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Cyclonic vortices that are weaker than tropical storm category can bring heavy precipitation as they propagate across the South China Sea and surrounding countries. Here we investigate the structure and dynamics responsible for the intensification of a Borneo vortex that moved from the north of Borneo across the South China Sea and impacted Vietnam and Thailand in late October 2018. This case study is examined using Met Office Unified Model (MetUM) simulations and a semi-geotriptic (SGT) balance approximation tool. Satellite observations and a MetUM simulation with 4.4 km grid initialised at 12:00 UTC on 21 October 2018 show that the westward-moving vortex is characterised by a coherent maximum in total column water and by a comma-shaped precipitation structure with the heaviest rainfall to the northwest of the circulation centre. The Borneo vortex comprises a low-level cyclonic circulation and a mid-level wave embedded in the background easterly shear flow, which strengthens with height up to around 7 km. Despite being in the tropics at 6∘ N, the low-level vortex and mid-level wave are well represented by SGT balance dynamics. The mid-level wave propagates along a vertical gradient in moist stability, i.e. the product between the specific humidity and the static stability, at 4.5 to 5 km and is characterised by a coherent signature in the potential vorticity, meridional wind, and balanced vertical velocity fields. The vertical motion is dominated by coupling with diabatic heating and is shifted relative to the potential vorticity so that the diabatic wave propagates westwards, relative to the flow, at a rate consistent with prediction from moist semi-geostrophic theory. Initial vortex development at low levels is consistent with baroclinic growth initiated by the mid-level diabatic Rossby wave, which propagates on baroclinic shear flow on the southern flank of a large-scale cold surge.

Protein-nucleic acid phase separation has been implicated in many diseases such as viral infections, neurodegeneration, and cancer. There is great interest in identifying condensate modulators (CMODs), which are small molecules that alter the dynamics and functions of phase-separated condensates, as a potential therapeutic modality. Most CMODs were identified in cellular high-content screens (HCS) where micron-scale condensates were characterized by fluorescence microscopy. These approaches lack information on protein dynamics, are limited by microscope resolution, and are insensitive to subtle condensation phenotypes missed by overfit analysis pipelines. Here, we evaluate two alternative cell-based assays: high-throughput single molecule tracking (htSMT) and proximity-based condensate biosensors using NanoBIT (split luciferase) and NanoBRET (bioluminescence resonance energy transfer) technologies. We applied these methods to evaluate condensation of the SARS-CoV-2 nucleocapsid (N) protein under GSK3 inhibitor treatment, which we had previously identified in our HCS campaign to induce condensation with well-defined structure-activity relationships (SAR). Using htSMT, we observed robust changes in N protein diffusion as early as 3 h post GSK3 inhibition. Proximity-based N biosensors also reliably reported on condensation, enabling the rapid assaying of large compound libraries with a readout independent of imaging. Both htSMT and proximity-based biosensors performed well in a screening format and provided information on CMOD activity that was complementary to HCS. We expect that this expanded toolkit for interrogating phase-separated proteins will accelerate the identification of CMODs for important therapeutic targets.

This paper reports on the integration of different modelling techniques to construct a unified conceptual model of structural evolution of the Pico del Águila anticline (External Sierras, southern Pyrenees, Spain). The structure is a well-known example of a detachment fold, which exhibits a N-S structural trend, perpendicular to the general structural trend of the southern Pyrenees (mainly E-W). Based on field observations of an unevenly distributed Triassic décollement, analogue modelling shows how to generate orogen-perpendicular structures which may result in transverse anticlines. The models show how contrasts between high and low friction patches in the basal décollement led to the formation of structures at high angle, centered over the high friction areas. Numerical models investigate the effect of a complex mechanical stratigraphy, characterized by an interlayering of competent and incompetent layers, plus syn-kinematic sedimentation in the fold growth. Based on field data and seismic interpretations, a 3D reconstruction and sequential geomechanical restoration of the Pico del Águila anticline suggests the coexistence of multiple folding mechanisms occurring simultaneously in different units and structural domains of the fold, leading to a complex strain pattern that can not be assessed by simplistic kinematic 2D approaches. By integrating the models with previous data in the region, the benefits and drawbacks of each modelling technique are discussed and an integrated model of structural evolution for the Pico del Águila anticline is presented. This enables a better comprehension of the structure as well as of the processes that drove the evolution of the N-S detachment anticlines in the External Sierras of the southern Pyrenees.

