Global Health

With ∼50% recurrent pregnancy loss cases being termed idiopathic (iRPL), understanding of contribution of male factors to iRPL is still lacking. Higher prevalence of sperm DNA fragmentation index (DFI) and lower sperm 5-methylcytosine (5-mC) levels have been previously reported in male partners of iRPL couples and shed light on importance of the male gamete in maintenance of a successful pregnancy. The present study aimed to determine the serum sex steroid hormone levels, sperm DFI and 5-mC and correlation between them in male partners of fertile and iRPL couples. Further, correlation between sperm DFI and 5-mC with semen parameters and paternal age in both groups were determined. 36 male partners of fertile couples and 45 male partners of women experiencing iRPL were enrolled for this study and semen and blood samples were collected. Serum testosterone and estradiol levels were measured by ELISA; sperm DFI and global 5-mC were determined by TUNEL assay and ELISA respectively. Significantly higher serum testosterone levels were noted in the iRPL group ( = 0.028). Incidence of sperm DNA fragmentation was found to be higher in the iRPL study group but with no significance difference. No significant differences in sperm 5-mC values were noted. Upon correlation analysis within both groups, strong significant negative correlation of sperm DFI % and 5-mC % was observed in the control group ( < 0.001) but not the iRPL group ( = 0.249). Hence, we infer that with lower 5-mC levels in sperm genome, there is a higher incidence of sperm DFI in fertile men. However, this trend is not noted in men of iRPL group which could possibly be due to other underlying epigenetic alterations in genomic regions probably unsusceptible to fragmentation. On the other hand, no significant correlations of semen parameters, testosterone, estradiol and paternal age with sperm DFI and 5-mC were noted in both groups.

Nonpharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic have disrupted the dynamics of respiratory syncytial virus (RSV) on a global scale; however, the cycling of RSV subtypes in the pre- and post-pandemic period remains poorly understood. Here, we used a two subtype RSV model supplemented with epidemiological data to study the impact of NPIs on the two circulating subtypes, RSV-A and RSV-B. The model is calibrated to historic RSV subtype data from the United Kingdom and Finland and predicts a tendency for RSV-A dominance over RSV-B immediately following the implementation of NPIs. Using a global genetic dataset, we confirm that RSV-A has prevailed over RSV-B in the post-pandemic period, consistent with a higher R for RSV-A. With new RSV infant monoclonals and maternal and elderly vaccines becoming widely available, these results may have important implications for understanding intervention effectiveness in the context of disrupted subtype dynamics.

This review explores how climate change is manifesting along existing lines of inequality and thus further exacerbating current health disparities with a particular focus on children and future generations. Climate change risk and vulnerability are not equally distributed, nor is the adaptive capacity to respond to its adverse effects, which include health consequences, economic impacts, and displacement. Existing lines of inequality are already magnifying the adverse effects of climate change. Today's children and future generations will experience a disproportionate number of adverse climate events than prior generations, especially children in lower-income populations, communities of color, and Indigenous communities. In order to mitigate the crisis of inequity accompanying the climate crisis, systemic action must be taken on a global scale - with a focus on protecting children and future generations, and in empowering youth-led environmental activism and engagement in climate policy. IMPACT STATEMENT: Our review offers a current summary of the ways in which inequality is manifesting with respect to climate change in children and future generations. Rather than use a systematic review, we opted to use a theoretical framework to guide our review. We divided the effects of climate change into three effect pathways: via disruptions in (i) climate and weather, (ii) ecosystems, and (iii) society. By dividing our review in this theoretical framework, we can better suggest targeted public health interventions at each effect level. Furthermore, we are able to successfully identify literature gaps and areas of future research.

Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts.

Ketamine has rapid-onset antidepressant activity in patients with treatment-resistant major depression (TRD). The safety and tolerability of racemic ketamine may be improved if given orally, as an extended-release tablet (R-107), compared with other routes of administration. In this phase 2 multicenter clinical trial, male and female adult patients with TRD and Montgomery-Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized on a 1:1:1:1:1 basis to receive double-blind R-107 doses of 30, 60, 120 or 180 mg, or placebo, twice weekly for a further 12 weeks. Nonresponders on day 8 exited the study. The primary endpoint was least square mean change in MADRS for each active treatment compared with placebo at 13 weeks, starting with the 180 mg dose, using a fixed sequence step-down closed test procedure. Between May 2019 and August 2021, 329 individuals were screened for eligibility, 231 entered the open-label enrichment phase (days 1-8) and 168 responders were randomized to double-blind treatment. The primary objective was met; the least square mean difference of MADRS score for the 180 mg tablet group and placebo was -6.1 (95% confidence interval 1.0 to 11.16, P = 0.019) at 13 weeks. Relapse rates during double-blind treatment showed a dose response from 70.6% for placebo to 42.9% for 180 mg. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation and minimal dissociation. The most common adverse events were headache, dizziness and anxiety. During the randomized phase of the study, most patient dosing occurred at home. R-107 tablets were effective, safe and well tolerated in a patient population with TRD, enriched for initial response to R-107 tablets. ClinicalTrials.gov registration: ACTRN12618001042235 .

The global aging population presents challenges that are particularly acute in China. Older Chinese adults' attitudes towards death significantly impact their quality of life. Death education is crucial for promoting positive perspectives on life and death. Narrative education offers a promising approach to facilitating death education. Integrating the Knowledge-Attitude-Practice (KAP) model into death education will enhance the feasibility and acceptability of death education programs.

Health policy and systems research (HPSR) can strengthen health systems and improve population health outcomes. In the Eastern Mediterranean Region (EMR), there is limited recognition of the importance of HPSR and funding remains the main challenge. This study seeks to: (1) assess the reporting of funding in HPSR papers published between 2010 and 2022 in the EMR, (2) examine the source of funding in the published HPSR papers in the EMR and (3) explore variables influencing funding sources, including any difference in funding sources for coronavirus disease 2019 (COVID-19)-related articles.

Monitoring wildlife health is essential for understanding global disease patterns, particularly as vector-borne infections extend the geographic ranges and thereby hosts due to environmental shifts. Anaplasma marginale, primarily impacting cattle, has economic implications and has been found in diverse hosts, yet its presence in capybaras (Hydrochoerus hydrochaeris), influential in tick-borne pathogen spread, lacks comprehensive understanding. From 2015 to 2022, 14 capybaras were surveyed across two different areas of northeastern Argentina. In 1 of 14 (7%) capybaras, the presence of A. marginale was confirmed through the amplification of specific genes, msp5 and msp1β. In addition, A. marginale DNA was detected in the capybara's blood sample through quantitative PCR, with a cycle threshold value of 30.81 (800 copies per reaction). Amplification of a fragment of the msp1α gene revealed PCR products of three different sizes, suggesting the presence of at least three coinfecting A. marginale variants in the capybara host. This study suggests that capybaras are wild hosts for A. marginale in the Ibera Wetlands in Argentina, potentially influencing the infection dynamics of both domestic and wild species. This finding highlights the necessity for thorough studies on the role of capybaras in disease dynamics, crucial for understanding wildlife health and the spread of disease.

Cognitive symptoms are often reported by those with a history of COVID-19 infection. No comprehensive meta-analysis of neurocognitive outcomes related to COVID-19 exists despite the influx of studies after the COVID-19 pandemic. This study meta-analysed observational research comparing cross-sectional neurocognitive outcomes in adults with COVID-19 (without severe medical/psychiatric comorbidity) to healthy controls (HCs) or norm-referenced data.

