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Predicting COVID-19 vaccine uptake: Comparing the health belief model and theory of planned behavior
Alshagrawi SS
The COVID-19 outbreak has had a significant impact on the global health landscape, underscoring the crucial role that vaccinations play in achieving herd immunity and reducing the effects of pandemics. Given the importance of this issue, it is imperative to gain a deeper understanding of the various factors that influence individuals' decisions to seek vaccination. This study aimed to compare the prediction level of the Health Belief Model (HBM), the Theory of Planned Behavior (TPB), and a combined model in explaining the intention of adults to receive COVID-19 immunization. A cross-sectional online survey was conducted among adults ( = 505) in Saudi Arabia. The survey contained variables related to the HBM and TPB. The prediction level of the two models as well as a combined model were evaluated utilizing Structural Equation Modeling (SEM). Among the recruited 505 participants, 88% fell within the 18 to 30 age range, and 54.5% were male. The proposed HBM model accounted for 68% of the variation in intention, whereas the TPB model explained 78.2% of the variation in COVID-19 vaccination intention. The combined model showed greater explanatory power (82%). The variables of susceptibility (β = 0.20,  < .001), severity (β = 0.49,  < .001), advantages (β = 0.63,  < .001), and obstacles (β = - 0.24,  < .001), perceptions of behavioral control (β = 1.58,  < .001) and attitudes (β = 0.44,  < .001) were found to significantly predict increased vaccination intentions in the combined model. However, the subjective norm construct did not significantly predict vaccination intentions (β = 0.06,  = .34). The TPB has greater explanatory power than the HBM in predicting the intention to obtain COVID-19 vaccination. However, the combined model showed a greater prediction level. Understanding and identifying people's perceived health beliefs and practices is critical for developing successful COVID-19 intervention methods.
Innovations in cell culture-based influenza vaccine manufacturing - from static cultures to high cell density cultivations
Zinnecker T, Reichl U and Genzel Y
Influenza remains a serious global health concern, causing significant morbidity and mortality each year. Vaccination is crucial to mitigate its impact, but requires rapid and efficient manufacturing strategies to handle timing and supply. Traditionally relying on egg-based production, the field has witnessed a paradigm shift toward cell culture-based methods offering enhanced flexibility, scalability, and process safety. This review provides a concise overview of available cell substrates and technological advancements. We summarize crucial steps toward process intensification - from roller bottle production to dynamic cultures on carriers and from suspension cultures in batch mode to high cell density perfusion using various cell retention devices. Moreover, we compare single-use and conventional systems and address challenges including defective interfering particles. Taken together, we describe the current state-of-the-art in cell culture-based influenza virus production to sustainably meet vaccine demands, guarantee a timely supply, and keep up with the challenges of seasonal epidemics and global pandemics.
"". A qualitative study on safer conception decision-making among HIV sero-different couples in Zimbabwe
Gitome S, Musara P, Chitukuta M, Mhlanga F, Mateveke B, Chirenda T, Mgodi N, Mutero P, Matubu A, Chareka G, Chasakara C, Murombedzi C, Makurumure T, Smith-Hughes C, Bukusi E, Cohen CR, Shiboski S, Darbes L, Rutherford GW, Chirenje ZM and Brown JM
Decision-making on childbearing and safer conception use in HIV sero-different couples involves an intricate balance of individual desires and perceived HIV acquisition risk. This paper addresses an important knowledge gap regarding HIV sero-different couples' considerations and the relationship and power dynamics involved when deciding to use a safer conception method. Between February and June 2019, we conducted semi-structured in-depth interviews among 14 men and 17 women, representing 17 couples, who exited the SAFER study - a pilot study assessing the feasibility, acceptability and cost-effectiveness of a safer conception programme for HIV sero-different couples in Zimbabwe. All couples in SAFER were provided with a choice of safer conception methods and were followed for up to 12 months of pregnancy attempts and 3 months following pregnancy. While couples generally perceived their safer conception discussions to be easy and consensus-driven, the decision-making process also involved complex gender dynamics and trade-offs in relationship power, which resulted in differing interpretations of what constituted a joint or shared couple decision. Participants regarded effective couple communication as an essential component of and precursor to good safer conception conversations and requested additional training in couple communication. Couples relied on information from healthcare providers to kickstart their safer conception discussions. Safer conception programmes should address relationship power imbalances, promote effective couple communication and offer healthcare provider support to enable HIV sero-different couples to make informed choices about conception in a manner that upholds their safety and reproductive autonomy.
Impacts of wildfire-season air quality on park and playground visitation in the Northwest United States
Mullan K, Avery T, Boise P, Leary CS, Rice WL and Semmens EO
A significant cost of wildfires is the exposure of local and regional populations to air pollution from smoke, which can travel hundreds of miles from the source fire and is associated with significant negative health consequences. Wildfires are increasing in frequency and intensity in the United States, driven by historic fire management approaches and global climate change. These influences will take many decades or longer to reverse, so the main opportunities for mitigating health effects involve minimizing human exposure through changes in behavior or infrastructure. One key recommendation for reducing pollution exposures during wildfire smoke events is to limit time and physical activity outdoors, but there is limited evidence on the extent to which people make this change. We estimate how use of parks and playgrounds changes with air quality during wildfire season in the northwest United States. We find small reductions in park and playground visits on moderately polluted days, and large reductions, to 50-60% of baseline visits, when pollution levels are high. Disaggregating results by neighborhood characteristics, we find a significantly greater behavioral response to moderate levels of air pollution in neighborhoods with higher socio-economic status, although responses to high levels of pollution are similar across neighborhood types.
Dupilumab improves pruritus and skin lesions in patients with prurigo nodularis: Pooled results from 2 phase 3 trials (LIBERTY-PN PRIME and PRIME2)
Yosipovitch G, Kim BS, Kwatra SG, Mollanazar NK, Ständer S, Satoh T, Mendes-Bastos P, Tsai TF, Laws E, Nivens MC, Maloney J, Shi G, Bansal A and Dubost-Brama A
Phase 3 PRIME/PRIME2 trials independently demonstrated efficacy and an acceptable safety profile of dupilumab adults with moderate-to-severe prurigo nodularis.
Accuracy of focused cardiac ultrasound interpretation among emergency and critical care medicine residents in Ethiopia: A multi-center cross-sectional study
Mekonen NM, Abicho TB, Asfaw KG, Leulseged TW, Mera NA, Habte YW, Moges FH, Birhan YA, Tesfaye M and Tesfaye B
Focused cardiac ultrasound (FoCUS) has emerged as a valuable tool in emergency and critical care medicine, allowing for rapid assessment of cardiac function and structure at the bedside. This rapid diagnostic technique holds particular promise in resource-limited settings like Ethiopia, where access to standard echocardiography may be limited and delayed. However, the accuracy of FoCUS interpretation is highly dependent on the operator's skills and expertise. To inform the design of effective interventions, the study aimed to assess the accuracy of FoCUS interpretation and associated factors among senior Emergency Medicine residents at two large referral teaching hospitals in Ethiopia.
Predictors of quality of life, economic impact, and loss to follow-up after open tibial shaft fractures in Ghana
Ativor V, Konadu-Yeboah D, O'Marr J, Brown K, Rodarte P, Kumah R, Quartey R, Awariyah D, Konadu P, Baidoo PK, Okike K, Morshed S, Shearer D and Roberts H
Open tibia fractures are associated with substantial morbidity and impact on quality of life. Despite increasing incidence in low-resource settings, most open tibia fracture research comes from high-resource settings. This study aimed to assess the impact of socioeconomic status on treatment modality and evaluate predictors of health-related quality of life following open tibia fractures in Ghana.
Advancing Global Validation and Implementation of Adult Sepsis Event Surveillance
Polito CC, Klompas M and Rhee C
Retrospect, advances and challenges in Chagas disease diagnosis: a comprehensive review
Schijman AG, Alonso-Padilla J, Britto C and Herrera Bernal CP
Chagas disease, caused by , affects millions worldwide. The 2030 WHO roadmap aims to eliminate it as a public health concern, emphasising the need for timely diagnosis to enhance treatment access. Current diagnostic algorithms, which rely on multiple tests, have prolonged turnaround times. This proves particularly problematic in resource-limited settings. Addressing this issue necessitates the validation and adoption of innovative tools. We explore recent developments in Chagas disease diagnosis, reviewing historical context and advancements. Despite progress, challenges persist. This article contributes to the understanding of current and future directions in this neglected healthcare area. Parasitological methods are simple but exhibit low sensitivity and require supplementary tests. Molecular methods, with automation potential, allow quantification and higher throughput. Serological tools show good performance but struggle with parasite antigenic diversity. Prioritising point-of-care tests is crucial for widespread accessibility and could offer a strategy to control disease impact. Ultimately, balancing achievements and ongoing obstacles is essential for comprehensive progress.
In praise of cooking gas subsidies: transitional fuels to advance health and equity
Gould CF, Bailis R, Balakrishnan K, Burke M, Espinoza S, Mehta S, Schlesinger SB, Suarez-Lopez JR and Pillarisetti A
Households that burn biomass in inefficient open fires-a practice that results in $1.6 trillion in global damages from health impacts and climate-altering emissions yearly-are often unable to access cleaner alternatives, like gas, which is widely available but unaffordable, or electricity, which is unattainable for many due to insufficient supply and reliability of electricity services. Governments are often reluctant to make gas affordable. We argue that condemnation of all fossil fuel subsidies is short-sighted and does not adequately consider subsidizing gas for cooking as a potential strategy to improve public health and reduce greenhouse gas emissions.
Assessment of cancer therapy-related cardiac dysfunction in breast cancer women using a new speckle tracking echocardiography index: The GAVS
Di Lisi D, Madaudo C, Ortello A, Rubino L, Scelfo D, Sinagra FP, Comparato F, Triolo OF, Rossetto L, Galassi AR and Novo G
Recently, peak atrial longitudinal strain (PALS) has emerged as a possible predictor of Cancer therapy-related cardiac dysfunction (CTRCD) in cancer patients (CP), in addition to left ventricular global longitudinal strain (GLS). Thus, considering the link between left atrium and left ventricle, the aim of this study was to assess the global atrio-ventricular strain (GAVS) in CP, to detect early cardiotoxicity.
Rationalizing irrational prescribing-infection-related attitudes and practices across paediatric surgery specialties in a hospital in South India
Surendran S, Nampoothiri V, Dhar P, Holmes A, Singh S and Charani E
Antibiotic use in paediatric surgical specialties is understudied. We investigated the antibiotic prescribing practices of paediatric general and cardiovascular surgical teams in a tertiary hospital in South India.
