A Randomized Trial of Brief Online Interventions to Facilitate Treatment Seeking for Social Anxiety

Objective: This study developed and evaluated a brief, single-session online intervention designed to facilitate treatment seeking among adults with clinically significant social anxiety (SA) symptoms, who generally seek treatment at exceptionally low rates. Method: Adults (N= 267) reporting significant SA symptoms were recruited online and randomized to a brief, single-session online intervention: Education consisted of brief psychoeducation and treatment resources, or Education+Motivation which added treatment seeking-focused motivational content adapted from Motivational Interviewing and Acceptance and Commitment Therapy. Attitudes, intentions, perceived control, and treatment seeking were assessed at Pre, Post, and one-month follow-up (FU). Results: Both interventions were feasible (90% completion) and improved all outcomes. At FU, 70% reported engaging in 1or more SA treatment-seeking behaviors. Education+Motivation was more effective than Education at improving treatment-seeking attitudes and behaviors. Conclusions: A brief online intervention with educational and motivational content is a promising direction for promoting treatment seeking for adults with SA symptoms

Characterization of Desulfovibrio fructosovorans sp. nov.

Desulfovibrio strain JJ isolated from estuarine sediment differed from all other described Desulfovibrio species by the ability to degrade fructose. The oxidation was incomplete, leading to acetate production. Fructose, malate and fumarate were fermented mainly to succinate and acetate in the absence of an external electron acceptor. The pH and temperature optima for growth were 7.0 and 35° C respectively. Strain JJ was motile by means of a single polar flagellum. The DNA base composition was 64.13% G+C. Cytochrome c3 and desulfoviridin were present. These characteristics established the isolate as a new species of the genus Desulfovibrio, and the name Desulfovibrio fructosovorans is proposed

Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor

Induction of lipolysis in murine white adipocytes, and stimulation of adenylate cyclase in adipocyte plasma membranes, by a tumour-produced lipid mobilizing factor, was attenuated by low concentrations (10−7–10−5 M) of the specific β3-adrenoceptor antagonist SR59230A. Lipid mobilizing factor (250 nM) produced comparable increases in intracellular cyclic AMP in CHOK1 cells transfected with the human β3-adrenoceptor to that obtained with isoprenaline (1 nM). In both cases cyclic AMP production was attenuated by SR59230A confirming that the effect is mediated through a β3-adrenoceptor. A non-linear regression analysis of binding of lipid mobilizing factor to the β3-adrenoceptor showed a high affinity binding site with a Kd value 78±45 nM and a Bmax value (282±1 fmole mg protein−1) comparable with that of other β3-adrenoceptor agonists. These results suggest that lipid mobilizing factor induces lipolysis through binding to a β3-adrenoceptor

Mindfulness-based interventions for people diagnosed with a current episode of an anxiety or depressive disorder: a meta-analysis of randomised controlled trials

Objective Mindfulness-based interventions (MBIs) can reduce risk of depressive relapse for people with a history of recurrent depression who are currently well. However, the cognitive, affective and motivational features of depression and anxiety might render MBIs ineffective for people experiencing current symptoms. This paper presents a meta-analysis of randomised controlled trials (RCTs) of MBIs where participants met diagnostic criteria for a current episode of an anxiety or depressive disorder. Method Post-intervention between-group Hedges g effect sizes were calculated using a random effects model. Moderator analyses of primary diagnosis, intervention type and control condition were conducted and publication bias was assessed. Results Twelve studies met inclusion criteria (n = 578). There were significant post-intervention between-group benefits of MBIs relative to control conditions on primary symptom severity (Hedges g = −0.59, 95% CI = −0.12 to −1.06). Effects were demonstrated for depressive symptom severity (Hedges g = −0.73, 95% CI = −0.09 to −1.36), but not for anxiety symptom severity (Hedges g = −0.55, 95% CI = 0.09 to −1.18), for RCTs with an inactive control (Hedges g = −1.03, 95% CI = −0.40 to −1.66), but not where there was an active control (Hedges g = 0.03, 95% CI = 0.54 to −0.48) and effects were found for MBCT (Hedges g = −0.39, 95% CI = −0.15 to −0.63) but not for MBSR (Hedges g = −0.75, 95% CI = 0.31 to −1.81). Conclusions This is the first meta-analysis of RCTs of MBIs where all studies included only participants who were diagnosed with a current episode of a depressive or anxiety disorder. Effects of MBIs on primary symptom severity were found for people with a current depressive disorder and it is recommended that MBIs might be considered as an intervention for this population

Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice

Insulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (β-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1−/− mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1−/− mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes

Leanness and Low Plasma Leptin in GPR17 Knockout Mice Are Dependent on Strain and Associated With Increased Energy Intake That Is Not Suppressed by Exogenous Leptin

