Uncovering the hidden socioeconomic impact of juvenile idiopathic arthritis and paving the way for other rare childhood diseases: an international, cross-disciplinary, patient-centered approach (PAVE Consortium).

Background: Juvenile idiopathic arthritis (JIA) refers to a heterogeneous group of rheumatic conditions in children. Novel drugs have greatly improved disease outcomes; however, outcomes are impacted by limited awareness of the importance of early diagnosis and adequate treatment, and by differences in access across health systems. As a result, patients with JIA continue to be at risk for short- and long-term morbidity, as well as impacts on virtually all aspects of life of the child and family.

Distinct Roles for Brain and Pancreas in Basal and Postprandial Glucose Homeostasis.

The glucose homeostasis system ensures that the circulating glucose level is maintained within narrow physiological limits both in the fasting (or basal) state and following a nutrient challenge. Although glucose homeostasis is traditionally conceptualized as a single overarching system, evidence reviewed here suggests that basal glycemia and glucose tolerance are governed by distinct control systems. Specifically, whereas glucose tolerance appears to be determined largely by interactions between insulin secretion and insulin sensitivity, basal-state glucose homeostasis is predominated by insulin-independent mechanisms governed largely by the brain.

GIS-based AHP analysis to recognize the COVID-19 concern zone in India.

This study was planned to identifying the Corona concerns zone during COVID-19 transmission in India. The death rate was very high due COVID-19 pandemic outbreaks which are one of the main reasons for impairment the countries, and it will takes several years for the re-establishment of the fundamental need to ensure the demand of public supply. Currently, like many countries around the world, India is also facing a drastic health crisis due to Corona virus disease.

[Acute pancreatitis in pediatrics as a complication of multi-systemic inflammatory syndrome associated with COVID-19: A case report].

In April 2020, UK studies informed a condition in children similar to incomplete Kawasaki disease or toxic shock syndrome. From that time onwards, papers on children suffering from similar conditions have been published in different parts of the world. Today the disease is named multisystem inflammatory syndrome in children (MIS-C) associated with Covid-19.

A 12-week randomized clinical trial investigating the potential for sucralose to affect glucose homeostasis.

The discovery of gut sweet taste receptors has led to speculations that non-nutritive sweeteners, including sucralose, may affect glucose control. A double-blind, parallel, randomized clinical trial, reported here and previously submitted to regulatory agencies, helps to clarify the role of sucralose in this regard. This was primarily an out-patient study, with 4-week screening, 12-week test, and 4-week follow-up phases.

Glucokinase activators (GKAs) promise a new pharmacotherapy for diabetics.

The glucose-phosphorylating enzyme glucokinase, a promising target for developing new antidiabetic agents, was identified through the combined efforts of basic research and human biochemical genetics. Allosteric glucokinase activators (GKAs) were discovered by high-throughput screening of a large compound library and first reported in 2003. GKAs stimulate insulin release and glucose metabolism in the liver thereby lowering blood sugar, and promising trials in humans demonstrate that they are highly effective in patients with type 2 diabetes mellitus.

The changing landscape of type 2 diabetes: the role of incretin-based therapies in managed care outcomes.

Background: The prevalence of diabetes is growing in the United States and, for many patients, blood glucose continues to be poorly managed. Significantly, more than half of people with type 2 diabetes mellitus (T2DM) have hemoglobin A1Cs greater than 7%. Several factors contribute to the failure to achieve treatment goals, including clinical inertia (the failure to initiate or advance therapy in a patient who is not at the evidence-based therapeutic goal) and failure to address all components of disease pathophysiology.

Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association.

The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: The ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.

Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association.

The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: the ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.

Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans.

Insulin and its signaling systems are implicated in both central and peripheral mechanisms governing the ingestion, distribution, metabolism, and storage of nutrients in organisms ranging from worms to humans. Input from the environment regarding the availability and type of nutrients is sensed and integrated with humoral information (provided in part by insulin) regarding the sufficiency of body fat stores. In response to these afferent inputs, neuronal pathways are activated that influence energy flux and nutrient metabolism in the body and ensure reproductive competency.

Diabetes, obesity, and the brain.

Recent evidence suggests a key role for the brain in the control of both body fat content and glucose metabolism. Neuronal systems that regulate energy intake, energy expenditure, and endogenous glucose production sense and respond to input from hormonal and nutrient-related signals that convey information regarding both body energy stores and current energy availability. In response to this input, adaptive changes occur that promote energy homeostasis and the maintenance of blood glucose levels in the normal range.

Leptin and insulin action in the central nervous system.

Body adiposity is known to be carefully regulated and to remain relatively stable for long periods of time in most mammalian species. This review summarizes old and recent data implicating insulin and leptin as key circulating signals to the central nervous system, particularly the ventral hypothalamus, in communicating the size and the distribution of body fat stores. This input ultimately alters food intake and energy expenditure to maintain constancy of the adipose depot.

Expression of collagenase-3 (MMP-13) in c-fos-induced osteosarcomas and chondrosarcomas is restricted to a subset of cells of the osteo-/chondrogenic lineage.

The interstitial collagenases have been suggested to play a critical role in bone formation, remodeling, and cancerogenesis. We have previously shown that during mouse development expression of collagenase-3 (MMP-13) is restricted to bone and cartilage (Gack et al., 1995; Tuckermann et al.

Clinical importance of insulin secretion and its interaction with insulin resistance in the treatment of type 2 diabetes mellitus and its complications.

Type 2 diabetes primarily develops from pathogenic defects in the mechanisms of insulin secretion and hepatic and peripheral insulin action. The consequent disruption of normal glucose metabolism involves a number of organ systems and is ultimately manifested in fasting and daytime hyperglycemia. Chronically elevated blood glucose concentrations determine the progression of the disease by further exacerbating insulin resistance and causing beta-cell exhaustion in addition to decreasing their responsiveness to glucose.

AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1 composite element.

The expression of MMP13 (collagenase-3), a member of the matrix metalloproteinase family, is increased in vivo as well as in cultured osteosarcoma cell lines by parathyroid hormone (PTH), a major regulator of calcium homeostasis. Binding sites for AP-1 and Cbfa/Runt transcription factors in close proximity have been identified as cis-acting elements in the murine and rat mmp13 promoter required for PTH-induced expression. The cooperative function of these factors in response to PTH in osteoblastic cells suggests a direct interaction between AP-1 and Cbfa/Runt transcription factors.

beta-cell dysfunction and failure in type 2 diabetes: potential mechanisms.

Type 2 diabetes is characterized by a progressive loss of beta-cell function throughout the course of the disease. The pattern of loss is an initial defect in early or first-phase insulin secretion, followed by a decreasing maximal capacity of glucose to potentiate all nonglucose signals. Last, a defective steady-state and basal insulin secretion develops, leading to complete beta-cell failure requiring insulin treatment.

Obesity, body fat distribution, insulin sensitivity and Islet beta-cell function as explanations for metabolic diversity.

Studies of metabolic processes have been enhanced by our understanding of the relationships among obesity, body fat distribution, insulin sensitivity and islet beta-cell function. Thus, we have learned that although insulin resistance is usually associated with obesity, even lean subjects can be insulin resistant due to the accumulation of visceral fat. Insulin sensitivity and beta-cell function are also intimately linked.

Mechanisms for hyperglycemia in the metabolic syndrome. The key role of beta-cell dysfunction.

Hyperglycemia in Type 2 diabetes represents a steady-state re-regulation of plasma glucose to a higher-than-normal level after an overnight fast. The underlying pathophysiology represents an interaction between impaired beta-cell function and peripheral and hepatic insulin resistance which leads to abnormal hepatic glucose production. Subjects with the Metabolic Syndrome are at an increased risk for Type 2 diabetes and often have one or both of these disorders present even when glucose tolerance is normal.

Central nervous system control of food intake.

New information regarding neuronal circuits that control food intake and their hormonal regulation has extended our understanding of energy homeostasis, the process whereby energy intake is matched to energy expenditure over time. The profound obesity that results in rodents (and in the rare human case as well) from mutation of key signalling molecules involved in this regulatory system highlights its importance to human health. Although each new signalling pathway discovered in the hypothalamus is a potential target for drug development in the treatment of obesity, the growing number of such signalling molecules indicates that food intake is controlled by a highly complex process.

Insulin and leptin: dual adiposity signals to the brain for the regulation of food intake and body weight.

Insulin and leptin are hypothesized to be 'adiposity signals' for the long-term regulation of body weight by the brain. Accordingly, a change in the plasma levels of leptin or insulin indicates a state of altered energy homeostasis and adiposity, and the brain responds by adjusting food intake to restore adipose tissue mass to a regulated level. The candidate site for the brain's detection of leptin adiposity signaling is the hypothalamic arcuate nucleus, where leptin inhibits expression neuropeptide Y and increases expression of the pro-opiomelanocortin (POMC) precursor of alphaMSH.

Reduced beta-cell function contributes to impaired glucose tolerance in dogs made obese by high-fat feeding.

The ability to increase beta-cell function in the face of reduced insulin sensitivity is essential for normal glucose tolerance. Because high-fat feeding reduces both insulin sensitivity and glucose tolerance, we hypothesized that it also reduces beta-cell compensation. To test this hypothesis, we used intravenous glucose tolerance testing with minimal model analysis to measure glucose tolerance (K(g)), insulin sensitivity (S(I)), and the acute insulin response to glucose (AIR(g)) in nine dogs fed a chow diet and again after 7 wk of high-fat feeding.