BackgroundAcute Respiratory Distress Syndrome (ARDS) is a devastating pulmonary inflammatory disorder, commonly precipitated by sepsis. Glucocorticoids are immunomodulatory steroids that can suppress inflammation. Their anti-inflammatory properties within tissues are influenced by their pre-receptor metabolism and amplification from inactive precursors by 11β-hydroxysteroid dehydrogenase type-1 (HSD-1). We hypothesised that in sepsis-related ARDS, alveolar macrophage (AM) HSD-1 activity and glucocorticoid activation are impaired, and associated with greater inflammatory injury and worse outcomes.MethodsWe analysed broncho-alveolar lavage (BAL) and circulating glucocorticoid levels, AM HSD-1 reductase activity and Receptor for Advanced Glycation End-products (RAGE) levels in two cohorts of critically ill sepsis patients, with and without ARDS. AM HSD-1 reductase activity was also measured in lobectomy patients. We assessed inflammatory injury parameters in models of lung injury and sepsis in HSD-1 knockout (KO) and wild type (WT) mice.ResultsNo difference in serum and BAL cortisol: cortisone ratios are shown between sepsis patients with and without ARDS. Across all sepsis patients, there is no association between BAL cortisol: cortisone ratio and 30-day mortality. However, AM HSD-1 reductase activity is impaired in patients with sepsis-related ARDS, compared to sepsis patients without ARDS and lobectomy patients (0.075 v 0.882 v 0.967 pM/hr/106 AMs, p=0.004). Across all sepsis patients (with and without ARDS), impaired AM HSD-1 reductase activity is associated with defective efferocytosis (r=0.804, p=0.008) and increased 30-day mortality. AM HSD-1 reductase activity negatively correlates with BAL RAGE in sepsis patients with ARDS (r=-0.427, p=0.017). Following intra-tracheal lipopolysaccharide (IT-LPS) injury, HSD-1 KO mice demonstrate increased alveolar neutrophil infiltration, apoptotic neutrophil accumulation, alveolar protein permeability and BAL RAGE concentrations compared to WT mice. Caecal Ligation and Puncture (CLP) injury in HSD-1 KO mice results in greater peritoneal apoptotic neutrophil accumulation compared to WT mice.ConclusionsAM HSD-1 reductase activity does not shape total BAL and serum cortisol: cortisone ratios, however impaired HSD-1 autocrine signalling renders AMs insensitive to the anti-inflammatory effects of local glucocorticoids. This contributes to the decreased efferocytosis, increased BAL RAGE concentrations and mortality seen in sepsis-related ARDS. Upregulation of alveolar HSD-1 activity could restore AM function and improve clinical outcomes in these patients.

