Faculty Bibliography

The period following basic training is a challenging one for young service members. They are away from family, training intensely for their future career fields, and may be navigating long distance relationships with intimate partners for the first time. Relationship problems are common and can significantly undermine adjustment and training. This study assessed an array of possible risk markers among partnered service members (SMs) as they arrived at technical training in the Department of the Air Force, along with a variety of relationship outcomes, and followed them (and some of their partners) for the subsequent 24 months. We then used Binary Classification and Regression Trees (CART) analysis to identify the optimal subset of predictor items and cut points to screen prospectively for negative relationship outcomes (i.e. significant relationship distress, relationship dissolution, occurrence of infidelity or intimate partner violence) at any follow-up assessment. We identified a 14-item screener that differentiated low risk (i.e. 32-42% chance of negative outcome) from moderate risk (68-70% chance of negative outcome) and high risk (88% chance of negative outcome) SMs, as well as differentiating low-to-moderate risk from high-risk SMs. This scoring flexibility allows the screening threshold to be matched to diverse programmatic goals, balancing the cost of potential prevention efforts against the level of risk. Early identification of at risk SMs will enable targeted prevention efforts.

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.

BACKGROUND:Understanding the size, gender composition, and cadre mix of the health workforce and how it has evolved across time and locations can inform policies for planning, recruitment, training, and retention of human resources for health (HRH), and improvement of access to the health-care workforce among populations. Using comparable and standardised data sources, we aim to describe the composition and density of health workers by sex among 20 cadres for 204 countries and territories over 1990-2023 and quantify workforce shortfalls relative to universal health coverage (UHC) attainment. METHODS:We used 1816 country-years of data from population-based surveys, 82 from censuses, 3888 from administrative sources, and 96 from scientific literature. We harmonised reported occupation in all sources with the International Standard Classification of Occupations 2008. We produced estimates for 20 cadres and the total health workforce disaggregated by sex using spatiotemporal Gaussian process regression, a standardised method in the Global Burden of Diseases, Injuries, and Risk Factors study. Finally, stochastic frontier meta-regression was used to estimate the minimum density of doctors, nurses and midwives, dentists, and pharmacists required to reach a score of 80 out of 100 on the UHC effective coverage index. FINDINGS/RESULTS:In 2023, there were 122·1 million (95% uncertainty interval 115·4-130·5) health workers across 20 cadres, an increase of 81·2 million (72·0-90·5) or 198·5% (161·9-245·6) relative to 1990. Of that total, there were 15·1 million (13·1-18·2) doctors, 33·2 million (30·8-36·3) nurses, 2·4 million (2·0-2·9) midwives, and 7·6 million (6·7-8·6) community health workers (CHWs). 68·9% (66·9-70·6) of all health workers in 2023 were female, and female health workers accounted for 71·4% (64·5-77·4) of net HRH workforce growth. Less than half of doctors were female (43·9%, 34·5-53·2) and most nurses (80·7%, 76·2-83·1), midwives (96·0%, 83·9-98·5), and CHWs (89·5%, 83·6-93·7) were female. Substantial differences in HRH density remained into 2023: sub-Saharan Africa had the lowest HRH densities across cadres, with the exception of CHWs, while high-income countries had the highest HRH densities. To reach 80 out of 100 on the UHC index, an additional 7·1 million (6·6-7·5) doctors, 23·9 million (21·8-26·1) nurses and midwives, 1·8 million (1·6-1·9) dentists, and 1·6 million (1·4-1·9) pharmacists are required globally. INTERPRETATION/CONCLUSIONS:The global health workforce has expanded substantially since 1990, largely due to women entering the formal health workforce. However, this expansion has been uneven across regions and persistent shortfalls remain in doctors, nurses and midwives, dentists, and pharmacists relative to moderate UHC attainment. Addressing these gaps will require expansion of training capacity, retention and remuneration policies for early-career workers, and gender-responsive workforce arrangements. FUNDING/BACKGROUND:Gates Foundation.

INTRODUCTION/UNASSIGNED:Chronic itch is a major burden, impacting the quality of life for one in four adults, and is closely associated with increased levels of anxiety, depression, and suicide. Despite its widespread burden, the precise mechanisms driving and sustaining chronic itch remain poorly understood. Non-histaminergic itch transmission in the spinal cord relies on the synaptic vesicle (SV) release of gastrin-releasing peptide (GRP) and the subsequent binding to the Gastrin-Releasing Peptide Receptor (GRPR). While SV exocytosis facilitates neurotransmitter release, such as GRP, SV endocytosis, mediated by key proteins including clathrin, adaptor associated kinase 1 (AAK1), and Dynamin (Dnm) are essential for retrieving and recycling SV from the presynaptic membrane to maintain signaling. Building upon evidence that AAK1- and Dnm-mediated endocytosis are viable targets to reverse pain, we characterized the role of these endocytic mediators in the regulation of synaptic transmission in itch pathways. METHODS/UNASSIGNED:We localized mRNA encoding AAK1, Dnm1 and Dnm3 within GRP positive neurons of the mouse dorsal root ganglia (DRG). Genetic and pharmacological disruption of AAK1, Dnm1 and Dnm3 were used to evaluate scratching behavior, locomotor activity, and anxiety-like behaviors. Finally, we assessed the impacts of these treatments on GRP release. RESULTS/UNASSIGNED:mRNA knockdown in both the DRG and spinal cord. Similarly, siRNA mediated knockdown of Dnm1 and Dnm3 in the DRGs also reduced scratching behavior. Crucially, these treatments decreased GRP release without altering locomotor activity or anxiety-like behaviors. DISCUSSION/UNASSIGNED:Together, these findings suggest that the disruption of SV recycling reduces itch related signaling and behavior without affecting normal motor functions, providing a new approach for chronic pruritus.

