One minute of stair climbing and descending reduces postprandial insulin and glucose with 3-min improving insulin resistance following a mixed meal in young adults: A Randomized Controlled Crossover Trial.

Background: Glycemic markers, including postprandial glucose, insulin, and insulin resistance, are strong predictors of morbidity and mortality in individuals with and without diabetes. Stair-climbing and -descending (SCD) at a comfortable pace for 3 minutes after a sugary beverage (300 kilocalories; 100% carbohydrate) lowers insulin, with insulin sensitivity improving in 10 minutes. If similar benefits are seen following consumption of a mixed meal is unknown. We hypothesize SCD will improve these markers in a dose-response manner following a mixed meal. Methods: In a randomized, controlled, crossover trial, young adults (N = 31) performed SCD for 0 (seated control), 1, 3, and 10 minutes after a mixed meal (650 kilocalories; 53% carbohydrates, 33% fat, and 14% protein). Differences in glucose, insulin, and insulin sensitivity (ISI) from baseline to 30 min were analyzed using a mixed-effects ANOVA. Results: A significant fixed-effect was found for change in glucose [F(2.551,67.17) = 4.724,p = 0.007)], insulin [F(2.692,74.49) = 11.28,p < 0.001)], and ISI [F(2.127,56.00) = 5.848,p = 0.004)]. Compared to the seated control (0 minutes), changes in glucose were lower after 1 minute (-14.0 (-7.2)mg/dL,p < 0.001), 3 minutes (-18.4 (-7.0)mg/dL,p = 0.0007), and 10 minutes (-10.0 (-8.1)mg/dL,p = 0.039); changes in insulin were lower after 1 minute (-1.8 (-0.9)µIU/mL,p = 0.0011), 3 minutes (-2.8 (-0.9)µIU/mL,p < 0.001), and 10 minutes (-1.1 (-0.9)µIU/mL,p = 0.033); and changes in ISI were significantly higher after 3 minutes (2.4 (1.5),p < 0.001) and 10 minutes (1.3 (1.6),p = 0.014) but not 1 minute (1.2 (1.5),p = 0.059). Conclusion: Postprandial glucose and insulin improved with 1 minute, and insulin resistance improved with 3 minutes, of SCD at a self-selected, comfortable pace, after consumption of a mixed meal in apparently healthy young adults. Protocol: Trial registration: ClinicalTrials.gov Identifier: NCT04232475.

Colchicine and plaque: A focus on atherosclerosis imaging.

Colchicine is an anti-inflammatory medication, classically used to treat a wide spectrum of autoimmune diseases. More recently, colchicine has proven itself a key pharmacotherapy in cardiovascular disease (CVD) management, atherosclerotic plaque modification, and coronary artery disease (CAD) treatment. Colchicine acts on many anti-inflammatory pathways, which translates to cardiovascular event reduction, plaque transformation, and plaque reduction. With the FDA's 2023 approval of colchicine for reducing cardiovascular events, a novel clinical pathway opens. This advancement paves the route for CVD management that synergistically merges lipid lowering approaches with inflammation inhibition modalities. This pioneering moment spurs the need for this manuscript's comprehensive review. Hence, this paper synthesizes and surveys colchicine's new role as an atherosclerotic plaque modifier, to provide a framework for physicians in the clinical setting. We aim to improve understanding (and thereby application) of colchicine alongside existing mechanisms for CVD event reduction. This paper examines colchicine's anti-inflammatory mechanism, and reviews large cohort studies that evidence colchicine's blossoming role within CAD management. This paper also outlines imaging modalities for atherosclerotic analysis, reviews colchicine's mechanistic effect upon plaque transformation itself, and synthesizes trials which assess colchicine's nuanced effect upon atherosclerotic transformation.

Bellwethers of change: population modelling of North Pacific humpback whales from 2002 through 2021 reveals shift from recovery to climate response.