Testing in Intermittent Sports-Importance for Training and Performance Optimization in Adult Athletes
Vigh-Larsen JF, Junge N, Cialdella-Kam L, Tomás R, Young L, Krustrup P, Mohr M and Nybo L
Performance in intermittent sports relies on the interplay between multiple physiological systems determining the capacity to perform short explosive efforts as well as repeated intense actions with limited recovery over the course of an entire game. Testing should reflect these demands to allow for sport- and position-specific capacity analyses that eventually may translate into optimized training and improved performance. This may include individual load management and optimized training prescription, intensity targeting for specific positions or individual athletes, as well as benchmarking for monitoring of training progression and enhanced engagement of athletes. This review provides an overview of available tests in different exercise domains identified as relevant (from assessment of single explosive actions to intermittent endurance capacity), forming the basis for recommendations on how to compose a comprehensive yet feasible test battery that may be integrated into the seasonal competition and training plan. The test procedures should cover the performance spectrum of relevance for the individual athlete-also in team sports to account for positional differences. We emphasize the benefits of sport-specific tests, highlight parameters of importance for test standardization, and discuss how the applied test battery may be supplemented with secondary tests directed toward specific energy systems to allow for more in-depth analyses when required (e.g., in terms of an underperforming athlete). The synergy between testing and tracking of match performance (utilizing time-motion or global positioning systems) is highlighted, and although tracking cannot substitute for testing, combining the tools may provide a comprehensive overview of the physiological demands and performance during competition contextualized to the athletes' maximal exercise capacity.
Improvement in quality of life after asfotase alfa treatment in adults with pediatric-onset hypophosphatasia: data from 5 patient-reported outcome measures
Dahir KM, Ing SW, Deal C, Messali A, Bates T and Rush ET
Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. This study assessed the impact of treatment with asfotase alfa on patient-reported outcomes (PROs) in adults with pediatric-onset HPP. A longitudinal, telephone-based survey was administered to eligible individuals enrolled in a patient support program. Interviews were conducted at study entry (prior to asfotase alfa initiation) and after 3, 6, and 12 mo. PROs-Patient Health Questionnaire-9 [PHQ-9], Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI:SHP], Patient-Reported Outcomes Measurement Information System 29 [PROMIS-29], and Routine Assessment of Patient Index Data 3 [RAPID3]-were assessed at each time point. Appropriate statistical tests were performed to assess score changes. Among 50 enrolled patients (mean age: 46 yr [SD: 15.4]; 80% female; 94% White), 49 were evaluable at 3 mo, 44 at 6 mo, and 29 at 12 mo. By month 3, statistically significant improvements from baseline were detected in PHQ-9 scores (10.6 vs 5.8 [ .0001]), PROMIS-29 domain scores (overall physical function: 38.0 vs 43.0 [ .001]; anxiety: 57.5 vs 51.5 [ .0011]; fatigue: 63.3 vs 55.3 [ .0001]; sleep disturbances: 58.8 vs 54.3 [ .0099]; ability to participate in social roles and activities: 42.6 vs 47.7 [ .0012]; and pain interference: 63.8 vs 58.4 [ .001]), and RAPID3 domain scores (functional status: 2.7 vs 1.1 [ .0001]; pain tolerance: 6.0 vs 3.2 [ .0001]; and global health estimate: 5.1 vs 2.7 [ .0001]). Improvements persisted at month 12. Patients also showed improvements in WPAI:SHP domain scores at month 6 (presenteeism: 39.6% vs 14.1% [ .0001] and work productivity loss: 41.9% vs 14.1% [ .0001]). Treatment with asfotase alfa was associated with improved quality of life across several domains.
Trapping of particles diffusing in cylindrical cavity of arbitrary length and radius by two small absorbing disks on the cavity side wall: Narrow escape theory and beyond
Dagdug L and Berezhkovskii AM
Narrow escape theory deals with the first passage of a particle diffusing in a cavity with small circular windows on the cavity wall to one of the windows. Assuming that (i) the cavity has no size anisotropy and (ii) all windows are sufficiently far away from each other, the theory provides an analytical expression for the particle mean first-passage time (MFPT) to one of the windows. This expression shows that the MFPT depends on the only global parameter of the cavity, its volume, independent of the cavity shape, and is inversely proportional to the product of the particle diffusivity and the sum of the window radii. Amazing simplicity and universality of this result raises the question of the range of its applicability. To shed some light on this issue, we study the narrow escape problem in a cylindrical cavity of arbitrary size anisotropy with two small windows arbitrarily located on the cavity side wall. We derive an approximate analytical solution for the MFPT, which smoothly goes from the conventional narrow escape solution in an isotropic cavity when the windows are sufficiently far away from each other to a qualitatively different solution in a long cylindrical cavity (the cavity length significantly exceeds its radius). Our solution demonstrates the mutual influence of the windows on the MFPT and shows how it depends on the inter-window distance. A key step in finding the solution is an approximate replacement of the initial three-dimensional problem by an equivalent one-dimensional one, where the particle diffuses along the cavity axis and the small absorbing windows are modeled by delta-function sinks. Brownian dynamics simulations are used to establish the range of applicability of our approximate approach and to learn what it means that the two windows are far away from each other.
ASO Visual Abstract: The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT PREDICT Study
Shah C, Whitworth P, Vicini FA, Narod S, Gerber N, Jhawar SR, King TA, Mittendorf EA, Willey SC, Rabinovich R, Gold L, Brown E, Patel A, Vargo J, Barry PN, Rock D, Friedman N, Bedi G, Templeton S, Brown S, Gabordi R, Riley L, Lee L, Baron P, Majithia L, Mirabeau-Beale KL, Reid VJ, Hirsch A, Hwang C, Pellicane J, Maganini R, Khan S, MacDermed DM, Small W, Mittal K, Borgen P, Cox C, Shivers SC and Bremer T
Uranium standards in drinking water: An examination from scientific and socio-economic standpoints of India
Jha SK, Patra AC, Verma GP, Jha V and Aswal DK
The detection of uranium in drinking water has ignited concerns among the public, regulators, and policymakers, particularly as around 1% of the 55,554 water samples in India have shown uranium levels surpassing the 60 µg/l guideline established by the Atomic Energy Regulatory Board (AERB) based on radiological toxicity. Further, the Bureau of Indian Standard (BIS), has given a limit of 30 µg/l, which is derived from World Health Organization (WHO) guidelines. Besides the chemical and radiological aspects associated with uranium, factors such as technological constraints in water purification, waste management, environmental factors, and socio-economic conditions significantly influence these guideline values, which are often overlooked. This manuscript explores the variations in approaches for establishing guideline values and highlights the uncertainties arising from dependence on various variables such as intake and usage patterns, inter- and intra-species distinctions, and epidemiological data. A critical analysis indicates that adherence to global guidelines may result in some undesirable environmental issues. By considering factors such as population dynamics, socio-economic conditions, and geological influences, we suggest that limit of 60 µg/l for uranium in drinking water is appropriate for India.
Characterization of second primary malignancies post CAR T-cell therapy: real-world insights from the two global pharmacovigilance databases of FAERS and VigiBase
Shen J, Hu R, Lin A, Jiang A, Tang B, Liu Z, Cheng Q, Miao K, Zhang J and Luo P
The FDA's alerts regarding the T-cell lymphoma risk post CAR-T therapy has garnered global attention, yet a comprehensive profile of second primary malignancies (SPMs) following CAR-T treatment is lacking.
Prevalence of MRSA in canine and feline clinical samples from one-third of veterinary practices in Germany from 2019-2021
Feuer L, Frenzer SK, Merle R, Leistner R, Bäumer W, Bethe A, Lübke-Becker A, Klein B and Bartel A
MRSA is a major contributor to AMR-related deaths. The WHO's global action plan emphasizes a One Health approach, acknowledging the connection between humans and their companion animals. It is agreed on that comprehensive AMR surveillance is needed.
Psychometric Analysis of the Heart Failure Somatic Perception Scale in Japanese Patients With Heart Failure
Hayashi K, Okada A, Jurgens CY, Ito S and Tsuchihashi-Makaya M
Patients with heart failure (HF) experience a wide variety of symptoms. Appropriate recognition of symptoms is important in HF care. The Heart Failure Somatic Perception Scale (HFSPS) measures the presence of HF symptoms and the degree to which physical symptoms are bothersome.
Liver Transplantation Profile Among Teenagers in the United States
Alqahtani SA, Stepanova M, Shah D, Al Shabeeb R, Eberly KE, Nguyen V, Ong J and Younossi ZM
Indications for liver transplantation (LT) vary across age groups. We identified predictors of outcomes for teenage LT waitlisted candidates and recipients in the United States from 2008 to 2022.
SNCA is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients
Chen C, Li Y, Li Y, Chen Z, Shi P, Xie Y and Qian S
Cuprotosis related genes (CRGs) have been proved to be potential therapeutic targets for coronavirus disease 2019 (COVID-19) and cancer, but their immune and molecular mechanisms in COVID-19 infection in Diffuse Large B-cell Lymphoma (DLBC/DLBCL) patients are rarely reported. Our research goal is first to screen the key CRGs in COVID-19 through univariate analysis, machine learning and clinical samples. Secondly, we determined the expression and prognostic role of key CRGs in DLBCL through pan-cancer analysis. We validated the expression levels and prognosis using multiple datasets and independent clinical samples and validated the functional role of key CRGs in DLBCL through cell experiments. Finally, we validated the expression levels of CRGs in COVID-19 infected DLBCL patients samples and analyzed their common pathways in COVID-19 and DLBCL. The results show that synuclein-alpha (SNCA) is the common key differential gene of COVID-19 and DLBCL. DLBCL cells confirm that high expression of SNCA can significantly promote cell apoptosis and significantly inhibit the cycle progression of DLBCL. High expression of SNCA can regulate the binding of major histocompatibility complexes (MHCs) and T cell receptor (TCR) by regulating immune infiltration of Dendritic cells, effectively enhancing T cell-mediated anti-tumor immunity and clearing cancer cells. In conclusion, SNCA may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our study provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL patients.
Eveningness is associated with more severe depressive symptoms independently of sleep quality and fatigue level only in first-episode but not recurrent depression in major depressive disorder
Hu S, Wang F, Huang Q, Chen Y, Lyu D, Zhou N, Wang M, Zhang M, Xu C, Mueller I, Yao G, Liu X, Zhang Q and Hong W
People with an evening chronotype have an increased risk of experiencing a major depressive disorder (MDD). It is unclear if this effect is predominantly related to the initial development of MDD or also present in recurrent episodes. The current study aimed to investigate if the association between chronotype and depressive severity in MDD patients is comparable in MDD patients with first and recurrent episodes. 386 MDD patients, 70.7% females and aged between 16 and 64, participated in the study. The Morningness - Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory (MFI20), and Quick Inventory of Depressive Symptomatology (QIDS-SR16) were administered to participants to determine chronotype, sleep quality, fatigue level, and depressive severity, respectively. Multivariate regression models were utilized to analyze how chronotype influences depressive severity. The study showed that chronotype, sleep quality, and fatigue level were all associated with depressive severity. Eveningness significantly predicted an increase in depressive severity independently of sleep quality and fatigue level only in patients with the first episode (-0.068,  = 0.010), but not in patients with recurrent episodes (0.013,  = 0.594). Circadian-focused treatment should be considered in first-episode depression only.
