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PubMed2026

Global Seroprevalence of Q Fever Antibodies to Coxiella burnetii in Children and Adolescents : A Systematic Review and Meta-analysis.

OBJECTIVE: To comprehensively determine global estimates of Q fever seroprevalence in children and adolescents by conducting a systematic review and meta-analysis. DATA SOURCES: Searches of published articles in MEDLINE, Embase and Scopus databases were conducted from inception until February 2025. STUDY SELECTION: Cross-sectional studies reporting seroprevalence of Q fever/ Coxiella burnetii antibodies, using any established laboratory test, in any population of healthy children and adolescents <20 years old were included. The quality of eligible articles was assessed using a modified Newcastle-Ottawa Scale. DATA EXTRACTION: Data from eligible articles were extracted using a standardized form, which included year of publication, year(s) the study was conducted, numbers of antibody-positive cases/specific population, age, country, geographic region, serology test used and antibody titer cutoff value. DATA SYNTHESIS: DerSimonian and Laird random effects models were used to calculate pooled seroprevalence estimates and 95% confidence intervals in data from 41 eligible articles reporting 42 studies comprising 9841 children and adolescents. Q fever seroprevalence was observed in multiple countries across 7 geographic regions, and varied markedly between countries and regions, with the highest estimate observed by an individual country in Ethiopia (45%) and by region in the Middle East (14%). Seroprevalence estimates were higher in older children and adolescents ≥10 years (15%) compared with younger children <10 years of age (8%). CONCLUSION: Despite varying geographical prevalence, our findings demonstrate that widespread exposure to Q fever antigens occurs across multiple global regions in children and adolescents to potentially serious C. burnetii infection, indicating that diagnostic surveillance and preventive measures should be considered in both endemic and previously unreported areas.

Humans↗

PubMed2026

Effectiveness of psychosocial and lifestyle interventions in promoting behaviour change and improving cognitive outcomes in older people with memory concerns: A systematic review.

BACKGROUND: Older adults with mild cognitive impairment or subjective cognitive decline have a greater dementia risk, particularly those from minority ethnic and socioeconomically disadvantaged backgrounds. Psychosocial and lifestyle interventions targeting modifiable risk factors offer hope for reducing risk, yet behavioural mechanisms remain unclear. This systematic review examines these mechanisms and associated outcomes. METHOD: We searched PubMed, Embase (Ovid), PsycINFO (Ovid), Web of Science, and Scopus for randomised control trials testing interventions that aimed to improve lifestyle and cognition in older adults with memory concerns. We explored behavioural mechanisms using the COM-B model and synthesised intervention effectiveness, overall and within underserved groups. We prioritised lower risk of bias studies. RESULTS: 26 studies described 23 randomised controlled trials (14 multidomain, 9 single domain interventions). Certainty of evidence that behaviour change was associated with cognition was low. Moderate-certainty evidence indicated that interventions providing a socially supportive environment and combining nutritional education and counselling for 6 + months improved diet. Physical activity improved primarily in interventions incorporating education, structured training, and enablement strategies (e.g., tailored programmes, providing tools). Interventions simultaneously targeting capability, opportunity and motivation showed greater overall effectiveness. Few studies recorded ethnicity (13%) or sociodemographic status (9%), and none explored their impact. CONCLUSIONS: Non-pharmacological interventions can help this population improve their lifestyles if they feel capable, equipped and motivated, highlighting the value of careful design and implementation. There is scarce evidence on how these interventions work for underserved populations. Future research should explore this to inform tailored interventions and develop equitable dementia prevention strategies.

Humans↗

PubMed2026

Determination of 13 per- and polyfluoroalkyl substances in human plasma samples using LC-MS/MS: application to capillary microsamples.

