Global Health

Higher stature and lower weight are associated with increased risk of fracture. However, the pathophysiology for the associations of height and weight with bone microarchitecture and geometry is unclear. We examined whether these associations were consistent with causation and/or with shared familial factors. In this cross-sectional study of 566 female twins aged 26-76 yr, a regression analysis for twin data, Inference about Causation by Examination of FAmilial CONfounding (ICE FALCON), was used for testing causation. The bone microarchitecture and geometry of the distal tibia was assessed using HR-pQCT and the StrAx1.0 software. Higher stature was associated with larger total bone cross-sectional area (CSA), lower total bone volumetric bone mineral density (vBMD), larger cortical CSA, thinner cortices, higher porosity of the total cortex, compact cortex, outer and inner transitional zone (TZ), lower cortical vBMD, and larger medullary CSA (regression coefficients () ranging from -.37 to .60, all <.05). Using ICE FALCON, the cross-pair cross-trait associations attenuated toward zero after adjusting for the within-individual association (absolute values of ranging from .05 to .31, all <.001). Higher weight was associated with higher total bone vBMD, larger cortical CSA and thicker cortices, lower porosity of the total cortex and inner TZ, and higher cortical vBMD ( ranging from -.23 to .34, all <.001), and thinner trabeculae, higher trabecular number, lower trabecular separation, and higher trabecular vBMD ( ranging from -.31 to .39, all <.05). Only cortical CSA attenuated toward zero after adjusting for the within-individual association between weight and bone microarchitecture (β = .042, =.046). Higher stature was associated with a weaker cortical, not trabecular bone traits, whereas higher weight was associated with stronger cortical and trabecular bone traits. The results were consistent with height having a causal effect on weaker cortical bone structure, whereas weight had a casual effect on the larger cortical CSA.

We aimed to summarise the extent and nature of published research about eye health and eye health services in Pacific Island Countries and Territories since 1980.

Postpartum hemorrhage is the leading cause of preventable maternal illness and death globally, and carries a disproportionately high burden of mortality in low-to-middle income countries. Tranexamic acid, an antifibrinolytic drug, has been widely adopted to control bleeding in trauma and other surgical conditions. Within the last decade, the World Health Organization updated their guidelines for the treatment of postpartum hemorrhage to include the use of tranexamic acid in all cases of postpartum hemorrhage. However, despite these guidelines, and the proven utility of tranexamic acid to treat postpartum hemorrhage, widespread adoption of tranexamic acid into global standards of care across professional organizations has not been achieved. It is important for healthcare providers to understand the etiologies of postpartum hemorrhage, the mechanism of action and adverse effect profile of tranexamic acid, and the available literature regarding the use of tranexamic acid to prevent and treat postpartum hemorrhage to provide the best care for the pregnant patient.

Domestic family violence (DFV) is a global health concern affecting one in three women worldwide. Women are vulnerable to DFV throughout their life; however, pregnancy introduces an increased risk of experiencing DFV for millions of women and birthing people.

Attention-deficit/hyperactivity disorder (ADHD) belongs to a phenotypically broad class of mental health disorders impacting social and cognitive functioning. Despite heritability estimates of 77%-88% and a global prevalence of up to 1 in 20 children, most of the underlying genetic etiology of the disorder remains undiscovered, making it challenging to obtain a clinical molecular genetic diagnosis and to develop new treatments (Biological Psychiatry, 2005, 57, 1313; Psychological Bulletin, 2009, 135, 608; Psychological Medicine, 2014, 44, 2223). Here we report the identification of a novel ultra-rare heterozygous loss-of-function (p.Q1625*) variant in a child with complex ADHD (i.e., comorbid mild intellectual disability [ID]) and a missense (p.G1748R) variant (allele frequency of 4.7 × 10) in a child with primary ADHD (i.e., absence of comorbid autism spectrum disorder [ASD], ID, or syndromic features) both in the SPTBN1 gene. Missense variants in SPTBN1 have been reported in individuals with developmental disorders, language and communication disorders, and motor delays in recent publications (Nature Genetics, 2021, 53, 1006; American Journal of Medical Genetics Part A, 2021, 185, 2037) and ClinVar, though most variants in ClinVar have uncertain disease associations. The functional impact of these 135 variants, including from the current study, were further assessed using prediction scores from the recently developed AlphaMissense tool and benchmarked against published functional studies on a subset of the variants. While heterozygous SPTBN1 variants have recently been associated with neurodevelopmental disorders characterized by global developmental delay, intellectual disability, and behavioral abnormalities, the two patients in the current study expand the phenotypic spectrum to include ADHD in the absence of more severe neurodevelopmental disorders, such as ASD and moderate to severe ID. Furthermore, the culmination of these data with existing reported cases suggests that variation including loss of function and missense events underlie a broader clinical spectrum than previously understood.

Hygiene has been identified as an important step in anticipating health-related pol-lution, with conflicting reports about consistent sanitation standards in the nation. This narrative review of published studies has led to the discussion of hand hygiene and health practices, as well as the identification of necessary methods that are available in low and middle-income countries. An effective survey of accessible information is conducted in this way based on re-view questions. A number of 372 articles were found on the web, and 32 articles were used in the final analysis. Overall, the standard of hand hygiene is set at 20.49%. Difficulties identified for the people in low or middle-income countries are poor awareness and sound information about hand hygiene, lack of resources including water, soap, hand scrubbing gel, etc., as mis-interpretations related to hand hygiene practices. People are paying more attention to healthcare-related illnesses as it becomes increasingly clear that most of them may be pre-vented. The free evidence-based practice states that to lower the danger of contamination, hand hygiene should be properly adhered to. The difficulties recognized in this review are reliable, with the discoveries of studies that have been led somewhere else. By conducting a basic ex-amination of the "Clean Care is Safer Care" as an excellent arrangement of WHO's global initiative activity on patient well-being programs, developing nations will have more time to consider the essential approaches for the use of fundamental disease prevention exercises in our health care settings.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained use primarily due to their weight-reduction effects, although a regulatory review was undertaken for potential suicidality concern.

(Mtb) exposure leads to a range of outcomes including clearance, latent TB infection (LTBI), and pulmonary tuberculosis (TB). Some heavily exposed individuals resist tuberculin skin test (TST) and interferon-gamma (IFNγ) release assay (IGRA) conversion (RSTR), which suggests that they employ IFNγ-independent mechanisms of Mtb control. Here, we compare monocyte epigenetic profiles of RSTR and LTBI from a Ugandan household contact cohort. Chromatin accessibility did not differ between uninfected RSTR and LTBI monocytes. By contrast, methylation significantly differed at 174 CpG sites and across 63 genomic regions. Consistent with previous transcriptional findings in this cohort, differential methylation was enriched in lipid- and cholesterol-associated pathways including the genes APOC3, KCNQ1, and PLA2G3. In addition, methylation was enriched in Hippo signaling, which is associated with cholesterol homeostasis and includes CIT and SHANK2. Lipid export and Hippo signaling pathways were also associated with gene expression in response to Mtb in RSTR as well as IFN stimulation in monocyte-derived macrophages (MDMs) from an independent healthy donor cohort. Moreover, serum-derived high-density lipoprotein from RSTR had elevated ABCA1-mediated cholesterol efflux capacity (CEC) compared to LTBI. Our findings suggest that resistance to TST/IGRA conversion is linked to regulation of lipid accumulation in monocytes, which could facilitate early Mtb clearance among RSTR subjects through IFNγ-independent mechanisms.IMPORTANCETuberculosis (TB) remains an enduring global health challenge with millions of deaths and new cases each year. Despite recent advances in TB treatment, we lack an effective vaccine or a durable cure. While heavy exposure to often results in latent TB latent infection (LTBI), subpopulations exist that are either resistant to infection or contain Mtb with interferon-gamma (IFNγ)-independent mechanisms not indicative of LTBI. These resisters provide an opportunity to investigate the mechanisms of TB disease and discover novel therapeutic targets. Here, we compare monocyte epigenetic profiles of RSTR and LTBI from a Ugandan household contact cohort. We identify methylation signatures in host lipid and cholesterol pathways with potential relevance to early TB clearance before the sustained IFN responses indicative of LTBI. This adds to a growing body of literature linking TB disease outcomes to host lipids.

Parkinson's disease (PD) is one of the most frequent age-associated neurodegenerative disorder. Presence of α-synuclein-containing aggregates in the substantia nigra pars compacta (SNpc) and loss of dopaminergic (DA) neurons are among the characteristic of PD. One of the hallmarks of PD pathophysiology is chronic neuroinflammation. Activation of glial cells and elevated levels of pro-inflammatory factors are confirmed as frequent features of the PD brain. Chronic secretion of pro-inflammatory cytokines by activated astrocytes and microglia exacerbates DA neuron degeneration in the SNpc. MicroRNAs (miRNAs) are among endogenous non-coding small RNA with the ability to perform post-transcriptional regulation in target genes. In that regard, the capability of miRNAs for modulating inflammatory signaling is the center of attention in many investigations. MiRNAs could enhance or limit inflammatory signaling, exacerbating or ameliorating the pathological consequences of extreme neuroinflammation. This review summarizes the importance of inflammation in the pathophysiology of PD. Besides, we discuss the role of miRNAs in promoting or protecting neural cell injury in the PD model by controlling the inflammatory pathway. Modifying the neuroinflammation by miRNAs could be considered a primary therapeutic strategy for PD.

This study aims to investigate the factors influencing parental willingness in COVID-19 vaccination for children in Japan in light of the introduction of pediatric vaccines.

