Reconstruction and Simulation of Neocortical Microcircuitry.

We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm(3) containing ~31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ~8 million connections with ~37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies. PAPERCLIP: VIDEO ABSTRACT.

Chromatin jets define the properties of cohesin-driven in vivo loop extrusion.

Complex genomes show intricate organization in three-dimensional (3D) nuclear space. Current models posit that cohesin extrudes loops to form self-interacting domains delimited by the DNA binding protein CTCF. Here, we describe and quantitatively characterize cohesin-propelled, jet-like chromatin contacts as landmarks of loop extrusion in quiescent mammalian lymphocytes. Experimental observations and polymer simulations indicate that narrow origins of loop extrusion favor jet formation. Unless constrained by CTCF, jets propagate symmetrically for 1-2 Mb, providing an estimate for the range of in vivo loop extrusion. Asymmetric CTCF binding deflects the angle of jet propagation as experimental evidence that cohesin-mediated loop extrusion can switch from bi- to unidirectional and is controlled independently in both directions. These data offer new insights into the physiological behavior of in vivo cohesin-mediated loop extrusion and further our understanding of the principles that underlie genome organization.

More than one million barriers fragment Europe's rivers.

Rivers support some of Earth's richest biodiversity1 and provide essential ecosystem services to society2, but they are often fragmented by barriers to free flow3. In Europe, attempts to quantify river connectivity have been hampered by the absence of a harmonized barrier database. Here we show that there are at least 1.2 million instream barriers in 36 European countries (with a mean density of 0.74 barriers per kilometre), 68 per cent of which are structures less than two metres in height that are often overlooked. Standardized walkover surveys along 2,715 kilometres of stream length for 147 rivers indicate that existing records underestimate barrier numbers by about 61 per cent. The highest barrier densities occur in the heavily modified rivers of central Europe and the lowest barrier densities occur in the most remote, sparsely populated alpine areas. Across Europe, the main predictors of barrier density are agricultural pressure, density of river-road crossings, extent of surface water and elevation. Relatively unfragmented rivers are still found in the Balkans, the Baltic states and parts of Scandinavia and southern Europe, but these require urgent protection from proposed dam developments. Our findings could inform the implementation of the EU Biodiversity Strategy, which aims to reconnect 25,000 kilometres of Europe's rivers by 2030, but achieving this will require a paradigm shift in river restoration that recognizes the widespread impacts caused by small barriers.

Expression and function of transient receptor potential melastatin 3 in the spinal afferent innervation of the mouse colon.

Abdominal pain is a cardinal symptom of inflammatory bowel disease (IBD). Transient receptor potential (TRP) channels contribute to abdominal pain in preclinical models of IBD, and TRP melastatin 3 (TRPM3) has recently been implicated in inflammatory bladder and joint pain in rodents. We hypothesized that TRPM3 is involved in colonic sensation and is sensitized during colitis. We used immunohistochemistry, ratiometric Ca2+ imaging, and colonic afferent nerve recordings in mice to evaluate TRPM3 protein expression in colon-projecting dorsal root ganglion (DRG) neurons, as well as functional activity in DRG neurons and colonic afferent nerves. Colitis was induced using dextran sulfate sodium (DSS) in drinking water. TRPM3 protein expression was observed in 76% of colon-projecting DRG neurons and was often colocalized with calcitonin gene-related peptide. The magnitudes of intracellular Ca2+ transients in DRG neurons in response to the TRPM3 agonists CIM-0216 and pregnenolone sulfate sodium were significantly greater in neurons from mice with colitis compared with controls. In addition, the percentage of DRG neurons from mice with colitis that responded to CIM-0216 was significantly increased. CIM-0216 also increased the firing rate of colonic afferent nerves from control and mice with colitis. The TRPM3 inhibitor isosakuranetin inhibited the mechanosensitive response to distension of wide dynamic range afferent nerve units from mice with colitis but had no effect in control mice. Thus, TRPM3 contributes to colonic sensory transduction and may be a potential target for treating pain in IBD.NEW & NOTEWORTHY This is the first study to characterize TRPM3 protein expression and function in colon-projecting DRG neurons. A TRPM3 agonist excited DRG neurons and colonic afferent nerves from healthy mice. TRPM3 agonist responses in DRG neurons were elevated during colitis. Inhibiting TRPM3 reduced the firing of wide dynamic range afferent nerves from mice with colitis but had no effect in control mice.