Per- and polyfluoroalkyl substances (PFAS) are chemicals widely applied in industrial processes and highly persistent in the environment, whose extensive use has been linked to adverse health effects. Venous plasma is the conventional matrix for PFAS assessment in blood, and LC-MS/MS is the most used quantification technique. Despite the relevance of this topic, biomonitoring data on human exposure to PFAS in Brazil remain limited. This study validated an LC-MS/MS method for determination of 13 PFAS in human plasma. Blood samples were collected from volunteers by phlebotomy, followed by protein precipitation with acetonitrile containing 1% formic acid (v/v) and solid-phase extraction. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column. The assay was linear over a calibration range of 0.2-20 ng/mL. Intra- and inter-assay precision (CV%) were within the ranges of 2.06-12.0% and 0.25-10.7%, respectively. As for accuracy, results were 89.0-112.9%. Matrix effect ranged from -1.31 to 0.05%. Stability after four freeze/thaw cycles and under autosampler conditions were also confirmed for all analytes. The method was applied to 40 paired venous and capillary plasma samples. Both measures exhibited high correlation (r = 0.926). PFOS was the only compound detected at concentrations ≥0.2 ng/mL (LLOQ) in all samples, with capillary plasma concentrations of 0.85-13.50 ng/mL. In summary, the method showed good validation performance and demonstrated the suitability of capillary plasma samples as an alternative matrix for PFAS quantification.

Humans↗

PubMed2026

Genome-wide identification and functional validation of asparagine synthetase genes (NtASNs) in Nicotiana tabacum.

Asparagine (Asn) is pivotal for plant nitrogen (N) metabolism and plays indispensable roles in plant growth, development, and stress tolerance. However, the systematic characteristics and core functions of asparagine synthetase genes (NtASNs) in tobacco remain unclear. Through a comprehensive genome-wide investigation, nine members of the NtASN gene family were identified. Subsequent CRISPR/Cas9-mediated knockout and overexpression assays of these NtASN genes revealed that NtASN1e, NtASN2a, and NtASN2b are the core genes responsible for Asn biosynthesis in tobacco. Their knockout reduced asparagine synthetase activity and Asn content, delayed seed germination by 2-3 days, and displayed elevated oxidative injury when exposed to salinity conditions. In contrast, overexpression of these genes elevated Asn accumulation. Subcellular localization analysis indicated that NtASN1e was localized to both the cytoplasm and chloroplasts, whereas NtASN2a exhibited dual localization in the cytoplasm and endoplasmic reticulum, and NtASN2b was mainly localized in the cytoplasm. This study systematically clarifies the evolutionary characteristics and core functions of the NtASN gene family and provides candidate genes for optimizing nitrogen metabolism and improving salt-stress adaptation in tobacco. These findings hold important practical significance for molecular breeding and product quality improvement in industrial crops.

Nicotiana↗

PubMed2026

Gene-environment interaction between perinatal oxytocin exposure and Pten mutation shapes epigenetic reprogramming of oxytocin signaling and behavior in mice.

Synthetic oxytocin (Pitocin) is the most commonly used pharmacologic agent for induction and augmentation of labor. Beyond its uterotonic effects, oxytocin plays a critical role in neurodevelopment and social behavior. Dysregulated oxytocin signaling has been implicated in autism spectrum disorder (ASD), raising concern that perinatal exposure to exogenous oxytocin may have lasting neurodevelopmental consequences. This study aimed to determine whether offspring harboring a genetic predisposition for ASD are differentially impacted by perinatal oxytocin exposures, with a focus on long-term oxytocin signaling and autism-like behavior. Pregnant mice carrying offspring with heterozygous mutations in phosphatase and tensin homolog deleted on chromosome ten (Pten), a well-established monogenic risk factor for ASD, received continuous oxytocin versus phosphate-buffered saline (PBS) control via micro-osmotic pumps during late gestation. Wild-type (WT) offspring exposed to each treatment served as a secondary control. Adult offspring were assessed for oxytocin receptor (Oxtr) methylation in the frontal cortex and hippocampus, oxytocin expression in the hypothalamus, serum oxytocin levels, and were subject to a battery of social and anxiety-related behavior tests. Perinatal oxytocin exposure produced genotype-dependent effects in offspring. Epigenetic analyses revealed bidirectional remodeling of Oxtr methylation in the frontal cortex and hippocampus, with increased exon 1 methylation in WT mice and decreased methylation in Pten-mutant mice, resulting in significant genotype-treatment interactions. Hypothalamic oxytocin expression increased following treatment regardless of genotype, though baseline levels were higher in Pten-mutant mice. Neither oxytocin treatment nor genotype impacted long-term serum oxytocin levels. Behavioral outcomes were modest but context-specific: repetitive behaviors and cognition performance were unchanged, but oxytocin-treated Pten-mutant mice exhibited increased anxiety-like behavior alongside improved social memory. In contrast, oxytocin-treated WT mice showed reduced social novelty preference. Exploratory analyses suggested potential sex-dependent trends. Our findings support a model in which genetic susceptibility shapes the epigenetic encoding of early-life hormonal signals, thereby recalibrating oxytocin system function and downstream behavioral outcomes. Together, these data highlight the context-dependent effects of perinatal oxytocin exposure and argue against uniformly beneficial or detrimental effects, emphasizing the importance of gene-environment interactions in neurodevelopmental trajectories.

