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### Question: Endoluminal graft repair for abdominal aortic aneurysms in high-risk patients and octogenarians: is it better than open repair? ### Context: To analyze the short-term and midterm results of open and endoluminal repair of abdominal aortic aneurysms (AAA) in a large single-center series and specifically in octogenarians.Between January 1997 and October 2000, 470 consecutive patients underwent elective repair of AAA. Conventional open repair (COR) was performed in 210 patients and endoluminal graft (ELG) repair in 260 patients. Ninety of the patients were 80 years of age or older; of these, 38 underwent COR and 52 ELG repair.Patient characteristics and risk factors were similar for both the entire series and the subgroup of patients 80 years or older. The overall complication rate was reduced by 70% or more in the ELG versus the COR groups. The postoperative death rate was similar for the COR and ELG groups in the entire series and lower (but not significantly) in the ELG 80 years or older subgroup versus the COR group. The 36-month rates of freedom from endoleaks, surgical conversion, and secondary intervention were 81%, 98.2%, and 88%, respectively. ### Long_Answer: The short-term and midterm results of AAA repair by COR or ELG are similar. The death rate associated with this new technique is low and comparable, whereas the complication rate associated with COR in all patients and those 80 years or older in particular is greater and more serious than ELG repair. Long-term results will establish the role of ELG repair of AAA, especially in elderly and high-risk patients. ### Final_Prediction: nan |
### Question: Does hinokitiol reduce matrix metalloproteinase expression by inhibiting Wnt/β-Catenin signaling in vitro and in vivo? ### Context: In this study, we investigated the effects of hinokitiol on matrix metalloproteinase (MMP)-1, -3, -13, collagen type II (Col2a1) and β-catenin expressions in rat chondrocytes induced by interleukin-1β and in an experimental rat model induced by intra-articular injection of mono-iodoacetate (MIA) into the knee.Chondrocytes were cultured from the articular cartilage of 2-week-old rats. Passaged chondrocytes were pretreated with hinokitiol for 2h followed by co-incubation with IL-1β for 24h. Quantitative real-time polymerase chain reaction and Western blotting were used to assess the expression of MMP-1, -3, -13, Col2a1 and β-catenin. Chondrocytes were also treated with Licl, Dickkopf-1, and/or hinokitiol for 24h, the MMP-1, -3, -13 and β-catenin protein levels determined by Western blotting. The in vivo effects of hinokitiol were assessed by morphological and histological analyses following MIA injection.Hinokitiol inhibited IL-1β-stimulated MMP-1,-3 and -13 expressions and IL-1β-induced activation of intracellular β-catenin proteins in cultured chondrocytes. In vivo, morphological and histological examinations demonstrated that hinokitiol significantly ameliorated cartilage degeneration. ### Long_Answer: Hinokitiol is an effective anti-inflammatory reagent that acts by inhibiting the Wnt/β-catenin signaling pathway and could be a promising therapeutic agent for the prevention and treatment of osteoarthritis. ### Final_Prediction: yes |
### Question: Endorectal 3D T2-weighted 1mm-slice thickness MRI for prostate cancer staging at 1.5Tesla: should we reconsider the indirects signs of extracapsular extension according to the D'Amico tumor risk criteria? ### Context: To evaluate the accuracy of a 3D-endorectal 1mm-thick slices MRI acquisition for local staging of low, intermediate and high D'Amico risk prostate cancer (PCa).178 consecutive patients underwent a multiparametric MRI protocol prior to radical prostatectomy (RP). T2W images were acquired with the 3D sampling perfection with application optimized contrasts using different flip angle evolutions (SPACE) sequence (5mn acquisition time). Direct and indirect MRI signs of extracapsular extension (ECE) were evaluated to predict the pT stage. The likelihood of SVI (seminal vesicle invasion) was also assessed.Histology showed ECE and SVI in 38 (21%) and 12 (7%) cases, respectively. MRI sensitivity and specificity to detect ECE were 55 and 96% if direct signs of ECE were used and 84 and 89% (p<0.05), if both direct and indirect signs were combined. D'Amico criteria did not influence MRI performance. Sensitivity and specificity for SVI detection were 83% and 99%. ### Long_Answer: 3D data sets acquired with the SPACE sequence provides a high accuracy for local staging of prostate cancer. The use of indirect signs of ECE may be recommended in low D'Amico risk tumors to optimise patient selection for active surveillance or focal therapy. ### Final_Prediction: nan |
### Question: Does characteristic epithelium with low-grade atypia appear on the surface of gastric cancer after successful Helicobacter pylori eradication therapy? ### Context: The incidence of gastric cancer after successful Helicobacter pylori eradication has been increasing. We previously reported that epithelium with low-grade atypia (ELA) appeared on the surface of gastric cancer after H. pylori eradication. Here, we investigate the clinical and biological characteristics of such ELA.We studied 27 cases of gastric cancer detected after successful H. pylori eradication therapy. We examined the prevalence of ELA among these cases and its significance for endoscopic discovery after H. pylori eradication. We additionally investigated the mucus, p53 and Ki67 expressions in ELA.Epithelium with low-grade atypia that continuous with the gastric tumor was detected in 22 of 27 cases (81%), a significantly greater percentage than that for controls (p < 0.01). We found that gastric-type mucin was frequently expressed in this epithelium. Neither p53- nor Ki67-positive cells were found in ELA, irrespective of their expression in tumor tissue. The presence of ELA was positively correlated with the clinical interval between H. pylori eradication and gastric cancer detection. ### Long_Answer: Epithelium with low-grade atypia on gastric cancer tissue, which may develop from gastric cancer cells, is frequently present after successful eradication therapy. This phenomenon could influence the practice of endoscopic diagnosis of gastric cancers. ### Final_Prediction: yes |
### Question: Is detection of EGFR mutations in plasma DNA from lung cancer patients by mass spectrometry genotyping predictive of tumor EGFR status and response to EGFR inhibitors? ### Context: EGFR mutations now guide the clinical use of EGFR-targeted therapy in lung cancer. However, standard EGFR mutation analysis requires a minimum amount of tumor tissue, which may not be available in certain situations. In this study, we combined a mass spectrometry genotyping assay (Sequenom) with a mutant-enriched PCR (ME-PCR) to detect EGFR mutations in free plasma DNA from patients with lung cancer.DNAs were extracted from 31 plasma samples from 31 patients and analyzed by both methods for EGFR Exon 19 deletion and EGFR L858R mutation. Results in plasma DNA samples were compared with EGFR mutation status obtained in tumor DNA (18/31 EGFR mutant). The relationship of EGFR mutation status in tumor and/or plasma samples to overall survival was assessed.The EGFR mutation status in plasma DNA was identical to the primary tumor in 61% of patients (19/31). By mass spectrometry genotyping, the plasma samples contained mutant DNA corresponding to 5/14 EGFR Exon 19 deletions and 3/4 EGFR L858R mutations previously diagnosed in the matched tumors. Two samples were positive in plasma DNA but negative in primary tumor tissue. Results were similar for samples studied by ME-PCR. For patients treated with erlotinib, overall survival was correlated with the presence of EGFR mutation in plasma and/or tumor tissue (p=0.002), with the two patients positive only in plasma DNA showing responses and favorable outcomes. ### Long_Answer: The detection of EGFR mutations in plasma DNA samples by mass spectrometry genotyping and ME-PCR is feasible. A positive EGFR result in plasma DNA has a high predictive value for tumor EGFR status and for favorable clinical course on EGFR-targeted therapy and could therefore be useful in guiding clinical decisions in patients with insufficient or unavailable tumor specimens. ### Final_Prediction: yes |
### Question: Is the unfolded protein response an important regulator of inflammatory genes in endothelial cells? ### Context: Oxidized 1-palmitoyl-2-arachidonyl-sn-3-glycero-phosphorylcholine (oxPAPC) accumulates in atherosclerotic lesions and in vitro studies suggest that it mediates chronic inflammatory response in endothelial cells (ECs). The goal of our studies was to identify pathways mediating the induction of inflammatory genes by oxPAPC.Using expression arrays, quantitative polymerase chain reaction (PCR), and immunoblotting we demonstrate that oxPAPC leads to endoplasmic reticulum stress and activation of the unfolded protein response (UPR) in human aortic ECs. Immunohistochemistry analysis of human atherosclerotic lesions indicated that UPR is induced in areas containing oxidized phospholipids. Using the UPR inducing agent tunicamycin and selective siRNA targeting of the ATF4 and XBP1 branches of the UPR, we demonstrate that these transcription factors are essential mediators of IL8, IL6, and MCP1 expression in human aortic ECs required for maximal inflammatory gene expression in the basal state and after oxPAPC treatment. We also identify a novel oxPAPC-induced chemokine, the CXC motif ligand 3 (CXCL3), and show that its expression requires XBP1. ### Long_Answer: These data suggest that the UPR pathway is a general mediator of vascular inflammation and EC dysfunction in atherosclerosis, and, likely, other inflammatory disorders. ### Final_Prediction: yes |
### Question: Role of MRI in the staging of breast cancer patients: does histological type and molecular subtype matter? ### Context: To assess the role of MRI in the pre-operative staging of patients with different histological types and molecular subtypes of breast cancer, by the assessment of the dimensions of the main tumour and identification of multifocal and/or multicentric disease.The study included 160 females diagnosed with breast cancer who underwent breast MRI for pre-operative staging. The size of the primary tumour evaluated by MRI was compared with the pathology (gold standard) using the Pearson's correlation coefficient (r). The presence of multifocal and/or multicentric disease was also evaluated.The mean age of patients was 52.6 years (range 30-81 years). Correlation between the largest dimension of the main tumour measured by MRI and pathology was worse for non-special type/invasive ductal carcinoma than for other histological types and was better for luminal A and triple-negative than for luminal B and Her-2 molecular subtypes. Multifocal and/or multicentric disease was present in 48 patients (30.0%), and it was more common in breast carcinomas classified as Her-2 molecular subtype. There was no statistically significant difference in the frequency of multifocal and/or multicentric tumours identified only by MRI in relation to histological type or molecular subtype. ### Long_Answer: The results of this retrospective study demonstrated that histological types and molecular subtypes might influence the MRI assessment of breast cancers, especially in the evaluation of tumour size. ### Final_Prediction: nan |
### Question: Are alcoholism treatments effective? ### Context: Project MATCH was the largest and most expensive alcoholism treatment trial ever conducted. The results were disappointing. There were essentially no patient-treatment matches, and three very different treatments produced nearly identical outcomes. These results were interpreted post hoc as evidence that all three treatments were quite effective. We re-analyzed the data in order to estimate effectiveness in relation to quantity of treatment.This was a secondary analysis of data from a multisite clinical trial of alcohol dependent volunteers (N = 1726) who received outpatient psychosocial therapy. Analyses were confined to the primary outcome variables, percent days abstinent (PDA) and drinks per drinking day (DDD). Overall tests between treatment outcome and treatment quantity were conducted. Next, three specific groups were highlighted. One group consisted of those who dropped out immediately; the second were those who dropped out after receiving only one therapy session, and the third were those who attended 12 therapy sessions.Overall, a median of only 3% of the drinking outcome at follow-up could be attributed to treatment. However this effect appeared to be present at week one before most of the treatment had been delivered. The zero treatment dropout group showed great improvement, achieving a mean of 72 percent days abstinent at follow-up. Effect size estimates showed that two-thirds to three-fourths of the improvement in the full treatment group was duplicated in the zero treatment group. Outcomes for the one session treatment group were worse than for the zero treatment group, suggesting a patient self selection effect. Nearly all the improvement in all groups had occurred by week one. The full treatment group had improved in PDA by 62% at week one, and the additional 11 therapy sessions added only another 4% improvement. ### Long_Answer: The results suggest that current psychosocial treatments for alcoholism are not particularly effective. Untreated alcoholics in clinical trials show significant improvement. Most of the improvement which is interpreted as treatment effect is not due to treatment. Part of the remainder appears to be due to selection effects. ### Final_Prediction: nan |
### Question: Does boron neutron capture therapy induce apoptosis of glioma cells through Bcl-2/Bax? ### Context: Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation.The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [60Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [60Co] γ-rays; Group C included cells treated with 8 Gy of [60Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis.Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [60Co] γ-rays (P < 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E treated with BPA-BNCT were significantly higher than those in Group B and Group C irradiated by [60Co] γ-rays (P < 0.01). The clonogenicity of glioma cells was reduced by BPA-BNCT compared with cells treated in the reactor (Group F, G, H, I), and with the control cells (P < 0.01). Upon BPA-BNCT treatment, the Bax level increased in glioma cells, whereas Bcl-2 expression decreased. ### Long_Answer: Compared with γ-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by BNCT may be related to activation of Bax and downregulation of Bcl-2. ### Final_Prediction: yes |
### Question: Coronary CT angiography and myocardial perfusion imaging to detect flow-limiting stenoses: a potential gatekeeper for coronary revascularization? ### Context: To evaluate the diagnostic accuracy of a combined non-invasive assessment of coronary artery disease with coronary CT angiography (CTA) and myocardial perfusion imaging (MPI) for the detection of flow-limiting coronary stenoses and its potential as a gatekeeper for invasive examination and treatment.In 78 patients (mean age 65 +/- 9 years) referred for coronary angiography (CA), additional CTA and MPI (using single-photon emission-computed tomography) were performed and the findings not communicated. Detection of flow-limiting stenoses (justifying revascularization) by the combination of CTA and MPI (CTA/MPI) was compared with the combination of quantitative coronary angiography (QCA) plus MPI (QCA/MPI), which served as standard of reference. The findings of both combinations were related to the treatment strategy (revascularization vs. medical treatment) chosen in the catheterization laboratory based on the CA findings. Sensitivity, specificity, positive and negative predictive value, and accuracy of CTA/MPI for the detection of flow-limiting coronary stenoses were 100% each. More than half of revascularization procedures (21/40, 53%) was performed in patients without flow-limiting stenoses and 76% (47/62) of revascularized vessels were not associated with ischaemia on MPI. ### Long_Answer: The combined non-invasive approach CTA/MPI has an excellent accuracy to detect flow-limiting coronary stenoses compared with QCA/MPI and its use as a gatekeeper appears to make a substantial part of revascularization procedures redundant. ### Final_Prediction: nan |
### Question: Are low free testosterone levels associated with prevalence and incidence of depressive symptoms in older men? ### Context: The prevalence of both low testosterone levels and depression increases with age. Currently, there is no consensus regarding the existence of an association. Our study analyses the cross-sectional association of testosterone levels with depressive symptoms and its prospective association with the development of incident depressive symptoms.Longitudinal population-based study; based on the data of the Longitudinal Aging Study Amsterdam (LASA) including 608 men aged >or=65 years (median age 75.6 years).Linear and logistic regression between total and free testosterone levels and depressive symptoms as measured by the Center of Epidemiologic Studies Depression (CES-D) scale, taking into account medical and lifestyle factors. Cox Proportional Hazards model was used to assess incident depressive symptoms.Unadjusted linear regression between square-root transformed CES-D scores and free testosterone levels showed a significant inverse association as a continuous variable (beta = -0.10, P < 0.05), lowest quartile compared to highest (beta = 0.12, P < 0.05) and with a threshold value of 170 pmol/l (beta = 0.13, P < 0.05). The results remained significant for the group below threshold after adjustment for all confounders (beta = 0.09, P < 0.05). Cox Proportional Hazards Model showed a decreased risk for incident depressive symptoms for men with higher free testosterone levels [HR = 0.997 CI (0.995-1.000)]. Men with the threshold value below 220 pmol/l were at increased risk of incident depressive symptoms [HR = 1.989 CI (1.173-3.374)]. ### Long_Answer: Free testosterone levels below 170 pmol/l are associated with depressive symptoms, while free testosterone levels below 220 pmol/l (lowest quintile of our population) predict the onset of depressive symptoms. ### Final_Prediction: yes |
### Question: Does desmocollin expression in oral atrophic lichen planus correlate with clinical behavior and DNA content? ### Context: Oral lichen planus (OLP) is a chronic mucocutaneous inflammatory disease, with some tendency toward malignant transformation. Markers are needed to identify the lesions at risk.A series of 82 biopsies from 70 patients with atrophic OLP was analyzed for desmocollin-1, E-cadherin, cyclin-dependent kinase 1 (cdk-1) and Rad-51 expression using immunohistochemistry and static DNA cytometry, with particular reference to clinical outcome.Desmocollin-1 and E-cadherin expression were each detected in 24.4% (20/82) of the samples. Of the positive samples, only eight specimens expressed both desmocollin-1 and E-cadherin. Strong desmocollin-1 and E-cadherin expression was found in 8.5% and 3.7% of OLP biopsies, respectively. Desmocollin-1 expression increased the risk of dysplasia 31.8-fold (95% confidence intervals (CI) 3.6-280.9; p = 0.0001), while E-cadherin was significantly related to cancer (odds ratio (OR) = 5.13; 95% CI 3.3-8.1; p = 0.001). In univariate survival analysis, desmocollin-1 was a significant predictor of both cancer (log-rank test; p = 0.033) and dysplasia (p = 0.0001), while E-cadherin predicted the development of cancer (p = 0.0001). Neither cdk-1 nor Rad-51 had any predictive value. Importantly, desmocollin-1 retained its value as the only independent predictor of dysplasia in the multivariate (Cox) model (adjusted Hazard Ratio (HR) = 44.13; 95% CI 3.7-525.6). ### Long_Answer: In atrophic OLP, desmocollin-1 is a powerful predictor of an important intermediate endpoint marker (dysplasia) in the causal pathway toward oral cancer. ### Final_Prediction: yes |
### Question: Does treatment with hESC-Derived Myocardial Precursors improve Cardiac Function after a Myocardial Infarction? ### Context: We previously reported the generation of a reporter line of human embryonic stem cells (hESCs) with enhanced green fluorescent protein (eGFP) expression driven by the α-myosin heavy chain (αMHC) promoter. The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs) in vitro. In this study, we evaluated the therapeutic effects of GFP+/αMHC+ cells isolated from the reporter line in a mouse model of myocardial infarction (MI).MI was generated in immunodeficient mice. hMPs were injected into murine infarcted hearts under ultrasound guidance at 3 days post-MI. Human fetal skin fibroblasts (hFFs) were injected as control. Cardiac function was evaluated by echocardiography. Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining.Compared with control, hMPs resulted in improvement of cardiac function post-MI with smaller infarct size, induced endogenous angiogenesis, and reduced apoptosis of host cardiomyocytes at the peri-infarct zone at 28 days post-MI. ### Long_Answer: Intramyocardial injection of hMPs improved cardiac function post-MI. The engraftment rate of these cells in the myocardium post-MI was low, suggesting that the majority of effect occurs via paracrine mechanisms. ### Final_Prediction: yes |
### Question: Is sNAI1 protein expression an independent negative prognosticator in muscle-invasive bladder cancer? ### Context: The prognosis of muscle-invasive bladder cancer is poor. Molecular prognosticators have gained increasing attention for individualized therapeutic options because they can identify patients with different prognoses.Tissue microarrays of formalin-fixed and paraffin-embedded tumor samples from 206 bladder cancer patients treated with cystectomy and chemotherapy were studied for SNAI1 protein expression by immunohistochemistry. SNAI1 expression was evaluated using an immunoreactive score (IRS). For statistical analysis, the patients were separated into two groups: those with tumor specimens negative for SNAI1 expression (IRS = 0), and the other positive for SNAI1 expression (IRS ≥1).Tumor samples from 42 patients showed negative SNAI1 expression, whereas the nuclei of tumor cells from 164 patients showed detectable nuclear staining of SNAI1. A Kaplan-Meier analysis of the bladder cancer patients with negative SNAI1 expression showed significantly reduced disease-specific survival (DSS) and progression-free survival (PFS) compared to the patients with positive expression (p = 0.010 and 0.013). A multivariate Cox regression analysis (adjusted for gender, age, tumor stage, tumor grade, lymph node metastasis, chemotherapy, and histologic subtype) again showed a significant correlation between patients lacking SNAI1 expression and DSS (p = 0.005; relative risk 2.31; 95 % confidence interval 1.28-4.17) or PFS (p = 0.004; relative risk 2.20; 95 % confidence interval 1.29-3.78) compared to patients with positive SNAI1 staining. ### Long_Answer: Loss of SNAI1 protein expression is an independent prognosticator for PFS and DSS in bladder cancer patients treated by radical cystectomy and adjuvant chemotherapy. Its prognostic value for neoadjuvant or adjuvant chemotherapy must be evaluated in further prospective randomized controlled trials. ### Final_Prediction: yes |
### Question: Iliosacral screw placement: are uniplanar changes realistic based on standard fluoroscopic imaging? ### Context: With the aim of improving the understanding of iliosacral screw placement, two hypotheses were tested: (1) standard intraoperative inlet and outlet images are not based on orthogonal coordinates, and (2) therefore making starting point and aim changes by moving perpendicular to the c-arm beam will displace the guide wire on the other intraoperative radiographic view.This is a prospective case series with review of intraoperative data from consecutive patients treated at a University Level I trauma center. The study group included ten consecutive patients with nondysmorphic upper sacral segments and unstable posterior pelvic ring injuries that required surgical treatment. Posterior surgical stabilization included iliosacral screw placement using a standardized three- view technique in the supine position. The main outcome measurement included the angles from the perpendicular required to achieve what have been considered the ideal inlet and outlet views intraoperatively. The angle arc for each patient created by the recorded angles was then determined.The average sagittal plane tilt required to achieve the ideal inlet view was 25 degrees (range, 21-33 degrees). The average sagittal plane tilt required to achieve the ideal outlet view was 42 degrees (range, 30-50 degrees). The average arc between the ideal inlet and outlet views was 67 degrees (range, 62-76 degrees). These views never created an orthogonal system. ### Long_Answer: We commonly work in orthogonal systems. Within these systems, it is possible to make a uniplanar correction by moving perpendicular to one plane or radiographic view. The ideal views to image the safe zone for iliosacral screw placement do not create an orthogonal system. When this average angle arc is placed on a graphic model of the pelvis, it becomes clear that the plane of the radiographic beam of the ideal inlet view is collinear with the anterior aspect of the upper two sacral bodies. The outlet view is oblique to the upper sacral bodies. Surgeons must keep this in mind when using fluoroscopic views to insert iliosacral screws. ### Final_Prediction: nan |
### Question: Do national survey of pediatric breathing systems use in the UK? ### Context: To determine current practice in the use of pediatric breathing systems in the UK.Whilst the Ayres T-Piece has been used extensively in pediatric anesthesia for nearly six decades, the circle system has undergone recent modifications. These have enhanced its suitability for pediatric use.A postal questionnaire was sent to all consultant members of the Association of Paediatric Anaesthetists (APA). This asked about standard breathing systems for induction, maintenance, and ventilation during anesthesia in three groups of children (neonates, infants, and older children less than 20 kg). Additional questions included if anesthetic rooms were used and scavenging routinely employed.Replies were received from 337 members, giving a response rate of 75%. The T-Piece was the predominant breathing system for induction in all age groups but the circle appears popular for maintenance, particularly in older children. Anesthetic rooms were used by 97% for induction and scavenging used by only 60% when using a T-Piece. ### Long_Answer: Despite significant improvements to the pediatric circle system and its practical advantages, the T-Piece remains the commonest breathing system used in smaller children by UK members of the APA. ### Final_Prediction: yes |
### Question: Is a functional SNP upstream of the beta-2 adrenergic receptor gene ( ADRB2 ) associated with obesity in Oceanic populations? ### Context: Obesity is a growing health concern in the Oceanic populations. To investigate the genetic factors associated with adult obesity in the Oceanic populations, the association of single nucleotide polymorphisms (SNPs) of the beta-2 adrenergic receptor (ADRB2) gene with obesity was examined in 694 adults living in Tonga and Solomon Islands.A screening for variation in 16 Oceanic subjects detected 17 SNPs in the entire region of ADRB2, of which nine SNPs including two non-synonymous ones, rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu), were further genotyped for all subjects. The rs34623097-A allele, at a SNP located upstream of ADRB2, showed the strongest association with risk for obesity in a logistic regression analysis adjusted for age, sex, and population (P=5.6 × 10(-4), odds ratio [OR]=2.5, 95% confidence interval [CI]=1.5-4.2). The 27Glu was also significantly associated with obesity in the single-point association analysis (P=0.013, OR=2.0, 95%CI=1.2-3.4); however, this association was no longer significant after adjustment for rs34623097 since these SNPs were in linkage disequilibrium with each other. A copy of the obesity-risk allele, rs34623097-A, led to a 1.6 kg/m(2) increase in body mass index (BMI; defined as weight in kilograms divided by height in meters squared) (P=0.0019). A luciferase reporter assay indicated that rs34623097-A reduced the transcriptional activity of the luciferase reporter gene by approximately 10% compared with rs34623097-G. An electrophoretic mobility shift assay demonstrated that rs34623097 modulated the binding affinity with nuclear factors. An evolutionary analysis implies that a G>A mutation at rs34623097 occurred in the Neandertal genome and then the rs34623097-A allele flowed into the ancestors of present-day humans. ### Long_Answer: The present results suggest that rs34623097-A, which would lead to lower expression of ADRB2, contributes to the onset of obesity in the Oceanic populations. ### Final_Prediction: yes |
### Question: Does bladder outlet obstruction influence mRNA expression of cholinergic receptors on sensory neurons in mice? ### Context: In patients with bladder outlet obstruction (BOO), dysregulation of bladder afferent neurons seems to contribute to irritative symptoms. Cholinergic receptors, addressed by both neuronal and non-neuronal (urothelial) acetylcholine, can alter neuronal excitability. Thus we investigated the influence of BOO on the expression of muscarinic (mAChR) and nicotinic (nAChR) acetylcholine receptors in the lumbosacral dorsal root ganglia (DRG) of mice.BOO was induced in 13 C57/BL6 mice by partial suturing of the urethra. Eleven mice were sham-operated (loose/freely movable suture around the urethra), and eleven untreated mice served as controls. Cystometry was performed five weeks later in conscious mice. DRG at segmental levels L5-S2 were dissected and real-time quantitative PCR was performed. Expression of mAChR subtypes M1-M5 and nAChR subunits α2-7, α9-10, β2-4 was examined.Expression of all mAChR subtypes and nAChR subunits α3-7, α10, β2-4 was detected. Expression of α2 and α9 was absent. Rank order of expression was M2>M4>M3>M5>M1, α3≥α6>α7>α4>α10>α5 and β2>β4>β3 in untreated animals. BOO mice presented distinct obstruction with development of residual urine. Sham mice showed only minimal BOO. Relative mRNA expression of nAChR subunits revealed significant reduction of α3, α5, α6, α10 and β4 in sham-operated vs. untreated mice. In BOO vs. sham-operated mice, reduction of nAChR subunits α10 (p=0.038) and α5 (p=0.053) was found. ### Long_Answer: BOO has a considerable impact on nAChR, but not on mAChR mRNA expression in sensory neurons. We hypothesize that a reduction in mRNA expression of nAChR subunits represents a link to altered sensitivity under non-obstructive conditions. ### Final_Prediction: yes |
### Question: Health insurance and mammography: would a Medicare buy-in take us to universal screening? ### Context: To determine whether health insurance expansions via a Medicare buy-in might plausibly increase mammography screening rates among women aged 50-64.Two waves of the Health and Retirement Study (HRS) (1994, 1996).A longitudinal study with most explanatory variables measured at the second wave of HRS (1994); receipt of mammography, number of physician visits, and breast self exam (BSE) were measured at the third wave (1996).Our sample included women aged 50-62 in 1994 who answered the second and third HRS interview (n = 4,583).From 1994 to 1996, 72.7 percent of women received a mammogram. Being insured increased mammography in both unadjusted and adjusted analyses. A simulation of universal insurance coverage in this age group increased mammography rates only to 75-79 percent from the observed 72.7 percent. When we accounted for potential endogeneity of physician visits and BSE to mammography, physician visits remained a strong predictor of mammography but BSE did not. ### Long_Answer: Even in the presence of universal coverage and very optimistic scenarios regarding the effect of insurance on mammography for newly insured women, mammography rates would only increase a small amount and gaps in screening would remain. Thus, a Medicare buy-in could be expected to have a small impact on mammography screening rates. ### Final_Prediction: nan |
### Question: Does long-term glycemic control influence the onset of limited joint mobility in type 1 diabetes? ### Context: Limited joint mobility (LJM) in childhood insulin-dependent (type 1) diabetes is associated with a substantially increased risk of microvascular complications. Cross-sectional studies have not demonstrated a relationship between LJM and metabolic control. This study was designed to determine whether glycemic control, as measured by glycohemoglobin (hgbA1C) levels from the onset of diabetes, is associated with the occurrence of LJM.Probands (n = 18) had hgbA1C values and recorded observation of joint function from soon after onset of their diabetes. Controls (n = 40) were matched to probands for gender and age at diagnosis and had follow-up beyond the age at which the proband was found to have LJM.The odds ratio for occurrence of LJM for the mean hgbA1C from diabetes onset was 1.46, 95% confidence limits 1.07 to 2.00. Thus, for every unit increase in average hgbA1C, there was approximately a 46% increase in the risk of LJM. When hgbA1C was dichotomized, the OR for hgbA1C of more than 8% was 2.55, and the OR was 4.54 if the hgbA1C was greater than 12%. Age at diagnosis and duration of diabetes were not independent prognostic factors for LJM. ### Long_Answer: Glycemic control from onset of diabetes is strongly associated with occurrence of LJM. ### Final_Prediction: yes |
### Question: Limitations of GD-EOB-DTPA-enhanced MRI: can clinical parameters predict suboptimal hepatobiliary phase? ### Context: This retrospective study included patients with chronic liver disease who underwent hepatocellular carcinoma screening with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) between 1 January 2011 and 30 November 2014. For each case, HBP was graded as adequate or suboptimal, based on Liver Image Reporting and Data System (LI-RADS) criteria. The following laboratory data obtained within 3 months of the MRI date was extracted: total bilirubin (TB), direct bilirubin (DB), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (ALP), albumin, activated partial thromboplastin time (aPTT), and International normalised ratio (INR). Model For End-Stage Liver Disease (MELD) scores were calculated as 3.78×ln[TB] + 11.2×ln[INR] + 9.57×ln[creatinine] + 6.43. Receiver operating characteristic (ROC) curve analysis was used to establish cut-off values for predicting suboptimal HBP.Of 284 patients, 242 (85.2%) patients (91; 57.6% male) had an adequate HBP and 42 (14.8%) patients (13; 61.9% male) had suboptimal HBP, with mean ages of 58.5±9.7 years and 55±12.7 years, respectively (p=0.096). Areas under the ROC curve for predicting suboptimal HBP were 0.85 (95%CI 0.79-0.91) for the MELD score, 0.88 (95%CI 0.82-0.93) for TB, and 0.91 (95%CI 0.86-0.95) for DB. Accuracy, positive likelihood ratios and cut-off values for predicting suboptimal HBP were, respectively: 86.7% and 11.2 for the MELD score ≥16.7, 88.2% and 28.7 for TB ≥4.3 mg/dl, and 91.1% and 36.4 for DB ≥1.3 mg/dl. SGOT, SGPT, and ALP were not statistically significantly different between the groups. ### Long_Answer: Cut-off levels of MELD score, DB, and TB can predict an suboptimal HBP with high accuracy. Prospective identification of patients with a high likelihood of an suboptimal HBP can help to avoid administering a more costly agent to patients who would not benefit from its unique properties. ### Final_Prediction: nan |
### Question: Does intensive training over 5 days improve colonoscopy skills long-term? ### Context: Poor standards in colonoscopy services and the introduction of a colorectal cancer screening program in the United Kingdom have highlighted the need to establish high-quality training and competency assessments in colonoscopy. The aims of this study were to evaluate the effectiveness of a 1-week hands-on colonoscopy course utilizing novel assessment tools.Twenty-one doctors with varying colonoscopy experience who attended an accelerated colonoscopy training week (ACTW) were prospectively studied. They were trained and assessed in key aspects of colonoscopy. Knowledge was assessed with a multiple choice question (MCQ) paper. Practical hand skills were taught and evaluated using a computer simulator and live case teaching. Actual colonoscopy performance was assessed using Direct Observation of Procedural Skills scores (DOPS) and an objective tri-split video score of insertion technique. Two independent trainers taught and assessed the trainees at the start and end of the ACTW and at a median of 9 months' follow-up.Following training there were significant improvements in the MCQ score (P < 0.001), the simulator test case times (P = 0.02, P = 0.003), and the global DOPS score (P < or = 0.02). All improvements following the accelerated training were sustained at a median follow-up of 9 months. ### Long_Answer: This study is the first in the literature to describe the positive, sustained impact of an intensive hands-on colonoscopy training course. Measurements of performance in key areas of skill acquisition improved following training. ### Final_Prediction: yes |
### Question: Do patients with prostate cancer continue to have excess mortality up to 15 years after diagnosis? ### Context: To estimate the population-based conditional 5-year relative survival rates for patients with prostate cancer (PCa).All 98 672 patients, aged 45-89 years, diagnosed in the Netherlands with PCa (clinical T stage 1-4) in the period 1989-2008 were selected from the Netherlands Cancer Registry and followed up until 2010. The conditional 5-year relative survival rate was estimated for every subsequent year of survival up to 15 years after diagnosis.The conditional 5-year relative survival rate decreased with survival time from diagnosis. Excess mortality (conditional 5-year relative survival rate <95%) for patients with clinical T1 stage only became manifest 5 years after diagnosis and increased to almost 10% after 10 years. Patients with more advanced disease (cT2-cT4) were found to have an excess mortality rate of 6-12% at diagnosis, which increased to 15-22% after 10 years. Excess mortality occurred earlier for the older age groups. The 5-year relative survival rate at diagnosis was <90% for all age groups of patients with cT3/cT4 disease and excess mortality for this group increased to >20% for those who had already survived for 5 years since diagnosis. ### Long_Answer: Patients with PCa were found to have excess mortality within 10 years of diagnosis. Excess mortality was found at an earlier timepoint for patients with a more advanced stage and for older age groups. Quantitative insight into conditional survival is useful for caregivers to help plan optimum cancer treatment and surveillance and to inform patients about their actual prognosis during follow-up, taking the current condition of the patient into account. ### Final_Prediction: yes |
### Question: Is wine consumption associated with a decreased risk of alcoholic cirrhosis in heavy drinkers? ### Context: While it was thought that all alcoholic beverages share a similar liver toxicity when drunk at a high level, recent epidemiological surveys have suggested that wine drinking might decrease the risk of alcoholic cirrhosis in heavy drinkers. Therefore, we performed a study aiming to analyse the type and the intake levels of alcoholic beverages in heavy drinkers according to the severity of the liver disease.This is a case-control study enrolling 42 cirrhotic and 60 non-cirrhotic patients. Liver status was assessed using clinical, biological, histological and ultrasonographic procedures. Alcohol consumption was recorded using the Lifetime Drinking History method.We did not find any significant differences in total alcohol consumption between cases and controls and, moreover, in our series, the relative percentage of pure alcohol drunk in wine was significantly higher in cirrhotic, than in non-cirrhotic, patients. ### Long_Answer: Our results confirm that the absence of a link between the type of alcoholic beverage and the occurrence of cirrhosis is still valid. ### Final_Prediction: no |
### Question: Sexual functioning and congenital heart disease: Something to worry about? ### Context: Although sexual problems in cardiac patients are receiving increasing attention, research on sexual functioning of patients with congenital heart disease is very scarce. Therefore, this study investigated sexual functioning in adults with congenital heart disease and compared this with that of matched, healthy control subjects.A descriptive, comparative study was conducted, in which 441 adults with congenital heart disease were matched to 441 healthy counterparts, according to age, gender, and marital status. The sample consisted of 53.5% males. Median age was 24 years. Disease-specific determinants of quality of life were assessed using the CHD-TAAQOL. This 77-item instrument includes five items referring to sexual problems. For each item, both the perceived frequency and the associated distress were scored.Sexual problems were perceived by 10% to 20% of the patients. When these problems occurred, they were distressing in 67% to 88% of the patients. Female patients reported significantly more often 'not enjoying having sex', 'being insecure about having sex', and 'not being aroused while having sex', and experienced more distress at 'being insecure about having sex' than male patients. Congenital heart disease patients reported significantly fewer 'not enjoying having sex' and 'worrying about your sex life' than healthy counterparts, but experienced more distress at 'worrying about your sex life'. ### Long_Answer: In this study, we found that only a minority of adults with congenital heart disease reported sexual problems. This suggests that sexual functioning in this group of patients is not as problematic as in some other cardiac populations. ### Final_Prediction: nan |
### Question: Does acetylcholine play a major role in mediating the endocrine responses to ghrelin , a natural ligand of the GH secretagogue receptor , in humans? ### Context: Ghrelin is a 28 amino residue peptide produced predominantly by the stomach with substantially lower amounts deriving from other central and peripheral tissues. Ghrelin is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R) and possesses a potent GH-releasing activity for which the acylation in serine 3 is essential. Ghrelin also possesses other endocrine and non-endocrine activities reflecting central and peripheral GHS-R distribution and stimulates PRL, ACTH and cortisol secretion, has been reported able to induce hyperglycaemia and to decrease insulin levels and has orexigenic activity. Moreover, ghrelin stimulates gastric motility and acid secretion and its action is mediated by acetylcholine which, in turn, is known to play a stimulatory influence on GH, ACTH and insulin secretion.In order to clarify the influence, if any, of acetylcholine on the endocrine activities of ghrelin, we studied the effects of cholinergic enhancement by pyridostigmine (PD, 120 mg p.o. at -60 minutes) and blockade by pirenzepine (PIR, 100 mg p.o. at -60 minutes) on GH, PRL, cortisol, insulin