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Post-exercise rehydration: a randomized cross-over trial comparing a 100% fruit juice, a glucose-based sports drink, and water.

BACKGROUND: Previous studies indicate that sports drinks may improve rehydration, compared to water, an effect likely achieved by manufacturing sports drinks to contain carbohydrates and sodium. However, there is a growing preference for natural products and a "food first" approach to sports nutrition. Fruit juices naturally contain similar concentrations of carbohydrates to sports drinks, but fruit juices may produce a more stable blood glucose profile. Fruit juices also naturally contain electrolytes, particularly potassium, but their potential as effective rehydration alternatives to sports drinks, which have higher sodium concentrations, is not well understood. This study compared the rehydration efficacy and glucose responses following consumption of a 100% fruit juice (Raw Hydrate&#xae;; FRU), a glucose-based sports drink (SPO), and water (WAT) after exercise-induced hypohydration. Importantly, rehydration beverages were matched for water volume, rather than total volume, to ensure that any potential differences in water balance were not due to unequal water volumes between trials, a limitation affecting previous rehydration research. METHODS: After familiarization, 17 adults (age: 28&#x2009;&#xb1;&#x2009;8&#x2009; years; BMI: 23.8&#x2009;&#xb1;&#x2009;2.9&#x2009;kg/m2) completed three trials in a randomized cross-over design. The participants cycled in the heat (~35&#xb0;C) to induce ~2% body mass loss (BML), then rehydrated over a 1&#x2009;h period in a laboratory (~21&#xb0;C) with a water volume equivalent to 150% of BML from either FRU, SPO, or WAT. This was followed by an additional 4&#x2009;h of seated rest (5&#x2009;h rehydration period), when blood glucose was measured (0, 0.25, 0.5, 0.75, 1, 1.5, and 2&#x2009;h after beverage consumption), and all urine produced was collected. RESULTS: During the 5&#x2009;h rehydration period, there was no effect of trial on total urine volume (FRU: 1266&#x2009;&#xb1;&#x2009;403&#x2009;mL, SPO: 1338&#x2009;&#xb1;&#x2009;361&#x2009;mL, WAT: 1394&#x2009;&#xb1;&#x2009;360&#x2009;mL; P&#x2009;=&#x2009;0.156) or water retention (FRU: 42&#x2009;&#xb1;&#x2009;12%, SPO: 37&#x2009;&#xb1;&#x2009;10%, WAT: 35&#x2009;&#xb1;&#x2009;11%; P&#x2009;=&#x2009;0.059). The blood glucose area under the curve differed by trial (P&#x2009;<&#x2009;0.001), with all beverages significantly different from each other (FRU: 10.12&#x2009;&#xb1;&#x2009;0.72 mmol/L/2h, SPO: 12.48&#x2009;&#xb1;&#x2009;1.34 mmol/L/2h, WAT: 7.90&#x2009;&#xb1;&#x2009;0.47 mmol/L/2h; P&#x2009;<&#x2009;0.003). CONCLUSION: Rehydration efficacy was similar between all beverages, but each elicited a distinct glycemic response. For sports drink consumers seeking a natural alternative or implementing a "food first" nutritional strategy, switching to a 100% fruit juice will not compromise rehydration effectiveness, but may elicit a lower blood glucose response. Although, it should be noted that an additional three participants were withdrawn from the study because of gastrointestinal issues after consuming the 100% fruit juice. This was likely a product of the present study's design, where a large volume of 100% fruit juice (average ~2,300 mL) was consumed in a short period of time (1&#x2009;h). Whilst this is a commonly used study design to robustly assess the rehydration efficacy of different beverages, future studies should distribute fluid intake over a longer duration, in order to improve ecological validity and reduce the risk of gastrointestinal issues.

Humans

Translating single-cell RNA sequencing into monocyte direct leukocyte subpopulation-transcript abundance assay ratio-based biomarkers (IFI27/PSAP or IFI27/CTSS) for clinical detection of viral infection.

