Using external morphology as a proxy for stomach size in Hemigrapsus sanguineus.

Stomach morphology can provide insights into an organism's diet. Gut size or length is typically inversely related to diet quality in most taxa, and has been used to assess diet quality in a variety of systems. However, it requires animal sacrifice and time-consuming dissections. Measures of external morphology associated with diet may be a simpler, more cost-effective solution. At the species level, external measures of the progastric region of the carapace in brachyuran crabs can predict stomach size and diet quality, with some suggestion that this approach may also work to examine individual diet preferences and specialization at the individual level; if so, the size of the progastric region could be used to predict trends in diet quality and consumption for individuals, which would streamline diet studies in crabs. Here, we tested whether external progastric region size predicts internal stomach size across latitude and time of year for individuals of the invasive Asian shore crab Hemigrapsus sanguineus. We found that the width of the progastric region increased at a faster rate with body size than stomach width. In addition, the width of the progastric region followed different trends across sites and over time compared to stomach width. Our results therefore suggest that the progastric region may not be used as a proxy for stomach size variation across individuals.

Long-Acting Injectable ART in Practice: A Mixed Methods Implementation Study Assessing the Feasibility of Using LAI ART in High Risk Populations and At Alternative Low Barrier Care Sites.

Long-acting injectable (LAI) antiretroviral therapy (ART) has the potential to change the lives of people living with HIV (PLWH). To ensure equitable access to new treatment modalities, we examined the feasibility and acceptability of administering Cabotegravir Rilpivirine Long Acting (CAB/RPV LA) to individuals who experience challenging social determinants of health (SDoH) and struggle with adherence to traditional oral ART. Quantitative and qualitative data were used to assess feasibility of utilizing ART at alternative clinic. Data were collected on individuals eligible to receive CAB/RPV LA at an alternative street-based clinic and on individuals receiving CAB/RPV LA at a traditional HIV clinic. After 6 months, participants were interviewed about their experience. Providers involved in the implementation were also interviewed about their experiences. Only one participant (out of 5) who received CAB/RPV LA at the alternative clinic received consistent treatment, whereas 17 out of 18 participants receiving CAB/RPV LA at the traditional clinic site were adherent. Participants and providers believed that LAI had potential for making treatment adherence easier, but identified several barriers, including discrepancies between patients' desires and their lifestyles, impact of LAI on interactions with the medical system, risk of resistance accompanying sub-optimal adherence, and need for a very high level of resources. While LAI has major potential benefits for high-risk patients, these benefits must be balanced with the complexities of implementation. Despite challenges that impacted study outcomes, improving treatment outcomes for PLWH requires addressing SDoH and substance use.

The thermoneutral zone in women takes an "arctic" shift compared to men.

Conventionally, women are perceived to feel colder than men, but controlled comparisons are sparse. We measured the response of healthy, lean, young women and men to a range of ambient temperatures typical of the daily environment (17 to 31 °C). The Scholander model of thermoregulation defines the lower critical temperature as threshold of the thermoneutral zone, below which additional heat production is required to defend core body temperature. This parameter can be used to characterize the thermoregulatory phenotypes of endotherms on a spectrum from "arctic" to "tropical." We found that women had a cooler lower critical temperature (mean ± SD: 21.9 ± 1.3 °C vs. 22.9 ± 1.2 °C, P = 0.047), resembling an "arctic" shift compared to men. The more arctic profile of women was predominantly driven by higher insulation associated with more body fat compared to men, countering the lower basal metabolic rate associated with their smaller body size, which typically favors a "tropical" shift. We did not detect sex-based differences in secondary measures of thermoregulation including brown adipose tissue glucose uptake, muscle electrical activity, skin temperatures, cold-induced thermogenesis, or self-reported thermal comfort. In conclusion, the principal contributors to individual differences in human thermoregulation are physical attributes, including body size and composition, which may be partly mediated by sex.

Shift from income breeding to capital breeding with latitude in the invasive Asian shore crab Hemigrapsus sanguineus.

