and parietal areas with those from frontal area to investigate whether BIS is really a topographically dependent or topographically independent variable.Twenty patients, ASA I-II, non-obese, aged 18-62 yr and with no neurological disorders were enrolled. Based on the 10-20 international landmarks, five silver dome electrodes were positioned: F7, C3, P7, Cz (common reference) and Fp1 (ground). Using frontal (F7-Cz), central (C3-Cz) and parietal (P7-Cz) electrode montages, the corresponding BIS values were simultaneously recorded with an Aspect A-1000 monitor (software v3.12). The BIS values were recorded at the propofol concentration allowing laryngeal mask insertion, which was maintained during the 10 min data collection period in absence of additional external stimuli. Data were analysed using the Kruskall-Wallis, Wilcoxon paired sign with Bonferroni correction, Bland-Altman and linear correlation tests.At the predicted effect target propofol concentration 4-8 microg ml(-1), the 10 min mean BIS (median [min-max]) were 32 [20-44], 46 [28-68] and 58 [41-72] for the frontal, central and parietal leads, respectively. Differences between these BIS recordings were statistically significant (P<0.0001, Kruskall-Wallis; P<0.005, Wilcoxon paired sign test). ### Long_Answer: The present results provide evidence that BIS index is a topographically dependent variable in patients receiving propofol anaesthesia. ### Final_Prediction: yes

### Question: Is context everything to the definition of clinical depression? ### Context: In arguing for the need to distinguish clinical depression from sadness, Horwitz and Wakefield argued for weighting consideration to nuances of life event stressors. Their definition of clinical depression corresponds to the concept of endogenous depression or melancholia, while their model would position reactive (or context specific) non-melancholic depressive disorders more as manifestations of 'sadness' rather than as clinical depression.We test their postulate by examining the extent to which 141 clinically diagnosed melancholic and non-melancholic depressed patients reported episodes as being preceded by a life event stressor or not--and the salience of any life stressor to episode onset and severity.While melancholic patients were more likely than non-melancholic patients to report episodes coming 'out of the blue' and to be more severe than might be expected from the severity of antecedent stressors, differences were more ones of degree and not absolute. Such context variables appeared, however, to differentiate melancholic and non-melancholic patients more consistently than depression symptom variables. As depression severity and impairment levels did not differ across the melancholic and non-melancholic patients, findings were unlikely to be artefacts of such factors. ### Long_Answer: The study finds some support for the Horwitz and Wakefield hypothesis of clinical (or, at least melancholic) depression requiring independence of context or an antecedent stressor, but with precision likely to be compromised by nuances intrinsic to assessment of life event stressors and their contribution to depression onset, difficulties in defining valid 'melancholic' and 'non-melancholic' depressive sub-groups and the parsimony of the hypothesis. ### Final_Prediction: nan

### Question: Does saphenous surgery correct perforator incompetence in the presence of deep venous reflux? ### Context: To determine which patients require subfascial endoscopic perforator surgery (SEPS) in addition to saphenous surgery to correct pathologic outward flow within incompetent medial calf perforating veins (IPVs).Sixty-two limbs of 47 patients undergoing sapheno-femoral ligation, stripping of the long saphenous vein in the thigh, and multiple phlebectomies (n = 51), sapheno-popliteal ligation and multiple phlebectomies (n = 10), or both (n = 1) were examined with color flow duplex ultrasound scan immediately before and a median of 14 weeks (range, 6 to 26 weeks) after the operations. Indications for surgery were varicose veins (n = 47, Clinical, Etiologic, Anatomic, Pathophysiologic grades C2&3), skin changes (n = 5, C4), and ulceration (n = 10, C5).Surgery resulted in a significant reduction in the total number of limbs in which IPVs were imaged (40/62 or 65% preoperatively vs 23/62 or 37% postoperatively, P <.01, chi2 test), a significant reduction in the proportion of perforators imaged that were incompetent (68/130 or 52% preoperatively vs 34/120 or 28% postoperatively, P <.01, chi2 test), and a reduction in median IPV diameter (4 mm, with a range of 1 to 11 mm preoperatively, vs 3, with a range of 1 to 8 mm postoperatively, P <.01, Mann-Whitney U test). IPVs remained in 8 of 41 (20%) limbs in which main stem reflux was abolished, compared with 15 of 21 (72%) limbs in which superficial or deep reflux remained (P <.01, chi2 test). ### Long_Answer: Eradication of main stem saphenous reflux corrects IPV reflux in most cases in which reflux is confined to the superficial system. However, in patients with superficial reflux that persists postoperatively, or when there is coexistent deep venous reflux, saphenous surgery alone fails to correct IPVs reflux. In these circumstances, the only way of reliably correcting pathologic outward flow in medial calf perforating veins is to perform SEPS. ### Final_Prediction: no

### Question: Does three-dimensional electroanatomic voltage mapping increase accuracy of diagnosing arrhythmogenic right ventricular cardiomyopathy/dysplasia? ### Context: Three-dimensional electroanatomic voltage mapping offers the potential to identify low-voltage areas that correspond to regions of right ventricular (RV) myocardial loss and fibrofatty replacement in patients with arrhythmogenic RV cardiomyopathy/dysplasia (ARVC/D).Thirty-one consecutive patients (22 men and 9 women; mean age, 30.8+/-7 years) who fulfilled the criteria of the Task Force of the European Society of Cardiology and International Society and Federation of Cardiology (ESC/ISFC) for ARVC/D diagnosis after noninvasive clinical evaluation underwent further invasive study including RV electroanatomic voltage mapping and endomyocardial biopsy (EMB) to validate the diagnosis. Multiple RV endocardial, bipolar electrograms (175+/-23) were sampled during sinus rhythm. Twenty patients (group A; 65%) had an abnormal RV electroanatomic voltage mapping showing > or =1 area (mean 2.25+/-0.7) with low-voltage values (bipolar electrogram amplitude <0.5 mV), surrounded by a border zone (0.5 to 1.5 mV) that transitioned into normal myocardium (>1.5 mV). Low-voltage electrograms appeared fractionated with significantly prolonged duration and delayed activation. In 11 patients (group B; 35%), electroanatomic voltage mapping was normal, with preserved electrogram voltage (4.4+/-0.7 mV) and duration (37.2+/-0.9 ms) throughout the RV. Low-voltage areas in patients from group A corresponded to echocardiographic/angiographic RV wall motion abnormalities and were significantly associated with myocyte loss and fibrofatty replacement at EMB (P<0.0001) and familial ARVC/D (P<0.0001). Patients from group B had sporadic disease and histopathological evidence of inflammatory cardiomyopathy (P<0.0001). During the time interval from onset of symptoms to the invasive study, 11 patients (55%) with electroanatomic low-voltage regions received an implantable cardioverter/defibrillator because of life-threatening ventricular arrhythmias, whereas all but 1 patient with a normal voltage map remained stable on antiarrhythmic drug therapy (P=0.02). ### Long_Answer: Three-dimensional electroanatomic voltage mapping enhanced accuracy for diagnosing ARVC/D (1) by demonstrating low-voltage areas that were associated with fibrofatty myocardial replacement and (2) by identifying a subset of patients who fulfilled ESC/ISFC Task Force diagnostic criteria but showed a preserved electrogram voltage, an inflammatory cardiomyopathy mimicking ARVC/D, and a better arrhythmic outcome. ### Final_Prediction: yes

### Question: Does aggressive angiomyxoma of pelvic parts exhibit oestrogen and progesterone receptor positivity? ### Context: Aggressive angiomyxoma of pelvic parts is a distinctive soft tissue tumour that chiefly involves the vulvar and perineal region of female patients. Several previous reports have demonstrated oestrogen receptor (ER) and/or progesterone receptor (PR) positivity in this neoplasm. The aim of this study was to confirm whether ER and/or PR positivity is present in aggressive angiomyxoma. We also wished to ascertain whether positivity may be found in the stromal cells of normal vulval skin and in other lesions at this site that can cause diagnostic confusion with aggressive angiomyxoma.Five aggressive angiomyxomas in female patients and one involving male pelvic soft parts were stained immunohistochemically with antibodies against ER and PR. Other samples studied were normal vulval skin (n = 7), fibroepithelial polyps of vulva (n = 7), vulval smooth muscle neoplasms (n = 5), vulval nerve sheath tumours (n = 2), vaginal angiomyofibroblastoma (n = 1), and pelvic myxoma (n = 1). Nuclear staining was classified as negative, weak, moderate, or strong and the proportion of positively staining cells was categorised as 0, < 10%, 10-50%, or > 50%.All five cases of aggressive angiomyxoma in female patients were positive for ER (two with weak intensity involving < 10% of cells and three with moderate intensity involving 10-50% of cells) and four of five cases were strongly positive for PR in > 50% of cells. The other case was negative for PR. There was no staining with antibodies to ER or PR in the single male patient with aggressive angiomyxoma. Other samples exhibiting positivity of the stromal cells for either ER or PR were normal vulval skin (five of seven, ER; two of seven, PR), fibroepithelial polyps (four of seven, ER; five of seven, PR), smooth muscle neoplasms (three of five, ER; four of five, PR), nerve sheath tumours (one of two, ER; one of two, PR), angiomyofibroblastoma (one of one, ER; one of one, PR), and pelvic myxoma (one of one, PR). ### Long_Answer: All cases of aggressive angiomyxoma of pelvic soft parts in female patients exhibited positivity for ER and/or PR. Because of its propensity to occur in female patients during the reproductive years, it is possible that aggressive angiomyxoma is a hormonally responsive neoplasm. However, dermal fibroblasts in normal vulval skin and stromal cells in a variety of vulval lesions can also be positive. ER or PR immunoreactivity cannot be used to distinguish aggressive angiomyxoma and its histological mimics. ### Final_Prediction: yes

