The Journal of Nutrition

Background: Early trophic feeding promotes gut maturation, feeding tolerance, and growth in preterm neonates. However, delays remain common despite recommendations for initiation within 24 hours of birth, especially in resource-limited settings. Evidence on feeding initiation timing and predictors among Ethiopian preterm neonates is limited. Objective: To determine time to trophic feeding initiation and identify predictors among preterm neonates admitted to Adama Hospital Medical College, Ethiopia. Methods: A hospital-based retrospective cohort study was performed on 436 randomly chosen preterm neonates admitted to NICU. Data extraction was performed using a structured checklist. Time to trophic feeding initiation was analyzed using Kaplan-Meier estimates, log-rank tests, and bivariable and multivariable Cox regression models . Adjusted hazard ratios with 95% CIs were reported. Results:The sample comprised 416 preterm neonates, of whom 311 (74.8%) started trophic feeding during follow-up, and 105 (25.2%) were censored. The rate of initiation of trophic feeding was 1.92 per 100 person-hours (95% CI 1.72 to 2.15). Median time to initiation was 42 hours (interquartile range 24 to 50). Independent predictors of feeding initiation were determined by multivariable analysis and included gestational age, birth weight, maternal anaemia, respiratory distress syndrome and necrotising enterocolitis. Neonates born at 34-36 weeks had earlier initiation than those born at <34 weeks (AHR 1.39; 95 % CI 1.09 to 1.78). Similarly, neonates with a birth weight of [&ge;]1500 g had an earlier initiation than those with a birth weight of <1500 g (AHR 1.41; 95% CI 1.04 to 1.91). Delayed initiation was associated with maternal anaemia (AHR 0.70; 95% CI 0.51-0.95), respiratory distress syndrome (AHR 0.67; 95% CI 0.51-0.88) and necrotising enterocolitis (AHR 0.48; 95% CI 0.33-0.69). Conclusions: Delayed trophic feeding remains common among preterm neonates. Standardized feeding protocols, strengthened maternal care, and individualized nutrition strategies are needed to improve neonatal outcomes in study area.

Micronutrient deficiencies are prevalent in Madagascar, where diets rely heavily on starchy staples and access to animal-source foods is limited. Small dried fish (SDF) are widely available, yet their nutritional value and health risks remain poorly documented. We combined market surveys, taxonomic identification, and micronutrient and heavy metal analyses of nine SDF types collected along National Road 7. The samples encompassed 33 fish families, were dominated by small pelagic species (Clupeidae and Engraulidae), and were appreciated by consumers. A daily portion (5 g for infants; 10 g for young children and women of childbearing age) contributed substantially to Recommended Nutrient Intakes (RNIs). Across samples and groups, SDF were rich (>30% of RNI) in selenium and, for infants and young children, in calcium. All samples were a source of (>15% of RNI), or rich in, phosphorus, whereas iron contributions were more variable but often substantial. Several samples exceeded 100% of RNIs for selenium, calcium, iron, or manganese in infants and young children, and some were also sources of magnesium and, less frequently, zinc. Vitamin A was absent from sun-dried samples but detected in a smoked freshwater type. Heavy metal concentrations varied markedly, and portions of several types led to estimated exposures to inorganic arsenic or cadmium exceeding reference values, whereas freshwater species and some pelagic types showed a more favorable nutrition-risk balance. Overall, SDF are affordable, nutrient-dense foods with strong potential to alleviate micronutrient deficiencies in Madagascar, while highlighting the need for type-specific guidance to balance nutritional benefits and contamination risks.

Background: Despite several trials on the hematological outcomes of intravenous (IV) iron in pregnancy, only few have examined its effect on birth outcomes. We estimated the causal effect of IV-iron on moderate or severe anaemia and birth outcomes. Methods: Women presenting to routine antenatal care in Pakistan with haemoglobin <10 g/dL were eligible for treatment. We used target trial emulation (TTE) methodology to estimate the effect of IV-iron treatment within 14 days of anaemia identification, compared to no treatment, on anaemia status at follow-up. A modified TTE analysis examined birth outcomes at delivery for singleton pregnancies, including birthweight, size-for-gestational-age, and mortality. We conducted a separate TTE for each of five gestational-age periods and pooled the results of each TTE. Results: We screened 3115 pregnancies of which 1715 were eligible for IV-iron; 1043 participants were treated during pregnancy. Those who received IV-iron had half the risk of moderate or severe anaemia in pregnancy compared with no treatment (pooled relative risk (RR) 0.40; 95% confidence interval (CI): 0.27, 0.59). The pooled effect of IV-iron on stillbirth suggested an 83% risk reduction (95% CI 55-94%), and trends were similar for perinatal and neonatal mortality. Conclusion: IV-iron treatment improved haematological status in pregnant women and was associated with a large reduction in stillbirth. Given limited data from randomised trials regarding fetal death and treatment earlier in pregnancy, this study contributes important information to the potential benefit of IV-iron in contexts where anaemia and its sequelae are a major public health problem.