Major global trends are reshaping health services delivery, and preparing current and future healthcare leaders requires an understanding of these trends. A well-designed leadership competency model can provide guidance for individuals, as well as for system-level leadership development and integration programmes.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first three months post-COVID-19 diagnosis. Data collected through the IDI-IR included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29±13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis (ROCM). Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age [Hazard Ratio (HR)=1.06, (p<0.001)], rituximab use (HR=21.2, p=0.05), diabetic ketoacidosis (HR=3.58, p=0.009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR=8.81, p<0.001). The utilization of rituximab and diabetic ketoacidosis along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory condition that imposes a significant healthcare burden worldwide. Accurate staging of COPD severity is crucial for patient management and treatment planning.

ObjectivesThe aim of this study was to develop the Remote Health Value Framework to evaluate the models of healthcare provision for workers in the oil and gas sector, predominantly situated in rural and remote areas.MethodsThe framework was co-designed with the leadership team in one global oil and gas company using a multi-criteria decision analysis approach with a conjoint analysis component. This was used to elicit and understand preferences and trade-offs among different value domains that were important to the stakeholders with respect to the provision of healthcare for its workers. Preference elicitation and interviews were conducted with a mix of health, safety, and environment (HSE) team and non-HSE managers and leaders.ResultsOut of five presented value domains, participants considered the attribute 'Improving health outcomes of employees' the most important aspect for the model of healthcare which accounted for 37.3% of the total utility score. Alternatively, the 'Program cost' attribute was least important to the participants, accounting for only 11.0% of the total utility score. The marginal willingness-to-pay analysis found that participants would be willing to pay A$9090 per utile for an improvement in a particular value attribute.ConclusionsThis is the first value framework for healthcare delivery in the oil and gas industry, contextualised by its delivery within rural and remote locations. It provides a systematic and transparent method for creating value-based healthcare models. This approach facilitates the evaluation of healthcare investments, ensuring they align with value domains prioritised by the HSE and leadership teams.

Recent spoligotyping results in the island nation of Indonesia had revealed the existence of Mycobacterium tuberculosis complex lineage 3 (MTBC L3) or Central Asian (CAS) strains. In this work, whole-genome sequencing (WGS) - based methods were used to search for the presence of MTBC L3.

Biopolymers like starch, a renewable and widely available resource, are increasingly being used to fabricate the films for eco-friendly packaging solutions. Starch-based edible films offer significant advantages for food packaging, including biodegradability and the ability to extend shelf life. However, they also present challenges such as moisture sensitivity and limited barrier properties compared to synthetic materials. These limitations can be mitigated by incorporating bioactive components, such as antimicrobial agents or antioxidants, which enhance the film's resistance to moisture and improve its barrier properties, making it a more viable option for food packaging. This review explores the emerging field of starch-based sustainable edible films enhanced with bioactive components for food packaging applications. It delves into fabrication techniques, structural properties, and functional attributes, highlighting the potential of these innovative films to reduce environmental impact and preserve food quality. Key topics discussed include sustainability issues, processing methods, performance characteristics, and potential applications in the food industry. The review provides a comprehensive overview of current research and developments in starch-based edible films, presenting them as promising alternatives to conventional food packaging that can help reduce plastic waste and environmental impact.

Recent years have seen a growing interest in the use of digital tools for delivering person-centred mental health care. Experience Sampling Methodology (ESM), a structured diary technique for capturing moment-to-moment variation in experience and behaviour in service users' daily life, reflects a particularly promising avenue for implementing a person-centred approach. While there is evidence on the effectiveness of ESM-based monitoring, uptake in routine mental health care remains limited. The overarching aim of this hybrid effectiveness-implementation study is to investigate, in detail, reach, effectiveness, adoption, implementation, and maintenance as well as contextual factors, processes, and costs of implementing ESM-based monitoring, reporting, and feedback into routine mental health care in four European countries (i.e., Belgium, Germany, Scotland, Slovakia).

Despite the implementation of non-pharmaceutical interventions, the threat of coronavirus disease 2019 (COVID-19) remains significant on a global scale. Identifying external factors contributing to its spread is crucial, especially given the World Health Organization's recommendation emphasizing access to water, sanitation, and hygiene as essential in curbing COVID-19. There is a notable discrepancy in access to sanitation facilities, particularly evident in low- and middle-income countries. However, there is a lack of quantitative assessments regarding these factors. This study examines various environmental, socioeconomic, water, sanitation, and hygiene factors and their associations with COVID-19 incidence. All regions in the Philippines were categorized into clusters based on socioeconomic factors. A conceptual structural equation model (SEM) was developed using domain knowledge. The best-fitting SEM for each cluster was determined, and associations between factors and COVID-19 incidence were estimated. The correlation analysis revealed that rainfall, minimum temperature, and relative humidity were positively correlated with weekly COVID-19 incidence in urban regions. Maximum temperature, mean temperature, wind speed, and wind direction were negatively correlated with weekly COVID-19 incidence in rural regions, with time lags of 0, 3, and 7 weeks. In urban regions (Cluster 1), factors such as urbanization rate (1.00), area (-0.93), and population (0.54) were found to be associated with weekly COVID-19 incidence. Conversely, in rural regions (Cluster 2), factors including area (0.17), basic sanitation (0.84), and wind direction (0.83) showed associations with weekly COVID-19 incidence. These factors were causally associated with a latent variable reflecting the hidden confounders associated with COVID-19 incidence. It is important to note that sanitation factors were associated only in rural regions. Improving access to sanitation facilities in rural regions of the Philippines is imperative to effectively mitigate disease transmission in future pandemics. Identification of the causal effect of unobserved confounders with COVID-19 incidence is recommended for future research.

Hepatocellular carcinoma (HCC) represents a significant global health challenge with high incidence and mortality rates. T cells and natural killer (NK) cells are pivotal in this context, yet HCC can evade immune surveillance. CD161 (KLRB1), a C-type lectin receptor, modulates immune responses and is expressed on NK cells and a subset of T cells. Its relevance in HCC remains poorly understood, with conflicting findings regarding its impact on patient prognosis.

The 2022 wildfires in New Mexico, United States, were unparalleled compared to past wildfires in the state in both their scale and intensity, resulting in poor air quality and a catastrophic loss of habitat and livelihood. Among all wildfires in New Mexico in 2022, six wildfires were selected for our study based on the size of the burn area and their proximity to populated areas. These fires accounted for approximately 90 % of the total burn area in New Mexico in 2022. We used a regional chemical transport model and data-fusion technique to quantify the contribution of these six wildfires (April 6 to August 22) on particulate matter (PM: diameter ≤ 2.5 μm) and ozone (O) concentrations, as well as the associated health impacts from short-term exposure. We estimated that these six wildfires emitted 152 thousand tons of PM and 287 thousand tons of volatile organic compounds to the atmosphere. We estimated that the average daily wildfire smoke PM across New Mexico was 0.3 μg/m, though 1 h maximum exceeded 120 μg/m near Santa Fe. Average wildfire smoke maximum daily average 8-h O (MDA8-O) contribution was 0.2 ppb during the study period over New Mexico. However, over the state 1 h maximum smoke O exceeded 60 ppb in some locations near Santa Fe. Estimated all-cause excess mortality attributable to short term exposure to wildfire PM and MDA8-O from these six wildfires were 18 (95 % Confidence Interval (CI), 15-21) and 4 (95 % CI: 3-6) deaths. Additionally, we estimate that wildfire PM was responsible for 171 (95 %: 124-217) excess cases of asthma emergency department visits. Our findings underscore the impact of wildfires on air quality and human health risks, which are anticipated to intensify with global warming, even as local anthropogenic emissions decline.