### Question: Is a mechanism for toxin insertion into membranes suggested by the crystal structure of the channel-forming domain of colicin E1? ### Context: Channel-forming colicins, including colicin E1, are a sub-family of bacteriocins. The toxic action of colicin E1 is derived from its ability to form a voltage-gated channel, which causes depolarization of the cytoplasmic membrane of sensitive Escherichia coli cells. In this process, the toxin-like colicin E1 molecule must undergo a substantial structural transition from a soluble state, in which it binds the target cell, to a membrane-bound state. Details of the structural changes that accompany this conversion may be directly applicable to other channel-forming toxins, as well as to the mechanism by which proteins insert into or cross membranes.The structure of the 190-residue channel-forming domain of colicin E1 in its soluble form has been solved at 2.5 A resolution. This structure contains 10alpha helices arranged in three layers (A-C) with a central hydrophobic helical hairpin in layer B, which is proposed to anchor the membrane-bound form in the bilayer. The extended N-terminal helix I provides a connection to the rest of the colicin E1 molecule, and the loop I-II may act as a hinge for re-orientation of the domain for membrane binding. A set of conserved positively charged residues on layer C may provide the docking surface on the molecule for membrane attachment. A large internal cavity between layers B and C may allow these layers to disengage, suggesting a mechanism for unfolding the molecule on the membrane that involves the perturbation of the interhelical hydrophobic interactions in layer C. ### Long_Answer: On the basis of the structure of the colicin E1 channel-forming domain, its comparison with the structure of the colicin A domain and the known requirement for initial electrostatic and subsequent hydrophobic interactions, molecular details of the docking, unfolding and insertion of the channel-forming domain into the membrane are proposed. The model for docking and initial interaction with the membrane positions the hydrophobic hairpin 'anchor' approximately parallel to the membrane surface. Hydrophobic interactions in the docking layer may then be displaced by interactions with the membrane, spreading the helices on the surface and exposing the hydrophobic hairpin for insertion into the membrane. ### Final_Prediction: yes

### Question: Does tumor-associated gene expression in disseminated tumor cells correlate with disease progression and tumor stage in colorectal cancer? ### Context: A possible correlation of disease progression and tumor stage in colorectal cancer patients with tumor-associated gene expression in disseminated tumor cells (DTC) was evaluated. Detection of DTC and expression of tumor-associated genes might be of clinical value with respect to individual patient prognosis, monitoring of therapy and as a surrogate tumor staging parameter.In a multicenter study, a total of 196 peripheral blood samples were collected from 76 patients with tumor stage Dukes' A to D and analyzed using a DTC detection assay consisting of immunomagnetic selection and expression analysis of the tumor-associated genes CEA, EGFR and GA733-2. DTC detection rates were assessed prior to surgery and post surgery in patients with tumor stage Dukes' A, B and C, and compared with results in metastatic patients. CEA serum protein levels were determined and compared with DTC and CEA expression, respectively.In a comparison analysis, EGFR and CEA expression was detected in 88% (p = 0.001) and 0% (p = 0.002) prior to surgery, in 66% (p = 0.001) and 20% (p = 0.002) post surgery, as well as in 15% (p < 0.0001) and 66% (p < 0.0001) of blood samples collected from metastatic patients, respectively. Expression of tumor-associated genes in DTC prior to surgery and in follow-up samples indicated an ongoing metastatic process. DTC detection rates in patients with Dukes' A (14%), Dukes' B (13%) and Dukes' C (40%) prior to surgery correlated statistically with the expected recurrence rate. There was no correlation between DTC expressing CEA and elevation of CEA serum protein levels. ### Long_Answer: EGFR and CEA gene expression correlated with disease progression and tumor stage. Detection of CEA expression in DTC might have a predictive value in colorectal cancer and may help to identify patients at a greater risk of relapse. DTC in peripheral blood collected prior to surgery as well as in follow-up samples have a prognostic clinical value. ### Final_Prediction: yes

### Question: Are tGFbeta family members key mediators in the induction of myofibroblast phenotype of human adipose tissue progenitor cells by macrophages? ### Context: The present study was undertaken to characterize the remodeling phenotype of human adipose tissue (AT) macrophages (ATM) and to analyze their paracrine effects on AT progenitor cells.The phenotype of ATM, immunoselected from subcutaneous (Sc) AT originating from subjects with wide range of body mass index and from paired biopsies of Sc and omental (Om) AT from obese subjects, was studied by gene expression analysis in the native and activated states. The paracrine effects of ScATM on the phenotype of human ScAT progenitor cells (CD34(+)CD31(-)) were investigated.Two main ATM phenotypes were distinguished based on gene expression profiles. For ScAT-derived ATM, obesity and adipocyte-derived factors favored a pro-fibrotic/remodeling phenotype whereas the OmAT location and hypoxic culture conditions favored a pro-angiogenic phenotype. Treatment of native human ScAT progenitor cells with ScATM-conditioned media induced the appearance of myofibroblast-like cells as shown by expression of both α-SMA and the transcription factor SNAIL, an effect mimicked by TGFβ1 and activinA. Immunohistochemical analyses showed the presence of double positive α-SMA and CD34 cells in the stroma of human ScAT. Moreover, the mRNA levels of SNAIL and SLUG in ScAT progenitor cells were higher in obese compared with lean subjects. ### Long_Answer: Human ATM exhibit distinct pro-angiogenic and matrix remodeling/fibrotic phenotypes according to the adiposity and the location of AT, that may be related to AT microenvironment including hypoxia and adipokines. Moreover, human ScAT progenitor cells have been identified as target cells for ScATM-derived TGFβ and as a potential source of fibrosis through their induction of myofibroblast-like cells. ### Final_Prediction: yes

### Question: Does bacteremia after intestinal transplantation in children correlate temporally with rejection or gastrointestinal lymphoproliferative disease? ### Context: Bacteremia occurs frequently after intestinal transplantation (ITx) in children. During our initial experience with this procedure, we noted that bacteremic episodes tended to occur simultaneously with the presence of rejection and/or gastrointestinal (GI) posttransplant lymphoproliferative disease (PTLD).To document the association of bacteremia with rejection and GI PTLD in pediatric ITx recipients.Retrospective analysis of all medical records from 62 children who underwent ITx between July 1990 and January 1998 at Children's Hospital of Pittsburgh. A bacteremic episode was defined as two positive blood cultures from different sites at the same time or from the same site at different times. Rejection and PTLD were defined using previously published criteria.A total of 39/62 ITx recipients had 133 blood stream infections (2.1 episodes/patient) including 121 episodes of bacteremia and 12 of fungemia. Enteric organisms were the most frequently recovered pathogens (Gram negative rods, n=76; enterococci, n=36). Enteric organisms were recovered as a single organism (n=57), with another enteric bacteria (n=23), or with coagulase negative staphylococci (CONS) (n=24). CONS were recovered as a single organism on 21 occasions. An obvious source of bacteremia was not found for 115/121 episodes. Endoscopy was performed for 107 of the 115 bacteremia episodes; an abnormal histology was identified in 74 revealing rejection (n=36), GI PTLD (n=21), or both (n=17). When endoscopy showed GI pathology, enteric organisms alone or in combination with CONS were recovered on 63/107 occasions, although CONS were recovered alone only 11 times. ### Long_Answer: Bacteremia accompanies GI rejection and intestinal PTLD in ITx recipients. Endoscopy should be performed to inspect the allograft when bacteremia occurs without an obvious source in these patients. This is especially true for patients with bacteremia due to enteric organisms. ### Final_Prediction: yes

### Question: Is colonic electrical activity a similar phenomena to small-bowel electrical activity? ### Context: This study was designed to investigate colonic spike bursts regarding 1) their migration behavior, 2) their pressure correlates, and 3) comparing colonic short spike bursts with spike bursts from migrating myoelectric complex from the small bowel.Rectosigmoid electromyography and manometry were recorded simultaneously in seven normal volunteers and electromyography alone in five others during two hours of fasting and for two hours after one 2,100-kJ meal. One patient with an ileostomy was also studied by the same method to record the migrating myoelectric complex from the terminal ileum during fasting.Three kinds of spike bursts were observed in the pelvic colon: rhythmic short spike bursts, migrating long spike bursts, and nonmigrating long spike bursts. The meal significantly increased the number of migrating and nonmigrating long spike bursts (from 25 to 38.7 percent of the recording time; P<0.01). These bursts of potentials showed a peak 15 minutes after the meal, which may be caused by the gastrocolic reflex. Migrating long spike bursts started anywhere along the rectosigmoid and migrated from there aborad 82 percent of the time and orad or in both directions in 10 or 7 percent of the time, respectively. They originated pressure waves 99 percent of the time. Short spike bursts were more frequent before the meal (15.1 percent before and 9.6 percent after the meal), but the difference was not significant; they neither propagated nor initiated pressure waves detected by the mini-balloon. ### Long_Answer: Migrating long spike bursts were the only potentials that migrated, sometimes for short distances. Short spike bursts are a different phenomenon from the small-bowel migrating myoelectric complex because they do not migrate; they can occur during the postprandial period and never originated intraluminal pressure waves. ### Final_Prediction: nan

### Question: Should metabolic surgery be offered in morbidly obese patients with type I diabetes? ### Context: Bariatric surgery has recently been endorsed as an effective treatment of type 2 diabetes (T2D) in severely obese patients. Little is known about its metabolic effects in type 1 diabetes (T1D). The objectives were to assess bariatric surgery outcomes in T1D obese patients who underwent either a biliopancreatic diversion (BPD) or a sleeve gastrectomy (SG) and who were matched with T2D obese patients requiring insulin therapy. The study setting was at a university-affiliated tertiary care center.Through retrospective analysis of prospectively collected data, ten patients with T1D (7 BPD, 3 SG) were matched with 20 patients with T2D (14 BPD, 6 SG) according to age, gender, type of surgery, initial Body Mass Index and insulin requirements (1:2 matching). Weight loss, diabetes control, and remission of co-morbidities were compared.Mean follow-up was 55.1 months. Mean Excess BMI Loss% tended to be greater in T1D patients compared to T2D (77.1% versus 68.3%, P = .14). The remission and improvement rates of T2D were 55% and 45% versus 0% and 90% for T1D. The remission rate of T2D was significantly greater after BPD (71.43%) compared to SG (16.67%, P = .04). Insulin requirements were significantly reduced in both groups after surgery (T1D: .44 ±.24 versus 1.09 ±.7 units/kg/d, P = 0.03, T2D: .03 ±.12 versus .89 ±.77 units/kg/d, P = .0001). Remission rates of hypertension and dyslipidemia were similar for T1D and T2D (66.7% versus 62.5%, P = .63 and 88.9% versus 75%, P = .23). ### Long_Answer: Even if metabolic surgery has limited effect on glycemic control in T1D, it improves insulin sensitivity and other co-morbidities. It should be considered as a therapeutic option in selected obese patients with metabolic syndrome and high cardio-vascular risk. ### Final_Prediction: nan

### Question: Does leucovorin rescue allow effective high-dose pralatrexate treatment and an increase in therapeutic index in mesothelioma xenografts? ### Context: To investigate the ability of leucovorin (LV) to abrogate dose-limiting toxicities of pralatrexate (PDX) while maintaining efficacy, in vivo.H2052 mesothelioma cells were treated with the antifolates methotrexate (MTX), PDX and pemetrexed, with and without LV rescue 24 h later. Cell killing was evaluated 48 h later. Female nude mice bearing H2052 xenografts were treated with varying doses and schedules of the antifolate PDX and LV.In vitro, H2052 cells were more sensitive to PDX as compared to MTX and pemetrexed. Administration of LV 24 h after antifolate treatment reduced efficacy of antifolates MTX and pemetrexed, but not PDX. In vivo, LV was found to reduce toxicity of PDX at the maximum tolerated dose without sacrificing efficacy. Lethal doses of PDX were rescued by LV, and mice bearing the H2052 tumor demonstrated prolonged and enhanced tumor regression. ### Long_Answer: High-dose PDX with subsequent LV rescue may be a viable treatment strategy in mesothelioma and other cancers. The inclusion of LV rescue into new and existing PDX treatment protocols should be explored as a way to expand the tolerability and effectiveness of PDX in the clinic. ### Final_Prediction: yes