Background: Evidence suggests chronic distress influences ovarian cancer (OC) etiology and metabolomic profiles. Here, we evaluated the association of a metabolite-based distress score (MDS) and OC risk. Methods: We included two matched case-control studies nested within the Nurses' Health Studies (N=584) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N=348). Metabolites were measured 3-27 years before diagnosis using liquid-chromatography tandem mass spectrometry. We examined the association of quintiles of MDS and 19 constituent metabolites with OC risk using unconditional logistic regression and stratified by tumor histotype, menopausal status, and age at diagnosis. Results: We observed women in the highest versus lowest quintile of MDS had an increased OC risk (OR=1.62,95%CI=1.03-2.54,ptrend=0.07), and type 2 tumors (OR=1.71,95%CI=1.03-2.83,ptrend=0.11). Associations were suggestively stronger for premenopausal and <69-year-old women, and driven by pseudouridine, and N2,N2-dimethylguanosine. Conclusion: Our findings suggest chronic distress-associated metabolic dysregulation may represent a novel OC risk factor, especially among younger women.

Background: Pro-inflammatory and high-environmental-impact diets both threaten population and planetary health, but whether the two objectives align or conflict across countries is unresolved. We tested whether a supply-based dietary inflammatory index (sDII) is coupled to greenhouse-gas (GHG), land and freshwater footprints, and whether a nutrition-feasible reallocation can lower both simultaneously. Methods: From FAO Food Balance Sheets we built sDII (12 inflammatory-weighted components; construct validity r=0.9999) and five per-capita footprints using three independent life-cycle inventories for 182 national food-supply series. For each country, constrained optimisation reallocated 13 food-group supplies under isoenergetic, protein-preserving and food-group-bound constraints, minimising sDII and GHG jointly (Pareto frontier). Health burden was estimated via pooled relative-risk meta-analysis and 2023 World Bank population data. Results: sDII was only weakly associated with GHG (Spearman rho=0.14), land (rho=0.13) and freshwater (rho=0.28) in 2023. The balanced-Pareto reallocation lowered both sDII and GHG in 182/182 series (100% synergy): population-weighted delta sDII=-0.235, GHG -37.5%, land -49.3%, water -17.2%, i.e. 4.28 Gt CO2e/yr avoided. The associated reduction in metabolic-syndrome burden was directionally consistent but modest (~1.1% of the prevalent pool, ~2.84 million cases). Results were robust to three life-cycle inventories and three feasibility-bound regimes. Conclusions: Anti-inflammatory and low-carbon goals are decoupled rather than conflicting, and an isoenergetic, protein-preserving reallocation reconciles them in every country. Environmental gains are large and robust; health gains are directionally consistent but modest--triangulation, not a causal claim.

Introduction Guatemala is the most populous country in Central America and a setting with unique opportunities for aging research. Approximately 40% of Guatemala's population is Indigenous Maya, who together speak 22 Mayan languages. Currently, there is no population-based aging study in Guatemala and few aging studies in Latin America among Indigenous populations. The Longitudinal Study of Aging in Guatemala (ELEGUA) aims to address these gaps by developing a nationally representative, population-based, longitudinal aging study modeled on the Health and Retirement Study and the Harmonized Cognitive Assessment Protocol, adapted to the cultural and linguistic context of Guatemala. The objective of this protocol is to describe the rationale and design of the ELEGUA pilot survey. Methods and analysis The ELEGUA pilot was a cross-sectional household survey of adults aged 40 years or older in Tecpan, Guatemala. Tecpan was chosen because its diverse population facilitated testing of study procedures in both Spanish and Kaqchikel, a common Mayan language. The survey included up to 600 households sampled using a multistage stratified cluster design. Within each household, one individual aged 40 years or older was selected, with oversampling of adults aged 55 years or older. This respondent completed a comprehensive questionnaire, including detailed cognitive tests, and provided physical measurements and a venous blood sample. Household respondents provided information on household economics and family structure, and an informant reported on the individual respondent's cognitive function. Data were collected using a computer-assisted personal interviewing system. Planned analyses include survey-weighted descriptive statistics and psychometric evaluation of the cognitive assessments. Ethics and dissemination Ethics approval was obtained from the ethics committees of the Institute of Nutrition of Central America and Panama, Maya Health Alliance, and the University of Michigan. Results will be disseminated through publications in peer-reviewed journals and presentations to local, national, and international audiences.