A large body of research has shown that schizophrenia patients demonstrate increased brain structural aging. Although this process may be coupled with aberrant changes in intrinsic functional architecture of the brain, they remain understudied. We hypothesized that there are brain regions whose whole-brain functional connectivity at rest is differently associated with brain structural aging in schizophrenia patients compared to healthy controls. Eighty-four male schizophrenia patients and eighty-six male healthy controls underwent structural MRI and resting-state fMRI. The brain-predicted age difference (b-PAD) was a measure of brain structural aging. Resting-state fMRI was applied to obtain global correlation (GCOR) maps comprising voxelwise values of the strength and sign of functional connectivity of a given voxel with the rest of the brain. Schizophrenia patients had higher b-PAD compared to controls (mean between-group difference + 2.9 years). Greater b-PAD in schizophrenia patients, compared to controls, was associated with lower whole-brain functional connectivity of a region in frontal orbital cortex, inferior frontal gyrus, Heschl's Gyrus, plana temporale and polare, insula, and opercular cortices of the right hemisphere (rFTI). According to post hoc seed-based correlation analysis, decrease of functional connectivity with the posterior cingulate gyrus, left superior temporal cortices, as well as right angular gyrus/superior lateral occipital cortex has mainly driven the results. Lower functional connectivity of the rFTI was related to worse verbal working memory and language production. Our findings demonstrate that well-established frontotemporal functional abnormalities in schizophrenia are related to increased brain structural aging.

Neonicotinoid insecticides (NEOs) dominate the global pesticide market because of their low cost and effectiveness. However, epidemiological studies regarding the potential adverse health effects of exposure to NEOs before birth and in early childhood are limited. Therefore, this study investigated the associations between NEO exposure before birth and during early childhood and neurodevelopment. A total of 273 mother-child pairs were enrolled in this study. Mothers provided urine samples in the third trimester and breast milk during the first and third months of lactation. Their children provided urine samples and were evaluated for neurodevelopment by using the Bayley Scales of Infant and Toddler Development, Third Edition at 2-3 years (N = 96) and the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) at 4-6 years (N = 63). The sum of the concentrations of seven NEOs (ΣNEOs) and the relative potency factor of NEOs, based on comparison with imidacloprid (IMI), were used to assess total exposure to NEOs. Multivariate linear regression analyses were conducted to assess the associations between prenatal and childhood exposure to NEOs and neurodevelopment. The results of the analysis revealed that clothianidin (CLO) and thiamethoxam were the most common NEOs to which children in the Taipei metropolitan area were exposed and that exposure concentrations were high in the Taipei metropolitan area. Imidacloprid was the most frequently detected NEO during the postnatal period. Additionally, exposure to NEOs through breast milk was low. Exposure to CLO, ΣNEOs, and IMI in boys aged 4-6 years was negatively correlated with WPPSI-IV Fluid Reasoning Index. The results of this study indicate that exposure during the third trimester to NEOs does not affect neurodevelopment but that childhood exposure to NEOs may, especially for boys. Further studies with larger sample sizes are required to confirm the sex-specific associations between NEO exposure and neurodevelopment.

Asthma and obesity are frequent outcomes among individuals born extremely preterm and are associated with decreased lifespan. Neonatal inflammation is associated with chronic neurodevelopmental disorders; however, it is less studied in association with other later childhood chronic disorders in this population.

The coronavirus disease 2019 (COVID-19), one of the most significant recent emerging infectious diseases, has evolved into a global pandemic, resulting in an unprecedented public health crisis with substantial morbidity. The aim of this study was to investigate the care experiences of nursing staff during the COVID-19 pandemic.

Genetic discrimination is an evolving phenomenon that impacts fundamental human rights such as dignity, justice and equity. Although, in the past, various definitions to better conceptualize genetic discrimination have been proposed, these have been unable to capture several key facets of the phenomenon. In this Perspective, we explore definitions of genetic discrimination across disciplines, consider criticisms of such definitions and show how other forms of discrimination and stigmatization can compound genetic discrimination in a way that affects individuals, groups and systems. We propose a nuanced and inclusive definition of genetic discrimination, which reflects its multifaceted impact that should remain relevant in the face of an evolving social context and advancing science. We argue that our definition should be adopted as a guiding academic framework to facilitate scientific and policy discussions about genetic discrimination and support the development of laws and industry policies seeking to address the phenomenon.

An estimated one billion people globally are exposed to hazardous levels of lead (Pb), resulting in intellectual disabilities for over 600,000 children each year. This critical issue aligns with the expanding worldwide population and the demand for food security, emphasizing the urgency of effectively addressing heavy metal pollution especially from Pb for sustainable development. Phytoremediation, a highly favoured approach in conjunction with conventional physical, chemical, and microbial methods, is a promising approach to mitigating soil and environmental contamination. In this review, we delve into a range of soil pollution mitigation strategies, with focus on the mechanisms that underpin the phytoremediation of environmental Pb. This detailed exploration sheds light on the efficacy and complexities of utilizing plants for the detoxification and removal of lead from contaminated environments. It also examines strategies to enhance phytoremediation by incorporating microbiology, composting, nanotechnology, and foliar spraying. The potential remediation strategies largely depend on the investigation and incorporation of environmentally friendly catalysts, as well as the utilization of innovative methods such as genetic engineering to improve phytoremediation processes. Studies have also shown that biochar has the capability to lower heavy metal concentrations in plant branches by over 50%, without affecting the pH of the soil. Specifically, magnetic biochar (MBC) has been shown to decrease lead levels in plants by up to 42%. Employing these methods showcases an effective strategy to enhance the efficacy of remediation techniques and fosters sustainable solutions to the pervasive issue of Pb pollution, thereby contributing to sustainable development efforts globally.

This case series sheds light on the pulmonary diseases afflicting artisanal gold miners in Chunya district, Mbeya, Tanzania. We present 3 cases from a group of 21 miners. The patients, ranging in age and mining exposure, exhibited symptoms of severe pulmonary conditions, including pneumoconiosis, pulmonary hypertension and Cor pulmonale, attributed to prolonged exposure to dust and inadequate protective measures in mining environments. These cases underscore the urgent need for enhanced occupational health standards and preventive strategies in artisanal mining communities.

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient-weight-ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multi-center study, 92 adult LDLT with a final GRWR<=0.6 performed at 12 international liver transplant (LT) centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation (PFM), development of SFSS, morbidity and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day and one-year mortality. Pre-operative MELD and inpatient status were independent predictors for SFSS (p<0.05). Pre-LT renal dysfunction was an independent predictor of survival (Hazard ratio- 3.1;95% ci 1.1,8.9, p=0.035). PFH or PFM were not predictive of SFSS or survival. We report the largest ever multi-center study of LDLT outcomes using ultralow-GRWR grafts and for the first-time validate the ILTS-iLDLT-LTSI consensus definition and grading of SFSS. Pre-operative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

Many patients with eating disorders report exercise as a central symptom of their illness-as a way to compensate for food intake, prevent weight-gain, and/or reduce negative affect. Previous findings show associations between maladaptive exercise and more severe eating disorder pathology, higher risk for relapse, other co-morbid symptoms, and worse treatment outcome.

Physical inactivity is a major global health concern, contributing to the rising non-communicable disease burden. Elucidating barriers and facilitators influencing participation is critical to promoting activity. This study aimed to synthesize the literature and analyze the extent of research on determinants of physical activity engagement.

Obesity is a global health concern, and understanding its prevalence among medical students is crucial for shaping targeted interventions. This systematic review and meta-analysis aim to comprehensively assess the prevalence of obesity and overweight among medical students.

Exergame-based training is currently considered a more promising training approach than conventional physical and/or cognitive training.

Malaria remains a significant public health challenge in Sub-Saharan Africa (SSA), particularly affecting under-five (UN5) children. Despite global efforts to control the disease, its prevalence in high-risk African countries continues to be alarming, with records of substantial morbidity and mortality rates. Understanding the association of multiple childhood, maternal, and household factors with malaria prevalence, especially among vulnerable young populations, is crucial for effective intervention strategies.

