The maternal and newborn health eCohort to track longitudinal care quality: study protocol and survey development
The MNH eCohort was developed to fill gaps in maternal and newborn health (MNH) care quality measurement. In this paper, we describe the survey development process, recruitment strategy, data collection procedures, survey content and plans for analysis of the data generated by the study. We also compare the survey content to that of existing multi-country tools on MNH care quality. The eCohort is a longitudinal mixed-mode (in-person and phone) survey that will recruit women in health facilities at their first antenatal care (ANC) visit. Women will be followed via phone survey until 10-12 weeks postpartum. User-reported information will be complemented with data from physical health assessments at baseline and endline, extraction from MNH cards, and a brief facility survey. The final MNH eCohort instrument is centered around six key domains of high-quality health systems including competent care (content of ANC, delivery, and postnatal care for the mother and newborn), competent systems (prevention and detection, timely care, continuity, integration), user experience, health outcomes, confidence in the health system, and economic outcomes. The eCohort combines the maternal and newborn experience and, due to its longitudinal nature, will allow for quality assessment according to specific risks that evolve throughout the pregnancy and postpartum period. Detailed information on medical and obstetric history and current health status of respondents and newborns will allow us to determine whether women and newborns at risk are receiving needed care. The MNH eCohort will answer novel questions to guide health system improvements and to fill data gaps in implementing countries.
Pertussis vaccine effectiveness following country-wide implementation of a hexavalent acellular pertussis immunization schedule in infants and children in Panama
Despite high pediatric vaccination coverage rates (VCRs), pertussis incidence has increased worldwide, including in several countries in Latin America in the last two decades. Given the few vaccine effectiveness (VE) studies in Latin American countries, this retrospective, observational, cohort study estimated the effectiveness of hexavalent acellular (aP) primary and booster vaccination (wP) against pertussis in infants (6.5-18.5 months) and children (18.5-48.5 and 48.5-72.5 months) in Panama. Age-specific incidence rates (IRs) were calculated for the vaccine's pre-initiation (2001-2013), initiation (2014), and post-initiation (2015-2019) periods. VCRs and trends were determined, and VE was analyzed using a case coverage or screening method to compare proportions of vaccinated cases and vaccinated individuals in the population. Between 2001-2019, 868 confirmed pertussis cases were reported in Panama; 712 (82.0%; 54.8 cases/year) during the pre-initiation period, 19 (2.2%; 19 cases/year) during the initiation period, and 137 (15.8%; 27.4 cases/year) during the post-initiation period. Panama underwent cyclical increases in IRs, which varied between age groups. VCRs increased for primary and booster doses. Between 2015 and 2019, third-dose yearly vaccine coverage increased, on average, 3.3%. Specifically, during the post-initiation period, 109/137 (79.6%) of cases were unvaccinated. Relative VE was estimated at 96.2% [95% CI: 86.5%, 98.9%] with three doses; 100% with 4 and 5 booster doses. Absolute VE was estimated at 99.3% with three doses only. These results show that vaccination played an important role in maintaining a low number of pertussis cases in Panama, affirming the need for sustained investment and commitment to vaccination programs.
Efficacy and Safety of bimekizumab in elderly patients: real-world multicenter retrospective study - IL PSO (Italian Landscape Psoriasis)
The aim of this multicenter observational study is to report data from real world on the use of bimekizumab in patients aged ≥ 65 years with moderate-to-severe plaque psoriasis. Elderly patients are poorly represented in clinical trials on bimekizumab for plaque psoriasis, and real-world studies are important to guide clinical choices. A retrospective multicenter study was conducted in 33 dermatological outpatient clinics in Italy. Patients aged ≥ 65 years, with moderate-to-severe plaque psoriasis and treated with bimekizumab were enrolled. No exclusion criteria were applied. Bimekizumab was administered following the Italian Guidelines for the management of plaque psoriasis and according to the summary of product characteristics, in adult patients who were candidates for systemic treatments. Overall, 98 subjects were included, and received bimekizumab up to week 36. Clinical and demographic data were collected before the initiation of treatment with bimekizumab. At baseline and each dermatological examination (4, 16, and 36 weeks), clinical outcomes were measured by the following parameters: (1) PASI score; (2) site-specific (scalp, palmoplantar, genital, nail) Psoriasis Global Assessment (PGA). At each visit, the occurrence of any adverse events (AEs) was recorded, including serious AEs and AEs leading to bimekizumab discontinuation. The mean PASI score was 16.6 ± 9.4 at baseline and significantly decreased to 4.3 ± 5.2 after 4 weeks ( < 0.001), and 1.1 ± 1.7 after 16 week ( < 0.001). This level of improvement was maintained after 36 weeks ( < 0.001). PASI ≤2 was recorded in 36 (36.7%) at week 4, 68% and 69.4% at week 16 and 36, respectively. By week 16, 86/98 (87.8%) patients reached PASI75, 71/98 (72.4%) obtained PASI90, and 52/98 (53.1%) PASI100. Binary logistic regression tests showed a significant association of PASI100 by week 4 with lower PASI at baseline. PASI 100 at 16 or 36 weeks was not associated with baseline PASI, obesity, age, gender, previously naïve state, and presence of psoriatic arthritis. Patients naïve to biologics at baseline had similar response to bimekizumab as non-naïve subjects. Bimekizumab is a suitable option for elder patients as it is effective, tolerated and has a convenient schedule.
Corrigendum to "Life expectancy gains from dietary modifications: a comparative modeling study in 7 countries" [Am J Clin Nutr 120 (2024) 170-177]
Sex differences in early-onset atrial fibrillation in Norwegian primary care: a retrospective national database analysis
Individual variation in the need for healthcare constitutes knowledge gaps for young atrial fibrillation (AF) patients. We aimed to estimate the prevalence and primary care burden of early-onset AF in Norway, emphasising sex differences, in a nationwide healthcare database.
Influence of Large-Scale Brain State Dynamics on the Evoked Response to Brain Stimulation
Understanding how spontaneous brain activity influences the response to neurostimulation is crucial for the development of neurotherapeutics and brain-computer interfaces. Localized brain activity is suggested to influence the response to neurostimulation, but whether fast-fluctuating (i.e., tens of milliseconds) large-scale brain dynamics also have any such influence is unknown. By stimulating the prefrontal cortex using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG), we examined how dynamic global brain state patterns, as defined by microstates, influence the magnitude of the evoked brain response. TMS applied during what resembled the canonical microstate C was found to induce a greater evoked response for up to 80 milliseconds compared to other microstates. This effect was found in a repeated experimental session, was absent during sham stimulation, and was replicated in an independent dataset. Ultimately, ongoing and fast-fluctuating global brain states, as probed by microstates, may be associated with intrinsic fluctuations in connectivity and excitation-inhibition balance and influence the neurostimulation outcome. We suggest that the fast-fluctuating global brain states be considered when developing any related paradigms. Previous findings suggested local spontaneous neural oscillations can influence neurophysiological response to stimuli. However, beyond the local oscillatory activity, the brain state is rapidly fluctuating on a millisecond time resolution on a global spatial scale. We investigated whether these rapid global fluctuations influenced the evoked response to brain stimulation. We used combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) to stimulate the prefrontal cortex while recording global brain states via EEG microstates. The evoked neurophysiological response was significantly larger when stimulation was applied after the occurrence of a specific global brain state (i.e., microstate C) linked to mind-wandering. The finding was selective to active stimulation, replicated for the same individuals in a repeated session, and replicated in an entirely independent dataset.