Acrylamide (ACR) is a water-soluble monomer with broad consumer applications, even in foods due to thermal processes. Acute exposure to ACR may lead to neurotoxic effects such as ataxia and skeletal muscle weakness in humans and experimental animals. Oxidative stress is the primary pathway in ACR toxicity; therefore, this study aimed to evaluate the possible protective effect of benzo[b]thiophene analogs as an antioxidant drug for ACR poisoning. For this purpose, adult zebrafish were chosen as the experimental model considering the 3Rs of research. Hydroxyl containing benzo[b]thiophene analogs, 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP) were injected via intraperitoneal (i.p.) route at an effective dose of 5 mg/kg one hour before the exposure of ACR (0.75 mM) for three days. ACR fish showed aberrant socio-behavior with low exploration, tight circling, negative scototaxis, disrupted aggression, and tight shoaling. These results indicated depression comorbid and anxiety-like phenotype. BP and EP partially reduced the aberrant socio-behavior. BP and EP elevated the antioxidant defense and reduced the oxidative damage in the brain caused by ACR. Cellular and tissular alterations caused by ACR were visualized through histopathological study. BP and EP administration reduced and repaired the cellular changes via the antioxidant mechanism. BP and EP altered the axonal growth and regeneration gene and synaptic vesicle cycle gene expression necessary for neurotransmission. This combined gain-of-function of redox mechanism at molecular, cellular, and tissular levels explains the behavioral improvement at the organismal level of the organization.

Fluoride exposure is a global public health concern. Understanding the knowledge, attitudes, and practices (KAP) of affected populations is essential for effective community management. This study aimed to develop and validate a KAP questionnaire to assess fluoride and its risk in general population. An extensive literature review and focus group discussions were conducted to construct the questionnaire. Content validity was assessed using the Content Validity Index (CVI) based on expert feedback. Factor analysis was performed for final tool validation, and item characteristics were analyzed using IBM SPSS v. 27 and IBM AMOS v. 26. A total of 300 responses were collected. Initially, 41 items were included in the questionnaire, which were reduced to 25 after expert review. The final version included 19 items, with an I-CVI ranging from 0.80 to 1.00, indicating no issues with item difficulty or discrimination. Cronbach's alpha ranged from 0.88 to 0.90, demonstrating good internal consistency. The Kaiser-Meyer-Olkin (KMO) value was 0.848, and Bartlett's test (χ = 6860.978, df = 156, p < 0.01) confirmed data suitability for factor analysis. Three constructs were extracted with factor loadings greater than 0.5. Confirmatory factor analysis demonstrated a good model fit. This study developed and validated a robust 19-item KAP questionnaire for assessing knowledge, attitudes, and practices related to fluoride exposure. The tool demonstrated excellent reliability, validity, and internal consistency, supporting its use in guiding effective community-level management and public health interventions in fluoride-endemic areas.

The coronavirus disease 2019 (COVID-19) pandemic, a global health crisis, profoundly impacted all aspects of daily life. Adolescence, a pivotal stage of psychological and social development, is heavily influenced by the psychosocial and socio-cultural context. Hence, it is imperative to thoroughly understand the psychosocial changes adolescents experienced during the pandemic and implement effective management initiatives.

Anemia is a common comorbidity of chronic kidney disease (CKD) that has been associated with increased risk of complications, healthcare expenditure, and reduced quality of life. In China, the treatment of anemia of CKD has been reported to be suboptimal in part because of a lack of awareness of the condition and its management. It is therefore important to raise awareness of the condition by estimating the future health and economic burden of anemia of CKD and also to understand how it may be addressed through proactive policies. This study aims to project the health and economic burden of anemia of CKD, in China, from 2023 to 2027 and to estimate the impact of a hypothetical intervention on related clinical and cost outcomes.

Continuous professional development among stakeholders involved in drug safety monitoring and surveillance is imperative in strengthening pharmacovigilance (PV) systems. The "Pharmacovigilance infrastructure and post-marketing surveillance system capacity building for regional medicine regulatory harmonization in East Africa" (PROFORMA) project aims to enhance the national PV infrastructure, post-marketing surveillance systems and clinical trial regulatory capabilities in Ethiopia, Tanzania, Kenya and Rwanda. To achieve this, training, including short-term training (STT) activities, at various levels is required. This article aims to describe the experiences of the authors during the development and implementation of STT in an attempt to improve the PV training landscape of these countries. To identify gaps, a baseline assessment of PV teaching and practices at the national medicines regulatory authorities (NMRAs) and medical universities was conducted. Five successive training sessions, tailored to each country's specific needs and regulatory environments, were conducted; three focusing on fundamental concepts in PV and two dedicated to training-of-trainers courses. The training targeted staff from PV units of the NMRAs and medical universities. Enabling participation from all four countries in the same training fostered cross-country learning and collaboration. The contribution of STT to university education and the operational methodologies within NMRAs are explored, showcasing the impact on knowledge transfer and skill development in each country. In conclusion, by investing strategically in STT activities and fostering partnerships with academic institutions and NMRAs, we demonstrated a sustainable approach to PV capacity strengthening in resource-limited settings. The success of this model underscores its potential for adoption and replication across the African continent, offering a valuable framework for strengthening drug safety regulation and ultimately protecting public health.

Many young people are exposed to risk factors that increase their risk of mental illness. Physical activity provision is an increasingly popular approach to protect against mental illness in the face of these risk factors. We examined the effectiveness of physical activity interventions for the promotion of mental health outcomes in at-risk children and adolescents. We searched health databases for randomised and non-randomised intervention studies, with no date restriction, and assessed risk of bias using the Cochrane Risk of Bias tools. We present a narrative synthesis of our results accompanied with a summary of available effect sizes. Thirty-seven reports on 36 studies were included, with multi-sport or yoga interventions the most popular intervention approaches (a combined 50% of included studies). Outcomes measured included internalising, self-evaluative, wellbeing, overall symptomatology, resilience, externalising, and trauma outcomes. We found that 63% of between-groups effects favoured the intervention arm, and 83% of within-groups effects favoured an intervention effect. While recognising high risk of bias, our findings provide evidence in support of the effectiveness of physical activity interventions for promoting mental health outcomes in at-risk young people. We encourage further work designed to better understand the intervention characteristics that may lead to positive benefits.

The management of () infections presents a substantial challenge to clinics and public health, emphasizing the urgent need for innovative strategies to address this issue. Quorum sensing (QS) is an intercellular communication mechanism that coordinates bacterial activities involved in various virulence mechanisms, such as acquiring host nutrients, facilitating biofilm formation, enhancing motility, secreting virulence factors, and evading host immune responses, all of which play a crucial role in the colonization and infection of . The LasI/R and RhlI/R sub-systems dominate in the QS system of . Macrophages play a pivotal role in the host's innate immune response to invasion, particularly through phagocytosis as the initial host defense mechanism. This study investigated the effects of 's QS system on THP-1 macrophages. Mutants of PAO1 with deletion, as well as their corresponding complemented strains, were obtained, and significant downregulation of QS-related genes was observed in the mutants. Furthermore, the and mutants exhibited significantly attenuated virulence in terms of biofilm formation, extracellular polymeric substances synthesis, bacterial adhesion, motility, and virulence factors production. When infected with and mutants, THP-1 macrophages exhibited enhanced scavenging ability against the mutants and demonstrated resistance to cytotoxicity, oxidative stress, inflammatory response, and apoptosis induced by the culture supernatants of these mutant strains. These findings offer novel insights into the mechanisms underlying how the mutation attenuates cytotoxicity, oxidative stress, inflammation, and apoptosis in macrophages induced by .IMPORTANCE is classified as one of the ESKAPE pathogens and poses a global public health concern. The QS system of this versatile pathogen contributes to a broad spectrum of virulence, thereby constraining therapeutic options for serious infections. This study illustrated that the mutation of the QS system plays a prominent role in attenuating the virulence of by affecting bacterial adhesion, biofilm formation, extracellular polymeric substances synthesis, bacterial motility, and virulence factors' production. Notably, THP-1 macrophages infected with mutant strains exhibited increased phagocytic activity in eliminating intracellular bacteria and enhanced resistance to cytotoxicity, oxidative stress, inflammation, and apoptosis. These findings suggest that targeted intervention toward the QS system is anticipated to diminish the pathogenicity of to THP-1 macrophages.

To examine patients' use of primary healthcare (PHC) before and after specialized rehabilitation and its relation with self-reported health and functioning.

This study addresses the gap in translatable models for investigating Enterohemorrhagic (EHEC) infections, particularly relevant to both canine and human health. EHEC is known to induce acute colitis in dogs, leading to symptoms like hemorrhagic diarrhea and hemolytic uremic syndrome, similar to those observed in humans. However, understanding the pathophysiology and developing treatment strategies have been challenging due to the lack of effective models that replicate the clinical disease caused by EHEC in both species. Our approach involved the development of colonoid-derived monolayers using intestinal tissues from healthy, client-owned dogs. These monolayers were exposed to EHEC, and the impact of EHEC was assessed through several techniques, including trans-epithelial electrical resistance (TEER) measurement, immunofluorescence staining for junction proteins and mucus, and scanning electron microscopy for morphological analysis. Modified culture with saline, which was intended to prevent bacterial overgrowth, maintained barrier integrity and cell differentiation. EHEC infection led to significant decreases in TEER and ZO-1 expression, but not in E-cadherin levels or mucus production. In addition, EHEC elicited a notable increase in tumor necrosis factor-alpha production, highlighting its distinct impact on canine intestinal epithelial cells compared to non-pathogenic . These findings closely replicate observations in dogs and humans with EHEC enteropathy, validating the canine colonoid-derived monolayer system as a translational model to study host-pathogen interactions in EHEC and potentially other clinically significant enteric pathogens.

