Comparing magnetic resonance liver fat fraction measurements with histology in fibrosis: the difference between proton density fat fraction and tissue mass fat fraction.

Objective: Magnetic resonance spectroscopy (MRS) provides a powerful method of measuring fat fraction. However, previous studies have shown that MRS results give lower values compared with visual estimates from biopsies in fibrotic livers. This study investigated these discrepancies and considered whether a tissue water content correction, as assessed by MRI relaxometry, could provide better agreement.

Management of conflict injuries to the upper limb. Part 1: assessment and early surgical care.

Upper limb injuries are common in conflict zones. The functions of the upper limb are impossible to replicate with prosthetic replacement and wherever possible attempts should be made to preserve the limb with further secondary reconstruction aimed at restoration of function. Casualty assessment, haemorrhage control and resuscitation are simultaneously undertaken at the receiving medical facility.

The Effectiveness of Single-Anastomosis Duodenoileal Bypass with Sleeve Gastrectomy/One Anastomosis Duodenal Switch (SADI-S/OADS): an Updated Systematic Review.

Single-anastomosis duodenoileal bypass with sleeve gastrectomy/one anastomosis duodenal switch (SADI-S/OADS) was developed as a bariatric operation with reduced overall morbidity and lasting weight loss results. We performed a systematic review of the literature, including 14 studies reporting on weight loss, comorbidity resolution, postoperative complications, and nutritional deficiencies following SADI-S. Twelve months after SADI-S, the mean total body weight lost ranged from 21.

PAF-R on activated T cells: Role in the IL-23/Th17 pathway and relevance to multiple sclerosis.

IL-23 is a potent stimulus for Th17 cells. These cells have a distinct developmental pathway from Th1 cells induced by IL-12 and are implicated in autoimmune and inflammatory disorders including multiple sclerosis (MS). TGF-β, IL-6, and IL-1, the transcriptional regulator RORγt (RORC) and IL-23 are implicated in Th17 development and maintenance.

A Behavioural Assessment of Social Anxiety and Social Motivation in Fragile X, Cornelia de Lange and Rubinstein-Taybi Syndromes.

Unique socio-behavioural phenotypes are reported for individuals with different neurodevelopmental disorders. Here, the effects of adult familiarity and nature of interaction on social anxiety and social motivation were investigated in individuals with fragile X (FXS; n = 20), Cornelia de Lange (CdLS; n = 20) and Rubinstein-Taybi (RTS; n = 20) syndromes, compared to individuals with Down syndrome (DS; n = 20). The Social Anxiety and Motivation Rating Scale was employed whilst participants completed four social tasks, each administered separately by a familiar adult, and also by an unfamiliar adult.

Lifespan trajectory of affect in Cornelia de Lange syndrome: towards a neurobiological hypothesis.

Background: Depressive symptomology and low affect are comparatively common in individuals with genetic disorders such as Cornelia de Lange syndrome. However, lifespan trajectories and associated person characteristics have not been examined. In this study, the trajectories for affect and associated behavioural characteristics were investigated in individuals with Cornelia de Lange syndrome with individuals with fragile X syndrome (FXS) comparable for chronological age and total number of behavioural indicators of ASD included for the purpose of contrast.

Developing a toolkit for the assessment and monitoring of musculoskeletal ageing.

The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The Medical Research Council-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of CIMA's objectives is to 'Identify and share optimal techniques and approaches to monitor age-related changes in all musculoskeletal tissues, and to provide an integrated assessment of musculoskeletal function'-in other words to develop a toolkit for assessing musculoskeletal ageing.

A coding and non-coding transcriptomic perspective on the genomics of human metabolic disease.

Genome-wide association studies (GWAS), relying on hundreds of thousands of individuals, have revealed >200 genomic loci linked to metabolic disease (MD). Loss of insulin sensitivity (IS) is a key component of MD and we hypothesized that discovery of a robust IS transcriptome would help reveal the underlying genomic structure of MD. Using 1,012 human skeletal muscle samples, detailed physiology and a tissue-optimized approach for the quantification of coding (>18,000) and non-coding (>15,000) RNA (ncRNA), we identified 332 fasting IS-related genes (CORE-IS).

Effects of 14 days of bed rest and following physical training on metabolic cost, mechanical work, and efficiency during walking in older and young healthy males.

In this study, we investigated: i) the effects of bed rest and a subsequent physical training program on metabolic cost (Cw), mechanical work and efficiency during walking in older and young men; ii) the mechanisms underlying the higher Cw observed in older than young men.Twenty-three healthy male subjects (N = 16 older adults, age 59.6±3.

Loss of maximal explosive power of lower limbs after 2 weeks of disuse and incomplete recovery after retraining in older adults.

Key Points: Disuse in older adults can critically decrease lower limb muscle power, leading to compromised mobility and overall quality of life. We studied how muscle power and its determinants (muscle mass, single muscle fibre properties and motor control) adapted to 2 weeks of disuse and subsequent 2 weeks of physical training in young and older people. Disuse decreased lower limb muscle power in both groups; however, different adaptations in single muscle fibre properties and co-contraction of leg muscles were observed between young and older individuals.

An experimental study of executive function and social impairment in Cornelia de Lange syndrome.

Background: Extreme shyness and social anxiety is reported to be characteristic of adolescents and adults with Cornelia de Lange syndrome (CdLS); however, the nature of these characteristics is not well documented. In this study, we develop and apply an experimental assessment of social anxiety in a group of adolescents and adults with CdLS to determine the nature of the social difficulties and whether they are related to impairments in executive functioning.

Methods: A familiar and unfamiliar examiner separately engaged in socially demanding tasks comprising three experimental conditions with a group of individuals with CdLS (n = 25; % male = 44; mean age = 22.