Implementation of Maternal and Newborn Health Mobile Phone E-Cohorts to Track Longitudinal Care Quality in Low- and Middle-Income Countries
The maternal and newborn health (MNH) eCohort is a new mixed-mode (in-person and phone) longitudinal survey aiming to provide data on novel and undermeasured dimensions of quality along the MNH continuum of care. We describe implementation experiences and lessons learned in Ethiopia, India, Kenya, and South Africa to inform future longitudinal mobile phone-based studies on health system quality.
Single-cell RNA sequencing reveals the effects of high-fat diet on oocyte and early embryo development in female mice
Obesity is a global health issue with detrimental effects on various human organs, including the reproductive system. Observational human data and several lines of animal experimental data suggest that maternal obesity impairs ovarian function and early embryo development, but the precise pathogenesis remains unclear.
What Do Breast Cancer Previvors Tell Us About Their Stories? To Know or Not to Know?
This study aimed to explore the (1) experiences of breast cancer previvor women during genetic testing; (2) perceptions of the impact of genetic testing on their personal, social, family, and professional lives; and (3) views on breast cancer prevention and follow-up processes. This study focused on the risk of breast cancer in persons with BRCA mutations.
Socioeconomic benefits associated with bats
While bats are tremendously important to global ecosystems, they have been and continue to be threatened by loss of habitat, food, or roosts, pollution, bat diseases, hunting and killing. Some bat species have also been implicated in the transmission of infectious disease agents to humans. While One Health efforts have been ramped up recently to educate and protect human and bat health, such initiatives have been limited by lack of adequate data on the pathways to ensure their support. For instance, data on the role of bats in supporting different components of human welfare assets would be utilized as a stepping stone to champion conservation campaigns. Unfortunately, these data are limited and efforts to synthesize existing literature have majorly focused on few components human welfare leaving other important aspects.
Enterobacter adelaidei sp. nov. Isolation of an extensively drug resistant strain from hospital wastewater in Australia and the global distribution of the species
Enterobacter species are included among the normal human gut microflora and persist in a diverse range of other environmental niches. They have become important opportunistic nosocomial pathogens known to harbour plasmid-mediated multi-class antimicrobial resistance (AMR) determinants. Global AMR surveillance of Enterobacterales isolates shows the genus is second to Klebsiella in terms of frequency of carbapenem resistance. Enterobacter taxonomy is confusing and standard species identification methods are largely inaccurate or insufficient. There are currently 27 named species and a total of 46 taxa in the genus distinguishable via average nucleotide identity (ANI) calculation between pairs of genomic sequences. Here we describe an Enterobacter strain, ECC3473, isolated from the wastewater of an Australian hospital whose species could not be determined by standard methods nor by ribosomal RNA gene multi-locus typing.
Process evaluation of an mHealth-based school education program to reduce salt intake scaling up in China (EduSaltS): a mixed methods study using the RE-AIM framework
An mHealth-based school health education platform (EduSaltS) was promoted in real-world China to reduce salt intake among children and their families. This progress evaluation explores its implementation process and influencing factors using mixed methods.
Maternal depression and early childhood development among children aged 24-59 months: the mediating effect of responsive caregiving
This study examined whether maternal depression is related to Early Childhood Developmental (ECD) delay among children by quantifying the mediating contribution of responsive caregiving. We used data from 1235 children (Children's mean age = 50.4 months; 582 girls, 653 boys, 93.9% were Han), selected through convenience sampling, in 2021. 4.7% of children had ECD delay, 34.3% of mothers had depression. Children with depressed mothers were less likely to receive responsive caregiving (OR 4.35, 95% CI 2.60-7.27), and those who did not receive responsive caregiving were more likely to experience ECD delay (OR 3.89, 95% CI 1.89-8.02). Responsive caregiving partly mediated the relationship between maternal depression and ECD. Early intervention for children with depressed mothers is worthy of further investigation.
Discursive framework for a multi-disease digital health passport in Africa: a perspective
Africa's dual burden of rising incidence of infectious diseases and increasing prevalence of non-communicable diseases (NCDs), such as cardiovascular diseases and diabetes, demands innovative approaches to disease surveillance, response, and cross-border health management in response to growing economic integration and global connectivity. In this context, we propose a discursive framework for the development and implementation of a multi-disease digital health passport (MDDHP) in Africa. The MDDHP would serve as a secure platform for storing and sharing individual health data, offering a comprehensive solution to track and respond to infectious diseases, facilitate the management of NCDs, and improve healthcare access across borders. Empowering individuals to proactively manage their health and improve overall outcomes is a key aspect of the MDDHP. In the paper, we examine the key elements necessary to effectively implement MDDHP, focusing on minimizing risks, maintaining efficacy, and driving its adoption while also taking into consideration the unique contexts of the continent. The paper is intended to provide an understanding of the key principles involved and contribute to the discussion on the development and successful implementation of MDDHP in Africa.
Proteomic analysis of carbapenem-resistant Klebsiella pneumoniae outer membrane vesicles under the action of phages combined with tigecycline
Klebsiella pneumoniae is the most commonly encountered pathogen in clinical practice. Widespread use of broad-spectrum antibiotics has led to the current global dissemination of carbapenem-resistant K. pneumoniae, which poses a significant threat to antibacterial treatment efficacy and public health. Outer membrane vesicles (OMVs) have been identified as carriers capable of facilitating the transfer of virulence and resistance genes. However, the role of OMVs in carbapenem-resistant K. pneumoniae under external pressures such as antibiotic and phage treatments remains unclear.
Exploring healthcare workers' perceptions of child health research at Kamuzu Central Hospital, Malawi: an interpretative phenomenological analysis
Children's health is a global public health priority and a determinant of development and sustainability. Its effective delivery and further improvements require constant and dedicated research on children, especially by child healthcare workers (HCWs). Studies have shown a high involvement of child HCWs from developed countries in child health research, with an under-representation from the global south in authorship and leadership in international collaborations. To our knowledge, there is very little literature on challenges faced by child HCWs in Malawi in conducting child health research. We sought to explore the lived experiences of child HCWs at Kamuzu Central Hospital (KCH) in Malawi by examining their perceptions of child health research and assessing the availability of child health research opportunities.
Research advances of biodegradable microplastics in wastewater treatment plant: Current knowledge and future directions
Plastic and microplastic pollution in the environment has become a significant global concern. Biodegradable plastics (BPs), as environmentally friendly alternatives to conventional plastics, have also emerged as a crucial topic of global discussion. The successful application of BPs appears to offer a solution to the potential ecological risks posed by conventional plastics. However, BPs have negative impacts on the ecological environment and human health. BPs can gradually degrade into biodegradable microplastics (BMPs) in the environment. Wastewater treatment plants (WWTPs) have become an undeniable source and sink of microplastics. With the production and application of BPs, BMPs will inevitably enter WWTPs. This paper reviews the pollution status, degradation behavior of BMPs, and their potential impact on wastewater treatment performance. The focus is on the environmental behavior of BMPs in wastewater treatment systems. The influences of BMPs on microbial communities, sludge treatment, and disposal are thoroughly discussed. The results indicate that BMPs are more easily decomposed into micro/nanoplastics and release additives compared to conventional microplastics. The effects of BMPs on microbial communities and wastewater treatment depend on their characteristics. The numerous oxygen-containing functional groups on the surface of BMPs enable them to serve a dual purpose as transport media and potential sources of environmental pollutants. Finally, in light of existing knowledge gaps, suggestions and prospects for future research on BMPs are proposed.
