Subchronic administration of phencyclidine produces hypermethylation in the parvalbumin gene promoter in rat brain

Aim: A deficit in parvalbumin neurons is found in schizophrenia and several animal models of the disease. In this preliminary study, we determined whether one such model, phencyclidine (PCP) administration, results in changes in DNA methylation in the rat Pvalb promoter. Materials & methods: DNA from hippocampus and prefrontal cortex from rats, which 6 weeks previously received either 2 mg/kg PCP or vehicle for 7 days, underwent bisulphite pyrosequencing to determine methylation. Results: PCP administration induced significantly greater methylation at one of two Pvalb CpG sites in both prefrontal cortex and hippocampus, while no significant difference was found in long interspersed nucleotide element-1, a global measure of DNA methylation. Conclusion: Subchronic PCP administration results in a specific hypermethylation in the Pvalb promoter which may contribute to parvalbumin deficits in this animal model of psychosis

Preventing crime in cooperation with the mental health care profession

Although major mental disorders do not have a central position in many criminological theories, there seems to be an evident relationship between these disorders and criminal behavior. In daily practice police officers and mental health care workers work jointly to prevent nuisance and crime and to keep the city livable. Examining the situations where the criminal justice system and mental health institutes are jointly involved to prevent crime, some pitfalls emerge that seem to threaten successful cooperation. There appear to be unrealistic expectations of the possibility to reduce the risk of reoffending by means of treatment and of the possibility to predict which offender poses a risk to society. Another complexity is the fact that both parties work from different backgrounds and pursue different goals. The way society and the criminal justice system deal with persons who are assumed to be a risk to the community because of a mental disorder demands a further investigation from a criminological perspective

Patient experience of NHS health checks: a systematic review and qualitative synthesis

$\textbf{Objective:}$ To review the experiences of patients attending NHS Health Checks in England. $\textbf{Design:}$ A systematic review of quantitative and qualitative studies with a thematic synthesis of qualitative studies. $\textbf{Data sources:}$ An electronic literature search of Medline, Embase, Health Management Information Consortium, Cumulative Index of Nursing and Allied Health Literature, Global Health, PsycInfo, Web of Science, OpenGrey, the Cochrane Library, National Health Service (NHS) Evidence, Google Scholar, Google, Clinical Trials.gov and the ISRCTN registry to 09/11/16 with no language restriction and manual screening of reference lists of all included papers. $\textbf{Inclusion criteria:}$ Primary research reporting experiences of patients who have attended NHS Health Checks. $\textbf{Results:}$ 20 studies met the inclusion criteria, 9 reporting quantitative data and 15 qualitative data. There were consistently high levels of reported satisfaction in surveys, with over 80% feeling that they had benefited from an NHS Health Check. Data from qualitative studies showed that the NHS Health Check had been perceived to act as a wake-up call for many who reported having gone on to make substantial lifestyle changes which they attributed to the NHS Health Check. However, some had been left with a feeling of unmet expectations, were confused about or unable to remember their risk scores, found the lifestyle advice too simplistic and non-personalised or were confused about follow-up. $\textbf{Conclusions:}$ While participants were generally very supportive of the NHS Health Check programme and examples of behaviour change were reported, there are a number of areas where improvements could be made. These include greater clarity around the aims of the programme within the promotional material, more proactive support for lifestyle change and greater appreciation of the challenges of communicating risk and the limitations of relying on the risk score alone as a trigger for facilitating behaviour change.This work was funded by a grant from Public Health England. JUS was funded by an NIHR Clinical Lectureship and FW by an NIHR Clinician Scientist award

Delivery and impact of the NHS Health Check in the first 8 years: a systematic review

Background: Since 2009, all eligible persons in England have been entitled to an NHS Health Check. Uncertainty remains about who attends, and the health-related impacts. Aim: To review quantitative evidence on coverage (the proportion of eligible individuals who attend), uptake (proportion of invitees who attend), and impact of NHS Health Checks. Design and setting: A systematic review and quantitative data synthesis. Included were studies or data reporting coverage or uptake and studies reporting any health-related impact that used an appropriate comparison group or before- and-after study design. Method: Eleven databases and additional internet sources were searched to November 2016. Results: Twenty-six observational studies and one additional dataset were included. Since 2013, 45.6% of eligible individuals have received a health check. Coverage is higher among older people, those with a family history of coronary heart disease, those living in the most deprived areas, and some ethnic minority groups. Just under half (48.2%) of those invited have taken up the invitation. Data on uptake and impact (especially regarding health-related behaviours) are limited. Uptake is higher in older people and females, but lower in those living in the most deprived areas. Attendance is associated with small increases in disease detection, decreases in modelled cardiovascular disease risk, and increased statin and antihypertensive prescribing. Conclusion: Published attendance, uptake, and prescribing rates are all lower than originally anticipated, and data on impact are limited, with very few studies reporting the effect of attendance on health-related behaviours. High-quality studies comparing matched attendees and non-attendees and health economic analyses are required

Compressive properties of commercially available polyurethane foams as mechanical models for osteoporotic human cancellous bone

<p>Abstract</p> <p>Background</p> <p>Polyurethane (PU) foam is widely used as a model for cancellous bone. The higher density foams are used as standard biomechanical test materials, but none of the low density PU foams are universally accepted as models for osteoporotic (OP) bone. The aim of this study was to determine whether low density PU foam might be suitable for mimicking human OP cancellous bone.</p> <p>Methods</p> <p>Quasi-static compression tests were performed on PU foam cylinders of different lengths (3.9 and 7.7 mm) and of different densities (0.09, 0.16 and 0.32 g.cm^-3), to determine the Young's modulus, yield strength and energy absorbed to yield.</p> <p>Results</p> <p>Young's modulus values were 0.08–0.93 MPa for the 0.09 g.cm^-3foam and from 15.1–151.4 MPa for the 0.16 and 0.32 g.cm^-3foam. Yield strength values were 0.01–0.07 MPa for the 0.09 g.cm^-3foam and from 0.9–4.5 MPa for the 0.16 and 0.32 g.cm^-3foam. The energy absorbed to yield was found to be negligible for all foam cylinders.</p> <p>Conclusion</p> <p>Based on these results, it is concluded that 0.16 g.cm^-3PU foam may prove to be suitable as an OP cancellous bone model when fracture stress, but not energy dissipation, is of concern.</p

