Evolution, Medicine, and Public Health

While SARS-CoV-2 and influenza continue to place a significant burden on population health, within-household differences in decisions towards vaccination and seeking care across these two pathogens, and across sociodemographic groups, remain largely unexplored. By conducting a household-level survey in Illinois, we found that many individuals made inconsistent decisions about vaccination: among all adults, 29% were vaccinated for only one of COVID-19 or influenza, and among those with children in the home, 39% lived with a child whose influenza or COVID-19 vaccination status differed from their own. A higher proportion of adults were vaccinated against COVID-19 compared to influenza, while the opposite was true for those younger than 18 years old. These differences hold even when accounting for disparities in coverage by age, race/ethnicity, political affiliation, and socioeconomic status. While vaccinated individuals consistently reported wanting to protect themselves or others, those who declined vaccination reported highly heterogeneous reasons ranging from resource constraints to distrust or misconceptions about vaccination. These differences are even more pronounced for COVID-19, with larger partisan gaps and higher refusal driven by safety concerns, lack of trust, or religious reasons than those who decide not to get the influenza vaccine. In contrast to vaccination, the decision to seek medical care when sick showed opposite sociodemographic trends, that are likely attributable to illness severity. Our findings highlight that closing gaps in COVID-19 and influenza vaccination coverage will require an integrative strategy that accounts for diverse motivations, fears, and barriers to access, while addressing social inequalities common to both diseases.

Background: Wearing facemasks and practising social distancing slow the spread of respiratory pathogens. However, in the event of a new pandemic emerging, the willingness of populations to voluntarily adopt these behaviours is unclear. Methods: A discrete choice experiment was conducted among 2,006 UK-based adults. Participants were presented with hypothetical scenarios describing the emergence of a respiratory virus pandemic and were asked to choose when they would wear facemasks and practise social distancing. A mixed multinomial logit model was used to jointly estimate how disease severity and prevalence, uncertainty in these quantities, and individual-level characteristics influence behavioural choices. Findings: Participants were averse to facemasks and social distancing in the absence of pandemic risk. For each ten-unit increase in severity (10 additional hospitalisations/1,000 infections), the odds of always wearing a facemask outside the home increased by 15.9% (95%CI: 14.3%, 17.5%), relative to rarely/never, and the odds of avoiding all people as much as possible increased by 16.4% (14.6%, 18.2%), relative to not avoiding anyone. Greater disease prevalence, uncertainty in disease severity or disease prevalence, a university education, prior COVID-19 vaccination and non-white ethnicity were also associated with choosing to always wear facemasks and avoid all people as much as possible. The probability of participants choosing to rarely/never wear facemasks varied from 13.4% (11.9%, 14.9%) in the lowest-risk scenario to 1.4% (1.2%, 1.7%) in the highest-risk scenario. Interpretation: Perceived risks of disease and associated uncertainty drive intention of UK adults to adapt their behaviour in a future pandemic.

Research on under-vaccination often segments populations using demographic or administrative variables that are operationally useful but fail to capture identity dimensions relevant to vaccination decisions. Drawing on social identity theory, we propose an identity-landscape approach distinguishing identity membership, identity centrality, and multidimensional identity structure. Using a cross-sectional survey of 1,000 UK parents, we measured 65 identity indicators, identity-importance ratings, and their association with attitudinal and behavioural hesitancy toward childhood vaccination using validated scales. Beyond established socio-demographic predictors, alternative-medicine and natural-lifestyle identities, as well as affiliation with social media networks, were linked to greater hesitancy. Greater centrality of religion and political affiliation within personal identity was also associated with higher hesitancy. Principal component analysis suggested that individuals actively engaged across multiple societal issues were more hesitant, whereas stereotypically male-gendered engagement was associated with lower hesitancy. An identity-focused population segmentation may identify previously unrecognized undervaccinated groups and inform innovative tailored immunization campaigns.

