Global Health

Food proteins and their peptides play a significant role in the important biological processes and physiological functions of the body. The peptides show diverse biological benefits ranging from anticancer to antihypertensive, anti-obesity, and immunomodulatory, among others. In this review, an overview of food protein digestion in the gastrointestinal tract and the mechanisms involved was presented. As some proteins remain resistant and undigested, the multifarious factors (e.g. protein type and structure, microbial composition, pH levels and redox potential, host factors, etc.) affecting their colonic fermentation, the derived peptides, and amino acids that evade intestinal digestion are thus considered. The section that follows focuses on the mechanisms of the peptides with anticancer, antihypertensive, anti-obesity, and immunomodulatory effects. As further considerations were made, it is concluded that clinical studies targeting a clear understanding of the gastrointestinal stability, bioavailability, and safety of food-based peptides are still warranted.

A lack of social relationships is increasingly recognized as a type 2 diabetes (T2D) risk. To investigate the underlying mechanism, we used male KK mice, an inbred strain with spontaneous diabetes. Given the association between living alone and T2D risk in humans, we divided the non-diabetic mice into singly housed (KK-SH) and group-housed control mice. Around the onset of diabetes in KK-SH mice, we compared H3K27ac ChIP-Seq with RNA-Seq using pancreatic islets derived from each experimental group, revealing a positive correlation between single-housing-induced changes in H3K27ac and gene expression levels. In particular, single-housing-induced H3K27ac decreases revealed a significant association with islet cell functions and GWAS loci for T2D and related diseases, with significant enrichment of binding motifs for transcription factors representative of human diabetes. Although these H3K27ac regions were preferentially localized to a polymorphic genomic background, SNVs and indels did not cause sequence disruption of enriched transcription factor motifs in most of these elements. These results suggest alternative roles of genetic variants in environment-dependent epigenomic changes and provide insights into the complex mode of disease inheritance.

This cross-sectional study aimed to evaluate work-related stress and the efficacy associated with the newly developed Find My Stress mobile application. The global impact of the COVID-19 pandemic has significantly influenced the quality of life, transcending geographical boundaries and inducing stress that has detrimentally affected health and work efficiency.

The 'Fit to Dance?' survey has been used in a number of studies to understand the health and wellbeing of dancers. These data have not been collected in Brazil as there is no validated questionnaire available in Brazilian Portuguese, culturally validated in Brazil with a scope as broad and comprehensive as that of 'Fit to Dance?'.

Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero.

Opioid analgesics are essential for managing acute and chronic pain in diseases such as cancer. Inadequate opioid access remains a major public health concern in low-income regions including Africa. This study aimed to provide updated and comprehensive data on changes in opioid consumption, specifically in Africa.

Rare diseases affect over 300 million people worldwide and are gaining recognition as a global health priority. Their inclusion in the UN Sustainable Development Goals, the UN Resolution on Addressing the Challenges of Persons Living with a Rare Disease, and the anticipated WHO Global Network for Rare Diseases and WHO Resolution on Rare Diseases, which is yet to be announced, emphasise their significance. People with rare diseases often face unmet health needs, including access to screening, diagnosis, therapy, and comprehensive health care. These challenges highlight the need for awareness and targeted interventions, including comprehensive education, especially in primary care. The majority of rare disease research, clinical services, and health systems are addressed with specialist care. WHO Member States have committed to focusing on primary health care in both universal health coverage and health-related Sustainable Development Goals. Recognising this opportunity, the International Rare Diseases Research Consortium (IRDiRC) assembled a global, multistakeholder task force to identify key barriers and opportunities for empowering primary health-care providers in addressing rare disease challenges.

The evaluation of particle-bound mercury (PBM) exposure is a crucial aspect of assessing the global cycle of mercury (Hg) and its adverse effects on human health and ecosystems. Nevertheless, the precise and reliable measurement of PBM remains a formidable task because of the costly and cumbersome equipment required, as well as the inadequate sensitivities exhibited by current analytical techniques. In this study, we provided a unique and straightforward approach utilising filter fiber-assisted matrix solid-phase dispersion (FF-MSPD) in conjunction with single-drop solution electrode discharge-induced cold vapor generation atomic fluorescence spectrometry (SD-SEGD-CVG-AFS) for the precise quantification of PBM. The PBM contained in a small filter was efficiently extracted with 200 μL of eluent (0.2 % L-cysteine and 4 % HCOOH) by FF-MSPD and subsequently converted to Hg using SD-SEGD-CVG, before being subjected to examination using AFS.

Tuberculosis continues to be a leading cause of infectious disease mortality, and effective screening and diagnosis remains crucial. Despite progress made, diagnostic gaps remain due to poor access to diagnostic tools and testing, particularly in rural and remote areas. As such, the development of target product profiles is essential in guiding the development of new diagnostic tools, however target product profiles often lack evidence-based information and do not consider trade-offs between test accuracy and accessibility.

Cost-effectiveness analyses have been conducted for many interventions for HIV/AIDS, malaria, syphilis, and tuberculosis, but they have not been conducted for all interventions that are currently recommended in all countries. To support national decision makers in the effective allocation of resources, we conducted a meta-regression analysis of published incremental cost-effectiveness ratios (ICERs) for interventions for these causes, and predicted ICERs for 14 recommended interventions for Global Fund-eligible countries.

Better access to tuberculosis testing is a key priority for fighting tuberculosis, the leading cause of infectious disease deaths in people. Despite the roll-out of molecular WHO-recommended rapid diagnostics to replace sputum smear microscopy over the past decade, a large diagnostic gap remains. Of the estimated 10·6 million people who developed tuberculosis globally in 2022, more than 3·1 million were not diagnosed. An exclusive focus on improving tuberculosis test accuracy alone will not be sufficient to close the diagnostic gap for tuberculosis. Diagnostic yield, which we define as the proportion of people in whom a diagnostic test identifies tuberculosis among all people we attempt to test for tuberculosis, is an important metric not adequately explored. Diagnostic yield is particularly relevant for subpopulations unable to produce sputum such as young children, people living with HIV, and people with subclinical tuberculosis. As more accessible non-sputum specimens (eg, urine, oral swabs, saliva, capillary blood, and breath) are being explored for point-of-care tuberculosis testing, the concept of yield will be of growing importance. Using the example of urine lipoarabinomannan testing, we illustrate how even tests with limited sensitivity can diagnose more people with tuberculosis if they enable increased diagnostic yield. Using tongue swab-based molecular tuberculosis testing as another example, we provide definitions and guidance for the design and conduct of pragmatic studies that assess diagnostic yield. Lastly, we show how diagnostic yield and other important test characteristics, such as cost and implementation feasibility, are essential for increased effective population coverage, which is required for optimal clinical care and transmission impact. We are calling for diagnostic yield to be incorporated into tuberculosis test evaluation processes, including the WHO Grading of Recommendations, Assessment, Development, and Evaluations process, providing a crucial real-life implementation metric that complements traditional accuracy measures.

The detection of plasticizers in the environment is important to prevent environmental risks and people's health hazards. Improving recycling efficiency of waste PVC still faced challenges.

Understanding how parasitoids respond to temperature is crucial for improving biological control strategies under the context of global warming. This study examined the suitability of Myzus persicae and its parasitoid Aphidius gifuensis to varying temperature conditions, as well as the stage-specific response of A. gifuensis to high temperatures.

Research has focused on the increased correction from a three-column osteotomy (3CO) during adult spinal deformity (ASD) surgery. However, an in-depth analysis on the performance of a 3CO in a cohort of complex spinal deformity cases has not been described.