and glucose responses to human acylated ghrelin (1.0 microg/kg i.v. at 0 minutes) in seven normal young volunteers [age (mean +/- SEM): 28.3 +/- 3.1 years; BMI: 21.9 +/- 0.9 kg/m2]. In the same subjects, the effects of PD and PIR on the GH response to GHRH (1.0 microg/kg i.v. at 0 minutes) have also been studied.The administration of ghrelin induced a prompt increase in circulating GH levels (hAUC: 5452.4 +/- 904.9 microg*min/L) which was markedly higher (P < 0.01) than that elicited by GHRH (966.9 +/- 20.50 microg*min/L). Ghrelin also induced a significant increase in PRL (1273.5 +/- 199.7 microg*min/L) and cortisol levels (15505.1 +/- 796.3 microg*min/L) and a decrease in insulin levels (Delta hAUC: -198.1 +/- 39.2 mU*min/L) which was preceded by an increase in plasma glucose levels (8743.8 +/- 593.0 mg*min/dL). The GH response to GHRH was markedly potentiated by PD (4363.3 +/- 917.3 microg*min/L; P < 0.01 vs. GHRH alone). In turn, PD did not modify either the GH response to ghrelin (6564.2 +/- 1753.5 microg*min/L) or its stimulatory effect on PRL and cortisol as well as its effects on insulin and glucose levels. The GH response to GHRH was inhibited by PIR (171.5 +/- 34.7 microg*min/L, P < 0.01 vs. GHRH alone) which, in turn, did not significantly modify the GH response to ghrelin (4044.0 +/- 948.8 microg*min/L). PIR also did not modify the effects of ghrelin on PRL, cortisol, insulin and glucose levels. ### Long_Answer: The endocrine activities of ghrelin are not affected significantly by cholinergic enhancement and muscarinic blockade. Thus, acetylcholine does not play a major role in the endocrine actions of ghrelin. Moreover, as the cholinergic system influences GH secretion via modulation of somatostatin release, the present data agree with the assumption that ghrelin is partially refractory to the influence of somatostatin. ### Final_Prediction: no |
### Question: Does exogenous wt-p53 enhance the antitumor effect of HSV-TK/GCV on C6 glioma cells? ### Context: To study on the antitumor effect of combining wt-p53 gene with suicide gene therapy (HSV-tk+GCV) for malignant gliomas.AdCMV-p53 was transfected into C6 glioma cells at MOI of (Multiplicity of infection) 0(G100), 10(TPG1), 100(TPG2), then AdCMV-tk was transducted to C6 glioma cells of G100, TPG1 and TPG2, respectively, at MOI of 100. The C6 glioma cells tranfected with both AdCMV-p53 and AdCMV-tk were exposed to various concentration of GCV. The cell survival rate was measured by MTT assay in vitro. Rat glioma model was established by injecting 5 x 10(5) C6 glioma cells into right caudate nucleus of SD rats. AdCMV-p53 and AdCMV-tk were injected into glioma on day 5 and 6, respectively. On day 7, ganciclovir (GCV) was administrated intraperitoneally at 15 mg/kg/day for 14 days. The survival time of all rats was observed. The growth of intracerebral tumors was monitored dynamically by enhanced MRI. Cell apoptosis was evaluated by TUNEL method. Expression of HSV-tk gene was identified by in situ hybridization and expression of exogenous p53 gene was detected with Western blotting.In vitro, wt-p53 significantly enhanced antitumor effect of HSV-tk/GCV. The concentration of GCV for ID50 of TPG2 cells (0.001 microg/ml GCV) was 10 times lower than that for the cells of tk-GCV group (MOI = 100), while the concentration of GCV for ID100 of TPG2 (0.01 microg/ml GCV) and TPG1(0.1 microg/ml GCV) was 100 and 10 times lower than that for the cells of tk-GCV group (MOI = 100), respectively. Apoptosis of C6 glioma cells also could be induced by transfection with wt-p53 gene slightly. For in vivo study, the survival time of tumor-bearing rats treated with HSV-TK/GCV or wt-p53 combined with HSV-TK/GCV was significantly prolonged and the intracerebral tumors were regressed and disappeared earlier in the combined gene therapy group than those in the HSV-TK/GCV therapy group as shown in enhanced MRI. However, only half dose of GCV for the rats treated with both wt-p53 and HSV-TK/GCV was needed to obtain the same efficacy as those rats treated with HSV-TK/GCV alone. These results indicate that the transfection of wt-p53 potentiates the effect of HSV-TK/GCV therapy. ### Long_Answer: The combination of HSV-tk/GCV system with wt-p53 gene transduction is optimal for clinical therapeutic trials of suicide gene therapy for malignant gliomas. ### Final_Prediction: yes |
### Question: Is atrial fibrillation an independent determinant of low cognitive function : a cross-sectional study in elderly men? ### Context: Cerebrovascular disease is increasingly recognized as a cause of dementia and cognitive decline. We have previously reported an association between hypertension and diabetes and low cognitive function in the elderly. Atrial fibrillation is another main risk factor for cerebrovascular disease. The aim of this study was to investigate whether atrial fibrillation is associated with low cognitive function in elderly men with and without previous manifest stroke.This was a cross-sectional study based on a cohort of 952 community-living men, aged 69 to 75 years, in Uppsala, Sweden. Cognitive functions were assessed by the Mini-Mental State Examination and the Trail Making Tests, and a composite z score was calculated. The relation between atrial fibrillation and cognitive z score was analyzed, with stroke and other vascular risk factors taken into account.All analyses were adjusted for age, education, and occupational level. Men with atrial fibrillation (n=44) had lower mean adjusted cognitive z scores (-0.26+/-0.11) than men without atrial fibrillation (+0.14+/-0.03; P=0.0003). The exclusion of stroke patients did not alter this relationship; the mean cognitive z score was -0.24+/-0.12 in the 36 men with atrial fibrillation and +0.17+/-0.03 in those without atrial fibrillation (P=0.0004), corresponding to a difference of 0.4 SDs between groups. Adjustments for 24-hour diastolic blood pressure and heart rate, diabetes, and ejection fraction did not change this relationship. Men with atrial fibrillation who were treated with digoxin (n=27) performed markedly better (-0.05+/-0.21) than those without treatment (n=9; -1.14+/-0.34; adjusted P=0.0005). Previous myocardial infarction was not associated with impaired cognitive results. ### Long_Answer: In these community-living elderly men, we found an association between atrial fibrillation and low cognitive function independent of stroke, high blood pressure, and diabetes. Interventional studies are needed to answer the question of whether optimal treatment of atrial fibrillation may prevent or postpone cognitive decline and dementia. ### Final_Prediction: yes |
### Question: Does trigeminal neuralgia increase cerebral blood flow in a focal cerebral ischemic model in rats? ### Context: To investigate the influences of trigeminal neuropathic pain on the cerebral blood flow in a ET-1 focal cerebral ischemia model.Male Sprague-Dawley (SD) rats (220-260 g) were randomly divided into a model group (trigeminal neuralgia, TN group) and a sham operation group (sham group). The TN group received bilateral infraorbital nerve chronic constriction surgery, and the sham group only underwent exposure of the infraorbital nerve. The mechanical pain threshold of the rats was continuously monitored for 30 days post surgery. On postoperative day 30, the animals were anesthetized, and 3 μL (120 pM/μL) ET-1 was injected into the surroundings of the middle cerebral artery (MCA) to establish a cerebral focal ischemia-reperfusion injury model in rats. The changes in cerebral blood flow of these two groups were monitored 30 min after the injection of ET-1.The mechanic pain threshold values between rats in the two groups were not significantly different (P>0.05). The threshold value in the TN group on postoperative day 9 significantly decreased compared with that before surgery (P<0.01). Between postoperative days 9 and 30, the pain threshold values in the TN group were significantly lower than those in the sham group (P<0.01). From postoperative day 10, the mean arterial pressure in the TN group significantly increased compared with that before surgery (P<0.05), and the blood pressure (BP) in the TN group was higher than that in the sham group between postoperative days 10 and 30 (P<0.05). After 75 min of ET-1 microinjection, the cerebral blood flow in the rat frontal cortex exhibited reperfusion, and the cerebral blood flow in the TN group was significantly higher than that in the sham group (P<0.05). In addition, the content of calcitonin gene-related peptide (CGRP) in the blood of rats in the TN group was significantly higher than that in the sham group (P<0.05). ### Long_Answer: Trigeminal neuropathic pain may increase the mean arterial pressure and the content of CGRP in the plasma of rats, thus increasing the cerebral blood flow in the frontal cortex of the ET-1 ischemia-reperfusion model. ### Final_Prediction: yes |
### Question: Can a one-day workshop alter surgeons' teaching practices? ### Context: A 1-day workshop, consisting of five sections with small group discussions and opportunities for practical application of participants' knowledge, was developed to enhance the teaching skills of practicing surgeons. Immediate and long-term follow-up surveys were completed by the participants.Post-workshop evaluations were obtained from all participants who took the workshop; follow-up surveys were mailed 4 to 6 months later.Workshop quality was rated as good (25%) or excellent (75%) by all participants. Follow-up survey results indicated that many participants had rarely/never utilized cited references, looked for additional resources on specific topics, or referred to the section syllabus/handout materials provided during the workshop. However, 100% of the participant respondents reported that they had changed the way they teach as a result of their workshop attendance. ### Long_Answer: An abbreviated course on surgical education can result in long-term changes in the participants' perceptions of their teaching practices. Further study is required to determine if these perceived changes in teaching practices, which the participants have directly attributed to their workshop attendance, have resulted in measurable improvement in their effectiveness and efficiency as teachers. ### Final_Prediction: nan |
### Question: Is cyclooxygenase-2 expression related to the epithelial-to-mesenchymal transition in human colon cancers? ### Context: Down-regulation of E-cadherin is a hallmark of the epithelial-to-mesenchymal transition (EMT). EMT progression in cancer cells is associated with the loss of certain epithelial markers and the acquisition of a mesenchymal phenotype, as well as migratory activities. Cyclooxygenase-2 (COX-2) expression is associated with tumor invasion and metastasis in colon cancer. This study investigated the relationship between E-cadherin and COX-2 in colon cancer cells and human colon tumors.Colon cancer cell lines and immunohistochemistry were used.E-cadherin expression was inversely related to the expressions of COX-2 and Snail in colon cancer cells. Ectopic expression of COX-2 or Snail reduced E-cadherin and induced a scattered, flattened phenotype with few intercellular contacts in colon cancer cells. Treatment of cancer cells with phorbol 12-myristate 13-acetate increased the expressions of COX-2 and Snail, decreased 15-hydroxyprostaglandin dehydrogenase expression, and increased the cells' motility. In addition, exposure to prostaglandin E(2) increased Snail expression and cell motility, and decreased E-cadherin expression. Membranous E-cadherin expression was lower in adenomas and cancers than in the adjacent, non-neoplastic epithelium. In contrast, the expressions of Snail and COX-2 were higher in cancers than in normal tissues and adenomas. The expressions of COX-2 and Snail increased in areas with abnormal E-cadherin expression. Moreover, COX-2 expression was related to higher tumor stages and was significantly higher in nodal metastatic lesions than primary cancers. ### Long_Answer: This study suggests that COX-2 may have a role in tumor metastasis via EMT. ### Final_Prediction: yes |
### Question: Is femoral bone preserved using cemented polished stems in young patients? ### Context: Techniques that ensure femoral bone preservation after primary THA are important in younger patients who are likely to undergo revision surgery.We examined femoral stem survival, bone deficiency at revision arthroplasty, and radiographic bone loss in hips implanted with a cemented polished double-taper stem in a cohort of patients younger than 55 years.We reviewed 197 hips (median patient age, 47 years; range, 16-54 years) after a minimum followup of 2 years (median, 7 years; range, 2-19 years) since primary THA. Clinically, we determined survival to major and minor stem revision and cases of bone deficiency requiring a long stem or impaction bone grafting or created by the need for femoral osteotomy at revision arthroplasty. Radiographically, we assessed stem loosening, femoral osteolysis, and femoral bone deficiency.Stem survival to major revision for aseptic loosening was 100% at 13 years and for any reason was 97% (95% CI, 93-100%). At revision of seven stems, a long stem was used in one hip, a total femoral replacement in one hip and impaction bone grafting in one hip. No femoral osteotomies were required. Bone was preserved in four hips by cement-within-cement stem exchange. No stems were radiographically loose. Proximal osteolysis was present in 11% of femurs. Femoral bone deficiency was graded as Paprosky Type I (97%) or II (3%) and Endo-Klinik Grade 0 (79%) or I (21%). ### Long_Answer: Cemented polished taper stems have high survival at 13 years in young patients and enable femoral bone preservation for subsequent revision. ### Final_Prediction: yes |
### Question: Do changes in the faecal microbiota of mares precede the development of post partum colic? ### Context: Disruptions in the gastrointestinal microbiota may trigger development of post partum colic.To determine the effects of the periparturient period on the faecal microbiome and identify associations between the faecal microbiota and post partum colic.Longitudinal case-control study.Pre- and post partum faecal samples were collected from mares on 3 farms in central Kentucky. Next generation sequencing of the V4 region of the 16S rRNA gene was performed on samples from 13 mares that developed colic, 13 mares that did not display colic and 5 nonpregnant controls.There were 4,523,727 sequences from 85 samples evaluated (mean ± s.d. 53,220 ± 29,160, range 8442-122,535). Twenty-five phyla were identified, although only Firmicutes, Verrucomicrobia, Actinobacteria and Proteobacteria were present at a relative abundance of 1% or greater. The faecal microbiota of late-term mares differed from nonpregnant mares, with differences in microbial community membership and structure but not the relative abundance of major phyla. There was limited impact of foaling and the post partum period on the faecal microbiome. Faecal samples obtained from mares prior to episodes of colic had significantly higher relative abundance of Proteobacteria (8.2%, P = 0.0006) compared with samples from mares that did not display colic (3.7%). All samples with a relative abundance of Firmicutes of ≤50% preceded colic, as did 6/7 (86%) samples with >4% Proteobacteria. Differences in microbiota membership and structure were also present between mares that developed large colon volvulus and matched controls that did not have colic. Sixty-one indicator operational taxon units were identified for the control (vs. volvulus) samples, and these were dominated by Lachnospiraceae (n = 38) and Ruminococcaceae (n = 8). ### Long_Answer: Foaling had minimal effects on the mares' faecal microbiota. Numerous differences in the faecal microbiota preceded colic. Associations between Firmicutes (particularly Lachnospiraceae and Ruminococcaceae) and Proteobacteria and development of colic could lead to measures to predict and prevent colic. The Summary is available in Chinese - see Supporting information. ### Final_Prediction: yes |
### Question: Do blood eosinophils from asymptomatic allergics have a reduced capacity to produce oxygen-free radicals? ### Context: The eosinophil granulocyte is an inflammatory cell that plays an active part in diseases such as asthma and rhinitis. This study aimed to investigate oxidative metabolism by blood eosinophils taken from allergic rhinitis patients, asthmatics, and nonallergic controls before and during the birch-pollen season.Twenty patients with allergy to birch pollen and seasonal symptoms of rhinitis, some of whom were also asthmatic, were followed before and during the birch-pollen season in Sweden. The cells were purified using a Percoll gradient and the MACS system. Eosinophil purity in all samples was > 95%. Oxidative metabolism was measured by a chemiluminescence (CL) assay, with luminol and lucigenin acting as enhancers, and PMA, serum-treated zymosan (STZ), interleukin (IL)-5, or RANTES as stimuli.The allergic subjects showed reduced luminol CL when activated before the season with PMA (P = 0.040) or STZ (P = 0.0055). This was not seen during pollen exposure. STZ-activated lucigenin CL was also reduced before the season (P = 0.0027). The reduction was most evident in the group with asymptomatic rhinitis. In terms of eosinophil stimulation, IL-5 and RANTES were equally effective in allergic and nonallergic subjects, both before and during the pollen season. ### Long_Answer: Blood eosinophils from asymptomatic allergics may have a lower capacity to produce oxygen-free radicals than eosinophils from nonallergics. ### Final_Prediction: yes |
### Question: Is there evidence of separate inflammatory or metabolic forms of preeclampsia? ### Context: To examine whether high insulin resistance versus high inflammation identifies subtypes of preeclampsia.A cytokine panel, glucose and insulin were measured in 37 preeclampsia plasma samples. Wilcoxon rank sum assessed median concentration of HOMA(IR) by pro-inflammatory:anti-inflammatory ratio. Regression stratifying by BMI and preterm birth was conducted.There was no difference in median HOMA(IR) by the pro-inflammatory:anti-inflammatory ratio (p = 0.16). No subsets scatterplot clusters emerged. A positive correlation between HOMAlog and the ratio was significant (p = 0.04). ### Long_Answer: No dichotomous subsets of preeclampsia by inflammation versus insulin resistance were detected. Contrary to our hypothesis, insulin resistance was higher as inflammation increased in preeclampsia. ### Final_Prediction: nan |
### Question: Exercise therapy in type 2 diabetes: is daily exercise required to optimize glycemic control? ### Context: Given the transient nature of exercise-induced improvements in insulin sensitivity, it has been speculated that daily exercise is preferred to maximize the benefits of exercise for glycemic control. The current study investigates the impact of daily exercise versus exercise performed every other day on glycemic control in type 2 diabetic patients.Thirty type 2 diabetic patients (age 60 ± 1 years, BMI 30.4 ± 0.7 kg/m(2), and HbA(1c) 7.2 ± 0.2%) participated in a randomized crossover experiment. Subjects were studied on three occasions for 3 days under strict dietary standardization but otherwise free-living conditions. Blood glucose homeostasis was assessed by continuous glucose monitoring over 48 h during which subjects performed no exercise (control) or 60 min of cycling exercise (50% maximal workload capacity) distributed either as a single session performed every other day or as 30 min of exercise performed daily.The prevalence of hyperglycemia (blood glucose>10 mmol/L) was reduced from 7:40 ± 1:00 h:min per day (32 ± 4% of the time) to 5:46 ± 0:58 and 5:51 ± 0:47 h:min per day, representing 24 ± 4 and 24 ± 3% of the time, when exercise was performed either daily or every other day, respectively (P<0.001 for both treatments). No differences were observed between the impact of daily exercise and exercise performed every other day. ### Long_Answer: A short 30-min session of moderate-intensity endurance-type exercise substantially reduces the prevalence of hyperglycemia throughout the subsequent day in type 2 diabetic patients. When total work is being matched, daily exercise does not further improve daily glycemia compared with exercise performed every other day. ### Final_Prediction: nan |
### Question: A prospective study on neonatal mortality and its predictors in a rural area in Burkina Faso: can MDG-4 be met by 2015? ### Context: To measure the neonatal mortality rate (NMR) and investigate its predictors in a rural area of Burkina Faso.A cohort of infants born in 24 villages in Banfora region was followed until the children were 6 months old. We estimated the risk of neonatal death and used logistic regression to identify its predictors.Among 864 live births followed to day 28, there were 40 neonatal deaths, a NMR of 46.3 per 1000 live births (95% confidence intervals (CI): 22 to 70). Multivariable regression identified twin birth (OR=11.5, 95% CI: 4.5 to 29.8), having a nulliparous mother (odds ratio (OR)=4.3, 95% CI: 1.5 to 12.1), and birth into a polygynous household (OR=2.1, 95% CI: 1.0 to 4.7) as main predictors of neonatal death. ### Long_Answer: The burden of neonatal mortality in rural Burkina Faso is very high and the observed NMRs in a predominantly rural country suggest that it is unlikely Burkina will meet fourth Millennium Development Goal (MDG-4) by 2015. ### Final_Prediction: nan |
### Question: Does lower risk in parous women suggest that hormonal factors are important in bladder cancer etiology? ### Context: Urinary bladder cancer is two to four times more common among men than among women, a difference in risk not fully explained by established risk factors. Our objective was to determine