Mechanistic studies further showed that such metabolic inflammation is related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect under prolonged nutritional excess
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Heart Disease and Stroke Statistics-2013 Update - 0 views
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shared by Nathan Goodyear on 09 Jul 13
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Inflammatory cause of metabolic syndrome via brain stress and NF-κB - 0 views
www.ncbi.nlm.nih.gov/...PMC3314172
metabolic syndrome TLR cytokines hypothalamus brain neurology metabolic syndrome NF-kappaB DIO diet induced obesity over nutrition nutrition inflammation
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intracellular stress-inflammation process for metabolic syndrome has been established in the central nervous system (CNS) and particularly in the hypothalamus
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the CNS and the comprised hypothalamus are known to govern various metabolic activities of the body including appetite control, energy expenditure, carbohydrate and lipid metabolism, and blood pressure homeostasis
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Reactive oxygen species (ROS) refer to a class of radical or non-radical oxygen-containing molecules that have high oxidative reactivity with lipids, proteins, and nucleic acids
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a large measure of intracellular ROS comes from the leakage of mitochondrial electron transport chain (ETC)
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Another major source of intracellular ROS is the intentional generation of superoxides by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
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there are other ROS-producing enzymes such as cyclooxygenases, lipoxygenases, xanthine oxidase, and cytochrome p450 enzymes, which are involved with specific metabolic processes
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To counteract the toxic effects of molecular oxidation by ROS, cells are equipped with a battery of antioxidant enzymes such as superoxide dismutases, catalase, peroxiredoxins, sulfiredoxin, and aldehyde dehydrogenases
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intracellular oxidative stress has been indicated to contribute to metabolic syndrome and related diseases, including T2D [72; 73], CVDs [74-76], neurodegenerative diseases [69; 77-80], and cancers
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intracellular oxidative stress is highly associated with the development of neurodegenerative diseases [69] and brain aging
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mitochondrial dysfunction in hypothalamic proopiomelanocortin (POMC) neurons causes central glucose sensing impairment
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Endoplasmic reticulum (ER) is the cellular organelle responsible for protein synthesis, maturation, and trafficking to secretory pathways
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ER stress has been associated to obesity, insulin resistance, T2D, CVDs, cancers, and neurodegenerative diseases
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under environmental stress such as nutrient deprivation or hypoxia, autophagy is strongly induced to breakdown macromolecules into reusable amino acids and fatty acids for survival
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intact autophagy function is required for the hypothalamus to properly control metabolic and energy homeostasis, while hypothalamic autophagy defect leads to the development of metabolic syndrome such as obesity and insulin resistance
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prolonged oxidative stress or ER stress has been shown to impair autophagy function in disease milieu of cancer or aging
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TLRs are an important class of membrane-bound pattern recognition receptors in classical innate immune defense
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overnutrition constitutes an environmental stimulus that can activate TLR pathways to mediate the development of metabolic syndrome related disorders such as obesity, insulin resistance, T2D, and atherosclerotic CVDs
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Isoforms TLR1, 2, 4, and 6 may be particularly pertinent to pathogenic signaling induced by lipid overnutrition
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hypothalamic TLR4 and downstream inflammatory signaling are activated in response to central lipid excess via direct intra-brain lipid administration or HFD-feeding
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overnutrition-induced metabolic derangements such as central leptin resistance, systemic insulin resistance, and weight gain
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these evidences based on brain TLR signaling further support the notion that CNS is the primary site for overnutrition to cause the development of metabolic syndrome.
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circulating cytokines can limitedly travel to the hypothalamus through the leaky blood-brain barrier around the mediobasal hypothalamus to activate hypothalamic cytokine receptors
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significant evidences have been recently documented demonstrating the role of cytokine receptor pathways in the development of metabolic syndrome components
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entral administration of TNF-α at low doses faithfully replicated the effects of central metabolic inflammation in enhancing eating, decreasing energy expenditure [158;159], and causing obesity-related hypertension
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Resistin, an adipocyte-derived proinflammatory cytokine, has been found to promote hepatic insulin resistance through its central actions
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both TLR pathways and cytokine receptor pathways are involved in central inflammatory mechanism of metabolic syndrome and related diseases.
