Mitochondrial kinase CMPK2 in immune homeostasis and disease: from metabolic regulation to inflammatory signaling.

Morbidity patterns, mortality, and antimicrobial resistance among children hospitalized in neonatal and pediatric intensive care units in a rural area of Vietnam.

RNA-based medicinal products represent a promising frontier in personalised medicine, offering sequence-specific disease targeting at various molecular levels, yet their clinical translation in the European Union (EU) may be hindered by regulatory uncertainty around definitions and evidence requirements; this study therefore aims to identify commonalities and differences in scientific and clinical characteristics of RNA-based therapeutics assessed by the European Medicines Agency to inform a classification framework supporting regulatory clarity and product development. A qualitative document analysis was conducted on 13 RNA-based therapeutics for non-infectious diseases that applied for EU marketing authorisation by March 2025, using EU regulatory documents including European Public Assessment Reports and Risk Management Plans to analyse descriptive, scientific and clinical characteristics, with data extraction validated via a dual-review process. Of the 13 products, 10 were approved, two refused and one withdrawn; they included five siRNAs, seven antisense oligonucleotides (ASOs) and one aptamer, primarily for rare diseases, with 12 acting through sequence-specific hybridisation to pre-mRNA or mRNA to suppress or modify protein production, often targeting liver diseases using delivery systems like GalNAc conjugation or lipid nanoparticles, while clinical challenges included limited efficacy data (e.g. small trials, surrogate endpoints) and recurring safety concerns including coagulation-related risks for ASOs, and notably risk profiles were not consistently linked to disease targets or RNA sequence. These findings highlight an opportunity for classification based on RNA mechanism and related chemical modifications conveying similar regulatory implications, suggesting that a structured framework could support knowledge pooling, which is especially useful for rare disease indications.

Background:Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory noninfectious disease of the bone that predominantly affects children and adolescents. Bisphosphonates (BPs) are used to treat of CNO with most clinical experience involving pamidronate. Neridronate (NER) is an amino BP with a chemical structure and potency close to pamidronate.Objectives:This study aims to evaluate the effectiveness and safety of NER in patients with CNO.Design:Monocentric retrospective cohort study.Methods:This is a retrospective cohort study conducted on patients included in the monocentric CAMELOT (Chronic non-bActerial osteoMyELitis: A mOnocentric regisTry) registry. Response to treatment was evaluated semiquantitatively based on clinical, laboratory, and radiological domains.Results:The cohort consisted of 27 subjects. Thirteen (48%) received NER alone. At baseline, patients receiving NER alone tended to have a higher rate of vertebral fractures than those treated with combination therapy (46% vs 29%; p = 0.4). The median number of peripheral lesions at magnetic resonance imaging was clearly lower in patients treated with NER alone (0 (interquartile range (IQR) 0–2) vs 2 (IQR 1–5); p = 0.01). An overall response (complete or partial) to NER was documented in all but one patient (96%). Six patients (22%) achieved a complete response in all the three domains, 83% of whom (n = 5) received NER without any other concomitant treatments. Interestingly, using a Receiver Operating Characteristic-derived cutoff of 2 years from CNO diagnosis, all patients who achieved a complete response (100%) had received NER within the first 2 years from diagnosis, compared with 57% (n = 12) of those who did not (p = 0.07). No long-term NER complications were observed.Conclusion:Neridronate appears to be a safe and effective option for CNO, particularly in patients with recent-onset disease, spinal involvement, and fewer peripheral lesions. Early initiation may be associated with higher rates of complete response, though further studies are needed to confirm these findings.

