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Global Health

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.
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.
"". 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.
Advancing Global Validation and Implementation of Adult Sepsis Event Surveillance
Polito CC, Klompas M and Rhee C
International Hackathon as a Tool to Augment Education, Collaboration, and Innovation in Global Neurosurgery
Razak SS, West TR, Tunsiricharoengul S, Nair-Kanneganti A, Perez NA, Mazurek MH, Gal Z, Duvall JB, Rigney GH, Cerda IH, Morcos MM, Keay E, Hernández AS, Lawton MT, Nahed BV and Quiñones-Hinojosa A
Health care providers' exposure to global surgical disparities is limited in current nursing and/or medical school curricula. For instance, global health is often associated with infectious diseases or maternal health without acknowledging the growing need for surgical care in low- and middle-income countries (LMICs). We propose an international virtual hackathon based on neurosurgical patient cases in under-resourced settings as an educational tool to bring awareness to global surgical disparities and develop relationships among trainees in different countries.
Associations of Amyloid Burden, White Matter Hyperintensities, and Hippocampal Volume With Cognitive Trajectories in the 90+ Study
Wang J, Ackley S, Woodworth DC, Sajjadi SA, Decarli CS, Fletcher EF, Glymour MM, Jiang L, Kawas C and Corrada MM
Amyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old.
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.
Madagascar urgently needs a 2024 national prevalence survey of HIV
Geoffroy A, Samison L, Randriatsarafara F, Randriantsara H, Randriamanantany ZA and Vanhecke C
Distribution and accumulation of UV filters (UVFs) and conservation status of Posidonia oceanica seagrass meadows in a prominent Mediterranean coastal tourist hub
Agawin NSR, García-Márquez MG, Espada DR, Freemantle L, Pintado Herrera MG and Tovar-Sánchez A
This study investigates the presence and impact of UV filters in Posidonia oceanica meadows in Formentera, a Mediterranean tourist hotspot. It highlights the distribution of inorganic (TiO2 and ZnO) and organic UV filters (UVFs) in different environmental matrices, their accumulation in seagrass tissues and their impact on the seagrass health. In the overlying and canopy waters of P. oceanica, Zn concentrations surpassed Ti, with three organic UVFs (benzophenone-3 [BP-3], avobenzone and homosalate [HMS]) consistently detected. Ti concentrations were generally higher than Zn in rhizosphere sediments, along with recurrent presence of octocrylene, HMS, 2-ethylhexyl methoxycinnamate (EHMC), and 4-methylbenzylidene camphor (4-MBC). Maximum Zn concentrations were found in canopy waters (3052.9 ng L). Both Ti and Zn were found in all P. oceanica tissues and leaf epiphytes across all study sites. Additional UVFs like octocrylene, avobenzone, and BP-8 were also detected in P. oceanica tissues and epiphytes. Elevated levels of octocrylene in leaf epiphytes (2112.1 ng g dw) and avobenzone in leaves (364.2 ng g dw) and leaf epiphytes (199.6 ng g dw) were observed in the Port of La Savina, the island's main entry port. Octocrylene concentrations (up to 2575 ng g dw) in rhizosphere sediments near sewage discharge points exceeded reported maxima, highlighting wastewater treatment plants as significant sources of organic UVFs. Correlational analyses suggested that the accumulation of octocrylene, avobenzone, and BP-3 negatively impacted P. oceanica's conservation status, affecting global density, density at 100 % cover, and leaf morphometry. Positive correlations were observed between leaf polyphenols (antioxidants) and concentrations of avobenzone, benzophenone-8 (BP-8), and BP-3, indicating potential oxidative stress induced by UVFs in P. oceanica. Our study underscores the pervasive presence of UV filters in P. oceanica habitats, with implications for seagrass health and conservation, especially in areas of high tourism and sewage discharge.
Improving hypertension control in Nigeria: early policy implications from the Hypertension Treatment in Nigeria program
Ogungbe O, Abasilim C, Huffman MD, Ojji D and
Hypertension poses a significant health burden globally. In Nigeria, hypertension prevalence is on the rise, with low rates of awareness, treatment, and control. This policy brief explores the critical gaps addressed by the Hypertension Treatment in Nigeria (HTN) Program, highlighting its strengths, initial outcomes, and scalability in primary care settings. The HTN Program employs an integrated, multilevel care model based on the World Health Organization's HEARTS technical package, including patient registration and empanelment, team-based care, training and supervision, a standardized treatment protocol, a health information management system, and a drug revolving fund to improve medication accessibility. By December 2023, hypertension treatment and control rates reached surpassing 90% and 50%, respectively, thus underscoring the program's impact. The HTN Program serves as a model for delivering integrated hypertension care in primary care. Results should be leveraged for political commitment and financing to evaluate and manage non-communicable diseases such as hypertension in primary care through federal and state primary health development agencies. Furthermore, incorporating metrics related to hypertension control and treatment into the Integrated Supportive Management Information System can enhance routine monitoring and evaluation.
Ethical Implications of Artificial Intelligence in Gastroenterology: The Co-pilot or the Captain?
Aggarwal N, Drew DA, Parikh RB and Guha S
Though artificial intelligence (AI) is being widely implemented in gastroenterology (GI) and hepatology and has the potential to be paradigm shifting for clinical practice, its pitfalls must be considered along with its advantages. Currently, although the use of AI is limited in practice to supporting clinical judgment, medicine is rapidly heading toward a global environment where AI will be increasingly autonomous. Broader implementation of AI will require careful ethical considerations, specifically related to bias, privacy, and consent. Widespread use of AI raises concerns related to increasing rates of systematic errors, potentially due to bias introduced in training datasets. We propose that a central repository for collection and analysis for training and validation datasets is essential to overcoming potential biases. Since AI does not have built-in concepts of bias and equality, humans involved in AI development and implementation must ensure its ethical use and development. Moreover, ethical concerns regarding data ownership and health information privacy are likely to emerge, obviating traditional methods of obtaining patient consent that cover all possible uses of patient data. The question of liability in case of adverse events related to use of AI in GI must be addressed among the physician, the healthcare institution, and the AI developer. Though the future of AI in GI is very promising, herein we review the ethical considerations in need of additional guidance informed by community experience and collective expertise.
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.
Global prevalence and predictors of scabies among prisoners: systematic review and meta-analysis
Delie AM, Bogale EK, Anagaw TF, Tiruneh MG, Fenta ET, Adal O and Kebede N
Scabies is a widespread issue in prisons due to overcrowded living conditions and limited healthcare resources. A recent study published in the Journal of Infection and Public Health discovered that the prevalence of scabies varies greatly among prisoners in different regions and facilities. This review aimed to determine the global prevalence and predictors of scabies among prisoners by conducting a systematic review and meta-analysis.
"A life-changing experience and the beginning of a lifelong commitment": experiences and impact of Global Health Community Service-Learning in undergraduate dental curriculum in Canada
Jessani A, Athanasakos A and Kachwinya S
Global Health Community Service-Learning (GHCSL) can have a profound professional and personal impact on learners. This pedagogy provides understanding of unfamiliar environments and challenges learners to step out of their comfort zones, adapt to new cultures, and navigate unique situations. Yet, there are relatively few studies exploring the experiences of learners participating in community service-learning placements in global regions as part of undergraduate dental curriculum. This study aimed to explore the experiences and impact of the GHCSL program in East Africa among undergraduate dental learners at the Schulich School of Dentistry.
Effect of web-based health education on nursing students' knowledge, adaptive healthy measures and attitudes regarding polycystic ovary syndrome: a randomized controlled trial
Mohamed RA, Taref NN, Osman NE, Keshta NHA, Alboghdady MA, Marzouk MM, Almowafy AA and Fadel EA
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting women of reproductive age, and it has emerged as a significant global public health issue. This study aimed to investigate the effects of web-based health education on nursing students' knowledge, adaptive healthy measures, and attitudes toward PCOS.
Enteroviruses: epidemic potential, challenges and opportunities with vaccines
Jartti M, Flodström-Tullberg M and Hankaniemi MM
Enteroviruses (EVs) are the most prevalent viruses in humans. EVs can cause a range of acute symptoms, from mild common colds to severe systemic infections such as meningitis, myocarditis, and flaccid paralysis. They can also lead to chronic diseases such as cardiomyopathy. Although more than 280 human EV serotypes exist, only four serotypes have licenced vaccines. No antiviral drugs are available to treat EV infections, and global surveillance of EVs has not been effectively coordinated. Therefore, poliovirus still circulates, and there have been alarming epidemics of non-polio enteroviruses. Thus, there is a pressing need for coordinated preparedness efforts against EVs.This review provides a perspective on recent enterovirus outbreaks and global poliovirus eradication efforts with continuous vaccine development initiatives. It also provides insights into the challenges and opportunities in EV vaccine development. Given that traditional whole-virus vaccine technologies are not suitable for many clinically relevant EVs and considering the ongoing risk of enterovirus outbreaks and the potential for new emerging pathogenic strains, the need for new effective and adaptable enterovirus vaccines is emphasized.This review also explores the difficulties in translating promising vaccine candidates for clinical use and summarizes information from published literature and clinical trial databases focusing on existing enterovirus vaccines, ongoing clinical trials, the obstacles faced in vaccine development as well as the emergence of new vaccine technologies. Overall, this review contributes to the understanding of enterovirus vaccines, their role in public health, and their significance as a tool for future preparedness.
