Are the Health of the Nation's targets attainable? Postal survey of general practitioners' views

The Health of the Nation's targets were introduced by the government in 1992 as part of a strategic approach to health.1 We aimed, in 1996, to elicit the views of general practitioners on the attainability of these targets

Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) in arsenic biomethylation and its role in arsenic-induced toxicity.

BackgroundIn humans, inorganic arsenic (iAs) is metabolized to methylated arsenical species in a multistep process mainly mediated by arsenic (+3 oxidation state) methyltransferase (AS3MT). Among these metabolites is monomethylarsonous acid (MMAIII), the most toxic arsenic species. A recent study in As3mt-knockout mice suggests that unidentified methyltransferases could be involved in alternative iAs methylation pathways. We found that yeast deletion mutants lacking MTQ2 were highly resistant to iAs exposure. The human ortholog of the yeast MTQ2 is N-6 adenine-specific DNA methyltransferase 1 (N6AMT1), encoding a putative methyltransferase.ObjectiveWe investigated the potential role of N6AMT1 in arsenic-induced toxicity.MethodsWe measured and compared the cytotoxicity induced by arsenicals and their metabolic profiles using inductively coupled plasma-mass spectrometry in UROtsa human urothelial cells with enhanced N6AMT1 expression and UROtsa vector control cells treated with different concentrations of either iAsIII or MMAIII.ResultsN6AMT1 was able to convert MMAIII to the less toxic dimethylarsonic acid (DMA) when overexpressed in UROtsa cells. The enhanced expression of N6AMT1 in UROtsa cells decreased cytotoxicity of both iAsIII and MMAIII. Moreover, N6AMT1 is expressed in many human tissues at variable levels, although at levels lower than those of AS3MT, supporting a potential participation in arsenic metabolism in vivo.ConclusionsConsidering that MMAIII is the most toxic arsenical, our data suggest that N6AMT1 has a significant role in determining susceptibility to arsenic toxicity and carcinogenicity because of its specific activity in methylating MMAIII to DMA and other unknown mechanisms

The Appearance of Four Basement Membrane Zone Antigens in Developing Human Fetal Skin

In order to study the ontogeny of various structural and antigenic components of the basement membrane zone of human skin, we have examined skin specimens from 20 aborted fetuses ranging in gestational ages from 6 to 25 weeks, utilizing light microscopy, transmission electron microscopy, and indirect immunofluorescence with antibodies to bullous pemphigoid antigen, laminin, type IV collagen, and to the antigen defined by KF-1 monoclonal antibody. Both laminin and type IV collagen were detectable as early as 6 weeks of gestational age. In contrast, bullous pemphigoid antigen and the antigen defined by KF- 1 antibody were not detectable before 10 weeks and 16 weeks, respectively. The appearance of bullous pemphigoid antigen correlated with stratification of the epidermis and the formation of hemidesmosomes and anchoring fibrils at the basement membrane zone. KF- 1 antigen is first expressed when the epidermis is further stratified, hemidesmosomes and anchoring fibrils are present in greater numbers and with increased frequency at the dermal-epidermal junction, and hair follicles have begun to bud downward from the basal layer of the epidermis. Our findings suggest an orderly sequence to the appearance of these basement membrane zone components within human skin

Food insecurity and severe mental illness: understanding the hidden problem and how to ask about food access during routine healthcare

SUMMARY Food insecurity occurs when an individual lacks the financial resources to ensure reliable access to sufficient food to meet their dietary, nutritional and social needs. Adults living with mental ill health, particularly severe mental illness, are more likely to experience food insecurity than the general adult population. Despite this, most interventions and policy reforms in recent years have been aimed at children and families, with little regard for other vulnerable groups. Initiating a conversation about access to food can be tricky and assessing for food insecurity does not happen in mental health settings. This article provides an overview of food insecurity and how it relates to mental ill health. With reference to research evidence, the reader will gain an understanding of food insecurity, how it can be assessed and how food-insecure individuals with severe mental illness can be supported. Finally, we make policy recommendations to truly address this driver of health inequality.</jats:p

Challenges of Incorporating Digital Health Technology Outcomes in a Clinical Trial: Experiences from PD STAT.

Digital health technologies (DHTs) have great potential for use as clinical trial outcomes; however, practical issues need to be addressed in order to maximise their benefit. We describe our experience of incorporating two DHTs as secondary/exploratory outcome measures in PD STAT, a randomised clinical trial of simvastatin in people with Parkinson's disease. We found much higher rates of missing data in the DHTs than the traditional outcome measures, in particular due to technical and software difficulties. We discuss methods to address these obstacles in terms of protocol design, workforce training and data management

Challenges of Incorporating Digital Health Technology Outcomes in a Clinical Trial: Experiences from PD STAT

\ua9 2022 - The authors. Published by IOS Press.Digital health technologies (DHTs) have great potential for use as clinical trial outcomes; however, practical issues need to be addressed in order to maximise their benefit. We describe our experience of incorporating two DHTs as secondary/exploratory outcome measures in PD STAT, a randomised clinical trial of simvastatin in people with Parkinson\u27s disease. We found much higher rates of missing data in the DHTs than the traditional outcome measures, in particular due to technical and software difficulties. We discuss methods to address these obstacles in terms of protocol design, workforce training and data management

Is There a Causal Association between Genotoxicity and the Imposex Effect?

