The coupling between healthspan and lifespan in depends on complex interactions between compound intervention and genetic background.

Aging is characterized by declining health that results in decreased cellular resilience and neuromuscular function. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of pharmacological anti-aging interventions. Here we assessed swimming performance as well as survival under thermal and oxidative stress across a nematode genetic diversity test panel to evaluate health effects for three compounds previously studied in the Intervention Testing Program and thought to promote longevity in different ways - NP1 (nitrophenyl piperazine-containing compound 1), propyl gallate, and resveratrol.

The role of quality of life data as an endpoint for collecting real-world evidence within geroscience clinical trials.

With geroscience research evolving at a fast pace, the need arises for human randomized controlled trials to assess the efficacy of geroprotective interventions to prevent age-related adverse outcomes, disease, and mortality in normative aging cohorts. However, to confirm efficacy requires a long-term and costly approach as time to the event of morbidity and mortality can be decades. While this could be circumvented using sensitive biomarkers of aging, current molecular, physiological, and digital endpoints require further validation.

Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes.

The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications.

Metformin treatment of diverse Caenorhabditis species reveals the importance of genetic background in longevity and healthspan extension outcomes.

Metformin, the most commonly prescribed anti-diabetes medication, has multiple reported health benefits, including lowering the risks of cardiovascular disease and cancer, improving cognitive function with age, extending survival in diabetic patients, and, in several animal models, promoting youthful physiology and lifespan. Due to its longevity and health effects, metformin is now the focus of the first proposed clinical trial of an anti-aging drug-the Targeting Aging with Metformin (TAME) program. Genetic variation will likely influence outcomes when studying metformin health effects in human populations.

Spaceflight affects neuronal morphology and alters transcellular degradation of neuronal debris in adult .

Extended space travel is a goal of government space agencies and private companies. However, spaceflight poses risks to human health, and the effects on the nervous system have to be better characterized. Here, we exploited the unique experimental advantages of the nematode to explore how spaceflight affects adult neurons .

Automated lifespan determination across Caenorhabditis strains and species reveals assay-specific effects of chemical interventions.

The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully manual survival assays.

Swim exercise in extends neuromuscular and gut healthspan, enhances learning ability, and protects against neurodegeneration.

Regular physical exercise is the most efficient and accessible intervention known to promote healthy aging in humans. The molecular and cellular mechanisms that mediate system-wide exercise benefits, however, remain poorly understood, especially as applies to tissues that do not participate directly in training activity. The establishment of exercise protocols for short-lived genetic models will be critical for deciphering fundamental mechanisms of transtissue exercise benefits to healthy aging.

Single swim sessions in C. elegans induce key features of mammalian exercise.

Background: Exercise exerts remarkably powerful effects on metabolism and health, with anti-disease and anti-aging outcomes. Pharmacological manipulation of exercise benefit circuits might improve the health of the sedentary and the aging populations. Still, how exercised muscle signals to induce system-wide health improvement remains poorly understood.

Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects.

Limiting the debilitating consequences of ageing is a major medical challenge of our time. Robust pharmacological interventions that promote healthy ageing across diverse genetic backgrounds may engage conserved longevity pathways. Here we report results from the Caenorhabditis Intervention Testing Program in assessing longevity variation across 22 Caenorhabditis strains spanning 3 species, using multiple replicates collected across three independent laboratories.

C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress.

The toxicity of misfolded proteins and mitochondrial dysfunction are pivotal factors that promote age-associated functional neuronal decline and neurodegenerative disease. Accordingly, neurons invest considerable cellular resources in chaperones, protein degradation, autophagy and mitophagy to maintain proteostasis and mitochondrial quality. Complicating the challenges of neuroprotection, misfolded human disease proteins and mitochondria can move into neighbouring cells via unknown mechanisms, which may promote pathological spread.

Analysis of microRNA-target interactions across diverse cancer types.

Little is known about the extent to which individual microRNAs (miRNAs) regulate common processes of tumor biology across diverse cancer types. Using molecular profiles of >3,000 tumors from 11 human cancer types in The Cancer Genome Atlas, we systematically analyzed expression of miRNAs and mRNAs across cancer types to infer recurrent cancer-associated miRNA-target relationships. As we expected, the inferred relationships were consistent with sequence-based predictions and published data from miRNA perturbation experiments.