Barriers and facilitators of improved nutritional support for patients newly diagnosed with cancer: a pre-implementation study
Beichmann B, Henriksen C, Paur I and Paulsen MM
Disease-related malnutrition affects a significant number of patients with cancer and poses a major social problem worldwide. Despite both global and national guidelines to prevent and treat malnutrition, the prevalence is high, ranging from 20 to 70% in all patients with cancer. This study aimed to explore the current practice of nutritional support for patients with cancer at a large university hospital in Norway and to explore potential barriers and facilitators of the intervention in the Green Approach to Improved Nutritional support for patients with cancer (GAIN), prior to implementation in a clinical setting.
Building a human lung from pluripotent stem cells to model respiratory viral infections
Turner DL, Amoozadeh S, Baric H, Stanley E and Werder RB
To protect against the constant threat of inhaled pathogens, the lung is equipped with cellular defenders. In coordination with resident and recruited immune cells, this defence is initiated by the airway and alveolar epithelium following their infection with respiratory viruses. Further support for viral clearance and infection resolution is provided by adjacent endothelial and stromal cells. However, even with these defence mechanisms, respiratory viral infections are a significant global health concern, causing substantial morbidity, socioeconomic losses, and mortality, underlining the need to develop effective vaccines and antiviral medications. In turn, the identification of new treatment options for respiratory infections is critically dependent on the availability of tractable in vitro experimental models that faithfully recapitulate key aspects of lung physiology. For such models to be informative, it is important these models incorporate human-derived, physiologically relevant versions of all cell types that normally form part of the lungs anti-viral response. This review proposes a guideline using human induced pluripotent stem cells (iPSCs) to create all the disease-relevant cell types. iPSCs can be differentiated into lung epithelium, innate immune cells, endothelial cells, and fibroblasts at a large scale, recapitulating in vivo functions and providing genetic tractability. We advocate for building comprehensive iPSC-derived in vitro models of both proximal and distal lung regions to better understand and model respiratory infections, including interactions with chronic lung diseases.
Evaluation of chimeric recombinant antigens for the serodiagnosis of Trypanosoma cruzi in dogs: a promising tool for Chagas disease surveillance
Fontes ND, Habib FL, Leony LM, Freitas NEM, Silva ÂAO, Dantas-Torres F, da Silva Sales KG, da Câmara ACJ, de Araújo-Neto VT, Amorim LDAF, Celedon PAF, Zanchin NIT and Santos FLN
Chagas disease (CD), a neglected parasitic disease caused by Trypanosoma cruzi, poses a significant health threat in Latin America and has emerged globally because of human migration. Trypanosoma cruzi infects humans and over 100 other mammalian species, including dogs, which are important sentinels for assessing the risk of human infection. Nonetheless, the serodiagnosis of T. cruzi in dogs is still impaired by the absence of commercial tests. In this study, we investigated the diagnostic accuracy of four chimeric recombinant T. cruzi IBMP antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) for detecting anti-T. cruzi antibodies in dogs, using latent class analysis (LCA).
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.
Unravelling heterogeneous malaria transmission dynamics in the Peruvian Amazon: insights from a cross-sectional survey
Pinedo-Cancino V, Arista KM, Baldeviano GC, Saavedra-Langer R, Arana A, Vásquez-Chasnamote ME, Valle-Campos A, Castro JC, Ventocilla JA, Smith ES, Lescano AG and Ruíz-Mesia L
Malaria remains a global health challenge, particularly in Peru's Loreto region. Despite ongoing efforts, high infection rates and asymptomatic cases perpetuate transmission. The Peruvian Ministry of Health's "Zero Malaria Plan" targets elimination. This novel study combines microscopic, molecular, and serological techniques to assess transmission intensity, identify epidemiological risk factors, and characterize species-specific patterns across villages. The findings aim to inform targeted interventions and support broader malaria elimination efforts in line with the Zero Malaria Plan initiative.
Association of ambient temperature on acute ischemic stroke in Yancheng, China
Qian K, Sun Q, Li Y and Chen J
Acute ischemic stroke (AIS) is a major global public health issue. There is limited research on the relationship between ambient temperature and AIS hospital admissions, and the results are controversial. Our objective is to assess the short-term impact of ambient temperature on the risk of AIS hospital admissions in Yancheng, China.
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.
Projection of the prevalence of tracheal, bronchus, and lung cancer incidence using cigarette smoking prevalence in Iran from 1990 to 2018: a comparison of latent period-based models with standard forecasting models
Mirahmadizadeh A, Hassanzadeh J, Moradi AM, Gheibi Z and Heiran A
Smoking is the major risk factor for tracheal, bronchus, and lung (TBL) cancers. We investigated the feasibility of projecting TBL cancer incidence using smoking incidence rates by incorporating a range of latent periods from the main risk factor exposure to TBL cancer diagnosis.
Cardiac involvement in Chagas disease and African trypanosomiasis
Sabino EC, Nunes MCP, Blum J, Molina I and Ribeiro ALP
Trypanosomiases are diseases caused by various species of protozoan parasite in the genus Trypanosoma, each presenting with distinct clinical manifestations and prognoses. Infections can affect multiple organs, with Trypanosoma cruzi predominantly affecting the heart and digestive system, leading to American trypanosomiasis or Chagas disease, and Trypanosoma brucei primarily causing a disease of the central nervous system known as human African trypanosomiasis or sleeping sickness. In this Review, we discuss the effects of these infections on the heart, with particular emphasis on Chagas disease, which continues to be a leading cause of cardiomyopathy in Latin America. The epidemiology of Chagas disease has changed substantially since 1990 owing to the emigration of over 30 million Latin American citizens, primarily to Europe and the USA. This movement of people has led to the global dissemination of individuals infected with T. cruzi. Therefore, cardiologists worldwide must familiarize themselves with Chagas disease and the severe, chronic manifestation - Chagas cardiomyopathy - because of the expanded prevalence of this disease beyond traditional endemic regions.
Utilizing social media for community risk communication in megacities: analysing the impact of WeChat group information interaction and perception on communication satisfaction during the COVID-19 pandemic in Shanghai
Chen Y, Chen Y, Yu S and Yu S
Against the backdrop of the global public health crisis, the COVID-19 pandemic has exposed significant disparities in the supply and demand of risk information related to public health crises, posing severe challenges to risk governance in megacities. Shanghai, China, introduced community WeChat groups for community communication, effectively facilitating the dissemination and response of grassroots information and providing a new path for interactive governance in the community.
Highly pathogenic avian influenza A (H5N1) virus
Kozak R, Bogoch II and Mubareka S
The strongest predictors of compliance with health protocols among marketers and guilds based on the transtheoretical model
Moslehi S, Tavan A, Narimani S, Shahbazzadeh F, Sedri N and Sabahi S
Global communication, an integral part of modern life, increases the risk of transmitting infectious diseases to individuals. Based on the transtheoretical model (TTM), this study aimed to identify the most effective factors in adherence to health protocols among marketers and guilds.
Multicenter, CT image-based anatomic assessment of patients with aortoiliac aneurysm undergoing endovascular repair with iliac branch devices
Panthofer A, Bresler AM, Olson SL, Kuramochi Y, Eagleton M, Böckler D, Schneider DB, Lyden SP, Blackwelder WC, Meadows W, Pauli T, DeRoo E and Matsumura JS
The Global Iliac Branch Study (NCT05607277) is an international, multicenter, retrospective cohort study of anatomic predictors of adverse iliac events (AIE) in aortoiliac aneurysms treated with iliac branch devices (IBDs).
Psychological distress among family caregivers of persons with Alzheimer's disease and related dementias in Uganda
Gumikiriza-Onoria JL, Nakigudde J, Mayega RW, Giordani B, Sajatovic M, Mukasa MK, Buwembo D, Lwere K and Nakasujja N
Alzheimer's disease and related dementias (ADRD) present growing global health challenges, especially in aging populations, such as Uganda. In Uganda, familial caregiving, predominantly undertaken by female relatives, is the primary form of support provided to patients with ADRD. Cultural stigma around dementia and limited access to support services amplify caregivers' challenges. This study examined psychological distress, depression, and quality of life (QoL) among family caregivers of patients with ADRD in Wakiso District, Uganda.
Safety and Effectiveness of COVID-19 Vaccines During Pregnancy: A Living Systematic Review and Meta-analysis
Ciapponi A, Berrueta M, Argento FJ, Ballivian J, Bardach A, Brizuela ME, Castellana N, Comandé D, Gottlieb S, Kampmann B, Mazzoni A, Parker EPK, Sambade JM, Stegelmann K, Xiong X, Stergachis A and Buekens P
Pregnant persons are susceptible to significant complications following COVID-19, even death. However, worldwide COVID-19 vaccination coverage during pregnancy remains suboptimal.
