Biomass-derived carbon dots as emerging visual platforms for fluorescent sensing.

Biomass-derived carbon dots (CDs) are non-toxic and fluorescently stable, making them suitable for extensive application in fluorescence sensing. The use of cheap and renewable materials not only improves the utilization rate of waste resources, but it is also drawing increasing attention to and interest in the production of biomass-derived CDs. Visual fluorescence detection based on CDs is the focus of current research. This method offers high sensitivity and accuracy and can be used for rapid and accurate determination under complex conditions. This paper describes the biomass precursors of CDs, including plants, animal remains and microorganisms. The factors affecting the use of CDs as fluorescent probes are also discussed, and a brief overview of enhancements made to the preparation process of CDs is provided. In addition, the application prospects and challenges related to biomass-derived CDs are demonstrated.

Impact of short-term, pharmacological CARM1 inhibition on skeletal muscle mass, function, and atrophy in mice.

Coactivator-associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of arginine residues on target proteins critical for health and disease. The purpose of this study was to characterize the effects of short-term, pharmacological CARM1 inhibition on skeletal muscle size, function, and atrophy. Adult mice (n = 10 or 11/sex) were treated with either a CARM1 inhibitor (150 mg/kg EZM2302; EZM) or vehicle (Veh) via oral gavage for 11-13 days and muscle mass, function, and exercise capacity were assessed. In addition, we investigated the effect of CARM1 suppression on unilateral hindlimb denervation (DEN)-induced muscle atrophy (n = 8/sex). We report that CARM1 inhibition caused significant reductions in the asymmetric dimethylation of known CARM1 substrates but no change in CARM1 protein or mRNA content in skeletal muscle. Reduced CARM1 activity did not affect body or muscle mass, however, we observed a decrease in exercise capacity and muscular endurance in male mice. CARM1 methyltransferase activity increased in the muscle of Veh-treated mice following 7 days of DEN, and this response was blunted in EZM-dosed mice. Skeletal muscle mass and myofiber cross-sectional area were significantly reduced in DEN compared with contralateral, non-DEN limbs to a similar degree in both treatment groups. Furthermore, skeletal muscle atrophy and autophagy gene expression programs were elevated in response to DEN independent of CARM1 suppression. Collectively, these results suggest that short-term, pharmacological CARM1 inhibition in adult animals affects muscle performance in a sex-specific manner but does not impact the maintenance and remodeling of skeletal muscle mass during conditions of neurogenic muscle atrophy.NEW & NOTEWORTHY Short-term pharmacological inhibition of coactivator-associated arginine methyltransferase 1 (CARM1) was effective at significantly reducing CARM1 methyltransferase function in skeletal muscle. CARM1 inhibition did not impact muscle mass, but exercise capacity was impaired, particularly in male mice, whereas morphological and molecular signatures of denervation-induced muscle atrophy were largely maintained in animals administered the inhibitor. Altogether, the role of CARM1 in neuromuscular biology remains complex and requires further investigation of its therapeutic potential in muscle-wasting conditions.

Beyond Pristine Metal-Organic Frameworks: Preparation of Hollow MOFs and Their Composites for Catalysis, Sensing, and Adsorption Removal Applications.

Metal-organic frameworks (MOFs) have been broadly applied to numerous domains with a substantial surface area, tunable pore size, and multiple unsaturated metal sites. Recently, hollow MOFs have greatly attracted the scientific community due to their internal cavities and gradient pore structures. Hollow MOFs have a higher tunability, faster mass-transfer rates, and more accessible active sites when compared to traditional, solid MOFs. Hollow MOFs are also considered to be candidates for some functional material carriers. For example, composite materials such as hollow MOFs and metal nanoparticles, metal oxides, and enzymes have been prepared. These composite materials integrate the characteristics of hollow MOFs with functional materials and are broadly used in many aspects. This review describes the preparation strategies of hollow MOFs and their composites as well as their applications in organic catalysis, electrochemical sensing, and adsorption separation. Finally, we hope that this review provides meaningful knowledge about hollow-MOF composites and their derivatives and offers many valuable references to develop hollow-MOF-based applied materials.

