Propuesta de rise completa
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This study aims to demonstrate how glucose levels affect beta cell regeneration in type 1 diabetic rats. Rats will be divided into three groups: non-diabetic controls, and two diabetic groups with induced high or moderate glucose levels. Glucose levels and glycated hemoglobin will be measured over six months. The researchers hypothesize that the group with moderate glucose levels will regenerate 50% of beta cells due to better glucose metabolism and control.
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This document discusses various animal models used to study diabetes. It begins by explaining what diabetes is and the role of insulin. It then outlines several models of insulin-dependent diabetes (IDDM) including those induced chemically through alloxan and streptozocin, viruses, surgery, genetics, and combinations thereof. Non-insulin dependent diabetes (NIDDM) models include those induced chemically through neonatal streptozocin treatment and genetically through transgenic techniques. Specific details are provided on commonly used species and procedures for many of these diabetes induction methods.
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Animal modelsof diabetes and obesity
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by: Suinil Kumar
M.pharm (pharmacology )
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Panjab university
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Anti diabetes
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- In the 16th century, diabetes was identified as a severe disorder affecting the whole body. The pancreas's role in diabetes was discovered in the 1870s but its function remained unknown.
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Lactose intolerance is the inability or insufficient ability to digest lactose, a sugar found in milk and milk products. Lactose intolerance is caused by a deficiency of the enzyme lactase, which is produced by the cells lining the small intestine. Lactase breaks down lactose into two simpler forms of sugar called glucose and galactose, which are then absorbed into the bloodstream.
Not all people with lactase deficiency have digestive symptoms, but those who do may have lactose intolerance. Most people with lactose intolerance can tolerate some amount of lactose in their diet.
People sometimes confuse lactose intolerance with cow milk allergy. Milk allergy is a reaction by the body's immune system to one or more milk proteins and can be life threatening when just a small amount of milk or milk product is consumed. Milk allergy most commonly appears in the first year of life, while lactose intolerance occurs more often in adulthood.
National Institute of Diabetes and Digestive and Kidney Diseases:
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The vagus nerve plays a key role in modulating inflammation and the immune system. Stimulating the vagus nerve through devices or certain activities can help treat inflammatory conditions like rheumatoid arthritis. Higher vagal tone, measured by heart rate variability during breathing, is associated with better health outcomes including reduced inflammation. The vagus nerve acts as a bidirectional communicator between the gut and the brain, reading signals from the gut microbiome and modulating inflammation. Maintaining a healthy gut microbiome and increasing vagal tone through practices like breathing and cold water can thus promote whole body health and relaxation.
"Insulin Independence" Summit on Capitol Hill
This document summarizes an international summit focused on achieving insulin independence for type 1 diabetes. The summit discussed:
- Differences between mouse and human islets that make curing diabetes in humans more complex than mice. Both immune protection and beta cell regeneration are needed.
- Existing therapies like immune tolerance agents that provide short term remission but long term regeneration is also needed to reverse the disease.
- New research showing pancreatic ducts can be transformed into insulin producing islets, but these need immune protection to survive.
- The summit aimed to advance both immune tolerance therapies and regeneration therapies to address the underlying causes of type 1 diabetes and ultimately achieve insulin independence.
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Diabetes is caused by the body's inability to produce or effectively use insulin. Insulin is a hormone produced in the pancreas that helps glucose enter cells to produce energy. In diabetes, beta cells in the pancreas do not produce enough insulin or cells do not respond properly to insulin, causing glucose to build up in the bloodstream instead of being used for energy. The main types of diabetes are type 1, an autoimmune disease where the immune system destroys beta cells, and type 2 where the body can no longer produce sufficient insulin to regulate blood glucose levels. Genetic and environmental factors both contribute to diabetes risk.
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Animal modelsof diabetes and obesity
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M.pharm (pharmacology )
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This document provides a historical overview of diabetes. Some key points include:
- The earliest known record of diabetes is from an Egyptian papyrus from around 1500 BC. The term "diabetes" comes from the Greek word for "siphon" and was coined in the 3rd century BC.
- In the 16th century, diabetes was identified as a severe disorder affecting the whole body. The pancreas's role in diabetes was discovered in the 1870s but its function remained unknown.
- In 1921-1923, Banting, Best, and Macleod discovered insulin and its role in controlling blood sugar levels, representing a major breakthrough in diabetes treatment.
