Partnering for Cures 2015 brought together innovative ideas and disruptive thinkers to transform the medical research system with insights such as: When trying to motivate people, remember that you…

Source: What disruptive thinkers in medical field think

Pancreatic cancer risk factors

Last Medical Review: 03/14/2016
Last Revised: 04/05/2016

What does Quora know about neuroendocrine cancer? by Connie b. DellobuonoAnswer by Connie b. Dellobuono:Many types of neuroendocrine tumors traditionally have been called “carcinoids” (meaning “can…

Source: What does Quora know about neuroendocrine cancer?

What does Quora know about neuroendocrine cancer? by Connie b. Dellobuono

Answer by Connie b. Dellobuono:

Many types of neuroendocrine tumors traditionally have been called “carcinoids” (meaning “cancer-like”) or “carcinoid tumors,” but these terms do not accurately account for their variable biology, histologic differences, and secretory potential.
Neuroendocrine tumors (NETs): Well-differentiated neoplasms that can be divided into grade 1 (G1) and grade 2 (G2) depending on proliferation and histology
Neuroendocrine carcinomas: Poorly differentiated grade 3 (G3) neuroendocrine neoplasms.
2.7-fold increase in incidence: According to Surveillance, Epidemiology, and End Results (SEER) data, the age-adjusted incidence of NETs rose from 1.9 to 5.25 cases per 100,000 people between 1973 and 2004.4 Diagnosed incidence of NETs is predicted to continue rising at a faster rate than other malignant neoplasms.
SEER data also demonstrate that the prevalence of NETs is similar to that of other types of gastrointestinal cancers. Most NETs occur sporadically. However, some may be associated with genetic syndromes, notably multiple endocrine neoplasia type 1 (MEN-1), as well as MEN-2a and MEN-2b. As with other solid tumors, 5-year survival rates for patients with NETs depend largely on the tumor histology and extent of disease.
About 50% of patients with reported disease stage have either regional or distant metastases at diagnosis.
Metastasis: Liver > Lung > bones
Primary/occurrence sites: lungs (25%), pancreas (20%), small intestines (55%), rectum (5%), others – 3% (adrenals,thyroid,cervix)
O. http://trp.cancer.gov/spores/abstracts/uiowa_neuroendocrine.htm
a. The pre-clinical component of this proposal will identify new theranostic targets on neuroendocrine tumor cells, design and synthesize peptides to hit these new targets, and test the most promising theranostic compounds in vivo. Oxytocin, melanocortin, and glucose-dependent insulinotropic peptide receptors are expressed on neuroendocrine tumors and are prime new targets in neuroendocrine tumors. We will design and synthesize peptides that can bind to each receptor; peptides that demonstrate high affinity and stability in vitro will then be tested as diagnositic PET imaging agents in pre-clinical models of bronchial, small bowel and pancreatic NETs.
b. It builds upon our discovery that RABL6A (a novel oncoprotein) is essential for PNET cell survival and proliferation, Akt/mTOR activity, and control of other clinically relevant PNET pathways, such as Rb1. Aim 2 is to identify genetic and proteomic biomarkers that discriminate NET type and prognosis.
c. The incidence of Neuroendocrine Tumors (NETs) has increased five-fold over the last three decades, and many patients do not develop symptoms until the tumors have metastasized. Further understanding of the molecular biologic basis of NETs holds the promise for improved diagnosis, imaging, and therapy.
d. targeting unique G-protein coupled receptor hetero-dimers such as somatostatin receptor/dopamine receptor conjugates that we have identified in NETs. Preliminary data demonstrate that these new targeting agents have high affinity binding to tumor cells; they are predicted to be highly specific for tumor cells as the hetero-dimeric receptors are rarely expressed in normal tissues.