The analysis uses a global 2010-2023 panel comprising 3,038 economy-years across 217 economies. It explicitly separates between-economy and within-economy estimands and tests the longitudinal interpretation using an identical-sample temporal analysis with cluster-aware coefficient contrasts, a formal isometric log-ratio sensitivity analysis, independent fixed-effects replication, and wild-cluster-bootstrap inference. The central finding is deliberately calibrated: cross-economy agreement cannot validate national sugar availability for longitudinal obesity surveillance. The study identifies temporal and construct instability without claiming that sugar is protective or that the mechanisms producing the instability have been identified. The manuscript aligns well with PLOS ONEs emphasis on technically sound, transparent and reproducible research of broad relevance. All data required to reproduce the findings, complete metadata, executable code, full-precision results, diagnostic outputs and a completed STROBE checklist are provided as S1-S5. Figures are provided separately as compliant 350-dpi TIFF files. The study used only publicly available, aggregated economy-year statistics and involved no individual participants, identifiable information or biological specimens; institutional ethics review and consent were therefore not required. This is original work; it is not under consideration elsewhere, and the sole author has approved the submission and accepts responsibility for its content. Funding and competing-interest declarations will be entered accurately in the submission portal. An Academic Editor with expertise in nutritional epidemiology, global health metrics, longitudinal panel methods, or food-system surveillance would be well placed to assess the work.

Background: Exclusive breastfeeding may protect infants against common infections and support healthy growth and development. Working mothers may face constraints on exclusive breastfeeding arising from work schedules, separation from their infants, and inadequate breastfeeding support. National evidence on the individual, healthcare-related, and contextual factors associated with exclusive breastfeeding among working Ghanaian mothers appears to remain limited. Design: Cross-sectional secondary analysis. Setting: Nationally representative survey covering urban and rural communities across all 16 administrative regions of Ghana. Participants: The analysis included 620 currently working mothers whose youngest living infants were aged 0-5 completed months and lived with them. The complete-case multivariable analysis included 619 mother-infant pairs. Primary outcome measure: Current exclusive breastfeeding, defined using the standard 24-hour infant-feeding indicator. Infants were classified as exclusively breastfed when they received breast milk without water, formula, animal milk, other liquids, or solid or semi-solid foods during the preceding day or night. Oral rehydration solution, vitamins, minerals and prescribed medicines were permitted. Aim: To estimate the prevalence of exclusive breastfeeding and examine its individual, healthcare-related and contextual correlates among working mothers of infants aged 0-5 months in Ghana. Methods: Birth Recode data from the 2022 Ghana Demographic and Health Survey were analysed. Unweighted frequencies and survey-weighted percentages described the study population. Design-adjusted Wald tests assessed bivariate associations. Survey-weighted binary logistic regression estimated adjusted odds ratios (AORs) and 95% confidence intervals (CIs), accounting for sampling weights, primary sampling units, and strata. Results: The survey-weighted prevalence of exclusive breastfeeding was 54.3% (95% CI: 49.2-59.3). Ethnicity, mode of delivery, region, and community poverty appeared to be statistically significant in the bivariate analyses. In the adjusted model, region was jointly associated with exclusive breastfeeding (p = 0.004). Mothers in the Northern (AOR = 4.93; 95% CI: 1.5-16.17) and Savannah (AOR = 4.22; 95% CI: 1.08-16.41) regions had higher odds than mothers in the Western Region. Mothers in low-education communities had lower odds than those in high-education communities (AOR = 0.54; 95% CI: 0.30-0.98). Although Guan mothers had higher odds than Akan mothers, the overall association with ethnicity was non-significant, and the estimate appeared imprecise. Maternal age, individual education, religion, parity, wealth, infant sex, antenatal care, postnatal care, and residence were not independently associated with exclusive breastfeeding. Conclusion: The prevalence estimate suggests that slightly more than half of working mothers exclusively breastfed their infants. Regional and community differences appeared more pronounced than those associated with most measured individual characteristics. Regionally responsive breastfeeding support and practical community education may contribute to improved coverage. Workplace recommendations require further evidence because employment conditions were not measured directly. Keywords: Exclusive breastfeeding; working mothers; infant feeding; maternal employment; regional inequalities; community education; Ghana; 2022 Ghana Demographic and Health Survey; survey-weighted analysis.

Background Excess sodium intake is a major contributor to the global burden of disease, but its role in infection susceptibility remains largely unexplored. Although sodium has been considered antimicrobial, high sodium intake may impair immune responses and host defense. We therefore examined whether habitual addition of salt to foods was associated with the long-term risk of incident infections. Methods We included 360,314 UK Biobank participants without prior hospital-treated infections. Frequency of adding salt to foods was self-reported at baseline. Incident infections were identified using ICD-10 codes from hospital and death records. Associations were assessed using multivariable Cox regression. Results Over a median follow-up of 14.3 years, 84?146 participants developed hospital-treated infections. Compared with those who never or rarely added salt, participants who sometimes, usually, and always added salt had progressively higher risks of incident infections (adjusted hazard ratios 1.04 [95% CI 1.03?1.06], 1.08 [1.06?1.11], and 1.29 [1.26?1.33], respectively; p for trend <0.001). The association remained robust across models and broadly consistent across pathogen types and infection sites. The association appeared stronger among participants with normal weight (P for interaction <0.001). Conclusions Habitual addition of salt to foods was associated with a dose-dependent higher risk of hospital-treated infections in this large prospective cohort. These findings extend the potential health relevance of excess sodium intake beyond cardiometabolic disease and suggest that lower habitual salt intake may have implications for infection risk. Further studies are needed to replicate these findings and clarify the underlying immunological mechanisms.

Mitochondria are central hubs for cellular metabolism and mitochondrial dysfunction is a hallmark of many chronic diseases. Consequently, changes in mitochondrial DNA copy number (mtDNA-CN), the number of mtDNA genomes per cell or tissue sample, are associated with diseases ranging from cancer and obesity to psoriasis and all-cause mortality. MtDNA-CN especially holds promise as a biomarker for neurodegenerative diseases, but whether and how mtDNA-CN changes with neurodegeneration is controversial. Here, we performed a systematic review and meta-analysis of 76 studies including 156 comparisons of mtDNA-CN in populations with or without a neurodegenerative disease to identify overall trends and potential moderators that explain variation among studies. Overall, mtDNA-CN was not statistically different with neurodegeneration, but heterogeneity among studies was extreme (I2 = 99.5%). The diagnosed disease explained the most variation. For example, Alzheimer's patients showed a 21% decrease in mtDNA-CN, but there was no change in mtDNA-CN with Parkinson's disease. Decreases in mtDNA-CN during neurodegeneration were also more extreme at older ages. Surprisingly, the tissue sampled for mtDNA-CN was not particularly influential, except for certain diseases. Studies published in earlier years also showed more extreme decreases in mtDNA-CN with neurodegeneration. Excessive heterogeneity persisted even after accounting for all moderators and their interactions (I2 = 85.7%). We conclude that the general perception of decreased mtDNA-CN with neurodegeneration is a vast oversimplification that may stem from legacy effects of early studies. However, mtDNA levels offer great promise as biomarkers for neurodegeneration, other diseases, and general health metrics, assuming appropriate complications can be considered.

Objective. To determine the publication rate of abstracts presented at the American Diabetes Association Scientific Sessions and to evaluate the association between statistical significance of study results and subsequent publication. Research Design and Methods. We conducted a retrospective cohort study of abstracts presented at the 2018 American Diabetes Association Scientific Sessions. The primary exposure was study result category (statistically significant vs. non-statistically significant findings), and the primary outcome was publication in an indexed journal within 5 years after conference presentation. Publication status was determined through PubMed/MEDLINE and Scopus searches. Adjusted relative risks (RRs) and 95% CIs were estimated using generalized linear models with Poisson distribution and robust variance. Results. Among 541 included abstracts, 321 (59.3%) were subsequently published in indexed journals. Abstracts reporting statistically significant findings had a higher publication rate than those reporting non-statistically significant findings (61.9% vs. 42.3%; p=0.002). In the adjusted analysis, abstracts with non-statistically significant findings had a lower likelihood of publication compared with those reporting statistically significant findings (adjusted RR 0.71 [95% CI 0.55-0.93]; p=0.013). Conclusions. Approximately four in ten abstracts presented at the ADA Scientific Sessions were not published within 5 years. Abstracts reporting non-statistically significant findings had a lower likelihood of subsequent publication, suggesting persistent publication bias in diabetology research. Future initiatives promoting the interpretation of effect estimates, confidence intervals and clinical relevance, rather than statistical significance alone, may help reduce selective dissemination of evidence

