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Effect of plasmapheresis versus standard medical treatment in patients with hypertriglyceridemia-associated acute pancreatitis complicated by early organ failure (PERFORM-R): Study design and rationale of a multicenter, pragmatic, registry-based randomized controlled trial.
Get PDFThe prevalence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing. Studies have demonstrated the association between higher initial plasma triglyceride (TG) levels and worse clinical prognosis; therefore, lowering plasma TG has been the mainstay when managing HTG-AP. For TG-lowering therapy, plasmapheresis, which is costly and of potential complications, is currently widely used to clear TG from plasma, but whether it confers clinical benefits is unclear. In this trial, we aimed to evaluate the effect of plasmapheresis versus standard medical treatment on the duration of organ failure in HTG-AP patients with early organ failure. This is a multicenter, pragmatic, registry-based, randomized controlled trial. Based on previous studies, up to 236 HTG-AP patients with early organ failure are projected to be randomly assigned to either the plasmapheresis group or the standard medical treatment group (insulin plus low molecular weight heparin therapy). The PERFORM registry will be used as the platform for patient enrollment. The primary outcome is organ failure-free days to 14 days of enrollment. Organ failure in this trial is defined as an individual sequential organ failure assessment (SOFA) score of two or more for the respiratory, cardiovascular, or renal system. Patients who died before day 14 will be assigned zero organ failure-free days. This trial will provide top-class evidence regarding the clinical impact of plasmapheresis in HTG-AP patients with early organ failure. The findings of this trial will have a direct influence on the current clinical practice concerning the management of HTG-AP.</p
Optimising a novel biofilm-based process using Neurospora discreta for enhanced treatment of lignin-rich wastewater
Get PDFPaper and pulp mills generate substantial volumes of wastewater containing lignin-derived compounds that are challenging to degrade using conventional wastewater treatment methods. This study presents a novel biofilm-based process for enhanced lignin removal in wastewater using the fungus Neurospora discreta, which effectively degrades lignin and forms robust biofilms at the air–liquid interface under specific conditions. The process was optimised using the Taguchi design of experiments approach, and three factors including pH, copper sulphate concentration, and trace element concentration were evaluated at three levels. Experimental data were analysed against three responses: lignin degradation efficiency and the activities of two ligninolytic enzymes (polyphenol oxidase and versatile peroxidase). The results indicated that wastewater pH was the most significant parameter affecting lignin degradation efficiency and enzyme activities. Over 70% lignin degradation was achieved at pH levels of 5 and 6 with copper sulphate concentrations above 4 mg/L, while degradation efficiency drastically dropped to 45% at a pH value of 7. Reversed-phase high-performance liquid chromatography analysis demonstrated the effects of the three factors on the polar and non-polar components of lignin in wastewater, revealing a clear decrease in all peak areas after treatment. Additionally, significant relationships were observed between biofilm properties (including porosity, water retention value, polysaccharide content, and protein content) and lignin removal efficiency. This study also reported for the first time the presence of versatile peroxidase, a ligninolytic enzyme, in Neurospora sp.</p
Dermatophyte Treatment Failure: A Rapid Global Response to an Emerging Global Health Issue.
Get PDFDermatomycoses, or fungal infections of the skin, hair, and nails, affect nearly a billion people worldwide, especially in countries with a low sociodemographic index (SDI) and amongst vulnerable populations such as young children. Rising global rates of dermatophytosis impose a considerable burden on dermatology and primary care facilities worldwide, particularly on the Indian subcontinent. These infections, often perceived as minor, can severely impact quality of life, causing discomfort, social embarrassment, and contributing to poor sleep.</p
Risk Factors and Hospitalizations Associated with Pediatric Adenovirus and Rotavirus Infections in Northern Lebanon
Get PDFBackground and Objectives: Acute gastroenteritis (AGE) is a major contributor to pediatric morbidity and mortality worldwide. There is a scarcity of data on AGE in North Lebanon, a region profoundly affected by the Syrian refugee crisis and water sanitation issues. This study examines the prevalence, risk factors, and seasonal variations in adenovirus and rotavirus infections in children with AGE in North Lebanon. Materials and Methods: A cross-sectional study was conducted from September 2022 to August 2023 on 400 children (1 month to 5 years old) with AGE that were admitted to pediatric departments of three private hospitals in North Lebanon. Stool samples were collected and tested using chromatographic immunoassays. Comprehensive demographic and clinical data were collected and analyzed. Results: Rotavirus was the most frequent viral agent (28%), followed by adenovirus (12.3%) and mixed infections (5.5%). Rotavirus vaccination demonstrated a significant protective effect, and lower infection rates were associated with breastfeeding and consumption of bottled water (p < 0.001). Higher infection rates correlated with lower levels of maternal education and household incomes (p < 0.001). Malnutrition significantly increased susceptibility to rotavirus infections (p < 0.001). Conclusions: This study emphasized the urgent need for targeted public health interventions in North Lebanon to mitigate the burden of rotavirus and adenovirus-induced acute gastroenteritis among children.</p
