Resistance to RevM10 inhibition reflects a conformational switch in the HIV-1 Rev response element

Nuclear export of certain HIV-1 mRNAs requires an interaction between the viral Rev protein and the Rev response element (RRE), a structured element located in the Env region of its RNA genome. This interaction is an attractive target for both drug design and gene therapy, exemplified by RevM10, a transdominant negative protein that, when introduced into host cells, disrupts viral mRNA export. However, two silent G->A mutations in the RRE (RRE61) confer RevM10 resistance, which prompted us to examine RRE structure using a novel chemical probing strategy. Variations in region III/IV/V of mutant RNAs suggest a stepwise rearrangement to RevM10 resistance. Mass spectrometry was used to directly assess Rev “loading” onto RRE and its variants, indicating that this is unaffected by RNA structural changes. Similarity in chemical footprints with mutant protein implicates additional host factors in RevM10 resistance.     

High prevalence of airway obstruction and pulmonary emphysema in urothelial (renal pelvis,ureter, and bladder) cancer patients

BackgroundCigarette smoking is a major cause of COPD, with patients also presenting complications that stem from other smoking-related diseases, including urothelial cancer. However, the prevalence of COPD or airflow obstruction in urothelial cancer patients has not been well studied.MethodsWe investigated the prevalence of airflow obstruction (FEV1/FVC < 70%) in newly diagnosed urothelial cancer patients and identified the risk factors for airflow obstruction in existing urothelial cancer patients. Additionally, we compared the characteristics of subjects who had been diagnosed with both airflow obstruction and urothelial cancer, and subjects whose airflow obstruction was discovered during health screenings.ResultsA total of 217 patients were newly diagnosed with urothelial cancer during the study period at our institution. Among all patients, 210 (96.8%) underwent an evaluable lung function test, in which 38.6% (81 patients) displayed airflow obstruction defined as FEV1/FVC < 70%. In urothelial cancer patients, age, smoking index (pack-years), and BMI proved to be significant risk factors for airflow obstruction in multivariate logistic regression (p = 0.007, p < 0.0001, and p = 0.035, respectively). Gender, cancer stage, and cancer location were not significant risk factors. Patients with both airflow obstruction and urothelial cancer showed a more advanced emphysematous change than subjects presenting with airflow obstruction alone (unpaired t-test, p = 0.0003).ConclusionsAirflow obstruction was identified in 38.6% of urothelial cancer patients. Age, smoking index (pack-years), and BMI were significant risk factors. A significantly higher emphysematous score was observed in subjects with urothelial cancer than in subjects with airway obstruction alone.     

22-Gauge biopsy needles have a better histological diagnostic yield in the discrimination of specific pancreatic solid neoplasms

Background: To overcome the limitations of using cytological specimen alone for the diagnosis of challenging pancreatic lesions, biopsy needles have been developed to procure histological specimens during EUS, especially for the discrimination of several specific pancreatic tumors requiring adequate histological samples. The aim of this study was to compare the diagnostic yield of EUS-guided 22-gauge (G) fine needle aspiration (FNA) needles and 22G fine needle biopsy (FNB) needles for sampling pancreatic masses.

Methods: We conducted a retrospective study of all EUS-guided sampling performed between November 2012 and April 2016. 422 cases sampled with a 22G FNA needle (N?=?254) or a 22G FNB needle (N?=?168) were recruited for this study. The specimen quality analyses, technical characteristics, accuracy, sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) for the pancreatic masses were reviewed and compared.

Results: There was no significant difference in the procurement of adequate histological specimens (75.0% vs. 79.5%; p?=?.277) or the presence of diagnostic histological specimens (71.3% vs. 77.4%; p?=?.155) between FNA and FNB groups, respectively. There were also no significant differences in the accuracy, sensitivity, specificity, PPVs, or NPVs of the cytological, histological, and overall analyses for FNA and FNB groups in the diagnosis of pancreatic malignancy. However, 22G biopsy needles demonstrated a better histological diagnostic yield in the discrimination of pancreatic adenocarcinoma and non-adenocarcinoma pancreatic neoplasms than 22G FNA needles (69.8% vs. 57.9%, p?=?.033).

Conclusions: 22G FNB needle demonstrated a better histological diagnostic yield in the differentiation between pancreatic adenocarcinoma and non-adenocarcinoma pancreatic neoplasms.     

Gender-specific associations of body mass index and waist circumference with type 2 diabetes mellitus in Chinese rural adults: The Henan Rural Cohort Study

Aim

To assess the relationship between various obesity categories according to body mass index (BMI) and waist circumference (WC) and risk of type 2 diabetes mellitus (T2DM) among Chinese rural adults.

