0.4–2% annual decline
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shared by Nathan Goodyear on 03 Sep 14
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Hypothalamic-Pituitary-Testicular Axis Disruptions in Older Men Are Differentially Link... - 0 views
press.endocrine.org/...jc.2007-1972
low T low Testosterone low T Testosterone aging LH hormone hormones men male SHBG
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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.
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Obesity was associated with progressively lower total and free T independent of the simultaneous decrease in SHBG.
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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.
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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.
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the effects of aging on testicular function can be moderated by increased LH compensation for many decades
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obesity impairs hypothalamic/pituitary function independent of age, arguably an adaptive response for which there should be no compensatory mechanism.
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Obesity is associated with insulin resistance (28), and the increased circulating insulin inhibits hepatic SHBG synthesis
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the SHBG increase with age may be related to relative IGF-I deficiency (27), although this has not been directly proven.
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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.
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The relationship between obesity and T can be bidirectional: low T may be the cause rather than consequence of obesity
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chronic alcohol abuse is known to suppress LH (40), our data showed no significant association among the three hormones or SHBG and alcohol intake.
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increase in total T in smokers occurs through a primary increase in SHBG with a compensatory rise in LH
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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
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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.
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shared by Nathan Goodyear on 09 Mar 15
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Effect of Magnolia officinalis and Phellodendron amurense (Relora®) on cortis... - 0 views
www.ncbi.nlm.nih.gov/...PMC3750820
Relora stress cortisol magnolia officinalis alternative medicine herbs herbal therapies
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Anemia in cancer - 0 views
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mild (10 g/dl—normal), moderate (8–10 g/dl), severe (6.5–8 g/dl) and life threatening (<6.5 g/dl or unstable patient) anemia
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Cancer itself can directly cause or exacerbate anemia either by suppressing hematopoiesis through bone marrow infiltration or production of cytokines that lead to iron sequestration, or by reduced red blood cell production
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in inflammatory anemia, iron deficiency should be defined by a low transferrin saturation of <20%, ferritin levels of <100 ng/ml and a low reticulocyte hemoglobin concentration of <32 pg
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Other cytokines, such as interleukin-6 (IL-6), IL-1 and interferon-γ, have also been shown to inhibit erythroid precursors in vitro [9], albeit to a lesser extent
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In inflammation, from whatever cause, IL-6 induces the liver to produce hepcidin. Hepcidin decreases iron absorption from the bowel and blocks iron utilization in the bone marrow
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nephrotoxic effects of particular cytotoxic agents such as platinum salts can also lead to the persistence of anemia through reduced Epo production by the kidney
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Currently two options are at the disposal of the clinician for the treatment of anemia in cancer patients: transfusion of packed red blood cells and the use of erythropoiesis-stimulating agents (ESAs)
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Transfusion of 1 unit of packed red blood cells has been estimated to result in an increase in the hemoglobin level of 1 g/dl in a normal-sized adult
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Recent concerns regarding the risk of thromboembolism in patients treated with ESA have been corroborated by the meta-analyses conducted by Tonnelli and Bennett
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Great review of anemia in Cancer: 1) blood loss 2) increased RBC loss 3) decreased RBC production Cancer infiltration of marrow can reduce hematopoiesis. Inflammatory cytokines can reduce hematopoiesis. Inflammatory cytokines can block Fe absorption. Chemo and radiation can cause anemia--particularily platinum based therapies.