A rapid method for triaging febrile patients by aetiology (e.g., viral or bacterial infection) using gene expression in peripheral blood (PB) is an intensively researched area. However, gene expression in blood represents a composite sum of gene expression of all the component cell types present in the sample. As a result, numerous genes are measured in most proposed signatures. Herein, we propose a simple ratio-based biomarker (RBB) called direct leukocyte subpopulation-transcript abundance assay (DIRECT LS-TA) that recapitulates gene expressions of a single cell type in PB (i.e., monocytes). Based on single-cell RNA sequencing (scRNAseq) data and bulk expression data, IFI27 and SIGLEC1 are found as interferon-stimulated genes (ISGs) predominantly expressed by monocytes. The DIRECT LS-TA method can use a simple ratio of two genes measured in PB as an RBB to represent the target gene expression in monocytes without the need for monocyte purification. Both scRNAseq and bulk RNA sequencing datasets were used to evaluate the correlation between ISG expression in monocytes and PB, with a particular focus on monocyte expression of IFI27. An iceberg plot of bulk transcriptome data was used to identify genes that were predominantly expressed by monocytes in PB. DIRECT LS-TA RBBs of the three genes (IFI27, IFI44L and SIGLEC1) were evaluated by group-wise comparison, receiver operating characteristic and meta-analysis. In addition, the conventional interferon (IFN) score was evaluated for comparison of diagnostic performance. In viral infection datasets, DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) was most intensely activated (p value by t test <1e-9) and had the best area under the curve (0.94) among the three potential monocyte ISGs analysed. DIRECT LS-TA SIGLEC1 was also another monocyte biomarker but showed a lower activation (p<9e-5). IFI27/PSAP showed better diagnostic performance than the conventional IFN score. On the other hand, IFI44L was not a predominant monocyte expression gene. DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) measured in PB was the best biomarker of viral infection and IFN activation among ISGs predominantly expressed by monocytes. It performed even better than the conventional IFN score which required quantification of eight genes. The results suggest that DIRECT LS-TA of IFI27 is a monocyte-informative biomarker which is easy to determine in PB without the need for cell sorting.

Humans

ALG-020572, an Antisense Oligonucleotide for the Treatment of Chronic Hepatitis B Virus Infection Discontinued for Drug-Induced Liver Injury.

Current treatment options for chronic HBV infection are suboptimal in that they fail to suppress HBsAg levels. ALG-020572 is an antisense oligonucleotide designed to reduce viral protein synthesis through degradation of HBV mRNA. ALG-020572-401 was a double-blind, randomized, placebo-controlled trial consisting of two parts. Part 1 (single-ascending doses) evaluated the pharmacokinetics, safety and tolerability of single doses of ALG-020572 or placebo in healthy participants. In Part 2 (multiple dosing), participants with non-cirrhotic HBeAg-negative, virologically suppressed chronic HBV infection were administered up to 7 doses of ALG-020572 to evaluate safety, pharmacokinetics and antiviral activity. In Part 1, 32 participants were randomized to ALG 020572 or placebo. Single doses of ALG-020572 up to 480&#x2009;mg were well tolerated. The most common treatment-emergent adverse event reported was injection site reaction. ALG-020572 was rapidly absorbed and plasma exposures increased with dose. In Part 2, 8 participants with non-cirrhotic HBeAg-negative virologically suppressed chronic hepatitis B infection were enrolled and received up to 7 doses of ALG-020572. The study was prematurely discontinued after 4 participants experienced significant alanine aminotransferase elevations that were subsequently attributed to drug-induced liver injury. Single doses of ALG-020572 demonstrated a favourable pharmacokinetic and safety profile in healthy participants. Unexpectedly, ALG-020572 was poorly tolerated in participants with chronic HBV infection, resulting in the early termination of the study and further development of ALG-020572 due to idiosyncratic drug-induced liver injury, suggesting caution is required in the development of this class of drugs. Trial Registration: Registered at clinicaltrials.gov: NCT0500102.

Adult

The future of pediatric vesicoureteral reflux management.