For the 40 years after the end of commercial whaling in 1976, humpback whale populations in the North Pacific Ocean exhibited a prolonged period of recovery. Using mark-recapture methods on the largest individual photo-identification dataset ever assembled for a cetacean, we estimated annual ocean-basin-wide abundance for the species from 2002 through 2021. Trends in annual estimates describe strong post-whaling era population recovery from 16 875 (± 5955) in 2002 to a peak abundance estimate of 33 488 (± 4455) in 2012. An apparent 20% decline from 2012 to 2021, 33 488 (± 4455) to 26 662 (± 4192), suggests the population abruptly reached carrying capacity due to loss of prey resources. This was particularly evident for humpback whales wintering in Hawai'i, where, by 2021, estimated abundance had declined by 34% from a peak in 2013, down to abundance levels previously seen in 2006, and contrasted to an absence of decline in Mainland Mexico breeding humpbacks. The strongest marine heatwave recorded globally to date during the 2014-2016 period appeared to have altered the course of species recovery, with enduring effects. Extending this time series will allow humpback whales to serve as an indicator species for the ecosystem in the face of a changing climate.

A collaborative and near-comprehensive North Pacific humpback whale photo-ID dataset.

We present an ocean-basin-scale dataset that includes tail fluke photographic identification (photo-ID) and encounter data for most living individual humpback whales (Megaptera novaeangliae) in the North Pacific Ocean. The dataset was built through a broad collaboration combining 39 separate curated photo-ID catalogs, supplemented with community science data. Data from throughout the North Pacific were aggregated into 13 regions, including six breeding regions, six feeding regions, and one migratory corridor. All images were compared with minimal pre-processing using a recently developed image recognition algorithm based on machine learning through artificial intelligence; this system is capable of rapidly detecting matches between individuals with an estimated 97-99% accuracy. For the 2001-2021 study period, a total of 27,956 unique individuals were documented in 157,350 encounters. Each individual was encountered, on average, in 5.6 sampling periods (i.e., breeding and feeding seasons), with an annual average of 87% of whales encountered in more than one season. The combined dataset and image recognition tool represents a living and accessible resource for collaborative, basin-wide studies of a keystone marine mammal in a time of rapid ecological change.

A wireless patch for the monitoring of C-reactive protein in sweat.

The quantification of protein biomarkers in blood at picomolar-level sensitivity requires labour-intensive incubation and washing steps. Sensing proteins in sweat, which would allow for point-of-care monitoring, is hindered by the typically large interpersonal and intrapersonal variations in its composition. Here we report the design and performance of a wearable and wireless patch for the real-time electrochemical detection of the inflammatory biomarker C-reactive (CRP) protein in sweat. The device integrates iontophoretic sweat extraction, microfluidic channels for sweat sampling and for reagent routing and replacement, and a graphene-based sensor array for quantifying CRP (via an electrode functionalized with anti-CRP capture antibodies-conjugated gold nanoparticles), ionic strength, pH and temperature for the real-time calibration of the CRP sensor. In patients with chronic obstructive pulmonary disease, with active or past infections or who had heart failure, the elevated concentrations of CRP measured via the patch correlated well with the protein's levels in serum. Wearable biosensors for the real-time sensitive analysis of inflammatory proteins in sweat may facilitate the management of chronic diseases.

Plaque Progression Differences Between Apixaban and Rivaroxaban in Patients With Atrial Fibrillation Measured With Cardiac Computed Tomography and Plaque Quantification.