Animals↗

PubMed2026

Insights into the mechanism of enhanced tetramethylpyrazine production in dehulled adlay fermented by Bacillus subtilis BJ3-2.

Tetramethylpyrazine (TTMP) is a vital bioactive alkaloid and characteristic flavor compound in fermented foods. Our previous study found that fermentation of adlay by Bacillus subtilis BJ3-2 efficiently accumulates TTMP, whereas the underlying high-yield mechanism remains unclear. This study investigated the fermentation characteristics, gene transcription and protein expression of B. subtilis BJ3-2 in dehulled adlay (BDA) and soybean (BSB), respectively, and elucidated the mechanism responsible for high-yield TTMP production. The results showed that glutamate, leucine and phenylalanine were major free amino acids in BDA. The TTMP yield in BDA at 48 h (6.11 mg/g dry weight) was 360-fold higher than that in BSB. Transcriptomic and proteomic analysis demonstrated that compared with the soybean substrate, dehulled adlay substrate significantly up-regulated the expression of alsSD and ilvBH genes and their encoding proteins in B. subtilis BJ3-2, which were involved in C5-branched dibasic acid metabolism, 2-oxocarboxylic acid metabolism, and valine, leucine and isoleucine biosynthesis. Meanwhile, acetoin degradation was inhibited by down-regulating acetoin dehydrogenase complex (acoABCL) in citrate cycle, glycolysis/gluconeogenesis and carbon metabolism. Additionally, nitrogen metabolism pathway was transcriptionally enhanced to guarantee sufficient ammonium supply. Notably, protein-protein interaction and molecular docking analyses revealed that acetohydroxyacid synthase (ilvBH) interacted tightly with α-acetolactate decarboxylase (alsD), potentially forming a metabolic channel for acetoin synthesis. In conclusion, the efficient synthesis of TTMP in BDA was primarily attributed to the high synthesis and low degradation of acetoin, and the moderate synthesis of ammonium/ammonia. This study provided a theoretical basis for the targeted and efficient biosynthesis of TTMP.

Bacillus subtilis↗

PubMed2026

Efficacy of NAs in combination with Peg-IFN for functional cure in patients with CHB: a meta-analysis of RCTs.

BACKGROUND: The goal of treating chronic hepatitis B (CHB) is to achieve functional cure. We aimed to evaluate the efficacy of the combination of nucleoside (acid) analogues (NAs) and pegylated interferon (Peg-IFN) on the functional cure of CHB patients at the EOT and at the EOF. METHOD: PubMed, Embase, and Web of Science were searched systematically up to March 15, 2025. Sixteen RCTs on CHB patients receiving combination or monotherapy were included. RESULT: Compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 14.05, 95% CI 6.13-32.20) and HBsAg seroconversion rate (RR: 12.82, 95% CI 5.08-32.33) at the EOT. Moreover, compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 7.70, 95% CI 4.24-13.98), HBsAg seroconversion rate (RR: 11.93, 95% CI 5.14-27.67) at the EOF. However, compared with Peg-IFN monotherapy, the combination therapy group did not show any improvement in HBsAg clearance rate, HBsAg seroconversion rate, and the rate of qHBsAg decrease > 1 log10 IU/mL at the EOT and the EOF. Moreover, in terms of safety, the Peg-IFN monotherapy group showed more ALT flares (ALT > 5 × ULN) during the treatment process. CONCLUSION: Compared with NAs therapy, Peg-IFN combined with NAs therapy significantly improves functional cure rate. However, combination therapy shows no additional advantage over Peg-IFN monotherapy in achieving functional cure. The Peg-IFN monotherapy group has a higher incidence of ALT flares than the combination therapy group.