This prebirth cohort study examined the relationship between breastfeeding duration and behavioral problems in five-year-old Japanese children.

A better understanding of lung cancer etiology and the development of screening biomarkers have important implications for lung cancer prevention.

In Mexico, anemia prevalence among women of reproductive age (WRA) decreased from 16.4% in 2006 to 11.6% in 2012, only to increase to 18.3% in 2016. The factors associated with this fluctuation are uncertain.

Despite a large growth in evidence on violence against women (VAW) over the last 25 years, VAW persists, as do gaps in the field's knowledge of how to prevent and respond to it. To ensure that research on VAW in low- and middle-income countries (LIMCs) is addressing the most significant gaps in knowledge, and to prioritise evidence needs to reduce VAW and better support victims/survivors, the Sexual Violence Research Initiative (SVRI) and Equality Institute (EQI) led a process of developing a global shared research agenda (GSRA) on VAW in LMICs.

Plastic pollution continuously accumulates in the environment and poses a global threat as it fragments into microplastics and nanoplastics that can harm ecosystems. To reduce the accumulation of microplastic and nanoplastic pollution, bioplastics made from biodegradable materials are promoted as a more sustainable alternative because it can degrade faster than plastics. However, plastics also leach out chemicals as they degrade and disintegrate, but the potential toxicity of these chemicals leaching out from plastics and especially bioplastics is poorly explored. Here, we determined the composition of leachates from plastics and bioplastics and tested their toxicity in Caenorhabditis elegans. LC-MS analysis of the plastic leachates revealed that bioplastics leached a wider array of chemicals than their counterpart plastics. Toxicity testing in our study showed that the leachates from plastics and bioplastics reduced lifespan, decreased locomotion, and induced neurotoxicity in C. elegans. Leachates from bioplastics reduced C. elegans lifespan more compared to leachates from plastics: by 7% to 31% for bioplastics and by 6% to 15% for plastics. Leachates from plastics decreased locomotion in C. elegans more compared to leachates from bioplastics: by 8% to 34% for plastics and by 11% to 24% for bioplastics. No changes were observed in the ability of the C. elegans to respond to mechanical stimuli. The leachates induced neurotoxicity in the following neurons at varying trends: cholinergic neurons by 0% to 53% for plastics and by 30% to 42% for bioplastics, GABAergic neurons by 3% to 29% for plastics and by 10% to 23% for bioplastics, and glutamatergic neurons by 3% to 11% for plastics and by 15% to 29% for bioplastics. Overall, our study demonstrated that chemicals leaching out from plastics and bioplastics can be toxic, suggesting that both plastics and bioplastics pose ecotoxicological and human health risks.

A prevalent challenge in neuropsychological assessment, particularly when utilizing instruments designed for controlled laboratory environments, is that the outcomes may not correspond to an individual's real-life status. Accordingly, assessments of visuospatial working memory (VSWM) conducted in such settings might fail to capture certain facets of this function, as it operates in real life. On the other hand, entirely ecological assessments may risk compromising internal validity. This study aimed to develop an intermediate mode of assessment that measures VSWM in older adults by employing a setting, a task, and a response format that aligns closely with both laboratory and ecological assessments. Furthermore, a preliminary investigation was carried out to study the variations in spatial cognition among different demographic groups.

CT1812 is a novel, brain penetrant small molecule modulator of the sigma-2 receptor (S2R) that is currently in clinical development for the treatment of Alzheimer's disease (AD). Preclinical and early clinical data show that, through S2R, CT1812 selectively prevents and displaces binding of amyloid beta (Aβ) oligomers from neuronal synapses and improves cognitive function in animal models of AD. SHINE is an ongoing Phase 2 randomized, double-blind, placebo-controlled clinical trial (COG0201) in participants with mild to moderate AD, designed to assess the safety and efficacy of 6 months of CT1812 treatment. To elucidate the mechanism of action in AD patients and pharmacodynamic biomarkers of CT1812, the present study reports exploratory cerebrospinal fluid (CSF) biomarker data from 18 participants in an interim analysis of the first set of patients in SHINE (part A). Untargeted mass spectrometry-based discovery proteomics detects >2000 proteins in patient CSF and has documented utility in accelerating the identification of novel AD biomarkers reflective of diverse pathophysiologies beyond amyloid and tau, and enabling identification of pharmacodynamic biomarkers in longitudinal interventional trials. We leveraged this technique to analyze CSF samples taken at baseline and after 6 months of CT1812 treatment. Proteome-wide protein levels were detected using tandem mass tag-mass spectrometry (TMT-MS), change from baseline was calculated for each participant, and differential abundance analysis by treatment group was performed. This analysis revealed a set of proteins significantly impacted by CT1812, including pathway engagement biomarkers (i.e., biomarkers tied to S2R biology) and disease modification biomarkers (i.e., biomarkers with altered levels in AD vs. healthy control CSF but normalized by CT1812, and biomarkers correlated with favorable trends in ADAS-Cog11 scores). Brain network mapping, Gene Ontology, and pathway analyses revealed an impact of CT1812 on synapses, lipoprotein and amyloid beta biology, and neuroinflammation. Collectively, the findings highlight the utility of this method in pharmacodynamic biomarker identification and providing mechanistic insights for CT1812, which may facilitate the clinical development of CT1812 and enable appropriate pre-specification of biomarkers in upcoming clinical trials of CT1812.

Problematic alcohol consumption is associated with risk behaviors associated with HIV transmission. Despite the high prevalence of problematic alcohol consumption in Ukraine, however, there are little empirical data examining its association with risk behaviors also associated with HIV transmission in men who have sex with men (MSM), a key population where HIV incidence is increasing, METHOD: Correlates of prevalent HIV infection and their association between drinking severity levels and behaviors also associated with increased likelihood of HIV acquisition were analyzed from a 2017 nationally representative survey (IBBS) of 4938 MSM in Ukraine using bivariate analyses and multivariate regression.

Depression ranks as one of the top five contributors to ill health in youth, the most formative period in life. Extensive research has highlighted the significant role of impulsivity in understanding depression. However, there has been limited exploration into how each dimension of impulsivity uniquely affect depressive symptoms, especially across crucial developmental stages like adolescence and young adulthood.

Disorganization is a nuclear dimension of psychosis, especially in schizophrenia. Despite its relevant association with poor prognosis and negative outcomes, it is still under-investigated compared to positive and negative symptoms, in particular at the onset of illness. This study explored disorganization in youth at Clinical High Risk for Psychosis (CHR-P) over a 2-year period. A sample of 180 CHR-P participants (50% males; 51.1% with baseline second-generation antipsychotic medication) recruited within a specialized CHR-P service completed the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Across the follow-up, we examined key associations of disorganization with other domains of psychopathology, functioning, and treatment response using Spearman's rank correlation coefficients and linear regression analyses. Our results showed a significant longitudinal reduction in disorganization severity levels across the follow-up. This decrease was significantly associated with improvements in negative symptoms and daily functioning, with a shorter duration of untreated psychiatric symptoms, and with baseline equivalent dose of antipsychotic medication. No significant longitudinal associations with other treatment component of the PARMS program were found. Our findings suggest a longitudinal improvement in disorganization dimension in CHR-P individuals, especially in the context of early interventions targeting reduction in the duration of untreated psychiatric symptoms and favoring a prompt antipsychotic therapy.