High-resolution epidemiological landscape from ~290,000 SARS-CoV-2 genomes from Denmark
Vast amounts of pathogen genomic, demographic and spatial data are transforming our understanding of SARS-CoV-2 emergence and spread. We examined the drivers of molecular evolution and spread of 291,791 SARS-CoV-2 genomes from Denmark in 2021. With a sequencing rate consistently exceeding 60%, and up to 80% of PCR-positive samples between March and November, the viral genome set is broadly whole-epidemic representative. We identify a consistent rise in viral diversity over time, with notable spikes upon the importation of novel variants (e.g., Delta and Omicron). By linking genomic data with rich individual-level demographic data from national registers, we find that individuals aged < 15 and > 75 years had a lower contribution to molecular change (i.e., branch lengths) compared to other age groups, but similar molecular evolutionary rates, suggesting a lower likelihood of introducing novel variants. Similarly, we find greater molecular change among vaccinated individuals, suggestive of immune evasion. We also observe evidence of transmission in rural areas to follow predictable diffusion processes. Conversely, urban areas are expectedly more complex due to their high mobility, emphasising the role of population structure in driving virus spread. Our analyses highlight the added value of integrating genomic data with detailed demographic and spatial information, particularly in the absence of structured infection surveys.
An evaluation of a multi-partner approach to increase routine immunization coverage in six northern Nigerian States
Global health partnerships are increasingly being used to improve coordination, strengthen health systems, and incentivize government commitment for public health programs. From 2012 to 2022, the Bill & Melinda Gates Foundation (BMGF) and Aliko Dangote Foundation (ADF) forged Memorandum of Understanding (MoU) partnership agreements with six northern state governments to strengthen routine immunization (RI) systems and sustainably increase immunization coverage. This mixed methods evaluation describes the RI MoUs contribution to improving program performance, strengthening capacity and government financial commitment as well as towards increasing immunization coverage.
Investigation of non-communicable diseases prevalence, patterns, and patient outcomes in hospitalized populations: a prospective observational study in three tertiary hospitals
Non-communicable diseases (NCDs) pose a significant global health challenge, constituting over 80% of mortality and morbidity. This burden is particularly pronounced in low- and middle-income countries (LMICs), including Ethiopia. Despite this, there's limited research on this issue in Africa. This study aims to investigate the prevalence, patterns, and outcomes of NCDs in hospitalized populations across three tertiary hospitals in Ethiopia.
The effects of a facilitator-enabled online multicomponent iSupport for dementia programme: A multicentre randomised controlled trial
Multicomponent interventions with carers of people with dementia demonstrate positive effects on the health and quality of life for carers and care recipients. The World Health Organization's iSupport for Dementia is an evidence-based online psychoeducation programme for carers. However, the programme was mainly implemented as a self-learning tool which might have limited its positive effects on carers and care recipients. Evidence for online multicomponent interventions with carers that incorporates the iSupport programme remains unknown.
Demographic and socioeconomic disparity in knowledge, attitude, and practice towards tuberculosis in Northwest, China: evidence from multilevel model study
Tuberculosis (TB) remains a serious global public health problem in China. The right knowledge, attitude, and practice (KAP) towards TB are indispensable to appropriate healthcare-seeking behaviors and treatment services timely. However, there are few studies that addressed the KAP towards TB in high-risk and under-developing regions in China. This study aims to evaluate the KAP towards TB in Ningxia Northwest, China, and identify factors that influence it. The findings can guide future health education and promotion interventions.
Success factors for interventions to reduce low-value imaging. Six crucial lessons learned from a practical case study in Norway
Substantial overuse of health care services is identified and intensified efforts are incited to reduce low-value services in general and in imaging in particular.
Process evaluation of a randomised controlled trial intervention designed to improve rehabilitation services for Aboriginal Australians after brain injury: the Healing Right Way Trial
Healing Right Way (HRW) aimed to improve health outcomes for Aboriginal Australians with stroke or traumatic brain injury by facilitating system-level access to culturally secure rehabilitation services. Using a stepped-wedge randomised controlled trial (RCT) design (ACTRN12618000139279, 30/01/2018), a two-pronged intervention was introduced in four rural and four urban hospitals, comprising 1.Cultural security training (CST) for staff and 2.Training/employment of Aboriginal Brain Injury Coordinators (ABIC) to support Aboriginal patients for 6-months post-injury. Three-quarters of recruited patients lived rurally. The main outcome measure was quality-of-life, with secondary outcomes including functional measures, minimum processes of care (MPC); number rehabilitation occasions of service received, and improved hospital experience. Assessments were undertaken at baseline, 12- and 26-weeks post-injury. Only MPCs and hospital experience were found to improve among intervention patients. We report on the process evaluation aiming to support interpretation and translation of results.
Global Trends in Childhood Sexual Abuse and Bullying Victimization: A Comprehensive Analysis from 1990 to 2019
: No comprehensive analysis has yet been published regarding global trends in childhood sexual abuse (CSA) and bullying victimization (BV). The present study offers a longitudinal perspective on their prevalence worldwide.
Non-malarial febrile illness: a systematic review of published aetiological studies and case reports from China, 1980-2015
Rapid point-of-care tests for malaria are now widely used in many countries to guide the initial clinical management of patients presenting with febrile illness. With China having recently achieved malaria elimination, better understanding regarding the identity and distribution of major non-malarial causes of febrile illnesses is of particular importance to inform evidence-based empirical treatment policy.
Application of the IOC Relative Energy Deficiency in Sport (REDs) Clinical Assessment Tool version 2 (CAT2) across 200+ elite athletes
This cross-sectional retrospective and prospective study implemented the 2023 International Olympic Committee Relative Energy Deficiency in Sport (REDs) Clinical Assessment Tool version 2 (CAT2) to determine the current severity of REDs (primary outcome) and future risk of bone stress injuries (BSI, exploratory outcome) in elite athletes.
Urate lowering therapy in patients starting hemodialysis limit gout flares occurrence: ten years retrospective study
Uncontrolled gout can cause articular impairment but is also associated with a global and cardiovascular excess mortality, especially in dialysis population. Data documented within existing research is not conclusive regarding gout flares evolution during hemodialysis and their control by urate lowering therapy (ULT). Without clear guidelines concerning hemodialysis patients management with chronic gout, this study proposes to investigate whether gout flare incidence reduction could be observed on this population treated by urate lowering therapy versus patients without treatment.