The Structure and Financing of Health Care Systems Affected How Providers Coped With COVID-19.

Policy Points We compared the structure of health care systems and the financial effects of the COVID-19 pandemic on health care providers in the United States, England, Germany, and Israel: systems incorporating both public and private insurers and providers. The negative financial effects on health care providers have been more severe in the United States than elsewhere, owing to the prevalence of activity-based payment systems, limited direct governmental control over available provider capacity, and the structure of governmental financial relief. In a pandemic, activity-based payment reverses the conventional financial positions of payers and providers and may prevent providers from prioritizing public health because of the desire to avoid revenue loss caused by declines in patient visits.

Minireview: Regulatory T Cells and Ovarian Cancer.

In the last 15 years, it has become apparent that ovarian cancer is recognized by the immune system, taking into account that T cell infiltration can be associated with increased overall survival. Several studies indicate that a correct combination of cluster of differentiation 8 and cluster of differentiation 4 T cells is key to fight tumor progression and that the presence of regulatory T cells (Tregs) infiltrating ovarian solid tumors (or present in ascites) is deleterious. Several markers that characterize Tregs include glucocorticoid-induced tumor necrosis factor receptor, cytotoxic T lymphocyte antigen-4, and forkhead box protein 3 (Foxp3). Research has shown that Tregs can infiltrate cancerous tissue and contribute to tumor growth by secreting immunosuppressive cytokines such as transforming growth factor beta and interleukin (IL)-10. Importantly, these cells might hamper the efficacy of immunotherapeutic approaches, thus strategies involving depletion or regulation of this population have been proposed and tested in experimental models. In this Minireview, we will discuss the relevance of Tregs in ovarian cancer and the experimental approaches destined to impair their immunosuppressive effects.

Opportunities and Challenges in the Design and Analysis of Biomass Supply Chains.

The biomass supply chain is one of the most critical elements of large-scale bioenergy production and in many cases a key barrier for procuring initial funding for new developments on specific energy crops. Most productions rely on complex transforming chains linked to feed and food markets. The term 'supply chain' covers various aspects from cultivation and harvesting of the biomass, to treatment, transportation, and storage. After energy conversion, the product must be delivered to final consumption, whether it is in the form of electricity, heat, or more tangible products, such as pellets and biofuels. Effective supply chains are of utmost importance for bioenergy production, as biomass tends to possess challenging seasonal production cycles and low mass, energy and bulk densities. Additionally, the demand for final products is often also dispersed, further complicating the supply chain. The goal of this paper is to introduce key components of biomass supply chains, examples of related modeling applications, and if/how they address aspects related to environmental metrics and management. The paper will introduce a concept of integrated supply systems for sustainable biomass trade and the factors influencing the bioenergy supply chain landscape, including models that can be used to investigate the factors. The paper will also cover various aspects of transportation logistics, ranging from alternative modal and multi-modal alternatives to introduction of support tools for transportation analysis. Finally gaps and challenges in supply chain research are identified and used to outline research recommendations for the future direction in this area of study.

Data for health system comparison and assessment in the African Region: A review of 63 indicators available in international databases.