The catalytic tetrad of Aedes aegypti Argonaute 2 is critical for the antiviral activity of the exogenous siRNA pathway
Get PDFViruses transmitted by biting arthropods, arboviruses, pose a significant global health and economic threat. Climate change is exacerbating this issue by expanding the range of disease-carrying vectors. Effective control of arbovirus transmission often relies on targeting the vectors, making it crucial to understand the interactions between the virus and its vector. The exogenous siRNA (exo-siRNA) pathway is a key antiviral defence mechanism in mosquitoes such as Aedes aegypti. Argonaute 2 (Ago2) is a central protein in this pathway, responsible for antiviral activity. While the PIWI domain of Ago proteins is known to mediate slicing activity, not all Ago proteins possess this slicing function. To understand the antiviral mechanism of Ago2 in Ae. aegypti, we aimed to confirm the presence of the catalytic tetrad, a group of amino acids known to be crucial for slicing activity. Here, we confirmed the tetrad (D740, E780, D812, and H950) in Ae. aegypti Ago2 and demonstrated its essential role in antiviral and siRNA pathway activity. Our findings show that the catalytic tetrad is necessary for the degradation of siRNA passenger strands. When the tetrad is absent, siRNA duplexes accumulate, leading to a loss of siRNA pathway function. This underscores the critical role of the tetrad in the antiviral defence mechanism of Ae. aegypti.</p
Categorization and Characterization of Snake Venom Variability through Intact Toxin Analysis by Mass Spectrometry
Get PDFThe variation in venom between and within snake species has significant implications for snakebite treatment. This highlights the critical importance of studying venom composition and its variations, not only for medical purposes but also from an evolutionary perspective. This study explores analytics for characterizing venom variability, focusing on venom toxin accurate masses, and emphasizes how the complexity of studying snake venom variability can be addressed by using liquid chromatography mass spectrometry (LC-MS) analysis with bioinformatics tools. This was demonstrated by investigating LC-MS data obtained from the venoms of 15 true cobras (Naja spp.), 5 mambas (Dendroaspis spp.) and 28 vipers (Crotalus and Bothrops spp.; total of 20 Elapidae and 28 Viperidae venoms), with newly developed bioinformatics tools. The measured LC-MS data was processed in an automated fashion and sorted based on the monoisotopic accurate masses of all toxins found, their peak intensities, and their retention times in LC. The data was then investigated using bioinformatic tools, before the toxin data available in open-source databases was used to predict the class of a toxin by means of its mass. This study highlights the importance of studying venom variability, which is performed by our combinatorial approach of intact-toxin analysis and toxin grouping by accurate mass.</p
Prospective longitudinal assessment of Albumin-to-Creatinine ratio (ACR) in a clinical cohort of people living with HIV in Gaborone, Botswana
Get PDFBackgroundPeople living with HIV (PLWH) in sub-Saharan Africa are vulnerable to end organ dysfunction such as albuminuria, which is associated with an increased risk of cardiovascular and renal events. However, the prevalence of persistent albuminuria among PLWH in Africa is unclear. This observational prospective study assessed for persistence of albuminuria in a cohort of PLWH on longterm antiretroviral therapy (ART) across various HIV service platforms in Gaborone, Botswana.MethodsA subgroup of ART treated PLWH (n = 867) from a larger cross-sectional study (n = 1537) assessing prevalence of albuminuria among PLWH at a referral hospital HIV clinic and satellite HIV clinics in Gaborone, were invited to participate in a 12-month long albuminuria prospective cohort study between January 2020 and March 2022. During three planned study visits, albumin-creatinine (ACR) was computed using urine albumin measured using immunoturbidimetric assay and urine creatinine using colorimetric assay (Jaffe method), at the Botswana Harvard HIV Reference Laboratory. ACR trajectory groups were identified using growth mixture models, and factors associated with ACR trajectory were analyzed using modified Poisson regression.ResultsAmong the 623 adults with complete data for all 3 study visits, their baseline median age was 50 (42–57) years with a median HIV disease duration of 13.1 (8.7–16.7) years, and 266 (42.7%) of them were female. Study participants were categorized into two ACR trajectory groups: low increasing ACR, N = 290 (46.5%) and moderate increasing ACR, N = 333 (53.5%) groups. ACR increased by 4.7 mg/g in the slow increasing ACR groups versus 11.5 mg/g in the moderate increasing ACR trajectory group by end of follow-up. Active use of Tenofovir, aRR 1.27 [95% CI 1.02–1.60], p = 0.036, or ACEi/ARB, aRR 1.31 [95% CI 1.07–1.61], p = 0.008, and an elevated baseline ACR, aRR 1.34 [95% CI 1.28–1.41], p < 0.001, were all associated with being in the moderate increasing ACR trajectory group.ConclusionChronic, treated HIV infection was associated with more than 5 fold increase in ACR over 12 months. Future studies should explore the extent to which modifiable risk factors and HIV specific factors for progressive increase in albuminuria could be aggressively controlled among PLWH.</p
Rebuilding trust and equity in Syria's health system: a governance-driven transition.