Presenting a Framework to Professionalize Health Supply Chain Management
Many countries have an insufficient supply of adequately skilled supply chain workers to manage health commodities, and no global standards in education or experience exist for the supply chain management (SCM) workforce managing health products. We present a professionalization framework for the health SCM workforce that provides a systematic process that countries can use to standardize and elevate the health SCM profession.
Navigating the Nexus of Bioethics and Geopolitics: Implications for Global Health Security and Scientific Collaboration
Bioethics plays a pivotal role in guiding ethical decision-making within the realm of medical research and healthcare. However, the influence of geopolitics on bioethical considerations, particularly regarding bioweapons research, remains an underexplored area. This study delves into the uncharted territory of how international political interests can intersect with bioethical principles, potentially shaping collaborative efforts and global health policies related to bioweapons research. Through a hypothetical scenario involving a hypothetical pathogen, a collaborative effort between unspecified countries, we examine the implications of such cooperation on global health governance, with a specific focus on bioweapons research. Ethical dilemmas surrounding responsible research, potential risks and benefits, equitable distribution of findings, and biosafety measures are explored. This analysis underscores the importance of transparent and responsible practices in bioweapons research amidst geopolitical tensions. By striking a balance between national interests and international solidarity, we advocate for robust bioethical frameworks to navigate such collaborations for the collective well-being of humanity and to mitigate potential risks associated with bioweapons research.
Individual and contextual factors associated with measles infection in Malaysia: a multilevel analysis
Despite effective vaccination strategies, measles remains a global public health challenge. The study explored individual and contextual factors associated with measles infection in Malaysia from 2018 to 2022, informing the development of targeted public health interventions.
A Post-reflective Examination of the Physical and Mental Health Suffering During COVID-19 Through the Lens of Christ's Kenotic and Redemptive Act
The COVID-19 global pandemic has brought unprecedented physical and mental health challenges to many, making the exploration of the spiritual dimension of suffering increasingly meaningful and relevant. Pope John Paul II's theologico-pastoral approach in Salvifici Doloris (SD) sheds light on how spiritual reflections and pastoral care anchored on the theology of Jesus Christ's sufferings can be put together to contribute to post-COVID-19 reflections. Given this context, this paper explores the perceptions and coping mechanisms of COVID-19 patients as they navigate the challenges of their illness. By examining patient experiences gleaned from medical and scientific journals, the study underscores the necessity of supporting individuals suffering from various diseases. As John Paul II thoughtfully remarks in Salvifici Doloris, there is a profound need to address patients' inquiries about "the cause, the reason, and equally, the purpose of suffering, and, in brief, a question about its meaning." Taking this into account, this paper contextualizes the theology of suffering articulated by Pope John Paul II in SD within the experiences of patients who contracted COVID-19 during the global pandemic. To embark on this discussion, the following themes about suffering are expounded: First, Insights into the Weight of Suffering Among Persons who Contracted COVID-19. Second, Understanding of Suffering in Salvifici Doloris, and Third, The Salvific Meaning of Suffering in COVID-19 and its Transformative Experience.
Discrimination and Racial Inequities in Self-reported Mental Health Among Immigrants and Canadian-Born Individuals in a Large, Nationally Representative Canadian Survey
We examined the link between discrimination and self-rated mental health (SRMH) among immigrants and Canadian-born individuals, stratified according to an individual's identification as racialized or white. Using data from Canada's General Social Survey (2014) (weighted N = 27,575,000) with a novel oversample of immigrants, we estimated the association of perceived discrimination with SRMH separately among immigrants and Canadian-born individuals and stratified by racialized status. Among immigrants, we also investigated whether age-at-arrival attenuated or strengthened associations. The prevalence of discrimination was higher among racialized compared to white immigrants (18.9% versus 11.8%), and among racialized compared to white non-immigrants (20.0% versus 10.5%). In the adjusted model with immigrants, where white immigrants not reporting discrimination were the referent group, both white (adjusted prevalence odds ratio [aPOR] 6.11, 95% confidence interval [CI] 3.08, 12.12) and racialized immigrants (aPOR 2.28, 95% CI 1.29, 4.04) who experienced discrimination reported poorer SRMH. The associations were weaker among immigrants who immigrated in adulthood. In the adjusted model with non-immigrants, compared to unexposed white respondents, Canadian-born white respondents who experienced discrimination reported poorer SRMH (aPOR 3.62, 95% CI 2.99, 4.40) while no statistically significant association was detected among racialized respondents (aPOR 2.24, 95% CI 0.90, 5.58). Racialized respondents experienced significant levels of discrimination compared to white respondents irrespective of immigrant status. Discrimination was associated with poor SRMH among all immigrants, with some evidence of a stronger association for white immigrants and immigrants who migrated at a younger age. For Canadian-born individuals, discrimination was associated with poor SRMH among white respondents only.
Functional characterization and structural basis of an efficient ochratoxin A-degrading amidohydrolase
Ochratoxin A (OTA) contamination in various agro-products poses a serious threat to the global food safety and human health, leading to enormous economic losses. Enzyme-mediated OTA degradation is an appealing strategy, and the search for more efficient enzymes is a prerequisite for achieving this goal. Here, a novel amidohydrolase, termed PwADH, was demonstrated to exhibit 7.3-fold higher activity than that of the most efficient OTA-degrading ADH3 previously reported. Cryo-electron microscopy structure analysis indicated that additional hydrogen-bond interactions among OTA and the adjacent residue H163, the more compact substrate-binding pocket, and the wider entry to the substrate-access cavity might account for the more efficient OTA-degrading activity of PwADH compared with that of ADH3. We conducted a structure-guided rational design of PwADH and obtained an upgraded variant, G88D, whose OTA-degrading activity was elevated by 1.2-fold. In addition, PwADH and the upgraded G88D were successfully expressed in the industrial yeast Pichia pastoris, and their catalytic activities were compared to those of their counterparts produced in E. coli, revealing the feasibility of producing PwADH and its variants in industrial yeast strains. These results illustrate the structural basis of a novel, efficient OTA-degrading amidohydrolase and will be beneficial for the development of high-efficiency OTA-degrading approaches.
Nationwide cost-effectiveness and quality of life analysis of minimally invasive distal pancreatectomy
This study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP).
FLUEnT: Transformer for detecting lung consolidations in videos using fused lung ultrasound encodings
Pneumonia is the leading cause of death among children around the world. According to WHO, a total of 740,180 lives under the age of five were lost due to pneumonia in 2019. Lung ultrasound (LUS) has been shown to be particularly useful for supporting the diagnosis of pneumonia in children and reducing mortality in resource-limited settings. The wide application of point-of-care ultrasound at the bedside is limited mainly due to a lack of training for data acquisition and interpretation. Artificial Intelligence can serve as a potential tool to automate and improve the LUS data interpretation process, which mainly involves analysis of hyper-echoic horizontal and vertical artifacts, and hypo-echoic small to large consolidations. This paper presents, Fused Lung Ultrasound Encoding-based Transformer (FLUEnT), a novel pediatric LUS video scoring framework for detecting lung consolidations using fused LUS encodings. Frame-level embeddings from a variational autoencoder, features from a spatially attentive ResNet-18, and encoded patient information as metadata combiningly form the fused encodings. These encodings are then passed on to the transformer for binary classification of the presence or absence of consolidations in the video. The video-level analysis using fused encodings resulted in a mean balanced accuracy of 89.3 %, giving an average improvement of 4.7 % points in comparison to when using these encodings individually. In conclusion, outperforming the state-of-the-art models by an average margin of 8 % points, our proposed FLUEnT framework serves as a benchmark for detecting lung consolidations in LUS videos from pediatric pneumonia patients.
