Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial.

Background: Daily methadone maintenance or buprenorphine treatment is the standard-of-care (SoC) medication for opioid use disorder (OUD). Subcutaneously injected, extended-release buprenorphine (BUP-XR) may be more effective-but there has been no superiority evaluation.

Methods: This pragmatic, parallel-group, open-label, multi-centre, effectiveness superiority randomised, controlled, phase 3 trial was conducted at five National Health Service community-based treatment clinics in England and Scotland.

Extended-release pharmacotherapy for opioid use disorder (EXPO): protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone.

Background: Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI).

An exploration of the impact of SARS-CoV-2 (COVID-19) restrictions on marginalised groups in the UK.

Background: To contain the spread of COVID-19 within the UK over the past year, there have been a series of local and national lockdowns. These restrictions are likely to have impacted upon the health and well-being of marginalised groups who rely on now closed social and community support services to stay healthy. An understanding of the experiences of marginalised people is important; therefore, this study aimed to explore the impact of the COVID-19 restrictions on the health and well-being of marginalised groups in the UK.

Differences in monocyte: lymphocyte ratio and Tuberculosis disease progression in genetically distinct populations of macaques.

Monocyte:lymphocyte ratio (M:L) has been identified as a risk factor in development of TB disease in children and those undergoing treatment for HIV in co-infected individuals. Retrospective analysis was performed using M:L data collected from TB modelling studies performed in Rhesus macaques of Indian genotype (RM), cynomolgus macaque of Chinese genotype (CCM) and cynomolgus macaque of Mauritian genotype (MCM), which found that the more susceptible populations (RM and MCM) had higher M:L ratios than the least susceptible population (CCM). Following Mycobacterium tuberculosis exposure, significant increases in M:L ratio were observed in susceptible RM and MCM within 12 weeks of TB infection, whereas M:L in CCM remained stable, suggesting that changes in M:L ratio may also act as a biomarker of TB disease progression.

Effect of one session of mirror therapy on phantom limb pain and recognition of limb laterality in military traumatic lower limb amputees: a pilot study.

Up to 70 % of military amputees suffer phantom limb pain (PLP), which is difficult to treat. PLP has been attributed to cortical reorganisation and associated with impaired laterality. Repeated sessions of mirror therapy (MT) can benefit PLP; however, anecdotal evidence suggests one MT session could be effective.

Correction: Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification.

[This corrects the article DOI: 10.1371/journal.pone.

Lessons learned from early rehabilitation of complex trauma at the Royal Centre for Defence Medicine.

During the recent conflicts in Iraq and Afghanistan, substantial numbers of service personnel survived devastating injuries, presenting significant challenges for early rehabilitation at Queen Elizabeth Hospital Birmingham. Royal Centre for Defence Medicine personnel augmented NHS therapy provision, gaining significant experience in rehabilitating complex trauma. Multidisciplinary working was key to delivering this service, with a unique rehabilitation coordinating officer position established to manage the rehabilitation pathway.

Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification.

A temporal study of gene expression in peripheral blood leukocytes (PBLs) from a Mycobacterium tuberculosis primary, pulmonary challenge model Macaca fascicularis has been conducted. PBL samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified RNAs hybridised to Operon Human Genome AROS V4.0 slides.

Evaluation of the Immunogenicity of Mycobacterium bovis BCG Delivered by Aerosol to the Lungs of Macaques.

Nine million cases of tuberculosis (TB) were reported in 2013, with a further 1.5 million deaths attributed to the disease. When delivered as an intradermal (i.

HSPB8 and the Cochaperone BAG3 Are Highly Expressed During the Synthetic Phase of Rat Myometrium Programming During Pregnancy.

The small heat shock protein (HSP) B family of proteins are a group of molecular chaperones that enable tissues to adapt to changes in their local environments during differentiation, stress, or disease conditions. The objective of this research was to characterize the expression of HSPB8 and its cochaperone Bcl2-associated athanogene 3 (BAG3) in nonpregnant (NP) and pregnant rat myometrium during myometrial programming. Rat myometrium was collected from NP and pregnant rats as well as 1 day postpartum (PP) and samples prepared for immunoblot and immunofluorescence analysis.

Beyond BMI: The Next Chapter in Childhood Obesity Management.

Pediatric obesity treatment has traditionally focused on body mass index (BMI) and has had limited success. Recent research has suggested new ways to approach this topic that focuses more on holistic measures of health and inclusion of a larger population of children. This paper discusses new evidence in the prevention of chronic disease and treatment of obesity that has a body positive and mental health lens as well as integrating research from several areas of health, including the prevention of chronic disease.

It's like rocket science…only more complex: challenges and experiences related to managing pediatric obesity in Canada.

Pediatric obesity is an urgent and complex public health issue. Approximately one-third of Canadian children are overweight or obese, a proportion that highlights the need for effective and accessible services to improve short- and long-term health risks. In our experience, we have encountered a number of challenges common in pediatric obesity management across our clinical and research centers.

Evidence for a role for interleukin-17, Th17 cells and iron homeostasis in protective immunity against tuberculosis in cynomolgus macaques.

Tuberculosis (TB) remains a major global public health problem. The only vaccine, BCG, gives variable protection, especially in adults, so several new vaccines are in clinical trials. There are no correlates of protective immunity to TB; therefore vaccines progress through lengthy and expensive pre-clinical assessments and human trials.

Are we underestimating diabetes-related lower-extremity amputation rates? Results and benefits of the first prospective study.

Objective: The objective of this study was to accurately determine the incidence of lower-extremity amputation using prospective data collection and to compare the results with those obtained by retrospective methods.