Background: Achieving universal health coverage in the African region requires health systems strengthening. Assessing and comparing health systems contributes to this process, but requires internationally comparable data. The European Observatory on Health Systems and Policies has produced Health Systems in Transition (HiT) reviews in Europe, Asia, North America and the Caribbean with a standardised template. This study explores data availability in international databases for the quantitative health and health system indicators in the HiT template for the WHO African region. Methods: We identified ten databases which contained data for 40 of the 80 original HiT indicators and an additional 23 proxy indicators to fill some gaps. We then assessed data availability for the resulting 63 indicators by country and time, i.e. first/last year of data, years of data available overall and since 2000, and we explored for each indicator (1) against the country with the greatest availability overall and (2) against annual availability for all years since 2000. Results: Overall data availability was greatest in South Africa (93.0% of possible total points) and least in South Sudan (59.5%). Since 2000, Uganda (60.4%) has had the highest data availability and South Sudan (37.2%) the lowest. By topic, data availability was the highest for health financing (91.4%; median start/end date 2000/2019) and background characteristics (88.5%; 1990/2020) and was considerably lower for health system performance (54.5%; 2000/2018) and physical and human resources (44.8%; 2004/2013). Data are available for different years in different countries, and at irregular intervals, complicating time series analysis. No data are available for service provision indicators. Conclusions: Gaps in data in international databases across time, countries, and topics undermine systematic health systems comparisons and assessments, regional health systems strengthening, and efforts to achieve universal health coverage. More efforts are needed to strengthen national data collection and management and integrate national data into international databases to support cross-country assessments, peer learning, and planning. In tandem, more research is needed to understand the specific historical, cultural, administrative, and technological determinants influencing country data availability, as well as the facilitators and barriers of data sharing between countries and international databases, and the potential of new technologies to increase timeliness of data.

Economic and Sustainability Impacts of Yield and Composition Variation in Bioenergy Crops: Switchgrass (Panicum virgatum L.).

Economically viable production of biobased products and fuels requires high-yielding, high-quality, sustainable process-advantaged crops, developed using bioengineering or advanced breeding approaches. Understanding which crop phenotypic traits have the largest impact on biofuel economics and sustainability outcomes is important for the targeted feedstock crop development. Here, we evaluated biomass yield and cell-wall composition traits across a large natural variant population of switchgrass (Panicum virgatum L.) grown across three common garden sites. Samples from 331 switchgrass genotypes were collected and analyzed for carbohydrate and lignin components. Considering plant survival and biomass after multiple years of growth, we found that 84 of the genotypes analyzed may be suited for commercial production in the southeastern U.S. These genotypes show a range of growth and compositional traits across the population that are apparently independent of each other. We used these data to conduct techno-economic analyses and life cycle assessments evaluating the performance of each switchgrass genotype under a standard cellulosic ethanol process model with pretreatment, added enzymes, and fermentation. We find that switchgrass yield per area is the largest economic driver of the minimum fuel selling price (MSFP), ethanol yield per hectare, global warming potential (GWP), and cumulative energy demand (CED). At any yield, the carbohydrate content is significant but of secondary importance. Water use follows similar trends but has more variability due to an increased dependence on the biorefinery model. Analyses presented here highlight the primary importance of plant yield and the secondary importance of carbohydrate content when selecting a feedstock that is both economical and sustainable.

30 years of primary health care reforms in Estonia: The role of financial incentives to achieve a multidisciplinary primary health care system.

Estonia has a legacy of hospital-focused service provision, but since the 1990s, has introduced a series of reforms to strengthen primary health care (PHC). The recent PHC reforms have placed an increasing focus on multidisciplinary care, involving home nurses, midwives, and physiotherapists, and emphasize PHC centres over single physician practices. These incremental reforms, without a supporting legal basis nor explicitly defined timelines and targets, nonetheless demonstrated the ability of financial incentives to drive change. EU structural funds in particular provided essential funding for infrastructure investments in PHC. Yet not all stakeholders supported these initiatives, largely due to the uncertain sustainability of funding. The EHIF also adjusted contract and payment terms to support PHC reforms, with some concessions to PHC providers operating as single practitioners. Despite substantial progress over the last three decades to shift the focus to PHC, there are some important bottlenecks that hinder the progress. These include PHC providers' hesitance to give up their freedom as single practitioners, low interest from specialists to start working at the PHC level, and a lack of financial incentives and adequate funding for a broader scope of PHC services. This looks to become more challenging in the future, as nearly half of family physicians are 60 years old or older. The development of the new PHC strategy in 2023 is very timely to comprehensively address these bottlenecks and to set the vision for the future of PHC in Estonia.

