Collagen scaffolds as a tool for understanding the biological effect of silicates

Dietary silicon is essential in the maintenance of bone and cartilage. However, the mechanism by which silicon, in the form of silicates, triggers a biological response has never been uncovered. Here we demonstrate the incorporation of orthosilicic acid (Si(OH)4), the form of silicon in the body, within collagen scaffolds for use as an in vitro platform to identify key genes affected by silicates. Ice-templated collagen–silicate scaffolds, containing 0.21 wt% silicon, were validated by examining the mRNA levels for an array of genes in human osteoblasts and mesenchymal stromal cells (MSC) after 48 h in culture. Several novel genes, such as tumor necrosis factor alpha (TNF), were identified as having potential links to orthosilicic acid, verifying that collagen–silicate scaffolds are a versatile platform for identifying novel mechanisms in which silicates regulate musculoskeletal tissue.The authors gratefully acknowledge the financial support of the Gates Cambridge Trust , ERC Advanced Grant 320598 3D-E and from the National Institute for Health Research. RJ is supported by the Medical Research Council (Grant number MC_US_A090_0008/Unit Programme number U1059).This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0167577X15300203#

Computer-Based and Online Therapy for Depression and Anxiety in Children and Adolescents

Objective: The purpose of this study was to provide an overview of computer-based and online therapies (e-therapy) to treat children and adolescents with depression and/or anxiety, and to outline programs that are evidence based or currently being researched. Methods: We began by defining the topic and highlighting the issues at the forefront of the field. We identified computer and Internet-based interventions designed to prevent or treat depression or anxiety that were tested with children and young people <18 years of age (or inclusive of this age range together with emerging adults). We included randomized controlled trials (RCTs). We summarized available relevant systematic reviews. Results: There is an increasing body of evidence that supports the use of computers and the Internet in the provision of interventions for depression and anxiety in children and adolescents. A number of programs have been shown to be effective in well-designed RCTs. Replication and long-term follow-up studies are needed to confirm results. Conclusions: There are now a range of effective computerized interventions for young people with depression and anxiety. This is likely to impact positively on attempts to make psychological therapies widely available to children and young people. We expect to see increased program sophistication and a proliferation of programs in the coming years. Research efforts, when developing programs, need to align with technological advances to maximize appeal. Implementation research is needed to determine the optimal modes of delivery and effectiveness of e-therapies in clinical practice. Given the large number of unproven program on the Internet, ensuring that there is clear information for patients about evidence for individual programs is likely to present a challenge

Whey Protein Augments Leucinemia and Post-Exercise p70S6K1 Activity Compared to a Hydrolysed Collagen Blend When in Recovery From Training With Low Carbohydrate Availability

We examined the effects of whey versus collagen protein on skeletal muscle cell signalling responses associated with mitochondrial biogenesis and protein synthesis in recovery from an acute training session completed with low carbohydrate (CHO) availability. In a repeated measures design (after adhering to a 36-h exercise-dietary intervention to standardise pre-exercise muscle glycogen), eight males completed a 75-min non-exhaustive cycling protocol and consumed 22 g of a hydrolysed collagen blend (COLLAGEN) or whey (WHEY) protein 45 min prior to exercise, 22 g during exercise and 22 g immediately post-exercise. Exercise decreased (P0.05) was observed for p53, Parkin and Beclin1 mRNA. Exercise suppressed (P<0.05) p70S6K1 activity in both conditions immediately post-exercise (≈ 25 fmol.min-1.mg-1). Post-exercise feeding increased p70S6K1 activity at 1.5 h post-exercise (P<0.05), the magnitude of which was greater (P <0.05) in WHEY (180 ± 105 fmol.min-1.mg-1) versus COLLAGEN (73 ± 42 fmol.min-1.mg-1). We conclude that protein composition does not modulate markers of mitochondrial biogenesis when in recovery from a training session deliberately completed with low CHO availability. In contrast, whey protein augments post-exercise p70S6K activity compared with hydrolysed collagen, as likely mediated via increased leucine availability

