Health needs assessment of young offenders in the youth justice system on Merseyside

Liverpool Health Observatory (LPHO) was commissioned to undertake a health needs assessment (HNA) for young offenders across the youth justice system on Merseyside. The HNA covers Liverpool, , Knowsley, Sefton, St Helens, Wirral and Halton. It includes a detailed description of the young offender population, both nationally and on Merseyside, and a brief review of relevant literature, as well as interviews with young people and health care staff, in both secure and community setting

Fixed odds betting terminal use and problem gambling across the Liverpool City region

Liverpool Public Health Observatory was commissioned to look at problem gambling, and Fixed Odds Betting Terminal (FOBT) use, across the Liverpool City Region. The aims of the project were to develop a local evidence base in relation to FOBT use and problem gambling, look at reasons for excess gambling, and to investigate the availability and adequacy of local support services for problem gamblers. The project included an online survey on FOBT use, licensing officer visits to Licensed Betting Offices across the region, as well as interviews with problem gamblers, and staff working with them, across the region

Health needs assessment for ex-Armed Forces personnel

Liverpool Health Observatory (LPHO) was commissioned to undertake a health needs assessment (HNA) for ex-Armed Forces personnel, and their families, in Cheshire and on Merseyside. The HNA focuses on personnel aged under 65. It includes a brief review of relevant literature, as well as a description of provision for ex-Armed Forces personnel at a local and national level

Rapid Health and Equality Impact Assessment (HEqIA)of Mersey Care NHS Trust’s Outline Business Case for Mental Health and Learning Disability Services

The aim of this assessment is to look at the health and equality impacts of Mersey Care's Outline Business Case which aims to: Establish home treatment as the norm; Refocusing in-patient services around patients who are acutely ill with shorter lengths of stay; Developing a local Psychiatric intensive Care in-patient Unit (PICU); Strengthen community and primary care services. The results of this Health and Equality Impact Assessment will be used to feed the Outline Business Cas

Top Tips for healthier providers of health-care in Merseyside and Cheshire

Top tips for healthier providers of health-care aims to support organisations in focusing on the actions they can take to improve the health their patients, their staff, and the wider community that they serve. It builds on a previous report that was carried out by Liverpool Public Health Observatory in 2006, which focused on hospitals. The report is a review of secondary data, alongside examples of local delivery from Merseyside and Cheshire

Rapid Health Impact Assessment for Royal Liverpool and Broadgreen University Hospitals Trust - ‘A New Health Service for Liverpool, World Class Hospitals, World Class Services’

The overall aim of this HIA was to maximise the health benefits, which could result from implementation of the proposals by the Royal Liverpool and Broadgreen Hospitals to redesign its services, develop a new hospital to replace the Royal Liverpool University Hospital (RLUH) on its existing site, and make further investment at Broadgreen Hospital. In order to do this, the following objectives had to be achieved; Identify and profile the population groups who will be affected by the proposal. Identify the potential positive and negative health impacts of the proposal and set out clearly who will be affected by these impacts. Make recommendations for the elimination or mitigation of negative impacts (or compensation for those affected). Make recommendations for the maximisation of positive impacts

Impaired hypertrophy in myoblasts is improved with testosterone administration

We investigated the ability of testosterone (T) to restore differentiation in multiple population doubled (PD) murine myoblasts, previously shown to have reduced differentiation in monolayer and bioengineered skeletal muscle cultures vs. their parental controls (CON) (Sharples et al., 2011, 2012 [7] and [26]). Cells were exposed to low serum conditions in the presence or absence of T (100 nM) ± PI3K inhibitor (LY294002) for 72 h and 7 days (early and late muscle differentiation respectively). Morphological analyses were performed to determine myotube number, diameter (μm) and myonuclear accretion as indices of differentiation and myotube hypertrophy. Changes in gene expression for myogenin, mTOR and myostatin were also performed. Myotube diameter in CON and PD cells increased from 17.32 ± 2.56 μm to 21.02 ± 1.89 μm and 14.58 ± 2.66 μm to 18.29 ± 3.08 μm (P ≤ 0.05) respectively after 72 h of T exposure. The increase was comparable in both PD (+25%) and CON cells (+21%) suggesting a similar intrinsic ability to respond to exogenous T administration. T treatment also significantly increased myonuclear accretion (% of myotubes expressing 5+ nuclei) in both cell types after 7 days exposure (P ≤ 0.05). Addition of PI3K inhibitor (LY294002) in the presence of T attenuated these effects in myotube morphology (in both cell types) suggesting a role for the PI3K pathway in T stimulated hypertrophy. Finally, PD myoblasts showed reduced responsiveness to T stimulated mRNA expression of mTOR vs. CON cells and T also reduced myostatin expression in PD myoblasts only. The present study demonstrates testosterone administration improves hypertrophy in myoblasts that basally display impaired differentiation and hypertrophic capacity vs. their parental controls, the action of testosterone in this model was mediated by PI3K/Akt pathway

