Faculty Bibliography

Adversities in early life compromise children's nurturing care and impact their development. This study explored the biopsychosocial conditions associated with electroencephalography (EEG)-based brain activity in children living in rural Bangladesh, a setting with high rates of malnutrition and suboptimal psychosocial stimulation. In a substudy of the Benefits and Risks of Iron Supplementation in Children (BRISC) study in Bangladesh, we recorded resting EEG brain activity in a random subsample of 440 children at 11 months and 594 children at 20 months of age. EEG band power measures were derived for delta, theta, alpha, and beta power bands. Validated tools were used to assess maternal depression, household food insecurity, and psychosocial stimulation. Children's anthropometry, venous hemoglobin and ferritin concentrations, and inflammation were also measured. Linear regression analyses were conducted to identify the concurrent and lagged biopsychosocial conditions associated with EEG-based brain activity. Growth, nutritional status, psychosocial stimulation, and household food security were associated with concurrent and lagged brain activity. The direction of association differed by EEG frequency band, but the majority of biopsychosocial conditions were positively associated with activity in the higher frequency bands and negatively with lower frequency bands. Our findings indicate that brain activity in children can be influenced by a range of biopsychosocial adversities. Children's nutrition, quality and quantity of psychosocial stimulation, and food security influence their current and later brain activity in this resource-limited setting in South Asia. TRIAL REGISTRATION: ACTRN12617000660381.

BACKGROUND:Road injuries are a leading cause of mortality and morbidity worldwide. Years of international efforts have aimed to strengthen policy engagement, including the 2020 UN General Assembly's proclamation of the Second Decade of Action for Road Safety (2021-30), targeting a 50% reduction in road traffic deaths and serious injuries by 2030. The aim of this study is to provide estimates to monitor progress and identify intervention gaps. METHODS:As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, we estimated incidence, mortality, and morbidity of road injuries for 204 countries and territories from 1990 to 2023. Four road injury types and 47 nature-of-injury categories were examined. Morbidity and mortality data from clinical records, vital registration, and police reports were harmonised using meta-analytic techniques to ensure consistency and correct for systematic bias. Incidence was modelled with the meta-regression tool Disease Modelling-Meta-Regression version 2.1 and cause-specific mortality with the Cause of Death Ensemble model, both incorporating location-specific covariates to support interpolation. Years of life lived with disability (YLDs) were estimated from the prevalence and severity of the nature of road injury, and years of life lost (YLLs) from the number of cause-specific deaths multiplied by the standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were the sum of YLLs and YLDs. All metrics were calculated with 95% uncertainty intervals (UIs). FINDINGS/RESULTS:In 2023, there were 50·9 million (95% UI 46·1-56·1) road injury incident cases, 1·34 million (1·04-1·58) deaths, and 75·3 million (59·8-89·2) DALYs globally. Road injuries were the leading global cause of death among males aged 10-39 years. Between 1990 and 2023, age-standardised incidence decreased by 38·3% (95% UI 36·9-39·7) and mortality decreased by 32·3% (6·1-49·0), but progress varied widely by World Bank income group. Mortality in low-income countries (43·8 [95% UI 31·7-56·0] deaths per 100 000 population) was approximately six times higher than in high-income countries (7·5 [7·1-7·9] deaths per 100 000), despite the high-income countries showing the highest age-standardised incidence rates (858·1 [95% UI 781·9-947·1] cases per 100 000). In the past decade, many countries achieved notable reductions in road injuries, but others, including Ghana and the USA, saw increases. More severe injuries tended to occur in low-income and middle-income countries. INTERPRETATION/CONCLUSIONS:Although global incidence, mortality, and DALY rates from road injuries have declined, progress remains uneven, with pronounced disparities across income groups reflecting systemic inadequacies in infrastructure, vehicle standards, enforcement, and post-crash care. Strengthening emergency response, improving road design, enforcing safety measures, and adapting policies to the evolving demographics remain essential. FUNDING/BACKGROUND:Gates Foundation.

