5,289 research outputs found
The Clinical Significance of Subclinical Thyroid Dysfunction.
Subclinical thyroid disease (SCTD) is defined as serum free T(4) and free T(3) levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's ag
Subclinical Hypothyroidism
IMPORTANCE Subclinical hypothyroidism, defined as an elevated serum thyrotropin (often
referred to as thyroid-stimulating hormone, or TSH) level with normal levels of free thyroxine
(FT4) affects up to 10% of the adult population.
OBSERVATIONS Subclinical hypothyroidism is most often caused by autoimmune (Hashimoto)
thyroiditis.However, serum thyrotropin levels rise as people without thyroid disease age; serum
thyrotropin concentrations may surpass the upper limit of the traditional reference range of 4 to
5mU/L among elderly patients. This phenomenon has likely led to an overestimation of the true
prevalence of subclinical hypothyroidism in persons older than 70 years. In patients who have
circulating thyroid peroxidase antibodies, there is a greater risk of progression from subclinical to
overt hypothyroidism. Subclinical hypothyroidism may be associated with an increased risk of
heart failure, coronary artery disease events, and mortality from coronary heart disease. In
addition, middle-aged patients with subclinical hypothyroidism may have cognitive impairment,
nonspecific symptoms such as fatigue, and altered mood. In the absence of large randomized
trials showing benefit from levothyroxine therapy, the rationale for treatment is based on the
potential for decreasing the risk of adverse cardiovascular events and the possibility of
preventing progression to overt hypothyroidism.However, levothyroxine therapymay be
associated with iatrogenic thyrotoxicosis, especially in elderly patients, and there is no evidence
that it is beneficial in persons aged 65 years or older.
CONCLUSIONS AND RELEVANCE Subclinical hypothyroidism iscommonand most individuals can
be observed without treatment. Treatment might be indicated for patients with subclinical
hypothyroidism and serum thyrotropin levels of 10mU/L or higher or for young and middle-aged
individuals with subclinical hypothyroidism and symptoms consistent with mild hypothyroidis
Emergence of interaction effects in Bose-Einstein condensation
We present a quantitative evaluation of the predictions of mean-field theory for describing a Bose-Einstein condensate in a magnetic trap by comparing directly with experimental observations. We study the release energy from ballistic expansion and the cloud density profile as a function of mean-field effects. Significant departure of the cloud shape from both the noninteracting limit and the strongly repulsive limit is observed for our parameters, consistent with theoretical prediction
Monocytic Cell Adhesion to Oxidised Ligands: Relevance to Cardiovascular Disease.
Atherosclerosis, the major cause of vascular disease, is an inflammatory process driven by entry of blood monocytes into the arterial wall. LDL normally enters the wall, and stimulates monocyte adhesion by forming oxidation products such as oxidised phospholipids (oxPLs) and malondialdehyde. Adhesion molecules that bind monocytes to the wall permit traffic of these cells. CD14 is a monocyte surface receptor, a cofactor with TLR4 forming a complex that binds oxidised phospholipids and induces inflammatory changes in the cells, but data have been limited for monocyte adhesion. Here, we show that under static conditions, CD14 and TLR4 are implicated in adhesion of monocytes to solid phase oxidised LDL (oxLDL), and also that oxPL and malondialdehyde (MDA) adducts are involved in adhesion to oxLDL. Similarly, monocytes bound to heat shock protein 60 (HSP60), but this could be through contaminating lipopolysaccharide. Immunohistochemistry on atherosclerotic human arteries demonstrated increased endothelial MDA adducts and HSP60, but endothelial oxPL was not detected. We propose that monocytes could bind to MDA in endothelial cells, inducing atherosclerosis. Monocytes and platelets synergized in binding to oxLDL, forming aggregates; if this occurs at the arterial surface, they could precipitate thrombosis. These interactions could be targeted by cyclodextrins and oxidised phospholipid analogues for therapy
High intensity interval running enhances measures of physical fitness but not metabolic measures of cardiovascular disease risk in healthy adolescents
The effect of moving to East Village, the former London 2012 Olympic and Paralympic Games Athletes' Village, on mode of travel (ENABLE London study, a natural experiment)
Background
Interventions to encourage active modes of travel (walking, cycling) may improve physical activity levels, but longitudinal evidence is limited and major change in the built environment / travel infrastructure may be needed. East Village (the former London 2012 Olympic Games Athletes Village) has been repurposed on active design principles with improved walkability, open space and public transport and restrictions on residential car parking. We examined the effect of moving to East Village on adult travel patterns.
Methods
One thousand two hundred seventy-eight adults (16+ years) seeking to move into social, intermediate, and market-rent East Village accommodation were recruited in 2013–2015, and followed up after 2 years. Individual objective measures of physical activity using accelerometry (ActiGraph GT3X+) and geographic location using GPS travel recorders (QStarz) were time-matched and a validated algorithm assigned four travel modes (walking, cycling, motorised vehicle, train). We examined change in time spent in different travel modes, using multilevel linear regresssion models adjusting for sex, age group, ethnicity, housing group (fixed effects) and household (random effect), comparing those who had moved to East Village at follow-up with those who did not.
Results
Of 877 adults (69%) followed-up, 578 (66%) provided valid accelerometry and GPS data for at least 1 day (≥540 min) at both time points; half had moved to East Village. Despite no overall effects on physical activity levels, sizeable improvements in walkability and access to public transport in East Village resulted in decreased daily vehicle travel (8.3 mins, 95%CI 2.5,14.0), particularly in the intermediate housing group (9.6 mins, 95%CI 2.2,16.9), and increased underground travel (3.9 mins, 95%CI 1.2,6.5), more so in the market-rent group (11.5 mins, 95%CI 4.4,18.6). However, there were no effects on time spent walking or cycling
Hemangioma as a rare cause of a neonatal cardiac tumor resulting in inflow obstruction of the tricuspid valve
Pediatric Cardiac Intensive Care Society Statement: Caring for Children With Critical Cardiac Disease Across the Globe
NADPH oxidase, NOX1, mediates vascular injury in ischemic retinopathy
<b>Aims:</b> Ischemic retinal diseases such as retinopathy of prematurity are major causes of blindness due to damage to the retinal microvasculature. Despite this clinical situation, retinopathy of prematurity is mechanistically poorly understood. Therefore, effective preventative therapies are not available. However, hypoxic-induced increases in reactive oxygen species (ROS) have been suggested to be involved with NADPH oxidases (NOX), the only known dedicated enzymatic source of ROS. Our major aim was to determine the contribution of NOX isoforms (1, 2, and 4) to a rodent model of retinopathy of prematurity. <b>Results:</b> Using a genetic approach, we determined that only mice with a deletion of NOX1, but not NOX2 or NOX4, were protected from retinal neovascularization and vaso-obliteration, adhesion of leukocytes, microglial accumulation, and the increased generation of proangiogenic and proinflammatory factors and ROS. We complemented these studies by showing that the specific NOX inhibitor, GKT137831, reduced vasculopathy and ROS levels in retina. The source of NOX isoforms was evaluated in retinal vascular cells and neuro-glial elements. Microglia, the immune cells of the retina, expressed NOX1, 2, and 4 and responded to hypoxia with increased ROS formation, which was reduced by GKT137831. <b>Innovation:</b> Our studies are the first to identify the NOX1 isoform as having an important role in the pathogenesis of retinopathy of prematurity. <b>Conclusions:</b> Our findings suggest that strategies targeting NOX1 have the potential to be effective treatments for a range of ischemic retinopathie
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