MraY (phospho-N-acetylmuramoyl-pentapeptide-transferase) inhibitory natural products are attractive molecules as candidates for a new class of antibacterial agents to combat antimicrobial-resistant bacteria. Structural optimization of these natural products is required to improve their drug-like properties for therapeutic use. However, chemical modifications of these natural products are painstaking tasks due to complex synthetic processes, which is a bottleneck in advancing natural products to the clinic. Here, we develop a strategy for a comprehensive in situ evaluation of the build-up library, which enables us to streamline the preparation of the analogue library and directly assess its biological activities. We apply this approach to a series of MraY inhibitory natural products. Through construction and evaluation of the 686-compound library, we identify promising analogues that exhibit potent and broad-spectrum antibacterial activity against highly drug-resistant strains in vitro as well as in vivo in an acute thigh infection model. Structures of the MraY-analogue complexes reveal distinct interaction patterns, suggesting that these analogues represent MraY inhibitors with unique binding modes. We further demonstrate the generality of our strategy by applying it to tubulin-binding natural products to modulate their tubulin polymerization activities.

Chronic kidney disease (CKD) affects approximately 14% of adults in the United States and is present in at least 10% of the population worldwide. Blood glucose and blood pressure control are imperative to adequately manage CKD as they are the only primary prevention measures for the condition. Recent changes in CKD evaluation and medication therapies that modify disease progression and aid in managing complications such as anemia of CKD have emerged, including a newly approved mineralocorticoid receptor antagonist and hypoxia-inducible factor-prolyl hydroxylase inhibitor, respectively. This focused update on CKD evaluation and management will review the most recent evidence and approved agents to support patients with CKD, including a review of glomerular filtration rate measurement methods such as CKD-EPI 2021 and utilization of cystatin C, Kidney Disease Improving Global Outcomes (KDIGO) guidelines, American Diabetes Association (ADA) guidelines, and primary literature supporting the use of newer agents in CKD. Checklists for managing blood pressure and blood glucose, CKD-mineral bone disorder, and anemia of CKD targeted for pharmacists are also provided. Additionally, a discussion of Centers for Medicare & Medicaid (CMS) coverage of agents approved for managing complications of CKD is included.

While ceftriaxone remains the first-line treatment for gonorrhoea, the US CDC recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021-2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176) and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was the highest among women (16.4%, 10/61), followed by men-who-have-sex-with-women (6.4%, 7/109), and men-who-have-sex-with-men (5.8%, 57/982). The prevalence of cefixime-resistant N. gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; and thus, cefixime treatment would have limited benefits in Australia.

Geroscience, or longevity biotechnology, has made impressive advances in recent years that have led to the founding of dozens of start-ups, nonprofits and advocacy organizations, and the formation of a global movement to defeat aging. The community envisions changes at the regulatory and policy levels and calls for increased funding for research. Nevertheless, progress in the field has not been matched by discussions about ethical, legal, and social implications, as longevity advocates assume that seeking to expand lifespan or healthspan is inherently desirable and permissible. In this essay, I make the case for the importance of putting ethics and society back into geroscience, along with three considerations for the longevity community. First, it should seek to understand the needs and attitudes of the public. Second, the community needs to define whether the field is primarily striving for healthy aging (increasing healthspan) or for extending years of life (lifespan). Third, it needs to define the role of investors and tech millionaires in shaping the field's priorities and direction. This last point raises the question of who is setting the direction of a field that can reshape the meaning of being human.

Harel-Yoon syndrome (HAYOS) is a unique neurodevelopmental genetic disorder characterized by hypotonia, spasticity, intellectual disability, hypertrophic cardiomyopathy, and global developmental delay. It primarily results from mutations in the ATAD3A gene, pivotal for mitochondrial function. This report presents a 5-year-old girl with HAYOS harboring a de novo heterozygous variant c.1064G>A; (p.G355D) in ATAD3A. Her clinical profile includes delayed milestones, hypotonia, spastic quadriplegia, and ptosis. Notably, dermatologic anomalies such as hypopigmentation, café au lait macules, and freckling are observed, expanding the known phenotype of HAYOS. The inclusion of dermatologic features challenges our understanding of the syndrome and emphasizes the importance of further research to elucidate the molecular connections between ATAD3A mutations and dermatologic manifestations.

Allergic rhinitis (AR) represents a significant global health concern that can give rise to numerous diseases and result in labor productivity. T regulatory (Treg) cells are pivotal players in the pathogenesis of AR, and their deficiencies are closely related to Prostaglandin E2 (PGE2). However, the downstream mechanisms of this relationship remain poorly understood.

This systematic review and meta-analysis aimed to evaluate the overall impact of Panax ginseng on lipid profile by synthesizing existing evidence. Cardiovascular Disease (CVD) is the leading cause of morbidity and mortality among the elderly population, and serum lipids play a crucial role in its development. Maintaining optimal levels of triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol is essential in reducing the risk of CVD. Ginsenosides, the active constituents in ginseng, have shown positive effects on lipid metabolism. This review aimed to provide a comprehensive understanding of the potential benefits of ginseng in managing dyslipidemia, which could have significant implications for the prevention and treatment of CVD.

Salinity, resulting from various contaminants, is a major concern to global crop cultivation. Soil salinity results in increased osmotic stress, oxidative stress, specific ion toxicity, nutrient deficiency in plants, groundwater contamination, and negative impacts on biogeochemical cycles. Leaching, the prevailing remediation method, is expensive, energy-intensive, demands more fresh water, and also causes nutrient loss which leads to infertile cropland and eutrophication of water bodies. Moreover, in soils co-contaminated with persistent organic pollutants, heavy metals, and textile dyes, leaching techniques may not be effective. It promotes the adoption of microbial remediation as an effective and eco-friendly method. Common microbes such as Pseudomonas, Trichoderma, and Bacillus often struggle to survive in high-saline conditions due to osmotic stress, ion imbalance, and protein denaturation. Halophiles, capable of withstanding high-saline conditions, exhibit a remarkable ability to utilize a broad spectrum of organic pollutants as carbon sources and restore the polluted environment. Furthermore, halophiles can enhance plant growth under stress conditions and produce vital bio-enzymes. Halophilic microorganisms can contribute to increasing soil microbial diversity, pollutant degradation, stabilizing soil structure, participating in nutrient dynamics, bio-geochemical cycles, enhancing soil fertility, and crop growth. This review provides an in-depth analysis of pollutant degradation, salt-tolerating mechanisms, and plant-soil-microbe interaction and offers a holistic perspective on their potential for soil restoration.

The aim of the study was to investigate the impact of the use of baby-friendly community initiative (BFCI) model on various stakeholders in the community.

This review summarizes current knowledge on blood pressure in children and adolescents (youth), with a focus on primary hypertension-the most common form of elevated blood pressure in this demographic. We examine its etiology, progression, and long-term cardiovascular implications. The review covers definitions and recommendations of blood pressure classifications, recent developments in measurement, epidemiological trends, findings from observational and clinical studies, and prevention and treatment, while identifying gaps in understanding and suggesting future research directions.

Public and patient involvement can provide crucial insights to optimise research by enhancing relevance and appropriateness of studies. The World Health Organization (WHO) engaged in an inclusive process to ensure that both technical experts and women had a voice in defining the research gaps and needs to increase or reintroduce the use of assisted vaginal birth (AVB) in settings where this intervention is needed but unavailable or underused.