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In quiescent state, NF-κB resides in the cytoplasm in an inactive form due to inhibitory binding by IκBα protein
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IKKβ activation via receptor-mediated pathway, leading to IκBα phosphorylation and degradation and subsequent release of NF-κB activity
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Research in the past decade has found that activation of IKKβ/NF-κB proinflammatory pathway in metabolic tissues is a prominent feature of various metabolic disorders related to overnutrition
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it happens in metabolic tissues, it is mainly associated with overnutrition-induced metabolic derangements, and most importantly, it is relatively low-grade and chronic
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this paradigm of IKKβ/NF-κB-mediated metabolic inflammation has been identified in the CNS – particularly the comprised hypothalamus, which primarily accounts for to the development of overnutrition-induced metabolic syndrome and related disorders such as obesity, insulin resistance, T2D, and obesity-related hypertension
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evidences have pointed to intracellular oxidative stress and mitochondrial dysfunction as upstream events that mediate hypothalamic NF-κB activation in a receptor-independent manner under overnutrition
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In the context of metabolic syndrome, oxidative stress-related NF-κB activation in metabolic tissues or vascular systems has been implicated in a broad range of metabolic syndrome-related diseases, such as diabetes, atherosclerosis, cardiac infarct, stroke, cancer, and aging
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intracellular oxidative stress seems to be a likely pathogenic link that bridges overnutrition with NF-κB activation leading to central metabolic dysregulation
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overnutrition is an environmental inducer for intracellular oxidative stress regardless of tissues involved
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excessive nutrients, when transported into cells, directly increase mitochondrial oxidative workload, which causes increased production of ROS by mitochondrial ETC
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oxidative stress has been shown to activate NF-κB pathway in neurons or glial cells in several types of metabolic syndrome-related neural diseases, such as stroke [185], neurodegenerative diseases [186-188], and brain aging
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central nutrient excess (e.g., glucose or lipids) has been shown to activate NF-κB in the hypothalamus [34-37] to account for overnutrition-induced central metabolic dysregulations
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overnutrition can present the cell with a metabolic overload that exceeds the physiological adaptive range of UPR, resulting in the development of ER stress and systemic metabolic disorders
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chronic ER stress in peripheral metabolic tissues such as adipocytes, liver, muscle, and pancreatic cells is a salient feature of overnutrition-related diseases
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recent literature supports a model that brain ER stress and NF-κB activation reciprocally promote each other in the development of central metabolic dysregulations
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when intracellular stresses remain unresolved, prolonged autophagy upregulation progresses into autophagy defect
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autophagy defect can induce NF-κB-mediated inflammation in association with the development of cancer or inflammatory diseases (e.g., Crohn's disease)
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The connection between autophagy defect and proinflammatory activation of NF-κB pathway can also be inferred in metabolic syndrome, since both autophagy defect [126-133;200] and NF-κB activation [20-33] are implicated in the development of overnutrition-related metabolic diseases
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Both TLR pathway and cytokine receptor pathways are closely related to IKKβ/NF-κB signaling in the central pathogenesis of metabolic syndrome
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Overnutrition, especially in the form of HFD feeding, was shown to activate TLR4 signaling and downstream IKKβ/NF-κB pathway
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TLR4 activation leads to MyD88-dependent NF-κB activation in early phase and MyD88-indepdnent MAPK/JNK pathway in late phase
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these studies point to NF-κB as an immediate signaling effector for TLR4 activation in central inflammatory response
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TLR4 activation has been shown to induce intracellular ER stress to indirectly cause metabolic inflammation in the hypothalamus
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central TLR4-NF-κB pathway may represent one of the early receptor-mediated events in overnutrition-induced central inflammation.
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cytokines and their receptors are both upstream activating components and downstream transcriptional targets of NF-κB activation
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central administration of TNF-α at low dose can mimic the effect of obesity-related inflammatory milieu to activate IKKβ/NF-κB proinflammatory pathways, furthering the development of overeating, energy expenditure decrease, and weight gain
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the physiological effects of IKKβ/NF-κB activation seem to be cell type-dependent, i.e., IKKβ/NF-κB activation in hypothalamic agouti-related protein (AGRP) neurons primarily leads to the development of energy imbalance and obesity [34]; while in hypothalamic POMC neurons, it primarily results in the development of hypertension and glucose intolerance
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shared by Nathan Goodyear on 21 Nov 13
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Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy: Observational ... - 0 views
jnci.oxfordjournals.org/...39.full
diabetes cardiovascular disease stroke androgen deprivation therapy prostate cancer
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Mechanisms of Edema Formation After Intracerebral Hemorrhage: Effects of Extravasated R... - 0 views
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shared by Nathan Goodyear on 13 Jan 15
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Intravenous Fluid Use in Athletes - 0 views
www.ncbi.nlm.nih.gov/...PMC3435915
IV intravenous fluid nutrition athletes athlete sports medicine sports exercise
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Treatment of exercise-associated hyponatremia with hypertonic IV infusion to correct plasma sodium levels is also a standard and accepted use of IV fluid infusions
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athletes who present for medical care with hypernatremia who cannot tolerate oral fluids can benefit from IV fluids
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Vaporization of sweat accounts for 80% of heat loss in hot, dry atmospheric conditions. This mechanism of water loss is the major contributor for exercise-associated dehydration
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Pre- and postexercise body weight measurements are the most common means to estimate overall water loss but are condition specific
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In highly trained endurance athletes, plasma volume and sodium serum concentration were preserved despite a 5% body weight loss
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In Ironman triathletes, dehydration to 5% body weight loss did not correlate with occurrence of medical complications
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hydration should begin hours prior to exercise, especially if known deficits are present, and fluids should be consumed at a slow, steady rate, with 5 to 7 mL/kg taken 4 hours prior to exercise
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Sodium concentration did not produce significant changes in the rate of absorption but was primarily dependent on carbohydrate concentration
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IV treatment of severe dehydration (>7% body weight loss), exertional heat illness, nausea, emesis, or diarrhea, and in those who cannot ingest oral fluids for other reasons, is clinically indicated
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A recent survey of the National Football League teams revealed that 75% (24 of 32) of the teams utilized IV infusion of fluids for prehydration in at least some otherwise healthy individuals
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In the National Football League, an average of 1.5 L of normal saline was administered approximately 2.5 hours prior to competition
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after 2 hours of exercise, the rectal temperature was 0.6° higher in the group not receiving IV infusion. Also, stroke volume and cardiac output were 11% to 16% lower in the control group versus the IV infusion group.
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Recent evidence suggests the etiology of EAMC is related to muscle fatigue and neuronal excitability
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there may be a subset of muscle cramping that is associated with a loss of both body fluid and sodium
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elevation of plasma volume by 200 to 300 mL via dextran infusion resulted in 15% increase in stroke volume, 4% increase in VO2 max, and an increase in the exercise time to fatigue
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Neither the tonicity nor mode of hydration resulted in improved speed of rehydration, greater fluid retention, or improved performance
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There are beneficial anecdotal reports of EAMC treatment in elite and professional-level athletes with IV hydration during the course of an event
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Plasma volume was better restored during rehydration with IV fluids at preexercise and 5 minutes of exercise. At 15 minutes, there was no difference between IV and oral rehydration
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More rapid restoration of plasma volume was accomplished in the IV treatment group with no advantages over oral rehydration in physiological strain, heat tolerance, ratings of perceived effort, or thermal sensations
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No difference was found in exercise time to exhaustion. IV and oral rehydration methods were equally effective. Heart rates were statistically higher in the oral rehydration group through 75 minutes of exercise, and there were higher increases in norepinephrine plasma concentrations
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No significant differences between the groups were found for time to recovery, number of days with pain, number of days with stiffness, sleep disturbance, fatigue, rectal temperature, and loss of appetite
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There may be physiological benefits of decreased heart rate and norepinephrine in athletes rehydrated via IV route
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Postexercise blood 1 hour and 24 hours showed no differences in circulating myoglobin or creatine kinase
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this should be reserved for high-level athletes with strong histories of symptoms in well-monitored settings.
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shared by Nathan Goodyear on 14 Nov 14
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JAMA Network | JAMA | Association of Testosterone Therapy With Mortality, Myocardial In... - 0 views
jama.jamanetwork.com/article.aspx
low T low testosterone mortality MI myocardial infarction stroke men male hormone hormones Testosterone
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The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and Pr... - 0 views
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Statin use and risk of diabetes mellitus - 0 views
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An increase in new onset diabetes, i.e., 3% in statin arm and 2.4% in placebo arm was reported. This was accompanied by increase in median value of glycated haemoglobin and was one of the earlier studies to report the increase in new onset diabetes in patients on statins
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Even after adjustment for potential confounders, statin therapy was associated with an increased risk of new-onset diabetes mellitus
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Another study also reported that as compared to placebo, statin group showed a higher risk of physician reported incident diabetes and it was also observed that risk was higher in women as compared to men
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Meta-analysis of randomized controlled trials by Sattar et al[25] involving 91140 non-diabetic patients showed that statin therapy was associated with 9% increased risk of incident diabetes
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A number of studies showed dose dependent association between statin administration and incident diabetes
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Treatment with atorvastatin and simvastatin may be associated with an increased risk of new onset diabetes as compared to pravastatin
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Increased incidence of diabetes was seen with atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial
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Increased insulin resistance secondary to statins was demonstrated in a prospective non randomised study in patients with coronary bypass surgery
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Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial
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Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial
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Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates p... - 0 views
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Physiotherapist in Gurgaon - 0 views
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Since its establishment in the year 2011, Krshna Physio Plus is aimed to provide patients with comprehensive, high quality and professional physiotherapy treatments and rehabilitation to people in need. The efficient team of three, Dr. Ravi Sahauta - A very well-known complex trauma surgeon and Orthopaedician, Dr. Dharm Pal Sharma - an ex-Air force Physio trainer and Dr. Parmila Sharma - an experienced and talented physio expert, Krshna Physio Plus is counted among the well-known Physiotherapy clinic in Gurgaon and Delhi/NCR regions. This clinic is one of the oldest organizations which was started with a vision to help people suffering from diverse dysfunctionalities with proper guidance and treatment which encompasses mainly physical, psychological, emotional, and social well being. With 8 centers in Delhi/NCR and Bihar, we are aimed at setting over 300 centers across Asia by 2020 and become the Physiotherapy clinic in Gurgaon. Moreover, KRSNA Physio Plus is well equipped with various advanced facilities and equipment used to treat people to assure patient satisfaction and fast recovery. We have with us Top Physiotherapist in Gurgaon and Delhi/NCR regions with us who are specialized in offering treatment in physiotherapy dealing with Orthopedic, Neurological, Pediatric, Cardio-pulmonary, and Sports Injury, etc. All the experts here put their best for providing the best results. Our experienced team of doctors and physiotherapists in Gurgaon who would be better able to diagnose what might be making it impossible for you to crane your neck, or pick articles off the floor, or simply kneel before your deity. Sports-Related Injuries Could Happen to Anyone It could be just that badminton match on a winter evening, or an office football match. Before you realize what is happening you've pulled a back muscle or your hamstring. Playing tug-of-war in colleges and office parties is fraught with the risk of a rotator cuff injury. Cricketers diving to save
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shared by indiacardiacsurg on 28 Oct 21
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New Technique by Low Cost Top 10 Heart Valve Surgeons in India Safer for Some High-Risk... - 0 views
www.briefingwire.com/...er-for-some-high-risk-patients
low-cost top 10 heart valve surgeons in India top 10 heart valve surgeons in India heart valve surgeons Heart Valve Replacement in India lowest price for heart valve replacement surgery in India Heart valve replacement surgeons in India
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"All patients had a successful TAVR without a coronary obstruction, stroke, or any major worry," stated low-cost top 10 heart valve surgeons in India. "They have been doing very well as they reached the 30-day-mark after undergoing the procedure." For Consultation International Helpline Number : +91-9370586696 Email id: enquiry@indiacardiacsurgerysite.com
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Mortality and Other Important Diabetes-Related Outcomes With Insulin vs Other Antihyper... - 0 views
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Homocysteine and MTHFR Mutations - 0 views
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Having only one mutation, ie, being heterozygous, is, from a medical perspective, irrelevant. Even when 2 MTHFR mutations are present (eg, 2 C677T mutations, or one C677T mutation and one A1298C mutation)
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Although these mutations do impair the regulation of homocysteine, adequate folate levels essentially “cancel out” this defect.
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Regardless of whether you have an MTHFR mutation in both genes or not, the treatment for elevated homocysteine is the same—dietary intervention and supplementation with folic acid and vitamins B6 and B12
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Overall, evidence from these studies indicates that, so long as the homocysteine level is normal, MTHFR mutations do not significantly increase the risk of heart attack or stroke
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Studies investigating the association of MTHFR mutations and venous blood clots have been inconsistent, with some studies showing a slight association, but most studies have not shown any association
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shared by Nathan Goodyear on 25 Apr 12
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Low serum testosterone, arterial stiffness and mortality in male haemodialysis patients - 0 views
ndt.oxfordjournals.org/...2971.abstract
low testosterone CVD mortality men male cardiovascular disease MI heart attack stroke
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shared by Nathan Goodyear on 10 Jul 12
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Allopregnanolone, a progesterone metabolite, i... [Ann Emerg Med. 2006] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...16546625
progesterone allopregnanolone hormone hormones brain neurology stroke
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Study Suggests Coenzyme Q10 Slows Functional Decline in Parkinson's Disease: National I... - 0 views
www.ninds.nih.gov/...kinsons_coenzymeq10_101402.htm
CoQ10 Parkinson's disease Huntington's ecitotoxic neurotoxic
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Journal of General Internal Medicine, Online First™ - SpringerLink - 0 views
www.springerlink.com/...b042807u865853t7
diet soda coke cardiovascular events stroke heart attack MI
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