Citations

AbstractAging is associated with cardiac contractile abnormalities, but the etiology of these contractile deficits is unclear. We hypothesized that cardiac contractile and regulatory protein expression is altered during aging. To investigate this possibility, left ventricular (LV) lysates were prepared from young (6 months) and old (24 months) Fischer344 rats. There are no age‐related changes in SERCA2 expression or phospholamban phosphorylation. Additionally, neither titin isoform expression nor phosphorylation differed. However, there is a significant increase in β‐isoform of the myosin heavy chain (MyHC) expression and phosphorylation of TnI and MyBP‐C during aging. In permeabilized strips of papillary muscle, force and Ca2+ sensitivity are reduced during aging, consistent with the increase in β‐MyHC expression and TnI phosphorylation. However, the increase in MyBP‐C phosphorylation during aging may represent a mechanism to compensate for age‐related contractile deficits. In isolated cardiomyocytes loaded with Fura‐2, the peak of the Ca2+ transient is reduced, but the kinetics of the Ca2+ transient are not altered. Furthermore, the extent of shortening and the rates of both sarcomere shortening and re‐lengthening are reduced. These results demonstrate that aging is associated with changes in contractile and regulatory protein expression and phosphorylation, which affect the mechanical properties of cardiac muscle.

Abstract Introduction Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. Methods This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome‐wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Results Around 5,139 differentially methylated CpG‐sites (q < 0.01, lΔβl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune‐related genes, such as CD40 , Galectin3 , OX40L , and STING , were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors’ total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG‐sites (q < 0.05, lΔβl > .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1 , S100A2 , ITGA4 , HLA‐C , and ADCYAP1 , have previously been linked to tumor progression in PCa. Conclusion Several differentially methylated genes involved in immune‐oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American‐specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.

AbstractObjectivesThe prevalence of celiac disease (CeD) is increasing, yet it is still underdiagnosed, in part because of its heterogeneous presentation. Diagnostic criteria are evolving and management with strict adherence to a gluten‐free diet is challenging for many. We aimed to characterize the clinical presentation of CeD among a large multicenter cohort of pediatric patients and to identify factors associated with gluten‐free diet adherence.MethodsPatients with CeD aged 0–18 years were recruited from 11 United States health centers. Parents completed surveys about gluten‐free diet adherence and patient electronic health records were reviewed. Logistic regression analyses were performed to identify risk factors associated with gluten exposure.ResultsCharts were reviewed for 460 children with a median age of 6.4 years. Abdominal pain was reported in 57% of the cohort, but diverse symptoms were identified. Parent surveys were completed for 455 participants. Sixty‐five (14%) participants were at high risk for gluten exposure based on parental reports of weekly or daily gluten exposure or eating gluten by choice in the past year. Participants under the age of 5 years had a lower risk of gluten exposure, while participants without repeat serology testing 18 months after initial diagnosis were at higher risk of gluten exposure.ConclusionsIn a large, multicenter cohort of pediatric CeD patients, clinical presentation is highly variable, necessitating a high index of suspicion to make a diagnosis. Parent surveys indicate that 14% of patients are at high risk of gluten exposure, with patient age and lack of close follow‐up associated with gluten‐free diet adherence.

Background The optimal duration for dual antiplatelet therapy (DAPT) after stent-assisted coiling (SAC) of intracranial aneurysms is unclear. Longer-term therapy may reduce thrombotic complications but increase the risk of bleeding complications. Methods A retrospective review of prospectively maintained data at 12 institutions was conducted on patients with unruptured intracranial aneurysms who underwent SAC between January 1, 2016 and December 31, 2020, and were followed ≥6 months postprocedure. The type and duration of DAPT, stent(s) used, outcome, length of follow-up, complication rates, and incidence of significant in-stent stenosis (ISS) were collected. Results Of 556 patients reviewed, 450 met all inclusion criteria. Nine patients treated with DAPT <29 days after SAC and 11 treated for 43–89 days were excluded from the final analysis as none completed their prescribed duration of treatment. Eighty patients received short-term DAPT. There were no significant differences in the rate of thrombotic complications during predefined periods of risk in the short, medium, or long-term treatment groups (1/80, 1.3%; 2/188, 1.1%; and 0/162, 0%, respectively). Similarly, no differences were found in the rate of hemorrhagic complications during period of risk in any group (0/80, 0%; 3/188, 1.6%; and 1/162, 0.6%, respectively). Longer duration DAPT did not reduce ISS risk in any group. Conclusions Continuing DAPT >42 days after SAC did not reduce the risk of thrombotic complications or in-stent stenosis, although the risk of additional hemorrhagic complications remained low. It may be reasonable to discontinue DAPT after 42 days following non-flow diverting SAC of unruptured intracranial aneurysms.

Ergonomic microbreaks such as the OR-Stretch can address work-related musculoskeletal pain among surgeons and potentially alleviate burnout and early retirement. Fifteen surgeons at a single institution completed two operative cases using the OR-Stretch, once using the Scheduled (every 45 min) timing strategy and once using the Self-Determined (between 30 and 60 min based on surgeon preference) strategy. Eight surgeons preferred the Scheduled timing strategy, and seven preferred Self-Determined ( p = .80). The stretch was skipped 16% of the time using the Scheduled strategy and 6% with the Self-Determined strategy ( p = .18). Personal interest, improved mental focus, and ease of remembering were cited as the most influential factors for continued usage, while the most influential factor for not continuing was forgetting to use it. Self-determined intervals for intraoperative microbreaks represent a valid and potentially preferable implementation approach. Efforts to promote long-term adoption of microbreaks should focus on reminding surgeons to use them during operations.

The Program for the Education and Enrichment of Relational Skills (PEERS®) is an evidence-based intervention developed for autistic individuals to support social communication, peer interactions, independence, and interpersonal relationships. Despite a demonstrated effectiveness for young autistic individuals in the US and several other countries, PEERS has yet to be modified to support the needs of autistic adults across the lifespan. The present study describes how our team sought autistic voices to adapt PEERS for adults of any age. Specifically, we aimed to address the needs of middle-aged and older adults and adapt the curriculum to be more neurodiversity-affirming. Between two cohorts that completed the program consecutively, we evaluated the acceptability of the adapted PEERS program and made refinements based on feedback from autistic participants and their study partners. Results indicated that Cohort 2 reported higher satisfaction with the PEERS components and overall program than Cohort 1, suggesting effective refinement. We present a framework of adaptations that more specifically address the needs of middle-aged and older adults in a neurodiverse-affirming way compared to previous iterations. Our approach to implementing an adapted PEERS curriculum across the adult lifespan may serve as a model for improved clinical care and cultivate the acceptance of neurodiversity in the interpersonal domains of autistic adults’ lives.

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget’s disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org .