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Reverse Decision Declining Romosozumab Use For Osteoporosis - 0 views

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    More than 100 NHS clinicians have urged the National Institute for Health and Care Excellence (NICE) to change its decision - declining recommendation of romosozumab, the first new osteoporosis medication for over a decade. In a joint letter published on January 2, the clinicians warned of the consequences of barring access to the drug to those who suffer the bone-weakening disease. The joint letter, led by the Royal Osteoporosis Society (ROS), raised concern over the scarcity of the drug pipeline for osteoporosis and lack of public funding for new research. It quoted recent government research that showed the National Institute for Health Research (NIHR) invested less than £1 million in osteoporosis research in 2020-21, against the £4.6 billion per year cost to the NHS of fractures. Craig Jones, chief executive of the Royal Osteoporosis Society said: "We're calling on NICE and the applicant company to get back round the table and work with us to ensure equal access to this important new treatment.
Nathan Goodyear

Utility, Limitations, and Pitfalls in Measuring Testosterone: An Endocrine Society Posi... - 0 views

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    This was a position statement from the Council of the Endocrine Society.  They looked at the reliability of free and total testosterone in serum and their conclusion: "...most assays for TT and FT are currently performed is decidedly unsatisfactory."  Enough said.  Interesting that they didn't look at salivary testosterone testing which has been shown to be extremely reliable and easy to perform.   I wonder how many physicians, insurance companies, state boards of medicine have read this statement?
arunaraayala

Sonam Kapoor: Sexism in the Society is Disgusting - Locality News - 0 views

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    Sonam Kapoor said ”I am not here to make money, although it would be nice” Mumbai: Sonam Kapoor is not the person to shred her words. The heroine has time and yet again voiced her feelings bravely. She is brave and never afraid to stance for what she trusts in. Newly, at a chat show, where ...
Nathan Goodyear

The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline - 1 views

  • the diagnostic sensitivity and specificity is said to be excellent (92–100%)
  • Measurement of salivary cortisol by ELISA and LC-MS/MS has been well validated in the United States
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    Endocrine society clinical  practice guideline's state proves validity of salivary cortisol testing.  Statement: "the diagnostic sensitivity and specificity is said to be excellent (92-100%)" and " Measurement of salivary cortisol by ELISA and LC-MS/MS has been well validated in the United States"
Nathan Goodyear

Use, misuse and abuse of androgens. The Endocrine... [Med J Aust. 2000] - PubMed - NCBI - 0 views

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    Endocrine society of australia guidelines for androgen therapy.
Nathan Goodyear

Subclinical Thyroid Dysfunction: A Joint Statement on Management from the American Asso... - 0 views

  • the potential benefits of early detection and treatment of subclinical thyroid dysfunction significantly outweigh the potential side-effects that could result from early diagnosis and therapy
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    Joint statement on early treatment of thyroid disease and subclinical thyroid dysfunction from The american association of clinical endocrinologists, the American Thyroid Association, and the Endocrine Society
Nathan Goodyear

Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Cli... - 0 views

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    the Endocrine Society clinical practice guideline to not screen for vitamin D deficiency, proves that this organization cannot be looked to for reliable analysis of scientific data
Nathan Goodyear

Low Steroid Levels Linked to Increased Risk of Cardiovascular Disease - 0 views

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    low DHEA associated with increased cardiovascular disease risk.  This was presented at the Endocrine Society 94th Annual meeting.
Nathan Goodyear

Postmenopausal Hormone Therapy: An Endocrine Society Scientific Statement - 0 views

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    "...in the subgroup of women starting HRT between ages 50 and 59 or less than 10 years after menopause...reduction of overall mortality and coronary artery disease."
Nathan Goodyear

Evidence for an Inhibitory Effect of Physiological Levels of Insulin on the Growth Horm... - 0 views

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    Insulin inhibits HGH production.  Key component of weight gain in our society today, with insulin resistance at an all time high.
Nathan Goodyear

Heavy Metal-induced Immunotoxicity and Its Mechanisms | ResearchGate - 0 views

  • Heavy Metal-induced Immunotoxicity and Its Mechanisms
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    Heavy Metal-induced Immunotoxicity and Its Mechanisms
wheelchairindia9