Herpes simplex virus type-1 (HSV-1) infections cause recurrent oral lesions and are the primary cause of infectious blindness and genital lesions in developed countries. HSV-1 can also lead to life-threatening infections in immunocompromised individuals. Currently, the primary class of antiviral therapeutics for HSV-1 treatment are nucleoside analogues such as acyclovir. However, these therapeutics are only partially effective and are subject to development of resistance. Thus, the development of new, effective antiviral agents, which can be used topically to inactivate HSV-1, is a necessity. We have recently demonstrated the potent antiviral activity of a family of biomimetic compounds. These 'peptoid' (N-substituted glycine) oligomers mimic the structure and activity of antimicrobial peptides like LL-37, while being highly resistant to proteases. Antiviral peptoids rapidly inactivate HSV-1 in vitro by disruption of the viral envelope, likely through interaction with the lipid phosphatidylserine on the outer membrane leaflet. To test the in vivo activity of these peptoids, we optimized a lip treatment model of HSV-1 infection. We demonstrate that delivery of a clinical isolate of HSV-1, strain 294.1, onto scarified lips of BALB/c mice led to reproducible lesions within 5 days. Treatment of these lesions on day 2 post infection with increasing concentrations of an antiviral peptoid resulted in a dose-dependent inhibition of lesion formation, comparable to acyclovir cream, and the host defense peptide LL-37. The same dose-dependence was observed when quantifying viral DNA from both the lip and the trigeminal ganglion by qPCR. The results demonstrate the ability of these peptoids to be developed as topical antiviral agents to prevent herpes labialis infections caused by HSV-1.

Systemic inflammation often accompanies obstructive sleep apnea (OSA), along with higher chances of heart-related metabolic issues. Although oral appliances serve as an accepted option instead of continuous positive airway pressure (CPAP), their influence on markers of systemic inflammation lacks clear evidence. The aim of this systematic review and meta-analysis was to assess changes in systemic inflammation markers following oral appliance therapy (OAT) among individuals diagnosed with OSA. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, a systematic review and meta-analysis was conducted. Databases such as PubMed, Embase, Scopus, Web of Science, and Cochrane Library were examined. Studies assessing inflammatory markers before and after therapy among adults with OSA undergoing OAT formed part of the selection. For pooling results, reliance was made upon a random-effects framework. The present research was registered in PROSPERO with the ID CRD420261340212. From a total of 1,974 records screened, six studies qualified for inclusion in the qualitative analysis; among them, two contributed data for each outcome assessed through meta-analysis. Despite pooling outcomes across trials, no meaningful changes emerged in tumor necrosis factor-alpha levels (p = 0.536), nor in C-reactive protein (p = 0.061), or interleukin-6 concentrations (p = 0.230). Consistency between study findings showed minimal variation (I² = 0%). Despite improved clinical results in OSA, OAT shows minor impact on markers of systemic inflammation. To confirm these findings, broader trials with rigorous and uniform designs are needed.

BACKGROUND:Hypertension is a leading contributor to cardiovascular disease in people with HIV (PWH), yet its underlying molecular mechanisms remain poorly understood. METHODS:We conducted a cross-sectional methylome-wide association study (MWAS) of blood pressure (BP) and arterial hypertension in 1131 PWH (739 women, 392 men; mean age 43 years) in the MACS/WIHS Combined Study (MWCCS), to identify differentially methylated positions (DMPs) and regions (DMRs) associated with SBP, DBP, and hypertension. RESULTS:We identified 59 DMPs associated with SBP and 60 associated with DBP [false discovery rate (FDR) P < 0.05], enriched in vascular, metabolic, and immune pathways. Top DMPs near ATP8B2 gene [3.8% DNA methylation (DNAm) per SD change in SBP], MIR378E gene (- 9.5% DNAm per SD change in SBP), SNORA114 gene (5.2% DNAm per SD change in DBP), and ANXA11 gene (- 7.9% DNAm per SD change in DBP). A total of 204 DMPs were associated with hypertension, including a top hypermethylated DMP near GSE1 gene [odds ratio = 0.014, 95% confidence interval (CI) 0.013-0.015, P = 1.32e-16] per 1% increase in DNAm. Gene enrichment analysis showed associations with BP-relevant tissues including kidney, brain, vasculature, and adipose tissue. We found 23 DMRs associated with DBP, including a 19-DMP region in CTBP1 gene, and 136 DMRs associated with hypertension, the largest spanning BAZ2A and LMNTD1 genes. CONCLUSION/CONCLUSIONS:We identified HIV/antiretroviral therapy (ART)-specific and shared epigenetic loci associated with BP traits, implicating neurovascular, renometabolic, and immune-regulatory pathways in HIV/ART-related hypertension.

