Revision of failed hip resurfacing to total hip arthroplasty rapidly relieves pain and improves function in the early post operative period

We reviewed the results of 25 consecutive patients who underwent revision of a hip resurfacing prosthesis to a total hip replacement. Revisions were performed for recurrent pain and effusion, infection and proximal femoral fractures. Both components were revised in 20 cases

Multiple generation distinct toxicant exposures induce epigenetic transgenerational inheritance of enhanced pathology and obesity

Three successive multiple generations of rats were exposed to different toxicants and then bred to the transgenerational F5 generation to assess the impacts of multiple generation different exposures. The current study examines the actions of the agricultural fungicide vinclozolin on the F0 generation, followed by jet fuel hydrocarbon mixture exposure of the F1 generation, and then pesticide dichlorodiphenyltrichloroethane on the F2 generation gestating females. The subsequent F3 and F4 generations and F5 transgenerational generation were obtained and F1-F5 generations examined for male sperm epigenetic alterations and pathology in males and females. Significant impacts on the male sperm differential DNA methylation regions were observed. The F3-F5 generations were similar in ∼50% of the DNA methylation regions. The pathology of each generation was assessed in the testis, ovary, kidney, and prostate, as well as the presence of obesity and tumors. The pathology used a newly developed Deep Learning, artificial intelligence-based histopathology analysis. Observations demonstrated compounded disease impacts in obesity and metabolic parameters, but other pathologies plateaued with smaller increases at the F5 transgenerational generation. Observations demonstrate that multiple generational exposures, which occur in human populations, appear to increase epigenetic impacts and disease susceptibility

The Discovery of a Potent, Selective, and Peripherally Restricted Pan-Trk Inhibitor (PF-06273340) for the Treatment of Pain

The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially “druggable” point of intervention. To deliver the safety profile required for chronic, nonlife threatening pain indications, highly kinase-selective Trk inhibitors with minimal brain availability are sought. Herein we describe how the use of SBDD, 2D QSAR models, and matched molecular pair data in compound design enabled the delivery of the highly potent, kinase-selective, and peripherally restricted clinical candidate PF-06273340

Prospects for progress on health inequalities in England in the post-primary care trust era : professional views on challenges, risks and opportunities

Background - Addressing health inequalities remains a prominent policy objective of the current UK government, but current NHS reforms involve a significant shift in roles and responsibilities. Clinicians are now placed at the heart of healthcare commissioning through which significant inequalities in access, uptake and impact of healthcare services must be addressed. Questions arise as to whether these new arrangements will help or hinder progress on health inequalities. This paper explores the perspectives of experienced healthcare professionals working within the commissioning arena; many of whom are likely to remain key actors in this unfolding scenario. Methods - Semi-structured interviews were conducted with 42 professionals involved with health and social care commissioning at national and local levels. These included representatives from the Department of Health, Primary Care Trusts, Strategic Health Authorities, Local Authorities, and third sector organisations. Results - In general, respondents lamented the lack of progress on health inequalities during the PCT commissioning era, where strong policy had not resulted in measurable improvements. However, there was concern that GP-led commissioning will fare little better, particularly in a time of reduced spending. Specific concerns centred on: reduced commitment to a health inequalities agenda; inadequate skills and loss of expertise; and weakened partnership working and engagement. There were more mixed opinions as to whether GP commissioners would be better able than their predecessors to challenge large provider trusts and shift spend towards prevention and early intervention, and whether GPs’ clinical experience would support commissioning action on inequalities. Though largely pessimistic, respondents highlighted some opportunities, including the potential for greater accountability of healthcare commissioners to the public and more influential needs assessments via emergent Health & Wellbeing Boards. Conclusions - There is doubt about the ability of GP commissioners to take clearer action on health inequalities than PCTs have historically achieved. Key actors expect the contribution from commissioning to address health inequalities to become even more piecemeal in the new arrangements, as it will be dependent upon the interest and agency of particular individuals within the new commissioning groups to engage and influence a wider range of stakeholders.</p

Integrating Machine Learning for Planetary Science: Perspectives for the Next Decade

Machine learning (ML) methods can expand our ability to construct, and draw insight from large datasets. Despite the increasing volume of planetary observations, our field has seen few applications of ML in comparison to other sciences. To support these methods, we propose ten recommendations for bolstering a data-rich future in planetary science.Comment: 10 pages (expanded citations compared to 8 page submitted version for decadal survey), 3 figures, white paper submitted to the Planetary Science and Astrobiology Decadal Survey 2023-203

Bridging the gap between research, policy, and practice: Lessons learned from academic-public partnerships in the CTSA network.

A primary barrier to translation of clinical research discoveries into care delivery and population health is the lack of sustainable infrastructure bringing researchers, policymakers, practitioners, and communities together to reduce silos in knowledge and action. As National Institutes of Health's (NIH) mechanism to advance translational research, Clinical and Translational Science Award (CTSA) awardees are uniquely positioned to bridge this gap. Delivering on this promise requires sustained collaboration and alignment between research institutions and public health and healthcare programs and services. We describe the collaboration of seven CTSA hubs with city, county, and state healthcare and public health organizations striving to realize this vision together. Partnership representatives convened monthly to identify key components, common and unique themes, and barriers in academic-public collaborations. All partnerships aligned the activities of the CTSA programs with the needs of the city/county/state partners, by sharing resources, responding to real-time policy questions and training needs, promoting best practices, and advancing community-engaged research, and dissemination and implementation science to narrow the knowledge-to-practice gap. Barriers included competing priorities, differing timelines, bureaucratic hurdles, and unstable funding. Academic-public health/health system partnerships represent a unique and underutilized model with potential to enhance community and population health