1. Pancreatic neuroendocrine tumors(pNET) are rare tumors accounting for less than 5% of pancreatic cancer. They are functionally and biologically heterogeneous and have not been studied in great detail until recently. Methods: We conducted a retrospective review of 79 consecutive patients with pNET diagnosed and treated at Thomas Jefferson University Hospital between the years of 2000 and 2010. Results: Of the 79 patients whose records were reviewed, 32 were male and 47 were female. Median age at diagnosis was 61 years. Two cases were associated with MEN1 syndrome. Primary tumor arose in the head, body and tail of the pancreas in 15, 10 and 26 patients, resp. In 6 patients, the tumor was multifocal. The neuroendocrine tumor was accompanied by pancreatic adenocarcinoma in 1 patient and intraductal papillary mucinous neoplasm in 3. In 10 patients, distant metastasis was detected, involving liver only. Tumor was functional in 9 patients: 5 insulinoma, 2 gastrinoma,1 glucagonoma and 1 VIPoma. As per TNM staging, 28, 22 and 10 patients were Stage I, II and III, and IV at diagnosis. Treatment by surgical resection was undertaken in 54 patients. In 21 patients, the tumor was discovered incidentally; 21 patients presented with abdominal pain. Other symptoms were irregular bowel movements, weight loss and jaundice. 51 of the 79 (64.5%) patients were alive at last follow up. On univariate analysis, median survival for females was 137 months vs 114 months for male. Median survival for patients with functional tumors was similar to those with nonfunctioning tumors (118 and 115 months, resp). Median survival for patients with Stage I, II, and III and Stage IV patients were 234,112 and 40 months resp. Median survival for patients who underwent surgical resection was 130 months vs those who did not (30 months). Conclusions: Majority of pNET were located in the body and tail of pancreas; an area requiring thorough scrutiny with special imaging studies for diagnosis. Only a minority of patients presented with liver metastasis(12%) and a smaller number showed hormonal activity (11%). Prognosis improved markedly in patients who underwent surgical resection. Therefore, whenever appropriate, surgical resection should be the treatment of choice in patients with pNET.
http://meetinglibrary.asco.org/content/118018-132
2.
Current therapeutic options for patients with progressive metastatic gastroenteropancreatic neuroendocrine tumour/neoplasm (GEP-NET/NEN) are limited. Treatment with SST analogues is method of choice, due to good symptoms control. [DOTA0, D-Phe1,Tyr3] octreotate[DOTATATE] has a higher affinity for SST2 receptors and thus is able to achieve longer disease control. The aim of this study was to evaluate long term radiological and clinical therapeutic effect of 90Y-DOTATATE in patients with progressive somatostatin receptor–positive small bowel and pancreatic neuroendocrine tumour/neoplasm (GEP-NET/NEN).The primary end point was assessing OS and PFS in long term follow-up. Methods: 67 patients progressing after treatment with SST analogues were inlcuded in the study. The mean treatment activity was 3.8GBq. The mean interval between therapies was 7 weeks (range 6 -9 weeks). Patients were treated up to mean a cumulative activity of 11.2 GBq. Due to pure beta emission (90Y) internal dosimetry was evaluated. Results: Median overall survival (OS) and progression-free survival (PFS) are shown in the Table. In univariate analysis Ki-67 (p=0.048) was the only significant factor influencing OS in pancreatic tumors. That was not confirmed in multivariate analysis. In small bowel tumors we defined three factors influencing survival in univariate analysis. These were: female gender (p=0.023), performance status at the beginning of therapy (p=0.031) and presence of liver metastases (p=0.026). Female gender (HR=0.30, 95% CI 0.11-0.81; p=0.018) was confirmed as positive prognostic factor in multivariate analysis. Factos influencing PFS were also assessed and will be presented as well. Conclusions: 90Y DOTATATE PRRT is effective in long term outcome (OS and PFS) in patient with advances progressive pancreatic and small bowel GEP-NET. This therapy is relatively safe as initial systemic therapy and after previous treatment with chemotherapy or somatostatine analogues as well.
http://meetinglibrary.asco.org/content/117474-132