BACKGROUND: Direct oral anticoagulants (DOACs) have been associated with less calcification and coronary plaque progression than warfarin. Whether different DOACs have different effects on coronary plaque burden and progression is not known. We compared the 12-month effects of apixaban and rivaroxaban on plaque characteristics and vascular morphology in patients with atrial fibrillation through quantitative cardiac computed tomographic angiography. STUDY QUESTION: In patients with nonvalvular atrial fibrillation using apixaban or rivaroxaban, are there differences in plaque quantification and progression measured with cardiac computed tomography? STUDY DESIGN: This is a post hoc analysis of 2 paired prospective, single-centered, randomized, open-label trials with blinded adjudication of results. In total, 74 patients were prospectively randomized in parallel trials: 29 to apixaban (2.5-5 mg BID) and 45 to rivaroxaban (20 mg QD). Serial cardiac computed tomographic angiography was performed at baseline and 52 weeks. MEASURES AND OUTCOMES: Comprehensive whole-heart analysis was performed for differences in the progression of percent atheroma volume (PAV), calcified plaque (CP) PAV, noncalcified plaque (NCP) PAV, positive arterial remodeling (PR) ≥1.10, and high-risk plaque (Cleerly Labs, New York, NY). RESULTS: Both groups had progression of all 3 plaque types (apixaban: CP 8.7 mm 3 , NCP 69.7 mm 3 , and LD-NCP 27.2 mm 3 ; rivaroxaban: CP 22.9 mm 3 , NCP 66.3 mm 3 , and LD-NCP 11.0 mm 3 ) and a total annual plaque PAV change (apixaban: PAV 1.5%, PAV-CP 0.12%, and PAV-NCP 0.92%; rivaroxaban: PAV 2.1%, PAV-CP 0.46%, and PAV-NCP 1.40%). There was significantly lower PAV-CP progression in the apixaban group compared with the rivaroxaban group (0.12% vs. 0.46% P = 0.02). High-risk plaque characteristics showed a significant change in PR of apixaban versus rivaroxaban ( P = 0.01). When the propensity score weighting model is applied, only PR changes are statistically significant ( P = 0.04). CONCLUSIONS: In both groups, there is progression of all types of plaque. There was a significant difference between apixaban and rivaroxaban on coronary calcification, with significantly lower calcific plaque progression in the apixaban group, and change in positive remodeling. With weighted modeling, only PR changes are statistically significant between the 2 DOACs.

Coronary plaque progression is greater in systemic lupus erythematosus than rheumatoid arthritis.

BACKGROUND: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are associated with a high incidence of cardiovascular disease. Coronary atherosclerosis, particularly total plaque and noncalcified plaque on coronary computed tomography angiography (CCTA) has been correlated with cardiovascular events. We compared baseline coronary plaque burden and progression by serial CCTA in SLE and RA patients. METHODS: We prospectively evaluated 44 patients who underwent serial CCTA examinations to quantify coronary plaque progression, 22 SLE patients, and 22 age- and sex-matched RA patients. Semiautomated plaque software was used for quantitative plaque assessment. Linear regression examined the effect of SLE diagnosis (versus RA) on annualized change in natural log-transformed total normalized atheroma volume (ln-TAV norm ) for low-attenuation, fibrofatty, fibrous, total noncalcified, densely calcified, and total plaque. RESULTS: No quantitative differences for any plaque types were observed at baseline between SLE and RA patients ( P = 0.330-0.990). After adjustment for baseline plaque and cardiovascular risk factors, the increase in ln-TAV norm was higher in SLE than RA patients for fibrous [Exp-ß: 0.202 (0.398), P = 0.0003], total noncalcified [Exp-ß: 0.179 (0.393), P = 0.0001], and total plaque volume [Exp-ß: 0.154 (0.501), P = 0.0007], but not for low-attenuation, fibrofatty, or densely calcified plaque ( P = 0.103-0.489). Patients with SLE had 80% more fibrous, 82% more noncalcified, and 85% more total plaque increase than those with RA. CONCLUSION: Coronary plaque volume was similar in RA and SLE at baseline. Progression was greater in SLE, which may explain the greater cardiovascular risk in this disease. Further research to evaluate screening and management strategies for cardiovascular disease in these high-risk patients is warranted.

Multiscale relationships between humpback whales and forage species hotspots within a large marine ecosystem.

Fluctuations in prey abundance, composition, and distribution can impact predators, and when predators and fisheries target the same species, predators become essential to ecosystem-based management. Because of the difficulty in collecting concomitant predator-prey data at appropriate scales in patchy environments, few studies have identified strong linkages between cetaceans and prey, especially across large geographic areas. During summer 2018, a line-transect survey for cetaceans and coastal pelagic species was conducted over the continental shelf and slope of British Columbia, Canada, and the US West Coast, allowing for a large-scale investigation of predator-prey spatial relationships. We report on a case study of humpback whales (Megaptera novaeangliae) and their primary prey-Pacific herring (Clupea pallasii), northern anchovy (Engraulis mordax), and krill-using generalized additive models to explore the relationships between whale abundance on 10-km transect segments and prey metrics. Prey metrics included direct measures of biomass densities on segments and an original hotspot metric. For each prey species, segments in the upper fifth percentile for biomass density (across all segments) were designated hotspots, and whale counts on a segment were evaluated for their relationship to number of hotspot segments (species-specific and multispecies) within 25, 50, or 100 km. Whale abundance was not strongly related to direct measures of biomass densities, whereas models using hotspot metrics were more effective at describing variation in whale abundance, underscoring that evaluating prey at relevant and measurable scales is critical in patchy, dynamic marine environments. Our analysis highlighted differences in the distribution and prey availability for three humpback whale distinct population segments (DPSs) as defined under the US Endangered Species Act, including threatened and endangered DPSs that forage within the California Current Large Marine Ecosystem. These linkages provide insights into which prey species whales may be targeting in different regions and across multiple scales and, consequently, how climatic variability and anthropogenic risks may differentially impact these distinct predator-prey assemblages. By identifying scale-appropriate prey hotspots that co-occur with humpback whale aggregations, and with targeted, consistent prey sampling and estimations of potential consumption rates by whales, these findings can help inform the conservation and management of humpback whales within an ecosystem-based management framework.

Type 1 diabetes mellitus diagnosis in young adult preceded by years of elevated postprandial and fasting glucose but normal HbA1c: A clinical example of discordance.

Herein, a case study of an individual with fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and postprandial blood glucose (PBG) measures from the 3 years preceding their type 1 diabetes mellitus diagnosis is used to highlight discordance among these common diagnostic tests. Data from the patient's own records, participation in clinical research, and healthcare provider were collated. Measures of FBG (90-160 mg/dL) and PBG (195-247 mg/dL) were elevated for 3 years with a normal HbA1c (5.0-5.4%) and without any symptoms. Overt symptoms, including polyuria, polydipsia, and unexplained weight loss, manifested 3 years later prompting the patient to contact their physician. Testing revealed an elevated HbA1c (9.8%) and presence of glutamic acid decarboxylase autoantibodies (GAD) (9 IU/mL). Daily body composition measures and weighed food logs from the 3 months preceding and 4 months after diagnosis illustrate the effects of glucose spilling and inadequate insulin levels. Both FBG and PBG indicated diabetes 3 years prior to HbA1c. While FBG, PBG, and HbA1c are considered equally appropriate for screening and diagnosing diabetes, this case study highlights the need to revisit important distinctions between these tests that explain their frequent discordance.

Effects of Mixed Nuts on Colonic Cell Proliferation and Ptgs2 and Rela Gene Expression.

BACKGROUND/AIM: Nut consumption is associated with lower risk of colorectal cancer (CRC). Previously, single nut varieties have been investigated but there is limited research on the consumption of a nut mixture and the underlying mechanisms. This study examined mixed nut consumption's effect on colonic cell proliferation, apoptosis, and gene expression involved in CRC. MATERIALS AND METHODS: Thirty 21-day old Sprague Dawley rats were divided into three groups: control (no nuts), pistachio or mixed nut for 8 weeks. Ki-67 quantitative immunostaining was used to mark proliferative cells and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay for apoptotic cells. Real-time quantitative polymerase chain reaction analysis was used to determine colonic gene expression of prostaglandin endoperoxide synthase 2 (Ptgs2), nuclear factor kappa-B p65 subunit (Rela), cyclin D1 (Ccnd1), peroxisome proliferator-activated receptor gamma (Pparg), O6-methylguanine-DNA-methyltransferase (Mgmt), 8-oxoguanine glycosylase (Ogg1), superoxide dismutase (Sod), and catalase (Cat). RESULTS: DNA damage, determined using 8-oxo-deoxyguanosin, was found to be lower in the mixed nut group only (p<0.05). Differences in proliferation and apoptosis among all three groups were not significant. Lower levels of the inflammatory marker, Ptgs2, were observed between the pistachio group and the control (p=0.035). The pistachio and mixed nut groups had lower levels of Rela compared to the control (p=0.029). Differences among diets for Ccnd1, Pparg, Mgmt, Ogg1, Sod, and Cat were not significant. CONCLUSION: Mixed nut consumption reduced DNA damage possibly via down-regulation of Rela inflammation gene expression without changes to colonic cell proliferation and apoptosis.