INTRODUCTION AND AIMS/OBJECTIVE:The bidirectional relationship between periodontitis and chronic kidney disease (CKD) underscores the importance of oral health in CKD management. However, interdisciplinary collaboration between dental and nephrology professionals remains limited. This study assessed dental professionals' knowledge, clinical experiences, referral patterns, perceived barriers, and attitudes towards integrated oral-renal care. METHODS:A cross-sectional web-based survey was conducted internationally in Asia, North America, Africa, Europe, South America, and Australia from November 2025 to February 2026. The instrument explored demographics, clinical exposure to CKD/end-stage kidney disease patients, self-assessed knowledge and confidence, referral/communication patterns, barriers to coordination, and interest in interdisciplinary protocols. Data from 89 valid responses were analysed using descriptive and inferential statistical methods. RESULTS:Respondents were predominantly experienced practitioners (74.2% with >10 years of practice; 67.4% had treated CKD patients; 53.9% dialysis patients). The self-assessed composite knowledge-and-confidence score for oral-renal interactions was moderate (mean 7.67/12). Referrals from nephrologists and direct interdisciplinary communication were infrequent. Primary barriers included a lack of a clear point of contact (51.7%) and a lack of shared patient records (50.6%). Oral health was rated as very or moderately important in CKD management by 94.4% of respondents, and 100% expressed definite or possible interest in formal interdisciplinary care protocols. CONCLUSIONS:Despite moderate self-assessed knowledge and substantial clinical exposure, structural and systems-level barriers appear to impede the integration of oral-renal care. Dental professionals nevertheless demonstrate near-universal motivation for interdisciplinary collaboration and strong interest in formal care protocols. CLINICAL RELEVANCE/CONCLUSIONS:Findings highlight the need for educational initiatives, standardized referral pathways, interoperable records, and policy support to advance multidisciplinary care for CKD patients.

IMPORTANCE/UNASSIGNED:Ischemic heart disease (IHD), the leading cause of death in the US, is predominantly due to modifiable risk factors. Estimates of IHD mortality attributable to risk factors provide evidence for health policy decision-making. OBJECTIVE/UNASSIGNED:To estimate the burden of IHD death attributable to risk factors in the US from 1990-2023. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The Global Burden of Disease Study 2023 (GBD 2023) used vital records and a broad set of epidemiologic data to estimate IHD death rates, risk factor exposure, and relative risk curves for risk-outcome pairs for 1990-2023 for the general population. Data analysis was performed from October 2024 to December 2025. EXPOSURE/UNASSIGNED:Twelve metabolic, behavioral, and environmental risk factors. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcomes were IHD death rates per 100 000 persons, counts, and attributable risks from 1990-2023 by age, sex, and US state. Estimates include 95% uncertainty intervals (UI). IHD death rates were estimated using ensemble modeling methods. Risk exposures were estimated using bayesian meta-regression methods. Relative risks were estimated following the Burden of Proof framework. RESULTS/UNASSIGNED:In 2023, there were 473 000 IHD deaths (95% UI, 414 000-510 000) in the US, a decrease of 58.7% (95% UI, 56.8%-61.0%) in age-standardized rate since 1990. Between 2010 and 2023, there was a 19.0% decrease (95% UI, 15.0%-22.9%) for males and a 24.5% decrease (95% UI, 20.3%-29.7%) for females in IHD death rates. High systolic blood pressure (SBP), dietary risks, and high low-density lipoprotein cholesterol (LDL-C) were the leading risk factors for IHD deaths in 2023, accounting for 47.2% (95% UI, 36.4%-57.0%), 38.6% (95% UI, 17.2%-56.8%), and 28.5% (95% UI, 19.3%-39.6%) of IHD deaths, respectively. Increased exposure to several risk factors substantially increased their attributable burden for IHD deaths in 2023, with high fasting plasma glucose (FPG) increasing 38.8% (95% UI, 11.5%-81.1%) and high body mass index (BMI) increasing 54.5% (95% UI, 41.8%-66.3%) since 1990. Smoking and particulate matter pollution had the greatest decrease in attributable IHD mortality since 1990, at 33.3% (95% UI, 23.6%-41.7%) and 74.9% (95% UI, 46.7%-88.8%), respectively. CONCLUSION AND RELEVANCE/UNASSIGNED:Per the results of this systematic analysis of GBD 2023, a total of 88.7% (95% UI, 83.4%-92.5%) of IHD deaths were attributable to modifiable risk factors in the US in 2023, with high SBP, dietary risks, and high LDL-C being the greatest contributors. High BMI and high FPG showed the largest attribution increases, while exposure to other risks did not increase significantly for the population.