BACKGROUND AND OBJECTIVE: Vesicoureteral reflux (VUR) is a common condition in pediatric urology, yet important uncertainties persist regarding risk stratification, imaging strategies, and prevention of long-term renal damage. Emerging technologies may help address these challenges. This review provides a forward-looking overview of recent advances in artificial intelligence (AI) and immunomodulation that may influence future management of pediatric VUR. METHODS: A forward-looking literature review was performed using the PubMed database (January 2000-March 2025), focusing on studies addressing AI, immunomodulation, or vaccination in the context of VUR and urinary tract infections. Criteria of inclusion were the relevance to pediatric VUR, the novelty of the proposed concept, the potential clinical implications and, for the AI literature, the existence of a clinical evaluation of the algorithm on a dataset from patients. KEY FINDINGS AND LIMITATIONS: AI-based models show promising performance in supporting clinical decision-making, including prediction of the need for voiding cystourethrography, automated grading of VUR, estimation of recurrent urinary tract infection risk and prediction of chemoprophylaxis. These tools may facilitate more individualized diagnostic and therapeutic strategies, although current evidence is largely retrospective and requires prospective validation. Immunization and immunomodulatory approaches aim to reduce infection burden and modulate inflammatory pathways associated with renal scarring. While early experimental and adult clinical data are encouraging, pediatric-specific evidence remains limited, and clinical applicability in children with VUR is not yet established. CONCLUSION: Artificial intelligence and immunologically targeted strategies represent complementary, emerging approaches that may contribute to more personalized management of pediatric VUR. At present, both should be regarded as exploratory tools whose clinical impact will depend on further validation and appropriately designed pediatric studies.

Humans

Diet and sleep among college student populations: a systematic review.

College students are at-risk for both poor diet and poor sleep. We aimed to systematically review the evidence regarding associations between diet and sleep health within this population. A comprehensive electronic search was conducted in PubMed, Embase, Scopus, Web of Science, and PsycINFO from the earliest possible date through February 6, 2026. A total of 57 studies representing 44 countries were retained; most were cross-sectional. There were 22 studies that examined dietary patterns in relation to sleep, generally showing that healthier diet patterns, including the Mediterranean Diet, were related to better sleep quality. Among 20 studies that examined individual foods or nutrients, there was evidence that fruits, vegetables, dairy, protein, and lower intake of sugar-sweetened beverages were linked to better sleep health, although some findings were mixed. Finally, 15 studies related meal timing to sleep quality, showing that breakfast skipping and later last meals were associated with poor sleep health. Overall, these studies reveal robust cross-sectional associations between diet and sleep among college students, but more longitudinal studies and randomized controlled trials are needed to evaluate directionality. Moreover, a key direction for future study is consideration of sleep and nutrition situated within the unique contexts of college settings and academic schedules.

Humans

Impact of a thermal care bundle on peri-operative hypothermia, surgical site infection, and readmissions in osteosynthesis patients: A randomised controlled trial.

BACKGROUND: Maintaining normothermia throughout the peri-operative period prevents the occurrence of complications related to hypothermia. OBJECTIVE: To determine the effect of a thermal care bundle with a short prewarming period on inadvertent peri-operative hypothermia (IPH), surgical site infection (SSI), and unplanned readmission among osteosynthesis patients, and to identify associated variables. DESIGN: Open-label, randomised controlled trial. SETTING: University hospital. PATIENTS: One hundred and forty-eight patients who underwent osteosynthesis surgery. INTERVENTION: The intervention group received the thermal care bundle, which consisted in prewarming patients 10&#x200a;min before anaesthesia delivery and maintaining body temperature with a forced air device during surgery and the immediate postoperative period; in addition, the operating room environmental temperature was kept at 21&#x200a;&#xb0;C, and fluids were warmed to 38&#x200a;&#xb0;C. MAIN OUTCOME MEASURES: For the primary objective, hypothermia was defined as core body temperature below 36&#x200a;&#xb0;C and measured using the 3M Spot On zero heat flux sensor. Core temperature was recorded upon admission to the pre-operative holding area and subsequently every 30&#x200a;min until postanaesthesia care unit (PACU) discharge. Secondary objectives were SSI and readmissions: a follow-up at 30 to 60 and 90&#x200a;days was performed by the principal investigator. RESULTS: All 148 patients completed the study, and there were no significant differences between the groups at baseline. At the start of surgery, the incidence of hypothermia was significantly lower in the bundle group (1.3 vs. 9.9% among controls; odds ratio&#x200a;=&#x200a;7.59, P &#x200a;=&#x200a;0.021). A significantly lower incidence of hypothermia was also observed at admission to the PACU (14.3% in the bundle group vs. 29.6% among controls; odds ratio&#x200a;=&#x200a;2.07; P &#x200a;=&#x200a;0.024). Application of the bundle increased patients' core body temperature by 0.13&#x200a;&#xb0;C (95% confidence interval (CI), 0.003 to 0.254; P &#x200a;=&#x200a;0.045). Patients in the bundle group had a slightly lower observed incidence of wound infections requiring readmission (odds ratio&#x200a;=&#x200a;0.35; 95% CI, 0.04 to 2.92), although this difference was not statistically significant ( P &#x200a;=&#x200a;0.332). CONCLUSIONS: The bundle reduces peri-operative hypothermia by up to 59%, but does not affect on SSI; factors like presurgery hospital stay, operating room and PACU occupancy were identified as risk factors for SSI. REGISTRATION: 21 July 2022: NCT05469958 (Clinical Trials.gov), first recruitment 15 August 2022.