Global public concern of childhood and adolescence suicide: a new perspective and new strategies for suicide prevention in the post-pandemic era
Kim S, Park J, Lee H, Lee H, Woo S, Kwon R, Kim S, Koyanagi A, Smith L, Rahmati M, Fond G, Boyer L, Kang J, Lee JH, Oh J and Yon DK
Suicide is the second leading cause of death in young people worldwide and is responsible for about 52,000 deaths annually in children and adolescents aged 5-19 years. Familial, social, psychological, and behavioral factors play important roles in suicide risk. As traumatic events such as the COVID-19 pandemic may contribute to suicidal behaviors in young people, there is a need to understand the current status of suicide in adolescents, including its epidemiology, associated factors, the influence of the pandemic, and management initiatives.
The role of N6-methyladenosine RNA methylation in the crosstalk of circadian clock and neuroinflammation in rodent suprachiasmatic nuclei
Filipovská E, Čočková Z, Černá B, Kubištová A, Spišská V, Telenský P and Bendová Z
N6-methyladenosine (mA) is the most abundant epitranscriptomic mark that regulates the fate of RNA molecules. Recent studies have revealed a bidirectional interaction between mA modification and the circadian clock. However, the precise temporal dynamics of mA global enrichment in the central circadian pacemaker have not been fully elucidated. Our study investigates the relationship between FTO demethylase and molecular clocks in primary cells of the suprachiasmatic nucleus (SCN). In addition, we examined the effects of lipopolysaccharide (LPS) on Fto expression and the role of FTO in LPS-induced reactive oxygen species (ROS) production in primary SCN cell culture. We observed circadian rhythmicity in the global mA levels, which mirrored the rhythmic expression of the Fto demethylase. Silencing FTO using siRNA reduced the mesor of Per2 rhythmicity in SCN primary cells and extended the period of the PER2 rhythm in SCN primary cell cultures from PER2::LUC mice. When examining the immune response, we discovered that exposure to LPS upregulated global mA levels while downregulating Fto expression in SCN primary cell cultures. Interestingly, we found a loss of circadian rhythmicity in Fto expression following LPS treatment, indicating that the decrease of FTO levels may contribute to mA upregulation without directly regulating its circadian rhythm. To explore potential protective mechanisms against neurotoxic inflammation, we examined ROS production following LPS treatment in SCN primary cell cultures pretreated with FTO siRNA. We observed a time-dependent pattern of ROS induction, with significant peak at 32 h but not at 20 h after synchronization. Silencing the FTO demethylase abolished ROS induction following LPS exposure, supporting the hypothesis that FTO downregulation serves as a protective mechanism during LPS-induced neuroinflammation in SCN primary cell cultures.
Impact of rehabilitation unit-based physical activity therapy versus symptomatic supportive treatment on older patients with advanced cancer: a non-randomized controlled study
Lu X, Wei S, Liang B, Huang C, Meng W, Zhang X and Chen X
Relatively few studies have investigated the effects of rehabilitation-based physical activity therapy as a treatment for older patients with advanced cancer. This study evaluated the effects of individualized precise and structured exercise interventions, prescribed by a rehabilitation physician, on fatigue, quality of life (QOL), and physical activity in older patients with advanced cancer.
Missing microbiomes: global underrepresentation restricts who research will benefit
Blake KS
Efficacy thresholds and target populations for antiviral COVID-19 treatments to save lives and costs: a modelling study
Le Rutte EA, Shattock AJ, Marcelino I, Goldenberg S and Penny MA
In 2023 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared endemic, yet hospital admissions have persisted and risen within populations at high and moderate risk of developing severe disease, which include those of older age, and those with co-morbidities. Antiviral treatments, currently only available for high-risk individuals, play an important role in preventing severe disease and hospitalisation within this subpopulation. Here, we further explore the public health and economic benefits of extending target populations for treatment, and assess efficacy thresholds for a treatment strategy to be cost-saving.
Imaging Assays to Detect DNA Damage in Trypanosome Parasites Using γH2A
Jumani RS, Thomas B and Rao SPS
Diseases caused by trypanosomatid parasites remain a significant unmet medical need for millions of people globally. Trypanosomatid parasites such as and subspecies of cause Chagas disease and human African trypanosomiasis (HAT), respectively. Although efforts to find novel treatments have been successful for HAT, Chagas disease is still treated with decades-old therapies that suffer from long treatment durations and severe safety concerns. We recently described the identification and characterization of the cyanotriazole compound class that kills trypanosomes, in vitro and in vivo, by selective inhibition of the trypanosome nuclear topoisomerase II enzyme. To evaluate whether inhibition of the topoisomerase II enzyme led to parasite death due to lethal double-strand DNA breaks, we developed assays for detecting DNA damage in both intracellular amastigotes of and bloodstream-form by using the canonical DNA damage marker γH2A. Herein, this article describes the protocols for detecting DNA damage using an immunofluorescence assessment of γH2A by microscopy in trypanosome parasites. Key features • Immunofluorescence-based assay to detect the γH2A response in and parasites. • Robust DNA damage pathway-based cellular assays to evaluate topoisomerase II poisons' ability to cause DNA damage. • A 384-well plate-based protocol allows high-resolution and high-throughput evaluation of compounds that cause DNA damage by measuring γH2A in intracellular parasites. • This assay could be modifiable for evaluation of DNA damage responses in various intracellular and extracellular eukaryotic pathogens.
Validity and reliability of the Greek Migraine-Specific Quality of Life Questionnaire (MSQ Version 2.1-GR)
Giannouli E, Giannouli E, Alexoudi A, Arvaniti C, Fakas N, Constantinidis TS, Kouremenos E, Mitsikostas DD and
To assess the validity and reliability of the Migraine-Specific Quality of Life Questionnaire 2.1 (MSQv.2.1) in a group of Greek migraineurs.
The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy
Hsu CY, Abdulrahim MN, Mustafa MA, Omar TM, Balto F, Pineda I, Khudair TT, Ubaid M and Ali MS
Proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol metabolism and cardiovascular diseases, has recently garnered attention for its emerging involvement in cancer biology. The multifunctional nature of PCSK9 extends beyond lipid regulation and encompasses a wide range of cellular processes that can influence cancer progression. Studies have revealed that PCSK9 can modulate signaling pathways, such as PI3K/Akt, MAPK, and Wnt/β-catenin, thereby influencing cellular proliferation, survival, and angiogenesis. Additionally, the interplay between PCSK9 and cholesterol homeostasis may impact membrane dynamics and cellular migration, further influencing tumor aggressiveness. The central role of the immune system in monitoring and controlling cancer is increasingly recognized. Recent research has demonstrated the ability of PCSK9 to modulate immune responses through interactions with immune cells and components of the tumor microenvironment. This includes effects on dendritic cell maturation, T cell activation, and cytokine production, suggesting a role in shaping antitumor immune responses. Moreover, the potential influence of PCSK9 on immune checkpoints such as PD1/PD-L1 lends an additional layer of complexity to its immunomodulatory functions. The growing interest in cancer immunotherapy has prompted exploration into the potential of targeting PCSK9 for therapeutic benefits. Preclinical studies have demonstrated synergistic effects between PCSK9 inhibitors and established immunotherapies, offering a novel avenue for combination treatments. The strategic manipulation of PCSK9 to enhance tumor immunity and improve therapeutic outcomes presents an exciting area for further investigations. Understanding the mechanisms by which PCSK9 influences cancer biology and immunity holds promise for the development of novel immunotherapeutic approaches. This review aims to provide a comprehensive analysis of the intricate connections between PCSK9, cancer pathogenesis, tumor immunity, and the potential implications for immunotherapeutic interventions.
Improved efficiency using sequential automated immunoassays for syphilis screening in blood donors
Cheng A, Das A, Styles CE, Naing Z, Rawlinson WD and Gosbell IB
Using sequential immunoassays for the screening of blood donors is well described for viral serology testing but not for the screening of syphilis. In this study, we report the evaluation results and 2-year sequential testing data using two highly sensitive automated serology assays, the Alinity s Syphilis chemiluminescent immunoassay for screening, with all repeatedly reactive samples then tested on the Elecsys Syphilis electrochemiluminescence immunoassay. We screened 1,767,782 blood donor samples between 7 July 2021 and 6 July 2023 and found the Alinity false-positive rate to be low at 0.08% (1,456/1,767,782). The common false-positive rate between the two assays was also low (3.83%, 58/1,514). Concordantly reactive samples were further tested using a particle agglutination test, a rapid plasma reagin test, and a fluorescent treponemal antibody absorption test. There were 262/1,376 concordantly reactive Alinity and Elecsys blood donor samples with reactivity on one or more of the confirmatory tests. A total of 26/1,376 donors had a current syphilis infection, 152/1,376 reported a past history of syphilis and had been treated, and 84/1,376 did not report a past history of syphilis. We suggest that future studies could explore the use of sequential immunoassays to aid in the serodiagnosis for syphilis.
Population modifiable risk factors associated with neonatal mortality in 35 sub-Saharan Africa countries: analysis of data from demographic and health surveys
Ahmed KY, Thapa S, Hassen TA, Tegegne TK, Dadi AF, Odo DB, Bizuayehu HM, Shifti DM, Belachew SA, Kibret GD, Ketema DB, Kassa ZY, Amsalu E, Bore MG, Seid A, Mesfin YM, Kibret KT, Huda MM, Mahmood S, Anyasodor AE and Ross AG
Sub-Saharan Africa (SSA) has the highest burden of neonatal mortality in the world. Identifying the most critical modifiable risk factors is imperative for reducing neonatal mortality rates. This study is the first to calculate population-attributable fractions (PAFs) for modifiable risk factors of neonatal mortality in SSA.
Multi-year analysis of the global preclinical antibacterial pipeline: trends and gaps
Gigante V, Alm RA, Melchiorri D, Rocke T, Arias CA, Czaplewski L, Fernandes P, Franceschi F, Harbarth S, Kozlov R, Lienhardt C, Ohmagari N, Ogilvie LA, Paul M, Rex JH, Silver LL, Spigelman M, Sati H and Cameron AM
Antimicrobial resistance (AMR) is a major global health threat estimated to have caused the deaths of 1.27 million people in 2019, which is more than HIV/AIDS and malaria deaths combined. AMR also has significant consequences on the global economy. If not properly addressed, AMR could immensely impact the world's economy, further increasing the poverty burden in low- and middle-income countries. To mitigate the risk of a post-antibiotic society, where the ability to effectively treat common bacterial infections is being severely threatened, it is necessary to establish a continuous supply of new and novel antibacterial medicines. However, there are gaps in the current pipeline that will prove difficult to address, given the time required to develop new agents. To understand the status of upstream antibiotic development and the challenges faced by drug developers in the early development stage, the World Health Organization has regularly assessed the preclinical and clinical antibacterial development pipeline. The review identifies potential new classes of antibiotics or novel mechanisms of action that can better address resistant bacterial strains. This proactive approach is necessary to stay ahead of evolving resistance patterns and to support the availability of effective treatment options. This review examines the trends in preclinical development and attempts to identify gaps and potential opportunities to overcome the numerous hurdles in the early stages of the antibacterial research and development space.
