Increased reaction times and reduced response preparation already starts at middle age

Generalized slowing characterizes aging and there is some evidence to suggest that this slowing already starts at midlife. This study aims to assess reaction time changes while performing a concurrent low-force and high-force motor task in young and middle-aged subjects. The high-force motor task is designed to induce muscle fatigue and thereby progressively increase the attentional demands. Twenty-five young (20-30 years, 12 males) and sixteen middle-aged (35-55 years, 9 males) adults performed an auditory two-choice reaction time task (CRT) with and without a concurrent low- or high-force motor task. The CRT required subjects to respond to two different stimuli that occurred with a probability of 70% or 30%. The motor task consisted of index finger abduction, at either 10% (10%-dual-task) or 30% (30%-dual-task) of maximal voluntary force. Cognitive task performance was measured as percentage of correct responses and reaction times.Middle-aged subjects responded slower on the frequent but more accurately on the infrequent stimuli of CRT than young subjects. Both young and middle-aged subjects showed increased errors and reaction times while performing under dual-task conditions and both outcome measures increased further under fatiguing conditions. Only under 30%-dual-task demands, an age-effect on dual-task performance was present. Both single- and dual-task conditions showed that already at mid-life response preparation is seriously declined and that subjects implement different strategies to perform a CRT task.<br/

Misidentification of meticillin-resistant Staphylococcus aureus by the Cepheid Xpert MRSA NxG assay, the Netherlands, February to March 2021

We describe two false-negative results in the detection of meticillin-resistant Staphylococcus aureus (MRSA) of sequence type 398 and spa type t011 using the Cepheid Xpert MRSA NxG assay. The isolates were recovered in late February and early March 2021 from two patients in different hospitals in the northern Netherlands. Variations between the two isolate genomes indicate that this MRSA strain might have been spreading for some time and could have disseminated to other regions of the Netherlands and other European countries

Chronic stressors and burnout in Dutch police officers: Two studies into the complex role of coping self-efficacy

IntroductionBurnout complaints are high for Dutch police officers. According to Hobfoll’s Conservation of Resources theory, resources such as coping self-efficacy can play an important role in the burnout process. The aim of this study was to investigate the buffering effect of coping self-efficacy on burnout, as well as a possible depletion effect of burnout on coping self-efficacy.MethodsAs such, this research consists of two studies namely, a two-wave study (N = 166) and three-wave study (N = 95) on Dutch police officers. They expand on previous research regarding coping resources and police burnout.ResultsBoth studies show that the chronic stressor, work scheduling, was positively associated with burnout. Also, coping self-efficacy weakened the effect of work scheduling (Study 1) and workload (Study 2) on burnout. Moreover, there was a direct negative relationship between burnout and coping self-efficacy.DiscussionThe results indicate that burnout can lead to lower coping resources, initiating a potential cycle of resource loss and burnout. Further investigation into this depletion effect is required to provide police officers and organisations with tools to prevent burnout

Daily Practice Experience of Baricitinib Treatment for Patients with Difficult-to-Treat Atopic Dermatitis:Results from the BioDay Registry

Clinical trials have shown that baricitinib, an oral selective Janus kinase 1/2 inhibitor, is effective for the treatment of moderate-to-severe atopic dermatitis. However, daily practice data are limited. Therefore, this multicentre prospective study evaluated the effectiveness and safety of 16-weeks' treatment with baricitinib in adult patients with moderate-to-severe atopic dermatitis in daily practice. A total of 51 patients from the BioDay registry treated with baricitinib were included and evaluated at baseline and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed using clinician- and patient-reported outcome measurements. Adverse events and laboratory assessments were evaluated at every visit. At week 16, the probability (95% confidence interval) of achieving Eczema Area and Severity Index ≤ 7 and numerical rating scale pruritus ≤ 4 was 29.4% (13.1-53.5) and 20.5% (8.8-40.9), respectively. No significant difference in effectiveness was found between dupilumab non-responders and responders. Twenty-two (43.2%) patients discontinued baricitinib treatment due to ineffectiveness, adverse events or both (31.4%, 9.8% and 2.0%, respectively). Most frequently reported adverse events were nausea (n = 6, 11.8%), urinary tract infection (n = 5, 9.8%) and herpes simplex infection (n = 4, 7.8%). In conclusion, baricitinib can be an effective treatment option for moderate-to-severe atopic dermatitis, including patients with non-responsiveness on dupilumab. However, effectiveness of baricitinib is heterogeneous, which is reflected by the high discontinuation rate in this difficult-to-treat cohort

Preventing socioeconomic inequalities in health behaviour in adolescents in Europe: Background, design and methods of project TEENAGE

Background Higher prevalence rates of unhealthy behaviours among lower socioeconomic groups contribute substantially to socioeconomic inequalities in health in adults. Preventing the development of these inequalities in unhealthy behaviours early in life is an important strategy to tackle socioeconomic inequalities in health. Little is known however, about health promotion strategies particularly effective in lower socioeconomic groups in youth. It is the purpose of project TEENAGE to improve knowledge on the prevention of socioeconomic inequalities in physical activity, diet, smoking and alcohol consumption among adolescents in Europe. This paper describes the background, design and methods to be used in the project. Methods/design Through a systematic literature search, existing interventions aimed at promoting physical activity, a healthy diet, preventing the uptake of smoking or alcohol, and evaluated in the general adolescent population in Europe will be identified. Studies in which indicators of socioeconomic position are included will be reanalysed by socioeconomic position. Results of such stratified analyses will be summarised by type of behaviour, across behaviours by type of intervention (health education, environmental interventions and policies) and by setting (individual, household, school, and neighbourhood). In addition, the degree to which effective interventions can be transferred to other European countries will be assessed. Discussion Although it is sometimes assumed that some health promotion strategies may be particularly effective in higher socioeconomic groups, thereby increasing socioeconomic inequalities in health-related behaviour, there is little knowledge about differential effects of health promotion across socioeconomic groups. Synthesizing stratified analyses of a number of interventions conducted in the general adolescent population may offer an efficient guidance for the development of strategies and interventions to prevent socioeconomic inequalities in health early in life