Human embryonic stem cells (hESCs) derived from blastocyst stage embryos present a primed state of pluripotency, whereas mouse ESCs (mESCs) display naïve pluripotency. Their unique characteristics make naïve hESCs more suitable for particular applications in biomedical research. This work aimed to derive hESCs from single blastomeres and determine their pluripotency state, which is currently unclear. We derived hESC lines from single blastomeres of 8-cell embryos and from whole blastocysts, and analysed several naïve pluripotency indicators, their transcriptomic profile and their trilineage differentiation potential. No significant differences were observed between blastomere-derived hESCs (bm-hESCs) and blastocyst-derived hESCs (bc-hESCs) for most naïve pluripotency indicators, including TFE3 localization, mitochondrial activity, and global DNA methylation and hydroxymethylation, nor for their trilineage differentiation potential. Nevertheless, bm-hESCs showed an increased single-cell clonogenicity and a higher expression of naïve pluripotency markers at early passages than bc-hESCs. Furthermore, RNA-seq revealed that bc-hESCs overexpressed a set of genes related to the post-implantational epiblast. Altogether, these results suggest that bm-hESCs, although displaying primed pluripotency, would be slightly closer to the naïve end of the pluripotency continuum than bc-hESCs.

Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC.

Pulse oximeters are essential for assessing blood oxygen levels in emergency departments, operating theatres, and hospital wards. However, although the role of pulse oximeters in detecting hypoxaemia and guiding oxygen therapy is widely recognised, their role in primary care settings is less clear. In this Viewpoint, we argue that pulse oximeters have a crucial role in risk-stratification in both hospital and primary care or outpatient settings. Our reanalysis of hospital and primary care data from diverse low-income and middle-income settings shows elevated risk of death for children with moderate hypoxaemia (ie, peripheral oxygen saturations [SpO] 90-93%) and severe hypoxaemia (ie, SpO <90%). We suggest that moderate hypoxaemia in the primary care setting should prompt careful clinical re-assessment, consideration of referral, and close follow-up. We provide practical guidance to better support front-line health-care workers to use pulse oximetry, including rethinking traditional binary SpO thresholds and promoting a more nuanced approach to identification and emergency treatment of the severely ill child.

Traditionally, behavioral, social, and health science researchers have relied on global/retrospective survey methods administered cross-sectionally (i.e., on a single occasion) or longitudinally (i.e., on several occasions separated by weeks, months, or years). More recently, social and health scientists have added daily life survey methods (also known as intensive longitudinal methods or ambulatory assessment) to their toolkit. These methods (e.g., daily diaries, experience sampling, ecological momentary assessment) involve dense repeated assessments in everyday settings. To facilitate research using daily life survey methods, we present SEMA ( http://www.SEMA3.com ), a platform for designing and administering intensive longitudinal daily life surveys via Android and iOS smartphones. SEMA fills an important gap by providing researchers with a free, intuitive, and flexible platform with basic and advanced functionality. In this article, we describe SEMA's development history and system architecture, provide an overview of how to design a study using SEMA and outline its key features, and discuss the platform's limitations and propose directions for future development of SEMA.

This study aims to identify the relationship between psychosocial factors and unmet needs among community-dwelling older adults who have received or who expect to receive formal home-based aged care services.

Populations who seek HIV pre-exposure prophylaxis (PrEP) are disproportionately affected by hepatitis A virus (HAV), hepatitis B virus (HBV) and human papillomavirus (HPV). We examined immunity/vaccination against these infections among participants in the Ontario PrEP cohort study (ON-PrEP).

Physicians and associate (non-physician) clinicians conduct cesarean sections in Tanzania and Malawi. Urogenital fistulas may occur as complications of cesarean section. Location and circumstances can indicate iatrogenic origin as opposed to ischemic injury following prolonged, obstructed labor.

Evaluate feasibility and impact of "Tracheostomy Team" on survival and length of stay (LOS) at a level IV NICU.

Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors.

Antibiotic resistance among bacteria is recognized as the primary factor contributing to the failure of treatment. In this research, our objective was to examine the prevalence of antibiotic resistance in H. pylori bacteria in Palestine. We enlisted 91 individuals suffering from dyspepsia, comprising 49 females and 42 males. These participants underwent esophagogastroduodenoscopy procedures with gastric biopsies. These biopsies were subsequently subjected to microbiological assessments and tested for their susceptibility to various antimicrobial drugs. Among the 91 patients, 38 (41.7%) exhibited the presence of H. pylori. Notably, Ciprofloxacin displayed the highest efficacy against H. pylori, followed by Levofloxacin, Moxifloxacin, and Amoxicillin, with resistance rates of 0%, 0%, 2.6%, and 18.4%, respectively. On the contrary, Metronidazole and Clarithromycin demonstrated the lowest effectiveness, with resistance percentages of 100% and 47.4%, respectively. The outcomes of this investigation emphasize that H. pylori strains within the Palestinian patient group exhibit substantial resistance to conventional first-line antibiotics like clarithromycin and metronidazole. However, alternative agents such as fluoroquinolones and amoxicillin remain efficacious choices. Consequently, we recommend favoring quinolone-based treatment regimens for H. pylori infections and adopting a more judicious approach to antibiotic usage among the Palestinian population.

Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes.

SARS-CoV-2 has become a global public health problem. Acute respiratory distress syndrome (ARDS) is the leading cause of death due to the SARS-CoV-2 infection. Pulmonary fibrosis (PF) is a severe and frequently reported COVID-19 sequela. In this study, an in vitro model of ARDS and PF caused by SARS-CoV-2 was established in MH-S, THP-1, and MRC-5 cells using pseudo-SARS-CoV-2 (PSCV). Expression of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and HIF-1α was increased in PSCV-infected MH-S and THP-1 cells, ARDS model, consistent with other profiling data in SARS-CoV-2-infected patients have been reported. Hypoxia-inducible factor-1 alpha (HIF-1α) siRNA and cobalt chloride were tested using this in vitro model. HIF-1α knockdown reduces inflammation caused by PSCV infection in MH-S and THP-1 cells and lowers elevated levels of CTGF, COLA1, and α-SMA in MRC-5 cells exposed to CPMSCV. Furthermore, apigetrin, a glycoside bioactive dietary flavonoid derived from several plants, including Crataegus pinnatifida, which is reported to be a HIF-1α inhibitor, was tested in this in vitro model. Apigetrin significantly reduced the increased inflammatory cytokine (IL-6, IL-1β, and TNF-α) expression and secretion by PSCV in MH-S and THP-1 cells. Apigetrin inhibited the binding of the SARS-CoV-2 spike protein RBD to the ACE2 protein. An in vitro model of PF induced by SARS-CoV-2 was produced using a conditioned medium of THP-1 and MH-S cells that were PSCV-infected (CMPSCV) into MRC-5 cells. In a PF model, CMPSCV treatment of THP-1 and MH-S cells increased cell growth, migration, and collagen synthesis in MRC-5 cells. In contrast, apigetrin suppressed the increase in cell growth, migration, and collagen synthesis induced by CMPSCV in THP-1 and MH-S MRC-5 cells. Also, compared to control, fibrosis-related proteins (CTGF, COLA1, α-SMA, and HIF-1α) levels were over two-fold higher in CMPSV-treated MRC-5 cells. Apigetrin decreased protein levels in CMPSCV-treated MRC-5 cells. Thus, our data suggest that hypoxia-inducible factor-1 alpha (HIF-1α) might be a novel target for SARS-CoV-2 sequela therapies and apigetrin, representative of HIF-1alpha inhibitor, exerts anti-inflammatory and PF effects in PSCV-treated MH-S, THP-1, and CMPVSC-treated MRC-5 cells. These findings indicate that HIF-1α inhibition and apigetrin would have a potential value in controlling SARS-CoV-2-related diseases.

Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.

To describe reasons for deviations from planned chemotherapy treatments in women with nonmetastatic breast cancer that contribute to less-than-planned receipt of chemotherapy.

