This document summarizes various approaches for managing type 1 diabetes, including the bionic pancreas, islet transplantation, and stem cell therapy. It notes that the bionic pancreas can help improve glucose control but has limitations like being invasive and not physiological. Islet transplantation via the Edmonton protocol can cure diabetes, but challenges remain in expanding the donor supply and improving techniques. Stem cell therapy shows promise if stem cells can be encapsulated to both differentiate into insulin-producing cells and avoid immune rejection. Overall, a cure exists on the horizon, but further progress is still needed to overcome immune issues and increase donor availability.
Emma Ridley, ANZIC-RC, Monash University and Alfred Health
Emma leads the ICU Nutrition Research Program at the Australian and New Zealand Intensive Care Research Centre, Melbourne, Australia and has 13 years of clinical dietetic experience, including as a senior dietitian in the ICU at The Alfred Hospital, Melbourne. Emma’s research interests include the clinical application of indirect calorimetry, as well as the effect of optimal nutrition delivery on short and long-term outcomes in ICU patients. Emma was awarded a prestigious Churchill Fellowship in 2011 to investigate the role of indirect calorimetry internationally and regularly delivers invited national and international presentations. Emma is on the management committee for the TARGET trial (the largest blinded enteral nutrition trial conducted in critical care) and has been a named investigator on $6.2 million dollars of research funding, including a project based on findings from her PhD of $2.3 million dollars (NCT03292237).
The utility of assessing gene expression in skin to evaluate treatment response: What becomes of all those skin biopsies? is presented by
Monique Hinchcliff MD, MS
Northwestern Scleroderma Program
Emma Ridley, ANZIC-RC, Monash University and Alfred Health
Emma leads the ICU Nutrition Research Program at the Australian and New Zealand Intensive Care Research Centre, Melbourne, Australia and has 13 years of clinical dietetic experience, including as a senior dietitian in the ICU at The Alfred Hospital, Melbourne. Emma’s research interests include the clinical application of indirect calorimetry, as well as the effect of optimal nutrition delivery on short and long-term outcomes in ICU patients. Emma was awarded a prestigious Churchill Fellowship in 2011 to investigate the role of indirect calorimetry internationally and regularly delivers invited national and international presentations. Emma is on the management committee for the TARGET trial (the largest blinded enteral nutrition trial conducted in critical care) and has been a named investigator on $6.2 million dollars of research funding, including a project based on findings from her PhD of $2.3 million dollars (NCT03292237).
The utility of assessing gene expression in skin to evaluate treatment response: What becomes of all those skin biopsies? is presented by
Monique Hinchcliff MD, MS
Northwestern Scleroderma Program
Recurrent pregnancy loss (RPL), also referred to as recurrent miscarriage or habitual abortion, is historically defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period.
This Presentation is made by Dr.Laxmi Shrikhande
Benjamin Korman, MD discusses the genetics of scleroderma and the genomic era. Genetics and genomics are complicated, and getting more so every day. Every patient is genetically unique, but new technology will make it easier to understand individuals’ genetic susceptibility to disease and response to therapy.
Radiation Therapy: Nutritional Strategies to Improve OutcomesJeanne M Wallace PhD
Presentation by Jeanne M. Wallace, PhD, CNC, at "Integrative Cancer Medicine: Clinical Applications of Cancer Strategies" conference April 26-29, 2013, Scottsdale AZ. Explore the mechanisms of tumor resistance to radiation therapy. Review diet, lifestyle, nutritional and botanical strategies for bolstering therapeutic efficacy. Employ selective radioprotectors to lessen injury to healthy tissues. Take into consideration the unfavorable consequences of radiotherapy, which can potentially increase the oncogenic potential of surviving tumor cells, and develop a plan for blocking these pathways. Cases will be presented from 15 yrs experience of the Nutritional Solutions team in counseling clients undergoing radiation therapy for Glioblastoma multiforme brain tumors, colorectal, head-and-neck, breast and gynecologic cancers.