Introduction Sleep and epilepsy have an established bidirectional relationship yet only one randomised controlled clinical trial has assessed the effectiveness of behavioural sleep interventions for children with epilepsy. The intervention was successful, but was delivered via face-to-face educational sessions with parents, which are costly and non-scalable to population level. The Changing Agendas on Sleep, Treatment and Learning in Epilepsy (CASTLE) Sleep-E trial addresses this problem by comparing clinical and cost-effectiveness in children with Rolandic epilepsy between standard care (SC) and SC augmented with a novel, tailored parent-led CASTLE Online Sleep Intervention (COSI) that incorporates evidence-based behavioural components.Methods and analyses CASTLE Sleep-E is a UK-based, multicentre, open-label, active concurrent control, randomised, parallel-group, pragmatic superiority trial. A total of 110 children with Rolandic epilepsy will be recruited in outpatient clinics and allocated 1:1 to SC or SC augmented with COSI (SC+COSI). Primary clinical outcome is parent-reported sleep problem score (Children’s Sleep Habits Questionnaire). Primary health economic outcome is the incremental cost-effectiveness ratio (National Health Service and Personal Social Services perspective, Child Health Utility 9D Instrument). Parents and children (≥7 years) can opt into qualitative interviews and activities to share their experiences and perceptions of trial participation and managing sleep with Rolandic epilepsy.Ethics and dissemination The CASTLE Sleep-E protocol was approved by the Health Research Authority East Midlands (HRA)–Nottingham 1 Research Ethics Committee (reference: 21/EM/0205). Trial results will be disseminated to scientific audiences, families, professional groups, managers, commissioners and policymakers. Pseudo-anonymised individual patient data will be made available after dissemination on reasonable request.Trial registration number ISRCTN13202325.

Chronic kidney disease (CKD) describes the long-term condition of impaired kidney function from any cause. CKD is common and associated with a wide array of complications including higher mortality, cardiovascular disease, hypertension, insulin resistance, dyslipidemia, sarcopenia, osteoporosis, aberrant immune function, cognitive impairment, mood disturbances and poor sleep quality. Glucocorticoids are endogenous pleiotropic steroid hormones and their excess produces a pattern of morbidity that possesses considerable overlap with CKD. Circulating levels of cortisol, the major active glucocorticoid in humans, are determined by a complex interplay between several processes. The hypothalamic-pituitary-adrenal axis (HPA) regulates cortisol synthesis and release, 11β-hydroxysteroid dehydrogenase enzymes mediate metabolic interconversion between active and inactive forms, and clearance from the circulation depends on irreversible metabolic inactivation in the liver followed by urinary excretion. Chronic stress, inflammatory states and other aspects of CKD can disturb these processes, enhancing cortisol secretion via the HPA axis and inducing tissue-resident amplification of glucocorticoid signals. Progressive renal impairment can further impact on cortisol metabolism and urinary clearance of cortisol metabolites. Consequently, significant interest exists to precisely understand the dysregulation of cortisol in CKD and its significance for adverse clinical outcomes. In this review, we summarize the latest literature on alterations in endogenous glucocorticoid regulation in adults with CKD and evaluate the available evidence on cortisol as a mechanistic driver of excess mortality and morbidity. The emerging picture is one of subclinical hypercortisolism with blunted diurnal decline of cortisol levels, impaired negative feedback regulation and reduced cortisol clearance. An association between cortisol and adjusted all-cause mortality has been reported in observational studies for patients with end-stage renal failure, but further research is required to assess links between cortisol and clinical outcomes in CKD. We propose recommendations for future research, including therapeutic strategies that aim to reduce complications of CKD by correcting or reversing dysregulation of cortisol.

Background Carbohydrate and protein dietary proportions have been debated as to whether higher or lower levels are optimal for diabetes metabolic control. Objective The objective of this study was to investigate the associations, interactions, and mediational relationships between a polygenic risk score (PRS), carbohydrate and protein intake, and physical activity level on type 2 diabetes (T2DM) by genetic ancestry, in European Americans and African Americans. A secondary objective examined the biological pathways associated with the PRS-linked genes and their relationships to dietary intake. Methods We performed a cross-sectional study in 9,393 participants: 83.3% European Americans and 16.7% African Americans from 7-NHLBI Care studies obtained from the database of Genotypes and Phenotypes. The main outcome was T2DM. Carbohydrate and protein intake derived from food frequency questionnaires were calculated as percent calories. Data were analyzed using multivariable generalized estimation equation models to derive odds ratios (OR) and 95% confidence intervals (CI). Ancestry-specific PRSs were constructed using joint-effects Summary Best Linear Unbiased Estimation in the train dataset and replicated in the test dataset. Mediation analysis was performed using VanderWeele’s method. Results The PRS in the highest tertile was associated with higher risk of T2DM in European Americans (OR = 1.25;CI = 1.03–1.51) and African Americans (OR = 1.54;1.14–2.09). High carbohydrate and low protein intake had lower risks of T2DM when combined with the PRS after adjusting for covariates. In African Americans, high physical activity combined with the high PRS and high protein diet was associated with a 28% lower incidence of T2DM when compared to low physical activity. In mediational models in African Americans, the PRS-T2DM association was mediated by protein intake in the highest tertile by 55%. The top PRS tertile had the highest magnitude of risks with metabolic factors that were significantly associated with T2DM, especially in European Americans. We found metabolic pathways associated with the PRS-linked genes that were related to insulin/IGF and ketogenesis/ketolysis that can be activated by moderate physical activity and intermittent fasting for better T2DM control. Conclusions Clinicians may want to consider diets with a higher portion of carbohydrates than protein, especially when the burden of high-risk alleles is great in patients with T2DM. In addition, clinicians and other medical professionals may want to emphasize the addition of physical activity as part of treatment regimen especially for African Americans. Given the metabolic pathways we identified, moderate physical activity and intermittent fasting should be explored. Researchers may want to consider longitudinal or randomized clinical trials to determine the predictive ability of different dietary patterns to inhibit T2DM in the presence of obesity and an elevated PRS.

Abstract Background Associations have been observed among genetic variants, dietary patterns, and metabolic syndrome (MetS). A gap in knowledge is whether a genetic risk score (GRS) and dietary patterns interact to increase MetS risk among African Americans. We investigated whether MetS risk was influenced by interaction between a GRS and dietary patterns among Whites and African Americans. A secondary aim examined if molecular genetic clusterings differed by racial ancestry. Methods We used longitudinal data over 4-visits (1987–1998) that included 10,681 participants aged 45–64y at baseline from the Atherosclerosis Risk in Communities study (8451 Whites and 2230 African Americans). We constructed a simple-count GRS as the linear weighted sum of high-risk alleles (0, 1, 2) from cardiovascular disease polymorphisms from the genome-wide association studies catalog associated with MetS risk. Three dietary patterns were determined by factor analysis of food frequency questionnaire data: Western, healthy, and high-fat dairy. MetS was defined according to the 2016 National Cholesterol Education Program Adult Treatment Panel III criteria but used 2017 American Heart Association/American College of Cardiology criteria for elevated blood pressure. Analyses included generalized linear model risk ratios (RR), 95% confidence intervals (CI), and Bonferroni correction for multiple testing. Results The Western dietary pattern was associated with higher risk for MetS across increasing GRS tertiles among Whites (p

To standardize materials and component characterization for next generation hydrogen production and energy generation solid oxide cell (SOC) technologies, test protocols are being established to facilitate comparison across the numerous laboratories and research institutions where SOC development for application in solid oxide fuel cells (SOFCs) and solid oxide electrolyzes cells (SOEC) is conducted. This paper proposes guiding protocols for fundamental electrical properties characterization of SOC materials, including temperature- and oxygen partial pressure (pO2)-dependent conductivity measurements, and use of the electromotive force for determining the transference numbers, or contributions of each charge carrier (i.e., ions and electrons), to the total conductivity. The protocol for Archimedes density measurements is also provided as an integral technique to both of these methods.

Abstract Background Despite their efficacy in the treatment of chronic inflammation, the prolonged application of therapeutic glucocorticoids (GCs) is limited by significant systemic side effects including glucocorticoid-induced osteoporosis (GIOP). 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates GCs in vivo, regulating tissue-specific exposure to active GC. We aimed to determine the contribution of 11β-HSD1 to GIOP. Methods Wild type (WT) and 11β-HSD1 knockout (KO) mice were treated with corticosterone (100 μg/ml, 0.66% ethanol) or vehicle (0.66% ethanol) in drinking water over 4 weeks (six animals per group). Bone parameters were assessed by micro-CT, sub-micron absorption tomography and serum markers of bone metabolism. Osteoblast and osteoclast gene expression was assessed by quantitative RT-PCR. Results Wild type mice receiving corticosterone developed marked trabecular bone loss with reduced bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Histomorphometric analysis revealed a dramatic reduction in osteoblast numbers. This was matched by a significant reduction in the serum marker of osteoblast bone formation P1NP and gene expression of the osteoblast markers Alp and Bglap. In contrast, 11β-HSD1 KO mice receiving corticosterone demonstrated almost complete protection from trabecular bone loss, with partial protection from the decrease in osteoblast numbers and markers of bone formation relative to WT counterparts receiving corticosterone. Conclusions This study demonstrates that 11β-HSD1 plays a critical role in GIOP, mediating GC suppression of anabolic bone formation and reduced bone volume secondary to a decrease in osteoblast numbers. This raises the intriguing possibility that therapeutic inhibitors of 11β-HSD1 may be effective in preventing GIOP in patients receiving therapeutic steroids.

Abstract Background Patients with rheumatoid arthritis (RA) experience extra-articular manifestations including osteoporosis and muscle wasting, which closely associate with severity of disease. Whilst therapeutic glucocorticoids (GCs) reduce inflammation in RA, their actions on muscle and bone metabolism in the context of chronic inflammation remain unclear. We utilised the TNF-tg model of chronic polyarthritis to ascertain the impact of therapeutic GCs on bone and muscle homeostasis in the context of systemic inflammation. Methods TNF-tg and wild-type (WT) animals received either vehicle or the GC corticosterone (100 μg/ml) in drinking water at onset of arthritis. Arthritis severity and clinical parameters were measured, serum collected for ELISA and muscle and bone biopsies collected for μCT, histology and mRNA analysis. In vivo findings were examined in primary cultures of osteoblasts, osteoclasts and myotubes. Results TNF-tg mice receiving GCs showed protection from inflammatory bone loss, characterised by a reduction in serum markers of bone resorption, osteoclast numbers and osteoclast activity. In contrast, muscle wasting was markedly increased in WT and TNF-tg animals receiving GCs, independently of inflammation. This was characterised by a reduction in muscle weight and fibre size, and an induction in anti-anabolic and catabolic signalling. Conclusions This study demonstrates that when given in early onset chronic polyarthritis, oral GCs partially protect against inflammatory bone loss, but induce marked muscle wasting. These results suggest that in patients with inflammatory arthritis receiving GCs, the development of interventions to manage deleterious side effects in muscle should be prioritised.

Background: Impaired alveolar macrophage (AM) efferocytosis may contribute to acute respiratory distress syndrome (ARDS) pathogenesis; however, studies are limited by the difficulty in obtaining primary AMs from patients with ARDS. Our objective was to determine whether an in vitro model of ARDS can recapitulate the same AM functional defect observed in vivo and be used to further investigate pathophysiological mechanisms.Methods: AMs were isolated from the lung tissue of patients undergoing lobectomy and then treated with pooled bronchoalveolar lavage (BAL) fluid previously collected from patients with ARDS. AM phenotype and effector functions (efferocytosis and phagocytosis) were assessed by flow cytometry. Rac1 gene expression was assessed using quantitative real-time PCR.Results: ARDS BAL treatment of AMs decreased efferocytosis (p = 0.0006) and Rac1 gene expression (p = 0.016); however, bacterial phagocytosis was preserved. Expression of AM efferocytosis receptors MerTK (p = 0.015) and CD206 (p = 0.006) increased, whereas expression of the antiefferocytosis receptor SIRPα decreased following ARDS BAL treatment (p = 0.036). Rho-associated kinase (ROCK) inhibition partially restored AM efferocytosis in an in vitro model of ARDS (p = 0.009).Conclusions: Treatment of lung resection tissue AMs with ARDS BAL fluid induces impairment in efferocytosis similar to that observed in patients with ARDS. However, AM phagocytosis is preserved following ARDS BAL treatment. This specific impairment in AM efferocytosis can be partially restored by inhibition of ROCK. This in vitro model of ARDS is a useful tool to investigate the mechanisms by which the inflammatory alveolar microenvironment of ARDS induces AM dysfunction.

The role of tissue specific metabolism of endogenous glucocorticoids (GCs) in the pathogenesis of human disease has been a field of intense interest over the last 20 years, fuelling clinical trials of metabolism inhibitors in the treatment of an array of metabolic diseases. Localised pre-receptor metabolism of endogenous and therapeutic GCs by the 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes (which interconvert endogenous GCs between their inactive and active forms) are increasingly recognised as being critical in mediating both their positive and negative actions on bone homeostasis. In this review we explore the roles of endogenous and therapeutic GC metabolism by the 11β-HSD enzymes in the context of bone metabolism and bone cell function, and consider future strategies aimed at modulating this system in order to manage and treat various bone diseases.

Larval shortnose sturgeon, reared at 17°C, were subjected to delayed feeding treatments of 0, 5, 10, 15, 18, and 23 days post-yolk absorption to examine effects of food deprivation on growth, survival, swimming activity, and escape capabilities. Starvation affected growth and survival but despite degree of starvation, larvae were able to resume growth and experience high survivorship following feeding. Specific growth rate based on larval dry weight for the period directly following first feeding was highest for the day 15 and 18 delayed feeding treatments. There were no differences in survival between the 0 and 5 day treatments, however survival was reduced to 71.2%, 45.4%, and 28.8% for 10, 15, and 18 day delayed feeding treatments, respectively. Shortnose sturgeon had a point-of-no-return (PNR; 55.7% initiated feeding) at ~19 days (or 42 days post-fertilization) following the full absorption of yolk. Mean percent swimming activity and swimming speeds showed an interaction between delayed feeding treatment and larval age, such that no differences were detected at 1 and 6 days post-yolk absorption, while these swimming behaviors generally increased or spiked as feeding was delayed for 10, 15, and 18 days post-yolk absorption. At 23 days post-yolk absorption, only swimming speed increased for larvae that were denied food for 18 days. While there was an interaction between delayed feeding treatments and age for proportion of larvae exhibiting an escape response, generally, larvae from all feeding treatments exhibited a positive escape response. There were also interactions between delayed feeding treatments and age post-yolk absorption for mean and maximum escape speeds, such that less aggressive escape responses were typically detected the longer larvae were denied food. Our research suggests that larval shortnose sturgeon increase physical activity during periods of starvation to find a food patch while remaining vigilant but maybe not as capable to defend against a predatory attack as fed individuals.

Cachexia is the involuntary loss of muscle and adipose tissue that strongly affects mortality and treatment efficacy in patients with cancer or chronic inflammatory disease. Currently, no specific treatments or interventions are available for patients developing this disorder. Given the well-documented involvement of pro-inflammatory cytokines in muscle and fat metabolism in physiological responses and in the pathophysiology of chronic inflammatory disease and cancer, considerable interest has revolved around their role in mediating cachexia. This has been supported by association studies that report increased levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in some, but not all, cancers and in chronic inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and rheumatoid arthritis (RA). In addition, preclinical studies including animal disease models have provided a substantial body of evidence implicating a causal contribution of systemic inflammation to cachexia. The presence of inflammatory cytokines can affect skeletal muscle through several direct mechanisms, relying on activation of the corresponding receptor expressed by muscle, and resulting in inhibition of muscle protein synthesis (MPS), elevation of catabolic activity through the ubiquitin-proteasomal system (UPS) and autophagy, and impairment of myogenesis. Additionally, systemic inflammatory mediators indirectly contribute to muscle wasting through dysregulation of tissue and organ systems, including GCs via the hypothalamus-pituitary-adrenal (HPA) axis, the digestive system leading to anorexia-cachexia, and alterations in liver and adipocyte behavior, which subsequently impact on muscle. Finally, myokines secreted by skeletal muscle itself in response to inflammation have been implicated as autocrine and endocrine mediators of cachexia, as well as potential modulators of this debilitating condition. While inflammation has been shown to play a pivotal role in cachexia development, further understanding how these cytokines contribute to disease progression is required to reveal biomarkers or diagnostic tools to help identify at risk patients, or enable the design of targeted therapies to prevent or delay the progression of cachexia.

