Is exercise training safe and effective for ALL heart failure patients: A retrospective service evaluation of a hospital based cardiac rehabilitation programme

The main purpose of this study was to investigate whether exercise training is safe and effective for all classifications of heart failure, female and elderly (70 years and above) heart failure patients and also those heart failure patients with significant co-morbidity. Much of the research into exercise training and heart failure has been carried out on middle aged men in NYHA II-III classification of heart failure who have no other significant co-existing conditions. This is not reflective of the population of heart failure patients in general. The cardiac rehabilitation records (n=1000) of heart failure patients who had attended an exercise programme at a hospital based NHS service over a period of ten years were retrospectively evaluated to investigate the safety and efficacy of exercise training. Analysis of baseline statistics and repeated outcome measures were used to investigate the significance of the service and to ascertain where similarities and differences lay with the research. 74% were male, the age range was 17-90 years and 52% of patients had one or more significant co-morbidity. The acute event incidence was recorded at four per 1000 patients. NYHA I patients, female, elderly heart failure patients and those with significant co-morbidity showed significant improvements in functional capacity and quality of life measures with exercise training (p< 0.05). However no conclusion on the effectiveness of exercise could be drawn for NYHA IV heart failure patients due to insufficient recorded data and reduced adherence to exercise sessions for this group. A hospital based exercise programme, therefore may not be the most appropriate setting for the NYHA IV patient. This study supports previous research of the benefit of exercise training in heart failure but broadens it further to show that exercise is safe for all heart failure patients and is also effective for all heart failure patients with the exception of NYHA IV patients where further investigation is needed

2003 Oregon Vineyard and Winery Report

This statewide survey report on vineyards and wineries in Oregon covers bearing and nonbearing acres, size of vineyard operation, variety and county, size distribution, prices, yields, crush, inventory, and sales. The report also contains some comparisons of data for 2002 and 2003. According to this report, the number of vineyards and wineries in Oregon reached a record high in 2003, with nearly 1.2 million cases of wine sold

2002 Oregon Vineyard and Winery Report

This statewide survey report on vineyards and wineries in Oregon covers bearing and nonbearing acres, size of vineyard operation, variety and county, size distribution, prices, yields, crush, inventory, and sales. The report also contains some comparisons of data for 2001 and 2002. According to this report, vineyards and wineries in the state continued to grow, although fewer grapes were produced in 2002 than in the previous year

Reduced grid-like theta modulation in schizophrenia

The hippocampal formation has been implicated in the pathophysiology of schizophrenia, with patients showing impairments in spatial and relational cognition, structural changes in entorhinal cortex, and reduced theta coherence with medial prefrontal cortex. Both the entorhinal cortex and medial prefrontal cortex exhibit a six-fold (or 'hexadirectional') modulation of neural activity during virtual navigation that is indicative of grid cell populations and associated with accurate spatial navigation. Here, we examined whether these grid-like patterns are disrupted in schizophrenia. We asked 17 participants with diagnoses of schizophrenia and 23 controls (matched for age, sex and IQ) to perform a virtual reality spatial navigation task during magnetoencephalography. The control group showed stronger 4-10 Hz theta power during movement onset, as well as hexadirectional modulation of theta band oscillatory activity in the right entorhinal cortex whose directional stability across trials correlated with navigational accuracy. This hexadirectional modulation was absent in patients, with a significant difference between groups. These results suggest that impairments in spatial and relational cognition associated with schizophrenia may arise from disrupted grid firing patterns in entorhinal cortex

Challenges and opportunities in coproduction: reflections on working with young people to develop an intervention to prevent violence in informal settlements in South Africa

