Faculty Bibliography

Underdiagnosis of cardiometabolic risk factors (CMRFs) may represent an unrecognised biological pathway contributing to dementia risk; yet remains poorly characterised in African and African diaspora populations. We quantified the prevalence and determinants of underdiagnosed hypertension and abnormal glycaemia across four cohorts comprising up to 7000 adults aged ≥40 years from Nigeria, Kenya, and The United States: Indianapolis, and North Texas. Underdiagnosis was defined as absence of self-reported diagnosis despite elevated systolic blood pressure ( ≥130 mmHg) or fasting blood glucose ( ≥100 mg/dL). Cohort-stratified analyses examined demographic, socioeconomic, cognitive, Alzheimer's genetic, and blood-based biomarker correlates. Underdiagnosis was pervasive in African cohorts. Elevated fasting glucose was associated with cognitive impairment in Kenya and North Texas, while severe hypertension and diabetes were linked to Alzheimer's disease-related biomarkers [pTau217/181, NFL and Aβ42/40] in North Texas (all p ≤ 0.05). These findings identify context-specific diagnostic gaps in populations at high dementia risk and highlight cardiometabolic detection as a mechanistic target for prevention.

Therapeutic options for chronic kidney disease (CKD) have expanded substantially in recent years, creating new opportunities to reduce residual kidney and cardiovascular risk through combination therapy. Evidence from large, randomized trials and meta-analyses demonstrates that sodium-glucose co-transporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), and glucagon-like peptide-1 (GLP-1) receptor agonists provide independent and additive benefits, with emerging data showing that select combinations may also improve safety. A risk-based approach, anchored in albuminuria and supported by validated risk equations, can guide treatment intensity, support more timely initiation of multidrug regimens, and improve health system efficiency. Addressing implementation barriers, advancing single-pill combinations, and leveraging adaptive and combination therapy trials will be essential to translate these therapeutic advances into improved long-term outcomes for people with CKD.

BACKGROUND:Understanding the research experiences of bereaved parents is necessary to advance palliative care. OBJECTIVE:To evaluate levels of and factors associated with bereaved parent comfort, benefit, and distress from research participation and to qualitatively explore research experiences. STUDY DESIGN/METHODS:Exploratory analysis of survey data from parents of infants who died in a level IV NICU (2010-2020). Fisher's exact and Chi-square tests were used to identify factors associated with parental comfort, distress, and benefit. Qualitative analyzed was performed using the constant comparative method. RESULTS:40/146 parents (27%) responded. 83% reported being "very comfortable" or "comfortable", 83% reported "some" to "a lot" of benefit, 26% reported "a great deal" to "a lot" of distress from participation. Goal-discordant care was significantly associated with distress. Research participation themes included "helping others", "processing experiences" and "re-living negative experiences". CONCLUSION/CONCLUSIONS:Bereaved NICU parents simultaneously experience distress, comfort, and benefit from research participation.

Breast implants are a fundamental adjunct in aesthetic and reconstructive breast surgery, with more than 3.5 million recipients in the United States. Implant rupture risk increases with device age, although modern cohesive silicone implants demonstrate markedly improved durability. The Food and Drug Administration does not mandate routine replacement, but recommends surveillance screening for silicone implant rupture beginning 5-6 years postplacement and every 2-3 years thereafter. However, no guidelines exist for managing asymptomatic ruptures in older adult patients. A scoping review was conducted in MEDLINE, Embase, and the Cochrane Library through January 2025 for guidelines on the management of asymptomatic implant rupture in older adult patients; none was identified. Evidence indicates that although surveillance can detect silent ruptures and minimize silicone migration, the clinical impact in older adult patients is limited given the low incidence of symptomatic complications with modern devices and reduced life expectancy. Risks of surveillance include false positives, overdiagnosis, patient anxiety, and unnecessary surgery-particularly relevant in older patients with higher perioperative complication rates. The authors propose discontinuing surveillance for asymptomatic silicone implants after age 75 years and foregoing routine implant exchange. In asymptomatic patients older than 75 with known or suspected rupture, observation is reasonable unless symptoms develop. Symptomatic cases should undergo diagnostic imaging and individualized risk-benefit discussion using a comprehensive geriatric assessment framework. A shared decision-making approach is emphasized, balancing surgical risks, patient comfort with uncertainty, and aesthetic concerns. These recommendations aim to optimize quality of life and avoid overtreatment in older adult patients with breast implants.