Testosterone enables growth and hypertrophy in fusion impaired myoblasts that display myotube atrophy: deciphering the role of androgen and IGF-I receptors

We have previously highlighted the ability of testosterone to improve differentiation and myotube hypertrophy in fusion impaired myoblasts that display reduced myotube hypertrophy at 72hrs (after transfer to low serum media) via multiple population doublings (PD) vs. their parental controls (CON); an observation which is abrogated via PI3K/Akt inhibition (Deane et al. 2013). However, whether the most predominant molecular mechanism responsible for T induced hypertrophy occurs directly via androgen receptor or indirectly via IGF-IR/PI3K/Akt pathway is currently debated. PD and CON C2C12 muscle cells were exposed to low serum conditions in the presence or absence of T (100 nM) ± inhibitors of AR (flutamide/F, 40 μm) and IGF-IR (Picropodophyllin/PPP, 150 nM) for 72 hrs and 7 days (early/late muscle differentiation respectively). T increased AR and Akt abundance, myogenin expression, and myotube hypertrophy, but not ERK1/2 activity in both CON and PD cell types. Akt activity was not increased significantly in either cell type with T. Testosterone was unable to promote early differentiation in the presence of IGF-IR inhibitor (PPP) yet still able to promote appropriate later increases in myotube hypertrophy and AR abundance despite IGF-IR inhibition. The addition of the AR inhibitor powerfully attenuated all T induced increases in differentiation and myotube hypertrophy with corresponding reductions in AR abundance, phosphorylated Akt, ERK1/2 and gene expression of IGF-I, myoD and myogenin with increases in myostatin mRNA both cell types. Interestingly, despite basally reduced differentiation and myotube hypertrophy, PD cells showed larger increased in AR abundance vs. CON cells, a response abrogated in the presence of AR but not IGF-IR inhibitors. Furthermore, T induced increases in Akt abundance were sustained despite the presence of IGF-IR inhibition in PD cells only. However, flutamide alone reduced IGF-IR mRNA in both cell types across time points, with an observed reduction in activity of ERK and Akt, perhaps suggesting that IGF-IR was transcriptionally regulated by AR. However, where testosterone increased AR protein content there was no increases observed in IGF-IR gene expression. Overall, this suggested that sufficient AR was important to enable normal gene expression of IGF-IR and downstream signalling, yet elevated levels of AR due to testosterone had no further effect on IGF-IR, despite testosterone increasing Akt abundance in the presence of IGF-IR inhibitor. In conclusion, testosterones ability to improve differentiation and myotube hypertrophy occurred predominately via increases in AR and Akt abundance in both CON and PD cells, with fusion impaired cells (PD) showing an increased responsiveness to T induced AR levels. Finally, T induced increases in myotube hypertrophy (but not early differentiation) occurred independently of upstream IGF-IR input, however it appears that normal AR function in basal conditions is required for adequate IGF-IR gene expression and downstream Akt abundance

Structural basis for the RING catalyzed synthesis of K63 linked ubiquitin chains

This work was supported by grants from Cancer Research UK (C434/A13067), the Wellcome Trust (098391/Z/12/Z) and Biotechnology and Biological Sciences Research Council (BB/J016004/1).The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis.PostprintPeer reviewe