### Question: Does tibial bone versican content decrease with zoledronate treatment in adult mice? ### Context: In bone remodeling, the expression and turnover of the proteoglycans versican and aggrecan are poorly understood. We report changes in adult mouse bone contents of versican and aggrecan associated with both age and treatment with the drug zoledronate. The data may have implications for experimental animal models of osteoporosis and related conditions.Versican and aggrecan are large, aggregating proteoglycans involved in skeletal development, but little is known about their roles in bone remodeling. The purpose of this study was to investigate versican and aggrecan contents in adult mouse bones, and changes in their contents in response to the bisphosphonate zoledronate (ZOL).Mice (9 weeks old) were treated with 125 μg/kg ZOL or vehicle for 3 or 15 weeks. Versican and aggrecan were isolated from tibial bones for Western blotting, automated integrated densitometry, and analysis (two-way ANOVA, α = 0.05).In ZOL-treated mouse bones, compared to vehicle, 340 and 60 kDa versican content decreased significantly, and 100 and 60 kDa aggrecan content decreased significantly (drug effect). In 24-week-old mouse bones, compared to 12 weeks, statistically significant decreases were observed in 340, 80, 60, and 11 kDa versican, and in 100, 70, and 40 kDa aggrecan (age effect). There was a statistically significant ZOL-age interaction for 330 kDa aggrecan. ### Long_Answer: This is the first study to assess physiological versican and aggrecan adaptations in adult mammalian bone tissue, in the presence and absence of ZOL. We observed large decreases in some versican and aggrecan species from 12 to 24 weeks. We also observed decreases in several versican and aggrecan species in the presence of ZOL. This indicates that bone proteoglycan expression and turnover may be important in bone remodeling. ### Final_Prediction: yes

### Question: Do trainees value feedback in case-based discussion assessments? ### Context: Feedback is important in learning, including in workplace-based assessments.AIM: To explore trainee's perceptions of the educational value of case-based discussions (CBDs) specifically focusing on feedback.An online questionnaire and interviews obtaining detailed descriptions of paediatric trainees at UK specialist training levels 1 and 2 views and experiences were used. Qualitative data were analysed using a thematic framework analysis.Trainees viewed CBDs as educationally valuable, aiding reflective learning, improving decision making skills and effecting a change in practice. Opinions varied regarding how useful they found the feedback. Feedback was perceived as more valuable from assessors who had a positive attitude towards CBDs, understood the process and had experience in leading them. Time constraints and assessments performed in less suitable environments had a negative impact on feedback. Trainees felt the choice of case played an important role, with challenging cases resulting in more beneficial feedback. ### Long_Answer: CBD assessments provide a new opportunity for good quality learning and feedback, providing there is a commitment to the educational aspects of the process by both trainer and trainee. Trainers being aware of the qualities of the discussions that result in successful feedback, could significantly improve their educational value. ### Final_Prediction: nan

### Question: Do fasting glucose levels within the high normal range predict cardiovascular outcome? ### Context: Diabetes mellitus and impaired glucose metabolism are associated with increased risk for cardiovascular disease (CVD). However, it is still not clear whether glucose levels can predict CVD risk among patients without diabetes. The primary aim of this study is to assess whether normoglycemic fasting plasma glucose (FPG) is associated with increased risk of CVD outcomes in healthy patients.We obtained blood measurements, data from physical examination, and medical and lifestyle information from 10,913 men and women who were evaluated in the Institute for Preventive Medicine of Sheba Medical Center. Enrolled were participants with FPG <100 mg/dL as well as 100 to 125 mg/dL, who were free of diagnosis of CVD. The participants were actively screened for coronary disease using a stress test. Primary end points were coronary heart disease or self-reported cerebral vascular disease.A total of 1,119 incident cases of CVD occurred during a mean follow-up of 4.3 years. Subjects with fasting glucose levels in the high normal range (95-99 mg/dL) had an increased CVD risk when compared with levels <80 mg/dL, (HR 1.53;CI 95% [1.22-1.91], P < .001). A multivariate model, adjusted for age, sex, family history of CVD, blood pressure, body mass index, smoking status, pharmacologic treatment, serum triglycerides, and high-density lipoprotein and low-density lipoprotein cholesterol levels, revealed an independent increased risk of CVD with rising FPG levels in the normal range. ### Long_Answer: Elevated CVD risk is strongly and independently associated with glucose levels within the normoglycemic range. Fasting plasma glucose may help in identifying apparently healthy persons with early metabolic abnormalities who are at increased risk for CVD before progression to prediabetes and overt diabetes mellitus. ### Final_Prediction: yes

### Question: Should anastomotic assessment with flexible sigmoidoscopy be routine following laparoscopic restorative left colorectal resection? ### Context: All consecutive patients undergoing left-sided colorectal resections for benign and malignant disease between August 2005 and April 2011 were included. Data regarding procedure, type of anastomosis and outcomes of IOFS were collected. A positive intra-operative leak test resulted in redoing the anastomosis and repeating the leak test.A total of 415 consecutive patients underwent hand-assisted laparoscopic colorectal resection with a colorectal/ileoanal anastomosis. All patients underwent IOFS. Seventeen patients had abnormality on IOFS. Fifteen patients had a positive air leak test. One patient had anastomotic bleeding. There was one stapler misfiring. Fourteen anastomoses were redone without diversion. One patient required diversion to protect the ileoanal anastomosis and another had already been diverted. Minor bleeding from the staple line in one patient resolved without intervention; however, he had a postoperative anastomotic leak needing surgical intervention. None of the patients who had a takedown and refashioning of the anastomosis following a positive leak on IOFS had postoperative anastomotic leakage or bleeding. Our overall anastomotic leak rate was 2.1%. ### Long_Answer: Intra-operative flexible sigmoidoscopy for restorative colorectal resection is safe and reliable and should be performed routinely to assess anastomotic integrity and bleeding. Refashioning the anastomosis after formal takedown would obviate the risk of leakage and is our recommended method of managing intra-operative leaks. ### Final_Prediction: nan

### Question: Is increasing overall physical activity and aerobic fitness associated with improvements in metabolic risk : cohort analysis of the ProActive trial? ### Context: Our aim was to examine the association between change in physical activity energy expenditure (PAEE), total body movement (counts per day) and aerobic fitness (maximum oxygen consumption [VO2max] over 1 year and metabolic risk among individuals with a family history of diabetes.Three hundred and sixty-five offspring of people with type 2 diabetes underwent measurement of energy expenditure (PAEE measured using the flex heart rate method), total body movement (daily activity counts from accelerometry data), [VO2max] predicted from a submaximal graded treadmill exercise test and anthropometric and metabolic status at baseline and 1 year (n = 321) in the ProActive trial. Clustered metabolic risk was calculated by summing standardised values for waist circumference, fasting triacylglycerol, insulin and glucose, blood pressure and the inverse of HDL-cholesterol. Linear regression was used to quantify the association between changes in PAEE, total body movement and fitness and clustered metabolic risk at follow-up.Participants increased their activity by 0.01 units PAEE kJ kg(-1) day(-1) over 1 year. Total body movement increased by an average of 9,848 counts per day. Change in total body movement (beta = -0.066, p = 0.004) and fitness (beta = -0.056, p = 0.003) was associated with clustered metabolic risk at follow-up, independently of age, sex, smoking status, socioeconomic status and baseline metabolic score. ### Long_Answer: Small increases in activity and fitness were associated with a reduction in clustered metabolic risk in this cohort of carefully characterised at-risk individuals. Further research to quantify the reduction in risk of type 2 diabetes associated with feasible changes in these variables should inform preventive interventions. ### Final_Prediction: yes

### Question: Does [ Good surgery result in older patients with stage 1 lung carcinoma ]? ### Context: To determine the influence of age on survival of patients undergoing resection for lung cancer.Retrospective.South-western part of the Netherlands.Follow-up information was gathered on patients who had undergone resection for stage I non-small cell lung cancer from 1984 through 1990 and had been registered by the Rotterdam Cancer Registry. Operative mortality, 2-year and 5-year survival in the age groups 20-59, 60-69 and 70 years and older were compared.Of the 630 patients (median age of 66 years) one-third was 70 years or older. Operative mortality was mainly determined by the type of operation: 6% after pneumonectomy versus 1% after lesser resections. Five-year survival declined with age from 65% to 48% and 43% (p < 0.01). After adjustment for non-related causes of death this difference decreased: 68%, 55%, 61% (p = 0.15). The main prognostic factor was tumour size. ### Long_Answer: Chronological age has a limited influence on the survival of patients with lung cancer and does not preclude surgical treatment. ### Final_Prediction: yes

### Question: Is fucosylation of IgG heavy chains increased in rheumatoid arthritis? ### Context: Glycosylation of IgG was suggested to be important in the etiology of rheumatoid diseases. Most studies addressed the amount of galactose, but recently we showed that fucose is highly increased in the juvenile chronic arthritis. The objective of this study was to determine fucosylation of IgG heavy chains in patients with rheumatoid arthritis (RA).IgG was purified from sera of 29 RA patients and 17 matching controls using ammonium sulfate precipitation and ion exchange. Heavy chains were separated by denaturing polyacrylamide gel electrophoresis and their fucosylation analysed using fucose-specific UEA I lectin.Fucose was found to be approximately 40% increased in RA patients with very high statistical significance (p = 0.00095). ### Long_Answer: Fucose on IgG heavy chains is significantly increased in patients with rheumatoid arthritis. ### Final_Prediction: yes

### Question: Is poor premorbid functioning a risk factor for suicide attempts in first-admission psychosis? ### Context: While poor premorbid functioning is associated with poorer outcomes in psychotic illnesses, little is known about whether it is also a risk factor for suicide attempts.The current study examined the association of premorbid functioning and suicide attempts in a county-wide cohort of first-admission inpatients.Data were derived from participants of the Suffolk County Mental Health Project (n=444) over the course of 48-month follow-up. Premorbid functioning was estimated and categorized (good vs. poor/declining) using the Premorbid Adjustment Scale (PAS).Poorer premorbid functioning was significantly associated with increased likelihood of a suicide attempt prior to first psychiatric hospital admission. Specifically, 33.0% of participants with poor/declining premorbid functioning had a history of suicide attempts compared to 23.5% with good premorbid functioning. Among participants with a prior attempt (n=126), poor premorbid functioning was significantly associated with an increased likelihood of additional attempts during the four years after first hospitalization. ### Long_Answer: Identifying those with poor premorbid functioning and prior histories of attempts could help clinicians target high-risk patients. Thus, greater attention to persons with both risk factors may form the basis for early interventions aimed towards reducing the risk for subsequent suicide attempts. ### Final_Prediction: nan

