First time whole genome sequencing of Mycobacterium bovis from the environment supports transmission at the animal-environment interface.

Spreading of Mycobacterium bovis causing animal tuberculosis (TB) at livestock-wildlife-environment interfaces remains a significant problem. Recently, we provided evidence of widespread environmental contamination of an endemic animal TB setting with viable and dormant M. bovis cells able to recover metabolic activity, making indirect transmission via environmental contamination plausible. We now report the first whole genome sequences of M. bovis recovered from the environment. We establish epidemiological links at the environment-animal interface by phylogenomic comparison of these M. bovis genomes with those isolated from livestock and wild ungulates from the same area. Environmental and animal genomes are highly intertwined and distribute similarly into the same M. bovis lineages, supporting several instances of environmental contamination. This study provides compelling evidence of M. bovis excretion into the environment and viability maintenance, supporting the environment as a potential source of new infection. These insights have clear implications for policy formulation, advocating environmental surveillance and an ecosystem perspective in TB control programs. ENVIRONMENTAL IMPLICATION: We report the first whole genome sequences of M. bovis from the environment and establish epidemiological links at the environment-animal interface, demonstrating close phylogenomic relatedness of animal and environmental M. bovis. Definitive evidence of M. bovis excretion into the environment with viability maintenance is provided, supporting the environment as a potential source of new infection. Implications of this work include methodological innovations offering a tool to resolve indirect transmission chains and support customized biosecurity measures. Policy formulation aiming at the control of animal tuberculosis and cost mitigation should consider these findings, encouraging environmental surveillance in official eradication programmes.

Adiposity, type 2 diabetes and atherosclerotic cardiovascular disease risk: Use and abuse of the body mass index.

The worldwide prevalence of individuals with an elevated body weight has increased steadily over the past five decades. Billions of research dollars have been invested to improve our understanding of the causes and consequences of having an elevated body weight. All this knowledge has, however, failed to influence populational body weight trajectories of most countries around the world. Research on the definition of "obesity" has also evolved. Body mass index (BMI), the most commonly used tool to make its diagnosis, has major limitations. In this review article, we will highlight evidence from observational studies, genetic association studies and randomized clinical trials that have shown the remarkable inter-individual differences in the way humans store energy as body fat. Increasing evidence also suggests that, as opposed to weight inclusive, lifestyle-based approaches, weight-centric approaches advising people to simply eat less and move more are not sustainable for most people for long-term weight loss and maintenance. It is time to recognize that this outdated approach may have produced more harm than good. On the basis of pathophysiological, genetic and clinical evidence presented in this review, we propose that it may be time to shift away from the traditional clinical approach, which is BMI-centric. Rather, emphasis should be placed on actionable lifestyle-related risk factors aiming at improving overall diet quality and increasing physical activity level in the general population.

Rescue of Mycobacterium bovis DNA Obtained from Cultured Samples during Official Surveillance of Animal TB: Key Steps for Robust Whole Genome Sequence Data Generation.

Epidemiological surveillance of animal tuberculosis (TB) based on whole genome sequencing (WGS) of Mycobacterium bovis has recently gained track due to its high resolution to identify infection sources, characterize the pathogen population structure, and facilitate contact tracing. However, the workflow from bacterial isolation to sequence data analysis has several technical challenges that may severely impact the power to understand the epidemiological scenario and inform outbreak response. While trying to use archived DNA from cultured samples obtained during routine official surveillance of animal TB in Portugal, we struggled against three major challenges: the low amount of M. bovis DNA obtained from routinely processed animal samples; the lack of purity of M. bovis DNA, i.e., high levels of contamination with DNA from other organisms; and the co-occurrence of more than one M. bovis strain per sample (within-host mixed infection). The loss of isolated genomes generates missed links in transmission chain reconstruction, hampering the biological and epidemiological interpretation of data as a whole. Upon identification of these challenges, we implemented an integrated solution framework based on whole genome amplification and a dedicated computational pipeline to minimize their effects and recover as many genomes as possible. With the approaches described herein, we were able to recover 62 out of 100 samples that would have otherwise been lost. Based on these results, we discuss adjustments that should be made in official and research laboratories to facilitate the sequential implementation of bacteriological culture, PCR, downstream genomics, and computational-based methods. All of this in a time frame supporting data-driven intervention.

