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Deviations from additivity in APOE4-mediated late-onset Alzheimer's disease risk across races and ethnicities
No full textAPOE's epsilon 4 haplotype (APOE4) is late onset Alzheimer's disease's (LOAD) strongest genetic risk factor. Therefore, accurately modeling APOE4's effect is critical to understanding LOAD. This is especially important as APOE4 odds ratios (OR) vary across racial and ethnic (R/E) groups. We analyzed the APOE4-LOAD association in 3,196 East Asian, 31,105 non-Hispanic White (White), 1,646 Hispanic and Latino (Hispanic), and 6,068 non-Hispanic Black (Black) participants using three genetic models: additive, genotypic, and a reparametrized model accounting for deviations from additivity (DA). Each model adjusted for age, sex, and genetic ancestry. We first calculated additive APOE4 ORs in each R/E group, finding East Asian participants had the largest APOE4 ORs (ORAPOE4: 5.2, 95%CI: 4.4-6.0) and Black participants among the smallest (ORAPOE4: 2.8, 95%CI: 2.6-3.1). Next, we generated APOE4 ORs for heterozygote and homozygote epsilon 4 carriers. These genotypic ORs were statistically the same as the additive APOE4 estimates for all models except homozygote East Asian participants. The measured homozygote East Asian estimate (ORAPOE4: 41.5, 95%CI: 22.1-88.8) was 57% higher than its predicted counterpart based on additivity, indicating significant non-additive contributions. Finally, we used a reparametrized model that adjusted for DA. Although equivalent to the genotypic model, this adjustment provided insight into DA while significantly improving model performance among Black participants. This report demonstrates that APOE4 estimates differ based on the genetic modeling strategy, introduces explicit DA adjustments in the APOE4-LOAD association, and cautions against blindly assuming additivity across R/E groups.</p
Application of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents to Autistic Youth: A Case Study
No full textAutism spectrum disorder (ASD) frequently presents alongside emotional disorders (e.g., anxiety, depression) in youth. Existing treatments for youth with ASD most often focus on social communication, behavior management, and daily living skills, with generally less focus placed on emotional symptoms. This paper describes the theoretical rationale for and application of the Unified Protocol for Transdiagnostic Treatment for Emotional Disorders in Adolescents (UP-A) to youth with ASD. A case example is presented to highlight adaptations to the UP-A and illustrate the impact of these adaptations on treatment engagement, process, and outcomes. The case reviewed in this study features an adolescent male presenting with generalized anxiety disorder and persistent depressive disorder with a current major depressive episode. His comorbid ASD informed the adaptations to the UP-A that are discussed throughout. Considerations for case conceptualization, treatment planning, and progress monitoring during UP-A treatment are also reviewed.</p
Two-Photon Polymerization: Emerging Applications and Innovations in Clinical and Regenerative Medicine
No full textTwo-photon polymerization (2PP) has enabled three-dimensional printing at micro- and nanometer level resolution, allowing for the fabrication of patient-specific implants and finely structured cell scaffolds. This comprehensive review highlights recent advancements in integrating 2PP across various medical specialties, emphasizing its potential role in clinical and translational settings including ophthalmology, orthopedics, neurology, dermatology, and otolaryngology. Despite technological achievements, significant challenges hinder its widespread use, which are also discussed. This includes scaling of manufacturing processes, ensuring long-term biocompatibility of fabricated structures, and a lack of 2PP research in other medical fields. Advancements in biomaterials, photoinitiators, and integrated fabrication approaches within 2PP could significantly impact clinical practice and further improve patient outcomes
The Influence of Visual Feedback on Neuromuscular Performance During Resistance Training in Healthy Older Adults
