Endogenous glucose production and gluconeogenesis during exercise in athletes on either a low-carbohydrate or mixed diet

INTRODUCTION. The LCHF diet produces major changes in whole-body substrate metabolism and energy stores such as reduced muscle and liver glycogen content, increased rates of fat oxidation and decreased rates of carbohydrate (CHO) oxidation. Despite reduced CHO availability, the rate of CHO oxidation that can be sustained during exercise in LCHF athletes is surprisingly high. The most probable source of this glucose is via the process of gluconeogenesis (GNG). However, endogenous glucose production (EGP) and GNG has not been studied during exercise in athletes on a LCHF diet. Therefore, the aim of this study was to determine if there are differences in EGP, GNG and glycogenolysis (GLY) during exercise in endurance-trained athletes who habitually eat either a mixed or LCHF diet. METHODS. Fourteen (7 LCHF, 7 Mix) endurance-trained male cyclists (VO₂max 61 ± 5 ml/kg/min LCHF; 6 3 ± 8 ml/kg/min Mix), matched for age (36 ± 6 y LCHF; 32 ± 5 y Mix), body composition (BMI 23.6 ± 1.8 LCHF; 23.4 ± 2.0 Mix) and relative peak power output (4.8 ± 0.4 W/kg LCHF; 5.0 ± 0.4 W/kg Mix), were recruited. Diets were analysed using the Automated Self-Administered 24-hour Recall (ASA24) analysis software. Participants cycled for 2 h at 55% of peak power output during which EGP was measured by infusion of [6,6- ²H₂ ]glucose, and fractional gluconeogenesis was measured by ingestion of ²H₂O. Blood samples were collected at regular intervals for isotope enrichment analysis. R ESULTS. Rates of GNG were similar during exercise in both the LCHF and mixed diet groups (2.8 ± 0.4 mg/kg/min LCHF; 2.5 ± 0.3 mg/kg/min Mix). The rates of GLY during exercise were significantly higher in the mixed diet group than the LCHF group (3.2 ± 0.7 mg/kg/min LCHF; 5.3 ± 0.9 mg/kg/min Mix) which resulted in significantly higher rates of EGP in the mixed diet group (6.0 ± 0.9 mg/kg/min LCHF; 7.8 ± 1.1 mg/kg/min Mix). There were significant differences in the mean fat oxidation rates (1.2 ± 0.2 g/min LCHF; 0.5 ± 0.2 g/min Mix) and CHO oxidation rates (1.3 ± 0.5 g/min LCHF; 3.1 ± 0.5 g/min Mix). Blood beta-hydroxbutyrate (βHB) concentrations were significantly higher in the LCHF group than in the mixed diet group throughout exercise but there were no differences in plasma glucose, plasma lactate, serum insulin or serum FFA concentrations. The diets of the two groups differed only in fat and CHO intake (%Protein / %Fat / %CHO: 21/72/7 LCHF; 16/33/51 Mix). DISCUSSION. Rates of fat oxidation and CHO oxidation were not associated with the rates of GNG. Apart from βHB, the precursor, substrate and insulin concentrations were remarkably similar in both groups and may have influenced GNG similarly in both groups. We conclude that rates of GNG are relatively stable across a broad range of habitual diets that can significantly alter substrate utilisation, and that dietary CHO modulates the rates of EGP via alterations in rates of GLY, both at rest and during exercise

Governing police-public encounters mediated by the use of Body-Worn Cameras

This paper explores emerging governance structures surrounding the use of Body-Worn Video (BWV) cameras in policing contexts, with specific reference to the UK. It reviews existing knowledge about the diffusion of BWV, in relation to the purpose of the technology, existing regulatory arrangements and the perceived benefits and impacts of the technology. The focus of the paper is the nature of police-citizen interactions mediated by this specific technology and roles played by emergent scrutiny mechanisms. The paper will identify and assess the different types of police-citizen interaction involving BWV, from armed responses to ‘stop and search’, and identify the existing rules, protocols and regulations governing their use in these scenarios. In the paper, it is argued that the rationale for the use of BWV in policing is well established, is afforded a good level of public support, and that it is also evident, that across UK police forces, there is differentiated use of the technology and associated governance mechanisms. The paper also establishes that across the UK there are novel emergent mechanisms used to govern BWV in relation to scrutiny and accountability. These include dedicated ‘scrutiny panels’, practices referred to as random ‘dip sampling’, as well as dedicated codes of practice and use protocols. Here, it is evident that across the UK the provision and practice of BWV deviates by police force and region, resulting in a governance ‘patchwork’. The core underlying argument is the technology diffuses and ‘lived experiences’ shape use over time, and that simultaneously mechanisms for oversight and accountability emerge and are shaped by existing institutional arrangements. The research presented in this paper derives from an ‘evidence led review’ conducted by the authors for Police Scotland in November-December 2021 (Webster, et al. 2022). This review included an extensive literature review and interviews with key stakeholders. The outcome of the review is intended to inform the future provision of BWV by Police Scotland

Highly enriched carbon and oxygen isotopes in carbonate-derived CO₂ at Gale crater, Mars

One objective of the Curiosity rover is to search for habitable conditions, past and present, on the surface of Mars. Carbonate minerals can record diagnostic signatures of their formation environment. This paper focuses on carbon and oxygen isotope measurements of carbonate minerals detected within the Gale crater. Notably, these carbonates are extremely enriched in 13C and 18O, more so than other Martian materials. We highlight two processes (evaporation-driven Rayleigh distillation and cryogenic precipitation) that could explain these isotopic enrichments and explore whether those processes are consistent with our current understanding of Mars. These isotopic values offer a poignant example of how the Martian carbon cycle differs from that on Earth without the influences of a biosphere

Seasonal Variations in Atmospheric Composition as Measured in Gale Crater, Mars

All MSL data used in this manuscript (REMS and SAM) are freely available on NASA's Planetary Data System (PDS) Geosciences Node, from within 6 months after receipt on Earth (http://pds‐geosciences.wustl.edu/missions/msl/). The mixing ratios developed and presented in this paper are available at a publicly available archive (dataverse.org: doi.org/10.7910/DVN/CVUOWW) as cited within the manuscript. The successful operation of the Curiosity rover and the SAM instrument on Mars is due to the hard work and dedication of hundreds of scientists, engineers, and managers over more than a decade. Essential contributions to the successful operation of SAM on Mars and the acquisition of SAM data were provided by the SAM development, operations, and test bed teams. The authors gratefully thank the SAM and MSL teams that have contributed in numerous ways to obtain the data that enabled this scientific work. We also thank NASA for the support of the development of SAM, SAM data analysis, and the continued support of the Mars Science Laboratory mission. The contribution of F. Lefèvre was supported by the Programme National de Planétologie (PNP). R. Navarro‐Gonzalez acknowledges support from the Universidad Nacional Autónoma de México (PAPIIT IN111619). LPI is operated by USRA under a cooperative agreement with the Science Mission Directorate of the National Aeronautics and Space Administration. We thank members of the SAM and larger MSL team for insightful discussions and support. In particular, we thank R. Becker and R. O. Pepin for careful review of data analysis and interpretation. We thank M. D. Smith for discussion of CRISM CO measurements. We thank A. Brunner, M. Johnson, and M. Lefavor for their development of customized data analysis tools used here and in other SAM publications.Peer reviewedPublisher PD

Primordial argon isotope fractionation in the atmosphere of Mars measured by the SAM instrument on Curiosity and implications for atmospheric loss

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102170/1/grl51048.pd

CD45-mediated control of TCR tuning in naive and memory CD8(+) T cells

Continuous contact with self-major histocompatibility complex (MHC) ligands is essential for survival of naive T cells but not memory cells. This surprising finding implies that T cell subsets may vary in their relative T-cell receptor (TCR) sensitivity. Here we show that in CD8(+) T cells TCR sensitivity correlates inversely with levels of CD5, a marker for strong self-MHC reactivity. We also show that TCR sensitivity is lower in memory CD8(+) T cells than naive cells. In both situations, TCR hypo-responsiveness applies only to short-term TCR signalling events and not to proliferation, and correlates directly with increased expression of a phosphatase, CD45 and reciprocal decreased expression of activated LCK. Inhibition by high CD45 on CD8(+) T cells may protect against overt TCR auto-MHC reactivity, while enhanced sensitivity to cytokines ensures strong responses to foreign antigens. (c) The Author(s) 20161991sciescopu

Homicide and geographic access to gun dealers in the United States

<p>Abstract</p> <p>Background</p> <p>Firearms are the most commonly used weapon to commit homicide in the U.S. Virtually all firearms enter the public marketplace through a federal firearms licensee (FFL): a store or individual licensed by the federal government to sell firearms. Whether FFLs contribute to gun-related homicide in areas where they are located, in which case FFLs may be a homicide risk factor that can be modified, is not known.</p> <p>Methods</p> <p>Annual county-level data (1993–1999) on gun homicide rates and rates of FFLs per capita were analyzed using negative binomial regression controlling for socio-demographic characteristics. Models were run to evaluate whether the relation between rates of FFLs and rates of gun homicide varied over the study period and across counties according to their level of urbanism (defined by four groupings, as below). Also, rates of FFLs were compared against FS/S – which is the proportion of suicides committed by firearm and is thought to be a good proxy for firearm availability in a region – to help evaluate how well the FFL variable is serving as a way to proxy firearm availability in each of the county types of interest.</p> <p>Results</p> <p>In major cities, gun homicide rates were higher where FFLs were more prevalent (rate ratio [RR] = 1.70, 95% CI 1.03–2.81). This association increased (p < 0.01) from 1993 (RR = 1.69) to 1999 (RR = 12.72), due likely to federal reforms that eliminated low-volume dealers, making FFL prevalence a more accurate exposure measure over time. No association was found in small towns. In other cities and in suburbs, gun homicide rates were significantly lower where FFLs were more prevalent, with associations that did not change over the years of the study period. FFL prevalence was correlated strongly (positively) with FS/S in major cities only, suggesting that the findings for how FFL prevalence relates to gun homicide may be valid for the findings pertaining to major cities but not to counties of other types.</p> <p>Conclusion</p> <p>Modification of FFLs through federal, state, and local regulation may be a feasible intervention to reduce gun homicide in major cities.</p

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Chronic kidney disease and valvular heart disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies conference

Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group