Faculty Bibliography

Diabetes mellitus affects both the peripheral and central nervous systems, giving rise to a spectrum of neurological complications that extend far beyond the traditional focus on diabetic peripheral neuropathy (DPN). Chronic hyperglycemia disrupts cellular homeostasis through increased formation of advanced glycation end-products, activation of inflammatory pathways, mitochondrial dysfunction, oxidative stress, and impaired neurovascular regulation. These disturbances converge to drive axonal degeneration, demyelination, synaptic injury, and progressive cognitive decline. Emerging evidence also highlights a critical role for gut dysbiosis and intestinal barrier dysfunction, which facilitate microbial translocation and systemic inflammation, ultimately disrupting the blood-brain barrier and amplifying neuroimmune injury. This narrative review synthesizes current mechanistic, clinical, and translational insights into how metabolic, inflammatory, vascular, and microbial pathways interact to produce diabetes-associated neurodegeneration. We summarize key molecular drivers-including mitochondrial ROS overproduction, microglial and astrocytic activation, endothelial dysfunction, and insulin resistance-while also describing their contributions to DPN, autonomic neuropathy, and diabetes-related cognitive impairment. We further integrate evidence from emerging therapeutic domains, including mitochondrial stabilizers, anti-inflammatory strategies, gut-microbiome modulation, and neurovascular-targeted interventions. Despite advances in understanding, disease-modifying therapies remain limited, and diagnostic tools for early detection are underutilized. Bridging these gaps will require longitudinal human studies, improved biomarkers, and integrative therapeutic approaches that target multiple convergent pathways. A deeper understanding of cross-talk among metabolic, immune, vascular, and microbial systems may enable earlier intervention and more effective strategies to mitigate the neurological burden of diabetes.

BACKGROUND:Parents frequently consult health care professionals because of infant regurgitation, crying and stool consistency. OBJECTIVE:) is an awareness tool for cow's milk allergy. We aimed to characterize the distribution of CoMiSS items in presumed healthy infants and developed centiles with these data. METHODS:Data from 2500 infants (median age 5.3 months [Q1-Q3: 2.6-8.8]) across 10 countries were analyzed by pooling individual-level data. RESULTS:Age distribution differed between countries (p < 0.001). Median (Q1; Q3) and mean (SD) total CoMiSS were 4 (2; 6) and 4 (2.6), respectively. Overall CoMiSS <10 was observed in 99%. Crying >3 hours/day occurred in 6.1% at 1-2 months, 4% between birth and 4 months, and <1.5% thereafter. Regurgitating > 5x/day occurred in 7-11% during the first 7 months (peak at 1-4 months: 16-17%) and decreased to <2-4% thereafter. Stool consistency accounted for 93.9% of the score. Atopic dermatitis and respiratory symptom scores are very low. CONCLUSIONS:CoMiSS is stable across age, with transiently higher crying and regurgitation scores below 4 months. CoMiSS ≥10 is uncommon in healthy infants. Age-specific CoMiSS centile charts provide a framework for interpreting common infant symptoms and identifying values warranting further evaluation. IMPACT/CONCLUSIONS:These data report on the prevalence of common manifestations in healthy infants and inform about normality according to age and different regions. Crying or distress and regurgitation scores are transiently more frequent during the first 4 months of life. Eczema and respiratory symptoms are seldom reported in presumed healthy infants. While caregivers and health care professionals consider regurgitation and crying or distress up to a certain limit as normal, atopic dermatitis and respiratory symptoms are not. These age-specific centile charts provide information on common infant symptoms and identify conditions that may warrant further evaluation.

Developing dry antimicrobial delivery systems that combine bioactive protection with biofilm-matrix disruption remains a major challenge. Building on a previously established protease-modulated pea protein isolate (PPI)-carvacrol nanoemulsion system, this study developed protease-assisted microcapsules designed to preserve carvacrol and promote the removal of preformed biofilms. Carvacrol-loaded nanoemulsions were prepared at pH 3.5, 7.0, and 10.0 and supplemented with pepsin or trypsin before spray-drying or freeze-drying with maltodextrin. Protease-specific interfacial modification markedly affected emulsion stability, powder structure, and encapsulation performance. At pH 7.0 and 10.0, trypsin reduced droplet size from 284.60 to 232.52 nm and from 149.13 to 140.38 nm, respectively. The resulting spray-dried microcapsules exhibited high encapsulation efficiency (>96%) and low surface carvacrol contents (0.95-1.24 mg/g). In contrast, pepsin caused pronounced destabilization under acidic conditions, particularly after freeze-drying, yielding porous powders with an encapsulation efficiency of 48.18% and a surface carvacrol content of 69.51 mg/g. Trypsin-assisted microcapsules achieved 90-99% removal of preformed Listeria innocua biofilm biomass within 1 h, whereas enzyme-free and pepsin-containing formulations generally remained below 40%. Microscopic observations confirmed extensive disruption and detachment of the biofilm structure. After one year at 4 °C, trypsin-loaded formulations retained high biofilm biomass removal activity (85-99% after 2 h). These findings demonstrate that protease-assisted microencapsulation can couple interfacial regulation during particle formation with enzyme-mediated biofilm-matrix disruption after rehydration, providing a sustainable carvacrol delivery platform with durable antibiofilm functionality.