Humans↗

PubMed2026

Role of omentin-1 in the global proteome of porcine pituitary cells: insights into proliferation- and apoptosis-related processes.

The anterior pituitary integrates endocrine regulation, cellular growth, and adaptive responses. Adipokines, secreted mainly by adipose tissue, act as hormonal signals linking metabolism, inflammation, appetite, and reproduction. They regulate hypothalamic-pituitary-ovarian axis by modulating hormone secretion and intracellular signaling. The presence of adipokine receptors in anterior pituitary suggests local metabolic-endocrine interactions. Omentin-1, predominantly expressed in visceral adipose tissue, participates in glucose metabolism and ovarian steroid regulation. Recent findings indicate that omentin-1 modulates tropic hormones, their receptors, and adipokine balance in anterior pituitary cells. We hypothesized that omentin-1 affects protein expression and signaling pathways involved in pituitary cell proliferation and apoptosis. This study examined its effects in anterior pituitary cells from Large White and Meishan pigs. Proteomic analysis identified 230 candidate differentially abundant proteins after omentin-1 treatment: 30 downregulated and 3 upregulated in Large White pigs, and 107 downregulated and 90 upregulated in Meishan pigs, associated with enriched 116 Gene Ontology terms. Key proteins were associated with cell cycle, DNA replication, gene expression, and posttranscriptional/posttranslational regulation. Responses differed between breeds. CDK5RAP2 and SIX1 were linked to proliferative control in Large White pigs, whereas AKT1S1 and RHOA were among the proteins associated with the broader proteomic response observed in Meishan pigs. Meishan pigs showed dynamic apoptotic protein regulation, including HTRA2, PARP2, and DFFA. Complementary in vitro experiments demonstrated that omentin-1 downregulated cyclins and caspase-3, upregulated BCL2, increased BCL2/BAX ratio, and modulated ERK1/2, AKT, AMPKα, and STAT3 phosphorylation. Together, these findings suggest that omentin-1 modulates proteomic networks and intracellular signaling associated with anterior pituitary cell function during the mid-luteal phase of the estrous cycle.

Animals↗

PubMed2026

Pretreatment EBV-DNA/TLG-Based Risk Stratification Is Associated With Survival Outcomes in Nonmetastatic Nasopharyngeal Carcinoma: An Exploratory Study.

Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5 months, 5-year PFS and OS for the whole cohort (n = 86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR = 3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR = 4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n = 59; 89.7%-58.3%). OS differed across groups (log-rank p = 0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.

Epstein–Barr virus DNA↗

PubMed2026

An allograft inflammatory factor enhances sperm viability by modulating intracellular calcium in oyster Crassostrea gigas.

