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Germ granules are germline ribonucleoprotein condensates that concentrate proteins and mRNAs essential for animal development. Although the DEAD-box RNA helicase Vasa is a conserved core germ granule component, its role within these condensates remains poorly understood. Using Drosophila and human cell systems, we showed that condensation of Oskar (Osk), the fly germ granule nucleator, occurred independently of Vasa. However, in late oocytes lacking Vasa, Osk-eGFP formed aggregates and exhibited markedly reduced exchange with the aggregate surroundings. Consistently, Vasa increased Osk-eGFP condensate recovery in cells. Additionally, mRNA localization to germ granules was not persistent in oocytes lacking Vasa, while in cells, co-expression of Vasa and Osk was necessary and sufficient for mRNA localization to condensates. Notably, localization of nanos messenger ribonucleoprotein (mRNP) to condensates reduced Vasa-dependent enhancement of Osk-eGFP exchange. Together, our study reveals the DEAD-box RNA helicase Vasa as a central regulator of condensate dynamics and mRNP localization in vivo and in cellulo.

The study was conducted to assess chicken handling practices and identify the major challenges affecting village-based chicken production in the East Gojam zone, Ethiopia. The study sites were selected randomly, while households were purposively selected based on their experience in chicken production and residence in rural areas. A cross-sectional study design was employed, and a standardized questionnaire was administered to 86 selected households. Data were analyzed using SPSS Version 20 software. The average flock size per household was 12.06 chickens, with 71.4% of them being indigenous breeds, and all were free scavengers. Almost all respondents supplemented their chickens with homemade grains and leftovers, although this was not adequate. Hens dominated the flock, and the cock-to-hen ratio was 1:3.97. Most respondents (52.3%) restocked their chickens by hatching at home. The major constraints of chicken production identified were diseases, predator attacks, poor hatchability, and a shortage of feed resources. Newcastle disease (ND) occurred in 54.1% of the households, and its occurrence was statistically associated with study woredas (χ 2 = 13.406, p value = 0.009). It caused high chicken mortality in the area. However, most of the respondents did not practice disease control and prevention biosecurity measures. Approximately 68.6% of households did not use the ND vaccine, 44.2% mixed newly purchased chickens with their own without quarantine, 71.4% allowed their chickens to have contact with neighboring flocks, and most households disposed of dead chickens outside their compounds, which may promote disease spread. Predators affected 78.6% of the household chickens. Therefore, it is essential to create awareness about proper chicken handling, vaccination, and implementing biosecurity measures to enhance the productivity and sustainability of village chicken production.

Forests provide many ecological and economic functions, but they are increasingly exposed to the invasion of various harmful insects. The bark beetle Dendroctonus micans and pine processionary moth Thaumetopoea pityocampa are highly destructive insect pests that kill living trees, leading to significant reductions in forest productivity and widespread tree death. In addition to these, Glyphodes pyloalis is another tree pest that damages mulberries, which are economically important for silk yarn production. In this study, a strain (27b2) from Beauveria bassiana was isolated from the cambium pests D. micans and Ips sexdentatus, which were collected dead from their natural habitat. Then, it was identified by morphological and molecular tests. The isolates of B. bassiana secondary metabolites were extracted from its extracellular medium and mycelium with ethyl acetate and acetone and then the efficacy of crude extracts against insect pests (D. micans adults and larvae), (Glyphodes pyloalis larvae and T. pityocampa larvae) was evaluated at concentrations of 500, 2000, and 5000 ppm. Consequently, it was determined that the ethyl acetate and acetone extracts of B. bassiana 27b2 showed a 100% lethal effect on D. micans adults and larvae, while the acetone extract showed a 100% lethal effect on T. pityocampa larvae. The data suggest that the secondary metabolites of isolate 27b2 may be utilized as bio-pesticides for the control of these pests. Also, this is the first study examining the lethal effects of secondary metabolites extracted from B. bassiana on T. pityocampa, and D. micans.