Variation in Testing for and Incidence of Celiac Autoimmunity in Canada: A Population-Based Study.

BACKGROUND & AIMS: The incidence of biopsy-confirmed celiac disease has increased. However, few studies have explored the incidence of celiac autoimmunity based on positive serology results. METHODS: A population-based cohort study assessed testing of tissue transglutaminase antibodies (tTG-IgA) in Alberta from 2012 to 2020. After excluding prevalent cases, incident celiac autoimmunity was defined as the first positive tTG-IgA result between 2015 and 2020. Testing and incidence rates for celiac autoimmunity were calculated per 1000 and 100,000 person-years, respectively. Incidence rate ratios (IRRs) were calculated to identify differences by demographic and regional factors. Average annual percent changes (AAPCs) assessed trends over time. RESULTS: The testing rate of tTG-IgA was 20.2 per 1000 person-years and remained stable from 2012 to 2020 (AAPC, 1.2%; 95% confidence interval [CI], -0.5 to 2.9). Testing was higher in female patients (IRR, 1.66; 95% CI, 1.65-1.66), those living in metropolitan areas (IRR, 1.39; 95% CI, 1.38-1.40), and in areas of lower socioeconomic deprivation (lowest compared to highest IRR, 1.24; 95% CI, 1.23-1.25). Incidence of celiac autoimmunity was 33.8 per 100,000 person-years and increased from 2015 to 2020 (AAPC, 6.2%; 95% CI, 3.1-9.5). Among those with tTG-IgA results ≥10 times the upper limit of normal, the incidence was 12.9 per 100,000 person-years. The incidence of celiac autoimmunity was higher in metropolitan settings (IRR, 1.28; 95% CI, 1.21-1.35) and in the least socioeconomically deprived areas compared to the highest (IRR, 1.22; 95% CI, 1.14-1.32). CONCLUSIONS: Incidence of celiac autoimmunity is high and increasing, despite stable testing rates. Variation in testing patterns may lead to underreporting the incidence of celiac autoimmunity in nonmetropolitan areas and more socioeconomically deprived neighborhoods.

Forecasting the Incidence and Prevalence of Inflammatory Bowel Disease: A Canadian Nationwide Analysis.

INTRODUCTION: Canada has a high burden of inflammatory bowel disease (IBD). Historical trends of IBD incidence and prevalence were analyzed to forecast the Canadian burden over the next decade. METHODS: Population-based surveillance cohorts in 8 provinces derived from health administrative data assessed the national incidence (2007-2014) and prevalence (2002-2014) of IBD. Autoregressive integrated moving average models were used to forecast incidence and prevalence, stratified by age, with 95% prediction intervals (PI), to 2035. The average annual percentage change (AAPC) with 95% confidence interval (CI) was calculated for the forecasted incidence and prevalence. RESULTS: The national incidence of IBD is estimated to be 29.9 per 100,000 (95% PI 28.3-31.5) in 2023. With a stable AAPC of 0.36% (95% CI -0.05 to 0.72), the incidence of IBD is forecasted to be 31.2 per 100,000 (95% PI 28.1-34.3) in 2035. The incidence in pediatric patients (younger than 18 years) is increasing (AAPC 1.27%; 95% CI 0.82-1.67), but it is stable in adults (AAPC 0.26%; 95% CI -0.42 to 0.82). The prevalence of IBD in Canada was 843 per 100,000 (95% PI 716-735) in 2023 and is expected to steadily climb (AAPC 2.43%; 95% CI 2.32-2.54) to 1,098 per 100,000 (95% PI 1,068-1,127) by 2035. The highest prevalence is in seniors with IBD (1,174 per 100,000 in 2023; AAPC 2.78%; 95% CI 2.75-2.81). DISCUSSION: Over the next decade, the Canadian health care systems will contend with the juxtaposition of rising incidence of pediatric IBD and a rising prevalence of overall IBD driven by the aging population.

Amygdala enlargement in temporal lobe epilepsy: Histopathology and surgical outcomes.