No full textCalaway, C, Elkins, E, Gastaldo, R, Sarama, J, Sands, R, Lamorta, R, Conn, M, and Signorile, JF. The influence of visual feedback on neuromuscular performance during resistance training in healthy older adults. J Strength Cond Res XX(X): 000-000, 2026-Visual feedback (VF) has shown to significantly improve strength, movement speed, and levels of motivation in athletic populations. To our knowledge, no study has examined the impact of graphical power feedback on lower- and upper-limb neuromuscular performance in healthy older adults. To determine the impact of live VF compared with that of no feedback (NoVF) on leg-press (LP) and chest-press (CP) peak power (PP) and average power (AP) using HUR (HUR Inc, Park Ridge, IL) pneumatic resistance training machines, 28 older adults (73.1 ± 6.7 years) completed 2 training sessions per week for 2 weeks separated by at least 48 hours of rest. In session 1, subjects were provided VF on the HUR tablets. During session 2, subjects were not provided with VF. Both groups completed 3 × 8 repetitions on each machine separated by 1-minute rests. Separate 2 × 2 × 3 (condition × week × set) repeated measures ANOVAs revealed condition, week, and set effects for LP-PP (p < 0.05) showing greater power with VF (MDiff ± SE = 23.8 ± 6.8 W, +4%) and across weeks and sets. For CP-PP, a condition effect was seen (p < 0.05), indicating greater VF performance (20.9 ± 9.7 W, +5%). Leg-press-average power and chest-press-average power both showed significance for all main effects (p < 0.05), showing greater performance with VF (25.6-25.8 W, +4-5%) and across weeks and sets; however, power only increased from sets 1-3 for CP-AP. Graphical VF is a viable tool for optimizing neuromuscular performance in older adults. Furthermore, greater power outputs in the subsequent LP sets for both PP and AP suggest a level of neuromuscular facilitation in the lower limbs, which warrants sufficient warm-up to maximize power during training.ABSTRACTCalaway, C, Elkins, E, Gastaldo, R, Sarama, J, Sands, R, Lamorta, R, Conn, M, and Signorile, JF. The influence of visual feedback on neuromuscular performance during resistance training in healthy older adults. J Strength Cond Res XX(X): 000-000, 2026-Visual feedback (VF) has shown to significantly improve strength, movement speed, and levels of motivation in athletic populations. To our knowledge, no study has examined the impact of graphical power feedback on lower- and upper-limb neuromuscular performance in healthy older adults. To determine the impact of live VF compared with that of no feedback (NoVF) on leg-press (LP) and chest-press (CP) peak power (PP) and average power (AP) using HUR (HUR Inc, Park Ridge, IL) pneumatic resistance training machines, 28 older adults (73.1 ± 6.7 years) completed 2 training sessions per week for 2 weeks separated by at least 48 hours of rest. In session 1, subjects were provided VF on the HUR tablets. During session 2, subjects were not provided with VF. Both groups completed 3 × 8 repetitions on each machine separated by 1-minute rests. Separate 2 × 2 × 3 (condition × week × set) repeated measures ANOVAs revealed condition, week, and set effects for LP-PP (p < 0.05) showing greater power with VF (MDiff ± SE = 23.8 ± 6.8 W, +4%) and across weeks and sets. For CP-PP, a condition effect was seen (p < 0.05), indicating greater VF performance (20.9 ± 9.7 W, +5%). Leg-press-average power and chest-press-average power both showed significance for all main effects (p < 0.05), showing greater performance with VF (25.6-25.8 W, +4-5%) and across weeks and sets; however, power only increased from sets 1-3 for CP-AP. Graphical VF is a viable tool for optimizing neuromuscular performance in older adults. Furthermore, greater power outputs in the subsequent LP sets for both PP and AP suggest a level of neuromuscular facilitation in the lower limbs, which warrants sufficient warm-up to maximize power during training
The CHI-RON Study: Using PCORnet® and Patient Engagement Strategies to Improve Diversity Among Research Participants in the Congenital Heart Initiative
Get PDFThe Congenital Heart Initiative-Redefining Outcomes and Navigation to Adult-Centered Care (CHI-RON) study is a unique collaboration between the PCORnet and Congenital Heart Initiative (CHI), the first patient powered registry for adult congenital heart disease (ACHD) patients. The CHI-RON study examines the effects of gaps in recommended care in ACHD.
Recruitment of racially diverse, younger, out-of-care, and male participants has been challenging in ACHD studies. Our goal was to design patient engagement and recruitment strategies to improve representation.
Launched in December 2020, patients from any location can self-enroll in the CHI registry, while the CHI-RON study (5/2022 - 10/2023) recruited ACHD patients at 12 sites participating in PCORnet. CHI-RON Recruitment methodology included a patient partner engagement toolkit and a recruitment algorithm using the PCORnet® Common Data Model designed specifically to improve diversity and reduce self-enrollment biases in comparison to the CHI registry.
ACHD patients, age 18 years or older, with the ability to complete PROs independently.
Demographic/Recruitment Statistics for study participants and Patient Engagement in Research Scale (PEIRS-22) for the study team partners.