Groundwater nitrate (NO) contamination is a global concern. The distribution patterns, enrichment mechanisms, and human health risks of NO contaminated groundwater were investigated using 144 groundwater samples collected from domestic and irrigation wells in the piedmonts of the North China Plain (Beijing and Shijiazhuang areas). The results showed that the groundwater was neutral to weakly alkaline, and 47% of the groundwater samples had NO concentrations exceeding 50 mg/L, a threshold proposed by world health organization to threaten infants up to 3 months. Groundwater NO concentrations were generally higher in the Beijing piedmont than in the Shijiazhuang piedmont and decreased with depth in both piedmonts. High-NO (> 50 mg/L) groundwater was distributed sporadically spatially and mainly was of Ca-Mg-HCO hydrochemical facies. Stable isotopes (D and O) compositions and NO/Cl ratios indicated that NO accumulation in groundwater was primarily due to use of N-fertilizers under agricultural practices, and was associated with groundwater recharge sources such as septic tank leakage and re-infiltration of reclaimed irrigation water. Water quality evaluation showed that groundwater quality was highly dependent on NO concentration, with entropy-weighted water quality index values increasing linearly with increasing NO concentrations. The potential health risk of high-NO groundwater was the most serious for infants in both the piedmonts. Therefore, reducing NO input from sources and drinking water intake is recommended to minimize the human health risk.

Coronavirus disease 2019 (COVID-19) led to a major global health crisis, leading to a worldwide pandemic. Several therapeutic interventions have been tried with varied results. The purpose of this academic work was to assess the efficacy of immunoglobulin M (IgM)-enriched Ig in the management of patients with severe COVID-19 pneumonia.

Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) infections. While resistance has already been reported in , combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of and to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR infections.IMPORTANCEThe emergence of carbapenem-resistant strains as a serious global health threat underscores the urgent need for effective treatment options. Although few drugs show promise against CR infections, resistance to both drugs has been reported. In this study, the molecular characterization of spontaneous cefiderocol-resistant variants, a CR strain with antagonism to sulbactam, and an strain with antagonism to avibactam, provides valuable insights into the mechanisms of resistance to cefiderocol. Some mechanisms observed are associated with mutations affecting efflux pumps, regulators, and iron homeostasis genes. These findings highlight the importance of understanding resistance mechanisms to optimize treatment options. They also emphasize the importance of early evaluation of drug synergies to address the challenges of antimicrobial resistance in infections.

Treatment of asymptomatic Abdominal Aortic Aneurysms (AAA) presents a clinical challenge, requiring a delicate balance between rupture risk, patient comorbidities, and intervention-related complications. International guidelines recommend intervention for specific AAA size thresholds, but these are based on historical trials with limited female representation. We aimed to analyse disease characteristics, AAA size at rupture, and intervention outcomes in patients with ruptured AAA from 2009 to 2023 to investigate the gap between guidelines and local realities.

Colistin is one of the last-line treatments for multi-drug resistant Gram-negative bacterial infections. The emergence of mobile colistin resistance genes has driven global concern and triggered the need for surveillance. Our report reveals the identification of and in Ecuador by employing a proximity ligation technique.

Minimising electronic cigarette (e-cigarette) uptake and encouraging vaping cessation have become important components of public health agendas. Given the success of well-designed anti-smoking campaigns, attention has turned to developing health communications that target vaping. Although prior work has identified a range of potentially effective campaign messages, several gaps in the literature remain. We aimed to (i) identify message themes perceived to be effective at minimising e-cigarette use and (ii) elicit opinion on how these message themes could be optimised in terms of message execution and delivery.

While it is well-established that exposure to dampness or mold in homes negatively affects physical health, the association with mental health remains less well evidenced. As plausible psychosocial and biological pathways exist between dampness and mold exposure and poor mental health, a review of evidence is required.

Patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) frequently develop arterial hyperoxaemia, which may be harmful. However, lower oxygen saturation targets may also lead to harmful episodes of hypoxaemia.

Liquiritin (LIQ), a bioactive flavonoid from Glycyrrhiza species, has shown significant potential in cancer therapy. LIQ exhibits potent inhibitory effects on various cancer cell types, including breast, lung, liver, and colon cancers, while demonstrating low toxicity towards healthy cells. Its anticancer mechanisms include inducing cell cycle arrest, promoting apoptosis, and modulating inflammation-related pathways. Additionally, LIQ impedes angiogenesis and enhances the efficacy of conventional chemotherapies through sensitization and synergistic effects with other natural compounds and targeted therapies. These multifaceted actions highlight LIQ as a promising candidate for further development as an anticancer agent. This abstract provides an overview of LIQ's chemistry, biological effects, and underlying mechanisms.

Airway hemorrhage requires rapid treatment to prevent adverse patient outcomes. Simulation education programs are challenged to recreate learning environments with adequate fidelity for team management of airway hemorrhage.

Diabetes mellitus (DM) manifests as a complex and chronic metabolic disorder, posing a significant threat to global public health and contributing substantially to mortality rates. It is characterized by elevated blood glucose levels or hyperglycemia and requires effective preventive and therapeutic strategies. One promising approach involves targeting the inhibition of α- glucosidase and α-amylase, key enzymes responsible for carbohydrate hydrolysis. Inhibiting these enzymes proves beneficial in reducing postprandial glucose levels and mitigating postprandial hyperglycemia. However, existing antidiabetic medications are associated with undesirable side effects, highlighting the need to develop new molecules with increased efficacy and reduced side effects. Traditional methods for designing such molecules are often lengthy and costly. To address this, computer-based molecular modeling tools offer a promising approach to evaluate the antidiabetic activities of chemical compounds. This review aims to compile information on chemical compounds assessed for their anti-diabetic activities through molecular modeling, with a particular focus on the period from 2020 to 2023.

This study provides a comprehensive analysis of global, continental, and national trends in the prevalence and mortality of prostate cancer (PC), breast cancer (BC), and thyroid cancer (TC). Utilizing 2021 Global Burden of Diseases (GBD2021) data, prevalence and death rates for 2021 were examined, with temporal trends from 1990 to 2021 analyzed via Joinpoint regression. Annual percentage change (APC) and average APC (AAPC) were calculated with 95% confidence intervals (CI). Distributive inequalities were quantified using the slope index of inequality and concentration index. In 2021, PC, BC, and TC showed higher global age-standardized prevalence rates (ASPR) in Europe and America compared to Africa and Asia, while higher age-standardized death rates (ASDR) for PC and BC were noted in Africa. Over the study period, significant global increases in ASPR were observed for PC (AAPC = 0.78, 95% CI: 0.67 to 0.89), BC (AAPC = 0.31, 95% CI: 0.24 to 0.37), and TC (AAPC = 1.42, 95% CI: 1.31 to 1.52). Conversely, ASDR significantly decreased for PC (AAPC = -0.83, 95% CI: -0.92 to -0.74), BC (AAPC = -0.48, 95% CI: -0.56 to -0.39), and TC (AAPC = -0.23, 95% CI: -0.29 to -0.17). Variations were observed across continents and time periods, affecting 204 countries and territories. higher social development index (SDI) levels were associated with a more pronounced burden of these cancers. The findings highlight significant global heterogeneity in prevalence, death rates, and temporal trends of endocrine cancers, with important implications for epidemiology and public health policies.

The global spread of infectious diseases caused by pathogenic bacteria significantly poses public health concerns, and methods for sensitive, selective, and facile diagnosis of bacteria can efficiently prevent deterioration and further spreading of the infections. The advent of nanozymes has broadened the spectrum of alternatives for diagnosing bacterial infections. Compared to natural enzymes, nanozymes exhibit the same enzymatic characteristics but offer greater economic efficiency, enhanced durability, and adjustable dimensions. The importance of early diagnosis of bacterial infection and conventional diagnostic approaches is introduced. Subsequently, the review elucidates the definition, properties, and catalytic mechanism of nanozymes. Eventually, the detailed application of nanozymes in detecting bacteria is explored, highlighting their utilization as biosensors that allow for accelerated and highly sensitive identification of bacterial infections and reflecting on the potential of nanozyme-based bacterial detection as a point-of-care testing (POCT) tool. A brief summary of obstacles and future perspectives in this field is presented at the conclusion of this review.

Purpose of this study is to evaluate patient characteristics, treatments and outcomes in bone metastasis radiotherapy practice. Patients for whom radiotherapy for bone metastasis was planned at 26 institutions in Japan between December 2020 and March 2021 were consecutively registered in this prospective, observational study. Study measures included patient characteristics, pain relief, skeletal-related events (SREs), overall survival and incidence of radiation-related adverse events. Pain was evaluated using a numerical rating scale (NRS) from 0 to 10. Irradiated dose was analyzed by the biologically effective dose (BED) assuming α/β = 10. Overall, 232 patients were registered; 224 patients and 302 lesions were fully analyzed. Eastern Cooperative Oncology Group Performance Status was 0/1/2/3/4 in 23%/38%/22%/13%/4%; 59% of patients had spinal metastases and 84% had painful lesions (NRS ≥ 2). BED was <20 Gy (in 27%), 20-30 Gy (24%), 30-40 Gy (36%) and ≥ 40 Gy (13%); 9% of patients were treated by stereotactic body radiotherapy. Grade 3 adverse events occurred in 4% and no grade 4-5 toxicity was reported. Pain relief was achieved in 52% at 2 months. BED is not related to pain relief. The cumulative incidence of SREs was 6.5% (95% confidence interval (CI) 3.1-9.9) at 6 months; no factors were significantly associated with SREs. With spinal lesions, 18% of patients were not ambulatory at baseline and 50% of evaluable patients in this group could walk at 2 months. The 6-month overall survival rate was 70.2% (95% CI 64.2-76.9%). In conclusion, we report real-world details of radiotherapy in bone metastasis.