3. NETs are a heterogeneous group of rare neoplasms. Preclinical studies have shown that IGFR overestimulation can lead to constitutional activation of mTOR pathway. The main objective of this study is to describe the activation status of IGF1R-mTOR pathway by immunohistochemistry in a series of NETs and to assess the association with IGF1R expression. Methods: We studied 69 paraffin tumour blocks: 28 pancreatic NETs (pNETs) (2 gastrinomas, 1 glucagonoma, 4 insulinomas and 21 non-functioning (nf) pNETs), 32 GI NETs (4 stomach, 8 colorectum, 18 ileum and 2 dudodenum) and 9 NETs from other origins (2 anterior mediastinum, 2 ovary, 3 bile duct and 2 kidney). The expression of IGF1R, phosphorylated (p) mTOR and (p)S6 has been determined by immunohistochemistry using anti-IGF1Rβ (sc-713), anti-Phospho-mTOR (S2448) (49F9, Cell Signaling) and anti-Phospho-S6 Ribosomal Protein (S235/336)(91B2, Cell Signaling). Results: Expression of IGF1R has been observed in 46 of 69 (66%) samples with the highest expression in 2/4 (50%) insulinomas, 5/21 nf pNETs (23%) and 3/18 ileum (17%). We have observed activation of the mTOR pathway by immunodetection of (p)mTOR in 14 of 69 samples (20%): 2/21 nf pNETs (9.5%), 1/8 colorectum (12.5%), 8/18 ileum (44%), 1/2 anterior mediastinum, 1/2 ovary, 1/3 biliar tract. We haven’t detected any (p)S6 activation in these samples. Consistent IGF1R-mTOR pathway activation was detected in 11/14 (78%) samples with mTOR positivity that also showed expression of IGF1R. The most relevant finding is that all of the 8 samples from ileum with activation of mTOR showed some degree of expression of IGF1R. Conclusions: 2/3 of NETs show varying levels of expression of IGF1R, but only 16% demonstrate activation of the IGF1R-mTOR pathway. While the positivity of (p)mTOR in pNETs is lower than expected, we have identified a subgroup of ileal NETs with consistent activation of both IGF1R and (p)mTOR which could help stratify patients in clinical trials involving modulation of this pathway. In contrast, none of the 69 samples studied was positive for (p)S6 which suggests this marker is not valid to be used in the clinic. Further validation studies are required to help clinical stratification for therapies against IGF1R mTOR pathways
http://meetinglibrary.asco.org/content/116148-132
4. Peptide receptor radionuclide therapy targets somatostatin receptors expressed on well differentiated neuroendocrine neoplasms. Retrospective monocentric studies indicate that peptide receptor radionuclide therapy is an effective treatment for patients with neuroendocrine neoplasms. Methods: We initiated a multi-institutional, prospective and board reviewed registry study for patients treated with peptide receptor radionuclide therapy. 450 patients were included and followed for a mean of 24.4 months. Patients were treated with Lutetium-177 (54%), Yttrium-90 (17%) or both radionuclides (29%). Primary neuroendocrine neoplasms were derived of pancreas (38%), small bowel 30%), unknown primary (19%), lung (4%) and colorectum (3,5%). Most neuroendocrine neoplasms were well differentiated with a proliferation rate below 20% in 54% and were pretreated by 1 or more therapies in 73%. Results: Overall survival of all patients from the beginning of therapy was 59 months in median. Median survival depended on radionuclides used (Yttrium-90: 38 months; Lutetium-177: not reached; both: 58 months), proliferation rate (G1: median not reached; G2: 58 months; G3: 33 months; unknown: 55 months) and origin of primary tumors (pancreas: 53 months; small bowel: not reached; unknown primary: 47 months; lung: 38 months) but not upon number of previous therapies. Median progression-free survival measured from last cycle of therapy accounted to 41 months for all patients. Progression-free survival of pancreatic neuroendocrine neoplasms was 39 months in median. Similar results were obtained for neuroendocrine neoplasms of unknown primary with a median of 38 months whereas neuroendocrine neoplasm of small bowel were progression-free for a median of 51 months. Side effects like G3-G4 nephrotoxicity or hematological function were observed in 0.2% and 2% of patients. Conclusions: Peptide receptor radionuclide therapy is effective for patients with G1-G2 neuroendocrine tumors irrespective of previous therapies with a survival advantage of several years compared to other therapies and only minor side effects.
http://meetinglibrary.asco.org/content/112410-132