Color discrimination in fixed saturation level of patients with acute traumatic injury.

Introduction: Traumatic brain injury (TBI) is an important public health concern and that may lead to severe neural sequels, such as color vision deficits. Methods: We evaluated the color vision of 10 TBI patients with normal cognitive function using a color discrimination test in a fixed saturation level. We also analyzed computerized tomography scans to identify the local of the brain damages. Results: Four TBI patients that had lesions in brain areas of the ventral visual streams, five TBI patients had lesions inferred in brain areas of the dorsal visual stream, and one TBI patient had lesion in the occipital area. All the patients had cognitive and color vision screened and they had characterized the chromatic discrimination at high and low saturation. All participants had no significant cognitive impairment in the moment of the color vision test. Additionally, they had perfect performance for discrimination of chromatic stimulus at high saturation and similar to controls (n = 37 age-matched participants). Three of four TBI patients with lesions in the ventral brain and one patient with lesion in the occipital area had impairment of the chromatic discrimination at low saturation. All TBI patients with lesions in the dorsal brain had performance similar or slightly worse than the controls. Conclusion: Chromatic discrimination at low saturation was associated to visual damage in the ventral region of the brain and is a potential tool for functional evaluation of brain damage in TBI patients.

Essential oil and fenchone extracted from Tetradenia riparia (Hochstetter.) Codd (Lamiaceae) induce oxidative stress in Culex quinquefasciatus larvae (Diptera: Culicidae) without causing lethal effects on non-target animals.

We investigated the larvicidal activity of the essential oil (EO) from Tetradenia riparia and its majority compound fenchone for controlling Culex quinquefasciatus larvae, focusing on reactive oxygen and nitrogen species (RONS), catalase (CAT), glutathione S-transferase (GST), acetylcholinesterase (AChE) activities, and total thiol content as oxidative stress indicators. Moreover, the lethal effect of EO and fenchone was evaluated against Anisops bouvieri, Diplonychus indicus, Danio rerio, and Paracheirodon axelrodi. The EO and fenchone (5 to 25 µg/mL) showed larvicidal activity (LC50 from 16.05 to 18.94 µg/mL), followed by an overproduction of RONS, and changes in the activity of CAT, GST, AChE, and total thiol content. The Kaplan-Meier followed by Log-rank (Mantel-Cox) analyses showed a 100% survival rate for A. bouvieri, D. indicus, D. rerio, and P. axelrodi when exposed to EO and fenchone (262.6 and 302.60 µg/mL), while α-cypermethrin (0.25 µg/mL) was extremely toxic to these non-target animals, causing 100% of death. These findings emphasize that the EO from T. riparia and fenchone serve as suitable larvicides for controlling C. quinquefasciatus larvae, without imposing lethal effects on the non-target animals investigated.

Benefits of Pair-Bond Duration on Reproduction in a Lifelong Monogamous Cooperative Passerine.

AbstractLong-term social and genetic monogamy is rare in animals except birds, but even in birds it is infrequent and poorly understood. We investigated possible advantages of monogamy in a colonial, facultative cooperatively breeding bird from an arid, unpredictable environment, the sociable weaver (Philetairus socius). We documented divorce and extrapair paternity of 703 pairs over 10 years and separated effects of pair duration from breeding experience by analyzing longitudinal and cross-sectional datasets. Parts of the colonies were protected from nest predation, thereby limiting its stochastic and thus confounding effect on fitness measures. We found that 6.4% of sociable weaver pairs divorced and 2.2% of young were extrapair. Longer pair-bonds were associated with more clutches and fledglings per season and with reproducing earlier and later in the season, when snake predation is lower, but not with increased egg or fledgling mass or with nestling survival. Finally, the number of helpers at the nest increased with pair-bond duration. Results were similar for protected and unprotected nests. We suggest that long-term monogamy is associated with a better capacity for exploiting a temporally unpredictable environment and helps to form larger groups. These results can contribute to our understanding of why long-term monogamy is frequently associated with unpredictable environments and cooperation.

Essential oil from Piper tuberculatum Jacq. (Piperaceae) and its majority compound ß-caryophyllene: mechanism of larvicidal action against Aedes aegypti (Diptera: Culicidae) and selective toxicity.