This study examines the concept of health advocacy and explores related scholarly material to understand its evolution from 1977 to 2021. The bibliometric analysis investigates the publication trends, most relevant authors, keywords-based clusters, research trends, author productivity, and future research areas in health advocacy. The relevant articles were extracted from the Scopus database and analyzed to identify and explore the most active authors, author-wise contribution to the sources, sub-research topics, core sources, top authors' production over time, global cited documents, thematic maps, word cloud, country-wise collaboration network and map, author keywords-based network, historiograph, and spectroscope. The study finds that health advocacy as a concept is under-explored and thus warrants a need for future research work. Limited authors have contributed to this theme, and the continuity of publication needs to be improved. The study highlights that there needs to be a robust framework to assess, evaluate, and implement health advocacy. The researchers are limited to only a few authors who have published in limited journals. The current study brings out the need for research and publications on health advocacy to develop a framework for assessing and implementing health advocacy. Also, the study highlights emerging themes of Coronavirus pandemic and emergency and disaster preparation. The niche themes that emerged during the survey highlight keywords such as agenda-setting and maternal health.

Infants with developmental risk factors are more likely to have feeding problems and develop chronic feeding disorders. Early detection and understanding of the progression of problematic feeding and its relationship with a child's biological functioning and the family feeding environment will enhance effective symptom management and development of interventions to prevent pediatric feeding disorders.

To understand the role of hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension (GH), in brain health earlier in life, we investigated the association of HDP with midlife cognition and brain health.

Considering an ever-growing global population, which hit 8 billion people in the fall of 2022, it is essential to find solutions to avoid croplands competition between human food and animal feed. Agricultural co-products such as soybean meals have become important components of the circular economy thanks to their use in animal feed. Their implementation was made possible by the addition of exogenous enzymes in the diet of monogastric animals, especially fungal carbohydrate-active enzymes (CAZymes). Here, we describe a time-course production and analysis of secretomes for the identification of CAZymes able to enhance the digestibility of soybean meals. Functional assays revealed that the release of nutrients and the degradation of pectins in soybean meals can be tightly interconnected. Using a comparative proteomics approach, we identified several fungal pectin-degrading enzymes leading to increased assimilable nutrients in the soluble fraction of soybean meals. Our results reinforce the importance of deconstructing pectic polysaccharides in feedstuffs and contribute to sharpen our understanding of the fungal enzymatic interplays involved in pectin hydrolysis.IMPORTANCEIn the present study, we developed a strategy to identify the key fungal enzymatic activities involved in the improvement of soybean meal (SBM) digestibility. Our data unravel the importance of pectin degradation for the release of nutrients from SBM and provide some insights regarding the degradation of rhamnogalacturonan-I (RG-I) by ascomycetes. Indeed, the hydrolysis of pectins and RG-I by human microbiota is well documented in the literature, but our knowledge of the fungal CAZymes at play for the degradation of soybean pectins remains hitherto underexplored. Due to its wide use in animal feed, improving the digestibility of SBM by enzymatic treatments is a current challenge for feed additive suppliers. Since non-starch polysaccharides and pectins have often been reported for their anti-nutritional role in SBM, we believe this study will provide new avenues toward the improvement of enzymatic cocktails for animal nutrition and health.

International Medical Programmes (IMPs) form a distinctive modality in medical education, with diverse student populations, English as a language of instruction and 'globalized' curricula. A lack of common understanding of IMPs' purposes and role in the medical education landscape triggers critiques. This study aims to document the effects of different discourses used to justify the purpose of IMPs.

parasites, the causative organism of malaria, caused over 600,000 deaths in 2022. In Mali, causes the majority of malaria cases and deaths and is transmitted seasonally. Anti-malarial immunity develops slowly over repeated exposures to and some aspects of this immunity (e.g., antibody titers) wane during the non-transmission, dry season. Here, we sequenced RNA from 33 pediatric blood samples collected during infections at the beginning or end of a transmission season, and characterized the host and parasite gene expression profiles for paired, consecutive infections. We found that human gene expression changes more over the course of one transmission season than between seasons, with signatures of partial development of an adaptive immune response during one transmission season and stability in gene expression during the dry season. Additionally, we found that gene expression did not vary with timing during the season and remained stable both across and between seasons, despite varying human immune pressures. Our results provide insights into the dynamics of anti-malarial immune response development over short time frames that could be exploited by future vaccine and prevention efforts.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide and is characterized by a complex interplay with skin microbiota, with often abnormally more abundant in AD patients than in healthy individuals (HE). harbors diverse strains with varied genetic compositions and functionalities, which exhibit differential connections with the severity of AD. However, the differences in strains between AD and HE remain unclear, with most variations seen at a specific geographic level, implying spontaneous adaptations rather than systematic distinctions. This study presents genomic and functional differences between these strains from AD and HE on both global and local levels. We observed reduced gene content diversity but increased functional variation in the global AD-associated strains. Two additional AD-dominant clusters emerged, with Cluster 1 enriched in transposases and Cluster 2 showcasing genes linked to adaptability and antibiotic resistance. Particularly, robust evidence illustrates that the lantibiotic operon of , involved in the biosynthesis of lantibiotics, was acquired horizontal gene transfer from environmental bacteria. Comparisons of the gene abundance profiles in functional categories also indicate limited zoonotic potential between human and animal isolates. Local analysis mirrored global gene diversity but showed distinct functional variations between AD and HE strains. Overall, this research provides foundational insights into the genomic evolution, adaptability, and antibiotic resistance of , with significant implications for clinical microbiology.IMPORTANCEOur study uncovers significant genomic variations in strains associated with atopic dermatitis. We observed adaptive evolution tailored to the disease microenvironment, characterized by a smaller pan-genome than strains from healthy skin both on the global and local levels. Key functional categories driving strain diversification include "replication and repair" and "transporters," with transposases being pivotal. Interestingly, the local strains predominantly featured metal-related genes, whereas global ones emphasized antimicrobial resistances, signifying scale-dependent diversification nuances. We also pinpointed horizontal gene transfer events, indicating interactions between human-associated and environmental bacteria. These insights expand our comprehension of 's genetic adaptation in atopic dermatitis, yielding valuable implications for clinical approaches.

Complementary feeding is considered appropriate when introduced timely at 6 months of age, and where it fulfils the minimum meal frequency, minimum dietary diversity and minimum acceptable diet. Sufficient evidence is available on the different individual indicators of appropriate complementary feeding.

In China, mitral valve regurgitation (MR) is the most common cardiovascular valve disease. However, patients in China typically experience a high incidence of this condition, coupled with a low level of health knowledge and a relatively low rate of surgical treatment. TikTok hosts a vast amount of content related to diseases and health knowledge, providing viewers with access to relevant information. However, there has been no investigation or evaluation of the quality of videos specifically addressing MR.

To monitor trends toward healthy and sustainable diets, there is a need for feasible survey tools, with cross-cultural validity, low-cost, and low-expertise requirements.

Endotoxins, or lipopolysaccharides (LPS), are potent immunostimulatory molecules of critical concern in bacterial recombinant protein expression systems. The gram-negative bacterium exhibits an interesting and unique phenotype characterized by the complete loss of LPS. In this study, we developed a novel system for producing recombinant proteins completely devoid of endotoxin contamination using LPS-deficient . We purified endotoxin-free functional green fluorescent protein, which reduced endotoxin contamination by approximately three orders of magnitude, and also purified the functional cytokine tumor necrosis factor (TNF)-α. Additionally, utilization of the Omp38 signal peptide of enabled the extracellular production of variable domain of heavy chain of heavy chain (VHH) antibodies. With these advantages, mNb6-tri-20aa, a multivalent VHH that specifically binds to the spike protein of severe acute respiratory syndrome coronavirus 2, was purified from the culture supernatant, and endotoxin contamination was reduced by a factor of approximately 2 × 10 compared with that in conventional expression systems. A virus neutralization assay demonstrated the functionality of the purified antibody in suppressing viral infections. Moreover, we applied our system to produce ozoralizumab, a multispecific VHH that binds to human TNF-α and albumin and are marketed as a rheumatoid arthritis drug. We successfully purified a functional antibody from endotoxin contamination. This system establishes a new, completely endotoxin-free platform for the expression of recombinant proteins, which distinguishes it from other bacterial expression systems, and holds promise for future applications.

Deregulation of transcription factors (TFs) leading to uncontrolled proliferation of tumor cells within the microenvironment represents a hallmark of cancer. However, the biological and clinical impact of transcriptional interference, particularly in multiple myeloma (MM) cells, remains poorly understood. The present study shows for the first time that MYC and JUNB, two crucial TFs implicated in MM pathogenesis, orchestrate distinct transcriptional programs. Specifically, our data revealed that expression levels of MYC, JUNB, and their respective downstream targets do not correlate and that their global chromatin-binding patterns are not significantly overlapping. Mechanistically, MYC expression was not affected by JUNB knockdown, and conversely, JUNB expression and transcriptional activity were not affected by MYC knockdown. Moreover, suppression of MYC levels in MM cells via targeting the master regulator BRD4 by either siRNA-mediated knockdown or treatment with the novel proteolysis targeting chimera (PROTAC) MZ-1 overcame bone marrow (BM) stroma cell/IL-6-induced MYC- but not MEK-dependent JUNB-upregulation and transcriptional activity. Consequently, targeting of the two non-overlapping MYC- and JUNB-transcriptoms by MZ-1 in combination with genetic or pharmacological JUNB-targeting approaches synergistically enhanced MM cell death, both in 2D and our novel dynamic 3D models of the BM milieu as well as in murine xenografts. In summary, our data emphasize the opportunity to employ MYC and JUNB dual-targeting treatment strategies in MM as another exciting approach to further improve patient outcomes.