Sex differences in the acute effect of stair-climbing on postprandial blood glucose levels: A randomized controlled trial.

Single, short stair climbing and descending (SCD) bouts of low to moderate intensity effectively lower postprandial blood glucose but previous reports have found conflicting results on interactions by sex during exercise. We hypothesize that SCD at a self-selected intensity will be equally effective at lowering postprandial blood glucose in males and females. Methods and Results: Thirty subjects (age: 23.8 (3.0) years) performed 0, 1, 3, and 10 min of SCD following consumption of a mixed meal. SCD was performed at a self-selected comfortable pace and all bouts ended at minute 28. Postprandial blood glucose was measured every 15 min for 1 h and analyzed as glucose over time, area under the curve (AUC), and incremental AUC (iAUC) using mixed-design ANOVAs with repeated measures. Although there was no interaction between sex and condition or time (p = .129 to .541) for glucose over time, AUC, or iAUC, there was a main effect for sex for glucose over time (p = .004) and AUC (p = .006), but not iAUC (p = .125). Females had higher blood glucose throughout each trial (22% (13 to 31%), p = .004) but both males' and females' postprandial blood glucose was lowered following 10 min of SCD relative to the seated control condition. Conclusions: Males and females benefited equally from single, short SCD bouts of low to moderate intensity despite females having higher blood glucose at all time points. Previous findings of sex differences in the attenuating effect of exercise on postprandial blood glucose are likely due to the use of absolute workloads leading to varying relative intensities.

Correlates of Primary Healthcare Access and the Moderating Effects of Gender: A Cross Sectional Analysis of Irish Migrants.

Despite long established comparatively poor health outcomes there has been limited research into the healthcare access of Irish migrants in the UK. This study examines the relationship between demography, self-reported health (SRH) and social support and healthcare access and the influence of gender on these associations. Data was collected as part of a community-based action research project with Irish migrants in London (n = 790). Hierarchical logistic regression was used to predict self-reported access to a GP (compared with no reported access). The effect of gender was measured via interactions entered in the second step of the model. Older participants and males were less likely to report GP access. SRH was a significant predictor. Gender moderated the relationship between SRH, social support, employment and GP access. Findings highlight the help-seeking vulnerability of male and older Irish migrants and the potential of social support in promoting healthcare access for males.

Evolution of Jigsaw - a National Youth Mental Health Service.

AIM: There has been a global movement towards transformation of youth mental health services, but limited information on the core principles and characteristics of these new services is available. Jigsaw is one such service, established in Ireland in 2006, with the intent of creating change in Ireland's system of mental healthcare for 12-25 year olds. The aim of this paper is to describe the evolution of Jigsaw services, which are now firmly embedded in the Irish system of care for young people, and recognized internationally as an established service network. METHODS: This paper describes provides an up-to-date description of the Jigsaw service model, key areas of evolution that have shaped this model, and identifies future directions in service development. RESULTS: Key attributes of the Jigsaw service model including therapeutic service, scope of practice, youth mental health promotion, youth participation, and monitoring/evaluation are described in this paper. Information on key enablers (funding and governance/quality) and service providers is also included. CONCLUSIONS: Information on the core principles and characteristics of youth mental health services is important. This paper addresses a gap in the literature by describing the Jigsaw service model, which continues to evolve so that it is responsive to the needs of young people.

Three minutes of moderate-intensity stair walking improves glucose and insulin but not insulin sensitivity or total antioxidant capacity.