Organisms vary in the timing of energy acquisition and use for reproduction. Thus, breeding strategies exist on a continuum, from capital breeding to income breeding. Capital breeders acquire and store energy for breeding before the start of the reproductive season, while income breeders finance reproduction using energy acquired during the reproductive season. Latitude and its associated environmental drivers are expected to heavily influence breeding strategy, potentially leading to latitudinal variation in breeding strategies within a single species. We examined the breeding strategy of the Asian shore crab Hemigrapsus sanguineus at five sites spanning nearly 10° of latitude across its invaded United States range. We hypothesized that the primary breeding strategy of this species would shift from income breeding to capital breeding as latitude increases. We found that though this species' breeding strategy is dominated by capital breeding throughout much of the range, income breeding increases in importance at lower latitudes. This latitudinal pattern is likely heavily influenced by the duration of the foraging and breeding seasons, which also vary with latitude. We also found that reproductive characteristics at the northern and southern edges of the invaded range were consistent with continued range expansion. We suggest that the reproductive flexibility of the Asian shore crab is a key facilitator of its continued invasion success. Our results highlight the influence of latitude on the breeding strategy of a species and emphasize the need for further research regarding the ecological importance and implications of flexibility in breeding strategies within species.

Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile. In parallel, brown and white fat were examined in a liver-specific transgenic MMA mouse model (Mmut-/- TgINS-Alb-Mmut). The MMA mice exhibited abnormal nonshivering thermogenesis with whitened brown fat and had an ineffective transcriptional response to cold stress. Treatment of the MMA mice with bezafibrates led to clinical improvement with beiging of subcutaneous fat depots, which resembled the distribution seen in the patients. These studies defined what we believe to be a novel lipodystrophy phenotype in patients with defects in the terminal steps of BCAA oxidation and demonstrated that beiging of subcutaneous adipose tissue in MMA could readily be induced with small molecules.

The Relationship Between Program and Applicant Characteristics With Applicant Program Signals in the 2022 Residency Recruitment Cycle: Findings From 3 Specialties.

PURPOSE: Continuing increases in application volume have driven a national dialogue to reform the residency recruitment process. Program signaling allows applicants to express interest in a program at the preinterview stage with the goal of helping programs identify applicants with more genuine interest in their programs. This study explored the relationship between program signals and program and applicant characteristics. METHOD: Participating dermatology, general surgery, and categorical internal medicine (IM) programs and applicants of the 2022 supplemental ERAS application (SuppApp) were included. Data from the SuppApp, the MyERAS Application for Residency Applicants (MyERAS), and the 2020 GME Track Survey were used. Cohen's h was used to determine effect size, and chi-squared was used to determine statistical significance. RESULTS: There was an uneven distribution of signals to programs, with 25% of programs receiving about half of the signals across all 3 specialties. Programs with larger numbers of both residents and applicants received greater numbers of program signals relative to their program density, although this effect was small ( h < 0.50, P < .001). No meaningful differences were seen across genders for any specialty. Only Hispanic applicants in IM sent a higher proportion of signals to programs with more underrepresented in medicine residents than White only applicants (40% vs 26%, h = 0.30, P < .001). Across all specialties, there was a small-to-moderate effect for international medical graduate (IMG) applicants sending a larger proportion of signals to programs with more IMG residents ( h < 0.80, P < .001). CONCLUSIONS: This first-year pilot study (i.e., SuppApp) provided initial evidence that supports the feasibility and fairness of program signals in residency selection. As program signals become more common across specialties, future research should continue to evaluate trends in where applicants send signals, and possible relationships between program and application characteristics.

Self-Reported Disadvantage in Medical School Admissions: A Call to Review, Revise, and Further Advance Holistic Review.

