Association of Epigenetic Age and Outcome in Critically Ill Patients

OBJECTIVES: DNA methylation can be used to determine an individual’s biological age, as opposed to chronological age, an indicator of underlying health status. This study aimed to assess epigenetic age in critically ill patients with and without sepsis to determine if higher epigenetic age is associated with admission diagnosis or mortality.DESIGN: Secondary analysis of whole blood DNA methylation data generated from a nested case–control study of critically ill septic and nonseptic patients.SETTING: Four tertiary care hospitals in Canada.INTERVENTIONS: None.PATIENTS: Critically ill patients with and without sepsis.MEASUREMENTS AND MAIN RESULTS: Epigenetic age was derived from DNA methylation data using the Hannum and PhenoAge algorithms and deviation from the patient’s chronological age in years was determined. Of the 66 patients with sepsis, 34 were male (51.5%), the mean age was 65.03 years and 25 patients (37.8%) died before discharge. Of the 68 nonseptic patients, 47 were male (69.1%), the mean age was 64.92 years and 25 (36.7%) died before discharge. Epigenetic age calculated using the PhenoAge algorithm showed a significant age acceleration of 4.97 years in septic patients (p = 0.045), but no significant acceleration in nonseptic patients. Epigenetic age calculated using the Hannum algorithm showed no significant acceleration in the septic or nonseptic patients. Similarly, in the combined septic and nonseptic cohorts, nonsurvivors showed an epigenetic age acceleration of 7.62 years (p = 0.004) using the PhenoAge algorithm while survivors showed no significant age acceleration. Survivor status was not associated with age acceleration using the Hannum algorithm.CONCLUSIONS: In critically ill patients, epigenetic age acceleration, as calculated by the PhenoAge algorithm, was associated with sepsis diagnosis and mortality

Herschel observations of EXtraordinary Sources: Analysis of the full Herschel/HIFI molecular line survey of Sagittarius B2(N)

A sensitive broadband molecular line survey of the Sagittarius B2(N) star-forming region has been obtained with the HIFI instrument on the Herschel Space Observatory, offering the first high-spectral resolution look at this well-studied source in a wavelength region largely inaccessible from the ground (625-157 um). From the roughly 8,000 spectral features in the survey, a total of 72 isotopologues arising from 44 different molecules have been identified, ranging from light hydrides to complex organics, and arising from a variety of environments from cold and diffuse to hot and dense gas. We present an LTE model to the spectral signatures of each molecule, constraining the source sizes for hot core species with complementary SMA interferometric observations, and assuming that molecules with related functional group composition are cospatial. For each molecule, a single model is given to fit all of the emission and absorption features of that species across the entire 480-1910 GHz spectral range, accounting for multiple temperature and velocity components when needed to describe the spectrum. As with other HIFI surveys toward massive star forming regions, methanol is found to contribute more integrated line intensity to the spectrum than any other species. We discuss the molecular abundances derived for the hot core, where the local thermodynamic equilibrium approximation is generally found to describe the spectrum well, in comparison to abundances derived for the same molecules in the Orion KL region from a similar HIFI survey.Comment: Accepted to ApJ. 64 pages, 14 figures. Truncated abstrac

How people with dementia and their families decide about moving to a care home and support their needs: development of a decision aid, a qualitative study

yesBackground: People with dementia and their relatives find decisions about the person with dementia living in a care home difficult. Methods: We interviewed 20 people with dementia or family carers around the time of this decision in order to design a decision-aid. Results: Decision-makers balanced the competing priorities of remaining somewhere familiar, family’s wish they remain at home, reduction of risk and effects on carer’s and person with dementia’s physical health. The person with dementia frequently resented their lack of autonomy as decisions about care home moves were made after insight and judgment were impaired. Family consultation usually helped carers but sometimes exacerbated tensions. Direct professional support was appreciated where it was available. There is a need for healthcare professionals to facilitate these conversations around decision-making and to include more than signposting to other organisations. Conclusions: There is a need for a healthcare professional facilitated decision-aid. This should detail what might change for the person with dementia and their carer, possible resources and alternatives and assist in facilitating discussion with the wider family; further research will develop and test a tool to facilitate decision making about place of care needs