Explaining the low-temperature limit of trees requires in situ information on the actual temperature conditions, the trees' phenology and freezing tolerance. Here, we report the seasonal course of freezing resistance and its response to local temperature in species of Larix and Abies, forming the treeline (4350-4400 m) in the south-eastern Himalayas, and Quercus and tree-size Rhododendron, reaching their upper limit in the immediate neighborhood (4270-4290 m). By linking tree-crown temperatures with on-site air temperature, we can utilize long-term meteorological records to hindcast critical freezing events. Deciduous Larix flushes earliest and exhibits the greatest freezing tolerance and largest safety margin. The evergreen species flush 2 months later and operate near their freezing damage limit. The conifers can compensate for freezing damage by rapid resprouting from small auxiliary buds, not an option for Quercus and Rhododendron with their bigger buds. Freezing damage does not appear to constrain the two treeline conifers. Their range limit most likely reflects the general low-temperature growth limit of the tree life form. Freezing tolerance is most likely controlling the upper limits of the evergreen broad-leaved species. The results offer a mechanistic explanation of the range limit of these high-elevation tree species.

OBJECTIVE:Cesarean delivery (CD) remains a key obstetric quality metric, particularly among nulliparous, term, singleton, vertex (NTSV) pregnancies. In 2024, NTSV CD rate at NYU-LI was 32.9%, exceeding The Joint Commission (TJC) benchmark of ≤30% and demonstrating racial and ethnic disparities. This study aimed to reduce the institutional NTSV CD rate to ≤30% through a multidisciplinary QI initiative while prospectively monitoring safety outcomes and racial disparities. STUDY DESIGN/METHODS:A single-site QI initiative was implemented from 2024-2025 incorporating provider education, patient-centered interventions (TeamBirth and structured labor huddles), standardized labor management, and performance monitoring through monthly case review, clinician feedback, and quarterly equity-focused data review. Outcome measures included monthly overall and quarterly race- and ethnicity-stratified NTSV CD rates. Process measures assessed adherence to evidence-based labor dystocia criteria. Balancing measures included postpartum hemorrhage (PPH) and TJC PC-06 rates. Temporal trends were evaluated using multivariable Poisson regression with adjustment for maternal age, gestational age at delivery, and body mass index. RESULTS:The overall NTSV CD rate decreased from 32.9% in 2024 to 27.8% in 2025, remaining below TJC benchmark in 10 of 12 months. Across the 8-quarter study period, there was a significant decline in the outcome over time (aRR per quarter 0.97, 95% CI 0.95-0.99, p=0.003). Reductions were observed across racial and ethnic groups, including among Black non-Hispanic patients (44.0% to 40.0%) and Asian non-Hispanic patients (37.0% to 29.6%). Adherence to evidence-based labor dystocia criteria remained high, while PPH and PC-06 rates remained stable. CONCLUSIONS:A standardized, multidisciplinary QI initiative was associated with NTSV cesarean delivery rate below the Joint Commission benchmark without increases in maternal or neonatal adverse outcomes. The initiative was also associated with partial reduction in racial disparities in cesarean delivery rates, although persistent inequities remained. Future PDSA cycles will focus on sustaining standardized care and advancing equitable obstetric outcomes.

BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) medications can reduce ADHD symptom severity in individuals with comorbid autism spectrum disorder (ASD). However, clinical guidance on pharmacological treatment of ADHD in this clinical population remains limited and inconsistent. Characterising real-world treatment patterns (ie, initiation timing, medication choices, switching, discontinuation) and the impact of alternative medication choices on clinical outcomes is critical for informing evidence-based management strategies. OBJECTIVE:To (1) characterise ADHD pharmacological treatment patterns in youth with ADHD+ASD versus ADHD alone and (2) assess whether using alternative ADHD medications versus methylphenidate is associated with differential changes in negative clinical outcomes among youth with ADHD+ASD. METHODS:This is a population-based cohort study using Swedish national registers. The study included children (<13 years) and adolescents (13-17 years) with an incident ADHD diagnosis between 2007 and 2018 and followed-up until 2021, comparing youth with co-occurring ASD (n=24 117) and ADHD alone (n=79 830). Descriptive outcomes included time to pharmacological treatment initiation, medication type, number of medication switches and discontinuations. The primary outcome was changes in rates of inpatient psychiatric hospitalisations, accidental injuries and specialist care visits for substance use, depressive or anxiety disorders in the 1 year after versus the 1 year before medication initiation. FINDINGS/RESULTS:Individuals with ADHD+ASD experienced longer delays to treatment initiation (12-14% initiated >12 months after diagnosis vs 7-8% in ADHD alone). Children with ADHD+ASD were slightly more likely to discontinue treatment within 3 months (16% vs 12%) and had the highest average number of medication switches within 3 years (2.6; IQR 0.0-2.0). In within-individual analyses, comparisons of alternative ADHD medications versus methylphenidate did not yield statistically significant differences after correcting for multiple comparisons. CONCLUSIONS:Children with ADHD+ASD experienced longer delays to treatment initiation and more frequent medication switching compared with those with ADHD only. The effects of alternative ADHD medication options on key negative clinical outcomes appeared similar to those of methylphenidate. CLINICAL IMPLICATIONS/CONCLUSIONS:These findings suggest that, rather than recommending fixed first-line and second-line treatments for individuals with ADHD-ASD, clinical guidelines should emphasise appropriate training as well as prompt and individualised treatment based on a shared decision-making process.