There is a growing body of evidence that indicates common environmental pollutants are capable of disrupting reproductive and developmental processes by interfering with the actions of endogenous hormones. Many reports of endocrine disruption describe changes in the normal development of organs and tissues that are consistent with genetic damage, and recent studies confirm that many chemicals classified to have hormone-modulating effects also possess carcinogenic and mutagenic potential. To date, however, there have been no conclusive examples linking genetic damage with perturbation of endocrine function and adverse effects in vivo. Here, we provide the first evidence of DNA damage associated with the development of imposex (the masculinization of female gastropods considered to be the result of alterations to endocrine-mediated pathways) in the dog-whelk Nucella lapillus. Animals (n = 257) that displayed various stages of tributyltin (TBT)-induced imposex were collected from sites in southwest England, and their imposex status was determined by physical examination. Linear regression analysis revealed a very strong relationship (correlation coefficient of 0.935, p < 0.0001) between the degree of imposex and the extent of DNA damage (micronucleus formation) in hemocytes. Moreover, histological examination of a larger number of dog-whelks collected from sites throughout Europe confirmed the presence of hyperplastic growths, primarily on the vas deferens and penis in both TBT-exposed male snails and in females that exhibited imposex. A strong association was found between TBT body burden and the prevalence of abnormal growths, thereby providing compelling evidence to support the hypothesis that environmental chemicals that affect reproductive processes do so partly through DNA damage pathways

Medical student‐led simulation in COVID‐19 crisis

Background: Simulation training is an effective tool for improving confidence in healthcare workers. During the recent COVID‐19 pandemic, large numbers of staff required re‐training to manage unfamiliar situations. We present a set of medical student‐led clinical simulation sessions and evaluate their effects on (i) confidence among redeployed healthcare workers managing COVID‐19 patients and (ii) medical students’ confidence as educators. / Methods: Half‐day simulation training sessions consisting of three COVID‐related clinical scenarios were devised by senior medical students and delivered to a group of approximately 150 healthcare workers over six repeated sessions prior to redeployment to COVID‐19 wards. We distributed an anonymous pre‐ and post‐simulation questionnaire to 36 participants in the final group exploring their experiences. The confidence scores were analysed using the Wilcoxon signed‐rank test. Following the delivery of teaching, medical students completed a questionnaire assessing their personal experiences of designing and delivering the exercises. / Results: Data are available for 35/36 participants approached. Respondents reported being significantly more confident after the training in all aspects of managing COVID‐19 patients, including triage, complex discharge, recognising deterioration, initiating basic life support, managing symptoms and advising on visiting policies (p < 0.001); 97% of respondents rated the training as useful. Thematic analysis of medical students’ responses demonstrated mutual benefit. / Discussion: This study demonstrates the strengths of simulation training in helping to build staff confidence in a rapidly evolving situation and highlights the value of medical students in supporting a hospital’s response to an outbreak. We recommend further studies of student‐led simulation exercises, including longer‐term follow‐up

Plasma Biomarkers for Detecting Hodgkin's Lymphoma in HIV Patients

The lifespan of people with human immunodeficiency virus (HIV) infection has increased as a result of effective antiretroviral therapy, and the incidences of the AIDS-defining cancers, non-Hodgkin's lymphoma and Kaposi sarcoma, have declined. Even so, HIV-infected individuals are now at greater risk of other cancers, including Hodgkin's lymphoma (HL). To identify candidate biomarkers for the early detection of HL, we undertook an accurate mass and elution time tag proteomics analysis of individual plasma samples from either HIV-infected patients without HL (controls; n = 14) and from HIV-infected patient samples with HL (n = 22). This analysis identified 60 proteins that were statistically (p<0.05) altered and at least 1.5-fold different between the two groups. At least three of these proteins have previously been reported to be altered in the blood of HL patients that were not known to be HIV positive, suggesting that these markers may be broadly useful for detecting HL. Ingenuity Pathway Analysis software identified “inflammatory response” and “cancer” as the top two biological functions associated with these proteins. Overall, this study validated three plasma proteins as candidate biomarkers for detecting HL, and identified 57 novel candidate biomarkers that remain to be validated. The relationship of these novel candidate biomarkers with cancer and inflammation suggests that they are truly associated with HL and therefore may be useful for the early detection of this cancer in susceptible populations