Non-communicable diseases (NCDs), including metabolic disorders, cardiovascular diseases, liver pathologies, and age-related syndromes, are a major global health challenge. Human placental extract (HPE) and related formulations, such as Laennec and porcine-derived extracts, have been investigated as cell-free therapeutic agents capable of modulating physiological and immunological pathways. A systematic literature review was conducted using PubMed, MEDLINE, Scopus, Google Scholar, and the National Library of Medicine databases. Only original English-language research articles were included. Data were extracted on the biochemical composition, mechanisms of action, and therapeutic outcomes of placental extracts in preclinical and clinical studies. HPE was shown to enhance liver function by reducing oxidative stress, promoting hepatocyte regeneration, and regulating apoptosis and autophagy. In metabolic disorders and cachexia, it preserved muscle and adipose tissue and alleviated symptoms of cirrhosis and metabolic dysfunction- associated steatohepatitis. Laennec and porcine extracts improved iron metabolism, reduced hepatic fibrosis, and enhanced glucose regulation in type 2 diabetes and non-alcoholic fatty liver disease. Additional reported effects included anti-aging properties, relief in chronic fatigue syndrome, and dermatological benefits, such as reduced hair loss and improved allergic contact dermatitis. Placental extracts, such as HPE, Laennec, and porcine formulations, show promise for treating NCDs, including metabolic disorders, liver pathologies, and age-related syndromes. Preclinical and clinical studies highlight their mechanisms, which involve reducing oxidative stress, promoting hepatocyte regeneration, regulating apoptosis/autophagy, and improving iron metabolism and glucose control. Benefits include alleviating cirrhosis, type 2 diabetes, cachexia, chronic fatigue, and dermatological issues like hair loss. While the evidence is encouraging, largescale trials are needed to confirm their efficacy and the underlying molecular pathways. Placental extracts exhibited diverse therapeutic effects across multiple NCDs, mediated by immunomodulatory, antioxidative, and metabolic regulatory mechanisms. While current evidence from preclinical and clinical studies is promising, large-scale, rigorously designed trials are needed to validate efficacy and clarify molecular pathways.

Understanding the value and causes of mortality and production losses for beef cattle in East Java, Indonesia.

Diagnosing and Investigating Heart Disease in Feedyard Cattle.

Background: Malnutrition remains a significant public health concern, particularly among children in developing countries. Identifying the risk factors associated with varying severity levels of malnutrition is essential for designing effective interventions and reducing its burden. Methods: This study employed ordinal logistic regression analysis to identify risk factors contributing to malnutrition among children aged 6 to 60 months attending the General Paediatrics Department of Amrita Institute of Medical Sciences, Kochi, following ethical committee approval. Nutritional status was assessed using the weight-for-age anthropometric index (Z-score) and categorized into three ordered groups: severely undernourished (< −3.0), moderately undernourished (−3.0 to −2.01), and nourished (≥ −2.0). Given the ordinal nature of the outcome variable, an ordinal logistic regression proportional odds model was applied to determine predictors of malnutrition. Results: The proportional odds model identified four significant risk factors associated with increasing severity of malnutrition: parity of more than two children, household size of six or fewer members, presence of infectious or noninfectious disease, and socioeconomic status. Among these factors, parity of more than two children emerged as the most significant predictor of malnutrition severity. Conclusion: Ordinal logistic regression proved to be an effective analytical approach for identifying determinants of malnutrition severity in children. The findings underscore the importance of addressing family size, household conditions, disease burden, and socioeconomic factors in nutrition-focused interventions. These results can inform policymakers and healthcare providers in developing targeted strategies to reduce childhood malnutrition and improve health outcomes

Helminthiasis is a fairly common parasitic disease in humans caused by various lower worms called helminths. In the Russian Federation, more than 4.5 million cases of helminthiasis were registered in 2016. According to the WHO Expert Committee, ascariasis annually affects approximately 900 million people worldwide, the majority of whom are preschool- and schoolage children. In the Russian Federation, 24,115 cases of ascariasis were registered in 2015. The true prevalence of helminthiasis is significantly higher. Due to changing economic and socioeconomic conditions, increased migration, and the importation of helminths common in tropical and subtropical climates, recent decades have seen an increase and emergence of new helminthic infestations. The possibility of a patient having a particular type of helminthiasis is largely ignored in clinical practice, leading to misdiagnosis, the development of complications, and the development of chronic disease. Helminthiasis is typically relatively asymptomatic, but in some cases, local manifestations become clinically prominent, and the disease can masquerade as infectious or non-infectious diseases.

