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Diet is a modifiable risk factor for chronic disease and a potential modulator of telomere length (TL). The study aim was to investigate associations between diet quality and TL in Australian adults after a 12-week dietary intervention with an almond-enriched diet (AED). Participants (overweight/obese, 50–80 years) were randomised to an AED (n 62) or isoenergetic nut-free diet (NFD, n 62) for 12 weeks. Diet quality was assessed using a Dietary Guideline Index (DGI), applied to weighed food records, that consists of ten components reflecting adequacy, variety and quality of core food components and discretionary choices within the diet. TL was measured by quantitative PCR in samples of lymphocytes, neutrophils, and whole blood. There were no significant associations between DGI scores and TL at baseline. Diet quality improved with AED and decreased with NFD after 12 weeks (change from baseline AED + 9·8 %, NFD − 14·3 %; P < 0·001). TL increased in neutrophils (+9·6 bp, P = 0·009) and decreased in whole blood, to a trivial extent (–12·1 bp, P = 0·001), and was unchanged in lymphocytes. Changes did not differ between intervention groups. There were no significant relationships between changes in diet quality scores and changes in lymphocyte, neutrophil or whole blood TL. The inclusion of almonds in the diet improved diet quality scores but had no impact on TL mid-age to older Australian adults. Future studies should investigate the impact of more substantial dietary changes over longer periods of time.
Medical care is predicated on ‘do no harm’, yet the urgency to find drugs and vaccines to treat or prevent COVID-19 has led to an extraordinary effort to develop and test new therapies. Whilst this is an essential cornerstone of a united global response to the COVID-19 pandemic, the absolute requirements for meticulous efficacy and safety data remain. This is especially pertinent to the needs of pregnant women; a group traditionally poorly represented in drug trials, yet a group at heightened risk of unintended adverse materno-fetal consequences due to the unique physiology of pregnancy and the life course implications of fetal or neonatal drug exposure. However, due to the complexities of drug trial participation when pregnant (be they vaccines or therapeutics for acute disease), many clinical drug trials will exclude them. Clinicians must determine the best course of drug treatment with a dearth of evidence from either clinical or preclinical studies, where at least in the short term they may be more focused on the outcome of the mother than of her offspring.
Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ; Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ, surfactant proteins (SFTP-A, -B, -C, and -D), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1. Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B. However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Cardiac strangulation is a rare and potentially deadly complication of epicardial pacemaker implantation. A young boy presenting with chest pain and tiredness almost 7 years after pacemaker implantation was found to have cardiac strangulation. Literature review revealed 22 cases reported to date with a worrying rise in the number of reports over the past 3 years. Strangulation is associated with implantation of leads at a young age and appears to be related to somatic growth. Serial assessment with chest X-ray and echocardiogram is recommended, at least until full adult growth is attained with further coronary artery imaging reserved for symptoms or suspicious echocardiographic findings. If cardiac strangulation is diagnosed prompt replacement of the offending system is needed.
Nutrition during the periconceptional period influences postnatal cardiovascular health. We determined whether in vitro embryo culture and transfer, which are manipulations of the nutritional environment during the periconceptional period, dysregulate postnatal blood pressure and blood pressure regulatory mechanisms. Embryos were either transferred to an intermediate recipient ewe (ET) or cultured in vitro in the absence (IVC) or presence of human serum (IVCHS) and a methyl donor (IVCHS+M) for 6 days. Basal blood pressure was recorded at 19–20 weeks after birth. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after varying doses of phenylephrine (PE). mRNA expression of signaling molecules involved in blood pressure regulation was measured in the renal artery. Basal MAP did not differ between groups. Baroreflex sensitivity, set point, and upper plateau were also maintained in all groups after PE stimulation. Adrenergic receptors alpha-1A (αAR1A), alpha-1B (αAR1B), and angiotensin II receptor type 1 (AT1R) mRNA expression were not different from controls in the renal artery. These results suggest there is no programmed effect of ET or IVC on basal blood pressure or the baroreflex control mechanisms in adolescence, but future studies are required to determine the impact of ET and IVC on these mechanisms later in the life course when developmental programming effects may be unmasked by age.
Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
Introduction: Prognostication is a significant challenge early in the post-cardiac arrest period. Common prognostic factors for neurological survival are unreliable (high false positive rates) until 72 hours post-cardiac arrest. It is not known whether there are a combination of factors that can be utilized earlier in the post-cardiac arrest period to accurately predict patient outcome. Our objective was to predict neurological outcome utilizing a novel combination of patient factors early in the post-cardiac arrest period. Methods: We conducted a retrospective cohort study using data from our local cardiac arrest registry. We included adult patients who obtained a return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). We excluded patients who did not survive for at least 24 hours post-ROSC and those who had a do not resuscitate (DNR) order within 2 hours of ROSC. We performed an ordinal regression analysis using the proportional odds model to predict neurological outcome (modified rankin score (mRS)). We included a good neurological outcome (mRS 0-2), poor neurological outcome (mRS 3-5), and dead (mRS 6) as an ordinal outcome. We included a number of patient demographics, intra- and post-cardiac arrest factors as covariates in our model. The predictive performance of our model was analyzed using receiver operating characteristic (ROC) curves for discrimination and Brier statistic for calibration. Results: We included 3448 patients in our analysis. We found that an initial shockable rhythm (odds ratio (OR) 4.1; 95% confidence interval (CI) 3.6, 5.4), the absence of pupillary reflexes (OR 3.5; 95% CI 2.4,4.8) and maximum motor score on the Glasgow Coma Scale (GCS) (OR 1.5; 95% CI 1.4,1.6) had the greatest association with improved neurologic outcome. Longer duration of resuscitation was associate with worse outcomes (OR 0.84, 95% CI 0.82,0.87). The overall performance of our model was excellent with an area under the ROC curve of 0.89 and a Brier statistic of 0.13. Conclusion: Our model predicted good neurological outcome with a high rate of accuracy, however external validation of the model is required. This model may be useful in providing initial risk stratification of patients in clinical practice and future research on post-cardiac arrest care.
Introduction: Despite recent advances in resuscitation, some patients remain in ventricular fibrillation (VF) after multiple defibrillation attempts during out-of-hospital cardiac arrest (OHCA). Vector change defibrillation (VC) and double sequential external defibrillation (DSED) have been proposed as alternate therapeutic strategies for OHCA patients with refractory VF. The primary objective was to determine the feasibility, safety and sample size required for a future cluster randomized controlled trial (RCT) with crossover comparing VC or DSED to standard defibrillation for patients experiencing refractory VF. Secondary objectives were to evaluate the intervention effect on VF termination and return of spontaneous circulation (ROSC). Methods: We conducted a pilot cluster RCT with crossover in four Canadian paramedic services and included all treated adult OHCA patients who presented in VF and received a minimum of three defibrillation attempts. In addition to standard cardiac arrest care, each EMS service was randomly assigned to provide continued standard defibrillation (control), VC or DSED. Services crossed over to an alternate defibrillation strategy after six months. Prior to the launch of the trial, 2,500 paramedics received in-person training for VC and DSED defibrillation using a combination of didactic, video and simulated scenarios. Results: Between March 2018 and September 2019, 152 patients were enrolled. Monthly enrollment varied from 1.4 to 6.1 cases per service. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no reported cases of defibrillator malfunction, skin burns, difficulty with pad placement or concerns expressed by paramedics, patients, families, or ED staff about the trial. In the standard defibrillation group, 66.6% of cases resulted in VF termination, compared to 82.0% in VC and 76.3% of cases in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively. Conclusion: Findings from our pilot RCT suggest the DOSE VF protocol is feasible and safe. VF termination and ROSC were higher with VC and DSED compared to standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact patient-centered, clinical outcomes
Antidepressant use has risen x3-5 in Western countries since the early 1990s, outstripping changes in depression incidence or prevalence. This represents a major public health challenge.
