Global Health

Influenza remains a serious global health concern, causing significant morbidity and mortality each year. Vaccination is crucial to mitigate its impact, but requires rapid and efficient manufacturing strategies to handle timing and supply. Traditionally relying on egg-based production, the field has witnessed a paradigm shift toward cell culture-based methods offering enhanced flexibility, scalability, and process safety. This review provides a concise overview of available cell substrates and technological advancements. We summarize crucial steps toward process intensification - from roller bottle production to dynamic cultures on carriers and from suspension cultures in batch mode to high cell density perfusion using various cell retention devices. Moreover, we compare single-use and conventional systems and address challenges including defective interfering particles. Taken together, we describe the current state-of-the-art in cell culture-based influenza virus production to sustainably meet vaccine demands, guarantee a timely supply, and keep up with the challenges of seasonal epidemics and global pandemics.

The COVID-19 outbreak has had a significant impact on the global health landscape, underscoring the crucial role that vaccinations play in achieving herd immunity and reducing the effects of pandemics. Given the importance of this issue, it is imperative to gain a deeper understanding of the various factors that influence individuals' decisions to seek vaccination. This study aimed to compare the prediction level of the Health Belief Model (HBM), the Theory of Planned Behavior (TPB), and a combined model in explaining the intention of adults to receive COVID-19 immunization. A cross-sectional online survey was conducted among adults ( = 505) in Saudi Arabia. The survey contained variables related to the HBM and TPB. The prediction level of the two models as well as a combined model were evaluated utilizing Structural Equation Modeling (SEM). Among the recruited 505 participants, 88% fell within the 18 to 30 age range, and 54.5% were male. The proposed HBM model accounted for 68% of the variation in intention, whereas the TPB model explained 78.2% of the variation in COVID-19 vaccination intention. The combined model showed greater explanatory power (82%). The variables of susceptibility (β = 0.20,  < .001), severity (β = 0.49,  < .001), advantages (β = 0.63,  < .001), and obstacles (β = - 0.24,  < .001), perceptions of behavioral control (β = 1.58,  < .001) and attitudes (β = 0.44,  < .001) were found to significantly predict increased vaccination intentions in the combined model. However, the subjective norm construct did not significantly predict vaccination intentions (β = 0.06,  = .34). The TPB has greater explanatory power than the HBM in predicting the intention to obtain COVID-19 vaccination. However, the combined model showed a greater prediction level. Understanding and identifying people's perceived health beliefs and practices is critical for developing successful COVID-19 intervention methods.

Decision-making on childbearing and safer conception use in HIV sero-different couples involves an intricate balance of individual desires and perceived HIV acquisition risk. This paper addresses an important knowledge gap regarding HIV sero-different couples' considerations and the relationship and power dynamics involved when deciding to use a safer conception method. Between February and June 2019, we conducted semi-structured in-depth interviews among 14 men and 17 women, representing 17 couples, who exited the SAFER study - a pilot study assessing the feasibility, acceptability and cost-effectiveness of a safer conception programme for HIV sero-different couples in Zimbabwe. All couples in SAFER were provided with a choice of safer conception methods and were followed for up to 12 months of pregnancy attempts and 3 months following pregnancy. While couples generally perceived their safer conception discussions to be easy and consensus-driven, the decision-making process also involved complex gender dynamics and trade-offs in relationship power, which resulted in differing interpretations of what constituted a joint or shared couple decision. Participants regarded effective couple communication as an essential component of and precursor to good safer conception conversations and requested additional training in couple communication. Couples relied on information from healthcare providers to kickstart their safer conception discussions. Safer conception programmes should address relationship power imbalances, promote effective couple communication and offer healthcare provider support to enable HIV sero-different couples to make informed choices about conception in a manner that upholds their safety and reproductive autonomy.

A significant cost of wildfires is the exposure of local and regional populations to air pollution from smoke, which can travel hundreds of miles from the source fire and is associated with significant negative health consequences. Wildfires are increasing in frequency and intensity in the United States, driven by historic fire management approaches and global climate change. These influences will take many decades or longer to reverse, so the main opportunities for mitigating health effects involve minimizing human exposure through changes in behavior or infrastructure. One key recommendation for reducing pollution exposures during wildfire smoke events is to limit time and physical activity outdoors, but there is limited evidence on the extent to which people make this change. We estimate how use of parks and playgrounds changes with air quality during wildfire season in the northwest United States. We find small reductions in park and playground visits on moderately polluted days, and large reductions, to 50-60% of baseline visits, when pollution levels are high. Disaggregating results by neighborhood characteristics, we find a significantly greater behavioral response to moderate levels of air pollution in neighborhoods with higher socio-economic status, although responses to high levels of pollution are similar across neighborhood types.

Open tibia fractures are associated with substantial morbidity and impact on quality of life. Despite increasing incidence in low-resource settings, most open tibia fracture research comes from high-resource settings. This study aimed to assess the impact of socioeconomic status on treatment modality and evaluate predictors of health-related quality of life following open tibia fractures in Ghana.

Phase 3 PRIME/PRIME2 trials independently demonstrated efficacy and an acceptable safety profile of dupilumab adults with moderate-to-severe prurigo nodularis.

Focused cardiac ultrasound (FoCUS) has emerged as a valuable tool in emergency and critical care medicine, allowing for rapid assessment of cardiac function and structure at the bedside. This rapid diagnostic technique holds particular promise in resource-limited settings like Ethiopia, where access to standard echocardiography may be limited and delayed. However, the accuracy of FoCUS interpretation is highly dependent on the operator's skills and expertise. To inform the design of effective interventions, the study aimed to assess the accuracy of FoCUS interpretation and associated factors among senior Emergency Medicine residents at two large referral teaching hospitals in Ethiopia.

Health care providers' exposure to global surgical disparities is limited in current nursing and/or medical school curricula. For instance, global health is often associated with infectious diseases or maternal health without acknowledging the growing need for surgical care in low- and middle-income countries (LMICs). We propose an international virtual hackathon based on neurosurgical patient cases in under-resourced settings as an educational tool to bring awareness to global surgical disparities and develop relationships among trainees in different countries.

Households that burn biomass in inefficient open fires-a practice that results in $1.6 trillion in global damages from health impacts and climate-altering emissions yearly-are often unable to access cleaner alternatives, like gas, which is widely available but unaffordable, or electricity, which is unattainable for many due to insufficient supply and reliability of electricity services. Governments are often reluctant to make gas affordable. We argue that condemnation of all fossil fuel subsidies is short-sighted and does not adequately consider subsidizing gas for cooking as a potential strategy to improve public health and reduce greenhouse gas emissions.

Amyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old.

Recently, peak atrial longitudinal strain (PALS) has emerged as a possible predictor of Cancer therapy-related cardiac dysfunction (CTRCD) in cancer patients (CP), in addition to left ventricular global longitudinal strain (GLS). Thus, considering the link between left atrium and left ventricle, the aim of this study was to assess the global atrio-ventricular strain (GAVS) in CP, to detect early cardiotoxicity.

Antibiotic use in paediatric surgical specialties is understudied. We investigated the antibiotic prescribing practices of paediatric general and cardiovascular surgical teams in a tertiary hospital in South India.

Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. This study assessed the impact of treatment with asfotase alfa on patient-reported outcomes (PROs) in adults with pediatric-onset HPP. A longitudinal, telephone-based survey was administered to eligible individuals enrolled in a patient support program. Interviews were conducted at study entry (prior to asfotase alfa initiation) and after 3, 6, and 12 mo. PROs-Patient Health Questionnaire-9 [PHQ-9], Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI:SHP], Patient-Reported Outcomes Measurement Information System 29 [PROMIS-29], and Routine Assessment of Patient Index Data 3 [RAPID3]-were assessed at each time point. Appropriate statistical tests were performed to assess score changes. Among 50 enrolled patients (mean age: 46 yr [SD: 15.4]; 80% female; 94% White), 49 were evaluable at 3 mo, 44 at 6 mo, and 29 at 12 mo. By month 3, statistically significant improvements from baseline were detected in PHQ-9 scores (10.6 vs 5.8 [ .0001]), PROMIS-29 domain scores (overall physical function: 38.0 vs 43.0 [ .001]; anxiety: 57.5 vs 51.5 [ .0011]; fatigue: 63.3 vs 55.3 [ .0001]; sleep disturbances: 58.8 vs 54.3 [ .0099]; ability to participate in social roles and activities: 42.6 vs 47.7 [ .0012]; and pain interference: 63.8 vs 58.4 [ .001]), and RAPID3 domain scores (functional status: 2.7 vs 1.1 [ .0001]; pain tolerance: 6.0 vs 3.2 [ .0001]; and global health estimate: 5.1 vs 2.7 [ .0001]). Improvements persisted at month 12. Patients also showed improvements in WPAI:SHP domain scores at month 6 (presenteeism: 39.6% vs 14.1% [ .0001] and work productivity loss: 41.9% vs 14.1% [ .0001]). Treatment with asfotase alfa was associated with improved quality of life across several domains.