France: Health System Review.

This review of the French health system analyses recent developments in health organisation and governance, financing, healthcare provision, recent reforms and health system performance. Overall health status continues to improve in France, although geographic and socioeconomic inequalities in life expectancy persist. The health system combines a social health insurance (SHI) model with an important role for tax-based revenues to finance healthcare. The health system provides universal coverage, with a broad benefits basket, but cost-sharing is required for all essential services. Private complementary insurance to cover these costs results in very low average out-of-pocket (OOP) payments, although there are concerns regarding solidarity, financial redistribution and efficiency in the health system. The macroeconomic context in the last couple of years in the country has been affected by the Covid-19 pandemic, which resulted in subsequent increases of total health expenditure in France in 2020 (3.7%) and 2021 (9.8%). Healthcare provision continues to be highly fragmented in France, with a segmented approach to care organization and funding across primary, secondary and long-term care. Recent reforms aim to strengthen primary care by encouraging multidisciplinary group practices, while public health efforts over the last decade have focused on boosting prevention strategies and tackling lifestyle risk factors, such as smoking and obesity with limited success. Continued challenges include ensuring the sustainability of the health workforce, particularly to secure adequate numbers of health professionals in medically underserved areas, such as rural and less affluent communities, and improving working conditions, remuneration and career prospects, especially for nurses, to support retention. The Covid-19 pandemic has brought to light some structural weaknesses within the French health system, but it has also provided opportunities for improving its sustainability. There has been a notable shift in the will to give more room to decision-making at the local level, involving healthcare professionals, and to find new ways of funding healthcare providers to encourage care coordination and integration.

CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy.

CARM1 (coactivator associated arginine methyltransferase 1) has recently emerged as a powerful regulator of skeletal muscle biology. However, the molecular mechanisms by which the methyltransferase remodels muscle remain to be fully understood. In this study, carm1 skeletal muscle-specific knockout (mKO) mice exhibited lower muscle mass with dysregulated macroautophagic/autophagic and atrophic signaling, including depressed AMP-activated protein kinase (AMPK) site-specific phosphorylation of ULK1 (unc-51 like autophagy activating kinase 1; Ser555) and FOXO3 (forkhead box O3; Ser588), as well as MTOR (mechanistic target of rapamycin kinase)-induced inhibition of ULK1 (Ser757), along with AKT/protein kinase B site-specific suppression of FOXO1 (Ser256) and FOXO3 (Ser253). In addition to lower mitophagy and autophagy flux in skeletal muscle, carm1 mKO led to increased mitochondrial PRKN/parkin accumulation, which suggests that CARM1 is required for basal mitochondrial turnover and autophagic clearance. carm1 deletion also elicited PPARGC1A (PPARG coactivator 1 alpha) activity and a slower, more oxidative muscle phenotype. As such, these carm1 mKO-evoked adaptations disrupted mitophagy and autophagy induction during food deprivation and collectively served to mitigate fasting-induced muscle atrophy. Furthermore, at the threshold of muscle atrophy during food deprivation experiments in humans, skeletal muscle CARM1 activity decreased similarly to our observations in mice, and was accompanied by site-specific activation of ULK1 (Ser757), highlighting the translational impact of the methyltransferase in human skeletal muscle. Taken together, our results indicate that CARM1 governs mitophagic, autophagic, and atrophic processes fundamental to the maintenance and remodeling of muscle mass. Targeting the enzyme may provide new therapeutic approaches for mitigating skeletal muscle atrophy.

Health and Care Data: Approaches to data linkage for evidence-informed policy.