INTRODUCTION/UNASSIGNED:"Positive" outcomes such as flourishing and personal recovery are important predictors of physical health, mental illness, quality of life, and all-cause mortality. However, behavioral health outcome measures often emphasize symptom reduction, while overlooking "positive" outcomes. The objective of this study is to describe (1) the outcomes most important to individuals with major depressive disorder (MDD) and (2) "positive" outcomes and psychiatric symptoms in a real-world sample of young adults with MDD. MATERIALS AND METHODS/UNASSIGNED:Forty-three participants aged 18-35 with a diagnosis of MDD receiving outpatient behavioral health treatment in an urban safety-net psychiatry department completed online surveys identifying factors most important to recovery and standardized measures of flourishing, personal recovery, functioning, and symptoms of depression and anxiety. RESULTS/UNASSIGNED:Most participants (61.9%) had high symptoms of depression (Patient Health Questionnaire-8 (PHQ-8) ≥ 10), 16.7% were flourishing (Flourishing Scale ≥ 48), and 41.9% had high personal recovery (Brief INSPIRE-O ≥ 50). Factors ranked as "most important" for personal recovery included coping well with stressful events (39.5%), functioning well (34.9%), and having hopes and dreams for the future (30.2%). Notably, among individuals with low depressive symptoms, 60.0% reported low flourishing and 31.3% reported low personal recovery. CONCLUSIONS/UNASSIGNED:Individuals with MDD value a diverse range of outcomes, and exhibit a large variation in levels of depressive symptoms and characteristics of "positive" mental health. Aligning outcome tracking with patient-defined goals may provide a more comprehensive understanding of overall mental health.

Type 2 diabetes (T2D) prevention efforts have largely focused on intervening when dysglycemia is already established. We propose that T2D prevention be reframed around prediabetes remission, with preservation and restoration of normoglycemia as the optimal clinical goal. The transition from normoglycemia through increasing dysglycemia to T2D is progressive and cumulatively shaped by biological, behavioral and environmental exposures across the life course. Prediabetes (intermediate hyperglycemia) remission is an achievable, pragmatic and measurable prevention target. Here we provide a life-course risk architecture for T2D integrating developmental, transitional and contextual determinants, defining critical windows of amplified metabolic vulnerability and potential restoration of normoglycemia. Precision prevention should target mechanistic heterogeneity, with aligned interventions that remain scalable, affordable and adaptable across socioeconomic settings. Our framework identifies ten priorities in T2D prevention, moving beyond traditional approaches toward context-specific, actionable interventions capable of altering the natural history of disease early in the life course and restoring metabolic health.

OBJECTIVE:To assess the association between child protective services (CPS) involvement and the risk and timing of intramuscular (IM) medication or physical restraint use in pediatric patients presenting to the emergency department (ED) with behavioral health concerns. METHODS:An electronic health record dataset spanning January 2021 to October 2023 was retrospectively analyzed. Individual cumulative incidence plots and Cox regression models were created to model the risk and risk rate of receiving either IM medication or being physically restrained by different levels of CPS involvement. Cox regression models were adjusted for age, legal sex, and race and ethnicity. RESULTS:We analyzed 6257 behavioral health encounters. Children in CPS custody had the highest cumulative incidence of receiving IM medication or being physically restrained compared to children with a new CPS report filed or children without any CPS involvement after 72 hours (IM medication: 17%, 6%, 5% respectively, p < 0.001, physical restraints: 8%, 4%, 3% respectively, p < 0.001). Compared to children without CPS involvement, children in CPS custody had a significantly higher risk rate of receiving IM medications (adjusted hazard ratio (aHR) 1.79, 95% Confidence Interval (CI) 1.01-3.18, p = 0.046), and physical restraints (aHR 2.71, 95% CI 1.35-5.43 p = 0.005). CONCLUSION/CONCLUSIONS:Children in CPS custody had a higher risk of receiving IM medication and being physically restrained during behavioral health encounters in a pediatric ED. Further work should focus on understanding the causal mechanisms and designing interventions that maximize optimal health outcomes for vulnerable children experiencing behavioral health emergencies.