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Lay summary of the manuscript published in Science. The Dana Foundation is a philanthropic organization that provided funding to our lab. I was responsible for securing this PR opportunity and for all copy.
Yo-yo dieting alters brain's response to stress: study
1) A study found that mice who went on calorie-restricted diets and lost 10-15% of their body weight had increased stress hormone levels and depressive-like behaviors when exposed to stress.
2) The dieting mice also had lasting epigenetic changes to genes related to stress and eating, even after returning to their normal weight.
3) When put in stressful situations later, the mice that had dieted ate more high-fat food than mice that had not dieted, suggesting dieting can reprogram brain responses to stress and food cravings.
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The study investigated whether decreased activity in the prefrontal cortex (PFC) of obese individuals is an inherent trait or acquired due to obesity. Using an animal model of diet-induced obesity in adult minipigs, the researchers found decreased PFC activity in obese minipigs compared to lean ones. This suggests the abnormal PFC activity is not predetermined but rather depends on nutritional factors. The obese minipigs also showed reduced activity in dopamine-regulating brain areas related to food reward and addiction. The minipig model provides insights into how overeating impacts brain function and metabolism in ways relevant to human obesity.
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This document provides information about various methods used to induce diabetes in experimental animal models. It discusses chemical agents like alloxan and streptozotocin that are commonly used to induce insulin-dependent diabetes by selectively destroying pancreatic beta cells. It also describes techniques like hormone administration, virus infection, and pancreatic resection surgery that can induce diabetes. Spontaneous animal models and transgenic animals with genetic modifications related to insulin/glucose homeostasis are also mentioned. The models discussed are used to study the pathophysiology of diabetes and evaluate new anti-diabetic drugs.
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The document provides information on calculating calorie requirements, indications for tube feeding, types of enteral formulas, methods of enteral feeding administration, and potential complications. It discusses formulas for different clinical conditions including renal, hepatic, diabetic and pulmonary. Continuous and bolus feeding methods are described. Common gastrointestinal complications like diarrhea, constipation and nausea are outlined along with potential causes and treatments. Electrolyte imbalances from enteral feeding and their management are also summarized.
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This document discusses various animal models used to study diabetes. It describes methods for inducing both type 1 diabetes (IDDM) and type 2 diabetes (NIDDM) in animals. For IDDM, models include chemical induction using alloxan or streptozocin, viral induction, surgical partial pancreatectomy, and genetic models like BB rats and NOD mice. For NIDDM, models include chemical induction using neonatal streptozocin or adrenaline, genetic obese models, hybrid crosses, and transgenic techniques. The document also discusses various in vitro methods used to study effects on pancreas, hepatocytes, muscle cells, adipocytes, and isolated tissues like diaphragm.
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This document discusses diabetes, chromium, insulin treatment, and two clinical studies on chromium supplements. It provides an overview of diabetes, how insulin works, and the two main types. It describes chromium as a mineral that enhances insulin and may help control blood sugar. One study found chromium supplements significantly lowered blood glucose in type 2 diabetics, while a second study found no effects on glucose levels or insulin resistance in people at risk for diabetes.
Protein calorie malnutrition
Protein-calorie malnutrition occurs when there is inadequate intake of protein and calories, resulting in loss of body mass and adipose tissue. It is commonly seen in developing countries due to limited food availability and quality. The main clinical presentations are kwashiorkor, characterized by protein deficiency despite adequate calories, and marasmus, which is overall starvation seen in infants. Vitamins are organic compounds essential for cell function that must be obtained through diet. They are divided into fat-soluble and water-soluble groups. Obesity results from excess caloric intake over expenditure and can be caused by overeating, physical inactivity, genetics, or certain diseases. It is associated with increased health risks and defined by a BMI over 30
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Lactose Intolerance
Lactose intolerance is the inability or insufficient ability to digest lactose, a sugar found in milk and milk products. Lactose intolerance is caused by a deficiency of the enzyme lactase, which is produced by the cells lining the small intestine. Lactase breaks down lactose into two simpler forms of sugar called glucose and galactose, which are then absorbed into the bloodstream.
Not all people with lactase deficiency have digestive symptoms, but those who do may have lactose intolerance. Most people with lactose intolerance can tolerate some amount of lactose in their diet.
