Faculty Bibliography

After myocardial infarction (MI), emergency hematopoiesis produces inflammatory myeloid cells that accelerate atherosclerosis and promote heart failure. Since the balance between glycolysis and mitochondrial metabolism regulates hematopoietic stem cell homeostasis, metabolic cues may influence emergency myelopoiesis. Here, we show in humans and female mice that hematopoietic progenitor cells increase fatty acid metabolism after MI. Blockade of fatty acid oxidation by deleting carnitine palmitoyltransferase (Cpt1A) in hematopoietic cells of Vav1

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.

CONTEXT/BACKGROUND:Obesity is associated with nonalcoholic fatty liver disease (NAFLD). Sleeve gastrectomy (SG) is an effective means of weight loss and improvement of NAFLD in adults; however, data regarding the efficacy of SG in the early stages of pediatric NAFLD are sparse. OBJECTIVE:To assess the impact of SG on hepatic fat content 1 year after SG in youth with obesity compared with nonsurgical controls with obesity (NS). DESIGN/METHODS:A 12-month prospective study in 52 participants (mean age, 18.2 ± .36 years) with obesity, comprising 25 subjects who underwent SG (84% female; median body mass index [BMI], 44.6 [42.1-47.9] kg/m2) and 27 who were NS (70% female; median BMI, 42.2 [38.7-47.0] kg/m2). MAIN OUTCOME MEASURES/METHODS:Hepatic fat content by computed tomography (liver/spleen ratio), abdominal fat by magnetic resonance imaging. RESULTS:Mean 12-month decrease in BMI was greater in SG vs NS (-12.5 ± .8 vs -.2 ± .5 kg/m2, P < .0001). There was a within-group increase in the liver-to-spleen (L/S) ratio in SG (.13 ± .05, P = .014) but not NS with a trend for a difference between groups (P = .055). All SG participants with an L/S ratio <1.0 (threshold for the diagnosis of NAFLD) before surgery had a ratio of >1.0 a year after surgery, consistent with resolution of NAFLD. Within SG, the 12-month change in L/S ratio was negatively associated with 12-month change in visceral fat (ρ = -.51 P = .016). CONCLUSIONS:Hepatic fat content as assessed by noncontrast computed tomography improved after SG over 1 year in youth with obesity with resolution of NAFLD in all subjects. This was associated with decreases in visceral adiposity.

Sleeve gastrectomy (SG) has many metabolic benefits and leads to improvements in testosterone levels, which means improvement in the Leydig cell function of the testis. However, data about the effects of SG on Sertoli cell function (as assessed by inhibin B) are not available. In this preliminary study, we evaluate, for the first time, the effect of SG in adolescents after SG. We evaluate 16 adolescent and young adult males, six of whom underwent SG and followed them for 2 years. We report that Leydig cell function (as assessed by testosterone levels) improved and was associated with degree of weight loss. Sertoli cell function improved only slightly in SG group and did not change compared to the nonsurgical controls, and these changes were not associated with degree of weight loss. Thus, we conclude that larger and long-term follow-up studies are required to evaluate the changes in Sertoli cell function after SG as that is integral to male fertility.Clinical Trial Registration: NCT02557438.

The ability of research networks and individual institutions to effectively and efficiently prepare, respond, and adapt to emergent challenges is essential for the biomedical research enterprise. At the beginning of 2021, a special Working Group was formed by individuals in the Clinical and Translational Science Award (CTSA) consortium and approved by the CTSA Steering Committee to explore "Adaptive Capacity and Preparedness (AC&P) of CTSA Hubs." The AC&P Working Group took a pragmatic Environmental Scan (E-Scan) approach of utilizing the diverse data that had been collected through existing mechanisms. The Local Adaptive Capacity framework was adapted to illustrate the interconnectedness of CTSA programs and services, while exposing how the demands of the pandemic forced them to quickly pivot and adapt. This paper presents a synopsis of the themes and lessons learned that emerged from individual sections of the E-Scan. Lessons learned from this study may improve our understanding of adaptive capacity and preparedness at different levels, as well as help strengthen the core service models, strategies, and foster innovation in clinical and translational science research.