Chagas disease, caused by , affects millions worldwide. The 2030 WHO roadmap aims to eliminate it as a public health concern, emphasising the need for timely diagnosis to enhance treatment access. Current diagnostic algorithms, which rely on multiple tests, have prolonged turnaround times. This proves particularly problematic in resource-limited settings. Addressing this issue necessitates the validation and adoption of innovative tools. We explore recent developments in Chagas disease diagnosis, reviewing historical context and advancements. Despite progress, challenges persist. This article contributes to the understanding of current and future directions in this neglected healthcare area. Parasitological methods are simple but exhibit low sensitivity and require supplementary tests. Molecular methods, with automation potential, allow quantification and higher throughput. Serological tools show good performance but struggle with parasite antigenic diversity. Prioritising point-of-care tests is crucial for widespread accessibility and could offer a strategy to control disease impact. Ultimately, balancing achievements and ongoing obstacles is essential for comprehensive progress.

To assess the validity and reliability of the Migraine-Specific Quality of Life Questionnaire 2.1 (MSQv.2.1) in a group of Greek migraineurs.

The detection of uranium in drinking water has ignited concerns among the public, regulators, and policymakers, particularly as around 1% of the 55,554 water samples in India have shown uranium levels surpassing the 60 µg/l guideline established by the Atomic Energy Regulatory Board (AERB) based on radiological toxicity. Further, the Bureau of Indian Standard (BIS), has given a limit of 30 µg/l, which is derived from World Health Organization (WHO) guidelines. Besides the chemical and radiological aspects associated with uranium, factors such as technological constraints in water purification, waste management, environmental factors, and socio-economic conditions significantly influence these guideline values, which are often overlooked. This manuscript explores the variations in approaches for establishing guideline values and highlights the uncertainties arising from dependence on various variables such as intake and usage patterns, inter- and intra-species distinctions, and epidemiological data. A critical analysis indicates that adherence to global guidelines may result in some undesirable environmental issues. By considering factors such as population dynamics, socio-economic conditions, and geological influences, we suggest that limit of 60 µg/l for uranium in drinking water is appropriate for India.

Worldwide, depression is known to contribute significantly to the global burden of disease. Considering pharmacists are among the most approachable healthcare providers, they are well-placed to assist people with depression achieve positive treatment outcomes.

To explore general practitioners' experiences and reflections on how the current Norwegian guideline for screening for gestational diabetes affects their clinical practice.

Patients with heart failure (HF) experience a wide variety of symptoms. Appropriate recognition of symptoms is important in HF care. The Heart Failure Somatic Perception Scale (HFSPS) measures the presence of HF symptoms and the degree to which physical symptoms are bothersome.

Antimicrobial resistance is an ongoing "one health" challenge of global concern. The acyl-ACP synthetase (termed AasS) of the zoonotic pathogen Vibrio harveyi recycles exogenous fatty acid (eFA), bypassing the requirement of type II fatty acid synthesis (FAS II), a druggable pathway. A growing body of bacterial AasS-type isoenzymes compromises the clinical efficacy of FAS II-directed antimicrobials, like cerulenin. Very recently, an acyl adenylate mimic, C10-AMS, was proposed as a lead compound against AasS activity. However, the underlying mechanism remains poorly understood. Here we present two high-resolution cryo-EM structures of AasS liganded with C10-AMS inhibitor (2.33 Å) and C10-AMP intermediate (2.19 Å) in addition to its apo form (2.53 Å). Apart from our measurements for C10-AMS' Ki value of around 0.6 μM, structural and functional analyses explained how this inhibitor interacts with AasS enzyme. Unlike an open state of AasS, ready for C10-AMP formation, a closed conformation is trapped by the C10-AMS inhibitor. Tight binding of C10-AMS blocks fatty acyl substrate entry, and therefore inhibits AasS action. Additionally, this intermediate analog C10-AMS appears to be a mixed-type AasS inhibitor. In summary, our results provide proof of principle that inhibiting salvage of eFA by AasS reverses the FAS II bypass. This facilitates the development of next-generation of anti-bacterial therapeutics, esp. the dual therapy consisting of C10-AMS scaffold derivatives combined with certain FAS II inhibitors.

People with an evening chronotype have an increased risk of experiencing a major depressive disorder (MDD). It is unclear if this effect is predominantly related to the initial development of MDD or also present in recurrent episodes. The current study aimed to investigate if the association between chronotype and depressive severity in MDD patients is comparable in MDD patients with first and recurrent episodes. 386 MDD patients, 70.7% females and aged between 16 and 64, participated in the study. The Morningness - Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory (MFI20), and Quick Inventory of Depressive Symptomatology (QIDS-SR16) were administered to participants to determine chronotype, sleep quality, fatigue level, and depressive severity, respectively. Multivariate regression models were utilized to analyze how chronotype influences depressive severity. The study showed that chronotype, sleep quality, and fatigue level were all associated with depressive severity. Eveningness significantly predicted an increase in depressive severity independently of sleep quality and fatigue level only in patients with the first episode (-0.068,  = 0.010), but not in patients with recurrent episodes (0.013,  = 0.594). Circadian-focused treatment should be considered in first-episode depression only.

Using sequential immunoassays for the screening of blood donors is well described for viral serology testing but not for the screening of syphilis. In this study, we report the evaluation results and 2-year sequential testing data using two highly sensitive automated serology assays, the Alinity s Syphilis chemiluminescent immunoassay for screening, with all repeatedly reactive samples then tested on the Elecsys Syphilis electrochemiluminescence immunoassay. We screened 1,767,782 blood donor samples between 7 July 2021 and 6 July 2023 and found the Alinity false-positive rate to be low at 0.08% (1,456/1,767,782). The common false-positive rate between the two assays was also low (3.83%, 58/1,514). Concordantly reactive samples were further tested using a particle agglutination test, a rapid plasma reagin test, and a fluorescent treponemal antibody absorption test. There were 262/1,376 concordantly reactive Alinity and Elecsys blood donor samples with reactivity on one or more of the confirmatory tests. A total of 26/1,376 donors had a current syphilis infection, 152/1,376 reported a past history of syphilis and had been treated, and 84/1,376 did not report a past history of syphilis. We suggest that future studies could explore the use of sequential immunoassays to aid in the serodiagnosis for syphilis.

Melioidosis is a tropical infection caused by the intracellular pathogen , an underreported and emerging global threat. As melioidosis-associated mortality is frequently high despite antibiotics, novel management strategies are critically needed. Therefore, we sought to determine whether functional changes in the host innate and adaptive immune responses are induced during acute melioidosis and are associated with outcome. Using a unique whole blood stimulation assay developed for use in resource-limited settings, we examined induced cellular functional and phenotypic changes in a cohort of patients with bacteremic melioidosis prospectively enrolled within 24 hours of positive blood culture and followed for 28 days. Compared to healthy controls, melioidosis survivors generated an IL-17 response mediated by Th17 cells and terminally-differentiated effector memory CD8 T cells (P < 0.05, both), persisting to 28-days after enrollment. Furthermore, melioidosis survivors developed polyfunctional cytokine production in CD8 T cells (P < 0.01). Conversely, a reduction in CCR6 CD4 T cells was associated with higher mortality, even after adjustments for severity of illness (P = 0.004). Acute melioidosis was also associated with a profound acute impairment in monocyte function as stimulated cytokine responses were reduced in classical, intermediate and non-classical monocytes. Impaired monocyte cytokine function improved by 28-days after enrollment. These data suggest that IL-17 mediated cellular responses may be contributors to host defense during acute melioidosis, and that innate immune function may be impaired. These insights could provide novel targets for the development of therapies and vaccine targets in this frequently lethal disease.

This study reviews global levels of ochratoxin A (OTA) in infant formula and cereal-based foods, using Monte Carlo simulation to assess risks. The review found 24 studies on global OTA levels in infant food and cereal-based products, using databases including PubMed, Scopus, Web of Science and Embase until March 2024. We estimated OTA exposure in infant food based on concentration, intake and body weight. The exposure and hazard quotient margin were calculated using BMDL10 and TDI values. Monte Carlo simulation evaluated human health risks from OTA in infant formula and cereal-based foods. A global study from 14 countries shows varying levels, surpassing EU limits in Tunisia, Ecuador, the USA, and generally in Africa, notably in infant cereals, which had higher levels than formula. Globally, OTA was present in 29.3% of the 3348 samples analyzed, with Lebanon at 95.2% and Brazil at 0%. Analysis indicates only non-carcinogenic risk for infants. While health risks for infants are mostly low, ongoing research and monitoring are vital to minimize OTA exposure in infant food.

