Mitochondrial disorders and cerebral folate deficiency are increasingly recognized as prevalent in autism spectrum disorder. The presentation will review evidence of mitochondrial dysfunction in ASD, including biomarkers and altered energy metabolism. Cerebral folate deficiency is also discussed, where an autoantibody against the folate receptor can block folate transport to the brain. Symptoms of cerebral folate deficiency and conditions associated with both ASD and this deficiency will be covered. Treatment of mitochondrial disorders focuses on prevention of regression, secondary effects, diets, and addressing cerebral folate deficiency with folinic acid supplementation. Over half of children with ASD from specialty clinics tested positive for the folate receptor autoantibody.
A review of epilepsy in the elderly, the etiopathogenesis, clinical challenges, diagnosis, use of antiseizure drugs and outcomes. Also the various special considerations in managing elderly patients with epilepsy.
A review of epilepsy in the elderly, the etiopathogenesis, clinical challenges, diagnosis, use of antiseizure drugs and outcomes. Also the various special considerations in managing elderly patients with epilepsy.
Presentation that looks at the current clinical research on possible causes of Autism Spectrum Disorders. Includes brief mention of the use of Homeobotanicals in secondary symptom treatment management.
PDCD is an abbreviation for pyruvate dehydrogenase complex deficiency, a genetic mitochondrial disorder in children which is frequently associated with lactic acidosis and neurological/neuromuscular symptoms.
Presentation that looks at the current clinical research on possible causes of Autism Spectrum Disorders. Includes brief mention of the use of Homeobotanicals in secondary symptom treatment management.
PDCD is an abbreviation for pyruvate dehydrogenase complex deficiency, a genetic mitochondrial disorder in children which is frequently associated with lactic acidosis and neurological/neuromuscular symptoms.
WFA's Girls of Promise program is a series of one-day conferences hosted at universities and designed to introduce eighth-grade girls to careers in ESTEM (economics, science, technology, engineering, and math) fields and amazing women role models at a critical time in their development.
Conferences follow one of two schedules. This slideshow is of Schedule B.
Crash analysis using 3 different ways including Point Tracking, accelerometers and analytical method, and understanding the crash concept. also error accounting.
Inborn errors of metabolism- focusing on its predominant adult onset forms, neurological perspective, clinical & biochemical approach to diagnosis, and neuroimaging findings.
-What are Standards of Care and why does the Mito community need such standards?
-Review the MMS's Standards of Care for Mitochondrial Disease and how they were developed.
-Outline upcoming MMS projects.
What you should know about genetic testing for mitochondrial disordersmitoaction
Amanda Balog, CGC, Senior Genetic Counselor, Mitochondrial and Metabolic Genetics, of GeneDx discusses: "What You Should Know About Genetic Testing for Mitochondrial Disorders."
Richard Frye, MD, PhD, FAAP, FAAN, CPI, will discuss:
*The enteric (gut) microbiome has an important influence on health and disease states in humans.
* The enteric microbiome influences the human host using chemical mediators, some of which can directly affect mitochondrial function
* Short chain fatty acids produced by gut bacteria not only modulate mitochondrial function and cellular regulatory pathways, but can also be used as mitochondrial fuels.
Exercise and nutrition in Mitochondrial Diseasemitoaction
Mark Tarnopolsky, MD, PhD, FRCP,
Depts. of Pediatrics (Neuromuscular + Neurometabolic Disease) and Medicine (Cell Biology/Metabolism, Neurology and Rehabilitation), McMaster University, Hamilton, CANADA
Diagnostic Testing for Mitochondrial Diseasemitoaction
Review traditional diagnostic pathways
Discuss newer testing that has become available in recent years
Review new approaches to attempt to shorten time to diagnosis and increase precision
How to Build Your Mitochondrial Medical Homemitoaction
Topics include:
The importance of a medical home for a mitochondrial disease patient.
Definition of a medical home.
How to establish a medical home.
Why a medical home is an important component of good patient advocacy.
Tips on maintaining a healthy medical home relationship.
Wees will describe theses issues primarily from a pediatric perspective, but she will give adult examples as well.
Wees is a patient advocate with Empowered Medical Advocacy. She assists parents and caregivers each week in navigating toward improved quality of life for their child and their families.
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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
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
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MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
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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
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Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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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.
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Mitochondrial Disorders and Cerebral Folate Deficiency in Autism Spectrum Disorder
1. Mitochondrial Disorders and
Cerebral Folate Deficiency in
Autism Spectrum Disorder
Richard E. Frye, M.D., Ph.D.
Director of Autism Research
Associate Professor of Pediatrics
Arkansas Children’s Hospital
2. The Rise in Autism
CDC estimates the prevalence of Autism Spectrum
Disorder is as high as 7 per 1,000 or 1 in 150!
Debate over whether this is due to a shift in diagnosis
or a true rise in the number of cases. Does it matter??
Either way there are a lot of children that need care.
6. The Etiology of Autism: More than Genetic Disorders
Estimated Prevalence of Genetic Abnormalities
Cytogenetic Abnormalities 5%
Fragile X 5%
Rett Syndrome (Females only) 5% (~1% overall)
Chromosomal Microarray 10%
Total 21%
This leaves about 79%+ children with ASD without an
identified genetic diagnosis.
.
(Schaefer and Mendelson, Genetics in Medicine, 2008)
7. New Understanding of Autism
• Autism is defined as a collection of symptoms
• Symptoms of Autism are associated with
underlying medical disorders in may cases
• In many cases, Autism is a multisystemic disorder
with primary neurological manifestations.
• The rise in Autism cases is probably due to complex
interactions between genetics, environment and
the dynamics of physiological development.
8. Mitochondrial Dysfunction and Cerebral
Folate Deficiency/Insufficiency is becoming
recognized as highly prevalent in autism
spectrum disorder
This talk will review
– Evidence for Mitochondrial Dysfunction in Autism
Spectrum Disorder
– Biomarkers for mitochondrial dysfunction
– Importance of cerebral folate deficiency/insufficiency
and the folate receptor autoantibody
– How cerebral folate deficiency/insufficiency is
diagnosed and treated
12. Biomarkers of Abnormal
Energy Metabolism
in Children with
Neurodevelopmental Disorders
A review of metabolic studies from 133
consecutive patients evaluated in a
medically-based autism clinic
Examined a wide range of metabolic markers
in children with autism including markers of
fatty-acid oxidation disorders
13. 6 Biomarkers Reviewed
4 Groups with high prevalence Identified
Lactate, Alanine-to-Lysine & Acyl-Carnitine 34.3%
with AST 53.0%
14.
15. Acyl-Carnitine Elevation Group
3-hydroxy-3-methylglutaryl is a metabolite of Acetyl-CoA, the
starting point of the citric acid cycle. Suggests that the citric acid
cycle is working inefficiently. It can also be seen in 3-hydroxy-3-
methylglutaryl-CoA lyase deficiency but at much higher levels.
17. Altered brain phospholipid and acylcarnitine profiles in propionic acid
infused rodents: further development of a potential model of autism
spectrum disorders. J Neurochem. 2010 Apr;113(2):515-29.
Derrick MacFabe et al.
18.
19. Defining Mitochondrial Disease
Several systematic criteria are used to diagnose mitochondrial
disease.
Here we consider the Morava et al. (2006) criteria which uses
the following findings:
I. Clinical
II. Metabolic and neuroimaging
III. Mitochondrial morphological
Patients are classified into 4 categories:
• Not likely (<=1)
• Possible (2-4 points)
• Probable (5-7 points)
• Definite (>=8 points).
•Score of 3+ suggests a muscle or skin biopsy should be done
20. I. Clinical signs and symptoms, 1 point/ symptom (max. 4 points)
Probably associated Might be associated Probably not
with ASD (% in ASD) with ASD associated with ASD
A. Muscular Muscle weakness Abnormal EMG Ophthalmoplegia†
(max. 2 points) (myopathies) Exercise intolerance Facies myopathica
Rhabdomyolysis
B. CNS Develop delay (100%) Extrapyramidal signs Stroke-like episode
(max. 2 points) Loss of skills (33%) Myoclonus Migraine
Seizures (25%) Pyramidal signs Cortical Blindness
Brainstem abnormal
C. Multisystem GI tract (7-91.4%) Heart Vision
(max. 3 points) Endocrine/growth Kidney Hearing
Familial (10.9%) Hematological
Neuropathy
† Scores 2 points. ‡ Scores 4 points.
EMG = electromyography
(Frye and Rossignol,
Ped Research, 2011)
21. II. Metabolic/imaging studies (max. 4 points)
Probably associated with ASD Might be associated Probably not associated
(% in ASD) with ASD with ASD
Elevated lactate† (17.1- 76.6%) Elevated CSF lactate† Ethylmalonic aciduria
Elevated L/P ratio (27.6%) Elevated CSF protein Leigh syndrome/MRI†
Elevated alanine† (36.0%) Elevated CSF alanine (0%)
Elevated lactate/MRS (11.1%) Urinary TA excretion†
Stroke-like picture/MRI
† Scores 2 points. ‡ Scores 4 points.
L/P = lactate/pyruvate;
TA = tricarbon acid.;
CSF = Cerebrospinal fluid
(Frye and Rossignol,
Ped Research, 2011)
22. III. Mitochondria Morphology (max. 4 points)
Probably associated with Might be associated with Probably not associated
ASD (% in ASD) ASD with ASD
Abnormal mitochondria/EM† COX-negative fibers‡
Reduced COX staining‡ Reduced SDH staining
Ragged red/blue fibers‡ SDH positive blood
vessels†
† Scores 2 points. ‡ Scores 4 points.
COX = cytochrome c oxidase; SDH = succinate dehydrogenase; EM = electron
microscopy
(Frye and Rossignol,
Ped Research, 2011)
23.
24.
25. Weissman et al 2008
Review of 25 children
diagnosed with autism
eventually diagnosed with a
mitochondrial disorder
High rate of non-neurologic
symptoms
High rate of fatigability – 68%
Unusual regression -- 60%
26. Morning Fasting Suspect Pyruvic Acid
CO2 Mitochondrial CMA
CMP LFTs Disorder MitoMet
mtDNA point mutations
Glucose Start Supplements
Lactic Acid L-Carnitine (Carnitor)
Amino Acids Ubiquinol (Douglas Labs)
Ammonia B-Complex (Supra-Nu Thera)
Acyl-Carnitine No Diagnosis
Creatine Kinase If Lab
Urine Organic Acids Muscle Biopsy
Abnormal
Histology
Suspect Repeat to
Electron Microscopy
Fatty Acid Confirm
Electron Transport Chain Studies
Disorder mtDNA Content Studies
RBC Zinc & Copper, Biotin
More Specific Diagnosis
Triglyceride & Cholesterol Panel
Urine Acyl-Glycine & Ketones Testing of Specific Genes
No Diagnosis mtDNA sequencing
Skin Biopsy with Fatty-acid
oxidation and electron transport Specific Therapy
chain studies, MitoMet
27. A New Type of Mitochondrial Disorder:
Complex IV Hyperfunction.
28. Electron Transport Chain Studies
From 14 Children with ASD
and Mitochondrial Disease
defined by Morava et al. criteria
32. Brain growth peaks just after the first year of life. Brain
growth requires energy. A deficit in energy during this
essential time may result in a failure in brain development
37. Treatment of
Mitochondrial Disease
• Prevention of Regression
– Avoid Dehydration
– Avoid Fever
– Avoid Viral Illness
– Avoid Specific Drugs
38. Treatment of Mitochondrial Disease
• Prevention of Regression
28 patients with ASD and mitochondrial disease.
17 individuals had a history of regression
71% (12 of 17) regressed with fever
24% (4 of 17) fever followed vaccination
39. Drug Interactions
• Antibiotics to avoid: • Antibiotics that are probably
– Linezolid and other oxazolidinone okay:
antibiotics – Fluoroquinolones
– Rifampin (Ciprofloxacin, floxin, levaquin),
– Tetracycline – Macrolides
– Chloramphenicol (azithromycin, clarithromycin, ert
hromycin)
– Imipenem
– Cephaloglycin,
– Cephalogycin
– Bactrim
– Beta-lactam (penicillin and
cephalosporin)
• Other substances to avoid :
– Alcohol
– Cigarette smoke
– monosodium glutamate
– Acetaminophen
– Antipsychotics
– Fasting
– Dehydration
– Sleep Deprivation
44. Antibodies to the FR1 (Folate Receptor 1) block folate from
crossing the blood-brain barrier. Since this is an energy dependent
process disorder of energy metabolism will also reduce folate
transport into the central nervous system
(Ramaekers and Quadros, in press)
45. Symptoms of Classic Cerebral Folate Deficiency
(Ramaekers et al., NEJM, 2005)
46. Conditions Associated with Autism and
Cerebral Folate Deficiency
Antibody Mediated Cerebral folate deficiency
• Infantile-onset cerebral folate deficiency
• Low-IQ autism with neurological deficits
Energy Mediated Cerebral Folate Deficiency syndromes
•Mitochondrial encephalopathies (deficits in mitochondrial
function)
Unknown Mechanisms (both mitochondrial and antibody?)
•Rett Syndrome
48. The Expanding Association between
Autism and Cerebral Folate Deficiency
Wide Range of Children with Autism Spectrum Disorder
Energy Mediated Cerebral Folate Deficiency syndromes
• Mitochondrial Complex IV Hyperfunction
(Frye and Naveux, Journal of Pediatric Neurology, 2012)
49. More than half of children with Autism Spectrum Disorder
referred to two autism specialty clinics test positive for
antibodies to the folate transporter (n=93)
Frye et al, Molecular Psychiatry, 2012
50. 75% of children with Autism Spectrum Disorder referred to
two autism specialty clinics test positive for one of the two
antibodies to the folate transporter
Frye et al, Molecular Psychiatry, 2012
51. 44 children with Autism and Positive autoantibodies were
treated with 2mg/kg of folinic acid in an open-label fashion for
a mean of 4 months and compared to a wait list control group
of children with autism and positive autoantibodies.
52. Reduced central nervous system folate results in
decreased de novo purine synthesis which leads to
decrease tetrahydrobiopterin (BH4) production
(Ramaekers et al., Neurology, 2003)