This document summarizes research on the potential anti-aging effects of the drug rapamycin. It describes a clinical trial that investigated the safety and impact of rapamycin supplementation in older adults. The trial found that rapamycin was generally safe and well-tolerated, with few adverse effects. It appeared to positively impact some measures of immune function and inflammation. However, the document notes that longer and larger studies are still needed to fully understand rapamycin's safety profile and ability to extend healthspan in humans.
Turbo Metabolism
Weight loss has got to be the most frustrating experience for many people, young and old alike. Eating foods that are just horrible, denying yourself foods you truly love and enjoy. Exercising, even though you absolutely hate exercising, and end up stiff as a board with no results. Finally Learn amazing secrets that will increase your metabolism, allowing your body to turn into a fat burning furnace day after day!
http://rapbank.com/go/5835/75255
Turbo Metabolism
Weight loss has got to be the most frustrating experience for many people, young and old alike. Eating foods that are just horrible, denying yourself foods you truly love and enjoy. Exercising, even though you absolutely hate exercising, and end up stiff as a board with no results. Finally Learn amazing secrets that will increase your metabolism, allowing your body to turn into a fat burning furnace day after day!
http://rapbank.com/go/5835/75255
This workshop is delivered by Dr. Daniel Santa Mina, a Registered Kinesiologist and Certified Exercise Physiologist with specialization in oncology. Dr. Daniel Santa Mina is a Scientist at the Princess Margaret Cancer Centre where he leads the Wellness and Exercise for Cancer Survivors Program (WE-Can) and an Assistant Professor in the Faculty of Kinesiology and Physical Education at the University of Toronto. His main areas of clinical-research focus are on the physiological, functional, and psychosocial effects of exercise for cancer survivors.
Sarcopenic obesity is a chronic condition, which is due to progressively aging populations, the increasing incidence of obesity, and lifestyle changes. The increasing prevalence of sarcopenic obesity in elderly has augmented interest in identifying the most effective treatment. This article aims at highlighting potential pathways to muscle impairment in obese individuals, the consequences that joint obesity and muscle impairment may have on health and disability, recent progress in management with attention on lifestyle management and pharmacologic therapy involved in reversing sarcopenic obesity. Recent findings: It has been suggested that a number of disorders affecting metabolism, physical capacity, and quality of life may be attributed to sarcopenic obesity. Excess dietary intake, physical inactivity, low-grade inflammation, insulin resistance and hormonal changes may lead to the development of sarcopenic obesity. Weight loss and exercise independently reverse sarcopenic obesity. Optimum protein intake appears to have beneficial effects on net muscle protein accretion in older adults. Myostatin inhibition causes favourable changes in body composition. Testosterone and growth hormone offer improvements in body composition but the benefits must be weighed against potential risks of therapy. GHRH-analog therapy is effective but further studies are needed in older adults. Summary: Lifestyle changes involving both diet-induced weight loss and regular exercise appear to be the optimal treatment for sarcopenic obesity. It is also advisable to maintain adequate protein intake. Ongoing studies will determine whether pharmacologic therapy such as myostatin inhibitors or GHRH-analogs have a role in the treatment of sarcopenic obesity.
The Challenges of Sarcopenia: Definition, Underlying Mechanisms, Intervention...InsideScientific
During this webinar, Drs. Peterson and Guralnik will discuss sarcopenia, the physiological mechanisms underlying the disease, and the current avenues of treatment and assessment that are being researched and developed for patients.
Sarcopenia is the age-related loss of muscle that causes decreased strength and functional limitations. Muscle loss occurs universally in people as we age, but some people lose muscle at an accelerated rate compared to others. While chronic disease can cause sarcopenia, it can also result from a sedentary lifestyle, hospitalizations and extended bed rest due to other conditions.
A gradual decline in muscle mass and strength begins around 30 years of age with this condition, and annual losses get larger throughout life. The self-reporting of functional difficulties to health care providers may give an indication that sarcopenia is present, but a more precise definition is needed for research and clinical use.