Our research investigates the societal implications of access to glucagon-like peptide-1 (GLP-1) agonists, particularly in light of recent clinical trials demonstrating the efficacy of semaglutide in reducing cardiovascular mortality. A decade-long analysis of Google Trends indicates a significant increase in searches for GLP-1 agonists, primarily in North America. This trend contrasts with the global prevalence of obesity. Given the high cost of GLP-1 agonists, a critical question arises: Will this disparity in medication accessibility exacerbate the global health equity gap in obesity treatment? This viewpoint explores strategies to address the health equity gap exacerbated by this emerging medication. Because GLP-1 agonists hold the potential to become a cornerstone in obesity treatment, ensuring equitable access is a pressing public health concern.

Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. These include near full-length sequence of genomes with KSHV K1 subtypes A, B, C, and F as well as subtype E, for which no full sequence was previously available. High levels of recombination were observed. Fourteen individuals (18%) showed evidence of infection with multiple KSHV variants (from two to four unique genomes). Twenty-six comparisons of sequences, obtained from various sampling sites including PBMC, tissue biopsies, oral fluids, and effusions in the same participants, identified near complete genome conservation between different biological compartments. Polymorphisms were identified in coding and non-coding regions, including indels in the K3 and K15 genes and sequence inversions here reported for the first time. One such polymorphism in KSHV ORF46, specific to the KSHV K1 subtype E2, encoded a mutation in the leucine loop extension of the uracil DNA glycosylase that results in alteration of biochemical functions of this protein. This confirms that KSHV sequence variations can have functional consequences warranting further investigation. This study represents the largest and most diverse analysis of KSHV genome sequences to date among individuals with KAD and provides important new information on global KSHV genomics.

Narrow escape theory deals with the first passage of a particle diffusing in a cavity with small circular windows on the cavity wall to one of the windows. Assuming that (i) the cavity has no size anisotropy and (ii) all windows are sufficiently far away from each other, the theory provides an analytical expression for the particle mean first-passage time (MFPT) to one of the windows. This expression shows that the MFPT depends on the only global parameter of the cavity, its volume, independent of the cavity shape, and is inversely proportional to the product of the particle diffusivity and the sum of the window radii. Amazing simplicity and universality of this result raises the question of the range of its applicability. To shed some light on this issue, we study the narrow escape problem in a cylindrical cavity of arbitrary size anisotropy with two small windows arbitrarily located on the cavity side wall. We derive an approximate analytical solution for the MFPT, which smoothly goes from the conventional narrow escape solution in an isotropic cavity when the windows are sufficiently far away from each other to a qualitatively different solution in a long cylindrical cavity (the cavity length significantly exceeds its radius). Our solution demonstrates the mutual influence of the windows on the MFPT and shows how it depends on the inter-window distance. A key step in finding the solution is an approximate replacement of the initial three-dimensional problem by an equivalent one-dimensional one, where the particle diffuses along the cavity axis and the small absorbing windows are modeled by delta-function sinks. Brownian dynamics simulations are used to establish the range of applicability of our approximate approach and to learn what it means that the two windows are far away from each other.

Indications for liver transplantation (LT) vary across age groups. We identified predictors of outcomes for teenage LT waitlisted candidates and recipients in the United States from 2008 to 2022.

Diseases caused by trypanosomatid parasites remain a significant unmet medical need for millions of people globally. Trypanosomatid parasites such as and subspecies of cause Chagas disease and human African trypanosomiasis (HAT), respectively. Although efforts to find novel treatments have been successful for HAT, Chagas disease is still treated with decades-old therapies that suffer from long treatment durations and severe safety concerns. We recently described the identification and characterization of the cyanotriazole compound class that kills trypanosomes, in vitro and in vivo, by selective inhibition of the trypanosome nuclear topoisomerase II enzyme. To evaluate whether inhibition of the topoisomerase II enzyme led to parasite death due to lethal double-strand DNA breaks, we developed assays for detecting DNA damage in both intracellular amastigotes of and bloodstream-form by using the canonical DNA damage marker γH2A. Herein, this article describes the protocols for detecting DNA damage using an immunofluorescence assessment of γH2A by microscopy in trypanosome parasites. Key features • Immunofluorescence-based assay to detect the γH2A response in and parasites. • Robust DNA damage pathway-based cellular assays to evaluate topoisomerase II poisons' ability to cause DNA damage. • A 384-well plate-based protocol allows high-resolution and high-throughput evaluation of compounds that cause DNA damage by measuring γH2A in intracellular parasites. • This assay could be modifiable for evaluation of DNA damage responses in various intracellular and extracellular eukaryotic pathogens.

Influenza viruses pose a significant burden on global human health. Influenza has a broad cellular tropism in the airway, but how infection of different epithelial cell types impacts replication kinetics and burden in the airways is not fully understood. Using primary human airway cultures, which recapitulate the diverse epithelial cell landscape of the human airways, we investigated the impact of cell type composition on virus tropism and replication kinetics. Cultures were highly diverse across multiple donors and 30 independent differentiation conditions and supported a range of influenza replication. Although many cell types were susceptible to influenza, ciliated and secretory cells were predominantly infected. Despite the strong tropism preference for secretory and ciliated cells, which consistently make up 75% or more of infected cells, only ciliated cells were associated with increased virus production. Surprisingly, infected secretory cells were associated with overall reduced virus output. The disparate response and contribution to influenza virus production could be due to different pro- and antiviral interferon-stimulated gene signatures between ciliated and secretory populations, which were interrogated with single-cell RNA sequencing. These data highlight the heterogeneous outcomes of influenza virus infections in the complex cellular environment of the human airway and the disparate impacts of infected cell identity on multiround burst size, even among preferentially infected cell types.

Relatively few studies have investigated the effects of rehabilitation-based physical activity therapy as a treatment for older patients with advanced cancer. This study evaluated the effects of individualized precise and structured exercise interventions, prescribed by a rehabilitation physician, on fatigue, quality of life (QOL), and physical activity in older patients with advanced cancer.

American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce. We describe the clinical characteristics and outcome of patients with ACL imported to a tertiary centre in Germany and determine whether species-specific therapy according to the 2014 "LeishMan" group recommendations is associated with cure.

Antimicrobial resistance (AMR) is a major global health threat estimated to have caused the deaths of 1.27 million people in 2019, which is more than HIV/AIDS and malaria deaths combined. AMR also has significant consequences on the global economy. If not properly addressed, AMR could immensely impact the world's economy, further increasing the poverty burden in low- and middle-income countries. To mitigate the risk of a post-antibiotic society, where the ability to effectively treat common bacterial infections is being severely threatened, it is necessary to establish a continuous supply of new and novel antibacterial medicines. However, there are gaps in the current pipeline that will prove difficult to address, given the time required to develop new agents. To understand the status of upstream antibiotic development and the challenges faced by drug developers in the early development stage, the World Health Organization has regularly assessed the preclinical and clinical antibacterial development pipeline. The review identifies potential new classes of antibiotics or novel mechanisms of action that can better address resistant bacterial strains. This proactive approach is necessary to stay ahead of evolving resistance patterns and to support the availability of effective treatment options. This review examines the trends in preclinical development and attempts to identify gaps and potential opportunities to overcome the numerous hurdles in the early stages of the antibacterial research and development space.

Cuprotosis related genes (CRGs) have been proved to be potential therapeutic targets for coronavirus disease 2019 (COVID-19) and cancer, but their immune and molecular mechanisms in COVID-19 infection in Diffuse Large B-cell Lymphoma (DLBC/DLBCL) patients are rarely reported. Our research goal is first to screen the key CRGs in COVID-19 through univariate analysis, machine learning and clinical samples. Secondly, we determined the expression and prognostic role of key CRGs in DLBCL through pan-cancer analysis. We validated the expression levels and prognosis using multiple datasets and independent clinical samples and validated the functional role of key CRGs in DLBCL through cell experiments. Finally, we validated the expression levels of CRGs in COVID-19 infected DLBCL patients samples and analyzed their common pathways in COVID-19 and DLBCL. The results show that synuclein-alpha (SNCA) is the common key differential gene of COVID-19 and DLBCL. DLBCL cells confirm that high expression of SNCA can significantly promote cell apoptosis and significantly inhibit the cycle progression of DLBCL. High expression of SNCA can regulate the binding of major histocompatibility complexes (MHCs) and T cell receptor (TCR) by regulating immune infiltration of Dendritic cells, effectively enhancing T cell-mediated anti-tumor immunity and clearing cancer cells. In conclusion, SNCA may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our study provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL patients.