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A Randomized Pilot Trial of a Moderate Carbohydrate Diet Compared to a Very Low Carbohy... - 0 views
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shared by wheelchairindia9 on 19 Mar 16
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Functional Knee Support - 0 views
www.wheelchairindia.com/...Tynor-Functional-Knee-Support
Functional Braces Best for: Sports injuries after surgery functional knee braces knee rehabilitation program knee injuries or knee surgery free movement of the knee joint decrease knee pain improve knee stability
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Tynor Functional Knee Support Functional knee Support is an anterior opening device, which offers the advantage of controlled compression around the knee and a rigid lateral support and immobilization. It allows normal flexion and free movement of the knee joint. Anterio Open able Easy application Controlled compression. Perfect lateral splinting. Anatomical design. Tynor Functional Knee Support Features Bi axial heavy duty aluminum hinge Mimics the natural knee joint Ensures full weight bearing. Allows free flexion movement Four way stretchable fabric Controlled and comfortable compression No buckling No vaso constriction Enhanced comfort Open patella design Release patellar pressure Hold the patella in position Can be used for Patellofemoral diseases Wrap design with anterior closing Easy application and removal on swollen or asymmetric knees Easy application and removal for weak or geriatric patients. Allows customized compression Offers flexibility in sizing Ergonomic design Anti tourniquet effect - ensures no constriction to blood flow Better grip of the product to the body. Anatomic construction- Better functionality and Snug fit.
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How We Read Oncologic FDG PET/CT | Cancer Imaging | Full Text - 0 views
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In early PET literature focusing on analysis of solitary pulmonary nodules, some researchers defined malignancy based on a SUVmax threshold of greater than 2.5
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Far more important than the SUVmax is the pattern rather than intensity of metabolic abnormality and the correlative CT findings
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Descriptively, we define SUV < 5 as “low intensity”, 5–10 as “moderate”, 10–15 as “intense” and >15 as “very intense”
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Evolving literature suggests that intensity of uptake is an independent prognostic factor and in some tumour subtypes superior to histopathologic characterisation.
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Our practice of thresholding the grey and colour scale to liver as detailed above results in similar image intensity to a fixed upper SUV threshold of 8 to 10
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The advantage of using the liver as a reference tissue is also aided by this organ having rather low variability in metabolic activity
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When the liver is abnormal and cannot be used as a reference organ, we use the default SUV setting of an upper SUV threshold of 8
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One of the most challenging aspects of oncologic FDG PET/CT review, however, is to recognise all the patterns of metabolic activity that are not malignant and which consequently confound interpretation
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Future articles in the “How I Read” series will address the specific details of reading PET/CT in various cancers
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For example, discordant low-grade activity in an enlarged lymph node in the setting of intense uptake in the primary tumour suggests it is unlikely malignant and more likely inflammatory or reactive
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By CT criteria the enlarged node is ‘pathologic’ but the discordantly low metabolic signature further characterises this is as non-malignant since such a node is not subject to partial volume effects and therefore the intensity of uptake should be similar to the primary site
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The exception is when the lymph node is centrally necrotic as a small rim of viable tumour is subject to partial volume effects with expectant lower intensity of uptake; integrating the CT morphology is therefore critical to reaching an accurate interpretation
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Small nodes that are visualised on PET are conversely much more likely to be metastatic as such nodes are subject to partial volume effects.
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The combination of FDG and a more specific tracer, which visualises the well-differentiated disease can be very useful to characterise this phenomenon
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For the majority of malignant processes, the intensity of metabolic abnormality correlates with degree of aggressiveness or proliferative rate.
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a negative PET/CT study in a patient with biopsy proven malignancy would be considered false-negative
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There, however, are a significant minority of tumours that utilise substrates other glucose such as glutamine or fatty acids as a source of the carbon atoms required for growth and proliferation
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This includes a subset of diffuse gastric adenocarcinomas, signet cell colonic adenocarcinomas and some sarcomas, particularly liposarcoma
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There may be a role for other radiotracers such as fluorothymidine (FLT) or amino acid substrates in this setting.
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Some tumours harbour mutations that result in defective aerobic mitochondrial energy metabolism, effectively simulating the Warburg effect
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Uterine fibroids, hepatic adenomas, fibroadenomas of the breast and desmoid tumours are benign or relatively benign lesions that can have quite high FDG-avidity.