### Question: Do pharmacological methyl group donors block skeletal metastasis in vitro and in vivo? ### Context: DNA hypomethylation was previously implicated in metastasis. In the present study, we examined whether methyl supplementation with the universal methyl donor S-adenosylmethionine (SAM) inhibits prostate cancer associated skeletal metastasis.Highly invasive human prostate cancer cells PC-3 and DU-145 were treated with vehicle alone, S-adenosylhomocysteine (SAH) or SAM and their effects on tumour cell proliferation, invasion, migration and colony formation were monitored. For in vivo studies, control (SAH) and SAM-treated PC-3 cells were injected into the tibia of Fox chase SCID mice and skeletal lesions were determined by X-ray and μCT. To understand possible mechanisms involved, we delineated the effect of SAM on the genome-wide methylation profile of PC-3 cells.Treatment with SAM resulted in a dose-dependent inhibition of tumour cell proliferation, invasion, cell migration, colony formation and cell cycle characteristics. Animals injected with 250 μM SAM-treated cells developed significantly smaller skeletal lesions, which were associated with increases in bone volume to tumour volume ratio and connectivity density as well as decreased trabecular spacing. Genome-wide methylation analysis showed differential methylation in several key signalling pathways implicated in prostate cancer including the signal transducer and activator of transcription 3 (STAT3) pathway. A selective STAT3 inhibitor decreased tumour cell invasion, effects which were less pronounced as compared with SAM. ### Long_Answer: These studies provide a possible mechanism for the role of DNA demethylation in the development of skeletal metastasis and a rationale for the use of hypermethylation pharmacological agents to impede the development and progression of skeletal metastasis. ### Final_Prediction: yes

### Question: Does foxp3 regulate human natural CD4+CD25+ regulatory T-cell-mediated suppression of xenogeneic response? ### Context: Cellular rejection of xenografts is predominantly mediated by CD4+ T cells. Foxp3 expressing human naturally occurring CD4+CD25+ regulatory T cells (nTregs) have been shown to suppress pathological and physiological immune responses, including the CD4+ T-cell-mediated anti-pig xenogeneic response in vitro. Although Foxp3 is required for nTreg development and their function, the precise role of Foxp3 in regulating Treg suppressive function in xenoimmune response remains to be identified.In vitro expanded human nTregs were transfected with fluorescein isothiocyanate -conjugated Foxp3 small interfering RNA (siRNA) by Lipofectamine 2000. Transfected nTregs were sorted by fluorescence-activated cell sorting, and then analyzed for Foxp3 gene and protein expression as well as their phenotypic characteristics. Human CD4+CD25- T cells were stimulated with xenogeneic pig peripheral blood mononuclear cell in the presence or absence of nTregs in a coculture or transwell system for evaluation of nTreg suppressive activity. The production of effector cytokines by xenoreactive CD4+CD25- T cells as well as suppressive cytokine by nTregs in their cocultures was examined by ELISA.The siRNA-mediated Foxp3 knockdown resulted in impaired nTreg anergic state, downregulated expression of nTreg function associated molecules, and reduced production of suppressive cytokines by nTregs, which together leading to impaired nTreg-mediated suppression of CD4+CD25- T-cell proliferation and their effector cytokine production in response to xenogeneic stimulation. ### Long_Answer: This study demonstrates that Foxp3 expression is required for human nTregs to maintain their suppressive function in the xenoimmune response. ### Final_Prediction: yes

### Question: Is serotonin Transporter Promoter Region ( 5-HTTLPR ) Polymorphism Associated With Paroxetine-Induced Ejaculation Delay in Dutch Men With Lifelong Premature Ejaculation? ### Context: To investigate the association between the 5-HT-transporter-gene-linked promoter region (5-HTTLPR) polymorphism and 20-mg paroxetine-induced ejaculation delay in men with lifelong premature ejaculation (LPE).This was a prospective study of 10 weeks of paroxetine treatment in 54 men with LPE. Intravaginal ejaculation latency time (IELT) was measured by stopwatch. Controls consisted of 92 Caucasian men. All men with LPE were genotyped for the 5-HTTLPR polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of the polymorphism were compared between patients and controls. Associations between the LL, SL, and SS genotypes and fold increase of mean IELT were investigated.Of the 54 patients, 43 (79.6%) responded to 20-mg paroxetine treatment with an ejaculation delay, whereas 11 patients (20.4%) did not respond; 44%, 18%, and 18% of the patients showed a fold increase in mean IELT of 2-10, 10-20, and more than 20, respectively. Of the 54 men, 14 (25.9%) had the LL genotype, 29 (53.7%) had the SL genotype, and 11 (20.4%) had the SS genotype. In the 92 controls, the LL, SL, and SS genotypes were present in 27 (29.3%), 41 (44.6%), and 24 (26.1%), respectively. No statistically significant differences were found in 5-HTTLPR allelic variations or in 5-HTTLPR gene variations. In all men treated with 20 mg paroxetine, analysis of variance of the natural logarithm of fold increase in the IELT showed no statistically significant difference according to genotype (p=0.83). ### Long_Answer: The 5-HTTLPR polymorphism is not associated with daily 20-mg paroxetine treatment-induced ejaculation delay in men with LPE. ### Final_Prediction: no

### Question: Correlation between the degree of air trapping in chest HRCT and cardiopulmonary exercise test parameters: could HRCT be a predictor of disease severity? ### Context: The purpose of this study was to examine whether the degree of air trapping in high resolution computed tomography (HRCT) of patients with histories of sulfur mustard gas exposure during suspended full expiration correlated with various parameters of the cardiopulmonary exercise test as the gold standard for assessment of pulmonary function.In this analytic study 75 male patients, each with a history of sulfur mustard gas exposure, were investigated. Each participant underwent an incremental cardiopulmonary exercise test, pulmonary function test and arterial oxygen saturation for hemoglobin measurement. For HRCT examination, both lungs were divided into three parts (upper, middle, and lower) and in each part images were separately observed from the involved area point of view (<25% ≤6/24;>25% ≥6/24).A total of 49.3% of the patients (37/75) had evidence of air trapping in over 25% of their lung segments. The mean age±SD in the patients with air trapping of =25% or<25% were 41.1±6.8 and 39.7±4.0 years, respectively (P=0.281). In our study there was no significant difference in pulmonary function test findings (FEV1, FVC and FEV1/FVC) between the two groups. There was no significant correlation with air trapping of =25% and any of the exercise test parameters. Also, no correlation was found between significant air trapping and exercise test findings in maximum exercise and anaerobic situations. ### Long_Answer: No correlation was found between HRCT and cardiopulmonary exercise test findings. HRCT is neither pathognomic of the disease nor a good predictor of disease severity but it might be suggestive of mustard lung injuries. ### Final_Prediction: nan

### Question: Does increased O-GlcNAcylation of NF-κB enhance Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy? ### Context: Hyperglycemia results in increased flux through the hexoxamine biosynthetic pathway. We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR).Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin. All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR.The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas. ### Long_Answer: The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR. ### Final_Prediction: yes

### Question: Is rEG gene expression associated with the infiltrating growth of gastric carcinoma? ### Context: The Reg gene is known to be involved in the growth of not only pancreatic B-cells, but also epithelial cells of the gastrointestinal tract and carcinoma of its lineage.Because, to the authors' knowledge, no studies have been reported regarding REG expression in gastric carcinoma, the authors investigated REG mRNA and REG protein expression using reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical study and correlated the results with the clinical features of gastric carcinoma.Using RT-PCR and Western blot analyses, reg mRNA and 16-kilodalton REG proteins were detected in two of eight human gastric carcinoma cell lines. Cytoplasmic localization of REG proteins in the cell lines was confirmed by fluorescent immunocytochemistry. The RT-PCR analysis revealed the presence of REG mRNA in as many as 77% (87 of 112 tumors) of primary gastric carcinoma tumors. Screening of a total of 195 patients with primary gastric carcinoma using immunoperoxidase staining revealed positive REG immunoreactivity in 60 of the 195 primary tumors (31%). REG expression in infiltrating tumors was found to be significantly higher compared with localized tumors (P < 0.05). Strong REG expression was noted in the cytoplasm of signet ring cell carcinoma tumors at a significantly higher incidence than in nonsignet ring cell tumors. Moreover, patients with REG-negative differentiated adenocarcinoma were found to have a significantly better prognosis compared with patients with REG-positive tumors. The incidence of venous invasion of REG-positive tumors was significantly higher than that of REG-negative tumors. ### Long_Answer: The results of the current study suggest that the expression of the REG gene is closely related to the infiltrating property of gastric carcinoma, and may be a prognostic indicator of differentiated adenocarcinoma of the stomach. ### Final_Prediction: yes

### Question: Do theory of planned behaviour cognitions predict self-reported or objective physical activity levels or change in the ProActive trial? ### Context: The objective was to test, in a trial cohort of sedentary adults at risk of Type 2 diabetes, whether theory of planned behaviour (TPB) cognitions about becoming more physically active predicted objective and self-reported activity levels and change.Participants of a randomized controlled trial underwent measurement at baseline, 6 and 12 months.Participants (N= 365, 30-50 years) were recruited via their parent or family history registers at 20 general practices in the UK. Energy expenditure was measured objectively at baseline and 1 year. Participants completed questionnaires assessing physical activity and beliefs about becoming more physically active over the next year at baseline, 6 and 12 months.Between baseline and 12 months, objective energy expenditure in the cohort increased by an average of 20 minutes of brisk walking per day. Based on the 252 participants who provided complete data, affective attitude and perceived behavioural control consistently predicted intention, but intention and perceived behavioural control failed to predict physical activity levels or change (p-values > .05). ### Long_Answer: Failure of the theory to predict behaviour and behaviour change may be due to inapplicability of the theory to this at-risk population or to trial participation and intensive measurement facilitating behaviour change without affecting measured cognitions, or lack of correspondence between cognitive and behavioural measures. A wide range of potential personal and environmental mediators should be considered when designing physical activity interventions among at-risk groups. High-quality experimental tests of the theory are needed in clinical populations. ### Final_Prediction: no