BackgroundWhile meat is a valuable source of nutrition, it can also serve as a vehicle for infectious and non-infectious diseases—especially when consumed raw. This risk becomes more serious when the meat harbors antimicrobial-resistant bacteria, often referred to as superbugs. This study assessed the health risks faced by consumers of raw beef in relation to infections from common enteric superbugs commonly transmitted through meat.MethodsThe investigation focused on detecting the prevalence of three key meat-borne bacteria—Salmonella, Shigella, and Escherichia coli—and evaluating their resistance to commonly used antibiotics. Bacterial identification was performed using culture techniques and biochemical tests, while antibiotic susceptibility was assessed via the disc diffusion method. The study also examined food safety practices at restaurants that serve raw beef, including hygiene measures and whether the meat underwent any thermal treatment. Health risk estimation was based on both likelihood factors (bacterial contamination and hygiene practices) and consequence factors (resistance to antibiotic treatments).ResultsMeat samples showed an overall bacterial contamination rate of 45.2%, with E. coli being the most prevalent (62.8%), followed by Shigella (32.7%) and Salmonella (4.4%). Alarmingly, 26.8% of the E. coli isolates were identified as the highly pathogenic E. coli O157:H7 strain. None of the restaurants applied any form of heat treatment (cooking or chilling) to the raw beef before serving, and 76% had poor hygiene practices based on bacterial contamination findings. All isolates were fully resistant to amoxicillin, and Salmonella strains also showed complete resistance to erythromycin. However, all bacteria remained 100% sensitive to chloramphenicol. Most isolates demonstrated multidrug resistance to commonly used antibiotics including ciprofloxacin, doxycycline, erythromycin, and streptomycin. The estimated health risk to raw beef consumers was high, primarily due to significant exposure levels and limited effectiveness of post-exposure treatment options.ConclusionThe combined effects of high bacterial contamination, poor hygiene, lack of heat treatment, and widespread antibiotic resistance pose a potential hygiene-associated risk to raw beef consumers. Reducing this risk requires prompt action, including raising public awareness, enforcing strict meat hygiene standards, and implementing strategies to curb antimicrobial resistance.

Equine asthma is a chronic, non-infectious inflammatory disease of the lower airways in horses, classified as mild to moderate (MEA) or severe (SEA). Its pathogenesis is not fully understood and is influenced by environmental and seasonal factors. In this cross-sectional study, seasonal effects on the bronchoalveolar lavage fluid (BALF) metabolome were investigated in asthmatic and non-asthmatic horses. The metabolome of 230 BALF samples from horses across different seasons, classified as cytologically unremarkable (CUA), MEA, or SEA, was analyzed using proton nuclear magnetic resonance spectroscopy (1H-NMR). Principal component analysis was performed for each season, and metabolite profiles were statistically compared between seasons within each group. Altered metabolites were subjected to pathway enrichment analysis using the FELLA R package. Asthmatic horses showed significant seasonal changes in metabolite concentrations between warm and cold seasons, whereas only trends were observed in CUA horses. Pathway analysis indicated enrichment of cholesterol metabolism across all groups. The mTOR signaling pathway was only enriched in SEA horses. Several metabolites—including valine, taurine and carnitine —were altered during the transition from winter to spring in asthmatic horses. These findings indicate that the winter to spring transition significantly modulates the airway metabolome in asthmatic horses, particularly in SEA-affected animals.

Cancer develops through unrestrained cell reproduction, which occurs because of genetic alterations, and it leads to 18.1% of fatalities from noninfectious diseases throughout India. The World Health Organization (WHO) and the United Nations Department of Economic and Social Affairs (UNDESA) report that cancer cases will experience substantial growth during the upcoming 20 years. Breast cancer leads to the highest number of female deaths, while lung cancer stands as the most common cause of death for males. The Global Cancer Observatory (GLOBOCAN) reports show that cancer cases increased from 18.1 million in 2018 to about 19 million in 2020. Current therapies have made progress, yet drug resistance and restricted selectivity, together with dangerous side effects, still prevent effective long-term treatment success. Kinase inhibitors have emerged as a promising class of targeted therapeutics that selectively modulate dysregulated signaling pathways involved in cancer progression. The field lacks a complete and recent evaluation of newly developed kinase inhibitors, which target multiple signaling pathways. The study systematizes and evaluates kinase inhibitors, which target receptor tyrosine kinases (RTKs) and sucrose non-fermenting-1/AMP-activated protein kinase (Snf1/AMPK). The review focuses on recently synthesized molecules (2020-2025) which target major receptors such as EGFR and VEGFR and MELK and acetyl coenzyme A-related pathways. The work presents a comprehensive summary of recent developments in the field while showing structural activity relationships and pointing out future research paths for anticancer-based kinase inhibitor development.