PURPOSE: This study examined how applicants interpret the self-reported disadvantaged (SRD) question in the American Medical College Application Service (AMCAS) application. METHOD: Data from 129,262 applicants who applied through AMCAS from 2017 through 2019 were used, including financial and family history, demographic characteristics, and work status and residence. Fifteen applicants from the 2020 and 2021 AMCAS cycles were interviewed about their experiences with the SRD question. RESULTS: Large effects were found for SRD applicants with fee assistance waivers ( h = 0.89), Pell grants ( h = 1.21), state or federal aid ( h = 1.10), and parents with less education ( h = 0.98) and non-SRD applicants with a large proportion of their education paid by family ( d = 1.03). Another large difference was found for reported family income distribution (73% of SRD applicants reporting family income < $50,000 vs 15% of non-SRD applicants). More SRD applicants were Black or Hispanic (26% vs 16% and 5% vs 5%), Deferred Action for Childhood Arrivals recipients (11% vs 2%), born outside the United States (32% vs 16%), and raised in a medically underserved area (60% vs 14%). There was a moderate effect for first-generation to college SRD applicants ( h = 0.61). SRD applicants had lower Medical College Admission Test scores ( d = 0.62) and overall and science grade point averages ( d = 0.50 and 0.49, respectively) but no meaningful differences in acceptance or matriculation rates. The interviews identified 5 themes: (1) unclear disadvantage definition; (2) different perceptions of disadvantage and overcoming challenges or obstacles ; (3) identification as disadvantaged or not; (4) SRD essay content; and (5) concerns about lack of transparency in how the SRD question is used in admissions. CONCLUSIONS: Revising the SRD question by including context, phrasing, and instructions for broader experience categories might be beneficial because of lack of transparency and understanding.

Predicting diet in brachyuran crabs using external morphology.

Morphological traits have often been used to predict diet and trophic position of species across many animal groups. Variation in gut size of closely related animals is known to be a good predictor of dietary habits. Species that are more herbivorous or that persist on low-quality diets often have larger stomachs than their carnivorous counterparts. This same pattern exists in crabs and in most species, individuals exhibit external markings on the dorsal side of their carapace that appear to align with the position and size of their gut. We hypothesized that these external markings could be used as an accurate estimate of the crab's cardiac stomach size, allowing an approximation of crab dietary strategies without the need to sacrifice and dissect individual animals. We used literature values for mean diet and standardized external gut size markings taken from crab photographs across 50 species to show that percent herbivory in the diet increases non-linearly across species of brachyuran crab with the external estimate of gut size. We also used data from dissections in four species to show that external gut markings were positively correlated with gut sizes, though the strength of this correlation differed across species. We conclude that when rough approximations of diet quality such as percent herbivory will suffice, measuring external carapace markings in crabs presents a quick, free, non-lethal alternative to dissections. Our results also provide important insights into tradeoffs that occur in crab morphology and have implications for crab evolution.

Perspectives on long-acting injectable HIV antiretroviral therapy at an alternative care site: a qualitative study of people with HIV experiencing substance use and/or housing instability.

INTRODUCTION: Adherence to daily oral antiretroviral therapy (ART) and regular clinic appointments can be challenging for individuals who experience adverse social determinants of health. Long-acting injectable ART administered outside of traditional clinic settings may be a promising solution to adherence barriers, but additional research is needed to assess patients' perspectives. This study assessed perspectives of people living with HIV (PLWH) who had difficulty with adherence to traditional HIV care models and evaluated feasibility and acceptability of receiving a long-acting ART injection at a location outside of a traditional HIV clinic to address barriers to HIV care. METHODS: Qualitative interviews (n = 26) were conducted with PLWH who had experienced barriers to adherence. Participants were referred to the study by staff from Project Trust, a drop in harm reduction and sexually transmitted infection/HIV clinic. The interviews were conducted between May and November 2021. Interviews were recorded, professionally transcribed, coded, and analyzed qualitatively using the integrated-Promoting Action on Research Implementation in Health Services framework. RESULTS: We identified 6 main themes regarding the acceptability of receiving a long-acting injection to treat HIV, and the acceptability and feasibility of receiving injections at an alternative care site. Participants specified that they: (1) have a general understanding about their HIV care and the importance of ART adherence, (2) prefer a long-acting injection over a daily pill regimen, (3) expressed concerns about injection safety and efficacy, (4) had specific logistical aspects around the delivery of long-acting injections, including location of injection administration, that they believed would improve their ability to adhere, (5) have confidence that they can become undetectable and then complete the oral lead-in required to begin receiving the injection, and (6) see potential barriers that remain a concern for successful adherence to long-acting injections. CONCLUSION: To better treat HIV among people who are living with challenging social determinants of health, interventions that include a long-acting injection in a non-traditional care setting may prove to be a promising treatment option.