La gestion des médicaments dans les simulations en établissement de santé

Objectif : Développer une politique et des procédures pour la gestion des médicaments réels et factices utilisés dans les simulations et la formation du personnel au Centre hospitalier universitaire Sainte-Justine. Description de la problématique : Plusieurs simulations et formations ont lieu au Centre hospitalier universitaire Sainte-Justine chaque année. Les gestionnaires du département de pharmacie reçoivent plusieurs demandes pour des médicaments réels ou factices malgré l’existence d’une politique et des procédures sur les simulations à l’hôpital. La décision quant au type de matériel à fournir leur revient. La procédure à appliquer doit être uniformisée pour permettre un accès équitable entre les divers secteurs, mais également pour assurer la sécurité du personnel et des patients. Résolution de la problématique : Nous avons d’abord effectué une revue de littérature pour comprendre les enjeux liés à la gestion des médicaments réels ou factices lors d’une simulation. Ensuite, nous avons fait des entrevues avec des pharmaciens participant aux simulations dans les centres hospitaliers universitaires, des gestionnaires des centres d’enseignement et des représentants des ordres professionnels pour dresser un portrait de la situation au Québec. Enfin, nous avons rédigé une politique ainsi qu’un algorithme décisionnel résumé. Conclusion : L’utilisation de médicaments dans les simulations est bénéfique, mais comporte des risques. Le choix de représentation médicamenteuse doit donc être évalué pour chaque simulation et tenir compte du but de l’exercice, des risques associés à chaque type de représentation médicamenteuse et de l’endroit où se déroule la simulation. Abstract Objective: To develop policies and procedures for managing real and mock medication used in simulation-based trainings at the Centre hospitalier universitaire Sainte-Justine and to create a decision-tree algorithm for the type of medication to supply. Problem description: Many simulation-based training sessions take place at the Centre hospitalier universitaire Sainte-Justine every year. Despite the existence of policies and procedures on simulation-based training at the hospital, members of the pharmacy department’s leadership teams receive a large number of requests for real and mock medication and therefore bear the responsibility to determine which type of supplies to provide. The procedure should be standardized to allow equitable access between departments, but also to ensure the safety of staff and patients. Problem resolution: First, we conducted a literature review to understand the issues associated with managing real and mock medication during simulation-based trainings. Furthermore, we conducted interviews with pharmacists involved in simulation-based trainings at the teaching hospitals, members of the pharmacy department’s leadership teams, and representatives from professional orders to obtain an overview of the situation in Quebec. Lastly, we drafted a policy and a summary decision-tree algorithm. Conclusion: The use of drugs in simulation-based trainings is beneficial, but it also entails certain risks. The type of medication to supply must therefore be evaluated for each simulation-based training and take into account the purpose of the training exercise, the risks associated with each type of medication, and the setting of the training

Quantification of upper body movements during gait in older adults and in those with Parkinson's disease: impact of acceleration realignment methodologies.

The upper body accelerations of people with Parkinson’s disease (PD) measured by inertial measurement units (IMUs) may contribute towards diagnostic algorithms and help track disease progression. Before extracting variables related to upper body motion, acceleration signals require realignment to a global reference; however, the impact of these techniques on the resulting upper body variables is unclear. Therefore, the aim of this investigation was to examine the impact of four different realignment methods designed to correct acceleration signals on a range of upper body variables in older adults and in patients with PD. Two minutes of continuous gait were measured in 54 community-dwelling older adults (71.1 �6.7 years) and 60 people with PD (age: 68.5 � 9.1 years). Three IMUs placed on the 5th lumbar vertebra, 7th cervical vertebra and the back of the head recorded the acceleration of the upper body. A selection of upper body variables sensitive to impaired upper body control in PD and four acceleration realignment methods were compared. A mixed-model ANOVA showed that the choice of realignment method significantly affected the values of upper body variables as well as their ability to discriminate between the PD and control group. Our findings indicate researchers and clinicians should be cautious when comparing upper body variables extracted from IMUs using different realignment methods, and consideration of realignmenttechnique will be important when identifying the most sensitive markers of disease presence and progression. Therefore, it’s strongly recommend that researchers consider and report their realignment methods when assessing upper body variables during gai

A psychosocial goal-setting and manualised support intervention for independence in dementia (NIDUS-Family) versus goal setting and routine care: a single-masked, phase 3, superiority, randomised controlled trial

BACKGROUND: Although national guidelines recommend that everyone with dementia receives personalised post-diagnostic support, few do. Unlike previous interventions that improved personalised outcomes in people with dementia, the NIDUS-Family intervention is fully manualised and deliverable by trained and supervised, non-clinical facilitators. We aimed to investigate the effectiveness of home-based goal setting plus NIDUS-Family in supporting the attainment of personalised goals set by people with dementia and their carers. METHODS: We did a two-arm, single-masked, multi-site, randomised, clinical trial recruiting patient-carer dyads from community settings. We randomly assigned dyads to either home-based goal setting plus NIDUS-Family or goal setting and routine care (control). Randomisation was blocked and stratified by site (2:1; intervention to control), with allocations assigned via a remote web-based system. NIDUS-Family is tailored to goals set by dyads by selecting modules involving behavioural interventions, carer support, psychoeducation, communication and coping skills, enablement, and environmental adaptations. The intervention involved six to eight video-call or telephone sessions (or in person when COVID-19-related restrictions allowed) over 6 months, then telephone follow-ups every 2-3 months for 6 months. The primary outcome was carer-rated goal attainment scaling (GAS) score at 12 months. Analyses were done by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN11425138. FINDINGS: Between April 30, 2020, and May 9, 2021, we assessed 1083 potential dyads for eligibility, 781 (72·1%) of whom were excluded. Of 302 eligible dyads, we randomly assigned 98 (32·4%) to the control group and 204 (67·5%) to the intervention group. The mean age of participants with dementia was 79·9 years (SD 8·2), 169 (56%) were women, and 133 (44%) were men. 247 (82%) dyads completed the primary outcome, which favoured the intervention (mean GAS score at 12 months 58·7 [SD 13·0; n=163] vs 49·0 [14·1; n=84]; adjusted difference in means 10·23 [95% CI 5·75-14·71]; p<0·001). 31 (15·2%) participants in the intervention group and 14 (14·3%) in the control group experienced serious adverse events. INTERPRETATION: To our knowledge, NIDUS-Family is the first readily scalable intervention for people with dementia and their family carers that improves attainment of personalised goals. We therefore recommend that it be implemented in health and care services. FUNDING: UK Alzheimer's Society