What does Quora know about neuroendocrine cancer?

What is the current status of research of neuro-endocrine tumors? by Connie b. DellobuonoAnswer by Connie b. Dellobuono:1. Breaktroughs [drugs, imaging, chemo/radiation] from Neuroendocrine Tumor R…

Source: What is the current status of research of neuro-endocrine tumors?

What is the current status of research of neuro-endocrine tumors? by Connie b. Dellobuono

Answer by Connie b. Dellobuono:

1. Breaktroughs [drugs, imaging, chemo/radiation] from Neuroendocrine Tumor Research Foundation
https://netrf.org/category/breakthroughs-from-the-field/
2. Neuroendocrine tumors in pets.
Neuroendocrine tumors are small masses that usually develop in the gastrointestinal tract, liver, or gall bladder. They are slow-growing, but typically metastasize
Symptoms of a neuroendocrine tumor depend on the location and size of the tumor, and may include loss of appetite, vomiting, constipation, and weight loss
There is no cure for this type of cancer unless the tumor can be completely removed with surgery. Alternative therapies often offer the best option for maintaining a pet’s quality of life
Medicinal mushrooms: In a published study conducted at the University of Pennsylvania’s School of Veterinary Medicine, dogs with hemangiosarcoma – an aggressive, malignant cancer that develops in the cells of blood vessels – were given a compound derived from a type of mushroom, Coriolus versicolor.
According to researchers, the patients given this compound had the longest survival times ever reported for dogs with this form of cancer. This is promising news, as this mushroom compound could offer an alternative to chemotherapy or a complementary treatment to traditional cancer therapies for dogs and people.
Chinese herbal medicine and acupuncture: Dr. Betsy Hershey is a board-certified veterinary oncologist and owner of Integrative Veterinary Oncology in Phoenix, Arizona. Dr. Hershey is also certified in veterinary acupuncture and has received extensive training in traditional Chinese veterinary medicine.
Dr. Hershey routinely incorporates Chinese herbal medicine and acupuncture, along with good nutrition, in her protocols for cancer patients. She is seeing dogs live longer with cancer when they receive complementary therapies in addition to chemotherapy. She is seeing years of remission time in these dogs, where chemotherapy alone only offers, on average, a year of remission and survival time.
Ozone therapy: Ozone therapy as a treatment for cancer is based on a very simple concept: Healthy cells thrive on oxygen. By contrast, the microbes that cause diseases like cancer are typically anaerobic, meaning they thrive in the absence of air or free oxygen. Total immersion of anaerobic life forms, like those that cause cancer, in an energetic form of pure oxygen (ozone) for a sufficient period of time has the ability to extinguish these disease-causing microbes.
There are many methods of administering ozone, however, it is primarily used in an IV fluid solution. It can also be used topically.
3. Clinical trials at Stanford: [imaging for early detection]
http://med.stanford.edu/clinicaltrials/trials/search?keyword=Neuroendocrine+Tumors&cId=29
4. Treatment of pancreatic neuroendocrine tumors may include a combination of surgery, hormone therapy, radiation therapy, and chemotherapy.
Surgery
Surgical removal of the tumor is considered the most effective treatment for islet cell tumors. Tumors that have not spread beyond the pancreas (localized tumors) may be removed along with a small portion of healthy tissue surrounding the tumor. This procedure is much less extensive than the type of surgery used to treat adenocarcinoma of the pancreas.
Hormone Therapy
Patients with functional pancreatic neuroendocrine tumors that cannot be surgically removed may benefit from monthly injections of octreotide, a synthetic hormone that controls hormone-related symptoms and may have the potential to slow tumor growth.
Radiation Therapy and Chemotherapy
Chemotherapy is usually reserved for patients whose pancreatic neuroendocrine tumors begin to grow during treatment with octreotide, or if a patient has symptoms from the tumor that are not well controlled by octreotide. In addition, chemotherapy may be used to treat tumors that contain fast-growing (undifferentiated) cells.
External-beam radiation therapy, which delivers radiation from a machine outside of the body, is typically only used to treat patients with pancreatic neuroendocrine tumors that are causing symptoms such as pain, particularly when they have metastasized to the bone.
MIBG Radiolabeled Therapy
Some pancreatic neuroendocrine tumors absorb a hormone called norepinephrine. These tumors may respond to a nuclear medicine technique called MIBG radiolabeled therapy. In this treatment, the patient is given an intravenous dose of MIBG, a protein that is similar to norepinephrine and is attached to a radioactive substance. The MIBG is absorbed by the tumor, permitting the radioactive substance to selectively destroy tumor cells.
Investigational Approaches
Researchers at Memorial Sloan Kettering are exploring new treatment approaches using a mouse model that exhibits pancreatic neuroendocrine tumors. This model will be used to conduct early-stage testing of new drug therapies and targeted antibody-based treatments. The pancreatic neuroendocrine tumor model also will be used to test a new class of drugs that may have the potential to block the production of a protein called cathepsin proteases, which are thought to promote the growth of pancreatic neuroendocrine tumors.