Salvage chemotherapy and autologous stem cell transplantation (ASCT) offer the opportunity to cure eligible patients with relapsed diffuse large B-cell lymphoma (DLBCL). Epigenetic alterations such as aberrant DNA methylation patterns have been linked to chemotherapy resistance in DLBCL. Oral Azacitadine (AZA) is a hypomethylating agent that inhibits DNA methyltransferase and has provided evidence of chemotherapy sensitization in DLBCL. In this phase I trial the safety and feasibility of two dose levels of AZA were investigated in combination with standard cytotoxic chemotherapy rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in relapsed DLBCL patients who were candidates for ASCT.

The intestinal microbiota regulates multiple host functions, including digestion and immune development. Our knowledge of the microbiota has been shaped by available technology, which primarily measures relative abundance. Quantitative, single-cell bacterial measurements would improve our understanding of microbiome biology, including the dynamics behind shifts in microbiota composition. We present microbiota flow cytometry (MicFLY), a single-cell technology that quantifies absolute bacterial abundance with species-level resolution. Using MicFLY, we can identify the major intestinal taxa, discriminate live from dead bacteria, measure heterogeneous mRNA expression, and concurrently quantify immunoglobulin A (IgA) and IgG binding to intestinal bacteria. Using longitudinal, quantitative microbiota analyses on a small cohort of preterm infants, we find that increases in IgA- and IgG-unbound bacteria from various Enterobacteriaceae species associate with the development of necrotizing enterocolitis (NEC). MicFLY single-cell technology thus enables fine-scale quantitative microbiota measurements for a deeper mechanistic understanding of compositional changes.

Protein folding dynamics emerge from subtle changes in intramolecular interactions, where hydration shapes free energy landscapes and influences conformational ensembles and supramolecular assembly. While these shape-shifting principles have been primarily explored in well-behaved systems with sharp transitions, their applicability to multidomain protein assemblies, particularly those containing partially folded or disordered regions, remains unclear. Here, we investigate how a single leucine-to-alanine mutation modulates the hierarchical interplay between folding, micelle formation, and macroscopic biomaterial behavior using two diblock protein block copolymers (BCPs): CE and C_L44AE. In solution, both BCPs exhibit spectral features consistent with their C/C_L44A monoblocks, with CE showing α-helical features and C_L44AE more disordered ones. Upon dehydration, however, both systems display increased structural order, with CE favoring β-sheets and C_L44AE adopting α-helical content. At the mesoscale, both BCPs assemble into amphiphilic micelles, but CE forms smaller, densely packed micelles, whereas C_L44AE generates larger micelles that template film networks of varying pore size depending on their packing density. These differences lead to distinct solvation behavior, with C_L44AE exhibiting greater uptake of predominantly mobile water, approximately twice that of CE, culminating in an actuation energy density of 2,043 kJ/m³, the highest reported for protein BCPs to date. Despite this increased uptake, C_L44AE shows reduced mechanical relaxation and a rougher DSC/TGA thermogram, indicative of a broader conformational ensemble compared to CE. Comparisons to monoblocks (C, C_L44A, E) and previously reported triblocks (CEC, C_L44AEC_L44A) further highlight the importance of asymmetric diblock architectures in promoting hydration-sensitive assemblies, laying the rational design groundwork for future high-performance, water-responsive protein biomaterials.