Synthesis and Neurobehavioral Evaluation of a Potent Multitargeted Inhibitor for the Treatment of Alzheimer's Disease
Khan MS, Khan Z, Jabir NR, Mehan S, Suhail M, Zaidi SK, Zughaibi TA, Abid M and Tabrez S
Alzheimer's disease (AD) poses a significant health challenge worldwide, affecting millions of individuals, and projected to increase further as the global population ages. Current pharmacological interventions primarily target acetylcholine deficiency and amyloid plaque formation, but offer limited efficacy and are often associated with adverse effects. Given the multifactorial nature of AD, there is a critical need for novel therapeutic approaches that simultaneously target multiple pathological pathways. Targeting key enzymes involved in AD pathophysiology, such as acetylcholinesterase, butyrylcholinesterase, beta-site APP cleaving enzyme 1 (BACE1), and gamma-secretase, is a potential strategy to mitigate disease progression. To this end, our research group has conducted comprehensive in silico screening to identify some lead compounds, including IQ6 (SSZ), capable of simultaneously inhibiting the enzymes mentioned above. Building upon this foundation, we synthesized SSZ, a novel multitargeted ligand/inhibitor to address various pathological mechanisms underlying AD. Chemically, SSZ exhibits pharmacological properties conducive to AD treatment, featuring pyrrolopyridine and N-cyclohexyl groups. Preclinical experimental evaluation of SSZ in AD rat model showed promising results, with notable improvements in behavioral and cognitive parameters. Specifically, SSZ treatment enhanced locomotor activity, ameliorated gait abnormalities, and improved cognitive function compared to untreated AD rats. Furthermore, brain morphological analysis demonstrated the neuroprotective effects of SSZ, attenuating Aβ-induced neuronal damage and preserving brain morphology. Combined treatment of SSZ and conventional drugs (DON and MEM) showed synergistic effects, suggesting a potential therapeutic strategy for AD management. Overall, our study highlights the efficacy of multitargeted ligands like SSZ in combating AD by addressing the complex etiology of the disease. Further research is needed to elucidate the full therapeutic potential of SSZ and the exploration of similar compounds in clinical settings, offering hope for an effective AD treatment in the future.
Digital Footprints of Obesity Treatment: GLP-1 Receptor Agonists and the Health Equity Divide
Azizi Z, Rodriguez F and Assimes TL
Our research investigates the societal implications of access to glucagon-like peptide-1 (GLP-1) agonists, particularly in light of recent clinical trials demonstrating the efficacy of semaglutide in reducing cardiovascular mortality. A decade-long analysis of Google Trends indicates a significant increase in searches for GLP-1 agonists, primarily in North America. This trend contrasts with the global prevalence of obesity. Given the high cost of GLP-1 agonists, a critical question arises: Will this disparity in medication accessibility exacerbate the global health equity gap in obesity treatment? This viewpoint explores strategies to address the health equity gap exacerbated by this emerging medication. Because GLP-1 agonists hold the potential to become a cornerstone in obesity treatment, ensuring equitable access is a pressing public health concern.
The Supreme Court Decision on Firearm Ownership for People Subject to Restraining Orders
Gostin LO and Vladeck SI
Sequencing of Kaposi's Sarcoma Herpesvirus (KSHV) genomes from persons of diverse ethnicities and provenances with KSHV-associated diseases demonstrate multiple infections, novel polymorphisms, and low intra-host variance
Marshall VA, Cornejo Castro EM, Goodman CA, Labo N, Liu I, Fisher NC, Moore KN, Nair A, Immonen T, Keele BF, Polizzotto MN, Uldrick TS, Mu Y, Saswat T, Krug LT, McBride KM, Lurain K, Ramaswami R, Yarchoan R and Whitby D
Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. These include near full-length sequence of genomes with KSHV K1 subtypes A, B, C, and F as well as subtype E, for which no full sequence was previously available. High levels of recombination were observed. Fourteen individuals (18%) showed evidence of infection with multiple KSHV variants (from two to four unique genomes). Twenty-six comparisons of sequences, obtained from various sampling sites including PBMC, tissue biopsies, oral fluids, and effusions in the same participants, identified near complete genome conservation between different biological compartments. Polymorphisms were identified in coding and non-coding regions, including indels in the K3 and K15 genes and sequence inversions here reported for the first time. One such polymorphism in KSHV ORF46, specific to the KSHV K1 subtype E2, encoded a mutation in the leucine loop extension of the uracil DNA glycosylase that results in alteration of biochemical functions of this protein. This confirms that KSHV sequence variations can have functional consequences warranting further investigation. This study represents the largest and most diverse analysis of KSHV genome sequences to date among individuals with KAD and provides important new information on global KSHV genomics.
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.
A comprehensive cancer center in the cloud powered by AI can reduce health disparities
Ngwa W, Pressley A, Wilson VM, Marlink R, Quintana Y, Chipidza F, Deville C, Quon H, Avery S, Patrick L and Ngwa K
Engagement and partnership with consumers and communities in the co-design and conduct of Research: Lessons from the INtravenous iron polymaltose for First Nations Australian patients with high FERRitin levels on haemodialysis (INFERR) clinical trial
Long S, Ross C, Koops J, Coulthard K, Nelson J, Shapkota AK, Hewett L, Tate-Baker J, Graham J, Mukula R, Tetteh C, Hoppo L, Cherian S, Pawar B, Chmielewski HL, Gold LM, Rathnayake G, Heron B, Brewster-O'Brien T, Karepalli V, Maple-Brown L, Batey R, Morris P, Davies J, Fernandes DK, Thomas S, Abeyaratne A, Lawton PD, Barzi F, Taylor S, Mayo M, Cass A and Majoni SW
Engagement and partnership with consumers and communities throughout research processes produces high quality research meeting community needs and promoting translation of research into improved policy and practice. Partnership is critical in research involving Aboriginal and/or Torres Strait Islander people (First Nations Peoples) to ensure cultural safety. We present lessons from the design, implementation and progress of the National Health and Medical Research Council funded INtravenous iron polymaltose for First Nations Australian patients with high FERRitin levels on hemodialysis (INFERR) clinical trial.
MHC class II proteins mediate sialic acid independent entry of human and avian H2N2 influenza A viruses
Karakus U, Sempere Borau M, Martínez-Barragán P, von Kempis J, Yildiz S, Arroyo-Fernández LM, Pohl MO, Steiger JA, Glas I, Hunziker A, García-Sastre A and Stertz S
Influenza A viruses (IAV) pose substantial burden on human and animal health. Avian, swine and human IAV bind sialic acid on host glycans as receptor, whereas some bat IAV require MHC class II complexes for cell entry. It is unknown how this difference evolved and whether dual receptor specificity is possible. Here we show that human H2N2 IAV and related avian H2N2 possess dual receptor specificity in cell lines and primary human airway cultures. Using sialylation-deficient cells, we reveal that entry via MHC class II is independent of sialic acid. We find that MHC class II from humans, pigs, ducks, swans and chickens but not bats can mediate H2 IAV entry and that this is conserved in Eurasian avian H2. Our results demonstrate that IAV can possess dual receptor specificity for sialic acid and MHC class II, and suggest a role for MHC class II-dependent entry in zoonotic IAV infections.
Genomic surveillance of malaria parasites in an indigenous community in the Peruvian Amazon
Cabrera-Sosa L, Nolasco O, Kattenberg JH, Fernandez-Miñope C, Valdivia HO, Barazorda K, Arévalo de Los Rios S, Rodriguez-Ferrucci H, Vinetz JM, Rosanas-Urgell A, Van Geertruyden JP, Gamboa D and Delgado-Ratto C
Hard-to-reach communities represent Peru's main challenge for malaria elimination, but information about transmission in these areas is scarce. Here, we assessed Plasmodium vivax (Pv) and P. falciparum (Pf) transmission dynamics, resistance markers, and Pf hrp2/3 deletions in Nueva Jerusalén (NJ), a remote, indigenous community in the Peruvian Amazon with high population mobility. We collected samples from November 2019 to May 2020 by active (ACD) and passive case detection (PCD) in NJ. Parasites were identified with microscopy and PCR. Then, we analyzed a representative set of positive-PCR samples (Pv = 68, Pf = 58) using highly-multiplexed deep sequencing assays (AmpliSeq) and compared NJ parasites with ones from other remote Peruvian areas using population genetics indexes. The ACD intervention did not reduce malaria cases in the short term, and persistent malaria transmission was observed (at least one Pv infection was detected in 96% of the study days). In Nueva Jerusalen, the Pv population had modest genetic diversity (He = 0.27). Pf population had lower diversity (He = 0.08) and presented temporal clustering, one of these clusters linked to an outbreak in February 2020. Moreover, Pv and Pf parasites from NJ exhibited variable levels of differentiation (Pv Fst = 0.07-0.52 and Pf Fst = 0.11-0.58) with parasites from other remote areas. No artemisin resistance mutations but chloroquine (57%) and sulfadoxine-pyrimethamine (35-67%) were detected in NJ's Pf parasites. Moreover, pfhrp2/3 gene deletions were common (32-50% of parasites with one or both genes deleted). The persistent Pv transmission and the detection of a Pf outbreak with parasites genetically distinct from the local ones highlight the need for tailored interventions focusing on mobility patterns and imported infections in remote areas to eliminate malaria in the Peruvian Amazon.
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.
Assessment of heat stress contributing factors in the indoor environment among vulnerable populations in Klang Valley using principal component analysis (PCA)
Muhamad SN, How V, Lim FL, Md Akim A, Karuppiah K and Mohd Shabri NSA
Rising global temperatures can lead to heat waves, which in turn can pose health risks to the community. However, a notable gap remains in highlighting the primary contributing factors that amplify heat-health risk among vulnerable populations. This study aims to evaluate the precedence of heat stress contributing factors in urban and rural vulnerable populations living in hot and humid tropical regions. A comparative cross-sectional study was conducted, involving 108 respondents from urban and rural areas in Klang Valley, Malaysia, using a face-to-face interview and a validated questionnaire. Data was analyzed using the principal component analysis, categorizing factors into exposure, sensitivity, and adaptive capacity indicators. In urban areas, five principal components (PCs) explained 64.3% of variability, with primary factors being sensitivity (health morbidity, medicine intake, increased age), adaptive capacity (outdoor occupation type, lack of ceiling, longer residency duration), and exposure (lower ceiling height, increased building age). In rural, five PCs explained 71.5% of variability, with primary factors being exposure (lack of ceiling, high thermal conductivity roof material, increased building age, shorter residency duration), sensitivity (health morbidity, medicine intake, increased age), and adaptive capacity (female, non-smoking, higher BMI). The order of heat-health vulnerability indicators was sensitivity > adaptive capacity > exposure for urban areas, and exposure > sensitivity > adaptive capacity for rural areas. This study demonstrated a different pattern of leading contributors to heat stress between urban and rural vulnerable populations.