As an important aquaculture bivalve, the Pacific oyster Crassostrea gigas faces severe constraints in artificial reproduction, where low sperm motility often leads to fertilization failure and limits the sustainable development of the oyster aquaculture industry. In the present study, the variation of sperm from different oyster individuals was observed, and high-quality sperm possessed intact, elongated flagella with no structural abnormalities, while low-quality sperm showed shortened flagella with frequent tangling or coiling defects. Transcriptomic analysis comparing high- and low-quality sperm revealed significantly reduced expression of genes associated with sperm motility and release (CgAIF1, CgAchR, CgSEX), sperm quality and development (CgEP4, CgIFi2b), and cryoprotection (CgISPs) in low-quality sperm. Notably, an allograft inflammatory factor (designed as CgAIF1) encoding EF-hand domain, known as Ca2+ binding activity, was among the most significantly downregulated in low-motility sperm. CgAIF1 is highly expressed in haemocytes, ganglia, and gonads of oysters. Incubation with the recombinant AIF1 protein (rCgAIF1) significantly improved sperm curvilinear velocity, thereby enhancing the overall motility of C. gigas sperm. Furthermore, rCgAIF1 incubation increased intracellular Ca2+ levels (2.13-fold at 30 min, 2.71-fold at 60 min) and superoxide dismutase (SOD) activity (1.44-fold at 30 min, 1.24-fold at 60 min) in sperm, suggesting potential roles in calcium homeostasis regulation and antioxidant defense. In conclusion, this study demonstrates that CgAIF1 significantly enhances motility of oyster sperm, providing a scientific basis for artificial breeding and seed production in oyster aquaculture.

Animals↗

PubMed2026

A randomized study of antibiotic prophylaxis after hypospadias repair in children.

BACKGROUND AND OBJECTIVE: Antibiotic resistance is a challenge in contemporary world. Urethroplasty for hypospadias is one of the most common urological surgeries performed around the world, yet, there is still no consensus on the use of antibiotics pre- and post-operatively. Our objective was to analyze the effectiveness of antibiotic prophylaxis and therapy before, during, and after hypospadias repair in children. METHODS: A prospective randomized trial was carried out including patients with coronal hypospadias who underwent urethroplasty performed by one surgeon. Urethral catheters were used in all cases for 10 days. Study participants were randomly assigned in a 1:1:1 ratio to receive a single intraoperative administration of antibiotics (Group I); an intraoperative antibiotic prophylaxis and antibiotic therapy for 10 days until the removal of urethral catheter (Group II); no antibiotic administration (Group III). Randomization was performed using computer-generated permuted blocks with randomly varying block sizes, prepared by an independent statistician. The results were analyzed using the analysis of variance (ANOVA). The following criteria were compared: postoperative functional complications, such as: urethral fistula, stenosis, diverticulum; wound infection symptoms: hyperemia of surgical site, pain during palpation, and symptomatic urinary tract infection. RESULTS: A total of 300 patients were included in the study. Two patients (2%) in Group I, two patients (2%) in Group II, and four patients (4%) in Group III had urethral fistulas, requiring surgery 6 months after primary repair, yet without statistical difference between groups. We found no significant difference in frequency of symptomatic UTIs between three groups (p = 0.182). CONCLUSION: There is no effect of antibiotic prophylaxis and therapy on the frequency of postoperative surgical and infectious complications after urethroplasty for coronal hypospadias repair in children.

Humans↗

PubMed2026

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I. = 50-66%) and Alzheimer's dementias(28.0% = 95%C.I. = 17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I. = 17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I. = 36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I. = 38.3-45.6%), anxiety(32.0%;95%C.I. = 26.5-37.6%), MDD + anxiety(24.7%;95%C.I. = 17.9-34.3%), and dementia(19.8%;95%C.I. = 12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I. = 21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I. = 12.0-46.0%), MDD in PVI patients (20.0%;95%C.I. = 13.0-29.0%); in coronary artery disease: MDD + anxiety(19.8%;95%C.I. = 16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I. = 0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I. = 0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I. = 0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans↗

PubMed2026

Non-parametric differential methylation analysis characterizes histotype-specific promoter regions in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a heterogenous disease with frequent late-stage diagnosis and high mortality rates, for which no reliable screening tests exist. In recent years, epigenetic biomarkers in the form of DNA methylation in CpG-rich regions have gained increased attention in the scientific community due to their robust nature and accessibility, allowing for diagnosis without the need for invasive surgery. In this study, we investigated the aberrant methylation of promoter regions in early stage EOC through non-parametric methods, with the purpose of characterizing candidate epigenetic biomarkers. The approach was used on a cohort of early stage EOC samples, and results were compared to existing programs for differential methylation. Significant regions were then used to construct a CpG panel for stratifying EOC histotypes through predictive classification in external data. Identified promoter regions were highly reproducible across cohorts, and the constructed CpG model stratified histotypes in external cohorts through predictive classification. Comparisons against other DMP and DMR callers showed a degree of homogeneity between results but also revealed promoter regions that were overlooked despite clear signs of aberrant methylation. Finally, EOC histotypes were found to differ in their methylation distribution types, and results indicate that methods sensitive to non-normally distributed data may be poorly suited to compare groups with different distribution types. The non-parametric approach identified aberrantly methylated promoter regions that were highly reproducible across cohorts. Results from predictive classification indicate that these regions may be useful for the purpose of EOC histotype stratification.