A Friendly Tricycle For The Disabled Users - 0 views

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    Those of all ages whose physical disabilities restrict their movement, affect their ability to earn a living or become valued members of society. Specially designed tricycles provide a mode of transport for the physically disabled allowing them much sought after independence and an opportunity for self support. The tricycles will enable freedom of movement and less dependency on others. Most of the people who depend on these tricycles are daily wage workers who have to travel long distances every day. The regular tricycles have no suspension and the riders are prone to spinal injuries. Most of them also cannot afford good medical care, and driving these tricycles for a long time affects. To deal with the problem, come up with a model tricycle that can be very useful to people who have a disability in their lower limbs, but a strong torso. The Handy tricycle to provide the ideal cycling experience for users advancement of upper body strength and toning for athletic events. Especially valuable to triathletes and challenged, it provides the perfect way to get in shape and stay that way. The tricycle achieves the true convenience of transportation while providing easy-to-use pedaling, steering and breaking controls. These are amongst the top selling handcycles on the market today. Handy is available in upright and recumbent versions. Hand powered front wheel drive. An internal hub-based gear shifting system is built into the front wheel.This provides ultra smooth shifting and is virtually maintenance-free. The entire front frame section is removable and connects easily, quickly and securely using a bolt-on system. The seat can be repositioned quickly and easily to allow the rider to achieve an optimally efficient distance between seat and handlebars.The rear wheels are removed using a single finger push system, allowing the bike to be broken down very quickly. Defined by two ways: Fork steer: It represent the majority of handcycles. They work well for both low
Nathan Goodyear

Press-pulse: a novel therapeutic strategy for the metabolic management of cancer | Nutr... - 0 views

  • A “press” disturbance was considered a chronic environmental stress on all organisms in an ecological community
  • “pulse” disturbances were considered acute events that disrupted biological communities to produce high mortality
  • Neoplasia involving dysregulated cell growth is the biological endpoint of the disease
  • ...84 more annotations...
  • Data from the American Cancer Society show that the rate of increase in cancer deaths/year (3.4%) was two-fold greater than the rate of increase in new cases/year (1.7%) from 2013 to 2017
  • cancer is predicted to overtake heart disease as the leading cause of death in Western societies
  • cancer can also be recognized as a metabolic disease.
  • glucose is first split into two molecules of pyruvate through the Embden–Meyerhof–Parnas glycolytic pathway in the cytosol
  • Aerobic fermentation, on the other hand, involves the production of lactic acid under normoxic conditions
  • persistent lactic acid production in the presence of adequate oxygen is indicative of abnormal respiration
  • Otto Warburg first proposed that all cancers arise from damage to cellular respiration
  • The Crabtree effect is an artifact of the in vitro environment and involves the glucose-induced suppression of respiration with a corresponding elevation of lactic acid production even under hyperoxic (pO2 = 120–160 mmHg) conditions associated with cell culture
  • the Warburg theory of insufficient aerobic respiration remains as the most credible explanation for the origin of tumor cells [2, 37, 51, 52, 53, 54, 55, 56, 57].
  • The main points of Warburg’s theory are; 1) insufficient respiration is the predisposing initiator of tumorigenesis and ultimately cancer, 2) energy through glycolysis gradually compensates for insufficient energy through respiration, 3) cancer cells continue to produce lactic acid in the presence of oxygen, and 4) respiratory insufficiency eventually becomes irreversible
  • Efraim Racker coined the term “Warburg effect”, which refers to the aerobic glycolysis that occurs in cancer cells
  • Warburg clearly demonstrated that aerobic fermentation (aerobic glycolysis) is an effect, and not the cause, of insufficient respiration
  • all tumor cells that have been examined to date contain abnormalities in the content or composition of cardiolipin
  • The evidence supporting Warburg’s original theory comes from a broad range of cancers and is now overwhelming
  • respiratory insufficiency, arising from any number mitochondrial defects, can contribute to the fermentation metabolism seen in tumor cells.
  • data from the nuclear and mitochondrial transfer experiments suggest that oncogene changes are effects, rather than causes, of tumorigenesis
  • Normal mitochondria can suppress tumorigenesis, whereas abnormal mitochondria can enhance tumorigenesis
  • In addition to glucose, cancer cells also rely heavily on glutamine for growth and survival
  • Glutamine is anapleurotic and can be rapidly metabolized to glutamate and then to α-ketoglutarate for entry into the TCA cycle
  • Glucose and glutamine act synergistically for driving rapid tumor cell growth
  • Glutamine metabolism can produce ATP from the TCA cycle under aerobic conditions
  • Amino acid fermentation can generate energy through TCA cycle substrate level phosphorylation under hypoxic conditions
  • Hif-1α stabilization enhances aerobic fermentation
  • targeting glucose and glutamine will deprive the microenvironment of fermentable fuels
  • Although Warburg’s hypothesis on the origin of cancer has created confusion and controversy [37, 38, 39, 40], his hypothesis has never been disproved
  • Warburg referred to the phenomenon of enhanced glycolysis in cancer cells as “aerobic fermentation” to highlight the abnormal production of lactic acid in the presence of oxygen
  • Emerging evidence indicates that macrophages, or their fusion hybridization with neoplastic stem cells, are the origin of metastatic cancer cells
  • Radiation therapy can enhance fusion hybridization that could increase risk for invasive and metastatic tumor cells
  • Kamphorst et al. in showing that pancreatic ductal adenocarcinoma cells could obtain glutamine under nutrient poor conditions through lysosomal digestion of extracellular proteins
  • It will therefore become necessary to also target lysosomal digestion, under reduced glucose and glutamine conditions, to effectively manage those invasive and metastatic cancers that express cannibalism and phagocytosis.
  • Previous studies in yeast and mammalian cells show that disruption of aerobic respiration can cause mutations (loss of heterozygosity, chromosome instability, and epigenetic modifications etc.) in the nuclear genome
  • The somatic mutations and genomic instability seen in tumor cells thus arise from a protracted reliance on fermentation energy metabolism and a disruption of redox balance through excess oxidative stress.
  • According to the mitochondrial metabolic theory of cancer, the large genomic heterogeneity seen in tumor cells arises as a consequence, rather than as a cause, of mitochondrial dysfunction
  • A therapeutic strategy targeting the metabolic abnormality common to most tumor cells should therefore be more effective in managing cancer than would a strategy targeting genetic mutations that vary widely between tumors of the same histological grade and even within the same tumor
  • Tumor cells are more fit than normal cells to survive in the hypoxic niche of the tumor microenvironment
  • Hypoxic adaptation of tumor cells allows for them to avoid apoptosis due to their metabolic reprograming following a gradual loss of respiratory function
  • The high rates of tumor cell glycolysis and glutaminolysis will also make them resistant to apoptosis, ROS, and chemotherapy drugs
  • Despite having high levels of ROS, glutamate-derived from glutamine contributes to glutathione production that can protect tumor cells from ROS
    • Nathan Goodyear
       
