Cannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models.

Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients.

Community advisory board members' perspectives on their contributions to a large multistate cluster RCT: a mixed methods study.

Background: Community advisory boards (CABs) are an established approach to ensuring research reflects community priorities. This paper examines two CABs that are part of the HEALing Communities Study which aims to reduce overdose mortality. This analysis aimed to understand CAB members' expectations, experiences, and perspectives on CAB structure, communication, facilitation, and effectiveness during the first year of an almost fully remote CAB implementation.

Mobile treatment for opioid use disorder: Implementation of community-based, same-day medication access interventions.

Background: Medications for Opioid Use Disorder (MOUD) are lifesaving, but <20 % of individuals in the US who could benefit receive them. As part of the NIH-supported HEALing Communities Study (HCS), coalitions in several communities in Massachusetts and Ohio implemented mobile MOUD programs to overcome barriers to MOUD receipt. We defined mobile MOUD programs as units that provide same-day access to MOUD at remote sites.

Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.

As central nervous system (CNS)-related disorders present an increasing cause of global morbidity, mortality, and high pressure on our healthcare system, there is an urgent need for new insights and treatment options. The endocannabinoid system (ECS) is a critical network of endogenous compounds, receptors, and enzymes that contribute to CNS development and regulation. Given its multifaceted involvement in neurobiology and its significance in various CNS disorders, the ECS as a whole is considered a promising therapeutic target.

A Qualitative Study of Health Equity's Role in Community Coalition Development.

Opioid overdose deaths are dramatically increasing in the United States and disproportionately affecting minority communities, with the increasing presence of fentanyl exacerbating this crisis. Developing community coalitions is a long-standing strategy used to address public health issues. However, there is a limited understanding of how coalitions operate amid a serious public health crisis.

Doing Health Policy Analysis: The Enduring Relevance of Simple Models Comment on "Modelling the Health Policy Process: One Size Fits All or Horses for Courses".

The analysis of health policy processes in low- and middle-income countries (LMICs) emerged as a research area in the early 1990s. In their recent editorial Powell and Mannion argue that such research can be deepened by applying public policy theory. In response, we raise three questions to consider: are public policy models fit for purpose in today's world in LMICs (and what other theory can be used)? Is using theory the most important factor in deepening such research? Why do we, as researchers, do this work? Ultimately, we argue that the value of simple models, such as those already used in health policy analysis, lies in their enduring relevance and widespread use.

Community coalition and key stakeholder perceptions of the community opioid epidemic before an intensive community-level intervention.

Introduction: Opioid overdoses are a major public health emergency in the United States. Despite effective treatments that can save lives, access to and utilization of such treatments are limited. Community context plays an important role in addressing treatment barriers and increasing access.

The Department of Veterans Affairs Gulf War Veterans' Illnesses Biorepository: Supporting Research on Gulf War Veterans' Illnesses.

Aims: To introduce a resource supporting research on Gulf War illness (GWI) and related disorders, the Gulf War Veterans' Illnesses Biorepository (GWVIB).

Methods: Gulf War era veterans (GWVs) are recruited nationally and enrolled via telephone and email/postal mail. Enrolled veterans receive annual telephone and mail follow-up to collect health data until their passing.

Sub-Cellular Metabolomics Contributes Mitochondria-Specific Metabolic Insights to a Mouse Model of Leigh Syndrome.

Direct injury of mitochondrial respiratory chain (RC) complex I by Ndufs4 subunit mutations results in complex I deficiency (CID) and a progressive encephalomyopathy, known as Leigh syndrome. While mitochondrial, cytosolic and multi-organelle pathways are known to be involved in the neuromuscular LS pathogenesis, compartment-specific metabolomics has, to date, not been applied to murine models of CID. We thus hypothesized that sub-cellular metabolomics would be able to contribute organelle-specific insights to known Ndufs4 metabolic perturbations.