What is the current status of research of neuro-endocrine tumors?

Partnering for Cures 2015 brought together innovative ideas and disruptive thinkers to transform the medical research system with insights such as: When trying to motivate people, remember that you…

Source: What disruptive thinkers in medical field think

Partnering for Cures 2015 brought together innovative ideas and disruptive thinkers to transform the medical research system with insights such as:

1. When trying to motivate people, remember that you can’t always herd cats, but you can move their food.
2. There is no substitute for patient input – it’s very different to hear from patients directly than it is to hear from translators trying to speak on their behalf.
3. Medicine should be at least as good as Netflix at analyzing data for the benefit of consumers.
4. Translate emotion into data to create powerful evidence.
5. The value of “optimal distance” in solving difficult problems cannot be ignored. The smartest people probably don’t work for you and may come from another field entirely.
6. Patients are already demanding their data – that ship has sailed. But they don’t just want the data, they want to be able to do something with the data.
7. It’s hard for people to talk about failure, but critical to advancing learning.
8. You never change things by fighting the existing reality. To change things, build a new model that makes the old one obsolete.
9. We charge forward until we hit a wall. Then we break the wall. And if we can’t, we scale the wall. Or build a door. Whatever it takes.
10. Success is never final.

If you want to study at night feeling alert, can you take an evening power nap/sleep-like r… by Connie b. Dellobuono

Answer by Connie b. Dellobuono:

Sleep early at 8pm (eyes covered, dim BR and cool temp). Set alarm 3hrs later and study for next 4hrs. Eat cracker with avocado, chewing slowly while studying. Chew some walnuts.
Here are substitutes for coffee [from wiki]:
Grain coffee and other substitutes can be made by roasting or decocting various organic substances. Some ingredients used include: almond, acorn, asparagus, malted barley, beechnut, beetroot, carrot, chicory root, corn, soybeans, cottonseed, dandelion root (see dandelion coffee), fig, roasted garbanzo beans, boiled-down molasses, okra seed, pea, persimmon seed, potato peel,[5] rye, sassafras pits, sweet potato, wheat bran.
The Native American tribes of what is now the Southeastern United States brewed a ceremonial drink containing caffeine, "asi", or the "black drink", from the roasted leaves and stems of Ilex vomitoria (Yaupon holly). European colonists adopted this beverage as a coffee-substitute, which they called "cassina".
Ground roasted chicory root has been sold commercially on a large scale since around 1970, and it has become a mainstream product, both alone and mixed with real coffee. It was widely used during the American Civil War on both sides, and has long enjoyed popularity especially in New Orleans, where Luzianne has long been a popular brand in this respect. Chicory mixed with coffee is also popular in South India, and is known as Indian filter coffee.
Postum is an instant type of coffee substitute made from roasted wheat bran, wheat and molasses. It reached its height of popularity in the United States during World War II when coffee was sharply rationed.
Examples
Barleycup is a similar product sold in the UK.
Camp Coffee is a mix of chicory and coffee from the UK, sold since 1876.
Nestlé Caro is made of roasted barley, malted barley, chicory, and rye and is used as a coffee substitute.
There are many dandelion (or chicory) based powdered coffee substitutes known as dandelion coffee.
Inka is a Polish drink made of rye, barley, chicory, and sugar beet, produced since 1971.
Ayurvedic Roast is a coffee substitute which borrows from both the American tradition of using roasted barley, rye, and chicory, and the Indian Ayurvedic system of health by adding the traditional herbs of ashwagandha, shatavari, and brahmi.
Ersatz is made of roasted rice, roasted peas, and roasted chicory.
Muckefuck, a generic term in Germany for coffee substitutes, possibly from the French "mocca faux".[9]
New Life Coffee produces a caffeine-free coffee substitute from roasted soybeans.[
Ricoré is a mix of chicory and coffee from France created in 1953, now produced by Nestlé.
Teeccino Caffé produces blends of coffee substitute from a variety of ingredients such as carob, chicory, and dandelion roots.[11]
Postum, once popular among Mormons, is made from roasted wheat bran, wheat and molasses.
Choffy is a recent substitute made from cacao and brewed like coffee.
Roasted chickpeas were noted as a coffee substitute as early as the 18th century Modern brands include Bueno Coffee Substitute in the continental United States and Machotes in Puerto Rico.

If you want to study at night feeling alert, can you take an evening power nap/sleep-like resting time earlier? How would you do it?

Does diet have an impact on brain injury recovery? by Connie b. Dellobuono

Answer by Connie b. Dellobuono:

Nutrition (high fat/ketogenic diet for brain) turns ON and OFF our genes. Nurture also helps our brain cell grow. We make more neurons with learning new movements/exercise. During sleep, our brain get rid of toxins.
Most of the brain's energy consumption goes into sustaining the electric charge (membrane potential) of neurons. Most vertebrate species devote between 2% and 8% of basal metabolism to the brain. In primates, however, the percentage is much higher—in humans it rises to 20–25%. The energy consumption of the brain does not vary greatly over time, but active regions of the cerebral cortex consume somewhat more energy than inactive regions; this forms the basis for the functional brain imaging methods. The brain typically gets most of its energy from oxygen-dependent metabolism of glucose (i.e., blood sugar), but ketones provide a major alternative source, together with contributions from medium chain fatty acids (caprylic and heptanoicacids), lactate, acetate,and possibly amino acids.
In humans and many other mammals, new neurons are created mainly before birth, and the infant brain contains substantially more neurons than the adult brain.[60] There are, however, a few areas where new neurons continue to be generated throughout life. The two areas for which adult neurogenesis is well established are the olfactory bulb, which is involved in the sense of smell, and the dentate gyrus of the hippocampus, where there is evidence that the new neurons play a role in storing newly acquired memories. With these exceptions, however, the set of neurons that is present in early childhood is the set that is present for life. Glial cells are different: as with most types of cells in the body, they are generated throughout the lifespan.
There has long been debate about whether the qualities of mind, personality, and intelligence can be attributed to heredity or to upbringing—this is the nature and nurture controversyAlthough many details remain to be settled, neuroscience research has clearly shown that both factors are important. Genes determine the general form of the brain, and genes determine how the brain reacts to experience. Experience, however, is required to refine the matrix of synaptic connections, which in its developed form contains far more information than the genome does. In some respects, all that matters is the presence or absence of experience during critical periods of development. In other respects, the quantity and quality of experience are important; for example, there is substantial evidence that animals raised in enriched environments have thicker cerebral cortices, indicating a higher density of synaptic connections, than animals whose levels of stimulation are restricted.