### Question: Are cYP2C9 and VKORC1 polymorphisms differently distributed in the Brazilian population according to self-declared ethnicity or genetic ancestry? ### Context: Warfarin-dosing pharmacogenetic algorithms have presented different performances across ethnicities, and the impact in admixed populations is not fully known.To evaluate the CYP2C9 and VKORC1 polymorphisms and warfarin-predicted metabolic phenotypes according to both self-declared ethnicity and genetic ancestry in a Brazilian general population plus Amerindian groups.Two hundred twenty-two Amerindians (Tupinikin and Guarani) were enrolled and 1038 individuals from the Brazilian general population who were self-declared as White, Intermediate (Brown, Pardo in Portuguese), or Black. Samples of 274 Brazilian subjects from Sao Paulo were analyzed for genetic ancestry using an Affymetrix 6.0(®) genotyping platform. The CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), and VKORC1 g.-1639G>A (rs9923231) polymorphisms were genotyped in all studied individuals.The allelic frequency for the VKORC1 polymorphism was differently distributed according to self-declared ethnicity: White (50.5%), Intermediate (46.0%), Black (39.3%), Tupinikin (40.1%), and Guarani (37.3%) (p<0.001), respectively. The frequency of intermediate plus poor metabolizers (IM+PM) was higher in White (28.3%) than in Intermediate (22.7%), Black (20.5%), Tupinikin (12.9%), and Guarani (5.3%), (p<0.001). For the samples with determined ancestry, subjects carrying the GG genotype for the VKORC1 had higher African ancestry and lower European ancestry (0.14±0.02 and 0.62±0.02) than in subjects carrying AA (0.05±0.01 and 0.73±0.03) (p=0.009 and 0.03, respectively). Subjects classified as IM+PM had lower African ancestry (0.08±0.01) than extensive metabolizers (0.12±0.01) (p=0.02). ### Long_Answer: The CYP2C9 and VKORC1 polymorphisms are differently distributed according to self-declared ethnicity or genetic ancestry in the Brazilian general population plus Amerindians. This information is an initial step toward clinical pharmacogenetic implementation, and it could be very useful in strategic planning aiming at an individual therapeutic approach and an adverse drug effect profile prediction in an admixed population. ### Final_Prediction: yes

### Question: Does a hypoxia-dependent upregulation of hypoxia-inducible factor-1 by nuclear factor-κB promote gastric tumour growth and angiogenesis? ### Context: The underlying mechanisms involved in the activation of hypoxia-inducible factor-1 (HIF-1) in gastric cancer remain unclear. As nuclear factor-κB (NF-κB) as well as HIF-1 have been implicated in angiogenesis of various cancers, we investigated their relationship in gastric cancer.Nuclear expressions of HIF-1α and NF-κB/RelA were assessed in 251 human gastric carcinoma specimens by immunohistochemical tissue array analysis. Stable human gastric cancer cells, infected with a retroviral vector containing super-suppressive mutant form of IκBα (IκBαM), were used for animal studies as well as cell culture experiments. Xenografted tumours were measured and IκBαM effects on angiogenesis and HIF-1α activation were assessed by immunohistochemistry, western blotting, luciferase reporter assay, and semiquantitative reverse transcription-polymerase chain reaction. In addition, NF-κB effects on the HIF-1α degradation and synthesis were examined.Hypoxia-inducible factor-1α activation positively correlated with RelA activation in clinical gastric cancer samples (P<0.001). The IκBαM overexpression suppressed tumour growth, microvessel density, and HIF-1α activation in xenografted tumours. Cell culture experiments showed that hypoxia-induced HIF-1α expression was reduced by NF-κB inhibition under hypoxic conditions at the translational level. ### Long_Answer: The hypoxia-dependent activation of the NF-κB/HIF-1α/VEGF pathway contributes, at least in part, to gastric cancer promotion via enhancement of angiogenesis. ### Final_Prediction: yes

### Question: Is expression of matrix metalloproteinase 9 a prognostic factor in patients with non-Hodgkin lymphoma? ### Context: Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of tumors that vary with regard to their biologic aggressiveness and clinical course. In in vitro studies, matrix metalloproteinase 9 (MMP9) was reportedly expressed by human NHL cells and elevated levels of MMP9 have been observed in a subset of patients with high-grade NHL.The expression of MMP2 and MMP9 was evaluated in 158 patients with NHL and the relation between the expression of these proteins and clinicopathologic factors was analyzed. All but 1 patient had received radiation therapy and 92 patients also were treated with intensive combination chemotherapy.Nearly all the patients with extranodal natural killer NK/T-cell lymphoma nasal type and anaplastic large cell lymphoma, T-cell/null cell type expressed MMP9. In contrast, only a small fraction of the patients with mucosa-associated lymphoid tissue (MALT) lymphomas and follicular lymphomas expressed MMP9. Approximately 50% of the diffuse large B-cell lymphoma (DLBCL) cases expressed MMP9. The expression of MMP2 was noted in some of the patients with DLBCL and nasal NK/T-cell lymphoma. The overall survival rates of patients who expressed MMP9 were significantly lower than that of those who did not. Such a correlation was not demonstrated in MMP2 expression. When MMP9 expression was analyzed in DLBLC patients, the overall survival rates of patients who expressed MMP9 were significantly lower than those who did not express MMP9. Chemotherapy was associated with better overall survival in DLBCL patients who expressed MMP9. Overall survival rates of T-cell/NK-cell lymphoma patients who expressed MMP9 appeared to be lower than that in those who did not express MMP9. However, chemotherapy was not found to improve overall survival in patients who expressed MMP9. ### Long_Answer: MMP9 expression was observed in patients with aggressive NHL and was characterized by poor overall survival. ### Final_Prediction: yes

### Question: Does eriocaulon buergerianum extract protect PC12 cells and neurons in zebrafish against 6-hydroxydopamine-induced damage? ### Context: Ericaulon buergerianum (Gujingcao) is an ophthalmic, anti-inflammatory and antimicrobial Chinese medicinal herb. This study aims to investigate the neuroprotective effects of Ericaulon buergerianum ethanol extract (EBE) and to elucidate its underlying action mechanism.The viability of dopaminergic (DA) neuron in zebrafish was examined by anti-tyrosine hydroxylase (TH) immunostaining. The locomotor activity of zebrafish was assessed with a digital video tracking system. The viability and cellular damage of the PC12 cells were determined by MTT and LDH assays respectively. The nuclear morphological changes in apoptotic cells were evaluated with DNA staining by Hoechst 33342 dye. Intracellular nitric oxide (NO) was quantified by DAF-FM diacetate staining. The expression of inducible nitric oxide synthase (iNOS) was determined by Western blot.EBE inhibited the 6-OHDA-induced decrease in total distance of movement in zebrafish. Pretreatments of EBE (25, 50, 100 and 200 μg/ml) increased the viability of 6-OHDA-damaged PC12 cells in a dose dependent manner. Protection against 6-OHDA-induced nuclear fragmentation and accumulation of apoptotic bodies was also observed in EBE pretreated cells. Anti-oxidative (inhibition of NO production and iNOS expression in PC12 cells in vitro) activities of EBE are related to its neuroprotective effects in 6-OHDA-induced DA neuron damage. ### Long_Answer: EBE exhibited significant neuroprotective activities in zebrafish, including recovery of dopaminergic neuron loss caused by 6-OHDA in a dose-dependent manner in vivo, inhibition of 6-OHDA-induced decrease of total distance in movement in zebrafish. The iNOS-NO pathway may be involved. ### Final_Prediction: yes

### Question: Is expression level of thymidylate synthase a good predictor of chemosensitivity to 5-fluorouracil in colorectal cancer? ### Context: It is important to seek the appropriate chemotherapy drugs to effectively eliminate colorectal cancers. To avoid unnecessary medication and uncomfortable side effects, it is important to estimate the chemosensitivity of cancers to 5-fluorouracil (5-FU) before chemotherapy.We examined thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene expressions in 23 colorectal cancers, using quantitative reverse transcription-polymerase chain reaction (RT-PCR). We then evaluated the relationship between TS and DPD gene expression levels and the sensitivity of colorectal cancers to 5-FU, as determined by histoculture drug response assay (HDRA).A significant increase in the TS expression score was observed in 5-FU-sensitive colorectal cancers (0.57 +/- 0.19) compared to 5-FU-resistant ones (1.16 +/- 0.98; P = 0.029), whereas no significant differences in DPD expression scores were observed in 5-FU-sensitive colorectal cancers (0.86 +/- 1.19) compared to 5-FU-resistant ones (0.56 +/- 1.05; P = 0.603). ### Long_Answer: TS mRNA may be useful as a predictor of the 5-FU chemosensitivity of colorectal cancers. ### Final_Prediction: yes

### Question: Is increasing age a predictor of short-term outcomes in esophagectomy : a propensity score adjusted analysis? ### Context: Esophagectomy is a high-risk surgical procedure. As the population ages, more elderly candidates are being evaluated for esophagectomy. The effects of patient age on outcomes after esophagectomy need to be evaluated.We identified all nonemergent esophagectomies in patients at least 18 years of age within the University HealthSystems Consortium Clinical Database/Resource Manager from 2009 to 2012. Using univariate and multivariate methods, the impact of increasing age on outcomes was analyzed. Additionally, propensity scoring was used to match patients to further investigate the effect of age on the stated outcomes.Increasing age is associated with increased mortality (p < 0.001), length of stay (p < 0.001), discharge to rehabilitative care (p < 0.001), and cost (p < 0.001). The effects of age on mortality (8.0 vs 4.2 %, p = 0.03) and discharge to rehabilitative care (44.1 vs 23.4 %, p < 0.01) were confirmed using propensity scoring, comparing patients above 80 with those age 70-79. ### Long_Answer: Increasing age has a significant impact on outcomes following esophagectomy, particularly mortality and discharge disposition. Compared to patients under age 80, patients at least 80 years of age considering esophagectomy should be recognized as a high-risk cohort, and these patients must be carefully risk-stratified, counseled, and selected for surgical intervention to prevent unnecessary hospitalization and mortality. ### Final_Prediction: yes

### Question: Does [ Insulin/PI3K signalling pathway regulate the expression of survivin in liver cancer HepG2 cells ]? ### Context: To determine the expression level changes of survivin, a inhibitor of apoptosis protein, followed by activation of insulin receptors in human hepatocellular carcinoma HepG2 cell line, and to investigate the signalling pathway involved in the regulation.Human hepatocellular carcinoma HepG2 cells were treated with insulin alone or pre-treated with LY294002, a specific inhibitor of PI3K signalling pathway, to determine whether blocking PI3K signaling can attenuate the up-regulation of survivin expression. Real time RT-PCR and Western blot analysis were used to measure survivin mRNA and protein changes before and after treatment, respectively.Without serum supplement, HepG2 cells expressed a small amount of survivin. Insulin induced survivin expression in a dose- and time-dependent fashion. Survivin expression was blocked if cells were pre-treated with LY294002 prior to insulin stimulation. ### Long_Answer: Insulin induces survivin expression via PI3K signalling pathway, suggesting that to interfere the key gene in this signalling pathway may block survivin expression, therefore, promoting apoptosis in hepatocellular carcinoma cells. ### Final_Prediction: yes

