scholarly journals A common androgen synthesis variant is associated with COVID susceptibility

2020 ◽  
Author(s):  
Jeffrey M. McManus ◽  
Navin Sabharwal ◽  
Peter Bazeley ◽  
Nima Sharifi
Keyword(s):  
Inflammatory Responses ◽  
Hormone Signaling ◽  
Test Results ◽  
Adrenal Androgens ◽  
Viral Susceptibility ◽  
Androgen Synthesis ◽  
Disease Outcomes ◽  
Inflammatory Processes ◽  
The Common ◽  
The Uk

A sex discordance in COVID exists, with males disproportionately affected. More broadly, sex differences in infectious and inflammatory processes are well known, with women tending to mount stronger immune responses than men. Although there is evidence that sex hormone signaling is immunomodulatory, including downregulation of immune/inflammatory responses by androgens, the existence of numerous other physiologic differences between the sexes leads to great uncertainty in attributing worse infectious disease outcomes in men to androgen signaling. No definitive genetic data exist to support androgen-mediated immune suppression for viral susceptibility, nor for adrenal androgens. Here we show an association between inheritance of the common adrenal-permissive missense-encoding variant HSD3B1(1245C), that enables androgen synthesis from adrenal precursors10, and susceptibility to COVID. The adrenal-permissive HSD3B1(1245C) has previously been linked to suppression of inflammation in severe asthma. In analysis of COVID test results from the UK Biobank, we show that in older (≥ 70 years of age) subjects, the adrenal-permissive variant is associated with a greater chance of being COVID-positive. The effect increases with the number of HSD3B1(1245C) alleles inherited and is greater in females such that increasing androgen synthesis confers risk approaching males. Our study suggests that a common androgen synthesis variant regulates immune susceptibility to COVID infection as well as potentially other immune and inflammatory processes.

Punk as Folk: Continuities and Tensions in the UK and Beyond

2020 ◽  
Author(s):  
Pete Dale
Keyword(s):  
Folk Music ◽  
Music Making ◽  
Collective Creativity ◽  
Living Tradition ◽  
Wide Range ◽  
The Us ◽  
The Common ◽  
The Individual ◽  
The Uk

Numerous claims have been made by a wide range of commentators that punk is somehow “a folk music” of some kind. Doubtless there are several continuities. Indeed, both tend to encourage amateur music-making, both often have affiliations with the Left, and both emerge at least partly from a collective/anti-competitive approach to music-making. However, there are also significant tensions between punk and folk as ideas/ideals and as applied in practice. Most obviously, punk makes claims to a “year zero” creativity (despite inevitably offering re-presentation of at least some existing elements in every instance), whereas folk music is supposed to carry forward a tradition (which, thankfully, is more recognized in recent decades as a subject-to-change “living tradition” than was the case in folk’s more purist periods). Politically, meanwhile, postwar folk has tended more toward a socialist and/or Marxist orientation, both in the US and UK, whereas punk has at least rhetorically claimed to be in favor of “anarchy” (in the UK, in particular). Collective creativity and competitive tendencies also differ between the two (perceived) genre areas. Although the folk scene’s “floor singer” tradition offers a dispersal of expressive opportunity comparable in some ways to the “anyone can do it” idea that gets associated with punk, the creative expectation of the individual within the group differs between the two. Punk has some similarities to folk, then, but there are tensions, too, and these are well worth examining if one is serious about testing out the common claim, in both folk and punk, that “anyone can do it.”

scholarly journals Transcriptomic Data Analysis Reveals a Down-Expression of Galectin-8 in Schizophrenia Hippocampus

2021 ◽  
Vol 11 (8) ◽  
pp. 973
Author(s):  
Maria Cristina Petralia ◽  
Rosella Ciurleo ◽  
Alessia Bramanti ◽  
Placido Bramanti ◽  
Andrea Saraceno ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Antipsychotic Agents ◽  
Standards Of Care ◽  
Specific Gene ◽  
Contributing Factors ◽  
Healthy Donors ◽  
Dorsolateral Prefrontal ◽  
Inflammatory Processes ◽  
Disease Specific

Schizophrenia (SCZ) is a severe psychiatric disorder with several clinical manifestations that include cognitive dysfunction, decline in motivation, and psychosis. Current standards of care treatment with antipsychotic agents are often ineffective in controlling the disease, as only one-third of SCZ patients respond to medications. The mechanisms underlying the pathogenesis of SCZ remain elusive. It is believed that inflammatory processes may play a role as contributing factors to the etiology of SCZ. Galectins are a family of β-galactoside-binding lectins that contribute to the regulation of immune and inflammatory responses, and previous reports have shown their role in the maintenance of central nervous system (CNS) homeostasis and neuroinflammation. In the current study, we evaluated the expression levels of the galectin gene family in post-mortem samples of the hippocampus, associative striatum, and dorsolateral prefrontal cortex from SCZ patients. We found a significant downregulation of LGALS8 (Galectin-8) in the hippocampus of SCZ patients as compared to otherwise healthy donors. Interestingly, the reduction of LGALS8 was disease-specific, as no modulation was observed in the hippocampus from bipolar nor major depressive disorder (MDD) patients. Prediction analysis identified TBL1XR1, BRF2, and TAF7 as potential transcription factors controlling LGALS8 expression. In addition, MIR3681HG and MIR4296 were negatively correlated with LGALS8 expression, suggesting a role for epigenetics in the regulation of LGALS8 levels. On the other hand, no differences in the methylation levels of LGALS8 were observed between SCZ and matched control hippocampus. Finally, ontology analysis of the genes negatively correlated with LGALS8 expression identified an enrichment of the NGF-stimulated transcription pathway and of the oligodendrocyte differentiation pathway. Our study identified LGALS8 as a disease-specific gene, characterizing SCZ patients, that may in the future be exploited as a potential therapeutic target.