Recurrent pregnancy loss (RPL), also referred to as recurrent miscarriage or habitual abortion, is historically defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period.
This Presentation is made by Dr.Laxmi Shrikhande
Benjamin Korman, MD discusses the genetics of scleroderma and the genomic era. Genetics and genomics are complicated, and getting more so every day. Every patient is genetically unique, but new technology will make it easier to understand individuals’ genetic susceptibility to disease and response to therapy.
Radiation Therapy: Nutritional Strategies to Improve OutcomesJeanne M Wallace PhD
Presentation by Jeanne M. Wallace, PhD, CNC, at "Integrative Cancer Medicine: Clinical Applications of Cancer Strategies" conference April 26-29, 2013, Scottsdale AZ. Explore the mechanisms of tumor resistance to radiation therapy. Review diet, lifestyle, nutritional and botanical strategies for bolstering therapeutic efficacy. Employ selective radioprotectors to lessen injury to healthy tissues. Take into consideration the unfavorable consequences of radiotherapy, which can potentially increase the oncogenic potential of surviving tumor cells, and develop a plan for blocking these pathways. Cases will be presented from 15 yrs experience of the Nutritional Solutions team in counseling clients undergoing radiation therapy for Glioblastoma multiforme brain tumors, colorectal, head-and-neck, breast and gynecologic cancers.
Strict Glycemic Control in Critically ill patients: The Demise of another ver...Prof. Mridul Panditrao
Prof. Mridul M. Panditrao tries to explain the pros and cons about the good strategy, whcih became controversial and almost obsolete. He also tries to tract the whole aspect of the phenomenon and reviews/ RCTs/
Strict (Tight) Glycemic control (SGC/TGC), as it is called, was and still is a good strategy. It can be defined as maintenance of the blood glucose level in the range of 80-110 mg /dl. with help of dose variable and intensive insulin therapy (IIT). Since its introduction, there have been conflicting reports of its efficacy and complications. This resulted in slow but steady neglect of this very good idea leading to its almost complete demise.
An effort has been made in this review, to impartially analyze all the available evidence and try to find the reasons for the negative publicity which led to the neglect or worse still, the wrong use of this protocol. Some suggestions for fair and proper implementation of the strategy are put forward.
etc/
Imeglimin, What is new?
By Dr. Usama Ragab Youssif
Lecturer of Medicine - Zagazig University
Agenda
Mitochondrial function and dysfunction
Mitochondrial (dys)function in diabetes
Diabetes core defects and Imeglimin
Imeglimin drug development and approval
Imeglimin and Heart
Diabetes mellitus (DM) is a disease of inadequate control of blood levels of glucose. It has many subclassifications, including type 1, type 2, maturity-onset diabetes of the young (MODY), gestational diabetes, neonatal diabetes, and steroid-induced diabetes. Type 1 and 2 DM are the main subtypes, each with different pathophysiology, presentation, and management, but both have a potential for hyperglycemia. This activity outlines the pathophysiology, evaluation, and management of DM and highlights the role of the interprofessional team in managing patients with this condition.
Objectives:
Describe the pathophysiology of diabetes mellitus.
Outline the epidemiology and risk factors of diabetes mellitus.
Review the treatment considerations and common complications of diabetes mellitus.
Identify the importance of improving collaboration and care coordination amongst the interprofessional team to enhance the delivery of care for patients affected by diabetes mellitus.
Access free multiple choice questions on this topic.
Go to:
Introduction
Diabetes mellitus is taken from the Greek word diabetes, meaning siphon - to pass through and the Latin word mellitus meaning sweet. A review of the history shows that the term "diabetes" was first used by Apollonius of Memphis around 250 to 300 BC. Ancient Greek, Indian, and Egyptian civilizations discovered the sweet nature of urine in this condition, and hence the propagation of the word Diabetes Mellitus came into being. Mering and Minkowski, in 1889, discovered the role of the pancreas in the pathogenesis of diabetes. In 1922 Banting, Best, and Collip purified the hormone insulin from the pancreas of cows at the University of Toronto, leading to the availability of an effective treatment for diabetes in 1922. Over the years, exceptional work has taken place, and multiple discoveries, as well as management strategies, have been created to tackle this growing problem. Unfortunately, even today, diabetes is one of the most common chronic diseases in the country and worldwide. In the US, it remains as the seventh leading cause of death.
Diabetes mellitus (DM) is a metabolic disease, involving inappropriately elevated blood glucose levels. DM has several categories, including type 1, type 2, maturity-onset diabetes of the young (MODY), gestational diabetes, neonatal diabetes, and secondary causes due to endocrinopathies, steroid use, etc. The main subtypes of DM are Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM), which classically result from defective insulin secretion (T1DM) and/or action (T2DM). T1DM presents in children or adolescents, while T2DM is thought to affect middle-aged and older adults who have prolonged hyperglycemia due to poor lifestyle and dietary choices. The pathogenesis for T1DM and T2DM is drastically different, and therefore each type has various etiologies, presentations, and treatments.
"Insulin Independence" Summit on Capitol HillDavid Edelman
These slides are from the April 24, 2013 "Insulin Independence" summit at the Canon House Office Building on Capitol Hill in Washington, DC. The event previewed the future of combination therapies to restore insulin production to people living with type 1 diabetes.
Something remarkable happens when some women with type 1 diabetes become pregnant: they start producing completely normal levels of insulin.
You read that correctly: one third of pregnant women, including those who’ve had it for 20 years or more, have reduced insulin needs during pregnancy. Some need no injected insulin at all. This knowledge may soon help everyone living with type 1 diabetes. How is this possible?
Two special things happen during pregnancy. First, the body relaxes the immune system to prevent it from harming the fetus. Second, it floods the body with hormones that promote growth. This causes something that researchers long thought was impossible: brand new islet cells start forming and producing insulin.
The combination therapy approach looks to mimic this effect and transform the treatment of diabetes.
Optimizing nutrition and growth for children with special Health care needs ...OlaAlkhars
Learning objectives
• Bone Growth Regulation and pattern
• Optimizing Nutrition And Bone Health in Children with Cerebral Palsy
• Developmental stages in child feeding
• Picky Eaters vs Avoidant/Restrictive Food Intake Disorder (ARFID)
Diabetes and Gut interplay
By Dr. Usama Ragab Youssif
In Gastro Canal Association Annual Conference
Agenda
Diabetes as the main player
Gut as the main player
Diabetes and gut in a separate game
Gut as game changer
Tips and tricks: diabetes drugs
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
1. Managing Curing Type 1 Diabetes
Jeremy Warshauer, PGY-2
Internal Medicine
UT Southwestern
2. Objectives
• Overview of type 1 diabetes
• Bionic Pancreas
• Islet Transplantation
• Stem Cell Therapy
3. Prevalence
• In 2012, 29.1 million Americans, or 9.3% of
the population, had diabetes
– 1.25 million American children and adults have
type 1 diabetes
• $245 billion in 2012 impact on economy
8. “Insulin is not a cure for
diabetes; it is a treatment. It
enables the diabetic to burn
sufficient carbohydrates, so
that proteins and fats may be
added to the diet in sufficient
quantities to provide energy
for the economic burdens of
life.”
– Sir Frederick Grant Banting
during his Nobel lecture on
September 15, 1925.
18. How much did the bionic pancreas
help?
• Average blood glucose reduced
– 159 mg/dL to 133 mg/dL (A1C = 6.2)
• Hypoglycemia reduced
– 3.7% to 1.5% of the time with a blood glucose
<60mg/dL
21. Problems with Bionic Pancreas
• Invasive
• Possibility of technology malfunction
• No stable preparation of glucagon
• Insulin time of onset
• Not physiologic
29. Why doesn’t everybody get this?
• Patient needs unstable glycemic control that
cannot be corrected by standard conventional
and intensive insulin therapies.
• Remaining challenges:
– expansion of the islet donor supply
– improving islet isolation techniques
– strategies to improve engraftment
– mediating the anti-inflammatory response post-
transplant
– improving recipient immunosuppression regimens.
30. Prevelancess Islet transplantation for typ
80
60
Edmonton
North America
International
40
20
Year
Islet transplant recipients per
year registered with CITR
Numberofislettransplantrecipients
0
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
umber of islet transplant recipientsfrom 1999–2013 in Edmonton, North Americaand International Islet Transplant Centers.
From the Clinical Islet Transplantation (CIT) Consortium
31. Stem cell Therapy
• 2 Key features:
– Ability to renew themselves through cell division
while remaining undifferentiated.
– When given the appropriate signals, stem cells can
differentiate into many specialized cell types.
32.
33.
34.
35.
36.
37.
38. Encapsulation
• Protect against immune rejection – Encaptra
device by Viacyte.
http://viacyte.com/products/vc-01-diabetes-therapy/
39. Conclusions
• A cure is in site, but there are several
obstacles that still must be overcome
– Immune modulation
– Not enough supply
40. References
• Bruni, A., et al. (2014). "Islet cell transplantation for the treatment of type 1 diabetes: recent
advances and future challenges." Diabetes Metab Syndr Obes 7: 211-223.
• Derr, R., et al. (2003). "Is HbA(1c) affected by glycemic instability?" Diabetes Care 26(10): 2728-
2733.
• Kudva, Y. C., et al. (2014). "Closed-loop artificial pancreas systems: physiological input to enhance
next-generation devices." Diabetes Care 37(5): 1184-1190.
• Peyser, T., et al. (2014). "The artificial pancreas: current status and future prospects in the
management of diabetes." Ann N Y Acad Sci 1311: 102-123.
• Pagliuca, F. W., et al. (2014). "Generation of functional human pancreatic beta cells in vitro." Cell
159(2): 428-439.
• Russell, S. J., et al. (2014). "Outpatient glycemic control with a bionic pancreas in type 1 diabetes."
N Engl J Med 371(4): 313-325.
• Shapiro, A. M., et al. (2006). "International trial of the Edmonton protocol for islet transplantation."
N Engl J Med 355(13): 1318-1330.
• Unger, R. H. and L. Orci (2010). "Paracrinology of islets and the paracrinopathy of diabetes." Proc
Natl Acad Sci U S A 107(37): 16009-16012.
• Unger, R. H. and A. D. Cherrington (2012). "Glucagonocentric restructuring of diabetes: a
pathophysiologic and therapeutic makeover." J Clin Invest 122(1): 4-12.
Editor's Notes
Endo
patients are able to live without restrictions
Shapiro et al. N Engl J Med 2006;355:1318-30.
Melton Lab from Harvard created a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive beta cells from hPSC in vitro that act essentially identical to human beta cells.
Molecular biography of a beta cell on top.
PH means polyhormonal cells – in-vitro-differentiated human pluripotent stem cells. Transcriptional analysis showed these cells resemble human fetal and not adult beta cells – show no insulin secretion, essentially are placebo.
SC-beta cells are stem-cell-derived beta cells
And primary beta represent primary human beta cells that were transplanted into the mice.
1. ES = embryonic stem cell – pluripotent cells derived from the inner cell mass of a 4-5 day old embryo (blastocyst) and have the potential to form derivatives from all 3 germ layers
2. Adult (or somatic) stem cells: can be reprogrammed to induced pluripotent stem cells (iPSCs) to express ES characteristics.
Transplanted the stem cells under the kidney capsule of immunocompromoised mice.
PH means polyhormonal cells – in-vitro-differentiated human pluripotent stem cells. Transcriptional analysis showed these cells resemble human fetal and not adult beta cells – show no insulin secretion, essentially are placebo.
SC-beta cells are stem-cell-derived beta cells
And primary beta represent primary human beta cells that were transplanted into the mice.
Shapiro, A. M., et al. (2006). "International trial of the Edmonton protocol for islet transplantation." N Engl J Med 355(13): 1318-1330.