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.
Investigating grey matter volumetric trajectories through the lifespan at the individual level
Shi R, Xiang S, Jia T, Robbins TW, Kang J, Banaschewski T, Barker GJ, Bokde ALW, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Brühl R, Martinot JL, Martinot MP, Artiges E, Nees F, Orfanos DP, Paus T, Poustka L, Hohmann S, Millenet S, Fröhner JH, Smolka MN, Vaidya N, Walter H, Whelan R, Schumann G, Lin X, Sahakian BJ, Feng J and
Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14-23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV). Group 1 show continuously decreasing GMV associated with higher neurocognitive performances than the other two groups during adolescence. Group 2 exhibit a slower rate of GMV decrease and lower neurocognitive performances compared with Group 1, which was associated with epigenetic differences and greater environmental burden. Group 3 show increasing GMV and lower baseline neurocognitive performances due to a genetic variation. Using the UK Biobank, we show these differences may be attenuated in mid-to-late adulthood. Our study reveals clusters of adolescent neurodevelopment based on GMV and the potential long-term impact.
DNA methylation, but not microRNA expression, is affected by in vitro THC exposure in bovine granulosa cells
Floccari S, Sabry R, Choux L, Neal MS, Khokhar JY and Favetta LA
A global increase in cannabis use has led to questions about its effects on fertility. The rise in consumption amongst women of reproductive age is a growing concern, as this group is vulnerable in terms of reproductive health. Ample evidence suggests that the psychoactive component of cannabis, Δ-Tetrahydrocannabinol (THC), interacts with the endocannabinoid system (ECS), that helps regulate mammalian reproduction. This study aimed to research the epigenetic effects of THC in bovine granulosa cells (GCs) by (1) investigating global DNA methylation via measuring 5-mC and 5-hmC levels; (2) measuring key methylation regulators, including the methylating enzymes DNMT1, DNMT3a, DNMT3b and the demethylases TDG and TET1/2/3; and (3) assessing fertility-associated miRNAs key in developmental competency, including miR-21, -155, -33b, -324 and -346.
PRC2-AgeIndex as a universal biomarker of aging and rejuvenation
Moqri M, Cipriano A, Simpson DJ, Rasouli S, Murty T, de Jong TA, Nachun D, de Sena Brandine G, Ying K, Tarkhov A, Aberg KA, van den Oord E, Zhou W, Smith A, Mackall C, Gladyshev VN, Horvath S, Snyder MP and Sebastiano V
DNA methylation (DNAm) is one of the most reliable biomarkers of aging across mammalian tissues. While the age-dependent global loss of DNAm has been well characterized, DNAm gain is less characterized. Studies have demonstrated that CpGs which gain methylation with age are enriched in Polycomb Repressive Complex 2 (PRC2) targets. However, whole-genome examination of all PRC2 targets as well as determination of the pan-tissue or tissue-specific nature of these associations is lacking. Here, we show that low-methylated regions (LMRs) which are highly bound by PRC2 in embryonic stem cells (PRC2 LMRs) gain methylation with age in all examined somatic mitotic cells. We estimated that this epigenetic change represents around 90% of the age-dependent DNAm gain genome-wide. Therefore, we propose the "PRC2-AgeIndex," defined as the average DNAm in PRC2 LMRs, as a universal biomarker of cellular aging in somatic cells which can distinguish the effect of different anti-aging interventions.
A new population for primary prevention of retinal diseases; a step toward improved global eye health beyond diabetes and prediabetes
Ebrahimi M and Sivaprasad S
Created with biorender.com.
Prediction of disease progression in individuals with subjective cognitive decline using brain network analysis
Deng S, Tan S, Song X, Lin X, Yang K, Li X and
The objective of this study is to explore potential differences in brain functional networks at baseline between individuals with progressive subjective cognitive decline (P-SCD) and stable subjective cognitive decline (S-SCD), as well as to identify potential indicators that can effectively distinguish between P-SCD and S-SCD.
A One Health framework for exploring zoonotic interactions demonstrated through a case study
Desvars-Larrive A, Vogl AE, Puspitarani GA, Yang L, Joachim A and Käsbohrer A
The eco-epidemiology of zoonoses is often oversimplified to host-pathogen interactions while findings derived from global datasets are rarely directly transferable to smaller-scale contexts. Through a systematic literature search, we compiled a dataset of naturally occurring zoonotic interactions in Austria, spanning 1975-2022. We introduce the concept of zoonotic web to describe the complex relationships between zoonotic agents, their hosts, vectors, food, and environmental sources. The zoonotic web was explored through network analysis. After controlling for research effort, we demonstrate that, within the projected unipartite source-source network of zoonotic agent sharing, the most influential zoonotic sources are human, cattle, chicken, and some meat products. Analysis of the One Health 3-cliques (triangular sets of nodes representing human, animal, and environment) confirms the increased probability of zoonotic spillover at human-cattle and human-food interfaces. We characterise six communities of zoonotic agent sharing, which assembly patterns are likely driven by highly connected infectious agents in the zoonotic web, proximity to human, and anthropogenic activities. Additionally, we report a frequency of emerging zoonotic diseases in Austria of one every six years. Here, we present a flexible network-based approach that offers insights into zoonotic transmission chains, facilitating the development of locally-relevant One Health strategies against zoonoses.
Alcohol control policy and alcohol-attributable disease burden in Finland and the Baltic countries: A longitudinal study 1995-2019
Månsson A, van der Velde L, Karlsson T, Beekmann L, Jonsson Stenberg E, Haagsma J, Castelpietra G, Agardh EE and Allebeck P
Alcohol remains a significant contributor to mortality and morbidity in Finland and the Baltic countries, particularly among men. This study aimed to assess alcohol policy restrictiveness in this region from 1995 to 2019 using a modified version of the Bridging the Gap (BtG-M) policy scale and examine its association with alcohol-related disease burden.
A call to stop extractive health research on South Asian diaspora communities in Canada
Agarwal G, Banerjee AT and Brar J
Assessing Acceptability of Biodegradable Contraceptive Implants in Kenya and Senegal
Cartwright AF, Callahan RL, Lawton A, Wong C, Muchiri O and Matan S
Contraceptive implants are popular in Africa, but barriers to removal exist. Biodegradable implants (BDIs) offer an alternative to the need for removal. This study explored potential user, provider, and other stakeholder perspectives on 2 BDI prototypes, revealing opportunities and challenges for introduction.
Spatial distribution and enrichment characteristics of selenium in paddy soil and rice around the Dongting Lake
Liu R, Zhou W, Yu D, Shang G, Zhou Y, Xu Z, Tang D, Cui H and Liao C
Selenium (Se) deficiency is a major global health issue. Given that the Dongting Lake region is a significant agricultural production area in China, its soil and geographical properties have a marked influence on Se accumulation in rice. Investigating these factors and their importance can provide technical guidance for the production of Se-rich rice locally and in other similar regions worldwide. Such studies can foster Se-enriched agricultural practices on a global scale, contributing to improved human health and environmental quality. Therefore, in this study, we investigated 15,403 paddy soil samples and their corresponding rice grains from the Dongting Lake area, by analyzing their Se content, spatial distribution, and bioaccumulation factor (BCF). The effects of parent materials, soil characteristics (physicochemical), and geographical factors on Se content in soil, rice grains, and BCF were also assessed. We found that the average Se content in the paddy soil of the Dongting Lake area was 0.43 mg/kg, which was 1.48 folds higher than the background Se content (0.29 mg/kg) in Chinese soil. The average Se content in rice grains was 0.06 mg/kg, surpassing the Chinese standard for Se-rich rice (0.04 mg/kg). Se distribution in the paddy soil and rice were the highest in the western and central regions and lowest in the eastern region. Se-enriched rice and Se-enriched rice fields are widely distributed in Dongting Lake area Seven parent materials significantly influenced soil Se and BCF. Correlation analysis revealed positive correlations between soil Se and soil organic matter (SOM), zinc, altitude, and mean annual precipitation. BCF was positively correlated with pH and mean annual temperature. The Random Forest model highlighted that SOM played a pivotal role in soil Se enrichment, being the most influential factor for both soil and rice enrichment (RR type), whereas pH exerted the most significant influence on soil enrichment without rice enrichment (RN type).
GRAPPA Debate: Targeted Small Molecules Versus Biologics as First-Line Systemic Therapy After Conventional Therapy for Moderate-to-Severe Psoriasis
Liao W, Armstrong AW and Callis Duffin K
In this debate at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, arguments were made contrasting the first-line use of oral targeted small-molecule drugs vs biologic therapy for the treatment of moderate-to-severe psoriasis (PsO) after failure of conventional therapy. Arguments in favor of small-molecule drugs included good efficacy and safety, patient preference, cost savings, global health equity, and environmental stewardship. Arguments in favor of biologics included superior efficacy, excellent safety, availability of long-term data, pediatric regulatory approvals, and potential benefit for comorbidities. By the end of the debate, there was recognition of significant pros and cons of each approach. Both small-molecule drugs and biologic therapy are valuable options for PsO treatment, and their use can be tailored toward specific individuals or healthcare systems.