Local environmental factors drive distributions of ecologically-contrasting mosquito species (Diptera: Culicidae)
Mosquitoes are important vectors of disease pathogens and multiple species are undergoing geographical shifts due to global changes. As such, there is a growing need for accurate distribution predictions. Ecological niche modelling (ENM) is an effective tool to assess mosquito distribution patterns and link these to underlying environmental preferences. Typically, macroclimatic variables are used as primary predictors of mosquito distributions. However, they likely undervalue local conditions and intraspecific variation in environmental preferences. This is problematic, as mosquito control takes place at the local scale. Utilising high-resolution (10 × 10 m) Maxent ENMs on the island of Bonaire as model system, we explore the influence of local environmental variables on mosquito distributions. Our results show a distinct set of environmental variables shape distribution patterns across ecologically-distinct species, with urban variables strongly associated with introduced species like Aedes aegypti and Culex quinquefasciatus, while native species show habitat preferences for either mangroves, forests, or ephemeral water habitats. These findings underscore the importance of distinct local environmental factors in shaping distributions of different mosquitoes, even on a small island. As such, these findings warrant further studies aimed at predicting high-resolution mosquito distributions, opening avenues for preventative management of vector-borne disease risks amidst ongoing global change and ecosystem degradation.
Metabolic and behavioural risk factors for cardiovascular diseases in Southern Latin America: analysis of the Global Burden of Disease 1990-2019
Cardiovascular diseases (CVDs) are the leading causes of global mortality. Modifiable behavioural and metabolic risk factors significantly contribute to the burden of CVD. Given the vast socio-demographic and health outcome heterogeneity in Latin America, similar southern Latin American countries (Argentina, Chile, and Uruguay) were analysed as a distinct group to describe the CVD death rates related to metabolic and behavioural risk factors.
Recovery of 240 metagenome-assembled genomes from coastal mariculture environments in South Korea
The mariculture industry has seen a rapid expansion in recent years due to the increasing global demand for seafood. However, the industry faces challenges from climate change and increased pathogen pressure. Additionally, the chemicals used to enhance mariculture productivity are changing ocean ecosystems. This study analyzed 36 surface-water metagenomes from South Korean mussel, oyster, scallop, and shrimp farms to expand our understanding of aquaculture microbial genetic resources and the potential impacts of these anthropogenic inputs. We recovered 240 non-redundant species-level metagenome-assembled genomes (MAGs), comprising 224 bacteria, 13 archaea, and three eukaryotes. Most MAGs were assigned to Proteobacteria, Bacteroidota, and Actinobacteriota, with 40.7% remaining unclassified at the species level. Among the three eukaryotic MAGs, one was identified as a novel lineage of green algae, highlighting the uncharacterized genetic diversity in mariculture environments. Additionally, 22 prokaryotic MAGs harbored 26 antibiotic and metal resistance genes, with MAGs carrying beta-lactamases being particularly prevalent in most farms. The obtained microbiome data from mariculture environments can be utilized in future studies to foster healthy, sustainable mariculture practices.
Effectiveness of a pediatric critical care pilot preceptor program: Improved confidence and competency outcomes among a cohort of professional nurses in Blantyre, Malawi
Availability of high-level pediatric training for nurses in Malawi is limited. To address this gap, a novel pediatric critical care nurse preceptor program was developed and implemented by pediatric nurse specialists.
The influence of nutrition in nodular thyroid pathology: a systematic review
Nodular thyroid pathologies (NThyPs) are prevalent thyroid diseases, with a steadily increasing global incidence. Although their exact causes remain uncertain, various modifying factors, such as nutrition, influence their development. We aimed to systematically identify and synthesize the influence of dietary exposures on NThyPs risk. PubMed, Scopus, Web of Science, and EMBASE were searched on June 14, 2024, to identify relevant studies. Data extraction included study characteristics, sociodemographic factors, dietary intake assessments and exposures, and NThyPs subtypes. Out of 14,730 articles retrieved, 55 observational or experimental studies, in English, Spanish, or Portuguese, that assessed nutrition's impact on NThyPs were included, excluding non-human studies, reviews, meta-analyses, and publications outside the study's scope. Forty studies investigated how distinct dietary patterns, macronutrients, minerals, and vitamins contributed to or mitigated NThyPs development. Fish and seafood, vegetables and fruits, and meat were other dietary exposures investigated. In fourteen of previously selected studies, drink consumption was also addressed. This systematic review (CRD420234003439) suggests that reducing processed foods, sugars, meat, and dietary iodine lowers NThyPs risk, while coffee, tea, alcohol, and dairy products demonstrates potential protective roles. Fish and seafood, and fruits and vegetables also exhibit protective properties; nevertheless, further research is necessary to establish definitive conclusions.
Factors influencing parental COVID-19 vaccination willingness for children in Japan
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.
Quality of life among adults with scabies: A community-based cross-sectional study in north-western Ethiopia
Scabies undermines quality of life through its highly disturbing disease symptoms, by distorting self-perception, and secondary to social stigma. Knowledge of its effect on quality of life in general and on specific aspects of day-to-day life is key to addressing the health needs of individual patients and to evaluating gains from community-based disease control interventions.
Tissue-Based Predictors of Impaired Right Ventricular Strain in Coronary Artery Disease: A Multicenter Stress Perfusion Study
Right ventricular (RV) dysfunction is known to impact prognosis, but its determinants in coronary artery disease are poorly understood. Stress cardiac magnetic resonance (CMR) has been used to assess ischemia and infarction in relation to the left ventricle (LV); the impact of myocardial tissue properties on RV function is unknown.
Prostate-specific antigen and health-related quality of life in individuals with advanced prostate cancer treated with apalutamide: a plain language summary of the SPARTAN and TITAN studies
This is a summary of a paper that describes the results of the SPARTAN and TITAN studies, which looked at whether a treatment called apalutamide can help treat individuals with advanced prostate cancer.The SPARTAN study included 1207 participants with nonmetastatic castration-resistant prostate cancer (or nmCRPC). The TITAN study included 1052 participants with metastatic castration-sensitive prostate cancer (or mCSPC). Treatment with apalutamide was compared with treatment with placebo. In both studies, all participants were also given androgen deprivation therapy (or ADT), which has been used for many years for the treatment of prostate cancer.The results showed that treatment with apalutamide plus ADT increased participants' survival time while their health-related quality of life stayed the same, compared with placebo plus ADT. Also, apalutamide plus ADT increased the length of time that the cancer did not spread to other parts of the body (metastasize) or did not continue to grow. In both studies, treatment with apalutamide plus ADT was associated with a deep decline in blood prostate-specific antigen (or PSA) levels (called a deep PSA decline). This additional analysis of the SPARTAN and TITAN studies was performed to understand whether the deep PSA decline in participants who received apalutamide plus ADT was linked to their overall health-related quality of life.
