Holmbergbitsch4926

erapy for severely unwell children with COVID-19/Paediatric-Inflammatory-Multisystem Syndrome-Temporally associated with SARS-CoV-2 together with their parents; processes to protect healthcare staff from moral harm and research/educational activity focused on paediatric-specific ethical arising during the pandemic.Pancreatic Ductal Adenocarcinoma (PDAC) displays a dismal prognosis due to late diagnosis and high chemoresistance incidence. For advanced disease stages or patients with comorbidities, treatment options are limited to gemcitabine alone or in combination with other drugs. While gemcitabine resistance has been widely attributed to the levels of one of its targets, RRM1, the molecular consequences of gemcitabine resistance in PDAC remain largely elusive. Here we sought to identify genomic, epigenomic, and transcriptomic events associated with gemcitabine resistance in PDAC and their potential clinical relevance. We found that gemcitabine-resistant cells displayed a co-amplification of the adjacent RRM1 and STIM1 genes. Interestingly, RRM1, but not STIM1, was required for gemcitabine resistance, while high STIM1 levels caused an increase in cytosolic calcium concentration. Higher STIM1-dependent calcium influx led to an impaired ER stress response and a heightened NFAT activity. Importantly, these findings were confirmed in patient and patient-derived xenograft samples. Taken together, our study uncovers previously unknown biologically relevant molecular properties of gemcitabine-resistant tumors, revealing an undescribed function of STIM1 as a rheostat directing the effects of calcium signaling and controlling epigenetic cell fate determination. It further reveals the potential benefit of targeting STIM1-controlled calcium signaling and its downstream effectors in PDAC.

To determine whether clinical tenderness can be considered a sign of inflammatory joint activity in patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PsA) and to assess other possible factors associated with tenderness.

Patients diagnosed with RA, PsA and OA underwent clinical and ultrasound examination of wrists and finger joints. Radiographs of the hands were scored for erosions, joint space narrowing (JSN), osteophytes and malalignment. Tipifarnib cost A binary damage score (positive if ≥1 erosion, JSN and/or presence of malalignment) was calculated. Differences in grey scale signs of synovitis and power Doppler (PD) between tender non-swollen (TNS) versus non-tender non-swollen (NTNS) joints were calculated. Disease duration was assessed,<2 years was regarded as early and >5 years as long-standing arthritis.

In total, 34 patients (9 early and 14 long-standing) from patients with RA, 31 patients (7 early and 15 long-standing) with PsA and 30 with OA were included. We found equal frequencies of PD signal between TNS and NTNS joints in RA (p=0.18), PsA (p=0.59) or OA (p=0.96). However, PD had a significant association with tenderness in early arthritis both in RA (p=0.02) and in PsA (p=0.02). The radiographic damage score showed significant association with tenderness in RA (p<0.01), PsA (p<0.01) and OA (p=0.04).

Tenderness might not always be a sign of active inflammation in RA, PsA and OA. While tenderness in early arthritis may be more related to inflammation, established disease is better explained by joint damage and malalignment.

Tenderness might not always be a sign of active inflammation in RA, PsA and OA. While tenderness in early arthritis may be more related to inflammation, established disease is better explained by joint damage and malalignment.

CD4

T cells have been suggested as the most disease-relevant cell type in rheumatoid arthritis (RA) in which RA-risk non-coding variants exhibit allele-specific effects on regulation of RA-driving genes. This study aimed to understand RA-specific signatures in CD4

T cells using multi-omics data, interpreting inter-omics relationships in shaping the RA transcriptomic landscape.

We profiled genome-wide variants, gene expression and DNA methylation in CD4

T cells from 82 patients with RA and 40 healthy controls using high-throughput technologies. We investigated differentially expressed genes (DEGs) and differential methylated regions (DMRs) in RA and localised quantitative trait loci (QTLs) for expression and methylation. We then integrated these based on individual-level correlations to inspect DEG-regulating sources and investigated the potential regulatory roles of RA-risk variants by a partitioned-heritability enrichment analysis with RA genome-wide association summary statistics.

A large numberhape the differential expression of a substantial fraction of DEGs in CD4+ T cells in patients with RA, reinforcing the importance of a multidimensional approach in disease-relevant tissues.

The health impacts of temperatures are gaining attention in Australia and worldwide. While a number of studies have investigated the association of temperatures with the risk of cardiovascular diseases, few examined out-of-hospital cardiac arrest (OHCA) and none have done so in Australia. This study examined the exposure-response relationship between temperatures, including heatwaves and OHCA in Brisbane, Australia.

A quasi-Poisson regression model coupled with a distributed lag non-linear model was employed, using OHCA and meteorological data between 1 January 2007 and 31 December 2019. Reference temperature was chosen to be the temperature of minimum risk (21.4°C). Heatwaves were defined as daily average temperatures at or above a heat threshold (90th, 95th, 98th, 99th percentile of the yearly temperature distribution) for at least two consecutive days.