Pyoderma gangrenosum (PG) is a rare, non-infectious inflammatory skin disease often associated with systemic disorders such as inflammatory bowel disease (IBD), malignancies, and autoimmune conditions. This study aimed to investigate the demographic characteristics, comorbidities, differential diagnoses, and treatment outcomes in patients with histopathologically confirmed PG at a tertiary referral hospital in Iran. This retrospective cross-sectional study included 58 patients diagnosed with PG at Rasool Akram Hospital between 2018 and 2023. Data were extracted from medical records and follow-up phone interviews. Variables included demographic information, smoking status, pathergy test results, underlying diseases, treatment regimens, and patient-reported satisfaction. Statistical analysis was performed using SPSS version 26. Among the 58 patients, 53.4% were female, and the mean age was 55.88 ± 13.83 years. Underlying conditions were present in 46.6% of patients, most commonly IBD (29.3%), malignancy (15.5%), and rheumatoid arthritis (10.3%). The most prescribed medications were prednisolone (96.6%), methotrexate (51.7%), and cyclosporine (39.7%). Patient satisfaction was highest for etanercept (100%), infliximab (83.3%), and methotrexate (60.0%). No statistically significant associations were found between gender and smoking status or between comorbidities and pathergy test results. PG is frequently associated with systemic diseases, particularly IBD and malignancy, suggesting a syndromic relationship. Multidisciplinary evaluation is recommended for affected patients. Treatment satisfaction was highest for biologics and immunosuppressants, providing direction for future clinical management and research.

A novel traditional Chinese medicine compound alleviates broiler ascites syndrome by modulating the IL-6/STAT3/FOXO3a signaling pathway.

Single-Center Investigation on the Prevalence, Risk Factors, and Outcomes of Non-infective Inflammatory Bowel Disease in Heart Transplant Recipients.

Infectious disease prioritization exercises have been part of national and international health surveillance. They typically use multi-criteria approaches and generally involve expert groups composed of physicians and public health specialists from various disciplines. However, little is known about the impact of multidisciplinarity composition itself. This paper builds on the 2023 infectious disease prioritization exercise conducted by the French High Council of Public health (HCSP) which employed a Multi-Criteria Decision-Making (MCDM) method; a model-based re-analysis of the initial prioritization is provided. Using multilevel modelling methods, we evaluated the impact of the contributions of non-infectious diseases physicians by testing two hypotheses: i) significant differences exist in risks ratings across specialties for several criteria; ii) these differences impact the final disease ranking. Using pediatricians as a case study and comparing them to infectious disease specialists (IDS), we found that pediatricians' ratings differed significantly for six out of eight criteria. Counterfactual analyses demonstrated that excluding pediatricians' responses or simulating a panel composed entirely of pediatricians altered the final disease classification. Our findings underscore that a multidisciplinary approach to disease risk assessment facilitates a broader -and likely more accurate- consideration of population needs.

ABSTRACT Purpose To investigate age-related differences in the clinical characteristics and etiologic distribution of uveitis. Methods We retrospectively analyzed 1190 consecutive uveitis patients, stratified into a younger group (<65 years, n = 720) and an older group (≥65 years, n = 470). Demographic variables, laterality, anatomic classification, pathological classification, and etiologic diagnoses were compared between age groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and age-related associations were visualized using forest plots. Results Infectious uveitis was significantly more frequent in older patients than in younger patients (31.3% vs. 14.0%; OR 2.79, p < 0.001), whereas noninfectious uveitis predominated in younger patients. Granulomatous inflammation was also more common in older patients (OR 2.50, p < 0.001). Among noninfectious entities, acute anterior uveitis, Behçet disease, diabetic iritis, and tubulointerstitial nephritis and uveitis syndrome were significantly more prevalent in younger patients, whereas malignant lymphoma was more frequent in older patients (OR 7.01, p = 0.010). Among infectious etiologies, herpetic anterior uveitis, endophthalmitis, cytomegalovirus retinitis, and infectious uveitis of unknown cause were significantly associated with older age. Subtype analyses revealed that posterior and necrotizing scleritis occurred exclusively in older patients, and that varicella-zoster virus anterior uveitis was significantly associated with older age. Conclusions Uveitis exhibits a marked age-dependent shift in etiology, from immune-mediated, noninfectious diseases in younger patients to infectious and neoplastic conditions in older patients. These findings highlight the importance of incorporating age into the diagnostic and therapeutic approach to uveitis.