Nationally-collected antidepressant data were used to assess the impact of "Doing Well", (DW) a novel depression care programme operating in Renfrewshire, Scotland. "Doing Well" implemented a model of “stepped collaborative care”, practitioner education and significant service redesign. Prescribing was compared for three groups: "DW" (76,000 population; clinical and educational intervention), "DW neighbours” (101,000 population; educational interventions only), and Scotland (no specific intervention).
A national rise in antidepressant prescriptions was stabilised for the "DW" group (graph). Antidepressant cost/item fell by 42% and 40% in both “DW” and “DW neighbours” groups but rose by 8% nationally.
Access to clinical interventions are required to reduce antidepressant prescriptions, but cost savings may be made with educational interventions alone.
The placenta develops alongside the embryo and fetus and is responsible for fetal gas exchange and nutrition. The placenta also has important immune and endocrine functions and thus undertakes to fulfill the roles played by various somatic organs in the post-natal situation (Figure 5.1). The placental membrane, the chorion, prevents the fetal and maternal blood from mixing, while allowing transport of molecules. The human placenta is haemochorial, which means that maternal blood contacts the chorionic placental membrane (fetal epitheliem).
Organisations and associated management practices are generally considered responsible for promoting employees' enjoyment of work. Our study, on the other hand, seeks to examine the capacity of individual workers to regulate their own experience of fun. We interviewed eight ‘remarkable’ workers who claimed to always (or nearly always) have fun at work. We utilised a critical realist approach in the analysis that enabled the consideration of both structure and agency in the experience of workplace fun. A key research finding was that participants possessed a strong sense of control over their own happiness at work, demonstrated in four ways: (1) a priority placed on fun, (2) a sense of responsibility for fun, (3) a positive orientation to the world and (4) a sense of mastery and challenge in work tasks. Research findings may inspire both individual workers and organisations to adopt an agentic outlook in the workplace, implementing strategies that enhance employee control.
Autism spectrum disorder (ASD) and schizophrenia (SCZ) are separate neurodevelopmental disorders that are both characterized by difficulties in social cognition and social functioning. Due to methodological confounds, the degree of similarity in social cognitive impairments across these two disorders is currently unknown. This study therefore conducted a comprehensive comparison of social cognitive ability in ASD and SCZ to aid efforts to develop optimized treatment programs.
In total, 101 individuals with ASD, 92 individuals with SCZ or schizoaffective disorder, and 101 typically developing (TD) controls, all with measured intelligence in the normal range and a mean age of 25.47 years, completed a large battery of psychometrically validated social cognitive assessments spanning the domains of emotion recognition, social perception, mental state attribution, and attributional style.
Both ASD and SCZ performed worse than TD controls, and very few differences were evident between the two clinical groups, with effect sizes (Cohen's d) ranging from 0.01 to 0.34. For those effects that did reach statistical significance, such as greater hostility in the SCZ group, controlling for symptom severity rendered them non-significant, suggesting that clinical distinctions may underlie these social cognitive differences. Additionally, the strength of the relationship between neurocognitive and social cognitive performance was of similar, moderate size for ASD and SCZ.
Findings largely suggest comparable levels of social cognitive impairment in ASD and SCZ, which may support the use of existing social cognitive interventions across disorders. However, future work is needed to determine whether the mechanisms underlying these shared impairments are also similar or if these common behavioral profiles may emerge via different pathways.
Currently no national guidelines exist for the management of scabies outbreaks in residential or nursing care homes for the elderly in the United Kingdom. In this setting, diagnosis and treatment of scabies outbreaks is often delayed and optimal drug treatment, environmental control measures and even outcome measures are unclear. We undertook a systematic review to establish the efficacy of outbreak management interventions and determine evidence-based recommendations. Four electronic databases were searched for relevant studies, which were assessed using a quality assessment tool drawing on STROBE guidelines to describe the quality of observational data. Nineteen outbreak reports were identified, describing both drug treatment and environmental management measures. The quality of data was poor; none reported all outcome measures and only four described symptom relief measures. We were unable to make definitive evidence-based recommendations. We draw on the results to propose a framework for data collection in future observational studies of scabies outbreaks. While high-quality randomised controlled trials are needed to determine optimal drug treatment, evidence on environmental measures will need augmentation through other literature studies. The quality assessment tool designed is a useful resource for reporting of outcome measures including patient-reported measures in future outbreaks.
Introduction: Despite significant advances in resuscitation efforts, there are some patients who remain in ventricular fibrillation (VF) after multiple shocks during out-of-hospital cardiac arrest (OHCA). Double sequential external defibrillation (DSED) has been proposed as a treatment option for patients in shock refractory VF. We sought to compare DSED to standard therapy with regards to VF termination and return of spontaneous circulation (ROSC) for patients presenting in shock refractory VF. Methods: We performed a retrospective review of all treated adult OHCA who presented in VF and received a minimum of three successive shocks over a two year period beginning on Jan 1, 2015 in four Canadian EMS agencies. Using ambulance call reports and defibrillator files, we compared VF termination (defined as the absence of VF at the rhythm check following defibrillation and 2 minutes of CPR) and VF termination into a perfusing rhythm with ROSC between patients who received standard therapy (CPR, defibrillation, epinephrine and antiarrhythmics) and those who received DSED (after on-line medical consultation) for shock refractory VF. Cases of traumatic cardiac arrest and those who presented in VF but terminated VF prior to 3 successive shocks were excluded. Results: Among 197 patients who met the study criteria for shock refractory VF, 161 (81.7%) patients received standard therapy and 36 (18.3%) received DSED. For the primary outcome, VF termination was significantly higher for DSED compared to standard therapy (63.9% vs 18.0%; Δ45.9%; 95% CI: 28.3 to 60.5). For the secondary outcome of VF termination into ROSC, DSED was associated with significantly higher ROSC compared to standard care (33.3% vs 13%; Δ20.3%; 95% CI:13.0 to 33.3). The median (IQR) number of failed standard shocks prior to DSED was 8 (6, 10). When DSED terminated VF, it did so with a single DSED shock in 69.6% of cases. Conclusion: Our observational findings suggest improved VF termination and ROSC are associated with DSED compared to standard therapy for shock refractory VF. An appropriately powered randomized controlled trial is required to assess the impact of DSED on patient-important outcomes.
Introduction: 9-1-1 telecommunicators receive minimal education on agonal breathing, often resulting in unrecognized out-of-hospital cardiac arrest (OHCA). We successfully piloted an educational intervention that significantly improved telecommunicators’ OHCA recognition and bystander CPR rates in Ottawa. We sought to better understand the operations of Canadian 9-1-1 communications centers (CC) in preparation for a multi-centre study of this intervention. Methods: We conducted a National survey of all Canadian CCs. Survey domains included information on organizational structure, dispatch system used, education curriculum, and performance monitoring. It was peer-reviewed, translated in French, pilot-tested, and distributed electronically using a modified Dillman method. We designated respondents in each CC before distribution and used targeted follow-up and small incentives to increase response rate. Respondents also described functioning of neighboring CCs if known. Results: We received information from 51/51 provincial and 1/25 territorial CCs, representing 99.7% of the Canadian population. CCs largely utilize the Medical Dispatch Priority System (MPDS) platform (93%), many are Province/Ministry regulated (50%) and most require a High School diploma as minimum entry level education (78%). Telecommunicators receive initial in-class training (median 1.3 months, IQR 0.3-1.9; range 0.1-2.2), often followed by a preceptorship (84.4%) (median 1.0 months, IQR 0.7-1.7; range 0.4-6.0). Educational curriculum includes information on agonal breathing in 41% of CC, without audio examples in 34%. Among responding CCs, over 39,000 suspected OHCA 9-1-1 calls are received annually. Few CCs maintain local performance statistics on OHCA recognition (25%), bystander CPR rates (25%) or survival rates (50%). Most (97%) expressed interest in future research collaborations. Conclusion: Most Canadian telecommunicators receive no or minimal education in recognizing agonal breathing. Further training and improved OHCA monitoring may assist recognition and enhance outcomes.