The effect of any temperature above the reference temperature was not statistically significant; whereas low temperatures (below reference temperature) increased OHCA risk. The effect of low temperatures was delayed for 1 day, sustained up to 3 days, peaking at 2 days following exposures. Heatwaves significantly increased OHCA risk across the operational definitions. When a threshold of 95th percentile of yearly temperature distribution was used to define heatwaves, OHCA risk increased 1.25 (95% CI 1.04 to 1.50) times. When the heat threshold for defining heatwaves increased to 99th percentile, the relative risk increased to 1.48 (1.11 to 1.96).

Low temperatures and defined heatwaves increase OHCA risk. link2 The findings of this study have important public health implications for mitigating strategies aimed at minimising temperature-related OHCA.

Low temperatures and defined heatwaves increase OHCA risk. The findings of this study have important public health implications for mitigating strategies aimed at minimising temperature-related OHCA.

This study investigated risk factors for poor earplug fit, with a focus on the association between hearing loss and personal attenuation ratings (PARs).

Earplug fit was assessed by obtaining PARs using a real ear at attenuation threshold (REAT) system. Hearing loss was assessed using the unoccluded hearing thresholds measured during the REAT testing and the results of a speech-in-noise test. Potential predictors of PARs were modelled using both simple and multiple linear regression. Hearing loss was the primary predictor of interest.

Data were collected from 200 workers at ten above-ground mining sites in the Midwestern USA. Workers reported wearing their hearing protection on average 73.9% of the time in a high noise environment (mean 8-hour time-weighted average noise exposure 85.5 dBA, range 65-103 dBA). One-quarter (26.7%) of workers were found to have a hearing loss (hearing threshold ≥25 dB across 1-4 kHz), and 42% reported symptoms of tinnitus. Workers with a hearing loss had a significantly lower PAR than those without a hearing loss (β=-5.1, SE=1.7).

The results of the adjusted regression models suggest that workers with hearing loss achieved significantly lower PARs than those without hearing loss. This association between hearing loss and hearing protection devices (HPD) fit brings into focus the potential benefit of fit checks to be included in hearing conservation programmes. Workers found to have hearing loss should be prioritised for fit testing, as their hearing impairment may be associated with poor HPD fit.

The results of the adjusted regression models suggest that workers with hearing loss achieved significantly lower PARs than those without hearing loss. This association between hearing loss and hearing protection devices (HPD) fit brings into focus the potential benefit of fit checks to be included in hearing conservation programmes. Workers found to have hearing loss should be prioritised for fit testing, as their hearing impairment may be associated with poor HPD fit.

The aim was to test if targeting managers with an educational intervention reduces absence among pregnant employees.

The study was a non-blinded cluster randomised trial conducted in hospitals and daycare institutions from two administrative Danish Regions and two Danish municipalities. Clusters (work units) were assigned randomly and non-blinded to either (1) intervention, where all managers were invited to participate in a 3-hour seminar addressing needs and options for adjustment of work in pregnancy, or (2) control, with practice as usual. link3 The primary outcome based on payroll data was long-term pregnancy-related absence, defined as ≥12.5% cumulated absence during pregnancy weeks 1-32. Intention-to-treat analysis was applied using mixed logistic regression.

Ninety work units were included (56 hospital departments and 34 daycare units) with 451 pregnant employees in the intervention group and 464 in the control group. Work units had on average 11 pregnant employees with no difference between the groups. 103 of the 216 invited managers (48%) participated in a the 3-hour seminar. In the intervention group, 154 (34%) had long-term pregnancy-related absence during pregnancy weeks 1-32 vs 166 (36%) in the control group. Relative odds of having long-term pregnancy-related absence, when being in the intervention group, was 1.06 (95% CI 0.71 to 1.58), with an interclass correlation coefficient of 0.07.

An educational intervention targeting managers did not reduce pregnancy-related absence among pregnant employees.

NCT03002987.

NCT03002987.

To describe critical features of the Ethiopian Pediatric Society (EPS) Quality Improvement (QI) Initiative and to present formative research on mentor models.

General and referral hospitals in the Addis Ababa area of Ethiopia.

Eighteen hospitals selected for proximity to the EPS headquarters, prior participation in a recent newborn care training cascade and minimal experience with QI.

Education in QI in a 2-hour workshop setting followed by implementation of a facility-based QI project with the support of virtual mentorship or in-person mentorship.

Primary outcome-QI progress, measured using an adapted Institute for Healthcare Improvement Scale; secondary outcome-contextual factors affecting QI success as measured by the Model for Understanding Success in Quality.

The dose and nature of mentoring encounters differed based on a virtual versus in-person mentoring approach. All QI teams conducted at least one large-scale change. Education of staff was the most common change implemented in both groups.