Unravelling the utility of modern sulfonylureas from cardiovascular outcome trials and landmark trials: expert opinion from an international panel.

Aim: The primary objective of this review is to develop practice-based expert group opinions on the cardiovascular (CV) safety and utility of modern sulfonylureas (SUs) in cardiovascular outcome trials (CVOTs).

Background: The United States Food and Drug Administration issued new guidance to the pharmaceutical industry in 2008 regarding the development of new antihyperglycemic drugs. The guidance expanded the scope for the approval of novel antihyperglycemic drugs by mandating CVOTs for safety.

Engineering Trienoic Fatty Acids into Cottonseed Oil Improves Low-Temperature Seed Germination, Plant Photosynthesis and Cotton Fiber Quality.

Alpha-linolenic acid (ALA, 18:3Δ9,12,15) and γ-linolenic acid \ (GLA, 18:3Δ6,9,12) are important trienoic fatty acids, which are beneficial for human health in their own right, or as precursors for the biosynthesis of long-chain polyunsaturated fatty acids. ALA and GLA in seed oil are synthesized from linoleic acid (LA, 18:2Δ9,12) by the microsomal ω-3 fatty acid desaturase (FAD3) and Δ6 desaturase (D6D), respectively. Cotton (Gossypium hirsutum L.

Family caregiver's experience of caring for an older adult with delirium: A systematic review.

Aim: To enhance understanding of how family caregivers perceive the experience of caring for an older adult with delirium across care settings and to identify the challenges in recognising and managing delirium to inform future research and best practices.

Method: A systematic literature review was conducted in five databases per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Primary or secondary peer-reviewed articles published between 1987 and October 2018 describing the experiences of family caregivers caring for older adults with delirium or delirium superimposed on dementia were included in the review.

Clinical impact of lung ultrasound monitoring for diagnosis of ventilator associated pneumonia: A diagnostic randomized controlled trial.

Purpose: Studies have shown that lung-ultrasound may be superior to chest x-ray (CXR) in diagnosing ventilator-associated pneumonia (VAP). This study investigated whether the use of lung-ultrasound monitoring could detect VAP earlier and improve patient outcome.

Methods: This was a single-center diagnostic randomized controlled trial.

Immune checkpoint CD47 molecule engineered islets mitigate instant blood-mediated inflammatory reaction and show improved engraftment following intraportal transplantation.

Instant blood-mediated inflammatory reaction (IBMIR) causes significant destruction of islets transplanted intraportally. Myeloid cells are a major culprit of IBMIR. Given the critical role of CD47 as a negative checkpoint for myeloid cells, we hypothesized that the presence of CD47 on islets will minimize graft loss by mitigating IBMIR.

Inherited Macular Dystrophies in a Tertiary Care Centre.

Background: Inherited macular dystrophies constitute a group of diseases characterized by bilateral central visual loss with symmetrical macular abnormalities usually presenting in the first two decades of life. The aim of this study were to find out the demographic characteristics and disease pattern of inherited retinal dystrophies in subjects attending retina outpatient department in a tertiary care center.

Methods: An observational study among twenty-six participants diagnosed as macular dystrophy visiting a tertiary care centre in Nepal, during January 2018 to June 2018 were included in the study.

Comparison of Lung Ultrasound to X-ray for Diagnosis of Pulmonary Complications after Cardiac Surgery in Children.

Background: The purpose of this study was to compare diagnostic performance of lung ultrasound in comparison to chest X-ray to detect pulmonary complication after cardiac surgery in children.

Methods: A prospective observational study was conducted in tertiary center of Nepal. 141 consecutive paediatric patients aged less than 14 years scheduled for cardiac surgery were enrolled during the 6 months period.

Influence of Arterial Blood Gas to Guide Extubation in Intensive Care Unit Patients after Spontaneous Breathing Trial.

Background: Arterial blood gas is required for extubation decision after spontaneous breathing trial in most of intensive care unit. This study was conducted to assess the influence of arterial blood gas for extubation after successful spontaneous breathing trial in intensive care unit patients planned for extubation.

Methods: It was prospective observation study conducted in all patients of age greater than eighteen year admitted in intensive care unit of tertiary care hospital for one year.

Effectiveness of Group Problem Management Plus (Group-PM+) for adults affected by humanitarian crises in Nepal: study protocol for a cluster randomized controlled trial.

Background: Globally, the lack of availability of psychological services for people exposed to adversities has led to the development of a range of scalable psychological interventions with features that enable better scale-up. Problem Management Plus (PM+) is a brief intervention of five sessions that can be delivered by non-specialists. It is designed for people in communities in low- and middle-income countries (LMIC) affected by any kind of adversity.

Isolation, Characterization, and Screening of Antimicrobial-Producing Actinomycetes from Soil Samples.

Actinomycetes are Gram-positive, facultative anaerobic fungus-like filamentous bacteria which remain on the top of the natural antibiotic producers. Due to the climatic and geographical diversity of Nepal, a wide range of microorganisms with potent source of antimicrobials are available. The objective of this study was to isolate, identify, and screen the potential antimicrobial-producing actinomycetes from soils covering different altitude range of Nepal.

Localized Immunomodulation with PD-L1 Results in Sustained Survival and Function of Allogeneic Islets without Chronic Immunosuppression.

Allogeneic islet transplantation is limited by adverse effects of chronic immunosuppression used to control rejection. The programmed cell death 1 pathway as an important immune checkpoint has the potential to obviate the need for chronic immunosuppression. We generated an oligomeric form of programmed cell death 1 ligand chimeric with core streptavidin (SA-PDL1) that inhibited the T effector cell response to alloantigens and converted T conventional cells into CD4Foxp3 T regulatory cells.

