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A pilot study protocol of a relational coordination training intervention among healthcare professionals in an Army medical center
No full textBackground: As patient care becomes more complex, high-quality communication and relationships among healthcare professionals are critical to coordinating care. Relational coordination (RC), a process of high-quality communication supported by shared goals, shared knowledge, and mutual respect, is positively associated with better patient (e.g., quality of care) and staff (e.g., job satisfaction, and retention) outcomes. A few researchers have found that communication skills training improves RC in civilian hospitals. However, researchers have not tested the feasibility of conducting communication skills training based on the RC framework among healthcare professionals in military hospitals. To address this gap, we propose conducting an RC training intervention in a military hospital. The primary aim of the proposed pilot study is to determine the feasibility (e.g., recruitment, retention, and completion rates) of conducting an RC training intervention in an Army medical center. The secondary aim is to explore the acceptability and usability of the RC training intervention. We will also explore changes in RC, quality of care, job satisfaction, and intent to stay among participants following the RC training intervention.
Methods: A single-group feasibility study will be conducted among nurses and physicians from three units (intensive care unit, medical-surgical, and labor and delivery unit). A convenience sample of licensed practical nurses (LPNs), registered nurses (RNs), resident physicians, and physicians from the participating units will be invited to complete a 1-h RC training intervention once a month for 3 months. Participants will complete RC, quality of care, job satisfaction, and intent to stay measures at baseline and 2 weeks after each RC training intervention session. To assess the feasibility of conducting an RC training intervention, we will examine recruitment/retention rates, intervention session completion rates, and survey measure completion rates. Acceptability will be assessed qualitatively through focus group interviews, and results will be used to refine the intervention and determine if the selected measures align with participant experiences. For our secondary aim, we will explore the acceptability of the RC training intervention through focus group interviews. We will also explore changes in outcome measures using descriptive statistics with 95% confidence intervals.
Discussion: Findings will establish the feasibility and acceptability of conducting an RC intervention in a military hospital and inform refinement of the intervention and study procedures prior to conducting a larger randomized controlled trial to establish efficacy
Positive feedback regulation between RpoS and BosR in the Lyme disease pathogen
No full textIn Borrelia burgdorferi, the causative agent of Lyme disease, differential gene expression is primarily governed by the alternative sigma factor RpoS (σS). Understanding the regulation of RpoS is crucial for elucidating how B. burgdorferi is maintained throughout its enzootic cycle. Our recent studies have shown that the homolog of Fur/PerR repressor/activator BosR functions as an RNA-binding protein that controls the rpoS mRNA stability. However, the mechanisms regulating BosR, particularly in response to host signals and environmental cues, remain largely unclear. In this study, we uncovered a positive feedback loop between RpoS and BosR, wherein RpoS post-transcriptionally regulates BosR levels. Specifically, mutation or deletion of rpoS significantly reduced BosR levels, whereas artificial induction of rpoS resulted in a dose-dependent increase in BosR levels. Notably, RpoS does not affect bosR mRNA levels but instead modulates the turnover rate of the BosR protein. Moreover, we demonstrated that environmental cues do not directly influence bosR expression but instead induce rpoS transcription and RpoS production, thereby enhancing BosR protein levels. These findings reveal a new layer of complexity in the RpoN-RpoS regulatory pathway, challenging the existing paradigm and suggesting a need to re-evaluate the factors and signals previously implicated in regulating RpoS via BosR. This study provides new insights into the intricate regulatory networks underpinning B. burgdorferi's adaptation and survival in its enzootic cycle.IMPORTANCELyme disease is the most prevalent arthropod-borne infection in the United States. The etiological agent, Borreliella (or Borrelia) burgdorferi, is maintained in nature through an enzootic cycle involving a tick vector and a mammalian host. RpoS, the master regulator of differential gene expression, plays a crucial role in tick transmission and mammalian infection of B. burgdorferi. This study reveals a positive feedback loop between RpoS and a Fur/PerR homolog. Elucidating this regulatory network is essential for identifying potential therapeutic targets to disrupt B. burgdorferi's enzootic cycle. The findings also have broader implications for understanding the regulation of RpoS and Fur/PerR family in other bacteria
Editorial: The immunosuppressive microenvironment in pediatric cancers: applications and considerations in immunotherapy
No full textPreventing Oral Dual Biofilm Development with Innovative Bioactive Varnishes
No full textThis study introduces innovative varnishes incorporating natural bioactive compounds to inhibit the formation of oral dual biofilms, a critical contributor to dental caries and other oral diseases. The purpose of this study was to evaluate the effectiveness of bioactive varnishes containing tt-farnesol, quercetin, and theobromine in inhibiting the formation of mixed Streptococcus mutans and Candida albicans biofilms. Mixed biofilms of Streptococcus mutans UA159 and Candida albicans SC5314 were grown in 96-well plates containing a specialized culture medium. Approximately 0.2 mL of experimental varnishes with A-1.5% or B-4.5% concentrations of tt-farnesol, quercetin, and theobromine were separately added to the wells using a disposable applicator, with a vehicle varnish (lacking bioactives) serving as the control. Biofilms were incubated at 37 °C with 5% CO2 for 24 h. Microbial viability was determined in terms of colony-forming units per milliliter (CFU/mL), and biofilm morphology was evaluated qualitatively via scanning electron microscopy (SEM). Statistical analyses were performed using ANOVA/Tukey tests at a 5% significance level. Varnishes A and B achieved significant reductions in microbial populations within the biofilms (p < 0.05) compared to the vehicle control (C). SEM imaging revealed marked structural disruptions in the biofilms, validating the quantitative results. Higher bioactive concentrations demonstrated enhanced inhibitory effects. Bioactive varnishes enriched with theobromine, quercetin, and tt-farnesol represent a novel and effective strategy for inhibiting oral dual biofilm development, offering a promising advancement in preventive dentistry
Two-Stage CD8+ CAR T-Cell Differentiation in Patients with Large B-Cell Lymphoma
No full textChimeric antigen receptor (CAR) T-cell therapy has expanded therapeutic options for patients with diffuse large B-cell lymphoma (DLBCL). However, progress in improving clinical outcomes has been limited by an incomplete understanding of CAR T-cell differentiation in patients. To comprehensively investigate CAR T-cell differentiation in vivo, we performed single-cell, multimodal, and longitudinal analyses of CD28-costimulated CAR T cells from infusion product and peripheral blood (day 8-28) of patients with DLBCL who were successfully treated with axicabtagene ciloleucel. Here, we show that CD8+ CAR T cells undergo two distinct waves of clonal expansion. The first wave is dominated by CAR T cells with an exhausted-like effector memory phenotype during the peak expansion period (day 8-14). The second wave is dominated by CAR T cells with a terminal effector phenotype during the post-peak persistence period (day 21-28). Importantly, the two waves have distinct ontogeny and are biologically uncoupled. Furthermore, lineage tracing analysis via each CAR T cell's endogenous TCR clonotype demonstrates that the two waves originate from different effector precursors in the infusion product. Precursors of the first wave exhibit more effector-like signatures, whereas precursors of the second wave exhibit more stem-like signatures. These findings suggest that pre-infusion heterogeneity mediates the two waves of in vivo clonal expansion. Our findings provide evidence against the intuitive idea that the post-peak contraction in CAR abundance is solely apoptosis or extravasation of short-lived CAR T cells from peak expansion. Rather, our findings demonstrate that CAR T-cell expansion and persistence are mediated by clonally, phenotypically, and ontogenically distinct CAR T-cell populations that serve complementary clinical purposes
Deciphering genetic regulation at single-cell resolution in gastric cancer
No full textUnderstanding cell-type-specific genetic regulation in gastric cancer is essential for uncovering disease susceptibility. By performing single-cell eQTL mapping in gastric tissues, Bian et al.1 identified previously uncharacterized regulatory genetic mechanisms, risk genes, and co-localization signals associated with gastric cancer susceptibility, providing insights into its pathogenesis and potential therapeutic approaches
Exploring Motivations for a Career in Geriatrics: Perspectives from fellows and recent graduates
No full textBackground: Recent literature reports declining numbers of medical trainees pursing a fellowship in geriatrics. The few qualitative studies that seek information as to why medical trainees choose geriatrics focus on what the subjects dislike about the field. The purpose of this study is to determine factors that motivated recent medical residency or fellowship graduates to pursue a career in geriatrics and gather information on the positive aspects of their career.
Methods: 13 eligible participants were interviewed, either current geriatric fellows or graduates from an accredited geriatric fellowship in the U.S. within the last 6 years. Interviews were transcribed and coded by the research team.
Results: There were 18 codes identified that were then divided into four themes: 1) personal experiences with older adults and geriatricians; 2) distinguishing characteristics of geriatrics as a specialty; 3) benefits and challenges of a career in geriatric medicine; and 4) expectations and recommendations for the future of geriatrics. Responses suggested close relationships with older adults, early clinical experiences in geriatrics, and having geriatrician mentors were common motivating factors. Benefits of a career in geriatrics, including good work-life integration, flexible career paths, supportive work environments, appreciative patients and caregivers, and making an impact, were met with challenges related to increased medical complexity and working in a system that does not value preventative care or the needs of older adults. Participants discussed the need for increased exposure to geriatrics in medical training and the need for geriatrics to further evolve as a specialty.
Conclusions: Common motivating factors included personal relationships with older adults and early clinical exposure to geriatrics. Findings suggest that participants consider their work to be rewarding with many lifestyle benefits, and the declining number of medical trainees pursuing geriatrics should be met with efforts to increase exposure to the field early in medical training
Genetic modulation of protein expression in rat brain
No full textGenetic variations in protein expression are implicated in a broad spectrum of common diseases and complex traits but remain less explored compared to mRNA and classical phenotypes. This study systematically analyzed brain proteomes in a rat family using tandem mass tag (TMT)-based quantitative mass spectrometry. We quantified 8,119 proteins across two parental strains (SHR/Olalpcv and BN-Lx/Cub) and 29 HXB/BXH recombinant inbred (RI) strains, identifying 597 proteins with differential expression and 464 proteins linked to cis-acting quantitative trait loci (pQTLs). Proteogenomics identified 95 variant peptides, and sex-specific analyses revealed both shared and distinct cis-pQTLs. We improved the ability to pinpoint candidate genes underlying pQTLs by utilizing the rat pangenome and explored the connections between pQTLs in rats and human disorders. Collectively, this study highlights the value of large proteo-genetic datasets in elucidating protein modulation in the brain and its links to complex central nervous system (CNS) traits