Humans↗

PubMed2026

Effect of levothyroxine therapy on albuminuria and glomerular function in patients with type 2 diabetes and subclinical Hypothyroidism: a randomized controlled pilot trial.

AIMS: To evaluate the effect of levothyroxine therapy on renal outcomes in patients with type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SCH) with background SGLT2 inhibitor therapy. METHODS: In this hypothesis generating open-label, randomized controlled pilot trial, adults with T2DM and SCH were assigned (1:1) to levothyroxine or no levothyroxine therapy and followed for 6 months. Primary outcomes were changes in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). RESULTS: Sixty participants were randomized (30 per group); 24 and 27 completed follow-up in the treatment and control groups respectively. UACR decreased with levothyroxine (-13.09 mg/g) and increased in controls (31.84 mg/g). The difference was significant in per-protocol (PP)(-44.93 mg/g; 95% CI -77.6 to -12.26; p = 0.008) but insignificant in intention to treat (ITT)(-35.61 mg/g; 95% CI -77.31 to 6.08; p = 0.092). eGFR changes were statistically insignificant in both ITT(4.65 mL/min/1.73 m2; 95% CI -8.3 to 17.6; p = 0.472) and PP(7.35 mL/min/1.73 m2; 95% CI -1.68 to 16.37; p = 0.108). Thyroid-stimulating hormone decreased significantly in treatment arm in comparison to control arm (p < 0.001) in ITT and PP. No adverse event was reported. CONCLUSIONS: Levothyroxine treatment showed trend toward improving albuminuria and eGFR without reaching statistical significance, suggesting possible renoprotective effect warranting further studies. CLINICAL TRIAL REGISTRATION: This trial is registered with Clinical Trial Registry of India (CTRI/2025/06/089606).

Humans↗

PubMed2026

Experimental evolution reveals contrasting adaptive landscapes in lab and field environments.

Experimental evolution is widely used to infer microbial responses to environmental change, yet most laboratory studies impose constant, well-mixed conditions that differ fundamentally from fluctuating, spatially structured field environments. We compared genomic evolution in the leaf litter-associated bacterium Curtobacterium strain MMLR14_002 under control and warming treatments in laboratory culture and in a complementary field experiment. Laboratory-derived isolates accumulated more mutations per genome and exhibited stronger locus-level parallelism, with mutations recurring in a small number of coding loci. Field-derived isolates accumulated fewer mutations per genome, and these mutations rarely occurred in the same coding loci across replicate populations. Instead, field isolates exhibited a higher proportion of intergenic mutations, with mutations recurring in the same intergenic regions across independent field deployments. When coding mutations were detected in the field, they were distributed across functionally diffuse targets and more often involved metabolic pathways than the core cellular processes repeatedly targeted during laboratory evolution. Warming itself did not consistently influence mutation accumulation or the genomic distribution of mutations; instead, laboratory and field contexts primarily shaped the accumulation, targets, and repeatability of genomic change. These results suggest that laboratory thermal evolution identifies adaptive routes favored under sustained selection but may overestimate coding-level parallelism under heterogeneous field conditions. Bridging laboratory and field evolution will likely require experimental designs that incorporate temporal variability and spatial heterogeneity characteristic of natural systems.IMPORTANCEA central goal of experimental evolution is to infer how microbes evolve in nature from laboratory studies. Here, we evaluate this assumption by comparing genomic evolution of a leaf litter-associated Curtobacterium strain in laboratory and field warming experiments to identify broad patterns rather than isolate the contribution of any single environmental factor. We find that the strong parallelism at coding loci observed under laboratory conditions is reduced in the field, while mutations recurring in the same intergenic regions across field deployments suggest that parallel evolution in nature may more often involve regulatory noncoding regions rather than coding targets. These results show that environmental context reshapes adaptive landscapes and may limit the parallelism of coding-level genomic responses inferred from homogeneous laboratory conditions.

experimental evolution↗

PubMed2026

Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.