### Question: Does selective Targeting of a Novel Epsin-VEGFR2 Interaction promote VEGF-Mediated Angiogenesis? ### Context: We previously reported that vascular endothelial growth factor (VEGF)-induced binding of VEGF receptor 2 (VEGFR2) to epsins 1 and 2 triggers VEGFR2 degradation and attenuates VEGF signaling. The epsin ubiquitin interacting motif (UIM) was shown to be required for the interaction with VEGFR2. However, the molecular determinants that govern how epsin specifically interacts with and regulates VEGFR2 were unknown.The goals for the present study were as follows: (1) to identify critical molecular determinants that drive the specificity of the epsin and VEGFR2 interaction and (2) to ascertain whether such determinants were critical for physiological angiogenesis in vivo.Structural modeling uncovered 2 novel binding surfaces within VEGFR2 that mediate specific interactions with epsin UIM. Three glutamic acid residues in epsin UIM were found to interact with residues in VEGFR2. Furthermore, we found that the VEGF-induced VEGFR2-epsin interaction promoted casitas B-lineage lymphoma-mediated ubiquitination of epsin, and uncovered a previously unappreciated ubiquitin-binding surface within VEGFR2. Mutational analysis revealed that the VEGFR2-epsin interaction is supported by VEGFR2 interacting specifically with the UIM and with ubiquitinated epsin. An epsin UIM peptide, but not a mutant UIM peptide, potentiated endothelial cell proliferation, migration and angiogenic properties in vitro, increased postnatal retinal angiogenesis, and enhanced VEGF-induced physiological angiogenesis and wound healing. ### Long_Answer: Distinct residues in the epsin UIM and VEGFR2 mediate specific interactions between epsin and VEGFR2, in addition to UIM recognition of ubiquitin moieties on VEGFR2. These novel interactions are critical for pathophysiological angiogenesis, suggesting that these sites could be selectively targeted by therapeutics to modulate angiogenesis. ### Final_Prediction: yes

### Question: Does intrapartum late deceleration develop more frequently in pre-eclamptic women with severe proteinuria? ### Context: Our purpose was to investigate the effect of proteinuria associated with pre-eclampsia on intrapartum fetal heart rate patterns.A retrospective study was performed involving 79 pregnant women with pre-eclampsia and 19 pregnant women with gestational hypertension (GH). Pre-eclampsia was then classified into two groups according to the degree of proteinuria (> or = or < 3 + dipstick), which was classified as severe urinary protein (UP; n = 35) and mild UP (n = 44) at delivery. Intrapartum fetal heart rate (FHR) monitoring was classified as either no deceleration, moderate variable deceleration, severe variable deceleration (sVD), prolonged deceleration (PD), occasional deceleration or recurrent late deceleration (rLD). We evaluated the prevalence of non-reassuring FHR (sVD, PD or rLD), the prevalence of intrauterine growth restriction (IUGR), and cord blood gas status in the three groups. The prevalence of non-reassuring FHR and cord blood gas status of these three groups was also compared with their prevalence in 65 women with low-risk pregnancies. Multiple logistic regression analysis was performed to determine the association between rLD and maternal-fetal parameters.Levels of systolic and diastolic blood pressure were similar among the three groups. Severe UP was diagnosed significantly earlier, was associated with significantly lower gestational age, and infants with lighter birth weight (P < 0.05) compared with GH and mild UP. The prevalence of IUGR in severe UP was higher than in GH (54%v. 21%, P < 0.05); however, no differences were found in the prevalence of IUGR between mild and severe UP (43%v. 54%, P = 0.33). The prevalence of non-reassuring FHR in GH was not statistically significant in the low-risk pregnancies (5%v. 9%, P = 0.58). In mild and severe UP, the non-reassuring FHRs were more predominant (30% and 43%, respectively) than in low-risk pregnancies and GH (P < 0.05). The rLD was more common in the group with severe UP and accounted for 40% of all FHR patterns. There was no difference in the incidence of low pH among the groups. However, fetuses in pregnancies involving severe UP were significantly hypoxemic when compared with others. Multiple logistic regression analysis showed that worsening proteinuria (odds ratio [OR], 5.5; 95% confidence interval [CI], 2.4-12.9) and IUGR (OR, 3.8; 95% CI, 1.2-11.5) increased the risk of rLD. Rates of preterm birth at less than 32 weeks (OR, 0.7; 95% CI, 0.2-2.5) and severe hypertension (OR, 0.5; 95% CI, 0.2-1.3) were not significant. ### Long_Answer: In pre-eclampsia, the presence of severe proteinuria is associated with an increased likelihood of rLD. ### Final_Prediction: yes

### Question: Flexion-extension cervical spine MRI in children with skeletal dysplasia: is it safe and effective? ### Context: Skeletal dysplasias may be associated with cervical spinal instability or stenosis. Cervical spine flexion-extension plain radiographs in children with skeletal dysplasia are difficult to interpret. The purpose of this study was to review the indications, efficacy, and safety of performing flexion-extension magnetic resonance imaging (MRI) under sedation/anesthesia in these children.Retrospective, Institutional Review Board-approved review of 31 children with skeletal dysplasia who underwent 38 cervical spine flexion-extension MRI studies under sedation/anesthesia. Indications included abnormal neurological examination, suspected instability, stenosis, or inconclusive findings on flexion-extension radiographs. Studies were performed by the radiology technologist as directed by the radiologist with an anesthesiologist present. MRI was evaluated for odontoid hypoplasia, os odontoideum, cerebrospinal fluid effacement, cord compression, spinal cord changes, cervical canal narrowing in the neutral, flexion, and extension positions. Neurological examinations were recorded before and after MRI to assess safety.The average age at MRI was 3 years, 2 months. In 6 patients whose plain radiographs showed C1-C2 or subaxial instability, flexion-extension MRI showed no cord compression. Nine patients with inconclusive plain radiographs had abnormal MRI findings. An os odontoideum not seen on plain radiographs was diagnosed in 3 patients on flexion-extension MRI. On the basis of the MRI findings, 14 patients underwent surgery, 9/14 had increased cord compression in flexion or extension compared with neutral, and observation was continued in 17 others. Patients who underwent surgery had significant cord compression on MRI. There were no significant changes in the neurological examinations after MRI. ### Long_Answer: Cervical spine flexion-extension MRI under sedation/anesthesia in children with skeletal dysplasia is safe under adequate supervision and is necessary to guide accurate medical and surgical decision making. Flexion-extension MRI is useful for identifying dynamic changes in canal diameter resulting in cord compression not seen on plain radiographs, and it is also useful for identifying patients with suspected plain film instability who may not have stenosis or cord compression on MRI. ### Final_Prediction: nan

### Question: Is there any association between TACSTD2, KIAA1253, Ku70 and mutant KRAS gene expression and clinical-pathological features of colorectal cancer? ### Context: Samples of tumor and normal tissue of patients surgically treated for colorectal cancer between July 2005 and July 2009 were stored in a tissue bank. These samples were studied with the technique of real-time polymerase chain reaction in respect to expression of the following genes: KRAS codon 12 mutation, TACSTD2, Ku70, and SERIN1.Tumor samples of 37 patients were studied. The mean age was 65.5 years. Twenty one patients (56.8%) were male. Nine patients (24.3%) were classified as TNM stage I, 11 patients (29.8%) as TNM stage II, eight patients (21.6%) as TNM stage III and nine patients (24.3%) as TNM stage IV. The Ku70 expression in poorly-differentiated tumors is significantly higher than in well and moderately-differentiated tumors (2.76 vs. 1.13; p<0.05). SERIN1, TACSTD2 and KRAS codon 12 mutation are not associated with clinical-pathological characteristics of colorectal cancer. ### Long_Answer: Ku70 expression in poorly-differentiated tumors is significantly higher than in well and moderately-differentiated colorectal tumors. ### Final_Prediction: nan

### Question: Is a history of early life parental loss or separation associated with successful cognitive-behavioral therapy in major depressive disorder? ### Context: There is a clinical need for evidence-based psychotherapy response biomarkers in major depressive disorder (MDD). Based on previous studies, we hypothesized that lower 24-h urinary cortisol levels and a history of early life stress/trauma would predict an improved antidepressant response to cognitive-behavioral therapy (CBT).50 currently depressed MDD subjects were enrolled. 24-h urine was collected and measured for cortisol levels by radioimmunoassay (RIA). Subjects were also administered early life stress/trauma measures at baseline: Global Perceived Early-Life Stress (GPELS), The Early Life Trauma Inventory (ELTI) and Klein Loss Scale (KLS). The efficacy of a twelve-week course of once-weekly CBT was evaluated by the primary outcome measure, the 24-item Hamilton Depression Rating Scale (HDRS24), at baseline and every four weeks, and the Beck Depression Inventory at baseline and weekly thereafter. 42 subjects had at least one complete follow-up visit (≥4 weeks of CBT), and 30 subjects completed the full 12-week course.Baseline 24-h urinary cortisol levels did not correlate with CBT's antidepressant response. Higher KLS scores, a measure of early life parental loss or separation, correlated with delta HDRS24 (rs=-0.39, padjusted=0.05). Complementary general linear model analysis revealed enhanced CBT efficacy in patients with a history of early life parental loss or separation [F(1,35)=6.65, p=0.01]. ### Long_Answer: Small sample size, Treatment-naïve population. ### Final_Prediction: yes

### Question: Does exercise reduce inflammation and oxidative stress in obesity-related liver diseases? ### Context: Weight reduction remains the most common therapy advocated for the treatment of obesity-related liver diseases. Recently, a beneficial effect of exercise regimens for liver dysfunction, independent of weight reduction, has been reported. Therefore, a retrospective analysis was conducted to determine whether exercise training without dietary restriction in obese, middle-age men influences the pathophysiology of abnormal liver function.A total of 108 subjects who completed a 12-wk exercise training program without any dietary restriction were analyzed in this study; these results were compared with those of 104 subjects who completed a 12-wk dietary restriction program. Furthermore, 42 of these subjects (from both groups) who had abnormal liver function and suspicious liver fibrosis by nonalcoholic fatty liver disease fibrosis score were analyzed to obtain a more concrete outcome for exercise-training effects.In exercise training, although the magnitude of body-weight reduction (-3.1% vs -8.5%), waist circumference (-4.0% vs -7.1%), and visceral adipose tissue area (-12.2% vs -22.5%) was significantly more modest than that achieved by dietary restriction, exercise training elicited equivalent reductions in serum alanine aminotransferase and gamma glutamyl transpeptidase levels (-20.6% vs -16.1% and -25.7% vs -34.0%) and equivalent improvement of insulin resistance (-29.7% vs -26.9%). Moreover, exercise training remarkably increased the serum adiponectin level (+33.4% vs +15.1%). Importantly, for subjects with abnormal liver function and suspicious liver fibrosis, exercise training was effective in reducing the serum levels of inflammation and oxidative stress markers: ferritin and thiobarbituric acid reactive substances (-25.0% vs +1.1% and -33.5% vs -10.5%). ### Long_Answer: Exercise training benefits the management of obesity-related liver diseases independent of detectable weight reduction. Particularly, these effects seem to be acquired through an improvement in the hepatic inflammatory condition and its related oxidative stress levels. ### Final_Prediction: yes