Efforts made in Europe and the US have used grip strength, gait speed and lean mass to define sarcopenia, but these definitions lead to large differences in prevalence rate and discordance in who is labelled as “sarcopenic”. To assess this condition, lean mass as measured by dual x-ray absorptiometry (DXA) may not accurately reflect actual muscle mass, but a new technique using dilution of deuterium-labelled creatine may prove to be superior in clinically diagnosing sarcopenia. Currently, a consensus has not been reached on the clinical outcome assessments that can be used by regulatory agencies to judge the effectiveness of drugs for sarcopenia.
A number of potential interventions are being explored to treat sarcopenia in older people, but no drugs are currently approved for this condition. The antidiabetic drug metformin shows promise in preventing many age-associated conditions, but appears to blunt the benefits of exercise on muscle. Senolytic drugs, which clear senescent cells, may improve muscle repair following injury preferentially in older individuals.
Sugar-sweetened beverage consumption in relation to diabetes and cardiovascul...My Healthy Waist
By Frank B. Hu, MD, PhD Professor of Nutrition and Epidemiology Harvard School of Public HealthChanning Laboratory, Harvard Medical School and Brigham and Women’s Hospital
Targeting abdominal obesity in diabetology: What can we do about it?My Healthy Waist
By Luc Van Gaal, MD, PhD, Professor of Medicine, Antwerp University Hospital, Faculty of Medicine, Department of Diabetology, Metabolism & Clinical Nutrition, Antwerp, Belgium
Austin Journal of Obesity & Metabolic Syndrome is an international scholarly peer reviewed Open Access journal, aims to promote the research in all the related fields of Metabolic Syndrome.
Austin Journal of Obesity & Metabolic Syndrome is a comprehensive Open Access peer reviewed scientific Journal that covers multidisciplinary fields. We provide limitless access towards accessing our literature hub with colossal range of articles. The journal aims to publish high quality varied article types such as Research, Review, Short Communications, Case Reports, Perspectives (Editorials), Clinical Images.
Austin Journal of Obesity & Metabolic Syndrome supports the scientific modernization and enrichment in Metabolic Syndromes research community by magnifying access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed member journals under one roof thereby promoting knowledge sharing, collaborative and promotion of multidisciplinary science.
This workshop is delivered by Dr. Daniel Santa Mina, a Registered Kinesiologist and Certified Exercise Physiologist with specialization in oncology. Dr. Daniel Santa Mina is a Scientist at the Princess Margaret Cancer Centre where he leads the Wellness and Exercise for Cancer Survivors Program (WE-Can) and an Assistant Professor in the Faculty of Kinesiology and Physical Education at the University of Toronto. His main areas of clinical-research focus are on the physiological, functional, and psychosocial effects of exercise for cancer survivors.
Sarcopenic obesity is a chronic condition, which is due to progressively aging populations, the increasing incidence of obesity, and lifestyle changes. The increasing prevalence of sarcopenic obesity in elderly has augmented interest in identifying the most effective treatment. This article aims at highlighting potential pathways to muscle impairment in obese individuals, the consequences that joint obesity and muscle impairment may have on health and disability, recent progress in management with attention on lifestyle management and pharmacologic therapy involved in reversing sarcopenic obesity. Recent findings: It has been suggested that a number of disorders affecting metabolism, physical capacity, and quality of life may be attributed to sarcopenic obesity. Excess dietary intake, physical inactivity, low-grade inflammation, insulin resistance and hormonal changes may lead to the development of sarcopenic obesity. Weight loss and exercise independently reverse sarcopenic obesity. Optimum protein intake appears to have beneficial effects on net muscle protein accretion in older adults. Myostatin inhibition causes favourable changes in body composition. Testosterone and growth hormone offer improvements in body composition but the benefits must be weighed against potential risks of therapy. GHRH-analog therapy is effective but further studies are needed in older adults. Summary: Lifestyle changes involving both diet-induced weight loss and regular exercise appear to be the optimal treatment for sarcopenic obesity. It is also advisable to maintain adequate protein intake. Ongoing studies will determine whether pharmacologic therapy such as myostatin inhibitors or GHRH-analogs have a role in the treatment of sarcopenic obesity.
The Challenges of Sarcopenia: Definition, Underlying Mechanisms, Intervention...InsideScientific
During this webinar, Drs. Peterson and Guralnik will discuss sarcopenia, the physiological mechanisms underlying the disease, and the current avenues of treatment and assessment that are being researched and developed for patients.
Sarcopenia is the age-related loss of muscle that causes decreased strength and functional limitations. Muscle loss occurs universally in people as we age, but some people lose muscle at an accelerated rate compared to others. While chronic disease can cause sarcopenia, it can also result from a sedentary lifestyle, hospitalizations and extended bed rest due to other conditions.
A gradual decline in muscle mass and strength begins around 30 years of age with this condition, and annual losses get larger throughout life. The self-reporting of functional difficulties to health care providers may give an indication that sarcopenia is present, but a more precise definition is needed for research and clinical use.
Efforts made in Europe and the US have used grip strength, gait speed and lean mass to define sarcopenia, but these definitions lead to large differences in prevalence rate and discordance in who is labelled as “sarcopenic”. To assess this condition, lean mass as measured by dual x-ray absorptiometry (DXA) may not accurately reflect actual muscle mass, but a new technique using dilution of deuterium-labelled creatine may prove to be superior in clinically diagnosing sarcopenia. Currently, a consensus has not been reached on the clinical outcome assessments that can be used by regulatory agencies to judge the effectiveness of drugs for sarcopenia.
A number of potential interventions are being explored to treat sarcopenia in older people, but no drugs are currently approved for this condition. The antidiabetic drug metformin shows promise in preventing many age-associated conditions, but appears to blunt the benefits of exercise on muscle. Senolytic drugs, which clear senescent cells, may improve muscle repair following injury preferentially in older individuals.
Sugar-sweetened beverage consumption in relation to diabetes and cardiovascul...My Healthy Waist
By Frank B. Hu, MD, PhD Professor of Nutrition and Epidemiology Harvard School of Public HealthChanning Laboratory, Harvard Medical School and Brigham and Women’s Hospital
Targeting abdominal obesity in diabetology: What can we do about it?My Healthy Waist
By Luc Van Gaal, MD, PhD, Professor of Medicine, Antwerp University Hospital, Faculty of Medicine, Department of Diabetology, Metabolism & Clinical Nutrition, Antwerp, Belgium
Austin Journal of Obesity & Metabolic Syndrome is an international scholarly peer reviewed Open Access journal, aims to promote the research in all the related fields of Metabolic Syndrome.
Austin Journal of Obesity & Metabolic Syndrome is a comprehensive Open Access peer reviewed scientific Journal that covers multidisciplinary fields. We provide limitless access towards accessing our literature hub with colossal range of articles. The journal aims to publish high quality varied article types such as Research, Review, Short Communications, Case Reports, Perspectives (Editorials), Clinical Images.
Austin Journal of Obesity & Metabolic Syndrome supports the scientific modernization and enrichment in Metabolic Syndromes research community by magnifying access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed member journals under one roof thereby promoting knowledge sharing, collaborative and promotion of multidisciplinary science.
Despite advances in treatment of bowel cancer, it remains the second most common cause of cancer death in the Western world. Use of drugs or nutritional supplements (chemoprevention) is an attractive strategy for prevention of bowel cancer in combination with other modalities such as population screening and endoscopic surveillance, particularly if the chemoprevention agent is safe, well tolerated and cost effective. This webinar describes existing evidence that omega-3 fatty acids have activity against bowel cancer. Recent completed and ongoing clinical trials of EPA for primary prevention of bowel cancer and prevention of metastatic disease are described. Current thinking about how omega-3 fatty acids might work against bowel cancer are also explained.
Should we screen for and treat childhood dyslipidemia?
The Rationale for ASCVD Prevention by Primordial and Primary Strategies
Pediatric guidelines
Selective Screening
2Treatment algorithm of childhood dyslipidemia
-8 years & 12-16 years
Dyslipidemia and lipid lowering-therapy {LLT}
in women through the course of life. Lipid loering drug safety profile .Aging is associated with an increasing burden of morbidity, especially for CVDs.
Elderly population should be screened for
Main CV risk factors :
T2D , HTN , Smoking , Dyslipidemia & Obesity
Comorbidities : CKD
Geriatric conditions: Functional Impairment
From Pregnancy to Menopause: Studies of Physical Activity, Behavior, and Ener...InsideScientific
Join Sharon Ladyman, PhD and Vicki Vieira-Potter, PhD as they present applications of rodent metabolic phenotyping with a focus on the effects of hormones and pregnancy on daily activity in mice.
A reduction in voluntary physical activity during pregnancy in mice is mediated by prolactin
Sharon Ladyman, PhD
Pregnancy is an energetically demanding challenge for the mother and as such, pregnant females undergo numerous metabolic adaptations to meet these demands, including increased food intake and a rapid lowering of energy expenditure and physical activity levels. A particularly striking example is a profound reduction in voluntary running wheel activity (RWA) that occurs as soon as mice become pregnant. We hypothesized that prolactin, one of the first hormones to increase in response to mating in rodents, drives the pregnancy-induced suppression of physical activity levels.
Neuronal and Metabolic Pathways Influenced by Sex Hormones
Vicki Vieira-Potter, PhD
Estrogen-sufficient females are more physically active than males and are protected against adipose tissue and systemic metabolic dysfunction. The mechanisms are not fully understood, but we demonstrate that ovarian removal causes significant mRNA changes in the nucleus accumbens (NAc) brain region (i.e., the reward center), which correlate significantly with physical inactivity. We hypothesize that sex differences in the NAc may help explain differences in physical activity and metabolism.
Obesity is very serious and concerned problem these days. Despite availability of many drugs in market to treat
obesity, no single drug is ideal for treating all sorts of problems caused by obesity. The obesity models available
for inducing obesity are by using chemicals and high fat diet. Wistar albino rats were used to study anti-obesity
activity of methanolic extract of Tricholepisglaberrima plant aerial parts at doses 100 mg/kg p.o. and 200
mg/kg p.o. against the standard orlistat 50 mg/kg p.o. in models of anti-obesity activity viz. High fat induced
obesity, Monosodium glutamate induced obesity model. The induction of obesity is done by diet (20
grams/animal/day) and Monosodium glutamate (oral). The study period is 28 days for both models. In both
models, the plant showed anti-obesity activity significantly at a dose of 100mg/kg and 200 mg/kgp.o. by
reducing the body weight, fat pads weight, total cholesterol, triglycerides, LDL, VLDL, biomarkers enzymes like
SGOT, SGPT and ALP, whereas significant increase in HDL levels was observed. Further multiple dose preclinical studies and clinical studies have to be carried out for proving for human obesity treatment.
The biological activities of methanolic extract of
Tricholepisglaberrima observed in this study
strongly indicated their great potential as anti-obese
and obesity associated complications like
hyprlipidemia. Oral administration of extracts
reduced the level of circulating lipids significantly,
resulting in the decrease of body weights in various
animal models of obesity bearing close
resemblance to human obesity. Extract appear to
show such activities by modulating the lipid
metabolism through the decreased activity in
lipogenesis or by inhibition of pancreatic lipase
activity.
The methanolic extract of aerial parts of
Tricholepisglaberrima at a dose of 200mg/kg b.w.
p.o. significantly reduced total cholesterol,
triglycerides, LDL, VLDL, biomarkers enzymes
like SGOT, SGPT and ALP, whereas significant
increase in HDL levels was observed.
Phytoconstituents like saponins, tannins and
flavonoids in METG may be responsible for its anti-obesity and anti-hyperlipidemic activities by
multiple actions.
Apart from anti-obesity and anti-hyperlipidemic
agent, It may also act as hepatoprotective agent due
to possessing significant reduction in SGOT, SGPT
and ALP levels and significant increase in HDL
levels respectively.
Thus it can be said that METG is effective in
ameliorating abnormalities in lipid profile and fat
accumulation in rats and results provides useful
information for the clinical research that this plant
can be used as herbal drug in the treatment of
obesity and hyperlipidemia. Further studies on this
extract may be focused on the possible mechanism
of action, isolation, characterization and
purification of active constituents which is
responsible for anti-obesity and anti-hyperlipidemic
activities.
2013 Cancer Survivorship Conference at Jefferson University Hospitalsjeffersonhospital
Jefferson's Cancer Survivorship Program will help you understand what it means to be a cancer survivor and what to expect from your cancer diagnosis, treatment and follow-up care. This Program is for current patients, cancer survivors and loved ones who have lived with a cancer diagnosis or have undergone cancer treatment at Jefferson.
Think Earth: Water Pollution, by Saugata DattaNathan Cone
This is the PowerPoint prepared by Dr. Saugata Datta (UTSA) for Texas Public Radio's Think Earth event held on October 7, 2022. The slide presentation focuses on water pollution, and matches with the audio on this page: https://www.tpr.org/tpr-events-initiatives/2022-09-28/think-earth-pollution
This is the PowerPoint prepared by Dawn Davies (Hill Country Alliance) for Texas Public Radio's Think Earth event held on October 7, 2022. The slide presentation focuses on light pollution, and matches with the audio on this page: https://www.tpr.org/tpr-events-initiatives/2022-09-28/think-earth-pollution
This is the PowerPoint prepared by Diane Rath (AACOG) for Texas Public Radio's Think Earth event held on October 7, 2022. The slide presentation focuses on air pollution, and matches with the audio on this page: https://www.tpr.org/tpr-events-initiatives/2022-09-28/think-earth-pollution
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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
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
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
The hemodynamic and autonomic determinants of elevated blood pressure in obes...
I'm Getting Older! Is there a pill for that? By Dr. Dean Kellogg
1. “Come on, Doc! I’m
getting older! Is there
a pill for that?
Dean L. Kellogg, Jr., MD. Ph.D.
Departments of Medicine and Physiology
University of Texas Health Science Center
and
Geriatric Research, Education, and Clinical Center
Audie L. Murphy VA Hospital
2. The Aging and the Geriatric Population
A Wide Spectrum
7. The Quest for ANTI-Aging Pills……
NIA’s Intervention Testing Program
PURPOSE:
To identify nutritional and pharmaceutical interventions
(already FDA approved) that could be safely employed
to extend the lifespan and healthspan of mice
10. •Acarbose-greater effect in males with small
effect in females-but had to be started in youth
•Rapamycin-greater effect in females-could be
started on ‘old’ mice’
2 Agents that extend lifespan in both
MALE and FEMALE laboratory
animals
13. Moai
Dig into the soil of
Rapa Nui and find
that there is more
than meets the eye!
RAPAMYCIN
(Sirolimus)
14. ITP: Mice on Rapamycin are “Younger”
in activity levels and coat appearance
Control Female RAPA Female
Control Male RAPA Male
ALL
Dead
9-14%
Lifespan
increase
Activity level
maintained in
males
RAPA effects
observed if
started late in
life
15. FDA Approved Uses Of
Rapamycin in Humans
• Rapamycin is FDA approved for use as an
immunosuppressive drug in preventing transplant rejection,
with drug eluting stents to limit coronary artery re-stenosis,
and for lymphangioleiomyomatosis.
• Rapalogs (drugs like rapamycin) are FDA approved for use
as cancer treatments.
• Most human studies of RAPA involved transplant patients
who take a combination of immunosuppressive drugs thus
interpretation of RAPA safety and effects are difficult.
16. Anti-aging Use of Rapamycin in
Healthy Humans
(Science, News & Analysis, 2013)
• Some researchers say NO.
• “Rapamycin leads to insulin resistance—a precursor of diabetes—in
mice and humans, and transplant recipients have developed
diabetes.”
• “I’d be very hesitant to be a participant” in a clinical trial, Miller
says.
• Some researchers say YES.
• “We don’t have a huge body of evidence of its effects in a healthy
older adult.”
IS RAPAMYCIN SAFE TO GIVE TO HEALTHY OLDER
PERSONS?
17. Inclusion Criteria
-Subjects all in good health with all chronic diseases
(hypertension, coronary artery disease, etc.)
clinically stable.
-AGE 80-95 (Phase 1)
-AGE 70-95 (Phase 2)
•Participants on therapy (either Rapamycin 1mg qD or
placebo) for the 4 months (Phase 1) or 2 months (Phase 2).
•Added RAPA or placebo to other medications subjects
were already taking
Study Design
18. Assessment of Rapamycin SAFETY
• Physical examinations
• Clinical blood work
• Urinalysis
• Oral Glucose Tolerance Tests
• EKG
• Self-reported side-effects
• Pts called on weekly basis
19. IMMUNOLOGICAL TESTS
Rapa improved antibody responses in older mice!
– PHASE 1 -Tests on Immunity
• Hepatitis B naïve participants are immunized with the hepatitis B
vaccine. Humoral (antibody titer) and cellular (T cell proliferation)
responses are assessed.
– PHASE 2 -Tests on Immunity
• Participants are immunized with the Flu vaccine. Humoral (antibody
titer) and cellular (T cell proliferation) responses are assessed.
– Tests on Inflammation
• Immune parameters characteristically altered by aging are
assessed. These include: i) serum cytokine levels; ii) variety of
white blood cell (B cell and T cells) studies.
21. COGNITIVE TESTS
• EXIT (Executive Interview 25-which
includes letter fluency)
• SLUMS (St. Louis University Mental Status
exam) includes memory test, digit span, and
animal fluency
• TAPS (Texas Assessment of Processing
Speed) a digit/symbol coding test available
in alternate forms to eliminate learning
effects
23. A B C
D E F
G H I
J K L
Pre Post Pre Post
PLACEBO RAPA
4.8
4.4
4.0
3.6
Albumin
Serumconcentration(g/dL)
Pre Post Pre Post
PLACEBO RAPA
4.8
4.4
4.0
3.6
Albumin
Serumconcentration(g/dL)
Weight
Weight(kg)
Pre Post Pre Post
PLACEBO RAPA
70
80
90
100
110
Weight
Weight(kg)
Pre Post Pre Post
PLACEBO RAPA
70
80
90
100
110
White blood cell count
WBCx103/μl
Pre Post Pre Post
PLACEBO RAPA
4
5
6
7
White blood cell count
WBCx103/μl
Pre Post Pre Post
PLACEBO RAPA
4
5
6
7
300
200
100
Triglycerides
Triglyceridesinserum(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
300
200
100
Triglycerides
Triglyceridesinserum(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
Low density lipoprotein
LDLconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
75
100
125
150
Low density lipoprotein
LDLconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
75
100
125
150
High density lipoprotein
HDLserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
30
50
70
High density lipoprotein
HDLserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
30
50
70
Serum protein
Serumprotein(g/dL)
Pre Post Pre Post
PLACEBO RAPA
6.5
7.0
7.5
Serum protein
Serumprotein(g/dL)
Pre Post Pre Post
PLACEBO RAPA
6.5
7.0
7.5
Hemoglobin A1c
HgbA1c(percent)
Pre Post Pre Post
PLACEBO RAPA
5.0
5.5
6.0
6.5
Hemoglobin A1c
HgbA1c(percent)
Pre Post Pre Post
PLACEBO RAPA
5.0
5.5
6.0
6.5
Platelets
Pre Post Pre Post
PLACEBO RAPA
150
200
250
Plateletsx103/μl
Platelets
Pre Post Pre Post
PLACEBO RAPA
150
200
250
Plateletsx103/μl
Calcium
Calciumserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
9.0
9.5
10.0
Calcium
Calciumserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
9.0
9.5
10.0
Hematocrit
Hematocrit(%)
Pre Post Pre Post
PLACEBO RAPA
35
40
45
Hematocrit
Hematocrit(%)
Pre Post Pre Post
PLACEBO RAPA
35
40
45
120
110
100
90
80
Fasting blood glucose
Glucoseserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
120
110
100
90
80
Fasting blood glucose
Glucoseserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
A B C
D E F
G H I
J K L
Pre Post Pre Post
PLACEBO RAPA
4.8
4.4
4.0
3.6
Albumin
Serumconcentration(g/dL)
Pre Post Pre Post
PLACEBO RAPA
4.8
4.4
4.0
3.6
Albumin
Serumconcentration(g/dL)
Weight
Weight(kg)
Pre Post Pre Post
PLACEBO RAPA
70
80
90
100
110
Weight
Weight(kg)
Pre Post Pre Post
PLACEBO RAPA
70
80
90
100
110
White blood cell count
WBCx103/μl
Pre Post Pre Post
PLACEBO RAPA
4
5
6
7
White blood cell count
WBCx103/μl
Pre Post Pre Post
PLACEBO RAPA
4
5
6
7
300
200
100
Triglycerides
Triglyceridesinserum(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
300
200
100
Triglycerides
Triglyceridesinserum(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
Low density lipoprotein
LDLconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
75
100
125
150
Low density lipoprotein
LDLconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
75
100
125
150
High density lipoprotein
HDLserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
30
50
70
High density lipoprotein
HDLserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
30
50
70
Serum protein
Serumprotein(g/dL)
Pre Post Pre Post
PLACEBO RAPA
6.5
7.0
7.5
Serum protein
Serumprotein(g/dL)
Pre Post Pre Post
PLACEBO RAPA
6.5
7.0
7.5
Hemoglobin A1c
HgbA1c(percent)
Pre Post Pre Post
PLACEBO RAPA
5.0
5.5
6.0
6.5
Hemoglobin A1c
HgbA1c(percent)
Pre Post Pre Post
PLACEBO RAPA
5.0
5.5
6.0
6.5
Platelets
Pre Post Pre Post
PLACEBO RAPA
150
200
250
Plateletsx103/μl
Platelets
Pre Post Pre Post
PLACEBO RAPA
150
200
250
Plateletsx103/μl
Calcium
Calciumserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
9.0
9.5
10.0
Calcium
Calciumserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
9.0
9.5
10.0
Hematocrit
Hematocrit(%)
Pre Post Pre Post
PLACEBO RAPA
35
40
45
Hematocrit
Hematocrit(%)
Pre Post Pre Post
PLACEBO RAPA
35
40
45
120
110
100
90
80
Fasting blood glucose
Glucoseserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
120
110
100
90
80
Fasting blood glucose
Glucoseserumconcentration(mg/dL)
Pre Post Pre Post
PLACEBO RAPA
CLINICAL
LAB TEST
RESULTS:
Blood chemistry
and Red Blood
Cells
•Reduced H/H
and indices within
RAPA and
between Groups
29. Subject and Family Comments
- “I couldn’t tell I was taking anything different.”
-“We saw a slight increase in his cognitive and memory
abilities on the med. Not marked but a very slight
increase.”
- “His overall disposition seemed better.”
-“He was more frisky on the rapamycin…..can you give
him some more?”
30. POSSIBLE ADVERSE REACTIONS
• Stomatitis (2 pts-1 Rapa and 1 placebo-resolved so
continued participation)
• Diarrhea (2 pts-ended participation)
• Acneform Facial Rash (1 pt-ended participation)
ALL POTENTIAL ADVERSE REACTIONS PREVIOUSLY
REPORTED IN TRANSPLANT PATIENTS
31. A Randomized Control Trial to Establish the Feasibility and Safety
of Rapamycin Treatment in an
Older Human Cohort: Immunological, Physical Performance, and
Cognitive Effects
Ellen Kraiga,b,*, Leslie A. Linehanb, Hanyu Lianga, Terry Q. Romoa,g, Qianqian Liuc,
Yubo Wue, Adriana D. Benavidesd, Tyler J. Curiela,e, Martin A. Javorsa,f, Nicolas Musia,e,g,
Laura Chiodog, Wouter Koekb,f, Jonathan A.L. Gelfonda,c, and Dean L. Kellogg, Jr.a,e,g
CONCLUSION:
Rapamycin is just as safe to use in healthy
older persons as transplant patients….but
what about benefits?
33. The Search for Rapamycin Benefits:
Cardiovascular Effects in 70+yo Persons
Initial Results:
IMPROVED CARDIAC
FUNCTION?
Measured by cardiac MRI
in 6 older persons
pre post
0
50
100
150
Flow: Transmitral Total Volume
ml
p = 0.0211
paired, parametric
41
42-no data
43
44
45
46