Anticholinergic and Sedative Medications Are Associated With Neurocognitive Performance of Well Treated People With Human Immunodeficiency Virus.

Background We previously showed that anticholinergic (ACH) medications contribute to self-reported neurocognitive impairment (NCI) in elderly people with human immunodeficiency virus (PWH). The current cross-sectional study further evaluated the effect of ACH and sedative drugs on neurocognitive function in PWH who underwent comprehensive neuropsychological evaluation. Methods A medication review was performed in PWH enrolled in the prospective Neurocognitive Assessment in Metabolic and Aging Cohort within the Swiss HIV Cohort Study. Neurocognitive functions were analyzed in 5 domains (motor skills, speed of information, attention/working memory, executive functions, and verbal learning memory). The effect of ACH and sedative medications on neurocognitive functioning was evaluated using linear regression models for the continuous (mean z-score) outcome and multivariable logistic regression models for the binary (presence/absence) outcome. Results A total of 963 PWH (80% male, 92% Caucasian, 96% virologically suppressed, median age 52) were included. Fourteen percent of participants were prescribed ≥1 ACH medication and 9% were prescribed ≥1 sedative medication. Overall, 40% of participants had NCI. Sedative medication use was associated with impaired attention/verbal learning and ACH medication use with motor skills deficits both in the continuous (mean z-score difference -0.26 to -0.14, P < .001 and P = .06) and binary (odds ratio [OR], ≥1.67; P < .05) models. Their combined use was associated with deficits in overall neurocognitive functions in both models (mean z-score difference -0.12, P = .002 and OR = 1.54, P = .03). These associations were unchanged in a subgroup analysis of participants without depression (n = 824). Conclusions Anticholinergic and sedative medications contribute to NCI. Clinicians need to consider these drugs when assessing NCI in PWH

X-chromosome and kidney function:evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.</p

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Conclusions Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome

Évaluation des travaux pratiques de sciences physiques et chimiques en classe de seconde

Professorat des collèges et lycéesLes sciences physiques et chimiques sont des sciences expérimentales par excellence. Elles nécessitent un enseignement basé sur l'observation et l’interprétation des phénomènes expérimentaux. Comme les élèves en classe de seconde ne se destinent pas tous à des études scientifiques, réussir à les intéresser est un véritable challenge. L’évaluation des séances de travaux pratiques ne permettrait-elle pas d’atteindre cet objectif ? Elle semble en outre intéressante car elle permet d’apprécier des connaissances et également des compétences. Pour qu’elle se fasse dans de bonnes conditions, il est important de choisir des supports appropriés et de définir précisément les critères d’évaluation. Bien que l’évaluation présente des inconvénients, ces derniers sont estompés par des avantages aux conséquences plus substantielles

Towards a less stringent groundwater body objective? Feedback from a French heavily industrial and urban study area

International audienceGroundwater Directive 2006/118/EC (Daughter to Water Framework Directive 2000/60/EC) establishes specific measures in order to prevent and control groundwater pollution. It specifically requires to assess plumes originating from punctual sources such as those due to industrial activities, in order to check if they do not spread and degrade the chemical state of the groundwater bodies. In 2012-2013, BRGM (French Geological Survey) supported by the AERMC (Water Agency on the Mediterranean Rhone River basin) carried out a study to assess the impact of industrial activities on the quality of groundwater bodies in the Rhône river basin. It enables to identify 10 groundwater bodies which were at risk of not reaching the groundwater environmental quality target set by the French application of the Groundwater Framework Directive. Some of these groundwater bodies impacted by persistent and widely spread contaminants such as chlorinated solvents are very unlikely to recover groundwater quality standard by 2027. In this context, AERMC and the BRGM initiated an innovative project in order to define a methodological framework to justify for an exemption of the current groundwater quality objectives and the possibility to propose a less stringent groundwater objective

Efeito do envelhecimento na secreção de vasopressina (VP) e na ingestão hídrica: interação central entre apelina e o neurotransmissor óxido nítrico (NO)