Radon-222 signatures of atmospheric dynamics in the Pech Merle Painted Cave, France: Consequences for management and conservation
Perrier F, Bourges F, Girault F, Lartiges B, Bonnet S, Genty D, Denele Y, Regard V, Régnier É, Bouquerel H, Lei B, Rivet T and Losno R
Radon-222, a radioactive noble gas with a half-life of 3.8 days produced by radium-226, is a health hazard in caves, but also a powerful tracer of atmospheric dynamics. Here we show how airborne radon-222 can be analysed in a cave with multiple openings, the Pech Merle Cave in South-West France. This two-level cave hosts prehistoric remains and Gravettian paintings in its lower level. Radon concentration, monitored at 15 points with one-hour sampling intervals for more than one year, including two points for more than three years, showed mean values from 1274 ± 11 to 5281 ± 20 Bq m, with transient values above 15,000 Bq m. Seasonal variations were observed, with a weak normal cycle (low in winter) at two points in the upper level and a pronounced inverse seasonal cycle (low in summer) at the other points in the cave. The radon-222 source (effective radium-226 concentration, EC) was measured in the laboratory for floor deposits, soil and rock samples. While EC values obtained for rocks and speleothems are smaller than 1 Bq kg, most EC values for soils are larger than 10 Bq kg. Quantitative modelling confirms that the floor fillings inside the cave are responsible for the stationary lower concentrations, while the higher concentrations observed in winter are explained by percolation of outside air, which collects radon-222 as it passes through the soil layers. In addition, Stored Available Radon (SAR) is sufficient to account for transient variations. While air currents occur when visitors enter the cave or when the cave is deliberately ventilated, the climatic processes revealed by their radon-222 signatures appear to be essentially natural. These processes, enhanced by global climate change, could cause or accelerate the deterioration of prehistoric paintings. Radon-222 source analysis using EC-based modelling and SAR appears essential for the preservation of underground heritage.
A Biallelic Variant of the RNA Exosome Gene, EXOSC4, Associated with Neurodevelopmental Defects Impairs RNA Exosome Function and Translation
Fasken MB, Leung SW, Cureton LA, Al-Awadi M, Al-Kindy A, van Hoof A, Khoshnevis S, Ghalei H, Al-Maawali A and Corbett AH
The RNA exosome is an evolutionarily conserved complex required for both precise RNA processing and decay. Pathogenic variants in EXOSC genes, which encode structural subunits of this complex, are linked to several autosomal recessive disorders. Here, we describe a missense allele of the EXOSC4 gene that causes a collection of clinical features in two affected siblings. This missense variant (NM_019037.3: exon3:c.560T>C), changes a leucine residue within a conserved region of EXOSC4 to proline (p.Leu187Pro). The two affected individuals show prenatal growth restriction, failure to thrive, global developmental delay, intracerebral and basal ganglia calcifications, and kidney failure. Homozygosity for the damaging variant was identified by exome sequencing with Sanger sequencing to confirm segregation. To explore the functional consequences of this amino acid change, we modeled EXOSC4-L187P in the corresponding budding yeast protein, Rrp41 (Rrp41-L187P). Cells that express Rrp41-L187P as the sole copy of the essential Rrp41 protein show growth defects. Steady-state levels of both Rrp41-L187P and EXOSC4-L187P are decreased compared to controls and EXOSC4-L187P shows decreased co-purification with other RNA exosome subunits. RNA exosome target transcripts accumulate in rrp41-L187P cells, including the 7S precursor of 5.8S rRNA. Polysome profiles show a decrease in actively translating ribosomes in rrp41-L187P cells as compared to control cells with incorporation of 7S pre-rRNA into polysomes. This work adds EXOSC4 to the structural subunits of the RNA exosome that have been linked to human disease and defines foundational molecular defects that could contribute to the adverse phenotypes caused by EXOSC pathogenic variants.
Confronting heat-related illnesses and deaths at mass gathering religious and sporting events
McCloskey B, Memish ZA, Sharma A, Traore T, Parker S and Zumla A
The mutual longitudinal mediating effects of psychological and physical disorders on cognitive impairment among older adults
Du M, Liu M and Liu J
The potential mutual effect of physical and psychological disorders on cognitive function is critical for preventing cognitive impairment among older adults. We aimed to investigate the mediating role of physical and psychological disorders in their associations with cognitive function.
Glucagon-Like Peptide-1 Receptor Agonists and Risk for Suicidal Ideation and Behaviors in U.S. Older Adults With Type 2 Diabetes : A Target Trial Emulation Study
Tang H, Lu Y, Donahoo WT, Shao H, Shi L, Fonseca VA, Guo Y, Bian J and Guo J
A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation and behaviors based on International Classification of Diseases codes.
Implications of fuel poverty for indoor black carbon concentrations from space heating
Targino AC, Krecl P, Guerrero F, Cubillos M, Cardoso JV and Toledo M
Despite the global transition towards cleaner energy sources observed over the last decade, disparities in access to clean energy persist worldwide. The dependence on biomass for household heating exacerbates fuel poverty, as economically vulnerable households face challenges in obtaining certified firewood and often resort to using contaminated biomass as a substitute, either partially or completely. We examined black carbon (BC) particle concentrations -a marker for combustion- during wood stove operation through a five-day case study in a typical Chilean household. BC increased rapidly following the ignition of the stove, with the combustion of dry Eucalyptus globulus logs yielding a substantially lower peak (5.29 μg/m) than when using unclean biomass: 35.75 μg/m with demolition wood and painted furniture, and 87.11 μg/m with the addition of a blend of particleboard with polystyrene foam. During the latter two events, BC particles remained indoors for about 20 h before the concentrations reverted to pre-spike levels. The slow decay in BC concentrations was further influenced by the infiltration of outdoor air. The mean indoor BC concentrations were comparable to or even exceeded those observed on busy roads in major cities worldwide. These results highlight the risks associated with limited access to clean fuels for indoor heating, alongside inadequate insulation. This study sheds light on the problem of fuel poverty and its adverse effects on health and well-being.
Tropism for ciliated cells is the dominant driver of influenza viral burst size in the human airway
Roach SN, Shepherd FK, Mickelson CK, Fiege JK, Thielen BK, Pross LM, Sanders AE, Mitchell JS, Robertson M, Fife BT and Langlois RA
Influenza viruses pose a significant burden on global human health. Influenza has a broad cellular tropism in the airway, but how infection of different epithelial cell types impacts replication kinetics and burden in the airways is not fully understood. Using primary human airway cultures, which recapitulate the diverse epithelial cell landscape of the human airways, we investigated the impact of cell type composition on virus tropism and replication kinetics. Cultures were highly diverse across multiple donors and 30 independent differentiation conditions and supported a range of influenza replication. Although many cell types were susceptible to influenza, ciliated and secretory cells were predominantly infected. Despite the strong tropism preference for secretory and ciliated cells, which consistently make up 75% or more of infected cells, only ciliated cells were associated with increased virus production. Surprisingly, infected secretory cells were associated with overall reduced virus output. The disparate response and contribution to influenza virus production could be due to different pro- and antiviral interferon-stimulated gene signatures between ciliated and secretory populations, which were interrogated with single-cell RNA sequencing. These data highlight the heterogeneous outcomes of influenza virus infections in the complex cellular environment of the human airway and the disparate impacts of infected cell identity on multiround burst size, even among preferentially infected cell types.
Impacts of climate change on water-related mosquito-borne diseases in temperate regions: A systematic review of literature and meta-analysis
Gizaw Z, Salubi E, Pietroniro A and Schuster-Wallace CJ
Mosquito-borne diseases are a known tropical phenomenon. This review was conducted to assesses the mechanisms through which climate change impacts mosquito-borne diseases in temperate regions. Articles were searched from PubMed, Scopus, Web of Science, and Embase databases. Identification criteria were scope (climate change and mosquito-borne diseases), region (temperate), article type (peer-reviewed), publication language (English), and publication years (since 2015). The WWH (who, what, how) framework was applied to develop the research question and thematic analyses identified the mechanisms through which climate change affects mosquito-borne diseases. While temperature ranges for disease transmission vary per mosquito species, all are viable for temperate regions, particularly given projected temperature increases. Zika, chikungunya, and dengue transmission occurs between 18 - 34°C (peak at 26 - 29°C). West Nile virus establishment occurs at monthly average temperatures between 14 - 34.3°C (peak at 23.7 - 25°C). Malaria establishment occurs when the consecutive average daily temperatures are above 16°C until the sum is above 210°C. The identified mechanisms through which climate change affects the transmission of mosquito-borne diseases in temperate regions include: changes in the development of vectors and pathogens; changes in mosquito habitats; extended transmission seasons; changes in geographic spread; changes in abundance and behaviours of hosts; reduced abundance of mosquito predators; interruptions to control operations; and influence on other non-climate factors. Process and stochastic approaches as well as dynamic and spatial models exist to predict mosquito population dynamics, disease transmission, and climate favorability. Future projections based on the observed relations between climate factors and mosquito-borne diseases suggest that mosquito-borne disease expansion is likely to occur in temperate regions due to climate change. While West Nile virus is already established in some temperate regions, Zika, dengue, chikungunya, and malaria are also likely to become established over time. Moving forward, more research is required to model future risks by incorporating climate, environmental, sociodemographic, and mosquito-related factors under changing climates.