People sometimes confuse lactose intolerance with cow milk allergy. Milk allergy is a reaction by the body's immune system to one or more milk proteins and can be life threatening when just a small amount of milk or milk product is consumed. Milk allergy most commonly appears in the first year of life, while lactose intolerance occurs more often in adulthood.
National Institute of Diabetes and Digestive and Kidney Diseases:
Brain gut connections(1)
The vagus nerve plays a key role in modulating inflammation and the immune system. Stimulating the vagus nerve through devices or certain activities can help treat inflammatory conditions like rheumatoid arthritis. Higher vagal tone, measured by heart rate variability during breathing, is associated with better health outcomes including reduced inflammation. The vagus nerve acts as a bidirectional communicator between the gut and the brain, reading signals from the gut microbiome and modulating inflammation. Maintaining a healthy gut microbiome and increasing vagal tone through practices like breathing and cold water can thus promote whole body health and relaxation.
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This document summarizes an international summit focused on achieving insulin independence for type 1 diabetes. The summit discussed:
- Differences between mouse and human islets that make curing diabetes in humans more complex than mice. Both immune protection and beta cell regeneration are needed.
- Existing therapies like immune tolerance agents that provide short term remission but long term regeneration is also needed to reverse the disease.
- New research showing pancreatic ducts can be transformed into insulin producing islets, but these need immune protection to survive.
- The summit aimed to advance both immune tolerance therapies and regeneration therapies to address the underlying causes of type 1 diabetes and ultimately achieve insulin independence.
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weight loss.pdf
By:Nader Al-assadi
Taiz university
Definition of weight loss:
Clinically important weight loss is defined as the loss of 10 pounds (4.5 kg) or >5% of one’s body weight over a period of 6–12 months.
Weight loss can be divided into 2 categories: involuntary or voluntary.
-1 Involuntary weight loss is a manifestation of cachexia associated with many disease states.
2- Voluntary weight loss, in the form of healthy dieting, is common among men and women. However, signifcant voluntary weight loss can herald a psychiatric illness such as an eating disorder, particularly among women.
K E Y T E R M S:
Anorexia Loss of the desire to eat.
Anorexia nervosa4 Intense fear of gaining weight and refusal to maintain weight at or above a minimally appropriate weight for height and age.
Bulimia nervosa4 Recurrent episodes of binge eating followed by recurrent compensatory behavior to prevent weight gain (ie, laxative abuse and self-induced vomiting).
Cachexia General muscle and/or fat wasting with malnutrition usually associated with chronic disease.
Involuntary weight loss The unintended loss of weight; sometimes not reported by the patient and only noted upon chart review.
Malnutrition Poor nutrition due to inadequate or unbalanced intake of nutrients or their impaired utilization.
Voluntary weight loss The conscious effort to lose weight; frequently not a complaint among those with eating disorders.
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1. Beta cells in the pancreas produce the hormone insulin which regulates blood sugar levels. Impairment of beta cells leads to diabetes. Studying beta cell development in zebrafish can provide insights into treating diabetes in humans.
2. Zebrafish have similarities to humans in genes associated with disease and drug responses, making them a useful model for studying beta cell development. Their pancreas contains beta cells clustered in islets as well as single beta cells in the tail.
3. Transcription factors like Pdx1 and Ptf1a are involved in early beta cell differentiation and maturation. Understanding their roles and how to generate new beta cells could lead to strategies for treating diabetes.
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Obesity is rising globally despite increased knowledge about diet and exercise. Risks include heart disease, stroke, diabetes, and some cancers. Factors causing obesity include an evolutionary tendency to efficiently store calories combined with current low activity, high calorie diets. Appetite is regulated by hormones that signal fullness or hunger. Gut hormones like GLP-1 and leptin help regulate food intake while ghrelin stimulates appetite. Adipose tissue also secretes hormones that impact metabolism.
Glucose metabolism student handout
1) The document discusses glucose metabolism, including digestion of carbohydrates in the gut, absorption of glucose in the small intestine, and regulation of blood glucose levels by insulin and glucagon.
2) Key aspects covered include the roles of the liver, pancreas, and kidneys in glucose metabolism. Glucose is absorbed into the bloodstream and transported to tissues.
3) Hormonal control maintains blood glucose within a narrow range, with insulin promoting glucose uptake and storage after meals and glucagon promoting glucose release during fasting.