Coproduction is widely recognised as essential to the development of effective and sustainable complex health interventions. Through involving potential end users in the design of interventions, coproduction provides a means of challenging power relations and ensuring the intervention being implemented accurately reflects lived experiences. Yet, how do we ensure that coproduction delivers on this promise? What methods or techniques can we use to challenge power relations and ensure interventions are both more effective and sustainable in the longer term? To answer these questions, we openly reflect on the coproduction process used as part of Siyaphambili Youth (‘Youth Moving Forward’), a 3-year project to create an intervention to address the social contextual factors that create syndemics of health risks for young people living in informal settlements in KwaZulu-Natal province in South Africa. We identify four methods or techniques that may help improve the methodological practice of coproduction: (1) building trust through small group work with similar individuals, opportunities for distance from the research topic and mutual exchanges about lived experiences; (2) strengthening research capacity by involving end users in the interpretation of data and explaining research concepts in a way that is meaningful to them; (3) embracing conflicts that arise between researchers’ perspectives and those of people with lived experiences; and (4) challenging research epistemologies through creating spaces for constant reflection by the research team. These methods are not a magic chalice of codeveloping complex health interventions, but rather an invitation for a wider conversation that moves beyond a set of principles to interrogate what works in coproduction practice. In order to move the conversation forward, we suggest that coproduction needs to be seen as its own complex intervention, with research teams as potential beneficiaries

Phenotypic Variation in the Group A Streptococcus Due to Natural Mutation of the Accessory Protein-Encoding Gene rocA

Populations of a bacterial pathogen, whether recovered from a single patient or from a worldwide study, are often a heterogeneous mix of genetically and phenotypically divergent strains. Such heterogeneity is of value in changing environments and arises via mechanisms such as gene gain or gene mutation. Here, we identify an isolate of serotype M12 group A Streptococcus (GAS) (Streptococcus pyogenes) that has a natural mutation in rocA, which encodes an accessory protein to the virulence-regulating two-component system CovR/CovS (CovR/S). Disruption of RocA activity results in the differential expression of multiple GAS virulence factors, including the anti-phagocytic hyaluronic acid capsule and the chemokine protease SpyCEP. While some of our data regarding RocA-regulated genes overlaps with previous studies, which were performed with isolates of alternate GAS serotypes, some variability was also observed. Perhaps as a consequence of this alternate regulatory activity, we discovered that the contribution of RocA to the ability of the M12 isolate to survive and proliferate in human blood ex vivo is opposite that previously observed in M1, M3, and M18 GAS strains. Specifically, rocA mutation reduced, rather than enhanced, survival of the isolate. Finally, we also present data from an analysis of rocA transcription and show that rocA is transcribed in both mono- and polycistronic mRNAs. In aggregate, our data provide insight into the important regulatory role of RocA and into the mechanisms and consequences of GAS phenotypic heterogeneity. IMPORTANCE This study investigates the regulatory and phenotypic consequences of a naturally occurring mutation in a strain of the bacterial pathogen the group A Streptococcus (Streptococcus pyogenes). We show that this mutation, which occurs in a regulator-encoding gene, rocA, leads to altered virulence factor expression and reduces the ability of this isolate to survive in human blood. Critically, the blood survival phenotype and the assortment of genes regulated by RocA differ compared to previous studies into RocA activity. The data are consistent with there being strain-or serotype-specific variability in RocA function. Given that phenotypic variants can lead to treatment failures and escape from preventative regimes, our data provide information with regard to a mechanism of phenotypic variation in a prevalent Gram-positive pathogen

Women’s experiences of early pregnancy loss services during the pandemic:A qualitative investigation

Problem: Early pregnancy losses [EPL] are common, varied, and require different courses of management and care. Background: In the UK, women who suspect or suffer a pregnancy loss are usually provided specialist care in early pregnancy assessment units [EPAUs]. Their configuration has recently been evaluated, but recommendations for change in-line with best practice for optimum outcomes were unable to be implemented due to the COVID-19 pandemic health system shock.Aim: To compare women’s experiences of EPAUs during the pandemic to themes previously found in qualitative work undertaken with women who utilised EPAUs before the pandemic.Methods: We conducted semi-structured virtual interviews, with women (N=32) who suffered an early pregnancy loss during the pandemic; analysing transcripts using Template Analysis, based on findings about women’s (pre-pandemic) experiences of EPAU from The VESPA Study.Findings: We report on seven key themes: Barriers to Accessing Services; Communication &amp; Information; Retention of Relational Care; Involvement in Care Decisions; Staffs’ Attitude or Approach; Efficiency of Service Delivery; Sensitive Patient Management. Discussion: Sensitive patient management and woman-staff interactions in EPAU settings remain a fundamental issue. Women also reported their experiences of EPAUs were comparatively worse during the pandemic.Conclusions: Women valued the care provided by EPAUs and found services to be efficient, despite pandemic-related restrictions. However, psychological recognition surrounding EPL and appropriate, sensitive, relational care and support continue to be areas in need of improvement. Our recommendation is to implement the improvements suggested by VESPA as a priority to ameliorate present sub-optimal experiences and prevent further deterioration.<br/