BACKGROUND: Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. METHODS: In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. RESULTS: Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P = 0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. CONCLUSIONS: Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).

Adolescent↗

PubMed2026

Sociodemographic and clinical characteristics associated with nocturnal enuresis among children in a tertiary care center in Cairo, Egypt: A cross-sectional study.

BACKGROUND: Nocturnal enuresis (NE) is a significant pediatric health concern that warrants increased attention from healthcare providers, educators, and society. This study aimed to determine the frequency of NE among children attending a tertiary care center in Cairo, Egypt, and to explore their sociodemographic characteristics and associated factors. METHODS: A cross-sectional study was conducted among 1587 children aged 6-16 years attending a tertiary care center in Cairo from December 2022 to February 2024. Data were obtained from parents via a structured questionnaire covering sociodemographic characteristics. Sleep problems were assessed via the Children's Sleep Habits Questionnaire. The multivariate logistic regression analysis was conducted to estimate the odds ratio and identify factors associated with NE. RESULTS: The total prevalence of NE among children attending a tertiary care center was 333 (21%). Our results indicated that being female and being older were associated with a lower likelihood of NE. Low socioeconomic status (OR = 5.559; 95% CI = 1.24-24.88), stressful events (OR = 3.697; 95% CI = 1.73-7.88), a family history of NE (OR = 26.231; 95% CI = 8.617-79.85), and sleep problems (OR = 13.233; 95% CI = 6.082-28.793) were associated with increased odds of NE. Furthermore, consuming caffeinated drinks before sleep, the presence of urinary tract infections, and intestinal infestations were also associated with NE. CONCLUSION: The findings of the present study confirm the multifactorial etiology of NE and identify several associated factors. Integrating these factors into screening and management programs may improve early identification and lead to more effective, tertiary care-specific preventive and therapeutic interventions.

Humans↗

PubMed2026

GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.

BACKGROUND: GPR3(G-protein-coupled receptor 3), an orphan G-protein-coupled receptor (GPCR) with constitutive Gs activity, is expressed in the brain, liver, ovary, and other tissues, regulating cell proliferation, differentiation, and apoptosis across the nervous, reproductive, immune, and metabolic systems. This review synthesizes evidence on its integrated signaling and physiological functions to address the lack of a comprehensive multisystem pathophysiology overview. METHODS: A systematic literature search was conducted on PubMed and Web of Science, using keywords such as "GPR3", "GPCR", "neurodegeneration", "metabolism", "immune", "reproduction", "agonist", "inhibitor", and "therapeutic target". This search identified GPR3's roles in neurodegenerative diseases, immune inflammation, reproduction, and energy metabolism. The analysis focused on signaling pathways, ligand regulation, and therapeutic potential. RESULTS: The research indicates that GPR3 is involved in neuronal survival, synaptic plasticity, and microglial activity via the cAMP/PKA, PI3K/Akt, and β - arrestin pathways. It promotes amyloid - β formation in Alzheimer's disease (AD), yet provides neuroprotection in Parkinson's disease (PD) models. It may contribute to anxiety/depression - like states, maintain oocyte meiotic arrest in the ovary, and activate thermogenic genes in adipose tissue. GPR3 modulates immune responses. Using oleic acid (OA) and diphenyleneiodonium (DPI) as activators, and AF64394 and cannabidiol (CBD) as antagonists, it shows potential in disease models. CONCLUSION: GPR3 acts as a central molecular hub integrating neural, metabolic, immune, and reproductive signaling, highlighting its potential as a therapeutic target for chronic multisystem disorders. However, its dual roles in certain pathologies and translation challenges necessitate further research.

Humans↗