Peptides for microbe-induced cancers: latest therapeutic strategies and their advanced technologies
Lin Z, Assaraf YG and Kwok HF
Cancer is a significant global health concern associated with multiple distinct factors, including microbial and viral infections. Numerous studies have elucidated the role of microorganisms, such as Helicobacter pylori (H. pylori), as well as viruses for example human papillomavirus (HPV), hepatitis B virus (HBV), and hepatitis C virus (HCV), in the development of human malignancies. Substantial attention has been focused on the treatment of these microorganism- and virus-associated cancers, with promising outcomes observed in studies employing peptide-based therapies. The current paper provides an overview of microbe- and virus-induced cancers and their underlying molecular mechanisms. We discuss an assortment of peptide-based therapies which are currently being developed, including tumor-targeting peptides and microbial/viral peptide-based vaccines. We describe the major technological advancements that have been made in the design, screening, and delivery of peptides as anticancer agents. The primary focus of the current review is to provide insight into the latest research and development in this field and to provide a realistic glimpse into the future of peptide-based therapies for microbe- and virus-induced neoplasms.
The evolving role of pharmacists in depression care: a scoping review
Shalash A and Zolezzi M
Worldwide, depression is known to contribute significantly to the global burden of disease. Considering pharmacists are among the most approachable healthcare providers, they are well-placed to assist people with depression achieve positive treatment outcomes.
To neutrally offer or strongly recommend? General practitioners' perspectives on screening for gestational diabetes according to the national guideline in Norway
Forthun I, Møen KA and Hjörleifsson S
To explore general practitioners' experiences and reflections on how the current Norwegian guideline for screening for gestational diabetes affects their clinical practice.
Implementation of a machine learning model in acute coronary syndrome and stroke risk assessment for patients with lower urinary tract symptoms
Shen TT, Liu CF and Wu MP
The global population is aging and the burden of lower urinary tract symptoms (LUTS) is expected to increase. According to the National Health Insurance Research Database, our previous studies have showed LUTS may predispose patients to cardiovascular disease. However, it is difficult to provide a personalized risk assessment in the context of "having acute coronary syndrome (ACS) and stroke." This study aimed to develop an artificial intelligence (AI)-based prediction model for patients with LUTS.
Dysfunctional host cellular immune responses are associated with mortality in melioidosis
Wright SW, Ekchariyawat P, Sengyee S, Phunpang R, Dulsuk A, Saiprom N, Thiansukhon E, Pattanapanyasat K, Korbsrisate S, Eoin West T and Chantratita N
Melioidosis is a tropical infection caused by the intracellular pathogen , an underreported and emerging global threat. As melioidosis-associated mortality is frequently high despite antibiotics, novel management strategies are critically needed. Therefore, we sought to determine whether functional changes in the host innate and adaptive immune responses are induced during acute melioidosis and are associated with outcome. Using a unique whole blood stimulation assay developed for use in resource-limited settings, we examined induced cellular functional and phenotypic changes in a cohort of patients with bacteremic melioidosis prospectively enrolled within 24 hours of positive blood culture and followed for 28 days. Compared to healthy controls, melioidosis survivors generated an IL-17 response mediated by Th17 cells and terminally-differentiated effector memory CD8 T cells (P < 0.05, both), persisting to 28-days after enrollment. Furthermore, melioidosis survivors developed polyfunctional cytokine production in CD8 T cells (P < 0.01). Conversely, a reduction in CCR6 CD4 T cells was associated with higher mortality, even after adjustments for severity of illness (P = 0.004). Acute melioidosis was also associated with a profound acute impairment in monocyte function as stimulated cytokine responses were reduced in classical, intermediate and non-classical monocytes. Impaired monocyte cytokine function improved by 28-days after enrollment. These data suggest that IL-17 mediated cellular responses may be contributors to host defense during acute melioidosis, and that innate immune function may be impaired. These insights could provide novel targets for the development of therapies and vaccine targets in this frequently lethal disease.
The impact of cytokines in neuroinflammation-mediated stroke
Kumari S, Dhapola R, Sharma P, Nagar P, Medhi B and HariKrishnaReddy D
Cerebral stroke is ranked as the third most common contributor to global mortality and disability. The involvement of inflammatory mechanisms, both peripherally and within the CNS, holds significance in the pathophysiological cascades following the initiation of stroke. After the onset of acute stroke, predominantly ischemic, a subsequent phase of neuroinflammation ensues. It is a dual-effect process that not only exacerbates injury, leading to cell death, but paradoxically, it also serves a shielding role in facilitating recovery. Cytokines serve as pivotal mediators within the inflammatory cascade, actively contributing to the progression of ischemic damage. Stroke is followed by increased expression of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, etc. leading to the recruitment and stimulation of glial cells and peripheral leukocytes at the site of injury, promoting neuroinflammation. Cytokines can directly induce neuronal injury and death through various mechanisms, including excitotoxicity, oxidative stress, HPA-axis activation, secretion of matrix metalloproteinase and apoptosis. They can also amplify the inflammatory response, leading to further neuronal damage. Therapeutic strategies aimed at modulating cytokine release, immune response and cytokine signalling or activity are being explored as potential interventions to mitigate neuroinflammation and its detrimental effects in stroke. In this review, we have given a concise summary of our current knowledge of the function of various cytokines, brain inflammation and various signalling and molecular pathways including JAK/STAT3, TGF-β/Smad, MAPK, HMGB1/TLR and NF-κB modulated cytokines regulation in stroke. Therapeutic agents such as MCC950, genistein, edaravone, minocycline, etc. targeting various cytokines-associated signalling pathways have shown efficacy in preclinical and clinical trials reducing the pathophysiology of the illness were also addressed in this study.
Characterizing Excretory-Secretory Products Proteome Across Larval Development Stages in
Castañeda S, Adeniyi-Ipadeola G, Wu Y, Suarez-Reyes C, Jain A, Ramírez JD and Weatherhead JE
and are parasitic nematodes that primarily infest the small intestines of humans and pigs, respectively. Ascariasis poses a significant threat to human health and swine health. Understanding larval development is crucial for developing novel therapeutic interventions that will prevent ascariasis in both humans and pigs. This study aimed to characterize the excretory-secretory (ES) proteome of different larval stages (L3-egg, L3-lung, L3-trachea) to identify potential targets for intervention to prevent -induced global morbidity.
Favorable breast cancer mortality-to-incidence ratios of countries with good human development index rankings and high health expenditures
Chou CY, Shen TT, Wang WC and Wu MP
Breast cancer is the most frequently diagnosed cancer among women worldwide. Mortality-to-incidence ratio (MIR) is a marker that reflects the efficacy and availability of screening interventions and treatment outcomes. MIR can be used to influence public health strategy. The association between the MIRs for breast cancer among countries with different economic statuses and health expenditure is important yet has been investigated. This study was aimed to elucidate the association between the breast cancer MIRs and the human development and health expenditure among different countries.
ChatGPT and assistive AI in structured radiology reporting: A systematic review
Sacoransky E, Kwan BYM and Soboleski D
The rise of transformer-based large language models (LLMs), such as ChatGPT, has captured global attention with recent advancements in artificial intelligence (AI). ChatGPT demonstrates growing potential in structured radiology reporting-a field where AI has traditionally focused on image analysis.
Incidence of Hospitalization due to Influenza-Associated Severe Acute Respiratory Infection During 2010-2019 in Bangladesh
Aleem MA, DeBord KR, Ahmed M, Rahman MZ, Rahman M, Islam MA, Alamgir ASM, Salimuzzaman M, Shirin T, Chisti MJ, Rahman M, Azziz-Baumgartner E, Chowdhury F and Iuliano AD
Global influenza-associated acute respiratory infections contribute to 3-5 million severe illnesses requiring hospitalization annually, with 90% of hospitalizations occurring among children < 5 years in developing countries. In Bangladesh, the inadequate availability of nationally representative, robust estimates of influenza-associated hospitalizations limits allocation of resources for prevention and control measures.
Assessing the presence of sustainability education in the curriculum of medical students and surgical trainees in Africa: A cross-sectional study
Zolo Y, Demissie MA, Echengi EM, Davis B, Ornella PF, Sichimba D, Dalle DU, Simo F, Sunday CI, Pulani Y and Esene I
Integrating sustainability principles into medical and surgical curricula raises awareness and empowers future healthcare professionals to adopt sustainable practices, reducing the environmental impact of surgical care. This study aims to assess the presence of sustainability education in African medical schools and surgical residency curricula to inform policymakers and educators in African healthcare systems.
The carbon footprint of health care delivery in Western Australia's public health system
Irwin A, Malik A, Vyas A, Bateman C and Joyce S
Health systems have a dual imperative to take action on climate change. First, they must develop climate resilient health services in response to the direct and indirect impacts of climate change on health. Second, they must reduce their own carbon footprint since health systems are a significant contributor to global greenhouse gas emissions.
An orbitocortical-thalamic circuit suppresses binge alcohol-drinking
Gimenez-Gomez P, Le T, Zinter M, M'Angale P, Duran-Laforet V, Freels TG, Pavchinskiy R, Molas S, Schafer DP, Tapper AR, Thomson T and Martin GE
Alcohol consumption remains a significant global health challenge, causing millions of direct and indirect deaths annually. Intriguingly, recent work has highlighted the prefrontal cortex, a major brain area that regulates inhibitory control of behaviors, whose activity becomes dysregulated upon alcohol abuse. However, whether an endogenous mechanism exists within this brain area that limits alcohol consumption is unknown. Here we identify a discrete GABAergic neuronal ensemble in the medial orbitofrontal cortex (mOFC) that is selectively recruited during binge alcohol-drinking and intoxication. Upon alcohol intoxication, this neuronal ensemble suppresses binge drinking behavior. Optogenetically silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. We find that this neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. We further show, using brain-wide analysis, that this neuronal ensemble projects widely, and that its projections specifically to the mediodorsal thalamus are responsible for regulating binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by halting alcohol intake. These results provide valuable insights into the complex nature of alcohol abuse and offers potential avenues for the development of mOFC neuronal ensemble-targeted interventions.
Computational Insights into Papaveroline as an In Silico Drug Candidate for Alzheimer's Disease via Fyn Tyrosine Kinase Inhibition
Bhat SS, Kulkarni SR, Uttarkar A and Niranjan V
Alzheimer's disease (AD) poses a significant global health challenge, necessitating the exploration of novel therapeutic strategies. Fyn Tyrosine Kinase has emerged as a key player in AD pathogenesis, making it an attractive target for drug development. This study focuses on investigating the potential of Papaveroline as a drug candidate for AD by targeting Fyn Tyrosine Kinase. The research employed high-throughput virtual screening and QSAR analysis were conducted to identify compounds with optimal drug-like properties, emphasizing adherence to ADMET parameters for further evaluation. Molecular dynamics simulations to analyze the binding interactions between Papaveroline and Staurosporine with Fyn Tyrosine Kinase over a 200-ns period. The study revealed detailed insights into the binding mechanisms and stability of the Papaveroline-Fyn complex, showcasing the compound's potential as an inhibitor of Fyn Tyrosine Kinase. Comparative analysis with natural compounds and a reference compound highlighted Papaveroline's unique characteristics and promising therapeutic implications for AD treatment. Overall, the findings underscore Papaveroline's potential as a valuable drug candidate for targeting Fyn Tyrosine Kinase in AD therapy, offering new avenues for drug discovery in neurodegenerative diseases. This study contributes to advancing our understanding of molecular interactions in AD pathogenesis and paves the way for further research and development in this critical area.