Latitudinal and temporal variation in injury and its impacts in the invasive Asian shore crab Hemigrapsus sanguineus.

Nonlethal injury is a pervasive stress on individual animals that can affect large portions of a population at any given time. Yet most studies examine snapshots of injury at a single place and time, making the implicit assumption that the impacts of nonlethal injury are constant. We sampled Asian shore crabs Hemigrapsus sanguineus throughout their invasive North American range and from the spring through fall of 2020. We then documented the prevalence of limb loss over this space and time. We further examined the impacts of limb loss and limb regeneration on food consumption, growth, reproduction, and energy storage. We show that injury differed substantially across sites and was most common towards the southern part of their invaded range on the East Coast of North America. Injury also varied idiosyncratically across sites and through time. It also had strong impacts on individuals via reduced growth and reproduction, despite increased food consumption in injured crabs. Given the high prevalence of nonlethal injury in this species, these negative impacts of injury on individual animals likely scale up to influence population level processes (e.g., population growth), and may be one factor acting against the widespread success of this invader.

Metabolic rates of the Asian shore crab Hemigrapsus sanguineus in air as a function of body size, location, and injury.

Rapid warming in the Gulf of Maine may influence the success or invasiveness of the Asian shore crab, Hemigrapsus sanguineus. To better predict the effects of climate change on this invasive species, it is necessary to measure its energy dynamics under a range of conditions. However, previous research has only focused on the metabolism of this intertidal species in water. We sampled adult crabs from three different sites and measured their metabolic rates in the air. We show that metabolic rate increases with body mass and the number of missing limbs, but decreases with the number of regenerating limbs, possibly reflecting the timing of energy allocation to limb regeneration. Importantly, metabolic rates measured here in the air are ~4× higher than metabolic rates previously measured for this species in water. Our results provide baseline measurements of aerial metabolic rates across body sizes, which may be affected by climate change. With a better understanding of respiration in H. sanguineus, we can make more informed predictions about the combined effects of climate change and invasive species on the northeast coasts of North America.

Twelve-month clinical outcomes after implantation of a new, modular, anterior shape-changing fluid optic intraocular lens.

PURPOSE: To report the initial safety and effectiveness profile for an anterior shape-changing, modular IOL, Juvene IOL (JIOL), for the treatment of aphakia and presbyopia after removal of the natural crystalline lens due to cataract. SETTING: 2 private practices in Monterrey and Tijuana, Mexico. DESIGN: Exploratory prospective multicenter open-label noncomparative clinical trial. METHODS: A convenience sample of patients aged 50 to 80 years with planned cataract surgery was recruited to undergo unilateral or bilateral implantation with the JIOL. Patients were required to complete an informed consent and be able to dilate to at least 6.0 mm pharmacologically, be in good overall health, and have no significant eye health history to qualify. Visual acuities, defocus curves, and contrast sensitivity were measured for all patients 12 months postoperatively. RESULTS: 51 of 58 eyes completed the 12-month visit. Intraoperative complication rates were extremely low (n = 1; missed base lens tab). The most frequent adverse events (AEs) were prolonged inflammation (N = 6) and cystoid macular edema (N = 4); all AEs were resolved without sequelae by the 12-month visit. The mean monocular logMAR corrected distance visual acuity, distance-corrected intermediate visual acuity, and distance-corrected near visual acuity were 0.01, 0.08, and 0.24, respectively. Defocus testing showed visual acuity > 20/40 from approximately +1.00 through -2.00 diopters. Binocular implantation (n = 16) provided superior performance over monocular implantation. CONCLUSIONS: The JIOL offers a new solution to treat presbyopia, providing clear functional vision performance across a range of distances with an acceptable initial safety profile.