Childhood obesity is a global public health issue, and the status of clinical practice guidelines (CPGs) as instruction manuals for the management of childhood obesity remains unclear. This study aims to identify and apprise the methodological and reporting quality of CPGs focused on childhood obesity and provide an overview of key recommendations.

The 2022 global outbreak of monkeypox virus (MPXV), previously confined to Central and West Africa, necessitates an enhanced understanding of its spread. Comprehensive genomic surveillance to understand the virus's evolution and spread is needed, particularly in Asia.

Peer support has been identified as an important aspect of rehabilitation for visually impaired adults. However, there is a limited exploration in rehabilitation studies literature of the identity-related impact of these interventions, both at an individual and collective level. Through attending to the discourses on blindness, well-being, and social inclusion that circulate in organization cultures, this article considers the role that peer support plays in forming "blind communities" with particular characteristics, and what these communities might model about life with blindness, both to newly blind persons and to society.

In 2023, Tennessee replaced $6.2 M in US Centers for Disease Control and Prevention (CDC) human immunodeficiency virus (HIV) prevention funding with state funds to redirect support away from men who have sex with men (MSM), transgender women (TGW), and heterosexual Black women (HSBW) and to prioritize instead first responders (FR), pregnant people (PP), and survivors of sex trafficking (SST).

For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms. To find the optimal individual dose and dosage strategy, specialized tools are used. Three tools have been proven useful to personalize drug treatments: therapeutic drug monitoring (TDM) of drug levels, pharmacogenetic testing (PG), and molecular neuroimaging.

Kidney allograft rejections are orchestrated by a variety of immune cells. Because of the complex histopathologic features, accurate pathological diagnosis poses challenges even for expert pathologists. The objective of this study was to unveil novel spatial indices associated with transplant rejection by using a spatial bioinformatic approach using 36-plex immunofluorescence image data.

Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce.

Tunneled hemodialysis catheters often have infectious or mechanical complications that require unplanned removal and replacement, but the optimal replacement strategy is unknown. This study described the real-world use of two strategies in Australia and compared the survival of replacement catheters inserted by either strategy.

In low-income countries, social norms play a significant role in intrahousehold food allocation practices. These norms can sometimes lead to discrimination against specific groups, posing a public health concern. This study focuses on the social norm surrounding food allocation within households and food taboos affecting adolescent girls in rural Ethiopia.

Understanding how pathogens spread across geographical space is fundamental for control measures such as vaccination. (the pneumococcus) is a respiratory bacterium responsible for a large proportion of infectious disease morbidity and mortality globally. Even in the post-vaccination era, the rates of invasive pneumococcal disease (IPD) remain stable in most countries, including Israel. To understand the geographical spread of the pneumococcus in Israel, we analysed 1174 pneumococcal genomes from patients with IPD across multiple regions. We included the evolutionary distance between pairs of isolates inferred using whole-genome data within a relative risk (RR) ratio framework to capture the geographical structure of . While we could not find geographical structure at the overall lineage level, the extra granularity provided by whole-genome sequence data showed that it takes approximately 5 years for invasive pneumococcal isolates to become fully mixed across the country.This article contains data hosted by Microreact.

The objective of this study was to utilize data from the Global Burden of Disease Study (GBD) 2019 to estimate the patterns and prevalence of mild traumatic brain injury (mTBI) from 1990 to 2019, with the intention of informing the development of efficacious intervention strategies.

SUMMARYSeveral examples of high-impact cross-species transmission of newly emerging or re-emerging bat-borne viruses, such as Sudan virus, Nipah virus, and severe acute respiratory syndrome coronavirus 2, have occurred in the past decades. Recent advancements in next-generation sequencing have strengthened ongoing efforts to catalog the global virome, in particular from the multitude of different bat species. However, functional characterization of these novel viruses and virus sequences is typically limited with regard to assessment of their cross-species potential. Our understanding of the intricate interplay between virus and host underlying successful cross-species transmission has focused on the basic mechanisms of entry and replication, as well as the importance of host innate immune responses. In this review, we discuss the various roles of the respective molecular mechanisms underlying cross-species transmission using different recent bat-borne viruses as examples. To delineate the crucial cellular and molecular steps underlying cross-species transmission, we propose a framework of overall characterization to improve our capacity to characterize viruses as benign, of interest, or of concern.

Metabolic risk factors significantly elevate the risk of cardiovascular diseases (CVDs) and are recognized as one of the primary contributors to these conditions. This study explored the trends and percentage changes in disability-adjusted life years (DALYs) attributable to metabolic risk factors for CVD from 1990 to 2019. Data from the Global Burden of Disease study was utilized to depict changes across metabolic risk factors by sociodemographic indices and sex groups. The Mann-Kendall test was employed to ascertain the significance of these trends. The findings indicate that the DALY percentage change over these years was more pronounced in low-middle and middle Socio-demographic Index (SDI) countries than in others. The most substantial percentage increase, approximately 60%, was observed in regions with low SDI, attributed to high body mass index (BMI). On average, the greatest DALYs were associated with high systolic blood pressure (SBP). Moreover, the trend for high low-density lipoprotein cholesterol and high SBP declined in countries with high SDI. It can be concluded that to mitigate the global mortality and morbidity from heart diseases, there needs to be a focused emphasis on managing metabolic risk factors, particularly in low-Middle and middle SDI countries.

Cardiovascular diseases (CVDs) stand as a predominant global health concern, introducing vast socioeconomic challenges. In addressing this pressing dilemma, enhanced diagnostic modalities have become paramount, positioning electrochemical biosensing as an instrumental innovation. This comprehensive review navigates the multifaceted terrain of CVDs, elucidating their defining characteristics, clinical manifestations, therapeutic avenues, and intrinsic risk factors. Notable emphasis is placed on pivotal diagnostic tools, spotlighting cardiac biomarkers distinguished by their unmatched clinical precision in terms of relevance, sensitivity, and specificity. Highlighting the broader repercussions of CVDs, there emerges an accentuated need for refined diagnostic strategies. Such an exploration segues into a profound analysis of electrochemical biosensing, encapsulating its foundational principles, diverse classifications, and integral components, notably recognition molecules and transducers. Contemporary advancements in biosensing technologies are brought to the fore, emphasizing pioneering electrode architectures, cutting-edge signal amplification processes, and the synergistic integration of biosensors with microfluidic platforms. At the core of this discourse is the demonstrated proficiency of biosensors in detecting cardiovascular anomalies, underpinned by empirical case studies, systematic evaluations, and clinical insights. As the narrative unfolds, it addresses an array of inherent challenges, spanning intricate technicalities, real-world applicability constraints, and regulatory considerations, finally, by casting an anticipatory gaze upon the future of electrochemical biosensing, heralding a new era of diagnostic tools primed to revolutionize cardiovascular healthcare.