Heavy Metal-Based Toxic Oxo-Pollutants Sequestration by Advanced Functional Porous Materials for Safe Drinking Water
ConspectusWater scarcity as a consequence of either environmental or economic actions is the most compelling global concern of the 21st century, as ∼2 billion people (26% of the total population) struggle to access safe drinking water and ∼3.6 billion (46% of the total population) lack access to clean water sanitation. In this context, groundwater pollution by toxic heavy metals and/or their oxo-pollutants, such as CrO, CrO, AsO, SeO, SeO, TcO, UO, etc., have been becoming rapidly growing global concerns. The severe toxicity upon bioaccumulation of these oxo-anions has prompted the US Environment Protection Agency (EPA) to mark these persistent and hazardous substances as priority pollutants. Additionally, the heavy-metal-based pollutants are difficult to transform into eco-friendly substances, thus presenting serious challenges toward human health and environmental preservation. To this end, the emergence of advanced functional porous materials (AFPMs), including metal-organic frameworks (MOFs), covalent organic frameworks (COFs), metal-organic polyhedrons (MOPs), porous organic polymers (POPs), etc., have presented extraordinary opportunities in material research and water treatment applications. The liberty in designing and structural tunability of AFPMs, facilitated by utilization of structure-encoded molecular building blocks, enables precise control over target-specificity and structure-property correlations. Bridging the gap between strategic material design and on-demand real-world application can facilitate the development of next-generation sorbents/ion-exchangers for efficient water treatment.In this Account, we summarize the recent advancements from our group toward the development of cutting-edge multifunctional ionic-porous sorbents, offering viable solutions toward providing clean and safe drinking water. Our vision allows us to comprehend this challenge through two strategic factors: efficient oxo-anion capture via ion-exchange and specific host-guest interactions via installation of modular functional groups. To provide an overview, we first highlight the different structural variants and coexistance of various toxic oxo-anions depending on the pH of the medium and their adverse effects. Next, we highlight the promising potential of water stable cationic MOFs toward selective remediation of toxic Cr(VI), Mn(VII), Tc(VI), Se(IV), Se(VI), U (VI), As(III), and As(V)-based toxic oxo-pollutants from water. In the subsequent sections, we summarize the target-specific design strategies and oxo-anion remediation performances of ionic porous organic polymers and hybrid functional porous materials. The key role of target-specific designability and/or structural fine-tuning of AFPMs toward preferential sorption of oxo-pollutants is systematically demonstrate. Particularly, the role of ion-exchange (anion-exchange) processes toward targeted oxo-pollutant capture by ionic AFPMs has been discussed in details. In several examples, the AFPMs were successful in reducing the toxic oxo-anion concentration levels lower than the permitted values for drinking water by the World Health Organizing Committee (WHO), showcasing their real-world applicability potency.Our contemporaneous endeavors in exploring ionic AFPMs for selective toxic oxo-anion sequestration may serve as a blueprint to researchers for future development of the next generation sorbent materials for energy-economically feasible water treatment methods.
Evaluating the Efficacy of a Digital Therapeutic (CT-152) as an Adjunct to Antidepressant Treatment in Adults With Major Depressive Disorder: Protocol for the MIRAI Remote Study
Major depressive disorder (MDD) is common worldwide and can be highly disabling. People with MDD face many barriers to treatment and may not experience full symptom relief even when treated. Therefore, new treatment modalities are needed for MDD. Digital therapeutics (DTx) may provide people with MDD an additional treatment option.
A Brief Alcohol Intervention (BAI) to reduce alcohol use and improve PrEP outcomes among men who have sex with men in Vietnam: study protocol for a randomized controlled trial
In Vietnam and other global settings, men who have sex with men (MSM) have become the population at greatest risk of HIV infection. Although HIV pre-exposure prophylaxis (PrEP) has been implemented as a prevention strategy, PrEP outcomes may be affected by low persistence and adherence among MSM with unhealthy alcohol use. MSM have a high prevalence of unhealthy alcohol use in Vietnam, which may affect PrEP outcomes.
Ruptured AAA: bridging the gap between international guidelines and local clinical realities
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.
The costs, health and economic impact of air pollution control strategies: a systematic review
Air pollution poses a significant threat to global public health. While broad mitigation policies exist, an understanding of the economic consequences, both in terms of health benefits and mitigation costs, remains lacking. This study systematically reviewed the existing economic implications of air pollution control strategies worldwide.
Enhancing Prehospital Care During the Conflict in Ukraine: NATO's Role in Global Health Engagement
The conflict in Ukraine, ongoing since 2014 and escalating with the Russian invasion in 2022, has unveiled profound challenges in prehospital care essential for the survival and recovery of warfighters and civilians alike, necessitating a detailed examination of the current medical response mechanisms and their effectiveness.
Use of primary healthcare services before and after specialized rehabilitation and its relation to changes in health and functioning: a longitudinal cohort study
To examine patients' use of primary healthcare (PHC) before and after specialized rehabilitation and its relation with self-reported health and functioning.
Factors associated with human papillomavirus, hepatitis A, hepatitis B and mpox vaccination uptake among gay, bisexual and other men who have sex with men in the UK- findings from the large community-based RiiSH-Mpox survey
Gay, bisexual, and other men who have sex with men (GBMSM) face a disproportionate burden of sexually transmitted infections and are eligible for targeted vaccinations for hepatitis A (HAV), hepatitis B (HBV), human papilloma virus (HPV) and mpox. This study examines the sociodemographic characteristics, sexual behaviours, and sexual healthcare service (SHS) use associated with vaccination uptake.
Discursive (mis)alignments in internationalization: The case of International Medical Programmes
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.
Conservative or liberal oxygen targets in patients on venoarterial extracorporeal membrane oxygenation
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.
Health Advocacy Trends and Unexplored Facets-A Bibliometric Analysis Based on SCOPUS Database
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.
Diverse clinical presentation of SPTBN1 variants: Complex versus primary attention-deficit/hyperactivity disorder
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.
Enterohemorrhagic (EHEC) disrupts intestinal barrier integrity in translational canine stem cell-derived monolayers
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.
Epigenetic programming of host lipid metabolism associated with resistance to TST/IGRA conversion after exposure to
(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.
Immune gene expression changes more during a malaria transmission season than between consecutive seasons
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.
Mutation of diminishes its cytotoxicity, oxidative stress, inflammation, and apoptosis on THP-1 macrophages
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.
Domestic and family violence and associated maternal and perinatal outcomes: A population-based retrospective cohort study
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.
Trajectory of Infant Problematic Feeding Symptoms: Study Protocol
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.
Short-Term Training, a Useful Approach for Sustainable Pharmacovigilance Knowledge Development in Tanzania, Kenya, Ethiopia and Rwanda
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.
Inside ANEMIA of CKD: Projecting the Future Burden of Anemia of Chronic Kidney Disease and Benefits of Proactive Management: A Microsimulation Model of the Chinese Population
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.
Impact of Immunoglobulin M-enriched Immunoglobulins on the Outcomes of Severe Coronavirus Disease 2019
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.
Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality
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.
Released bacterial ATP shapes local and systemic inflammation during abdominal sepsis
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.