As of October 2023, a total of 2652 participants were recruited through CHI-RON recruitment methodology while 1326 were self-enrolled in the CHI. CHI-RON recruitment methodologies have increased representation when compared with self-enrolled CHI participants in terms of ethnicity (10.9% vs. 7.4% Hispanic, P<0.001), race (5.4% vs. 2.6%, Black/African American, P<0.001), sex (41% vs. 28% male, P<0.001), younger age (35.5 +/-12.8 y vs. 43.5±14.5 y, P<0.001), and education (33.4% vs. 24% high school equivalent or less, P<0.001).Most study team patient partners (n=12, 86%) reported a very to extremely high degree of engagement (PEIRS-22 average score 101.6), especially in the subdomains of contributions, support, feeling valued, and benefits.
Patient engagement and novel recruitment strategies are critical to improving the inclusion of under-represented populations in clinical research and ensuring alignment with the needs of ACHD patients
Comorbidity Burden and Biologic Access in an Uninsured Psoriasis Population: A 20-Year Descriptive Study
No full textPsoriasis is a chronic immune-mediated disease associated with multiple systemic comorbidities. Biologic therapies have transformed the management of moderate-to-severe psoriasis; however, their high cost remains a major barrier for uninsured and socioeconomically disadvantaged individuals. The Psoriasis Biologics Center for Indigent Patients at Jackson Memorial Hospital provides a structured dermatology access model for underserved populations.
We conducted a descriptive retrospective cohort study of patients with moderate-to-severe psoriasis receiving biologic therapy through a dedicated safety-net access program between 2005 and 2025. Patient demographics, comorbidities, and management strategies were obtained from electronic medical records and standardized intake questionnaires. Only descriptive statistics were performed; standardized disease severity and quality-of-life measures such as the Psoriasis Area and Severity Index (PASI) or the Dermatology Life Quality Index (DLQI) were not available.
A total of 450 patients (mean age 52.6 years; 54% female) were included. Nearly half (49.8%) presented with at least one systemic comorbidity. The most common were psoriatic arthritis (35.1%), hypertension (31.3%), diabetes mellitus (20%), cardiovascular disease (19.1%), obesity (13.8%), and dyslipidemia (12.2%). Psychiatric comorbidities included depression (9.6%) and anxiety (3.8%). Infectious conditions occurred at higher-than-expected frequencies, including hepatitis B/C (3.8%), latent tuberculosis (3.6%), and human immunodeficiency virus (HIV) (2.7%). Care delivery was organized within a structured safety-net model that incorporated standardized screening protocols, referral pathways, and multidisciplinary coordination to support biological access for uninsured patients.
This 20-year descriptive cohort characterizes comorbidity burden and biologic access within an indigent psoriasis population. This study does not assess clinical outcomes or treatment effectiveness. These findings describe a care delivery framework that may inform future health system and health equity-focused initiatives
Towards cell-based therapy of alopecia areata: Autologous human Vδ2 + Foxp3 + γδTreg cells restore hair-follicle immune privilege and promote hair regrowth in human alopecia areata models ex vivo and in vivo
No full textWhile regulatory T cells (Tregs) control autoimmune diseases (AID), the role of evolutionarily older Foxp3
γδTregs is much less understood. We noted that both lesional and non-lesional skin of patients with alopecia areata (AA), one of the most common AID, contains significantly more Vδ1
/Foxp3
γδTregs than healthy scalp skin. Therefore, we investigated how human γδTregs impact experimentally induced AA in human scalp skin xenotransplants on SCID/beige mice in vivo. Peripheral autologous human Vδ2
/Foxp3
γδTregs were expanded and pre-activated in vitro and then injected intradermally into scalp skin xenografts before or after induction of AA. These γδTregs reduced the perifollicular lymphocytic infiltrate, restored hair follicle immune privilege (HF-IP), prevented AA onset, and promoted hair regrowth in established AA lesions. In parallel, γδTregs co-cultured with organ-cultured, MICA/B-overexpressing human scalp HFs suppressed pathogenic CD8
/NKG2D
T-cell activity and counteracted all AA hallmarks ex vivo-including HF-IP collapse, HF dystrophy, and premature IFNγ-induced catagen-via IL-10 and TGF-β1 secretion, contact-dependent inhibition, and adenosine generation through CD39/CD73. These findings in a model human AID introduce human γδTregs as clinically important regulatory lymphocytes and invite the use of autologous peripheral Vδ2