Dematiaceous hyphomycetes are widely distributed throughout the world. They can live either saprophytically or parasitically and are commonly found growing on dead wood, in soil, and in aquatic environments. During an ongoing survey of saprophytic fungi in multiple southern provinces of China, two Distoseptispora-like and one Kirschsteiniothelia-like strains were isolated from decaying wood. Five barcodes (i.e., ITS, SSU, LSU, RPB2, and TEF1) were amplified and sequenced. Of these markers, ITS, LSU, RPB2, and TEF1 were selected for Distoseptispora, whereas ITS, LSU, and SSU were used for Kirschsteiniothelia. Based on maximum likelihood (ML) and Bayesian inference (BI) phylogenetic analyses, combined with morphological characteristics, three new species, Distoseptispora linchunlingensis, D. xinganensis, and Kirschsteiniothelia guiyangensis, are proposed. This study provides detailed illustrations, phylogenetic trees, and morphological descriptions to clarify the taxonomic status of the three new species, thereby improving our understanding of the diversity of dematiaceous hyphomycetes in Hainan, Guangxi, and Guizhou provinces, China.

Long QT syndrome (LQTS) predisposes to syncope and sudden cardiac death. Type 5 LQTS, linked to KCNE1 variants, is rare. A teenage female presented with recurrent syncope. ECG showed QTc 485 ms. Genetic testing identified KCNE1 and RYR2 variants. Beta-blockers and ICD prevented events. The case highlights diagnostic and genotype-phenotype challenges.

Chronic Interstitial Nephritis in Agricultural Communities (CINAC) represents a major public health challenge, primarily affecting young to middle-aged agricultural workers. Clinically, CINAC is characterized by low-grade proteinuria, a bland urinary sediment, and rapidly progressive renal failure. Kidney biopsies disclose large dysmorphic lysosomes containing electron-dense non-membrane aggregates in proximal tubular cells. Although the disease was long attributed to recurrent episodes of dehydration, its pathophysiology is now recognized as more complex. Indeed, the heat-stress hypothesis alone does not adequately explain the heterogeneous geographic distribution of CINAC. Converging epidemiological, environmental, and toxicological evidence suggests a significant role for chronic exposure to pesticides. Several classes of agrochemicals experimentally demonstrated cumulative nephrotoxicity, involving oxidative stress, tubular apoptosis, and mitochondrial and lysosomal dysfunction. The frequent detection of pesticide residues in drinking water and soils within endemic regions indicates chronic low-dose exposure, sometimes independent of direct occupational handling. Heat stress likely acts as a cofactor, amplifying toxicity through dehydration, reduced renal perfusion, and intratubular concentration of toxins. Overall, CINAC appears to result from a multifactorial etiology dominated by exposure to agrochemical mixtures, underscoring the need for integrated and sustainable prevention strategies including depollution and/or reversed osmosis of drinkable water. La néphrite interstitielle chronique des communautés agricoles («Chronic Interstitial Nephritis in Agricultural Communities» : CINAC)) constitue un enjeu majeur de santé publique, touchant principalement les travailleurs agricoles jeunes sans comorbidité. Cliniquement, la CINAC se manifeste par une protéinurie faible, un sédiment urinaire peu contributif et une insuffisance rénale rapidement progressive. Histologiquement, de volumineux lysosomes dysmorphiques contenant des agrégats électron-denses non membranaires ont été décrits au sein des cellules tubulaires proximales. Longtemps attribuée aux épisodes répétés de déshydratation, sa physiopathologie apparaît aujourd’hui plus complexe. En effet, cette hypothèse du stress thermique, seule, ne rend pas compte de la distribution géographique hétérogène de la maladie. Des données épidémiologiques, environnementales et toxicologiques convergent vers un rôle prépondérant de l’exposition chronique aux pesticides. Plusieurs classes agrochimiques présentent, en effet, une néphrotoxicité cumulative démontrée expérimentalement, impliquant stress oxydatif, apoptose tubulaire, et dysfonction lysosomale et mitochondriale. La présence fréquente de résidus de pesticides dans l’eau et les sols des zones endémiques indique une exposition chronique à faibles doses, parfois indépendante de l’activité professionnelle directe. Le stress thermique semble jouer un rôle de co-facteur, amplifiant la toxicité via la déshydratation, l’hypoperfusion rénale et la concentration des toxiques au niveau tubulaire. La CINAC semble résulter d’une étiologie multifactorielle dominée par l’exposition à des mélanges agrochimiques, nécessitant des stratégies de prévention intégrées et durables telles que la dépollution et/ou l’osmose inversée de l’eau potable.