Clinician's experiences with involuntary commitment for substance use disorder: A qualitative study of moral distress.

Background: Petitions for involuntary commitment of people living with a substance use disorder (SUD) have almost doubled since 2011 in Massachusetts through the policy Section 35. However, the efficacy of this controversial policy remains unclear, and clinicians differ on whether it ought to be used. This study examines how clinicians decide whether to use Section 35 and their experiences of moral distress, the negative feeling that occurs when a clinician is required to pursue a treatment option against their moral judgement due to institutional constraints, associated with its use.

Novel mitochondrial and cytosolic purification pipeline for compartment-specific metabolomics in mammalian disease model tissues.

Introduction: Mitochondria represent an important milieu for studying the pathogenesis of several major diseases. The need for organelle-level metabolic resolution exists, as mitochondrial/cytosolic metabolites are often diluted beyond detection limits in complex samples. Compartment-specific studies are still hindered by the lack of efficient, cost-effective fractioning methods-applicable to laboratories of all financial/analytical standing.

Cervical intraepithelial neoplasia grade 3 in a patient following Gardasil vaccination.

Essentially all cervical dysplasia is caused by human papilloma virus (HPV). Three HPV vaccines have been available, with Gardasil-9 being the most recently approved in the USA. Gardasil-9 covers high-risk HPV strains 16, 18, 31, 33, 45, 52 and 58 as well as low-risk strains 6 and 11.

Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort.

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive head impacts and has been associated with amyotrophic lateral sclerosis (ALS), a fatal, degenerative neuromuscular disorder. The Department of Veterans Affairs Biorepository Brain Bank (VABBB) is a tissue repository that collects antemortem disease progression data and postmortem central nervous system tissue from veterans with ALS. We set out to determine the frequency of co-morbid ALS and CTE in the VABBB cohort and to characterize the clinical, genetic, and pathological distinctions between participants with ALS only and those with both ALS and CTE (ALS+CTE).

Femoral Nerve Block Intervention in Neck of Femur Fracture (FINOF): a randomised controlled trial.

Objective: Fractured neck of femur is a severely painful condition with significant mortality and morbidity. We investigated whether early and continuous use of femoral nerve block can improve pain on movement and mobility after surgery in older participants with fragility neck of femur fracture.

Design: Prospective single-centre, randomised controlled pragmatic trial.

Why do policies change? Institutions, interests, ideas and networks in three cases of policy reform.

Policy researchers have used various categories of variables to explain why policies change, including those related to institutions, interests and ideas. Recent research has paid growing attention to the role of policy networks-the actors involved in policy-making, their relationships with each other, and the structure formed by those relationships-in policy reform across settings and issues; however, this literature has largely ignored the theoretical integration of networks with other policy theories, including the '3Is' of institutions, interests and ideas. This article proposes a conceptual framework integrating these variables and tests it on three cases of policy change in Burkina Faso, addressing the need for theoretical integration with networks as well as the broader aim of theory-driven health policy analysis research in low- and middle-income countries.

Prescribing opioid analgesics for chronic non-malignant pain in general practice - a survey of attitudes and practice.

Background: This study replicates a previous postal survey of general practitioners (GPs) to explore whether attitudes to opioid prescribing have changed at a time when the number of opioid prescriptions issued in primary care has increased.

Methods: With permission, a 57-item survey instrument previously utilised with GPs in the South-west of England was circulated to 214 GPs in city-centre practices in the East Midlands. The survey instrument included items relating to practice context, prescribing patterns and attitudes about analgesic medication, perceived prescribing frequency and reluctance to prescribe.

A framework on the emergence and effectiveness of global health networks.

Since 1990 mortality and morbidity decline has been more extensive for some conditions prevalent in low- and middle-income countries than for others. One reason may be differences in the effectiveness of global health networks, which have proliferated in recent years. Some may be more capable than others in attracting attention to a condition, in generating funding, in developing interventions and in convincing national governments to adopt policies.