whether hormonal and reproductive factors are involved in female bladder cancer.We analyzed data from two population-based studies: the Los Angeles-Shanghai Bladder Cancer Study, with 349 female case-control pairs enrolled in Los Angeles and 131 female cases and 138 frequency-matched controls enrolled in Shanghai, and the California Teachers Study (CTS), a cohort of 120,857 women with 196 incident cases of bladder urothelial carcinoma diagnosed between 1995 and 2005. We also conducted a meta-analysis summarizing associations from our primary analyses together with published results.In primary data analyses, parous women experienced at least 30% reduced risk of developing bladder cancer compared with nulliparous women (Shanghai: OR = 0.38, 95% CI: 0.13-1.10; CTS: RR = 0.69, 95% CI: 0.50-0.95) consistent with results of a meta-analysis of nine studies (summary RR = 0.73, 95% CI: 0.63-0.85). The CTS, which queried formulation of menopausal hormone therapy (HT), revealed a protective effect for use of combined estrogen and progestin compared with no HT (RR = 0.60, 95% CI: 0.37-0.98). Meta-analysis of three studies provided a similar effect estimate (summary RR = 0.65, 95% CI: 0.48-0.88). ### Long_Answer: A consistent pattern of reduced bladder cancer risk was found among parous women and those who used estrogen and progestin for HT. ### Final_Prediction: yes |
### Question: Is pre-treatment symptom cluster in breast cancer patients associated with worse sleep , fatigue and depression during chemotherapy? ### Context: The concept of symptom clusters is relatively new in cancer patients' symptom management. This study, which spanned four cycles of chemotherapy, combined three commonly seen pre-treatment symptoms in cancer patients (i.e. sleep disturbances, fatigue and depression) into one symptom cluster, to explore the associations between pre-treatment cluster categories and longitudinal profiles of these same symptoms during chemotherapy.This was a prospective study. Seventy-six women with newly diagnosed stage I-III breast cancer, scheduled to receive at least four cycles of adjuvant or neoadjuvant anthracycline-based chemotherapy participated. Data were collected at seven time points before and during treatment. Sleep quality was measured with the Pittsburgh Sleep Quality Index. Fatigue was measured with the Multidimensional Fatigue Symptom Inventory--Short Form. Depressive symptoms were measured with the Center of Epidemiological Studies--Depression. Patients were divided into three groups based on the number of symptoms they experienced before the start of chemotherapy (i.e. no symptoms, 1-2 symptoms or all three symptoms) and a symptom cluster index (SCI) was computed.All women reported worse sleep, more fatigue and more depressive symptoms during treatment compared with baseline (all p's<0.01); however, those women with a higher SCI (i.e. more symptoms pre-treatment) continued to experience worse symptoms during treatment compared with those who began with fewer symptoms (all p's<0.01). ### Long_Answer: A higher clinically relevant-based pre-treatment symptom cluster was associated with more sleep disturbances, greater fatigue and more depressive symptoms during chemotherapy. Specific interventions for these pre-treatment symptoms may improve the frequency and severity of these same symptoms during chemotherapy, when they are most severe and most disruptive to quality of life. ### Final_Prediction: yes |
### Question: Are hypokalemia and hypothermia associated with 30-day mortality in patients with acute paraquat poisoning? ### Context: Clinical predictors associated with acute paraquat (PQ) poisoning have not been systematically studied.To identify independent predictors of death in patients with acute PQ poisoning.This is a retrospective study executed in the emergency department of a university hospital. One hundred three consecutive patients poisoned with PQ between January 1999 and December 2004 were enrolled. Urine PQ concentration, electrolyte and renal function, detailed history, and Acute Physiology and Chronic Health Evaluation II were extracted from medical records. The outcome measure was 30-day mortality. Multivariate analysis was done by Cox-proportional hazard regression model. Receiver operating characteristics area under the curve was calculated for selected predictors.The crude 30-day mortality was 67.9% (70 of 103). Independent predictors of death were acute renal failure (hazard ratio, 3.53; 95% confidence interval, 1.97-6.32), hypokalemia (2.07, 1.21-3.51), hypothermia (2.91, 1.67-5.07), suicide (2.11, 1.04-4.29), and self-reported ingested dose (2.06, 1.38-3.06). The receiver operating characteristics area under the curve of serum potassium concentrations, maximal urine PQ concentrations, and Acute Physiology and Chronic Health Evaluation II scores were 0.75 (95% confidence interval, 0.60-0.81), 0.71 (0.66-0.84), and 0.80 (0.71-0.88), respectively. Under the cutoff value of 3.6 mEq/L, hypokalemia had a sensitivity of 75% and specificity of 54% in predicting mortality. ### Long_Answer: The identified risk factors may allow better identification of those at greater mortality risk. Future development of a tailored clinical scoring system incorporating the identified risk factors for acute PQ poisoning may be of great help. ### Final_Prediction: yes |
### Question: Is plasma S100A12 level associated with cardiovascular disease in hemodialysis patients? ### Context: S100A12 is an endogenous receptor ligand for advanced glycation end products. Cardiovascular disease remains a major cause of morbidity and mortality in patients with chronic kidney disease. In this study, we report cross-sectional data on 550 hemodialysis patients and assess the relationship between plasma S100A12 level and cardiovascular disease.A cross-sectional study of 550 maintenance hemodialysis patients was conducted. We investigated the past history of cardiovascular disease and quantified the plasma level of S100A12 protein in all participants.Plasma S100A12 level was higher in hemodialysis patients with cardiovascular disease (n=197; 33.8 ± 28.1 ng/ml) than in those without it (n=353; 20.2 ± 16.1 ng/ml; P<0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13 to 1.44; P<0.001) was identified as an independent factor associated with the prevalence of cardiovascular disease. The other factors associated with the prevalence of cardiovascular diseases were the presence of diabetes mellitus (OR, 2.81; 95% CI, 1.79 to 4.41; P < 0.001) and high-sensitivity CRP level (OR, 1.02; 95% CI, 1.00 to 1.05; P=0.046). Furthermore, the plasma S100A12 level (OR, 1.30; 95% CI, 1.09 to 1.54; P=0.004) was significantly associated with cardiovascular disease even in hemodialysis patients without diabetes mellitus (n=348). ### Long_Answer: These results suggest that the plasma S100A12 protein level is strongly associated with the prevalence of cardiovascular disease in hemodialysis patients. ### Final_Prediction: yes |
### Question: Is motor cortical processing causally involved in object recognition? ### Context: Motor activity during vicarious experience of actions is a widely reported and studied phenomenon, and motor system activity also accompanies observation of graspable objects in the absence of any actions. Such motor activity is thought to reflect simulation of the observed action, or preparation to interact with the object, respectively.Here, in an initial exploratory study, we ask whether motor activity during observation of object directed actions is involved in processes related to recognition of the object after initial exposure. Single pulse Transcranial Magnetic Stimulation (TMS) was applied over the thumb representation of the motor cortex, or over the vertex, during observation of a model thumb typing on a cell-phone, and performance on a phone recognition task at the end of the trial was assessed. Disrupting motor processing over the thumb representation 100 ms after the onset of the typing video impaired the ability to recognize the phone in the recognition test, whereas there was no such effect for TMS applied over the vertex and no TMS trials. Furthermore, this effect only manifested for videos observed from the first person perspective. In an additional control condition, there was no evidence for any effects of TMS to the thumb representation or vertex when observing and recognizing non-action related shape stimuli. ### Long_Answer: Overall, these data provide evidence that motor cortical processing during observation of object-directed actions from a first person perspective is causally linked to the formation of enduring representations of objects-of-action. ### Final_Prediction: yes |
### Question: Vacuum extraction: is there any need to improve the current training in the UK? ### Context: The objective of this study was to assess the use and efficacy of delivery by vacuum extraction or ventouse in routine clinical practice and to assess some aspects of the procedure that may reflect the quality of training in this technique.Women's demographic profiles and delivery details were collected in both the prospective (B) and retrospective (A) arm of the study. In addition, in the prospective arm of the study two custom-designed forms were used: the obstetrician recorded their perception of where the vacuum cup had been placed on one form while on a second form the pediatrician indicated the actual site of the cup placement as observed from the position of the chignon. All the diagrams of cup placement were reviewed by one of the authors, who was blinded to the outcome of the procedure.The vacuum extractor was the first instrument to be used in 79% and 87% of the instrumental deliveries in groups A and B, respectively, with corresponding failure rates of 20% and 21%. Although an occipito-posterior position was diagnosed in 11% of cases of group A and 14% of cases of group B, the specifically designed occipito-posterior cup was not used at all. The vacuum cup was considered to have been applied suboptimally in 40% of the cases where attempted vacuum delivery failed. ### Long_Answer: The high rate of inappropriate positioning of the cup may reflect difficulty in accurately applying the cup, perhaps due to caput or malposition, but may also represent poor assessment of the orientation and position of the fetal skull and therefore be indicative of a need for improvement in training methods. ### Final_Prediction: nan |
### Question: Does genome-wide investigation reveal pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection? ### Context: There are striking similarities between the innate immune systems of invertebrates and vertebrates. Caenorhabditis elegans is increasingly used as a model for the study of innate immunity. Evidence is accumulating that C. elegans mounts distinct responses to different pathogens, but the true extent of this specificity is unclear. Here, we employ direct comparative genomic analyses to explore the nature of the host immune response.Using whole-genome microarrays representing 20,334 genes, we analyzed the transcriptional response of C. elegans to four bacterial pathogens. Different bacteria provoke pathogen-specific signatures within the host, involving differential regulation of 3.5-5% of all genes. These include genes that encode potential pathogen-recognition and antimicrobial proteins. Additionally, variance analysis revealed a robust signature shared by the pathogens, involving 22 genes associated with proteolysis, cell death and stress responses. The expression of these genes, including those that mediate necrosis, is similarly altered following infection with three bacterial pathogens. We show that necrosis aggravates pathogenesis and accelerates the death of the host. ### Long_Answer: Our results suggest that in C. elegans, different infections trigger both specific responses and responses shared by several pathogens, involving immune defense genes. The response shared by pathogens involves necrotic cell death, which has been associated with infection in humans. Our results are the first indication that necrosis is important for disease susceptibility in C. elegans. This opens the way for detailed study of the means by which certain bacteria exploit conserved elements of host cell-death machinery to increase their effective virulence. ### Final_Prediction: yes |
### Question: A caring partnership: can we gain control? ### Context: The health care system in the United States is in trouble. Patients and physicians are becoming increasingly unhappy with the system. There has been a progressive deterioration in trust in the system and in patient-doctor interactions.The history of the evolution of medicine as a profession over the past 350 years is briefly reviewed. The forces that have changed a paternalistic, but caring, system into one that is no longer paternalistic, but also less caring, are discussed. It is suggested that the current market-driven, industrial model is failing both patients and physicians, and that it is too costly. ### Long_Answer: The case is presented for patients and physician to join forces to work for reforms of the system, to encourage more physicians to take up careers in primary care, to fund health insurance for the uninsured, and to subsidize the education of future physicians. These approaches should help restore trust and a caring partnership between patients and their physicians. This partnership is necessary for attaining the reforms suggested. ### Final_Prediction: nan |
### Question: Does prophylactic mesalamine treatment decrease postoperative recurrence of Crohn 's disease? ### Context: Recurrence of Crohn's disease frequently occurs after surgery. A randomized controlled trial was performed to determine if mesalamine is effective in decreasing the risk of recurrent Crohn's disease after surgical resection is performed.One hundred sixty-three patients who underwent a surgical resection and had no evidence of residual disease were randomized to a treatment group (1.5 g mesalamine twice a day) or a placebo control group within 8 weeks of surgery. The follow-up period was a maximum of 72 months.The symptomatic recurrence rate (symptoms plus endoscopic and/or radiological confirmation of disease) in the treatment group was 31% (27 of 87) compared with 41% (31 of 76) in the control group (P = 0.031). The relative risk of developing recurrent disease was 0.628 (90% confidence interval, 0.40-0.97) for those in the treatment group (P = 0.039; one-tail test) using an intention-to-treat analysis and 0.532 (90% confidence interval, 0.32-0.87) using an efficacy analysis. The endoscopic and radiological rate of recurrence was also significantly decreased with relative risks of 0.654 (90% confidence interval, 0.47-0.91) in the effectiveness analysis and 0.635 (90% confidence interval, 0.44-0.91) in the efficacy analysis. There was only one serious side effect (pancreatitis) in subjects in the treatment group. ### Long_Answer: Mesalamine (3.0 g/day) is effective in decreasing the risk of recurrence of Crohn's disease after surgical resection is performed. ### Final_Prediction: yes |
### Question: Are oxygen uptake kinetics modified when using a respiratory snorkel? ### Context: The aim of this study was to compare VO2 kinetics during constant power cycle exercise measured using a conventional facemask (CM) or a respiratory snorkel (RS) designed for breath-by-breath analysis in swimming.VO2 kinetics parameters-obtained using CM or RS, in randomized counterbalanced order-were compared in 10 trained triathletes performing two submaximal heavy-intensity cycling square-wave transitions. These VO2 kinetics parameters (ie, time delay: td1, td2; time constant: τ1, τ2; amplitude: A1, A2, for the primary phase and slow component, respectively) were modeled using a double exponential function. In the case of the RS data, this model incorporated an individually determined snorkel delay (ISD).Only td1 (8.9 ± 3.0 vs 13.8 ± 1.8 s, P<.01) differed between CM and RS, whereas all other parameters were not different (τ1 = 24.7 ± 7.6 vs 21.1 ± 6.3 s; A1 = 39.4 ± 5.3 vs 36.8 ± 5.1 mL x min(-1) x kg(-1); td2 = 107.5 ± 87.4 vs 183.5 ± 75.9 s; A2' (relevant slow component amplitude) = 2.6 ± 2.4 vs 3.1 ± 2.6 mL x min(-1) x kg(-1) for CM and RS, respectively). ### Long_Answer: Although there can be a small mixture of breaths allowed by the volume of the snorkel in the transition to exercise, this does not appear to significantly influence the results. Therefore, given the use of an ISD, the RS is a valid instrument for the determination of VO2 kinetics within submaximal exercise. ### Final_Prediction: nan |
### Question: Does lidocaine given intravenously improve conditions for laryngeal mask airway insertion during propofol target-controlled infusion? ### Context: Patient response to laryngeal mask airway insertion during propofol induction depends on many factors. Lidocaine has been used to reduce cardiovascular responses, coughing, and bucking induced by tracheal intubation. The aim of this study was to determine the effects of intravenous lidocaine on laryngeal mask airway insertion conditions during the induction of anaesthesia with propofol target-controlled infusion.Eighty patients, 16-54 years of age, weighing between 45 and 100 kg, who underwent minor surgery, were randomly divided into two groups (the lidocaine and control groups). Anaesthesia was induced with propofol target-controlled infusion at a target plasma concentration of 6 microg ml. The lidocaine group received 1.5 mg kg of lidocaine 50 s after starting target-controlled infusion and the control group received an equivalent volume of saline. Laryngeal mask airways were inserted when propofol effect-site concentrations reached 2.5 microg ml. Laryngeal mask airway insertion conditions (mouth opening, gagging, coughing, movements, laryngospasm, overall ease of insertion, and hiccups) were assessed, and haemodynamic responses were monitored for 3 min after laryngeal mask airway insertion.No significant differences were observed between the two groups in terms of haemodynamic responses. However, the lidocaine group showed lower incidences of coughing (5 vs. 22.5%), gagging (25 vs. 55%), and laryngospasm (2.5 vs. 17.5%) (P < 0.05). ### Long_Answer: Pretreatment with intravenous lidocaine 1.5 mg kg during induction with propofol target-controlled infusion improves laryngeal mask airway insertion conditions. ### Final_Prediction: yes |
### Question: Does trypanosoma cruzi ( Chagas ' disease agent ) reduce HIV-1 replication in human placenta? ### Context: Several factors determine the risk of HIV mother-to-child transmission (MTCT), such as coinfections in placentas from HIV-1 positive mothers with other pathogens. Chagas' disease is one of the most endemic zoonoses in Latin America, caused by the protozoan Trypanosoma cruzi. The purpose of the study was to determine whether T. cruzi modifies HIV infection of the placenta at the tissue or cellular level.Simple and double infections were carried out on a placental histoculture system (chorionic villi isolated from term placentas from HIV and Chagas negative mothers) and on the choriocarcinoma BeWo cell line. Trypomastigotes of T. cruzi (VD lethal strain), either purified from mouse blood or from Vero cell cultures, 24 h-supernatants of blood and cellular trypomastigotes, and the VSV-G pseudotyped HIV-1 reporter virus were used for the coinfections. Viral transduction was evaluated by quantification of luciferase activity. Coinfection with whole trypomastigotes, either from mouse blood or from cell cultures, decreased viral pseudotype luciferase activity in placental histocultures. Similar results were obtained from BeWo cells. Supernatants of stimulated histocultures were used for the simultaneous determination of 29 cytokines and chemokines with the Luminex technology. In histocultures infected with trypomastigotes, as well as in coinfected tissues, IL-6, IL-8, IP-10 and MCP-1 production was significantly lower than in controls or HIV-1 transducted tissue. A similar decrease was observed in histocultures treated with 24 h-supernatants of blood trypomastigotes, but not in coinfected tissues. ### Long_Answer: Our results demonstrated that the presence of an intracellular pathogen, such as T. cruzi, is able to impair HIV-1 transduction in an in vitro system of human placental histoculture. Direct effects of the parasite on cellular structures as well as on cellular/viral proteins essential for HIV-1 replication might influence viral transduction in this model. Nonetheless, additional mechanisms including modulation of cytokines/chemokines at placental level could not be excluded in the inhibition observed. Further experiments need to be conducted in order to elucidate the mechanism(s) involved in this phenomenon. Therefore, coinfection with T. cruzi may have a deleterious effect on HIV-1 transduction and thus could play an important role in viral outcome at the placental level. ### Final_Prediction: yes |
### Question: Does anthrax lethal toxin suppress high glucose induced VEGF over secretion through a post-translational mechanism? ### Context: To prove anthrax lethal toxin (LeTx) blocks the mitogen activated protein kinases (MAPKs) activation by degrading the MAPK/ERK kinases (MEKs) to suppress vascular endothelial growth factor (VEGF) secretion.Human adult retinal pigmented epithelium (ARPE) cells were cultured and treated with normal glucose, high glucose or high glucose with LeTx for additional 24, 48 or 72h for viable cell count. Total RNA from the ARPE was isolated for reverse transcription polymerase chain reaction (RT-PCR). The conditioned medium of ARPE cells treated in different group for 48h was filtered and diluted to detect the concentration of VEGF by enzyme-linked immunosorbant assays. Evaluate the role of MEK/MAPK pathway in the secretion of VEGF by immunoblotting.In this study, we proved high glucose induced activation of the MAPK extracellular signal-regulated kinase (ERK1/2) and p38 in the ARPE cell line was blocked by anthrax LeTx. LeTx also inhibited high glucose induced ARPE cell over proliferation. ### Long_Answer: LeTx suppressed high glucose induced VEGF over secretion in the ARPE cells, mainly through a post-translational mechanism. ### Final_Prediction: yes |
### Question: Is nOX2 up-regulation associated with artery dysfunction in patients with peripheral artery disease? ### Context: Oxidative stress seems to play a role in impairing flow-mediated dilation (FMD) in patients with peripheral artery disease (PAD) but the underlying mechanism is still undefined. We evaluated whether NOX2, the catalytic core of NADPH oxidase, the most important producer of reactive oxidant species (ROS), is implicated in impairing FMD.We measured FMD, urinary isoprostanes, a marker of oxidative stress, nitric oxide generation by serum levels of nitrite/nitrate (NOx), and serum levels of soluble NOX2-derived peptide (sNOX2-dp), a marker of NOX2 activation, in 50 PAD patients and 50 controls. Also, we performed an interventional cross-over study to assess if propionyl-L-carnitine (PLC) (6g/day), vs. placebo, was able to affect FMD via an oxidative stress-mediated mechanism.Compared to controls, patients with PAD had enhanced sNOX2-dp and isoprostanes and reduced NOx and FMD. Multiple linear regression analysis showed that FMD was independently associated with sNOX2-dp. After PLC infusion FMD increased while sNOX2-dp and isoprostanes significantly decreased; no changes were observed after placebo. In vitro study by incubating platelets or white cells with PLC demonstrated a significant inhibition of p47(phox) translocation on cellular surface and ROS generated by NOX2 activation. ### Long_Answer: This study suggests that in PAD patients ROS generated by NOX2 contribute to reduce FMD and that the administration of an antioxidant is able to improve arterial dilatation via NOX2 inhibition. ### Final_Prediction: yes |
### Question: Effectiveness of diabetes flow sheet in controlling blood pressure: should family medicine teams in Zenica use recommended guidelines? ### Context: Blood pressure (BP) is one of the important parameters for controlling Diabetes Mellitus (DM). European Society of Cardiology recommended optimal level for DM BP<130/80 mmHg.AIM: We wanted to assess the level of BP for our DM patients after using specific guidelines for DM.Retrospective medical record (audit) has been conducted among 853 DM patients older then 18 years. We checked patient charts among 19 FM teams two years before (May 2003-May 2005) and two years after (May 2005-May 2007) implementation of the DM guidelines in Family Medicine (FM) clinic in Zenica. We divided FM teams based on their patients BP values; optimal level of BP<130/80 mmHg; suboptimal level when systolic BP 130-140mmHg and diastolic 85-90 mmHg and that with inadequate level with BP>140/90mmHg.853 DM patient charts were analysed, 46 per FM team. Average age of DM patients was greater than 60 years and average age of doctors was 46.6. Percentage of BP inadequate level was smaller after implementation of DM guidelines in most of FM teams. For optimal level BP<130/80 mmHg, significant improvement was seen after implementation of DM guidelines for: 6/19 teams (p<0.0001), 2/19 teams (p<0.001) and 2/19 teams (p<0.01). ### Long_Answer: After implementation of BP guidelines for DM patients, BP can be improved in patients treated by FM teams and guidelines should be used. ### Final_Prediction: nan |
### Question: Does conventional transbronchial needle aspiration decrease the rate of surgical sampling of intrathoracic lymphadenopathy? ### Context: Previous studies have suggested a decreased need for the surgical biopsy of intrathoracic lymph nodes (LNs) due to improved diagnostic rates utilizing transbronchial needle aspiration (TBNA) with endobronchial ultrasound and endoscopic ultrasound. The goal of this study was to determine whether conventional TBNA using combined cytologic and histologic analysis of tissue specimens impacted the rates of surgical diagnostic biopsies of patients with intrathoracic lymphadenopathy.Retrospective review at a single academic center. All mediastinal and hilar tissue samples submitted for pathologic analysis over an 8.4-year period were analyzed. Patients were categorized into a "before" group and an "after" group based on two different time periods. The before group underwent only cytologic analysis of Wang needle (19-gauge or 21-gauge) aspirates. The after group had cytologic analysis of aspirates as well as histologic analysis of needle "core" (19 gauge) biopsy specimens. The groups were compared for the rate of intrathoracic LNs sampled by surgical means vs TBNA and the number of times that TBNA averted the need for a surgical diagnostic procedure.The success of TBNA increased significantly in the after group compared to that in the before group. The yield for the successful sampling of mediastinal and hilar LNs increased from 53 to 91% (p < 0.001) in the before group vs the after group. TBNA averted a surgical biopsy in 35% of the before cases compared to 66% of the after cases (p < 0.001). ### Long_Answer: Conventional TBNA using large-bore needles with both cytology and surgical pathology evaluation decreases the need for surgical sampling of the mediastinum to diagnose thoracic lymphadenopathy. ### Final_Prediction: yes |
### Question: Is prostate cancer diagnosed by the 5 region biopsy method significant disease? ### Context: The 5 region method of prostate biopsy takes standard sextant biopsies and additional systematic biopsies of the far lateral and middle aspects of the prostate gland. This method has been shown to increase the cancer detection rate of prostate biopsy by 35% over the standard sextant biopsy method, and it is most effective in patients with prostate specific antigen less than 10. Concern has arisen that by taking additional biopsies, cancers are being detected which would otherwise be clinically insignificant. We compare pathological findings of radical prostatectomy specimens detected by the 5 region and sextant biopsy methods to determine if there is a significant difference between tumors diagnosed by each method.A total of 21 patients enrolled in the 5 region prostate biopsy study with biopsy proved prostate cancer underwent radical prostatectomy. Prostatectomy specimens of 5 zone detected cancers in 11 cases were compared to sextant method detected cancer in 10. Radical prostatectomy specimens were analyzed for tumor volume, ploidy status, Gleason score and TNM pathological stage. Tumor volumes were determined by point counting morphometric analysis using an overlying grid. Tumor ploidy status was determined by deoxyribonucleic acid (DNA) image analysis.Mean tumor volume was 2.4 cc (range 0.10 to 9.6, median 1.4) for 5 region detected cancers versus 1.9 cc (range 0.10 to 6.1, median 1.0) for sextant method detected cancers. This difference was not statistically significant (p = 0.643). Mean DNA index was 1.1 (range 0.93 to 1.64) for 5 region detected cancer compared to 1.4 (range 0.96 to 2.2) for sextant method detected cancer. Overall there were 8 diploid tumors and 3 aneuploid tumors in the 5 region group compared to 4 diploid tumors and 6 aneuploid tumors in the sextant group. Mean Gleason scores were not significantly different for the 5 region (6.5) and sextant (6.7) groups (p = 0.672). Final tumor stage for the 5 region group was 4 pT3 (36%) and 7 pT2 (64%) tumors compared to 2 pT3 (20%) and 8 pT2 (80%) tumors for the sextant group. ### Long_Answer: Our data demonstrated no significant difference in tumor volume, DNA ploidy status, Gleason score or final pathological tumor stage between tumors diagnosed using the 5 region versus sextant biopsy techniques. ### Final_Prediction: yes |
### Question: Does the political use of poll result about public support for a privatized healthcare system in Canada? ### Context: Within the context of the political debate on privatization of healthcare funding in Canada, this paper examines the nature and the various role of polls.To reach this objective we rely on available commercial polls and statistical surveys and qualitatively analyse them to illustrate methodological and logical problems as well as to distinguish between what we call the 'informative' and the 'political' use of poll results.We first draw a portrait of Quebecers' and Canadians' positions on the healthcare system and use this portrait to highlight a certain number of logical and methodological issues related to the political use of polls. Our analysis shows that public support for privatization of the healthcare system, as presented in the polls, is a construct whose logical underpinnings and methodological validity are extremely weak. ### Long_Answer: We then discuss those results to argue that polls are not only used to represent the public's preferences but are also political tools used to shape those preferences. ### Final_Prediction: yes |
### Question: Is tolerance induced by IL-6 deficient donor heart significantly involved in myeloid-derived suppressor cells ( MDSCs )? ### Context: Transplant tolerance induced by IL-6 deficient donor is supported by regulatory T cells (Tregs). However, it is unknown whether innate immunoregulatory cells such as myeloid-derived suppressor cells (MDSCs) are involved in the process.In this study, we demonstrate the role of MDSCs by transplanting IL-6 deficient heart grafts into wild-type recipients in a murine allogeneic transplant model.Our data further revealed that utilization of IL-6 deficient heart grafts could cause a significant prolongation of allograft survival (Mantel-Cox Test, p = 0.001; Gehan-Breslow-Wilcoxon Test, p = 0.0016) and a remarkable increase of the frequency of CD11b + Gr1(-low) in the recipients' spleens (p = 0.0028). ### Long_Answer: MDSCs rather than Th17 cells are closely involved in induced tolerance by IL-6 deficient donor heart. This unveiled mechanism of targeting IL-6 or its signaling pathway may provide a novel insight into preventing allograft rejection for non-sensitized transplant recipients. ### Final_Prediction: yes |
### Question: Do comparison of canine stifle kinematic data collected with three different targeting models? ### Context: To model the kinematics of the canine stifle in 3 dimensions using the Joint Coordinate System (JCS) and compare the JCS method with linear and segmental models.In vivo biomechanical study.Normal adult mixed breed dogs (n=6).Dogs had 10 retroreflective markers affixed to the skin on the right pelvic limb. Dogs were walked and trotted 5 times through the calibrated space and the procedure was repeated 5 days later. Sagittal flexion and extension angle waveforms acquired during each trial with all 3 models (JCS, Linear, and Segmental) were produced simultaneously during each gait. The JCS method provided additional internal/external and abduction/adduction angles. Comparison of sagittal flexion and extension angle waveforms was performed with generalized indicator function analysis (GIFA) and Fourier analysis. A normalization procedure was performed.Each model provided consistent equivalent sagittal flexion-extension data. The JCS provided consistent additional internal/external and abduction/adduction. Sagittal waveform differences were found between methods and testing days for each dog at a walk and a trot with both GIFA and Fourier analysis. After normalization, differences were less with Fourier analysis and were unaltered with GIFA. ### Long_Answer: Whereas all methods produced similar flexion-extension waveforms, JCS provided additional valuable data. ### Final_Prediction: yes |
### Question: Kinking, coiling, and tortuosity of extracranial internal carotid artery: is it the effect of a metaplasia? ### Context: Morphological anomalies of the extracranial internal carotid artery (ICA) cause symptomatic cerebrovascular insufficiency in 4-16% of the cases. The aim of the present study is to evaluate macroscopic and microscopic features of a group of extracranial ICA anomalies, specifically kinking, coiling, and tortuosity, eventually affecting the surgical approach.From January 2003 to December 2005, 10 out of 169 (6%) revascularized patients (pts) were operated upon because of an ICA anomaly. They were all but two symptomatics. Seven pts were treated by ICA transection and end-to-side reimplantation of the ICA at the level of the carotid bulb; three pts were treated by ICA resection and end-to-end anastomosis. In all the cases a segment of ICA was resected; in three cases one more segment was also obtained from a common carotid artery (CCA) and these specimens were histologically examined. Patients were followed-up through a 3-year period.No pts died and none suffered of neurologic events. Duplex scan and arteriographic postoperative control showed the correct surgical reconstruction. Matching preoperative clinical findings with presence or absence of significant atherosclerotic stenotic lesion, we found out a positive cerebral CT in one pt (20%) in both groups; fluent neurological deficit was preeminent in pts with pure ICA anomalies (40% vs. 0%) (P = 0.2); pts with pure ICA anomalies were significantly younger than 65 years old (80% vs. 0%) (P = 0.03) and males were more involved by pure ICA anomalies (60% vs. 40%) (P = 0.1). The histological examination of ICA specimens showed a reduction of elastic fibers and muscular cells with a compensative increase of connective fibers. ### Long_Answer: At our knowledge this is the first study focused on ICA anomalies like kinking, coiling, and tortuosity, comparing histologic features of CCA and ICA specimens coming from the same affected carotid axis. Our results, although preliminary, show elastic and muscular tissue substituted by loose connective tissue, configuring a metaplasia of tunica media limited to the ICA. Our hypothesis is that extracranial ICA, being a segment of transition between an elastic vessel (CCA) and a muscular vessel (intracranial ICA), is particularly subject to metaplastic transformation, analogously to other transition zones in human body. Our purpose is now to confirm by ultrastructural and molecular biology techniques, in a wider series, the presence of this metaplasia, since this could condition also the revascularization techniques. ### Final_Prediction: nan |
### Question: Are spinal cord stimulation in complex regional pain syndrome : cervical and lumbar devices comparably effective? ### Context: Spinal cord stimulation (SCS) has been used since 1967 for the treatment of patients with chronic pain. However, long-term effects of this treatment have not been reported. The present study investigated the long-term effects of cervical and lumbar SCS in patients with complex regional pain syndrome type I.Thirty-six patients with a definitive implant were included in this study. A pain diary was obtained from all patients before treatment and 6 months and 1 and 2 years after implantation. All patients were asked to complete a seven-point Global Perceived Effect (GPE) scale and the Euroqol-5D (EQ-5D) at each post-implant assessment point.The pain intensity was reduced at 6 months, 1 and 2 years after implantation (P<0.05). However, the repeated measures ANOVA showed a statistically significant, linear increase in the visual analogue scale score (P=0.03). According to the GPE, at least 42% of the cervical SCS patients and 47% of the lumbar SCS patients reported at least 'much improvement'. The health status of the patients, as measured on the EQ-5D, was improved after treatment (P<0.05). This improvement was noted both from the social and from the patients' perspective. Complications and adverse effects occurred in 64% of the patients and consisted mainly of technical defects. There were no differences between cervical and lumbar groups with regard to outcome measures. ### Long_Answer: SCS reduced the pain intensity and improves health status in the majority of the CRPS I patients in this study. There was no difference in pain relief and complications between cervical and lumbar SCS. ### Final_Prediction: yes |
### Question: Are clinicians failing to supply adequate information when requesting a histopathological investigation? ### Context: There is a perception among histopathologists that specimens are often received without adequate clinical details. This is the first study to determine the adequacy of information provided when histopathological investigations are requested.Two thousand sequential requests for histological examination were assessed for adequacy and completeness.There was no significant difference in the demographic details supplied by physicians and surgeons. Clinical details were inadequate in 6.1% of cases: those from physicians were significantly more often adequate (98.7% v 90.6%) and more often included a diagnosis (74.4% v 38.8%) than those from surgeons. Physicians were more likely to supply their name and contact number but requests frequently lacked details of the sender. ### Long_Answer: Specimens are infrequently received with inadequate demographic details, but clinical details and details of the sender are more often lacking. Education of clinical colleagues is required if pathologists are to manage the demand for the service. ### Final_Prediction: nan |
### Question: Do skin receptors and intradermal nerves generate the sensory double peak? ### Context: The cause of the double peak observed at submaximal stimulation of sensory nerves is unknown. The first peak is generated under the cathode and the second under the anode. The double peak is thought to arise from intradermal nerves or skin receptors, and in this study we tested this assumption.We studied the effect of different stimulus durations on anodal peak latency in volunteers. Biphasic anodal stimulation was used to investigate the latent additive effect of the trailing negative phase on the partial depolarization induced by the initial positive phase. We further tested the maximal amplitude of anode-generated potentials to estimate the number of neural structures involved in their generation.Increased stimulus duration caused anode-generated potential delay. Biphasic stimulation increased anode-generated amplitude 4-fold compared with monophasic stimulation. The anode-generated potential produced up to 85% of the supramaximal cathode-generated amplitude. ### Long_Answer: The results suggest that the double peak arises from anodal break excitation and not from intradermal nerves or receptors. ### Final_Prediction: no |
### Question: Does induction of heme oxygenase-1 ameliorate vascular dysfunction in streptozotocin-induced type 2 diabetic rats? ### Context: To explore the effects of heme oxygenase-1 (HO-1) on vascular dysfunction in high fat diet streptozotocin-induced type 2 diabetic (T2D) rats.Rats received a high-fat diet followed by a low dose of streptozotocin (30 mg/kg) to induce T2D. T2D rats were treated with hemin (1, 5, or 25mg/kg) or carbon monoxide-releasing molecule-2 (CORM-2, 5 mg/kg) for 4 weeks. Isometric contractions of aortic rings were measured. The expression of cyclooxygenase-2 (COX-2) and activities of HO, SOD, and MDA were evaluated.The fasting blood glucose, blood insulin levels, and IR index in T2D rats were higher than those in the control group, which were ameliorated by HO-1 inducer hemin. The antidiabetic effect was accompanied by enhanced HO activity. The vascular relaxation response to ACh was decreased in T2D rats, while treatment with hemin could prevent such decrease in vasorelaxation. An increase in COX-2 expression was found in the aortas of T2D rats. Treatment of T2D rats with COX-2 inhibitor NS398 restored ACh-induced vasodilation. COX-2 overexpression in T2D rats was inhibited by hemin. Hemin treatment also inhibited the decline of SOD activity and the increase of MDA content in the aorta of T2D rats. CORM-2, an agent which releases the HO-1 product CO, could mimic the beneficial effect of hemin. ### Long_Answer: Induction of HO-1 with hemin ameliorates the abnormality of endothelium-dependent vascular relaxation in T2D rats. A possible mechanism involves suppression of reactive oxygen species production and inhibition of COX-2 up-regulation induced by diabetes mellitus. ### Final_Prediction: yes |
### Question: Does bosentan ameliorate the expression of fibrotic related growth factors and collagen-1 in diabetic mice? ### Context: To investigate the potential beneficial effect of bosentan in ameliorating fibrotic agents in diabetic mice.Male 6-week old C57BL/6 mice were divided into 3 groups (N=20): Control group, diabetes mellitus (DM) group and DM-B group (diabetes with bosentan group). Streptozotocin (STZ) was injected as 200 mg/Kg for single dose, i.p. (intraperitoneal injection). Fasting blood glucose (FBG) was measured at 0-, 1-, 2-week after STZ injection to confirm that diabetes was induced in the mice. Bosentan (100mg/Kg) and placebo was given i.g. (intragastric administration) once a day immediately after STZ injection for 18 weeks. The mRNA expression of tissue growth factor beta (TGF-b), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) and collagen-1 were evaluated by RT-PCR and real-time PCR. Differences in the data between the groups were compared by Student t-test for independent samples.After 18 weeks of diabetic situation, FBG of DM-B mice was significantly higher than that of control mice and was similar with that of DM mice (DM mice vs. control mice, p<0.001; DM-B vs. control mice, p<0.001; DM mice vs. DM-B mice, p>0.05). The cardiac VEGF mRNA (a potent angiogenic factor) level in DM-B mice was significantly higher than DM mice (p<0.01). The heart of DM-B mice also showed lower expression of fibrotic genes (TGF-b, CTGF and collagen-1) than DM mice (p<0.01). ### Long_Answer: These findings indicate the potential usefulness of an ET receptor antagonist bosentan in the amelioration of fibrotic agents, which may promote tissue fibrosis. This may provide a promising therapeutical strategy for diabetic cardiac fibrosis. ### Final_Prediction: yes |
### Question: Does temporal gene expression profiling reveal CEBPD as a candidate regulator of brain disease in prosaposin deficient mice? ### Context: Prosaposin encodes, in tandem, four small acidic activator proteins (saposins) with specificities for glycosphingolipid (GSL) hydrolases in lysosomes. Extensive GSL storage occurs in various central nervous system regions in mammalian prosaposin deficiencies.Our hypomorphic prosaposin deficient mouse, PS-NA, exhibited 45% WT levels of brain saposins and showed neuropathology that included neuronal GSL storage and Purkinje cell loss. Impairment of neuronal function was observed as early as 6 wks as demonstrated by the narrow bridges tests. Temporal transcriptome microarray analyses of brain tissues were conducted with mRNA from three prosaposin deficient mouse models: PS-NA, prosaposin null (PS-/-) and a V394L/V394L glucocerebrosidase mutation combined with PS-NA (4L/PS-NA). Gene expression alterations in cerebrum and cerebellum were detectable at birth preceding the neuronal deficits. Differentially expressed genes encompassed a broad spectrum of cellular functions. The number of down-regulated genes was constant, but up-regulated gene numbers increased with age. CCAAT/enhancer-binding protein delta (CEBPD) was the only up-regulated transcription factor in these two brain regions of all three models. Network analyses revealed that CEBPD has functional relationships with genes in transcription, pro-inflammation, cell death, binding, myelin and transport. ### Long_Answer: These results show that: 1) Regionally specific gene expression abnormalities precede the brain histological and neuronal function changes, 2) Temporal gene expression profiles provide insights into the molecular mechanism during the GSL storage disease course, and 3) CEBPD is a candidate regulator of brain disease in prosaposin deficiency to participate in modulating disease acceleration or progression. ### Final_Prediction: yes |
### Question: Does analysis of 7 immunohistochemical markers in male germ cell tumors demonstrate the prognostic significance of p53 and MIB-1? ### Context: Various prognostic factors have been investigated in order to predict the minority of male germ cell tumor (GCT) patients who will develop resistant disease. However, no prognostic system has been proven accurate.Paraffin-embedded tissue specimens, obtained from primary lesions during the initial diagnosis of 83 advanced chemotherapy-treated GCT male patients, were stained for 7 immunohistochemical markers: p53, bax, bcl-2, MIB-1, topoisomerase IIa, c-kit and COX-2. The percentage of positive cells for each marker was measured for each patient. Cox regression was used for the prognostic factor analysis.All patients were followed for a median of 4 years. Nineteen patients had seminoma and 64 non-seminomatous GCT. In univariate analysis, only p53 (hazard ratio (HR) = 4.01, 95% confidence interval (CI) = 1.25-12.84, p = 0.019) and MIB-1 (HR = 3.16, 95% CI = 1.06-9.45, p = 0.039) were found to be prognostic for disease-specific survival. The best prognostic cut-off values of p53 and MIB-1 were 10% and 30% respectively. In multivariate analysis, these two markers obtained independent significance only when considered in combination (HR = 6.63, 95% CI = 1.40-31.41, p = 0.017, for patients with one or both markers above their cut-off), while the International Germ Cell Consensus Cancer Group (IGCCCG) risk was the most significant (HR = 7.99, 95% CI = 1.96-32.52, p = 0.004, for the high-risk group). However, the expression of these markers seemed to be significantly correlated with known prognostic factors. Nevertheless, we identified 34 patients of low IGCCCG risk expressing both markers below their cut-off with excellent survival. ### Long_Answer: Among 7 immunohistochemical markers, p53 and MIB-1 demonstrated prognostic significance. Their combination may contribute to improvement of the accuracy of the currently approved prognostic system (IGCCCG). ### Final_Prediction: yes |
### Question: Is increased insulinogenic index an independent determinant of nonalcoholic fatty liver disease activity score in patients with normal glucose tolerance? ### Context: Although insulin resistance is involved in nonalcoholic fatty liver disease, role of abnormalities in early phase of insulin secretion has not been examined.We examined which anthropometric and metabolic parameters, including insulinogenic index during oral glucose tolerant test, were independently associated with the disease activity of nonalcoholic fatty liver disease.A total of 114 consecutive biopsy-proven nonalcoholic fatty liver disease patients without type 2 diabetes were enrolled.Age, aspartate aminotransferase, free fatty acid, ferritin type IV collagen, hyaluronic acid, procollagen N-terminal peptide, fasting plasma glucose and 2-h insulin after glucose loading were significantly higher in patients with impaired glucose tolerance than those with normal glucose tolerance. Multiple stepwise regression analysis revealed that glycated haemoglobin, decreased density ratio of liver to spleen in computed tomography and increased insulinogenic index were independently associated with nonalcoholic fatty liver disease activity score in normal glucose tolerance patients, whereas aspartate aminotransferase and 2-h insulin in impaired glucose tolerance subjects. However, there were no significant independent correlations between insulinogenic index and steatosis grade/fibrosis stage in normal glucose tolerance patients. ### Long_Answer: The present study suggests that increased early phase of insulin secretion may contribute to nonalcoholic fatty liver disease activity score in patients with normal glucose tolerance. ### Final_Prediction: yes |
### Question: Do functional P2Y2 nucleotide receptors mediate uridine 5'-triphosphate-induced intimal hyperplasia in collared rabbit carotid arteries? ### Context: Extracellular uridine 5'-triphosphate (UTP) induces mitogenic activation of smooth muscle cells (SMCs) through binding to P2Y2 nucleotide receptors. P2Y2 receptor mRNA is upregulated in intimal lesions of rat aorta, but it is unclear how this G-protein-coupled receptor contributes to development of intimal hyperplasia.This study used a silicone collar placed around rabbit carotid arteries to induce vascular injury and intimal thickening. Collar placement caused rapid upregulation of P2Y2 receptor mRNA in medial SMCs before appearance of neointima. Fura-2 digital imaging of single SMCs was used to measure changes in myoplasmic calcium concentration (Ca(m)) in response to P2Y receptor agonists. In contrast to UDP, activation by UTP or adenosine 5'-triphosphate (ATP) greatly increased Ca(m), which indicates upregulation of functional P2Y2 receptors at which UTP and ATP are equipotent agonists. The number of responsive cells was significantly greater for freshly dispersed SMCs from collared arteries than for controls. Perivascular infusion of UTP (100 micromol/L) within the collar significantly enhanced neointimal development. Intimas that resulted from UTP exposure were infiltrated by macrophages. Moreover, increased expression of osteopontin occurred in response to in situ application of UTP. ATP or UTP also stimulated osteopontin expression in cultured SMCs in a dose-dependent manner. Furthermore, P2Y2 antisense oligonucleotide inhibited osteopontin expression induced by UTP. ### Long_Answer: These findings indicate for the first time a role for the UTP/ATP receptor, P2Y2, in development of intimal hyperplasia associated with atherosclerosis and restenosis. ### Final_Prediction: yes |
### Question: Is wound contraction attenuated by fasudil inhibition of Rho-associated kinase? ### Context: Dermal scarring and scar contracture result in restriction of movement. There are no effective drugs to prevent scarring. RhoA and Rho-associated kinase have emerged as regulators of fibrosis and contracture. Fasudil, a Rho-associated kinase inhibitor, has been demonstrated to have antifibrotic effects in models of liver, renal, and cardiac fibrosis. The role of fasudil in preventing dermal scarring and contractures has not been studied. The authors used a rat model of dermal wound healing to assess the effects of fasudil with regard to the prevention of scarring.Human scar tissue and surrounding normal skin were immunostained for RhoA and Rho-associated kinase. Full-thickness wounds were created on Wistar-Han rats, and fasudil (30 mg/kg/day) or saline was continuously delivered subcutaneously. Wound contraction was measured by gravitational planimetry. After 21 days, tissue was harvested for Masson's trichrome, hematoxylin and eosin, Ki-67, and CD31 staining. Fibroblast-populated collagen lattices were used to assess the mechanistic effects of fasudil on contractility. Myofibroblast formation was assessed in the presence of fasudil.Human scar tissue in the remodeling phase of repair showed increased expression of RhoA and Rho-associated kinase in scar tissue compared with surrounding normal tissue. Fasudil inhibited wound contraction as compared with controls. Hematoxylin and eosin and Masson's trichrome were similar between groups. Fasudil did not alter angiogenesis or proliferation. Fasudil inhibited fibroblast contractility and myofibroblast formation in vitro. ### Long_Answer: There is growing evidence that the RhoA/Rho-associated kinase pathway plays an important role in wound healing and scar contracture. The authors present data showing that inhibition of Rho-associated kinase hinders fibroblast contractility and may be beneficial in preventing scar contracture. ### Final_Prediction: yes |
### Question: Is plasma homocysteine a risk factor for recurrent vascular events in young patients with an ischaemic stroke or TIA? ### Context: Young patients with an ischaemic stroke or transient ischaemic attack (TIA) often have no vascular risk factors. Hyper-homocysteinaemia is an established risk factor for stroke in elderly patients but it is uncertain whether it is also important for the prognosis of young ischaemic stroke and TIA patients. We examined the possible effect of the plasma homocysteine level on the risk of recurrent vascular events in patients between 18 and 45 years of age.The study population consisted of 161 consecutive patients with a recent cerebral infarction or TIA. Data on the primary event and the homocysteine level were collected retrospectively from hospital records. General practitioners and patients were contacted by telephone to record vascular events and the type of medication used during the follow-up period. Vascular events included cerebral infarction, TIA, pulmonary embolism, venous thrombosis, myocardial infarction and peripheral arterial disease.A Kaplan- Meier curve showed a dose effect relationship between event-free survival time and tertiles of the homocysteine level (Log rank statistic 5.91; p=0.05). The Cox hazard ratio, after adjustment for homocysteine lowering treatment, was 1.7 (95 % CI, 1.1 to 2.8) for any vascular outcome event, 1.9 (95% CI, 1.1 to 3.0) for arterial outcome events and 1.8 (95 % CI, 1.1 to 2.9) for cerebral outcome events. ### Long_Answer: In spite of our small number of outcome events we found a significant association at the 95% confidence level between homocysteine level and the risk of recurrent vascular events in young patients with an ischaemic stroke or TIA. The association is of the same magnitude as in elderly people. ### Final_Prediction: yes |
### Question: Do cannabinoid receptor agonists and antagonists stimulate insulin secretion from isolated human islets of Langerhans? ### Context: The role of cannabinoid receptors in human islets of Langerhans has not been investigated in any detail, so the current study examined CB1 and CB2 receptor expression by human islets and the effects of pharmacological cannabinoid receptor agonists and antagonists on insulin secretion.Human islets were isolated from pancreases retrieved from heart-beating organ donors. Messenger RNAs encoding human CB1 and CB2 receptors were amplified from human islet RNA by RT-PCR and receptor localization within islets was identified by immunohistochemistry. Dynamic insulin secretion from human islets perifused with buffers supplemented with CB1 and CB2 receptor agonists and antagonists was quantified by radioimmunoassay.RT-PCR showed that both CB1 and CB2 receptors are expressed by human islets and immunohistochemistry indicated that receptor expression co-localized with insulin-expressing β-cells. Perifusion experiments using isolated human islets showed that insulin secretion was reversibly stimulated by both CB1 and CB2 receptor agonists, with CB1 receptor activation associated with increased basal secretion whereas CB2 receptors were coupled to initiation and potentiation of insulin secretion. Antagonists at CB1 (N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) and CB2 (N-(1,3-Benzodioxol-5-ylmethyl)-1,2-dihydro-7-methoxy-2-oxo-8-(pentyloxy)-3-quinoline carboxamide) receptors failed to inhibit the stimulatory effects of the respective agonists and, unexpectedly, reversibly stimulated insulin secretion. ### Long_Answer: These data confirm the expression of CB1 and CB2 receptors by human islets and indicate that both receptor subtypes are coupled to the stimulation of insulin secretion. They also implicate involvement of CB1/2 receptor-independent pathways in the antagonist-induced stimulatory effects. ### Final_Prediction: yes |
### Question: Does peptide leukotriene receptor antagonist diminish pancreatic edema formation in rats with cerulein-induced acute pancreatitis? ### Context: This study was designed to evaluate the protective effect of a peptide leukotriene receptor antagonist, pranlukast hydrate, against pancreatic injuries during acute pancreatitis.Acute pancreatitis was induced in rats by intravenous infusion of a supramaximal dose of cerulein (5 micrograms/kg h for 4 h). In this model marked hyperamylasemia, a significant increase in pancreatic water content, and a significant increase in pancreatic microvascular leakage of Evans blue dye were observed. Pancreatic subcellular redistribution of the lysosomal enzyme cathepsin B from the lysosomal fraction to the zymogen fraction was also observed.Pretreatment with pranlukast hydrate at a dose of 10 micrograms/kg (twice, 8 and 4 h before cerulein infusion) significantly inhibited these pancreatic injuries, including hyperamylasemia, increased pancreatic microvascular permeability, and redistribution of cathepsin B in pancreatic acinar cells. ### Long_Answer: These results suggest that peptide leukotrienes may be involved in the pathogenesis of acute pancreatitis in the early stage of the disease and that peptide leukotriene receptor antagonist might be of therapeutic value for treatment of acute pancreatitis. ### Final_Prediction: yes |
### Question: Does diabetes mellitus have an impact on the prognosis for patients with cervical cancer? ### Context: To evaluate the impact of comorbid diabetes mellitus (DM) on prognoses among patients with cervical cancer.We analyzed cervical cancer outcomes in patients who treated in two hospitals retrospectively. Patients were divided into those with DM and those without. Clinicopathologic parameters, disease-free survival (DFS), and overall survival (OS) rates were evaluated.Of the 494 patients, 50 had DM. These were more likely to be older than those in the non-DM group and their body mass index (BMI) was higher. They showed higher levels of tumor markers and had more combined diseases. They were less likely to have had surgical treatment. Among these patients, 12 (24%) experienced a recurrence (hazard ratio, HR, 1.484; 95% confidence interval, CI, 0.746-2.951). Differences in DFS did not show statistical significance. In the OS analysis, 11 (22%) in the DM group and 62 (14%) in the non-DM group died (HR, 1.239; 95% CI, 0.606-2.533). No statistically significant differences were also observed for cancer-specific death (HR, 1.246; 95% CI, 0.567-2.737). Those with DM and an adenocarcinoma tended to have an increased risk of dying compared with the non-DM patients with an adenocarcinoma (HR, 3.673; 95% CI, 0.990-13.625), but this difference was not statistically significant (p=0.0518). ### Long_Answer: Diabetes mellitus did not have an impact on the prognosis for patients with cervical cancers. In those with an adenocarcinoma, patients with diabetes tended to have an increased risk of dying compared with the non-DM group, but this difference was not statistically significant. ### Final_Prediction: nan |
### Question: Is nurse-administered propofol sedation safe for patients with obstructive sleep apnea undergoing routine endoscopy : a pilot study? ### Context: Nurse-administered propofol sedation (NAPS) is now in widespread use. The safety profile of NAPS for routine endoscopic procedures in patients with obstructive sleep apnea (OSA) is unknown.To compare outcomes of patients with and without OSA undergoing routine endoscopic procedures with NAPS and standard conscious sedation (CS) with benzodiazepines and narcotics.Retrospective cohort study.A total of 215 patients were placed in one of four groups: OSA patients undergoing endoscopy with NAPS, OSA patients undergoing endoscopy with standard CS, non-OSA patients undergoing endoscopy with NAPS, and non-OSA patients undergoing endoscopy with standard CS. Procedures were generally accomplished faster with NAPS. There was no statistically significant difference in complication rates or overall outcomes in patients with OSA when compared to non-OSA patients when either NAPS or CS was utilized. ### Long_Answer: Routine endoscopic procedures using NAPS are safe in patients with documented OSA, with complication rates comparable to when using CS. NAPS helped to decrease procedure times in general. ### Final_Prediction: yes |
### Question: Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? ### Context: To evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure (HF) are adopted in clinical practice.The ESC-HF Long-Term Registry is a prospective, observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries, members of the European Society of Cardiology (ESC). From May 2011 to April 2013, a total of 12,440 patients were enrolled, 40.5% with acute HF and 59.5% with chronic HF. Intravenous treatments for acute HF were heterogeneously administered, irrespective of guideline recommendations. In chronic HF, with reduced EF, renin-angiotensin system (RAS) blockers, beta-blockers, and mineralocorticoid antagonists (MRAs) were used in 92.2, 92.7, and 67.0% of patients, respectively. When reasons for non-adherence were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4% of the cases, respectively. About 30% of patients received the target dosage of these drugs, but a documented reason for not achieving the target dosage was reported in almost two-thirds of them. The more relevant reasons for non-implantation of a device, when clinically indicated, were related to doctor uncertainties on the indication, patient refusal, or logistical/cost issues. ### Long_Answer: This pan-European registry shows that, while in patients with acute HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines, when the reasons for non-adherence are taken into account. Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written. ### Final_Prediction: nan |
### Question: Does interleukin-2 receptor antibody reduce rejection risk in low immunological risk or tacrolimus-treated intermediate immunological risk renal transplant recipients? ### Context: The use of interleukin-2 receptor antibody (IL-2Ra) induction has been associated with reduced rejection rates in renal transplant recipients. However, the effect of IL-2Ra induction on graft and patient outcomes in renal transplant recipients with differing immunological risk remains unclear.Using Australia and New Zealand Dialysis and Transplant Registry, renal transplant recipients in Australia between 1995 and 2005 were included. Recipients were stratified into low immunological risk (primary grafts with < or = 2 human leucocyte antigen (HLA)-mismatches and panel-reactive antibody (PRA) < 10%) or intermediate immunological risk (subsequent grafts or >2 HLA-mismatches or PRA > 25%) recipients. Recipients receiving T-cell depletive induction therapy or steroid and/or calcineurin-free inhibitor regimens were excluded. Outcomes analysed included the presence of rejection at 6 months, estimated glomerular filtration rate at 1 and 5 years, graft and patient survival.218 of 1220 (18%) low-risk and 883 of 3204 (28%) intermediate-risk recipients received IL-2Ra. In intermediate-risk recipients, IL-2Ra induction was associated with a 26% reduction in the incidence of acute rejection; but this benefit was restricted only to recipients initiated on cyclosporine-based immunosuppressive regimens. In contrast, the use of IL-2Ra in low-risk recipients was not associated with reduced rejection risk. There was no association between IL-2Ra induction and other graft or patient outcomes in both low- and intermediate-risk recipients. ### Long_Answer: This registry analysis suggests that IL-2Ra induction may be associated with a reduction in rejection risk in cyclosporine-treated intermediate immunological risk recipients, but not in low-risk renal transplant recipients. ### Final_Prediction: no |
### Question: Does infant feeding mode affect early growth and body composition? ### Context: Differences in the growth pattern of breastfed (BF) and formula-fed (FF) infants are well-recognized and have been attributed to differences in nutrient intake. However, the impact of qualitative and quantitative differences in nutrient intake on the body composition of BF and FF infants has been unclear. Furthermore, it is unknown whether putative differences in body composition persist beyond weaning.Prospective cohort study.Repeated anthropometric and body composition measurements were performed on 40 BF and 36 FF infants at 0.5, 3, 6, 9, 12, 18, and 24 months of age. A multicomponent body composition model based on total body water by deuterium dilution, total body potassium by whole body counting, and bone mineral content by dual-energy x-ray absorptiometry was used to estimate fat-free mass (FFM) and fat mass (FM). Independent measurements of FFM and FM were made using total body electrical conductivity and dual-energy x-ray absorptiometry. By design, infants were either exclusively BF or FF from birth to 4 months of age; thereafter, the feeding mode was at the discretion of the parents. Infant food intake was measured at 3, 6, 12, and 24 months of age using 3-day weighed-intake records. Data were analyzed by repeated measures analysis of variance.Weight velocity was higher in FF than BF infants age 3 to 6 months, and higher in FF than BF girls 6 to 9 months of age. Adjusted for gender and baseline values, BF infants had lower total body water at 3 months, lower total body potassium at 3 to 24 months, and lower bone mineral content at 12 months. The multicomponent model indicated that FFM was lower in BF than FF infants at 3 months, and FM and %FM were higher in BF than FF infants at 3 and 6 months (boys only). Total body electric conductivity confirmed lower FFM in BF than FF infants at 3 months, as well as at 6 and 9 months; FM and %FM were higher in BF than FF at 3 and 6 months, and 9 months (boys only). Intakes of energy, protein, fat, and carbohydrate were lower in BF than FF infants at 3 and 6 months, and were positively correlated with weight gain and FFM gain, but not FM gain. No differences in nutrient intakes were observed at 12 or 24 months. ### Long_Answer: Infant feeding mode is associated with differences in body composition in early infancy which do not persist into the second year of life. ### Final_Prediction: yes |
### Question: Is childhood abuse or neglect associated with increased vasomotor symptom reporting among midlife women? ### Context: This study tested the hypothesis that women exposed to childhood abuse or neglect would have an increased likelihood of reporting hot flashes and night sweats during the menopausal transition.This hypothesis was evaluated in 332 white and African American women participating in the Study of Women's Health Across the Nation Mental Health Study, a prospective investigation of women transitioning through menopause. Childhood abuse and neglect were measured once with the Child Trauma Questionnaire. Vasomotor symptoms (any/none hot flashes, night sweats) were reported annually over 8 years. Associations between maltreatment and vasomotor symptoms were estimated with generalized estimating equations.Childhood abuse or neglect was associated with increased reporting of hot flashes (odds ratio = 1.73, 95% CI: 1.23-2.43) and night sweats (odds ratio = 1.75, 95% CI: 1.26-2.43) in age-adjusted models. Results persisted in multivariable models and across several types of abuse and neglect. ### Long_Answer: The experience of childhood abuse and neglect is associated with increased vasomotor symptom reporting in adulthood. The sequelae of childhood abuse and neglect may persist well into adulthood to influence the occurrence of vasomotor symptoms at midlife. ### Final_Prediction: yes |
### Question: Should young age be a contra-indication to breast conservation treatment in Chinese women? ### Context: It has been proposed that young women should not be treated by breast conservation treatment because of a higher risk of local recurrences and worse survival. We therefore examined whether breast conservation treatment in young Chinese women yielded inferior clinical outcomes compared to modified radical mastectomy.Retrospective study.Clinical oncology department in a public hospital in Hong Kong.A total of 258 Chinese women with invasive breast cancer, aged below 40 years, and referred between January 1994 and July 2006.A total of 124 (48%) and 134 (52%) patients were treated by breast conservation treatment and modified radical mastectomy, respectively. Mastectomy patients tended to have larger primary tumours (P<0.001) and more nodal involvement (P<0.001). At a median follow-up of 6.5 years, there was no significant difference in the local failure-free survival rate (92% vs 93%, P=0.324) and loco-regional failure-free survival rate (89% vs 88%, P=0.721) in patients having breast conservation treatment and mastectomy. Probably due to their earlier presentation with disease, the former actually had better 6-year distant failure-free survival (88% vs 71%, P=0.002) and overall survival (92% vs 81%, P=0.173) rates. Multivariate analyses showed that both the resection margin status (hazard ratio=2.77, P=0.050) and the presence of peritumoural vascular invasion (hazard ratio=3.01, P=0.038) were independent predictors of local recurrence; the nodal status (hazard ratio=3.91, P<0.001) was the only predictive factor for overall survival. The choice of breast conservation treatment (vs modified radical mastectomy) had no apparent adverse impact on all the clinical outcome parameters analysed. ### Long_Answer: Breast conservation treatment is a reasonable option for many suitably selected young Chinese women. ### Final_Prediction: nan |
### Question: Does multiparametric magnetic resonance imaging predict clinical outcomes in patients with chronic liver disease? ### Context: Multiparametric magnetic resonance (MR) imaging has been demonstrated to quantify hepatic fibrosis, iron, and steatosis. The aim of this study was to determine if MR can be used to predict negative clinical outcomes in liver disease patients.Patients with chronic liver disease (n=112) were recruited for MR imaging and data on the development of liver related clinical events were collected by medical records review. The median follow-up was 27months. MR data were analysed blinded for the Liver Inflammation and Fibrosis score (LIF; <1, 1-1.99, 2-2.99, and ⩾3 representing normal, mild, moderate, and severe liver disease, respectively), T2∗ for liver iron content and proportion of liver fat. Baseline liver biopsy was performed in 102 patients.Liver disease aetiologies included non-alcoholic fatty liver disease (35%) and chronic viral hepatitis (30%). Histologically, fibrosis was mild in 54 (48%), moderate in 17 (15%), and severe in 31 (28%) patients. Overall mortality was 5%. Ten patients (11%) developed at least one liver related clinical event. The negative predictive value of LIF<2 was 100%. Two patients with LIF 2-2.99 and eight with LIF⩾3 had a clinical event. Patients with LIF⩾3 had a higher cumulative risk for developing clinical events, compared to those with LIF<1 (p=0.02) and LIF 1-1.99 (p=0.03). Cox regression analysis including all 3 variables (fat, iron, LIF) resulted in an enhanced LIF predictive value. ### Long_Answer: Non-invasive standardised multiparametric MR technology may be used to predict clinical outcomes in patients with chronic liver disease. ### Final_Prediction: yes |
### Question: Can ultrasound biomicroscopy be used to predict accommodation accurately? ### Context: Clinical accommodation testing involves measuring either accommodative optical changes or accommodative biometric changes. Quantifying both optical and biometric changes during accommodation might be helpful in the design and evaluation of accommodation restoration concepts. This study aims to establish the accuracy of ultrasound biomicroscopy (UBM) in predicting the accommodative optical response (AOR) from biometric changes.Static AOR from 0 to 6 diopters (D) stimuli in 1-D steps were measured with infrared photorefraction and a Grand Seiko autorefractor (WR-5100 K; Shigiya Machinery Works Ltd., Hiroshima, Japan) in 26 human subjects aged 21 to 36 years. Objective measurements of accommodative biometric changes to the same stimulus demands were measured from UBM (Vu-MAX; Sonomed Escalon, Lake Success, NY) images in the same group of subjects. AOR was predicted from biometry using linear regressions, 95% confidence intervals, and 95% prediction intervals.Bland-Altman analysis showed 0.52 D greater AOR with photorefraction than with the Grand Seiko autorefractor. Per-diopter changes in accommodative biometry were: anterior chamber depth (ACD): -0.055 mm/D, lens thickness (LT): +0.076 mm/D, anterior lens radii of curvature (ALRC): -0.854 mm/D, posterior lens radii of curvature (PLRC): -0.222 mm/D, and anterior segment length (ASL): +0.030 mm/D. The standard deviation of AOR predicted from linear regressions for various biometry parameters were: ACD: 0.240.300.240.430.50 D. ### Long_Answer: UBM measured parameters can, on average, predict AOR with a standard deviation of 0.50 D or less using linear regression. UBM is a useful and accurate objective technique for measuring accommodation in young phakic eyes. ### Final_Prediction: nan |
### Question: Does autocrine motility factor receptor expression imply an unfavourable prognosis in resected stage I pulmonary adenocarcinomas? ### Context: Pulmonary adenocarcinomas constitute a different histological subtype among the histological subtypes of non small cell lung carcinomas by showing comparably unfavourable rates of prognosis and different immunobiological features. Autonomous motility of tumour cells plays an important role in the regulation of local invasion and distant metastasis of tumour lesions which have great impact on overall survival. AMF (Autocrine motility factor) is a tumour secreted cytokine that stimulates motility during invasion and metastasis via its receptor, AMFR. We conducted an immunohistochemical study to investigate AMFR expression in pulmonary adenocarcinomas and its effect on survival.We assessed AMFR expression using a monoclonal antibody (3F3A) in a total of 32 surgical specimens with stage I pulmonary adenocarcinomas that underwent curative resection. We analyzed AMFR expression as a possible prognostic factor on survival and its correlations with clinicopathological features.A total of 19 (59.3%) specimens showed AMFR expression. The 3-year survival rates of AMFR positive and AMFR negative patients were 47.3% and 84.6%, respectively, which was a significant difference (P = 0.0197). The univariate predictors of surgical outcome were AMFR expression (P = 0.032) and perineural invasion (P = 0.038). However, multivariate analysis revealed AMFR expression (P = 0.045) as the only independent prognostic factor. ### Long_Answer: AMFR expression predicts an unfavourable surgical outcome in patients with stage I pulmonary adenocarcinomas. ### Final_Prediction: yes |
### Question: Is immunodominant PstS1 antigen of mycobacterium tuberculosis a potent biological response modifier for the treatment of bladder cancer? ### Context: Bacillus Calmette Guerin (BCG)-immunotherapy has a well-documented and successful clinical history in the treatment of bladder cancer. However, regularly observed side effects, a certain degree of nonresponders and restriction to superficial cancers remain a major obstacle. Therefore, alternative treatment strategies are intensively being explored. We report a novel approach of using a well defined immunostimulatory component of Mycobacterium tuberculosis for the treatment of bladder cancer. The phosphate transport protein PstS1 which represents the phosphate binding component of a mycobacterial phosphate uptake system is known to be a potent immunostimulatory antigen of M. tuberculosis. This preclinical study was designed to test the potential of recombinant PstS1 to serve as a non-viable and defined immunotherapeutic agent for intravesical bladder cancer therapy.Mononuclear cells (PBMCs) were isolated from human peripheral blood and stimulated with PstS1 for seven days. The activation of PBMCs was determined by chromium release assay, IFN-gamma ELISA and measurement of lymphocyte proliferation. The potential of PstS1 to activate monocyte-derived human dendritic cells (DC) was determined by flow cytometric analysis of the marker molecules CD83 and CD86 as well as the release of the cytokines TNF-alpha and IL-12. Survival of presensitized and intravesically treated, tumor-bearing mice was analyzed by Kaplan-Meier curve and log rank test. Local and systemic immune response in PstS1-immunotherapy was investigated by anti-PstS1-specific ELISA, splenocyte proliferation assay and immunohistochemistry.Our in vitro experiments showed that PstS1 is able to stimulate cytotoxicity, IFN-gamma release and proliferation of PBMCs. Further investigations showed the potential of PstS1 to activate monocyte-derived human dendritic cells (DC). In vivo studies in an orthotopic murine bladder cancer model demonstrated the therapeutic potential of intravesically applied PstS1. Immunohistochemical analysis and splenocyte restimulation assay revealed that local and systemic immune responses were triggered by intravesical PstS1-immunotherapy. ### Long_Answer: Our results demonstrate profound in vitro activation of human immune cells by recombinant PstS1. In addition, intravesical PstS1 immunotherapy induced strong local and systemic immune responses together with substantial anti-tumor activity in a preclinical mouse model. Thus, we have identified recombinant PstS1 antigen as a potent immunotherapeutic drug for cancer therapy. ### Final_Prediction: yes |
### Question: Are y chromosome losses exceedingly rare in prostate cancer and unrelated to patient age? ### Context: Loss of the Y chromosome is a frequently reported chromosomal abnormality in many tumor types. This study was undertaken to investigate the frequency of Y chromosome losses and this chromosomal abnormality might play a potential role in prostate cancer.A preexisting prostate cancer tissue microarray (TMA) containing samples of 3,261 patients treated by radical prostatectomy with clinical follow-up data was used in this study. TMA sections were analyzed by fluorescence in situ hybridization (FISH) using a dual labeling probe for the centromeres of the X and Y chromosome.Unequivocal losses of the Y chromosome were seen in only 12 of 2,053 analyzable cases. No significant associations were found between Y loss and patient age, pT stage, and the risk of PSA recurrence. Interestingly, in our study the presence of Y losses was significantly associated with high Gleason grade (P = 0.0034). ### Long_Answer: Loss of the Y chromosome is a rare event in prostate cancer. Y losses occur in much higher rates in most other cancer types. For this reason, we suggest that the expression of at least one Y chromosome gene is essential for prostate epithelial cells and it is possible that such a gene could represent a suitable target for future therapy of prostate cancer. ### Final_Prediction: yes |
### Question: Are portable PET probes a novel tool for intraoperative localization of tumor deposits? ### Context: Positron emission tomography (PET) identifies cancer deposits by detecting sites of gamma emissions that are released from radioactively labeled molecules targeting tumor to formulate a PET image. Correlating preoperative PET scans with intraoperative findings remains a challenge. We investigated whether high-energy gamma emissions detected by a novel hand-held PET probe would detect tumors and offer a real-time method to localize tumor intraoperatively. Furthermore, we investigated the novel beta probe, which detects emissions at a shorter range than gamma emissions, making them undetectable by PET scanners, but potentially valuable for close range intraoperative detection of tumor deposits.Six-to-eight-week-old athymic mice were injected with one of four possible tumor cell lines: gastric, pancreas, squamous cell and breast cancer. After tumors reached at least 1 cm in size, they were euthanized and imaged with a micro-PET imager. Hand-held gamma and beta probes were then used in vivo and ex vivo to measure high-energy gamma and beta emissions.The portable PET probes detected high-energy gamma and beta emissions from all tumors evaluated. These emissions were reproducible and we established that beta emissions correlate with high-energy gamma emissions and conventional PET scans. There was a strong positive correlation (R = 0.8) between gamma and beta counts. Beta emission showed a stronger correlation than gamma emission with overall tissue radioactivity. ### Long_Answer: This study is the first to demonstrate that gamma emission detected by conventional PET imaging correlates with beta emissions. This study shows that compared to detection of gamma emissions, beta counts may offer superior real-time localization of tumor deposits. Intraoperative portable PET probe may become a useful way to exploit tumor biology and PET technology to guide real-time tissue characterization during surgery. ### Final_Prediction: yes |
### Question: Is proteasome activation by hepatitis C core protein reversed by ethanol-induced oxidative stress? ### Context: The proteasome is a major cellular proteinase. Its activity is modulated by cellular oxidants. Hepatitis C core protein and ethanol exposure both cause enhanced oxidant generation. The aim was to investigate whether core protein, by its ability to generate oxidants, alters proteasome activity and whether these alterations are further affected by ethanol exposure.These interactions were examined in Huh-7 cell lines that expressed inducible HCV core protein and/or constitutive cytochrome P450 2E1 (CYP2E1) and as purified components in a cell-free system. Chymotrypsin-like proteasome activity was measured fluorometrically.Proteasome activity in core-positive 191-20 cells was 20% higher than that in core-negative cells and was enhanced 3-fold in CYP2E1-expressing L14 cells. Exposure of core-positive cells to glutathione ethyl ester, catalase, or the CYP2E1 inhibitor diallyl sulfide partially reversed the elevation of proteasome activity in core-positive cells, whereas ethanol exposure suppressed proteasome activity. The results indicate that proteasome activity was up-regulated by low levels of core-induced oxidative stress but down-regulated by high levels of ethanol-elicited stress. These findings were partially mimicked in a cell-free system. Addition of core protein enhanced the peptidase activity of purified 20S proteasome containing the proteasome activator PA28 and was further potentiated by addition of liver mitochondrial and/or microsome fractions. However, proteasome activation was significantly attenuated when fractions were obtained from ethanol-fed animals. ### Long_Answer: HCV core protein interacts with PA28, mitochondrial, and endoplasmic reticulum proteins to cause low levels of oxidant stress and proteasome activation, which is dampened during ethanol metabolism when oxidant generation is higher. ### Final_Prediction: yes |
### Question: Does clinical use of cyclooxygenase inhibitors impair vitamin B-6 metabolism? ### Context: A low circulating vitamin B-6 concentration, which is an independent risk factor for cardiovascular disease, is commonly seen in human inflammation.We investigated whether cyclooxygenase inhibitors alter vitamin B-6 metabolism.To investigate whether subjects taking a cyclooxygenase inhibitor had an altered vitamin B-6 profile, we conducted a cross-sectional study that involved 150 rheumatoid arthritis patients, with and without cyclooxygenase inhibitor treatments. C57BL/6J mice and hyperlipidemic Syrian hamsters received drug regimens that reflected clinical nonsteroidal antiinflammatory drug (NSAID) uses in treating human inflammation. The impact of long-term physiologic use of selective and nonselective cyclooxygenase inhibitors on vitamin B-6 metabolism was systematically investigated in these independent in vivo models.Patients who were taking cyclooxygenase inhibitors had lower circulating pyridoxal-5'-phosphate, especially those taking NSAIDs >6 mo. Long-term celecoxib and naproxen use reduced hepatic pyridoxal-5'-phosphate in mice. Nonselective cyclooxygenase inhibitor naproxen significantly decreased vitamin B-6 vitamers in the kidney. ### Long_Answer: To our knowledge, we show novel findings that long-term physiologic doses of cyclooxygenase inhibitor may impede the synthesis of the coenzymatically active form of vitamin B-6. Because the cause of vitamin B-6 depletion in inflammation remains unknown, this study provides a potential mechanism that could account for the poor vitamin B-6 status in human inflammation. Moreover, this study further raises concerns about the long-term clinical use of antiinflammatory NSAIDs in humans. Vitamin B-6 status should be carefully monitored in long-term NSAID users. Future randomized placebo-controlled studies are needed to determine the impacts of antiinflammatory cyclooxygenase inhibitor use on vitamin B-6 metabolism in humans. ### Final_Prediction: yes |
### Question: Does oxidative stress inhibit IFN-alpha-induced antiviral gene expression by blocking the JAK-STAT pathway? ### Context: Unresponsiveness to IFN-alpha is common in chronic hepatitis C. Since conditions associated with an increased oxidative stress (advanced age, steatosis, fibrosis, iron overload, and alcohol consumption) reduce the likelihood of response, we hypothesized that oxidative stress may affect the antiviral actions of IFN-alpha.We examined in a human hepatocellular carcinoma cell line (Huh-7) the effect of hydrogen peroxide (H2O2), as a generator of oxidative stress, on the IFN-alpha signaling pathway.Pretreatment of Huh-7 cells with 0.5-1 mM H2O2 resulted in the suppression of the IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression. The reduced expression of these genes was associated to H2O2 -mediated suppression of the IFN-alpha-induced assembly of signal transducer and activator of transcription (STAT) factors to specific promoter motifs on IFN-alpha-inducible genes. This was accomplished by preventing the IFN-alpha-induced tyrosine phosphorylation of STAT-1 and STAT-2 through the inactivation of the upstream receptor associated tyrosine kinases, JAK-1 and Tyk-2. The suppression was fast, occurring within 5mins of pretreatment with H2O2, and did not require protein synthesis. ### Long_Answer: In conclusion, oxidative stress impairs IFN-alpha signaling and might cause resistance to the antiviral action of IFN-alpha in chronically HCV infected patients with high level of oxidative stress in the liver. ### Final_Prediction: yes |
### Question: Is dementia special care really special? ### Context: To quantify differences in care provided to nursing home (NH) residents with dementia living on and off dementia special care units (SCUs).Cross-sectional study using propensity score adjustment for resident and NH characteristics.Free-standing NHs in nonrural U.S. counties that had an SCU in 2004 (N=1,896).Long-stay (>or = 90 days) NH residents with a diagnosis of Alzheimer's disease or dementia and at least moderate cognitive impairment (N=69,131).Resident-level NH care processes such as physical restraints, bed rails, feeding tubes, psychotropic medications, and incontinence care.There was no difference in the use of physical restraints (adjusted odds ratio (AOR)=0.94, 95% confidence interval (CI)=0.79-1.11), but SCU residents were less likely to have had bed rails (AOR=0.55, 95% CI=0.46-0.64) and to have been tube fed (AOR=0.36, 95% CI=0.30-0.43). SCU residents were more likely to be on toileting plans (AOR=1.23, 95% CI=1.08-1.39) and less likely to use pads or briefs in the absence of a toileting plan (AOR=0.73, 95% CI=0.61-0.88). SCU residents were more likely to have received psychotropic medications (AOR=1.23, 95% CI=1.05-1.44), primarily antipsychotics (SCU=44.9% vs non-SCU=30.0%). ### Long_Answer: SCU residents received different care than comparable non-SCU residents. Most strikingly, SCU residents had greater use of antipsychotic medications. ### Final_Prediction: nan |
### Question: Do a short echo proton magnetic resonance spectroscopy study of the left mesial-temporal lobe in first-onset schizophrenic patients? ### Context: Past 1H magnetic resonance spectroscopy (MRS) studies of the temporal lobe in schizophrenic patients have shown decreased levels of N-acetylaspartate (NAA) suggesting reduced neuronal density in this region. However, the measured volumes have been large and included contributions from mostly white matter.Short echo 1H MRS was used to measure levels of NAA and other metabolites (i.e., glutamate and glutamine) from a 6 cm3 volume in the left mesial-temporal lobe of 11 first-episode schizophrenic patients and 11 healthy control subjects of comparable age, gender, handedness, education, and parental education levels. Spectra were quantified without operator interaction using automated software developed in our laboratory. Metabolite levels were normalized to the internal water concentration of each volume studied. Images were also obtained to determine temporal lobe gray and white matter volumes.No significant differences were found between levels of NAA or other metabolites, or gray and white matter volumes, in first-episode schizophrenic patients and comparison subjects. ### Long_Answer: Since the volume studied was small compared to previous studies and contained mostly gray matter, this result suggests consequential NAA decreases may be restricted to regions of white matter. ### Final_Prediction: yes |
### Question: Are somatic mutations in peroxisome proliferator-activated receptor-gamma rare events in human cancer cells? ### Context: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor activated after binding a lipophilic ligand, such as naturally occurring 15dPGJ2. There is striking evidence that PPAR-gamma activation leads not only to an increase in insulin sensitivity, but also to tumor cell apoptosis and cell cycle arrest. A growing number of diabetes mellitus II patients currently benefit from treatment with synthetic PPAR-gamma agonists, the thiazolidinediones (TZDs), which sensitize peripheral cells towards insulin. Furthermore, some TZDs are undergoing clinical investigations for the treatment of malignant diseases. Therefore, detailed information on the frequency of genetic alterations of PPAR-gamma in malignant tumor cells is necessary.PPAR-gamma DNA of 33 histologically different tumor cells was isolated, purified, and all coding regions were separately amplified by PCR. The coding exons were then analyzed by single-stranded conformational polymorphism (SSCP) and bidirectional DNA sequencing.In five breast cancer brain metastasis samples from patients and 28 cancer cell lines derived from lymphoma, glioblastoma, and breast carcinoma we found only one coding region shift in exon 5b of the glioblastoma U373 DNA. This silent mutation does not lead to a change in amino acid alignment. No further polymorphisms, including those which have already been described, could be detected in any other sample. ### Long_Answer: We conclude that somatic mutations in the PPAR gene are exceedingly rare events in malignant tumor cells. This makes PPAR-gamma more unlikely to act as a tumor suppressor gene, making it a stable and suitable target for TZD biological cancer therapy. ### Final_Prediction: yes |
### Question: Is elevated serum uric acid associated with high circulating inflammatory cytokines in the population-based Colaus study? ### Context: The relation of serum uric acid (SUA) with systemic inflammation has been little explored in humans and results have been inconsistent. We analyzed the association between SUA and circulating levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor- α (TNF-α) and C-reactive protein (CRP).This cross-sectional population-based study conducted in Lausanne, Switzerland, included 6085 participants aged 35 to 75 years. SUA was measured using uricase-PAP method. Plasma TNF-α, IL-1β and IL-6 were measured by a multiplexed particle-based flow cytometric assay and hs-CRP by an immunometric assay. The median levels of SUA, IL-6, TNF-α, CRP and IL-1β were 355 µmol/L, 1.46 pg/mL, 3.04 pg/mL, 1.2 mg/L and 0.34 pg/mL in men and 262 µmol/L, 1.21 pg/mL, 2.74 pg/mL, 1.3 mg/L and 0.45 pg/mL in women, respectively. SUA correlated positively with IL-6, TNF-α and CRP and negatively with IL-1β (Spearman r: 0.04, 0.07, 0.20 and 0.05 in men, and 0.09, 0.13, 0.30 and 0.07 in women, respectively, P<0.05). In multivariable analyses, SUA was associated positively with CRP (β coefficient ± SE = 0.35±0.02, P<0.001), TNF-α (0.08±0.02, P<0.001) and IL-6 (0.10±0.03, P<0.001), and negatively with IL-1β (-0.07±0.03, P = 0.027). Upon further adjustment for body mass index, these associations were substantially attenuated. ### Long_Answer: SUA was associated positively with IL-6, CRP and TNF-α and negatively with IL-1β, particularly in women. These results suggest that uric acid contributes to systemic inflammation in humans and are in line with experimental data showing that uric acid triggers sterile inflammation. ### Final_Prediction: yes |
### Question: Association of the DRD4 exon III polymorphism with smoking in fifteen-year-olds: a mediating role for novelty seeking? ### Context: This study was designed to examine the role of DNA variants of the dopamine D4 receptor gene (DRD4) in smoking experimentation in adolescents and to determine the extent to which novelty seeking (NS) could account for a possible effect of DRD4 on tobacco use.Participants were from a longitudinal study of an original birth cohort (born 1986-1988) of 384 children from a high-risk community sample. At age 15 years, adolescents completed a self-report questionnaire measuring tobacco consumption and temperament (Junior Temperament and Character Inventory). DNA was taken from 303 participants (144 males, 159 females) and genotyped for the DRD4 exon III polymorphism.DRD4 was associated with smoking status and NS in males but not in females. Males with the seven repeat allele exhibited more smoking involvement (p<.002) and scored higher in NS (p<.002) than males without this allele. In addition, elevated tobacco use was related to a higher level of NS in both males and females (p<.001). Multiple regression analyses revealed that NS mediated the relationship between DRD4 and smoking in males. ### Long_Answer: These findings highlight the importance of considering the mechanisms underlying the association between genetic factors and tobacco use separately by gender and, possibly, by developmental period. ### Final_Prediction: nan |
### Question: 23-Hour observation solely for identification of missed injuries after trauma: is it justified? ### Context: The use of an observation period to identify missed injuries in trauma patients has gained favor in recent years. This study was undertaken in a population of patients with minimal or no identified injuries to determine the following: whether a period of in-patient observation identifies missed injuries; demographic factors associated with missed injuries; and morbidity of missed injuries.Over 4 years at a Level I trauma center, 4,738 patients were observed for 23 hours. Of these patients, 630 were converted to full admission and were reviewed. All medical records were reviewed for reason for observation, reason for conversion to full admission, and presence of missed injury.In the 4,738 patients observed, 35 had a missed injury identified. No clinical factors studied were associated with identifying a missed injury. Of the 35 patients that had a missed injury, 21 did not have clinically relevant injuries, whereas the 14 remaining patients did. All of the 14 required prolonged hospital admissions and 9 underwent invasive procedures. ### Long_Answer: Of over 4,700 observed trauma patients, less than 0.5% remained hospitalized for significant missed injuries. No factors were identified that predicted missed injuries. Twenty-three-hour observation for the purpose of identifying missed injuries after thorough emergency department evaluation may not be justified. ### Final_Prediction: nan |
### Question: Cyclosporine challenge test revisited: does it predict outcome after solitary pancreas transplantation? ### Context: The selection of patients for solitary pancreas transplantation (PTA) requires identification of individuals who will not develop acute renal dysfunction in response to immunosuppressants. A cyclosporine challenge test (CCT) was developed to predict post-PTA kidney dysfunction secondary to calcineurin inhibitor immunosuppressants. We now report on the long-term follow-up of patients who received a PTA after undergoing a CCT.Twelve potential PTA recipients were administered cyclosporine A (CsA) for 6 wk. Creatinine clearance (CrCl) was measured at 2, 4, and 6 wk. Those who did not fail the CCT received PTA. Baseline and post-transplant CrCl were retrospectively evaluated in the original cohort and in a group of matched patients who received PTA without a CCT.Of the original 12 recipients evaluated with the CCT, 6 received PTA. CrCl was followed for a mean of 45.8 months. Of the 4 who remained alive, 2 went on to develop renal failure (CrCl<30 mL/min) at 18 and 65 months post-transplant. The baseline CrCl was higher in PTA recipients who had not been selected to be studied with CCT than those that were (117 +/- 32 vs 78 +/- 13 mL/min). By 12 months post-PTA, the CrCl was no longer different between the groups selected to be screened with CCT and those that were not. ### Long_Answer: CCT may help predict risk for short-term changes in renal function (<18 months) in response to CsA. CCT may be most helpful in candidates for PTA with borderline renal insufficiency (60-80 mL/min). ### Final_Prediction: nan |
### Question: Is ischemic preconditioning cardioprotective in senescent human myocardium? ### Context: Cellular and functional changes secondary to aging could impair myocardial tolerance to ischemia and affect the heart's response to ischemic preconditioning.We investigated the impact of cardiac aging on preconditioning in right atrial trabeculae of adult patients (< or = 55 years) and senescent patients (> or = 70 years) with coronary artery disease. Specimens were subjected to 30 minutes of simulated ischemia (hypoxic substrate-free superfusion) with and without 5 minutes of ischemic pretreatment. Postischemic contractile recovery was measured and expressed as percentage of base line force values.During the reoxygenation period, trabeculae of adult patients but not those of senescent patients improved after ischemic preconditioning. After 40 minutes of reoxygenation, preconditioned adult trabeculae developed 57% +/- 5% of their preischemic force (nonpreconditioned control 44% +/- 5%, p < 0.01), senescent trabeculae recovered to 44% +/- 4% (control 45% +/- 3%). Especially myocardium from adult patients with Canadian Cardiovascular Society (CCS) stage III angina pectoris treated with ACE inhibitors recovered well (70% +/- 7%; control 50% +/- 8%, p < 0.01), contrasting with trabeculae from patients with CCS stage II angina (44% +/- 5%; control 40% +/- 10%). Ischemia-inducible Hsp70 (human heat shock protein) was additionally measured after reoxygenation. Total Hsp70 mRNA was elevated in preconditioned myocardium along with its contractile recovery (r = 0.33, p = 0.07). Because the control transcription, analyzing 18S rRNA and beta-actin, was reduced by ischemia but recovered in preconditioned trabeculae, relative Hsp70 mRNA was not altered. ### Long_Answer: Our data indicate that ischemic preconditioning has no beneficial effect on the postischemic functional recovery of senescent human myocardium. ### Final_Prediction: no |
### Question: β-2 agonists in sport: are the anti-doping rules meeting the needs of asthmatic athletes? ### Context: (a) To review the methacholine tests performed in our laboratory up until 2008; (b) to compare them with previously reported data in 2006 and (c) to examine if the anti-doping rules are meeting the needs of asthmatic athletes who really need bronchodilator treatment.Between April 2004 and September 2008, 89 high-level athletes were examined in our laboratory in order to obtain an abbreviated therapeutic use exemption for β-2 agonists. Of these, 50 men (23.31 (7.05) years) and 23 women (20.68 (5.94) years) performed a methacholine inhalation test with increasing concentrations of methacholine (0.025, 0.25, 2.5, 5, 10 and 25 mg/ml) until a fall of 20% in forced expiratory volume in 1 s (FEV(1)) was achieved.31 candidates (42.5%) had a provocative concentration causing a 20% fall in FEV(1) (PC(20))<2 mg/ml; 12 (16.4%) were between 2 and 4 mg/ml; 8 (11%) between 4.1 and 8 mg/ml and 22 candidates (30.1%) had a PC(20)>8 mg/ml. Seven of the 73 candidates had an obstructive pattern in the spirometry at rest, demonstrated by a FEV(1)%<70% but with a FEV(1)>70% of the reference value. ### Long_Answer: The anti-doping regulations with respect to β-2 agonists need to be reviewed, and measures should be adopted to include a fall of 70% in FEV(1)% as an obstruction criterion to indicate a bronchodilation test and to extend the criterion for a positive methacholine test to a PC(20) of 8 mg/ml. ### Final_Prediction: nan |
### Question: Can trained field community workers identify stroke using a stroke symptom questionnaire as well as neurologists? ### Context: Stroke is a leading cause of morbidity and mortality worldwide. There is a paucity of data from South Asia where stroke is highly prevalent. Validated tools administrable by community health workers (CHWs) are required to identify stroke in the community in a resource-strapped region such as this.The study was conducted in a transitional slum in Karachi, Pakistan. Questionnaire to Verify Stroke-Free Status (QVSFS) was adapted and translated into Urdu. Two CHWs, trained by a neurologist, selected 322 community-dwelling subjects using purposive sampling. Each CHW collected data independently, which was validated by a vascular neurologist who directly examined each participant. To assess the effect of audit and feedback, data from the final 10% of the subjects were collected after a second training session for the CHWs. Sensitivity, specificity, and Cohen kappa were determined for the CHW-administered questionnaire against neurovascular assessment.Mean age of participants was 56.5 years with 71% of participants being women. The sensitivity and specificity of the questionnaire of detecting stroke was 77.1% (confidence interval [CI], 64.1-86.9) and 85.8% (CI, 83.5-87.5), respectively. The chance-corrected agreement using the Cohen kappa statistic was .51 (CI, .38-.60). Kappa ranged from .37 to .58 for each of the 7 stroke symptoms. Hemianesthesia (72.9%) and hemiplegia (64.6%) were the most sensitive symptoms. The performance and agreement improved from moderate to substantial after audit and feedback. ### Long_Answer: We found a reasonable sensitivity and specificity and moderate agreement between CHW-administered QVSFS and assessment by a vascular neurologist. ### Final_Prediction: nan |
### Question: Cost-effective therapy remission assessment in lymphoma patients using 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography: is an end of treatment exam necessary in all patients? ### Context: The aim of this study was to evaluate the necessity of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) after end of treatment in lymphoma patients who had an interim FDG-PET/CT.In 38 patients with Hodgkin's disease (HD) and 30 patients with non-Hodgkin's lymphoma (NHL) interim PET/CT (intPET) after two to four cycles of chemotherapy and PET/CT after completion of first-line treatment (endPET) were carried out. Cost reduction was retrospectively calculated for the potentially superfluous endPET examinations.In 31 (82%) HD patients, intPET demonstrated complete remission (CR) which was still present on endPET. The remaining seven HD patients (18%) had partial remission (PR) on intPET. For NHL, 22 (73%) patients had CR on intPET analysis which was still present on endPET. In the remaining eight NHL patients, intPET revealed PR in seven and stable disease in one patient. None of all intPET complete responders progressed until the end of therapy. Thus, of the 196 PET/CT's carried out in our study population, 53 endPET's (27.0%) were carried out in interim complete responders. ### Long_Answer: End-treatment PET/CT is unnecessary if intPET shows CR and the clinical course is uncomplicated. An imaging cost reduction of 27% in our study population could have been achieved by omitting end of treatment FDG-PET/CT in interim complete responders. ### Final_Prediction: nan |
### Question: Are brain atrophy and lesion load related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes? ### Context: The objective of this work is to study the relationship between the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in CSF, with both T2 lesion volume (T2LV) accumulation and brain atrophy (percentage change of brain volume-PCBV-and brain parenchyma fraction-BPF) in patients with clinically isolated syndromes (CIS) suggestive of demyelination.Twenty-four CIS patients were included in this prospective study. IgG oligoclonal bands (OCGB) and LS-OCMB were determined in paired serum and CSF samples within 3 months since clinical onset. Brain MRI studies were scheduled at baseline, 3 months, first and second years after CIS onset. Differences in T2LV, PCBV and BPF between CIS patients according to the type of OCB were studied.Nine patients had no OCB; 15 had only OCGB, and seven had OCGB + LS-OCMB present in the CSF. LS-OCMB were associated with greater T2LV in all scheduled MRI studies. At the end of follow-up (year 2), it was threefold higher in patients with these antibodies than in those without LS-OCMB (3.95 cm(3) vs. 1.36 cm(3), p = 0.001). At that point, brain atrophy was also higher in patients with LS-OCMB (BPF, 0.73 in LS-OCMB+ patients vs. 0.76 in negative ones, p = 0.03). The rate in brain atrophy was higher in the first group of patients as well. Considering only patients with OCGB, the presence of LS-OCMB was also related to greater T2LV, T2LV increase and a trend towards higher atrophy rate. ### Long_Answer: The presence of LS-OCMB in the first event suggestive of demyelination is related to an early increase in lesion load and brain atrophy. These data are in line with prospective studies showing the clinical prognostic value of LS-OCMB. ### Final_Prediction: yes |
### Question: Do activities Patients and Nurses Undertake to Promote Patient Participation? ### Context: To describe and understand activities patients and nurses undertake to enact patient participation in nursing care.This observational study was conducted on two medical units at a public hospital in Australia. Twenty-eight nurse-patient dyads were observed for at least 4 hr. Data were collected from November 2013 to February 2014.Field notes were collected and were analyzed both inductively and deductively.Nurse-patient interactions promoted patient participation through dialogue and knowledge sharing. Less evident was patient involvement in planning or self-care. Nurses exerted control over patient care, which influenced the extent of patient participation. ### Long_Answer: Patient participation appears to be difficult to enact. Nurses' controlling approach, influenced by organizational issues, was in conflict with a patient-centered approach to care. Nurse-patient communication is one aspect of patient-centered care enacted more frequently. ### Final_Prediction: yes |
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