Metabolic rates in the squareback marsh crab Armases cinereum.

Metabolic rate is a basic individual metric that extends beyond the individual to link the ecology of populations, communities, and ecosystems via its role as a central component of energy budgets. Metabolic rates are often measured indirectly by quantifying respiration under simplified, standard laboratory conditions. This approach limits the application of these measurements to a small range of conditions that commonly do not reflect natural field conditions. We measured metabolic rates of the squareback marsh crab Armases cinereum under field conditions. Previous work highlights that movement of individual A. cinereum, especially females, provides a potential spatial subsidy of energy, as individuals consume foods in salt marshes and then transfer the resulting energy to upland forest ecosystems. We show that metabolic rate increases with size for both males and females and that metabolic rates are influenced by temperature and by whether females are vitellogenic. The metabolic rates that we measured more closely approximate field metabolic rates than standard metabolic rates and demonstrate that individual crabs experience high energy expenditures, reducing the amount of energy that may be transferred as a subsidy between marsh and forest as a result of the daily movements of individual crabs. Our measurements are therefore also a key component for the construction of an energy budget for this species.

Experiences and effectiveness of occupational therapy interventions delivered in the acute setting: a mixed methods systematic review protocol.

OBJECTIVE: The objective of this review is to synthesize and integrate the best available evidence on the experiences and effectiveness of occupational therapy interventions delivered in the acute setting. INTRODUCTION: Occupational therapy is a client-centered health profession promoting health and well-being through occupation. In acute hospital settings, occupational therapy interventions are provided to patients to maximize function, prevent readmission, and promote safe discharge. Recent studies have demonstrated that occupational therapy has modified its practice in acute settings to include advocacy, team facilitation, and rapid clinical reasoning. This review will investigate not only the effectiveness of occupational therapy interventions, but also the experiences of patients, caregivers, and clinicians in the acute setting. INCLUSION CRITERIA: This review will consider qualitative, quantitative, and mixed methods studies on the experiences and effectiveness of occupational therapy interventions delivered in acute settings. For the qualitative component, the experiences of patients and caregivers receiving any occupational therapy intervention, and clinicians directly or indirectly involved in delivering occupational therapy interventions, will be investigated. For the quantitative component, occupational therapy interventions will be compared with non-occupational therapy interventions, no intervention, wait-list, or other inactive or active (usual care) control interventions. Patient outcomes will include impairment, activities of daily living, psychological outcomes, and quality of life, while health system outcomes will include health care utilization and patient flow. METHODS: The databases to be searched include CINAHL, Cochrane Controlled Trials Register, MEDLINE (Ovid), OT Seeker, PsycINFO (Ovid), and Scopus. Study selection, critical appraisal, data extraction, and data synthesis and integration will utilize the JBI segregated approach to mixed methods systematic reviews. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020206363.

1-13C-propionate breath testing as a surrogate endpoint to assess efficacy of liver-directed therapies in methylmalonic acidemia (MMA).