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Common examples where patients have commenced active therapy but the referrer is requesting “staging” includes hormonal therapy (eg. tamoxifen) in breast cancer, oral capecitabine in colorectal cancer or high dose steroids in Hodgkin’s lymphoma
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Without intravenous contrast, additional identification of typical oncologic complications such as pulmonary embolism or venous thrombosis cannot be identified
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If the study is performed as an “interim” restaging study after commencement of therapy but before completion, in order to reach a valid or clinically useful conclusion findings must be interpreted in the context of known changes that occur at a specific timing and type of therapy
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The most well studied use of interim PET is in Hodgkin’s lymphoma where repeat PET after two cycles of ABVD-chemotherapy provides powerful prognostic information and may improve outcomes by enabling early change of management
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Nutrients | Free Full-Text | Vitamin C Status Correlates with Markers of Metabolic and ... - 0 views
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The CHALICE (Canterbury Health, Ageing and Lifecourse) study is a unique New Zealand study comprising a comprehensive database of determinants of health
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The CHALICE cohort of 404 individuals aged 50 years had an average vitamin C intake of ~110 mg/day, which should provide adequate plasma concentrations [14]. Despite this, a significant proportion of the participants had inadequate plasma vitamin C status
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plasma vitamin C was negatively associated with blood triglycerides, HbA1c and insulin, and positively associated with HDL levels.
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No correlation was found between plasma vitamin C and the two indicators of heart health; blood pressure and cardiovascular risk score.
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A high proportion (63%) of our participants had inadequate plasma vitamin C concentrations (i.e., <50 µmol/L)
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The association of low vitamin C with obesity in this study replicates results in the literature [35,40,41,42,43,44], and it is apparent that individuals with higher weight require higher intakes of vitamin C to reach adequate vitamin C status
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higher plasma vitamin C status is associated with lower circulating levels of blood triglycerides, insulin and HbA1c
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A role for vitamin C in the prevention or management of diabetes and/or metabolic syndrome has been suggested
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In this study, we also demonstrate lower levels of mild cognitive impairment in those with high vitamin C status
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The odds of mild cognitive impairment were twice as high for those below 23 μmol/L plasma vitamin C concentration.
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animal models have shown that the brain is the last organ to be depleted of the vitamin during prolonged deficiency
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A recent animal study has shown that moderate vitamin C deficiency may play a role in accelerating amyloid plaque accumulation in Alzheimer’s disease
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New study: vitamin C levels correlate with cognitive and metabolic health. What is your vitamin C level? Despite the adequate levels of vitamin C intake, a large % of the individuals had inadequate vitamin C levels which points to a demand issue. Higher oxidative stress, chronic inflammation... would drive demand for vitamin C higher. Lower vitamin C levels were associated with more metabolic disease, ie. DM, and more cognitive decline.
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Hyperthermia as an immunotherapy strategy for cancer - 1 views
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After antigen uptake at tumor sites, APCs have the ability to create a robust response by entering lymphoid compartments and programming lymphocytes
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Hyperthermia differs fundamentally from fever in that it elevates the core body temperature without changing the physiological set point
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mor cells [2]. Although significant cell killing could be achieved by heating cells or tissues to temperatures > 42°C for 1 or more hours, the application, measurement and consistency of this temperature range within the setting of cancer clinical trials
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mild temperature hyperthermia (ie, within the fever-range, 39–41°C)
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moderate hyperthermia (41°C)
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Hsps ensure appropriate post-translational protein folding, and are able to refold denatured proteins, or mark irreversibly damaged proteins for destruction
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the ability of fever-range hyperthermia to induce reactive immunity against tumor antigens through DCs and NK-cells is likely mediated by Hsps
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Hsps support the malignant phenotype of cancer cells by not only affecting the cells’ survival, but also participating in angiogenesis, invasion, metastasis and immortalization mechanisms
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Hsps released from stressed or dying cells activate dendritic cells (DCs), transforming them into mature APCs
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In theory, fever-range hyperthermia may take advantage of tumor cell Hsps by inducing their release from tumor cells and augmenting DC priming against tumor antigens
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In several models of hyperthermia, heat-treated tumors exhibited improved DC priming and generation of systemic immunity to tumor cell
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hyperthermia alone can enhance antigen display by tumor cells, thus rendering them even more susceptible to programmed immune clearance
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Hsps may exert an adjuvant effect by bolstering MHC class II and co-stimulatory molecule expression by DCs
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thermal ablation of liver tumors in particular has demonstrated an ability to potentiate immune responses [57, 58] and elicit robust T-cell infiltrates at ablation sites
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specific Hsp, Hsp70, directly inhibits apoptosis pathways in cancer cells, as demonstrated in human pancreatic, prostate and gastric cancer cells
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Cross-priming is the ability of extracellular Hsps complexed to tumor peptides to be internalized and presented in the context of MHC class I molecules on APCs, thus allowing potent priming of CTLs against tumor antigens
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It has been reported that Hsps are generated from necrotic tumor cell lysates, but not from tumor cells undergoing apoptosis
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tumor cells exposed to hyperthermia in the heat shock range (42°C for 4h) prior to lysing, DC activation and cross-priming were significantly enhanced with the application of heat
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Due to the ability of Hsps to activate DCs directly by chaperoning tumor antigens upon their release [28], it is possible that both local and regional immune stimulation can be achieved with hyperthermia.
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support the use of hyperthermia as an inducer of Hsps to serve as ‘danger signals’, activating antitumor immune responses
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whole-body hyperthermia not only augments immune responses, but also stimulates the migration of skin-derived DCs to draining lymph nodes
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In mice treated with fever-range whole-body hyperthermia, tumor growth was significantly inhibited and NK-cell infiltration increased
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exposure to fever-range hyperthermia resulted in improved endogenous NK-cell cytotoxicity to several cancer types
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The combined effects of hyperthermia on lymphoid tissue endothelium and lymphocytes can promote immune surveillance and increase the probability of naive lymphocytes leaving the circulation and encountering their cognate antigen displayed by DCs in lymphoid organs.
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In independent clinical studies, whole-body hyperthermia resulted in a transient decrease in circulating lymphocytes in patients with advanced cancer [12, 94, 99, 100], a finding which mirrored observations in animal models in which lymphocyte entry into lymph noeds was increased following hyperthermia treatment [93]. Enhanced recruitment of lymphocytes to lymphoid tissues may be exploited in the treatment of malignancies.
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The initial tumor antigen presentation and initiation of clonal expansion of CTLs transpires in the lymph nodes and cannot take place outside this specialized compartment
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the ability of DCs present in the lymph nodes to stimulate an anti-tumor immune response is critical
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shared by Nathan Goodyear on 26 Sep 17
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Alzheimer's Disease Clinical and Research Update for Health Care Practitioners - 0 views
www.ncbi.nlm.nih.gov/...PMC3776389
Alzheimer's disease cognition memory Alzheimers brain brain health alpha-GPC phosphatidyl serine Huperzine A choline
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Alpha GPC, phosphatidylserine, Huperzine A, and choline show promise as nutraceutical agents for enhancing cognitive performance and slowing cognitive decline
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Alpha GPC, also known as L-Alpha Glycerylphosphorylcholine, a naturally occurring form of choline, acts as a parasympathomimetic acetylcholine precursor and has shown promise in improving cognitive symptoms related to AD, vascular dementia, and multi-infarct dementia
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Phosphatidylserine is a widely abundant anionic phospholipid in the human body and has been shown to improve age-related cognitive changes
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Huperzine A (a natural cholinesterase inhibitor) has been linked to improved memory performance in elderly people with benign forgetfulness, as well as patients with AD and vascular dementia
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Cholinesterase inhibitors have been shown to have neuroprotective properties in patients with mild [37] as well as moderate-to-advanced AD
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