Synthetic insecticides have been the primary approach in controlling Aedes aegypti; however, their indiscriminate use has led to the development of resistance and toxicity to non-target animals. In contrast, essential oils (EOs) are alternatives for vector control. This study investigated the mechanism of larvicidal action of the EO and ß-caryophyllene from Piper tuberculatum against A. aegypti larvae, as well as evaluated the toxicity of both on non-target animals. The EO extracted from P. tuberculatum leaves was majority constituted of ß-caryophyllene (54.8%). Both demonstrated larvicidal activity (LC50 of 48.61 and 57.20 ppm, p < 0.05), acetylcholinesterase inhibition (IC50 of 57.78 and 71.97 ppm), and an increase in the production of reactive oxygen and nitrogen species in larvae after exposure to the EO and ß-caryophyllene. Furthermore, EO and ß-caryophyllene demonstrate no toxicity to non-target animals Toxorhynchites haemorrhoidalis, Anisops bouvieri, and Diplonychus indicus (100% of survival rate), while the insecticide α-cypermethrin was highly toxic (100% of death). The results demonstrate that the EO from P. tuberculatum and ß-caryophyllene are important larvicidal agents.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 2.

The field of neuromodulation has evolved significantly over the past decade. Developments include novel indications and innovations of hardware, software, and stimulation techniques leading to an expansion in scope and role of these techniques as powerful therapeutic interventions. In this review, which is the second part of an effort to document and integrate the basic fundamentals and recent successful developments in the field, we will focus on classic paradigms for electrode placement as well as new exploratory targets, mechanisms of neuromodulation using this technique and new developments, including focused ultrasound driven ablative procedures.

O campo da neuromodulação evoluiu significativamente na última década. Esse progresso inclui novas indicações e inovações de hardware, software e técnicas de estimulação, levando a uma expansão das áreas clínicas cobertas e no papel dessas técnicas como intervenções terapêuticas eficazes. Nesta revisão, que é a segunda parte de um esforço para documentar e integrar os fundamentos básicos e os desenvolvimentos recentes e bem-sucedidos no campo, vamos nos concentrar em paradigmas clássicos para colocação de eletrodos, bem como em novos alvos exploratórios, mecanismos de neuromodulação usados por esta técnica e novos desenvolvimentos, incluindo procedimentos ablativos orientados por ultrassom focalizado.

Oxidative stress induction by essential oil from Piper alatipetiolatum (Piperaceae) triggers lethality in the larvae of Culex quinquefasciatus (Diptera: Culicidae).

Culex quinquefasciatus is the main vector of lymphatic filariasis in Brazil, which present resistance to commercial insecticides. Nowadays, essential oils (EOs) exhibiting larvicidal activity, such as those derived from Piper alatipetiolatum, provide a promising alternative for vector control, including Culex species. This study aimed to investigate the larvicidal activity and the oxidative stress indicators of the EO from P. alatipetiolatum in Cx. quinquefasciatus larvae. The EO was extracted from P. alatipetiolatum leaves using the hydrodistillation method, resulting in a yield of 7.2 ± 0.1%, analysed by gas chromatography coupled with spectrometry and gas chromatography coupled with flame ionization detector (GC-MS and GC-FID), and evaluated against Cx. quinquefasciatus larvae. Reactive Oxygen and Nitrogen Species (RONS), Catalase (CAT), glutathione-S-transferase (GST), acetylcholinesterase (AChE), and Thiol levels were used as oxidative stress indicators. Analysis by CG-MS and CG-FID revealed that the main compound in the EO was the oxygenated sesquiterpene ishwarone, constituting 78.6% of the composition. Furthermore, the EO exhibited larvicidal activity, ranging from 26 to 100%, with an LC50 of 4.53 µg/mL and LC90 of 15.37 µg/mL. This activity was accompanied by a significant increase in RONS production, alterations in CAT, GST, AChE activity, and thiol levels compared to the control groups (p < 0.05). To the best of our knowledge, this is the first report describing the larvicidal activity and oxidative stress induced by the EO from P. alatipetiolatum against Cx. quinquefasciatus larvae. Therefore, we propose that this EO shows promise as larvicidal agent for the effective control of Cx. quinquefasciatus larvae.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1.

Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Nas últimas três décadas, a estimulação cerebral profunda (ECP) se tornou um tratamento bem estabelecido para doença de Parkinson (DP) e outros transtornos do movimento. A eficácia a longo prazo na DP foi bem documentada para a melhora dos sintomas motores cardinais da DP e das complicações induzidas pelo uso do levodopa, como as flutuações motoras e as discinesias. O momento da seleção do paciente é crucial para se obter os benefícios ideais da ECP, antes que as complicações da DP se tornem irreversíveis. O objetivo desta primeira parte da revisão é examinar os conceitos fundamentais da ECP na prática clínica, discutindo os aspectos históricos, a seleção de pacientes, os potenciais efeitos da ECP nos sintomas motores e não motores da doença e o manejo prático dos pacientes após a cirurgia.

Somatic gene mutation patterns and burden influence outcomes with enasidenib in relapsed/refractory IDH2-mutated AML.

Limited treatment options are available for patients with relapsed/refractory acute myeloid leukemia (R/R AML). We recently reported results from the phase 3 IDHENTIFY trial (NCT02577406) showing improved response rates and event-free survival with enasidenib monotherapy compared with conventional care regimens (CCR) in heavily pretreated, older patients with late-stage R/R AML bearing IDH2 mutations. Here we investigated the prognostic impact of mutational burden and different co-mutation patterns at study entry within the predominant IDH2 variant subclasses, IDH2-R140 and IDH2-R172. The prognostic relevance of these variants is well documented in newly diagnosed AML, but data are lacking in R/R AML. In this large R/R AML patient cohort, targeted next-generation sequencing at baseline (screening) revealed distinct co-mutation patterns and mutational burden between subgroups bearing different IDH2 variants: variant IDH2-R140 was associated with greater mutational burden and was enriched predominantly with poor-risk mutations, including FLT3, RUNX1, and NRAS, while variant IDH2-R172 was associated with lower mutational burden and was preferentially co-mutated with DNMT3A. In multivariable analyses, RAS and RTK pathway mutations were significantly associated with decreased overall survival, after adjusting for treatment arm, IDH2 variant, and mutational burden. Importantly, enasidenib-mediated survival benefit was more pronounced in patients with IDH2-R172 variants.

Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells.

Chemical modulation of proteins enables a mechanistic understanding of biology and represents the foundation of most therapeutics. However, despite decades of research, 80% of the human proteome lacks functional ligands. Chemical proteomics has advanced fragment-based ligand discovery toward cellular systems, but throughput limitations have stymied the scalable identification of fragment-protein interactions. We report proteome-wide maps of protein-binding propensity for 407 structurally diverse small-molecule fragments. We verified that identified interactions can be advanced to active chemical probes of E3 ubiquitin ligases, transporters, and kinases. Integrating machine learning binary classifiers further enabled interpretable predictions of fragment behavior in cells. The resulting resource of fragment-protein interactions and predictive models will help to elucidate principles of molecular recognition and expedite ligand discovery efforts for hitherto undrugged proteins.

House dust mite sublingual allergen immunotherapy tablet is safe and well-tolerated in Dutch clinical practice.

Background: Half (49%) of clinically diagnosed allergic rhinitis (AR) patients are sensitized to house dust mite (HDM). If allergen avoidance and symptomatic medication fail, allergen immunotherapy may be indicated. Objective: We investigated safety and tolerability of HDM-sublingual immunotherapy by HDM-SLIT tablets in Dutch daily clinical practice. Methods: Daily intake of 12 SQ-HDM SLIT-tablet was investigated in a prospective, multicenter, observational study (EUPAS43753). It comprised 4 consultations in 1 year. Data on safety, tolerability, treatment satisfaction, symptomatic medication, compliance, and clinical effectiveness (Control of Allergic Rhinitis and Asthma Test; CARAT) were collected. Descriptive and longitudinal regression data analysis were performed. Results: Adult patients (n = 415), mean (SD) age 36.6 (12.2) years, 61.4% female and 36% asthmatic were included. The preponderance (65.1%) experienced adverse events (AEs). These, mostly mild (67%), AEs comprised: oral allergic reactions (58.6%), respiratory (12.4%) and gastrointestinal symptoms (9.4%). Sixty (14.5%) patients stopped due to AEs and 76 (18.3%) for non-AE reasons. CARAT scores improved clinically significant by 6 points and symptomatic medication use decreased from 96.1% to 77.4%. Most patients (74.5%) tolerated the treatment and were compliant (>86.5%). The majority of patients (62.4%) and investigators (69.4%) were satisfied with treatment. Conclusions: HDM SLIT-tablet is a safe and well-tolerated AR treatment. AEs occur often but are mostly mild and decreasing during the first year. CARAT scores improved and symptomatic medication use decreased suggesting better control of AR with treatment. Compliance, tolerability, and treatment satisfaction are good. However, patient follow-up and compliance remain important points of attention when initiating treatment.