Appendiceal inflammation affects the length of stay following appendicectomy amongst children: a myth or reality?

The effect of the severity of appendiceal inflammation on post-operative stay in children following appendicectomy has shown conflicting results. This study was conducted to determine the association between the severity of appendiceal inflammation and post-operative stay amongst children undergoing open appendicectomy. A retrospective cohort study was conducted at a District General Hospital for two years.

miR-34a repression in proneural malignant gliomas upregulates expression of its target PDGFRA and promotes tumorigenesis.

Glioblastoma (GBM) and other malignant gliomas are aggressive primary neoplasms of the brain that exhibit notable refractivity to standard treatment regimens. Recent large-scale molecular profiling has revealed distinct disease subclasses within malignant gliomas whose defining genomic features highlight dysregulated molecular networks as potential targets for therapeutic development. The "proneural" designation represents the largest and most heterogeneous of these subclasses, and includes both a large fraction of GBMs along with most of their lower-grade astrocytic and oligodendroglial counterparts.

Diagnostic accuracy of white cell count and C-reactive protein for assessing the severity of paediatric appendicitis.

Objectives: Simple investigations like white cell count (WCC) and C-reactive protein (CRP) may help to improve the accuracy of diagnosis in paediatric appendicitis. We evaluated the diagnostic accuracy of WCC and CRP for the severity of acute appendicitis in children.

Design: Cross-sectional study.

General surgical adverse events in a UK district general hospital-lessons to learn.

Background: An adverse event (AE) is defined as an unintended injury or complication caused by healthcare management rather than the disease process that may prolong admission and lead to disability or death. This study retrospectively assessed all reported general surgery-related AEs in a district general hospital in the south-east of England.

Methods: All general surgical AEs arising from adult inpatient admissions between 2002 and 2007, that had been reported to the risk management team, following completion of the standard 'Adverse Incident Report Form', were retrospectively reviewed.

Nonsteroidal anti-inflammatory drugs-associated colopathy.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used worldwide, and their complications in the upper gastrointestinal tract are well described in the literature and well known to clinicians. However, complications in the large bowel are being increasingly recognized and reported. This review aims to address the different aspects of NSAIDs-associated colopathy.

Epstein-Barr virus (EBV) positive anal B cell lymphoma: a case report and review of literature.

This case report is on a very rare case of giant anal canal ulcer with rectal prolapse causing total faecal incontinence. An elderly patient in her eighties presented to the emergency department with complaints of a mass protruding thorough anus along with fresh rectal bleeding. Examination revealed a large ulcer measuring 6 cm x 8 cm involving the entire anal canal with rectal prolapse.

Laparoscopic colorectal surgery in Great Britain and Ireland--where are we now?

Objective: We aimed to gather information from the members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) to assess trends in the current practice of laparoscopic colorectal surgery.

Methods: A postal questionnaire survey of the members of ACPGBI.

Results: The response rate was 37% (200/540).

A survey of the timing and approach to the surgical management of cholelithiasis in patients with acute biliary pancreatitis and acute cholecystitis in the UK.

Background: Recent management guidelines and randomised clinical trials have provided evidence-based guidance to the management of acute biliary pancreatitis and acute cholecystitis.

Methods: A questionnaire was sent to the 1086 members of the Association of Surgeons of Great Britain and Ireland. There were 583 responders (54%).

The effectiveness of new criteria for colorectal fast track clinics.

INTRODUCTION: Fast Track Colorectal Clinics are becoming a requirement to meet the government's 10-day rule for patients with suspected cancers to be seen by a specialist. However, such clinics soon tend to get overwhelmed by huge numbers of referrals, many of them inappropriate. The Association of Coloproctology of Great Britain and Ireland has published criteria for appropriate referral.

Laparoscopic reduction of an acute gastric volvulus and repair of a hernia of Bochdalek.

We report a case of an acute strangulated gastric volvulus in a hernia of Bochdalek in an adult female patient that was repaired successfully via the laparoscopic approach. A left-sided diaphragmatic hernia contained a strangulated but viable gastric volvulus and a noncompromised colon. The contents of the hernia were reduced, and the 4-cm congenital diaphragmatic defect was primarily repaired with nonabsorbable sutures.