Coupling between skeletal muscle fiber size and capillarization is maintained during healthy aging.

Background: As muscle capillarization is related to the oxidative capacity of the muscle and the size of muscle fibres, capillary rarefaction may contribute to sarcopenia and functional impairment in older adults. Therefore, it is important to assess how ageing affects muscle capillarization and the interrelationship between fibre capillary supply with the oxidative capacity and size of the fibres.

Methods: Muscle biopsies from healthy recreationally active young (22 years; 14 men and 5 women) and older (74 years; 22 men and 6 women) people were assessed for muscle capillarization and the distribution of capillaries with the method of capillary domains.

Reasons for non-recruitment of eligible patients to a randomised controlled trial of secondary prevention after intracerebral haemorrhage: observational study.

Background: Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH.

Method: By the end of May 2015, 158 participants had been recruited at 108 active sites in RESTART.

Anabolic resistance assessed by oral stable isotope ingestion following bed rest in young and older adult volunteers: Relationships with changes in muscle mass.

Background & Aims: Aging and experimental bed rest are associated with muscle atrophy and resistance to post-prandial stimulation of protein synthesis or anabolic resistance (AR). We have used in young and older adult volunteers, during short-term bed rest, a quick and non-invasive method, based on a single oral bolus of the stable isotope L[ring-H]phenylalanine (DPhe), to determine post-prandial AR, defined as ratio between irreversible hydroxylation and incorporation into body protein of ingested phenylalanine.

Methods: We compared in older (O, 59 ± 1 y) and young (Y, 23 ± 1 y) healthy male volunteers the effects of two-week bed rest on post-prandial protein kinetics, assessed during absorption of a standard ready-to-use oral nutritional supplement, through stable-labeled isotope amino acid DPhe, diluted in water, given as single oral load.

Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss.

Background: A hypothesis exists whereby an exercise- or dietary-induced negative energy balance reduces human subcutaneous white adipose tissue (scWAT) mass through the formation of brown-like adipocyte (brite) cells. However, the validity of biomarkers of brite formation has not been robustly evaluated in humans, and clinical data that link brite formation and weight loss are sparse.

Objectives: We used rosiglitazone and primary adipocytes to stringently evaluate a set of biomarkers for brite formation and determined whether the expression of biomarker genes in scWAT could explain the change in body composition in response to exercise training combined with calorie restriction in obese and overweight women (n = 79).

iGEMS: an integrated model for identification of alternative exon usage events.

DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations.

New horizons in the implementation and research of comprehensive geriatric assessment: knowing, doing and the 'know-do' gap.

In this paper, we outline the relationship between the need to put existing applied health research knowledge into practice (the 'know-do gap') and the need to improve the evidence base (the 'know gap') with respect to the healthcare process used for older people with frailty known as comprehensive geriatric assessment (CGA). We explore the reasons for the know-do gap and the principles of how these barriers to implementation might be overcome. We explore how these principles should affect the conduct of applied health research to close the know gap.

Greater loss in muscle mass and function but smaller metabolic alterations in older compared with younger men following 2 wk of bed rest and recovery.

This investigation aimed to compare the response of young and older adult men to bed rest (BR) and subsequent rehabilitation (R). Sixteen older (OM, age 55-65 yr) and seven young (YM, age 18-30 yr) men were exposed to a 14-day period of BR followed by 14 days of R. Quadriceps muscle volume (QVOL), force (QF), and explosive power (QP) of leg extensors; single-fiber isometric force (Fo); peak aerobic power (V̇o2peak); gait stride length; and three metabolic parameters, Matsuda index of insulin sensitivity, postprandial lipid curve, and homocysteine plasma level, were measured before and after BR and after R.

Muscle structural assembly and functional consequences.

The relationship between muscle structure and function has been a matter of investigation since the Renaissance period. Extensive use of anatomical dissections and the introduction of the scientific method enabled early scholars to lay the foundations of muscle physiology and biomechanics. Progression of knowledge in these disciplines led to the current understanding that muscle architecture, together with muscle fibre contractile properties, has a major influence on muscle mechanical properties.

The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial.

Background: Alcoholic hepatitis (AH) is a distinct presentation of alcoholic liver disease arising in patients who have been drinking to excess for prolonged periods, which is characterised by jaundice and liver failure. Severe disease is associated with high short-term mortality. Prednisolone and pentoxifylline (PTX) are recommended in guidelines for treatment of severe AH, but trials supporting their use have given heterogeneous results and controversy persists about their benefit.

A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.

Background: Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health.

Results: One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.

Straight to flexible sigmoidoscopy: rationalization of 2-week wait referrals in suspected colorectal cancer.

Aim: The 2-week wait pathway was designed to decrease the time from presentation to primary care of patients with 'red flag' symptoms of suspected cancer for review by a specialist for the diagnosis or exclusion of cancer. In our tertiary referral centre we have found that 968 colonoscopies per year are required to satisfy the demand for the 2-week wait, leading to limited colonoscopy availability for other services. We sought to determine the yield of colorectal cancer found at colonoscopy referred via the 2-week wait and referenced to the original red flag symptoms.

A study of T₁ relaxation time as a measure of liver fibrosis and the influence of confounding histological factors.

Liver biopsy is the standard test for the assessment of fibrosis in liver tissue of patients with chronic liver disease. Recent studies have used a non-invasive measure of T1 relaxation time to estimate the degree of fibrosis in a single slice of the liver. Here, we extend this work to measure T1 of the whole liver and investigate the effects of additional histological factors such as steatosis, inflammation and iron accumulation on the relationship between liver T1 and fibrosis.

Prednisolone or pentoxifylline for alcoholic hepatitis.

Background: Alcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists.