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Adaptive thermogenesis by brown adipose tissue (BAT) dissipates calories as heat, making it an attractive anti-obesity target. Yet how BAT contributes to circulating metabolite exchange remains unclear. Here, we quantified metabolite exchange in BAT and skeletal muscle by arteriovenous metabolomics during cold exposure in fed male mice. This identified unexpected metabolites consumed, released and shared between organs. Quantitative analysis of tissue fluxes showed that glucose and lactate provide ~85% of carbon for adaptive thermogenesis and that cold and CL316,243 trigger markedly divergent fuel utilization profiles. In cold adaptation, BAT also dramatically increases nitrogen uptake by net consuming amino acids, except glutamine. Isotope tracing and functional studies suggest glutamine catabolism concurrent with synthesis via glutamine synthetase, which avoids ammonia buildup and boosts fuel oxidation. These data underscore the ability of BAT to function as a glucose and amino acid sink and provide a quantitative and comprehensive landscape of BAT fuel utilization to guide translational studies.

UNLABELLED: It is unknown whether febrile infants 29 to 60 days old with positive urinalysis results require routine lumbar punctures for evaluation of bacterial meningitis. OBJECTIVE: To determine the prevalence of bacteremia and/or bacterial meningitis in febrile infants ≤60 days of age with positive urinalysis (UA) results. METHODS: Secondary analysis of a prospective observational study of noncritical febrile infants ≤60 days between 2011 and 2019 conducted in the Pediatric Emergency Care Applied Research Network emergency departments. Participants had temperatures ≥38°C and were evaluated with blood cultures and had UAs available for analysis. We report the prevalence of bacteremia and bacterial meningitis in those with and without positive UA results. RESULTS: Among 7180 infants, 1090 (15.2%) had positive UA results. The risk of bacteremia was higher in those with positive versus negative UA results (63/1090 [5.8%] vs 69/6090 [1.1%], difference 4.7% [3.3% to 6.1%]). There was no difference in the prevalence of bacterial meningitis in infants ≤28 days of age with positive versus negative UA results (∼1% in both groups). However, among 697 infants aged 29 to 60 days with positive UA results, there were no cases of bacterial meningitis in comparison to 9 of 4153 with negative UA results (0.2%, difference -0.2% [-0.4% to -0.1%]). In addition, there were no cases of bacteremia and/or bacterial meningitis in the 148 infants ≤60 days of age with positive UA results who had the Pediatric Emergency Care Applied Research Network low-risk blood thresholds of absolute neutrophil count

ObjectiveThe circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on the role of essential amino acids.MethodsMice were fed diets depleted of specific essential amino acids and their behavioral rhythms were monitored and tryptophan was selected for downstream analyses. The role of tryptophan metabolism in modulating circadian homeostasis was studied using isotope tracing as well as transcriptomic- and metabolomic- analyses.ResultsDietary tryptophan depletion alters behavioral rhythms in mice. Furthermore, tryptophan metabolism was shown to be regulated in a time- and light- dependent manner. A multi-omics approach and combinatory diet/light interventions demonstrated that tryptophan metabolism modulates temporal regulation of metabolism and transcription programs by buffering photic cues. Specifically, tryptophan metabolites regulate central circadian functions of the suprachiasmatic nucleus and the core clock machinery in the liver.ConclusionsTryptophan metabolism is a modulator of circadian homeostasis by integrating environmental cues. Our findings propose tryptophan metabolism as a potential point for pharmacologic intervention to modulate phenotypes associated with disrupted circadian rhythms.

Brown adipose tissue (BAT) demonstrates extraordinary metabolic capacity. Previous research using conventional radio tracers reveals that BAT can act as a sink for a diverse menu of nutrients; still, the question of how BAT utilizes these nutrients remains unclear. Recent advances in mass spectrometry (MS) coupled to stable isotope tracing methods have greatly improved our understanding of metabolism in biology. Here, we have developed a BAT-tailored metabolomics and stable isotope tracing protocol using, as an example, the universally labeled 13C-glucose, a key nutrient heavily utilized by BAT. This method enables metabolic roadmaps to be drawn and pathway fluxes to be inferred for each nutrient tracer within BAT and its application could uncover new metabolic pathways not previously appreciated for BAT physiology.

Organic reaction mechanisms are often represented by the electron-pushing formalism and reaction coordinate diagrams. These representations pose a challenge to students because valuable information is encoded within each representation, and students must know how to reason about mechanisms using both. Hence, it is important to understand whether and how students consider these two representations when reasoning about reaction mechanisms. We have collected responses to a writing-to-learn assignment administered in a second-semester organic chemistry laboratory course to investigate students' reasoning. The assignment was designed to elicit students' reasoning about the most likely of two mechanisms for a catalyzed intramolecular aldol reaction when given the electron-pushing scheme and reaction coordinate diagram for both mechanisms. As part of the assignment, students submitted initial drafts, participated in content-focused peer review, and submitted revised drafts. We analyzed each component using a mixed methods approach to identify students' reasoning about the most likely reaction pathway and how their reasoning changed after peer review and revision. In this article, we present a quantitative overview of changes students made about their decisions for the most likely reaction pathway and how these changes are related to providing and receiving feedback. Additionally, we present our analysis of the features of representations students used to reason about the likelihood of alternative reaction mechanisms. This study demonstrates how existing research about students' reasoning with representations was operationalized for classroom practice using writing-to-learn. Furthermore, the analysis illustrates how writing-to-learn to can be used to develop students' reasoning and offers implications for teaching students to reason about reaction mechanisms using multiple representations.