      reason to eliminate glutamine in cancer patients and even GSH with cancer patients
  • It is clear that adaptability to environmental stress is greater in normal cells than in tumor cells, as normal cells can transition from the metabolism of glucose to the metabolism of ketone bodies when glucose becomes limiting
  • Mitochondrial respiratory chain defects will prevent tumor cells from using ketone bodies for energy
  • glycolysis-dependent tumor cells are less adaptable to metabolic stress than are the normal cells. This vulnerability can be exploited for targeting tumor cell energy metabolism
  • In contrast to dietary energy reduction, radiation and toxic drugs can damage the microenvironment and transform normal cells into tumor cells while also creating tumor cells that become highly resistant to drugs and radiation
  • Drug-resistant tumor cells arise in large part from the damage to respiration in bystander pre-cancerous cells
  • Because energy generated through substrate level phosphorylation is greater in tumor cells than in normal cells, tumor cells are more dependent than normal cells on the availability of fermentable fuels (glucose and glutamine)
  • Ketone bodies and fats are non-fermentable fuels
  • Although some tumor cells might appear to oxidize ketone bodies by the presence of ketolytic enzymes [181], it is not clear if ketone bodies and fats can provide sufficient energy for cell viability in the absence of glucose and glutamine
  • Apoptosis under energy stress is greater in tumor cells than in normal cells
  • A calorie restricted ketogenic diet or dietary energy reduction creates chronic metabolic stress in the body
  • . This energy stress acts as a press disturbance
  • Drugs that target availability of glucose and glutamine would act as pulse disturbances
  • Hyperbaric oxygen therapy can also be considered another pulse disturbance
  • The KD can more effectively reduce glucose and elevate blood ketone bodies than can CR alone making the KD potentially more therapeutic against tumors than CR
  • Campbell showed that tumor growth in rats is greater under high protein (>20%) than under low protein content (<10%) in the diet
  • Protein amino acids can be metabolized to glucose through the Cori cycle
  • The fats in KDs used clinically also contain more medium chain triglycerides
  • Calorie restriction, fasting, and restricted KDs are anti-angiogenic, anti-inflammatory, and pro-apoptotic and thus can target and eliminate tumor cells through multiple mechanisms
  • Ketogenic diets can also spare muscle protein, enhance immunity, and delay cancer cachexia, which is a major problem in managing metastatic cancer
  • GKI values of 1.0 or below are considered therapeutic
  • The GKI can therefore serve as a biomarker to assess the therapeutic efficacy of various diets in a broad range of cancers.
  • It is important to remember that insulin drives glycolysis through stimulation of the pyruvate dehydrogenase complex
  • The water-soluble ketone bodies (D-β-hydroxybutyrate and acetoacetate) are produced largely in the liver from adipocyte-derived fatty acids and ketogenic dietary fat. Ketone bodies bypass glycolysis and directly enter the mitochondria for metabolism to acetyl-CoA
  • Due to mitochondrial defects, tumor cells cannot exploit the therapeutic benefits of burning ketone bodies as normal cells would
  • Therapeutic ketosis with racemic ketone esters can also make it feasible to safely sustain hypoglycemia for inducing metabolic stress on cancer cells
    • Nathan Goodyear
       
