Functional inhibition of deep brain non-visual opsins facilitates acute long day induction of reproductive recrudescence in male Japanese quail :Deep brain photoreceptors in birds

For nearly a century, we have known that brain photoreceptors regulate avian seasonal biology. Two photopigments, vertebrate ancient opsin (VA) and neuropsin (OPN5), provide possible molecular substrates for these photoreceptor pathways. VA fulfills many criteria for providing light input to the reproductive response, but a functional link has yet to be demonstrated. This study examined the role of VA and OPN5 in the avian photoperiodic response of Japanese quail (Coturnix japonica). Non-breeding male quail were housed under short days (6L:18D) and received an intracerebroventricular infusion of adeno-associated viral vectors with shRNAi that selectively inhibited either VA or OPN5. An empty viral vector acted as a control. Quail were then photostimulated (16L:8D) to stimulate gonadal growth. Two long days significantly increased pituitary thyrotrophin-stimulating hormone β-subunit (TSHβ) and luteinizing hormone β-subunit (LHβ) mRNA of VA shRNAi treated quail compared to controls. Furthermore, at one week there was a significant increase, compared to controls, in both hypothalamic gonadotrophin releasing hormone-I (GnRH-I) mRNA and paired testicular mass in VA shRNAi birds. Opn5 shRNAi facilitated the photoinduced increase in TSHβ mRNA at 2 days, but no other differences were identified compared to controls. Contrary to our expectations, the silencing of deep brain photoreceptors enhanced the response of the reproductive axis to photostimulation rather than preventing it. In addition, we show that VA opsin plays a dominant role in the light-dependent neuroendocrine control of seasonal reproduction in birds. Together our findings suggest the photoperiodic response involves at least two photoreceptor types and populations working together with VA opsin playing a dominant role

Interferon gamma responses to proteome-determined specific recombinant proteins: Potential as diagnostic markers for ovine Johne’s disease

Johne’s disease (JD), or paratuberculosis is a fatal enteritis of animals caused by infection with Mycobacterium avium subspecies paratuberculosis (Map). There may be a long subclinical phase with no signs of clinical disease. Diagnosis of JD is problematic and no test can reliably detect sub-clinical disease. Th1 responses to Map are believed to be activated first with a later switch to Th2 responses and progression to clinical disease. Detection of a cell-mediated response, indicated by interferon gamma (IFN-) produced in response to mycobacterial antigens, may give an early indication of infection. Crude extracts of Map (PPDj) have been used to detect the cell-mediated response, but more specific, quantifiable antigens would improve the test. Thirty Map-specific proteins were screened for their ability to raise a cell-mediated response in subclinically infected sheep. Four proteins were selected and tested using blood from subclinical animals and controls from a JD-free flock. Three proteins elicited IFN- levels which were higher in the subclinical group than in the control group, two were statistically significant. Thus these proteins have the ability to discriminate groups of infected and uninfected animals and may have use in diagnosis of JD

Challenges of investigating a large food-borne norovirus outbreak across all branches of a restaurant group in the United Kingdom, October 2016

During October and November 2016, over 1,000 customers and staff reported gastroenteritis after eating at all 23 branches of a restaurant group in the United Kingdom. The outbreak coincided with a new menu launch and norovirus was identified as the causative agent. We conducted four retrospective cohort studies; one among all restaurant staff and three in customers at four branches. We investigated the dishes consumed, reviewed recipes, interviewed chefs and inspected restaurants to identify common ingredients and preparation methods for implicated dishes. Investigations were complicated by three public health agencies concurrently conducting multiple analytical studies, the complex menu with many shared constituent ingredients and the high media attention. The likely source was a contaminated batch of a nationally distributed ingredient, but analytical studies were unable to implicate a single ingredient. The most likely vehicle was a new chipotle chilli product imported from outside the European Union, that was used uncooked in the implicated dishes. This outbreak exemplifies the possibility of rapid spread of infectious agents within a restaurant supply chain, following introduction of a contaminated ingredient. It underlines the importance of appropriate risk assessments and control measures being in place, particularly for new ingredients and ready-to-eat foods

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effectiveness of national and subnational infection prevention and control interventions in high-income and upper-middle-income countries: a systematic review

Evidence-based guidance for national infection prevention and control (IPC) programmes is needed to support national and global capacity building to reduce health-care-associated infection and antimicrobial resistance. In this systematic review we investigate evidence on the effectiveness of IPC interventions implemented at national or subnational levels to inform the development of WHO guidelines on the core components of national IPC programmes. We searched CENTRAL, CINAHL, Embase, MEDLINE, and WHO IRIS databases for publications between Jan 1, 2000, and April 19, 2017. 29 studies that met the eligibility criteria (ie, economic evaluations, cluster-randomised trials, non-randomised trials, controlled before-and-after studies, and interrupted time-series studies exploring the effective of these interventions) were categorised according to intervention type: multimodal, care bundles, policies, and surveillance, monitoring, and feedback. Evidence of effectiveness was found in all categories but the best quality evidence was on multimodal interventions and surveillance, monitoring, and feedback. We call for improvements in study design, reporting of research, and quality of evidence particularly from low-income countries, to strengthen the uptake and international relevance of IPC interventions

Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders.

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called episignatures ). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders

Life and living in advanced age: a cohort study in New Zealand - Te Puāwaitanga o Nga Tapuwae Kia Ora Tonu, LiLACS NZ: Study protocol

The number of people of advanced age (85 years and older) is increasing and health systems may be challenged by increasing health-related needs. Recent overseas evidence suggests relatively high levels of wellbeing in this group, however little is known about people of advanced age, particularly the indigenous Māori, in Aotearoa, New Zealand. This paper outlines the methods of the study Life and Living in Advanced Age: A Cohort Study in New Zealand. The study aimed to establish predictors of successful advanced ageing and understand the relative importance of health, frailty, cultural, social & economic factors to successful ageing for Māori and non-Māori in New Zealand

Open Research, and Professional and Technical Support Staff

This short report summarises some reflections of professional and technical support staff on their perspectives on open research. The reflections are based on input to, and discussions at, a community workshop and roundtable event co-convened by UKRN and Jisc on 20th February 2023. The report is intended to inform discussions within groups of staff in similar roles, across different professional and academic groupings in institutions, and with other stakeholders such as funders