BACKGROUND:Tuberculosis (TB) is the leading global cause of death from a single infectious agent. Recent reductions in global health funding have threatened TB control, making comprehensive assessment of TB, HIV-related TB, and drug-resistant TB burdens before these disruptions essential for shaping effective responses. The WHO End TB Strategy sets targets of a 95% reduction in TB deaths and a 90% reduction in TB incidence between 2015 and 2035. Using results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, this study aims to assess the burden of TB and multidrug-resistant TB (MDR-TB) across 204 countries and territories, and to evaluate progress towards the WHO End TB incidence and mortality targets. METHODS:We quantified TB mortality using the Cause of Death Ensemble modelling platform with global vital registration, surveillance, verbal autopsy, and minimally invasive tissue sampling data. For TB morbidity estimation, we simultaneously modelled incidence, prevalence, and mortality by age and sex using DisMod-MR 2.1. A population attributable fraction (PAF) approach was applied to stratify morbidity and mortality estimates by HIV and drug-resistance status. We also calculated disability-adjusted life-years (DALYs) as the sum of years of life lost and years lived with disability. For the risk factor analysis, a comparative risk assessment framework was used and PAFs were derived for alcohol use, smoking, and high fasting plasma glucose to determine the proportion of TB burden associated with these risk factors. FINDINGS/RESULTS:In 2023, there were an estimated 9·11 million (95% uncertainty interval 8·04-10·3) incident cases of all-form TB, 1·22 million (0·98-1·49) deaths, and 54·6 million (43·8-65·5) DALYs globally. HIV-related TB comprised 781 000 (690 000-879 000) incident cases and 210 000 (142 000-279 000) deaths, contributing 11·0 million (7·56-14·3) DALYs. MDR-TB accounted for 466 000 (198 000-1 080 000) incident cases, 102 000 (31 700-238 000) deaths, and 3·96 million (1·31-9·01) DALYs. From 2015 to 2023, global all-form TB incidence rates declined by 19·2% (17·8-20·5) and deaths declined by 22·6% (4·7-35·7); declines were larger for drug-susceptible TB than for MDR-TB. Sub-Saharan Africa and south Asia had the highest mortality burdens in 2023; reductions in all-form TB incidence and mortality were uneven between 2000 and 2023, with limited progress in both measures in Latin America and the Caribbean. Removing smoking, alcohol use, and high fasting plasma glucose would reduce global TB deaths to 768 000 (592 000-970 000) and DALYs to 34·9 million (27·8-43·8) in 2023; MDR-TB deaths would decrease to 77 200 (23 400-183 000) and DALYs to 3·12 million (1·03-7·29). INTERPRETATION/CONCLUSIONS:Global progress towards WHO End TB targets is disparate and fragile. Although many regions achieved meaningful gains, others have stagnated in recent years. The complexity of TB prevention is amplified by divergent MDR-TB trends, the persistent burden of HIV, and growing exposure to modifiable risk factors. Recent volatility in global health financing threatens to further destabilise this vulnerable epidemiological landscape; concerted action is urgently needed to temper disruptions and preserve progress. FUNDING/BACKGROUND:Gates Foundation.