Monkeypox disease (MPX) is a zoonotic, re-emerging viral disease that started with epidemics in Africa in 1958, with high death rates. The current research assessed the community awareness about the re-emerging Monkeypox infection, its mode of transmission, clinical manifestations, and prevention. Their attitudes toward MPX, infected persons, and the prophylactic measures were evaluated. An online questionnaire was distributed to all community sectors in Al-Jouf region, Saudi Arabia. Among 411 participants, Saudi citizens reported the highest response (94.9%). The average knowledge score was 22.48 out of 30. More than half of the participants correctly identified Monkeypox as a viral infectious disease (78.8%), manifested by rash (69.1%), and required isolation (75.4%). However, knowledge gaps were noticed, where about half of the participants were uncertain about the presence of the vaccine, and transmission via contact with wild animals. Participants' attitudes their worry about the viral spread, and 76.4% agreed on getting the protective vaccine. Attitudes toward reaching out to MPX-infected individuals were more mixed, with a notable level of hesitancy or stigma regarding contact with MPX-infected people. There are satisfactory levels of knowledge about MPX in nearly all aspects except for the ways of transmission and the availability of vaccination. A positive attitude to know more about MPX, strictly follow the prophylactic measures, and take the vaccine. Hesitancy regarding social contact with infected individuals was obvious. This highlights the urgent need to prepare education programs targeting these aspects.

Coenzyme Q (CoQ) is a hydrophobic lipid primarily synthesized in the mitochondria, though it is also present in non-mitochondrial membranes. However, the metabolic pathways that regulate intracellular CoQ distribution are unknown. This study identifies a key role for the mevalonate pathway in regulating CoQ distribution. The mevalonate pathway synthesizes isopentenyl pyrophosphate (IPP) as the precursor metabolite for both CoQ and cholesterol. We show that CoQ synthesis remains stable regardless of whether the mevalonate pathway is upregulated or downregulated. Upregulation of HMG-CoA reductase (HMGCR), indicative of increased mevalonate flux, enhances cholesterol ester synthesis without altering CoQ levels. When the pathway is downregulated, cholesterol synthesis declines, yet mitochondrial CoQ levels are preserved. Under these limiting conditions, mitochondria reduce CoQ export to maintain their internal CoQ pool. While this adaptation sustains mitochondrial respiration, it diminishes extramitochondrial CoQ availability and sensitizes cells to ferroptosis. These findings uncover a mitochondria-driven mechanism that preserves respiratory function by prioritizing CoQ retention during metabolic stress.

Diabetic nephropathy (DN) is a major complication of diabetes, largely driven by chronic hyperglycaemia and oxidative stress. This study investigated the dose-dependent effects of protocatechuic acid (PCA) on DN, focusing on its potential to attenuate ferroptosis and apoptosis in a streptozotocin-induced type 1 diabetes rat model.Thirty-two Wistar Albino rats were divided into four groups (n = 8): Control, Diabetes, Diabetes + PCA 50 mg/kg, and Diabetes + PCA 100 mg/kg. After 12 weeks, kidney tissues were evaluated histologically (Perls' Prussian blue, PAS), immunohistochemically (Bax, Bcl-2, Caspase-3, Caspase-9, ACSL4, GPx4, TFR-1), and by TUNEL assay.Diabetic rats exhibited iron accumulation, tubular dilatation, intracellular vacuolisation, sclerotic glomeruli, and mesangial expansion (p < 0.05), while tubular atrophy, hyaline deposition, and mononuclear infiltration were unchanged (p > 0.05). Apoptotic and ferroptotic markers (Bax, Caspase-3, Caspase-9, ACSL4, TFR-1) increased, and Bcl-2 and GPx4 decreased (p < 0.001). PCA treatment, particularly at the 100 mg/kg dose, significantly attenuated the expression of apoptotic and ferroptotic markers and reduced the number of TUNEL-positive cells (p < 0.001). These findings suggest that PCA modulates cell death by upregulating Bcl-2 and GPx4 while downregulating Bax, Caspase-3, Caspase-9, ACSL4, and TFR-1 in renal tissues. While PCA effectively suppressed these molecular markers of injury, it did not lead to significant improvements in systemic renal function parameters such as serum creatinine and BUN. Thus, PCA may serve as a potential agent for mitigating cellular damage in diabetic kidney injury by targeting specific cell death pathways.