Correspondence on 'Technique and impact on first pass effect primary results of the ASSIST global registry' by Gupta
Sacks D
Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease
Wang D, Zhou BY, Xiang L, Chen XY and Feng JX
In this editorial, we comment on the article by Chen . Metabolic dysfunction-associated fatty liver disease (MAFLD) is a global public health burden whose incidence has risen concurrently with overweight and obesity. Given its detrimental health impact, early identification of at-risk individuals is crucial. MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy, imaging, or blood biomarkers, and one of the following conditions: Overweight/ obesity, type 2 diabetes mellitus, or metabolic dysregulation. However, in large-scale epidemiological studies, liver biopsies are not feasible. The application of techniques such as ultrasonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy is restricted by their limited sensitivity, low effectiveness, high costs, and need for specialized software. Blood biomarkers offer several advantages, particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical. Analysis of cumulative effects of excess high-normal blood alanine aminotransferase (ALT) levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods. Accordingly, investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring, enabling timely intervention and management and improving patient outcomes.
Beyond surface: Unveiling ecological and economic ramifications of microplastic pollution in the oceans
Kurniawan TA, Mohyuddin A, Othman MHD, Goh HH, Zhang D, Anouzla A, Aziz F, Casila JC, Ali I and Pasaribu B
Every year, the global production of plastic waste reaches a staggering 400 million metric tons (Mt), precipitating adverse consequences for the environment, food safety, and biodiversity as it degrades into microplastics (MPs). The multifaceted nature of MP pollution, coupled with its intricate physiological impacts, underscores the pressing need for comprehensive policies and legislative frameworks. Such measures, alongside advancements in technology, hold promise in averting ecological catastrophe in the oceans. Mandated legislation represents a pivotal step towards restoring oceanic health and securing the well-being of the planet. This work offers an overview of the policy hurdles, legislative initiatives, and prospective strategies for addressing global pollution due to MP. Additionally, this work explores innovative approaches that yield fresh insights into combating plastic pollution across various sectors. Emphasizing the importance of a global plastics treaty, the article underscores its potential to galvanize collaborative efforts in mitigating MP pollution's deleterious effects on marine ecosystems. Successful implementation of such a treaty could revolutionize the plastics economy, steering it towards a circular, less polluting model operating within planetary boundaries. Failure to act decisively risks exacerbating the scourge of MP pollution and its attendant repercussions on both humanity and the environment. Central to this endeavor are the formulation, content, and execution of the treaty itself, which demand careful consideration. While recognizing that a global plastics treaty is not a panacea, it serves as a mechanism for enhancing plastics governance and elevating global ambitions towards achieving zero plastic pollution by 2040. Adopting a life cycle approach to plastic management allows for a nuanced understanding of possible trade-offs between environmental impact and economic growth, guiding the selection of optimal solutions with socio-economic implications in mind. By embracing a comprehensive strategy that integrates legislative measures and technological innovations, we can substantially reduce the influx of marine plastic litter at its sources, safeguarding the oceans for future generations.
[Smoking cessation influencing factors and interventions in adolescents]
Jia XK and Xiao L
Smoking can negatively influence the development of the respiratory and cardiovascular systems of adolescents and increase the risk for chronic diseases in adulthood. Promotion smoking cessation in adolescents is important for the protection of adolescent health and reduction of smoking rate in adults. Although many foreign studies have explored the influencing factors and interventions for smoking cessation in adolescents, limited relevant studies have been conducted in China, especially the study of smoking cessation intervention, which is still in its infancy, so the research and practice in this field need to be strengthened. This paper summarizes the factors associated with smoking cessation in adolescents both at home and abroad from the perspective of individual, family, school, and social surrounding, and introduce existing smoking cessation interventions for adolescents to provide references for future studies.
Identification of novel variants in BRF1 gene from patient with developmental delay, hearing abnormality, and nervous system anomalies
Yin H, Yu Y and Shen Y
Cerebellofaciodental syndrome characterized with dysmorphic features, intellectual disability, and brain anomalies. Now its clinical spectrum expanded more manifestations including bilateral sensorineural hearing impairment and inner ear malformation. Here, we report a 14-month-old boy with global developmental delay and hearing disorder. Whole exome sequencing (WES) revealed the compound heterozygous variants [NM_001519.4: c.652 T > G (p.W218G); c.915 + 1G > T] in the BRF1 gene which inherited from his parents, respectively. The MRI results showed hypoplastic cerebellar vermis, enlarged cisterna magna, and prominent fourth ventricle, the rehabilitation therapy failed to improve the symptoms for our patient. Our finding expands the genetic spectrum of BRF1 variants, which indicates patients with the developmental delay caused by BRF1 variants require other treatments instead of rehabilitation.
Mind the Gap in Kidney Care: Translating What We Know Into What We Do
Luyckx VA, Tuttle KR, Abdellatif D, Correa-Rotter R, Fung WWS, Haris A, Hsiao LL, Khalife M, Kumaraswami LA, Loud F, Raghavan V, Roumeliotis S, Sierra M, Ulasi I, Wang B, Lui SF, Liakopoulos V and Balducci A
Biofortification of Triticum species: a stepping stone to combat malnutrition
Kumar J, Saini DK, Kumar A, Kumari S, Gahlaut V, Rahim MS, Pandey AK, Garg M and Roy J
Biofortification represents a promising and sustainable strategy for mitigating global nutrient deficiencies. However, its successful implementation poses significant challenges. Among staple crops, wheat emerges as a prime candidate to address these nutritional gaps. Wheat biofortification offers a robust approach to enhance wheat cultivars by elevating the micronutrient levels in grains, addressing one of the most crucial global concerns in the present era.
Integrative genomic reconstruction of carbohydrate utilization networks in bifidobacteria: global trends, local variability, and dietary adaptation
Arzamasov AA, Rodionov DA, Hibberd MC, Guruge JL, Kazanov MD, Leyn SA, Kent JED, Sejane K, Bode L, Barratt MJ, Gordon J and Osterman A
Bifidobacteria are among the earliest colonizers of the human gut, conferring numerous health benefits. While multiple Bifidobacterium strains are used as probiotics, accumulating evidence suggests that the individual responses to probiotic supplementation may vary, likely due to a variety of factors, including strain type(s), gut community composition, dietary habits of the consumer, and other health/lifestyle conditions. Given the saccharolytic nature of bifidobacteria, the carbohydrate composition of the diet is one of the primary factors dictating the colonization efficiency of Bifidobacterium strains. Therefore, a comprehensive understanding of bifidobacterial glycan metabolism at the strain level is necessary to rationally design probiotic or synbiotic formulations that combine bacterial strains with glycans that match their nutrient preferences. In this study, we systematically reconstructed 66 pathways involved in the utilization of mono-, di-, oligo-, and polysaccharides by analyzing the representation of 565 curated metabolic functional roles (catabolic enzymes, transporters, transcriptional regulators) in 2973 non-redundant cultured Bifidobacterium isolates and metagenome-assembled genomes (MAGs). Our analysis uncovered substantial heterogeneity in the predicted glycan utilization capabilities at the species and strain level and revealed the presence of a yet undescribed phenotypically distinct subspecies-level clade within the Bifidobacterium longum species. We also identified Bangladeshi isolates harboring unique gene clusters tentatively implicated in the breakdown of xyloglucan and human milk oligosaccharides. Predicted carbohydrate utilization phenotypes were experimentally characterized and validated. Our large-scale genomic analysis considerably expands the knowledge of carbohydrate metabolism in bifidobacteria and provides a foundation for rationally designing single- or multi-strain probiotic formulations of a given bifidobacterial species as well as synbiotic combinations of bifidobacterial strains matched with their preferred carbohydrate substrates.
Metabolic Profiles of Encapsulated Chondrocytes Exposed to Short-Term Simulated Microgravity
Bergstrom AR, Glimm MG, Houske EA, Cooper G, Viles E, Chapman M, Bourekis K, Welhaven HD, Brahmachary PP, Hahn AK and June RK
The mechanism by which chondrocytes respond to reduced mechanical loading environments and the subsequent risk of developing osteoarthritis remains unclear. This is of particular concern for astronauts. In space the reduced joint loading forces during prolonged microgravity (10 ) exposure could lead to osteoarthritis (OA), compromising quality of life post-spaceflight. In this study, we encapsulated human chondrocytes in an agarose gel of similar stiffness to the pericellular matrix to mimic the cartilage microenvironment. We then exposed agarose-chondrocyte constructs to simulated microgravity (SM) using a rotating wall vessel (RWV) bioreactor to better assess the cartilage health risks associated with spaceflight. Global metabolomic profiling detected a total of 1205 metabolite features across all samples, with 497 significant metabolite features identified by ANOVA (FDR-corrected p-value < 0.05). Specific metabolic shifts detected in response to SM exposure resulted in clusters of co-regulated metabolites, as well as key metabolites identified by variable importance in projection scores. Microgravity-induced metabolic shifts in gel constructs and media were indicative of protein synthesis, energy metabolism, nucleotide metabolism, and oxidative catabolism. The microgravity associated-metabolic shifts were consistent with early osteoarthritic metabolomic profiles in human synovial fluid, which suggests that even short-term exposure to microgravity (or other reduced mechanical loading environments) may lead to the development of OA.
Variability in self-reported and biomarker-derived tobacco smoke exposure patterns among individuals who do not smoke by poverty income ratio in the USA
Titus AR, Shelley D and Thorpe LE
Tobacco smoke exposure (TSE) among individuals who do not smoke has declined in the USA, however, gaps remain in understanding how TSE patterns across indoor venues-including in homes, cars, workplaces, hospitality venues, and other areas-contribute to TSE disparities by income level.
Core-Shell Gel Nanofiber Scaffolds Constructed by Microfluidic Spinning toward Wound Repair and Tissue Regeneration
Dong Y, Ding Z, Bai Y, Lu LY, Dong T, Li Q, Liu JD and Chen S
Growing demand for wound care resulting from the increasing chronic diseases and trauma brings intense pressure to global medical health service system. Artificial skin provides mechanical and microenvironmental support for wound, which is crucial in wound healing and tissue regeneration. However, challenges still remain in the clinical application of artificial skin since the lack of the synergy effect of necessary performance. In this study, a multi-functional artificial skin is fabricated through microfluidic spinning technology by using core-shell gel nanofiber scaffolds (NFSs). This strategy can precisely manipulate the microstructure of artificial skin under microscale. The as-prepared artificial skin demonstrates superior characteristics including surface wettability, breathability, high mechanical strength, strain sensitivity, biocompatibility and biodegradability. Notably, this artificial skin has the capability to deliver medications in a controlled and sustained manner, thereby accelerating the wound healing process. This innovative approach paves the way for the development of a new generation of artificial skin and introduces a novel concept for the structural design of the unique core-shell gel NFSs.
