Effect of Rhesus D incompatibility on schizophrenia depends on offspring sex.

Rhesus D incompatibility increases risk for schizophrenia, with some evidence that risk is limited to male offspring. The purpose of this study is to determine whether risk for schizophrenia due to Rhesus D incompatibility differs by offspring sex using a nuclear family-based candidate gene approach and a meta-analysis approach. The genetic study is based on a sample of 277 nuclear families with RHD genotype data on at least one parent and at least one child diagnosed with schizophrenia or related disorder. Meta-analysis inclusion criteria were (1) well-defined sample of schizophrenia patients with majority born before 1970, (2) Rhesus D incompatibility phenotype or genotype data available on mother and offspring, and by offspring sex. Two of ten studies, plus the current genetic study sample, fulfilled these criteria, for a total of 358 affected males and 226 affected females. The genetic study found that schizophrenia risk for incompatible males was significantly greater than for compatible offspring (p=0.03), while risk for incompatible and compatible females was not significantly different (p=.32). Relative risks for incompatible males and females were not significantly different from each other. Meta-analysis using a larger number of affected males and females supports their difference. Taken together, these results provide further support that risk of schizophrenia due to Rhesus D incompatibility is limited to incompatible males, although a weak female incompatibility effect cannot be excluded. Sex differences during fetal neurodevelopment should be investigated to fully elucidate the etiology of schizophrenia

Screening chest radiography: results from a Greek cross-sectional survey

BACKGROUND: Public health authorities worldwide discourage the use of chest radiography as a screening modality, as the diagnostic performance of chest radiography does not justify its application for screening and may even be harmful, since people with false positive results may experience anxiety and concern. Despite the accumulated evidence, various reports suggest that primary care physicians throughout the world still prescribe chest radiography for screening. We therefore set out to index the use of chest radiography for screening purposes among the healthy adult population and to analyze its relationship with possible trigger factors. METHODS: The study was designed as a cross-sectional survey. Five thousand four hundred and ninety-nine healthy adults, coming from 26 Greek provinces were surveyed for screening practice habits in the nationwide anticancer study. Data were obtained for the use of screening chest radiography. Impact of age, gender, tobacco exposure, family history positive for malignancies and professional-risk for lung diseases was further analyzed. RESULTS: we found that 20% (n = 1099) of the surveyed individuals underwent chest radiography for screening purposes for at least one time during the previous three years. Among those, 24% do so with a frequency equal or higher than once yearly, and 48% with a frequency equal or higher than every three years. Screening for chest radiography was more commonly adopted among males (OR 1.130, 95% CI 0.988–1.292), pensioners (OR 1.319, CI 1.093–1.593) and individuals with a positive family history for lung cancer (OR 1.251, CI 0.988–1.583). Multivariate analysis confirmed these results. CONCLUSION: Despite formal recommendations, chest radiography for screening purposes was a common practice among the analyzed sample of Greek adults. This practice is of questionable value since the positive predictive value of chest radiography is low. The implementation of even a relatively inexpensive imaging study on a national scale would greatly burden health economics and the workload of radiology departments

Emergency medical services preparedness in dual disasters: war in the era of COVID-19 in Armenia