Sexual and reproductive health needs and rights continue to be not only unmet but actively deprioritized in humanitarian settings. This disproportionately exacerbates inequities in maternal and newborn health, leading to increased maternal morbidity and mortality. Poor maternal health outcomes often go unnoticed in emergency settings in which competing priorities mean that monitoring maternal morbidity and mortality is frequently excluded from the initial response. The World Health Organization's MPDSR (Maternal Perinatal Death Surveillance and Review) system is a widely accepted standard for monitoring maternal morbidity and mortality; however, it is not recommended for the acute phase-defined as the first 6 months-of a humanitarian crisis because of feasibility constraints. This highlights the need for adapted approaches for surveillance and response during acute humanitarian crises. As part of its focus on reproductive health in humanitarian settings, M&#xe9;decins Sans Fronti&#xe8;res adapted the MPDSR tool for Tigray, Ethiopia, in 2020 and has since implemented the tool in Sudan after war erupted in April 2023. Although doing so has involved challenges, the results have been instrumental in informing programming, even during complex emergencies. This clinical perspective describes the M&#xe9;decins Sans Fronti&#xe8;res experience implementing a R-MDSR (Rapid Maternal Death Surveillance and Review) system in Sudan during the early stages of the escalating 2023 crisis. This commentary offers a reflective and, at times, critical account of the implementation of R-MDSR and demonstrates the feasibility and role of the tool in driving timely, action-oriented interventions to improve maternal health in fragile and conflict-affected settings.

The Coronavirus Diseases (COVID-19) pandemic led to excess mortality in many countries, i.e., to more deaths than expected. Older individuals generally had higher absolute risks of excess death. The complex dynamics of infection, vaccination and excess mortality have not yet been captured in one comprehensive model. With nationwide and unselected data from Statistics Netherlands, we analyzed the impact of documented infection and vaccination on excess mortality during 2020 and 2021 in the Dutch population aged over 63 on 1 January 2020 (n&#x2009;=&#x2009;3,826,770) by incorporating relative survival into a multi-state model considering COVID-19 (re)infection, vaccination and death. Background mortality was based on the observed mortality in 2015-2019 per sex, age and month of the year. All analyses were performed for the total cohort as well as stratified per sex and age category. The absolute excess mortality in 2020-2021 was 0.34% (95% confidence interval 0.32-0.37), comprising 4.41% of the observed mortality. It was higher in men (except in the youngest age group) and older individuals. Excess mortality occurred mostly during the first four weeks after a positive COVID-19 test, but also thereafter. If infection occurred after vaccination, excess mortality was still observed, but considerably less than without prior vaccination. These patterns were observed in all groups. In conclusion, these analyses demonstrate the substantial impact of COVID-19 on excess mortality during and after acute SARS-CoV-2 infection in individuals aged over 63 years. Moreover, the results show a reduction of excess mortality after vaccination for all groups in this cohort.