Suicide is the second leading cause of death in young people worldwide and is responsible for about 52,000 deaths annually in children and adolescents aged 5-19 years. Familial, social, psychological, and behavioral factors play important roles in suicide risk. As traumatic events such as the COVID-19 pandemic may contribute to suicidal behaviors in young people, there is a need to understand the current status of suicide in adolescents, including its epidemiology, associated factors, the influence of the pandemic, and management initiatives.

Cancer is a significant global health concern associated with multiple distinct factors, including microbial and viral infections. Numerous studies have elucidated the role of microorganisms, such as Helicobacter pylori (H. pylori), as well as viruses for example human papillomavirus (HPV), hepatitis B virus (HBV), and hepatitis C virus (HCV), in the development of human malignancies. Substantial attention has been focused on the treatment of these microorganism- and virus-associated cancers, with promising outcomes observed in studies employing peptide-based therapies. The current paper provides an overview of microbe- and virus-induced cancers and their underlying molecular mechanisms. We discuss an assortment of peptide-based therapies which are currently being developed, including tumor-targeting peptides and microbial/viral peptide-based vaccines. We describe the major technological advancements that have been made in the design, screening, and delivery of peptides as anticancer agents. The primary focus of the current review is to provide insight into the latest research and development in this field and to provide a realistic glimpse into the future of peptide-based therapies for microbe- and virus-induced neoplasms.

N6-methyladenosine (mA) is the most abundant epitranscriptomic mark that regulates the fate of RNA molecules. Recent studies have revealed a bidirectional interaction between mA modification and the circadian clock. However, the precise temporal dynamics of mA global enrichment in the central circadian pacemaker have not been fully elucidated. Our study investigates the relationship between FTO demethylase and molecular clocks in primary cells of the suprachiasmatic nucleus (SCN). In addition, we examined the effects of lipopolysaccharide (LPS) on Fto expression and the role of FTO in LPS-induced reactive oxygen species (ROS) production in primary SCN cell culture. We observed circadian rhythmicity in the global mA levels, which mirrored the rhythmic expression of the Fto demethylase. Silencing FTO using siRNA reduced the mesor of Per2 rhythmicity in SCN primary cells and extended the period of the PER2 rhythm in SCN primary cell cultures from PER2::LUC mice. When examining the immune response, we discovered that exposure to LPS upregulated global mA levels while downregulating Fto expression in SCN primary cell cultures. Interestingly, we found a loss of circadian rhythmicity in Fto expression following LPS treatment, indicating that the decrease of FTO levels may contribute to mA upregulation without directly regulating its circadian rhythm. To explore potential protective mechanisms against neurotoxic inflammation, we examined ROS production following LPS treatment in SCN primary cell cultures pretreated with FTO siRNA. We observed a time-dependent pattern of ROS induction, with significant peak at 32 h but not at 20 h after synchronization. Silencing the FTO demethylase abolished ROS induction following LPS exposure, supporting the hypothesis that FTO downregulation serves as a protective mechanism during LPS-induced neuroinflammation in SCN primary cell cultures.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol metabolism and cardiovascular diseases, has recently garnered attention for its emerging involvement in cancer biology. The multifunctional nature of PCSK9 extends beyond lipid regulation and encompasses a wide range of cellular processes that can influence cancer progression. Studies have revealed that PCSK9 can modulate signaling pathways, such as PI3K/Akt, MAPK, and Wnt/β-catenin, thereby influencing cellular proliferation, survival, and angiogenesis. Additionally, the interplay between PCSK9 and cholesterol homeostasis may impact membrane dynamics and cellular migration, further influencing tumor aggressiveness. The central role of the immune system in monitoring and controlling cancer is increasingly recognized. Recent research has demonstrated the ability of PCSK9 to modulate immune responses through interactions with immune cells and components of the tumor microenvironment. This includes effects on dendritic cell maturation, T cell activation, and cytokine production, suggesting a role in shaping antitumor immune responses. Moreover, the potential influence of PCSK9 on immune checkpoints such as PD1/PD-L1 lends an additional layer of complexity to its immunomodulatory functions. The growing interest in cancer immunotherapy has prompted exploration into the potential of targeting PCSK9 for therapeutic benefits. Preclinical studies have demonstrated synergistic effects between PCSK9 inhibitors and established immunotherapies, offering a novel avenue for combination treatments. The strategic manipulation of PCSK9 to enhance tumor immunity and improve therapeutic outcomes presents an exciting area for further investigations. Understanding the mechanisms by which PCSK9 influences cancer biology and immunity holds promise for the development of novel immunotherapeutic approaches. This review aims to provide a comprehensive analysis of the intricate connections between PCSK9, cancer pathogenesis, tumor immunity, and the potential implications for immunotherapeutic interventions.

MRSA is a major contributor to AMR-related deaths. The WHO's global action plan emphasizes a One Health approach, acknowledging the connection between humans and their companion animals. It is agreed on that comprehensive AMR surveillance is needed.

The FDA's alerts regarding the T-cell lymphoma risk post CAR-T therapy has garnered global attention, yet a comprehensive profile of second primary malignancies (SPMs) following CAR-T treatment is lacking.

Every year, the global production of plastic waste reaches a staggering 400 million metric tons (Mt), precipitating adverse consequences for the environment, food safety, and biodiversity as it degrades into microplastics (MPs). The multifaceted nature of MP pollution, coupled with its intricate physiological impacts, underscores the pressing need for comprehensive policies and legislative frameworks. Such measures, alongside advancements in technology, hold promise in averting ecological catastrophe in the oceans. Mandated legislation represents a pivotal step towards restoring oceanic health and securing the well-being of the planet. This work offers an overview of the policy hurdles, legislative initiatives, and prospective strategies for addressing global pollution due to MP. Additionally, this work explores innovative approaches that yield fresh insights into combating plastic pollution across various sectors. Emphasizing the importance of a global plastics treaty, the article underscores its potential to galvanize collaborative efforts in mitigating MP pollution's deleterious effects on marine ecosystems. Successful implementation of such a treaty could revolutionize the plastics economy, steering it towards a circular, less polluting model operating within planetary boundaries. Failure to act decisively risks exacerbating the scourge of MP pollution and its attendant repercussions on both humanity and the environment. Central to this endeavor are the formulation, content, and execution of the treaty itself, which demand careful consideration. While recognizing that a global plastics treaty is not a panacea, it serves as a mechanism for enhancing plastics governance and elevating global ambitions towards achieving zero plastic pollution by 2040. Adopting a life cycle approach to plastic management allows for a nuanced understanding of possible trade-offs between environmental impact and economic growth, guiding the selection of optimal solutions with socio-economic implications in mind. By embracing a comprehensive strategy that integrates legislative measures and technological innovations, we can substantially reduce the influx of marine plastic litter at its sources, safeguarding the oceans for future generations.

Sub-Saharan Africa (SSA) has the highest burden of neonatal mortality in the world. Identifying the most critical modifiable risk factors is imperative for reducing neonatal mortality rates. This study is the first to calculate population-attributable fractions (PAFs) for modifiable risk factors of neonatal mortality in SSA.

In 2023 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared endemic, yet hospital admissions have persisted and risen within populations at high and moderate risk of developing severe disease, which include those of older age, and those with co-morbidities. Antiviral treatments, currently only available for high-risk individuals, play an important role in preventing severe disease and hospitalisation within this subpopulation. Here, we further explore the public health and economic benefits of extending target populations for treatment, and assess efficacy thresholds for a treatment strategy to be cost-saving.

Global influenza-associated acute respiratory infections contribute to 3-5 million severe illnesses requiring hospitalization annually, with 90% of hospitalizations occurring among children < 5 years in developing countries. In Bangladesh, the inadequate availability of nationally representative, robust estimates of influenza-associated hospitalizations limits allocation of resources for prevention and control measures.

A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation and behaviors based on International Classification of Diseases codes.

Disorders of gut-brain interaction (DGBI) are characterized by debilitating symptoms not explained by structural or biochemical abnormalities. While functional conditions present with complex, likely heterogeneous pathophysiology, we aimed to investigate if proxy measures of sociocultural and environmental factors are associated with the prevalence of various DGBI in populations across the world.