Get PDFIn December, 2024, after more than 50 years in power in Syria, the regime of the Assad family was swept away. This dramatic political shift illuminated the state of health in Syria, exposing widespread fractures in a health system that has been politicised and fragmented, including widespread erosion of public trust in medical care.1 Health has been decimated during Syria's almost 14-year conflict by attacks on infrastructure, the forced exodus of health-care workers, and severe under-resourcing. The emergence of subnational health systems since early in the conflict has fragmented health-care delivery, leading to parallel governance structures.1 Syria's new transitional government, led by transitional President Ahmed al-Sharaa, therefore faces a profound challenge: how to re-establish trust in services and rebuild a cohesive, development-focused, resilient health-care system from these fragmented pieces.</p
Sero-epidemiology of measles Immunoglobulin G antibodies among newborn from South East Asia and sub-Saharan Africa: an observational, multicentre study.
Get PDFObjectivesTo investigate the transplacental acquisition of measles immunoglobulin (Ig)G in newborns at delivery in Bangladesh, Bhutan, India, Ethiopia, Mozambique, Kenya, Nigeria, Mali, and South Africa.MethodsArchived cord serum, from a multicenter study on Group B Streptococcus, were tested for measles IgG using a commercial enzyme link immunosorbent assay (ELISA). We tested 323 randomly selected samples from each of the sites. Models using various measles antibody decay rates in infancy were explored.ResultsOverall, 2,907 cord serum samples were analyzed. At birth, 49.9% of newborns were measles IgG seronegative. Measles seronegativity ranged from 21.7% in Nigeria to 73.4% in Bhutan. The adjusted odds of seronegativity in infants of mothers born after measles vaccination implementation was 1.78 times that for infants born to unvaccinated mothers (adjusted odds ratio 1.78; 95% confidence interval 1.43-2.21; P <0.001). Modeling measles-IgG kinetics predicted that 70.8%, 88.3%, and 100% of infants would be seronegative by 2, 4, and 6 months, respectively, without further exposure.ConclusionsOur findings suggest low transplacental acquisition of measles IgG in newborns, which is likely to yield susceptibility to measles infection at a very young age. The currently recommended measles vaccine schedules in low- and middle-income countries (LMICs), with the first dose recommended from 9 months of age and onward, warrant reconsideration, including the need for earlier dosing schedules.</p
Delayed correct diagnoses in emerging disease outbreaks: Historical patterns and lessons for contemporary responses
Get PDFBackgroundThe gap between early diagnostic assumptions and final diagnoses in disease outbreaks represents a persistent challenge in global health despite advancements in diagnostic and response capabilities.ObjectivesTo analyze the unfolding 2025 outbreak in the Democratic Republic of Congo (DRC) through the lens of historical cases where initial misattributions contributed to delayed recognition of novel or unexpected threats with varying public health consequences; identifying patterns from past outbreaks that can inform current diagnostic approaches and response strategies.SourcesWe selected illustrative examples from peer-reviewed publications, focusing on cases with initial diagnostic uncertainties that highlight specific diagnostic patterns relevant to the current DRC outbreak. For the ongoing DRC outbreak, we analyzed official World Health Organization Africa bulletins and communications from the DRC Ministry of Health through February and early March 2025.ContentAs of beginning of April 2025, health authorities continue investigating clusters of unexplained acute febrile illness in Équateur Province with clinical features that were initially being suggestive of a viral haemorrhagic fever. Primary VHF pathogens have now been excluded. From selected historical and recent outbreaks, it can be deduced that diagnostic challenges extend beyond individual cognition to include structural biases in global health systems, methodological limitations and sociocultural factors.ImplicationsWe identified five evidence-informed interventions to mitigate diagnostic delays: systematic consideration of multiple working hypotheses, development of sustainable local diagnostic capacity, enhancement of clinician-to-public-health communication networks, implementation of cognitive debiasing strategies, and strengthening of One Health surveillance platforms. Historical ‘misdiagnoses’ offer crucial lessons for transforming outbreak response from reactive to anticipatory, potentially averting future epidemics through earlier, more accurate recognition of emerging pathogens within their complex ecological and social contexts.</p