Does a purpose-designed Decision Aid for women considering elective egg freezing (EEF) impact decisional conflict and other decision-related outcomes?

Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long-lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8-9 years. This follow-up study aimed to examine whether these findings persisted into adolescence.

In 2019, an estimated 4.95 million deaths were linked to antimicrobial resistance (AMR). Vaccines can prevent many of these deaths by averting both drug-sensitive and resistant infections, reducing antibiotic usage, and lowering the likelihood of developing resistance genes. However, their role in mitigating AMR is currently underutilized. This article builds upon previous research that utilizes Vaccine Value Profiles-tools that assess the health, socioeconomic, and societal impact of pathogens-to inform vaccine development. We analyze the effects of 16 pathogens, covered by Vaccine Value Profiles, on AMR, and explore how vaccines could reduce AMR. The article also provides insights into vaccine development and usage. Vaccines are crucial in lessening the impact of infectious diseases and curbing the development of AMR. To fully realize their potential, vaccines must be more prominently featured in the overall strategy to combat AMR. This requires ongoing investment in research and development of new vaccines and the implementation of additional prevention and control measures to address this global threat effectively.

This study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions.

Oral squamous cell carcinoma (OSCC) represents the primary form of oral cancer, posing a significant global health threat. The existing chemotherapy options are accompanied by notable side effects impacting patient treatment adherence. Consequently, the exploration and development of novel substances with enhanced anticancer effects and fewer side effects have become pivotal in the realms of biological and chemical science.

Despite the well-known benefits of physical activity, physical inactivity is presently a global health pandemic. Allied healthcare providers, such as chiropractors, knowingly recognise the importance of physical activity and are prepared to routinely discuss and/or counsel patients on this topic; however, little is known about Australian chiropractors in the physical activity setting. Our aim was to explore and identify factors associated with physical activity promotion among Australian chiropractors, including their knowledge of the physical activity and sedentary behaviour guidelines and their own levels of physical activity.

Coronary heart disease (CHD) is the leading cause of deaths and disability worldwide. Cardiac rehabilitation (CR) effectively reduces the risk of future cardiac events and is strongly recommended in international clinical guidelines. However, CR program quality is highly variable with divergent data systems, which, when combined, potentially contribute to persistently low completion rates. The QUality Improvement in Cardiac Rehabilitation (QUICR) trial aims to determine whether a data-driven collaborative quality improvement intervention delivered at the program level over 12 months: (1) increases CR program completion in eligible patients with CHD (primary outcome), (2) reduces hospital admissions, emergency department presentations and deaths, and costs, (3) improves the proportion of patients receiving guideline-indicated CR according to national and international benchmarks, and (4) is feasible and sustainable for CR staff to implement routinely.

Healthcare organizations worldwide face persistent challenges relating to turnover and intention to leave the nursing profession among registered nurses. Factors contributing to their retention and well-being at work include high job satisfaction, professional competence, and self-efficacy. Few multicenter studies have investigated these factors in relation to work experience in a Nordic context. Therefore, this study aimed to investigate job satisfaction, professional competence, and self-efficacy among registered nurses.

Bacteria in nature often form surface-attached communities that initially comprise distinct subpopulations, or patches. For pathogens, these patches can form at infection sites, persist during antibiotic treatment, and develop into mature biofilms. Evidence suggests that patches can emerge due to heterogeneity in the growth environment and bacterial seeding, as well as cell-cell signaling. However, it is unclear how these factors contribute to patch formation and how patch formation might affect bacterial survival and evolution. Here, we demonstrate that a 'rich-get-richer' mechanism drives patch formation in bacteria exhibiting collective survival (CS) during antibiotic treatment. Modeling predicts that the seeding heterogeneity of these bacteria is amplified by local CS and global resource competition, leading to patch formation. Increasing the dose of a non-eradicating antibiotic treatment increases the degree of patchiness. Experimentally, we first demonstrated the mechanism using engineered Escherichia coli and then demonstrated its applicability to a pathogen, Pseudomonas aeruginosa. We further showed that the formation of P. aeruginosa patches promoted the evolution of antibiotic resistance. Our work provides new insights into population dynamics and resistance evolution during surface-attached bacterial growth.

Cervical cancer remains the second most common cause of death in women and poses a growing public health challenge. It is urgent to increase cervical cancer screening rates in Kenya as per the 2018 Kenya National Cancer Screening Guidelines. Addressing access to care may serve as a target to achieve this goal; however, how individual dimensions of access to care are associated with the utilization of cervical cancer screening services in low- and middle-income countries, including Kenya, remains unclear. This study aimed to examine how different aspects of access to care (affordability, availability, geographical access, and social influence) were associated with cervical cancer screening among Kenyan women of reproductive age.

Two out of three family caregivers are female. However, current trends show that men are more likely to undertake caregiving duties, yet female caregivers report a higher burden. This paper analyzed data from long-term family caregivers to determine whether, under similar circumstances, gender differences in caregiving persist. We examined whether the observed gender gap affects caregivers' satisfaction with their health and quality of life.

The COVID-19 pandemic, resulting from the emergence of the novel coronavirus SARS-CoV-2, posed unprecedented challenges to global health systems as no proven therapy was available. Initially, COVID-19 convalescent plasma (CCP) from recovered COVID-19 patients showed promise as a therapeutic option. However, the efficacy of this approach was closely correlated with the neutralizing antibody titer in the administered plasma and thus effectiveness was not always guaranteed. In response, hyperimmune immunoglobulins (hIG) derived from CCP obtained by apheresis from recovered or vaccinated individuals emerged as a potential alternative. hIG were purified through stringent chromatographic processing from CCP units and displayed varying results in clinical trials, although it seems likely that they improved outcomes compared to placebo or CCP at day 28, particularly in unvaccinated patients. The variability in the effect of hIG likely stems from factors such as the timing of outcome assessment, the administered dose of hIG, the patients' immunological background, and the matching between the variant infecting patients and the neutralization ability of the immunoglobulin batch, which depended on the timing of the CCP collection. Despite logistical challenges and high production costs, hIG showcase advantages over CCP, offering versatility in administration routes and eliminating the need for blood matching, thus facilitating administration in the community, and allowing for variant-specific preparations. hIG appear to be of particular importance in the treatment of immunocompromised patients and patients with persistent COVID-19, although studies in these populations are lacking. Non-human alternatives, such as equine-derived hIG and recombinant hIG, may provide a solution to the logistical challenges of large-scale hIG preparation. Further study is needed to explore these avenues. Establishing the infrastructure for large-scale hIG production independent of plasma donations emerges as a strategic approach for future pandemics, justifying exploration and promotion by health authorities.

Digenetic trematodes, including blood flukes, intestinal flukes, liver flukes, lung flukes, and pancreatic flukes, are highly diverse and distributed widely. They affect at least 200 million people worldwide, so better understanding of their global distribution and prevalence are crucial for controlling and preventing human trematodiosis. Hence, this scoping review aims to conduct a comprehensive investigation on the spatio-temporal distribution and epidemiology of some important zoonotic digenetic trematodes.