### Question: Do age-specific normal values for the incremental shuttle walk test in a healthy British population? ### Context: The Incremental Shuttle Walk Test (ISWT) is an important functional and prognostic marker in chronic disease. Aging has a detrimental effect on exercise performance. The objective of this study was to produce normal age-specific values for the ISWT in a healthy British population and to explore whether additional variables improve the accuracy of a predictive equation.Healthy subjects (N = 152), aged 40 to 90 years, were recruited. Data collection occurred over 2 study visits. Anthropometric and demographic data were collected, and lung function and quadriceps maximal voluntary contraction were measured. An accelerometer was worn for 2 consecutive days at home. The Duke Activity Status Index was completed, and the greatest distance from 2 ISWTs was recorded.One hundred forty subjects (56 men) with mean age (SD) of 59.4 (11.0) years completed 2 ISWTs. Forced expiratory volume in 1 second (FEV(1)) was 109.1% (14.56%) predicted and ISWT distance was 737 m (183 m). Age-specific normal values for the ISWT were observed: mean (lower limit of normal)--40 to 49 years, 824 m (765 m); 50 to 59 years, 788 m (730 m); 60 to 69 years, 699 m (649 m); and 70 years and older, 633 m (562 m). A predictive equation was developed from 114 subjects. Age, body mass index, FEV(1), quadriceps maximal voluntary contraction, and Duke Activity Status Index contributed to ISWT distance predicting 50.4% of the variation in performance. ### Long_Answer: We have developed age-specific normal values for performance on the ISWT in a healthy British population. However, even using practical, clinically relevant variables, it is not possible to accurately predict exercise capacity from a regression equation. ### Final_Prediction: yes

### Question: Does recombinant human interleukin-6 induce hepatocyte growth factor production in cancer patients? ### Context: Experiments in animals demonstrate an important role for interleukin-6 (IL-6) in liver regeneration. It is suggested that IL-6 initiates hepatocyte growth factor (HGF) synthesis.The aim of the study was to examine the effect of exogenously administered recombinant human IL-6 (rhIL-6), in doses of 0.5, 1.0, 2.5, 5, 10 and 20 micrograms/kg/day, on HGF serum levels in humans. Serum HGF levels were measured on days 1, 2, 3, 8 and 15 and were correlated with serum amyloid A (SAA) and C-reactive protein (CRP).Median HGF levels increased to 124% at day 3 (P < 0.05) and 157% (P < 0.05) at day 8 as compared to 100% levels at day 1. An IL-6 dose-dependent increase in HGF was found at day 8 (R = 0.53, P < 0.02). The percentual change in serum HGF level at day 8 correlated with IL-6 serum levels at day 1 R = 0.59, P < 0.01). HGF levels did not correlate with CRP and SAA. ### Long_Answer: In humans, rhIL-6 administration resulted in an increase in serum HGF levels. ### Final_Prediction: yes

### Question: Is ultrasonographically detected non-alcoholic fatty liver disease an independent predictor for identifying patients with insulin resistance in non-obese , non-diabetic middle-aged Asian adults? ### Context: We assessed the association among ultrasonographically detected non-alcoholic fatty liver disease (US-NAFLD), metabolic syndrome (MetS), and insulin resistance (IR) in non-obese, non-diabetic middle-aged adults, to find out whether US-NAFLD is independently associated with IR in this population.A total of 5,878 non-obese (body mass index, ≥ 18.5 and < 25), non-diabetic individuals were analyzed. IR was estimated with the homeostasis model assessment index (HOMA2-IR) and defined when HOMA2-IR ≥ 1.5. MetS was defined by the Adult Treatment Panel III (ATP III) criteria.MetS was present in 381 (6.5%) participants, IR was present in 801 (13.6%) participants, and US-NAFLD was present in 1,611 (27.4%) participants. The increase in the prevalence of US-NAFLD closely followed the increase in the number of metabolic components diagnosed according to the ATP III criteria (15.2%, 28.5%, 48.0%, 65.7%, 71.4%, and 100% for 0, 1, 2, 3, 4, and 5 metabolic components, respectively, P < 0.001). US-NAFLD showed a significantly higher odds ratio (OR) for IR, regardless of the number of metabolic components (OR (95% confidence interval) of 3.48 (2.45-4.94), 3.63 (2.74-4.82), 3.19 (2.29-4.44), and 2.43 (1.43-3.81) for 0, 1, 2, and ≥ 3 metabolic components, respectively, P < 0.001 for all values). MetS showed a low sensitivity (0.22) for the identification of individuals with IR, and either US-NAFLD alone (0.60) or US-NAFLD with MetS (0.66) improved sensitivity with acceptable trade-off in specificity. ### Long_Answer: US-NAFLD was an independent predictor for IR, irrespective of the number of metabolic components of MetS in the non-obese, non-diabetic middle-aged Asian adults. US-NAFLD could identify individuals with IR that cannot be identified by MetS in this population. ### Final_Prediction: yes

### Question: Is increased expression of Ki-67 in mantle cell lymphoma associated with de-regulation of several cell cycle regulatory components , as identified by global gene expression analysis? ### Context: Mantle cell lymphoma (MCL) is an aggressive disease. Patients with this malignancy have a median survival of 3 years. To better understand disease progression, which is characterized by increased proliferation, we analyzed the gene expression of MCL with different proliferative indices, as determined by immunohistochemical staining for Ki-67. Furthermore, primary and relapsed tumors were compared to identify the possible growth advantages possessed by cells which persist after therapy and which might evolve into a tumor relapse.Twenty-one samples of MCL were analyzed, using the Affymetrix U95Av2 chip, containing probes for approximately 12,000 transcripts. Samples with a high versus low fraction of Ki-67+ cells were compared as were relapsed versus primary tumors. Immunohistochemistry was used to confirm the expression of some gene products.A distinct genetic signature, consisting of 32 genes, was found when comparing Ki-67high with Ki-67low MCL. The signature consisted of genes involved in cellular processes, such as mitotic spindle formation, gene transcription and cell cycle regulation, e.g. components of the p53 and retinoblastoma protein (pRb) pathways. Of note, cyclin D1, the hallmark of MCL, as well as Ki-67 were up-regulated in the samples with a high proliferative index. Comparing primary vs. relapsed tumors, 26 individual genes were found, several involved in cell adhesion. Furthermore, increased expression of transferrin receptor was found in the relapsed tumors. ### Long_Answer: A genetic signature distinguishing Ki-67high MCL from Ki-67low was established. The generated signature was used to assign new MCL samples to the high proliferative group, validating the association between these genes and proliferation in MCL. ### Final_Prediction: yes

### Question: Is operative Autonomy among Senior Surgical Trainees during Infrainguinal Bypass Operations Associated with Worse Long-term Patient Outcomes? ### Context: In an era of rapidly evolving surgical training, intraoperative teaching remains paramount to the education of surgical trainees. The impact of surgical trainees' level of expertise on outcomes after infrainguinal bypass surgery, a technically demanding operation, remains unknown. The purpose of this study was to explore the effects of surgical residents' experience on outcomes after infrainguinal bypass surgery.Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified patients who underwent infrainguinal bypass from 2005 to 2012. Patients were stratified according to the training level of the most senior operating trainee. Univariate and multivariate analyses, as well as propensity score matched analysis, were performed to compare patient cohorts on operative time, length of hospital stay (LOS), bleeding, early graft failure, unplanned readmission, and 30-day mortality.A total of 19,579 patients were identified, of which 35.6% were female and 64.4% were male; mean age was 67.6 years. A PGY1 (postgraduate year) was the highest level trainee operating on 2.5%, a PGY2-4 for 26.2%, and a PGY5+ (postgraduate year 5 or greater) for 37.1%. Attending surgeons operated without trainees on 34.2%. PGY5+s were more likely to operate on patients who were younger, non-White, male, and on dialysis. In multivariable analysis, involvement of any surgical trainee was associated with procedures that took a greater length of time, had a greater odds of blood transfusion, and necessitated a longer hospital LOS relative to procedures performed by an attending surgeon alone. Only bypasses wherein PGY5+s were involved were associated with greater odds of early graft failure, unplanned readmission, and 30-day mortality when compared with procedures done without trainee involvement. After excluding lower extremity bypasses in which an attending surgeon operated without a trainee, propensity score matching analysis showed that patients operated on by PGY5+s had longer operative time (4.11 vs. 3.96 hr, P < 0.0001) and greater rates of postoperative bleeding (9.77% vs. 8.15%, P = 0.004) relative to patients operated on by attendings assisted by PGY1-4s, but no statistically significant difference in LOS, early graft failure, unplanned readmission, and perioperative mortality. ### Long_Answer: Operative involvement of senior trainees was associated with worse outcomes during infrainguinal bypass, potentially reflecting a lesser extent of attending surgeon involvement, but no difference in patient outcomes after bypass procedure. ### Final_Prediction: no