Piperaquine (PPQ) is widely used in combination with dihydroartemisinin as a first-line treatment against malaria. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the () and increased copies of (). We generated a cross between a Cambodia-derived multidrug-resistant KEL1/PLA1 lineage isolate (KH004) and a drug-susceptible Malawian parasite (Mal31). Mal31 harbors a wild-type (3D7-like) allele and a single copy of , while KH004 has a chloroquine-resistant (Dd2-like) allele with an additional G367C substitution and multiple copies of . We recovered 104 unique recombinant parasites and examined a targeted set of progeny representing all possible combinations of variants at and . We performed a detailed analysis of competitive fitness and a range of PPQ susceptibility phenotypes with these progenies, including PPQ survival assay, area under the dose response curve, and a limited point IC. We find that inheritance of the KH004 allele is required for reduced PPQ sensitivity, whereas copy number variation in further decreases susceptibility but does not confer resistance in the absence of additional mutations in . A deep investigation of genotype-phenotype relationships demonstrates that progeny clones from experimental crosses can be used to understand the relative contributions , , and parasite genetic background to a range of PPQ-related traits. Additionally, we find that the resistance phenotype associated with parasites inheriting the G367C substitution in pfcrt is consistent with previously validated PPQ resistance mutations in this transporter.IMPORTANCEResistance to piperaquine, used in combination with dihydroartemisinin, has emerged in Cambodia and threatens to spread to other malaria-endemic regions. Understanding the causal mutations of drug resistance and their impact on parasite fitness is critical for surveillance and intervention and can also reveal new avenues to limiting the evolution and spread of drug resistance. An experimental genetic cross is a powerful tool for pinpointing the genetic determinants of key drug resistance and fitness phenotypes and has the distinct advantage of quantifying the effects of naturally evolved genetic variation. Our study was strengthened since the full range of copies of KH004 was inherited among the progeny clones, allowing us to directly test the role of the copy number on resistance-related phenotypes in the context of a unique allele. Our multigene model suggests an important role for both loci in the evolution of this multidrug-resistant parasite lineage.

Advanced hepatocellular carcinoma (HCC) represents a significant global health burden, whose treatment has been recently revolutionized by the advent of biologic treatments. Despite that, innovative therapeutic regimens and approaches, especially immune-based, remain to be explored aiming at extending the therapeutic benefits to a wider population of patients.

This comprehensive review explores the multifaceted role of sortilin, a key receptor in lipid metabolism, within the context of cardiovascular diseases (CVDs), the leading cause of global mortality.

Renal fibrosis is the result of all chronic kidney diseases and is becoming a major global health hazard. Currently, traditional treatments for renal fibrosis are difficult to meet clinical needs due to shortcomings such as poor efficacy or highly toxic side effects. Therefore, therapeutic strategies that target the kidneys are needed to overcome these shortcomings. Drug delivery can be attained by improving drug stability and addressing controlled release and targeted delivery of drugs in the delivery category. By combining drug delivery technology with nanosystems, controlled drug release and biodistribution can be achieved, enhancing therapeutic efficacy and reducing toxic cross-wise effects. This review discusses nanomaterial drug delivery strategies reported in recent years. Firstly, the present review describes the mechanisms of renal fibrosis and anti-renal fibrosis drug delivery. Secondly, different nanomaterial drug delivery strategies for the treatment of renal injury and fibrosis are highlighted. Finally, the limitations of these strategies are also discussed. Investigating various anti-renal fibrosis drug delivery strategies reveals the characteristics and therapeutic effects of various novel nanosystem-derived drug delivery approaches. This will serve as a reference for future research on drug delivery strategies for renal fibrosis treatment.

Communication is fundamental to effective surgical coaching. This can be challenging for training during image-guided procedures where coaches and trainees need to articulate technical details on a monitor. Telestration devices that annotate on monitors remotely could potentially overcome these limitations and enhance the coaching experience. This study aims to evaluate the value of a novel telestration device in surgical coaching.

Digital phenotyping (DP) enables objective measurements of patient behavior and may be a useful tool in assessments of quality-of-life and functional status in neuro-oncology patients. We aimed to identify trends in mobility among patients with glioblastoma (GBM) using DP.

Objectives-This report examines changes in telemedicine use among U.S. adults between 2021 and 2022 by selected sociodemographic and geographic characteristics. Methods-Data from the 2021 and 2022 National Health Interview Survey were used to assess changes between these 2 years in the percentage of adults who used telemedicine in the previous 12 months, by sex, age, race and Hispanic origin, family income, education, region of residence, urbanization level, and health insurance coverage. Results-Overall, the percentage of adults who used telemedicine in the past 12 months decreased from 37.0% in 2021 to 30.1% in 2022. This pattern was observed across several sociodemographic and geographic characteristics, such as sex, family income, education, region, and urbanization level. Women, adults with a college degree or higher, and adults living in more urban areas were all more likely to use telemedicine in 2022. In 2021 and 2022, uninsured adults ages 18-64 were less likely to use telemedicine compared with those who had private or public insurance, while adults age 65 and older who had Medicare only were less likely to use telemedicine compared with those with other types of insurance. However, for both age groups, telemedicine use decreased from 2021 to 2022 for all insurance types except public coverage for adults ages 18-64. Summary-National Health Interview Survey data may be used to monitor national trends and understand patterns of telemedicine use by sociodemographic and geographic characteristics as the transition forward from the global COVID-19 pandemic continues.

In KEYNOTE-522 (NCT03036488), neoadjuvant pembrolizumab+chemotherapy then adjuvant pembrolizumab significantly improved pathological complete response and event-free survival vs neoadjuvant chemotherapy in early-stage triple-negative breast cancer (TNBC). We report patient-reported outcomes (PROs) from KEYNOTE-522.

Stroke is a significant public health challenge as it is the second most common cause of death and the third leading cause of disability globally. Additionally, stroke incidence and the number of stroke deaths has been rising. Efforts to prevent stroke have been made, including high-risk approaches where patients are screened for cardiovascular risk factors, and population-based approaches which attempt to reduce stroke rates by improving overall population health.

Gastrointestinal cancer poses a considerable global health risk, encompassing a heterogeneous spectrum of malignancies that afflict the gastrointestinal tract. It is significant to develop efficacious therapeutic agents, as they are indispensable for both the treatment and prevention of this formidable disease.

Electroencephalogram (EEG)-based emotion recognition has become a research hotspot in the field of brain-computer interface. Previous emotion recognition methods have overlooked the fusion of multi-domain emotion-specific information to improve performance, and faced the challenge of insufficient interpretability. In this paper, we proposed a novel EEG emotion recognition model that combined the asymmetry of the brain hemisphere, and the spatial, spectral, and temporal multi-domain properties of EEG signals, aiming to improve emotion recognition performance. Based on the 10-20 standard system, a global spatial projection matrix (GSPM) and a bi-hemisphere discrepancy projection matrix (BDPM) are constructed. A dual-stream spatial-spectral-temporal convolution neural network is designed to extract depth features from the two matrix paradigms. Finally, the transformer-based fusion module is used to learn the dependence of fused features, and to retain the discriminative information. We conducted extensive experiments on the SEED, SEED-IV, and DEAP public datasets, achieving excellent average results of 98.33/2.46 %, 92.15/5.13 %, 97.60/1.68 %(valence), and 97.48/1.42 %(arousal) respectively. Visualization analysis supports the interpretability of the model, and ablation experiments validate the effectiveness of multi-domain and bi-hemisphere discrepancy information fusion.

Accurate skin lesion segmentation from dermoscopic images is of great importance for skin cancer diagnosis. However, automatic segmentation of melanoma remains a challenging task because it is difficult to incorporate useful texture representations into the learning process. Texture representations are not only related to the local structural information learned by CNN, but also include the global statistical texture information of the input image. In this paper, we propose a transFormer network (SkinFormer) that efficiently extracts and fuses statistical texture representation for Skin lesion segmentation. Specifically, to quantify the statistical texture of input features, a Kurtosis-guided Statistical Counting Operator is designed. We propose Statistical Texture Fusion Transformer and Statistical Texture Enhance Transformer with the help of Kurtosis-guided Statistical Counting Operator by utilizing the transformer's global attention mechanism. The former fuses structural texture information and statistical texture information, and the latter enhances the statistical texture of multi-scale features. Extensive experiments on three publicly available skin lesion datasets validate that our SkinFormer outperforms other SOAT methods, and our method achieves 93.2% Dice score on ISIC 2018. It can be easy to extend SkinFormer to segment 3D images in the future. Our code is available at https://github.com/Rongtao-Xu/SkinFormer.

