Type I interferon and mitochondrial dysfunction are associated with dysregulated cytotoxic CD8+ T cell responses in juvenile systemic lupus erythematosus.

Juvenile systemic lupus erythematosus (JSLE) is an autoimmune condition which causes significant morbidity in children and young adults and is more severe in its presentation than adult-onset SLE. While many aspects of immune dysfunction have been studied extensively in adult-onset SLE, there is limited and contradictory evidence of how cytotoxic CD8+ T cells contribute to disease pathogenesis and studies exploring cytotoxicity in JSLE are virtually non-existent. Here, we report that CD8+ T cell cytotoxic capacity is reduced in JSLE versus healthy controls, irrespective of treatment or disease activity.

New York State Climate Impacts Assessment Chapter 05: Ecosystems.

The people of New York have long benefited from the state's diversity of ecosystems, which range from coastal shorelines and wetlands to extensive forests and mountaintop alpine habitat, and from lakes and rivers to greenspaces in heavily populated urban areas. These ecosystems provide key services such as food, water, forest products, flood prevention, carbon storage, climate moderation, recreational opportunities, and other cultural services. This chapter examines how changes in climatic conditions across the state are affecting different types of ecosystems and the services they provide, and considers likely future impacts of projected climate change.

The Owner Will See You Now: The Road to Entrepreneurship for Diverse Veterinarians.

The veterinary field needs more racial diversity to reflect pet owners and the general population. The problem is compounded when we examine diversity in veterinary practice ownership and other entrepreneurial endeavors. The road to business ownership is challenging for minority veterinarians, who must work harder to prove themselves to skeptical clients in a historically white profession.

Challenging Palliative Resection of a Massive Metachronous Cervical Lymph Node Metastasis from Osteosarcoma and Reconstruction with a Cervicothoracic Rotation Flap: Case Report and Review of Literature.

This article describes an uncommon metastasis from a rare site of osteosarcoma and a not so often used regional flap to reconstruct a large anterior and lateral neck defect following tumor resection surgical palliation.

Systemic lupus erythematosus patients have unique changes in serum metabolic profiles across age associated with cardiometabolic risk.

Objectives: Cardiovascular disease through accelerated atherosclerosis is a leading cause of mortality for patients with systemic lupus erythematosus (SLE), likely due to increased chronic inflammation and cardiometabolic defects over age. We investigated age-associated changes in metabolomic profiles of SLE patients and healthy controls (HCs).

Methods: Serum NMR metabolomic profiles from female SLE patients (n = 164, age = 14-76) and HCs (n = 123, age = 13-72) were assessed across age by linear regression and by age group between patients/HCs (Group 1, age ≤ 25, n = 62/46; Group 2, age = 26-49, n = 50/46; Group 3, age ≥ 50, n = 52/31) using multiple t tests.

Atherosclerosis Progression in the APPLE Trial Can Be Predicted in Young People With Juvenile-Onset Systemic Lupus Erythematosus Using a Novel Lipid Metabolomic Signature.

Objective: Patients with juvenile-onset systemic lupus erythematosus (JSLE) have increased atherosclerosis risk. This study investigated novel atherosclerosis progression biomarkers in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, the largest investigator-led randomized control trial of atorvastatin versus placebo for atherosclerosis progression in JSLE, using carotid intima-media thickness (CIMT) as the primary outcome.

Methods: Unsupervised clustering of baseline CIMT and CIMT progression over 36 months was used to stratify patients with JSLE.

Impact of puberty, sex determinants and chronic inflammation on cardiovascular risk in young people.

Worrying trends of increased cardiovascular disease (CVD) risk in children, adolescents and young people in the Modern Era have channelled research and public health strategies to tackle this growing epidemic. However, there are still controversies related to the dynamic of the impact of sex, age and puberty on this risk and on cardiovascular health outcomes later in life. In this comprehensive review of current literature, we examine the relationship between puberty, sex determinants and various traditional CVD-risk factors, as well as subclinical atherosclerosis in young people in general population.

Dietary Nitrate Supplementation Enhances Performance and Speeds Muscle Deoxyhaemoglobin Kinetics during an End-Sprint after Prolonged Moderate-Intensity Exercise.

Short-term dietary nitrate (NO3−) supplementation has the potential to enhance performance during submaximal endurance, and short-duration, maximal-intensity exercise. However, it has yet to be determined whether NO3− supplementation before and during submaximal endurance exercise can improve performance during a short-duration, maximal-intensity end-sprint. In a randomised, double-blind, crossover study, 9 recreationally active men ingested NO3−-rich (BR: 8 mmol NO3−/day) and NO3−-depleted (PL: 0.

Humoral responses against HDL are linked to lipoprotein traits, atherosclerosis, inflammation and pathogenic pathways during early arthritis stages.

Objective: Chronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis in RA. Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL). This study aimed to characterize the specificity, clinical relevance and emergence of humoral responses against HDL along disease course, especially during the earliest phases of arthritis.

Investigating sex differences in T regulatory cells from cisgender and transgender healthy individuals and patients with autoimmune inflammatory disease: a cross-sectional study.

Background: Sexual dimorphisms, which vary depending on age group and pubertal status, have been described across both the innate and adaptive immune system. We explored the influence of sex hormones on immune phenotype in the context of adolescent health and autoimmunity.

Methods: In this cross-sectional study, healthy, post-pubertal cisgender individuals (aged 16-25 years); healthy, pre-pubertal cisgender individuals (aged 6-11 years); transgender individuals (aged 18-19 years) undergoing gender-affirming treatment (testosterone in individuals assigned female sex at birth and oestradiol in individuals assigned male sex at birth); and post-pubertal cisgender individuals (aged 14-25 years) with juvenile-onset systemic lupus erythematosus (SLE) age-matched to cisgender individuals without juvenile-onset SLE were eligible for inclusion.

Diet and Systemic Lupus Erythematosus (SLE): From Supplementation to Intervention.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterised by immune dysregulation affecting multiple organs. Current anti-inflammatory treatments used in SLE are associated with unwanted side-effects. Dietary supplementation has been suggested as a safe and effective addition to conventional treatment, but evidence of efficacy in SLE or preventing associated comorbidities is uncertain.

CD8+ T-Cells in Juvenile-Onset SLE: From Pathogenesis to Comorbidities.

Diagnosis of systemic lupus erythematosus (SLE) in childhood [juvenile-onset (J) SLE], results in a more severe disease phenotype including major organ involvement, increased organ damage, cardiovascular disease risk and mortality compared to adult-onset SLE. Investigating early disease course in these younger JSLE patients could allow for timely intervention to improve long-term prognosis. However, precise mechanisms of pathogenesis are yet to be elucidated.

Sex Differences in Lipid Metabolism: Implications for Systemic Lupus Erythematosus and Cardiovascular Disease Risk.

It is known that healthy women during childbearing years have a lower risk of cardiovascular disease (CVD) and coronary heart disease compared to age matched men. Various traditional risk factors have been shown to confer differential CVD susceptibilities by sex. Atherosclerosis is a major cause of CVD and mortality and sex differences in CVD risk could be due to reduced atherogenic low and very low-density lipoproteins (LDL and VLDL) and increased atheroprotective high density lipoproteins (HDLs) in women.

Challenges in Implementing Cardiovascular Risk Scores for Assessment of Young People With Childhood-Onset Autoimmune Rheumatic Conditions.

Cardio-vascular risk (CVR) stratification tools have been implemented in clinical practice to guide management decision for primary prevention of cardiovascular disease. Less is known about how we can optimally estimate the CVR in children and adolescents or about the reliability of the risk stratification tools validated in adult populations. Chronic inflammation associated with autoimmune rheumatic disease (ARD) drives an increased risk for accelerated atherosclerosis in patients of all ages.

The Role of Immunometabolism in the Pathogenesis of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder in which pathogenic abnormalities within both the innate and adaptive immune response have been described. In order to activated, proliferate and maintain this immunological response a drastic upregulation in energy metabolism is required. Recently, a greater understanding of these changes in cellular bioenergetics have provided new insight into the links between immune response and the pathogenesis of a number of diseases, ranging from cancer to diabetes and multiple sclerosis.

Metabolomics Defines Complex Patterns of Dyslipidaemia in Juvenile-SLE Patients Associated with Inflammation and Potential Cardiovascular Disease Risk.

Cardiovascular disease (CVD) is a leading cause of mortality in patients with juvenile-onset systemic lupus erythematosus (JSLE) associated with atherosclerosis. The interplay between dyslipidaemia and inflammation-mechanisms that drive atherosclerosis-were investigated retrospectively in adolescent JSLE patients using lipoprotein-based serum metabolomics in patients with active and inactive disease, compared to healthy controls (HCs). Data was analysed using machine learning, logistic regression, and linear regression.

Lipid metabolism in autoimmune rheumatic disease: implications for modern and conventional therapies.

Suppressing inflammation has been the primary focus of therapies in autoimmune rheumatic diseases (AIRDs), including rheumatoid arthritis and systemic lupus erythematosus. However, conventional therapies with low target specificity can have effects on cell metabolism that are less predictable. A key example is lipid metabolism; current therapies can improve or exacerbate dyslipidemia.

Plant-based dietary changes may improve symptoms in patients with systemic lupus erythematosus.

Introduction: Previous studies have reported that patients affected by systemic lupus erythematosus (SLE) are interested in using diet to treat fatigue, cardiovascular disease and other symptoms. However, to date, there is insufficient information regarding the ways for patients to modify their diet to improve SLE symptoms. We investigated the relationship between the eating patterns of SLE patients and their self-reported disease symptoms and general aspects of health.

Sex hormones drive changes in lipoprotein metabolism.

Women have a reduced cardiovascular disease (CVD) risk compared with men, which could be partially driven by sex hormones influencing lipid levels post puberty. The interrelationship between sex hormones and lipids was explored in pre-pubertal children, young post-pubertal cis-men/women, and transgender individuals on cross-sex-hormone treatment (trans-men/women) using serum metabolomics assessing 149 lipids. High-density lipoproteins (HDL, typically atheroprotective) were significantly increased and very-low- and low-density lipoproteins (typically atherogenic) were significantly decreased in post-pubertal cis-women compared with cis-men.