BACKGROUND AND AIMS: This study examined the effect of moderate intensity stair stepping exercise on the glycemic response, and antioxidant capacity (TAC) during an oral glucose tolerance test (OGTT). METHODS AND RESULTS: Thirty participants (women = 12) completed 4 OGTTs during rest or stair walking bouts of 1, 3, and 10 min in a randomized order. Blood was collected at baseline and 30 min during the OGTTs and analyzed for glucose, insulin, TAC, and lactate. Glucose concentrations were decreased following the 10 min (-22.69 (-34.66 to -10.72) mg/dL, p < 0.002) and 3 min (-15.37 (-25.05 to -5.69) mg/dL, p < 0.004) bouts but not the 1 min bout (-6.18 (-19.54 to 7.18) mg/dL, p = 0.352). Insulin concentrations were decreased following the 10 min (-6.11 (-8.86 to -3.36 µIU/dL), p < 0.001) and 3 min (-2.589 (-4.54 to -0.63) µIU/dL, p < 0.012) bouts but not the 1 min bout (-0.37 (-1.87 to 1.13) µIU/dL, p = 0.616). Insulin sensitivity index values showed a significant increase in the 10-min trial (1.81 (0.03-3.58), p < 0.048), but not during the 3 min (0.65 (-0.66 to 1.96) p = 0.317) or 1 min trial (0.13 (-1.58 to 1.84) p = 0.878). There was no omnibus effect for trial in TAC (p = 0.132, η2 = 0.07). There was no interaction between trial and time for blood lactate (p = 0.621, η2 = 0.02). CONCLUSION: This study provides evidence bouts as short as 3 min decrease postprandial blood glucose and insulin levels but longer bouts are needed to affect insulin sensitivity.

LDL receptor and pathogen processes: Functions beyond normal lipids.

Although the role of the LDL receptor concerning lipids is well known, its role in various viral and parasitic infections, and in regulating the inflammatory response is poorly understood. Several infectious agents use the LDL receptor as a port of entry, and others depend on it for their cycle of infection. In this review, we focus on the discovery, structure, and normal function of the LDL receptor, as well as its role in a selection of infections. The LDL receptor plays an important role in certain infections and is a potential target for treatment deserving further research.

A single one-minute, comfortable paced, stair-climbing bout reduces postprandial glucose following a mixed meal.

BACKGROUND AND AIMS: Postprandial blood glucose (PBG) is an independent predictor of disease and mortality risk. To date, the shortest, single, moderate-intensity exercise intervention to reduce PBG is a 1 min bout of stair stepping during an oral glucose tolerance test. Whether this effect translates to real meal consumption is unknown. METHODS AND RESULTS: Subjects (N = 30) participated in a randomized controlled crossover trial performing 0 min (seated control), 1 min, 3 min or 10 min of stair climbing and descending bouts (SCD) at a self-selected pace after consumption of a mixed meal on four separate visits. Compared to control, all SCD reduced PBG at least one timepoint: at 30-min the 3 min (-10.8 (-18.7 to -2.8) mg/dL, p = 0.010) and 10 min (-36.3 (-46.4 to -26.3) mg/dL), p < .001), and at 45-min the 1 min (-7.3 (-13.9 to -0.7) mg/dL, p = 0.030, 3 min (-8.7 (-13.9 to -3.6) mg/dL, p = 0.002 and 10 min SCD (-12.2 (-18.2 to -6.1)mg/dL, p < 0.000) reduced PBG. The area under the curve (AUC) for PBG was lower following the 3 min (-4.4% (-7.5 to -1.4%), p = 0.006) and 10 min (-8.9% (-12.4 to -5.3%), p < 0.001), while the incremental AUC (iAUC) was reduced only following the 10 min (-38.0% (-63.7 to -12.3%), p = 0.005) SCD. All SCD were rated by subjects as very light to light intensity. CONCLUSIONS: Single, subjectively "light" intensity stair climbing and descending bouts as short as 1 min in duration attenuate the postprandial glucose response in normal weight individuals following consumption of a mixed meal. More pronounced effects require longer bouts in a dose-dependent manner.