Chronic stressors and burnout in Dutch police officers: Two studies into the complex role of coping self-efficacy

INTRODUCTION: Burnout complaints are high for Dutch police officers. According to Hobfoll's Conservation of Resources theory, resources such as coping self-efficacy can play an important role in the burnout process. The aim of this study was to investigate the buffering effect of coping self-efficacy on burnout, as well as a possible depletion effect of burnout on coping self-efficacy. METHODS: As such, this research consists of two studies namely, a two-wave study ( N  = 166) and three-wave study ( N  = 95) on Dutch police officers. They expand on previous research regarding coping resources and police burnout. RESULTS: Both studies show that the chronic stressor, work scheduling, was positively associated with burnout. Also, coping self-efficacy weakened the effect of work scheduling (Study 1) and workload (Study 2) on burnout. Moreover, there was a direct negative relationship between burnout and coping self-efficacy. DISCUSSION: The results indicate that burnout can lead to lower coping resources, initiating a potential cycle of resource loss and burnout. Further investigation into this depletion effect is required to provide police officers and organisations with tools to prevent burnout

Real-world Experience of Abrocitinib Treatment in Patients with Atopic Dermatitis and Hand Eczema:Up to 28-week Results from the BioDay Registry

Limited daily practice data on the effect of abrocitinib in patients with atopic dermatitis are available. The aim of this multicentre prospective study is to evaluate the effectiveness and safety of abrocitinib in patients with atopic dermatitis treated in daily practice. In a subgroup, the effectiveness of abrocitinib on hand eczema was evaluated. A total of 103 patients from the BioDay registry were included in the study: week 4 (n = 95), week 16 (n = 61) and week 28 (n = 39). At week 28, the Eczema Area and Severity Index (EASI)-50/75/90 was achieved by 81.8%, 57.6%, and 18.2%, respectively, and the weekly average pruritus numerical rating scale ≤ 4 by 62.9%. The effectiveness of abrocitinib was not significantly different between dupilumab non-responders and dupilumab-naïve patients/responders, and between upadacitinib non-responders and upadacitinib-naïve patients/responders. Mean ± standard deviation Hand Eczema Severity Index decreased from 27.4 ± 27.7 at baseline to 7.7 ± 12.1 at week 28 (n = 31). Thirty-two patients (31.1%) discontinued treatment due to ineffectiveness (n = 17), adverse events (n = 9) or both (n = 3). The most frequently reported adverse event was nausea (n = 28). In conclusion, abrocitinib is an effective treatment for atopic dermatitis and can be effective for patients with previous inadequate response to dupilumab or upadacitinib. Furthermore, hand eczema can improve in patients treated with abrocitinib for atopic dermatitis.</p

Induction of a common microglia gene expression signature by aging and neurodegenerative conditions : a co-expression meta-analysis

INTRODUCTION: Microglia are tissue macrophages of the central nervous system that monitor brain homeostasis and react upon neuronal damage and stress. Aging and neurodegeneration induce a hypersensitive, pro-inflammatory phenotype, referred to as primed microglia. To determine the gene expression signature of priming, the transcriptomes of microglia in aging, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) mouse models were compared using Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: A highly consistent consensus transcriptional profile of up-regulated genes was identified, which prominently differed from the acute inflammatory gene network induced by lipopolysaccharide (LPS). Where the acute inflammatory network was significantly enriched for NF-κB signaling, the primed microglia profile contained key features related to phagosome, lysosome, antigen presentation, and AD signaling. In addition, specific signatures for aging, AD, and ALS were identified. CONCLUSION: Microglia priming induces a highly conserved transcriptional signature with aging- and disease-specific aspects

Immune hyperreactivity of Aβ plaque-associated microglia in Alzheimer's disease

Alzheimer's disease (AD) is strongly associated with microglia-induced neuroinflammation. Particularly, Aβ plaque-associated microglia take on an "activated" morphology. However, the function and phenotype of these Aβ plaque-associated microglia are not well understood. We show hyperreactivity of Aβ plaque-associated microglia upon systemic inflammation in transgenic AD mouse models (i.e., 5XFAD and APP23). Gene expression profiling of Aβ plaque-associated microglia (major histocompatibility complex II+ microglia) isolated from 5XFAD mice revealed a proinflammatory phenotype. The upregulated genes involved in the biological processes (gene ontology terms) included: "immune response to external stimulus" such as Axl, Cd63, Egr2, and Lgals3, "cell motility", such as Ccl3, Ccl4, Cxcr4, and Sdc3, "cell differentiation", and "system development", such as St14, Trpm1, and Spp1. In human AD tissue with similar Braak stages, expression of phagocytic markers and AD-associated genes, including HLA-DRA, APOE, AXL, TREM2, and TYROBP, was higher in laser-captured early-onset AD (EOAD) plaques than in late-onset AD plaques. Interestingly, the nonplaque parenchyma of both EOAD and late-onset AD brains, the expression of above-mentioned markers were similarly low. Here, we provide evidence that Aβ plaque-associated microglia are hyperreactive in their immune response and phagocytosis in the transgenic AD mice as well as in EOAD brain tissue. We suggest that Aβ plaque-associated microglia are the primary source of neuroinflammation related to AD pathology