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Nathan Goodyear

Immunoexcitotoxicity offers new insight in brain injury related research, care - 0 views

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    Great, though brief, review of immunoexcitotoxicity as it relates to CTE.
Nathan Goodyear

Testosterone Deficiency, Cardiac Health, and Older Men - 0 views

  • Studies have shown pharmacological doses of testosterone to relax coronary arteries when injected intraluminally [39] and to produce modest but consistent improvement in exercise-induced angina and reverse associated ECG changes [40]. The mechanism of action is via blockade of calcium channels with effect of similar magnitude to nifedipine
    • Nathan Goodyear
       
      This directly refutes the recent studies (3) that Testosterone therapy increases cardiovascular events.
    • Nathan Goodyear
       
      Testosterone acts as a calcium channel blocker inducing vasodilation.
  • men with chronic stable angina pectoris, the ischaemic threshold increased after 4 weeks of TRT and a recent study demonstrates improvement continuing beyond 12 months [
  • Exercise capacity in men with chronic heart failure increased after 12 weeks
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  • Studies have shown an inverse relationship between serum testosterone and fasting blood glucose and insulin levels
  • Medications such as chronic analgesics, anticonvulsants, 5ARIs, and androgen ablation therapy are associated with increased risk of testosterone deficiency and insulin resistance
  • Women with T2D or metabolic syndrome characteristically have low SHBG and high free testosterone
    • Nathan Goodyear
       
      This stands in polar opposite of that with men.
  • Hypogonadism is a common feature of the metabolic syndrome
  • The precise interaction between insulin resistance, visceral adiposity, and hypogonadism is, as yet, unclear but the important mechanisms are through increased aromatase production, raised leptin levels, and increase in inflammatory kinins
  • levels of testosterone are reduced in proportion to degree of obesity
  • Men should be encouraged to combine aerobic exercise with strength training. As muscle increases, glucose will be burned more efficiently and insulin levels will fall. A minimum of 30 minutes exercise three times weekly should be advised
  • Testosterone increases levels of fast-twitch muscle fibres
  • By increasing testosterone, levels of type 2 fibres increase and glucose burning improves
  • Weight loss will increase levels of testosterone
  • studies now clearly show that low testosterone leads to visceral obesity and metabolic syndrome and is also a consequence of obesity
  • In the case of MMAS [43], a baseline total testosterone of less than 10.4 nmol/L was associated with a greater than 4-fold incidence of type 2 diabetes over the next 9 years
  • There is high level evidence that TRT improves insulin resistance
  • Low testosterone predicts increased mortality and testosterone therapy improves survival in 587 men with type 2 diabetes
  • A similar retrospective US study involved 1031 men with 372 on TRT. The cumulative mortality was 21% in the untreated group versus 10% ( ) in the treated group with the greatest effect in younger men and those with type 2 diabetes
  • the presence of ED has been shown to be an independent risk factor, particularly in hypogonadal men, increasing the risk of cardiac events by over 50%
  • A recent online publication on ischaemic heart disease mortality in men concluded optimal androgen levels are a biomarker for survival
  • inverse associations between low TT or FT (Table 2) and the severity of CAD
  • A recent 10 year study from Western Australia involving 3690 men followed up from 2001–2010 concluded that TT and FT levels in the normal range were associated with decreased all-cause and cardiovascular mortality, for the first time suggesting that both low and DHT are associated with all-cause mortality and higher levels of DHT reduced cardiovascular risk
  • TDS is associated with increased cardiovascular and all-cause mortality
  • The effect of treatment with TRT reduced the mortality rate of treated cohort (8.4%) to that of the eugonadal group whereas the mortality for the untreated remained high at 19.2%
  • hypogonadal men had slightly increased triglycerides and HDL
  • Men with angiographically proven CAD (coronary artery disease) have significantly lower testosterone levels [29] compared to controls ( ) and there was a significant inverse relationship between the degree of CAD and TT (total testosterone) levels
  • TRT has also been shown to reduce fibrinogen to levels similar to fibrates
  • men treated with long acting testosterone showed highly significant reductions in TC, LDL, and triglycerides with increase in HDL, associated with significant reduction in weight, BMI, and visceral fat
  • Low androgen levels are associated with an increase in inflammatory markers
  • In the Moscow study, C-reactive protein was reduced by TRT at 30 weeks versus placebo
  • In some studies, a decline in diastolic blood pressure has been observed, after 3–9 months [24, 26] and in systolic blood pressure
  • A decline was noted in IL6 and TNF-alpha
  • No studies to date show an increase in LUTS/BPH symptoms with higher serum testosterone levels
  • TRT has been shown to upregulate PDE5 [65] and enhance the effect of PDE5Is (now an accepted therapy for both ED and LUTS), it no longer seems logical to advice avoidance of TRT in men with mild to moderate BPH.
    • Nathan Goodyear
       