Quality Assessment of TikTok as a Source of Information About Mitral Valve Regurgitation in China: Cross-Sectional Study
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.
Genetic and antigenic characterization of two diarrhoeicdominant rotavirus A genotypes G3P[12] and G14P[12] circulating in the global equine population
Equine rotavirus species A (ERVA) G3P[12] and G14P[12] are two dominant genotypes that cause foal diarrhoea with a significant economic impact on the global equine industry. ERVA can also serve as a source of novel (equine-like) rotavirus species A (RVA) reassortants with zoonotic potential as those identified previously in 2013-2019 when equine G3-like RVA was responsible for worldwide outbreaks of severe gastroenteritis and hospitalizations in children. One hurdle to ERVA research is that the standard cell culture system optimized for human rotavirus replication is not efficient for isolating ERVA. Here, using an engineered cell line defective in antiviral innate immunity, we showed that both equine G3P[12] and G14P[12] strains can be rapidly isolated from diarrhoeic foals. The genome sequence analysis revealed that both G3P[12] and G14P[12] strains share the identical genotypic constellation except for VP7 and VP6 segments in which G3P[12] possessed VP7 of genotype G3 and VP6 of genotype I6 and G14P[12] had the combination of VP7 of genotype G14 and VP6 of genotype I2. Further characterization demonstrated that two ERVA genotypes have a limited cross-neutralization. The lack of an broad cross-protection between both genotypes supported the increased recent diarrhoea outbreaks due to equine G14P[12] in foals born to dams immunized with the inactivated monovalent equine G3P[12] vaccine. Finally, using the structural modelling approach, we provided the genetic basis of the antigenic divergence between ERVA G3P[12] and G14P[12] strains. The results of this study will provide a framework for further investigation of infection biology, pathogenesis and cross-protection of equine rotaviruses.
A Review of the Difficulties Faced by Low and Middle-income Countries in Hygiene and Healthcare Practices
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.
Psychosocial alterations during the COVID-19 pandemic and the global burden of anxiety and major depressive disorders in adolescents, 1990-2021: challenges in mental health amid socioeconomic disparities
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.
The Role of Tranexamic Acid in Postpartum Hemorrhage: A Narrative Review
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.
Protective Effect of Sulfur-Containing Heterocyclic Analogs Against Acrylamide-Induced Behavioral and Biochemical Alterations in Zebrafish
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.
Dysregulated immunologic landscape of early host response in melioidosis
Melioidosis, a neglected tropical infection caused by Burkholderia pseudomallei, commonly presents as pneumonia or sepsis with mortality rates up to 50% despite appropriate treatment. A better understanding of the early host immune response to melioidosis may lead to new therapeutic interventions and prognostication strategies to reduce disease burden. Whole blood transcriptomic signatures in 164 melioidosis patients and 70 patients with other infections hospitalized in northeastern Thailand enrolled within 24 hours following hospital admission were studied. Key findings were validated in an independent melioidosis cohort. Melioidosis was characterized by upregulation of interferon signaling responses compared to other infections. Mortality in melioidosis was associated with excessive inflammation, up-regulated type 2 immune responses and a dramatic decrease in T cell-mediated immunity compared to survivors. We identified and independently confirmed a five-gene predictive set classifying fatal melioidosis (validation cohort: an area under the receiver operating characteristic curve 0.83, 95% CI: 0.67-0.99). In conclusion, this study highlights the intricate balance between innate and adaptive immunity during fatal melioidosis and can inform future precision medicine strategies for targeted therapies and prognostication in this severe infection.
Development and Psychometric Validation of Population-Based Knowledge Attitudes and Practices-Questionnaire on Fluoride (PBKAP-QF)
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.
A time-course analysis of secretomes reveals the importance of pectin-degrading enzymes to increase the digestibility of soybean meal
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.
MicroRNAs Modulating Neuroinflammation in Parkinson's disease
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.
Genomic and functional divergence of strains from atopic dermatitis patients and healthy individuals: insights from global and local scales
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.
Occurrences of nitrate-contaminated groundwater in the piedmont aquifers: hydrogeochemical characteristics and health risks
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.
Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant spp
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.
How can the microbial community in watershed sediment maintain its resistance in the presence of shifting antibiotic residuals?
The widespread presence of antibiotics in global watershed environments poses a serious threat to public health and ecosystems. It is essential to examine the resistance of microbial communities in watershed environments in response to shifting antibiotic residues. Sediment samples were collected from seven sites across a watershed, encompassing surface sediment (0-10 cm) and bottom sediment (30-40 cm) depths. The aim was to replicate exposure scenarios to different antibiotics (oxytetracycline (OTC) and sulfadiazine (SD)) at varying concentrations (0, 10, and 100 μg/L) in sediment overlying water, within controlled laboratory settings. The study findings revealed significant variations in the microbial community structure of sediments between different treatments, with distinct differences observed in the upper stream and top sediment layers compared to the sediments located downstream and in the bottom layers. After the introduction of antibiotics, a significant decrease in microbial nodes was observed in the genus-level co-occurrence network analysis of the bottom sediment layer, particularly in the OTC treatment groups. In contrast, the downstream region displayed more robust correlations among the top 20 genera than the upstream area. There was no significant variance observed in the expression of Antibiotic resistance genes (ARGs), consisting of tetracycline resistance genes (tetC, tetG, tetM, tetW, and tetX) and sulfonamide resistance genes (sul1, sul2, and sul3), between sediments in the top and bottom layers. Nevertheless, downstream samples exhibited significantly higher levels of ARGs when compared to upstream samples. Network correlation analysis indicated notably lower correlations between ARGs and bacterial genera in sediments from upstream or surface layers compared to those in downstream or deeper layers. Moreover, correlations in the sediments from surface layers and upstream regions showed a decreasing trend with increasing SD exposure concentrations, while those in deeper layers and downstream areas remained relatively stable. The presence of antibiotics notably enhanced the correlation between sediment properties and ARGs, particularly emphasizing associations with total carbon, nitrogen, and sulfur content. However, the introduction of SD and OTC resulted in a decrease in the influence of these sediment factors on microbial community functions related to sulfur and nitrogen metabolism, as indicated by KEGG (Kyoto Encyclopedia of Genes and Genomes) annotation. The research provided empirical evidence on how microbial resistance responds to changes in antibiotics in sediment samples taken from various depths and locations within a watershed. It emphasized the urgent need for heightened awareness of the movement and alteration of antibiotic resistance patterns in watershed ecosystems.
Detection of mobile colistin resistance genes and in from Ecuadorian children
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.
Exploring perceptions of anti-vaping message themes: A qualitative study of Australian adolescents and adults
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.
A State-of-the-Science Review of the Effect of Damp- and Mold-Affected Housing on Mental Health
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.
Physical activity interventions for the promotion of mental health outcomes in at-risk children and adolescents: a systematic review
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 Anticancer Journey of Liquiritin: Insights into Its Mechanisms and Therapeutic Prospects
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.
Development of Airway Hemorrhage Simulation Scenarios With Pilot of an Airway Team Leader Assessment Tool
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.
Advancements in Computational Approaches for Antidiabetic Drug Discovery: A Review
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.