Kidney cancer, a type of urogenital cancer, imposes a high burden on patients. Despite this, no recent research has evaluated the burden of this type of cancer in the Middle East and North Africa (MENA) region. This study explored the burden of kidney cancer from 1990 to 2019 according to age, sex and socio-demographic index (SDI). The Global Burden of Disease (GBD) 2019 data was utilized to estimate the incidence, death, and disability-adjusted life-years (DALYs) caused by kidney cancer. These estimates were reported as counts and as age-standardised rates with 95% uncertainty intervals (UIs). The estimated age-standardised incidence, mortality, and DALY rates of kidney cancer in 2019 were 3.2 (2.8-3.6), 1.4 (1.2-1.6), and 37.2 (32.0-42.6) per 100,000, respectively. Over the period from 1990 to 2019, these rates have increased by 98.0%, 48.9%, and 37.7%, respectively. In 2019, the United Arab Emirates, Qatar, and Lebanon had the largest age-standardised incidence, mortality, and DALY rates. The smallest age-standardised incidence rates were seen in Yemen, Afghanistan, and the Syrian Arab Republic. Additionally, the smallest age-standardised mortality and DALY rates were observed in the Syrian Arab Republic, Yemen, and Morocco. The highest incidence rates were found among individuals aged 75-79 in both males and females. In 2019, the MENA/Global DALY ratio exceeded one for females aged 5-19 age and males aged 5-14, compared to 1990age groups in males. The burden of kidney cancer consistently rose with increasing SDI levels from 1990 to 2019. The increasing burden of kidney cancer highlights the urgent need for interventions aimed at improving early diagnosis and treatment in the region.

There are only two major statements which define alcohol policy development at the global level. There has not been any comparative analysis of the details of these key texts, published in 2010 and 2022 respectively, including how far they constitute similar or evolving approaches to alcohol harm.

The Repeat Expansion Diseases (REDs) arise from the expansion of a disease-specific short tandem repeat (STR). Different REDs differ with respect to the repeat involved, the cells that are most expansion prone and the extent of expansion. Furthermore, whether these diseases share a common expansion mechanism is unclear. To date, expansion has only been studied in a limited number of REDs. Here we report the first studies of the expansion mechanism in induced pluripotent stem cells derived from a patient with a form of the glutaminase deficiency disorder known as Global Developmental Delay, Progressive Ataxia, And Elevated Glutamine (GDPAG; OMIM# 618412) caused by the expansion of a CAG-STR in the 5' UTR of the glutaminase (GLS) gene. We show that alleles with as few as ~ 120 repeats show detectable expansions in culture despite relatively low levels of R-loops formed at this locus. Additionally, using a CRISPR-Cas9 knockout approach we show that PMS2 and MLH3, the constituents of MutLα and MutLγ, the 2 mammalian MutL complexes known to be involved in mismatch repair (MMR), are essential for expansion. Furthermore, PMS1, a component of a less well understood MutL complex, MutLβ, is also important, if not essential, for repeat expansion in these cells. Our results provide insights into the factors important for expansion and lend weight to the idea that, despite some differences, the same mechanism is responsible for expansion in many, if not all, REDs.

The vagina hosts a community of microorganisms known as the vaginal microbiota. This community is relatively stable and straightforward, with Lactobacillus species being the most dominant members. The vaginal microbiota has various functions that are essential for maintaining human health and balance. For example, it can metabolise dietary nutrients, produce growth factors, communicate with other bacteria, modulate the immune system, and prevent the invasion of harmful pathogens. When the vaginal microbiota is disrupted, it can lead to diseases and infections. The observed disturbance is distinguished by a reduction in the prevalence of Lactobacillus and a concurrent rise in the number of other bacterial species that exhibit a higher tolerance to low oxygen levels. Gynecologic cancers are a group of cancers that affect the female reproductive organs and tissues, such as the ovaries, uterus, cervix, vagina, vulva, and endometrium. These cancers are a major global health problem for women. Understanding the complex interactions between the host and the vaginal microorganisms may provide new insights into the prevention and treatment of gynecologic cancers. This could improve the quality of life and health outcomes for women.

Elevated atmospheric carbon dioxide (eCO) can affect plant growth and physiology, which can, in turn, impact herbivorous insects, including by altering pollen or plant tissue nutrition. Previous research suggests that eCO can reduce pollen nutrition in some species, but it is unknown whether this effect is consistent across flowering plant species. We experimentally quantified the effects of eCO across multiple flowering plant species on plant growth in 9 species and pollen chemistry (%N an estimate for protein content and nutrition in 12 species; secondary chemistry in 5 species) in greenhouses. For pollen nutrition, only buckwheat significantly responded to eCO, with %N increasing in eCO; CO treatment did not affect pollen amino acid composition but altered secondary metabolites in buckwheat and sunflower. Plant growth under eCO exhibited two trends across species: plant height was taller in 44% of species and flower number was affected for 63% of species (3 species with fewer and 2 species with more flowers). The remaining growth metrics (leaf number, above-ground biomass, flower size, and flowering initiation) showed divergent, species-specific responses, if any. Our results indicate that future eCO is unlikely to uniformly change pollen chemistry or plant growth across flowering species but may have the potential to alter ecological interactions, or have particularly important effects on specialized pollinators.

Coronary artery disease (CAD) is known as the leading cause of disability and death globally. Anxiety disorders are also recognized as common types of mental disorders that substantially impact global health. Iran ranks among the countries with a high incidence of CAD and anxiety disorders. Therefore, the present study aims to determine the potential association and epidemiological aspects of anxiety and CAD within the population of Mashhad, the second most popoulos city in Iran.

is a Gram-negative facultative intracellular bacterial pathogen that is classified by the Centers for Disease Control and Prevention as a Tier 1 Select Agent. infection causes the disease tularemia, also known as rabbit fever. Treatment of tularemia is limited to few effective antibiotics which are associated with high relapse rates, toxicity, and potential emergence of antibiotic-resistant strains. Consequently, new therapeutic options for tularemia are needed. Through screening a focused chemical library and subsequent structure-activity relationship studies, we have discovered a new and potent inhibitor of intracellular growth of , D8-03. Importantly, D8-03 effectively reduces bacterial burden in mice infected with . Preliminary mechanistic investigations suggest that D8-03 works through a potentially novel host-dependent mechanism and serves as a promising lead compound for further development.

Endometriosis affects 10-15% of women of reproductive age and is considered a critical gynecological problem. Endometriosis causes pain and infertility, both of which can impair the patient's quality of life. Sleep disorders account for the most bothersome presentation of impaired quality of life. This study investigated the frequency and severity of sleep disorders in women with endometriosis.

Natural bioactives possess a wide range of chemical structures that can exert a plethora of pharmacological and toxicological actions, resulting in neuroprotection or neurotoxicity. These pharmacodynamic properties can positively or negatively impact human and animal global healthcare. Remarkably, Ayurvedic botanical Cannabis has been used worldwide by different ethnicities and religions for spiritual, commercial, recreational, nutraceutical, cosmeceutical, and medicinal purposes for centuries. Cannabis-based congeners have been approved by the United States of America's (USA) Food & Drug Administration (FDA) and other global law agencies for various therapeutic purposes. Surprisingly, the strict laws associated with possessing cannabis products have been mitigated in multiple states in the USA and across the globe for recreational use. This has consequently led to a radical escalation of exposure to cannabis-related substances of abuse. However, there is a lacuna in the literature on the acute and chronic effects of Cannabis and its congeners on various neuropathologies. Moreover, in the post-COVID era, there has been a drastic increase in the incidence and prevalence of numerous neuropathologies, leading to increased morbidity and mortality. There is an impending necessity for a safe, economically viable, multipotent, natural bioactive to prevent and treat various neuropathologies. The ayurvedic herb, Cannabis is one of the oldest botanicals known to humans and has been widely used. However, the comprehensive effect of Cannabis on various neuropathologies is not well established. Hence, this review presents effects of Cannabis on various neuropathologies.

