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Evaluating the association of apolipoprotein E genotype and cognitive resilience in SuperAgers
No full text"SuperAgers" are oldest-old adults (ages 80+) whose memory performance more closely resembles middle-aged adults. The present study examined apolipoprotein E (APOE) allele frequency in non-Hispanic Black (NHB) and non-Hispanic White (NHW) SuperAgers compared to controls and Alzheimer's disease dementia cases.
In 18,080 participants from eight cohorts, harmonized clinical diagnostics and memory, executive function, and language domain scores were used to identify SuperAgers, cases, and controls across age-defined bins.
NHW SuperAgers had significantly lower frequency of APOE-ε4 alleles and higher frequency of APOE-ε2 alleles compared to all cases and controls, including oldest-old controls. Similar patterns were found in a small yet substantial sample of NHB SuperAgers; however, not all comparisons with controls reached significance.
We demonstrated strong evidence that APOE allele frequency relates to SuperAger status. Further research is needed with a larger sample of NHB SuperAgers to determine if mechanisms conferring cognitive resilience differ across race groups.
Apolipoprotein E (APOE) allele frequency differs between SuperAgers and cases APOE allele frequency differs between non-Hispanic White SuperAgers and controls The relationship of APOE and non-Hispanic Black SuperAger status is unclear
ID#: 2211973 - Infarct mass and left ventricular mass predict sudden arrhythmic events, and do not predict non-sudden arrhythmic deaths in patients with coronary artery disease
No full textCardiovascular Risk Biomarkers Moderate the Associations Between Different Sleep Stage Durations and Global Cognition in Older Black Adults
No full textAbstract Tu0068: The Microanatomy of the Human Hemodialysis Fistula Maturation and Failure
No full textApplication 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
Driving Collective Change: Understanding the Role of Internal Communication, Organizational Trust, and Efficacy in Employees’ Issue-Driven Collective Activism Intention Toward Police Brutality Issues
No full textThis study explored how organizations' dialogic internal communication about their stance to end police brutality toward African Americans influenced employees' issue-driven collective activism intention to address police brutality toward African Americans. An online survey was conducted to recruit 401 eligible participants. Results found that dialogic internal communication about stance on police brutality toward African American issues positively predicted employees' organizational trust which was positively associated with their self-efficacy and collective efficacy. Moreover, both employees' self-efficacy and collective efficacy mediated the relationship between their organizational trust and issue-driven collective activism intention to anti-police brutality toward African Americans. Several theoretical and practical implications are also discussed.</p
Analysis of VHI-10 in Patients with Comorbid Primary Muscle Tension Dysphonia and Emotional Disturbances
No full textThe goal of this study was to determine if coexisting emotional disturbance affects Voice Handicap Index-10 (VHI-10) scores in patients with primary muscle tension dysphonia (pMTD). We hypothesize that those with emotional disturbances will have a higher perceived voice handicap, and therefore higher VHI-10 scores.
Retrospective chart review.
We reviewed the medical charts of patients diagnosed with pMTD at initial voice evaluation in 2019. We included patients in the emotional disturbances group if they self-reported depression, anxiety, or acute stress; were diagnosed with a depressive episode, major depressive disorder, anxiety disorder, or severe acute stress episode; or received a score ≥5 on the Patient Health Questionnaire-9 depression screener, indicating at least mild levels of depression. We used univariable and multivariable linear regression models to analyze the severity of VHI-10 scores, prevalence of abnormal VHI-10 scores, and compare International Classification of Diseases, Tenth Revision diagnoses and VHI-10 scores between groups.
Three-hundred twenty-nine patients met the selection criteria. One-hundred nineteen patients had an emotional disturbance, and 210 patients did not. There was no significant association between higher VHI-10 scores and patients with emotional disturbances. Patients with a diagnosis of depressive episode had higher VHI-10 scores, with an average of 15.7, compared to the rest of the sample, with an average of 11.7 (P = 0.01). No association was found between higher VHI-10 scores and diagnosis of anxiety, though anxiety was the most common comorbidity with depression. An increase in age was also found to correlate with an increase in VHI-10 score, and identifying as Hispanic or Latino was correlated with lower VHI-10 scores.
Patients with coexisting emotional disturbance and pMTD do not have significantly higher perceived voice handicap than patients with pMTD and no emotional disturbance. Patients with pMTD and a history of depressive episode had greater perceived voice handicap
P-1210. Real-World Efficacy and Safety of Meropenem-Vaborbactam in Patients with Moderate to Severe Renal Impairment
No full textBackground Meropenem-vaborbactam (MEV) is a novel β-lactam β-lactamase inhibitor combination approved in the United States for the treatment of complicated urinary tract infections caused by resistant organisms. Its spectrum includes carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. Limited data exist on the use of MEV in patients with reduced renal function. This study compared clinical characteristics and outcomes between patients with moderate to severe renal impairment and those with mild or no impairment. Methods This was a real-world, multicenter, retrospective cohort study conducted between 2017 and 2025 in adult patients who received MEV for ≥72 hours. Patients with KDOQI CKD stages 3-5 or GFR < 60 mL/min/1.73m2 or on chronic dialysis were assigned to the renal impairment (RI) group. All other patients were assigned to the non-impaired (NI) group. The primary outcome was clinical success, defined as resolution or improvement in signs of infection without recurrence. Secondary outcomes included 30-day all-cause mortality, 30-day microbiologic recurrence, 30-day hospital readmission, and occurrence of treatment-emergent adverse events. Results Seventy-two patients were included in the RI group and 151 patients were included in the NI group. The median baseline eGFR was 52.3 vs. 91.3 mL/min/1.73m2 in the RI and NI groups, respectively. Nearly half (47%) of patients in the RI group were receiving chronic dialysis. Clinical success was achieved in 76% of patients in the RI group compared to 79% in the NI group (p=0.60). Thirty-day all-cause mortality was 20.8% in the RI group vs. 23.8% the in the NI group (p=0.62). Thirty-day microbiological recurrence and hospital readmission rates were similar between the two groups. Adverse events were rare in both groups and similar in incidence (2.8% vs. 2.6% in the RI and NI groups, respectively [p=0.96]). Conclusion This study demonstrated the clinical outcomes of MEV when used in patients with moderate to severe renal impairment. Prospective randomized trials in this patient population are needed to validate these findings. Disclosures Kevin W. Garey, PharmD, MS, FIDSA, FASHP, Acurx: Grant/Research Support|Merck & Co.: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support Wesley D. Kufel, Pharm.D., BCPS, BCIDP, Merck & Co.: Grant/Research Support|Shionogi, Inc: Grant/Research Support|Shionogi, Inc: Honoraria Tamara Krekel, PharmD, BCPS, BCIDP, AbbVie: Advisor/Consultant|AbbVie: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria Taylor Morrisette, PharmD, MPH, AbbVie Inc: Advisor/Consultant|AbbVie Inc.: Grant/Research Support|Copeland, Stair Valz & Lovell: Expert Testimony|Infectious Diseases Special Edition: Honoraria|Stellus Rx: Grant/Research Support Travis J. Carlson, PharmD, BCIDP, Aimmune Therapeutics, Inc.: Speaker bureau Venugopalan Veena, PharmD, Merck: Grant/Research Support Vasilios Athans, PharmD, BCIDP, Astellas Pharma: Advisor/Consultant Kimberly C. Claeys, PharmD, PhD, bioMérieux: Advisor/Consultant|bioMérieux: Honoraria Michael J. Rybak, PharmD, PhD, MPH, Abbvie: Grant/Research Support|Innoviva: Grant/Research Support|Melina: Grant/Research Support|Merck: Grant/Research Support|Shionogi: Grant/Research Suppor
MAPK14 converges on key transcriptional machinery to promote vascular smooth muscle cell degeneration in abdominal aortic aneurysm
No full textVascular smooth muscle cell (VSMC) degeneration is a major mechanism underlying abdominal aortic aneurysm (AAA) formation. However, the upstream signaling pathways that converge on the transcriptional machinery to drive VSMC degeneration remain elusive. Here, we integrated single-nucleus (sn) multi-omics, chromatin immunoprecipitation (ChIP)-seq, and wet lab validation to identify transcriptional effectors of VSMC-MAPK14, which we previously reported to promote AAA. Compared with wild-type (WT) mice, VSMC-Mapk14 knockout (KO) mice displayed reduced VSMC degeneration, as evidenced by decreased expression of markers of endoplasmic reticulum stress, the unfolded protein response, fibrosis, and apoptosis, after 7 days of Ang II infusion. SnRNA-seq revealed increased VSMCs and reduced fibroblast and immune cell populations in KOs. Reclustering VSMCs revealed an increased proportion of contractile cluster and a reduced proportion of fibrotic cluster in KOs. The VSMC differentiation gene program and upstream pathways were upregulated, whereas degeneration pathways, including extracellular matrix remodeling, inflammation, and apoptosis, were downregulated in KO VSMCs. snATAC-seq and validation revealed increased serum response factor (SRF) motif activity and expression but reduced RUNX2 expression in KO VSMCs. Integrative analysis of snATAC-seq, ChIP-seq, and bulk RNA-seq identified the MYOCD/SRF/CArG triad as the driver of the contractile gene program following Mapk14 loss. We further found that the expression of Bcl2, a novel MYOCD/SRF/CArG target, was increased in Mapk14 KO VSMCs. Loss of Mapk14 attenuated MRTFA protein abundance via increased ubiquitin‒proteasome degradation, which was attributed to reduced USP10 protein expression. These findings reveal MAPK14-driven transcriptomic and epigenomic landscapes that promote VSMC degeneration by suppressing SRF/MYOCD/CArG while activating RUNX2 and MRTFA. Our study provides mechanistic insight into MAPK14-mediated VSMC degeneration and provides a basis for MAPK14-targeted therapeutic strategies for AAA