ABSTRACT Purpose To validate the previously established association between vitamin D levels and non-infectious ocular inflammatory diseases and to assess for a potential relationship between vitamin D levels and subtypes of infectious ocular inflammation. Methods This retrospective case-control study identified 1468 cases and 490 controls with a measured serum 25-hydroxy vitamin level. Cases included patients diagnosed with infectious or noninfectious ocular inflammation while controls had a normal eye exam. The primary outcome was the odds of ocular inflammatory disease in participants with normal versus low serum vitamin D levels. Separate sub-analyses for vitamin D levels in individual types of infectious inflammation (endophthalmitis, orbital cellulitis, herpetic keratitis, other infectious keratitis, other infectious causes) and noninfectious ocular inflammation were performed. Results Cases had significantly lower serum vitamin D levels than controls (29 ± 12.7 vs 33 ± 12.7 nanograms per milliliter (p < 0.001)). In multivariate regression analysis, the odds of having infectious or non-infectious ocular inflammation were 2.7 times higher in patients with hypovitaminosis D compared to those with normal vitamin D levels [Odds ratio (OR) = 2.74, 95% Confidence interval (CI) = 2.19–3.44, p < 0.001)]. The odds of developing infectious or non-infectious inflammation decreased by 3% for every unit increase in vitamin D level (OR = 0.97, 95% CI = 0.97–0.98, p < 0.001). Low vitamin D levels were significantly associated with non-infectious intraocular inflammation (p < 0.001) and with all included subtypes of infectious ocular inflammation (p ≤ 0.001). Conclusions Low vitamin D is associated with increased risk of infectious and non-infectious ocular inflammation in a retrospective study.

BackgroundPyrexia of Unknown Origin (PUO) represents a persistent diagnostic challenge in clinical practice. In South Asian regions, this challenge is compounded by a high burden of endemic infections, resource constraints, and varied clinical practices. This systematic review aimed to synthesize the available evidence on the etiology, diagnostic approaches, management, and systemic barriers related to PUO in the region to inform improved clinical guidelines and health policies.MethodsA systematic literature search was conducted in major electronic databases following PRISMA 2020 guidelines and registered prospectively in PROSPERO (CRD420251170142). Observational studies and case series reporting PUO among all populations in South Asian countries were included. Dual independent screening, data extraction, and quality assessment were performed. Risk of bias was evaluated using the Joanna Briggs Institute (JBI) tools for observational studies and QUADAS-2 for diagnostic accuracy studies. Findings were synthesized narratively due to substantial clinical and methodological heterogeneity.ResultsThirty-seven studies were included, with infectious diseases predominating, most commonly tuberculosis, enteric fever, and scrub typhus. Non-infectious inflammatory diseases and malignancies accounted for significant minorities. Diagnostic yield varied substantially across studies, with higher yields reported in settings with greater access to advanced diagnostic modalities. Key systemic barriers included limited laboratory and imaging capacity, high rates of empirical antimicrobial use, absence of standardized diagnostic protocols, and patient-related factors like late presentation and cost. Management was largely empirical, with third-generation cephalosporins and doxycycline commonly used. A striking geographical imbalance in evidence was noted, with most studies originating from India.ConclusionsPUO in South Asia is characterized by a heterogeneous etiological spectrum, persistent diagnostic uncertainty, and widespread reliance on empirical management. The findings indicate that it is necessary to develop standardized, context-appropriate PUO definitions and diagnostic algorithms, improve access to targeted investigations, and strengthen antimicrobial stewardship to enhance patient care in resource-limited settings. Future research must address the significant geographical gaps in evidence and focus on implementing standardized approaches across the region.

To evaluate the diagnostic potential of direct immunofluorescence using a monoclonal antibody and its derived recombinant antibody fragments for specific detection of Acanthamoeba in human clinical corneal samples. A previously characterized monoclonal antibody and 2 recombinant fragments derived from it were fluorescently labeled and tested in direct immunofluorescence assays against Acanthamoeba trophozoites and cysts in axenic culture, followed by testing in formalin-fixed, paraffin-embedded corneal sections. Specificity was assessed by examining reactivity against fungi, bacteria, and human corneal tissue. All fluorescently labeled antibodies recognized Acanthamoeba trophozoites and cysts in culture with no observed cross-reactivity against bacterial or fungal cultures or human keratinocytes. In corneal sections, the antibodies clearly detected Acanthamoeba in samples from patients with amoebic keratitis, with labeling correlating to parasite morphology. No specific signal was observed in corneal sections from fungal keratitis, bacterial keratitis, or noninfectious disease controls, although varying levels of background autofluorescence were noted in some non-Acanthamoeba specimens. Findings were consistent across monoclonal and recombinant antibody formats. Direct immunofluorescence using monoclonal and recombinant antibodies is a promising diagnostic strategy for specific detection of Acanthamoeba in human corneal samples. These proof-of-concept results support further validation in larger cohorts and extension to corneal scraping samples to determine diagnostic performance for early detection of amoebic keratitis.