HPA axis related genes and response to psychological therapies: genetics and epigenetics

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner

The utility of the SCAS-C/P to detect specific anxiety disorders among clinically anxious children

Questionnaire measures offer a time and cost-effective alternative to full diagnostic assessments for identifying and differentiating between potential anxiety disorders and are commonly used in clinical practice. Little is known, however, about the capacity of questionnaire measures to detect specific anxiety disorders in clinically anxious preadolescent children. This study aimed to establish the ability of the Spence Children’s Anxiety Scale (SCAS) subscales to identify children with specific anxiety disorders in a large clinic-referred sample (N = 1,438) of children aged 7 to 12 years. We examined the capacity of the Separation Anxiety, Social Phobia, Generalized Anxiety, and Physical Injury Fears (phobias) subscales to discriminate between children with and without the target disorder. We also identified optimal cutoff scores on subscales for accurate identification of children with the corresponding disorder, and examined the contribution of child, mother, and father reports. The Separation Anxiety subscale was able to accurately identify children with separation anxiety disorder, and this was replicated across all 3 reporters. Mother- and father-reported Social Phobia subscales also accurately identified children with social anxiety disorder, although child report was only able to accurately detect social anxiety disorder in girls. Using 2 or more reporters improved the sensitivity of the Separation Anxiety and Social Phobia subscales but reduced specificity. The Generalized Anxiety and Physical Injury Fears subscales failed to accurately identify children with the corresponding disorders. These findings have implications for the potential use of mother-, father-, and child-report SCAS subscales to detect specific disorders in preadolescent children in clinical settings

Risk Factors for Marburg Hemorrhagic Fever, Democratic Republic of the Congo

We conducted two antibody surveys to assess risk factors for Marburg hemorrhagic fever in an area of confirmed Marburg virus transmission in the Democratic Republic of the Congo. Questionnaires were administered and serum samples tested for Marburg-specific antibodies by enzyme-linked immunosorbent assay. Fifteen (2%) of 912 participants in a general village cross-sectional antibody survey were positive for Marburg immunoglobulin G antibody. Thirteen (87%) of these 15 were men who worked in the local gold mines. Working as a miner (odds ratio [OR] 13.9, 95% confidence interval [CI] 3.1 to 62.1) and receiving injections (OR 7.4, 95% CI 1.6 to 33.2) were associated with a positive antibody result. All 103 participants in a targeted antibody survey of healthcare workers were antibody negative. Primary transmission of Marburg virus to humans likely occurred via exposure to a still unidentified reservoir in the local mines. Secondary transmission appears to be less common with Marburg virus than with Ebola virus, the other known filovirus

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Influence of the synthesis route on sol–gel SiO2–TiO2 (1:1) xerogels and powders

International audienceFive different sol–gel routes are used in order to synthesize mixed SiO2–TiO2 materials. Simple mixing of the Ti and Si precursors, prehydrolyzing of TEOS, modification of the Ti alkoxide with acetic acid, isoamyl alcohol and acetylacetone lead to translucent gels with different time of gelation. Different techniques such as TGA, DTA, XRD and IR spectroscopy are used to characterize each material. IR spectroscopy revealed the presence of Si–O–Ti and Si–O–Si bonds for all the xerogels letting suppose a composite microstructure of the gels. Pre-hydrolyzing of TEOS and modification of Ti alkoxide with isoamyl alcohol are the most appropriate routes to retain the anatase phase up to 1100 8C

Mixed SiO2–TiO2 (1:1) sol–gel films on mild steel substrates: Sol composition and thermal treatment effects

International audienceMixed SiO2–TiO2 (1:1) sol–gel films have been deposited on mild steel substrates by spin coating. Different sol compositions have been realised and all of them have produced transparent and electrically non conductive films except in the case of high acidic sol. Special attention has been paid on the thermal treatment (in air) of those films. Evolution of the microstructure of the films with thermal treatment have been characterised by scanning electron microscopy (SEM), glancing incidence X-ray diffraction (GIXD), atomic force microscopy (AFM) and X-ray reflectometry (XRR). Electrical insulating behaviour and micro-hardness evolution have been evaluated. In order to avoid the creation and the diffusion of the oxide substrate layer leading to the destruction of the sol–gel films, the main parameter to control is then the couple time/ temperature of the thermal treatmen

Evolution of the structure with the composition and the defect arrangement in the gadolinium and samarium doped and co-doped ceria systems: A molecular dynamics study

