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This weak response is observed across diverse Wolbachia strains from both nematode and insect hosts suggesting a potential pan-Wolbachia transcriptional response during host development that diverged more than 700 million years ago.Oxidative stress causes damage to cells by creating reactive oxygen species (ROS) and the overproduction of ROS have been linked to the onset of premature aging. We previously found that a brap-2 (BRCA1 associated protein 2) mutant significantly increases the expression of phase II detoxification enzymes in C. elegans An RNAi suppression screen to identify transcription factors involved in the production of gst-4 mRNA in brap-2 worms identified SEM-4 as a potential candidate. Here, we show that knockdown of sem-4 suppresses the activation of gst-4 caused by the mutation in brap-2 We also demonstrate that sem-4is required for survival upon exposure to oxidative stress and that SEM-4 is required for expression of the transcription factor SKN-1C. These findings identify a novel role for SEM-4 in ROS detoxification by regulating expression of SKN-1C and the phase II detoxification genes.Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by mutation of the dystrophin gene. Pharmacological therapies that function independently of dystrophin and complement strategies aimed at dystrophin restoration could significantly improve patient outcomes. Previous observations have suggested that serotonin pathway modulation ameliorates dystrophic pathology, and re-application of serotonin modulators already used clinically would potentially hasten availability to DMD patients. In our study, we used dystrophin-deficient sapje and sapje-like zebrafish models of DMD for rapid and easy screening of several classes of serotonin pathway modulators as potential therapeutics. None of the candidate drugs tested significantly decreased the percentage of zebrafish exhibiting the dystrophic muscle phenotype in the short-term birefringence assay or lengthened the lifespan in the long-term survival assay. Although we did not identify an effective drug, we believe our data is of value to the DMD research community for future studies, and there is evidence that suggests serotonin modulation may still be a viable treatment strategy with further investigation. Given the widespread clinical use of selective serotonin reuptake inhibitors, tricyclic antidepressants and reversible inhibitors of monoamine oxidase, their reapplication to DMD is an attractive strategy in the field's pursuit to identify pharmacological therapies to complement dystrophin restoration strategies.
We sought to evaluate the association between low birth weight (LBW) and outcomes following neonatal cardiac surgery in a low-income and middle-income country setting where LBW prevalence is high and its impact on surgical outcomes is undefined.
Single-centre retrospective cohort study.
Referral paediatric hospital in Southern India PATIENTS All neonatal cardiac surgical cases between January 2011 and December 2018. LBW was defined as <2.5 kg.
Patient demographics, corrective versus palliative surgery and postoperative outcomes were collected from the institutional database which undergoes regular audit as part of International Quality Improvement Collaborative for Congenital Heart Disease. In-hospital mortality was the primary outcome measure.
Of 569 neonatal cardiac operations, 123 (21.6%) had LBW (mean 2.2±0.3 kg); 18.7% <2 kg and 21.1% were preterm (<37 weeks). Surgery type (corrective vs palliative) or non-cardiac anomalies were not associated with birth weight. Birth weight did not correlate with ICU length of stay (LOS) and mechanical ventilation but was lower in those with postoperative sepsis. Overall in-hospital mortality was 7.0%; LBW neonates had higher mortality (OR 2.16, 95% CI 1.09 to 4.29, p=0.025). Multivariable analyses revealed birth weight (OR per 100 g decrease in weight 1.12; 95% CI 1.03 to 1.22), age at surgery (OR per day increase in age of 0.93; 95% CI 0.87 to 0.99) and palliative intervention (OR 4.46 (95% CI 1.91 to 10.44) as independent predictors of in-hospital mortality.
LBW adversely impacts in-hospital mortality outcomes following neonatal cardiac surgery in a resource-limited setting without increase in ICU or hospital LOS.
LBW adversely impacts in-hospital mortality outcomes following neonatal cardiac surgery in a resource-limited setting without increase in ICU or hospital LOS.
Prolonged sitting and inadequate sleep are a growing concern in society and are associated with impairments to cardiometabolic health and cognitive performance. However, the combined effect of prolonged sitting and inadequate sleep on measures of health and cognitive performance are unknown. In addition, the circadian disruption caused by shiftwork may further impact workers' cardiometabolic health and cognitive performance. This protocol paper outlines the methodology for exploring the impact of simultaneous exposure to prolonged sitting, sleep restriction and circadian disruption on cardiometabolic and cognitive performance outcomes.
This between-subjects study will recruit 208 males and females to complete a 7-day in-laboratory experimental protocol (1 Adaptation Day, 5 Experimental Days and 1 Recovery Day). learn more Participants will be allocated to one of eight conditions that include all possible combinations of the following dayshift or nightshift, sitting or breaking up sitting and 5 hour or 9 hour sleep od consent. Study findings will be disseminated via scientific publications and conference presentations.
This study has been registered on Australian New Zealand Clinical Trials Registry (12619001516178) and is currently in the pre-results stage.
This study has been registered on Australian New Zealand Clinical Trials Registry (12619001516178) and is currently in the pre-results stage.
Central nervous system depressants (CNSDs) such as opioids, benzodiazepine and Z-hypnotics are commonly used. However, CNSDs may influence cognitive function, especially in older hospitalised patients with comorbidities. The aim was to examine the association between CNSD use and cognitive function in older patients. We assessed global and domain specific cognitive function, among hospitalised older patients, including covariates for comorbidity, anxiety and depression.
Cross-sectional hospital-based study.
Data was collected consecutively from inpatients at somatic wards of a general university hospital.
Older patients between 65 and 90 years with/without CNSD use for ≥4 weeks.
The main outcome was cognitive function assessed by Cognistat. Secondary outcomes were routine clinical tests in the wards (mini-mental state examination (MMSE), trail making test (TMT) A and B, and clock drawing tests). Analyses were bivariate and multiple linear regression, adjusted for age, gender, and education. Covariates were comorbidity, depression and anxiety scores.
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