Vitamin D and obesity

Obesity is a significant health problem world-wide, particularly in developed nations. Vitamin D deficiency is pandemic, and has been implicated in a wide variety of disease states. This paper seeks to examine the consistently reported relationship between obesity and low vitamin D concentrations, with reference to the possible underlying mechanisms. The possibility that vitamin D may assist in preventing or treating obesity is also examined, and recommendations for future research are made. There is a clear need for adequately-powered, prospective interventions which include baseline measurement of 25D concentrations and involve adequate doses of supplemental vitamin D. Until such studies have been reported, the role of vitamin D supplementation in obesity prevention remains uncertain.Simon Vanlin

Integrative MicroRNA and Proteomic Approaches Identify Novel Osteoarthritis Genes and Their Collaborative Metabolic and Inflammatory Networks

BACKGROUND: Osteoarthritis is a multifactorial disease characterized by destruction of the articular cartilage due to genetic, mechanical and environmental components affecting more than 100 million individuals all over the world. Despite the high prevalence of the disease, the absence of large-scale molecular studies limits our ability to understand the molecular pathobiology of osteoathritis and identify targets for drug development. METHODOLOGY/PRINCIPAL FINDINGS: In this study we integrated genetic, bioinformatic and proteomic approaches in order to identify new genes and their collaborative networks involved in osteoarthritis pathogenesis. MicroRNA profiling of patient-derived osteoarthritic cartilage in comparison to normal cartilage, revealed a 16 microRNA osteoarthritis gene signature. Using reverse-phase protein arrays in the same tissues we detected 76 differentially expressed proteins between osteoarthritic and normal chondrocytes. Proteins such as SOX11, FGF23, KLF6, WWOX and GDF15 not implicated previously in the genesis of osteoarthritis were identified. Integration of microRNA and proteomic data with microRNA gene-target prediction algorithms, generated a potential "interactome" network consisting of 11 microRNAs and 58 proteins linked by 414 potential functional associations. Comparison of the molecular and clinical data, revealed specific microRNAs (miR-22, miR-103) and proteins (PPARA, BMP7, IL1B) to be highly correlated with Body Mass Index (BMI). Experimental validation revealed that miR-22 regulated PPARA and BMP7 expression and its inhibition blocked inflammatory and catabolic changes in osteoarthritic chondrocytes. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that obesity and inflammation are related to osteoarthritis, a metabolic disease affected by microRNA deregulation. Gene network approaches provide new insights for elucidating the complexity of diseases such as osteoarthritis. The integration of microRNA, proteomic and clinical data provides a detailed picture of how a network state is correlated with disease and furthermore leads to the development of new treatments. This strategy will help to improve the understanding of the pathogenesis of multifactorial diseases such as osteoarthritis and provide possible novel therapeutic targets

Integrative MicroRNA and Proteomic Approaches Identify Novel Osteoarthritis Genes and Their Collaborative Metabolic and Inflammatory Networks

BACKGROUND: Osteoarthritis is a multifactorial disease characterized by destruction of the articular cartilage due to genetic, mechanical and environmental components affecting more than 100 million individuals all over the world. Despite the high prevalence of the disease, the absence of large-scale molecular studies limits our ability to understand the molecular pathobiology of osteoathritis and identify targets for drug development. METHODOLOGY/PRINCIPAL FINDINGS: In this study we integrated genetic, bioinformatic and proteomic approaches in order to identify new genes and their collaborative networks involved in osteoarthritis pathogenesis. MicroRNA profiling of patient-derived osteoarthritic cartilage in comparison to normal cartilage, revealed a 16 microRNA osteoarthritis gene signature. Using reverse-phase protein arrays in the same tissues we detected 76 differentially expressed proteins between osteoarthritic and normal chondrocytes. Proteins such as SOX11, FGF23, KLF6, WWOX and GDF15 not implicated previously in the genesis of osteoarthritis were identified. Integration of microRNA and proteomic data with microRNA gene-target prediction algorithms, generated a potential "interactome" network consisting of 11 microRNAs and 58 proteins linked by 414 potential functional associations. Comparison of the molecular and clinical data, revealed specific microRNAs (miR-22, miR-103) and proteins (PPARA, BMP7, IL1B) to be highly correlated with Body Mass Index (BMI). Experimental validation revealed that miR-22 regulated PPARA and BMP7 expression and its inhibition blocked inflammatory and catabolic changes in osteoarthritic chondrocytes. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that obesity and inflammation are related to osteoarthritis, a metabolic disease affected by microRNA deregulation. Gene network approaches provide new insights for elucidating the complexity of diseases such as osteoarthritis. The integration of microRNA, proteomic and clinical data provides a detailed picture of how a network state is correlated with disease and furthermore leads to the development of new treatments. This strategy will help to improve the understanding of the pathogenesis of multifactorial diseases such as osteoarthritis and provide possible novel therapeutic targets

Veno-Arterial Extracorporeal Membrane Oxygenation Rescue in a Patient With Pulmonary Hypertension Presenting for Revision Total Hip Arthroplasty: A Case Report and Narrative Review

Patients with pulmonary hypertension (PH) are at an increased risk of perioperative morbidity and mortality when undergoing non-cardiac surgery. We present a case of a 57-year-old patient with severe PH, who developed cardiac arrest as the result of right heart failure, undergoing a revision total hip arthroplasty under combined spinal epidural anesthesia. Emergent veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) was undertaken as rescue therapy during the pulmonary hypertensive crisis and a temporizing measure to provide circulatory support in an intensive care unit (ICU). We present a narrative review on perioperative management for patients with PH undergoing non-cardiac surgery. The review goes through the updated hemodynamic definition, clinical classification of PH, perioperative morbidity, and mortality associated with PH in non-cardiac surgery. Pre-operative assessment evaluates the type of surgery, the severity of PH, and comorbidities. General anesthesia (GA) is discussed in detail for patients with PH regarding the benefits of and unsubstantiated arguments against GA in non-cardiac surgery. The literature on risks and benefits of regional anesthesia (RA) in terms of neuraxial, deep plexus, and peripheral nerve block with or without sedation in patients with PH undergoing non-cardiac surgery is reviewed. The choice of anesthesia technique depends on the type of surgery, right ventricle (RV) function, pulmonary artery (PA) pressure, and comorbidities. Given the differences in pathophysiology and mechanical circulatory support (MCS) between the RV and left ventricle (LV), the indications, goals, and contraindications of VA-ECMO as a rescue in cardiopulmonary arrest and pulmonary hypertensive crisis in patients with PH are discussed. Given the significant morbidity and mortality associated with PH, multidisciplinary teams including anesthesiologists, surgeons, cardiologists, pulmonologists, and psychological and social worker support should provide perioperative management