Adult

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans

Acceptability of alcohol-based hand rub during neonatal care in rural Ugandan households: a qualitative study nested within the BabyGel trial.

BACKGROUND: Poor access to water, sanitation and hygiene exacerbates the spread of infections among newborns. The BabyGel cluster randomised trial assessed the effectiveness of a community-level alcohol-based hand rub with a training component in reducing infection or death rates among newborns in Uganda. OBJECTIVE: Nested in the BabyGel trial, this study investigated the acceptability of the BabyGel intervention among mothers and household members in Eastern Uganda, using the Theoretical Framework of Acceptability. METHODS: In 2022, we conducted individual semistructured interviews with mothers, and group interviews with mothers and other household members, all recruited from intervention-arm clusters. Thematic analysis combined inductive and deductive coding, structured by the framework's seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy. RESULTS: Twenty mothers and 14&#xa0;household members participated in 10 individual and 10 small group interviews. Participants found the intervention generally acceptable, appreciating its convenience and perceived protection against infection. Many described hand hygiene changes that persisted beyond the intervention period. However, concerns related to its harmful effects, spiritual beliefs and social tensions with visitors occasionally influenced its use. CONCLUSION: Alcohol-based hand rub combined with a training component was generally well accepted, driven by perceived health and practical benefits, although concerns related to safety, belief systems and social dynamics remained. Because data collection coincided with the COVID-19 pandemic, a period of heightened hygiene awareness, the acceptability observed could differ in nonpandemic periods. Culturally adapted education, community engagement and reinforcement of correct use may enhance acceptability and sustainability in similar settings.

Humans

Hydroxyl Radical Inactivation of Vesicle-Cloaked and Free Murine Norovirus: Linking Biomolecular Oxidation to Lifecycle Disruption and Infectivity Loss.

Hydroxyl radicals (&#x2022;OH) play a central role in inactivating human viruses during advanced oxidation processes for water and wastewater treatment, solar disinfection, and natural attenuation in sunlit aquatic environments. Human norovirus, a leading cause of gastroenteritis, is efficiently transmitted through water and exhibits strong environmental persistence. The recent discovery of vesicle-cloaked virus clusters (viral vesicles) further challenges water treatment and reuse, particularly for norovirus elimination. We investigated &#x2022;OH inactivation kinetics and mechanisms of murine norovirus 1 (MNV-1), a human norovirus surrogate, in free-virus and vesicle-cloaked forms. &#x2022;OH rapidly inactivated both MNV-1 vesicles and free MNV-1 with second rate constants of &#x223c;1010 M-1 s-1; however, the vesicle membrane provided a 2.24-fold protective effect to cloaked MNV-1, resulting in slower inactivation kinetics than those of free MNV-1. &#x2022;OH oxidized viral capsid proteins and genomes together with vesicle proteins and lipids, resulting in impaired CD300lf receptor and cell-based binding, disrupted genome replication, and diminished viral assembly. Despite these biochemical and functional impairments, most vesicle structures remained largely intact following &#x2022;OH exposure. This study establishes a quantitative framework linking biomolecular damage to viral infectivity loss through functional impairment and lifecycle disruption, providing mechanistic insights into advance water disinfection strategies and public health protection.

Norovirus

Characteristics and functions of a cell adhesion molecule PvCadN in Penaeus vannamei during WSSV infection.