Introduction: Emergency Medical Services (EMS) is a critical part of Disaster Medicine and has the ability to limit morbidity and mortality in a disaster event with sufficient training and experience. Emergency systems in Armenia are in an early stage of development and there is no Emergency Medicine residency training in the country. As a result, EMS physicians are trained in a variety of specialties. Armenia is also a country prone to disasters, and recently, the ArmenianEMSsystem was challenged by two concurrent disasters when the 2020 Nagorno-Karabakh War broke out in the midst of the SARS-CoV-2/coronavirus disease 2019 (COVID-19) pandemic. Study Objective: This study aims to assess the current state of disaster preparedness of the Armenian EMS system and the effects of the simultaneous pandemic and war on EMS providers. Methods: This was a cross-sectional study conducted by anonymous survey distributed to physicians still working in the Yerevan EMS system who provided care to war casualties and COVID-19 patients. Results: Survey response rate was 70.6%.Most participants had been a physician (52.1%) or EMS physician (66.7%) for three or less years. The majority were still in residency (64.6%). Experience in battlefield medicine was limited prior to the war, with the majority reporting no experience in treating mass casualties (52.1%), wounds from explosives (52.1%), or performing surgical procedures (52.1%), and many reporting minimal to no experience in treating gunshot wounds (62.5%), severe burns (64.6%), and severe orthopedic injuries (64.6%). Participants had moderate experience in humanitarian medicine prior to war. Greater experience in battlefield medicine was found in participants with more than three years of experience as a physician (z-score −3.26; P value <.01) or as anEMS physician (z-score −2.76; P value <.01) as well as being at least 30 years old (z-score −2.11; P value = .03). Most participants felt they were personally in danger during the war at least sometimes (89.6%). Conclusion: Prior to the COVID-19 pandemic and simultaneous 2020 Nagorno-Karabakh War, EMS physicians in Armenia had limited training and experience in Disaster Medicine. This system, and the frontline physicians on whom it relies, was strained by the dual disaster, highlighting the need for Disaster Medicine training in all prehospital medical providers

The oncogene AAMDC links PI3K-AKT-mTOR signaling with metabolic reprograming in estrogen receptor-positive breast cancer

Adipogenesis associated Mth938 domain containing (AAMDC) represents an uncharacterized oncogene amplified in aggressive estrogen receptor-positive breast cancers. We uncover that AAMDC regulates the expression of several metabolic enzymes involved in the one-carbon folate and methionine cycles, and lipid metabolism. We show that AAMDC controls PI3K-AKT-mTOR signaling, regulating the translation of ATF4 and MYC and modulating the transcriptional activity of AAMDC-dependent promoters. High AAMDC expression is associated with sensitization to dactolisib and everolimus, and these PI3K-mTOR inhibitors exhibit synergistic interactions with anti-estrogens in IntClust2 models. Ectopic AAMDC expression is sufficient to activate AKT signaling, resulting in estrogen-independent tumor growth. Thus, AAMDC-overexpressing tumors may be sensitive to PI3K-mTORC1 blockers in combination with anti-estrogens. Lastly, we provide evidence that AAMDC can interact with the RabGTPase-activating protein RabGAP1L, and that AAMDC, RabGAP1L, and Rab7a colocalize in endolysosomes. The discovery of the RabGAP1L-AAMDC assembly platform provides insights for the design of selective blockers to target malignancies having the AAMDC amplification

Violent Recidivism: A Long-Time Follow-Up Study of Mentally Disordered Offenders

Background: In this prospective study, mentally disordered perpetrators of severe violent and/or sexual crimes were followed through official registers for 59 (range 8 to 73) months. The relapse rate in criminality was assessed, compared between offenders sentenced to prison versus forensic psychiatric care, and the predictive ability of various risk factors (criminological, clinical, and of structured assessment instruments) was investigated. Method: One hundred perpetrators were consecutively assessed between 1998 and 2001 by a clinical battery of established instruments covering DSM-IV diagnoses, psychosocial background factors, and structured assessment instruments (HCR-20, PCL-R, and life-time aggression (LHA)). Follow-up data was collected from official registers for: (i) recidivistic crimes, (ii) crimes during ongoing sanction. Results: Twenty subjects relapsed in violent criminality during ongoing sanctions (n = 6) or after discharge/parole (n = 14). Individuals in forensic psychiatric care spent significantly more time at liberty after discharge compared to those in prison, but showed significantly fewer relapses. Criminological (age at first conviction), and clinical (conduct disorder and substance abuse/dependence) risk factors, as well as scores on structured assessment instruments, were moderately associated with violent recidivism. Logistic regression analyses showed that the predictive ability of criminological risk factors versus clinical risk factors combined with scores from assessment instruments was comparable, with each set of variables managing to correctly classify about 80% of all individuals, but the only predictors that remained significant in multiple models were criminological (age at first conviction, and a history of substance abuse among primary relatives). Conclusions: Only one in five relapsed into serious criminality, with significantly more relapses among subjects sentenced to prison as compared to forensic psychiatric care. Criminological risk factors tended to be the best predictors of violent relapses, while few synergies were seen when the risk factors were combined. Overall, the predictive validity of common risk factors for violent criminality was rather weak