Cardiovascular diseases are among the leading causes of death and disability worldwide, including in Iran. Identifying their risk factors is essential for implementing cost-effective preventive interventions. This study aimed to determine the prevalence of behavioral risk factors for non-communicable diseases and their relationship with of cardiovascular diseases risk level in Urmia City, Iran. This cross-sectional study involved 10,000 individuals aged 30 years and older who underwent risk assessment in 2023. Participants were selected through multi-stage cluster sampling. Data were collected using a researcher-designed checklist within the Integrated Health System and analyzed using, employing independent t-tests and Chi-square tests. The prevalence of risk factors was: history of diabetes (12.22%), hypertension (17.24%), high cholesterol (14.93%), family history of diabetes (4.25%), pre-diabetes (7.19%), and pre-hypertension (29.33%). The distribution of risk levels was as follows: 91.15% of participants was classified as having a risk level below 10%, 8.24% between 10 and 20%, 0.33% between 20 and 30%, and 0.28% above 30%. There was a significant positive correlation between risk level and fasting blood sugar, cholesterol, systolic and diastolic blood pressure, age, body mass index (BMI), and waist circumference. The implementation of the risk assessment program and the identification of risk factors at early stages will help in the regular follow-up of high-risk individuals, provide them with necessary health care, and lead to the prevention or early diagnosis of disease.

Impella 5.5 pumps are increasingly used in cardiogenic shock (CS) for extended hemodynamic support (>14 days). Rates of adverse events have not been well-characterized during longer durations of support. Therefore, we sought to define patient characteristics and adverse event rates in short versus extended duration of Impella 5.5 support (DOS). Baseline demographics, clinical characteristics, and serious adverse events defined as death or serious deterioration of health (Serious Adverse Event (SAE): hemolysis, stroke, renal failure, and vascular complications) were analyzed. SAE exposure adjusted event rates were compared between patients supported &#x2264;14 days (short DOS cohort) and >14 days (extended DOS cohort). Among the 2262 patients enrolled across 31 sites in the LOQI (Long-Term Outcome and Quality Impella) registry, 443 patients were supported with the Impella 5.5. Compared to the extended duration cohort, the short duration cohort were older, had a greater proportion of women, and had a higher incidence of hypertension. Event adjusted exposure rate (EAER) was significantly lower in the extended versus short DOS cohort for cumulative SAEs, (EAER: 0.0776 vs. 0.0235 events/day; p<0.001) as well as each of the individual components: hemolysis (0.011 vs. 0.0029), stroke (0.0086 vs. 0.0024), renal failure (0.0177 vs. 0.005), vascular complications (0.0124 vs. 0.0053), and bleeding (0.0235 vs. 0.0061). In a real-world setting, extended use of Impella 5.5 for >14 days did not increase the rate of serious adverse events and was able to provide hemodynamic support to a heterogenous group of patients presenting with cardiogenic shock with stable device performance.

This case describes a female infant with RAF1-related Noonan syndrome who developed severe hypertrophic obstructive cardiomyopathy, pulmonary hypertension, and cardiorespiratory failure that responded to trametinib treatment but ultimately progressed to death following dose tapering and discontinuation of therapy. To the best of our knowledge, this is the first case with detailed respiratory information in a trametinib-treated patient with RASopathy-related pulmonary disease.

Donation after circulatory death (DCD) has re-emerged as a means of expanding the donor heart pool. Current clinical practice relies mainly on direct procurement followed by normothermic machine perfusion or on thoraco-abdominal normothermic regional perfusion. This paper details the practical aspects with an alternative strategy: direct procurement followed by hypothermic oxygenated perfusion (HOPE). Key technical considerations include prevention of bubble formation in albumin-containing solutions and early machine priming to avoid ischemic delays. The final acceptance of grafts is based on a functional warm ischemic time <30&#x202f;min, satisfactory cardioplegic flush and anatomy, and stable, uneventful machine perfusion. Though this approach does not permit functional assessment of the graft, early results suggest that when strict donor and procedural criteria are observed, outcomes are favorable. Direct procurement of the DCD heart with HOPE offers a simplified, logistically efficient preservation method that avoids donor blood recirculation. Further studies are warranted to refine candidate selection and assess long-term results.

