Calcific Aortic Valve Disease:the Role of Bacteria as Trigger of a Chronic Inflammation
Calcific Aortic Valve DiaseaseCalcific aoric valve disease (CAVD) is extremely common worldwide, affecting almost 50% of the population over 85 years of age, with a lethality higher than 50% at 2 years for symptomatic patients, unless aortic-valve replacement is performed. CAVD is characterized by slowly progressive fibro-calcific remodelling of the valve leaflets causing aortic stenosis. The spectrum of the disease progression starts with leaflet degeneration and progresses from early lesions to valve stenosis/obstruction, which is initially mild to moderate but eventually becomes severe. Risk factors for CAVD partly overlap those for atherosclerosis but also intake age-related tissue changes and effects of comorbiditiies (e.g. renal failure) in the overall complex mechanisms of valve leaflet degeneration, which is, at present, unpreventable, leaving aortic valve repair the only treatment option for severe aortic stenosis. In the first phase of the disease the valve becomes thickened and mildly calcified, then the disease evolves to severe valve calcification with impaired leaflet motion and vast blood flow obstruction. Calcific AS valves show advanced osteogenic metaplasia with the presence of osteoblast-like cells and chondrocytes associated with dense inflammatory infiltrates. Bacteria have been detected in the absence of diagnosis of acute infective endocarditis, but their role is still unknown. Different bacterial species (C. acnes (59%), E. faecalis (16%), S. aureus (15%), and S. pyogenes (10%)) have been typed and intramural bacterial colonization has been observed in patients with calcified structural valvular heart disease. Indeed, it has been recently demonstrated that bacterial infections can directly affect osteoblast differentiation/activation. The Authors hypothesized that a subclinical or latent valvular bacterial infiltration facilitates a chronic inflammation and contributes to accelerated structural valve degeneration. An interdisciplinary team has been established to investigate the infective, biochemical and structural features of calcific aortic valve disease.
Longitudinal Evolution of Biomarkers of Dysautonomia and Inflammation During Sepsis in Children...
SepsisAutonomic Nervous SystemThe Autonomic Nervous System (ANS) regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. Many studies have investigated induced stimulation of the vagus nerve and its therapeutic effect in inhibiting TNFα (Tumor Necrosis Factor alpha) secretion, and therefore the risk of hypotension, septic shock, organ dysfunction during inflammation. While the anti-inflammatory effect of the autonomic nervous system on inflammation has been well studied, conversely, the effect of major inflammation on the balance of the autonomic nervous system is more difficult to understand. The inflammatory reflex could be overwhelmed and the regulatory centers of the brainstem dysregulated during situations of extreme inflammation.
Time-restricted Feeding to Reduce Inflammation in Fanconi Anemia
Fanconi AnemiaThe main reason for this research study is to determine whether time-restricted eating will reduce inflammation in the bodies of persons with Fanconi anemia (FA) and whether time-restricted eating will improve function in people with FA and neurological changes. Participants will be asked to eat for only 8 hours out of 24 hours in a day.
MR Evidence of Cardiac Inflammation Post-Stroke
StrokeIschemic2 moreThe present study is an investigator initiated, single-centre, prospective, proof-of-concept cohort study aiming to enroll 44 patients with acute middle cerebral artery (MCA) ischemic stroke, involving the right (n=22) and left (n=22) MCA territories and 24 control patients with acute focal neurological symptoms but no evidence of acute brain infarct on DWI-MRI.
NETs: Protection or Harm in Neonatal Inflammation or Infection
Necrotizing Enterocolitis (NEC)This is a prospective in vitro cell biology study of polymorphonuclear leukocyte (PMN) protein synthesis in response to PAF. PMNs from cord blood of premature human infants at risk for NEC (birth weight between 501 - 1500 grams) and PMNs from cord blood of healthy term infants will be isolated and stimulated with PAF, a biologically active phospholipid implicated in the pathogenesis of NEC. NEC, a disease of prematurity with an incidence of 10.1% of infants born weighing between 501 - 1500 grams, is associated with significant morbidity and mortality. We will compare the protein synthesis of inflammatory modulators, including Interleukin 6 Receptor alpha (IL-6R alpha) and Retinoic Acid Receptor alpha (RAR alpha) proteins to protein synthesis responses already observed in PMNs isolated from healthy adults. Furthermore, we will characterize the expression and activity of the mammalian target of rapamycin (mTOR) translational protein synthesis control pathway in PMNs isolated from preterm and term infants and compare those results with previous observations in PMNs isolated from adults. This pathway is known to regulate IL-6R alpha and RAR alpha protein expression in PMNs isolated from adults. We will also follow those premature infants at risk for NEC clinically to determine which infants develop NEC and what risk factors may be associated with NEC in this population.