An indispensable prerequisite for answering research questions in health services research is the availability and accessibility of comprehensive, high-quality data. It can be assumed that health services research in the coming years will be increasingly based on data linkage, i.e., the linking, or connecting, of several data sources based on suitable common key variables. A range of approaches to data collection, storage, linkage and availability exists across countries, particularly for secondary research purposes (i.e., the use of data initially collected for other purposes), such as health systems research. The main goal of this review is to develop an overview of, and gain insights into, current approaches to linking data sources in the context of health services research, with the view to inform policy, based on existing practices in high-income countries in Europe and beyond. In doing so, another objective is to provide lessons for countries looking for possible or alternative approaches to data linkage. Thirteen country case studies of data linkage approaches were selected and analysed. Rather than being comprehensive, this review aimed to identify varied and potentially useful case studies to showcase different approaches to data linkage worldwide. A conceptual framework was developed to guide the selection and description of case studies. Information was first identified and collected from publicly available sources and a profile was then created for each country and each case study; these profiles were forwarded to appropriate country experts for validation and completion. The report presents an overview of the included countries and their case studies (Chapter 2), with key data per country and case study in the appendices. This is followed by a closer look at the possibilities of using routine data (Chapter 3); the different approaches to linkage (Chapter 4); the different access routes for researchers (Chapter 5); the use of data for research from electronic patient or health records (Chapter 6); foundational considerations related to data safety, privacy and governance (Chapter 7); recent developments in cross-border data sharing and the European Health Data Space (Chapter 8); and considerations of changes and responses catalysed by the COVID-19 pandemic as related to the generation and secondary use of data (Chapter 9). The review ends with overall conclusions on the necessary characteristics of data to inform research relevant for policy and highlights some insights to inspire possible future solutions - less or more disruptive - for countries looking to expand their use of data (Chapter 10). It emphasises that investing in data linkage for secondary use will not only contribute to the strengthening of national health systems, but also promote international cooperation and contribute to the international visibility of scientific excellence.

A randomized comparison of laparoscopic, magnetically anchored, and flexible endoscopic cameras in performance and workload between laparoscopic and single-incision surgery.

BACKGROUND: This study aimed to evaluate the surgeon performance and workload of a next-generation magnetically anchored camera compared with laparoscopic and flexible endoscopic imaging systems for laparoscopic and single-site laparoscopy (SSL) settings. METHODS: The cameras included a 5-mm 30° laparoscope (LAP), a magnetically anchored (MAGS) camera, and a flexible endoscope (ENDO). The three camera systems were evaluated using standardized optical characteristic tests. Each system was used in random order for visualization during performance of a standardized suturing task by four surgeons. Each participant performed three to five consecutive repetitions as a surgeon and also served as a camera driver for other surgeons. Ex vivo testing was conducted in a laparoscopic multiport and SSL layout using a box trainer. In vivo testing was performed only in the multiport configuration and used a previously validated live porcine Nissen model. RESULTS: Optical testing showed superior resolution for MAGS at 5 and 10 cm compared with LAP or ENDO. The field of view ranged from 39 to 99°. The depth of focus was almost three times greater for MAGS (6-270 mm) than for LAP (2-88 mm) or ENDO (1-93 mm). Both ex vivo and in vivo multiport combined surgeon performance was significantly better for LAP than for ENDO, but no significant differences were detected for MAGS. For multiport testing, workload ratings were significantly less ex vivo for LAP and MAGS than for ENDO and less in vivo for LAP than for MAGS or ENDO. For ex vivo SSL, no significant performance differences were detected, but camera drivers rated the workload significantly less for MAGS than for LAP or ENDO. CONCLUSION: The data suggest that the improved imaging element of the next-generation MAGS camera has optical and performance characteristics that meet or exceed those of the LAP or ENDO systems and that the MAGS camera may be especially useful for SSL. Further refinements of the MAGS camera are encouraged.

What have European countries done to prevent the spread of COVID-19? Lessons from the COVID-19 Health system response monitor.