Corruption exists at all levels of our global society and is a potential threat to food security, food safety, equity, and social justice. However, there is a knowledge gap in the role and impact of corruption within the context of the global food system. We aimed to systematically review empirical literature focused on corruption in the global food system to examine how it is characterized, the actors involved, its potential impacts, and the solutions that have been proposed to address corruption in the food system.

The global effort to combat the COVID-19 pandemic highlights the pivotal role of vaccination in public health, particularly considering emerging severe acute respiratory syndrome-coronavirus-2 variants. While priority has been given to immunising vulnerable populations, children remain a significant unvaccinated group, prompting NHS England to include them in their new vaccination strategy. The role parents play in child healthcare decisions, specifically regarding COVID-19 vaccination, is crucial, and the Health Belief Model (HBM) provides a framework for understanding parental vaccination behaviour.

The high prevalence and economic burden of heart failure remain a challenge to global health. This lifelong disease leads to a buildup of permanent heart damage, making early detection and frequent monitoring crucial for effective treatment. N-terminal proBNP (NT-proBNP) is an important biomarker for monitoring the disease state, but current commercial and research NT-proBNP assays require phlebotomy and bulky equipment or do not satisfy clinical requirements such as sensitivity and detection thresholds. Here, we report a point-of-care (POC) compatible microfluidic digital immunoassay that can quantify the NT-proBNP concentration in a small volume of whole blood. Our automated microfluidic device takes whole blood samples mixed with biotinylated detection antibodies and passes through a plasma filter to react with a capture antibody-functionalized sensor surface. Streptavidin-coated gold nanoparticles (GNPs) are then released to mark the surface-bound single NT-proBNP immunocomplexes and recorded with bright-field microscopy. NT-proBNP concentrations in the sample are quantified via a hybrid digital/analog calibration curve. Digital counts of bound GNPs are used as readout signal at low concentrations for high sensitivity detection, and GNP pixel occupancies are used at high concentrations for extended dynamic range. With this approach, we detected NT-proBNP in the range of 8.24-10 000 pg/mL from 7 μL of whole blood in 10 min, with a limit of detection of 0.94 pg/mL. Finally, the method was validated with 15 clinical serum samples, showing excellent linear correlation ( = 0.998) with Roche's Elecsys proBNP II assay. This evidence indicates that this method holds promise for decentralized monitoring of heart failure.

This study aims to analyze if the results from different serological assays, used alone or combined, could match the outcome of challenge infection with foot-and-mouth disease virus (FMDV) after vaccination in cattle. Day-of-challenge sera from animals that had been vaccinated 21 days before with monovalent formulations containing inactivated A Iran 96 or A Iran 99 virus strains were used. Challenge and serology were performed with A22 Iraq strain. IgG1 titers and total-IgG avidity indexes were significantly higher in protected animals (p < 0.01) while IgG2-titers were not related to protection (p > 0.05). An IgG1 avidity ELISA was developed to analyze in one step, IgG1 levels and avidity. This assay estimated protection with 96 % accuracy. A strong agreement with challenge results was achieved (K = 0.85), suggesting a role of high-affinity IgG1 in protection against FMDV. These results support the assessment of the single dilution IgG1-Avidity ELISA to predict cross-protection in FMDV-vaccinated cattle.

The efficacy of sotagliflozin in patients with diabetes and recent worsening of heart failure was shown in the SOLOIST-WHF trial. However, the cost-effectiveness of sotagliflozin in these patients has not been previously investigated.

Nanoplastics (NPs) represent a growing concern for global environmental health, particularly in marine ecosystems where they predominantly accumulate. The impact of NPs on marine benthic organisms, such as bivalves, raises critical questions regarding ecological integrity and food safety. Traditional methods for assessing NP toxicity are often limited by their time-intensive nature and ethical considerations. Herein, we explore the toxicological effects of NPs on the marine bivalve , employing a combination of cellular assays and advanced modeling techniques. Results indicate a range of adverse effects at the organismal level, including growth inhibition (69.5-108%), oxidative stress, lipid peroxidation, and DNA damage in bivalves, following exposure to NPs at concentrations in the range of 1.6 × 10-1.6 × 10 particles/mL (p/mL). Interestingly, the growth inhibition predicted by models (54.7-104%), based on cellular proliferation assays, shows strong agreement with the outcomes of NP exposure. Furthermore, we establish a clear correlation between cytotoxicity observed and the toxicological responses at the organismal level. Taken together, this work suggests that the integration of computational modeling with toxicity assays can predict the detrimental effects of NPs on bivalves, offering insightful references for assessing the environmental risk assessment of NPs in marine benthic ecosystems.

Chronic hepatitis B and C are among the most significant infectious diseases worldwide, and are major risk factors for liver cirrhosis and liver cancer. In Japan, comprehensive hepatitis measures are implemented for the testing and treatment of viral hepatitis, thus enabling the early diagnosis of liver cancer. Nevertheless, patients with decompensated cirrhosis and liver cancer often have unfavorable prognoses and require repetitive long-term treatment. In fiscal year 2018, an integrated policy of medical expense subsidies and research was established in Japan that aimed to alleviate patients' financial burden and launch the clinical registry of advanced liver disease. Over time, updates to the eligibility for the subsidy increased access to patients and has led to an increased number of beneficiaries. Additionally, the accumulation of clinical data in the registry has revealed the treatment choices for these diseases. However, the disparities in efforts across prefectures have also become evident. Raising public awareness of the policy and tightening the multisector healthcare network are keys to success in supporting qualifying patients with advanced liver disease.

Hypertension, which stands as a leading global health challenge, demands a dynamic approach for its effective management. The traditional methods of managing hypertension, centered on periodic clinic visits for blood pressure measurement and pharmacological interventions, are increasingly being complemented and enhanced by digital technologies. The integration of wearable devices, mobile applications, personalized treatments, and telehealth solutions into healthcare system is reshaping traditional hypertension care. Digitalization of hypertension management extends to population health, in addition to individual patient benefits, aimed at preventing and controlling hypertension on a broader scale. However, this digital revolution in hypertension management brings forth challenges related to data security, data accuracy, equitable access, and standardization of devices by international regulatory agencies. Addressing these issues is equally important to ensure that the benefits of digital technologies are accessible to everyone, irrespective of socio-economic factors. This paper concludes with a forward-looking perspectives, emphasizing the potential of digitalization to modify the landscape of hypertension management.

PURPOSE OF REVIEW: To analyze how social and structural determinants of health and social injustice impact the risk of obesity, its treatment and treatment outcomes, and to explore the implications for prevention and future treatment interventions. RECENT FINDINGS: Racial and ethnic minorities, such as non-Hispanic Black adults and Hispanic adults, and adults with a low socioeconomic status have a greater risk of obesity than non-Hispanic white adults and adults with a high socioeconomic status. The underlying causes of obesity disparities include obesogenic neighborhood environments, inequities in access to obesity treatment, and lack of access to affordable nutrient-dense foods. Experts have called for interventions that address the social and structural determinants of obesity disparities. Population-based interventions that focus on improving neighborhood conditions, discouraging the consumption of unhealthy foods and beverages, expanding access to obesity treatment, and ensuring equitable access to fruits and vegetables have been proven to be effective. There is a growing body of evidence that shows the relationship between social and structural determinants of health and injustice on disparities in obesity among racial and ethnic minorities and individuals with a low SES. Population-based, equity-focused interventions that address the underlying causes of obesity disparities are needed to reduce obesity disparities and improve the health outcomes of minoritized and marginalized groups.