Aging, Lifestyle and Inflammation in Veterans Exercising
InflammationAging2 moreOver half of adults in this country are overweight. This increases risk for heart and blood pressure problems, cancer, stroke and arthritis. While it is difficult to lose large amounts of weight and keep it off, even small amounts of weight loss can improve health. Furthermore, fat is increasingly recognized as a source of substances that increase inflammation. It may be that some of the adverse consequences of being overweight are due to increased inflammation. We are asking you to volunteer for a research study in which you may lose a moderate amount of weight and increase your activity. It is important that you read and understand the information on this form. The purposes of these studies are to determine the influence(s) of age and body composition on the production of inflammatory chemicals by fat (adipose tissue), the mechanisms controlling this, and if a weight loss and aerobic exercise intervention results in a decrease in inflammation.
Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset...
Still's DiseaseAdult-Onset3 moreBackground: Inflammatory conditions can cause symptoms like fevers, arthritis, and rash. Systemic juvenile idiopathic arthritis (sJIA) is one of these conditions. So is adult-onset Still s disease (AOSD). Their causes are unknown. Researchers want to learn more about these conditions. This includes genetic changes and environmental factors. Objective: To study sJIA and AOSD in children and adults over time. Eligibility: People with known or suspected sJIA, AOSD, or similar inflammatory condition Design: Participants will be screened with a phone call. Participants will have 1 visit. It may be outpatient or they may be admitted to the clinic. The visit may last up to 5 days. Participants will have: Medical history Physical exam Musculoskeletal exam Questions about overall health and quality of life, disease activity, functional status, and cognitive ability. Participants may also have: Pictures taken of their skin, joints, or spine Blood, urine, and stool tests Scans or X-rays of joints with arthritis Chest X-ray Heart tests Skin biopsy. The skin will be numbed. The top layers of a small area will be scraped off. Participants who have a joint aspiration may provide a fluid sample. The joint will be prepared, then fluid is removed by needle. A corticosteroid may be injected. Participants who have a bone marrow biopsy may provide sample cells. Participants may be seen by NIH specialists. Members of the participant s family and healthy volunteers may give blood or saliva samples for genetic testing. Participants may repeat some study tests every 6 months.
Impacts of Lentils on Metabolism and Inflammation
HypertriglyceridemiaInflammation2 moreThe overall goal of this investigation is to determine gut microbiome dependent and independent impacts of pulse consumption on metabolic resilience and metabolic risk profiles for type 2 diabetes (T2D) and cardiovascular disease (CVD) risk. Specifically, pulse crop consumption has unrealized potential to fundamentally alter how the body responds to disease promoting metabolic stresses of postprandial triglyceride and inflammation responses. The specific objectives are to (1) Determine the impact of green lentil consumption on postprandial triglyceride (TG) and inflammation responses to a high-fat meal challenge. (2) Determine the extent to which the gut microbiome and changes in the gut microbiome induced by pulse consumption influence health impacts (3) Measure metabolomic profiles to elucidate underlying mechanisms linking pulse consumption to improved health. To achieve these objectives investigators will determine the effects of green lentil on high impact risk factors of large postprandial triglyceride excursions and inflammation, composition of and changes in the gut microbiomes, and both gut and serum metabolomes in overweight/obese (OW/OB) individuals with elevated risk. The 12-week intervention will consist of consumption of 4.6 or 0 cups of pulses per week across 7 pre-made meals (matched for macronutrient content (except fiber) provided to experimental and control groups. The following hypotheses will be tested in the proposed investigation: H1: Lentil consumption lower postprandial TG and inflammation responses and improve overall metabolic health. H2: Characteristics of the gut microbiome and changes in the gut microbiome induced by lentil consumption substantially influence health impacts of pulse consumption. H3: Features of the fecal and serum metabolomes distinguishing lentil and control treatments correspond to metabolic pathways elucidating potential gut microbiome dependent and independent mechanisms linking pulse consumption to improved health.
Safety and Effectiveness of Drop-free Small Incision Cataract Surgery
CataractOcular Inflammation2 moreThis is a randomized control trial comparing the effects of subconjunctival triamcinolone administration during surgery to topical prednisolone drops on the development of post-operative inflammation and macular edema in manual small incision cataract surgery.
Relationships Among Inflammation, Physical and Mental Health in Subjects With Chronic Inflammatory...
Chronic Infectious DiseaseChronic Skin Disease6 moreThe prevalence of common mental disorders is high in patients with chronic inflammatory physical diseases(e.g., autoimmune or infectious diseases). The traditional explanatory causation model in which physical symptoms and related disability drive mental health problems is now called into question, and evidence has accumulated supporting more complex interactions whereby psychiatric disorders can both result from and contribute to the progression of physical diseases. In the present project, the investigators will focus on comorbidity of depression and anxiety symptoms or syndromes with chronic inflammatory skin diseases (psoriasis, hidradenitis suppurativa and atopic dermatitis) or chronic infectious diseases (chronic HBV and HIV infection). The study is aimed to clarify the mechanisms underlying the high frequency of those comorbidities. It will overcome the main limitations of previous investigations and use innovative statistical tools to model complex interrelationships and causal links among the assessed variables. The identification of key variables driving the causal chain of determinants of poor global health and quality of life may impact treatment outcome and models of care.