4 5827774745222842168
The document discusses carbohydrate metabolism and diabetes. It begins by defining the different types of carbohydrates and outlining carbohydrate digestion and absorption. It then discusses glucose regulation and the hormones insulin and glucagon. Insulin helps regulate blood glucose levels by promoting glucose uptake and storage, while glucagon has opposing effects. The document also outlines the classification, causes, and characteristics of the main types of diabetes: type 1, type 2, and gestational diabetes. It concludes by mentioning some acute complications of diabetes like diabetic ketoacidosis.
05.Endocrine System 4 Blocks @eduwaves360.pdf
This patient presents with a skin rash involving thickened, velvety, hyperpigmented plaques in the axillae. This skin condition is known as acanthosis nigricans and is most likely associated with insulin resistance and obesity, as seen in polycystic ovarian syndrome. Acanthosis nigricans typically manifests in intertriginous areas like the axillae and neck and is not seen in niacin deficiency, gastric lymphoma, or other endocrine disorders listed as options.
Diabetes mellitus
This document provides an overview of diabetes mellitus, including its classification into type 1 and type 2 diabetes. It defines each type, describing their pathophysiology, causes, signs and symptoms. Type 1 diabetes results from the body's immune system attacking insulin-producing beta cells in the pancreas. Type 2 involves insulin resistance and reduced insulin secretion. Diagnostic tests and treatment options are also reviewed, along with pancreatic anatomy and the role of insulin in regulating blood sugar levels. Complications of diabetes and collaborative care approaches are briefly mentioned.
Diabetes mellitus
This document provides an overview of diabetes mellitus, including its classification into type 1 and type 2 diabetes. It defines each type, describing their pathophysiology, causes, signs and symptoms. Type 1 diabetes results from the body's immune system attacking insulin-producing beta cells in the pancreas. Type 2 involves insulin resistance and reduced insulin secretion. Diagnostic tests and treatment options are also reviewed, along with pancreatic anatomy and the role of insulin in regulating blood sugar levels. Complications of diabetes and collaborative care approaches are briefly mentioned.
Food-Matrix-and-Gherlin-Hormone
This document summarizes a study that investigated the effects of food matrix on circulating levels of the appetite-regulating hormone acylated ghrelin. The study involved two randomized crossover trials that compared isoenergetic meals with different food matrices. Trial A compared almond extracts with different protein coatings, while Trial B compared raw almonds and almond oil. Blood samples were taken before and after the meals to measure acylated ghrelin and lipid levels. The results found no significant difference in post-prandial acylated ghrelin levels between the food matrices tested. However, triglyceride levels were significantly different after almond products. The study concluded that food matrix did not significantly impact acylated
CHO metabolism206-2005.ppt
Carbohydrates provide the largest source of calories and include starch, lactose, and sucrose. The small intestine breaks down carbohydrates into monosaccharides like glucose through digestion by enzymes attached to the intestinal wall. These monosaccharides are then absorbed into the bloodstream and transported to tissues like muscle and liver to be used for energy or stored as glycogen for later use.
Endocrine System
Hormones regulate many bodily functions through feedback mechanisms. Insulin and glucagon regulate blood glucose levels through negative feedback with the pancreas. When blood glucose levels rise, the pancreas secretes insulin to lower them. Leptin from fat cells signals satiety in the brain. Melatonin from the pineal gland controls circadian rhythms and its use can help with jet lag by resynchronizing the body clock. Thyroxine from the thyroid increases metabolism and helps control body temperature.
4 2155-6156-3-182 randa
This research article studied the effects of quercetin (QCT) on experimentally induced diabetes in rats. Rats were divided into three groups: a control group, a diabetic group induced with streptozotocin (STZ), and a QCT-treated group that received QCT before and after STZ induction. Blood glucose levels increased significantly in the diabetic group but decreased in the QCT-treated group. Histological analysis found that STZ caused pancreatic beta cell degeneration and inflammation in the diabetic group. QCT treatment reversed many of these changes in the pancreas and increased beta cell numbers. Immunohistochemistry revealed that STZ increased iNOS and caspase-3, markers of inflammation and apoptosis, while QCT
Adiponektin
1) Mice were fed a high-fat, high-sucrose diet to induce metabolic perturbations associated with obesity. 2) The mice then received gene therapy targeting adiponectin, an anti-inflammatory hormone reduced in obesity. 3) The gene therapy successfully elevated levels of adiponectin in serum and muscle tissue. This ameliorated the metabolic abnormalities caused by the diet by reducing weight gain, fat accumulation, and improving glucose tolerance and insulin sensitivity.
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Resume
Juan Carlos Torres Sanchez is seeking research experience in immunology and virology. He has a B.A. from the University of Puerto Rico-Cayey Campus and conducted research as part of the Summer Bridge Program and a high school student research program. His research experience includes participating in a high school student research program and authoring a paper on predicting mutations and strain comparison of Clostridium Tetani's toxin. He has skills in teamwork, organization, responsibility, time efficiency, microscopy techniques, micropipetting, and scientific review paper writing.
Lab assignment 3
This document provides instructions for laboratory writing assignments for the University of Puerto Rico - Cayey RISE Program. Students are asked to write an 8-10 sentence summary paragraph of 160-170 words for each assignment. They must complete an attached template and email it to Dr. Elena Gonzalez for grading using the provided rubric. Within two days, students must email the assignment to the instructor with any corrections. The rubric assesses the purpose and techniques, biological competence, English competence, and critical thinking demonstrated in the summary.
Lab assignment 2 revised
1) The document provides instructions for laboratory writing assignments as part of the RISE Program at the University of Puerto Rico - Cayey. It details the requirements for assignment summaries, including length, formatting, and grading rubric.
2) Three sample laboratory assignment summaries are included as examples. The first summarizes experiments involving column chromatography and SDS-PAGE gel electrophoresis to isolate and identify proteins from egg whites. The second describes experiments and a sheep brain dissection in a neurobiology workshop. The third explains in silico structure-based drug design to discover new drugs through computer modeling of protein-drug interactions.
3) The assignments and examples demonstrate techniques used in biomedical research laboratories to
Lab assignment 1 revised 2
The document provides instructions and templates for laboratory writing assignments as part of the RISE Program at the University of Puerto Rico - Cayey. It details 3 workshops that students participated in to learn various laboratory techniques. The first workshop covered microscopy techniques including bright field, dark field, and phase contrast microscopy as well as photomicrography. The second workshop involved using micropipettes, performing aseptic techniques, and working with bacteria. The third workshop over 3 days taught techniques in DNA isolation, polymerase chain reaction, electrophoresis, protein separation, and detection of oncogenes and oncoproteins. The document emphasizes that mastery of these laboratory techniques is important for scientific discovery and diagnostic applications in
Bioinformatics, comparative genemics and proteomics
Bioinformatics uses computer tools to analyze genomic DNA sequences and takes a more global perspective in experimental design. Comparative genomics studies the relationship of genome structure and function across species, exploiting similarities and differences to infer evolutionary changes. Proteomics is the large-scale study of protein structure and function, analyzing the complete set of proteins specified by a genome. Together, bioinformatics, comparative genomics, and proteomics have helped gather knowledge about mycobacteriophages and improve disease research.
P pt rise insilico 2
This document summarizes research into discovering inhibitors for the histone-lysine N-methyltransferase SETD2 through in silico methods. The researchers generated pharmacophore models of the S-adenosyl methionine binding site of SETD2 and screened a database of over 150,000 compounds. Top hits with predicted binding energies below -9 kcal/mol were identified, and future work will involve refining models, screening more databases, and testing top compounds in assays. The goal is to identify novel SETD2 inhibitors for potential use in cancer treatment targeting epigenetic changes.
In silico discovery of histone methyltranferase 1
This study investigated potential inhibitors of the histone methyltransferase SETD2 using in silico methods. Two pharmacophore models were generated and used to screen a database of 150,000 compounds, filtering it to 31,669 potential leads. Molecular docking ranked these by predicted binding energy, identifying 58 compounds with binding energies from -9.7 to -9.0 kcal/mol. Further refinement of the models and testing of top-scoring compounds may reveal inhibitors of histone methylation and cancer progression.
Biblio 3 official
This document summarizes a research article that evaluated cystatin C as a potential biomarker for Amyotrophic Lateral Sclerosis (ALS). The study found that cystatin C concentration decreased in the cerebral spinal fluid but increased in the plasma of ALS patients compared to healthy individuals. Cystatin C levels in cerebral spinal fluid were also found to correlate with patient survival time, demonstrating its potential utility as a prognostic biomarker. The results suggest cystatin C may play a neuroprotective role in ALS and represent an important step towards identifying a biomarker that could aid in early detection and monitoring of the disease.