Cell adhesion not only maintains the integrity of the organism, but also plays an important role in the immune system, which is involved in modulation in the interaction between host and virus. In this study, a novel cell adhesion molecule from Penaeus vannamei, designated as PvCadN, was investigated. It had the typical molecular characteristics of cadherin family, with multiple extracellular cadherin repeat domains, a transmembrane region, and a conserved &#x3b2;-catenin-binding motif. Pvcadn is expressed ubiquitously across all detected tissues, with the highest transcriptional level in gills. RNA interference-mediated silencing of pvcadn significantly impaired the adhesion ability of shrimp hemocytes. Upon WSSV infection, pvcadn showed a tissue-specific expression pattern, with upregulation in gills and downregulation in hemocytes. Knockdown of pvcadn markedly suppressed the transcription of WSSV immediate-early gene ie1 and replication of the viral genome in vivo, suggesting that PvCadN acted as a potential virus-associated molecule. Furthermore, it was found that PvCadN was regulated by Lv&#x3b2;-catenin, a core molecule in the Wnt signaling pathway that functions in innate immunity, at the transcriptional and protein levels. Silencing of lv&#x3b2;-catenin significantly downregulated pvcadn transcription, and Lv&#x3b2;-catenin bound directly to the Cadherin C domain of PvCadN. In summary, the study revealed that PvCadN was a key cell adhesion molecule involved in WSSV infection, which was regulated by Lv&#x3b2;-catenin. Our findings will provide fundamental data for further investigation into cadherin-mediated immune regulation in shrimp, and offer new insights for the prevention and control of WSSV.

Animals

Emergence of Babesia naoakii infection in Indonesian domestic cattle, a new host record in water buffaloes, and characterization of complete mitochondrial protein-coding genes.

Babesia (B.) naoakii, previously referred to as Babesia sp. Mymensingh, is a recently characterized tick-borne haemoprotozoan parasite of cattle. In Indonesia, we first reported its presence in 2022 from clinically affected cattle in Central Java. To investigate the wider epidemiology of this neglected ruminant-associated Babesia species, we surveyed apparently healthy cattle (Bos indicus) and water buffaloes (Bubalus bubalis) across three districts of Java, Indonesia. A PCR assay targeting the B. naoakii-specific apical membrane antigen 1 (ama1) gene detected the parasite occurrence in 34.39% of assessed cattle (87/253; 95% CI: 28.80-40.44%) and 30.77% of water buffaloes (12/39; 95% CI: 18.47-46.52%). These results represent the first record of B. naoakii infection in water buffaloes in the country and confirm that the parasite circulates in subclinically infected bovine hosts. To characterise this apicomplexan parasite further at the molecular level, we assembled in full length the three mitochondrial protein-coding genes (PCGs): cytochrome c oxidase subunits 1 (cox1) and 3 (cox3), as well as cytochrome b (cytb). These genes were reconstructed by next-generation sequencing of blood DNA collected during the acute haemolytic-phase of B. naoakii infection, from calves that subsequently succumbed to the disease in the endemic area. Phylogenetic analyses of the concatenated amino-acid sequences of cox1, cox3, and cytb placed the Indonesian isolates within a well-supported monophyletic clade, distinct from all previously characterised ruminant-associated Babesia species and sister to the Babesia bigemina/Babesia ovata lineage. This placement confirmed species identity and reinforced the genetic distinctiveness of B. naoakii in Indonesia. Notably, although B. naoakii circulates in peripheral blood and mirrors the diagnostic behaviour of the mild pathogen B. bigemina, its clinical impact more closely resembles that of the severe pathogenic B. bovis, particularly in young animals. This diagnostic-clinical discordance highlights the need for B. naoakii-specific molecular surveillance and species-level differentiation in regions of co-endemicity. Given the high prevalence in subclinically B. naoakii-infected adults, the documented severity of babesiosis in calves, and the potential for substantial economic losses, broader epidemiological investigations and species-specific control measures for B. naoakii are urgently performed. The same holds true for future epizootiological investigations of underdiagnosed B. naoakii-infections possibly circulating in Indonesian endemic ruminant bovids such as the banteng (Bos javanicus), the lowland anoa (Bubalus depressicornis) and the tamaraw (Bubalus mindorensis).

Animals

Fracture-related infection following open forefoot fractures caused by dropped objects.