      What about just starting with normalization of Testosterone levels first.
  • Several meta-analyses have failed to show a link between TRT and development of prostate cancer [66] but some studies have shown a tendency for more aggressive prostate cancer in men with low testosterone
    • Nathan Goodyear
       
      And if one would have looked at their estrogen levels, I guarantee they would have been found to be elevated.
  • low bioavailable testosterone and high SHBG were associated with a 4.9- and 3.2-fold risk of positive biopsy
  • Current EAU, ISSAM, and BSSM guidance [1, 2] is that there is “no evidence TRT is associated with increased risk of prostate cancer or activation of subclinical cancer.”
  • Men with prostate cancer, treated with androgen deprivation, develop an increase of fat mass with an altered lipid profile
  • Erectile dysfunction is an established marker for future cardiovascular risk and the major presenting symptom leading to a diagnosis of low testosterone
wheelchairindia9

Shower Wheelchair - 0 views

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    Commode chairs are portable toilets, designed to be placed at the bedside of a disabled individual whose activity is very limited. It is typically consist of a frame and a waste receptacle that can be easily removed and emptied. Having such a device close at hand is especially helpful for those too debilitated to make the trip to the bathroom. So, if someone close to needs the support and convenience that commodes can offer, the right place. Adapted and assisted toileting systems help provide independence while being designed to be practical, versatile and comfortable, as well as, easy to clean. These adjustable toilets and commodes can be used as a freestanding commode chair, over the toilet, on the toilet, or as a shower chair. Commode Wheelchair Rainbow 6 Features: Frame Material : M.S.Chrome Plated. Single Seat with center cut commode. Both Option Available In Single Seat. Plastic Commode Seat With Pot. Cushioned Top Cover. Square Pan Commode Pan . Removable Pan. Commode Wheelchair Rainbow 6 Measurements: Frame Style : Foldable Open Position Wheel To Wheel Width In : 26" (Inches) Seat Width : 18" (Inches) Total Width in Closing Position : 11" (Inches) Rear Wheel Size : 24" (Inches) Front Wheel Size : 8" (Inches) Seat to Floor Height : 19" (Inches) Seat Depth : 18" (Inches) Total Height : 34" (Inches) Max User Weight Capacity : 110 (kgs) Net Weight : 19.5 (kgs) Armrest : Fixed Footrest : Fixed Wheel Quality : Rear Tyre Solid Tube Less Rear Wheel Lock : Yes Hand Brakes : No Drop Back Handle : No Providing a wide range of commode wheelchairs which are specially designed for aged and physically challenged people. These wheelchairs can be used for indoor toilet purposes. Fabricated using quality raw material, these wheelchairs are suitable for western as well as Indian toilets. This advanced technology involved wheelchair has a comfortable seat and made of a strong steel frame. This chair is very durable
wheelchairindia9