Hypertensive Disorders of Pregnancy and Brain Health in Midlife: The CARDIA Study
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.
Smart Nanozymes for Diagnosis of Bacterial Infection: The Next Frontier from Laboratory to Bedside Testing
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.
Multi-institutional prospective observational study of radiotherapy for metastatic bone tumor
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.
Endocrine cancer trends 1990-2021: global disparities and health inequalities
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.
Decreasing the burden of non-alcoholic fatty liver disease: From therapeutic targets to drug discovery opportunities
Non-alcoholic fatty liver disease (NAFLD) presents a pervasive global pandemic, affecting approximately 25 % of the world's population. This grave health issue not only demands urgent attention but also stands as a significant economic concern on a global scale. The genesis of NAFLD can be primarily attributed to unhealthy dietary habits and a sedentary lifestyle, albeit certain genetic factors have also been recorded to contribute to its occurrence. NAFLD is characterized by fat accumulation in more than 5 % of hepatocytes according to histological analysis, or >5.6 % of lipid volume fraction in total liver weight in patients. The pathophysiology of NAFLD/non-alcoholic steatohepatitis (NASH) is multifactorial and the mechanisms underlying the progression to advanced forms remain unclear, thereby representing a challenge to disease therapy. Despite the substantial efforts from the scientific community and the large number of pre-clinical and clinical trials performed so far, only one drug was approved by the Food and Drug Administration (FDA) to treat NAFLD/NASH specifically. This review provides an overview of available information concerning emerging molecular targets and drug candidates tested in clinical studies for the treatment of NAFLD/NASH. Improving our understanding of NAFLD pathophysiology and pharmacotherapy is crucial not only to explore new molecular targets, but also to potentiate drug discovery programs to develop new therapeutic strategies. This knowledge endeavours scientific efforts to reduce the time for achieving a specific and effective drug for NAFLD or NASH management and improve patients' quality of life.
Physical activity and planetary health: A scoping review
The behaviors and attitudes associated with event attendance and engagement in physical and sporting activities exert a significant impact on planetary health. This scoping review aims to scrutinize existing literature, elucidate concepts, investigate methodologies, and identify knowledge gaps pertaining to physical activity behavior within the context of planetary health.
Duration of face down positioning following full-thickness macular hole repair: A protocol for a randomized pilot study
Full-thickness macular holes (FTMH) are defects in the fovea involving all neural retinal layers. They reduce patients' visual acuity (VA) and impact their quality of life. FTMHs are repaired with pars plana vitrectomy (PPV) with intraocular gas tamponade and post-operative face-down positioning (FDP). There is no consensus regarding the ideal positioning requirements following FTMH repair and there lacks clear guidelines on the topic. While analysis of global practice patterns indicates that between 5-7 days is the most common duration suggested by surgeons, there is significant heterogeneity in surgeon preferences. There is, however, biological plausibility to support minimal or even no FDP following surgery and given the disabling nature of FDP for patients, there is a need to better assess key patient outcomes with different FDP durations. As such, this prospective randomized controlled pilot trial will compare 3-days of FDP to 7-days of FDP following PPV for FTMH.
Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice
Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching . High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.
Pathways of exposure to Vibrio Cholerae in an urban informal settlement in Nairobi, Kenya
Cholera is a diarrhoeal disease caused by Vibrio cholerae (V. cholerae) bacterium, with strains belonging to serogroups 01 and 0139 causing a huge proportion of the disease. V. cholerae can contaminate drinking water sources and food through poor sanitation and hygiene. This study aimed to identify environmental routes of exposure to V. cholerae within Mukuru informal settlement in Nairobi. We collected nine types of environmental samples (drinking water, flood water, open drains, surface water, shaved ice, raw produce, street food, soil, and public latrine swabs) over 12 months. All samples were analysed for V. cholerae by culture and qPCR, then qPCR-positive samples were quantified using a V. cholerae DNA standard. Data about the frequency of contact with the environment was collected using behavioural surveys. Of the 803 samples collected, 28.5% were positive for V. cholerae by qPCR. However, none were positive for V. cholerae by culture. V. cholerae genes were detected in majority of the environmental water samples (79.3%), including open drains, flood water, and surface water, but were only detected in small proportions of other sample types. Vibrio-positive environmental water samples had higher mean V. cholerae concentrations [2490-3469 genome copies (gc) per millilitre (mL)] compared to drinking water samples (25.6 gc/mL). Combined with the behavioural data, exposure assessment showed that contact with surface water had the highest contribution to the total V. cholerae exposure among children while ingestion of municipal drinking water and street food and contact with surface water made substantial contributions to the total V. cholerae exposure for adults. Detection of V. cholerae in street food and drinking water indicates possible risk of exposure to toxigenic V. cholerae in this community. Exposure to V. cholerae through multiple pathways highlights the need to improve water and sanitation infrastructure, strengthen food hygiene practices, and roll out cholera vaccination.
Resilience throughout COVID-19: Unmasking the realities of COVID-19 and vaccination facilitators, barriers, and attitudes among Black Canadians
Black communities have suffered disproportionately higher numbers of COVID-19 cases and deaths in Canada. Recognizing the significance of supporting targeted strategies with vulnerable populations extends beyond the COVID-19 pandemic, as it addresses longstanding health disparities and promotes equitable access to healthcare. The present study investigated 1) experiences with COVID-19, 2) COVID-19's impact, and 3) factors that have influenced COVID-19 vaccine acceptance and uptake among stakeholders and partners from the Federation of Black Canadians' (FBC). We conducted semi-structured interviews with 130 individuals and four focus groups with FBC, including stakeholders and partners, between November 2021 and June 2022. The semi-structured interviews and focus group discussions were conducted virtually over Zoom and lasted about 45 minutes each. Conversations from interviews and focus groups were transcribed and coded professionally using team-based methods. Themes were developed using an inductive-deductive approach and defined through consensus. The deductive approach was based on Consolidated Framework for Implementation Research (CFIR) domains and constructs. First, regarding experiences with COVID-19, 36 codes were identified and mapped onto 13 themes. Prominent themes included 39 participants who experienced highly severe COVID-19 infections, 25 who experienced stigma, and 18 who reported long recovery times. Second, COVID-19 elicited lifestyle changes, with 23 themes emerging from 62 codes. As many as 97 participants expressed feelings of isolation, while 63 reported restricted mobility. Finally, participants discussed determinants that influenced their vaccination decisions, in which 46 barriers and four facilitators were identified and mapped onto nine overarching themes. Themes around the CFIR domains Individuals, Inner Setting, and Outer Setting were most prominent concerning vaccine adoption. As for barriers associated with the constructs limited available resources and low motivation, 55 (41%) and 46 (34%) of participants, respectively, mentioned them most frequently. Other frequently mentioned barriers to COVID-19 vaccines fell under the construct policies & laws, e.g., vaccine mandates as a condition of employment. Overall, these findings provide a comprehensive and contextually rich understanding of pandemic experiences and impact, along with determinants that have influenced participants' vaccination decisions. Furthermore, the data revealed diverse experiences within Black communities, including severe infections, stigma, and vaccine-related challenges, highlighting the importance of targeted interventions, support, and consideration of social determinants of health in addressing these effects.