O trabalho executado no programa de iniciação científica se deu na elaboração de uma revisão bibliográfica. Os objetivos da revisão foram descrever a relação entre Angiotensina II (Ang II) e adipocina anti-inflamatória apelina, verificar a provável relação entre apelina e o SARS-CoV-2 e identificar o possível papel da apelina em indivíduos obesos e idosos infectados pelo SARS-CoV-2. O surto de Síndrome Respiratória Aguda Grave Coronavírus 2 (SARS-CoV-2) atingiu o status de pandemia, que ficou conhecida como COVID-19. O SARS-CoV-2 age além do sistema respiratório e tem ações sistêmicas no SNC, renal e cardiovascular e apresenta associação ao Sistema Renina-Angiotensina-Aldosterona. A Ang II regula a pressão arterial e o equilíbrio hidro-eletrolítico. A porta de entrada para o vírus acontece pela ligação da ECA2. A degradação da Ang II em Ang 1-7 depende da ECA 2, como consequência, maior quantidade de Ang II favorecendo reações inflamatórias. Foi observada a alta taxa de óbitos em indivíduos obesos e idosos. A revisão busca entender porque esses indivíduos são mais suscetíveis e apresentam quadros inflamatórios mais severos. A resposta imunológica causada pela infecção leva a um quadro conhecido como tempestade de citocinas. Estudos apontam que a apelina, com propriedades anti-inflamatórias, pode ajudar na recuperação contra covid-19. A apelina exibe potencial tratamento para COVID-19, por meio da supressão da produção de ECA e Ang-II. Em indivíduos obesos, apesar dos mecanismos permanecerem desconhecidos, a alteração na produção de adipocinas, incluindo a apelina, é um mecanismo em potencial para explicar o efeito na gravidade da infecção. A obesidade está associada à maior produção de ANG II e na alteração da expressão da ECA2, consequentemente um acúmulo de ang II e maior estímulo a reações hiper inflamatórias. A ECA2 está expressa no tecido adiposo, possivelmente, o excesso de adiposidade leva a uma maior severidade da infecção. O SARS-CoV-2 ao inibir a ECA2 potencializaria a inflamação já existente nesses indivíduos. No que se sabe sobre o envelhecimento, a ideia de que fatores associados à idade, como a ativação crônica do SRAA, regulam negativamente o sistema apelinérgico e estão relacionados ao mau prognóstico e a maior taxa de óbitos em idosos infectados. A função do sistema apelinérgico durante o envelhecimento está reduzida. É reconhecido que a apelina é importante na indução da sede. O envelhecimento está relacionado ao aumento dos níveis de citocinas pró-inflamatórias e redução dos níveis de citocinas anti-inflamatórias. Os desequilíbrios eletrolíticos foram descritos em mais da metade dos casos de hospitalização. Os distúrbios mais ocorrentes são: a hiponatremia e a síndrome de secreção inapropriada do hormônio antidiurético. Indivíduos obesos e idosos infectados pelo SARS-CoV-2 podem apresentar alta taxa de óbitos relacionado à disfunção do sistema apelinérgico. Por ora, é preciso realizar mais estudos para que essa hipótese seja comprovada

Geochemical and Visual Indicators of Hydrothermal Fluid Flow through a Sediment-Hosted Volcanic Ridge in the Central Bransfield Basin (Antarctica)

In the austral summer of 2011 we undertook an investigation of three volcanic highs in the Central Bransfield Basin, Antarctica, in search of hydrothermal activity and associated fauna to assess changes since previous surveys and to evaluate the extent of hydrothermalism in this basin. At Hook Ridge, a submarine volcanic edifice at the eastern end of the basin, anomalies in water column redox potential (Eh) were detected close to the seafloor, unaccompanied by temperature or turbidity anomalies, indicating low-temperature hydrothermal discharge. Seepage was manifested as shimmering water emanating from the sediment and from mineralised structures on the seafloor; recognisable vent endemic fauna were not observed. Pore fluids extracted from Hook Ridge sediment were depleted in chloride, sulfate and magnesium by up to 8% relative to seawater, enriched in lithium, boron and calcium, and had a distinct strontium isotope composition (87Sr/86Sr = 0.708776 at core base) compared with modern seawater (87Sr/86Sr ?0.70918), indicating advection of hydrothermal fluid through sediment at this site. Biogeochemical zonation of redox active species implies significant moderation of the hydrothermal fluid with in situ diagenetic processes. At Middle Sister, the central ridge of the Three Sisters complex located about 100 km southwest of Hook Ridge, small water column Eh anomalies were detected but visual observations of the seafloor and pore fluid profiles provided no evidence of active hydrothermal circulation. At The Axe, located about 50 km southwest of Three Sisters, no water column anomalies in Eh, temperature or turbidity were detected. These observations demonstrate that the temperature anomalies observed in previous surveys are episodic features, and suggest that hydrothermal circulation in the Bransfield Strait is ephemeral in nature and therefore may not support vent biota

Epigenome-wide association studies identify DNA methylation associated with kidney function

Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex. Lead CpGs at PTPN6/PHB2, ANKRD11, and TNRC18 map to active enhancers in kidney cortex. At PTPN6/PHB2 cg19942083, methylation in kidney cortex associates with lower renal PTPN6 expression, higher eGFR, and less renal fibrosis. The regions containing the 243 eGFR-associated (P < 1e-05) CpGs are significantly enriched for transcription factor binding sites of EBF1, EP300, and CEBPB (P < 5e-6). Our findings highlight kidney function associated epigenetic variation

Application of systematic reviews in speech-and-language therapy

Background: Systematic reviews are increasingly being carried out in speech-and-language therapy and are used by practitioners, service commissioners, policy-makers and researchers to inform decision-making, as the body of evidence available about speech-and-language therapy grows. Although systematic reviewing is developing to incorporate new methods of review and synthesis, there are currently limitations in the use of some types of systematic reviews within speech-and-language therapy. Aims: The purpose of this paper is to provide an overview of the steps involved in the systematic review process and the range of options available. It highlights some challenges to using this process in speech-and-language therapy, with examples based in part on the authors' experiences of involvement in two systematic reviews. A number of developments in systematic review methodology will be outlined and several new approaches to reviewing, both within and outside of speech-and-language therapy, are introduced. These include realist synthesis, evidence-based practice briefs, speech BITE™ and the journal Evidence-Based Communication Assessment and Intervention. Main contribution: This paper highlights some of the current benefits and limitations of systematic reviews in speech-and-language therapy. It will facilitate readers to use and carry out systematic reviews in the speech-and-language therapy field. Conclusions: Systematic reviews are useful in speech-and-language therapy, but awareness of their limitations is important to practitioners, commissioners, policy-makers and researchers. New developments may further increase the benefits of systematic reviews