The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed our lives and the delivery of healthcare. The pandemic also led to widespread disruption in the research activities and training of pre-doctoral, post-doctoral, and early career faculty researchers. This mini-review uses the Local Adaptive Capacity Framework to describe successful practices, challenges, and lessons learned on how Clinical and Translational Science Award (CTSA) hubs have used their expertise, resources, and collaborations to advance clinical and translational science research and workforce development while facing and adapting to a pandemic. Data for this mini-review were taken from the scientific literature (23 articles) and the Research Performance Progress Reports of 50 unique CTSA hubs (40 TL1 and 50 KL2 awards). Institutions responded in innovative ways to the disruption of the COVID-19 pandemic. Electronic and virtual platforms were used to overcome challenges related to physical distancing, laboratory closures, and travel bans. The importance of mentorship and well-being led to the creation of new virtual programs to expand mentoring and networking beyond the home institution and to promote well-being and resilience. These solutions to translational workforce development can be implemented to address future public health emergencies.

Despite higher bone mineral density (BMD), women with obesity are at an increased risk of fracture compared to normal-weight women. Optimal adolescent bone accrual is critical for normal peak bone mass acquisition and future bone health. Whereas several studies have examined the impact of low body weight on bone accrual in youth, data are lacking regarding the impact of obesity on bone accrual. We examined bone accrual over one year in young women with moderate to severe obesity (OB) (n = 21) versus normal-weight controls (NWC) (n = 50). Participants were 13-25 years old. We used dual-energy X-ray absorptiometry to assess areal BMD (aBMD) and high resolution peripheral quantitative computed tomography (distal radius and tibia) to assess volumetric BMD (vBMD), bone geometry, and microarchitecture. Analyses were controlled for age and race. The mean age was 18.7 ± 2.7 years. OB and NWC were similar for age, race, height, and physical activity. OB had a higher BMI (p < 0.0001) and younger menarchal age (p = 0.022) than NWC. Over one year, OB did not demonstrate the increase in total hip BMD observed in NWC (p = 0.03). Increases in percent cortical area and cortical thickness, and cortical and total vBMD at the radius were lower in OB than in NWC (p ≤ 0.037). Groups did not differ for tibial bone accrual. We demonstrate that longitudinal bone accrual is impaired at the total hip and radial cortex in young women with obesity, raising concerns regarding their future bone health.

BACKGROUND AND OBJECTIVES:Internal neurofibromas, including plexiform neurofibromas (PNF), can cause significant morbidity in patients with neurofibromatosis type 1 (NF1). PNF growth is most pronounced in children and young adults, with more rapid growth thought to occur in a subset of PNF termed distinct nodular lesions (DNL). Growth behavior of internal neurofibromas and DNL in older adults is not well documented; yet knowledge thereof is important for patient risk stratification and clinical trial design. The primary objective of this study was to evaluate the long-term growth behavior of internal neurofibromas in adults with NF1. Secondary objectives were to correlate tumor growth behavior with patient-specific, tumor-specific, and patient-reported variables. METHODS:In this prospective cohort study, internal neurofibromas were identified on coronal short TI inversion recovery sequences on baseline and follow-up whole-body MRIs (WBMRIs). Tumor growth and shrinkage were defined as a volume change ≥20%. The association between tumor growth and patient-specific (baseline age, sex, and genotype), tumor-specific (morphology, location, DNL presence on baseline WBMRI, and maximum standardized uptake value on baseline PET imaging), and patient-reported variables (endogenous and exogenous hormone exposure, pain intensity, and quality of life) was assessed using the Spearman correlation coefficient and Kruskal-Wallis test. RESULTS:Of 106 patients with a baseline WBMRI obtained as part of a previous research study, 44 had a follow-up WBMRI. Three additional patients with WBMRIs acquired for clinical care were included, generating 47 adults for this study. The median age during baseline WBMRI was 42 years (range 18-70). The median time between WBMRIs was 10.4 years. Among 324 internal neurofibromas, 62.8% (56% of PNF and 62.1% of DNL) shrank spontaneously without treatment and 17.1% (17.9% of PNF and 13.8% of DNL) grew. Growth patterns were heterogeneous within participants. Patient-specific, tumor-specific, and patient-reported variables (including endogenous and exogenous hormone exposure) were not strong predictors of tumor growth. DISCUSSION:Internal neurofibroma growth behavior in older adults differs fundamentally from that in children and young adults, with most tumors, including DNL, demonstrating spontaneous shrinkage. Better growth models are needed to understand factors that influence tumor growth. These results will inform clinical trial design for internal neurofibromas.