Bifidobacteria are among the earliest colonizers of the human gut, conferring numerous health benefits. While multiple Bifidobacterium strains are used as probiotics, accumulating evidence suggests that the individual responses to probiotic supplementation may vary, likely due to a variety of factors, including strain type(s), gut community composition, dietary habits of the consumer, and other health/lifestyle conditions. Given the saccharolytic nature of bifidobacteria, the carbohydrate composition of the diet is one of the primary factors dictating the colonization efficiency of Bifidobacterium strains. Therefore, a comprehensive understanding of bifidobacterial glycan metabolism at the strain level is necessary to rationally design probiotic or synbiotic formulations that combine bacterial strains with glycans that match their nutrient preferences. In this study, we systematically reconstructed 66 pathways involved in the utilization of mono-, di-, oligo-, and polysaccharides by analyzing the representation of 565 curated metabolic functional roles (catabolic enzymes, transporters, transcriptional regulators) in 2973 non-redundant cultured Bifidobacterium isolates and metagenome-assembled genomes (MAGs). Our analysis uncovered substantial heterogeneity in the predicted glycan utilization capabilities at the species and strain level and revealed the presence of a yet undescribed phenotypically distinct subspecies-level clade within the Bifidobacterium longum species. We also identified Bangladeshi isolates harboring unique gene clusters tentatively implicated in the breakdown of xyloglucan and human milk oligosaccharides. Predicted carbohydrate utilization phenotypes were experimentally characterized and validated. Our large-scale genomic analysis considerably expands the knowledge of carbohydrate metabolism in bifidobacteria and provides a foundation for rationally designing single- or multi-strain probiotic formulations of a given bifidobacterial species as well as synbiotic combinations of bifidobacterial strains matched with their preferred carbohydrate substrates.

Global terrestrial water supplies are rapidly depleting due to the consequences of climate change. Water scarcity results in an inevitable compromise of safe hygiene and sanitation practices, leading to the transmission of water-borne infectious diseases, and the preventable deaths of over 800.000 people each year. Moreover, almost 500 million people lack access to toilets and sanitation systems. Ecosystems are estimated to be contaminated by 6.2 million tons of nitrogenous products from human wastewater management practices. It is therefore imperative to transform toilet and sewage systems to promote equitable access to water and sanitation, improve public health, conserve water, and protect ecosystems. Here, the integration of emerging technologies in toilet and sewage networks to repurpose toilet and wastewater systems is reviewed. Potential applications of these systems to develop sustainable solutions to environmental challenges, promote public health, and advance person-centered healthcare are discussed.

Integrating sustainability principles into medical and surgical curricula raises awareness and empowers future healthcare professionals to adopt sustainable practices, reducing the environmental impact of surgical care. This study aims to assess the presence of sustainability education in African medical schools and surgical residency curricula to inform policymakers and educators in African healthcare systems.

The mechanism by which chondrocytes respond to reduced mechanical loading environments and the subsequent risk of developing osteoarthritis remains unclear. This is of particular concern for astronauts. In space the reduced joint loading forces during prolonged microgravity (10 ) exposure could lead to osteoarthritis (OA), compromising quality of life post-spaceflight. In this study, we encapsulated human chondrocytes in an agarose gel of similar stiffness to the pericellular matrix to mimic the cartilage microenvironment. We then exposed agarose-chondrocyte constructs to simulated microgravity (SM) using a rotating wall vessel (RWV) bioreactor to better assess the cartilage health risks associated with spaceflight. Global metabolomic profiling detected a total of 1205 metabolite features across all samples, with 497 significant metabolite features identified by ANOVA (FDR-corrected p-value < 0.05). Specific metabolic shifts detected in response to SM exposure resulted in clusters of co-regulated metabolites, as well as key metabolites identified by variable importance in projection scores. Microgravity-induced metabolic shifts in gel constructs and media were indicative of protein synthesis, energy metabolism, nucleotide metabolism, and oxidative catabolism. The microgravity associated-metabolic shifts were consistent with early osteoarthritic metabolomic profiles in human synovial fluid, which suggests that even short-term exposure to microgravity (or other reduced mechanical loading environments) may lead to the development of OA.

In this editorial, we comment on the article by Chen . Metabolic dysfunction-associated fatty liver disease (MAFLD) is a global public health burden whose incidence has risen concurrently with overweight and obesity. Given its detrimental health impact, early identification of at-risk individuals is crucial. MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy, imaging, or blood biomarkers, and one of the following conditions: Overweight/ obesity, type 2 diabetes mellitus, or metabolic dysregulation. However, in large-scale epidemiological studies, liver biopsies are not feasible. The application of techniques such as ultrasonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy is restricted by their limited sensitivity, low effectiveness, high costs, and need for specialized software. Blood biomarkers offer several advantages, particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical. Analysis of cumulative effects of excess high-normal blood alanine aminotransferase (ALT) levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods. Accordingly, investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring, enabling timely intervention and management and improving patient outcomes.

Health systems have a dual imperative to take action on climate change. First, they must develop climate resilient health services in response to the direct and indirect impacts of climate change on health. Second, they must reduce their own carbon footprint since health systems are a significant contributor to global greenhouse gas emissions.

and are parasitic nematodes that primarily infest the small intestines of humans and pigs, respectively. Ascariasis poses a significant threat to human health and swine health. Understanding larval development is crucial for developing novel therapeutic interventions that will prevent ascariasis in both humans and pigs. This study aimed to characterize the excretory-secretory (ES) proteome of different larval stages (L3-egg, L3-lung, L3-trachea) to identify potential targets for intervention to prevent -induced global morbidity.

Alcohol consumption remains a significant global health challenge, causing millions of direct and indirect deaths annually. Intriguingly, recent work has highlighted the prefrontal cortex, a major brain area that regulates inhibitory control of behaviors, whose activity becomes dysregulated upon alcohol abuse. However, whether an endogenous mechanism exists within this brain area that limits alcohol consumption is unknown. Here we identify a discrete GABAergic neuronal ensemble in the medial orbitofrontal cortex (mOFC) that is selectively recruited during binge alcohol-drinking and intoxication. Upon alcohol intoxication, this neuronal ensemble suppresses binge drinking behavior. Optogenetically silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. We find that this neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. We further show, using brain-wide analysis, that this neuronal ensemble projects widely, and that its projections specifically to the mediodorsal thalamus are responsible for regulating binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by halting alcohol intake. These results provide valuable insights into the complex nature of alcohol abuse and offers potential avenues for the development of mOFC neuronal ensemble-targeted interventions.

Growing demand for wound care resulting from the increasing chronic diseases and trauma brings intense pressure to global medical health service system. Artificial skin provides mechanical and microenvironmental support for wound, which is crucial in wound healing and tissue regeneration. However, challenges still remain in the clinical application of artificial skin since the lack of the synergy effect of necessary performance. In this study, a multi-functional artificial skin is fabricated through microfluidic spinning technology by using core-shell gel nanofiber scaffolds (NFSs). This strategy can precisely manipulate the microstructure of artificial skin under microscale. The as-prepared artificial skin demonstrates superior characteristics including surface wettability, breathability, high mechanical strength, strain sensitivity, biocompatibility and biodegradability. Notably, this artificial skin has the capability to deliver medications in a controlled and sustained manner, thereby accelerating the wound healing process. This innovative approach paves the way for the development of a new generation of artificial skin and introduces a novel concept for the structural design of the unique core-shell gel NFSs.

To describe the trajectories of linguistic, cognitive-communicative, and health-related quality of life (HRQOL) outcomes after stroke in persons with aphasia.

Despite the availability of effective vaccines against the three primary pathogens (, type b, and ) that cause bacterial meningitis, this condition remains a significant cause of morbidity, neurologic sequelae, and mortality among children and adults living in low-income and middle-income countries.

 The global geriatric population is increasing, leading to a higher prevalence of non-communicable diseases, including depression. This condition often remains underdiagnosed and untreated disease.

Teledentistry, a blend of dentistry and telecommunications used to provide dental care from a distance, holds great promise in enhancing public health, especially in reaching communities with limited access. However, putting it into practice has its own set of obstacles and background variables. It is frequently difficult to obtain dental treatment, especially in rural or economically underdeveloped areas. By removing geographical constraints and offering virtual consultations and diagnostics, teledentistry provides a solution. The quick development of technology, such as portable electronics and high-speed internet, has increased accessibility and efficiency in communication, which has aided in the acceptance of teledentistry. Getting traditional dental care can be costly, particularly for people without insurance. As an affordable substitute for traditional dental care, teledentistry may lower overhead expenses related to physical dental offices. Early interventions and preventive care can greatly enhance oral health results and lessen the need for later, more invasive procedures. There are disparities in the availability of digital gadgets and internet connectivity. The laws that control telehealth services might differ greatly between nations and areas. While teledentistry can help with remote consultations and triage, it might not be able to do thorough examinations or other diagnostic treatments that need in-person attendance. Delivering dependable, top-notch telemedicine services in developing areas can pose challenges. Certain dentists might hesitate to utilize teledentistry due to concerns about the quality of care, liability issues, or potential impacts on their traditional practice models. It could be difficult to get patients to accept and use teledentistry services. This review is undertaken to assess the effectiveness of teledentistry in public health as well as legal and regulatory considerations for practicing teledentistry. Teledentistry might be the future of the oral health sector, thus fully capitalizing on this enormous opportunity to change how oral therapies are administered. Patients, dentists, and the dental community at large will need to have highly open minds. For the community's well-being and to gain its trust, ethical considerations are crucial. The outcomes of teledentistry can be attained by overcoming the obstacles and using comprehensive methods and approaches. It was noted that teledentistry is a potential strategy that combines dental care with telecommunication technology to enhance patient outcomes, reduce healthcare inequalities, and expand access to oral health services. The delivery of oral healthcare is being revolutionized by teledentistry, especially in light of contemporary issues including geographic restrictions, lack of access to dental treatment, and the ongoing global health crisis.