Occurrence, evaluation, and human health risk assessment of ochratoxin a in infant formula and cereal-based baby food: a global literature systematic review
Ahmad MS, Alanazi YA, Alrohaimi Y, Shaik RA, Alrashidi S, Al-Ghasham YA, Alkhalifah YS and Ahmad RK
This study reviews global levels of ochratoxin A (OTA) in infant formula and cereal-based foods, using Monte Carlo simulation to assess risks. The review found 24 studies on global OTA levels in infant food and cereal-based products, using databases including PubMed, Scopus, Web of Science and Embase until March 2024. We estimated OTA exposure in infant food based on concentration, intake and body weight. The exposure and hazard quotient margin were calculated using BMDL10 and TDI values. Monte Carlo simulation evaluated human health risks from OTA in infant formula and cereal-based foods. A global study from 14 countries shows varying levels, surpassing EU limits in Tunisia, Ecuador, the USA, and generally in Africa, notably in infant cereals, which had higher levels than formula. Globally, OTA was present in 29.3% of the 3348 samples analyzed, with Lebanon at 95.2% and Brazil at 0%. Analysis indicates only non-carcinogenic risk for infants. While health risks for infants are mostly low, ongoing research and monitoring are vital to minimize OTA exposure in infant food.
Production and evaluation of a new set of recombinant antigens for the serological diagnosis of Human cysticercosis
Melki J, Kouadio TN, Nowakowski M, Razafiarimanga Z, Soumahoro MK, Peltres S and Jambou R
Human cysticercosis caused by Taenia soliun (T. soliun) is endemic in certain areas of Latin America, Asia and Sub-Saharan Africa. Neurocysticercosis (NCC) is mainly diagnosed by neuroimaging, which, in most cases, is unavailable in endemic areas. Due to their high sensitivity and specificity, serological tests such as enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) based on the glycosylated fraction of the cyst CS50 are widely used for the detection of the anti-cysticercus IgG antibodies despite their significant cost and the need of cysticercus material. Given their cost-effectivess and simplicity, immunoassays based on recombinant proteins could provide new alternatives for human cysticercosis diagnosis: such tests would be aimed at screening those people living in remote areas who need further examination. To date, however, no test using recombinant antigens is commercially available. Herein, five recombinant proteins (R14, R18, R93.1, R914.1, and R915.2) were produced, three of which (R93.1, R914.1, and R915.2) were newly identified from the cyst fluid. Evaluation of the diagnostic performance of these recombinant antigens by ELISA was done using sera from 200 epileptic and non-epileptic individuals in comparison with the WB-CS50 as the reference serological method. Recombinant proteins-based ELISA showed a level of diagnostic performance that is inferior than the reference serological method, but similar to that of the native antigen ELISA for human cysticercosis (commonly used for screening). Further optimization of expression conditions is still needed in order to improve proteins solubility and enhance diagnostic performance for human cysticercosis detection. However, this preliminary evaluation of the recombinant antigens has shown their potential valuable use for screening cysticercosis in patients with epilepsy attending dispensaries in remote areas. Future studies should be conducted to evaluate our recombinant antigens in a large group of patients with different stages of NCC, and in correlation with imaging findings.
"Asian" Heart Failure
Yoo SGK, Lam CSP and Sweitzer NK
Derivation of water quality criteria for paraquat, bisphenol A and carbamazepine using quantitative structure-activity relationship and species sensitivity distribution (QSAR-SSD)
Xu YQ, Huang P, Li XW, Liu SS and Lu BQ
The risk assessment of an expanding array of emerging contaminants in aquatic ecosystems and the establishment of water quality criteria rely on species sensitivity distribution (SSD), necessitating ample multi-trophic toxicity data. Computational methods, such as quantitative structure-activity relationship (QSAR), enable the prediction of specific toxicity data, thus mitigating the need for costly experimental testing and exposure risk assessment. In this study, robust QSAR models for four aquatic species (Rana pipiens, Crassostrea virginica, Asellus aquaticus, and Lepomis macrochirus) were developed using leave-one-out (LOO) screening variables and the partial least squares algorithm to predict toxicity data for paraquat, bisphenol A, and carbamazepine. These predicted data can be integrated with experimental data to construct SSD models and derive hazardous concentration for 5 % of species (HC) for the criterion maximum concentration. The chronic water quality criterion for paraquat, bisphenol A, and carbamazepine were determined at 6.7, 11.1, and 3.5 μg/L, respectively. The QSAR-SSD approach presents a viable and cost-effective method for deriving water quality criteria for other emerging contaminants.
An inhibitory mechanism of AasS, an exogenous fatty acid scavenger: Implications for re-sensitization of FAS II antimicrobials
Huang H, Chang S, Cui T, Huang M, Qu J, Zhang H, Lu T, Zhang X, Zhou C and Feng Y
Antimicrobial resistance is an ongoing "one health" challenge of global concern. The acyl-ACP synthetase (termed AasS) of the zoonotic pathogen Vibrio harveyi recycles exogenous fatty acid (eFA), bypassing the requirement of type II fatty acid synthesis (FAS II), a druggable pathway. A growing body of bacterial AasS-type isoenzymes compromises the clinical efficacy of FAS II-directed antimicrobials, like cerulenin. Very recently, an acyl adenylate mimic, C10-AMS, was proposed as a lead compound against AasS activity. However, the underlying mechanism remains poorly understood. Here we present two high-resolution cryo-EM structures of AasS liganded with C10-AMS inhibitor (2.33 Å) and C10-AMP intermediate (2.19 Å) in addition to its apo form (2.53 Å). Apart from our measurements for C10-AMS' Ki value of around 0.6 μM, structural and functional analyses explained how this inhibitor interacts with AasS enzyme. Unlike an open state of AasS, ready for C10-AMP formation, a closed conformation is trapped by the C10-AMS inhibitor. Tight binding of C10-AMS blocks fatty acyl substrate entry, and therefore inhibits AasS action. Additionally, this intermediate analog C10-AMS appears to be a mixed-type AasS inhibitor. In summary, our results provide proof of principle that inhibiting salvage of eFA by AasS reverses the FAS II bypass. This facilitates the development of next-generation of anti-bacterial therapeutics, esp. the dual therapy consisting of C10-AMS scaffold derivatives combined with certain FAS II inhibitors.
Navigating the Health Care Landscape for an Ageing Population: An International Survey of Strategies and Priorities
Bruyère O, Demonceau C and Kergoat MJ
The global increase in the older population, which is expected to reach 1.5 billion by 2050, poses significant challenges for publicly funded health care systems. Life expectancy, although positive, is leading to an increase in chronic diseases requiring complex and costly health and social solutions. This study explores key strategies to address these challenges.
American Cutaneous Leishmaniasis: Imported cases in Berlin 2000-2023
Lindner AK, Moreno-Del Castillo MC, Wintel M, Equihua Martinez G, Richter J, Kurth F, Pfäfflin F, Zoller T, Gertler M, Georgi S, Nürnberg M, Hülso C, Bernhard J, Kotsias SK, Seigerschmidt A, van Loon W, Mockenhaupt F, Kampmann B and Harms G
American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce. We describe the clinical characteristics and outcome of patients with ACL imported to a tertiary centre in Germany and determine whether species-specific therapy according to the 2014 "LeishMan" group recommendations is associated with cure.
Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study
Suphavilai C, Ko KKK, Lim KM, Tan MG, Boonsimma P, Chu JJK, Goh SS, Rajandran P, Lee LC, Tan KY, Shaik Ismail BB, Aung MK, Yang Y, Sim JXY, Venkatachalam I, Cherng BPZ, Spruijtenburg B, Chan KS, Oon LLE, Tan AL, Tan YE, Wijaya L, Tan BH, Ling ML, Koh TH, Meis JF, Tsui CKM and Nagarajan N
The emerging fungal pathogen Candida auris poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual C auris isolates detected in Singapore, and to determine whether they constitute a novel clade distinct from all previously known C auris clades (I-V).
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.
Fish Iridoviridae: infection, vaccination and immune response
Leiva-Rebollo R, Labella AM, Gémez-Mata J, Castro D and Borrego JJ
Each year, due to climate change, an increasing number of new pathogens are being discovered and studied, leading to an increase in the number of known diseases affecting various fish species in different regions of the world. Viruses from the family Iridoviridae, which consist of the genera Megalocytivirus, Lymphocystivirus, and Ranavirus, cause epizootic outbreaks in farmed and wild, marine, and freshwater fish species (including ornamental fish). Diseases caused by fish viruses of the family Iridoviridae have a significant economic impact, especially in the aquaculture sector. Consequently, vaccines have been developed in recent decades, and their administration methods have improved. To date, various types of vaccines are available to control and prevent Iridoviridae infections in fish populations. Notably, two vaccines, specifically targeting Red Sea bream iridoviral disease and iridoviruses (formalin-killed vaccine and AQUAVAC IridoV, respectively), are commercially available. In addition to exploring these themes, this review examines the immune responses in fish following viral infections or vaccination procedures. In general, the evasion mechanisms observed in iridovirus infections are characterised by a systemic absence of inflammatory responses and a reduction in the expression of genes associated with the adaptive immune response. Finally, this review also explores prophylactic procedure trends in fish vaccination strategies, focusing on future advances in the field.
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.