Post coital aortic dissection: a case report

<p>Abstract</p> <p>Background</p> <p>Sudden onset peri- or post-coital cardiovascular disease is well documented in the literature including myocardial infarction, pulmonary embolus and subarachnoid haemorrhage. The occurrence of aortic dissection in this setting has been reported only once previously.</p> <p>Case presentation</p> <p>We report the case of a 47 year old man who developed sudden onset right leg pain during coitus. This was initially believed to be neurological due to nerve impingement but an MRI failed to identify a prolapse. On further review after 6 weeks, pulses were noted to be absent in the patient's right leg and an urgent vascular review with investigation identified a dissection of the aorta which was subsequently successfully treated.</p> <p>Conclusion</p> <p>This case illustrates a rare presentation of aortic dissection and demonstrates the importance of a thorough vascular assessment in the presence of sudden onset limb pain.</p

MEF2A regulates mGluR-dependent AMPA receptor trafficking independently of Arc/Arg3.1

© 2018 The Author(s). Differential trafficking of AMPA receptors (AMPARs) to and from the postsynaptic membrane is a key determinant of the strength of excitatory neurotransmission, and is thought to underlie learning and memory. The transcription factor MEF2 is a negative regulator of memory in vivo, in part by regulating trafficking of the AMPAR subunit GluA2, but the molecular mechanisms behind this have not been established. Here we show, via knockdown of endogenous MEF2A in primary neuronal culture, that MEF2A is specifically required for Group I metabotropic glutamate receptor (mGluR)-mediated GluA2 internalisation, but does not regulate AMPAR expression or trafficking under basal conditions. Furthermore, this process occurs independently of changes in expression of Arc/Arg3.1, a previously characterised MEF2 transcriptional target and mediator of mGluR-dependent long-term depression. These data demonstrate a novel MEF2A-dependent mechanism for the regulation of activity-dependent AMPAR trafficking

Introduction: Interrogating the 'everyday' politics of emotions in international relations

The focus on the everyday in this Special Issue reveals different kinds of emotional practices, their political effects and their political contestation within both micro- and macro-politics in international relations. The articles in this Special Issue address the everyday negotiation of emotions, shifting between the reproduction of hegemonic structures of feelings and emancipation from them. In other words, the everyday politics of emotions allows an exploration of who gets to express emotions, what emotions are perceived as (il)legitimate or (un)desirable, how emotions are circulated and under what circumstances. Consequently, we identify two thematic strands which emerge as central to an interrogation of ‘everyday’ emotions in international relations and which run through each of the contributions: first, an exploration of the relationship between individual and collective emotions and, second, a focus on the role of embodiment within emotions research and its relationship with the dynamics and structures of power

Graded reductions in pre-exercise muscle glycogen impair exercise capacity but do not augment cell skeletal muscle signalling: implication for CHO periodisation

We examined the effects of graded muscle glycogen on exercise capacity and modulation of skeletal muscle signalling pathways associated with the regulation of mitochondrial biogenesis. In a repeated measures design, eight males completed a sleep-low, train-low model comprising an evening glycogen depleting cycling protocol followed by an exhaustive exercise capacity test (8 x 3 min at 80% PPO, followed by 1 min efforts at 80% PPO until exhaustion) the subsequent morning. Following glycogen depleting exercise, subjects ingested a total of 0 g kg-1 (L-CHO), 3.6 g kg-1 (M-CHO) or 7.6 g kg-1 (H-CHO) of carbohydrate during a 6 h period prior to sleeping, such that exercise was commenced the next morning with graded (P < 0.05) muscle glycogen concentrations (Mean ± SD) (L-CHO: 88 ± 43, M-CHO: 185 ± 62, H-CHO: 278 ± 47 mmol kg-1 dw). Despite differences (P < 0.05) in exercise capacity at 80% PPO between trials (L-CHO: 18 ± 7, M-CHO: 36 ± 3, H-CHO: 44 ± 9 min) exercise induced comparable AMPKThr172 phosphorylation (~4 fold) and PGC-1α mRNA expression (~5 fold) post- and 3 h post-exercise, respectively. In contrast, exercise nor CHO availability affected the phosphorylation of p38MAPKThr180/Tyr182, CaMKIIThr268 or mRNA expression of p53, Tfam, CPT-1, CD36 or PDK4. Data demonstrate that when exercise is commenced with muscle glycogen below 300 mmol kg-1 dw, further graded reductions of 100 mmol kg-1 dw impair exercise capacity but do not augment skeletal muscle cell signaling

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia