共找到 20 条结果
Better evaluation of the contribution of the main diseases, injuries, and risk factors for mortality and life expectancy is crucial for more efficient policy making at the national and subnational levels in Iran. The aim of this study is to assess the effect of emerging causes of mortality on health, specifically COVID-19, which can help policy makers implement preventive measures in similar situations. In this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we present estimates of cause-specific mortality at the national and subnational levels in Iran from 1990 to 2023. New to this iteration of GBD, we present a decomposition analysis of the contribution of specific causes of death to net gain or loss in life expectancy across 31 provinces of Iran. We used an array of data sources including censuses, vital registration, and surveys for national and subnational estimates. The two leading causes of death in Iran were ischaemic heart disease and stroke in both 1990 and 2019. However, in 2020 and 2021, the COVID-19 pandemic displaced the leading causes of death, ranking first with age-standardised mortality rates of 286·2 deaths (95% uncertainty interval 267·9-310·5) per 100 000 in 2020 and 250·0 deaths (233·2-272·5) per 100 000 in 2021. COVID-19 ranked second and tenth in 2022 and 2023, respectively. Life expectancy at birth for both sexes combined declined from 78·0 years (77·7-78·1) in 2019 to 74·3 years (74·0-74·4) in 2020. It steadily recovered to 78·8 years (78·5-79·2) in 2023. COVID-19 was the main cause of loss in life expectancy, by 4·19 years, between 2019 and 2020. There was a net gain of 12·4 years in life expectancy in Iran from 1990 to 2023. The net gain at the national level can be mostly attributed to reduced mortality from ischaemic heart disease (2·61 years), stroke (1·63 years), neonatal disorders (1·26 years), transport injuries (0·88 years), and neoplasms (0·64 years). The decline in mortality rates of major causes continued to 2023 despite the pandemic. An exception was Alzheimer's disease, which showed a 4·0% increase in rate between 2019 and 2023 and led to a net loss of 0·04 years in life expectancy since 1990. Diabetes led to a net loss of 0·09 years since 1990. There were variations between provinces in terms of age-standardised rates and the net change in life expectancy before and after the COVID-19 pandemic. The COVID-19 pandemic disrupted the rising trend of life expectancy in Iran, varying across provinces. Findings show that the health-care infrastructure and policies in Iran were not efficient in controlling the pandemic in 2020 and 2021, mainly due to inadequate vaccination coverage and timeliness, specifically for vulnerable subgroups. Sanctions may have aggravated the effect of COVID-19 on loss in life expectancy of Iranians. Despite the pandemic, the declining trend in age-standardised rates for top causes of mortality has continued to 2023, leading to a full recovery of life expectancy and underscoring the ultimate resilience of Iran's health system. Gates Foundation.
The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Early identification of patients at risk of developing severe disease remains a clinical challenge for scrub typhus. We aimed to identify serum cytokine profiles associated with disease severity and validate potential biomarkers for early risk stratification of patients with scrub typhus. We conducted a retrospective multicenter study to analyze serum cytokine/chemokine profiles and clinical data of 51 scrub typhus patients and 13 control patients at presentation to the hospital. We further performed longitudinal monitoring of the cytokine/chemokine dynamics in 11 of these patients. The findings were then validated in two different hospitals (n = 88). Of 44 cytokines/chemokines tested, 32 were detectable in the serum samples of the patients. Compared with control patients, patients with scrub typhus showed significant elevation of 22 and reductions of 3 cytokines/chemokines (P < 0.05). The serum soluble programmed death-ligand 1 (sPD-L1) levels differed significantly across severity groups (P = 0.04) and trended lower during recovery (P = 0.082). sPD-L1 demonstrated a significant trend with increasing severity and showed superior performance to conventional markers in distinguishing patients with organ dysfunction. Receiver operating characteristic analysis of sPD-L1 levels at hospital admission confirmed high discriminatory power, with AUCs of 0.997 and 0.981 in the two validation cohorts. This multicenter study identified sPD-L1 as a potential early biomarker for early risk stratification of patients with scrub typhus. Scrub typhus, caused by Orientia tsutsugamushi, affects over one million people annually in the Asia-Pacific region, with an in-hospital mortality rate of more than 30% among patients with severe disease. Early identification of patients at high risk of progression to multi-organ failure remains a major clinical challenge. Timely risk stratification to identify high-risk patients is essential to prevent poor clinical outcomes. This study identifies soluble programmed death-ligand 1 as a potential early biomarker that distinguishes patients at risk of developing severe disease within the first week of hospitalization.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is one of the most prevalent liver diseases globally, contributing to both economic and health-related challenges. We aimed to evaluate the global, regional, and national burden of MASLD from 1990 to 2023, quantify the contribution of identified modifiable risk factors, and project future prevalence up to the year 2050. Estimates of MASLD prevalence and disability-adjusted life-years (DALYs) were produced by age, sex, region, Socio-demographic Index (SDI), and Healthcare Access and Quality (HAQ) index across 204 countries and territories from 1990 to 2023 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The MASLD burden attributable to three risk factors (smoking, high BMI, and high fasting plasma glucose) was assessed as part of the GBD comparative risk assessment. As a secondary analysis, we used these estimates to forecast MASLD prevalence up to 2050 using fasting plasma glucose and mean BMI as predictors. Furthermore, to examine the relative contributions of population ageing, population growth, and changes in MASLD prevalence rate to the forecasted changes in case counts from 2023 to 2050, we conducted a decomposition analysis. In 2023, approximately 1·3 billion (95% uncertainty interval [UI] 1·2 to 1·4) individuals were estimated to be living with MASLD (ie, 16·1% of the global population), with an age-standardised prevalence rate of 14 429·3 (95% UI 13 268·3 to 15 990·6) per 100 000 population, representing a percentage increase of 142·7% (95% UI 139·2 to 146·7) in crude numbers from 1990 (0·5 billion [0·5 to 0·6]) and of 28·6% (27·8 to 29·5) in the rate (11 217·2 [10 276·8 to 12 467·0] per 100 000 in 1990). An estimated 3·6 million (2·8 to 4·5) total DALYs were attributable to MASLD worldwide in 2023, corresponding to an age-standardised DALY rate of 39·6 (31·2 to 49·9) per 100 000 population. Despite a 116·3% (93·3 to 139·4) increase in crude DALYs (from 1·7 million [1·3 to 2·1] in 1990), its age-standardised estimate remained consistent (1·8% [-8·6 to 12·8]) from 1990 (38·9 [30·1 to 49·8] per 100 000) to 2023. There was substantial variation in age-standardised estimates across regions. North Africa and the Middle East had the highest prevalence rate (29 246·1 [26 848·3 to 32 048·7] per 100 000) and Andean Latin America showed the highest DALY rate (152·3 [114·1 to 194·7] per 100 000). By contrast, the high-income Asia Pacific region had the lowest prevalence rate (8653·5 [7923·7 to 9592·8] per 100 000) and east Asia had the lowest DALY rate (16·3 [13·5 to 19·9] per 100 000) among all GBD regions. North Africa and the Middle East showed disproportionately higher prevalence rates relative to other regions with similar SDIs. Lower SDIs and HAQs were associated with higher age-standardised DALY rates. The age-standardised prevalence rate was consistently higher in males (15 616·4 [14 349·2 to 17 263·3] per 100 000 people in 2023) than in females (13 245·2 [12 132·0 to 14 692·6] per 100 000 people), and peaked at age 80-84 years in both sexes. The number of MASLD prevalent cases was the highest in younger adults, peaking at age 35-39 years for males and age 55-59 years for females. Among the risk factors for MASLD, high fasting plasma glucose presented the largest contribution to the age-standardised DALY rate of total MASLD in 2023 (2·2 [95% UI 1·6 to 3·1] per 100 000 people), followed by high BMI (1·4 [0·6 to 2·4] per 100 000 people) and smoking (1·0 [0·3 to 1·8] per 100 000 people). Our forecasting model estimates that 1·8 billion (95% UI 1·6 to 2·0) individuals are likely to have MASLD by 2050, representing a 42·0% increase from 2023. The age-standardised prevalence rate is expected to increase to 15 774·9 (95% UI 14 613·9 to 17 336·2) per 100 000 people in 2050, representing an average annual percentage change of 0·3% (95% UI 0·3-0·3). According to our decomposition analysis, this change will be primarily due to population growth, particularly in sub-Saharan Africa and North Africa and Middle East, and less by population ageing or epidemiological change. With a global prevalence of 16·1% and approximately 1·3 billion people already living with MASLD in 2023, the condition has and will continue to have substantial health and economic impacts worldwide. An inverse association between the HAQ Index and age-standardised DALY rates suggests that countries with lower health-care access and quality might be less well positioned to manage the growing MASLD burden, underscoring the need for strengthened health-system capacity in these settings. Gates Foundation.
Cyanobacteria of the Microcystis genus often form blooms in freshwater and estuarine environments, producing microcystin, a toxin harmful to animals and humans. The analysis of water samples for the detection of toxic Microcystis is usually time-consuming and not effective when the organisms are in pre-bloom concentrations, resulting in exposure of animals and humans to toxins. Thus, early detection of the presence of microcystin-producing Microcystis is crucial. In this work, we present a method based on loop-mediated isothermal amplification (LAMP) to detect the presence of Microcystis cells capable of producing microcystins. Specific primers were designed for the mcyJ gene (biosynthetic gene cluster mcy) and detection of LAMP products was visualized using different approaches, including a fluorescent dye in the reaction mix (pre-stained LAMP), the addition of a posteriori staining using SybrGreen (post-stained LAMP), colorimetric, and lateral flow reaction stripes. The limit of detection (LoD) of the LAMP assay was estimated based on DNA quantification by quantitative real-time PCR (qPCR). The pre-stained, post-stained and colorimetric assays applied to Microcystis NIES cultures achieved the same detection limit of 28 pg/μL of DNA corresponding to 1490 ± 620 toxic Microcystis cells mL-1, within 12.2 min, with 100% sensitivity. The lateral flow reached the lowest LoD, giving a positive signal at a DNA concentration of 2.8 pg/μL (equivalent to ca. 150 toxic Microcystis cells mL-1). The method was applied successfully to various natural water samples. The LAMPs can be optimized for local in-situ use, enabling rapid adaptive monitoring and management of aquatic ecosystems.
Root rot disease incited by Rhizoctonia solani, is one of destructive soil-borne diseases which constrains faba bean (Vicia faba L.) productivity. In the present research, pathogenicity of R. solani isolates was determined and potential of putative Trichoderma species were evaluated as a biological control in both in vitro as well greenhouse conditions. The most aggressive isolate of R. solani was determined with morphological characterization and sequencing of ITS rDNA. In vitro antagonistic potential of Trichoderma atroviride and Trichoderma asperellum against R. solani was evaluated by dual culture technique, and in greenhouse trials compared with a standard fungicide recommendation for comparison of efficacy. Both Trichoderma spp., strongly inhibited mycelia growth of R. solani in vitro, with inhibition ranging from over 85% for the most effective isolates. Trichoderma spp. applied to the soil under greenhouse conditions had significant influences on these trends significantly less damping-off and root rot disease incidence with an increase in the percentage of healthy surviving plants than the infected control. T. asperellum provided more efficient disease suppression than T. atroviride, whereas the chemical fungicide resulted in the greatest reduction of disease. Furthermore, Trichoderma-treated plants had higher activities of defense-related enzymes such as catalase, peroxidase and polyphenol oxidase which indicated the induction of systemic resistance. These results indicate that Trichoderma spp., mainly T. asperellum, can be a good alternative or supplement to chemical fungicides for the integrated disease management of R. solani-mediated root rot disease in V. faba L. under field conditions.
Maternal high-fat diet (HFD) increases the risk of metabolic disorders in offspring. Placental inflammation acts as a critical mediator with poorly addressed etiology. Recently HFD-induced gut dysbiosis is demonstrated to be a key driver of systemic inflammation. Whether inflammatory signals triggered by HFD-induced gut dysbiosis are transmitted to the placenta via the maternal-fetal axis warrant further investigation. This study aims to elucidate the mechanistic connection between maternal gut dysbiosis and placental inflammation, thereby offering insights into microbiota-mediated developmental origins of metabolic diseases in offspring. Female C57BL/6 mice were exposed to high fat diet (HFD) for 5 weeks prior to mating with male mice. Gut microbiota was profiled by using 16 S rRNA sequencing and fecal short-chain fatty acids (SCFAs) were quantified by GC-MS from HFD pregnant mice at gestational day 18.5 (G18.5). Mice were sacrificed at G18.5, and placenta histopathological analysis as well as inflammatory markers and lipopolysaccharide (LPS) level were analyzed. Anti-inflammatory effects of butyrate were evaluated in vitro by using HTR-8/Svneo cells and in vivo through gestational supplementation (0.3 mg/g body weight) in HFD-fed dams. Maternal HFD exposure induced significant placental inflammation as well as hepatic steatosis in the offspring. HFD-fed dams exhibited distinct gut dysbiosis with reduced fecal and serum SCFAs, which was accompanied by elevated placental LPS levels and exacerbated inflammatory responses. Butyrate treatment suppressed the expression of inflammatory cytokines in vitro through down-regulating the phosphorylation of NF-κB, ERK1/2 signaling pathways via G-protein-coupled receptor 41 (GPR41). Furthermore, gestational butyrate intervention effectively alleviated placental inflammation and mitigated fetal hepatic lipid deposition in HFD-exposed offspring. Placental inflammation caused by maternal HFD is closely associated with gut microbiota dysbiosis. Butyrate supplementation during gestation reduces placental inflammation and ameliorated offspring hepatic steatosis, highlighting the therapeutic potential of butyrate for mitigating the adverse metabolic programming effects upon maternal HFD exposure.
BACKGROUND: The diagnosis and treatment of leptospirosis in high-burden, low-resource settings pose a challenge due to the limited availability of confirmatory diagnostics. Therefore, the initiation of treatment relies primarily on the clinical assessment of patients suspected of having leptospirosis in resource-poor settings. This study aimed to both early diagnostic indicators and predictors of disease severity. METHODS: A total of 170 patients suspected of having leptospirosis admitted to selected hospitals in Western Province, Sri Lanka were enrolled. MAT, qPCR, and culture were used for confirmatory diagnosis. Patients with confirmed leptospirosis were grouped as severe and non severe based on presenting with at least one organ failure and/or dysfunction. RESULTS: Out of 170 leptospirosis suspected patients, 79 (46.47%) were confirmed by PCR (n = 49), MAT (n = 44) and/or culture (n = 2). Myalgia, oliguria, elevated neutrophils, serum creatinine, serum urea, SGOT, SGPT and CRP, decreased lymphocytes, haemoglobin and platelets had a significant association with confirmed leptospirosis. Of patients with confirmed leptospirosis, 51 were categorized as non severe and 28 were categorized as severe. Leptospirosis severity was correlated with decreased haemoglobin, lymphocyte and platelet counts, and elevated WBC, neutrophil, K+, SGOT, SGPT, serum urea, serum creatinine, total and direct bilirubin and CRP. A bacterial load between 1.21 × 102 to 1.26 × 106 (median 3,326) Leptospira/ml was reported with no significant association between severity of the disease and leptospiraemia. CONCLUSION: Clinical and basic laboratory findings play a crucial role in supporting the diagnosis of leptospirosis and predicting disease severity, particularly in tropical, resource-poor settings.
Wheat as a major staple crop faces productivity constraints, especially in rain-fed and arid areas of Pakistan. Ecofriendly alternatives using indigenous plant growth promoting (PGP) microorganisms may help enhance crop performance. This study evaluated PGP traits of indigenous strains of two under-characterized Trichoderma species, that is, Trichoderma afroharzianum ISO-02 and Trichoderma brevicrassum ISO-03, using in vitro and in planta assays with cell-free culture filtrates (CFCF) or spore-based formulations. To the best of our knowledge, this is the first comparative study evaluating CFCF and spore-based formulations of strains of T. afroharzianum and T. brevicrassum on wheat growth. Briefly, ISO-02 produced higher levels of IAA (9.91 µg/mL) and ammonia (11.63 µg/mL) than ISO-03. Moreover, ISO-02 exhibited significantly higher phosphate (1.15 ± 0.01 mm) and zinc-solubilization indices (1.46 ± 0.03 mm), and produced pectinolytic enzymes and siderophores. The CFCF, or spore suspensions of ISO-02, both in plates and pots, produced significantly higher germination, with increased chlorophyll contents and growth parameters on a consistent basis at p ≤ 0.05. The results also suggested a role of extracellular metabolites in growth stimulation of wheat. The present study demonstrated multifunctional PGP traits of T. afroharzianum ISO-02 and T. brevicrassum ISO-03, supporting their potential application as sustainable biofertilizers specifically for wheat cultivation.
Naringinase is an industrially important enzyme system with applications in citrus debittering, aroma enhancement, and the production of bioactive flavonoid aglycones. Accurate identification of true naringinase-producing microorganisms remains challenging due to the dual-enzyme nature of naringinase, which requires coordinated α-L-rhamnosidase and β-D-glucosidase activities. Conventional screening methods based on naringin agar or single chromogenic substrates often generate false-positive results, as they fail to distinguish partial enzyme producers from microorganisms capable of complete naringin hydrolysis. In this study, a single-plate, one-step dual chromogenic screening assay was developed for reliable identification of true naringinase producers. The method employs p-nitrophenyl-α-L-rhamnopyranoside and X-gal to simultaneously detect α-L-rhamnosidase and β-glycosidase-like activities, producing distinct yellow and blue signals, respectively. The spatial separation of these chromogenic products enables unambiguous differentiation of microbial enzymatic profiles on a single agar plate. The assay was validated using bacterial strains with known enzymatic characteristics and further confirmed by spectrophotometric enzyme assays and thin-layer chromatography. Only isolates exhibiting both chromogenic responses demonstrated complete biotransformation of naringin to naringenin. A positive correlation between chromogenic halo diameter and measured enzyme activity was also observed. The proposed assay provides a simple, reliable, and scalable platform for high-throughput screening of naringinase-producing microorganisms in applied microbiology and biotechnology.
Tuberculosis (TB), a deadly infectious disease caused by Mycobacterium tuberculosis (Mtb), was the second leading cause of death from a single infectious agent after COVID-19 in 2022, killing nearly twice as many people as AIDS, and still affecting more than 10 million people every year. Traditional diagnostic methods have the problems of low sensitivity, poor specificity, long time consuming and high cost. MPT64 is a 24-kDa protein secreted by Mtb during its propagation. It only exists in the Mtb complex and is one of the important antigens for the serological diagnosis of tuberculosis. Based on the principle of one-step substrate capture and detection probe with aptamer specific recognition of MPT64, this study proposed an innovative and efficient strategy for Mtb detection through serum testing using an buffer system integrated with dual aptamer modified surface-enhanced Raman scattering (SERS) biosensor. By incubating NBA Raman reporter molecules on the surface of Gold-core silver-shell nanoparticles and coupling MPT64 aptamer A to form reporter probes; and modifying MPT64 aptamer-B onto the surface of magnetic beads to form capturing probes, which together constitute the detection system. This study constructed a curve showing the logarithmic relationship between the standard concentration of MPT64 and Raman intensity. Within the concentration range of 1 × 10-3 to 1 × 104 ng/mL, a good linear relationship was obtained (R2 = 0.9963), with a detection limit of 20 fg/mL. In 25 human serum samples (10 positive and 15 negative), the aptamer-SERS biosensor system achieved 100% sensitivity and specificity, and was capable of quantitatively detecting tuberculosis biomarkers, providing a reliable detection method for tuberculosis diagnosis.
During the COVID-19 pandemic, international border restrictions, along with traveler screening and quarantine, were implemented to limit virus spread. This study analyzes the epidemiological and genomic profiles of SARS-CoV-2 infections imported into Kinshasa (DRC) during the restrictions period in 2021. As part of the national response to the pandemic, self-reported demographic and clinical data were collected from travelers entering the DRC via N'djili-Kinshasa International Airport. SARS-CoV-2 infection was diagnosed using RT-PCR, and positive samples were subjected to whole genome sequencing (WGS) to determine variant types and viral lineages. The impact of the virus's genomic profile on the clinical presentation of travelers and on the COVID-19 epidemiology in the DRC was then assessed. Of 102,810 included travelers, 1037 (1.0%) tested positive for SARS-CoV-2 and reported significantly more nausea, diarrhea, and weight loss than uninfected travelers (p < 0.001). SARS-Cov-2-infected travelers were predominantly under 43 years old (p < 0.001) and primarily from France (24.8%) and Belgium (19.5%). Of the 105 WGS analyzed, 86 (81.9%) were variants of concern (VOCs), 14 (13.3%) were variants under monitoring (VUM), and the main genomic lineages identified were Delta-B.1.617.2 (24.8%), Alpha-B.1.1.7 (10.5%), Delta-AY.122 (7.6%), and B.1.620 (5.7%). The Delta-VOC was the most prevalent among positive travelers (61/86) and appeared to cause more symptomatic infections than non-Delta variants, although one-third of positive travelers reported no symptoms. SARS-CoV-2 importation into Kinshasa (DRC) mirrored global variant circulation patterns at the study's time. This genomic landscape was consistent with in-country clinical observations, emphasizing the importance of robust border surveillance and adaptive public health strategies during pandemics.
Rodents are substantial reservoirs of zoonotic viruses with regular human exposure restricted to a limited number of species. Numerous rodent species have been shown to harbor emerging viruses, including paramyxoviruses and hepaciviruses. Reed voles (Alexandromys fortis), a rodent species that inhabits grasslands and riparian environments throughout East Asia, remain poorly characterized in terms of their viral diversity. In this study, 258 A. fortis specimens collected from rural areas in Gyeonggi Province, Republic of Korea (ROK) were screened for paramyxoviruses and subjected to metagenomic next-generation sequencing. Genome characterization, phylogenetic and cophylogenetic assessments, and prediction of signal peptidase cleavage sites were performed to analyze the molecular features of the identified viruses. Zoonotic potential was evaluated using a genome-based machine-learning model. A nearly complete genome of a novel paramyxovirus, designated as Pyeongtaek Alexandromys paramyxovirus (PyAPV), was identified in six A. fortis specimens, with all sequences clustering within the genus Jeilongvirus. A nearly complete genome of a rodent-associated hepacivirus was also obtained from four specimens and classified as a distinct lineage within the species Hepacivirus J. These findings demonstrate the role of A. fortis as a natural reservoir of emerging viruses and expand current knowledge of rodent-associated viral diversity in the ROK.
Understanding the mechanistic impact of fostamatinib, a spleen tyrosine kinase inhibitor, in severe COVID-19 using biomarkers associated with disease severity is crucial for the development of host-directed therapeutics. We analyzed samples from a randomized clinical trial to investigate the impact of fostamatinib on multiple inflammatory biomarkers associated with COVID-19 disease severity. Secondary analyses of biomarkers from a randomized clinical trial. Multicenter randomized clinical trial. A total of 400 adults hospitalized with COVID-19 were enrolled in a phase 3 randomized clinical trial. Absolute neutrophil counts (ANCs) were analyzed across 392 patients and biomarkers were measured in 190 patients with available plasma samples. Adults hospitalized with COVID-19 were randomized to receive either fostamatinib (150 mg bid) or placebo. ANCs and 24 biomarkers were assessed at day 0 and over time using a multiplexed Meso Scale Discovery assay (Meso Scale Diagnostics LLC, Rockville, MD). At day 0, participants with World Health Organization ordinal scale 5-7 had elevated ANC counts, compared with ordinal scale 4. In addition, the levels of neutrophil-associated biomarkers, inflammatory cytokines, and mediators of endothelial dysfunction at day 0 were increased in the participants who were ordinal scale 5-7 vs. ordinal scale 4. Randomization to fostamatinib compared with placebo resulted in a decrease in ANC and several neutrophil-associated biomarkers, pro-inflammatory cytokines, and mediators of endothelial dysfunction/tissue damage. This differential finding was also demonstrated in a subgroup of patients (n = 85) with a hypoinflammatory phenotype. Missing plasma samples and neutral phase 3 trial results. Randomization to fostamatinib resulted in lower neutrophil counts and levels of circulating biomarkers in hospitalized patients with COVID-19; however, the observed impact of fostamatinib was modest compared with prior studies.
Monocrotophos (MCP) is a widely used insecticide in agriculture, but its high toxicity poses significant environmental and health risks. The biodegradation of monocrotophos by indigenous microbes is crucial in reducing its toxicity. The present study was aimed at assessing plant growth- stimulating factors and the biodegradable ability of monocrotophos of two indigenous soil bacterial strains, CAB1 and SD8, isolated from monocrotophos-contaminated agricultural soils in Mysuru and Mandya, Karnataka, India. Biodegradation was evaluated using spectroscopy and chromatography, with substrate degradation confirmed by the disappearance of the main peak in HPLC profiles and intermediate metabolites identified through FTIR and LC-MS analyses. Molecular characterization identified CAB1 as Stenotrophomonas pavanii (OQ861163) and SD8 as Brevibacillus parabrevis (OQ881083). Results showed that the two bacterial strains utilized MCP as their sole carbon source and exhibited biodegradation rates of 88% and 90%, respectively, under optimal conditions. Results further showed that S. pavanii CAB1 and B. parabrevis SD8 produced ammonia, IAA, catalase, and cellulase, and demonstrated phosphorus and zinc solubilization. The degradation ability of CAB1 and SD8 is attributed to the presence of the opd gene and the opdA gene. Trimethyl phosphate, dimethyl phosphate, cyclohexanone, 2- cyclohexylidene, oxalic acid, and isohexyl pentyl esters were the non-toxic intermediates produced during the biodegradation of MCP. The strains S. pavanii CAB1 and B. parabrevis SD8 can be employed, alongside a microbial consortium formulation, for the detoxification of hazardous pollutants in contaminated soils and promotion of plant growth.
The number of published isothermal amplification assays has increased substantially in recent years. Unfortunately, no harmonized guidelines, such as the Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines, exist for publishing these methods, often resulting in incomplete reporting of assay composition and performance. In this study, we systematically evaluated nine published loop-mediated isothermal amplification (LAMP) assays for the detection of Pseudomonas aeruginosa. We aimed to assess whether publications provide (i) sufficient information on assay composition to allow implementation and reproduction and (ii) robust data on assay performance to evaluate their applicability. Assays were screened for basic functionality, analytical specificity, sensitivity, and limit of detection (LOD) in head-to-head experiments with qPCR. Four assays lacked essential composition details, and almost all did not report DNA concentrations or replicate numbers. Only six assays consistently amplified target DNA. Analytical specificity testing with 19 non-target strains contradicted previously reported 100% specificity, with only 3 maintaining specificity above 90% in our evaluation. Sensitivity testing with 13 P. aeruginosa strains confirmed 100% sensitivity for two assays. However, LOD experiments revealed significantly higher values than originally reported, with qPCR outperforming all LAMP assays. These findings highlight substantial discrepancies between published data and real-world assay performance. The absence of standardized formats, consistent units, and complete methodological details undermines replicability. Although this study focused on P. aeruginosa, the identified issues are widely relevant across different microbial targets. We advocate for increased publication standards and quality controls to ensure transparency, utility, and comparability of isothermal amplification assays and to support their translation into clinical and environmental applications.IMPORTANCEOver the past decade, numerous isothermal amplification-based assays for the detection of pathogens or health-relevant microorganisms have been proposed, each claiming progress from the state-of-the-art and applicability to both clinical specimens and/or environmental samples. However, many published assays lack essential methodological details, and reported performance metrics are often inconsistent or incomparable. Using Pseudomonas aeruginosa as a representative model organism, we set out to test whether all details required for implementing assays were provided by original publications and if important assay characteristics were reproducible. The results of this systemic benchmarking of nine published loop-mediated isothermal amplification assays revealed major discrepancies between reported and experimentally measured performance in terms of specificity, sensitivity, and limit of detection. By highlighting the crucial elements that need to be reported, this work aims to improve the transparency, reproducibility, and overall quality of isothermal amplification assays, fostering their broader application across different research settings.
Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses. GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0-19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs). Globally, in 2023, there were an estimated 377 000 incident childhood cancer cases (95% UI 288 000-489 000), 144 000 deaths (131 000-162 000), and 11·7 million (10·7-13·2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27·0% (15·5-36·1) globally, from 197 000 (173 000-218 000) in 1990, but increased in the WHO African region by 55·6% (25·5-92·4), from 31 500 (24 900-38 500) to 49 000 (42 600-58 200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26·5% (26·5-26·5) in GBD 2017 to 10·5% (8·1-13·1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47·3% (42·2-52·0) of global childhood cancer deaths in 2023. Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum. St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.
Chili pepper powder plays a crucial role in kimchi fermentation; however, its use may result in fungal contamination. Therefore, analyzing its mycobiome is vital to maintain quality control standards. In this study, we used internal transcribed spacer (ITS)2 amplicon sequencing to compare fungal communities in commercially available Korean and Chinese chili pepper powders widely used in Korea (n = 9 per group). Ascomycota was the predominant phylum in the Chinese and Korean chili pepper powders. Chinese powder samples exhibited higher genus-level diversity and were notably enriched in Vishniacozyma, whereas Korean powders showed relative enrichment in Fusarium and Issatchenkia. Species richness tended to be higher in Chinese than Korean samples (2.20 ± 0.42 vs. 1.82 ± 0.39). Beta diversity analysis revealed a distinct compositional separation between samples based on origin (permutational multivariate analysis of variance, P < 0.01). The distribution of potentially toxin-related genera also varied by origin: Aspergillus and Penicillium were more abundant in Chinese powders, whereas Fusarium predominated in Korean powders. Although detection at the genus level does not directly indicate mycotoxin contamination, origin-specific enrichment patterns suggest distinct toxin risk profiles warranting additional investigation. These findings underscore the importance of systematically monitoring fungal and mycotoxin-producing communities in chili pepper powders and evaluating the impact of kimchi fermentation on mycotoxin persistence and mitigation. Such measures are essential for improving food safety and traceability. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Rhubarb, a popular culinary ingredient, is notably high in oxalates, which can contribute to the formation of kidney stones, particularly in individuals susceptible to hyperoxaluria. In light of emerging evidence showcasing the beneficial properties of lactic acid bacteria in dietary oxalate degradation, this study endeavors to identify specific LAB strains capable of efficaciously reducing oxalate levels in rhubarb-based juice. A total of 34 LAB strains, isolated from traditional dairy products, were screened for oxalate-degrading potential. The strains characterized included Lactiplantibacillus plantarum, Levilactobacillus brevis, Enterococcus faecalis, Enterococcus faecium, and Streptococcus thermophilus. Employing titration, an enzymatic oxalate assay, and HPLC, we evaluated the oxalate degradation capabilities of each isolate. Notably, Levilactobacillus brevis (M8) emerged as the most effective strain, exhibiting remarkable oxalate-degrading activity. Subsequently, the strain was utilized in the fermentation of rhubarb-based juice, leading to an optimized fermentation process that involved varying sugar substrates and incubation periods. Fermentation with Levilactobacillus brevis (M8) over a 96-h period resulted in a significant 17.5% reduction in oxalate content, decreasing the concentration from 10.44 mmol/L in the control to 8.50 mmol/L in the optimized fermented juice, while maintaining desirable sensory attributes. The findings underpin the promising application of Levilactobacillus brevis (M8) as an adjunct in the formulation of functional, low-oxalate beverages for at-risk populations.
Intrahepatic cholestasis of pregnancy (ICP), a liver disorder associated with adverse fetal outcomes, is characterized by elevated bile acid levels and placental inflammation by the TGR5. However, the interplay among the gut microbiome, bile acid metabolism, and ICP-associated placental inflammation remains unexplored. We aimed to investigate the role of the gut microbiota in regulating bile acid metabolism and placental inflammation, and to identify potential probiotic-based therapies for ICP in C57BL/6 mice. Immunohistochemical analysis of human placentas revealed significantly higher inflammation and decreased TGR5 expression in ICP compared with controls. In vivo and in vitro assays confirmed the anti-inflammatory effects of TGR5 activation. Using 16S rRNA sequencing and metabolomics, ICP mice exhibited a distinct gut microbiota composition and reduced abundance of bile salt hydrolase (BSH)-producing bacteria (e.g., Lactobacillus), accompanied by a significant decrease in the proportion of secondary bile acids. Transplanting fecal microbiota from ICP donors into healthy mice reproduced the disease phenotype of ICP, confirming the pathogenic role of gut microbiota dysbiosis. Supplementation with BSH-enriched Lactobacillus paragasseri LPG-9 remodeled the bile acid profile, thereby activating placental TGR5 to inhibit TLR4-NF-κB signaling and promoting hepatic bile acid excretion via BSEP.