Dilip Mahalanabis, an esteemed Indian pediatrician, revolutionized global health through his pioneering work in combatting diarrheal diseases, particularly during the Bangladesh War of Independence in 1971. His development of oral rehydration therapy (ORT) provided a simple, cost-effective solution that significantly reduced mortality rates among cholera patients. Mahalanabis' dedication to equitable healthcare, evidenced by his leadership roles in organizations such as the World Health Organization (WHO), underscores his legacy as a champion for vulnerable populations. ORT's widespread adoption has democratized treatment, empowering communities and drastically reducing mortality rates associated with diarrheal diseases.

To assess the quality of YouTube videos for patient education on shoulder dislocation.

To examine the associations of cardiorespiratory fitness with executive function, episodic memory, and global cognition and sex differences in these associations in community-dwelling older adults with amnestic mild cognitive impairment.

Patellofemoral instability (PFI) is a common condition in children and adolescents, ranging from mild discomfort and mal-tracking to lateral patellar dislocation [1]. A number of anatomical risk factors have been described in the literature, such as trochlear dysplasia, patella alta, excessive tibial tuberosity to trochlear groove (TT-TG) distance, patellar tilt and soft tissue alterations [2]. Among them, TD has been identified as the main anatomical risk factor with the strongest association with PFI [1, 2]. In the study by Dejour et al. [2] radiographically observed TD was identified in 96% of patients with a history of patellofemoral dislocation [1, 2]. Patients with Dejour Type D dysplasia are characterized by a prominent and convex lateral facet with a vertical connection to a hypoplastic medial facet (Figure 1), which provides inadequate tracking of the patella in the trochlea during flexion leading to patella subluxation [2]. Non-operative treatment of lateral patellar dislocation presents a rate of re-dislocation up to 70% within 24 months of the first episode [3]. Sulcus deepening trochleoplasty is indicated for Type B and D dysplasia, in order to improve patella tracking, reduce the rate of re-dislocation and achieve good functional outcomes [2, 4]. Trochlea dysplasia is defined as a shallow or flattened groove with decreased resistance to lateral patellar translation. TD can be assessed on computed tomography (CT) and magnetic resonance imaging (MRI) with the use of overlapping axial images and are able to show perfectly the global shape of the femoral trochlea [2]. The thresholds for identifying trochlear dysplasia are established based on the sulcus angle ≥ 145°, medial/lateral trochlea facet asymmetry < 40%, trochlear depth < 3 mm and lateral trochlear inclination ≤ 11° and therefore it can be used in young adolescents [4, 5]. A deep knowledge of anatomic variations and abnormalities of the patellofemoral joint, which may predispose to PFI, is crucial in order to choose the appropriate treatment for each patient.

To evaluate the quality of meniscus-related TikTok videos to better understand their value for patient education.

Chronic hepatitis B (CHB) remains a major threat to global public health, affecting 296 million people worldwide. Although there is no curative treatment for CHB today, the virus can be effectively controlled with current antiviral treatment strategies. Since HBsAg loss can rarely (1%) be achieved with current nucleos(t)ide analogues (NA) options, lifelong treatment is usually required in HBeAg-negative patients. In recent years, guidelines have stated that long-term NA treatments can be discontinued for HBeAg-negative patients without achieving HBsAg loss. There is no general consensus on how discontinuation of NA can be included in the treatment approach. This review aimed to evaluate the current literature regarding the discontinuation of NA treatment in HBeAg-negative patients. Patients with HBeAg-negative CHB who have a higher chance of response after discontinuation of NA therapy can be defined as non-cirrhotic patients who have low HBsAg, HBcrAg, and HBV RNA levels at the discontinuation of treatment and accept close follow-up. The management of relapses that develop after NA discontinuation in patients is also unclear. The agent used in NA treatment itself may also affect the pattern of relapse development. Relapse after NA treatment occurs significantly slower and less frequently with entecavir compared to other regimens, including tenofovir dipivoxil. Prospective studies are needed in order to maintain the chance of HBsAg clearance in case of exacerbation and to treat acute exacerbations that can be fatal in a timely manner. Algorithms to be developed for use after discontinuation of NA treatment will help the clinician manage the patient safely.

COVID-19 is a severe infectious disease caused by a SARS-CoV-2 infection. It has caused a global pandemic and can lead to acute respiratory distress syndrome (ARDS). Beyond the respiratory system, the disease manifests in multiple organs, producing a spectrum of clinical symptoms. A pivotal factor in the disease's progression is autoimmunity, which intensifies its severity and contributes to multi-organ injuries. The intricate interaction between the virus' spike protein and human proteins may engender the generation of autoreactive antibodies through molecular mimicry. This can further convolute the immune response, with the potential to escalate into overt autoimmunity. There is also emerging evidence to suggest that COVID-19 vaccinations might elicit analogous autoimmune responses. Advanced technologies have pinpointed self-reactive antibodies that target diverse organs or immune-modulatory proteins. The interplay between autoantibody levels and multi-organ manifestations underscores the importance of regular monitoring of serum antibodies and proinflammatory markers. A combination of immunosuppressive treatments and antiviral therapy is crucial for managing COVID-19-associated autoimmune diseases. The review will focus on the generation of autoantibodies in the context of COVID-19 and their impact on organ health.

Retinitis pigmentosa (RP) accounts for 2 percent of global cases of blindness. The RP10 form of the disease results from mutations in isoform 1 of inosine 5'-monophosphate dehydrogenase (IMPDH1), the rate-limiting enzyme in the purine nucleotide synthesis pathway. Retinal photoreceptors contain specific isoforms of IMPDH1 characterized by terminal extensions. Considering previously reported significantly varied kinetics among retinal isoforms, the current research aimed to investigate possible structural explanations and suitable functional sites for the pharmaceutical targeting of IMPDH1 in RP.

(Burm.f.) Nees has been recommended to relieve symptoms and decrease the severity of COVID-19. The clinical study aimed to investigate the efficacy and safety of ethanolic extract (APE).

With an aging global population, the prevalence of frailty in patients with traumatic spinal injury (TSI) is steadily increasing. The aim of the current study is to evaluate the utility of the Orthopedic Frailty Score (OFS) in assessing the risk of adverse outcomes in patients with isolated TSI requiring surgery, with the hypothesis that frailer patients suffer from a disproportionately increased risk of these outcomes.

Older people constitute an overlooked vulnerable population in humanitarian crises. Lebanon is a small country that hosts the largest number of refugees per capita in the world. With exacerbating socioeconomic conditions, exclusionary policies against refugees, and a fragmented humanitarian system, the status of older Syrian refugees (OSRs) requires special attention. This study aimed to explore OSRs' unmet needs, coping strategies, available humanitarian services, and some indicators of the humanitarian inclusion standards focusing on the shelter, health, nutrition and food security, and water, sanitation and hygiene sectors. We conducted a convergent mixed-methods study between December 2021 and March 2022 in the North and Bekaa, including a cross-sectional survey with 461 participants and 14 semi-structured interviews. Results show that OSRs lived in inappropriate shelters (cold, leaking rainwater), especially in informal tented settlements. High rent prices pushed refugee households with elderly to prioritize paying rent at the expense of other needs such as food and medication, particularly when food cash transfer is the sole source of income, jeopardizing food security and intake. Access to dignifying and accessible bathing facilities was compromised in ITSs with shared facilities. Substantial medical costs hindered OSRs access to healthcare such as surgeries. Due to the crisis, chronic medications are not always available in dispensaries for subsidized cost, pushing OSRs to non-compliance and selling food assistance to buy medications. Soaring fuel prices hindered OSRs access to heating and transportation to receive healthcare. No efforts were reported in collecting data on OSRs' needs, targeting them with information on services, or soliciting feedback for programming, especially in the absence of any age-tailored interventions. Findings shed light on the precarious living conditions of OSRs in Lebanon and add to the body of evidence documenting their invisibility to the humanitarian response. An age-inclusive response is needed through holistic, tailored, and sustainable interventions.