INTRODUCTION: This study evaluated the rate of fracture-related infection (FRI) of open forefoot fractures caused by dropped objects, and examined associations of treatment characteristics, including intravenous and oral antibiotics and operative debridement, with FRI. METHODS: Patients aged 18-80 years who sustained an open metatarsal or phalanx fracture caused by a dropped object between January 2021 and June 2024 were retrospectively identified from two Level 1 trauma centers. The primary outcome was FRI, determined based on the FRI consensus criteria. FRI rates were compared between those who underwent irrigation and debridement (I&D) at bedside versus in the operating room, and between those who received oral versus intravenous (IV) antibiotics. Patient characteristics were also analyzed to determine host factors associated with FRI. RESULTS: A total of 86 patients (median age 41 years [IQR: 29-56], 58% male) were included. Eighty-five patients (99%) received antibiotics, 31 (36%) of whom received intravenous antibiotics. Sixty-six patients (77%) received an I&D at presentation, 57 (66%) at bedside and 9 (10%) in the operating room. Thirteen patients (15%, 95% CI: 8.3%-24%) developed FRI. No significant difference in FRI rate was found between patients who underwent I&D at bedside versus in the operating room (12% versus 11%, p&#x202f;>&#x202f;0.99). Among patients who did not undergo I&D in the operating room, no significant difference in FRI rate was found between patients who received oral versus IV antibiotics (17% versus 13%, p&#x202f;=&#x202f;0.74). Insulin-dependent diabetes was associated with an increased risk of FRI (60% versus 12%, p&#x202f;=&#x202f;0.02). CONCLUSIONS: In this cohort, one in seven patients developed FRI. No statistically significant differences in FRI rates were observed by I&D setting (bedside versus operative) or antibiotic route (oral versus IV), including in a subgroup analysis excluding patients treated with operating room I&D. These findings are limited by sample size and potential treatment selection bias and should not be interpreted as evidence of equivalence. Management should be individualized based on clinical judgement, resource availability, and patient factors. These findings can help guide the management protocols for "dropped objects" open forefoot fractures presenting to urgent care and the emergency department. LEVEL OF EVIDENCE: Therapeutic Level III.

Humans

The neuroendoscopic factors affecting outcome of endoscopic third ventriculostomy in pediatric patients with post infectious hydrocephalus.

BACKGROUND: The role of endoscopic third ventriculostomy(ETV) in infective hydrocephalus remains uncertain. Infection alters cerebrospinal-fluid composition, flow-dynamics, absorptive capacity, undermining the effectiveness of ETV. AIMS AND OBJECTIVES: This study aims to describe the intraventricular morphological findings and its correlation with ETV outcomes in a cohort of paediatric infective hydrocephalus. METHODOLOGY: Total 98 cases of infective HCP underwent ETV, were studied for intraventricular findings. Thin transparent third ventricular floor were considered as type-1, transluscent as type-2, floor with granuloma as type-3 and unidentifiable anatomy as type-4. Infective deposits were sent for histopathology. RESULT: Overall ETV was successful in 46 patients (46.93%). Success rate of ETV in type 1 (72.7%) was better than type-2 (50%) and type-3 (33.3%). The difference between type-1 and type-3 was statistically significant, p&#xa0;=&#xa0;0.01. The success rate in presence of pre-pontine adhesions (46 cases) was 34.7%, significantly lower than the 66.6% observed in their absence (p&#xa0;=&#xa0;0.005). ETV was not successful in all the 7 cases withy type-4 floor. Tissue biopsy confirmed microbiological diagnosis in 13 cases and helped in modifying pharmacological treatment as per culture (two with tuberculosis and three with fungal infection). CONCLUSION: ETV offers a meaningful therapeutic option in post-infectious HCP. Endoscopic appearance of the third ventricular floor and the pre-pontine space may predict its outcome. A thin, transparent floor in the absence of cisternal adhesions is associated with best outcomes, while progressive floor thickening, granuloma formation, and pre pontine fibrosis each correlate with declining success rates. The culture from exudates often helps in achieving organism oriented pharmaco-therapy that improves ETV success rate.

Humans

Whole cell inactivated poly-bacterial preparation MV130 effect on nasal mucosal immunity and experimental human pneumococcal carriage: double-blind randomised controlled trial with controlled human infection model.