scholarly journals Cardiorespiratory fitness assessment using risk-stratified exercise testing and dose–response relationships with disease outcomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomas I. Gonzales ◽  
Kate Westgate ◽  
Tessa Strain ◽  
Stefanie Hollidge ◽  
Justin Jeon ◽  
...  
Keyword(s):  
Cardiorespiratory Fitness ◽  
Maximal Oxygen Consumption ◽  
Estimation Method ◽  
The Novel ◽  
Exercise Tests ◽  
Metabolic Equivalent ◽  
Fitness Assessment ◽  
Disease Outcomes ◽  
All Cause Mortality ◽  
The Uk

AbstractCardiorespiratory fitness (CRF) is associated with mortality and cardiovascular disease, but assessing CRF in the population is challenging. Here we develop and validate a novel framework to estimate CRF (as maximal oxygen consumption, VO2max) from heart rate response to low-risk personalised exercise tests. We apply the method to examine associations between CRF and health outcomes in the UK Biobank study, one of the world’s largest and most inclusive studies of CRF, showing that risk of all-cause mortality is 8% lower (95%CI 5–11%, 2670 deaths among 79,981 participants) and cardiovascular mortality is 9% lower (95%CI 4–14%, 854 deaths) per 1-metabolic equivalent difference in CRF. Associations obtained with the novel validated CRF estimation method are stronger than those obtained using previous methodology, suggesting previous methods may have underestimated the importance of fitness for human health.

scholarly journals The use of real life contexts in the CTA: Some unintended consequences

Pythagoras ◽  
2009 ◽  
Vol 0 (69) ◽  
Author(s):  
Sarah Bansilal
Keyword(s):  
South Africa ◽  
Real Life ◽  
Unintended Consequences ◽  
Assessment Programme ◽  
Assessment Tasks ◽  
The Usa ◽  
The Common ◽  
The Uk ◽  
Assessment Activities

The Common Tasks for Assessment (CTA) was a new assessment programme that was introduced in 2002 in South Africa for all Grade 9 learners. The purpose of this paper is to articulate some concerns around the use of contextualised assessment activities in the CTA. The study reported here was carried out in 2003. Data for the study was generated from lesson observations and interviews with the participant teachers and groups of learners. It is argued that although the intentions behind the design of the CTA are well meaning and noble, there are in fact some learners who may be unintentionally disadvantaged by the design of the CTA which uses an extended context as a source for all the assessment tasks. In this paper two unintended consequences of using ‘real life’ contexts are identified and the implications of these are discussed, by linking the observations to research carried out in the UK and the USA.

The legal and ethical aspects of telemedicine. 1: Confidentiality and the patient's rights of access

1997 ◽  
Vol 3 (4) ◽  
pp. 179-187 ◽  
Author(s):  
Ben Stanberry
Keyword(s):  
Medical Records ◽  
Common Law ◽  
Medical Data ◽  
Legal Obligation ◽  
The European Union ◽  
Ethical Aspects ◽  
Patients Rights ◽  
Patient’S Rights ◽  
The Common ◽  
The Uk

This paper reviews the principle of confidentiality and the rights of access by patients to their medical records. Confidentiality has been germane to the ethics of medical practice since the time of Hippocrates but the nature of the legal obligation of confidence does not have such a clear pedigree. The introduction of crossborder telemedical consultations presents a very real danger to maintaining the confidentiality of medical data. While both the common law and statute law can be used to prevent the unauthorized interception and disclosure of medical data and protect the patient's rights of access and ownership in the UK, it is the harmonization regime of the European Union that will bring comprehensive regulation and legal clarity to the protection of patients' rights within an increasingly international medical super-specialty'.

scholarly journals Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2and Cytokines

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Bona Linke ◽  
Yannick Schreiber ◽  
Bettina Picard-Willems ◽  
Patrick Slattery ◽  
Rolf M. Nüsing ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Innate Immune ◽  
Prostaglandin E ◽  
Murine Bone Marrow ◽  
Activated Platelets ◽  
Monocytes And Macrophages ◽  
Inflammatory Processes ◽  
Necrosis Factor