International audience<div id="as0005"&gt<p id="sp0075"&gtWe investigate the evolution of the <a href="https://www.sciencedirect.com/topics/engineering/fluorite" title="Learn more about fluorite from ScienceDirect's AI-generated Topic Pages" class="topic-link"&gtfluorite</a&gt structure in the Ce<sub&gt1-x</sub&gtM<sub&gtx</sub&gtO<sub&gt2-x/2</sub&gt system with Gd and Sm as <a href="https://www.sciencedirect.com/topics/chemistry/lanthanoid-atom" title="Learn more about Rare Earth from ScienceDirect's AI-generated Topic Pages" class="topic-link"&gtRare Earth</a&gt (RE) doping cations and Gd/Sm as co-doping couple using Molecular Dynamics at 298&nbsp;K. Doping cations and <a href="https://www.sciencedirect.com/topics/engineering/oxygen-vacancy" title="Learn more about oxygen vacancies from ScienceDirect's AI-generated Topic Pages" class="topic-link"&gtoxygen vacancies</a&gt are introduced in the CeO<sub&gt2</sub&gt fluorite lattice through two different arrangements the Random one and the Neighbour one. The evolution of the lattice parameter is compared with different models and experimental data extracted from the literature. Results concerning the chemical expansion and the oxygen vacancy radius are commented. The calculation of the <a href="https://www.sciencedirect.com/topics/engineering/radial-distribution-function" title="Learn more about Radial Distribution Function from ScienceDirect's AI-generated Topic Pages" class="topic-link"&gtRadial Distribution Function</a&gt (RDF) allows to observe two components for the Ce-Ce, Ce-M and M-M (M&nbsp;=&nbsp;Gd, Sm, Gd/Sm) bond length as it is the case in the C-type RE<sub&gt2</sub&gtO<sub&gt3</sub&gt structure. The <a href="https://www.sciencedirect.com/topics/physics-and-astronomy/percolation" title="Learn more about percolation from ScienceDirect's AI-generated Topic Pages" class="topic-link"&gtpercolation</a&gt concept is introduced and discussed based on the evolution of the M-M group size distribution and the M-O coordination number.</p&gt</div&g

Molecular dynamics study in the Ce0.9M0.1O1.95 (M=Gd, Sm) doped and co-doped CeO2 systems: Structure and oxygen diffusion

International audienceDoped ceria is known for its high ionic conductivity which is limited by the creation of defect clusters. We investigate using Molecular Dynamics the evolution of the structure and oxygen diffusivity of the Ce0.9M0.1O1.95 (M = Gd, Sm) doped and co-doped CeO2 systems. Two configurations concerning the introduction of the doping ions and oxygen vacancies inside the structure are generated and compared, the random one (R) and the neighbor one (N). The pair potential parameter set is chosen among three sets by comparison with experimental data. The pair correlation function first peak is fitted by a lognormal function to take into account the asymmetry. The evolution of the coefficient of thermal expansion, the coordination number and the bond lengths of the different ion pairs with the temperature, is presented. The influence of the local C-type sesquioxide M2O3 structure on those parameters is discussed. No significant positive co-doping effect on the oxygen diffusion process is revealed. The random configuration of the defects leads to the highest oxygen diffusivity and to the lower activation energy whatever the doping ion (Gd, Sm or Gd/Sm)

X-ray diffractometry analysis of r.f.-magnetron-sputtered chromium/chromium nitride coatings

The eVect of nitrogen content on the microstructure of chromium-based coatings deposited by r.f. magnetron sputtering was studied using various X-ray diVraction techniques. Cr, Cr2N and CrN were the major phases identified, respectively, for 5, 34 and 50 at.% by recording h/2h and glancing incidence (1°) scans. Between these well- identified crystallographic structures, we have noted a peak broadening with poor intensities that could be interpreted as mixtures of Cr, Cr2N and/or Cr(N) phases. The influence of nitrogen on the preferred crystal orientation of the films was investigated. Highly textured Cr(110) and CrN (111) were evidenced, and texture was found to be a function of nitrogen content in the sputtering atmosphere. Finally, the Langford method was applied for line profile analyses leading to results concerning crystallite sizes and strains

X-Ray reflectometry study of diamond-like carbon films obtained by plasma-assisted chemical vapor deposition

X-Ray reflectivity is used to determine the electron density profiles normal to the surface of diamond-like carbon DLC films Ž . prepared by plasma-enhanced chemical vapor deposition PE-CVD . Average values of the scattering lengths obtained from the Ž . specular reflection data and elastic recoil detection analysis ERDA hydrogen measurements are used to calculate the average mass density of the films. The density is shown to be strongly dependent on the hydrogen content. This depends on the plasma parameters. Argon diluted methane plasma produces homogeneous DLC films but generally with a lower density than the films prepared from pure or He diluted plasmas. These later plasmas produce films with a high density contrast and higher densities