Background: Sexual and gender minorities (SGM), including men who have sex with men (MSM) and transgender women, often face stigma, legal constraints, and limited access to sexual and reproductive health services. These conditions restrict prevention and care, increasing vulnerability to HIV and human papillomavirus (HPV) infections. While strong HIV-HPV interaction is documented in high-income settings, evidence from low- and middle-income countries remains limited. This study examines the burden, co-infection dynamics, and progression of HPV infection and anal dysplasia among MSM and transgender women in Pakistan. Methods: A cross-sectional study was conducted between September 2015 and October 2016 among men who have sex with men (MSM) and transgender women recruited from sexual health and antiretroviral therapy centers in Karachi. Eligible participants were aged [&ge;]18 years and self-reported anal sex within the past 6 months (N=298). Two anal specimens were collected for HPV DNA detection and genotyping using PCR, and anal squamous intraepithelial lesions (ASIL) were assessed cytologically using the Bethesda classification. Associations were estimated using Cox proportional hazards regression algorithms to derive prevalence ratios (PRs). Results: Among participants, 44% (n=133) were living with HIV. Overall HPV prevalence was 65.1%, rising to 87% among HIV-positive individuals compared to 48% among those without HIV ({chi}{superscript 2}p[&le;]0.001). Likewise 28.9% of participants living with HIV were infected with two or more than two types of HPV as compared with 18.8% participants without HIV ({chi}{superscript 2}p[&le;]0.001). HIV infection was strongly associated with HPV acquisition (adjusted PR 2.81, 95% CI 2.16-3.82). Among HPV-positive participants (n=194), 58.8% were co-infected with HIV. High-risk HPV was highly prevalent among those living with HIV (83.2% vs. 35.3% ({chi}{superscript 2}p[&le;]0.001)), with HPV16 as the dominant oncogenic type. Multiple HPV infections were more common among HIV-positive individuals ({chi}{superscript 2}p[&le;]0.001), and HIV seropositivity was 3.43 (95% CI: 2.55-3.51) times higher among those with high-risk HPV. Co-infected participants demonstrated prolonged smoking, longer duration of sex work, high-intensity sex work with limited condom negotiation, and higher prevalence of anal warts (all p<0.05). Anal dysplasia (ASIL) was present in 35% of participants and was higher among HIV-positive individuals (42.4% vs. 28.1%, p<0.001). HIV-HPV co-infection was independently associated with ASIL (adjusted PR 1.75, 95% CI 1.07-2.88), while high-risk HPV further amplified this risk (PR 3.04, 95% CI 1.75-5.26). Conclusion: These findings demonstrate a biological continuum in HIV-positive MSM and transgender women, where HIV increases HPV acquisition, persistence, and multiplicity, accelerating progression to anal dysplasia. This reflects a syndemic shaped by biological interaction and structural vulnerability. Integrating HPV screening and vaccination within HIV services is essential to interrupt progression to cancer in this high-risk population.

Lower cognitive ability measured in childhood or late adolescence has been consistently associated with higher mortality risk across adulthood. However, this evidence largely relies on single assessments, leaving it unclear to what extent mortality risk reflects cognitive differences established early in life versus developmental divergence during adolescence - a period of substantial neurocognitive plasticity. Using two nationally representative Swedish cohorts comprising 9,412 males born in 1948 and 1953, we linked cognitive ability assessed in primary school at age 13 years and military conscription at age 18 years to all-cause and cause-specific mortality recorded in nationwide registers through 2025. We decomposed late-adolescent cognitive ability into childhood cognitive level and adolescent cognitive change and evaluated their independent associations with mortality. Childhood cognitive level (HR = 0.81; 95% CI, 0.78-0.85) and adolescent cognitive change (HR = 0.84; 95% CI, 0.79-0.89) independently predicted lower mortality risk, also after adjustment for parental education. Childhood cognitive level and adolescent cognitive change showed partially distinct cause-specific patterns. Childhood cognitive level was most strongly associated with mortality from intrinsic causes, whereas adolescent cognitive change showed relatively stronger associations with external causes, particularly accidental deaths. Although adolescent cognitive change was associated with psychosocial factors including education and psychiatric diagnosis at conscription, its association with mortality persisted after adjustment for these factors. These findings suggest that cognitive development during adolescence carries independent prognostic information regarding long-term survival beyond cognitive level established by late childhood, highlighting adolescence as a consequential period for lifelong health.

