The expression of Mirc1/Mir17–92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients

Introduction

Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17–92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17–92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment.

Hepatic Artery Resection for Bismuth Type III and IV Hilar Cholangiocarcinoma: Is Reconstruction Always Required?

Objective

The objective of the study is to examine the feasibility of hepatic artery resection (HAR) without subsequent reconstruction (RCS) in specified patients of Bismuth type III and IV hilar cholangiocarcinoma.

Methods

We retrospectively reviewed 63 patients who underwent hepatic artery resection for Bismuth type III and IV hilar cholangiocarcinoma. These patients were subsequently enrolled into two groups based on whether the artery reconstruction was conducted. Postoperative morbidity and mortality, and long-term survival outcome were compared between the two groups.

Results

There were 29 patients in HAR group and 34 patients in the HAR + RCS group. Patients with hepatic artery reconstruction tended to have longer operative time (545.6?±?143.1 min vs. 656.3?±?192.8 min; P?=?0.013) and smaller tumor size (3.0?±?1.1 cm vs. 2.5?±?0.9 cm; P?=?0.036). The R0 resection margin was comparable between the HAR group and HAR?+?RCS group (86.2 vs. 85.3%; P?>?0.05). Twelve patients (41.4%) with 24 complications in HAR group and 13 patients (38.2%) with 25 complications in HAR?+?RCS group were recorded (P?=?0.799). The postoperative hepatic failure rate (13.8 vs. 5.9%) and postoperative mortality rate (3.4% vs. 2.9%) were also comparable between the two groups. In the HAR group, the overall 1-, 3-, and 5-year survival rates were 72, 41, and 19%, respectively; while in the HAR?+?RCS group, the overall 1-, 3-, and 5-year survival rates were 79, 45, and 25%, respectively (P?=?0.928).

Conclusions

Hepatic artery resection without reconstruction is also a safe and feasible surgical procedure for highly selected cases of Bismuth type III and IV hilar cholangiocarcinoma.

     

RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study

Background  

Pneumonia is among the main causes of illness and death in children <5 years of age. There is a need to better describe the epidemiology of viral community-acquired pneumonia (CAP) in developing countries.     

Soluble Angiotensin-Converting Enzyme 2 in Human Heart Failure: Relation With Myocardial Function and Clinical Outcomes

BackgroundAngiotensin-converting enzyme 2 (ACE2) is an endogenous counterregulator of the renin-angiotensin system. The relationship between soluble ACE2 (sACE2), myocardial function, and clinical outcomes in patients with chronic systolic heart failure is not well established.Methods and ResultsWe measured sACE2 activity in 113 patients with chronic systolic heart failure (left ventricular ejection fraction [LVEF] ≤35%, New York Heart Association Class II-IV). Comprehensive echocardiography was performed at the time of blood sampling. We prospectively examined adverse clinical events (death, cardiac transplant, and heart failure hospitalizations) over 34 ± 17 months. Patients who had higher sACE2 plasma activity were more likely to have a lower LVEF (Spearman's r = –0.36, P < .001), greater right ventricular systolic dysfunction (r = 0.33, P < .001), higher estimated pulmonary artery systolic pressure (r = 0.35, P = .002), larger left ventricular end-diastolic diameter (r = 0.23, P = .02), and higher plasma NT-proBNP levels (r = 0.35, P < .001). sACE2 was less associated with diastolic dysfunction (r = 0.19, P = .05), and was similar between patients with ischemic and nonischemic cardiomyopathies. There was no relationship between sACE2 activity and markers of systemic inflammation. After adjusting for NT-proBNP and LVEF, sACE2 activity remained an independent predictor of adverse clinical events (HR = 1.7 [95% CI: 1.1–2.6], P = .018).ConclusionsElevated plasma sACE2 activity was associated with greater severity of myocardial dysfunction and was an independent predictor of adverse clinical events.     