A multifaceted ecological approach to explore links between environmental factors and the epidemiology of disorders of gut-brain interaction
Fairlie T, Shah A, Wong RK, Fang X, Ghoshal UC, Kashyap PC, Mulak A, Lee YY, Sperber AD, Koloski N, Moy N, Talley NJ, Jones MP and Holtmann G
Disorders of gut-brain interaction (DGBI) are characterized by debilitating symptoms not explained by structural or biochemical abnormalities. While functional conditions present with complex, likely heterogeneous pathophysiology, we aimed to investigate if proxy measures of sociocultural and environmental factors are associated with the prevalence of various DGBI in populations across the world.
Authors response: "Association between elevated lactate and clinical outcomes in adults with diabetic ketoacidosis"
Kumar A, Doola R, Zahumensky A, Shaikh A, Tabah A, Laupland KB and Ramanan M
Long-term impact of 10-valent pneumococcal conjugate vaccine in Kenya: Nasopharyngeal carriage among children in a rural and an urban site six years after introduction
Verani JR, Omondi D, Odoyo A, Odiembo H, Ouma A, Ngambi J, Aol G, Audi A, Kiplangat S, Agumba N, Munywoki PK, Onyango C, Hunsperger E, Farrar JL, Kim L, Kobayashi M, Breiman RF, Pimenta FC, da Gloria Carvalho M, Lessa FC, Whitney CG and Bigogo G
Kenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1-2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya.
Repurposing Sewage and Toilet Systems: Environmental, Public Health, and Person-Centered Healthcare Applications
Yigci D, Bonventre J, Ozcan A and Tasoglu S
Global terrestrial water supplies are rapidly depleting due to the consequences of climate change. Water scarcity results in an inevitable compromise of safe hygiene and sanitation practices, leading to the transmission of water-borne infectious diseases, and the preventable deaths of over 800.000 people each year. Moreover, almost 500 million people lack access to toilets and sanitation systems. Ecosystems are estimated to be contaminated by 6.2 million tons of nitrogenous products from human wastewater management practices. It is therefore imperative to transform toilet and sewage systems to promote equitable access to water and sanitation, improve public health, conserve water, and protect ecosystems. Here, the integration of emerging technologies in toilet and sewage networks to repurpose toilet and wastewater systems is reviewed. Potential applications of these systems to develop sustainable solutions to environmental challenges, promote public health, and advance person-centered healthcare are discussed.
Interleukin-1 receptor 1 deficiency worsens hepatocellular carcinoma, while gemcitabine treatment alleviates the hepatocellular carcinoma-induced increase in intra-hepatic immune cells
Chu CS, Chen HP, Lin PH, Cheng CC, Kuo HY, Fan PH, Peng WH and Wu LL
Primary liver cancer, particularly hepatocellular carcinoma (HCC), represents a substantial global health challenge. Although immune checkpoint inhibitors are effective in HCC treatment, several patients still experience disease progression. Interleukin-1 (IL-1) regulates immunity and inflammation. We investigate the role of IL-1 in HCC development and progression and determine the potential therapeutic impact of gemcitabine in treating HCC.
Perception of couples' on multipurpose prevention technology attribute choice: the case of MTN 045
Dandadzi A, Young AM, Musara P, Shapley-Quinn MK, Kemigisha D, Mutero P, Mgodi NM, Etima J and Minnis AA
Multipurpose prevention technologies (MPTs) are products capable of simultaneously addressing multiple sexual and reproductive health needs such as unwanted pregnancy, STIs including HIV-1, and other reproductive tract infections. MPTs are urgently needed to address the double burden of unplanned pregnancy and HIV. While condoms are currently the only accessible MPTs, they are not solely under a woman's control, and female condoms face limitations due to poor acceptability and high cost.
Discontinuation of Nucleos(t)ide Analogues in HBeAg Negative Chronic Hepatitis B Patients: Risks and Benefits
Korkmaz P and Demirtürk N
Chronic hepatitis B (CHB) remains a major threat to global public health, affecting 296 million people worldwide. Although there is no curative treatment for CHB today, the virus can be effectively controlled with current antiviral treatment strategies. Since HBsAg loss can rarely (1%) be achieved with current nucleos(t)ide analogues (NA) options, lifelong treatment is usually required in HBeAg-negative patients. In recent years, guidelines have stated that long-term NA treatments can be discontinued for HBeAg-negative patients without achieving HBsAg loss. There is no general consensus on how discontinuation of NA can be included in the treatment approach. This review aimed to evaluate the current literature regarding the discontinuation of NA treatment in HBeAg-negative patients. Patients with HBeAg-negative CHB who have a higher chance of response after discontinuation of NA therapy can be defined as non-cirrhotic patients who have low HBsAg, HBcrAg, and HBV RNA levels at the discontinuation of treatment and accept close follow-up. The management of relapses that develop after NA discontinuation in patients is also unclear. The agent used in NA treatment itself may also affect the pattern of relapse development. Relapse after NA treatment occurs significantly slower and less frequently with entecavir compared to other regimens, including tenofovir dipivoxil. Prospective studies are needed in order to maintain the chance of HBsAg clearance in case of exacerbation and to treat acute exacerbations that can be fatal in a timely manner. Algorithms to be developed for use after discontinuation of NA treatment will help the clinician manage the patient safely.
Meniscus-Related Videos on TikTok Are Widely Viewed and Shared but the Educational Quality for Patients Is Poor
D'Ambrosi R and Hewett TE
To evaluate the quality of meniscus-related TikTok videos to better understand their value for patient education.
Relations Between Cardiorespiratory Fitness and Cognition in Older Adults With Amnestic Mild Cognitive Impairment From the Aerobic Exercise and Cognitive Training (ACT) Trial: Sex Differences
Yu F, Salisbury D, Pituch KA and Lin FV
To examine the associations of cardiorespiratory fitness with executive function, episodic memory, and global cognition and sex differences in these associations in community-dwelling older adults with amnestic mild cognitive impairment.
Dr. Dilip Mahalanabis (1934-2022): Trailblazer in Diarrheal Disease Management
Kawalkar U, Mankar A, Kogade P and Naitam D
Dilip Mahalanabis, an esteemed Indian pediatrician, revolutionized global health through his pioneering work in combatting diarrheal diseases, particularly during the Bangladesh War of Independence in 1971. His development of oral rehydration therapy (ORT) provided a simple, cost-effective solution that significantly reduced mortality rates among cholera patients. Mahalanabis' dedication to equitable healthcare, evidenced by his leadership roles in organizations such as the World Health Organization (WHO), underscores his legacy as a champion for vulnerable populations. ORT's widespread adoption has democratized treatment, empowering communities and drastically reducing mortality rates associated with diarrheal diseases.
Source-Dependent Quality Variation in Shoulder Dislocation Videos on YouTube
Kaymakoglu M, Aksoy T, Kolac UC, Ozdemir E, DePhillipo NN, Huri G and Familiari F
To assess the quality of YouTube videos for patient education on shoulder dislocation.
The Assessment of Geriatric Depression Among Primary Healthcare Physicians in Buraidah City, Saudi Arabia
Aljarallah JA and Sekhar C
 The global geriatric population is increasing, leading to a higher prevalence of non-communicable diseases, including depression. This condition often remains underdiagnosed and untreated disease.
Epidemiology and Clinical Outcomes of Bacterial Meningitis in Children and Adults in Low- and Middle-Income Countries
Villalpando-Carrión S, Henao-Martínez AF and Franco-Paredes C
Despite the availability of effective vaccines against the three primary pathogens (, type b, and ) that cause bacterial meningitis, this condition remains a significant cause of morbidity, neurologic sequelae, and mortality among children and adults living in low-income and middle-income countries.
Defining Trajectories of Linguistic, Cognitive-Communicative, and Quality of Life Outcomes in Aphasia: Longitudinal Observational Study Protocol
Cherney LR, Kozlowski AJ, Domenighetti AA, Baliki MN, Kwasny MJ and Heinemann AW
To describe the trajectories of linguistic, cognitive-communicative, and health-related quality of life (HRQOL) outcomes after stroke in persons with aphasia.
Beyond the Chair: Exploring the Boundaries of Teledentistry
Malpe M, Choudhari SG, Nagtode N and Muntode Gharde P
Teledentistry, a blend of dentistry and telecommunications used to provide dental care from a distance, holds great promise in enhancing public health, especially in reaching communities with limited access. However, putting it into practice has its own set of obstacles and background variables. It is frequently difficult to obtain dental treatment, especially in rural or economically underdeveloped areas. By removing geographical constraints and offering virtual consultations and diagnostics, teledentistry provides a solution. The quick development of technology, such as portable electronics and high-speed internet, has increased accessibility and efficiency in communication, which has aided in the acceptance of teledentistry. Getting traditional dental care can be costly, particularly for people without insurance. As an affordable substitute for traditional dental care, teledentistry may lower overhead expenses related to physical dental offices. Early interventions and preventive care can greatly enhance oral health results and lessen the need for later, more invasive procedures. There are disparities in the availability of digital gadgets and internet connectivity. The laws that control telehealth services might differ greatly between nations and areas. While teledentistry can help with remote consultations and triage, it might not be able to do thorough examinations or other diagnostic treatments that need in-person attendance. Delivering dependable, top-notch telemedicine services in developing areas can pose challenges. Certain dentists might hesitate to utilize teledentistry due to concerns about the quality of care, liability issues, or potential impacts on their traditional practice models. It could be difficult to get patients to accept and use teledentistry services. This review is undertaken to assess the effectiveness of teledentistry in public health as well as legal and regulatory considerations for practicing teledentistry. Teledentistry might be the future of the oral health sector, thus fully capitalizing on this enormous opportunity to change how oral therapies are administered. Patients, dentists, and the dental community at large will need to have highly open minds. For the community's well-being and to gain its trust, ethical considerations are crucial. The outcomes of teledentistry can be attained by overcoming the obstacles and using comprehensive methods and approaches. It was noted that teledentistry is a potential strategy that combines dental care with telecommunication technology to enhance patient outcomes, reduce healthcare inequalities, and expand access to oral health services. The delivery of oral healthcare is being revolutionized by teledentistry, especially in light of contemporary issues including geographic restrictions, lack of access to dental treatment, and the ongoing global health crisis.