Both gender and HIV stigma are known to contribute to poor retention to antiretroviral therapy (ART), but little is known how they interact in decisions about adherence or default by people living with HIV (PLWH). This qualitative study explored HIV stigma and gender interaction in PLWH's care decisions in Mozambique. Transcribed data from semi-structured interviews of 68 men and 71 women living with HIV, were coded and analyzed for themes of HIV stigma, gender norms and treatment continuation and interruption pathways, using both deductive and inductive coding approaches. Stigma experiences were found to be influenced by gender roles. Anticipation of stigma was common across the narratives of PLWH, while women had more experiences of enacted stigma, particularly by their intimate partners. Women's treatment interruptions were influenced by fear of partner's negative reaction. Men's narratives showed internalized stigma and delayed treatment due to anticipated stigma and masculine norm of strength. Severe internalized stigma was found among single mothers, who without economic or moral support defaulted treatment. Women's pathway to adherence was facilitated by their caregiver role and support from partner or kin family. Men's adherence was facilitated by experience of severe symptoms, provider role and by support from their mother or partner. Results indicate that linkage of stigma to gender roles interact in treatment decisions in three main ways. First, HIV stigma and unequal gender norms can work jointly as a barrier to adherence. Secondly, those resisting restrictive gender norms found it easier to manage HIV stigma for the benefit of treatment adherence. Thirdly, some gender norms also facilitated adherence and stigma management. Programs targeted at HIV stigma reduction and improving ART adherence among heterosexual populations should be built on an understanding of the local gender norms and include socially and culturally relevant gender sensitive and transformative activities.

This study aimed to assess the percentage of patients treated according to the European Society for Medical Oncology (ESMO) 2018 guidelines for breakthrough cancer pain (BTcP) and the impact of guidelines adherence on patients' quality of life (QoL).

Health-related fitness directly depends on the level of physical activity of the individual. Inactivity contributes to around 3.3% of all deaths, making the lack of exercise and sedentary lifestyles among the young generation a current source of concern. There is a paucity of research on the association between PA and health-related physical fitness among young people. In the perspective of this, the objective of this research was to find out the effect of PA levels on physical fitness in healthy adults.

Hepatitis C is a global public health threat, affecting 56 million people worldwide. The World Health Organization has committed to eliminating hepatitis C by 2030. Although new treatments have revolutionised the treatment and care of people with hepatitis C, treatment uptake has slowed in recent years, drawing attention to the need for innovative approaches to reach elimination targets. One approach involves using existing notifiable disease data to contact people previously diagnosed with hepatitis C. Within these disease surveillance systems, however, competing tensions exist, including protecting individual rights to privacy and autonomy, and broader public health goals. We explore these issues using hepatitis C and Australia's legislative and regulatory frameworks as a case study. We examine emerging uses of notification data to contact people not yet treated, and describe some of the ethical dilemmas associated with the use and non-use of this data and the protections that exist to preserve individual rights and public health. We reveal weaknesses in rights protections and processes under Australian public health and human rights legislation and argue for consultation with and involvement of affected communities in policy and intervention design before notification data is used to increase hepatitis C treatment coverage.

Oral conditions disproportionately affect mothers and children in Sub-Saharan Africa, due to biological vulnerabilities, a scarcity of oral health workers, deficient preventive strategies, and gender-based barriers to care. The World Health Organization (WHO) recommends integrating oral health into broader health delivery models, to reduce these disparities. We propose integrating preventive oral healthcare into community-based programs to bridge these gaps. We examine integrating preventive oral healthcare into Western Kenya's Chamas for Change () community-based program which aims to reduce maternal and child health disparities. incorporates women's health and microfinance programs best practices to produce a low-cost, community-driven, sustainable, and culturally acceptable health delivery platform. Our strategy is based on the Maternal and Child Oral Health Framework and uses the WHO Basic Package of Oral Care principles. This framework prioritizes community involvement, cultural sensitivity, regular screenings, and seamless integration into general health sessions. We discuss the strengths, weaknesses, opportunities, and threats to enriching with oral health promotion activities. It is crucial to assess the effectiveness, sustainability, and acceptability of the proposed strategy through implementation and evaluation. Future studies should investigate the long-term impact of integrated oral health models on community health and oral health disparity reduction in Africa.

Performance Based Financing (PBF) supports realization of universal health coverage by promoting bargaining between purchasers and health service providers through identifying priority services and monitoring indicators. In PBF, purchasers use health statistics and information to make decisions rather than merely reimbursing invoices. In this respect, PBF shares certain elements of strategic health purchasing. PBF implementation began in Ethiopia in 2015 as a pilot at one hospital and eight health centers. Prior to this the system predominantly followed input-based financing where providers were provided with a predetermined budget for inputs for service provision. The purpose of the study is to determine whether the implementation of PBF is cost-effective in improving maternal and child health in Ethiopia compared to the standard care.

Dragon fruit has significant economic value in many countries due to has excellent nutritional content, health advantages, and adaptability to different climates, making it an important crop in the global fruit industry. This study aimed to gather comprehensive nutritional data on three dragon fruit cultivars by analysing the levels of micronutrients, fibre, carbohydrates, antioxidants, vitamins, and minerals in their pulps. Uniform dragon fruit samples underwent thorough analysis for proximate composition, mineral content, pigments, antioxidants, and vitamin C, with statistical methods used to assess significant differences among the parameters studied. The proximate composition analysis revealed significant differences among the three dragon fruit cultivars. Among the proximate components, protein (0.40 ± 0.02 g/100 g), moisture (91.33 ± 0.88%), crude fibre (0.32 ± 0.07 g/100 g), and ash (1.27 ± 0.09 g/100 g) were more abundant in than in and . On the other hand, had higher carbohydrate (17.02 ± 0.63 g/100 g) and energy (69.74 ± 2.44 kcal/100 g) contents. K (7.23 ± 0.35 mg/100 g), Ca (1.61 ± 0.13 mg/100 g), Fe (1.84 ± 0.05 mg/100 g), and Zn (0.37 ± 0.034 mg/100 g) are highly abundant in . Additionally, had the highest anthocyanin content (120.15 ± 3.29 mg/g FW) and total carotenoid content (72.51 ± 1.62 mg/g FW), along with the highest vitamin C content (8.92 ± 0.13 mg/g FW) and total soluble phenolic content (572.48 ± 20.77 mg/100 g). Its remarkable antioxidant activity was further highlighted by the lowest SC value (13.50 ± 0.4 mg/mL) for its DPPH radical scavenging capacity. The total soluble sugar content was highest in (8.72 ± 0.30 g/100 g FW). Hierarchical clustering analysis revealed distinct trait and genotype associations; among the studied cultivars, demonstrated superior performance across multiple traits. Correlation analysis indicated significant positive correlations among several traits, while principal component analysis highlighted the contribution of each trait to overall variance, with PC1 explaining 73.95% of the total variance. This study highlights the nutritional variations among dragon fruit cultivars, with showing superior performance, guiding dietary planning and functional food development.

Hypertension is one of the most common chronic diseases in older people, and the prevalence is on the rise as the global population ages. Hypertension is closely associated with many adverse health outcomes, including cardiovascular disease, chronic kidney disease and mortality, which poses a substantial threat to global public health. Reasonable blood pressure (BP) management is very important for reducing the occurrence of adverse events. Frailty is an age-related geriatric syndrome, characterized by decreased physiological reserves of multiple organs and systems and increased sensitivity to stressors, which increases the risk of falls, hospitalization, fractures, and mortality in older people. With the aging of the global population and the important impact of frailty on clinical practice, frailty has attracted increasing attention in recent years. In older people, frailty and hypertension often coexist. Frailty has a negative impact on BP management and the prognosis of older hypertensive patients, while hypertension may increase the risk of frailty in older people. However, the causal relationship between frailty and hypertension remains unclear, and there is a paucity of research regarding the efficacious management of hypertension in frail elderly patients. The management of hypertension in frail elderly patients still faces significant challenges. The benefits of treatment, the optimal BP target, and the choice of antihypertensive drugs for older hypertensive patients with frailty remain subjects of ongoing debate. This review provides a brief overview of hypertension in frail older adults, especially for the management of BP in this population, which may help in offering valuable ideas for future research in this field.

Human mobility has challenged malaria elimination efforts and remains difficult to routinely track. In Brazil, administrative records from the Ministry of Health allow monitoring of mobility locally and internationally. Although most imported malaria cases are between municipalities in Brazil, detailed knowledge of patterns of mobility is limited. Here, we address this gap by quantifying and describing patterns of malaria-infected individuals across the Amazon. We used network analysis, spatial clustering, and linear models to quantify and characterize the movement of malaria cases in Brazil between 2004 and 2022. We identified sources and sinks of malaria within and between states. We found that between-state movement of cases has become proportionally more important than within-state, that source clusters persisted longer than sink clusters, that movement of cases into sinks was seasonal while movement out of sources was not, and that importation is an impediment for subnational elimination in many municipalities. We elucidate the vast travel networks of malaria infected individuals that characterize the Amazon region. Uncovering patterns of malaria case mobility is vital for effective microstratification within Brazil. Our results have implications for intervention stratification across Brazil in line with the country's goal of malaria elimination by 2035.