With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.

Inappropriate antibiotic use contributes to antimicrobial resistance, a global public health threat. The non-specific manifestations of dengue, itself a growing public health threat, leads to avoidable empiric antibiotic prescription, particularly in children. In a national pooled population-based cross-sectional study, we evaluated child and physician characteristics associated with antibiotics prescription in confirmed dengue cases in Taiwan.

HIV stigma is a social determinant of health that can influence multiple health outcomes, including adherence to antiretroviral therapy (ART), engagement in HIV care, and viral suppression levels in people with HIV (PWH). In Peru, where the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW), stigma may play an important role in healthcare engagement. To understand the relationship between stigma and two outcome variables, ART adherence and engagement in HIV care in 400 MSM and TGW, we assessed factors from the Behavioral Model for Vulnerable Populations at two HIV clinics that tailor services for sexual and gender minorities. While some predisposing, need, and enabling resource factors were associated with optimal (≥ 90%) ART adherence or engagement in HIV care, none of the stigma subscales were correlated, suggesting that when LGBTQ-affirming care is provided to MSM/TGW, stigma may not influence HIV-related outcomes.

A factor constraining the elimination of dog-mediated human rabies is limited information on the size and spatial distribution of free-roaming dog populations (FRDPs). The aim of this study was to develop a statistical model to predict the size of free-roaming dog populations and the spatial distribution of free-roaming dogs in urban areas of Nepal, based on real-world dog census data from the Himalayan Animal Rescue Trust (HART) and Animal Nepal. Candidate explanatory variables included proximity to roads, building density, specific building types, human population density and normalised difference vegetation index (NDVI). A multivariable Poisson point process model was developed to estimate dog population size in four study locations in urban Nepal, with building density and distance from nearest retail food establishment or lodgings as explanatory variables. The proposed model accurately predicted, within a 95 % confidence interval, the surveyed FRDP size and spatial distribution for all four study locations. This model is proposed for further testing and refinement in other locations as a decision-support tool alongside observational dog population size estimates, to inform dog health and public health initiatives including rabies elimination efforts to support the 'zero by 30' global mission.

Forced displacement is a significant issue globally, and it affected 112 million people in 2022. Many of these people have found refuge in low- and middle-income countries. Migrants and refugees face complex and specialized health challenges, particularly in the area of mental health. This study aims to provide an in-depth qualitative assessment of the multi-level barriers that migrants face in accessing mental health services in Germany, Macao (Special Administrative Region of China), the Netherlands, Romania, and South Africa. The ultimate objective is to inform tailored health policy and management practices for this vulnerable population.

We investigated the association between early sexual debut and HIV infection among adolescents and young adults. Analyzing data from nationally representative Population-Based HIV Impact Assessment (PHIA) surveys in 11 African countries, the research employed a multivariate logistic regression model to assess the relationship between the early sexual debut and new HIV infections in the age group of 10-24 years. The results revealed a significant and robust association, indicating that young individuals who experienced early sexual debut were approximately 2.65 times more likely to contract HIV than those who did not, even after accounting for other variables. These findings align with prior research suggesting that early initiation of sexual activity may increase vulnerability to HIV infection due to factors such as biological susceptibility and risky behaviors like low condom use and multiple sexual partners. The implications of these findings for HIV prevention strategies are substantial, suggesting that interventions aimed at delaying sexual debut could be an effective component in reducing HIV risk for this population. Targeted sex education programs that address the risks of early sexual debut may play a pivotal role in these prevention efforts. By employing a comprehensive approach, there is a possibility to advance efforts towards ending AIDS by 2030.

Tools for assessing a country's capacity in the face of public health emergencies must be reviewed, as they were not predictive of the COVID-19 pandemic. Social cohesion and risk communication, which are related to trust in government and trust in others, may have influenced adherence to government measures and mortality rates due to COVID-19.

Dementia is a major global public health challenge, and with the growing elderly population, its prevalence is expected to increase in the coming years. In Sweden, municipalities are responsible for providing special housing for the elderly (SÄBO), which offers services and care for older individuals needing specific support. SÄBO is both the person´s home and a care environment and workplace. Polypharmacy in patients with dementia is common and increases the risk of medication interactions. Involving clinical pharmacists in medication reviews has been shown to enhance medication safety and improve prescribing practices. However, the views of the standard care team involved in medication prescribing, administration, monitoring and documentation on integrating pharmacist services have received less attention. Thus, this study aims to explore how pharmacists' contributions can enhance medication safety, improve patient care efficiency, and potentially alleviate the workload of general practitioners for people with dementia living in special housing.

Racialized economic segregation, a key metric that simultaneously accounts for spatial, social and income polarization in communities, has been linked to adverse health outcomes, including morbidity and mortality. Due to the spatial nature of this metric, the association between health outcomes and racialized economic segregation could also change with space. Most studies assessing the relationship between racialized economic segregation and health outcomes have always treated racialized economic segregation as a fixed effect and ignored the spatial nature of it. This paper proposes a two-stage Bayesian statistical framework that provides a broad, flexible approach to studying the spatially varying association between premature mortality and racialized economic segregation while accounting for neighborhood-level latent health factors across US counties. The two-stage framework reduces the dimensionality of spatially correlated data and highlights the importance of accounting for spatial autocorrelation in racialized economic segregation measures, in health equity focused settings.

YouTube, a widely recognized global video platform, is inaccessible in China, whereas Bilibili and TikTok are popular platforms for long and short videos, respectively. There are many videos related to laryngeal carcinoma on these platforms. This study aims to identify upload sources, contents, and feature information of these videos on YouTube, Bilibili, and TikTok, and further evaluate the video quality.

Dementia is a major global public health concern that is increasingly leading to morbidity and mortality among older adults. While studies have focused on the risk factors and care provision, there is currently limited knowledge about the spatial risk pattern of the disease. In this study, we employ Bayesian spatial modelling with a stochastic partial differential equation (SPDE) approach to model the spatial risk using complete residential history data from the Danish population and health registers. The study cohort consisted of 1.6 million people aged 65 years and above from 2005 to 2018. The results of the spatial risk map indicate high-risk areas in Copenhagen, southern Jutland and Funen. Individual socioeconomic factors and population density reduce the intensity of high-risk patterns across Denmark. The findings of this study call for the critical examination of the contribution of place of residence in the susceptibility of the global ageing population to dementia.

Cervical cancer (CC) continues to be a significant global health issue, which in part can be attributed to disparities in access to CC screening services. This study aims to conduct a trend of CC in Kazakhstan and to compare attitudes towards the screening program between women living in urban and rural areas. In the first stage, we conducted a trend study of CC indicators in Kazakhstan using official statistics. In the second stage, a cross-sectional study was conducted using a structured questionnaire to assess adherence to screening. The trend study reveals a decline in cervical cancer mortality rates (from 7.15 to 5.93 per 100,000 female inhabitants) over the period studied, while the incidence remains stable (from 18.51 to 19.38 per 100,000 female inhabitants). Regional variations in Period Prevalence rates were observed. Significant differences were found in screening participation rates between urban n = 41 (74%) and rural n = 23 (38%) women, p < 0.001, as well as awareness of the screening program (urban: n = 15 (27%), rural: n = 35 (58%), p < 0.001). The trend study highlights a decrease in cervical cancer mortality rates over the specified period, accompanied by a consistent incidence rate. Additionally, regional disparities in period prevalence rates of cervical cancer were observed. The primary factor contributing to the low adherence of rural women to screening was found to be a lack of awareness regarding the screening program. Therefore, increasing awareness about the importance of screening is crucial for improving adherence rates among rural women in Kazakhstan.