BACKGROUND:Falls among older adults are associated with increased morbidity, mortality, and healthcare costs; therefore, it is critical to assess modifiable risk factors. This study aimed to determine if low protein intake among older women was associated with injuries among fallers. METHODS:The Women's Health Initiative ancillary studies, Live Long Study (LLS), Food Intake (FI), and Objective Physical Activity and Cardiovascular Health in Older Women study (OPACH) were combined for analyses (n = 6,580; n = 1,285 fallers). Protein intake was assessed by food frequency questionnaires at LLS/FI/OPACH baseline. Participants completed fall calendars for 13 months and self-reported injuries in interviews. Logistic regression determined odds ratios (OR) and 95% confidence intervals (CI) for risk of injurious falls and falls with fracture. Diabetes medication use had a significant interaction between protein density and fall with any injury; thus, models were stratified. RESULTS:Of the participants who fell, 841 (65.4%) fell without injury, 444 (34.6%) fell with injury, and 70 (7.7%) fell with fracture. Lower protein density (<15% calories from protein) increased risk of fracture from falling (OR: 1.73; 95% CI: 1.02-2.92) compared to those with higher protein density (≥15% calories from protein). Among participants with diabetes medication use and lower protein density, the OR for any injury from falling was 5.54 (95% CI: 1.79-17.19) compared to those with higher protein density though based on a small subgroup. CONCLUSION/CONCLUSIONS:Lower protein density increased risk of injurious falls. Dietary and medication screening may facilitate selection and tailoring for behavioral falls prevention to reduce injurious falls and fractures.

The emergency department is a high-need setting for patient-facing artificial intelligence (PF-AI) because it functions as both a health care safety net and, increasingly, a digital front door for unscheduled acute care. We define PF-AI as tools that interact directly with patients to collect information, deliver tailored communication, and support decision making under clinician governance. This article presents a constrained framework for where PF-AI may add value across the emergency care journey-including structured intake, patient education, multilingual communication, and postdischarge follow-up-and where strict boundaries are required given risks of undertriage, confabulated content, workflow burden, privacy harm, inequitable access, cost escalation, and medico-legal ambiguity. We map operational touchpoints from prearrival to follow-up, specify information-flow and accountability checkpoints, and propose a human oversight model with defined escalation roles. The framework emphasizes equity, interoperability, usability, privacy, safety verification, and auditability, recognizing that PF-AI should augment rather than replace clinician judgment or existing non-AI workflows.

KEY POINTS/CONCLUSIONS:We developed assays to measure genetic variant effects on polycystin-1, the protein mutated in most autosomal dominant polycystic kidney disease. All tested pathogenic variants disrupted either polycystin-1 ciliary trafficking or channel function. Trafficking and channel function of some pathogenic variants was restored by low temperature culture to promote polycystin folding. BACKGROUND:Autosomal dominant polycystic kidney disease (ADPKD) is the leading monogenic cause of kidney failure and affects millions of people worldwide. Despite the prevalence of ADPKD, limited mechanistic understanding has hindered therapeutic development. Most ADPKD is caused by loss-of-function variants in polycystin-1 (PC1). METHODS:We developed assays that quantify the effect of nontruncating variants on PC1 ciliary localization, membrane trafficking, and polycystin channel function. RESULTS:We evaluated 29 nontruncating variants in PC1 and found that pathogenic variants disrupt two molecular phenotypes: ( 1 ) localization of PC1 at the primary cilium or ( 2 ) polycystin ion channel activity. Ciliary localization of a subset of polycystin variants was restored when cells were cultured at low temperature. A subset of variants with localization restored by low temperature formed functional channels. CONCLUSIONS:This study demonstrated that disruptions in polycystin ciliary trafficking and channel function are common causes of ADPKD. Defects in ciliary trafficking and channel function can be rescued for a subset of pathogenic variants, establishing a foundation for polycystin-targeted therapies in ADPKD.

OBJECTIVES/OBJECTIVE:Loneliness is a well-established longitudinal predictor of depression in later life, yet the mechanisms through which this association unfolds remain unclear. This study examined the direct and indirect effects of loneliness on subsequent depressive symptoms in late life, with particular emphasis on persistent loneliness over time. METHODS:Community-dwelling, older Israeli adults (N = 1216; M age = 81.1 years) completed annual assessments of loneliness and depressive symptoms over three years. Structural equation modelling was used to estimate autoregressive pathways, prospective effects of loneliness on subsequent depressive symptoms, and indirect effects operating through the persistent loneliness. Models were adjusted for age, sex, education, marital status, financial status, self-rated health, living arrangement, religiosity, and Holocaust survivor status. RESULTS:Loneliness and depressive symptoms both demonstrated substantial temporal stability over time. After adjusting for prior depressive symptoms and sociodemographic covariates, loneliness remained a significant prospective predictor of subsequent depressive symptoms. Decomposition of longitudinal effects, however, indicated that indirect pathways, transmitted through persistent loneliness, accounted for a greater proportion of the total longitudinal association than direct prospective effects. In fact, direct prospective effects were not statistically significant after accounting for indirect pathways. Baseline loneliness and depressive symptoms did not predict study attrition, supporting the robustness of the longitudinal findings. CONCLUSIONS:The association between loneliness and subsequent depressive symptoms in later life appears to operate primarily through persistent loneliness rather than through direct prospective effects. These findings suggest that chronic loneliness functions as a longitudinal pathway sustaining depressive symptoms over time. Interventions that mitigate loneliness in late life may also reduce depression among older adults.