      Ketones are much more than energy adaptabilit, but actually are therapeutic.
  • ketone bodies can inhibit histone deacetylases (HDAC) [229]. HDAC inhibitors play a role in targeting the cancer epigenome
  • Therapeutic ketosis reduces circulating inflammatory markers, and ketones directly inhibit the NLRP3 inflammasome, an important pro-inflammatory pathway linked to carcinogenesis and an important target for cancer treatment response
  • Chronic psychological stress is known to promote tumorigenesis through elevations of blood glucose, glucocorticoids, catecholamines, and insulin-like growth factor (IGF-1)
  • In addition to calorie-restricted ketogenic diets, psychological stress management involving exercise, yoga, music etc. also act as press disturbances that can help reduce fatigue, depression, and anxiety in cancer patients and in animal models
  • Ketone supplementation has also been shown to reduce anxiety behavior in animal models
  • This physiological state also enhances the efficacy of chemotherapy and radiation therapy, while reducing the side effects
  • lower dosages of chemotherapeutic drugs can be used when administered together with calorie restriction or restricted ketogenic diets (KD-R)
  • Besides 2-DG, a range of other glycolysis inhibitors might also produce similar therapeutic effects when combined with the KD-R including 3-bromopyruvate, oxaloacetate, and lonidamine
    • Nathan Goodyear
       
      oxaloacetate is a glycolytic inhibitor, as is doxycycline, and IVC.
  • A synergistic interaction of the KD diet plus radiation was seen
  • It is important to recognize, however, that the radiotherapy used in glioma patients can damage the respiration of normal cells and increase availability of glutamine in the microenvironment, which can increase risk of tumor recurrence especially when used together with the steroid drug dexamethasone
  • Poff and colleagues demonstrated that hyperbaric oxygen therapy (HBOT) enhanced the ability of the KD to reduce tumor growth and metastasis
  • HBOT also increases oxidative stress and membrane lipid peroxidation of GBM cells in vitro
  • The effects of the KD and HBOT can be enhanced with administration of exogenous ketones, which further suppressed tumor growth and metastasis
  • Besides HBOT, intravenous vitamin C and dichloroacetate (DCA) can also be used with the KD to selectively increase oxidative stress in tumor cells
  • Recent evidence also shows that ketone supplementation may enhance or preserve overall physical and mental health
  • Some tumors use glucose as a prime fuel for growth, whereas other tumors use glutamine as a prime fuel [102, 186, 262, 263, 264]. Glutamine-dependent tumors are generally less detectable than glucose-dependent under FDG-PET imaging, but could be detected under glutamine-based PET imaging
  • GBM and use glutamine as a major fuel
  • Many of the current treatments used for cancer management are based on the view that cancer is a genetic disease
  • Emerging evidence indicates that cancer is a mitochondrial metabolic disease that depends on availability of fermentable fuels for tumor cell growth and survival
  • Glucose and glutamine are the most abundant fermentable fuels present in the circulation and in the tumor microenvironment
  • Low-carbohydrate, high fat-ketogenic diets coupled with glycolysis inhibitors will reduce metabolic flux through the glycolytic and pentose phosphate pathways needed for synthesis of ATP, lipids, glutathione, and nucleotides
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    Cancer is a mitochondrial disease? So says the well published Dr Seyfried. Glucose and glutamine drive cancer growth.
pharmacybiz

