Jefferson College of Health Sciences

HIV infection remains a major global health challenge due to its complex pathogenesis and lifelong persistence in people living with HIV (PLWH). A central barrier to eradication is the virus's ability to establish long-lived latent reservoirs in different tissues, including the central nervous system (CNS), where it evades immune clearance and antiretroviral therapy (ART). These reservoirs, seeded early during infection, fuel viral rebound if ART is interrupted, requiring lifelong treatment. In the CNS, HIV persists despite systemic viral suppression because of limited ART penetration across the blood-brain barrier (BBB), and infection of long-lived cells such as microglia and perivascular macrophages. Although modern ART regimens significantly reduce viral burden and HIV-related morbidity, they do not eliminate neurocognitive complications. Suboptimal CNS drug penetration and certain ART-associated toxicities contribute to CNS dysfunction, persistent neuroinflammation, and accelerated aging of the brain. As PLWH now experience increased life expectancy, prolonged exposure to ART and persistent low-level viral activity exacerbate chronic inflammation, immune activation, and metabolic dysregulation, collectively accelerating neurobiological aging. These pathological processes contribute to the development of HIV-associated neurocognitive disorders (HAND), which affect nearly half of virally suppressed PLWH. This review examines HIV-associated inflammation, neurotoxic pathways, and accelerated aging in PLWH in the modern ART era.

Language production is known to operate on different levels of representation. ‘Flow’ in writing results from parallelism in the coordination of subsequent planning units. In this article we discuss three points arising from Roeser et al. (2025b): (1) parallel processing results in non-additive effects; (2) study of the production of multisentence texts permits testing of questions around how language production is co-ordinated in real time, and, more generally; and (3) statistical models must closely align with what we know about the cognitive process of what is being studied.

Buprenorphine (BUP) is widely used in the treatment of neonatal opioid withdrawal syndrome (NOWS). However, the most compounded formulation contains 30% ethanol, despite regulatory and clinical concerns regarding ethanol exposure in pediatric patients. Thus, this research aimed to develop an ethanol-free sublingual (SL) gel formulation of BUP that would be safe, stable, and suitable for NOWS. Multiple polymers were screened as gelling agents, with hydroxypropyl methylcellulose (HPMC) emerging as the ideal base polymer for the formulation due to its optimal pH, rheological characteristics, and stability. The formulated gels were stored at room temperature and refrigerated conditions for 30 days and evaluated for stability using pH, rheology, and liquid chromatography-mass spectrometry. BUP content was between 90-110% of the labeled amount of the dosage form (75 µg/mL) at all time-points, and the pH remained close to physiological values. Release studies demonstrated a drug release of 23-24% for SL gels without surfactants stored at room temperature and refrigerated conditions, respectively. Incorporation of non-ionic surfactants (Tween 20 and Tween 80) significantly increased drug release to 33% and 40%, respectively, reflecting enhanced solubilization and improved mucosal penetration. The ethanol-free formulation demonstrated physicochemical stability and favorable release characteristics suitable for neonatal administration. These findings represent a meaningful advance in the development of safer pediatric formulations for NOWS.

Choline has been recognized as an essential nutrient involved in various physiological functions critical to human health. Adequate daily intake of choline has been established by the US National Academy of Medicine in 1998, considering choline requirements for different ages, sex differences and physiological states (e.g., pregnancy). By serving as a precursor for acetylcholine and phospholipids, choline is important for cholinergic transmission and the structural integrity of cell membranes. In addition, choline is involved in lipid and cholesterol transport and serves as a methyl donor after oxidation to betaine. Extracellular choline is transported across the cell membrane via various transport systems (high-affinity and low-affinity choline transporters) with distinct features and roles. An adequate dietary intake of choline during pregnancy supports proper fetal development, and throughout life supports brain, liver, and muscle functions, while choline deficiency is linked to disease states like fatty liver. Choline has important roles in neurodevelopment, cognition, liver function, lipid metabolism, and cardiovascular health. While its signaling role has been considered mostly indirect via acetylcholine and phosphatidylcholine which are synthesized from choline, emerging evidence supports a role for choline as an intracellular messenger acting on Sigma-1R, a non-opioid intracellular receptor. These new findings expand the cell signaling repertoire and increase the current understanding of the role of choline while warranting more research to uncover the molecular mechanisms and significance in the context of GPCR signaling, the relevance for physiology and disease states.