Observation of Replica Symmetry Breaking in Standard Mode-Locked Fiber Laser.

We report the first experimental demonstration of the replica symmetry breaking (RSB) phenomenon in a fiber laser system supporting standard mode-locking (SML) regime. Though theoretically predicted, this photonic glassy phase remained experimentally undisclosed so far. We employ an ytterbium-based mode-locked fiber laser with a very rich phase diagram. Two phase transitions are observed separating three different regimes: cw, quasi-mode-locking (QML), and SML. The regimes are intrinsically related to the distinct dynamics of intensity fluctuations in the laser spectra. We set the connection between the RSB glassy phase with frustrated modes and onset of L-shaped intensity distributions in the QML regime, which impact directly the replica overlap measure.

Outcomes and adverse events in older acute lymphoblastic Leukemia patients treated with a pediatric-inspired protocol with Pegylated or native Asparaginase.

This retrospective report presents the outcomes and adverse events (AEs) observed in 73 patients aged 60 years or older diagnosed with Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (Ph-negative ALL) treated with a pediatric-inspired protocol incorporating either Pegylated (PEG-ASP) or Native Asparaginase (EC-ASP). Notably, 61% of patients experienced AEs of Grade III-IV severity. The most prevalent AEs included thrombosis (35.6%), febrile neutropenia (38.4%), and transaminitis (34.2%). AEs did not translate into significant differences concerning overall survival, leukemia-free survival, or early mortality. Furthermore, we observed a reduction in early mortality rates (11% vs. 20%) and an increase in median overall survival (54 vs. 48 months) compared to our previous data. These findings suggest that the utilization of a pediatric-inspired chemotherapy protocol, with ASP, is an effective and well-tolerated therapeutic option for older patients with Ph-negative ALL. However, it emphasizes the importance of diligent monitoring and close follow-up throughout treatment.

BioDeepfuse: a hybrid deep learning approach with integrated feature extraction techniques for enhanced non-coding RNA classification.

The accurate classification of non-coding RNA (ncRNA) sequences is pivotal for advanced non-coding genome annotation and analysis, a fundamental aspect of genomics that facilitates understanding of ncRNA functions and regulatory mechanisms in various biological processes. While traditional machine learning approaches have been employed for distinguishing ncRNA, these often necessitate extensive feature engineering. Recently, deep learning algorithms have provided advancements in ncRNA classification. This study presents BioDeepFuse, a hybrid deep learning framework integrating convolutional neural networks (CNN) or bidirectional long short-term memory (BiLSTM) networks with handcrafted features for enhanced accuracy. This framework employs a combination of k-mer one-hot, k-mer dictionary, and feature extraction techniques for input representation. Extracted features, when embedded into the deep network, enable optimal utilization of spatial and sequential nuances of ncRNA sequences. Using benchmark datasets and real-world RNA samples from bacterial organisms, we evaluated the performance of BioDeepFuse. Results exhibited high accuracy in ncRNA classification, underscoring the robustness of our tool in addressing complex ncRNA sequence data challenges. The effective melding of CNN or BiLSTM with external features heralds promising directions for future research, particularly in refining ncRNA classifiers and deepening insights into ncRNAs in cellular processes and disease manifestations. In addition to its original application in the context of bacterial organisms, the methodologies and techniques integrated into our framework can potentially render BioDeepFuse effective in various and broader domains.

Description and Pathogenicity of Colletotrichum kapreanum sp. nov, a Cherelle Wilt Pathogen Belonging to the Gigasporum Species Complex.

Similar to cacao pod rot, cherelle wilt decreases production from cacao fields. Among all known fungal pathogens of the cacao, Colletotrichum spp. are common infectious agents that affect the cherelles and pods of cacao; thus, cacao diseases are often classified by stage. Therefore, knowing whether these pathogens are common in both fruit stages is necessary for implementing disease control measures. Symptoms of cherelle wilt were found in cacao plants in Pangasinan, Philippines, in 2022. The fungal strain obtained from the lesion was found to be pathogenic towards cherelles, but not towards pods. The strain was classified as an unknown species belonging to the gigasporum species complex, based on the morphological and molecular phylogenetic analyses of ITS, GAPDH, CHS1, ACT, and TUB2. We propose Colletotrichum kapreanum sp. nov. as a causal agent of cacao cherelle wilt, but not pod rot.