Although some European countries imposed measures that successfully slowed the transmission of Covid-19 during the first year of the pandemic, others struggled, either because they acted slowly or implemented measures ineffectively. In this paper we consider the European experience with public health measures designed to prevent transmission of COVID-19. Based on literature and country responses described in the COVID-19 Health System Response Monitor from March 2020 to December 2020, we consider some critical aspects of public health policy responses. These include the importance of public health capacity that can scale up surveillance and outbreak control, including effective testing and contract tracing, of clear messaging based on an understanding of human behaviour, policies that address the undesirable consequences of necessary measures, such as support for those isolating or unable to earn, and the ability to implement at pace and scale a major vaccine rollout. We conclude that for countries to be successful at preventing COVID-19 transmission, there is a need for a clear strategy with explicit goals and a whole systems approach to implementation.

Transformations in the landscape of primary health care during COVID-19: Themes from the European region.

The COVID-19 pandemic has dramatically impacted primary health care (PHC) across Europe. Since March 2020, the COVID-19 Health System Response Monitor (HSRM) has documented country-level responses using a structured template distributed to country experts. We extracted all PHC-relevant data from the HSRM and iteratively developed an analysis framework examining the models of PHC delivery employed by PHC providers in response to the pandemic, as well as the government enablers supporting these models. Despite the heterogenous PHC structures and capacities across European countries, we identified three prevalent models of PHC delivery employed: (1) multi-disciplinary primary care teams coordinating with public health to deliver the emergency response and essential services; (2) PHC providers defining and identifying vulnerable populations for medical and social outreach; and (3) PHC providers employing digital solutions for remote triage, consultation, monitoring and prescriptions to avoid unnecessary contact. These were supported by government enablers such as increasing workforce numbers, managing demand through public-facing risk communications, and prioritising pandemic response efforts linked to vulnerable populations and digital solutions. We discuss the importance of PHC systems maintaining and building on these models of PHC delivery to strengthen preparedness for future outbreaks and better respond to the contemporary health challenges.

European countries' responses in ensuring sufficient physical infrastructure and workforce capacity during the first COVID-19 wave.

The COVID-19 pandemic has placed unprecedented pressure on health systems' capacities. These capacities include physical infrastructure, such as bed capacities and medical equipment, and healthcare professionals. Based on information extracted from the COVID-19 Health System Reform Monitor, this paper analyses the strategies that 45 countries in Europe have taken to secure sufficient health care infrastructure and workforce capacities to tackle the crisis, focusing on the hospital sector. While pre-crisis capacities differed across countries, some strategies to boost surge capacity were very similar. All countries designated COVID-19 units and expanded hospital and ICU capacities. Additional staff were mobilised and the existing health workforce was redeployed to respond to the surge in demand for care. While procurement of personal protective equipment at the international and national levels proved difficult at the beginning due to global shortages, countries found innovative solutions to increase internal production and enacted temporary measures to mitigate shortages. The pandemic has shown that coordination mechanisms informed by real-time monitoring of available health care resources are a prerequisite for adaptive surge capacity in public health crises, and that closer cooperation between countries is essential to build resilient responses to COVID-19.

Providing health services effectively during the first wave of COVID-19: A cross-country comparison on planning services, managing cases, and maintaining essential services.

The COVID-19 pandemic triggered abrupt challenges for health care providers, requiring them to simultaneously plan for and manage a rise of COVID-19 cases while maintaining essential health services. Since March 2020, the COVID-19 Health System Response Monitor, a joint initiative of the European Observatory on Health Systems and Policies, the WHO Regional Office for Europe, and the European Commission, has documented country responses to COVID-19 using a structured template which includes a section on provision of care. Using the information available on the platform, this paper analyzes how countries planned services for potential surge capacity, designed patient flows ensuring separation between COVID-19 and non-COVID-19 patients, and maintained routine services in both hospital and ambulatory settings. Despite very real differences in the organization of health and care services, there were many similarities in country responses. These include transitioning the management of COVID-19 mild cases from hospitals to outpatient settings, increasing the use of remote consultations, and cancelling or postponing non-urgent services during the height of the first wave. In the immediate future, countries will have to continue balancing care for COVID-19 and non-COVID-19 patients to minimize adverse health outcomes, ideally with supporting guidelines and COVID-19-specific care zones. Looking forward, policymakers will have to consider whether strategies adopted during the COVID-19 pandemic will become permanent features of care provision.