Sepsis is the leading cause of death in hospitals and is very common in intensive care units (ICUs). Sleep is frequently interrupted in the hospital setting, especially within the ICU. Patients who sleep poorly have worse outcomes, such as increased mortality and longer hospital stays; however, the molecular basis remains poorly understood. In this study, we utilized a mouse model to investigate the impact of sleep interruption on subsequent sepsis. We found that sleep interruption aggravated sepsis, as evidenced by higher mortality rates (88% in mice with interrupted sleep vs 57% in mice with normal sleep; P&#x2009;=&#x2009;0.0045) and worse disease scores. This effect occurred in both females and males. Sleep interruption increased circulating T cells and CD8+ T-cell activation during sepsis. Sleep interruption also increased the levels of serum cytokines (including IL-23 before sepsis was induced, and IL-6, TNF-&#x3b1;, MCP-1, and IL-10 after sepsis), and amplified macrophage cytokine production ex vivo. These ex vivo effects were largely dependent on Toll-like receptor 2 (TLR2), and sleep interruption no longer exacerbated sepsis in TLR2 knockout mice. Interestingly, the effects of sleep interruption on sepsis were reversed by 48&#x2009;hours of recovery sleep, consistent with a mechanism involving altered gene expression rather than epigenetic changes. RNA sequencing identified 680 genes that were significantly up- or downregulated in macrophages from animals subject to sleep interruption, including multiple genes related to pathogen defense and cytokine signaling. Our study confirms that good sleep is essential to maximize sepsis survival and provides insight into the molecular basis whereby poor sleep alters immune function.

Cervical cancer is the fourth most common cancer in women worldwide. In Chile, 13,093 women died from cervical cancer between 2002 and 2022, making it the second leading cause of death for women aged 25 to 64, after breast cancer. Since 2019, Chile has been promoting molecular-based HPV screening to reduce cervical cancer incidence and mortality. To describe the prevalence, genotypic distribution, and temporal trends of HPV in Chilean and immigrant women based on a 10-year surveillance program conducted from 2014 to 2023. During the study period, 8,324 samples were collected from 7,410 Chilean and 908 foreing women aged 25 to 64 in five primary care centers in Santiago. HPV DNA of cervical smears were amplified by qPCR. Genotyping was performed by PCR-RLB and Sanger sequencing. HPV was detected in 17.06% of Chilean and 23.11% of foreign women, with infection rates increasing over the 10-year period. The highest positivity rate was observed in the 25-34 age group for Chilean (23.82%) and for foreign (29.26%) women. The most frequent High-Risk genotypes were HPV-16, HPV-31, and HPV-59 in Chilean women; and HPV-16, HPV-58, and HPV-66 in foreign women. Low-Risk genotypes increased with age, being more prevalent in immigrants (55.30%) than in Chilean women (42.46%). HPV infection rates have been increasing over time. HR genotypes different than HPV-16/18 were the most common, followed by HPV-16. This information is crucial for HPV surveillance, evaluation of vaccination programs, and prevention of cervical cancer in Chile.

Managing acute leukemia during pregnancy poses clinical challenges requiring a balance between maternal treatment and fetal preservation. From 2019 to 2024, 22 pregnant women were diagnosed with acute leukemia, including 7 acute lymphoblastic leukemia, 15 cases of acute myeloid leukemia, of which 1 was acute promyelocytic leukemia. Diagnosis occurred in the first, second, and third trimesters in 5, 10, and 7 patients, respectively. Nine patients elected pregnancy termination, one had a spontaneous abortion, one had intrauterine fetal demise, and three experienced concurrent maternal and fetal death. Eight patients delivered via elective cesarean section, including one twin pregnancy, resulting in 9 live births. Four neonates (including one twin pregnancy) were exposed to in utero chemotherapy, with no observed congenital anomalies. Chemotherapy was administered to 11 patients, including 3 during pregnancy, all achieving temporary disease control. These findings provide real-world data to inform the management of acute leukemia during pregnancy.

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