Efforts to understand the global variability in cognitive profiles in patients with epilepsy have been stymied by the lack of a standardized diagnostic system. This study examined the cross-cultural applicability of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) in a cohort of patients with temporal lobe epilepsy (TLE) in India that was diverse in language, education, and cultural background.

Intermittent Preventive Treatment of schoolchildren (IPTsc) is recommended by WHO as a strategy to protect against malaria; To explore whether IPTsc with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) cause a selection of molecular markers in Plasmodium falciparum genes associated with resistance in children in seven schools in Tanga region, Tanzania.

Current classification systems for irritable bowel syndrome (IBS) based on bowel habit do not consider psychological impact. We validated a classification model in a UK population with confirmed IBS, using latent class analysis, incorporating psychological factors. We applied this model in the Rome Foundation Global Epidemiological Survey (RFGES), assessing impact of IBS on the individual and the healthcare system, as well as examining reproducibility.

The global allocation of vaccines during the COVID-19 pandemic is widely perceived as unfair. Priority was given to countries that paid the most with little or no concern for who needed the vaccines the most. No satisfactory institutions have been established to allocate vaccines in a future pandemic. In this paper, we join reformers in proposing a new scheme for vaccine distribution: a global auction for vaccines where profits are distributed fairly to participating countries. Our proposal improves upon previous suggestions morally by taking countries' differing valuations of money and vaccines seriously. Since an auction is in the interest of both vaccine manufacturers and high-income countries, it is also politically feasible. A global redistributive auction for vaccines thus promises to be a robust and morally desirable way to allocate vaccines.

We aimed to evaluate the safety and efficacy of antithrombotic strategies by age in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention in AUGUSTUS.

Exposure to ozone (O) has been associated with cardiovascular outcomes in humans, yet the underlying mechanisms of the adverse effect remain poorly understood. We aimed to investigate the association between O exposure and glycerophospholipid metabolism in healthy young adults. We quantified plasma concentrations of phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) using a UPLC-MS/MS system. Time-weighted personal exposures were calculated to O and co-pollutants over 4 time windows, and we employed orthogonal partial least squares discriminant analysis to discern differences in lipids profiles between high and low O exposure. Linear mixed-effects models and mediation analysis were utilized to estimate the associations between O exposure, lipids, and cardiovascular physiology indicators. Forty-three healthy adults were included in this study, and the mean (SD) time-weighted personal exposures to O was 9.08 (4.06) ppb. With shorter exposure durations, O increases were associated with increasing PC and lysoPC levels; whereas at longer exposure times, the opposite relationship was shown. Furthermore, two specific lipids, namely lysoPC a C26:0 and lysoPC a C17:0, showed significantly positive mediating effects on associations of long-term O exposure with pulse wave velocity and systolic blood pressure, respectively. Alterations in specific lipids may underlie the cardiovascular effects of O exposure.

Little is known about how the associations between active transportation and community participation may vary across national contexts. Using representative datasets from China, Ghana, India, Mexico, Russia, and South Africa collected in the Study on Global Ageing and Adult Health (N = 33,535), we estimated multi-group confirmatory factor analyses, tests of measurement invariance, and predictive models. Standardized coefficients were equivalent across countries and showed a modest positive association between active transportation and community participation (the variance explained by active transportation ranged from 1.3% to 7.5% across countries). These results suggest that supporting active transportation can help mitigate negative environmental and health changes associated with increased vehicular travel and support social capital via community participation.

Sarcoglycanopathies encompass four distinct forms of limb-girdle muscular dystrophies (LGMD), denoted as LGMD R3-R6, arising from mutations within the SGCA, SGCB, SGCG, and SGCD genes. The global prevalence of sarcoglycanopathies is low, making it challenging to study these diseases. The principal objective of this study was to explore the spectrum of mutations in a cohort of Russian patients with sarcoglycanopathies and to ascertain the frequency of these conditions in the Russian Federation. We conducted a retrospective analysis of clinical and molecular genetic data from 49 Russian patients with sarcogycan genes variants. The results indicated that variants in the SGCA gene were found in 71.4 % of cases, with SGCB and SGCG genes each exhibiting variants in 12.2 % of patients. SGCD gene variants were detected in 4.1 % of cases. Bi-allelic pathogenic and likely pathogenic variants were identified in 46 of the 49 cases of sarcoglycanopathies: LGMD R3 (n = 34), LGMD R4 (n = 4), LGMD R5 (n = 6), and LGMD R6 (n = 2). A total of 31 distinct variants were identified, comprising 25 previously reported and 6 novel variants. Two major variants, c.229C > T and c.271G > A, were detected within the SGCA, constituting 61.4 % of all mutant alleles in Russian patients with LGMD R3. Both LGMD R6 cases were caused by the homozygous nonsense variant c.493C > T p.(Arg165Ter) in the SGCD gene. The incidence of sarcoglycanopathies in the Russian Federation was estimated to be at least 1 in 4,115,039, which is lower than the reported incidence in other populations.

Parental allergic diseases and smoking influence respiratory disease in the offspring but it is not known whether they influence fractional exhaled nitric oxide (FeNO) in the offspring. We investigated whether parental allergic diseases, parental smoking and FeNO levels in parents were associated with FeNO levels in their offspring.

Vagal nerve stimulation (VNS) is an adjunctive therapy to pharmacological treatment in patients with drug-resistant epilepsy. This study aimed to assess the efficacy of VNS therapy for seizure frequency reduction and improving quality of life (QOL) measures in children with refractory epilepsy and to evaluate the correlation between the perspectives of families and those of the treating team.

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.

To describe the pattern of the prevalence of mental health problems during the first year of the COVID-19 pandemic and examine the impact of containment measures on these trends.

Steatotic liver disease (SLD) is a highly prevalent chronic liver disease with significant challenges for global health. The pathophysiology of SLD involves an interplay among genetic, endocrine, and metabolic factors. Successful management of SLD entails accurate diagnosis and disease monitoring through noninvasive methods such as advanced imaging techniques and biomarkers. Many emerging pharmacotherapies for SLD are now in the pipeline, which target different pathways like collagen turnover, fibrogenesis, inflammation, and metabolism. The recent approval of resmetirom for noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) has been a milestone in addressing the unmet medical need for an efficacious SLD treatment. Finally, the potential of personalized medicine approaches and interdisciplinary cooperation in improving patient outcomes and reducing disease burden should be strongly pursued. SIGNIFICANCE STATEMENT: The healthcare burden due to steatotic liver disease (SLD) is enormous. This perspective sheds light on the recent advances in understanding the pathophysiology and diagnosis of SLD as well as promising drug development approaches.

Maternal autoimmune rheumatic diseases can influence the outcomes of children through several life stages. During pregnancy, maternal inflammation and autoantibodies can hinder fetal development and lead to growth restriction, preterm birth, and low birth weight; prematurity, especially at extreme gestational ages, can in turn impair future child health. Treatment with compatible immunomodulatory drugs and preventive medications aims to keep maternal disease under control and minimise the risk of adverse pregnancy outcomes. However, concerns have been raised about the effects of immunomodulatory drugs on neonatal conditions (ie, the risk of serious infections, inadequate responses to vaccinations, and organ toxicity) and long-term outcomes (metabolic and cardiovascular problems and neurodevelopmental disorders). Among the unmet needs of parents with autoimmune rheumatic diseases, there is the estimation of risk for the children to develop autoimmune disorders and the need for reassurance about parenting capacity while living with a chronic condition. This Series paper provides a comprehensive overview of the literature and guidance on discussing these topics with patients.