The effect of six rounds of single dose mass treatment with diethylcarbamazine or ivermectin on Wuchereria bancrofti infection and its implications for lymphatic filariasis elimination

Annual mass treatment with single-dose diethylcarbamazine (DEC) or ivermectin (IVM) in combination with albendazole (ALB) for 4-6 years is the principal tool of lymphatic filariasis (LF) elimination strategy. This placebo-controlled study examined the potential of six rounds of mass treatment with DEC or IVM to eliminate Wuchereria bancrofti infection in humans in rural areas in south India. A percentage of 54-75 of the eligible population (> or =15 kg body weight) received treatment during different rounds of treatment - 27.4% in the DEC arm and 30.7% in the IVM arm received all six treatments, 4.8% and 5.6% received none, and the remainder received one to five treatments. After six cycles of treatment, the microfilaria (Mf) prevalence in treated communities dropped by 86% in the DEC arm (P < 0.01) (n = 5 villages) and by 72% in the IVM arm (P < 0.01) (n = 5 villages), compared with 37% in the placebo arm (P < 0.05) (n = 5 villages). The geometric mean intensity of Mf fell by 91% (t = 8.11, P < 0.05), 84% (t = 6.91, P < 0.05) and 46% (t = 2.98, P < 0.05) in the DEC, IVM and placebo arms, respectively. The proportion of high-count Mf (>50 Mf per 60 mm(3) of blood) carriers was reduced by 94% (P < 0.01) in the DEC arm and by 90% (P < 0.01) in the IVM arm. Among those who received all six treatments, 1.4% in the DEC arm and 2.4% in the IVM arm remained positive for Mf. Two of five villages in the DEC arm and one of five in the IVM arm showed zero Mf prevalence, but continued to have low levels of transmission of infection. The results also indicate that DEC is as effective as or slightly better than IVM against microfilaraemia. Results from this and other recent operational studies proved that single-dose treatment with antifilarials is very effective at community level, feasible, logistically easier and cheap and hence a highly appropriate strategy to control or eliminate LF. Higher treatment coverage than that observed in this study and a few more than six cycles of treatment and more effective treatment tools/strategies may be necessary to reduce microfilaraemia to zero level in all communities, which may lead to elimination of LF.     

RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet

Background

Role of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients.

Family history of diabetes is associated with enhanced adipose lipolysis: Evidence for the implication of epigenetic factors

Aims

Type 2 diabetes is associated with insulin resistance, adipose hypertrophy and increased lipolysis. The heritability of these traits has been determined by associating them with a family history of diabetes.

Metabolic syndrome and associated factors among psychiatric patients in Jimma University Specialized Hospital,South West Ethiopia

Background

Metabolic syndrome is a multisystem disorder which coined to describe the recognized clustering of metabolic and cardiovascular abnormalities including obesity, hypertension, dyslipidemia, and abnormalities of glucose homeostasis.

Left atrial abnormality by electrocardiogram predicts left ventricular hypertrophy by echocardiography in the presence of right bundle-branch block

Background: Left ventricular hypertrophy (LVH) on the electrocardiogram (ECG) may be masked in the presence of complete right bundle-branch block (RBBB). Left bundle-branch block on the ECG is associated with LVH at autopsy in 93% of hearts studied. However, RBBB does not predict LVH and the usual ECG criteria applied for LVH may not be reliable in the presence of RBBB. Hypothesis: The study was undertaken to evaluate left atrial (LA) abnormality as a criterion for the diagnosis of LVH in the presence of RBBB. Methods: Left atrial abnormality in the ECG was assessed by two independent observers as a criterion of LVH in the presence of RBBB in 100 patients, and data were compared with those of 50 patients without LA abnormality. Results: Left ventricular hypertrophy was confirmed by echocardiographic determination of left ventricular (LV) mass in both groups. Observers reliably differentiated between hy-pertrophied and normal-sized LV in the presence of RBBB by using LA abnormality as an ECG criterion when correlated with LV mass determined by echocardiography. Observer 1 correctly detected LVH in 88% and Observer 2 in 82% of patients. False positive diagnosis was made in 12 and 18% of patients by Observers 1 and 2, respectively. Observers' performance of recognition of LA abnormality in the present study was 94%. Results showed sensitivity of 76 and 70% and specificity of 84 and 92% for Observers 1 and 2, respectively. Left ventricular mass increased significantly and was diagnostic of LVH in 92% of patients with LA abnormality. Left ventricular mass was high in 84% of patients when corrected by body surface area. LVH in the presence of RBBB by the ECG was found in only seven patients (5%) when six commonly used conventional criteria of diagnosis of LVH by ECG were employed. Regression analysis found LA abnormality to be a strong independent predictor of increased LV mass. Multiple regression analysis revealed that age, body mass index, body surface area, and frontal axis are also significant predictors of LV mass. Conclusion: The results obtained by the correlation of LA abnormality by ECG and LVH by echocardiography conclude that LA abnormality by ECG was significantly diagnostic of LV hypertrophy in the presence of RBBB.     

农村人群空腹血糖水平与腰臀比及体质指数关系的研究

目的 了解农村人群空腹血糖(fasting blood glucose,FBG)水平的分布及其与体质指数(body mass index,BMI)、腰臀比(waist-hip ratio,WHR)的关系.方法 于2011年对安庆周边(东至县)农村地区人群进行横断面调查,收集相关资料,用多元Logistic回归分析WHR、BMI与糖尿病(diabetes mellitus,DM)之间的关系.结果 共2 890例研究对象纳入分析,平均FBG为(5.81±1.53) mmol/L,DM粗患病率为9.9％,年龄标化患病率为3.2％;随着BMI的增加,FBG水平和DM患病率也呈增加趋势;BMI、WHR达肥胖标准(全身性肥胖或腹型肥胖)人群的FBG水平及DM患病率均比各自正常人群高.将BMI和WHR同时纳入模型,并在调整了年龄、性别、胆固醇、三酰甘油、舒张压、收缩压后,多元Logistic回归分析结果显示,WHR与DM患病相关联(OR=5.76,95％ CI:2.67～12.43),而BMI与DM患病的关联性无统计学意义.结论 腹型肥胖与DM患病有关,提示腹型肥胖者易发生DM.