Biblio 2 official
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons and usually results in death within 2-5 years of symptom onset. Researchers used nuclear magnetic resonance (NMR) spectroscopy to analyze cerebral spinal fluid (CSF) samples from ALS patients and controls to search for biomarkers in early ALS. The study found that NMR spectroscopy, when combined with other analytical techniques, could detect changes in certain CSF metabolite concentrations for ALS patients. However, the mechanisms of ALS are complex and no single biomarker has been identified that could replace regular patient checkups.
Biblio 1 official
This document summarizes a research study that aimed to identify biomarkers for amyotrophic lateral sclerosis (ALS) through profiling of cerebrospinal fluid from ALS patients and control subjects. The study utilized surface-enhanced laser desorption/ionization-time of flight mass spectrometry to analyze cerebrospinal fluid samples. Three potential biomarkers - transthyretin, cystatin C, and carboxy-terminal fragment of neuroendocrine protein 7B2 - were identified, and two were validated as biomarkers that distinguished ALS patients from control subjects.
Juan carlos ppt als
This document discusses using proteomics and metabolomics techniques to identify biomarkers for early detection of Amyotrophic Lateral Sclerosis (ALS). It describes previous proteomics studies that identified three biomarkers in CSF and interest in cystatin C as a diagnostic biomarker. Metabolomics studies using NMR on CSF have also found 17 relevant metabolites and perturbations in glucose metabolism. The conclusion is that proteomics and metabolomics show promise as techniques for early ALS detection but require further validation studies.
Juan carlos review paper final
Proteomics and metabolomics studies are investigating biomarkers for early detection of amyotrophic lateral sclerosis (ALS). Proteomics identified three biomarkers, including decreased transthyretin and increased cystatin C levels. Metabolomics identified 17 potential biomarkers by analyzing cerebrospinal fluid and found perturbations in glucose metabolism. While these areas of research have advanced biomarker identification, validation of results is still needed. Continued studies may allow biomarkers to be used in routine patient checkups to enable early diagnosis and treatment of ALS.
Reflection 3 official
Leiddy Alvarado gave a seminar about her research using metabolomic techniques like NMR and MS to identify biomarkers for early detection of breast cancer recurrence in patients. Her research has identified eleven potential biomarkers and passed pre-validation testing, giving hope that a simple blood test could predict prognosis without invasive surgery. If fully validated and commercialized, this technique could allow patients to learn their prognosis through a basic blood test instead of surgery or high medical costs. Metabolomic studies may also be useful for detecting biomarkers of other diseases beyond cancer.
Reflection 2 official
The seminar exposed the author to new concepts in proteomics and biomarkers. Biomarkers help trace cancers by identifying sets of proteins encoded in a genome. Mass spectrometry is important for discovering protein biomarkers by analyzing serum and tissue samples. However, proteomics presents challenges in determining which potential biomarkers identified are most likely to be valid, as many may be identified but require further validation stages to identify the ones most effective. It is difficult to reach the final validation stage, requiring perseverance from investigators.
The reflection abut te first seminar
Jessian Muñoz, a graduate student at New Jersey Medical School, gave a seminar discussing cancer stem cells and their role in brain tumors. Cancer stem cells may be the primary cause of brain tumors, as chemotherapy often fails to target these cells specifically. The seminar addressed how cancer stem cells can reemerge after treatment and explained the discovery of microRNAs' involvement in cancer signaling. Jessian's presentation demonstrated how scientific understanding advances and how personal goals can change during one's studies.
Trabajo yunque + guanica
This document compares the Yunque Rainforest and Guanica Dry Forest biomes in Puerto Rico. The Yunque Rainforest receives 200-400 cm of annual precipitation and supports a diversity of broadleaf trees, epiphytes, and 200+ plant species. The Guanica Dry Forest receives 150-200 cm annually with a long dry season, and its plants like button mangroves and acacias have adaptations like thorns and reduced leaves to resist water loss. Methodologies conducted in each forest examined soil properties, temperature, and vegetation differences driven by their distinct climates.
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Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
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There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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Breast cancer: Post menopausal endocrine therapy
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
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Propuesta de rise completa
- 1. Comparison of glucose levels in the regeneration of beta cells in type 1 diabetes. Juan Carlos Torres Sanchez
- 2. Introduction