Background: It is well-established that males have a higher mortality risk than females. Immune cells and their function are known to undergo characteristic changes during aging, and immune cells are known to have sex differences. Immune cells and their function have been linked to mortality risk, but no studies have investigated to what degree, if at all, Immune Cell Biomarkers (ICBs) contribute to the known differences in mortality risk by sex. Methods: Using participant data from the Health and Retirement Study (n = 8,822), we applied multivariable linear regressions adjusting for age, cytomegalovirus (CMV) serostatus, sex, and race/ethnicity to identify differences by sex in 48 immune cell biomarker (ICB, e.g. T cells, B cells, Monocytes, etc.) percentages and counts (measured in 2016). We studied how the associations between ICBs and mortality risk differ by sex using stratified Cox Proportional Hazard (CPH) models. We estimated how inclusion of sex explained the relationship between ICBs and all-cause mortality, and conversely, how inclusion of individual and all ICBs combined explain the relationship between sex and all-cause mortality using multivariable modeling approaches. Results: Differences in ICBs by sex range between 2-38% (39/48 statistically significant). 9 ICBs were significantly associated with mortality risk in the entire sample. While different ICBs were significantly associated with mortality risk in the stratified analyses, particularly with respect to monocyte, B cell, and NK cell populations, adjusting for sex modestly influenced the hazard ratios of the ICBs (sex: 8 ICBs, percent change <5.4%). Furthermore, individual and cumulative contributions of ICBs in explaining the differences in mortality risk by sex were not significant.

Background: Persons with disabilities, particularly deaf individuals, remain a largely overlooked population in sexual and reproductive health (SRH) programming globally, with this gap especially pronounced in low- and middle-income countries. Deafness imposes substantial barriers to accessing information and services that are routinely available to hearing peers, further exacerbated in the post-COVID-19 era. This study assessed deaf adolescents' knowledge of and access to SRH education and services in Wakiso District, Uganda, and explored systemic, institutional, community, and adolescent-level factors shaping access. Methods: A mixed-methods cross-sectional study was conducted at Wakiso Secondary School for the Deaf from July 2022 to January 2023. Quantitative data were collected from 70 consecutively sampled deaf adolescents aged 13-19 years using a structured questionnaire. Qualitative data were gathered through key informant interviews (KIIs) with four purposively selected stakeholders and a focus group discussion (FGD) with deaf adolescent students. Qualitative data were analysed thematically. Results: The mean participant age was 17 years (SD {+/-}1.8); 65.7% were female. A large majority (88.6%) had heard of SRH components, and 98.6% perceived a need for SRH education or services. However, 84.3% reported challenges accessing these services at least 85% of the time. No participant had ever received SRH education or services through a formal health facility. The FGD revealed that adolescents' conceptualisation of SRH was narrow, centred on body hygiene and HIV prevention, while service-seeking was reactive and symptom-driven. Five cross-cutting themes emerged from the KIIs and were reinforced by FGD findings: communication barriers; inadequate and inaccessible services; family and community isolation; existing platforms and positive practices; and negative provider attitudes and limited capacity. The school nurse emerged as the sole functional SRH access point for most participants. Conclusion: Despite high awareness and near-universal perceived need, deaf adolescents in Uganda face profound multilevel barriers to SRH access. Structural, psychosocial, and knowledge-related barriers interact to exclude this population from formal health services. Findings call for disability-responsive SRH integration into health systems, training of health workers in accessible communication, community capacity building, and co-design of SRH programmes with deaf adolescents.

Aim: Cross-sectional summaries of periodontitis based on clinical attachment loss (CAL) are, by definition, conditioned on surviving teeth. Because the most severely affected teeth are more likely to have been lost, these measures may underestimate cumulative disease burden and show an artificial flattening (attenuation) of severity with age. We hypothesised that measures more sensitive to severe attachment loss would show greater attenuation at older ages than measures defined across a broader range of sites. Materials and Methods: Using nationally representative data from adults aged 30+ years in NHANES 2009-2014, we examined age-specific trajectories across multiple continuous measures of periodontal severity and assessed whether divergence between measures followed the pattern predicted under severity-dependent tooth loss. Results: The proportion of observable sites declined from 93% at ages 30-34 to 68% at 80+ years, establishing the structural basis for the divergence observed across severity measures. All severity measures showed nonlinear attenuation with age, with distortion increasing with severity threshold. Higher-threshold measures exhibited the greatest attenuation, while lower-threshold measures showed more stable trajectories. Conclusions: Cross-sectional summaries of periodontitis reflect disease among surviving teeth rather than cumulative damage across teeth originally at risk. Attenuation at older ages is consistent with depletion of the most severely affected teeth rather than biological slowing. Distortion varies by measure, with higher-threshold and mean-based indices most affected, whereas the CAL 3+ mm threshold provides a more stable basis for age comparisons.

Antibody-dependent enhancement (ADE) is a major concern across orthoflavivirus infections, yet how multiple viral exposures shape enhancement risk remains incompletely understood. Here, we integrated serosurveillance from Saude, Brazil with functional immunologic analyses to define how yellow fever virus (YFV)-associated orthoflavivirus immune histories influence ADE phenotypes. Using serocomplex-specific anti-premembrane antibody profiling validated by microneutralization assays, plasma samples were stratified into YFV-only, YFV+DENV, and YFV+DENV+ZIKV exposure groups. In Fc gamma receptor-bearing U937 cells, YFV-only plasma demonstrated minimal enhancement activity, whereas cumulative orthoflavivirus exposure generated broader ADE phenotypes across heterologous viruses. In IFNAR1-/- passive-transfer models, YFV-only plasma did not enhance ZIKV or DENV2 infection in vivo. In contrast, YFV+DENV plasma increased ZIKV viremia and accelerated mortality kinetics, while YFV+DENV+ZIKV plasma demonstrated concentration-dependent enhancement phenotypes. Collectively, these findings indicate that isolated YFV immunity does not predispose to ADE, whereas cumulative orthoflavivirus exposure generates antibody repertoires capable of producing concentration-dependent enhancement in vivo.

Atherosclerosis is a systemic vascular process linked to cardiovascular, cognitive and renal outcomes. DNA methylation (DNAm)-based scores of atherosclerosis may capture cumulative biological processes underlying vascular aging. Here, we examined associations of DNAm scores for coronary artery calcification (DNAm-CAC) and carotid plaque (DNAm-cPlaque), derived from a large study of imaging-based subclinical atherosclerosis, with prevalent and incident outcomes in two population-based cohorts of older adults: the Health and Retirement Study (HRS; n = 3,875) and The Irish Longitudinal Study on Ageing (TILDA; n = 487). Higher DNAm scores were associated with adverse cardiometabolic profiles and socioeconomic indicators. In HRS, higher DNAm-CAC was associated with prevalent cardiovascular disease (odds ratio per SD, 1.16; 95% confidence interval (CI), 1.07-1.26), lower cognitive function ({beta} = -0.50, 95% CI -0.68 to -0.32) and lower estimated glomerular filtration rate (eGFR; -1.7 ml min-1 1.73 m-2, 95% CI -2.6 to -0.8) in unadjusted models. After adjustment for demographic and clinical risk factors, DNAm-CAC ({beta} = -0.29, 95% CI -0.46 to -0.13) and DNAm-cPlaque ({beta} = -0.24, 95% CI -0.42 to -0.06) remained associated with lower cognitive function, and DNAm-cPlaque was associated with incident cognitive impairment or dementia (hazard ratio per SD, 1.16; 95% CI, 1.01-1.32). Associations were attenuated after further adjustment for race/ethnicity and socioeconomic indicators. In TILDA, higher DNAm-cPlaque was associated with worse cognitive performance (incidence rate ratio, 1.11; 95% CI, 1.01-1.21), increased risk of incident cardiovascular disease (hazard ratio, 1.18; 95% CI, 1.00-1.42) and lower eGFR, with consistent associations observed for DNAm-CAC. These findings suggest that DNAm-based scores of atherosclerosis capture systemic vascular processes linked to multiple age-related outcomes across populations. Further work is needed to clarify the biological pathways reflected by these scores and their relation to cumulative and socially patterned vascular risk.

Background Bacterial fitness is shaped by interactions between genome variation and environmental context, yet how these interactions determine its predictability and heritability remains unclear. In the clinically important pathogens of Klebsiella pneumoniae, a leading cause of hospital-acquired infections, this question is particularly pressing. Despite extensive genomic characterization, we still lack a systematic understanding of how genome-wide variation translates into fitness across diverse environments in K. pneumoniae. Methods We filled this gap by profiling a systematic collection of 1,462 clinical K. pneumoniae isolates across 214 diverse environmental and pharmacological stress conditions using high-throughput chemical genomics. Fitness was quantified from colony growth and integrated with whole-genome sequencing data. Genome-wide association analyses identified genetic determinants of fitness, and machine learning models incorporating genomic features were used to predict fitness.Results Fitness exhibited a strongly environment-dependent genetic architecture, with modest but significant concordance between genetic background and phenotypic variation. Under antibiotic and stress-combination conditions, fitness was driven by discrete, high-effect determinants, including known resistance genes, resulting in stronger signals and improved predictability. In contrast, non-antibiotic environments showed more polygenic and distributed architectures with weaker associations. Genome-wide analyses identified both established and previously uncharacterized genes linked with fitness across conditions. Resistance and virulence determinants exhibited clear context-dependent trade-offs, conferring fitness advantages under selection but imposing costs in non-selective environments. Consistent with this, plasmid carriage showed environment- and genotype-dependent fitness effects, with benefits under antibiotic pressure and measurable costs otherwise. Genomic variant-based models for fitness prediction achieved moderate performance (Mean Spearman correlation ({rho}) = 0.36 (95% CI: 0.18-0.67) for predicted versus observed values in unseen data) across conditions, with improved accuracy under strong antibiotic selective pressures, and produced well-calibrated prediction intervals with high coverage. Despite strong population structure effect on predictions, models captured predictive gene and SNP biomarkers for fitness. Conclusion These findings highlight that bacterial fitness is an emergent property of genome-environment interactions rather than a fixed attribute of genotype. This work establishes a unified high-dimensional genotype-phenotype framework linking genomic variation to fitness across diverse conditions in a major pathogen, with broader implications for other pathogenic bacterial species.

Background: Antimicrobial resistance is the world's silent pandemic. The public knowledge, attitudes, and practices (KAP) about antibiotic usage are strongly related to the growing problem in Nepal. Methods: A cross-sectional descriptive survey was done to 263 respondents. Information on KAP regarding antibiotics, primary healthcare sources, and demography was collected through a questionnaire. To identify health literacy gaps and characteristics that contribute to improper antibiotic use, this study assessed these variables across an age group from 18 to 60 years. Descriptive statistics analysis was performed to analyze the data. Results: The majority of respondents were between the ages of 18 and 39 (85.1%), female (63.1%), and had at least a bachelor's degree (67.8%). Significant misunderstandings about antibiotics remained, even though 77.6% of respondents correctly recognized antibiotics as effective against bacteria; 44.1% incorrectly believed that antibiotics cure viral diseases, and 87.8% felt that antibiotics should be stopped right away if adverse effects develop. In practice, 52.9% acknowledged quitting antibiotics as soon as symptoms improved, despite 89.4% consulting doctors. Additionally, 43% of respondents said they have taken antibiotics without a prescription, frequently due to pharmacist recommendations (21.67%) and financial or geographical constraints. The main sources of information were doctors (11.07%) and pharmacist-doctor combinations (14.88%), yet 81.8% of respondents said they had never heard of the phrase antimicrobial resistance. Conclusion: There is a significant lack between theoretical understanding and practical application, despite the high levels of fundamental knowledge toward the prohibition of non-prescription sales. Self-medication and early withdrawal are still common inappropriate practices. It is crucial to implement focused teaching initiatives that highlight the differences between bacterial and viral diseases as well as the risks associated with leftover medicine. It is advised to use digital platforms for younger demographics and to strengthen the role of pharmacists in order to reduce AMR.

Background: Periodontitis is defined by cumulative, irreversible tissue destruction, yet population-based measurement typically relies on cross-sectional indicators derived from retained teeth. Destruction that occurred earlier in life, particularly disease severe enough to result in tooth loss, is structurally excluded from these measures, potentially leading to systematic underestimation of lifetime periodontal burden. Objective: To develop and evaluate a measurement framework that estimates lifetime periodontal burden from cross-sectional data by explicitly incorporating informative tooth loss under etiological uncertainty. Methods: Data were drawn from 10,324 adults aged [&ge;]30 years participating in the 20090-2016 National Health and Nutrition Examination Survey (NHANES) who completed full-mouth periodontal examination and glycated hemoglobin (HbA1c) testing. Lifetime periodontal burden was estimated by combining observed clinical attachment loss in retained teeth with probabilistic contributions from missing teeth, using three alternative age-stratified attribution schedules derived from epidemiological studies of periodontal extraction. Performance was compared with conventional measures of periodontal severity and extent using distributional analyses, correlations with HbA1c, discrimination of diabetes status, and relative importance analysis. Age-adjusted models were treated as sensitivity analyses. Results: Estimated lifetime periodontal burden exhibited strong, monotonic age gradients across glycemic categories, in contrast to more attenuated patterns observed for severity and extent. Across attribution schedules, lifetime burden showed stronger correlations with HbA1c ({rho} = 0.30-0.32) than conventional measures. In multivariable models including all indices, lifetime burden retained an independent association with HbA1c, whereas severity and extent contributed little unique information. Discriminative performance for diabetes status was consistently higher for lifetime burden than for conventional measures and remained stable across attribution schedules. Conclusions: Lifetime periodontal burden can be estimated from cross-sectional data by explicitly modelling informative tooth loss rather than restricting measurement to retained teeth. Incorporating historical tissue loss under uncertainty yields a more coherent representation of cumulative periodontal destruction than snapshot-based measures and provides a methodological basis for life-course-oriented periodontal epidemiology.

Clonal hematopoiesis of indeterminate potential (CHIP) represents the age-related expansion of hematopoietic stem cells with preleukemic mutations. However, its association with all-cause and cause-specific mortality has not been well characterized in older adults. We aimed to evaluate whether CHIP is associated with all-cause and cause-specific mortality in a population of older women in the United States. Our study included 6,704 participants in the Women?s Health Initiative Long Life Study (WHI-LLS) without hematologic malignancy. The co-primary exposures were any CHIP (variant allele frequency [VAF] [&ge;] 2%) and large CHIP (VAF [&ge;] 10%), and the primary outcome was all-cause mortality. Multivariable-adjusted Cox proportional hazards models tested the associations of CHIP and CHIP subtypes with all-cause and cause-specific mortality. Any CHIP and large CHIP were independently associated with all-cause mortality, with multivariable-adjusted hazard ratios (aHRs) of 1.12 (95% confidence interval [CI] 1.04-1.21; P = 0.003) and 1.28 (95% CI 1.15-1.43; P < 0.001), respectively. In gene-specific analyses, non-DNMT3A CHIP was associated with all-cause mortality (aHR: 1.22 [95% CI: 1.12-1.34], P < 0.001), while DNMT3A CHIP was not (aHR: 1.07 [95% CI: 0.98-1.18], P = 0.13). Furthermore, large CHIP was associated with cardiovascular (aHR: 1.29 [95% CI: 1.08-1.55], P = 0.006), cancer (aHR: 1.49 [95% CI: 1.11-2.02], P = 0.009), and neurologic (aHR: 1.40 [95% CI: 1.07-1.84], P = 0.02) death. In this cohort of older women, CHIP, particularly large clones and non-DNMT3A CHIP, was associated with all-cause and cause-specific mortality. These findings suggest that clonal size and subtype may differentially influence mortality risk.

Background: Diabetes mellitus (DM) worsens pulmonary tuberculosis (TB) and drives systemic hyper-inflammation, but the underlying mechanisms remain unknown. Neutrophils have key roles in TB immunopathology and lung cavitation. Here, we determine the role of neutrophils in DMTB patients and in driving TB immunopathology. Methods: Sputum and plasma from 30 TB and 30 DMTB patients were analysed for proteases and cytokines using Luminex bead array. Whole blood transcriptomics identified transcriptional differences. Single-cell RNA sequencing characterised neutrophil subsets and dysregulated pathways. Neutrophil function of poorly-controlled DM patients (HbA1c>8%) and healthy controls (HC) were examined following Mycobacterium tuberculosis stimulation, including reactive oxygen species (ROS), neutrophil extracellular traps (NETs), and phagocytosis. Pathways were interrogated using chemical inhibitors, protein array and western blot. Results: Compared to non-diabetic TB patients, poorly-controlled DMTB patients showed up-regulated sputum MMP-8 and MMP-9, associated with increased collagen-destruction and lung cavity formation. Circulating neutrophil count and neutrophil-derived plasma MMP-8 were up-regulated, alongside transcriptional enrichment of extracellular matrix degradation and inflammatory pathways including TNF and RAGE. Single-cell profiling identified reduced cycling neutrophil subset and myelocytes in DMTB, with overall reduced antibacterial and cell-killing signatures. Ex vivo mycobacterial stimulation of DM neutrophils increased ROS and MMP-9 with impaired NETs and delayed phagocytosis. TNFR1, TNFR2, and RAGE were up-regulated. RAGE inhibition with rosiglitazone mitigated Mtb-induced ROS and MMP-8 release. Conclusion: DM worsens neutrophil-driven tissue destruction and inflammation in TB via dysregulated TNF and RAGE-signalling, priming neutrophils towards immunopathology. Targeting RAGE alongside tight glycaemic control may dampen neutrophil hyper-inflammatory responses to limit tissue destruction.

Maternal health during pregnancy is critical for favorable birth outcomes and long-term wellbeing of both mothers and infants. Women in rural, malaria-endemic regions face unique biological and socioeconomic challenges that may increase the risk of adverse pregnancy outcomes (APOs). This study investigated the incidence and determinants of APOs among pregnant women attending antenatal care at Webuye sub-County Hospital in Western Kenya, a rural malaria-endemic setting. We conducted a retrospective cohort analysis utilizing previously collected data of 300 women enrolled during early pregnancy and followed through delivery. Maternal demographic, clinical, and infection-related factors were assessed, and associations with APOs were evaluated using chi-square tests and multivariable logistic regression. Maternal age and gestational age at enrollment were significantly associated with malaria history (P<0.001). Maternal BMI abnormality (124.5/1000 pregnancies), anemia (99.3/1000), fetal or neonatal death (81.3/1000), and preterm birth (43.8/1000) were observed (all P<0.001), suggesting a substantial burden. Younger mothers (<20 years) and older mothers (>35 years) were significantly more likely to develop anemia (P =0.026), and prior malaria infection further increased anemia risk (P =0.02). Abnormal urinalysis findings indicative of urinary tract infection were significantly associated with low birthweight (P =0.031). No significant associations were found between APOs and infant sex, parity, gravidity, or maternal ABO blood type. These findings highlight a substantial burden of APOs in this rural population, exceeding national and global estimates. Strengthening malaria prevention, nutritional support, urinary infection screening, and encouraging early antenatal care attendance are critical to improving maternal and neonatal outcomes. Targeted interventions for adolescent and older mothers, along with enhanced point-of-care diagnostics, may reduce preventable complications in similar resource-limited, malaria-endemic settings.

Methicillin-resistant Staphylococcus (MRS) infections are a significant public health concern. Anterior nares serve as a major reservoir and source of spread of MRS ssp. People living with HIV (PLWHIV) tend to be at higher risk of colonisation with MRS organisms due to frequent healthcare exposure. We assessed the prevalence of MRS nasal carriage and associated factors among PLWHIV at the HIV clinic of Kiruddu National Referral Hospital, Kampala, Uganda, from May to July 2024. Nasal swabs from 256 PLWHIV were cultured, and microbiological isolation was performed at MBN Clinical Laboratories. Prevalence was calculated as proportions, and logistic regression identified associations with clinical and socio-demographic factors (p < 0.05). Of 256 participants, 163 (63.7%) carried Staphylococcus, with 82 (32%) identified as MRS carriers (8.9% MRSA, 23% MRCoNS). Frequent hospital visits ([&ge;]3) (adjusted incidence risk ratio [A-IRR] = 1.18 x 107, p < 0.001), second-line antiretroviral therapy (ART) (A-IRR = 3.82, p = 0.041), and unsuppressed viral load (>1000 copies/mL) (adjusted odds ratio [AOR] = 11.3, 95% CI: 2.11-60.58, p = 0.005) were significantly associated with MRS carriage. Mask-wearing was protective against MRCoNS (A-IRR = 1.66, 95% CI: 1.06-2.58, p = 0.026). MRS isolates exhibited high resistance to erythromycin (81.7%) and trimethoprim-sulfamethoxazole (79.3%), but susceptibility to linezolid (93.9%). MRS nasal carriage is prevalent among PLWHIV. Individuals with frequent health care contact and those on second-line ART regimens are more susceptible to MRS colonization, while individuals who wear face masks and those with an undetectable HIV viral load are less susceptible. Antimicrobial Resistance (AMR) surveillance within HIV programs, enhanced infection control, ART adherence, and targeted screening for high-risk groups are critical to mitigate colonization.