Previous studies have shown that agonists of GPR17 stimulate, while antagonists inhibit feeding. However, whole body knockout of GPR17 in mice of the C57Bl/6 strain did not affect energy balance, whereas selective knockout in oligodendrocytes or pro-opiomelanocortin neurons provided protection from high fat diet-induced obesity and impaired glucose homeostasis. We reasoned that whole body knockout of GPR17 in mice of the 129 strain might elicit more marked effects because the 129 strain is more susceptible than the C57Bl/6 strain to increased sympathetic activity and less susceptible to high fat diet-induced obesity. Consistent with this hypothesis, compared to wild-type mice, and when fed on either a chow or a high fat diet, GPR17 -/- mice of the 129 strain displayed increased expression of uncoupling protein-1 in white adipose tissue, lower body weight and fat content, reduced plasma leptin, non-esterified fatty acids and triglycerides, and resistance to high fat diet-induced glucose intolerance. Not only energy expenditure, but also energy intake was raised. Administration of leptin did not suppress the increased food intake in GPR17 -/- mice of the 129 strain, whereas it did suppress food intake in GPR17 +/+ mice. The only difference between GPR17 +/- and GPR17 +/+ mice of the C57Bl/6 strain was that the body weight of the GPR17 -/- mice was lower than that of the GPR17 +/+ mice when the mice were fed on a standard chow diet. We propose that the absence of GPR17 raises sympathetic activity in mice of the 129 strain in response to a low plasma fuel supply, and that the consequent loss of body fat is partly mitigated by increased energy intake

Routine gastric residual volume measurement to guide enteral feeding in mechanically ventilated infants and children : the GASTRIC feasibility study

Background The routine measurement of gastric residual volume to guide the initiation and delivery of enteral feeding, is widespread in paediatric intensive care and neonatal units, but has little underlying evidence to support it. Objective(s) To answer the question: Is it feasible to conduct a trial of not measuring gastric residual volume on clinical outcomes in mechanically ventilated infants and children in the UK? Design A mixed methods study involving five linked work packages in two parallel arms, neonatal units and paediatric intensive care units. 1. A survey of units to establish current UK practice. 2. qualitative interviews with healthcare professionals and caregivers of children admitted to either setting. 3. A modified two-round e-Delphi survey to investigate health care professionals’ opinions on trial design issues and to obtain consensus on outcomes. 4. National databases were examined to determine the potential eligible populations. 5. Two consensus meetings, of health care professionals and parents to review the data and agreed consensus on outcomes that had not reached consensus in the e-Delphi. Participants and setting Parents of children with experience of ventilation and tube feeding in both neonatal units and in paediatric intensive care units, and health care professionals working in neonatal units and paediatric intensive care units. Results Baseline surveys showed the practice of gastric residual volume measurement was very common: 96% PICUs and 65% in neonatal units. Ninety percent of parents both from neonatal units and paediatric intensive care units supported a future trial, whilst highlighting concerns around possible delays in detecting complications. Health care professionals also indicated a trial was feasible, with 84% of staff willing to participate in a trial. Concerns expressed by junior nurses about the intervention arm of not measuring gastric residual volumes were addressed by developing a simple flowchart and education package. The trial design survey and e-Delphi study gained consensus on trial 12 PICU and 9 neonatal unit outcome measures and identified acceptable inclusion and exclusion criteria. Given the differences in physiology, disease processes, environments, staffing and outcomes of interest, two different trials are required in the two settings. Database analyses subsequently showed trials were feasible in both settings in terms of patient numbers. Of 16222 children who met the inclusion criteria in PICU 12 629 stayed > 3 days. In neonatal units, 15 375 neonates <32 weeks age. Finally, the two consensus meetings demonstrated ‘buy in’ from the wider UK neonatal communities and paediatric intensive care units and enabled us to discuss and vote on the outcomes that did not achieve consensus in the e-Delphi study. Conclusions and future work Two separate UK trials (one in neonatal units and one in paediatric intensive care units) are feasible to conduct, but they cannot be combined due to differences in outcome measures and treatment protocols, reflecting the distinctness of the two specialties

Requirements for systemic sclerosis expert centres in the Netherlands: a Delphi consensus study

Introduction: Systemic sclerosis is a rare and complex disease. Optimal management of patients requires knowledge and experience and, importantly, intensive collaboration between hospitals and multidisciplinary teams. Definition and recognition of expert centres in systemic sclerosis is currently lacking, which complicates collaboration between centres and leaves patients poorly informed. The aim of this study was to develop a set of requirements for two types of systemic sclerosis centres in order to establish a nationwide structure for an optimal and transparent organization of care. Methods: A three-round Delphi study was conducted among a panel of rheumatologists working at university or regional hospitals across the Netherlands. Prior to the final consensus round, a session with a patient panel (N = 22) was held. The results of this meeting were described in the last round for rheumatologists. Criteria were divided into five categories: (1) medical care, (2) case load, (3) collaboration, (4) research, (5) training of staff, and (6) other. In the first round, criteria derived from literature were proposed and participants could add criteria that were missing. For every item, participants could indicate if they thought the item should be included for two types of systemic sclerosis centres: (1) systemic sclerosis expert centre or (2) systemic sclerosis treatment centres. Consensus was reached when more than 85% of the panel agreed. Results: In total, 47 rheumatologists participated in Delphi round 1, 35 in round 2 and 43 in round 3. Additional suggestions were added by the patient panel (n = 22). Consensus was reached for the requirements of systemic sclerosis expert centres (45 items) and systemic sclerosis treatment centres (29 items) including minimal caseloads of annual suspected systemic sclerosis cases and total patients in care. Conclusion: Requirements of centres for systemic sclerosis care in the Netherlands were established in this study. Feasibility of certification should be evaluated next. Our proposed list can serve as a model for other countries.Pathophysiology and treatment of rheumatic disease