Cp Child Wheelchair - 0 views

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    young children have a different set of needs than adults. Aesthetically, devices designed for kids are often sleek and colorful, and functionally, they are typically lightweight and adjustable. As any parent knows, young people don't stay the same size for long and since a wheelchair is a major purchase -- don't want a simple growth spurt to render it useless. Wheelchair category offers models that feature seat width and depth adjustability, elevating legrests, and other versatile features. As a weight-bearing activity is critical to proper physical and mental function-which is why children with cerebral palsy, who may sit for stretches in a wheelchair and typically are unable to stand on their own, can benefit greatly from pediatric standers as part of a comprehensive pediatric rehabilitation program. Pediatric standers are offered in passive, active and mobile formats: Passive standers stay in one place and feature a support surface, active standers allow reciprocal movement of the extremities while in a standing position, and mobile standers enable users to self-propel. Cerebral Palsy Wheelchair: Cerebral Palsy Wheelchair Description: The model designed for cerebral palsy child only. Ultra light weight aluminium alloy frame. Seat Width 38 cms (15"). Net Weight: 18.5 kgs. Epoxy powder coated frame. Detachable arm rest & foot rest provided. Elevated and swinging foot rest. Elevated foot rest provided to elevate leg angle. Height adjustable and detachable head rest. Hydraulic reclining high back for a comfortable posture. Hydraulic adjustable seat angle. Detachable back and seat pad. Extra cushion upholstery provided to under arm, head & calg Foldable. Lever and paddle brakes provided. Safety belt provided. Maintenance free rear solid wheels. Cloth look like water proof upholstery. Anti wheels for better safety and stability. Extra cushion upholstery provided to under arm, head & leg. Folding action. Lever and paddle brakes provide
wheelchairindia9

Chair For Cerebral Palsy Child - 0 views

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    Cerebral palsy (CP) is a group of conditions caused by medical abnormalities in the development of a fetus or the early life of a child. These lead to damage or delayed development in the brain. The disorder is permanent and, though it does not worsen with age, the level of functionality of a person with cerebral palsy varies widely: in some cases, effects may be very minor, while in others, movement is impaired to the extent that a wheelchair is required. Common complications associated with CP vary by the type of CP disorder but can include vision problems, seizures, learning disabilities, and issues speaking, writing, and performing other tasks. Cerebral palsy causes problems with muscle tone, movement, balance and/or coordination. Symptoms and effects range from mild to severe. In some infants, problems are evident soon after birth. In others, diagnosis comes in later infancy or toddlerhood. Cerebral Palsy Wheelchair Description: The model designed for cerebral palsy child only. Ultra light weight aluminium alloy frame. Seat Width 38 cms (15"). Net Weight: 18.5 kgs. Epoxy powder coated frame. Detachable arm rest & foot rest provided. Elevated and swinging foot rest. Elevated foot rest provided to elevate leg angle. Height adjustable and detachable head rest. Hydraulic reclining high back for a comfortable posture. Hydraulic adjustable seat angle. Detachable back and seat pad. Extra cushion upholstery provided to under arm, head & calg Foldable. Lever and paddle brakes provided. Safety belt provided. Maintenance free rear solid wheels. Cloth look like water proof upholstery. Anti wheels for better safety and stability. Extra cushion upholstery provided to under arm, head & leg Folding action. Lever and paddle brakes provided. Safety belt provided. Maintenance free rear solid wheels. Cerebral Palsy Wheelchair Recline system: Recline system provides kids with the most comfortable resting environment. It also allows stretching abdomin
nucosmeticclinic

PRP Therapy - Non Surgical Hair Loss Treatment for Men and Women - 0 views

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    PRP Therapy or Platelet Rich Plasma Therapy is an effective non-surgical hair loss treatment for men and women. PRP Therapy makes efficient utilization of a growth enhancing blood constituent called platelets, which when combined together with plasma, results in an unprecedented increase in the hair follicles across the treated areas.
wheelchairindia9

Recliner Wheelchair - 0 views

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    Reclining Back Wheelchair( bed cum wheelchair ) which are suitable for indoor as well as outdoor purposes. These wheel chairs are manufactured using high quality material to ensure high strength and durability. Wheelchairs are available in foldable frames and are capable for maximum weight. Reclining wheelchairs are available in standard folding frames with extended head supports and seat widths up to 24" wide. The recline mechanism is attendant operated with levers much like a bicycle brake lever. The levers operate hydraulic (pump) mechanisms for a smooth adjustment. Using this Recliner Wheelchair mechanism, the chair back can easily and frequently be positioned to any angle. Reclining Wheelchair 609 GC: Reclining Wheelchair 609 GC is one of the multipurpose chairs which boast of features like reclining, inbuilt commode, customized armrest and footrest and foldable nature of the chair. Reclining Wheelchair 609 GC Features: The wheelchair can be folded within very easily within seconds, making it easier during travels and outings. The backrest of the chair can be easily reclined, giving the user the freedom to relax by not moving up from the chair. The footrest can be inclined and adjusted so as to make the user comfortable during reclining or otherwise. A well paded thigh support is an add-on to the footrest. The front and rear wheels of the chair are designed and placed in such a way so as to support the reclining of the user, making it a very safe and friendly wheelchair. The inbuilt commode has its seat just underneath the main seat of the chair; it can be used by just removing the main seat. The Wheelchair can also be folded from between by just removing the commode and the chair's seat. This Wheelchair's functionality gives the user total freedom. Easy to fold and unfold within seconds. Reclining Wheelchair 609 GC Measurements: Frame Style : Foldable Frame Material : MS Chrome Plated open position wheel to wheel width in : 26" (inch
Ciara Usher

The Best Bed I Ever Had - 1 views

Craftmatic electric and adjustable bed is the best bed I have ever had! It only takes a second to fall asleep whenever I sleep on it. I like the massage because it eases my body after a tiring day...

Craftmatic adjustable beds

started by Ciara Usher on 20 May 11 no follow-up yet
Nathan Goodyear

Hypothalamic-Pituitary-Testicular Axis Disruptions in Older Men Are Differentially Link... - 0 views

  • 0.4–2% annual decline
  • the age trend in free T was more substantial (−1.3% per annum)
  • The core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total T and progressively blunted free T associated with higher LH.
  • ...16 more annotations...
  • Obesity was associated with progressively lower total and free T independent of the simultaneous decrease in SHBG.
  • our data highlight the fact that LH was unchanged or even lower in older men in the face of lower T in obesity, suggesting that there may be a failure at the hypothalamic-pituitary level.
  • a change in BMI from nonobese to obese may be equivalent to a 15 yr fall in T.
  • This pattern supports the hypothesis that different underlying mechanisms influence the functions of the HPT axis: age predominantly affects testicular function, whereas obesity impairs hypothalamic/pituitary function.
  • the effects of aging on testicular function can be moderated by increased LH compensation for many decades
  • obesity impairs hypothalamic/pituitary function independent of age, arguably an adaptive response for which there should be no compensatory mechanism.
  • the concurrent but opposite (and separate) effects of obesity and age on SHBG
  • SHBG was negatively associated with increasing strata of obesity
  • Obesity is associated with insulin resistance (28), and the increased circulating insulin inhibits hepatic SHBG synthesis
  • the SHBG increase with age may be related to relative IGF-I deficiency (27), although this has not been directly proven.
  • Obesity is associated with peripheral and central insulin resistance (30) and proinflammatory cytokine production (TNFα and IL-6) from adipocytes (31) and central nervous system endocannibinoid release (32), all of which are potential candidates for abrogating hypothalamic endocrine and downstream reproductive axis functions.
    • Nathan Goodyear
       
      The HPA axis effect may be the result of inflammation.
  • The relationship between obesity and T can be bidirectional: low T may be the cause rather than consequence of obesity
  • chronic alcohol abuse is known to suppress LH (40), our data showed no significant association among the three hormones or SHBG and alcohol intake.
  • increase in total T in smokers occurs through a primary increase in SHBG with a compensatory rise in LH
  • the effects of obesity (BMI or waist circumference) was by far the most important determinant of variance in total T, whereas age per se was important for SHBG, LH, and free T with comorbidity and smoking being comparatively minor contributors
  • It is noteworthy that these predisposing lifestyle and health factors are modifiable. This implies that the apparent age-related decline in T may constitute a barometer of health and thus be potentially preventable and/or reversible.
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    Age induced decline in Testosterone is more associated with a decline in leydig cell function and thus elevated LH will be associated.  In contrast, obesity is more of a HPA axis disruption and thus LH may be normal to low.  The pulse amplitude is decrease.  No change in pulse frequency is noted.   With obesity, a decline in TT and fT was independent of SHBG. Aging is associated with a greater decrease in fT versus TT.
Nathan Goodyear

Renin-angiotensin system and cancer: A review - 0 views

  • crucial role of the RAS in the development and maintenance of cancer
  • kidneys, which produce renin in response to decreased arterial pressure, reduced sodium in the distal tubule, or sympathetic nervous system activity via the β-adrenergic receptors
  • Renin is secreted from the juxtaglomerular cells into the bloodstream where it encounters angiotensinogen (AGN), normally produced by the liver
  • ...22 more annotations...
  • Renin catalyses the conversion of AGN to angiotensin I (ATI), which is quickly cleaved by angiotensin converting enzyme (ACE) to form angiotensin II (ATII)
  • ATII triggers the release of aldosterone from the adrenal glands, which stimulates reabsorption of sodium and water and thereby increases blood volume and blood pressure
  • ATII also acts on smooth muscle to cause vasoconstriction of the arterioles
  • ATII promotes the release of antidiuretic hormone from the posterior pituitary gland, which results in water retention and triggers the thirst reflex
  • ability of non-CSCs to ‘de-differentiate’ into CSCs due to epigenetic or environmental factors, which further increases the complexity of tumour biology and treatment
  • efficacy of RAS modulators on cancer in both cancer models and cancer patients
  • A localised (‘paracrine’) RAS mechanism has been identified in many types of cancers, and interruption of the control of the RAS is thought to be the basis for its role in cancer
  • Components of the RAS are expressed by these CSCs, supporting the hypothesis of the presence of a ‘paracrine RAS’ in regulating these CSCs
  • Renin is an enzyme normally released by the kidneys in response to falling arterial pressure
  • a study of GBM demonstrating overexpression of PRR coupled with the observation that inhibition of renin reduces cellular proliferation and promotes apoptosis
  • PRR has been found to be vital for normal Wnt signalling
  • A major focus of PRR research is its relationship with Wnt signalling
  • suggest a crucial role for PRR activation on the proliferation of CSCs, possibly via Wnt/β-catenin signalling, leading to carcinogenesis.
  • Angiotensin converting enzyme (ACE), also known as CD143, is the endothelial-bound peptidase which physiologically converts ATI to ATII
  • ACE is crucial in the regulation of blood pressure, angiogenesis and inflammation
  • results suggest that an overactive ACE promotes cancer growth and progression, and an inhibited or low-activity ACE may have cancer-protective effects
  • When bound to ATII or ATIII it causes vasoconstriction by stimulating the release of vasopressin, reabsorption of water and sodium by promoting secretion of aldosterone and insulin, fibrosis, cellular growth and migration, pro-inflammation, glucose release from the liver, increased plasma triglyceride concentration, and reduced gluconeogenesis
  • ATIIR1 is a G-protein-coupled receptor, with downstream signalling involved in vasodilation, hypertrophy and NF-κB activation leading to TNF-α and PAI-1 expression
  • ATIIR1 has well-documented links with cancer, with one study demonstrating its overexpression in ~20% of breast cancer patients
  • the effect of RAS dysregulation has been associated with increased VEGF expression and angiogenesis in cancers
  • In ovarian and cervical cancer, ATIIR1 overexpression has been shown to be an indicator of tumour invasiveness
  • administration of ATIIR1 blockers (ARBs) have been associated with reduced tumour size, reduction in tumour vascularisation, lower occurrence of metastases, and lower VEGF levels
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    Great review on RAS in cancer.
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