Understanding diagnostic capacities is essential to addressing healthcare provision and inequity, particularly in low-income and middle-income countries. This study used routine data to assess trends in rapid diagnostic test (RDT) reporting, supplies and unmet needs across national and 47 subnational (county) levels in Kenya.

This study aims to assess both socioeconomic and climatic factors of cholera morbidity in Mozambique considering both spatial and temporal dimensions.

High doses of glucocorticoids and severe weight loss can cause osteoporosis. We present a case of glucocorticoid-induced osteoporosis and cachexia in an 18-year-old woman who experienced severe appetite loss leading to weight loss, amenorrhea, and multiple thoracolumbar compression fractures.

Sepsis causes millions of deaths per year worldwide and is a current global health priority declared by the WHO. Sepsis-related deaths are a result of dysregulated inflammatory immune responses indicating the need to develop strategies to target inflammation. An important mediator of inflammation is extracellular adenosine triphosphate (ATP) that is released by inflamed host cells and tissues, and also by bacteria in a strain-specific and growth-dependent manner. Here, we investigated the mechanisms by which bacteria release ATP. Using genetic mutant strains of (), we demonstrate that ATP release is dependent on ATP synthase within the inner bacterial membrane. In addition, impaired integrity of the outer bacterial membrane notably contributes to ATP release and is associated with bacterial death. In a mouse model of abdominal sepsis, local effects of bacterial ATP were analyzed using a transformed bearing an arabinose-inducible periplasmic apyrase hydrolyzing ATP to be released. Abrogating bacterial ATP release shows that bacterial ATP suppresses local immune responses, resulting in reduced neutrophil counts and impaired survival. In addition, bacterial ATP has systemic effects via its transport in outer membrane vesicles (OMV). ATP-loaded OMV are quickly distributed throughout the body and upregulated expression of genes activating degranulation in neutrophils, potentially contributing to the exacerbation of sepsis severity. This study reveals mechanisms of bacterial ATP release and its local and systemic roles in sepsis pathogenesis.

Achieving simultaneous cerebral blood flow (CBF) and oxygenation measures, specifically for point-of-care injury monitoring in prolonged field care, requires the implementation of appropriate methodologies and advanced medical device design, development, and evaluation. The near-infrared spectroscopy (NIRS) method measures the absorbance of light whose attenuation is related to cerebral blood volume and oxygenation. By contrast, diffuse correlation spectroscopy (DCS) allows continuous noninvasive monitoring of microvascular blood flow by directly measuring the degree of light scattering because of red blood cell (RBC) movement in tissue capillaries. Hence, this study utilizes these two optical approaches (DCS-NIRS) to obtain a more complete hemodynamic monitoring by providing cerebral microvascular blood flow, hemoglobin oxygenation and deoxygenation in hemorrhage, and hypoxia-induced injuries.

This cross-sectional study examined whether religious coping buffered the associations between racial discrimination and several modifiable cardiovascular disease (CVD) risk factors-systolic and diastolic blood pressure (BP), glycated hemoglobin (HbA1c), body mass index (BMI), and cholesterol-in a sample of African American women and men.

The World Health Organization identified vaccine hesitancy as one of the top 10 threats to global health. Vaccine hesitancy is defined as a delay in acceptance or refusal of vaccination despite the availability of vaccination services. Because vaccine safety concerns are important contributors to hesitancy, people who have experienced adverse events following immunization (AEFI) may be at especially high risk for subsequent vaccine hesitancy. The Defense Health Agency Immunization Healthcare Division (DHA IHD) provides specialized vaccine care to persons who have experienced AEFI. The impact of this specialized vaccine care on subsequent vaccine hesitancy has not been fully explored.

We investigated the association between outdoor artificial light-at-night (ALAN) exposure and cardiometabolic risk in the GCAT study. We included 9,752 participants from Barcelona (59% women). We used satellite images (30m resolution) and estimated photopic illuminance and the circadian-regulation relevant melanopic illuminance (melanopic EDI). We explored the association between ALAN exposure and prevalent obesity, hypertension, and diabetes with logistic regressions. We assessed the relationship with incident cardiometabolic diseases ascertained through electronic health records (mean follow-up 6.5 years) with Cox proportional hazards regressions. We observed an association between photopic illuminance and melanopic EDI and prevalent hypertension, Odds ratio (OR) = 1.09 (95% CI, 1.01-1.16) and 1.08 (1.01-1.14) per interquartile range increase (0.59 and 0.16 lux, respectively). Both ALAN indicators were linked to incident obesity (hazard ratio [HR] = 1.29, 1.11-1.48 and 1.19, 1.05-1.34) and haemorrhagic stroke (HR = 1.73, 1.00-3.02 and 1.51, 0.99-2.29). Photopic illuminance was associated with incident hypercholesterolemia in all participants (HR = 1.17, 1.05-1.31) and with angina pectoris only in women (HR = 1.55, 1.03-2.33). Further research in this area and increased awareness on the health impacts of light pollution are needed. Results should be interpreted carefully since satellite-based ALAN data do not estimate total individual exposure.

Occupational burnout among healthcare workers has continued to climb, impacting workforce well-being, patient safety, and retention of qualified personnel. Burnout in military healthcare workers, who have had the added stress of increased deployments, remains unknown. Although certain leadership styles have been associated with lower rates of burnout, the association between adaptive leadership and burnout in military healthcare has not previously been described. The aim of this study is to examine the role of adaptive leadership in burnout among military healthcare workers following the Coronavirus Disease 2019 (COVID-19) pandemic.

Military members and first responders may, at moment's notice, be asked to assist in incidents that may result in radiation exposure such as Operation Tomadachi in which the U.S. Navy provided significant relief for the Fukushima Daiichi Nuclear Reactor accident in Japan after an earthquake and tsunami in 2011. We are also currently facing potential threats from nuclear power plants in the Ukraine should a power disruption to a nuclear plant interfere with cooling or other safety measures. Exposure to high doses of radiation results in acute radiation syndrome (ARS) characterized by symptoms arising from hematopoietic, gastrointestinal, and neurovascular injuries. Although there are mitigators FDA approved to treat ARS, there are currently no FDA-approved prophylactic medical interventions to help protect persons who may need to respond to radiation emergencies. There is strong evidence that manganese (Mn) has radiation protective efficacy as a promising prophylactic countermeasure.

The ongoing conflict in Ukraine from Russian invasion presents a critical challenge to medical planning in the context of multi-domain battle against a peer adversary deploying conventional weapon systems. The potential escalation of preventable morbidity and mortality, reaching a scale unprecedented since World War II, underscores the paramount importance of effective phases of care from Point of Injury (PoI)/Point of Wounding (PoW) or Point of Exposure (PoE) to Role 1 (R1) and Role 2 (R2) echelons of care.The NATO Vigorous Warrior (VW) Live Exercise (LIVEX) serves as a strategic platform for NATO and its partners, providing an opportunity to challenge operational concepts, experiment, innovate life-saving systems, and foster best practices across the Alliance.

To evaluate the potential association between suicidality and glucagon-like peptide-1 receptor agonists (GLP-1RAs), as well as other medications used for obesity and diabetes, using comprehensive global data.

Anemia is a significant global health issue, affecting over a billion people worldwide, according to the World Health Organization. Generally, the gold standard for diagnosing anemia relies on laboratory measurements of hemoglobin. To meet the need in clinical practice, physicians often rely on visual examination of specific areas, such as conjunctiva, to assess pallor. However, this method is subjective and relies on the physician's experience. Therefore, we proposed a deep learning prediction model based on three input images from different body parts, namely, conjunctiva, palm, and fingernail. By incorporating additional body part labels and employing a fusion attention mechanism, the model learns and enhances the salient features of each body part during training, enabling it to produce reliable results. Additionally, we employ a dual loss function that allows the regression model to benefit from well-established classification methods, thereby achieving stable handling of minority samples. We used a retrospective data set (EYES-DEFY-ANEMIA) to develop this model called Body-Part-Anemia Network (BPANet). The BPANet showed excellent performance in detecting anemia, with accuracy of 0.849 and an F1-score of 0.828. Our multi-body-part model has been validated on a prospectively collected data set of 101 patients in National Taiwan University Hospital. The prediction accuracy as well as F1-score can achieve as high as 0.716 and 0.788, respectively. To sum up, we have developed and validated a novel non-invasive hemoglobin prediction model based on image input from multiple body parts, with the potential of real-time use at home and in clinical settings.

Microplastics and nanoplastics (MNPs) are present in urban dust and the aquatic environments of industrialized cities. MNPs in the human body accumulate in the lymphoid follicles, Peyer's patches of the gastrointestinal tract, and pulmonary vascular endothelial cells, which slowly result in toxicity. Since previous studies introduced curcumin as a natural protective agent against environmental toxins, we reviewed preclinical studies that had used curcumin to protect organs or cells from toxicity secondary to exposure to MNPs. It was found that exposure to MNPs resulted in osteolysis, immunotoxicity, thyroid disturbances, nephrotoxicity, neurotoxicity, hepatotoxicity, pulmonary toxicity, gastrointestinal toxicity, cardiovascular toxicity, and especially endocrine, and reproductive toxicity. Nevertheless, except for one study reviewed, curcumin restored all oxidative and histopathological damages induced by MNPs to normal due to curcumin's inherent antioxidant, antiapoptotic, anti-inflammatory, and anti-proliferative properties.