Adapting behavioural interventions to compensate for cognitive dysfunction in persons with opioid use disorder

Treatment for opioid use disorder (OUD) is often in the context of biobehavioural interventions, consisting of medication for OUD (for example, methadone and buprenorphine), which is accompanied by psychoeducation and/or behavioural therapies. Patients with OUD often display weaknesses in cognitive function that may impact the efficacy of such behavioural interventions.A review of the literature was conducted to: (1) describe common cognitive dysfunction profiles among patients with OUD, (2) outline intervention approaches for patients with OUD, (3) consider the cognitive demands that interventions place on patients with OUD and (4) identify potential accommodation strategies that may be used to optimise treatment outcomes.Cognitive profiles of patients with OUD often include weaknesses in executive function, attention, memory and information processing. Behavioural interventions require the patients’ ability to learn, understand and remember information (placing specific cognitive demands on patients). Accommodation strategies are, therefore, needed for patients with challenges in one or more of these areas. Research on accommodation strategies for patients with OUD is very limited. We applied research from populations with similar cognitive profiles to form a comprehensive collection of potential strategies to compensate for cognitive dysfunction among patients with OUD. The cognitive profiles and accommodation strategies included in this review are intended to inform future intervention research aimed at improving outcomes among patients with OUD.     

Selective killing of cancer cells by leaf extract of Ashwagandha: identification of a tumor-inhibitory factor and the first molecular insights to its effect.

PURPOSE: Ashwagandha is regarded as a wonder shrub of India and is commonly used in Ayurvedic medicine and health tonics that claim its variety of health-promoting effects. Surprisingly, these claims are not well supported by adequate studies, and the molecular mechanisms of its action remain largely unexplored to date. We undertook a study to identify and characterize the antitumor activity of the leaf extract of ashwagandha. EXPERIMENTAL DESIGN: Selective tumor-inhibitory activity of the leaf extract (i-Extract) was identified by in vivo tumor formation assays in nude mice and by in vitro growth assays of normal and human transformed cells. To investigate the cellular targets of i-Extract, we adopted a gene silencing approach using a selected small hairpin RNA library and found that p53 is required for the killing activity of i-Extract. RESULTS: By molecular analysis of p53 function in normal and a variety of tumor cells, we found that it is selectively activated in tumor cells, causing either their growth arrest or apoptosis. By fractionation, purification, and structural analysis of the i-Extract constituents, we have identified its p53-activating tumor-inhibiting factor as with a none. CONCLUSION: We provide the first molecular evidence that the leaf extract of ashwagandha selectively kills tumor cells and, thus, is a natural source for safe anticancer medicine.     

Prevalence of HBV infection among the healthy Nepalese males: a serological survey

Sera from 478 healthy Nepalese male population, inhabiting various districts of five development regions of Nepal were collected from October 1996 to March 1997 and examined for the presence of HBsAg by third generation ELISA and Latex agglutination test in the laboratory of Central Department of Microbiology, Tribhuvan University, Kirtipur. The surface antigen was detected by ELISA in 4.0% (19/478) of subjects studied. However, different results were obtained in Latex agglutination test. The correlation between the results obtained from these two different tests is statistically significant (chi2=85.11, P<0.05). The results obtained from ELISA showed the probability of Nepal to fall in WHO category of intermediate endemicity zone for hepatitis B infection. The percent positivity of HBsAg was found to increase steadily from Eastern (2%) to Far Western (6.2%) development regions. Among the districts studied, Kailali district gave characteristically high prevalence followed by Rukum and Kaski. Other, districts representing for the prevalence are Sankhuwasabha, Jhapa, Ramechhap, Sarlahi, Dhanusa, Baglung, Gulmi, Palpa and Dang. None of the samples represented from Kathmandu valley were positive for HBsAg. The age groups of 16-20 years and 36-40 years were found to be associated with the hepatitis B infection. Furthermore, various percent prevalence of the infection were encountered from 16 to 40 years subjects and a single case was also observed from 63 years old man. All the samples recorded positive for HBsAg from ELISA were assayed for the amount of ALT as a liver function test. Where, 15.8% (3/19) of the infected subjects had impaired liver function, hence it showed that, the subjects with high ALT to be the possible carrier of the HBV. Conversely, the remaining 84.2% (16/19) of the total HBsAg positive subjects were concluded to have the infection either at incubation or at prodrome period.     

The vulpius procedure for correction of equinus deformity in patients with hemiplegia

Spasm or contracture of gastrocnemius causes an equinus deformity of the ankle in both cerebral palsy and hemiplegia. Its release is therefore required in the treatment of those patients who do not respond to conservative measures. The Vulpius procedure is a simple and effective method for the release of gastrocnemius and is particularly indicated when long periods of immobilisation of the foot and ankle are not desirable. We have used this procedure with good results to correct an equinus deformity in 230 adults with a cerebrovascular accident and various associated medical conditions. It is not only effective in cerebral palsy, but should be considered at an early stage in all adult patients with deformity of the ankle and foot in whom spasm of gastrocnemius is the major cause.