Imbalance between fat production and consumption causes various metabolic disorders. Nonalcoholic fatty liver disease (NAFLD), one such pathology, is characterized by abnormally increased fat synthesis and subsequent fat accumulation in hepatocytes1,2. While often comorbid with obesity and insulin resistance, this disease can also be found in lean individuals, suggesting specific metabolic dysfunction2. NAFLD has become one of the most prevalent liver diseases in adults worldwide, but its incidence in both children and adolescents has also markedly increased in developed nations3,4. Progression of this disease into nonalcoholic steatohepatitis (NASH), cirrhosis, liver failure, and hepatocellular carcinoma in combination with its widespread incidence thus makes NAFLD and its related pathologies a significant public health concern. Here, we review our understanding of the roles of dietary carbohydrates (glucose, fructose, and fibers) and the gut microbiota, which provides essential carbon sources for hepatic fat synthesis during the development of NAFLD.

NAFLD has alarmingly increased, yet FDA-approved drugs are still lacking. An excessive intake of fructose, especially in liquid form, is a dietary risk factor of NAFLD. While fructose metabolism has been studied for decades, it is still controversial how fructose intake can cause NAFLD. It has long been believed that fructose metabolism solely happens in the liver and accordingly, numerous studies have investigated liver fructose metabolism using primary hepatocytes or liver cell lines in culture. While cultured cells are useful for studying detailed signaling pathways and metabolism in a cell-autonomous manner, it is equally important to understand fructose metabolism at the whole-body level in live organisms. In this regard, recent in vivo studies using genetically modified mice and stable isotope tracing have tremendously expanded our understanding of the complex interaction between fructose-catabolizing organs and gut microbiota. Here, we discuss how the aberrant distribution of fructose metabolism between organs and gut microbiota can contribute to NAFLD. We also address potential therapeutic interventions of fructose-elicited NAFLD.

On May 25, 2018, the European Union’s (EU) General Data Protection Regulation (GDPR) came into effect. The GDPR is expected to reshape web use and overhaul data privacy laws beyond Europe in how businesses and organizations can handle customer and user information. Only a month after, California passed the California Consumer Privacy Act of 2018 (CCPA). The CCPA is one of the most significant regulations overseeing data-collection practices of businesses in the United States. It is the first of its kind and is expected to provide the most comprehensive data privacy measures in the United States. As such, the combined CCPA and GDPR data privacy regulations will likely usher in a tidal wave of changes, most likely setting new data privacy standards for other jurisdictions to model.Drawing from these events, this Note will examine the EU’s and California’s newest data privacy laws, studying the immediate and potential effects of GDPR and CCPA regulations on the existing data privacy regime. Through a comparative study of GDPR and CCPA provisions, this Note attempts to answer key questions in discourse today—to what extent are the CCPA and GDPR moving towards convergence or divergence, and how will the laws affect businesses and consumers? Is the U.S. data privacy environment veering away from its hands-off approach and drawing closer to the comprehensive approach of the EU data privacy regime? This Note will explore these questions looking at two particular provisions in the GDPR and CCPA: (1) the opt-in vs. opt-out consent and (2) the right to be forgotten/right to delete personal data.Lastly, this Note analyzes the practical implications of the GDPR and CCPA regulations on businesses in terms of how receptive businesses are to the regulations, how well businesses strive to conform to the regulatory boundaries of data privacy regimes, and whether the regulations will have the intended effect of strengthening consumer rights by putting heavier restrictions on businesses.

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This article explores the implementation of social prescribing in a Canadian regional health system, specifically in the province of British Columbia. The social prescribing model aims to support healthy aging by integrating community services with traditional acute care. Fraser Health, a regional health authority, has established a team dedicated to integrating social prescribing into the health system through collaboration with various partners. The article emphasizes the importance of funding stability, partnerships, organizational capacity, program evaluation, and strategic planning in sustaining and expanding the social prescribing model. [Extracted from the article]

Introduction: Older adults with higher needs are ideal candidates for social prescribing interventions, given the complex and intersectoral nature of their needs. This article describes findings from a developmental evaluation of 19 social prescribing programs for older adults at risk of frailty. Methods: An evaluation of the programs was conducted from 2020 to 2023. We used data from three components of the evaluation: (1) initial evaluation data collected in 2020 and 2021; (2) program profiles developed in 2022; and (3) co-creation sessions conducted in 2023. Results: From startup until March 2023, the programs served a total of 2544 older adults. The community connectors identified factors at the individual, interpersonal, institutional, community and policy levels that contributed to the successful implementation and delivery of their programs (e.g. physician champions, communities of practice, strong pre-existing relationships with the health care system), as well as challenges (e.g. limited capacity of family physicians, lack of community resources). There was strong agreement among community connectors that successful social prescribing programs should include the following core elements: (1) making connections to needed community resources; (2) co-creation of a wellness plan with long-term clients or clients who require intensive supports; (3) ongoing follow-up and check-ins for clients with wellness plans; and (4) an assessment and triaging process for the prioritization of clients. Conclusion: To leverage the full potential of social prescribing interventions, it is essential that programs engage with a range of health and social care providers, that community connectors are skilled and well supported, and that adequate investments are made in the nonprofit and voluntary sector. [ABSTRACT FROM AUTHOR]