### Question: Are hepatobiliary organic anion transporters differentially regulated in acute toxic liver injury induced by carbon tetrachloride? ### Context: Hepatobiliary transporters are down-regulated in cholestasis, but their expression in acute, non-cholestatic, cytokine-mediated liver injury is unknown. Thus we studied the molecular mechanisms, by which sodium taurocholate cotransporting polypeptide (Ntcp), organic anion transporting polypeptide 1 (Oatp1), Oatp2, Oatp4, multidrug-resistance protein 2 (Mrp2) and bile salt export pump (Bsep) are regulated in liver injury induced by carbon tetrachloride (CCl(4)).mRNA and protein levels were determined in rats 24 and 72h after CCl(4) injection. Transporter gene transcription and binding activities of Ntcp and Mrp2 transactivators were assessed by nuclear runoff and electrophoretic mobility shift assays.mRNA levels significantly declined to 41+/-44% for Ntcp, 65+/-41% for Oatp1 and 64+/-28% for Oatp2, but remained unchanged for Oatp4, canalicular Mrp2 and Bsep. Protein levels declined only for Oatp4 (-50+/-17%) and Ntcp (-23+/-13%) at 24h. Reduced mRNA levels (Ntcp, Oatp1, Oatp2) were associated with decreased transcriptional activities. Binding activity of Ntcp transactivators (hepatocyte nuclear factor 1 alpha (HNF1alpha) and CAAT enhancer binding protein alpha (C/EBPalpha) were reduced by 24h, whereas retinoid X receptor alpha (RXRalpha):retinoid acid receptor alpha (RARalpha) as transactivator of both Ntcp and Mrp2 remained unaltered. Recovery of acute hepatitis and changes in gene expression occurred after 72h. ### Long_Answer: Acute liver injury results in down-regulation of basolateral organic anion transporters similar to liver regeneration after partial hepatectomy, but in contrast to endotoxin-induced cholestasis. Maintained binding activity of RXRalpha:RARalpha may explain differences in Mrp2 expression. ### Final_Prediction: yes

### Question: Is increase in use of non-invasive ventilation for infants with severe bronchiolitis associated with decline in intubation rates over a decade? ### Context: To redress the paucity of studies evaluating non-invasive respiratory support in bronchiolitis patients.Following ethics committee approval, the clinical database of a tertiary 23-bed paediatric intensive care unit (PICU) was reviewed for bronchiolitis admissions from January 2000 to December 2009. Length of stay (LOS), ventilatory requirements and risk factors, including prematurity, respiratory syncytial virus (RSV) status, chronic lung, neuromuscular, immune and congenital heart disease, were analysed.Of 8,288 admissions, 520 (6.27 %) had bronchiolitis with 343 (65.9 %) having RSV. Median (±SD) age and LOS were 2.78 months and 2.68 (±4.32) days. One (0.2 %) patient died. Assisted ventilation was required for 399 (76.7 %) patients. A total of 114 (28.6 %) patients were intubated directly and 285 (71.4 %) had a trial of non-invasive ventilation (NIV). Significant increase in the use of NIV was seen (2.8 %/year) with decline in intubation rates (1.9 %/ year) (p = 0.002). Of NIV patients, 237 (83.2 %) needed only NIV and 48 (16.8 %) failed and therefore needed intubation. The median LOS was shorter in those who succeeded NIV (2.38 ± 2.43 days) compared to those with invasive ventilation (5.19 ± 6.34 days) and those who failed NIV (8.41 ± 3.44 days). Presence of a risk factor increased the chances of failing NIV from 6 to 10 %. ### Long_Answer: NIV was successful in the vast majority of patients, particularly in those without risk factors and halved the LOS in intensive care. Failure of NIV was associated with increased duration of invasive ventilation and PICU LOS. A prospective study comparing different techniques of NIV will be helpful in defining the risks of failure of NIV. ### Final_Prediction: yes

### Question: Variations in hysterectomy rates in Ontario: does the indication matter? ### Context: To examine variations in rates of hysterectomy for the five main indications for the procedure in regions of Ontario.Cross-sectional population-based analysis of hospital discharge abstracts.All acute care facilities in Ontario.All 65,599 women whose hospital record contained a procedure code indicating that a hysterectomy was performed between Apr. 1, 1988, and Mar. 31, 1991. Duplicate cases, records of cancelled procedures and nonresidents were excluded.Crude and age-adjusted rates of hysterectomy, by indication, for each region of Ontario.Five indications accounted for more than 80% of hysterectomies performed. The median age-adjusted rate of hysterectomy for Ontario regions during the study period was 6.25 per 1000 women, with a 2.7-fold variation among regions. The regions with rates of hysterectomy in the highest quartile tended to be rural, and those with rates in the lowest quartile tended to be urban areas with teaching hospitals. When rates of hysterectomy for specific indications were examined, they showed substantial variations among regions in the rate of the procedure for menstrual hemorrhage (18-fold variation), uterine prolapse (9.3-fold) and endometriosis (6.3-fold). A smaller but still significant variation was shown in the rate of hysterectomy for leiomyoma (2.3-fold). Regional variation in the rate of hysterectomy for cancer (2.5-fold) was not statistically significant. ### Long_Answer: There are large interregional variations in rates of hysterectomy, especially for indications that are more discretionary than others (i.e., menstrual hemorrhage, uterine prolapse and endometriosis) and less variation in rates when treatment options and diagnosis are clear-cut. This result suggests the need for more definitive practice guidelines on treatment of the indications for which the rate is more variable. ### Final_Prediction: nan

### Question: Does nitric oxide attenuate cardiomyocytic apoptosis via diminished mitochondrial complex I up-regulation from cardiac ischemia-reperfusion injury under cardiopulmonary bypass? ### Context: This study tested the hypothesis that cardioplegic solution supplemented with a nitric oxide donor agent attenuates postischemic cardiomyocytic apoptosis by reduction of mitochondrial complex I up-regulation during global cardiac arrest under cardiopulmonary bypass.Twenty-four anesthetized dogs supported by total vented bypass were divided evenly into 4 groups (n = 6) and subjected to 60 minutes of hypothermic ischemia followed by 4 degrees C multidose crystalloid cardioplegic solution infusion. Hearts received either standard crystalloid cardioplegic solution (control), crystalloid cardioplegic solution supplemented with 2 mmol/L L-arginine (L-Arg group), crystalloid cardioplegic solution supplemented with 400 micromol/L N(G)-monomethyl-L-arginine (L-NMMA group), or crystalloid cardioplegic solution supplemented with 100 micromol/L of NO donor compound (3-morpholinosydnonimine; SIN-1 group). After 60 minutes of cardioplegic arrest, the heart was reperfused for a total of 240 minutes after discontinuation of bypass. The occurrence of cardiomyocytic apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and Western blot analysis of caspase-3.The occurrence of cardiomyocytic apoptosis was significantly reduced in SIN-1 and L-Arg groups compared with the control group. Mitochondrial complex I mRNA was up-regulated in the control group, and its expression was significantly higher in the L-NMMA group but significantly reduced in the SIN-1 and L-Arg groups. Western blot analysis of Bcl-2 and cytochrome c, an index of mitochondrial damage in postischemic myocardium, revealed a similar pattern. ### Long_Answer: Nitric oxide-supplemented crystalloid cardioplegic solution diminished postischemic cardiomyocytic apoptosis after global cardiac arrest under cardiopulmonary bypass, possibly via prevention of mitochondrial complex I up-regulation. ### Final_Prediction: yes

### Question: Is notch-1 down-regulation by curcumin associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells? ### Context: Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. Therefore, the down-regulation of Notch signaling may be a novel approach for pancreatic cancer therapy. It has been reported that curcumin down-regulates many genes that are known to promote survival and also up-regulates genes that are known promoters of apoptosis in pancreatic cancer cells in vitro. It also has been reported that there is cross-talk between Notch-1 and another major cell growth and apoptotic regulatory pathway, the nuclear factor kappaB (NF-kappaB) pathway, which is down-regulated by both curcumin and reduction of Notch-1 levels. However, to the authors' knowledge to date, no studies have determined whether the down-regulation of Notch-1 signaling, resulting in the inactivation of NF-kappaB activity, contributes to curcumin-induced cell growth inhibition and apoptosis in pancreatic cancer cells.The authors used multiple molecular approaches, such as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, an apoptosis assay, gene transfection, real-time reverse transcriptase-polymerase chain reaction analysis, Western blot analysis, and an electrophoretic mobility shift assay to measure the DNA binding activity of NF-kappaB.Curcumin inhibited cell growth and induced apoptosis in pancreatic cancer cells. Notch-1, Hes-1, and Bcl-XL expression levels concomitantly were down-regulated by curcumin treatment. These results correlated with the inactivation of NF-kappaB activity and increased apoptosis induced by curcumin. The down-regulation of Notch-1 by small-interfering RNA prior to curcumin treatment resulted in enhanced cell growth inhibition and apoptosis. ### Long_Answer: The current results provide the first demonstration to the authors' knowledge that the Notch-1 signaling pathway is associated mechanistically with NF-kappaB activity during curcumin-induced cell growth inhibition and apoptosis of pancreatic cells. These results suggest that the down-regulation of Notch signaling by curcumin may be a novel strategy for the treatment of patients with pancreatic cancer. ### Final_Prediction: yes

### Question: Do physical signs reflect the degree of airflow obstruction in patients with asthma or chronic obstructive pulmonary disease? ### Context: The aim of the study was to relate the physical signs of the chest to the degree of airflow obstruction in asthma and COPD.113 patients with COPD and 76 patients with asthma were recruited from general practice. A standard physical examination of the chest was performed by trained medical students. Physical signs were related to the degree of airflow obstruction.the signs correlating closely with the degree of airflow obstruction were: a prolonged expiratory phase, low-standing diaphragm, decreased expiratory breath sounds, noisy inspiratory sounds, and decreased diaphragmatic excursions. There was a fair correlation between the number of physical signs and the degree of airflow obstruction. This was especially the case in asthma (r = 0.62), but it was less clear in COPD (r = 0.45). Sensitivity of separate physical signs to detect airflow obstruction was less than 50%, but at least one of the signs was present in 70% of the patients with obstruction. Specificity of separate signs was more than 85%, apart from wheezing in asthma. ### Long_Answer: the combination of physical signs can offer relevant information in monitoring the severity of airflow obstruction in asthma and COPD. ### Final_Prediction: nan

### Question: Do sLC26A6 and SLC26A7 anion exchangers have a distinct distribution in human kidney? ### Context: The anion transporters SLC26A6 (PAT1) and SLC26A7, transporting at least chloride, oxalate, sulfate and bicarbonate, show a distinct expression and function in different mammalian species. They are expressed in kidney, but their exact localization in human kidney has not been studied. We therefore examined SLC26A6 and A7 expression in human kidneys.The localization of SLC26A6 and A7 in different segments of human nephrons was studied by RT-PCR and immunohistochemistry by comparing to the tubular markers PNRA, CD10, Tamm-Horsfall antigen, high molecular weight cytokeratin, CK7, AQP2 and H(+)V-ATPase.In human kidney, SLC26A6 is expressed in distal segments of proximal tubules, parts of the thin and thick ascending limbs of Henle's loops, macula densa, distal convoluted tubules and a subpopulation of intercalated cells of collecting ducts. SLC26A7 is expressed in extraglomerular mesangial cells and a subpopulation of intercalated cells of collecting ducts. ### Long_Answer: Our results show that in human kidney SLC26A6 and A7 have a distinct, partially overlapping expression in distal segments of nephrons. The distribution partly differs from that found previously in rodent kidneys. ### Final_Prediction: yes