Testicular tumors represent the most common malignancy among young men. Nevertheless, the pathogenesis and molecular underpinning of testicular tumors remain largely elusive. We aimed to delineate the intricate intra-tumoral heterogeneity and the network of intercellular communication within the tumor microenvironment. A total of 40,760 single-cell transcriptomes were analyzed, encompassing samples from six individuals with seminomas, two patients with mixed germ cell tumors, one patient with a Leydig cell tumor, and three healthy donors. Five distinct malignant subclusters were identified in the constructed landscape. Among them, malignant 1 and 3 subclusters were associated with a more immunosuppressive state and displayed worse disease-free survival. Further analysis identified that APP-CD74 interactions were significantly strengthened between malignant 1 and 3 subclusters and 14 types of immune subpopulations. In addition, we established an aberrant spermatogenesis trajectory and delineated the global gene alterations of somatic cells in seminoma testes. Sertoli cells were identified as the somatic cell type that differed the most from healthy donors to seminoma testes. Cellular communication between spermatogonial stem cells and Sertoli cells is disturbed in seminoma testes. Our study delineates the intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors, offering novel insights for targeted therapy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Persons with disabilities in LMICs facing numerous challenges in accessing essential healthcare services. However, this understanding is lacking so far in LMICs and Bangladesh. This study aimed to explore the pattern and determinants of healthcare services access among persons with disabilities in Bangladesh. We analysed data from 4293 persons with disabilities extracted from the 2021 National Survey on Persons with Disabilities. The outcome variable was healthcare services access within three months of the survey, categorized as either "yes" or "no" based on perceived needs. Several individual, household, and community-level factors were considered as explanatory variables. We utilized a multilevel mixed-effect logistic regression model to explore the association of the outcome variable with explanatory variables. The analysis included stratification by age groups: 0-17 years and 18-95 years. One out of every four persons with disabilities in Bangladesh reported that they could not access healthcare services based on their needs within three months of the survey. The main reasons for not accessing services were healthcare costs (52.10%), followed by lack of family support (27.0%), and absence of healthcare facilities in their areas of residence (10.10%). Among those who did receive healthcare services, the majority reported accessing them from governmental hospitals (26.49%), followed by village practitioner (20.52%), and private healthcare centres (19.87%). There was a higher likelihood of accessing healthcare services among persons with disabilities residing in households with higher wealth quintiles and living in the Chattogram and Sylhet divisions. Unmarried or divorced/widowed/separated persons with disabilities reported lower likelihoods of accessing healthcare services. The findings of this study emphasize the need for policies and programs to ensure healthcare services for persons with disabilities in Bangladesh. This entails raising awareness about the importance of providing healthcare services for this demographic, as well as considering healthcare services as part of social safety net programs.

Given the context of significant global warming and the intensification of extreme climate events in the last century, large-scale reforestation and afforestation have been recognized as effective strategies to mitigate the climate crisis. Since the 1970s, China has launched several afforestation programs aimed at regional ecological protection, playing an important role in reaching carbon neutrality by 2060. This study provided a detailed analysis of the growth suitability of the main planted conifers (Pinus sylvestris var. mongolica and Pinus tabulaeformis) and broadleaves (Populus spp., Robinia pseudoacacia) in the semi-arid northern China. We compared the radial growth trends of plantations and their responses to extreme droughts from 1980 to 2018. Growth of most plantations has significantly increased over time, but broadleaves showed recent growth reductions in the past decade, which may be related to tree age and reduced soil moisture. Nevertheless, under warmer climate scenarios, the growth of plantations is forecasted to continue increasing. Broadleaves showed a better post-drought recovery, probably linked to their anisohydric behavior, than conifers, which presented a better resistance to drought. Growth of conifers depended more on warmer temperature and better precipitation conditions during the growing season, whereas broadleaves mainly reacted to warm temperature. Additionally, pre-drought growth levels weakened resilience components, while post-drought precipitation compensated for drought-induced growth deficit. Growth and resilience were negatively related to tree age, while higher stand density reduced growth. This assessment and projections of growth and drought resilience indicate the sustainability of most plantations in semi-arid regions, but future warmer and drier conditions may lead to an uncertain future regarding forest health and reduce their carbon sink potential.

This letter addresses the research presented by Sun et al. on the integration of digital subtraction angiography (DSA) with conventional surgical drainage for chronic subdural hematoma (CSDH), focusing on precision in targeting the middle meningeal artery (MMA). The study demonstrates a reduction in hematoma recurrence and drainage tube indwelling times, highlighting the procedural benefits without added complications. The letter suggests further research directions, including the potential for personalized surgical approaches based on MMA anatomy variations, and emphasizes the importance of this technique in enhancing neurosurgical outcomes.

The resistance of foodborne pathogens to antimicrobial agents is a potential danger to human health. Hence, establishing the status of good agricultural practices (GAPs) and the antimicrobial susceptibility of major foodborne pathogens has a significant programmatic implication in planning interventions. The objective of this study was to assess the gap in attaining GAP and estimate the prevalence and antimicrobial susceptibility profile of Salmonella in vegetable farms fertilized with animal manure in Addis Ababa, Ethiopia. A total of 81 vegetable farms from four sub-cities in Addis Ababa were visited, and 1119 samples were collected: soil (n = 271), manure (n = 375), vegetables (n = 398), and dairy cattle feces (n = 75). Additional data were collected using a structured questionnaire. Isolation of Salmonella was done using standard microbiology techniques and antimicrobial susceptibility testing was conducted using disk diffusion assays. Carriage for antimicrobial resistance genes was tested using polymerase chain reaction (PCR). Among the 81 vegetable farms visited, 24.7% used animal manure without any treatment, 27.2% used properly stored animal manure and 80.2% were easily accessible to animals. The prevalence of Salmonella was 2.3% at the sample level, 17.3% at the vegetable farm level, and 2.5% in vegetables. The highest rate of resistance was recorded for streptomycin, 80.7% (21 of 26), followed by kanamycin, 65.4% (17 of 26), and gentamicin, 61.5% (16 of 26). Multidrug resistance was detected in 61.5% of the Salmonella isolates. Vegetable farms have a gap in attaining GAPs, which could contribute to increased contamination and the transfer of antimicrobial resistance to the vegetables. The application of GAPs, including proper preparation of compost and the appropriate use of antimicrobials in veterinary practices, are recommended to reduce the emergence and spread of antimicrobial resistance.

The global spread of H5 clade 2.3.4.4 highly pathogenic avian influenza (HPAI) viruses threatens poultry and public health. The continuous circulation of these viruses has led to their considerable genetic and antigenic evolution, resulting in the formation of eight subclades (2.3.4.4a-h). Here, we examined the antigenic sites that determine the antigenic differences between two H5 vaccine strains, H5-Re8 (clade 2.3.4.4g) and H5-Re11 (clade 2.3.4.4h). Epitope mapping data revealed that all eight identified antigenic sites were located within two classical antigenic regions, with five sites in region A (positions 115, 120, 124, 126, and 140) and three in region B (positions 151, 156, and 185). Through antigenic cartography analysis of mutants with varying numbers of substitutions, we confirmed that a combination of mutations in these eight sites reverses the antigenicity of H5-Re11 to that of H5-Re8, and vice versa. More importantly, our analyses identified H5-Re11_Q115L/R120S/A156T (H5-Re11 + 3) as a promising candidate for a broad-spectrum vaccine, positioned centrally in the antigenic map, and offering potential universal protection against all variants within the clade 2.3.4.4. H5-Re11 + 3 serum has better cross-reactivity than sera generated with other 2.3.4.4 vaccines, and H5-Re11 + 3 vaccine provided 100% protection of chickens against antigenically drifted H5 viruses from various 2.3.4.4 antigenic groups. Our findings suggest that antigenic regions A and B are immunodominant in H5 viruses, and that antigenic cartography-guided vaccine design is a promising strategy for selecting a broad-spectrum vaccine.

To assess rates of traversing barriers to care to access optimal clinical outcomes in people with migraine internationally.

Investigate whether the coexistence of pain and depressive symptoms is a risk factor for cognitive decline in individuals aged 50 or older.

The One Health approach, recognizing the interconnectedness of human, animal, and environmental health, has gained significance amid emerging zoonotic diseases and antibiotic resistance concerns. This paper aims to demonstrate the utility of a collaborative tool, the SIEGA, for monitoring infectious diseases across domains, fostering a comprehensive understanding of disease dynamics and risk factors, highlighting the pivotal role of One Health surveillance systems. Raw whole-genome sequencing is processed through different species-specific open software that additionally reports the presence of genes associated to anti-microbial resistances and virulence. The SIEGA application is a Laboratory Information Management System, that allows customizing reports, detect transmission chains, and promptly alert on alarming genetic similarities. The SIEGA initiative has successfully accumulated a comprehensive collection of more than 1900 bacterial genomes, including Salmonella enterica, Listeria monocytogenes, Campylobacter jejuni, Escherichia coli, Yersinia enterocolitica and Legionella pneumophila, showcasing its potential in monitoring pathogen transmission, resistance patterns, and virulence factors. SIEGA enables customizable reports and prompt detection of transmission chains, highlighting its contribution to enhancing vigilance and response capabilities. Here we show the potential of genomics in One Health surveillance when supported by an appropriate bioinformatic tool. By facilitating precise disease control strategies and antimicrobial resistance management, SIEGA enhances global health security and reduces the burden of infectious diseases. The integration of health data from humans, animals, and the environment, coupled with advanced genomics, underscores the importance of a holistic One Health approach in mitigating health threats.