BACKGROUND: Bacterial mucosal immunotherapy has shown protection of children and adults from both viral and bacterial respiratory infections, offering the potential to reduce antimicrobial use, and hence also control antimicrobial resistance (AMR). Pneumococcal carriage of vaccine type Streptococcus pneumoniae remains high in Malawi despite infant conjugate vaccination and AMR is increasing. We compared nasal inflammation following sublingual bacterial immunotherapy including S. pneumoniae (MV130, Inmunotek, Spain) or placebo and determined the effect in an experimental human pneumococcal carriage model. METHODS: A double-blind, randomised, placebo-controlled trial in healthy adult volunteers was conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants were randomly allocated to receive MV130 or placebo sublingually once daily for 42 days. Mucosal inflammation (neutrophil to T cell ratio, NTR) was measured in nasal micro-biopsies. Post-treatment, participants were challenged with 160,000 CFU/naris S. pneumoniae 6B (Spn6b). Experimental pneumococcal carriage rates post inoculation were compared between the two arms. All participants completing the study were included in the analysis. Prospective trial registration: PACTR202403820001276. FINDINGS: 107 participants were enrolled and randomised to MV130/placebo between May and December 2024. There were no serious adverse events, complete compliance was good (72%) and all adverse events were mild. 96 participants (53 male, 43 female) completed the study with 52 participants randomised to MV130 and 44 to placebo. There was no difference in mucosal inflammation (neutrophil to T cell ratio) at day 14 of the intervention MV130 NTR median = 0.737 (IQR 0.294, 2.059) and placebo NTR = 0.831 (IQR 0.450, 2.073), p = 0.64. Secondary analyses showed a rise in mucosal neutrophils after MV130 treatment and after experimental pneumococcal inoculation. There was no difference in nasal or serum anti-pneumococcal immunoglobulin or in experimental pneumococcal carriage proportion between MV130 (12/52, 23%) and placebo (10/44, 23%) groups (unadjusted risk ratio 1.02 (CI 0.49-2.12) p = 1.0). INTERPRETATION: MV130 induced non-specific mild neutrophil inflammation of the nasal mucosa but had no protective effect against experimental human pneumococcal carriage. FUNDING: Wellcome Trust.

Humans

Comparative evaluation of molecular technologies for the identification of prevalent non-tuberculous mycobacteria in pulmonary infections: a systematic review and meta-analysis.

BACKGROUND: The increasing prevalence of non-tuberculous mycobacteria pulmonary disease (NTM PD) is a burden to public health. Successful management of NTM PD critically depends on accurate species identification and reliable drug susceptibility testing to guide appropriate antibiotic therapy. Emerging molecular technologies offer rapid diagnostic solutions compared to conventional methods, but their performance varies. This study aims to provide a comprehensive evaluation of current molecular techniques for NTM identification and to present a global antibiotic resistance profile. METHODS: A systematic literature search was conducted in PubMed and Web of Science for studies published between 2005 and 2024. Studies applying molecular methods for NTM identification and resistance detection in humans were included. Data on study characteristics, diagnostic methods, sample types, sample sizes, identification sensitivity, and drug susceptibility results were extracted. Meta-analysis was performed using R with the meta4diag package. The quality of included studies was assessed using the QUADAS-2 tool. RESULTS: The analysis included 49 studies on NTM identification and 33 studies on antibiotic resistance. For species identification, all evaluated molecular technologies (MALDI-TOF MS, PCR-based methods, Sequencing, DNA chip, and DNA strip) demonstrated high pooled sensitivities (>0.92). Subgroup analysis revealed that sample type significantly affected performance for MALDI-TOF MS. Preliminary analysis of antibiotic resistance rates revealed varying patterns. For slowly growing mycobacteria, a significantly high Ethambutol resistance rate was observed in M. avium (69.20%). Among rapidly growing mycobacteria, resistance to Imipenem was notable (54.22%), and Clarithromycin resistance varied significantly within the Mycobacterium abscessus complex. CONCLUSION: Emerging molecular technologies have revolutionized the methodology for NTM identification with excellent performance. However, their performance can be influenced by sample type, particularly for MALDI-TOF MS. The alarming and heterogeneous antibiotic resistance patterns also highlight the critical need for rapid and accurate species identification and drug susceptibility testing to inform effective therapeutic strategies. Key messagesMolecular technologies demonstrate high accuracy for NTM identification.Antibiotic resistance is a serious concern with variations among NTM species and subspecies.Rapid and accurate species identification and drug susceptibility testing are crucial for guiding effective clinical management of NTM PD.