Does diet have an impact on brain injury recovery?

What could be the cause of this yeast infection? by Connie b. Dellobuono

Answer by Connie b. Dellobuono:

Have you been eating sugary foods? Avoid cheese, sugary food and eat alkaline foods (aloe vera, coconut, fish and veggies). Eat more fermented and raw veggies (probiotic caps, prebiotic such as garlic, carrots,parsley, kiwi,papaya,pineapple) and wash (mouth, skin tissues) with diluted vinegar. For the mouth, you can prepare a mouth wash of eucalyptus oil and water.
From wiki:
Candida yeasts are generally present in healthy humans, frequently part of the human body's normal oral and intestinal flora, and particularly on the skin;however, their growth is normally limited by the human immune system and by competition of other microorganisms, such as bacteria occupying the same locations in the human body.[34] Candida requires moisture for growth, notably on the skin.[35] For example, wearing wet swimwear for long periods of time is believed to be a risk factor.[36] In extreme cases, superficial infections of the skin or mucous membranes may enter into the bloodstream and cause systemic Candida infections.
Factors that increase the risk of candidiasis include HIV/AIDS, mononucleosis, cancer treatments, steroids, stress, antibiotic usage, diabetes, and nutrient deficiency. Hormone replacement therapy and infertility treatments may also be predisposing factors.[37] Treatment with antibiotics can lead to eliminating the yeast's natural competitors for resources in the oral and intestinal flora; thereby increasing the severity of the condition.[38] A weakened or undeveloped immune system or metabolic illnesses are significant predisposing factors of candidiasis.[39] Almost 15% of people with weakened immune systems develop a systemic illness caused by Candida species.[40] Diets high in simple carbohydrates have been found to affect rates of oral candidiases.[41]
C. albicans was isolated from the vaginas of 19% of apparently healthy women, i.e., those who experienced few or no symptoms of infection. External use of detergents or douches or internal disturbances (hormonal or physiological) can perturb the normal vaginal flora, consisting of lactic acid bacteria, such as lactobacilli, and result in an overgrowth of Candida cells, causing symptoms of infection, such as local inflammation.[42] Pregnancy and the use of oral contraceptives have been reported as risk factors.[43] Diabetes mellitus and the use of antibiotics are also linked to increased rates of yeast infections.[43]
In penile candidiasis, the causes include sexual intercourse with an infected individual, low immunity, antibiotics, and diabetes. Male genital yeast infections are less common, and incidences of infection are only a fraction of those in women; however, yeast infection on the penis from direct contact via sexual intercourse with an infected partner is not uncommon.

What could be the cause of this yeast infection?

Do stimulants (amphetamines, cocaine) cause downregulation of glutamate signalling (in addi… by Connie b. Dellobuono

Answer by Connie b. Dellobuono:

Glutamate (Glutamic acid) is the most prominent neurotransmitter in the body, and it is the main excitatory neurotransmitter,[1] being present in over 50% of nervous tissue.[2] Glutamate was initially discovered to be a neurotransmitter in insect studies in the early 1960s.
Glutamate is also used by the brain to synthesize GABA (γ-Aminobutyric acid), the main inhibitory neurotransmitter of the mammalian central nervous system, which plays a role in regulating neuronal excitability throughout the nervous system and is also directly responsible for the regulation of muscle tone in humans. Glutamate receptors are also expressed in pancreatic islet cells. Small unmyelinated sensory nerve terminals in the skin also express NMDA and non-NMDA (glutamate) receptors.
Source: Wiki
——-
Glutamate down-regulation can be lead to Alzheimer's disease (a type 3 diabetes).
Alcohol and narcotics () shrink the brain. Poor nutrition, drugs/narcotics, alcohol, advancing age, infection and other neurotoxins downregulate glutamate receptors.
Glutamate receptors are thought to be responsible for the reception and transduction of umami taste stimuli. As we age, we have decreasing number of taste buds, decreasing muscle tones, skin tissues are more sensitive to pain and decreasing number of glutamate receptors.
Connie's comments
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From wiki:
Autoimmunity and antibody interactions with glutamate receptors and their subunit genes.
Various neurological disorders are accompanied by antibody or autoantigen activity associated with glutamate receptors or their subunit genes (e.g. GluR3 in Rasmussen's encephalitis,[31] and GluR2 in nonfamilial olivopontocerebellar degeneration.[In 1994 GluR3 was shown to act as an autoantigen in Rasmussen's encephalitis, leading to speculation that autoimmune activity might underlie the condition.[33] Such findings "suggest" links between glutamate receptors and autoimmune interactions are possible and may be significant in some degenerative diseases,[32] however the exact role of such antibodies in disease manifestation is still not entirely known.[
Excitotoxicity
Overstimulation of glutamate receptors causes neurodegeneration and neuronal damage through a process called excitotoxicity. Excessive glutamate, or excitotoxins acting on the same glutamate receptors, overactivate glutamate receptors (specifically NMDARs), causing high levels of calcium ions (Ca2+) to influx into the postsynaptic cell.[35]
High Ca2+ concentrations activate a cascade of cell degradation processes involving proteases, lipases, nitric oxide synthase, and a number of enzymes that damage cell structures often to the point of cell death.[36] Ingestion of or exposure to excitotoxins that act on glutamate receptors can induce excitotoxicity and cause toxic effects on the central nervous system.[37] This becomes a problem for cells, as it feeds into a cycle of positive feedback cell death.
Glutamate excitotoxicity triggered by overstimulation of glutamate receptors also contributes to intracellular oxidative stress. Proximal glial cells use a cystine/glutamate antiporter (xCT) to transport cystine into the cell and glutamate out. Excessive extracellular glutamate concentrations reverse xCT, so glial cells no longer have enough cystine to synthesize glutathione (GSH), an antioxidant.[38] Lack of GSH leads to more reactive oxygen species (ROSs) that damage and kill the glial cell, which then cannot reuptake and process extracellular glutamate.[39] This is another positive feedback in glutamate excitotoxicity. In addition, increased Ca2+ concentrations activate nitric oxide synthase (NOS) and the over-synthesis of nitric oxide (NO). High NO concentration damages mitochondria, leading to more energy depletion, and adds oxidative stress to the neuron as NO is a ROS.[40]
Neurodegeneration
In the case of traumatic brain injury or cerebral ischemia (e.g., cerebral infarction or hemorrhage), acute neurodegeneration caused by excitotoxicity may spread to proximal neurons through two processes. Hypoxia and hypoglycemia trigger bioenergetic failure; mitochondria stop producing ATP energy. Na+/K+-ATPase can no longer maintain sodium/potassium ion concentration gradients across the plasma membrane. Glutamate transporters (EAATs), which use the Na+/K+ gradient, reverse glutamate transport (efflux) in affected neurons and astrocytes, and depolarization increases downstream synaptic release of glutamate.[41] In addition, cell death via lysis or apoptosis releases cytoplasmic glutamate outside of the ruptured cell.[42] These two forms of glutamate release cause a continual domino effect of excitotoxic cell death and further increased extracellular glutamate concentrations.
Glutamate receptors' significance in excitotoxicity also links it to many neurogenerative diseases. Conditions such as exposure to excitotoxins, old age, congenital predisposition, and brain trauma can trigger glutamate receptor activation and ensuing excitotoxic neurodegeneration. This damage to the central nervous system propagates symptoms associated with a number of diseases.

Do stimulants (amphetamines, cocaine) cause downregulation of glutamate signalling (in addition to dopamine)?