Diagnostic Accuracy in Detecting Fungal Infection with Ultra-Low-Dose Computed Tomography (ULD-CT) Using Filtered Back Projection (FBP) Technique in Immunocompromised Patients.

Purpose: To compare the accuracy of ultra-low-dose (uLDCT) to standard-of-care low-dose chest CT (LDCT) in the detection of fungal infection in immunocompromised (IC) patients. Method and Materials: One hundred IC patients had paired chest CT scans performed with LDCT followed by uLDCT. The images were independently reviewed by three chest radiologists who assessed the image quality (IQ), diagnostic confidence, and detection of major (macro nodules, halo sign, cavitation, consolidation) and minor (4-10 mm nodules, ground-glass opacity) criteria for fungal disease using a five-point Likert score. Discrepant findings were adjudicated by a fourth chest radiologist. Box-whisker plots were used to analyze IQ and diagnostic confidence. Inter-rater reliability was assessed using interclass correlation coefficients (ICCs). The statistical difference between LDCT and uLDCT results was assessed using Wilcoxon paired test. Results: Lung reconstructions had IQ and diagnostic confidence scores (mean ± std) of 4.52 ± 0.47 and 4.63 ± 0.51 for LDCT and 3.85 ± 0.77 and 4.01 ± 0.88 for uLDCT. The images were clinically acceptable except for uLDCT in obese patients (BMI ≥ 30 kg/m2), which had an IQ ranking from poor to excellent (scores 1 to 5). The accuracy in detecting major and minor radiological findings with uLDCT was 96% and 84% for all the patients. The inter-rater agreements were either moderate, good, or excellent, with ICC values of 0.51-0.96. There was no significant statistical difference between the uLDCT and LDCT ICC values (p = 0.25). The effective dose for uLDCT was one quarter that of LDCT (CTDIvol = 0.9 mGy vs. 3.7 mGy). Conclusions: Thoracic uLDCT, at a 75% dose reduction, can replace LDCT for the detection of fungal disease in IC patients with BMI < 30.0 kg/m2.

The effects of the ß1-adrenergic receptor antagonist bisoprolol administration on mirabegron-stimulated human brown adipose tissue thermogenesis.

AIM: Pharmacological stimulation of human brown adipose tissue (BAT) has been hindered by ineffective activation or undesirable off-target effects. Oral administration of the maximal allowable dose of mirabegron (200 mg), a ß3-adrenergic receptor (ß3-AR) agonist, has been effective in stimulating BAT thermogenesis and whole-body energy expenditure. However, this has been accompanied by undesirable cardiovascular effects. Therefore, we hypothesized that combining mirabegron with a ß1-AR antagonist could suppress these unwanted effects and increase the stimulation of the ß3-AR and ß2-AR in BAT. METHODS: We performed a randomized crossover trial (NCT04823442) in 8 lean men. Mirabegron (200 mg) was administered orally with or without the ß1-AR antagonist bisoprolol (10 mg). Dynamic [11C]-acetate and 2-deoxy-2-[18F]fluoro-d-glucose PET/CT scans were performed sequentially after oral administration of mirabegron ± bisoprolol. RESULTS: Compared to room temperature, mirabegron alone increased BAT oxidative metabolism (0.84 ± 0.46 vs. 1.79 ± 0.91 min-1, p = 0.0433), but not when combined with bisoprolol. The metabolic rate of glucose in BAT, measured using [18F]FDG PET, was significantly higher with mirabegron than mirabegron with bisoprolol (24 ± 10 vs. 16 ± 8 nmol/g/min, p = 0.0284). Bisoprolol inhibited the mirabegron-induced increase in systolic blood pressure and heart rate. CONCLUSION: The administration of bisoprolol decreases the adverse cardiovascular effects of mirabegron. However, the provided dose also blunted the mirabegron-stimulated increase in BAT lipolysis, thermogenesis, and glucose uptake. The attenuation in BAT blood flow induced by the large dose of bisoprolol may have limited BAT thermogenesis.