Research Design And Methods: The study was carried out over a 3-year period in a large district general hospital covering a clearly defined and relatively static population. All diabetic inpatients with foot problems were identified and followed-up until discharge or death.

Increased quantal release of acetylcholine at the neuromuscular junction following scald injury in the rat.

Following severe burns, patients frequently develop a profound resistance to nondepolarizing neuromuscular blockers. Several mechanisms have been proposed to account for this, including upregulation of nicotinic acetylcholine receptors. We investigated the effects of a 30% body surface area (BSA) scald on neuromuscular transmission in slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) of rats.

Effect of clenbuterol on sarcoplasmic reticulum function in single skinned mammalian skeletal muscle fibers.

We examined the effect of the beta2-agonist clenbuterol (50 microM) on depolarization-induced force responses and sarcoplasmic reticulum (SR) function in muscle fibers of the rat (Rattus norvegicus; killed by halothane overdose) that had been mechanically skinned, rendering the beta2-agonist pathway inoperable. Clenbuterol decreased the peak of depolarization-induced force responses in the extensor digitorum longus (EDL) and soleus fibers to 77.2 +/- 9.

Electrophysiology of the neuromuscular junction of the laminin-2 (merosin) deficient C57 BL/6J dy2J/dy2J dystrophic mouse.

The C57 BL/6J dy2J/dy2J dystrophic mouse expresses an abnormal truncated form of the alpha2 subunit of the protein laminin-2 (or merosin), which is unable to form a stable link between the extracellular matrix and the dystrophin-associated proteins, resulting in muscular dystrophy. Morphological abnormalities of the peripheral nervous system and neuromuscular junction have also been reported. The electrophysiological properties of the neuromuscular junctions of diaphragm, extensor digitorum longus (EDL), and soleus from C57 BL/6J dy2J/dy2J mice and controls are described.

Effects of clenbuterol and ICI118551, a selective beta 2-antagonist, on the growth of skeletal muscle of suckling rats.

The beta 2-adrenergic agonist, clenbuterol, was administered to lactating rats (4 mg/kg diet) from post-partum day 1 to day 19, or directly injected into neonate rats (0.1 and 1.0 mg/kg body weight) from post-partum day 3 until day 15.

Effect of the beta 2-adrenergic agonist clenbuterol on the growth of fast- and slow-twitch skeletal muscle of the dystrophic (C57BL6J dy2J/dy2J) mouse.

Clenbuterol (4mg/kg in diet for 21 days) had no statistically significant effect on whole body growth. It did cause a significant increase (18.2%) in wet weight of the fast twitch muscle extensor digitorum longus (EDL) and a corresponding 14.

Rundown and reactivation of ATP-sensitive potassium channels (KATP) in mouse skeletal muscle.

Dissociated single fibers from the mouse flexor digitorum brevis (FDB) muscle were used in patch clamp experiments to investigate the mechanisms of activation and inactivation of KATP in mammalian skeletal muscle. Spontaneous rundown of channel activity, in many excised patches, occurred gradually over a period of 10-20 min. Application of 1.

Mechanism of action of a K+ channel activator BRL 38227 on ATP-sensitive K+ channels in mouse skeletal muscle fibres.

1. Investigations were made into the effects of BRL 38227, a potassium channel activator, on ATP-sensitive potassium channels (K+ATP channels) in single fibres dissociated from the flexor digitorum brevis muscle of C57BL/6J mice. 2.

Low quantal content of the endplate potential reduces safety factor for neuromuscular transmission in the diaphragm of the newborn rat.

We have used phrenic nerve-hemidiaphragm preparations from rats aged 11-28 days to determine the electrophysiological basis of the three-fold increase in sensitivity of the neonatal neuromuscular junction to non-depolarizing neuromuscular blocking drugs. The mean resting membrane potential (RMP) of intact muscle fibres at 19-21 degrees C increased from -67.1 (SEM 0.

Septal grafts improve acquisition of an operant timing task after fimbria-fornix lesions in rats: Role of the interval between lesion and transplantation surgeries.

In a previous study we evaluated the conditions under which septal grafts could ameliorate performance of rats with fimbria-fornix lesions in an operant differential reinforcement of low rates of responding (DRL) task. Although the best recovery was demonstrated by the group in which the grafts were made 10 days following the lesion surgery, this factor (lesion-graft interval) was confounded with the developmental stage of the donor tissue, and it was suggested that the age of the embryonic donor was a more significant factor than the lesion graft interval in achieving good recovery. The present study provides a better control of embryonic age of the donor tissues, and we report that cholinergic rich septal grafts implanted into the host hippocampus either immediately or 11 days following fimbria-fornix lesion yielded better recovery than when the grafts were implanted after longer (8 weeks) lesion-graft intervals.

Unilateral dopamine lesions in neonatal, weanling and adult rats: comparison of rotation and reaching deficits.

The aim of this study was to compare the functional effects of neonatal, weanling and adult lesions of the dopaminergic (DA) mesencephalic neurones on paw-reaching behaviour. The mesotelencephalic DA pathway was destroyed unilaterally in neonatal (3 and 7 day), weanling (21 day) and adult (2 months) rats by local injection of 6-hydroxydopamine into the medial forebrain bundle at the level of the lateral hypothalamus, followed by behavioural studies conducted 2 months later. Amphetamine and apomorphine induced similar rates of rotation irrespective of the age of the lesion.

Effect of clenbuterol on skeletal muscle atrophy in mice induced by the glucocorticoid dexamethasone.

1. The ability of clenbuterol to antagonize the catabolic effect of the glucocorticoid dexamethasone on the skeletal muscles, soleus, gastrocnemius and extensor digitorum longus was studied in mice. 2.