School food environments contribute to children's nutritional intake and overall health. As such, the World Health Organization and other public health organizations encourage policies that restrict children's access and exposure to foods and beverages that do not build health in and around schools. This global scoping review explores the presence and characteristics of policies that restrict competitive food sales and marketing for unhealthy foods across 193 countries using evidence from policy databases, grey literature, peer-reviewed literature, and primary policy documents. Policies were included if they were nationally mandated and regulated marketing and/or competitive foods in the school environments. Worldwide, only 28% of countries were found to have any national-level policy restricting food marketing or competitive food sales in schools: 16% of countries restrict marketing, 25% restrict competitive foods, and 12% restrict both. Over half of policies were found in high-income countries. No low-income countries had either policy type. Eight marketing policies (27%) and 14 competitive foods policies (29%) lacked explicit guidelines for either policy monitoring or enforcement. Future research is needed to assess the prevalence of policies aimed at improving other key aspects of the school food environment, such as dietary quality of school meals or food procurement, as well as assess implementation and efficacy of existing policies.

Conventional environmental health research is primarily focused on isolated chemical exposures, neglecting the complex interactions between multiple pollutants that may synergistically or antagonistically influence toxicity, thereby posing unexpected health risks. In this study, we address this knowledge gap by introducing an explainable machine learning (ML) approach with Feature Localized Intercept Transformed-Shapley Additive Explanations (FLIT-SHAP) designed to extract the dose-response relationships of specific pollutants in mixtures. In contrast to traditional SHAP, FLIT-SHAP can localize the global intercept to elucidate mixture effects, which is crucial for understanding the oxidative potential (OP) of ambient particulate matter (PM). Assessing multi-pollutant OP using FLIT-SHAP revealed both synergistic (55-63 %) and antagonistic (25-42 %) effects in laboratory-controlled OP data, but an antagonistic (33-66 %; lower OP) effect in ambient PM. Notably, the FLIT-SHAP approach demonstrated higher prediction accuracy (R = 0.99) compared to the additive model (R = 0.89) when evaluated against real-world PM samples. Quinones, such as phenanthrenequinone, play a more significant role in PM than previously recognized. Through this study, we highlighted the potential of FLIT-SHAP to enhance toxicity predictions and aid decision-making in the field of environmental health.

Risk prediction tools for colorectal cancer (CRC) have potential to improve the efficiency of population-based screening by facilitating risk-adapted strategies. However, such an applicable tool has yet to be established in the Chinese population. In this study, a risk score was created using data from the China Kadoorie Biobank (CKB), a nationwide cohort study of 409,854 eligible participants. Diagnostic performance of the risk score was evaluated in an independent CRC screening programme, which included 91,575 participants who accepted colonoscopy at designed hospitals in Zhejiang Province, China. Over a median follow-up of 11.1 years, 3,136 CRC cases were documented in the CKB. A risk score was created based on nine questionnaire-derived variables, showing moderate discrimination for 10-year CRC risk (C-statistic =0.68, 95% CI: 0.67-0.69). In the CRC screening programme, the detection rates of CRC were 0.25%, 0.82%, and 1.93% in low-risk (score <6), intermediate-risk (score: 6-19), and high-risk (score >19) groups, respectively. The newly developed score exhibited a C-statistic of 0.65 (95% CI: 0.63-0.66), surpassing the widely adopted tools such as the Asia-Pacific Colorectal Screening (APCS), modified APCS, and Korean Colorectal Screening scores (all C-statistics =0.60). In conclusion, we developed a novel risk prediction tool that is useful to identify individuals at high risk of CRC. A user-friendly online calculator was also constructed to encourage broader adoption of the tool.

Child physical abuse, a type of child maltreatment (CM), poses a significant global public health concern. Nonaccidental fractures and soft tissue injuries, which encompass any action that directly or indirectly harms a child, are the primary indicators of physical abuse in children.

Vaccines against influenza and many other infectious diseases require multiple boosters in addition to the primary dose to improve efficacy, but this approach is not ideal for compliance. The multiple doses could potentially be replaced by sustained or pulsatile release of antigens encapsulated in degradable microparticles (MPs). The efficacy of a vaccine is improved by adding an adjuvant, which can be co-delivered from the particles to enhance immunogenicity. Here, we developed degradable poly-lactic-co-glycolic acid (PLGA) (7-17 kDa) MPs capable of sustained release of ultraviolet killed influenza virus (A/PR/8/34) (kPR8) vaccine and the natural killer T (NKT) cell agonist alpha-galactosylceramide (α-GalCer) and tested their effectiveness at providing long-term protection against influenza virus infection in mice. Multiple formulations were developed for encapsulating the virus and adjuvant separately, and in combination. The MPs exhibited sustained release of both the virus and the adjuvant lasting more than a month. Co-encapsulation significantly increased the encapsulation efficiency (EE) of the vaccine but reduced the release duration. On the other hand, co-encapsulation led to a reduction in EE for the α-GalCer and a change in release profile to a higher initial burst followed by a linear release compared to a low initial burst and slower linear release. The α-GalCer also had considerably longer release duration compared to the vaccine. Mice injected with particle formulations co-encapsulating kPR8 and α-GalCer were protected from a lethal influenza virus infection 30 weeks after vaccination. This study demonstrates that PLGA MP based vaccines are promising for providing effective vaccination and possibly for replacing multiple doses with a single injection.

The link between trauma exposure and psychotic disorders is well-established. Further, specific types of trauma may be associated with specific psychotic symptoms. Network analysis is an approach that can advance our understanding of the associations across trauma types and psychotic symptoms.

Cerebrovascular diseases remain a critical focus of medical research due to their substantial impact on global health. Carotid stenosis, often associated with atherosclerosis and advancing age, profoundly affects cerebral blood supply and white matter integrity. This study aims to assess how age-related white matter changes (ARWMC) score, applied to cortex and Basal Ganglia, relates to cardiovascular and cerebrovascular events in patients who underwent carotid endarterectomy (CEA).

Neurodegenerative diseases, such as Alzheimer's disease, pose a significant global health challenge with their complex etiology and elusive biomarkers. In this study, we developed the Alzheimer's Identification Tool (AITeQ) using ribonucleic acid-sequencing (RNA-seq), a machine learning (ML) model based on an optimized ensemble algorithm for the identification of Alzheimer's from RNA-seq data. Analysis of RNA-seq data from several studies identified 87 differentially expressed genes. This was followed by a ML protocol involving feature selection, model training, performance evaluation, and hyperparameter tuning. The feature selection process undertaken in this study, employing a combination of four different methodologies, culminated in the identification of a compact yet impactful set of five genes. Twelve diverse ML models were trained and tested using these five genes (CNKSR1, EPHA2, CLSPN, OLFML3, and TARBP1). Performance metrics, including precision, recall, F1 score, accuracy, Matthew's correlation coefficient, and receiver operating characteristic area under the curve were assessed for the finally selected model. Overall, the ensemble model consisting of logistic regression, naive Bayes classifier, and support vector machine with optimized hyperparameters was identified as the best and was used to develop AITeQ. AITeQ is available at: https://github.com/ishtiaque-ahammad/AITeQ.