Humans

Suicidality risk of cancer caregivers: a systematic review and meta-analysis of observational studies.

BACKGROUND: The increase in the number of global cancer cases is expected to lead to a greater caregiving burden. However, few studies have investigated the risk of suicidality among cancer caregivers. OBJECTIVE: The aim of this systematic review was to explore the risk of suicidality among cancer caregivers. METHODS: For this systematic review, a comprehensive search of the PubMed, Embase, Cochrane, Web of Science databases, PsycINFO and Scopus databases was conducted from inception to 16 July 2025. A meta-analysis was performed to determine the odds ratios (ORs) for case-control and cross-sectional studies and the adjusted hazard ratios (aHRs) for cohort studies. RESULTS: Seven studies were included (four cohort studies, one case-control study and two cross-sectional studies), and 638,188 study subjects and 4,203,957 nonexposed subjects. The meta-analyses revealed that the ORs was 1.91 (95% confidence interval [CI]: 1.46-2.49) in the case-control study, cross-sectional studies, and one cohort study which reported ORs, and the aHRs was 1.32 (95% CI: 1.16-1.50) in the three cohort studies. Caregivers of patients with highly aggressive cancers had a greater risk of suicidality (aHR = 1.66; 95% CI: 1.48-1.86). Within the first 7&#x2009;years following a patient's cancer diagnosis, the risk of suicidality among caregivers remained elevated (aHR = 1.42; 95% CI: 1.04-1.94). CONCLUSION: The results indicate the need for both clinical and societal awareness to reduce the risk of suicidality among cancer caregivers, especially those with highly aggressive cancers. TRIAL REGISTRATION: Registered prospectively in PROSPERO (https://www.crd.york.ac.uk/prospero/) with the registration number (PROSPERO CRD420251011926) and date of registration(15/03/2025).

Humans

Genome-wide identification and characterization of ABC transporters and their expression in response to saline-alkaline stress and WSSV infection in Fenneropenaeus chinensis.

ATP-binding cassette (ABC) transporters play crucial roles in stress responses across organisms, yet their functions in Fenneropenaeus chinensis remain largely unknown. In this study, we identified 42 FcABC genes (FcABCs) in the F. chinensis genome and analyzed their phylogenetic relationships, gene structures, and chromosomal distributions. Phylogenetic analysis grouped the FcABCs into eight subfamilies (ABCA-ABCH), with conserved motif and domain compositions within each subfamily. Expression analysis showed that several FcABC genes, including FcABCG5, FcABCA1, and FcABCC3, were significantly induced under saline-alkaline stress in gill and hepatopancreas tissues. In contrast, most FcABCs were downregulated after WSSV challenge, though a subset (e.g., FcABCB1, FcABCC1) exhibited early upregulation. Functional validation via RNA interference demonstrated that knockdown of FcABCG5 increased shrimp mortality under saline-alkaline stress. Cis-regulatory element analysis revealed an enrichment of stress- and immune-related elements in FcABC promoters. Protein-protein interaction network predictions indicated potential roles for FcABCs in cholesterol metabolism and organic anion transport. Our findings provide insights into the roles of FcABC genes in stress adaptation and immune defense, offering candidate genes for the breeding of stress-resistant shrimp varieties.

Animals

Human endogenous retroviruses leading to autoimmune diseases.

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and were long regarded as inert remnants of ancestral retroviral infections. Increasing evidence indicates that HERVs are active genomic elements capable of influencing transcriptional programs, modulating immune responses, and contributing to disease pathogenesis. Under physiological conditions, HERV expression is tightly controlled by epigenetic mechanisms; however, infections, chronic inflammation, aging, and diverse environmental stimuli can promote HERV reactivation. HERV-derived RNAs and proteins engage innate immune sensors and trigger antiviral-like responses through mechanisms of viral mimicry, leading to activation of type I interferon and other inflammatory pathways. HERV dysregulation has been associated with disease-relevant immune pathways. This review summarizes recent advances linking HERVs to autoimmune disease pathogenesis and discusses their potential translational relevance as biomarkers and therapeutic targets.

Humans