Reversal of infall in SgrB2(M) revealed by Herschel/HIFI observations of HCN lines at THz frequencies

To investigate the accretion and feedback processes in massive star formation, we analyze the shapes of emission lines from hot molecular cores, whose asymmetries trace infall and expansion motions. The high-mass star forming region SgrB2(M) was observed with Herschel/HIFI (HEXOS key project) in various lines of HCN and its isotopologues, complemented by APEX data. The observations are compared to spherically symmetric, centrally heated models with density power-law gradient and different velocity fields (infall or infall+expansion), using the radiative transfer code RATRAN. The HCN line profiles are asymmetric, with the emission peak shifting from blue to red with increasing J and decreasing line opacity (HCN to H$^{13}$CN). This is most evident in the HCN 12--11 line at 1062 GHz. These line shapes are reproduced by a model whose velocity field changes from infall in the outer part to expansion in the inner part. The qualitative reproduction of the HCN lines suggests that infall dominates in the colder, outer regions, but expansion dominates in the warmer, inner regions. We are thus witnessing the onset of feedback in massive star formation, starting to reverse the infall and finally disrupting the whole molecular cloud. To obtain our result, the THz lines uniquely covered by HIFI were critically important.Comment: A&A, HIFI special issue, accepte

A UK survey of COVID‐19 related social support closures and their effects on older people, people with dementia, and carers

Abstract Objectives The aim of this national survey was to explore the impact of COVID‐19 public health measures on access to social support services and the effects of closures of services on the mental well‐being of older people and those affected by dementia. Methods A UK‐wide online and telephone survey was conducted with older adults, people with dementia, and carers between April and May 2020.The survey captured demographic and postcode data, social support service usage before and after COVID‐19 public health measures, current quality of life, depression, and anxiety. Multiple linear regression analysis was used to explore the relationship between social support service variations and anxiety and well‐being. Results 569 participants completed the survey (61 people with dementia, 285 unpaid carers, and 223 older adults). Paired samples t‐tests and X2‐tests showed that the mean hour of weekly social support service usage and the number of people having accessed various services was significantly reduced post COVID‐19. Multiple regression analyses showed that higher variations in social support service hours significantly predicted increased levels of anxiety in people with dementia and older adults, and lower levels of mental well‐being in unpaid carers and older adults. Conclusions Being unable to access social support services due to COVID contributed to worse quality of life and anxiety in those affected by dementia and older adults across the UK. Social support services need to be enabled to continue providing support in adapted formats, especially in light of continued public health restrictions for the foreseeable future. This article is protected by copyright. All rights reserved

Overexpression of RAD51 suppresses recombination defects: a possible mechanism to reverse genomic instability

RAD51, a key protein in the homologous recombinational DNA repair (HRR) pathway, is the major strand-transferase required for mitotic recombination. An important early step in HRR is the formation of single-stranded DNA (ss-DNA) coated by RPA (a ss-DNA-binding protein). Displacement of RPA by RAD51 is highly regulated and facilitated by a number of different proteins known as the ‘recombination mediators’. To assist these recombination mediators, a second group of proteins also is required and we are defining these proteins here as ‘recombination co-mediators’. Defects in either recombination mediators or co-mediators, including BRCA1 and BRCA2, lead to impaired HRR that can genetically be complemented for (i.e. suppressed) by overexpression of RAD51. Defects in HRR have long been known to contribute to genomic instability leading to tumor development. Since genomic instability also slows cell growth, precancerous cells presumably require genomic re-stabilization to gain a growth advantage. RAD51 is overexpressed in many tumors, and therefore, we hypothesize that the complementing ability of elevated levels of RAD51 in tumors with initial HRR defects limits genomic instability during carcinogenic progression. Of particular interest, this model may also help explain the high frequency of TP53 mutations in human cancers, since wild-type p53 represses RAD51 expression

The ARUBA trial:current status, future hopes

Background and Purpose— Report on the status of an on-going National Institutes of Neurological Disorders and Stroke (NINDS)-supported clinical trial of management of unbled brain arteriovenous malformations. Summary of Review— Begun in April 2007 with 3 centers, the trial has grown to 65 centers, and has randomized 124 patients through mid-June 2010 en route to the planned 400. The current literature continues to support the rationale for the trial. Conclusions— ARUBA is steadily approaching its monthly randomization goals and has already reached the number needed to test the maximum published interventional complication rates against the minimum hemorrhage rates for natural history. </jats:p