Quantifying nutrient recovery efficiency and loss from compost-based urban agriculture.

The use of compost in urban agriculture offers an opportunity to increase nutrient recycling in urban ecosystems, but recent studies have shown that compost application often results in phosphorus (P) being applied far in excess of crop nutrient demand, creating the potential for P loss through leachate and runoff. Management goals such as maximizing crop yields or maximizing the mass of nutrients recycled from compost may inadvertently result in P loss, creating a potential ecosystem disservice. Here, we report the results from the first two years of an experimental study in which four different crops grown in raised-bed garden plots with high background P and organic matter received one of two types of compost (municipal compost made from urban organics waste, or manure-based compost) at two different levels (applied based on crop N or P demand), while additional treatments received synthetic N and P fertilizer or no soil amendments.

Direct Photorelease of Alcohols from Boron-Alkylated BODIPY Photocages.

BODIPY photocages allow the release of substrates using visible light irradiation. They have the drawback of requiring reasonably good leaving groups for photorelease. Photorelease of alcohols is often accomplished by attachment with carbonate linkages, which upon photorelease liberate CO and generate the alcohol.

A Synergistic Genetic Engineering Strategy Induced Triacylglycerol Accumulation in Potato () Leaf.

Potato is the 4th largest staple food in the world currently. As a high biomass crop, potato harbors excellent potential to produce energy-rich compounds such as triacylglycerol as a valuable co-product. We have previously reported that transgenic potato tubers overexpressing , , and genes produced considerable levels of triacylglycerol.

Multiple social platforms reveal actionable signals for software vulnerability awareness: A study of GitHub, Twitter and Reddit.

The awareness about software vulnerabilities is crucial to ensure effective cybersecurity practices, the development of high-quality software, and, ultimately, national security. This awareness can be better understood by studying the spread, structure and evolution of software vulnerability discussions across online communities. This work is the first to evaluate and contrast how discussions about software vulnerabilities spread on three social platforms-Twitter, GitHub, and Reddit.

Depression among TB patients and associated factors in Kathmandu Valley, Nepal.

Introduction: When tuberculosis (TB) and depression co-occur, there is greater risk for comorbidities, disability, suffering, and health-related costs. Depression is also associated with poor treatment adherence in patients with TB. The major aim of this study was to assess the symptoms of depression and associated factors among TB patients currently receiving directly observed treatment short-course (DOTS) treatment.

Social innovation in diagnostics: three case studies.

Background: Diagnostics are essential for identifying and controlling diseases. However, limited access to diagnostics hinders public health efforts in many settings. Social innovation may provide a framework for expanding access to diagnostics in the global south.

Accommodation-Free Head Mounted Display with Comfortable 3D Perception and an Enlarged Eye-box.

An accommodation-free displays, also known as Maxwellian displays, keep the displayed image sharp regardless of the viewer's focal distance. However, they typically suffer from a small eye-box and limited effective field of view (FOV) which requires careful alignment before a viewer can see the image. This paper presents a high-quality accommodation-free head mounted display (aHMD) based on pixel beam scanning for direct image forming on retina.

Lung Cancer in a Tertiary Hospital in Nepal: Clinical-Radiological Profile and Histological Subtypes.

Background: Lung cancer is the most common cancer worldwide and in Nepal. Non small cell carcinoma is the commoner histological type. The incidence of adenocarcinoma subtype is increasing globally.

Intimate partner violence in Nepal: Latent patterns and association with depressive symptoms.

Existing data suggest that there are distinct patterns (or classes) of intimate partner violence (IPV) experience that depart from dichotomous categorizations used to monitor progress toward Sustainable Development Goal 5.2. Less is known about the patterning of IPV in non-Western settings.

Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta-Analysis.

Objective: To investigate the effect of therapies on radiographic progression in patients with axial spondyloarthritis (SpA).

Methods: A comprehensive database search for studies assessing radiographic progression in axial SpA (particular treatment versus no treatment of interest) was performed. Study-specific standardized mean differences in treatment outcomes at 2 and ≥4 years were estimated and combined using random-effects models.

Cell-type-specific drug-inducible protein synthesis inhibition demonstrates that memory consolidation requires rapid neuronal translation.

New protein synthesis is known to be required for the consolidation of memories, yet existing methods of blocking translation lack spatiotemporal precision and cell-type specificity, preventing investigation of cell-specific contributions of protein synthesis. Here we developed a combined knock-in mouse and chemogenetic approach for cell-type-specific drug-inducible protein synthesis inhibition that enables rapid and reversible phosphorylation of eukaryotic initiation factor 2α, leading to inhibition of general translation by 50% in vivo. We use cell-type-specific drug-inducible protein synthesis inhibition to show that targeted protein synthesis inhibition pan-neuronally and in excitatory neurons in the lateral amygdala (LA) impaired long-term memory.

Utility of Precision Medicine in the Management of Diabetes: Expert Opinion from an International Panel.

Aim: The primary objective of this review is to develop a practice-based expert group opinion on the role of precision medicine with a specific focus on sulfonylureas (SUs) in diabetes management.

Background: The clinical etiology, presentation and complications of diabetes vary from one patient to another, making the management of the disease challenging. The pre-eminent feature of diabetes mellitus (DM) are chronically elevated blood glucose concentrations; however, in clinical practice, the exclusion of autoimmunity, pregnancy, pancreatic disease or injury and rare genetic forms of diabetes is crucial.