OBJECTIVES: Amygdala enlargement is detected on magnetic resonance imaging (MRI) in some patients with drug-resistant temporal lobe epilepsy (TLE), but its clinical significance remains uncertain We aimed to assess if the presence of amygdala enlargement (1) predicted seizure outcome following anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) and (2) was associated with specific histopathological changes. METHODS: This was a case-control study. We included patients with drug-resistant TLE who underwent ATL-AH with and without amygdala enlargement detected on pre-operative MRI. Amygdala volumetry was done using FreeSurfer for patients who had high-resolution T1-weighted images. Mann-Whitney U test was used to compare pre-operative clinical characteristics between the two groups. The amygdala volume on the epileptogenic side was compared to the amygdala volume on the contralateral side among cases and controls. Then, we used a two-sample, independent t test to compare the means of amygdala volume differences between cases and controls. The chi-square test was used to assess the correlation of amygdala enlargement with (1) post-surgical seizure outcomes and (2) histopathological changes. RESULTS: Nineteen patients with and 19 patients without amygdala enlargement were studied. Their median age at surgery was 38 years for cases and 39 years for controls, and 52.6% were male. There were no statistically significant differences between the two groups in their pre-operative clinical characteristics. There were significant differences in the means of volume difference between cases and controls (Diff = 457.2 mm3, 95% confidence interval [CI] 289.6-624.8; p < .001) and in the means of percentage difference (p < .001). However, there was no significant association between amygdala enlargement and surgical outcome (p = .72) or histopathological changes (p = .63). SIGNIFICANCE: The presence of amygdala enlargement on the pre-operative brain MRI in patients with TLE does not affect the surgical outcome following ATL-AH, and it does not necessarily suggest abnormal histopathology. These findings suggest that amygdala enlargement might reflect a secondary reactive process to seizures in the epileptogenic temporal lobe.

Effects of Exercise Training on Muscle Mass and Physical Function in Patients with Hepatocellular Carcinoma After Diagnosis: A Systematic Review.

BACKGROUND AND AIMS: Decreased muscle mass and physical function are common complications in hepatocellular carcinoma (HCC) patients who are associated with increased morbidity and mortality. Thus, there have been targeted efforts to prevent and/or improve both by enrolling these patients in exercise training programs. We performed a systematic review to evaluate the effects of exercise training on muscle mass and physical function in people with HCC after diagnosis. METHODS: A systematic literature search was conducted using the Medline, Base, PubMed, Cochrane and Scopus, and trial registries, through April 2023 for studies that assessed the effects of an exercise training program in adults with HCC. The primary outcomes were muscle mass and physical function. To assess the risk of bias, we used the Quality Assessment Tool for Quantitative Studies from the Effective Public Health Practice Project. RESULTS: Eight studies met inclusion criteria, comprising a total of 809 participants. Interventions included aerobic exercise training, resistance exercise training, balance and flexibility training, or home-based exercise training. Four studies showed statistically significant improvements in at least one muscular outcome. Three studies showed a maintenance of muscular outcomes, and one study showed a decrease in muscle mass. Four articles showed statistically improvements in at least one physical fitness variable, and two showed a maintenance of physical function variable. CONCLUSION: Together, the results suggest that patients may benefit from physical exercise training after treatment to improve muscle mass and physical function.

Age-Specific Association of Co-Morbidity With Home-Time After Acute Stroke.

OBJECTIVE: To examine the association of co-morbidity with home-time after acute stroke and whether the association is influenced by age. METHODS: We conducted a province-wide study using linked administrative databases to identify all admissions for first acute ischemic stroke or intracerebral hemorrhage between 2007 and 2018 in Alberta, Canada. We used ischemic stroke-weighted Charlson Co-morbidity Index of 3 or more to identify those with severe co-morbidity. We used zero-inflated negative binomial models to determine the association of severe co-morbidity with 90-day and 1-year home-time, and logistic models for achieving ≥ 80 out of 90 days of home-time, assessing for effect modification by age and adjusting for sex, stroke type, comprehensive stroke center care, hypertension, atrial fibrillation, year of study, and separately adjusting for estimated stroke severity. We also evaluated individual co-morbidities. RESULTS: Among 28,672 patients in our final cohort, severe co-morbidity was present in 27.7% and was associated with lower home-time, with a greater number of days lost at younger age (-13 days at age < 60 compared to -7 days at age 80+ years for 90-day home-time; -69 days at age < 60 compared to -51 days at age 80+ years for 1-year home-time). The reduction in probability of achieving ≥ 80 days of home-time was also greater at younger age (-22.7% at age < 60 years compared to -9.0% at age 80+ years). Results were attenuated but remained significant after adjusting for estimated stroke severity and excluding those who died. Myocardial infarction, diabetes, and cancer/metastases had a greater association with lower home-time at younger age, and those with dementia had the greatest reduction in home time. CONCLUSION: Severe co-morbidity in acute stroke is associated with lower home-time, more strongly at younger age.

Supporting Emergency Medical Services Clinicians Through Acute and Sustained Crises With Informal Peer Support and Intentional Acts of Kindness: The Emergency Medical Services Code Lavender Program.

OBJECTIVE: Given the recommendations against the use of critical incident stress debriefing, the emergency medical services (EMS) Code Lavender program was created as a mechanism to consistently recognize and reach out to EMS clinicians after acute crisis events, offer nonintrusive informal peer support and acts of kindness, and provide stepwise support via mental health professionals as needed. The study aimed to assess program utilization and evaluate the program's impact on EMS clinicians' perceptions of support and resources available to them after an acute crisis event. METHODS: Anonymous surveys were distributed before program implementation and 18 months later. Program utilization was tracked using REDCap (Vanderbilt University, Nashville, TN). Fisher exact tests and logistic regression were used to analyze the survey results. RESULTS: Within 30 months, 87 referrals were made. Seventy-seven preprogram (59% response rate) and 104 intraprogram (88% response rate) surveys were collected. There were no differences between respondents by sex or role. There were significant improvements in knowing where to go for help (from 40% to 85%, P < .001) and willingness to seek help if needed (from 40% to 59%, P = .02). CONCLUSION: The implementation of an EMS Code Lavender program led to significant increases in EMS clinician self-reported knowledge of where to go and willingness to seek help after acute crisis events.

Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Acute pancreatitis is a common disease with significant associated morbidity and mortality. We performed a systematic review and meta-analysis of population-based studies to explore the changing temporal trends of acute pancreatitis incidence globally. METHODS: We performed a systematic literature search to identify population-based studies reporting the annual incidence of acute pancreatitis. Abstracts were assessed independently to identify applicable articles for full-text review and data extraction. Joinpoint temporal trend analyses were performed to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs). The AAPCs were pooled in a meta-analysis to capture the overall and regional trends in acute pancreatitis incidence over time. Temporal data were summarized in a static map and an interactive, web-based map. RESULTS: Forty-four studies reported the temporal incidence of acute pancreatitis (online interactive map: https://kaplan-acute-pancreatitis-ucalgary.hub.arcgis.com/). The incidence of acute pancreatitis has increased from 1961 to 2016 (AAPC, 3.07%; 95% CI, 2.30% to 3.84%; n = 34). Increasing incidence was observed in North America (AAPC, 3.67%; 95% CI, 2.76% to 4.57%; n = 4) and Europe (AAPC, 2.77%; 95% CI, 1.91% to 3.63%; n = 23). The incidence of acute pancreatitis was stable in Asia (AAPC, -0.28%; 95% CI, -5.03% to 4.47%; n = 4). CONCLUSIONS: This meta-analysis provides a comprehensive overview of the global incidence of acute pancreatitis over the last 56 years and demonstrates a steadily rising incidence over time in most countries of the Western world. More studies are needed to better define the changing incidence of acute pancreatitis in Asia, Africa, and Latin America.

Global Hospitalization Trends for Crohn's Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses.

BACKGROUND & AIMS: The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century. METHODS: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries. RESULTS: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence). CONCLUSIONS: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems.

Exploring the acute effects of running on cerebral blood flow and food cue reactivity in healthy young men using functional magnetic resonance imaging.

Acute exercise suppresses appetite and alters food-cue reactivity, but the extent exercise-induced changes in cerebral blood flow (CBF) influences the blood-oxygen-level-dependent (BOLD) signal during appetite-related paradigms is not known. This study examined the impact of acute running on visual food-cue reactivity and explored whether such responses are influenced by CBF variability. In a randomised crossover design, 23 men (mean ± SD: 24 ± 4 years, 22.9 ± 2.1 kg/m2 ) completed fMRI scans before and after 60 min of running (68% ± 3% peak oxygen uptake) or rest (control). Five-minute pseudo-continuous arterial spin labelling fMRI scans were conducted for CBF assessment before and at four consecutive repeat acquisitions after exercise/rest. BOLD-fMRI was acquired during a food-cue reactivity task before and 28 min after exercise/rest. Food-cue reactivity analysis was performed with and without CBF adjustment. Subjective appetite ratings were assessed before, during and after exercise/rest. Exercise CBF was higher in grey matter, the posterior insula and in the region of the amygdala/hippocampus, and lower in the medial orbitofrontal cortex and dorsal striatum than control (main effect trial p ≤ .018). No time-by-trial interactions for CBF were identified (p ≥ .087). Exercise induced moderate-to-large reductions in subjective appetite ratings (Cohen's d = 0.53-0.84; p ≤ .024) and increased food-cue reactivity in the paracingulate gyrus, hippocampus, precuneous cortex, frontal pole and posterior cingulate gyrus. Accounting for CBF variability did not markedly alter detection of exercise-induced BOLD signal changes. Acute running evoked overall changes in CBF that were not time dependent and increased food-cue reactivity in regions implicated in attention, anticipation of reward, and episodic memory independent of CBF.

Challenges of considering both extremities of the weight status spectrum to better understand obesity: insights from the NUTRILEAN project in constitutionally thin individuals.

BACKGROUND/OBJECTIVES: While the physiology of obesity has been so extensively investigated to date, only an extremely small number of studies (less than 50) have focused on the other extremity of the weight spectrum: constitutional thinness. Yet, this important state of underweight in the absence of any eating disorders provides a mirror model of obesity that might be particularly insightful in understanding obesity. Nevertheless, important methodological and recruitment-related issues appear when it comes to this complex constitutionally thin phenotype, as experienced by our research group with the realization of the ongoing NUTRILEAN clinical trial. To face this challenge, the present paper aims at identifying, analyzing, and discussing the quality of such recruitment processes in publications about constitutional thinness. METHODS: In this order, a group of experts collectively created a new grading system to assess the level of rigour and quality achieved by each study based on different criteria. RESULTS: The main results were that (i) metabolic-related biasing criteria were poorly observed despite being crucial, (ii) recruitment processes were not detailed enough and with sufficient explicitness, and (iii) recruiting among already identified patients would be associated with both higher sample sizes and better scores of quality. CONCLUSIONS: The present work encourages investigators to adopt a high level of rigour despite the complexity and duration of recruitment processes for this specific population, and readers to pay close attention to the quality of recruitment when interpreting the data. To better understand obesity and its physiological adaptations, it seems essential not only to compare it to normal-weight conditions, but also to the other extremity of the weight status spectrum represented by constitutional thinness.

Associations of objectively measured physical activity, sedentary time and cardiorespiratory fitness with adipose tissue insulin resistance and ectopic fat.

BACKGROUND/OBJECTIVES: Inadequate movement, excess adiposity, and insulin resistance augment cardiometabolic risk. This study examined the associations of objectively measured moderate-to-vigorous intensity physical activity (MVPA), sedentary time and cardiorespiratory fitness (CRF), with adipose tissue insulin resistance and ectopic fat. METHODS: Data were combined from two previous experimental studies with community volunteers (n = 141, male = 60%, median (interquartile range) age = 37 (19) years, body mass index (BMI) = 26.1 (6.3) kg·m-2). Adipose tissue insulin resistance was assessed using the adipose tissue insulin resistance index (Adipo-IR); whilst magnetic resonance imaging (MRI) was used to measure liver, visceral (VAT) and subcutaneous abdominal adipose tissue (ScAT). Sedentary time and MVPA were measured via an ActiGraph GT3X+ accelerometer. Generalized linear models examined the association of CRF, MVPA, and sedentary time with Adipo-IR and fat depots. Interaction terms explored the moderating influence of age, sex, BMI and CRF. RESULTS: After controlling for BMI and cardiometabolic variables, sedentary time was positively associated with Adipo-IR (ß = 0.68 AU [95%CI = 0.27 to 1.10], P < 0.001). The association between sedentary time and Adipo-IR was moderated by age, CRF and BMI; such that it was stronger in individuals who were older, had lower CRF and had a higher BMI. Sedentary time was also positively associated with VAT (ß = 0.05 L [95%CI = 0.01 to 0.08], P = 0.005) with the relationship being stronger in females than males. CRF was inversely associated with VAT (ß = -0.02 L [95%CI = -0.04 to -0.01], P = 0.003) and ScAT (ß = -0.10 L [95%CI = -0.13 to -0.06], P < 0.001); with sex and BMI moderating the strength of associations with VAT and ScAT, respectively. CONCLUSIONS: Sedentary time is positively associated with adipose tissue insulin resistance which regulates lipogenesis and lipolysis. CRF is independently related to central fat storage which is a key risk factor for cardiometabolic disease.

External Validation of the Passive Surveillance Stroke Severity Indicator.

BACKGROUND: The Passive Surveillance Stroke Severity (PaSSV) Indicator was derived to estimate stroke severity from variables in administrative datasets but has not been externally validated. METHODS: We used linked administrative datasets to identify patients with first hospitalization for acute stroke between 2007-2018 in Alberta, Canada. We used the PaSSV indicator to estimate stroke severity. We used Cox proportional hazard models and evaluated the change in hazard ratios and model discrimination for 30-day and 1-year case fatality with and without PaSSV. Similar comparisons were made for 90-day home time thresholds using logistic regression. We also linked with a clinical registry to obtain National Institutes of Health Stroke Scale (NIHSS) and compared estimates from models without stroke severity, with PaSSV, and with NIHSS. RESULTS: There were 28,672 patients with acute stroke in the full sample. In comparison to no stroke severity, addition of PaSSV to the 30-day case fatality models resulted in improvement in model discrimination (C-statistic 0.72 [95%CI 0.71-0.73] to 0.80 [0.79-0.80]). After adjustment for PaSSV, admission to a comprehensive stroke center was associated with lower 30-day case fatality (adjusted hazard ratio changed from 1.03 [0.96-1.10] to 0.72 [0.67-0.77]). In the registry sample (N = 1328), model discrimination for 30-day case fatality improved with the inclusion of stroke severity. Results were similar for 1-year case fatality and home time outcomes. CONCLUSION: Addition of PaSSV improved model discrimination for case fatality and home time outcomes. The validity of PASSV in two Canadian provinces suggests that it is a useful tool for baseline risk adjustment in acute stroke.

The effect of acute and chronic exercise on hepatic lipid composition.

Exercise is recommended for those with, or at risk of nonalcoholic fatty liver disease (NAFLD), owing to beneficial effects on hepatic steatosis and cardiometabolic risk. Whilst exercise training reduces total intrahepatic lipid in people with NAFLD, accumulating evidence indicates that exercise may also modulate hepatic lipid composition. This metabolic influence is important as the profile of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) dramatically affect the metabolic consequences of hepatic lipid accumulation; with SFA being especially lipotoxic. Relatedly, obesity and NAFLD are associated with hepatic PUFA depletion and elevated SFA. This review summarizes the acute (single bout) and chronic (exercise training) effects of exercise on hepatic lipid composition in rodents (acute studies: n = 3, chronic studies: n = 13) and humans (acute studies: n = 1, chronic studies: n = 3). An increased proportion of hepatic PUFA after acute and chronic exercise is the most consistent finding of this review. Mechanistically, this may relate to an enhanced uptake of adipose-derived PUFA (reflecting habitual diet), particularly in rodents. A relative decrease in the proportion of hepatic MUFA after chronic exercise is also documented repeatedly, particularly in rodent models with elevated hepatic MUFA. This outcome is related to decreased hepatic stearoyl-CoA desaturase-1 activity in some studies. Findings regarding hepatic SFA are less consistent and limited by the absence of metabolic challenge in rodent models. These findings require confirmation in well-controlled interventions in people with NAFLD. These studies will be facilitated by recently validated magnetic resonance spectroscopy techniques, able to precisely quantify hepatic lipid composition in vivo.

A comparison of meal-related appetite, food reward and eating behaviour traits in people with and without spinal cord injury.

Persons with a spinal cord injury (SCI) are at a heightened risk of obesity. However, little is known about the effect of SCI on factors that influence energy intake. This study compared measures of food reward, eating behaviour traits, and appetite perceptions between adults with and without SCI. Twenty wheelchair dependent persons with chronic (>1 year) SCI (C1-T12) and twenty non-SCI individuals matched for BMI, age and sex participated. Following a familiarisation visit, participants consumed a breakfast meal, normalised for resting metabolic rate (RMR), and provided subjective appetite perceptions every 30 min for 4 h. Subsequently, energy intake was determined via an ad libitum lunch meal. Explicit liking, explicit wanting, implicit wanting and relative preference were assessed in a hungry and fed state via the Leeds Food Preference Questionnaire prior to and following the lunch meal. Eating behaviour traits were assessed via the Adult Eating Behaviour Questionnaire, Control of Eating Questionnaire, Reasons Individuals Stop Eating Questionnaire, and Three-Factor Eating Questionnaire Revised 18-item version. Sweet appeal bias was greater for explicit liking, explicit wanting, and relative preference in the group with SCI compared to the non-SCI group (p ≤ 0.024). The group with SCI also reported higher levels of cognitive restraint and satiety responsiveness (p ≤ 0.029). No group differences in postprandial appetite perceptions (p ≥ 0.690) or energy intake relative to RMR were seen (p = 0.358). However, the group with SCI demonstrated a trend toward a lower absolute energy intake (p = 0.063). In conclusion, food reward for sweet foods was greater in the group with SCI. Further, our findings suggest that acute appetite perceptions, including satiety profiles, are not different between persons with and without SCI.

Influence of water-based exercise on energy intake, appetite, and appetite-related hormones in adults: A systematic review and meta-analysis.

Single bouts of land-based exercise suppress appetite and do not typically alter energy intake in the short-term, whereas it has been suggested that water-based exercise may evoke orexigenic effects. The primary aim was to systematically review the available literature investigating the influence of water-based exercise on energy intake in adults (PROSPERO ID number CRD42022314349). PubMed, Medline, Sport-Discus, Academic Search Complete, CINAHL and Public Health Database were searched for peer-reviewed articles published in English from 1900 to May 2022. Included studies implemented a water-based exercise intervention versus a control or comparator. Risk of bias was assessed using the revised Cochrane 'Risk of bias tool for randomised trials' (RoB 2.0). We identified eight acute (same day) exercise studies which met the inclusion criteria. Meta-analysis was performed using a fixed effects generic inverse variance method on energy intake (8 studies (water versus control), 5 studies (water versus land) and 2 studies (water at two different temperatures)). Appetite and appetite-related hormones are also examined but high heterogeneity did not allow a meta-analysis of these outcome measures. We identified one chronic exercise training study which met the inclusion criteria with findings discussed narratively. Meta-analysis revealed that a single bout of exercise in water increased ad-libitum energy intake compared to a non-exercise control (mean difference [95% CI]: 330 [118, 542] kJ, P = 0.002). No difference in ad libitum energy intake was identified between water and land-based exercise (78 [-176, 334] kJ, P = 0.55). Exercising in cold water (18-20 °C) increased energy intake to a greater extent than neutral water (27-33 °C) temperature (719 [222, 1215] kJ; P < 0.005). The one eligible 12-week study did not assess whether water-based exercise influenced energy intake but did find that cycling and swimming did not alter fasting plasma concentrations of total ghrelin, insulin, leptin or total PYY but contributed to body mass loss 87.3 (5.2) to 85.9 (5.0) kg and 88.9 (4.9) to 86.4 (4.5) kg (P < 0.05) respectively. To conclude, if body mass management is a person's primary focus, they should be mindful of the tendency to eat more in the hours after a water-based exercise session, particularly when the water temperature is cold (18-20 °C).

Analytical Performance of the Factory-Calibrated Flash Glucose Monitoring System FreeStyle Libre2TM in Healthy Women.

Continuous glucose monitoring (CGM) is used clinically and for research purposes to capture glycaemic profiles. The accuracy of CGM among healthy populations has not been widely assessed. This study assessed agreement between glucose concentrations obtained from venous plasma and from CGM (FreeStyle Libre2TM, Abbott Diabetes Care, Witney, UK) in healthy women. Glucose concentrations were assessed after fasting and every 15 min after a standardized breakfast over a 4-h lab period. Accuracy of CGM was determined by Bland-Altman plot, 15/15% sensor agreement analysis, Clarke error grid analysis (EGA) and mean absolute relative difference (MARD). In all, 429 valid CGM readings with paired venous plasma glucose (VPG) values were obtained from 29 healthy women. Mean CGM readings were 1.14 mmol/L (95% CI: 0.97 to 1.30 mmol/L, p < 0.001) higher than VPG concentrations. Ratio 95% limits of agreement were from 0.68 to 2.20, and a proportional bias (slope: 0.22) was reported. Additionally, 45% of the CGM readings were within ±0.83 mmol/L (±15 mg/dL) or ±15% of VPG, while 85.3% were within EGA Zones A + B (clinically acceptable). MARD was 27.5% (95% CI: 20.8, 34.2%), with higher MARD values in the hypoglycaemia range and when VPG concentrations were falling. The FreeStyle Libre2TM CGM system tends to overestimate glucose concentrations compared to venous plasma samples in healthy women, especially during hypoglycaemia and during glycaemic swings.