This study identified a method for assessing the alignment between undergraduate medical education program learning objectives and graduate medical education program competencies. Using a modified Delphi approach in which the number of rounds (3) and consensus (70% agreement) were determined a priori, the study sought to align objectives and competency measures between the programs. The authors invited panelists from Sidney Kimmel Medical College at Thomas Jefferson University to independently respond to a questionnaire via an email invitation. In the questionnaire, panelists made 46 decisions about the alignment between the undergraduate medical education program learning objectives and the Accreditation Council for Graduate Medical Education Harmonized Milestones subcompetencies. Approximately, 57% (26/46) of the decisions reached a consensus that there was an alignment between the objectives and the subcompetencies. By aligning the objective and subcompetencies, this study provided a first step toward closing the gap in the communication of student competencies.

ObjectivesTo capture nursing home staff perspectives on the benefits and challenges related to caring for residents living with Alzheimer’s disease and other related dementias. These perspectives will inform the initial development of strategies to help with staff retention. DesignA secondary qualitative analysis of semi-structured interviews conducted with nursing home staff, which was embedded within a pragmatic clinical trial. Setting and ParticipantsPurposive sampling was used to capture perspectives of staff spanning across job roles from 23 nursing homes. MethodsDuring the parent study primary analysis, staff experiences providing dementia care were consistently described. In response, this study completed a secondary analysis of study data using thematic analysis to identify benefits and challenges of caring for this population. ResultsAnalysis of nursing home staff (n=327) interviews captured benefits and challenges of caring for residents living with dementia. Three themes reflected staff perspectives of the benefits, including valuing interpersonal relationship with residents (e.g., learning about residents’ likes, dislikes, history), providing care fosters a sense of purpose, and the variability of the job from day-to-day (e.g., getting to use different strategies to interact with residents). Two themes portrayed the challenges staff articulated, including feeling discouraged due to ineffective care strategies (e.g., not being able to manage residents’ behaviors) and the toll that caring for this resident population takes on staff mental health (e.g., death of residents). Conclusions and ImplicationsNursing home staff report benefits and challenges to providing care to people with dementia. In order to assist with staff retention and lower staff turnover, nursing home administrators need to take into consideration how to help their staff manage the challenges and facilitate the benefits through the implementation of organizational strategies.

This study presents automated atlas-based magnetization transfer (MT) measurements of the typically developing pediatric cervical spinal cord (SC). We report normative MT ratio (MTR) values from the whole cervical cord white matter (WM) and WM tracts, examining variations with age, sex, height, and weight. MT scans of 33 healthy females (mean age=12.8) and 22 males (mean age=13.09) were acquired from the cervical SC (C2-C7) using a 3.0T MRI. Data were processed using the SC Toolbox, segmented, and registered to the PAM50 template. Affine and non-rigid transformations co-registered the PAM50 WM atlas to subject-specific space. MTRs were measured for the specific WM tracts (left and right dorsal fasciculus gracilis, dorsal fasciculus cuneatus, and lateral corticospinal tracts [LCST]) and the whole WM. Descriptive statistics, correlation analysis, and unpaired t-tests (p<0.05) assessed relationships with age, height, weight, and sex. Normative MTR measurements were obtained from all regions. The coefficients of variation were low to moderate. No significant differences (p>0.05) were found across all the cervical levels. However, significant sex differences were observed in whole WM (p=0.04) and LCST (p=0.03). MTR values correlated positively with age, with significant correlations at C5 (r=0.3, p false discovery rate=0.04). A decreasing trend in MTR values across levels was found for whole WM (r=-0.2, p<0.001). This study provides an understanding of MTR values in pediatric cervical SC and their variations by sex, age, height, and weight, providing a baseline for comparisons in pediatric SC diseases.