A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus

The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses

Percutaneous injuries among dental professionals in Washington State

BACKGROUND: Percutaneous exposure incidents facilitate transmission of bloodborne pathogens such as human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV). This study was conducted to identify the circumstances and equipment related to percutaneous injuries among dental professionals. METHODS: We used workers' compensation claims submitted to the Department of Labor and Industries State Fund during a 7-year period (1995 through 2001) in Washington State for this study. We used the statement submitted by the injured worker on the workers' compensation claim form to determine the circumstances surrounding the injury including the type of activity and device involved. RESULTS: Of a total of 4,695 accepted State Fund percutaneous injury claims by health care workers (HCWs), 924 (20%) were submitted by dental professionals. Out of 924 percutaneous injuries reported by dental professionals 894 (97%) were among dental health care workers in non-hospital settings, including dentists (66, 7%), dental hygienists (61, 18%) and dental assistants (667, 75%). The majority of those reporting were females (638, 71%). Most (781, 87%) of the injuries involved syringes, dental instruments (77, 9%), and suture needles (23%). A large proportion (90%) of injuries occurred in offices and clinics of dentists, while remainder occurred in offices of clinics and of doctors of medicine (9%), and a few in specialty outpatient facilities (1%). Of the 894 dental health care workers with percutaneous injuries, there was evidence of HBV in 6 persons, HCV in 30 persons, HIV in 3 persons and both HBV and HVC (n = 2) exposure. CONCLUSION: Out of hospital percutaneous injuries are a substantial risk to dental health professionals in Washington State. Improved work practices and safer devices are needed to address this risk

Mechanisms Involved in Nicotinic Acetylcholine Receptor-Induced Neurotransmitter Release from Sympathetic Nerve Terminals in the Mouse Vas Deferens

Prejunctional nicotinic acetylcholine receptors (nAChRs) amplify postganglionic sympathetic neurotransmission, and there are indications that intraterminal Ca2+ stores might be involved. However, the mechanisms by which nAChR activation stimulates neurotransmitter release at such junctions is unknown. Rapid local delivery (picospritzing) of the nAChR agonist epibatidine was combined with intracellular sharp microelectrode recording to monitor spontaneous and field-stimulation-evoked neurotransmitter release from sympathetic nerve terminals in the mouse isolated vas deferens. Locally applied epibatidine (1 µM) produced ‘epibatidine-induced depolarisations’ (EIDs) that were similar in shape to spontaneous excitatory junction potentials (SEJPs) and were abolished by nonselective nAChR antagonists and the purinergic desensitizing agonist α,β-methylene ATP. The amplitude distribution of EIDs was only slightly shifted towards lower amplitudes by the selective α7 nAChR antagonists α-bungarotoxin and methyllcaconitine, the voltage-gated Na+ channel blocker tetrodotoxin or by blocking voltage-gated Ca2+ channels with Cd2+. Lowering the extracellular Ca2+ concentration reduced the frequency of EIDs by 69%, but more surprisingly, the Ca2+-induced Ca2+ release blocker ryanodine greatly decreased the amplitude (by 41%) and the frequency of EIDs by 36%. Ryanodine had no effect on electrically-evoked neurotransmitter release, paired-pulse facilitation, SEJP frequency, SEJP amplitude or SEJP amplitude distribution. These results show that activation of non-α7 nAChRs on sympathetic postganglionic nerve terminals induces high-amplitude junctional potentials that are argued to represent multipacketed neurotransmitter release synchronized by intraterminal Ca2+-induced Ca2+ release, triggered by Ca2+ influx directly through the nAChR. This nAChR-induced neurotransmitter release can be targeted pharmacologically without affecting spontaneous or electrically-evoked neurotransmitter release

Biology, Methodology or Chance? The Degree Distributions of Bipartite Ecological Networks

The distribution of the number of links per species, or degree distribution, is widely used as a summary of the topology of complex networks. Degree distributions have been studied in a range of ecological networks, including both mutualistic bipartite networks of plants and pollinators or seed dispersers and antagonistic bipartite networks of plants and their consumers. The shape of a degree distribution, for example whether it follows an exponential or power-law form, is typically taken to be indicative of the processes structuring the network. The skewed degree distributions of bipartite mutualistic and antagonistic networks are usually assumed to show that ecological or co-evolutionary processes constrain the relative numbers of specialists and generalists in the network. I show that a simple null model based on the principle of maximum entropy cannot be rejected as a model for the degree distributions in most of the 115 bipartite ecological networks tested here. The model requires knowledge of the number of nodes and links in the network, but needs no other ecological information. The model cannot be rejected for 159 (69%) of the 230 degree distributions of the 115 networks tested. It performed equally well on the plant and animal degree distributions, and cannot be rejected for 81 (70%) of the 115 plant distributions and 78 (68%) of the animal distributions. There are consistent differences between the degree distributions of mutualistic and antagonistic networks, suggesting that different processes are constraining these two classes of networks. Fit to the MaxEnt null model is consistently poor among the largest mutualistic networks. Potential ecological and methodological explanations for deviations from the model suggest that spatial and temporal heterogeneity are important drivers of the structure of these large networks