/Foxp3
γδTregs as a cell-based therapy for AA and possibly other CD8
T cell-dependent AIDs characterized by IP collapse
P-1215. In vitro activity of Sulbactam-durlobactam and Standard-of-Care Antibiotics against Acinetobacter baumannii-calcoaceticus complex isolates from wound and urinary tract sources: ACNBio Study 2023-2025
No full textBackground Acinetobacter baumannii most often causes nosocomial bacteremia and pneumonia. However, A. baumannii is becoming an important cause of a broader range of infections including skin and soft tissue infection (SSTI) and urinary tract infections (UTI). This study aims to evaluate the in vitro activity of sulbactam-durlobactam and other clinically utilized antibiotics against A. baumannii-calcoaceticus complex isolates isolated from non-respiratory and non-bloodstream sources. Methods Samples included 193 A. baumannii-calcoaceticus complex isolates collected from 2023-2025 across 19 states. Susceptibility tests for sulbactam-durlobactam (durlobactam fixed concentration of 4 mg/L), and comparator agents were conducted by manual broth microdilution and interpreted according to CLSI and FDA (cefiderocol) standards. Results A. baumannii complex isolates were primarily cultured from skin and soft tissue (56.5%), followed by urinary tract (31.6%) and other sources (11.9%) including bone biopsy, fluid aspirate etc. ICU patients contributed 20% of the isolates. Sulbactam-durlobactam was observed to be highly active (98.5% susceptible [S]; MIC50/90 1/4 mg/L), demonstrating greater activity than ampicillin-sulbactam (41.5% S; MIC50/90 8/32 mg/L) and meropenem (32.1% S; MIC50/90 32/128 mg/L). Sulbactam-durlobactam also displayed high susceptibility rates across sample sources, ranging from 97.3% (skin and soft tissue) to 100% (urine). The MIC50/90 and susceptibility rates for all other agents including tetracycline derivatives are shown in Table 1. Notably, among the carbapenem-resistant A. baumannii (CRAB) isolates (n=130) in the collection, sulbactam-durlobactam retained high activity (97.7% S) relative to ampicillin-sulbactam (16.2% S). Cefiderocol inhibited 97.7% and 75.4% of isolates at CLSI and FDA susceptible breakpoints, respectively. Conclusion The data reported here are consistent with results from surveillance studies among non-respiratory and bloodstream isolates and show that sulbactam-durlobactam demonstrates in vitro activity against clinical A. baumannii complex isolates from urinary tract and SSTI sources, including isolates that are resistant to ampicillin-sulbactam, carbapenems, and cefiderocol. Disclosures Tomefa E. Asempa, PharmD, Innoviva: Grant/Research Support Robin R. Chamberland, PhD D(ABMM), bioMerieux: Advisor/Consultant|Pattern Bioscience, Inc.: Advisor/Consultant|Pattern Bioscience, Inc.: Grant/Research Support Jonathan Hand, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Ferring: Grant/Research Support|Innoviva: Advisor/Consultant|Janssen: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Scynexis: Grant/Research Support|The Antibiotic Resistance Leadership Group (ARLG): Grant/Research Support|The Antibiotic Resistance Leadership Group (ARLG): Honoraria Amanda Harrington, PhD, Beckman Coulter: Grant/Research Support|bioMerieux/BioFire: Advisor/Consultant|bioMerieux/BioFire: Grant/Research Support|bioMerieux/BioFire: Honoraria|BioRad: Advisor/Consultant|Selux: Grant/Research Support Wesley D. Kufel, Pharm.D., BCPS, BCIDP, Merck & Co.: Grant/Research Support|Shionogi, Inc: Grant/Research Support|Shionogi, Inc: Honoraria Lars Westblade, PhD, Elements Materials Technology: Grant/Research Support|Hardy Diagnostics: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Selux Diagnostics: Grant/Research Support|Shionogi: Advisor/Consultant|SNIPRBIOME: Grant/Research Support Thomas Kirn, MD PhD, BD: Advisor/Consultant|BD: Honoraria Brian Mochon, PhD, D(ABMM), Shionogi: Advisor/Consultant Mark Fisher, PhD, Shionogi Inc.: Advisor/Consultant Rebekah Dumm, PhD D(ABMM), BD: Advisor/Consultant|BD: Grant/Research Support|Biomerieux: Advisor/Consultant|Biomerieux: Grant/Research Support|Diasorin: Grant/Research Support|Pattern Biosciences: Grant/Research Support|Qiagen: Grant/Research Support|Roche Diagnostics: Advisor/Consultant|Shionogi: Advisor/Consultant David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Advisor/Consultant|Innoviva: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Suppor