Background: Self-reported confidence in health information seeking does not reliably predict accurate health knowledge, yet the population-level distribution of this discordance and its demographic predictors have received limited direct study. This study aimed to identify and characterize a Confident-Incorrect phenotype among U.S. adults: individuals with high perceived health information competence who simultaneously hold inaccurate or fatalistic beliefs about cancer. Methods: Cross-sectional analysis of HINTS 7 (N = 7,278). A Confidence Index (3-item digital literacy composite (Cronbach's = 0.674) and an Evidence-Consistent Knowledge Score (factual cancer knowledge minus a cancer fatalism composite; fatalism subscale = 0.563) were computed and combined into a discordance framework. Median-split classification produced four phenotypes. Gaussian Mixture Model clustering with four components provided moderate independent validation (inter-method agreement = 65.2%). Survey-weighted multinomial logistic regression (n = 5,771; McFadden pseudo-R2 = 0.129) examined phenotype predictors. Results: An estimated 20.3% of U.S. adults were classified as Confident-Incorrect. They reported confidence levels similar to Well-Informed adults (z = 0.72 vs. 0.82) but scored 2.8-fold lower on objective cancer knowledge (0.74 vs. 2.06 out of 4) and exhibited the highest cancer fatalism of any phenotype (3.17 vs. 1.65 out of 4). Only 14.3% correctly identified alcohol as a cancer risk factor (vs. 58.8% of Well-Informed adults). Cancer screening rates did not differ meaningfully across phenotypes. Lower education (OR = 0.754), Hispanic ethnicity (OR = 1.788), non-Hispanic Black race (OR = 1.893), higher social media use (OR = 1.097), and lower trust in scientists (OR = 0.749) independently predicted Confident-Incorrect membership. Conclusions: An estimated one in five U.S. adults is overconfident in health information competence while holding substantially inaccurate beliefs about cancer prevention. Cancer screening rates did not follow the expected gradient across phenotypes, a null finding that cautions against inferring immediate behavioral impact from observed belief gaps. Interventions targeting specific factual errors and cancer fatalism are more likely to reach this group than general health literacy programs.

The VACS 2.0 Frailty Index was developed using the VA health records system to identify frailty and predict mortality in older Veterans that were living with HIV. Systemic inflammatory indices have been associated with frailty, but little is known about the association between frailty and immunosenescence. We aim to investigate the potential link between soluble inflammatory indices, T cell expression of exhaustion and senescence markers, and frailty as measured by the VACS 2.0 index. We analyzed a one-time blood draw for plasma levels of inflammatory indices, T cell subsets and expression of exhaustion and senescence markers, and calculated VACS 2.0 index scores in a cohort of 30 older (>65 years) Veteran participants. We found that VACS 2.0 scores correlated with the number of prescribed medications in the older Veterans. Soluble TNF receptor levels strongly correlated with VACS 2.0 frailty scores. How these soluble TNF receptors are generated and whether they mechanistically contribute to frailty warrants further investigation.

Background Human challenge trials provide a unique opportunity to quantify pathogen infectivity in terms of the probability of infection given an inoculated dose. However, between-pathogen comparisons are often distorted by individual heterogeneity in host susceptibility and by differences in background immunity across trial populations. We examined how dose-dependent infection risks differ across common respiratory viruses when such heterogeneity is explicitly incorporated. Methods We conducted a systematic review of human challenge trials for four respiratory viruses: respiratory syncytial virus (RSV), influenza virus, rhinovirus, and adenovirus. Using the extracted data, we fitted dose-response models under different distributional assumptions, allowing both continuous susceptibility variation and discrete immune fractions. We compared alternative heterogeneity models and evaluated pathogen-specific dose-response patterns using original and scaled dose metrics. Results All four viruses showed substantial heterogeneity in host susceptibility, and models assuming homogeneous susceptibility were unsupported. RSV and influenza were best described by models with a distinct immune or effectively non-susceptible subgroup, and the estimated immune proportions were approximately 40% and 25%, respectively. In contrast, rhinovirus and adenovirus were better explained by continuously distributed susceptibility, with little evidence of a fully immune subgroup. On a scaled dose axis, rhinovirus and adenovirus showed steeper increases in infection risk with dose than RSV and influenza. Conclusions The structure of susceptibility heterogeneity differs across common respiratory viruses, which in turn shapes dose-dependent infection risks. Incorporating this heterogeneity is essential for valid cross-pathogen comparison and for interpreting human challenge data in epidemiologic and public health contexts.