Our goal was to systematically review the most commonly used validated questionnaires in recent global literature on stress urinary incontinence (SUI) treatment.

As human life expectancy continues to rise, becoming a pressing global concern, it brings into focus the underlying mechanisms of aging. The increasing lifespan has led to a growing elderly population grappling with age-related diseases (ARDs), which strains healthcare systems and economies worldwide. While human senescence was once regarded as an immutable and inexorable phenomenon, impervious to interventions, the emerging field of geroscience now offers innovative approaches to aging, holding the promise of extending the period of healthspan in humans. Understanding the intricate links between aging and pathologies is essential in addressing the challenges presented by aging populations. A substantial body of evidence indicates shared mechanisms and pathways contributing to the development and progression of various ARDs. Consequently, novel interventions targeting the intrinsic mechanisms of aging have the potential to delay the onset of diverse pathological conditions, thereby extending healthspan. In this narrative review, we discuss the most promising methods and interventions aimed at modulating aging, which harbor the potential to mitigate ARDs in the future. We also outline the complexity of senescence and review recent empirical evidence to identify rational strategies for promoting healthy aging.

The need for a global core competency and capability framework for advanced practice physiotherapy is important due to the rapidly changing nature of health care delivery internationally and the need to standardize advanced practice physiotherapy.

In June 2024, the African Journal of Reproductive Health will begin its 28th year of publication. The International Conference on Population and Development (ICPD), held in 1994 in Cairo, was the impetus to start this peer-reviewed learned journal in the context of the anticipated increase in activities relating to sexual and reproductive health and rights in sub-Saharan Africa, to document achievements and successes while also pinpointing areas requiring remedial actions. Undoubtedly, the Journal has achieved these objectives in many phenomenal respects. First published as a biannual in 1997, the Journal became a quarterly in 2000, bimonthly in 2010, and, since January 2022, has been a monthly. The Journal is now ranked among the most influential in the fields of reproductive health and reproductive medicine not only in Africa1,2 , but worldwide3,4 .

Male infertility is a pressing global issue, prompting the need for biomarkers correlating with seminal parameters for diagnosis. Our study investigated 10 biochemical and energetic parameters in the seminal plasma and blood sera of fertile (25 subjects) and infertile (88 subjects) Polish men, correlations between their levels in seminal plasma and semen quality, and correlations between blood sera and seminal plasma levels of examined parameters. Infertile men displayed elevated seminal plasma glucose and fructose but reduced HDL levels compared to fertile men. We observed also weak negative correlations between seminal plasma triglycerides and sperm concentration in both groups. Moreover, infertile men exhibited positive correlations between seminal plasma HDL/LDL concentrations and sperm concentration. Fertile men showed moderate negative correlations between glucose/triglycerides concentrations and sperm count and between seminal plasma triglycerides levels and sperm vitality. Semen volume correlated with triglycerides (negative) and fructose (positive) concentrations in infertile men. Sperm motility correlated negatively with total cholesterol, LDL, and triglycerides concentrations in fertile men, and weakly with AMP-activated protein kinase in infertile men. Weak negative correlations between seminal plasma fructose/AMP-activated protein kinase concentrations and sperm progressive motility were observed in infertile men, whereas in fertile men seminal plasma AMP-activated protein kinase levels were positively correlated with progressive motility. Correlation analysis between blood serum and seminal plasma parameters revealed intriguing connections, notably regarding LDL, AMP-activated protein kinase, and carnitine, suggesting systemic influences on seminal plasma composition. These findings emphasize the complex interplay between metabolic factors and sperm parameters, offering promising directions for future research in male infertility diagnostics and therapeutics.

Asylum seekers, migrants, and refugees from African countries may have significant health needs, resulting in economic implications for receiving countries around the world. The risk of mental illness is higher in these communities because of factors like violence, deprivation, and post-immigration challenges.

The 17 Workshop on Recent Issues in Bioanalysis (17 WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with this NEW Regulation" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17 edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication covers the recommendations on Mass Spectrometry Assays, Regulated Bioanalysis/BMV (Part 1A) and Regulatory Inputs (Part 1B). Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 7 and 8 (2024), respectively.

Chemical contamination and pollution are an ongoing threat to human health and the environment. The concern over the consequences of chemical exposures at the global level continues to grow. Because resources are constrained, there is a need to prioritize interventions focused on the greatest health impact. Data, especially related to chemical exposures, are rarely available for most substances of concern, and alternate methods to evaluate their impact are needed.

Routine HIV viral load testing is important for evaluating HIV treatment outcomes, but conventional viral load testing has many barriers including expensive laboratory equipment and lengthy results return times to patients. A point-of-care viral load testing technology, such as GeneXpert HIV-1 quantification assay, could reduce these barriers by decreasing cost and turnaround time, however real-world performance is limited. We conducted a secondary analysis using 900 samples collected from participants in two studies to examine the performance of GeneXpert as point-of-care viral load compared to standard-of-care testing (which was conducted with two centralized laboratories using traditional HIV-1 RNA PCR quantification assays). The two studies, Opt4Kids (n = 704 participants) and Opt4Mamas (n = 820 participants), were conducted in western Kenya from 2019-2021 to evaluate the effectiveness of a combined intervention strategy, which included point-of-care viral load testing. Paired viral load results were compared using four different thresholds for virological non-suppression, namely ≥50, ≥200, ≥400, ≥1000 copies/ml. At a threshold of ≥1000 copies/mL, paired samples collected on the same day: demonstrated sensitivities of 90.0% (95% confidence interval [CI] 68.3, 98.8) and 66.7% (9.4, 99.2), specificities of 98.4% (95.5, 99.7) and 100% (96.5, 100), and percent agreements of 97.7% (94.6, 99.2) and 99.1% (95.0, 100) in Opt4Kids and Opt4Mamas studies, respectively. When lower viral load thresholds were used and the paired samples were collected an increasing number of days apart, sensitivity, specificity, and percent agreement generally decreased. While specificity and percent agreement were uniformly high, sensitivity was lower than expected. Non-specificity of the standard of care testing may have been responsible for the sensitivity values. Nonetheless, our results demonstrate that GeneXpert may be used reliably to monitor HIV treatment in low- and middle- income countries to attain UNAID's 95-95-95 HIV goals.

There is limited understanding of how social determinants of health (SDOH) impact family decision-making when seeking surgical care for children. Our objectives of this study are to identify key family experiences that contribute to decision-making when accessing surgical care for children, to confirm if family experiences impact delays in care, and to describe differences in family experiences across populations (race, ethnicity, socioeconomic status, rurality).

Uganda has a high demand for neurosurgical and neurological care. 78% of the over 50 million population reside in rural and remote communities where access to neurosurgical and neurological services is lacking. This study aimed to determine the feasibility, appropriateness, and usability of mobile neuro clinics (MNCs) in providing neurological care to rural and remote Ugandan populations.

Uncorrected refractive errors pose a significant challenge globally, particularly in remote regions of low-middle income countries where access to optometric care is often limited. Telerefraction, which involves refraction by a trained technician followed by real-time consultation with remote optometrist, is a promising approach for such remote settings. This study aimed to evaluate the accuracy of this model.

HIV, opioid use disorder (OUD), and mental health challenges share multiple syndemic risk factors. Each can be effectively treated with routine outpatient appointments, medication management, and psychosocial support, leading implementers to consider integrated screening and treatment for OUD and mental health in HIV care. Provider perspectives are crucial to understanding barriers and strategies for treatment integration.

The role of early life stressors in subjective aging is weakly understood, especially in low- to middle-income countries. This paper investigated how early life stressors encountered in armed conflict influence subjective age among Vietnamese older adults who experienced war over decades of their early life.