Comparative evaluation of disease dynamics in wild boar and domestic pigs experimentally inoculated intranasally with the European highly virulent African swine fever virus genotype II strain "Armenia 2007"
Sánchez-Cordón PJ, Lean FZX, Batten C, Steinbach F, Neimanis A, Le Potier MF, Wikström-Lassa E, Wynne F, Strong R, McCleary S, Crooke H, Gavier-Widén D and Núñez A
Since the reintroduction of African swine fever virus (ASFV) in Europe in 2007 and its subsequent spread to Asia, wild boar has played a crucial role in maintaining and disseminating the virus. There are significant gaps in the knowledge regarding infection dynamics and disease pathogenesis in domestic pigs and wild boar, particularly at the early infection stage. We aimed to compare domestic pigs and wild boar infected intranasally to mimic natural infection with one of the original highly virulent genotype II ASFV isolates (Armenia 2007). The study involved euthanising three domestic pigs and three wild boar on days 1, 2, 3, and 5 post-infection, while four domestic pigs and four wild boar were monitored until they reached a humane endpoint. The parameters assessed included clinical signs, macroscopic lesions, viremia levels, tissue viral load, and virus shedding in nasal and rectal swabs from day 1 post-infection. Compared with domestic pigs, wild boar were more susceptible to ASFV, with a shorter incubation period and earlier onset of clinical signs. While wild boar reached a humane endpoint earlier than domestic pigs did, the macroscopic lesions were comparatively less severe. In addition, wild boar had earlier viremia, and the virus was also detected earlier in tissues. The medial retropharyngeal lymph nodes were identified as key portals for ASFV infection in both subspecies. No viral genome was detected in nasal or rectal swabs until shortly before reaching the humane endpoint in both domestic pigs and wild boar, suggesting limited virus shedding in acute infections.
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.
Perilipin2 depletion causes lipid droplet enlargement in the ovarian corpus luteum in mice
Ibayashi M, Tatsumi T and Tsukamoto S
Lipid droplets (LDs) are endoplasmic reticulum-derived organelles that store neutral lipids (mostly triglycerides and cholesterol esters) within a phospholipid monolayer and appear in most eukaryotic cells. Perilipins (PLINs, comprising PLIN1-5) are abundant LD-associated proteins with highly variable expression levels among tissues. Although PLINs are expressed in the mammalian ovaries, little is known about their subcellular localization and physiological functions. In this study, we investigated the localization of PLIN1-3 and their relationship with LD synthesis using mCherry-HPos reporter mice, thereby enabling the visualization of LD biogenesis in vivo. PLIN2 and PLIN3 were localized as puncta in granulosa cells with low levels of LD synthesis in developing follicles. This localization pattern was quite different from that of PLIN1, which was mainly localized in the theca and interstitial cells with high levels of LD synthesis. In the corpus luteum, where LD synthesis is highly induced, PLIN2 and PLIN3 are abundant in the particulate structures, whereas PLIN1 is poorly distributed. We also generated global Plin2-deficient mice using the CRSPR/Cas9 system and demonstrated that the lack of PLIN2 did not alter the distribution of PLIN1 and PLIN3 but unexpectedly induced LD enlargement in the corpus luteum. Collectively, our results suggest that the localization of PLIN1-3 is spatiotemporally regulated and that PLIN2 deficiency influences LD mobilization in the corpus luteum within the ovaries.
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
Theory of change for addressing sex and gender bias, invisibility and exclusion in Australian health and medical research, policy and practice
Gadsden T, Hallam L, Carcel C, Norton R, Woodward M, Chappell L and Downey LE
Sex and gender are inadequately considered in health and medical research, policy and practice, leading to preventable disparities in health and wellbeing. Several global institutions, journals, and funding bodies have developed policies and guidelines to improve the inclusion of diverse participants and consideration of sex and gender in research design and reporting and the delivery of clinical care. However, according to recent evaluations, these policies have had limited impact on the inclusion of diverse research participants, adequate reporting of sex and gender data and reducing preventable inequities in access to, and quality provision of, healthcare. In Australia, the Sex and Gender Policies in Medical Research (SGPMR) project aims to address sex and gender bias in health and medical research by (i) examining how sex and gender are currently considered in Australian research policy and practice; (ii) working with stakeholders to develop policy interventions; and (iii) understanding the wider impacts, including economic, of improved sex and gender consideration in Australian health and medical research. In this paper we describe the development of a theory of change (ToC) for the SGPMR project. The ToC evolved from a two-stage process consisting of key stakeholder interviews and a consultation event. The ToC aims to identify the pathways to impact from improved consideration of sex and gender in health and medical research, policy and practice, and highlight how key activities and policy levers can lead to improvements in clinical practice and health outcomes. In describing the development of the ToC, we present an entirely novel framework for outlining how sex and gender can be appropriately considered within the confines of health and medical research, policy and practice.
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.
Moving from idea to reality: The barriers and enablers to implementing Child and Family Hubs policy into practice in NSW, Australia
Calik A, Liu HM, Montgomery A, Honisett S, Van Munster KA, Morris T, Eapen V, Goldfeld S, Hiscock H, Eastwood J and Woolfenden S
Adverse childhood experiences can impact physical and mental health throughout the lifespan. To support families experiencing adversity and improve child health and developmental equity, an integrated, multi-sector response is required. Child and Family Hubs (Hubs) are a feasible and acceptable approach to providing such a response. In the Australian context, a number of federal and New South Wales (NSW) state policies support an integrated, multi-sector response using Hubs to support families experiencing adversity. This study examined NSW policy stakeholder and health service manager perspectives on the barriers and enablers to translating policy into practice in the implementation of Child and Family Hubs.
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.
Is the frequency of breakfast consumption associated with life satisfaction in children and adolescents? A cross-sectional study with 154,151 participants from 42 countries
López-Gil JF, Tully MA, Cristi-Montero C, Brazo-Sayavera J, Gaya AR, Calatayud J, López-Bueno R and Smith L
The promotion of daily breakfast consumption and the importance of making appropriate breakfast choices have been underscored as significant public health messages. The aim of this study was to examine the relationship between breakfast frequency and life satisfaction in large and representative samples of school-going children and adolescents aged 10-17 years from 42 different countries.
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.
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.
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.
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.
"We do others' Jobs": a qualitative study of non-nursing task challenges and proposed solutions
Al-Akash H, Aldarawsheh A, Elshatarat R, Sawalha M, Saifan A, Al-Nsair N, Saleh Z, Almagharbeh W, Sobeh D and Eltayeb M
Non-nursing tasks (NNTs) have become a prevalent issue among healthcare professionals, affecting nurses globally. This study delves into the experiences of Jordanian nurses regarding NNTs, aiming to uncover challenges and propose solutions within the Jordanian healthcare context.
A peer mentoring program for eating disorders: improved symptomatology and reduced hospital admissions, three years and a pandemic on
Raspovic A, Duck R, Synnot A, Caldwell B, Phillipou A, Castle D, Newton R, Brennan L, Jenkins Z, Cunich M, Maguire S and Miskovic-Wheatley J
Peer support involves people (mentors) using their own experiences to assist others (mentees). The impetus to include peer support in eating disorder recovery is high, however research on implementation of peer roles in eating disorder management is limited. A previous pilot study found positive but preliminary results for a Peer Mentor Program (PMP) for eating disorders. The PMP has since developed over time, including broadening its eligibility criteria and shifting to predominantly online delivery during COVID-19. This study aimed to evaluate the updated version of the PMP, on a larger and more diverse group of mentees.
From traditional to transactional: exploration of khat use in Ethiopia through an interpretative phenomenological analysis
Wood EA, Case SJ, Collins SL, Stark H and Wilfong T
Khat, a naturally growing stimulant, has seen a significant increase in both consumption and cultivation in eastern Ethiopia. This reliance on khat in the region comes despite its known physiological complications, with users unable to restrict khat use due to its pervasive impact on their livelihood. This qualitative study sought to understand the meaning that those in eastern Ethiopia attribute to khat and explore their firsthand experiences with the substance. In June and July of 2023, six unstructured interviews were conducted among residents of the Haramaya District in Ethiopia. To promote a holistic comprehension of the participants' lived experiences, an interpretative phenomenological analysis approach was employed when collecting and analyzing the data. Participant responses were coded independently from one another by two different researchers identifying superordinate and corresponding subordinate themes. Among the participants, six superordinate themes were captured: economic backbone of the region, market disruption & fluctuation, pesticide use, societal relationships around khat, applications of khat, and access to healthcare. The participants' responses indicated that the normalization of khat use, coupled with the downplaying of its addictive potential, has established a framework where khat consumption is not only allowed but, in some cases, even encouraged. The unique interplay between communal practice and individual preservation creates a cyclical effect of using khat to supplement energy to farm khat and then sell or stimulate further work on their farm. This study illuminates the transitionfrom what was once the traditional or spiritual use of khat, to a more practical use for ensuring economic livelihood.
Genetic analysis of feline parvovirus reveals predominance of feline parvovirus -G1 group among cats in China
Wang R, Gao D, Chen P, Mouzahim M, Muhammad S, Weidong Y, Zhongqi Q, Yilmaz A, Yilmaz H and Umar S
Feline parvovirus (FPV) or feline panleukopenia virus is a highly contagious, life-threatening infectious virus in cats. Although FPV vaccination is routinely practiced in China, clinical diseases continue to occur. The investigation of genotypes and viral evolution can contribute to the prevention, diagnosis, and treatment of FPV. Therefore, this study aimed to provide an up-to-date understanding of the epidemiological, genotypic, and phylogenetic characteristics of FPV. In total, 152 rectal swabs were collected from diseased cats. All swab samples were tested for FPV using molecular methods. Amplification of the complete viral protein 2 (VP2) gene was performed for further analysis and to infer the genotypic and evolutionary characteristics of FPV. Of the 152 samples, FPV DNA was detected in 17 (17/152, 11.18%). Cats with FPV showed variable clinical signs such as dehydration, anorexia, fever, vomiting, and blood-stained diarrhea. Furthermore, VP2 sequences were identified in 17 PCR-positive cats, confirming the presence of FPV. Phylogenetic and nucleotide pairwise identity analyses revealed high genetic similarity among FPV sequences (99.6-100%) and clustered them into the FPV-G1 group. Amino acid analysis indicated a novel mutation (Ala91Ser) in all VP2 gene sequences amplified in this study. Our study provides baseline epidemiological data for the better prevention of FPV with respect to vaccination strategies. Genotypic and phylogenetic analyses confirm that FPV-G1 was the predominant FPV group in infected cats in Kunshan. Therefore, a rigorous countrywide investigation of the genotypic and evolutionary characteristics of FPV is warranted.