Platelets are well known for their role in hemostasis and are also increasingly recognized for their roles in the innate immune system during inflammation and their regulation of macrophage activation. Here, we aimed to study the influence of platelets on the production of inflammatory mediators by monocytes and macrophages. Analyzing cocultures of platelets and murine bone marrow-derived macrophages or human monocytes, we found that collagen-activated platelets release high amounts of prostaglandin E2(PGE2) that leads to an increased interleukin- (IL-) 10 release and a decreased tumor necrosis factor (TNF)αsecretion out of the monocytes or macrophages. Platelet PGE2mediated the upregulation of IL-10 in both cell types via the PGE2receptor EP2. Notably, PGE2-mediated IL-10 synthesis was also mediated by EP4 in murine macrophages. Inhibition of TNFαsynthesis via EP2 and EP4, but not EP1, was mediated by IL-10, since blockade of the IL-10 receptor abolished the inhibitory effect of both receptors on TNFαrelease. This platelet-mediated cross-regulation between PGE2and cytokines reveals one mechanism how monocytes and macrophages can attenuate excessive inflammatory responses induced by activated platelets in order to limit inflammatory processes.

scholarly journals Current challenges for women in orthopaedics

2021 ◽  
Vol 2 (10) ◽  
pp. 893-899
Author(s):  
Maryam Ahmed ◽  
Laura C. Hamilton
Keyword(s):  
Patient Outcomes ◽  
Lessons Learned ◽  
Business Sector ◽  
Left Behind ◽  
Diversity And Inclusion ◽  
The World ◽  
Female Surgeons ◽  
The Common ◽  
The Uk ◽  
The Military

Orthopaedics has been left behind in the worldwide drive towards diversity and inclusion. In the UK, only 7% of orthopaedic consultants are female. There is growing evidence that diversity increases innovation as well as patient outcomes. This paper has reviewed the literature to identify some of the common issues affecting female surgeons in orthopaedics, and ways in which we can address them: there is a wealth of evidence documenting the differences in the journey of men and women towards a consultant role. We also look at lessons learned from research in the business sector and the military. The ‘Hidden Curriculum’ is out of date and needs to enter the 21st century: microaggressions in the workplace must be challenged; we need to consider more flexible training options and support trainees who wish to become pregnant; mentors, both male and female, are imperative to provide support for trainees. The world has changed, and we need to consider how we can improve diversity to stay relevant and effective. Cite this article: Bone Jt Open 2021;2-10:893–899.

scholarly journals Before writing that script: use of antipsychotic medication in patients with dementia in a CMHTOA

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S96-S96
Author(s):  
Adaora Obiekezie ◽  
Roohi Afshan ◽  
Jack Healy
Keyword(s):  
Antipsychotic Medication ◽  
Psychological Symptoms ◽  
Antipsychotic Treatment ◽  
Community Mental Health Team ◽  
Mental Health Team ◽  
Diagnosis Of Dementia ◽  
Independent Review ◽  
The Common ◽  
The Uk ◽  
Current Guidelines

AimsA 2009 independent review commissioned by the UK government to review the use of antipsychotic medication in patients diagnosed with dementia produced the Time for Action report, often referred to as the Banerjee Report. It highlighted the common practise of using antipsychotics in the treatment of Behavioural and Psychological Symptoms of Dementia (BPSD) and the clinical issues this could raise especially when these medications were not being regularly reviewed. The audti was therefore carried out to determine whether patinets with BPSD in a Community Mental Health Team for Older adults (CMHTOA) in Mid Surrey, who had been diagnosed with BPSD, were being adequately assessed and managed in line with the current guidelines.MethodPatients with a diagnosis of dementia open to one of three teams in the CMHTOA during the months of October and November 2019 were identified, those being prescribed antipsychotic medication were selected and data from their electronic records collected and analysed to determine if clinicians: a) identified and documented the target behaviours, b) carried out a structured assessment using an ABC chart before commencing medication, c) reviewed the antipsychotic medication 6 weeks after it was commenced.ResultOf the 87 patients with a diagnosis of Dementia from October to November 2019, 18 were on antipsychotic medication. 100% of these had target behaviours identified and clearly documented, a sixth had a structured assessment prior to starting medication and 61% had been reviewed after the first 6 weeks of starting antipsychotics.ConclusionThe findings showed that a good proprotion of patients did not have the required structured assessment before commencement of treatment and that more needed to be done by way of improving regular reviews after antipsychotic treatment is commenced.

scholarly journals Emergency Management of Acute on Chronic Liver Disease

2006 ◽  
Vol 5 (1) ◽  
pp. 3-7
Author(s):  
AJ Portal ◽  
Keyword(s):  
Liver Disease ◽  
Emergency Management ◽  
Chronic Liver Disease ◽  
Media Coverage ◽  
Recent Change ◽  
Chronic Liver ◽  
The Common ◽  
Complications Of Cirrhosis ◽  
The Uk ◽  
Licensing Laws

Chronic liver disease is becoming more common in the UK. There has been much media coverage due to recent change in licensing laws and celebrity figures suffering from cirrhosis. This review highlights the common complications of cirrhosis that frequently present to the acute physician, focussing on initial presentation and subsequent management, based on the current best available evidence.

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