The distribution of fat-soluble compounds (including antioxidants) in follicular fluid (FF) remains sparsely documented in relation to in vitro fertilization (IVF) outcomes and existing studies have reported diverging associations. This study aimed to describe plasma and FF concentrations of fat-soluble micronutrients in women undergoing IVF and to analyze their adjusted associations with ovarian function, embryo development and pregnancy outcomes. In 2021-2022, plasma and FF samples were collected from 82 women (first IVF cycle) at oocyte puncture, along with lifestyle data covering the three preceding months. Eleven compounds (two tocopherols, three xanthophylls, five carotenes and retinol) were quantified. All compounds were detected in both compartments (lowest in FF) except phytoene, undetectable in FF. Plasma and FF -tocopherol concentrations were positively associated with plasma estradiol levels before oocyte puncture (both p<0.01) while FF -carotene and lycopene were inversely associated with plasma progesterone concentrations (p=0.01 and 0.02, respectively). Plasma phytofluene and phytoene were positively associated with mature oocyte rate (p=0.03 and p=0.01, respectively), while FF retinol was negatively associated (p=0.03). Carotenes, tocopherols and retinol were inversely associated with later IVF outcomes: fertilization rate (p<0.001 for plasma g-tocopherol, 0.02 for FF retinol), top-quality embryo (p=0.02 for plasma phytofluene), biochemical pregnancy at day 7 post-embryo transfer (p=0.05 for plasma -tocopherol, 0.02 for plasma -carotene), clinical pregnancy (p=0.03 for plasma -tocopherol, 0.01 for plasma phytoene) and live birth (p=0.04 for plasma -tocopherol, 0.02 for plasma phytoene). Plasma and FF g-tocopherol were positively associated with embryo fragmentation (both p<0.05). Finally, among xanthophylls, only plasma {beta}-cryptoxanthin was positively associated with plasma progesterone concentrations (p=0.02). Our findings of heterogeneous associations between tocopherols, carotenes, retinol and IVF outcomes across the stages of IVF suggest a beneficial effect limited to early outcomes and support a complex and context-dependent role of these compounds in female reproduction. This manuscript has been submitted to PlosOne on August 19, 2026.

Background: Oral dysbiosis has been associated with oral squamous cell carcinoma (OSCC); however, most microbiome studies rely on 16S ribosomal RNA (rRNA) gene sequencing, limiting species-level taxonomic resolution. Methods: Dental plaque, saliva, and tumor tissue samples from 10 patients with OSCC and dental plaque and saliva samples from 10 healthy controls were analyzed in this exploratory cross-sectional study. DNA was extracted and subjected to shotgun metagenomic sequencing using the Illumina MiSeq platform. Sequence reads were quality filtered with fastp, taxonomically classified using Kraken2 v2.1.3, and species-level abundances were re-estimated with Bracken v2.9 following the removal of human reads and low abundance taxa. Relative abundances were compared using the Mann Whitney U test with the Benjamini Hochberg false discovery rate correction, while the Bray Curtis principal coordinate analysis was used as an exploratory approach to visualize microbial community patterns. Results: Shotgun metagenomic sequencing revealed distinct bacterial community profiles across the oral microenvironment. Dental plaque exhibited the highest taxonomic diversity and relative abundance. The control plaque was enriched in Streptococcus koreensis, Capnocytophaga sp. oral taxon 878, Treponema sp. Marseille Q4132, and Leptotrichia sp. oral taxon 498, whereas the plaque from patients with OSCC showed a higher relative abundance of Pyramidobacter piscolens, Parvimonas parva, and Gemella sanguinis. Salivary samples displayed lower diversity and a more homogeneous composition, predominantly comprising Capnocytophaga endodontalis, Prevotella jejuni, Aggregatibacter aphrophilus, and Gemella sanguinis. The tumor tissue showed relatively higher abundance of Sellimonas catena, Escherichia coli, Solobacterium moorei, and Lacrimispora sp. HJ 01. Conclusions: This exploratory study provides species-level characterization of the oral microbiome across multiple oral microenvironments in OSCC and generates hypotheses for future integrative metagenomic and functional studies investigating the potential contribution of oral bacterial communities to OSCC pathogenesis.

Background: Vitamin K prophylaxis is universally recommended for newborns to prevent life threatening vitamin K deficiency bleeding. Although not on the immunization schedule, vitamin K prophylaxis is often coadministered with hepatitis B birth dose and erythromycin ophthalmic ointment, and rising hesitancy around vaccines/preventive care may spill over into vitamin K administration. Methods: We conducted a retrospective cohort study using Truveta electronic health record data with linked mother-child dyads. Live births to mothers aged 15-49 from January 1, 2019 through June 30, 2026 were included. Vitamin K administration was defined as documentation on the birth date or following day. Logistic regression assessed sociodemographic predictors of non-receipt, and interrupted time series analysis evaluated changes after January 2026. Results: Among 1,026,375 infants, 995,628 (96.97%) had documented vitamin K administration. Non-receipt increased from an average of 2.1% during 2019-2022 to 4.3% in 2025 and 6.1% in 2026, reaching 8.10% in June 2026. Older maternal age, non-Hispanic or Latino ethnicity, Medicaid or unknown insurance, and year of delivery were associated with greater odds of non-receipt. After January 2026, there was no immediate step change, but the odds of vitamin K receipt declined an additional 10% per month (OR: 0.90; 95% CI, 0.88-0.91). Conclusions: Vitamin K non-receipt increased over the study period and accelerated after January 2026. Because vitamin K recommendations were not changed by the January vaccine schedule, this association may reflect broader impacts to confidence in newborn preventive care. Future studies should examine causal mechanisms, parental decision-making, and associated clinical outcomes.

Importance: Chronic stress may contribute to adverse health outcomes through cumulative physiologic dysregulation. Allostatic load (AL), a composite measure of multisystem physiologic burden, may capture biologic effects of structural, social, and psychosocial stress not reflected by self-reported measures. Objective: To evaluate racial and ethnic differences in AL among women with familial cancer risk and examine how socioeconomic status, psychosocial factors, clinical characteristics, and health behaviors contribute to variations in AL. Design: Cross-sectional study of underrepresented minority participants enrolled in the HERSTORY cohort from October 2023 through September 2025, with comparison participants from the UCLA ATLAS biobank. Setting: UCLA academic health system. Participants: The study included 303 racially and ethnically diverse female HERSTORY participants aged [&ge;]35 years with a family history of cancer and matched non-Hispanic White female ATLAS participants (n=709). Exposures: Race and ethnicity, age, neighborhood deprivation, cancer history and stage, depression, perceived stress, cancer worry, and physical activity. Main Outcomes and Measures: The primary outcome was AL, calculated from cardiometabolic and organ-function measures. A secondary index incorporated race- and ethnicity-specific neutrophil-to-lymphocyte ratio (NLR) derived from 326,826 women in the UCLA Health population. Multivariable regression models evaluated factors associated with elevated AL. Results: Compared with matched non-Hispanic White participants, Black and Asian/Pacific Islander HERSTORY participants had significantly higher AL after adjustment. Hispanic/Latina participants did not have significantly elevated AL. Older age, greater area-level socioeconomic deprivation, and depression were independently associated with higher AL. Prior cancer diagnosis, cancer worry and perceived stress were not significantly associated with AL, whereas regular physical activity was associated with lower AL. Among cancer patients, advanced stage was associated with greater AL. Conclusions and Relevance: This study demonstrates elevated AL among understudied racial/ethnic minority groups with familial cancer risk and identifies associations with neighborhood deprivation, depression, and physical activity. The association between cancer stage and AL suggests that physiologic stress may reflect variation in cancer burden. The lack of association with perceived stress and cancer worry further indicates that physiologic and self-reported psychosocial measures capture distinct dimensions of stress. The development of race/ethnicity-specific NLR thresholds derived from large population samples provide a benchmark for future studies.

Background: Inequalities exist for many health outcomes, but there is limited evidence regarding menstrual symptoms despite their importance for health and wellbeing. We aimed to investigate inequalities in menstrual symptoms according to socioeconomic position and childhood adversity. Methods: In two generations (G0 mothers and G1 offspring) from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK prospective cohort study, we examined associations of multiple indicators of socioeconomic position (SEP) and adverse childhood experiences (ACEs) with menstrual symptoms (pain, abnormal uterine bleeding, and premenstrual syndrome (PMS) measured 3-8-years post-birth in G0 and 17-21-years-old in G1), using multivariable logistic regression. Samples ranged from 4,828 to 9,335 G0 participants and 1,288 to 2,757 G1 participants depending on the exposure-outcome association. Missing data were addressed using multiple imputation and inverse probability weighting. Results: Financial difficulties were associated with greater odds of menstrual pain (G1 OR 1.41; 95% CI 1.07, 1.86: G0 OR 1.55; 95% CI 1.36, 1.76) and irregular cycles (G1 OR 1.60; 95% CI 1.12, 2.29: G0 OR 1.48; 95% CI 1.27, 1.72) in both generations, as well as with short/long cycle lengths in G0 only. Lower education and manual social class were also associated with these three menstrual symptoms in at least one generation. Conversely, higher SEP was associated with PMS in both generations. Higher cumulative ACEs were consistently associated with menstrual pain (4+ compared to none: G1 OR 2.15; 95% CI 1.48, 3.11: G0 OR 1.52; 95% CI 1.29, 1.80) and irregular cycles (G1 OR 1.92; 95% CI 1.20, 3.09: G0 OR 1.54; 95% CI 1.26, 1.87) but not cycle length. Lower parental education, financial difficulties, and cumulative ACEs were associated with heavy bleeding in G1 offspring only, whereas financial difficulties, own manual social class, and cumulative ACEs were associated with prolonged bleeding in G0 mothers only. Higher cumulative ACEs were also associated with PMS in G1 offspring only. Conclusions: We found evidence of inequalities according to socioeconomic disadvantage and childhood adversity for multiple menstrual symptoms, although some associations were only observed in one generation. Findings suggest that menstrual symptoms are disproportionately experienced by socially and socioeconomically disadvantaged women.

Background: Patients receiving anti-TNF treatment for chronic inflammatory disease display impaired antibody responses, but it remains unclear how immune memory formation is affected. We evaluated antibody responses and memory B cells (Bmem) after COVID-19 booster vaccination in inflammatory bowel disease (IBD) patients receiving anti-TNF treatment. Methodology: Blood was sampled at baseline, 1, and 6 months after WH1/BA.5 bivalent or XBB.1.5 monovalent vaccination from 27 IBD patients receiving intravenous anti-TNF and 44 controls. Neutralizing antibodies were measured using an infectious virus assay. SARS-CoV-2 spike receptor binding domain (RBD)-specific serum IgG was quantified by ELISA, and RBD-specific Bmem were immunophenotyped by flow cytometry using recombinant proteins from ancestral, Omicron BA.1, BA.5, XBB.1.5, and JN.1 variants. Results: Serum IgG to vaccine RBD and neutralizing antibodies in patients increased pre to 1 month post-vaccination, but were lower than controls. Ancestral-, BA.5- and XBB.1.5-specific Bmem increased after vaccination but were significantly lower in patients than controls. Within RBD-specific Bmem, frequencies of recently activated CD21lo cells were increased after vaccination, and were higher in patients than controls. Fewer antigen-specific Bmem in patients expressed IgG4, and more expressed IgG3 or IgD following vaccination. Following vaccination, more RBD-specific Bmem recognized multiple viral variants. However, patients had fewer Bmem that could bind to subvariants than controls. Conclusion: Antibody and Bmem responses to COVID-19 booster vaccination in anti-TNF-treated IBD patients displayed reduced capacity, durability and cross-reactivity, suggesting impaired immune memory for protection against breakthrough infection. This supports the recommendation for annual booster vaccination to prevent severe disease and viral spread.

Community Health Promoters (CHPs) connect households with formal health services. In maternal nutrition, they provide counselling, follow-up and referrals. However, pregnant women experiencing poverty, food insecurity, and socio-cultural issues in resource-constrained settings may be unable to act on nutritional advice. While social protection could alleviate such socioeconomic issues, maternal nutrition and social safety nets operate in institutional silos, creating gaps that systematically exclude vulnerable mothers from essential relief. This qualitative study examines how CHPs navigate these gaps across three underserved Kenyan settings. We analysed semi-structured interviews of 12 purposively selected CHPs from a broader study of 75 stakeholders, using the Braun and Clarke thematic analysis framework. CHPs described recurrent gaps between household needs and resources available through formal maternal health, nutrition, and social protection systems. CHPs stepped in; extending follow-up care, brokering information, negotiating access, and spending personal resources with inadequate formal mechanisms. They experienced emotional and relational pressure from community mistrust, cultural limitations, administrative gatekeeping, digital-system failures, heavy workloads, and performance targets tied to unreliable pay. These insights reveal that CHPs act as invisible safety nets for fragmented services, taking on burdens that official programs overlook. We describe this as workforce cost absorption. Recognising this hidden contribution is important for workforce planning and for designing integrated maternal nutrition and social protection programs.

Objective: To determine whether paradoxical relief, feeling unusually better after a seizure compared to before it, is more common after functional/dissociative seizures (FDS) than epileptic seizures (ES), quantify its diagnostic accuracy, and explore its relationship with preictal symptoms. Methods: Consecutive patients admitted to a tertiary epilepsy unit for prolonged inpatient EEG monitoring underwent a structured clinical interview on admission, before final multidisciplinary diagnostic classification. Preictal dissociative and autonomic/somatic symptom burden was assessed using items adapted from established questionnaires. Diagnostic classification incorporated clinical history, seizure semiology, video electroencephalography findings, and collateral information. Patients with dual or indeterminate diagnoses were excluded. Associations with paradoxical relief were examined using logistic regression, followed by an exploratory mediation analysis. Results: Of 176 patients assessed, 66 with FDS and 65 with ES were included. Paradoxical relief was reported by 46/66 patients with FDS (69.7%) and 10/65 with ES (15.4%; unadjusted odds ratio [OR] 12.65, 95% confidence interval [CI] 5.57 to 31.09). As a diagnostic signal for FDS, paradoxical relief had 69.7% sensitivity (95% CI 57.1 to 80.4), 84.6% specificity (95% CI 73.5 to 92.4), a positive likelihood ratio of 4.53 (2.51 to 8.19), and a negative likelihood ratio of 0.36 (0.24 to 0.52). FDS diagnosis remained independently associated with paradoxical relief after adjustment (OR 10.59, 95% CI 3.42 to 38.06). In a parallel mediation analysis, dissociative symptom burden showed a significant indirect effect, accounting for 19.5% of the association between diagnostic group and relief, whereas the indirect effect through somatic/autonomic symptom burden was not significant. Significance: Paradoxical relief is substantially more common after FDS than ES and may provide a simple, clinically useful diagnostic signal. Its absence does not exclude FDS, and the finding requires external validation. The association with dissociative symptoms is exploratory and supports prospective investigation of whether relief reflects transient resolution of a disturbed, disembodied preictal state.

Background: Fibrosis, characterised by excessive accumulation of collagen type I (COL1), is a common feature of chronic diseases, including liver diseases (LDs), chronic kidney disease (CKD) and heart failure (HF). COL1 degradation products can be detected in urine by proteomics/ peptidomics analyses and may serve as non-invasive biomarkers of fibrosis. We aimed to identify a common molecular signature of fibrosis across these diseases that may ultimately guide interventions to slow disease progression and prevent organ damage. Methods: Using capillary electrophoresis coupled to mass spectrometry (CE-MS), naturally occurring COL1 degradation products (peptides) in the urine of patients with fibrotic disease, LDs (n=127), CKD (n=263) or HF (n=187), were investigated and compared with the same number of matched controls. Disease-associated COL1 peptides were identified separately for each condition, and peptides showing consistent associations across the three diseases were selected to define a common fibrosis signature. A support vector machine model based on the selected peptides was developed and validated in independent cohorts of patients with LDs (n=110), CKD (n=93), HF (n=32) and controls (n=643). Results: We identified a common fibrotic signature consisting of 50 COL1 degradation products, mainly downregulated in fibrosis. A model based on these peptides achieved a strong performance, with an area under the receiver operating characteristic curve (AUC) of 0.935 (95% confidence interval (CI) 0.917-0.953, p<0.0001) in an external validation cohort comprising pooled disease groups (LDs, CKD, and HF) and controls. Performance was maintained in LDs, CKD and HF, with AUCs of 0.917 (95% CI 0.890-0.944, p<0.0001), 0.951 (95% CI 0.931-0.971, p<0.0001) and 0.950 (95% CI 0.903-0.997, p<0.0001), respectively. The model scores were significantly associated with fibrosis stage in LDs (p=0.0097) and with interstitial fibrosis and tubular atrophy in CKD (p=0.045). Conclusion: A model of urinary COL1 peptides captures a shared collagen degradation signature across organs and diseases, enabling the non-invasive assessment of fibrosis irrespective of its origin. As these peptides exclusively reflect collagen degradation, the findings suggest impaired collagen degradation as a driver in fibrosis. Future clinical studies are warranted to evaluate the utility of this model for early fibrosis detection and earlier implementation of anti-fibrotic interventions.