A longitudinal and cross-sectional study of plasma neurofilament light chain concentration in Charcot-Marie-Tooth disease

Advances in genetic technology and small molecule drug development have paved the way for clinical trials in Charcot-Marie-Tooth disease (CMT); however, the current FDA-approved clinical trial outcome measures are insensitive to detect a meaningful clinical response. There is, therefore, a need to identify sensitive outcome measures or clinically relevant biomarkers. The aim of this study was to further evaluate plasma neurofilament light chain (NFL) as a disease biomarker in CMT. Plasma NFL was measured using SIMOA technology in both a cross-sectional study of a US cohort of CMT patients and longitudinally over 6 years in a UK CMT cohort. In addition, plasma NFL was measured longitudinally in two mouse models of CMT2D. Plasma concentrations of NFL were increased in a US cohort of patients with CMT1B, CMT1X and CMT2A but not CMT2E compared with controls. In a separate UK cohort, over a 6-year interval, there was no significant change in plasma NFL concentration in CMT1A or HSN1, but a small but significant reduction in patients with CMT1X. Plasma NFL was increased in wild type compared to GARSC201R mice. There was no significant difference in plasma NFL in GARSP278KY compared to wild type mice. In patients with CMT1A, the small difference in cross-sectional NFL concentration vs healthy controls and the lack of change over time suggests that plasma NFL may lack sufficient sensitivity to detect a clinically meaningful treatment response in adulthood

Relation of Cumulative Low-Level Lead Exposure to Depressive and Phobic Anxiety Symptom Scores in Middle-Age and Elderly Women

Background: Different lines of evidence suggest that low-level lead exposure could be a modifiable risk factor for adverse psychological symptoms, but little work has explored this relation

Racial and Ethnic Differences in Total Knee Arthroplasty in the Veterans Affairs Health Care System, 2001-2013

OBJECTIVE: To examine black-white and Hispanic-white differences in total knee arthroplasty from 2001 to 2013 in a large cohort of patients diagnosed with osteoarthritis (OA) in the Veterans Affairs (VA) health care system. METHODS: Data were from the VA Musculoskeletal Disorders cohort, which includes data from electronic health records of more than 5.4 million veterans with musculoskeletal disorders diagnoses. We included white (non-Hispanic), black (non-Hispanic), and Hispanic (any race) veterans, age ≥50 years, with an OA diagnosis from 2001-2011 (n = 539,841). Veterans were followed from their first OA diagnosis until September 30, 2013. As a proxy for increased clinical severity, analyses were also conducted for a subsample restricted to those who saw an orthopedic or rheumatology specialist (n = 148,844). We used Cox proportional hazards regression to examine racial and ethnic differences in total knee arthroplasty by year of OA diagnosis, adjusting for age, sex, body mass index, physical and mental diagnoses, and pain intensity scores. RESULTS: We identified 12,087 total knee arthroplasty procedures in a sample of 473,170 white, 50,172 black, and 16,499 Hispanic veterans. In adjusted models examining black-white and Hispanic-white differences by year of OA diagnosis, total knee arthroplasty rates were lower for black than for white veterans diagnosed in all but 2 years. There were no Hispanic-white differences regardless of when diagnosis occurred. These patterns held in the specialty clinic subsample. CONCLUSION: Black-white differences in total knee arthroplasty appear to be persistent in the VA, even after controlling for potential clinical confounders