Queuosine (Q) is a hypermodified 7-deaza-guanosine nucleoside exclusively synthesized by bacteria. This micronutrient and its respective nucleobase form queuine (q) are salvaged by humans either from gut microflora or digested food. Depletion of Q-tRNA in human or mouse cells causes protein misfolding that triggers endoplasmic reticular stress and the activation of the unfolded protein responses. In vivo, this reduces the neuronal architecture of the mouse brain affecting learning and memory. Herein, a sensitive method for quantifying free q and Q in human blood was developed, optimised and validated. After evaluating q/Q extraction efficiency in several different solid-phase sorbents, Bond Elut PBA (phenylboronic acid) cartridges were found to have the highest extraction recovery for q (82%) and Q (71%) from pooled human plasma. PBS with 4% BSA was used as surrogate matrix for method development and validation. An LC-MS/MS method was validated across the concentration range of 0.0003-1 µM for both q and Q, showing excellent linearity (r = 0.997 (q) and r = 0.998 (Q)), limit of quantification (0.0003 µM), accuracy (100.39-125.71%) and precision (CV% < 15.68%). In a sampling of healthy volunteers (n = 44), there was no significant difference in q levels between male (n = 14; mean = 0.0068 µM) and female (n = 30; mean = 0.0080 µM) participants (p = 0.50). Q was not detected in human plasma. This validated method can now be used to further substantiate the role of q/Q in nutrition, physiology and pathology.

Familial concordance of weight status is an emerging field of study that may guide the development of interventions that operate beyond the individual and within the family context. There is a dearth of published data for concordance of weight status within Pakistani households.

There is an often-held assumption that the engagement of clinicians and healthcare organizations in research improves healthcare performance at various levels. Previous reviews found up to 28 studies suggesting a positive association between the engagement of individuals and healthcare organizations in research and improvements in healthcare performance. The current study sought to provide an update.

Musculoskeletal injuries (MSKIs) among active duty soldiers result in more than 10 million limited duty days each year and account for more than 70% of the medically nondeployable population. Overuse injuries in lower limbs from running, foot marching long distances with heavy loads, and lifting heavy objects are the most common types of injuries in the military. Physical training and rehabilitation exercises for greater resiliency through aerobic, muscle strength, endurance, and agility conditioning programs can prevent or reduce the effects of MSKIs if Soldiers adhere to proper biomechanics and training techniques. We are introducing a three-dimensional (3D) camera-based platform for Optical Screening and Conditioning for Injury Resilience (OSCIR) that is designed to identify and correct high-risk movement patterns based on quantifiable biomechanical measurements in clinical or field settings. Our goal is to improve resilience to MSKI by offering greater access to quality of movement skills in warfighters through an autonomous device that can be used in Sports Medicine and Reconditioning Team (SMART) clinics and High-Intensity Tactical Training (HITT) sites.

Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction. This was a sensitivity analysis of a drug (tetracosactide; TCS10) targeting melanocortin receptors (MCRs) in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders.

Poverty-related diseases (PRD) remain amongst the leading causes of death in children under-5 years in sub-Saharan Africa (SSA). Clinical practice guidelines (CPGs) based on the best available evidence are key to strengthening health systems and helping to enhance equitable health access for children under five. However, the CPG development process is complex and resource-intensive, with substantial scope for improving the process in SSA, which is the goal of the Global Evidence, Local Adaptation (GELA) project. The impact of research on PRD will be maximized through enhancing researchers and decision makers' capacity to use global research to develop locally relevant CPGs in the field of newborn and child health. The project will be implemented in three SSA countries, Malawi, South Africa and Nigeria, over a 3-year period. This research protocol is for the monitoring and evaluation work package of the project. The aim of this work package is to monitor the various GELA project activities and evaluate the influence these may have on evidence-informed decision-making and guideline adaptation capacities and processes. The specific project activities we will monitor include (1) our ongoing engagement with local stakeholders, (2) their capacity needs and development, (3) their understanding and use of evidence from reviews of qualitative research and, (4) their overall views and experiences of the project.

Multi-drug-resistant tuberculosis (MDR-TB) infections are a public health concern. Since 2017, the Ministry of Health (MoH) in Zambia, in collaboration with its partners, has been implementing decentralised MDR-TB services to address the limited community access to treatment. This study sought to explore the role of collaboration in the implementation of decentralised multi drug-resistant tuberculosis services in Zambia.

Limited research exists on the comorbidity of pulmonary tuberculosis with non-communicable diseases (NCDs) and its implications for healthcare utilization in Indonesia. The lack of investigation into NCD comorbidity among pulmonary tuberculosis patients could adversely affect both the healthcare system and the national health insurance scheme. Understanding the NCD comorbidity among pulmonary tuberculosis patients, associated factors, and healthcare utilization is crucial for ensuring the effective and efficient delivery of health services.

Type 2 diabetes mellitus is a chronic disease and one of the fastest- growing global health emergencies of the 21st century. The relationships between hope level, social support, disease perception, and self-management behaviors are still unclear. Therefore, this study aimed to create a structural equation model to investigate the underlying mechanisms of self-management behaviors in patients with type 2 diabetes mellitus and provide a theoretical basis for future interventions.

This article focuses on the workplace experiences of peer workers with a diagnosis of borderline personality disorder (BPD) in mental healthcare settings in Australia. Our article is located at the intersection of political, social, cultural, and legislative forces that have fostered the development of peer work as a paid profession. We draw on the concept of stigma to analyse findings from qualitative interviews with peer workers conducted in [state], Australia. By examining peer work in the broader context of lifeworlds of BPD, we address the interplay of work and professional identity, and the experience of a profoundly stigmatised diagnosis at this intersection.Our findings demonstrate the physical and emotional effects of stigma and how it produces boundaries and inequalities between peer workers and other health practitioners. These boundaries are reinforced by invisible markers that delineate what is expected, 'normal' and deemed professional in the workplace. Moreover, these same medico-socio-political relations help shape peer workers' identities and experiences. The development of peer workforces in mental healthcare service delivery is a prominent area of reform in Australia and internationally. Our research highlights the urgency of efforts to transform current socio-cultural-political relations that inhibit peer workers in their roles and impact workplace experiences.

This narrative review was planned to explore the efficacy of plasma-rich protein in musculoskeletal injuries, emphasising its impact on inflammatory markers, growth factors and the healing process. Musculoskeletal disorders pose a significant global health concern, with the plasmarich protein therapy emerging as a promising rehabilitative technique due to its potential to enhance healing. The therapy utilises the patients' cells to stimulate growth, repair tissues, and modulate inflammation, offering a shift towards patient-friendly, non-hospitalised treatment. Through the modulation of inflammatory phases, stimulation of proliferative phases, and enhancement of remodelling phases, the plasma-rich protein therapy contributes to the expedited healing of musculoskeletal injuries. Clinical evidence supports its efficacy in reducing recovery time and managing pain, underscoring its therapeutic potential in musculoskeletal rehabilitation.

Whether cardiac impairment can be fully discarded in McArdle disease-the paradigm of 'exercise intolerance', caused by inherited deficiency of the skeletal muscle-specific glycogen phosphorylase isoform ('myophosphorylase')-remains to be determined.

This review presents a comprehensive overview of the rapidly evolving digital healthcare industry, aiming to provide a broad understanding of the recent landscape and directions for the future of digital healthcare.

This article presents a systematic review of recent advancements in telemedicine architectures for continuous monitoring, providing a comprehensive overview of the evolving software engineering practices underpinning these systems. The review aims to illuminate the critical role of telemedicine in delivering healthcare services, especially during global health crises, and to emphasize the importance of effectiveness, security, interoperability, and scalability in these systems.

Climate change is a phenomenon that has had, and will continue to have, wide-ranging effects on the world in both the near and distant future. With regards to human health, research has demonstrated the impact of climate change on heat-related illness, mental health, and vector-borne infectious diseases. Through a review of the literature, this paper aims to elucidate both current and future consequences of climate change on cellulitis, a type of skin infection that is associated with significant morbidity, mortality, and cost. Factors such as elevated temperature, pollution, rising sea levels, and the increased frequency of natural disasters pose an alarming risk for the increased proliferation of infections such as cellulitis. Lastly, in light of these trends, this paper will address potential strategies individuals can implement to reduce the effects of climate change on cellulitis.

Leptospirosis is a global health concern, particularly in tropical regions, with clinical symptoms varying from mild fever to severe organ dysfunction. We present a case of a 57-year-old male with septic shock and acute kidney injury due to acute leptospirosis. The patient's rapid progression to shock within a day of generalized symptoms was unusual. The patient's infection ultimately resolved with ceftriaxone and he was discharged after 14 days of therapy. The pathogenesis of severe leptospirosis is believed to be due to vasculitis, with organ damage caused by the leptospira bacteria and immune-mediated mechanisms. Diagnostic investigations include blood cultures and polymerase chain reactions, which are beneficial for early diagnosis. The management of patients depends on the severity of symptoms and other health conditions, as well as antibiotics and hydration. However, leptospirosis can lead to a wide range of complications, including neurological, ocular, hematological, and gastrointestinal involvement, necessitating vigilant monitoring and management.

Sepsis is a leading global cause of mortality, and predicting its outcomes is vital for improving patient care. This study explored the capabilities of ChatGPT, a state-of-the-art natural language processing model, in predicting in-hospital mortality for sepsis patients.