Addressing the environmental, community and health impacts of resource development: Challenges across scales, sectors and sites

Work that addresses the cumulative impacts of resource extraction on environment, community, and health is necessarily large in scope. This paper presents experiences from initiating research at this intersection and explores implications for the ambitious, integrative agenda of planetary health. The purpose is to outline origins, design features, and preliminary insights from our intersectoral and international project, based in Canada and titled the “Environment, Community, Health Observatory” (ECHO) Network. With a clear emphasis on rural, remote, and Indigenous communities, environments, and health, the ECHO Network is designed to answer the question: How can an Environment, Community, Health Observatory Network support the integrative tools and processes required to improve understanding and response to the cumulative health impacts of resource development? The Network is informed by four regional cases across Canada where we employ a framework and an approach grounded in observation, “taking notice for action”, and collective learning. Sharing insights from the foundational phase of this five-year project, we reflect on the hidden and obvious challenges of working across scales, sectors, and sites, and the overlap of generative and uncomfortable entanglements associated with health and resource development. Yet, although intersectoral work addressing the cumulative impacts of resource extraction presents uncertainty and unresolved tensions, ultimately we argue that it is worth staying with the trouble

Addressing the environmental, community and health impacts of resource development: Challenges across scales, sectors and sites

Work that addresses the cumulative impacts of resource extraction on environment, community, and health is necessarily large in scope. This paper presents experiences from initiating research at this intersection and explores implications for the ambitious, integrative agenda of planetary health. The purpose is to outline origins, design features, and preliminary insights from our intersectoral and international project, based in Canada and titled the “Environment, Community, Health Observatory” (ECHO) Network. With a clear emphasis on rural, remote, and Indigenous communities, environments, and health, the ECHO Network is designed to answer the question: How can an Environment, Community, Health Observatory Network support the integrative tools and processes required to improve understanding and response to the cumulative health impacts of resource development? The Network is informed by four regional cases across Canada where we employ a framework and an approach grounded in observation, “taking notice for action”, and collective learning. Sharing insights from the foundational phase of this five-year project, we reflect on the hidden and obvious challenges of working across scales, sectors, and sites, and the overlap of generative and uncomfortable entanglements associated with health and resource development. Yet, although intersectoral work addressing the cumulative impacts of resource extraction presents uncertainty and unresolved tensions, ultimately we argue that it is worth staying with the trouble

Purpose in life as a resilience factor for brain health: diffusion MRI findings from the Midlife in the U.S. study

IntroductionA greater sense of purpose in life is associated with several health benefits relevant for active aging, but the mechanisms remain unclear. We evaluated if purpose in life was associated with indices of brain health.MethodsWe examined data from the Midlife in the United States (MIDUS) Neuroscience Project. Diffusion weighted magnetic resonance imaging data (n=138; mean age 65.2 years, age range 48-95; 80 females; 37 black, indigenous, and people of color) were used to estimate microstructural indices of brain health such as axonal density, and axonal orientation. The seven-item purpose in life scale was used. Permutation analysis of linear models was used to examine associations between purpose in life scores and the diffusion metrics in white matter and in the bilateral hippocampus, adjusting for age, sex, education, and race.Results and discussionGreater sense of purpose in life was associated with brain microstructural features consistent with better brain health. Positive associations were found in both white matter and the right hippocampus, where multiple convergent associations were detected. The hippocampus is a brain structure involved in learning and memory that is vulnerable to stress but retains the capacity to grow and adapt through old age. Our findings suggest pathways through which an enhanced sense of purpose in life may contribute to better brain health and promote healthy aging. Since purpose in life is known to decline with age, interventions and policy changes that facilitate a greater sense of purpose may extend and improve the brain health of individuals and thus improve public health

Metal on metal hip resurfacing versus uncemented custom total hip replacement - early results

<p>Abstract</p> <p>Introduction</p> <p>There is no current consensus on the most appropriate prosthesis for treating symptomatic osteoarthritis (OA) of the hip in young, active patients. Modern metal on metal hip resurfacing arthroplasty (HR) has gained popularity as it is theoretically more stable, bone conserving and easier to revise than total hip arthroplasty. Early results of metal on metal resurfacing have been encouraging. We have compared two well matched cohorts of patients with regard to function, pain relief and patient satisfaction.</p> <p>Methods</p> <p>This prospective study compares 2 cohorts of young, active patients treated with hip resurfacing (137 patients, 141 hips) and custom uncemented (CADCAM) stems (134 patients, 141 hips). All procedures were performed by a single surgeon. Outcome measures included Oxford, WOMAC and Harris hip scores as well as an activity score. Statistical analysis was performed using the unpaired student's t-test.</p> <p>Results</p> <p>One hundred and thirty four and 137 patients were included in the hip replacement and resurfacing groups respectively. The mean age of these patients was 54.6 years. The mean duration of follow up for the hip resurfacing group was 19.2 months compared to 13.4 months for the total hip replacement group.</p> <p>Pre operative oxford, Harris and WOMAC scores in the THA group were 41.1, 46.4 and 50.9 respectively while the post operative scores were 14.8, 95.8 and 5.0. In the HR group, pre- operative scores were 37.0, 54.1 and 45.9 respectively compared to 15.0, 96.8 and 6.1 post operatively. The degree of improvement was similar in both groups.</p> <p>Conclusion</p> <p>There was no significant clinical difference between the patients treated with hip resurfacing and total hip arthroplasty in the short term.</p