Dr Nik Kotecha OBE - Distinguished Alumni Award Winner 2022 - 0 views

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    Dr Nik Kotecha OBE, chairman of Morningside Pharmaceuticals and the Randal Charitable Foundation, has won the Distinguished Alumni Award at Imperial College London's Alumni Awards 2022. The annual awards honour outstanding alumni who have demonstrated sustained excellence in their personal and professional achievements and have made a substantial impact on society. Dr Kotecha, who founded Morningside in 1991, which manufactures and supplies generic and branded medicines to the UK and globally, said: "I'm thrilled to be honoured by the university in this way. "As a child growing up in Leicester my family had very little, but I was fortunate to be given opportunities to gain a good education. After finishing my degree in Newcastle; Professor Steve Ley FRS at Imperial College took a chance in accepting me into his eminent group and this really was the opportunity I needed to forge a career.
fitspresso

https://www.thefastleanpro.us/ - 0 views

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    Fast Lean Pro™ (official) | weight lose Formula thefastleanpro.us · by Fast Lean Pro Fast Lean Pro Only $49/Bottle Limited Time Offer! Fast Lean Pro Special Deal + Special 51% Discount Save $300 + 180 Days Money Back Guarantee FastLeanPro The #1 Solution To natural metabolism booster helps you lose weight quickly without starving yourself. Fast Lean Pro is a natural powder supplement for weight loss that has recently been developed by Japanese scientists. Regular Price: $99/per bottle Only for: $49/per bottle What Is Fast Lean Pro? Fast Lean Pro is a powdered dietary powdery supplement designed to aid in weight loss. It contains a unique combination of ingredients that are believed to activate the body's "fasting switch" to optimize results. This product focuses not only on weight loss but also on promoting cellular rejuvenation, fasting, and a healthy metabolism. The concept behind Fast Lean Pro is that incorporating fasting into one's lifestyle can lead to positive outcomes irrespective of individual food choices and eating habits. To comprehend the mechanism of the Fast Lean Pro process, it is necessary to delve into its specific details. One of the few weight loss pills on the market that contains Fibersol is Fast Lean Pro. This safe, specialized fiber adds bulk to its weight when combined with water, curbing your appetite before it throws off your meal plan. If you're trying to lose weight or curb your appetite, Fast Lean Pro can help. Supporting substances such as niacin and chromium contribute to this. The body can further benefit from these nutrients, such as through improved metabolic regulation. Fast lean Pro is non-GMO, vegan friendly, and contains no artificial ingredients or stimulants. Fast Lean Pro is a weight loss product that promotes the body's natural self-feeding process. The body naturally removes old, damaged cells through a process known as autophagy to encourage cell regeneration and repair. Recent studies by a group
indian-health

Top 12 Cardiologists in Bangalore Leaders in the Treatment of Coronary Artery Disease - 0 views

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    Best cardiac surgery hospitals Bangalore recently received the coveted three-star rating from the Society of Thoracic Surgeons (STS) for its patient care and outcomes in isolated coronary artery bypass grafting (CABG) procedures.
Nathan Goodyear

Testosterone decreases after ingestion of sugar (glucose) | Endocrine Society - 0 views

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    sugar intake can decrease Testosterone levels by as much as 25% in men.
Nathan Goodyear

Pleasure Eating Triggers Body's Reward System and May Stimulate Overeating - 0 views

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    Ghrelin plays a role in overeating.  This is not much of a surprise as Ghrelin has been shown to be a major appetite driver and has been linked to higher calorie intake of foods.
Nathan Goodyear

Dentition, Dental Health Habits, and Dementia: The Leisure World Cohort Study - Paganin... - 0 views

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    good oral hygiene associated with a lower risk of dementia.
Nathan Goodyear

Testosterone Therapy in Men with Androgen Deficiency Syndromes: An Endocrine Society Cl... - 0 views

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    androgen deficiency and guidelines for Testosterone therapy.  Nice review of statistics and symptoms.  Many symptoms of low T go unrecognized.
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