BACKGROUND:WHO's Global Oral Health Action Plan (GOHAP) targets include a 10% relative reduction in the combined prevalence of main oral conditions by 2030. The first GOHAP evaluation was planned for 2023, with subsequent evaluations scheduled for 2026 and 2030. The aim of this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 was to evaluate global and regional progress (2019-23) towards this target and related complementary indicators. METHODS:Using modelled estimates from epidemiological surveys and registries in 204 countries and territories, we estimated the age-standardised prevalence of untreated caries in deciduous and permanent teeth, severe periodontitis, edentulism, other oral disorders and orofacial clefts, and the age-standardised incidence of lip and oral cavity cancer. Progress towards GOHAP targets was measured by comparing the percentage change from 2019 to 2023 in the above indicators against the stated GOHAP target of a 10% relative reduction. FINDINGS/RESULTS:Globally, the age-standardised prevalence of main oral conditions declined (-1·55% [95% uncertainty interval -2·32 to -0·82]) between 2019 and 2023, but global cases increased by 3·07% (2·32 to 3·75), from 3·62 billion (3·35 to 3·95) to 3·73 billion (3·45 to 4·06). Among complementary indicators, reductions in age-standardised prevalence were observed for untreated caries in permanent teeth (-1·99% [-2·49 to -1·40]) whereas the age-standardised incidence of lip and oral cavity cancer increased (8·35% [0·13 to 16·32]), as did the age-standardised prevalence of orofacial clefts (2·25% [0·77 to 3·83]). Progress was heterogeneous across GBD super-regions, with south Asia having the largest reductions in the age-standardised prevalence of main oral conditions (-3·34% [-4·95 to -1·80]) and untreated caries in deciduous teeth (-9·09% [-17·62 to -0·08]). Sub-Saharan Africa showed the largest increase in prevalent cases of main oral conditions (9·51% [8·09-10·94]) and age-standardised incidence of lip and oral cavity cancer (14·86% [1·19-32·45]). The high-income super-region had an increase in the age-standardised prevalence of main oral conditions (1·24% [0·56-1·96]) and untreated caries in deciduous teeth (9·21% [6·60-11·89]). INTERPRETATION/CONCLUSIONS:Our modelled estimates of global trends in the prevalence of oral conditions from 2019 to 2023 suggest that early progress is modest and, at the current pace, insufficient to meet the 2030 GOHAP targets. Accelerated, equity-focused prevention and integration of essential oral health-care services within primary care and universal health coverage are needed, alongside strengthened oral cancer control and congenital anomaly care. FUNDING/BACKGROUND:The Gates Foundation.

Advances in regenerative dentistry have significantly improved the management of bone deficiencies present at, or resulting from, tooth extraction when implant placement or other prosthetic restoration is planned. The integration of biologic mediators, osteoconductive scaffolds, and resorbable barrier membranes has contributed to more predictable regenerative outcomes in appropriately selected cases. Growth factor-enhanced matrices may provide complementary biologic and structural properties that support site development. Xenografts offer long-term volumetric stability, while allografts demonstrate more active remodeling potential; when combined with biologic stimulation, these materials are intended to enhance angiogenesis, cellular recruitment, and graft incorporation. This article reviews the biologic mechanisms, clinical applications, and handling characteristics of these regenerative materials from clinical, radiographic, and histologic perspectives. When used individually or synergistically they support predictable hard- and soft-tissue regeneration, optimize implant site development, and enhance long-term implant stability and esthetic outcomes.