A reversal of fortune: Comparison of health system responses to COVID-19 in the Visegrad group during the early phases of the pandemic.

This paper analyses the health policy response to the COVID-19 pandemic in the four Visegrad countries - Czechia, Hungary, Poland, and Slovakia - in spring and summer 2020. The four countries implemented harsh transmission prevention measures at the beginning of the pandemic and managed to effectively avoid the first wave of infections during spring. Likewise, all four relaxed most of these measures during the summer and experienced uncontrolled growth of cases since September 2020. Along the way, there has been an erosion of public support for the government measures. This was mainly due to economic considerations taking precedent but also likely due to diminished trust in the government. All four countries have been overly reliant on their relatively high bed capacity, which they managed to further increase at the cost of elective treatments, but this could not always be supported with sufficient health workforce capacity. Finally, none of the four countries developed effective find, test, trace, isolate and support systems over the summer despite having relaxed most of the transmission protection measures since late spring. This left the countries ill-prepared for the rise in the number of COVID-19 infections they have been experiencing since autumn 2020.

Roles of Hormone Replacement Therapy and Menopause on Osteoarthritis and Cardiovascular Disease Outcomes: A Narrative Review.

Osteoarthritis (OA) is a highly prevalent condition characterized by degradation of the joints. OA and cardiovascular disease (CVD) are leading contributors to disease burden worldwide, with a high level of overlap between the risk factors and occurrence of both conditions. Chief among the risk factors that contribute to OA and CVD are sex and age, which are both independent and interacting traits. Specifically, the prevalence of both conditions is higher in older women, which may be mediated by the occurrence of menopause. Menopause represents a significant transition in a women's life, and the rapid decline in circulating sex hormones, estrogen and progesterone, leads to complex physiological changes. Declines in hormone levels may partially explain the increase in prevalence of OA and CVD in post-menopausal women. In theory, the use of hormone therapy (HT) may buffer adverse effects of menopause; however, it is unclear whether HT offers protective effects for the onset or progression of these diseases. Studies have shown mixed results when describing the influence of HT on disease risk among post-menopausal women, which warrants further exploration. The roles that increasing age, female sex, HT, and CVD play in OA risk demonstrate that OA is a multifaceted condition. This review provides a timely consolidation of current literature and suggests aims for future research directions to bridge gaps in the understanding of how OA, CVD, and HT interact in post-menopausal women.

The CARM1 transcriptome and arginine methylproteome mediate skeletal muscle integrative biology.

OBJECTIVE: Coactivator-associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of arginine residues on target proteins to regulate critical processes in health and disease. A mechanistic understanding of the role(s) of CARM1 in skeletal muscle biology is only gradually emerging. The purpose of this study was to elucidate the function of CARM1 in regulating the maintenance and plasticity of skeletal muscle. METHODS: We used transcriptomic, methylproteomic, molecular, functional, and integrative physiological approaches to determine the specific impact of CARM1 in muscle homeostasis. RESULTS: Our data defines the occurrence of arginine methylation in skeletal muscle and demonstrates that this mark occurs on par with phosphorylation and ubiquitination. CARM1 skeletal muscle-specific knockout (mKO) mice displayed altered transcriptomic and arginine methylproteomic signatures with molecular and functional outcomes confirming remodeled skeletal muscle contractile and neuromuscular junction characteristics, which presaged decreased exercise tolerance. Moreover, CARM1 regulates AMPK-PGC-1α signalling during acute conditions of activity-induced muscle plasticity. CONCLUSIONS: This study uncovers the broad impact of CARM1 in the maintenance and remodelling of skeletal muscle biology.