Unveiling the intricacies of COVID-19: Autoimmunity, multi-organ manifestations and the role of autoantibodies
Ding Z, Wei X, Pan H, Shi H and Shi Y
COVID-19 is a severe infectious disease caused by a SARS-CoV-2 infection. It has caused a global pandemic and can lead to acute respiratory distress syndrome (ARDS). Beyond the respiratory system, the disease manifests in multiple organs, producing a spectrum of clinical symptoms. A pivotal factor in the disease's progression is autoimmunity, which intensifies its severity and contributes to multi-organ injuries. The intricate interaction between the virus' spike protein and human proteins may engender the generation of autoreactive antibodies through molecular mimicry. This can further convolute the immune response, with the potential to escalate into overt autoimmunity. There is also emerging evidence to suggest that COVID-19 vaccinations might elicit analogous autoimmune responses. Advanced technologies have pinpointed self-reactive antibodies that target diverse organs or immune-modulatory proteins. The interplay between autoantibody levels and multi-organ manifestations underscores the importance of regular monitoring of serum antibodies and proinflammatory markers. A combination of immunosuppressive treatments and antiviral therapy is crucial for managing COVID-19-associated autoimmune diseases. The review will focus on the generation of autoantibodies in the context of COVID-19 and their impact on organ health.
extract versus placebo in the treatment of COVID-19: a double-blinded randomized control trial
Kanokkangsadal P, Mingmalairak C, Mukkasombat N, Kuropakornpong P, Worawattananutai P, Khawcharoenporn T, Sakpakdeejaroen I, Davies NM and Itharat A
(Burm.f.) Nees has been recommended to relieve symptoms and decrease the severity of COVID-19. The clinical study aimed to investigate the efficacy and safety of ethanolic extract (APE).
Insights on the conformation and appropriate drug-target sites on retinal IMPDH1 using the 604-aa isoform lacking the C-terminal extension
Elyasi-Ebli P, Yazdanparast R, Gharaghani S and Barzegari E
Retinitis pigmentosa (RP) accounts for 2 percent of global cases of blindness. The RP10 form of the disease results from mutations in isoform 1 of inosine 5'-monophosphate dehydrogenase (IMPDH1), the rate-limiting enzyme in the purine nucleotide synthesis pathway. Retinal photoreceptors contain specific isoforms of IMPDH1 characterized by terminal extensions. Considering previously reported significantly varied kinetics among retinal isoforms, the current research aimed to investigate possible structural explanations and suitable functional sites for the pharmaceutical targeting of IMPDH1 in RP.
Determinants of Intention to Uptake COVID-19 Vaccination Among Saudi Adults: Application of the Health Belief Model
Alshagrawi SS
The pandemic caused by COVID-19 has had a profound effect on global health. Due to its potential impact on the efficacy of pandemic control measures, vaccine hesitancy (VH) in relation to COVID-19 has emerged as a significant concern. The attainment of herd immunity is contingent on the rate of COVID-19 vaccine adoption. Despite this, there have been reports of reluctance toward the COVID-19 vaccine. This study seeks to investigate the effect of constructs that influence adults' intentions to receive COVID-19 vaccination using the Health Belief Model (HBM).
Artificial Intelligence-Clinical Decision Support System in Infectious Disease Control: Combatting Multidrug-Resistant with Machine Learning
Jian MJ, Lin TH, Chung HY, Chang CK, Perng CL, Chang FY and Shang HS
The World Health Organization has identified (KP) as a significant threat to global public health. The rising threat of carbapenem-resistant (CRKP) leads to prolonged hospital stays and higher medical costs, necessitating faster diagnostic methods. Traditional antibiotic susceptibility testing (AST) methods demand at least 4 days, requiring 3 days on average for culturing and isolating the bacteria and identifying the species using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), plus an extra day for interpreting AST results. This lengthy process makes traditional methods too slow for urgent clinical situations requiring rapid decision-making, potentially hindering prompt treatment decisions, especially for fast-spreading infections such as those caused by CRKP. This research leverages a cutting-edge diagnostic method that utilizes an artificial intelligence-clinical decision support system (AI-CDSS). It incorporates machine learning algorithms for the swift and precise detection of carbapenem-resistant and colistin-resistant strains.
Developing an Ethical Evaluation Framework for Coercive Antimicrobial Stewardship Policies
Johnson T
Antimicrobial resistance (AMR) has been declared one of the top ten global public health threats facing humanity. To address AMR, coercive antimicrobial stewardship policies are being enacted in some settings. These policies, like all in public health, require ethical justification. Here, I introduce a framework for ethically evaluating coercive antimicrobial stewardship policies on the basis of ethical justifications (and their limitations). I consider arguments from effectiveness; duty of easy rescue; tragedy of the commons; responsibility-tracking; the harm principle; paternalism; justice and development; a precautionary approach; and professional duties. I consider how these justifications might form the basis for developing a comprehensive ethical framework, and the need for this to be context-specific and aligned with the priorities, evidence and needs of the particular jurisdictions in which a policy is to be enacted. I demonstrate how the ethical justifications might be used by reference to an example policy of the EU ban on the use of certain human-critical antibiotics for livestock, before concluding with challenges for further development of the framework.
Reducing maternal and child oral health disparities in Sub-Saharan Africa through a community-based strategy
Adeniyi A, Akama G, Lukandu O, Ikemeri JE, Jumah A, Chelagat S, Kasuya A, Ruhl L, Songok J and Christoffersen-Deb A
Oral conditions disproportionately affect mothers and children in Sub-Saharan Africa, due to biological vulnerabilities, a scarcity of oral health workers, deficient preventive strategies, and gender-based barriers to care. The World Health Organization (WHO) recommends integrating oral health into broader health delivery models, to reduce these disparities. We propose integrating preventive oral healthcare into community-based programs to bridge these gaps. We examine integrating preventive oral healthcare into Western Kenya's Chamas for Change () community-based program which aims to reduce maternal and child health disparities. incorporates women's health and microfinance programs best practices to produce a low-cost, community-driven, sustainable, and culturally acceptable health delivery platform. Our strategy is based on the Maternal and Child Oral Health Framework and uses the WHO Basic Package of Oral Care principles. This framework prioritizes community involvement, cultural sensitivity, regular screenings, and seamless integration into general health sessions. We discuss the strengths, weaknesses, opportunities, and threats to enriching with oral health promotion activities. It is crucial to assess the effectiveness, sustainability, and acceptability of the proposed strategy through implementation and evaluation. Future studies should investigate the long-term impact of integrated oral health models on community health and oral health disparity reduction in Africa.
Exosomal miRNA-146a-5p Derived from Senescent Hepatocellular Carcinoma Cells Promotes Aging and Inhibits Aerobic Glycolysis in Liver Cells via Targeting IRF7
Yang S, Li A, Lv L, Zheng Z, Liu P, Min J and Wei J
Hepatocellular carcinoma (HCC) is a major global health challenge. Chemotherapy can cause HCC cells to become senescent. Senescent HCC cells play an important role in inhibiting or promoting cancer by producing extracellular vesicles with a senescence-associated secretory phenotype (EV-SASP). miRNA can be strongly upregulated in EV-SASP during the aging process and can substantially alter the phenotypic characteristics of cells. MiRNA microarray analysis revealed that miRNA-146a-5p was highly expressed in oxaliplatin- and HO-induced senescent Huh7 cells, and RT‒PCR confirmed its significant upregulation in exosomes. The transcriptome sequencing results of Huh7 cells overexpressing miRNA-146a-5p suggested that miRNA-146a-5p could regulate HCC cell glycolysis. Subsequently, a dual luciferase assay was used to verify whether miRNA-146a-5p can interact with IRF7 to promote aging. The key functions of miRNA-146a-5p and IRF7 in aerobic glycolysis in liver cancer cells were determined through experiments analyzing glucose uptake, lactate production, the oxygen consumption rate (OCR) and the proton efflux rate (PER). Subsequently, the regulatory effect of IRF7 on the key glycolytic gene PFKL was confirmed through luciferase reporter assays. The western blot experiment results showed that miR-146a-5p can activate CHK2 and p53 phosphorylated proteins by targeting IRF7, and upregulate p21 protein. Overexpression of miRNA-146a-5p effectively inhibited the aerobic glycolytic function of HCC cells. Moreover, silencing IRF7 effectively inhibited aerobic glycolysis. MiR-146a-5p. MiR-146a-5p can activate the phosphorylation of CHK2 phosphorylation protein and its downstream protein p53 by targeting IRF7, and the activated p53 upregulates the expression of p21. Our study revealed that exosomal miRNA-146a-5p produced by aging HCC cells, can inhibit HCC cell proliferation through inhibiting aerobic glycolysis and promote HCC cell aging by activating CHK2/p53/p21 signaling way by targeting IRF7.
Assessment of Anaesthesia Teams' Non-Technical Skills in Clinical Practice before and after Simulation-Based Team Training: A Quasiexperimental Study
Finstad AS, Bjørshol CA, Aase I, Røislien J and Ballangrud R
In situ simulation-based team training of non-technical skills is considered an important initiative for preventing adverse events caused by poor teamwork among healthcare personnel. This study aimed to assess the non-technical skills of anaesthesia personnel before and after in situ simulation-based team training in a clinical setting.
Testing Cancer Patients for HIV: Just Do It
Salvaña EMT
Hypertension in frail older adults: current perspectives
Li L, Duan L, Xu Y, Ruan H, Zhang M, Zheng Y and He S
Hypertension is one of the most common chronic diseases in older people, and the prevalence is on the rise as the global population ages. Hypertension is closely associated with many adverse health outcomes, including cardiovascular disease, chronic kidney disease and mortality, which poses a substantial threat to global public health. Reasonable blood pressure (BP) management is very important for reducing the occurrence of adverse events. Frailty is an age-related geriatric syndrome, characterized by decreased physiological reserves of multiple organs and systems and increased sensitivity to stressors, which increases the risk of falls, hospitalization, fractures, and mortality in older people. With the aging of the global population and the important impact of frailty on clinical practice, frailty has attracted increasing attention in recent years. In older people, frailty and hypertension often coexist. Frailty has a negative impact on BP management and the prognosis of older hypertensive patients, while hypertension may increase the risk of frailty in older people. However, the causal relationship between frailty and hypertension remains unclear, and there is a paucity of research regarding the efficacious management of hypertension in frail elderly patients. The management of hypertension in frail elderly patients still faces significant challenges. The benefits of treatment, the optimal BP target, and the choice of antihypertensive drugs for older hypertensive patients with frailty remain subjects of ongoing debate. This review provides a brief overview of hypertension in frail older adults, especially for the management of BP in this population, which may help in offering valuable ideas for future research in this field.
Influence of Physical Activity on Health-Related Fitness in Young Adults: An Observational Research
Buttar KK, Kacker S and Saboo N
Health-related fitness directly depends on the level of physical activity of the individual. Inactivity contributes to around 3.3% of all deaths, making the lack of exercise and sedentary lifestyles among the young generation a current source of concern. There is a paucity of research on the association between PA and health-related physical fitness among young people. In the perspective of this, the objective of this research was to find out the effect of PA levels on physical fitness in healthy adults.
Aral Sea environmental disasters area population's physical activity level assessment - the first step for targeted health promotion
Baspakova A, Aldanova A, Zinalieva A, Umbetova A, Makhashbay A and Rakhmanov Y
Aim: We aimed to assess the physical activity and sedentary behavior of the population living in the Aral Sea area using the Global Physical Activity Questionnaire.
Provider and administrator attitudes and experiences with implementing telebuprenorphine during the COVID-19 pandemic: a mixed-methods survey
Tofighi B, Lopez R, Araujo G, Lee JD, Samuels EA, Wightman RS and Butner J
This mixed-methods study assessed buprenorphine provider and administrator perceptions and experiences in offering telebuprenorphine during the COVID-19 pandemic.