Early Last Interglacial ocean warming drove substantial ice mass loss from Antarctica

The future response of the Antarctic ice sheet to rising temperatures remains highly uncertain. A useful period for assessing the sensitivity of Antarctica to warming is the Last Interglacial (LIG) (129 to 116 ky), which experienced warmer polar temperatures and higher global mean sea level (GMSL) (+6 to 9 m) relative to present day. LIG sea level cannot be fully explained by Greenland Ice Sheet melt (∼2 m), ocean thermal expansion, and melting mountain glaciers (∼1 m), suggesting substantial Antarctic mass loss was initiated by warming of Southern Ocean waters, resulting from a weakening Atlantic meridional overturning circulation in response to North Atlantic surface freshening. Here, we report a blue-ice record of ice sheet and environmental change from the Weddell Sea Embayment at the periphery of the marine-based West Antarctic Ice Sheet (WAIS), which is underlain by major methane hydrate reserves. Constrained by a widespread volcanic horizon and supported by ancient microbial DNA analyses, we provide evidence for substantial mass loss across the Weddell Sea embayment during the LIG, most likely driven by ocean warming and associated with destabilization of subglacial hydrates. Ice sheet modeling supports this interpretation and suggests that millennial-scale warming of the Southern Ocean could have triggered a multimeter rise in global sea levels. Our data indicate that Antarctica is highly vulnerable to projected increases in ocean temperatures and may drive ice–climate feedbacks that further amplify warming

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

Relative sea-level rise around East Antarctica during Oligocene glaciation

During the middle and late Eocene (∼48-34 Myr ago), the Earth's climate cooled and an ice sheet built up on Antarctica. The stepwise expansion of ice on Antarcticainduced crustal deformation and gravitational perturbations around the continent. Close to the ice sheet, sea level rosedespite an overall reduction in the mass of the ocean caused by the transfer of water to the ice sheet. Here we identify the crustal response to ice-sheet growth by forcing a glacial-hydro isostatic adjustment model with an Antarctic ice-sheet model. We find that the shelf areas around East Antarctica first shoaled as upper mantle material upwelled and a peripheral forebulge developed. The inner shelf subsequently subsided as lithosphere flexure extended outwards from the ice-sheet margins. Consequently the coasts experienced a progressive relative sea-level rise. Our analysis of sediment cores from the vicinity of the Antarctic ice sheet are in agreement with the spatial patterns of relative sea-level change indicated by our simulations. Our results are consistent with the suggestion that near-field processes such as local sea-level change influence the equilibrium state obtained by an icesheet grounding line

Risk thresholds for alcohol consumption : combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Background Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12.5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5.6 years [5th-95th percentile 1.04-13.5]) from 71 011 participants from 37 studies. Findings In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5.4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1.14, 95% CI, 1.10-1.17), coronary disease excluding myocardial infarction (1.06, 1.00-1.11), heart failure (1.09, 1.03-1.15), fatal hypertensive disease (1.24, 1.15-1.33); and fatal aortic aneurysm (1.15, 1.03-1.28). By contrast, increased alcohol consumption was loglinearly associated with a lower risk of myocardial infarction (HR 0.94, 0.91-0.97). In comparison to those who reported drinking >0-100-200-350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively. Interpretation In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe