Designing a Perioperative Mind-Body Intervention for Peripheral Vascular Interventions.

Background: Peripheral vascular interventions (PVIs) performed under procedural sedation and analgesia (PSA) can be associated with anxiety and poor compliance with patient instructions during surgery. Mind-body interventions (MBIs) such as meditation have demonstrated the potential to decrease perioperative anxiety, though this area is understudied, and no tailored interventions have been developed for the vascular surgical patient population. Objectives: We aimed to design a perioperative MBI that specifically targeted vascular surgical patients undergoing PVIs under PSA. We sought to perform this in a scientifically rigorous, multi-disciplinary collaborative manner. Methods: Following the Obesity-Related Behavioral Intervention Trials (ORBIT) model, we designed (Phase 1a) and then refined (Phase 1b) a MBI for patients undergoing PVIs under PSA to decrease perioperative anxiety and sedation and facilitate patient intraoperative compliance. Phase 1a involved a literature review, informal information gathering and synthesis, and drafting a preliminary protocol for a perioperative MBI. Phase 1b involved assembling a multi-disciplinary expert panel of perioperative and mind-body clinicians and researchers to improve the MBI using an iterative, modified Delphi approach. Results: The modified Delphi process was completed, and a consensus was reached after three iterations. The resulting MBI consisted of two seven-minute preoperative guided meditations on the day of surgery, including diaphragmatic breathing, body scans, and guided imagery emphasizing awareness of the ipsilateral leg where the vascular surgery was performed. A document delineating the integration of the MBI into the operating room workflow was produced, including details regarding the intervention's timing, duration, and modality. Conclusion: Using a multi-specialty expert panel, we designed a novel MBI in the form of a guided meditation with elements of mindfulness and guided imagery to decrease anxiety and increase intraoperative compliance for patients undergoing PVIs under PSA. A prospective pilot study is being planned to test the program's feasibility.

Comparison of healthcare resource use and cost between influenza and COVID-19 vaccine coadministration and influenza vaccination only.

OBJECTIVE: To compare healthcare resource utilization (HCRU) and all-cause medical costs among individuals aged ≥50 years who received influenza and COVID-19 vaccines on the same day and those who received influenza vaccine only. METHODS: We conducted a retrospective cohort study leveraging Optum's de-identified Clinformatics DataMart from 8/31/2021 to 7/31/2023. Individuals aged ≥50 years continuously enrolled in health plans for 1 year prior and until 7/31/2023 were included. Two cohorts were formed based on vaccination status between 8/31/2022 and 1/31/2023: co-administered influenza and COVID-19 vaccines (co-admin cohort) and influenza vaccine only (influenza cohort). Associations between vaccination status and all-cause, influenza-related, COVID-related, pneumonia-related, and cardiorespiratory-related hospitalization, outpatient or emergency room visits and all-cause medical costs were estimated by weighted generalized linear models, adjusting for confounding by stabilized inverse probability of treatment weighting. RESULTS: 613,156 (mean age: 71) and 1,340,011 (mean age: 72) individuals were included in the co-admin and influenza cohorts, respectively. After weighting, the baseline characteristics were balanced between cohorts. The co-admin cohort was at statistically significant lower risk of all-cause (RR: 0.95, 95% CI: 0.93-0.96), COVID-19-related (RR: 0.59, 95% CI: 0.56-0.63), cardiorespiratory-related (RR: 0.94, 95% CI: 0.93-0.96) and pneumonia-related (RR: 0.86, 95% CI: 0.83-0.90) hospitalization but not influenza-related hospitalizations (RR: 0.91, 95% CI: 0.81, 1.04) compared with the influenza cohort. Co-administration was associated with 3% lower all-cause medical cost (cost ratio: 0.974, 95% CI: 0.968, 0.979) during the follow-up period compared to receiving influenza vaccine only. LIMITATIONS: Limitations include the potential residual confounding bias in observational data, measurement errors from claims data, and that the cohort was followed for a single season. CONCLUSION: Receiving co-administered COVID-19 and influenza vaccines versus only receiving influenza vaccination reduced the risk of HCRU, especially COVID-19-related hospitalization and all-cause medical costs. Increasing vaccine coverage, particularly for COVID-19, might have public health and economic benefits.

Economic burden of cardiorespiratory hospitalizations associated with respiratory syncytial virus among United States adults in 2017-2019.

Morbidity and mortality caused by respiratory syncytial virus (RSV) in older adults and those with underlying health conditions can be potentially alleviated through vaccination. To assist vaccine policy decision-makers and payers, we estimated the annual economic burden of RSV-associated cardiorespiratory hospitalizations among insured US adults aged ≥18 y in the Merative MarketScan claims database from September through August of 2017-2018 and 2018-2019. Negative binomial regression models were used to estimate the number of RSV-associated cardiorespiratory hospitalizations using MarketScan-identified cardiorespiratory diagnosis codes in the presence or absence of RSV circulation per weekly laboratory test positivity percentages from the Centers for Disease Control and Prevention. This number was multiplied by mean cardiorespiratory hospitalization costs to estimate total costs for RSV-associated cardiorespiratory hospitalizations. Number and cost for International Classification of Diseases (ICD)-coded RSV hospitalizations were quantified from MarketScan. In 2017-2018 and 2018-2019, respectively, 18,515,878 and 16,462,120 adults with commercial or Medicare supplemental benefits were assessed. In 2017-2018, 301,248 cardiorespiratory hospitalizations were observed; 0.32% had RSV-specific ICD codes, costing $44,916,324, and 5.52% were RSV-associated cardiorespiratory hospitalizations, costing $734,078,602 (95% CI: $460,826,580-$1,103,358,799). In 2018-2019, 215,525 cardiorespiratory hospitalizations were observed; 0.34% had RSV-specific ICD codes, costing $33,053,105, and 3.14% were RSV-associated cardiorespiratory hospitalizations, costing $287,549,472 (95% CI: $173,377,778-$421,884,259). RSV contributes to substantial economic burden of cardiorespiratory hospitalizations among US adults. Modeling excess risk using viral positivity data provides a comprehensive estimation of RSV hospitalization burden and associated costs, compared with relying on ICD diagnosis codes alone.

Vaccine preparation time, errors, satisfaction, and preference of prefilled syringes versus RSV vaccines requiring reconstitution: randomized, time and motion study.

AIM: The current study compared preparation time, errors, satisfaction, and preference for a prefilled syringe (PFS) versus two RSV vaccines requiring reconstitution (VRR1 and VRR2) in a randomized, single-blinded time and motion study. METHODS: Pharmacists, nurses, and pharmacy technicians were randomized to a preparation sequence of the three vaccines. Participants read instructions, then consecutively prepared the three vaccines with a 3-5-min washout period in between. Preparations were video recorded and reviewed by a trained pharmacist for preparation time and errors using predefined, vaccine-specific checklists. Participant demographics, satisfaction with vaccine preparation, and vaccine preference were recorded. Within-subjects analysis of variance was used to compare preparation time. Mixed-effects Poisson and ordered logistic regression models were used to compare the number of preparation errors and satisfaction scores, respectively. RESULTS: Sixty-three pharmacists (60%), nurses (35%), and pharmacy technicians (5%) participated at four sites in the United States. The least squares mean preparation time per dose for PFS was 141.8 s (95% CI = 156.8-126.7; p <.0001) faster than for VRR1, 103.6 s (95% CI = 118.7-88.5; p <.0001) faster than for VRR2, and 122.7 s (95% CI = 134.2-111.2; p <.0001) faster than the pooled VRRs. Overall satisfaction (combined "Very" and "Extremely") was 87.3% for PFS, 28.6% for VRR1, and 47.6% for VRR2. Most participants (81.0%) preferred the PFS vaccine. LIMITATIONS: The study is limited by the inability to completely blind observers. To minimize the effects of order, we utilized a 3-sequence block design; however, the order in which the vaccines were prepared may have affected outcomes. Participants were assessed once, whereas if repeated preparations were performed there may have been trained efficiencies gained for each vaccine. CONCLUSION: PFS vaccines can greatly simplify the vaccine preparation process, allowing administrators to prepare almost four times more doses per hour than with vial and syringe systems.

Dab2 (Disabled-2), an adaptor protein, regulates self-renewal of hair follicle stem cells.

Disabled 2 (Dab2), an adaptor protein, is up regulated in the hair follicle stem cells (HFSCs); however, its role in any tissue stem cells has not been studied. In the present study, we have reported that Dab2 conditional knockout (Dab2-cKO) mice exhibited a delay in the HF cycle due to perturbed activation of HFSCs. Further, Dab2-cKO mice showed a reduction in the number of HFSCs and reduced colony forming ability of HFSCs. Dab2-cKO mice showed extended quiescence of HFSCs concomitant with an increased expression of Nfatc1. Dab2-cKO mice showed a decreased expression of anti-aging genes such as Col17a1, decorin, Sirt2 and Sirt7. Dab2-cKO mice did not show full hair coat recovery in aged mice thereby suggesting an accelerated aging process. Overall, we unveil for the first time, the role of Dab2 that regulate activation and self-renewal of HFSCs.

Implementation and Evaluation of a National Well-Being Curriculum for KL2 Scholars.

Introduction: The study aimed to pilot test a well-being curriculum for KL2 scholars to be used across the Clinical and Translational Science Award consortium. Methods: Between November 2022, and May 2023, 36 KL2 scholars from 25 hubs participated in the program. The General Well-Being Index for U.S. Workers and the Patient Reported Outcomes Measurement Information System (PROMIS-29) were completed by scholars before and after the program. Results: Postparticipation, there was a trend of improvement in the domains of well-being, sleep, anxiety, and fatigue. Conclusion: Implementing a virtual synchronous well-being curriculum allowed the scholars to connect across the consortium and improve their well-being.

Evaluation of a microphysiological human placental barrier model for studying placental drug transfer.

Understanding drug transport across the placental barrier is important for assessing the potential fetal drug toxicity and birth defect risks. Current in vivo and in vitro models have structural and functional limitations in evaluating placental drug transfer and toxicity. Microphysiological systems (MPSs) offer more accurate and relevant physiological models of human tissues and organs on a miniature scale for drug development and toxicology testing. MPSs for the placental barrier have been recently explored to study placental drug transfer. We utilized a multilayered hydrogel membrane-based microphysiological model composed of human placental epithelial and endothelial cells to replicate the key structure and function of the human placental barrier. A macroscale human placental barrier model was created using a transwell to compare the results with the microphysiological model. Placental barrier models were characterized by assessing monolayer formation, intercellular junctions, barrier permeability, and their structural integrity. Three small-molecule drugs (glyburide, rifaximin, and caffeine) that are prescribed or taken during pregnancy were studied for their placental transfer. The results showed that all three drugs crossed the placental barrier, with transfer rates in the following order: glyburide (molecular weight, MW = 494 Da) < rifaximin (MW = 785.9 Da) < caffeine (MW = 194.19 Da). Using non-compartmental analysis, we estimated human pharmacokinetic characteristics based on in vitro data from both MPS and transwell models. While further research is needed, our findings suggest that MPS holds potential as an in vitro tool for studying placental drug transfer and predicting fetal exposure, offering insights into pharmacokinetics.

The YBX3 RNA-binding protein posttranscriptionally controls SLC1A5 mRNA in proliferating and differentiating skeletal muscle cells.

In humans, skeletal muscles comprise nearly 40% of total body mass, which is maintained throughout adulthood by a balance of muscle protein synthesis and breakdown. Cellular amino acid (AA) levels are critical for these processes, and mammalian cells contain transporter proteins that import AAs to maintain homeostasis. Until recently, the control of transporter regulation has largely been studied at the transcriptional and posttranslational levels. However, here, we report that the RNA-binding protein YBX3 is critical to sustain intracellular AAs in mouse skeletal muscle cells, which aligns with our recent findings in human cells. We find that YBX3 directly binds the solute carrier (SLC)1A5 AA transporter messenger (m)RNA to posttranscriptionally control SLC1A5 expression during skeletal muscle cell differentiation. YBX3 regulation of SLC1A5 requires the 3' UTR. Additionally, intracellular AAs transported by SLC1A5, either directly or indirectly through coupling to other transporters, are specifically reduced when YBX3 is depleted. Further, we find that reduction of the YBX3 protein reduces proliferation and impairs differentiation in skeletal muscle cells, and that YBX3 and SLC1A5 protein expression increase substantially during skeletal muscle differentiation, independently of their respective mRNA levels. Taken together, our findings suggest that YBX3 regulates AA transport in skeletal muscle cells, and that its expression is critical to maintain skeletal muscle cell proliferation and differentiation.

What is well-being? A scoping review of the conceptual and operational definitions of occupational well-being.

Well-being is a multifaceted construct that is used across disciplines to portray a state of wellness, health, and happiness. While aspects of well-being seem universal, how it is depicted in the literature has substantial variation. The aim of this scoping review was to identify conceptual and operational definitions of well-being within the field of occupational health. Broad search terms were used related to well-being and scale/assessment. Inclusion criteria were (1) peer-reviewed articles, (2) published in English, (3) included a measure of well-being in the methods and results section of the article, and (4) empirical paper. The searches resulted in 4394 articles, 3733 articles were excluded by reading the abstract, 661 articles received a full review, and 273 articles were excluded after a full review, leaving 388 articles that met our inclusion criteria and were used to extract well-being assessment information. Many studies did not define well-being or link their conceptual definition to the operational assessment tool being used. There were 158 assessments of well-being represented across studies. Results highlight the lack of a consistent definitions of well-being and standardized measurements.

Well-being grants in an academic medical center: A case example.

Academic medical centers (AMCs) rely on engaged and motivated faculty for their success. Significant burnout among clinical and research faculty has resulted in career disengagement and turnover. As such, AMCs must be vested in cultivating faculty engagement and well-being through novel initiatives that support faculty. The Well-Being Education Grants program was established by the Office for Well-Being within the Center for Faculty Development at Massachusetts General Hospital to provide the impetus many faculty needed to dedicate time to their well-being, demonstrating that investments in multi-component interventions around faculty well-being require resources and funding.

A Randomized Controlled Trial of Community-Delivered Heated Hatha Yoga for Moderate-to-Severe Depression.

Objective: To evaluate feasibility, acceptability, and preliminary efficacy of heated yoga to treat moderate-to-severe depression.Design: An 8-week randomized controlled trial (RCT) of heated yoga versus waitlist control was conducted from March 2017 to August 2019.Methods: Participants in the yoga condition were asked to attend heated yoga classes at 2 community heated yoga studios at least twice weekly. We assessed acceptability and feasibility using exit interview and attendance data, respectively. The primary intervention efficacy outcome variable was change in the Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) score from baseline to post-intervention (week 8).Results: We randomized 80 participants and included 65 (mean [± SD] age 32.7 [± 11.7] years; 81.5% female) in the analyses (yoga n = 33, waitlist n = 32). The mean IDS-CR score at baseline was 35.6 (± 7.9) for the full sample, 36.9 (± 8.8) for yoga participants, and 34.4 (± 6.7) for waitlist participants. Participants attended an average of 10.3 (± 7.1) total classes over the 8-week intervention period. Yoga participants had a significantly greater pre- to post-intervention reduction in IDS-CR scores than waitlist participants (Cohen d = 1.04, P < .001). More yoga participants (59.3%; n = 16) than waitlist participants (6.3%; n = 2) evidenced larger treatment responses (IDS-CR ≥ 50% decrease in symptoms). Participants rated the heated yoga and its aftereffects positively in exit interviews.Conclusions: Approximately 1 heated yoga session per week (mean of 10.3 classes over 8 weeks) was associated with significantly greater reduction in depression symptoms than a waitlist control. Participants rated heated yoga positively. Taken together, results suggest feasibility, acceptability, and preliminary efficacy for patients with depression and warrant further research using active control conditions.Trial Registration: ClinicalTrials.gov identifier: NCT02607514.

Physiologically Based Pharmacokinetic Modeling of Extracellular Vesicles.

Extracellular vesicles (EVs) are lipid membrane bound-cell-derived structures that are a key player in intercellular communication and facilitate numerous cellular functions such as tumor growth, metastasis, immunosuppression, and angiogenesis. They can be used as a drug delivery platform because they can protect drugs from degradation and target specific cells or tissues. With the advancement in the technologies and methods in EV research, EV-therapeutics are one of the fast-growing domains in the human health sector. Therapeutic translation of EVs in clinics requires assessing the quality, safety, and efficacy of the EVs, in which pharmacokinetics is very crucial. We report here the application of physiologically based pharmacokinetic (PBPK) modeling as a principal tool for the prediction of absorption, distribution, metabolism, and excretion of EVs. To create a PBPK model of EVs, researchers would need to gather data on the size, shape, and composition of the EVs, as well as the physiological processes that affect their behavior in the body. The PBPK model would then be used to predict the pharmacokinetics of drugs delivered via EVs, such as the rate at which the drug is absorbed and distributed throughout the body, the rate at which it is metabolized and eliminated, and the maximum concentration of the drug in the body. This information can be used to optimize the design of EV-based drug delivery systems, including the size and composition of the EVs, the route of administration, and the dose of the drug. There has not been any dedicated review article that describes the PBPK modeling of EV. This review provides an overview of the absorption, distribution, metabolism, and excretion (ADME) phenomena of EVs. In addition, we will briefly describe the different computer-based modeling approaches that may help in the future of EV-based therapeutic research.

Epithelial-to-mesenchymal transition status correlated with ultrastructural features, and TP53 mutation in patient-derived oral cancer cell lines.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) is a highly prevalent cancer in the Indian subcontinent. The major cause of mortality in OSCC patients is metastasis. Epithelial-to-mesenchymal transition (EMT) marks an important step in the metastatic process. Additionally, TP53, an important tumor suppressor gene, is also a significant determinant of the treatment outcome, and also plays a role in EMT. Therefore, understanding the interconnections between ultrastructural features, EMT status and TP53 mutational status is of vital importance. METHODS AND RESULTS: The ultrastructure of five OSCC cell lines was visualized by transmission electron microscopy. Trans-well invasion and migration assays as well as scratch-wound assay, and the expression of various EMT-related genes were utilized to assess the EMT status of the cell lines. The TP53 exons were amplified for the ACOSC3, ACOSC4 and ACOSC16 cell lines and sequenced and the mutations in the gene were identified by sequence alignment. The TP53 mutation in the UPCI:SCC029B cell line has been previously reported, while UPCI:SCC040 has been reported to harbor a wild type TP53. The ACOSC4 cell line which showed the shortest intercellular gaps, also had the least invasive and migratory potential. Interestingly, ACOSC4 showed the highest expression of E-cadherin and the lowest expression of Vimentin, TWIST1, ZEB1, and MMPs. Additionally, TP53 gene of ACOSC4 was unmutated, whereas the ACOSC3 and ACOSC16 harbored TP53 mutations. The mutation in ACOSC3 (R196*) was also found in 7 TCGA samples. Similarly, the UPCI:SCC040 cell line that harbors a wild type TP53 showed shorter intracellular gaps. CONCLUSIONS: Cellular migratory properties are associated with cellular ultrastructure, epithelial-to-mesenchymal transition status and the status of TP53 mutation in the genome.

Secretory phospholipase (sPLA2-IIA) regulates breast cancer stem cells differentiation and metastatic potential.

Breast cancer is the second most cancer worldwide in females. The primary factor responsible for tumor recurrence is the presence of breast cancer stem cells (BCSCs), which escape the chemo-radiotherapy. In this study, we have investigated the role of Secretory phospholipase-A2 Group 2A (sPLA2-IIA) that is overexpressed in BCSCs of MCF7 and MDA-MB-231 breast cancer cell lines. Further, overexpression of sPLA2-IIA revealed an increased EGFR/JNK/c-JUN/c-FOS signaling in BCSCs, while sPLA2-IIA knockdown significantly reduced the percentage of BCSCs and decreased signaling in both the cell lines. Importantly, sPLA2-IIA knockdown showed differentiation of BCSCs. Strikingly, PET imaging showed a decreased metastatic potential of BCSCs. Our study revealed a novel role of sPLA2-IIA in regulating BCSCs, which play a crucial role in regulating the differentiation and metastatic potential of BCSCs.

A Needs Assessment of Older Bangladeshi Immigrants in New York During the COVID-19 Pandemic.

Though immigrants from Bangladesh are a fast-growing and under-resourced immigrant community in the United States, little has been studied about their overall health and social needs. Older immigrant adults from Bangladesh are at increased risk for adverse effects from the COVID-19 pandemic, as they have existing risk factors for isolation including language barriers and more recent immigration. This study examined measures of health and connectedness amongst 297 South Asian adults in New York City who were 60 years or older using a phone-based survey instrument. Surveys were conducted from August 2021 to April 2022. We found that immigrants from Bangladesh were more likely to report a higher effect of the COVID-19 pandemic on financial and food insecurity and faced significantly higher levels of loneliness than South Asian immigrants from other countries. Our findings suggest that older immigrants from Bangladesh disproportionally face social isolation compared to older immigrants from other South Asian countries and our study encourages further research and intervention for this immigrant subgroup.