The Application of Australian Rights Protections to the Use of Hepatitis C Notification Data to Engage People 'Lost to Follow Up'
Saich F, Walker S, Hellard M, Stoové M and Seear K
Hepatitis C is a global public health threat, affecting 56 million people worldwide. The World Health Organization has committed to eliminating hepatitis C by 2030. Although new treatments have revolutionised the treatment and care of people with hepatitis C, treatment uptake has slowed in recent years, drawing attention to the need for innovative approaches to reach elimination targets. One approach involves using existing notifiable disease data to contact people previously diagnosed with hepatitis C. Within these disease surveillance systems, however, competing tensions exist, including protecting individual rights to privacy and autonomy, and broader public health goals. We explore these issues using hepatitis C and Australia's legislative and regulatory frameworks as a case study. We examine emerging uses of notification data to contact people not yet treated, and describe some of the ethical dilemmas associated with the use and non-use of this data and the protections that exist to preserve individual rights and public health. We reveal weaknesses in rights protections and processes under Australian public health and human rights legislation and argue for consultation with and involvement of affected communities in policy and intervention design before notification data is used to increase hepatitis C treatment coverage.
Analytical review of the inf l uence of socio-economic factors on the state of pharmaceutical care for patients with cardiovascular diseases
Bilousova NA and Mykhalchuk VM
Aim: To investigate the influence of socio-economic factors on the state of pharmaceutical provision of patients with cardiovascular diseases.
Knowledge, attitudes, practices, and perception of COVID-19 preventive measures among adult residents of Matadi (Democratic Republic of the Congo) after the third epidemic wave
Munyeku-Bazitama Y, Okitale-Talunda P, Nsio-Mbeta J, Mpingabo-Ilunga P, Tshiminyi-Munkamba P, Umba-Phuati A, Kimfuta J, Ango-Phukuta F, Makindu G, Mufwaya-Nsene R, Asari R, Makimoto S, Ahuka-Mundeke S, Isono M, Makiala-Mandanda S and Muyembe-Tamfum JJ
Several governments from African countries, including the Democratic Republic of the Congo (DRC), implemented stringent public health measures to curb COVID-19 transmission in the early phases of the pandemic. While these restrictive measures are believed to have contributed to lowering case incidence and related mortality in DRC, data on the population's knowledge and adherence are limited. This study aimed to assess the knowledge, perception, attitudes, and practices of COVID-19 preventive measures and associated factors among adult residents of Matadi, thereby generating evidence for a strategy adjustment as the COVID-19 response is transitioning from emergency to control status.
Process Mapping Midwifery Students' Clinical Placement in Sierra Leone: Identifying Facilitators and Barriers
Mann J, Lemor E, Fornah F, Juana-Kamara P, Fullah MA, Sonnie M and van de Water B
Improving midwifery education is critical to improving maternal and infant health outcomes in Sierra Leone. A significant priority within midwifery education is to strengthen the clinical teaching and students' hands-on experience in the clinical setting. To identify facilitators and challenges within midwifery students' clinical placements and to highlight areas to strengthen the clinical midwifery education system as well as the role of preceptors. We conducted a participatory process mapping with two schools of midwifery in Sierra Leone to detail steps taken by practicing midwives and midwifery faculty when students are placed in clinical settings for midwifery rotations. There were 42 participants from the Bo and Makeni regions of Sierra Leone. Participants included midwifery faculty from the Schools of Midwifery in Makeni and Bo, clinical midwives from two regional government hospitals, clinical midwives from two affiliated community health centers, and midwives from the District Health Management Teams. Three recurring themes emerged in the process. First, there was always some element of preparing or teaching the student. Second, there were administrative tasks to coordinate between the schools, clinical sites, and students, before, during, and after clinical placements. And third, there were elements of communication and collaboration between schools and clinical sites/preceptors that could be improved through shared understanding and standardization. Additional themes were inconsistencies across activities before, during, and after students' clinical placement and limited opportunities and confusion around systems of evaluating all components of the clinical placement experience. This study provides insight into the process of midwifery students' clinical placement and highlights facilitators to be standardized and some modifiable barriers to be addressed. As Sierra Leone and many other similar countries in sub-Saharan Africa attempt to strengthen students' clinical education through educating and developing preceptors, processing mapping can be a useful tool.
Identifying factors influencing local governments' adoption of comprehensive smoke-free policies: an event history analysis based on panel data from 36 key cities in China (2013-2021)
Feng W, Qin B, Jin X and Li S
The issue of tobacco control remains a significant concern for public health worldwide. In recent years, remarkable progress has been made toward adopting smoke-free measures in indoor public places. Although China has yet to introduce a national regulation, specifically for smoke-free public places, more than a dozen cities have successively approved and implemented comprehensive smoke-free regulations. Different cities in China have diverse attitudes and behaviors toward smoke-free policies; however, the reasons for these policy differences and the influencing factors have not received sufficient attention and research.
Enhancing Human Health and Wellbeing through Sustainably and Equitably Unlocking a Healthy Ocean's Potential
Fleming LE, Landrigan PJ, Ashford OS, Whitman EM, Swift A, Gerwick WH, Heymans JJ, Hicks CC, Morrissey K, White MP, Alcantara-Creencia L, Alexander KA, Astell-Burt T, Berlinck RGS, Cohen PJ, Hixson R, Islam MM, Iwasaki A, Praptiwi RA, Raps H, Remy JY, Sowman G, Ternon E, Thiele T, Thilsted SH, Uku J, Ockenden S and Kumar P
A healthy ocean is essential for human health, and yet the links between the ocean and human health are often overlooked. By providing new medicines, technologies, energy, foods, recreation, and inspiration, the ocean has the potential to enhance human health and wellbeing. However, climate change, pollution, biodiversity loss, and inequity threaten both ocean and human health. Sustainable realisation of the ocean's health benefits will require overcoming these challenges through equitable partnerships, enforcement of laws and treaties, robust monitoring, and use of metrics that assess both the ocean's natural capital and human wellbeing. Achieving this will require an explicit focus on human rights, equity, sustainability, and social justice. In addition to highlighting the potential unique role of the healthcare sector, we offer science-based recommendations to protect both ocean health and human health, and we highlight the unique potential of the healthcare sector tolead this effort.
Comparative analysis of nutrient composition and antioxidant activity in three dragon fruit cultivars
Yasmin A, Sumi MJ, Akter K, Rabbi RHM, Almoallim HS, Ansari MJ, Hossain A and Imran S
Dragon fruit has significant economic value in many countries due to has excellent nutritional content, health advantages, and adaptability to different climates, making it an important crop in the global fruit industry. This study aimed to gather comprehensive nutritional data on three dragon fruit cultivars by analysing the levels of micronutrients, fibre, carbohydrates, antioxidants, vitamins, and minerals in their pulps. Uniform dragon fruit samples underwent thorough analysis for proximate composition, mineral content, pigments, antioxidants, and vitamin C, with statistical methods used to assess significant differences among the parameters studied. The proximate composition analysis revealed significant differences among the three dragon fruit cultivars. Among the proximate components, protein (0.40 ± 0.02 g/100 g), moisture (91.33 ± 0.88%), crude fibre (0.32 ± 0.07 g/100 g), and ash (1.27 ± 0.09 g/100 g) were more abundant in than in and . On the other hand, had higher carbohydrate (17.02 ± 0.63 g/100 g) and energy (69.74 ± 2.44 kcal/100 g) contents. K (7.23 ± 0.35 mg/100 g), Ca (1.61 ± 0.13 mg/100 g), Fe (1.84 ± 0.05 mg/100 g), and Zn (0.37 ± 0.034 mg/100 g) are highly abundant in . Additionally, had the highest anthocyanin content (120.15 ± 3.29 mg/g FW) and total carotenoid content (72.51 ± 1.62 mg/g FW), along with the highest vitamin C content (8.92 ± 0.13 mg/g FW) and total soluble phenolic content (572.48 ± 20.77 mg/100 g). Its remarkable antioxidant activity was further highlighted by the lowest SC value (13.50 ± 0.4 mg/mL) for its DPPH radical scavenging capacity. The total soluble sugar content was highest in (8.72 ± 0.30 g/100 g FW). Hierarchical clustering analysis revealed distinct trait and genotype associations; among the studied cultivars, demonstrated superior performance across multiple traits. Correlation analysis indicated significant positive correlations among several traits, while principal component analysis highlighted the contribution of each trait to overall variance, with PC1 explaining 73.95% of the total variance. This study highlights the nutritional variations among dragon fruit cultivars, with showing superior performance, guiding dietary planning and functional food development.
Lived experiences of people impacted by gun violence: qualitative analysis of the prescriptions for repair project
Rice HE, Owen M, Johnson A, Swandell J, Phifer Nicholson C, Provencher S, Horne E, Solomon C, Ratliff W, Knechtle W, Campbell D, Smith R and Graves L
Restorative justice interventions can help address the harm created by gun violence, although few restorative justice programs focus solely on survivors or loved ones of victims of gun violence. Our aim was to assess how gun violence impacts those injured by firearms through qualitative analysis of their lived experiences.
Trematode Genomics and Proteomics
Rinaldi G, Loukas A and Sotillo J
Trematode infections stand out as one of the frequently overlooked tropical diseases, despite their wide global prevalence and remarkable capacity to parasitize diverse host species and tissues. Furthermore, these parasites hold significant socio-economic, medical, veterinary and agricultural implications. Over the past decades, substantial strides have been taken to bridge the information gap concerning various "omic" tools, such as proteomics and genomics, in this field. In this edition of the book, we highlight recent progress in genomics and proteomics concerning trematodes with a particular focus on the advances made in the past 5 years. Additionally, we present insights into cutting-edge technologies employed in studying trematode biology and shed light on the available resources for exploring the molecular facets of this particular group of parasitic helminths.
Orthopedic Frailty Score and adverse outcomes in patients with surgically managed isolated traumatic spinal injury
Mohammad Ismail A, Hildebrand F, Forssten MP, Ribeiro MAF, Chang P, Cao Y, Sarani B and Mohseni S
With an aging global population, the prevalence of frailty in patients with traumatic spinal injury (TSI) is steadily increasing. The aim of the current study is to evaluate the utility of the Orthopedic Frailty Score (OFS) in assessing the risk of adverse outcomes in patients with isolated TSI requiring surgery, with the hypothesis that frailer patients suffer from a disproportionately increased risk of these outcomes.
Compliance with the breakthrough cancer pain European guidelines and impact on patients' quality of life: an observational prospective study
Bossi P, Pietrzyńska T, Margarit Ferri C, Mansilla I, Tellone V, Fioravanti S, Di Loreto G and Comandini A
This study aimed to assess the percentage of patients treated according to the European Society for Medical Oncology (ESMO) 2018 guidelines for breakthrough cancer pain (BTcP) and the impact of guidelines adherence on patients' quality of life (QoL).
Time to Treat the Climate and Nature Crisis as One Indivisible Global Health Emergency
Abbasi K, Ali P, Barbour V, Benfield T, Bibbins-Domingo K, Hancocks S, Horton R, Laybourn-Langton L, Mash R, Sahni P, Sharief WM, Yonga P and Zielinski C
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