The challenge of sustaining effectiveness over time: the case of the global network to stop tuberculosis.

Where once global health decisions were largely the domain of national governments and the World Health Organization, today networks of international organizations, governments, private philanthropies and other entities are actively shaping public policy. However, there is still limited understanding of how global networks form, how they create institutions, how they promote and sustain collective action, and how they adapt to changes in the policy environment. Understanding these processes is crucial to understanding their effectiveness: whether and how global networks influence policy and public health outcomes.

Knowledge and networks - key sources of power in global health: Comment on "Knowledge, moral claims and the exercise of power in global health".

Shiffman rightly raises questions about who exercises power in global health, suggesting power is a complex concept, and the way it is exercised is often opaque. Power that is not based on financial strength but on knowledge or experience, is difficult to estimate, and yet it may provide the legitimacy to make moral claims on what is, or ought to be, on global health agendas. Twenty years ago power was exercised in a much less complex health environment.

Can frameworks inform knowledge about health policy processes? Reviewing health policy papers on agenda setting and testing them against a specific priority-setting framework.

This article systematically reviews a set of health policy papers on agenda setting and tests them against a specific priority-setting framework. The article applies the Shiffman and Smith framework in extracting and synthesizing data from an existing set of papers, purposively identified for their relevance and systematically reviewed. Its primary aim is to assess how far the component parts of the framework help to identify the factors that influence the agenda setting stage of the policy process at global and national levels.

'Scaling-up is a craft not a science': Catalysing scale-up of health innovations in Ethiopia, India and Nigeria.

Donors and other development partners commonly introduce innovative practices and technologies to improve health in low and middle income countries. Yet many innovations that are effective in improving health and survival are slow to be translated into policy and implemented at scale. Understanding the factors influencing scale-up is important.

Femoral nerve block Intervention in Neck of Femur fracture (FINOF): study protocol for a randomized controlled trial.

Background: Hip fractures are very painful leading to lengthy hospital stays. Conventional methods of treating pain are limited. Non-steroidal anti-inflammatories are relatively contraindicated and opioids have significant side effects.

Brokering the boundary between science and advocacy: the case of intermittent preventive treatment among infants.

The process of translating research into policy has gained considerable attention in recent years and a number of studies have investigated the nexus between the two 'worlds' of research and policy. One issue that has been little addressed is about the boundaries between research and advocacy: how far scientists do, or should, promote particular findings to policy makers and others. This article analyses a particular intervention in malaria control and the Consortium set up to accelerate its potential implementation.

Has global fund support for civil society advocacy in the former Soviet Union established meaningful engagement or 'a lot of jabber about nothing'?

Although civil society advocacy for health issues such as HIV transmission through injecting drug use is higher on the global health agenda than previously, its impact on national policy reform has been limited. In this paper we seek to understand why this is the case through an examination of civil society advocacy efforts to reform HIV/AIDS and drugs-related policies and their implementation in three former Soviet Union countries. In-depth semi-structured interviews were conducted in Georgia, Kyrgyzstan and Ukraine by national researchers with representatives from a sample of 49 civil society organizations (CSOs) and 22 national key informants.

Circus monkeys or change agents? Civil society advocacy for HIV/AIDS in adverse policy environments.

This paper explores the factors enabling and undermining civil society efforts to advocate for policy reforms relating to HIV/AIDS and illicit drugs in three countries in Eastern Europe and Central Asia: Georgia, Kyrgyzstan and Ukraine. It examines how political contexts and civil society actors' strengths and weaknesses inhibit or enable advocacy for policy change - issues that are not well understood in relation to specific policy areas such as HIV/AIDS, or particular regions of the world where national policies are believed to be major drivers of the HIV/AIDS epidemic. The study is based on in-depth interviews with representatives of civil society organizations (CSOs) (n = 49) and national level informants including government and development partners (n = 22).