This mixed-methods study assessed buprenorphine provider and administrator perceptions and experiences in offering telebuprenorphine during the COVID-19 pandemic.

Restorative justice interventions can help address the harm created by gun violence, although few restorative justice programs focus solely on survivors or loved ones of victims of gun violence. Our aim was to assess how gun violence impacts those injured by firearms through qualitative analysis of their lived experiences.

Antimicrobial resistance (AMR) has been declared one of the top ten global public health threats facing humanity. To address AMR, coercive antimicrobial stewardship policies are being enacted in some settings. These policies, like all in public health, require ethical justification. Here, I introduce a framework for ethically evaluating coercive antimicrobial stewardship policies on the basis of ethical justifications (and their limitations). I consider arguments from effectiveness; duty of easy rescue; tragedy of the commons; responsibility-tracking; the harm principle; paternalism; justice and development; a precautionary approach; and professional duties. I consider how these justifications might form the basis for developing a comprehensive ethical framework, and the need for this to be context-specific and aligned with the priorities, evidence and needs of the particular jurisdictions in which a policy is to be enacted. I demonstrate how the ethical justifications might be used by reference to an example policy of the EU ban on the use of certain human-critical antibiotics for livestock, before concluding with challenges for further development of the framework.

A healthy ocean is essential for human health, and yet the links between the ocean and human health are often overlooked. By providing new medicines, technologies, energy, foods, recreation, and inspiration, the ocean has the potential to enhance human health and wellbeing. However, climate change, pollution, biodiversity loss, and inequity threaten both ocean and human health. Sustainable realisation of the ocean's health benefits will require overcoming these challenges through equitable partnerships, enforcement of laws and treaties, robust monitoring, and use of metrics that assess both the ocean's natural capital and human wellbeing. Achieving this will require an explicit focus on human rights, equity, sustainability, and social justice. In addition to highlighting the potential unique role of the healthcare sector, we offer science-based recommendations to protect both ocean health and human health, and we highlight the unique potential of the healthcare sector tolead this effort.

In situ simulation-based team training of non-technical skills is considered an important initiative for preventing adverse events caused by poor teamwork among healthcare personnel. This study aimed to assess the non-technical skills of anaesthesia personnel before and after in situ simulation-based team training in a clinical setting.

Improving midwifery education is critical to improving maternal and infant health outcomes in Sierra Leone. A significant priority within midwifery education is to strengthen the clinical teaching and students' hands-on experience in the clinical setting. To identify facilitators and challenges within midwifery students' clinical placements and to highlight areas to strengthen the clinical midwifery education system as well as the role of preceptors. We conducted a participatory process mapping with two schools of midwifery in Sierra Leone to detail steps taken by practicing midwives and midwifery faculty when students are placed in clinical settings for midwifery rotations. There were 42 participants from the Bo and Makeni regions of Sierra Leone. Participants included midwifery faculty from the Schools of Midwifery in Makeni and Bo, clinical midwives from two regional government hospitals, clinical midwives from two affiliated community health centers, and midwives from the District Health Management Teams. Three recurring themes emerged in the process. First, there was always some element of preparing or teaching the student. Second, there were administrative tasks to coordinate between the schools, clinical sites, and students, before, during, and after clinical placements. And third, there were elements of communication and collaboration between schools and clinical sites/preceptors that could be improved through shared understanding and standardization. Additional themes were inconsistencies across activities before, during, and after students' clinical placement and limited opportunities and confusion around systems of evaluating all components of the clinical placement experience. This study provides insight into the process of midwifery students' clinical placement and highlights facilitators to be standardized and some modifiable barriers to be addressed. As Sierra Leone and many other similar countries in sub-Saharan Africa attempt to strengthen students' clinical education through educating and developing preceptors, processing mapping can be a useful tool.

Trematode infections stand out as one of the frequently overlooked tropical diseases, despite their wide global prevalence and remarkable capacity to parasitize diverse host species and tissues. Furthermore, these parasites hold significant socio-economic, medical, veterinary and agricultural implications. Over the past decades, substantial strides have been taken to bridge the information gap concerning various "omic" tools, such as proteomics and genomics, in this field. In this edition of the book, we highlight recent progress in genomics and proteomics concerning trematodes with a particular focus on the advances made in the past 5 years. Additionally, we present insights into cutting-edge technologies employed in studying trematode biology and shed light on the available resources for exploring the molecular facets of this particular group of parasitic helminths.

Hepatocellular carcinoma (HCC) is a major global health challenge. Chemotherapy can cause HCC cells to become senescent. Senescent HCC cells play an important role in inhibiting or promoting cancer by producing extracellular vesicles with a senescence-associated secretory phenotype (EV-SASP). miRNA can be strongly upregulated in EV-SASP during the aging process and can substantially alter the phenotypic characteristics of cells. MiRNA microarray analysis revealed that miRNA-146a-5p was highly expressed in oxaliplatin- and HO-induced senescent Huh7 cells, and RT‒PCR confirmed its significant upregulation in exosomes. The transcriptome sequencing results of Huh7 cells overexpressing miRNA-146a-5p suggested that miRNA-146a-5p could regulate HCC cell glycolysis. Subsequently, a dual luciferase assay was used to verify whether miRNA-146a-5p can interact with IRF7 to promote aging. The key functions of miRNA-146a-5p and IRF7 in aerobic glycolysis in liver cancer cells were determined through experiments analyzing glucose uptake, lactate production, the oxygen consumption rate (OCR) and the proton efflux rate (PER). Subsequently, the regulatory effect of IRF7 on the key glycolytic gene PFKL was confirmed through luciferase reporter assays. The western blot experiment results showed that miR-146a-5p can activate CHK2 and p53 phosphorylated proteins by targeting IRF7, and upregulate p21 protein. Overexpression of miRNA-146a-5p effectively inhibited the aerobic glycolytic function of HCC cells. Moreover, silencing IRF7 effectively inhibited aerobic glycolysis. MiR-146a-5p. MiR-146a-5p can activate the phosphorylation of CHK2 phosphorylation protein and its downstream protein p53 by targeting IRF7, and the activated p53 upregulates the expression of p21. Our study revealed that exosomal miRNA-146a-5p produced by aging HCC cells, can inhibit HCC cell proliferation through inhibiting aerobic glycolysis and promote HCC cell aging by activating CHK2/p53/p21 signaling way by targeting IRF7.

Aim: We aimed to assess the physical activity and sedentary behavior of the population living in the Aral Sea area using the Global Physical Activity Questionnaire.

The World Health Organization has identified (KP) as a significant threat to global public health. The rising threat of carbapenem-resistant (CRKP) leads to prolonged hospital stays and higher medical costs, necessitating faster diagnostic methods. Traditional antibiotic susceptibility testing (AST) methods demand at least 4 days, requiring 3 days on average for culturing and isolating the bacteria and identifying the species using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), plus an extra day for interpreting AST results. This lengthy process makes traditional methods too slow for urgent clinical situations requiring rapid decision-making, potentially hindering prompt treatment decisions, especially for fast-spreading infections such as those caused by CRKP. This research leverages a cutting-edge diagnostic method that utilizes an artificial intelligence-clinical decision support system (AI-CDSS). It incorporates machine learning algorithms for the swift and precise detection of carbapenem-resistant and colistin-resistant strains.

The issue of tobacco control remains a significant concern for public health worldwide. In recent years, remarkable progress has been made toward adopting smoke-free measures in indoor public places. Although China has yet to introduce a national regulation, specifically for smoke-free public places, more than a dozen cities have successively approved and implemented comprehensive smoke-free regulations. Different cities in China have diverse attitudes and behaviors toward smoke-free policies; however, the reasons for these policy differences and the influencing factors have not received sufficient attention and research.

Aim: To investigate the influence of socio-economic factors on the state of pharmaceutical provision of patients with cardiovascular diseases.

Several governments from African countries, including the Democratic Republic of the Congo (DRC), implemented stringent public health measures to curb COVID-19 transmission in the early phases of the pandemic. While these restrictive measures are believed to have contributed to lowering case incidence and related mortality in DRC, data on the population's knowledge and adherence are limited. This study aimed to assess the knowledge, perception, attitudes, and practices of COVID-19 preventive measures and associated factors among adult residents of Matadi, thereby generating evidence for a strategy adjustment as the COVID-19 response is transitioning from emergency to control status.

The pandemic caused by COVID-19 has had a profound effect on global health. Due to its potential impact on the efficacy of pandemic control measures, vaccine hesitancy (VH) in relation to COVID-19 has emerged as a significant concern. The attainment of herd immunity is contingent on the rate of COVID-19 vaccine adoption. Despite this, there have been reports of reluctance toward the COVID-19 vaccine. This study seeks to investigate the effect of constructs that influence adults' intentions to receive COVID-19 vaccination using the Health Belief Model (HBM).