Childhood obesity is a complex public health challenge with profound implications for both physical and psychological well-being. A significant portion of the global population struggles with obesity. Sedentary lifestyles, increased consumption of ultra-processed foods, and socioeconomic disparities are major contributors. The COVID-19 pandemic has further exacerbated these issues, leading to a surge in obesity rates among children. The consequences of childhood obesity extend beyond immediate health issues like type 2 diabetes and cardiovascular diseases; obese children are at higher risk for psychological problems such as depression, anxiety, and low self-esteem, which can persist into adulthood. These health challenges also impose substantial economic burdens due to increased healthcare costs and reduced productivity. This paper synthesizes findings from various articles to provide an overview of the causes, consequences, and preventive strategies related to childhood obesity. It highlights the varied nature of obesity, including genetic, environmental, and lifestyle factors, and discusses the profound impact on physical health, socioemotional skills, and mental health. Additionally, it examines the global challenge of childhood obesity, particularly in developing nations, and emphasizes the importance of preventive measures, family and parental behaviors, and effective policy interventions.

Adolescents experience rapid physical, cognitive, and psychosocial growth in their transition from childhood to adulthood, affecting health outcomes and well-being. Health-related quality of life (HRQoL) is a useful indicator of health outcomes, assessed in the current study along with associated determinants.

The role of long noncoding RNA (lncRNA) in tumors, particularly in gastrointestinal tumors, has gained significant attention. Accumulating evidence underscores the interaction between various lncRNAs and diverse molecular pathways involved in cancer progression. One such pivotal pathway is the PI3K/AKT pathway, which serves as a crucial intracellular mechanism maintaining the balance among various cellular physiological processes for normal cell growth and survival. Frequent dysregulation of the PI3K/AKT pathway in cancer, along with aberrant activation, plays a critical role in driving tumorigenesis. LncRNAs modulate the PI3K/AKT signaling pathway through diverse mechanisms, primarily by acting as competing endogenous RNA to regulate miRNA expression and associated genes. This interaction significantly influences fundamental biological behaviors such as cell proliferation, metastasis, and drug resistance. Abnormal expression of numerous lncRNAs in gastrointestinal tumors often correlates with clinical outcomes and pathological features in patients with cancer. Additionally, these lncRNAs influence the sensitivity of tumor cells to chemotherapy in multiple types of gastrointestinal tumors through the abnormal activation of the PI3K/AKT pathway. These findings provide valuable insights into the mechanisms underlying gastrointestinal tumors and potential therapeutic targets. However, gastrointestinal tumors remain a significant global health concern, with increasing incidence and mortality rates of gastrointestinal tumors over recent decades. This review provides a comprehensive summary of the latest research on the interactions of lncRNA and the PI3K/AKT pathway in gastrointestinal tumor development. Additionally, it focuses on the functions of lncRNAs and the PI3K/AKT pathway in carcinogenesis, exploring expression profiles, clinicopathological characteristics, interaction mechanisms with the PI3K/AKT pathway, and potential clinical applications.

The current literature shows similar clinical outcomes between first metatarsophalangeal (MTP) joint arthrodesis and synthetic cartilage implant (SCI) hemiarthroplasty in the treatment of hallux rigidus; however, prior studies have not reported validated patient-reported outcome measures (PROMs). To our knowledge, this is the first study to compare PROMs using 6 domains of the validated Patient-Reported Outcomes Measurement Information System (PROMIS) in patients treated for hallux rigidus with MTP joint arthrodesis and with SCI hemiarthroplasty. In addition, this novel study provides comparative data on the complication and revision rates for each procedure.

() infection and nonalcoholic fatty liver disease (NAFLD) represent significant concerns in global health. However, the precise relationship between and NAFLD remains a subject of ongoing debate. This study endeavors to elucidate the association between infection and the susceptibility to NAFLD. Furthermore, we aim to investigate the interplay among infection, NAFLD, and metabolic syndrome (MetS).

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) poses a significant threat to the global swine industry. Vaccination is a preventive measure against viral infections. However, the use of vaccines in livestock healthcare programs faces the challenge of safety and delayed immune responses. Earlier studies have shown the potential of modified Bazhen powder as an immunomodulator with significant biological properties, but its effect on vaccines against HP-PRRSV is yet to be studied. This study elucidated how modified Bazhen powder could improve the safety and efficacy of the conventional PRRSV vaccine by evaluating T-cell responses, antibody levels, clinical symptoms, levels of viremia, organ health, and cytokine production. The results revealed that the oral application of modified Bazhen powder in combination with PRRS vaccination improved both cellular and humoral immunity, accelerated viremia clearance, improved lung injury scores, and reduced viral load in the tonsils. The modified Bazhen powder also effectively reduced inflammatory responses following a PRRSV challenge. These findings further highlight the pharmacological properties of modified Bazhen powder as a potential oral immunomodulatory agent that could enhance vaccine efficacy and ensure broad-spectrum protection against HP-PRRSV in pigs.

There are few reliable and feasible quality assurance methods to support scaling up of psychological interventions delivered by non-specialist providers. This paper reports on the phased development and validation of a digitally administered Knowledge of Problem Solving (KOPS) measure to assess competencies associated with a "task-shared" problem-solving intervention for adolescents with diverse mental health problems in India. Phase 1 established key competencies required to deliver the intervention, followed by item generation for a corresponding knowledge-based competency measure that could be administered efficiently through e-learning systems. In phase 2, items were refined based on responses from an "experienced" reference sample comprising 17 existing counsellors with direct experience of the problem-solving intervention, and a "novice" sample with 14 untrained university students and NGO staff. In phase 3, we evaluated two parallel versions of the measure in a validation sample ( = 277) drawn from universities and NGOs. The resulting 17-item measure was structured around a hypothetical case, followed by multiple-choice questions that asked about the most appropriate response to a practice-based scenario. The difficulty level of the test items was well matched to the ability level of participants (i.e. most items being of moderate difficulty and few items being easy or difficult). Only one item showed a negative discrimination index and was removed from the 17-item forms. The final 16-item version of the KOPS measure provides a scalable digital method to assess key psychotherapeutic competencies among non-specialists, particularly in relation to a transdiagnostic problem-solving intervention. Similar formats could be deployed more widely alongside e-learning programmes to expand the global workforce capable of delivering evidence-based psychological interventions.

Currently ischemic stroke poses a serious disease burden globally, and high fasting plasma glucose is one of the important risk factors. The aim of this study was to investigate the disease burden of ischemic stroke due to fasting glucose during 1990-2019 in China, to estimate the effect of age, period, and cohort on the trend of ischemic stroke disease burden, and to predict the disease burden of ischemic stroke in 2020-2030.

Global discussions on health systems strengthening have lately tilted towards increasing investments in human resources for health to address health workforce challenges, especially shortages and employment. Countries have, as a result, increased investments in the health workforce by expanding the production and recruitment of the needed health workforce, with the resultant effects of increasing health workforce budget space and the unending clamour by health policy actors for further increases. Despite these calls, there has been no wage bill affordability and budget space analysis to rationalise the sustainable production of and demand for health workers, which is the thrust of Ghana's current health workforce policy and strategy. Using an adapted approach (the Asamani approach), the study modelled the supply of some essential health workers and their associated cost of employment, compared it with the modelled budget space for health workforce employment and then drew conclusions on the wage bill sustainability for policy consideration. Of the seven cadres considered in the study (doctors, professional nurses, midwives, enrolled nurses, community health nurses, pharmacists and biomedical scientists), who constitute about 97% of the wage bill, the study found the baseline stock to be 129 378 in 2022, which was estimated to increase to 199 715 by 2027 and 254 466 by 2032 with corresponding wage bills of US$869.4 million and US$ 1.1 billion, respectively, holding routine salary increases constant. The budget space for health was, meanwhile, projected to be US$899.3 million and US$1.1 billion in 2022 and 2032 respectively, out of a projected overall government fiscal space of US$7 billion per year. This study concludes that, given current levels and mix of production, Ghana was estimated to expend an average of 88% of its health budget space as wage bill cost. This was 54.4% over the global median and 95.6% over the African Region's median, making the current regime unsustainable.

Acute kidney injury (AKI) is easily missed and underdiagnosed in routine clinical care. Timely AKI management is important to decrease morbidity and mortality risks. We recently implemented an AKI e-alert at the University Medical Center Utrecht, comparing plasma creatinine concentrations with historical creatinine baselines, thereby identifying patients with AKI. This alert is limited to data from tertiary care, and primary care data can increase diagnostic accuracy for AKI. We assessed the added value of linking primary care data to tertiary care data, in terms of timely diagnosis or excluding AKI.

The study explores barriers and suggestions for improving viral load testing (VLT) uptake in Tanzania, revealing that only 58% of patients receive VLT annually, contrary to the Tanzanian National Guidelines toward the 95-95-95 UNAIDS targets. Twelve individual interviews and three patient-focus groups were conducted as part of a qualitative study conducted in six human immunodeficiency virus (HIV) clinics in Dar es Salaam to identify potential suggestions for access enhancement, as well as barriers to VLT uptake. Using King's theory of goal attainment, we found that missing appointments was the primary individual barrier to VLT uptake, along with limited knowledge among individuals living with HIV. Participants also face system-level barriers, such as a lack of integrated care and evening service availability. The study suggests that, despite challenges, there is potential for improvement in the uptake and quality of VLT services in Tanzanian public health facilities through a holistic approach.

Cataract is a leading cause of global blindness, affecting around 33% of blind individuals worldwide. It significantly impacts individuals' well-being, independence, and quality of life, posing a substantial economic burden. India's rapidly ageing population necessitates an examination of cataract prevalence and treatment disparities. No attempts have been made to address socioeconomic variation in treatment disparities of effective cataract treatment coverage among older adults in India.