This article aims to expose the revitalization of Siriah Gadang cultural values in Galombang dance performed in Guguak village, Pariangan, Tanah Datar Regency, West Sumatra. Siriah Gadang is almost extinct because it is very rarely used. It is a cultural object with the same function as Cara-no, which is currently used for Galombang dance performances. To achieve this goal, qualitative research was used through observation, documentation, in-depth interviews, and Focus Group Discussion (FGD) techniques. The data obtained were analyzed using the Miles and Haberman model. It was found that the cultural values in Siriah Gadang are customary values, ethical values, social values, religious values, and leadership values reflected in the philosophy of the Minang-kabau people "adaik basandi syarak, syarak basandi Kitabullah." [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is accompanied by pain, inflammation and muscle weakness. Skeletal muscle inflammation and inactivity are independently associated with muscle insulin resistance and atrophy. Our objective was to identify early molecular and biochemical markers in muscle from a rodent model of RA relative to control and subsequently identify commonality in muscle gene expression between this model and muscle from RA patients. Pain behaviour and locomotor activity were measured in a collagen-induced arthritis (CIA) model of RA (n = 9) and control (n = 9) rats. Energy substrates and metabolites, total alkaline-soluble protein:DNA ratio and mRNA abundance of 46 targeted genes were also determined in Extensor digitorum longus muscle. Expression of targeted mRNAs was quantified in Vastus Lateralis muscle from RA patients (n = 7) and healthy age-matched control volunteers (n = 6). CIA rats exhibited pain behaviour (p

ObjectiveTo determine which anthropometric measures are the strongest discriminators of incident type 2 diabetes (T2DM) among White and Black males and females in a large U.S. cohort.MethodsWe used Atherosclerosis Risk in Communities study data from 12,121 participants aged 45-64 years without diabetes at baseline who were followed for over 11 years. Anthropometric measures included a body shape index (ABSI), body adiposity index (BAI), body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), and waist to hip to height ratio (WHHR). All anthropometric measures were repeated at each visit and converted to Z-scores. Hazard ratios and 95% confidence intervals adjusted for age were calculated using repeated measures Cox proportional hazard regression analysis. Akaike Information Criteria was used to select best-fit models. The magnitude of the hazard ratio effect sizes and the Harrell's C-indexes were used to rank the highest associations and discriminators, respectively.ResultsThere were 1,359 incident diabetes cases. Higher values of all anthropometric measures increased the risk for development of T2DM (p < 0.0001) except ABSI, which was not significant in White and Black males. Statistically significant hazard ratios ranged from 1.26-1.63 for males and 1.15-1.88 for females. In general, the largest hazard ratios were those that corresponded to the highest Harrell's C-Index and lowest Akaike Information Criteria values. Among White and Black males and females, BMI, WC, WHR, and WHtR were comparable in discriminating cases from non-cases of T2DM. ABSI, BAI, and WHHR were inferior discriminators of incident T2DM across all race-gender groups.ConclusionsBMI, the most commonly used anthropometric measure, and three anthropometric measures that included waist circumference (i.e., WC, WHR, WHtR) were the best anthropometric discriminators of incident T2DM across all race-gender groups in the ARIC cohort.