PURPOSE: To develop a safe and noninvasive in vivo assay of hepatic propionate oxidative capacity. METHODS: A modified 1-13C-propionate breath test was administered to 57 methylmalonic acidemia (MMA) subjects, including 19 transplant recipients, and 16 healthy volunteers. Isotopomer enrichment (13CO2/12CO2) was measured in exhaled breath after an enteral bolus of sodium-1-13C-propionate, and normalized for CO2 production. 1-13C-propionate oxidation was then correlated with clinical, laboratory, and imaging parameters collected via a dedicated natural history protocol. RESULTS: Lower propionate oxidation was observed in patients with the severe mut0 and cblB subtypes of MMA, but was near normal in those with the cblA and mut- forms of the disorder. Liver transplant recipients demonstrated complete restoration of 1-13C-propionate oxidation to control levels. 1-13C-propionate oxidation correlated with cognitive test result, growth indices, bone mineral density, renal function, and serum biomarkers. Test repeatability was robust in controls and in MMA subjects (mean coefficient of variation 6.9% and 12.8%, respectively), despite widely variable serum methylmalonic acid concentrations in the patients. CONCLUSION: Propionate oxidative capacity, as measured with 1-13C-propionate breath testing, predicts disease severity and clinical outcomes, and could be used to assess the therapeutic effects of liver-targeted genomic therapies for MMA and related disorders of propionate metabolism. TRIAL REGISTRATION: This clinical study is registered in www.clinicaltrials.gov with the ID: NCT00078078. Study URL: http://clinicaltrials.gov/ct2/show/NCT00078078.

Sexual Dimorphisms in Adult Human Brown Adipose Tissue.

OBJECTIVE: This study aimed to quantify and compare the amount, activity, and anatomical distribution of cold-activated brown adipose tissue (BAT) in healthy, young, lean women and men. METHODS: BAT volume and 18 F-fluorodeoxyglucose uptake were measured by positron emission tomography and computerized tomography in 12 women and 12 men (BMI 18.5-25 kg/m2 , aged 18-35 years) after 5 hours of exposure to their coldest temperature before overt shivering. RESULTS: Women had a lower detectable BAT volume than men (P = 0.03), but there was no difference after normalizing to body size. The mean BAT glucose uptake and relative distribution of BAT did not differ by sex. 18 F-fluorodeoxyglucose uptake consistent with BAT was observed in superficial dorsocervical adipose tissue of 6 of 12 women but only 1 of 12 men (P = 0.02). This potential BAT depot would pose fewer biopsy risks than other depots. CONCLUSIONS: Despite differences in adiposity and total BAT volume, we found that healthy, lean, young women and men do not differ in the relative amount, glucose uptake, and distribution of BAT. Dorsocervical 18 F-fluorodeoxyglucose uptake was more prevalent in women and may be a remnant of interscapular BAT seen in human newborns. Future studies are needed to discern how BAT contributes to whole-body thermal physiology and body weight regulation in women and men.

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity.

The current obesity pandemic results from a physiological imbalance in which energy intake chronically exceeds energy expenditure (EE), and prevention and treatment strategies remain generally ineffective. Approaches designed to increase EE have been informed by decades of experiments in rodent models designed to stimulate adaptive thermogenesis, a long-term increase in metabolism, primarily induced by chronic cold exposure. At the cellular level, thermogenesis is achieved through increased rates of futile cycling, which are observed in several systems, most notably the regulated uncoupling of oxidative phosphorylation from ATP generation by uncoupling protein 1, a tissue-specific protein present in mitochondria of brown adipose tissue (BAT). Physiological activation of BAT and other organ thermogenesis occurs through ß-adrenergic receptors (AR), and considerable effort over the past 5 decades has been directed toward developing AR agonists capable of safely achieving a net negative energy balance while avoiding unwanted cardiovascular side effects. Recent discoveries of other BAT futile cycles based on creatine and succinate have provided additional targets. Complicating the current and developing pharmacological-, cold-, and exercise-based methods to increase EE is the emerging evidence for strong physiological drives toward restoring lost weight over the long term. Future studies will need to address technical challenges such as how to accurately measure individual tissue thermogenesis in humans; how to safely activate BAT and other organ thermogenesis; and how to sustain a negative energy balance over many years of treatment.

Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity.

BACKGROUNDMirabegron is a ß3-adrenergic receptor (ß3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that ß3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTSChronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSIONThese findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of ß3-AR agonists as a treatment for metabolic disease.TRIAL REGISTRATIONClinicaltrials.gov NCT03049462.FUNDINGThis work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).