Trochlea Dysplasia as the Major Anatomic Risk Factors for Patellofemoral Joint Instability: An Infographic as a Visual Learning Tool
Vasiliadis AV, Troupis T, Chrysikos D, Chytas D and Noussios G
Patellofemoral instability (PFI) is a common condition in children and adolescents, ranging from mild discomfort and mal-tracking to lateral patellar dislocation [1]. A number of anatomical risk factors have been described in the literature, such as trochlear dysplasia, patella alta, excessive tibial tuberosity to trochlear groove (TT-TG) distance, patellar tilt and soft tissue alterations [2]. Among them, TD has been identified as the main anatomical risk factor with the strongest association with PFI [1, 2]. In the study by Dejour et al. [2] radiographically observed TD was identified in 96% of patients with a history of patellofemoral dislocation [1, 2]. Patients with Dejour Type D dysplasia are characterized by a prominent and convex lateral facet with a vertical connection to a hypoplastic medial facet (Figure 1), which provides inadequate tracking of the patella in the trochlea during flexion leading to patella subluxation [2]. Non-operative treatment of lateral patellar dislocation presents a rate of re-dislocation up to 70% within 24 months of the first episode [3]. Sulcus deepening trochleoplasty is indicated for Type B and D dysplasia, in order to improve patella tracking, reduce the rate of re-dislocation and achieve good functional outcomes [2, 4]. Trochlea dysplasia is defined as a shallow or flattened groove with decreased resistance to lateral patellar translation. TD can be assessed on computed tomography (CT) and magnetic resonance imaging (MRI) with the use of overlapping axial images and are able to show perfectly the global shape of the femoral trochlea [2]. The thresholds for identifying trochlear dysplasia are established based on the sulcus angle ≥ 145°, medial/lateral trochlea facet asymmetry < 40%, trochlear depth < 3 mm and lateral trochlear inclination ≤ 11° and therefore it can be used in young adolescents [4, 5]. A deep knowledge of anatomic variations and abnormalities of the patellofemoral joint, which may predispose to PFI, is crucial in order to choose the appropriate treatment for each patient.
Lysophosphatidic acid receptor 1 inhibition: a potential treatment target for pulmonary fibrosis
Volkmann ER, Denton CP, Kolb M, Wijsenbeek-Lourens MS, Emson C, Hudson K, Amatucci AJ, Distler O, Allanore Y and Khanna D
Lysophosphatidic acid (LPA)-mediated activation of LPA receptor 1 (LPAR1) contributes to the pathophysiology of fibrotic diseases such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). These diseases are associated with high morbidity and mortality despite current treatment options. The LPA-producing enzyme autotaxin (ATX) and LPAR1 activation contribute to inflammation and mechanisms underlying fibrosis in preclinical fibrotic models. Additionally, elevated levels of LPA have been detected in bronchoalveolar lavage fluid from patients with IPF and in serum from patients with SSc. Thus, ATX and LPAR1 have gained considerable interest as pharmaceutical targets to combat fibrotic disease and inhibitors of these targets have been investigated in clinical trials for IPF and SSc. The goals of this review are to summarise the current literature on ATX and LPAR1 signalling in pulmonary fibrosis and to help differentiate the novel inhibitors in development. The mechanisms of action of ATX and LPAR1 inhibitors are described and preclinical studies and clinical trials of these agents are outlined. Because of their contribution to numerous physiologic events underlying fibrotic disease, ATX and LPAR1 inhibition presents a promising therapeutic strategy for IPF, SSc and other fibrotic diseases that may fulfil unmet needs of the current standard of care.
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.
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.
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.
By the numbers and in their own words: A mixed methods study of unmet needs and humanitarian inclusion of older Syrian refugees in Lebanon
Al Omari S, Honein-AbouHaidar G and Mehio Sibai A
Older people constitute an overlooked vulnerable population in humanitarian crises. Lebanon is a small country that hosts the largest number of refugees per capita in the world. With exacerbating socioeconomic conditions, exclusionary policies against refugees, and a fragmented humanitarian system, the status of older Syrian refugees (OSRs) requires special attention. This study aimed to explore OSRs' unmet needs, coping strategies, available humanitarian services, and some indicators of the humanitarian inclusion standards focusing on the shelter, health, nutrition and food security, and water, sanitation and hygiene sectors. We conducted a convergent mixed-methods study between December 2021 and March 2022 in the North and Bekaa, including a cross-sectional survey with 461 participants and 14 semi-structured interviews. Results show that OSRs lived in inappropriate shelters (cold, leaking rainwater), especially in informal tented settlements. High rent prices pushed refugee households with elderly to prioritize paying rent at the expense of other needs such as food and medication, particularly when food cash transfer is the sole source of income, jeopardizing food security and intake. Access to dignifying and accessible bathing facilities was compromised in ITSs with shared facilities. Substantial medical costs hindered OSRs access to healthcare such as surgeries. Due to the crisis, chronic medications are not always available in dispensaries for subsidized cost, pushing OSRs to non-compliance and selling food assistance to buy medications. Soaring fuel prices hindered OSRs access to heating and transportation to receive healthcare. No efforts were reported in collecting data on OSRs' needs, targeting them with information on services, or soliciting feedback for programming, especially in the absence of any age-tailored interventions. Findings shed light on the precarious living conditions of OSRs in Lebanon and add to the body of evidence documenting their invisibility to the humanitarian response. An age-inclusive response is needed through holistic, tailored, and sustainable interventions.
Cost-effectiveness of implementing performance-based financing for improving maternal and child health in Ethiopia
Koricho MA, Dinsa GD and Khuzwayo N
Performance Based Financing (PBF) supports realization of universal health coverage by promoting bargaining between purchasers and health service providers through identifying priority services and monitoring indicators. In PBF, purchasers use health statistics and information to make decisions rather than merely reimbursing invoices. In this respect, PBF shares certain elements of strategic health purchasing. PBF implementation began in Ethiopia in 2015 as a pilot at one hospital and eight health centers. Prior to this the system predominantly followed input-based financing where providers were provided with a predetermined budget for inputs for service provision. The purpose of the study is to determine whether the implementation of PBF is cost-effective in improving maternal and child health in Ethiopia compared to the standard care.
Gender and stigma in antiretroviral treatment adherence in Mozambique: A qualitative study
Viisainen K, Baumgart Dos Santos M, Sunderbrink U and Couto A
Both gender and HIV stigma are known to contribute to poor retention to antiretroviral therapy (ART), but little is known how they interact in decisions about adherence or default by people living with HIV (PLWH). This qualitative study explored HIV stigma and gender interaction in PLWH's care decisions in Mozambique. Transcribed data from semi-structured interviews of 68 men and 71 women living with HIV, were coded and analyzed for themes of HIV stigma, gender norms and treatment continuation and interruption pathways, using both deductive and inductive coding approaches. Stigma experiences were found to be influenced by gender roles. Anticipation of stigma was common across the narratives of PLWH, while women had more experiences of enacted stigma, particularly by their intimate partners. Women's treatment interruptions were influenced by fear of partner's negative reaction. Men's narratives showed internalized stigma and delayed treatment due to anticipated stigma and masculine norm of strength. Severe internalized stigma was found among single mothers, who without economic or moral support defaulted treatment. Women's pathway to adherence was facilitated by their caregiver role and support from partner or kin family. Men's adherence was facilitated by experience of severe symptoms, provider role and by support from their mother or partner. Results indicate that linkage of stigma to gender roles interact in treatment decisions in three main ways. First, HIV stigma and unequal gender norms can work jointly as a barrier to adherence. Secondly, those resisting restrictive gender norms found it easier to manage HIV stigma for the benefit of treatment adherence. Thirdly, some gender norms also facilitated adherence and stigma management. Programs targeted at HIV stigma reduction and improving ART adherence among heterosexual populations should be built on an understanding of the local gender norms and include socially and culturally relevant gender sensitive and transformative activities.
Spatiotemporal analysis of within-country imported malaria in Brazilian municipalities, 2004-2022
Arisco NJ, Peterka C and Castro MC
Human mobility has challenged malaria elimination efforts and remains difficult to routinely track. In Brazil, administrative records from the Ministry of Health allow monitoring of mobility locally and internationally. Although most imported malaria cases are between municipalities in Brazil, detailed knowledge of patterns of mobility is limited. Here, we address this gap by quantifying and describing patterns of malaria-infected individuals across the Amazon. We used network analysis, spatial clustering, and linear models to quantify and characterize the movement of malaria cases in Brazil between 2004 and 2022. We identified sources and sinks of malaria within and between states. We found that between-state movement of cases has become proportionally more important than within-state, that source clusters persisted longer than sink clusters, that movement of cases into sinks was seasonal while movement out of sources was not, and that importation is an impediment for subnational elimination in many municipalities. We elucidate the vast travel networks of malaria infected individuals that characterize the Amazon region. Uncovering patterns of malaria case mobility is vital for effective microstratification within Brazil. Our results have implications for intervention stratification across Brazil in line with the country's goal of malaria elimination by 2035.
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.
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