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Evidence Based Medecine Flashcards

1
Q

Systems biology

A

The systematic study of complex interactions in biological systems/ looking at the whole puzzle rather than one piece

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2
Q

Goal of systems biology

A

To better understand the whole process that happens in a biological system, opposite of usual reductionist approach

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3
Q

How does systems biology study biological systems

A

By perturbing/disturbing them either biologically, genetically or chemically and monitoring the gene and informational pathway responses and ultimately formulating the mathematical models that describe the structure of the system and it’s response to individual perturbations

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4
Q

Emergent properties

A

Properties of an entire system or organism that are not necessarily evident/obvious from just looking at individual components
“The whole is greater than the sum of its parts”
Ex personalities neuron

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5
Q

Levels of systems biology

A

Genes, proteins, tissues, organs and organ systems

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6
Q

Purpose of systems biology

A

Predict outcomes and responses in a living system (uses bioinformatics)

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7
Q

Bioinformatics

A

Complex mathematical modelling used to predict outcomes and responses
Field that develops tools to understand data

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8
Q

Omics

A

Looks at both genome and other components

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9
Q

Geneomics

A

Study of an organisms complete set of DNA

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10
Q

Prenomics

A

Study of all the set of proteins produced within a biological unit (organ, organism, organ system)

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11
Q

Metabolics

A

Study of metabolism within a givin unit(cell, tissue, organ, organism)

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12
Q

Reduction vs integration

A

Systems biology is abt putting together rather than taking apart, integration rather than reduction

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13
Q

Isolated models

A

Molecules, cells, organs or tissue
Reduction
Exquisite control over experimental conditions
Can explain mechanisms

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14
Q

Integrated models

A

Whole body or organism approach
Less control over variables
Viewed as less
More important

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15
Q

Biological concepts of health from the systems biology perspective of the adult human

A
  1. Each adult human can be considered as a unique biological system
  2. The adult human biological system has a control and communication network (CCN) that coordinates our functions (networking)
  3. The CCN controls and processes information flow in the adult human
  4. The CCN is the focal point of health in the adult human
  5. Aging and disease are processes which represent compromised functions/structure of the CCN
  6. Systems biology is an integrated approach to health disease and aging and should enhance medical and healthcare practice
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16
Q

Emergent property

A

A collection or complex system has but which the individual members do not have

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17
Q

7 characteristics of life

A
  1. Responsiveness to environment
  2. Growth and change
  3. Ability to reproduce
  4. Have a metabolism and breath
  5. Maintain homeostasis
  6. Be made of cells
  7. Pass traits to offspring
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18
Q

Robert Sapolsky

A

Neurologist and primatologist
Explores long term health impacts of stress

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19
Q

Components of the CCN

A

(Which all interact)
- the central nervous system
- the peripheral nervous system
- the endocrine system
- support and defence system

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20
Q

Properties of the CCN

A

1.Controls and coordinates the function of all physiological systems and individual organs including itself
2. It’s always on
3. It is distributed throughout the entire body
4. Each component of the network has multiple functions
5. Information flow is chemical based via cell to cell connection

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21
Q

Inputs of health disease and aging

A

The CCN is the integrator of inputs of health disease and aging
genetics, 🧬
environment ☀️
lifestyle 🏋️

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22
Q

Seven dimensions of human health

A

Spiritual
Physical
Mental
Emotional
Environmental
Social
Occupational

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23
Q

Examples of diseases resulting from diminished/abnormal function of CCN

A

Diabetes, atherosclerosis
Cancer, autoimmune diseases
Depression, ADHD
Have primary portion of CCN affected

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24
Q

Examples of reduced function CCN with aging

A

Impaired memory, Alzheimer’s, (central nervous system)
Diminishes touch sensitivity (peripheral)
Impaired wound healing (support and defence)

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25
P4 Medecine
Personalized, predictive, preventative, participatory Informed by each person’s unique, genetic and genomic & environmental information
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Research in medecine and healthcare
-experimental models in health research - human studies, basic experimental designs (non clinical, clinical) -evidence based medecine - new dimensions in medecine and healthccare
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Types of models for human medical and health research
A- simulations with math models/computer (in silico) B- in vitro (in glass) and ex vitro (out of the living) models C- Animal models D- Human participants
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Purpose of in vitro and exvitro research
-allows for more controlled experimental conditions (isolating something without system) - Understanding fundamental mechanisms
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Examples of in vitro and ex vitro research
Isolated and beating heart, culturing cells, growing skin, transformed cancer cells
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Nematodes and fruit flies
Animal models for research Both used extensively to study genetics
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C. Elegans
Nematode (40% genetic homology to human) Easy to study Cheap Short life cycle Self fertilizers Can be frozen, thawed and remain viable Transparent. Facilitates study of cell differentiation
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Research examples c elegans
Embryonic metabolism Using fluorescent light to follow digestion of a nutrient, synthesis of proteins, cholesterol etc.
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Drospholia Melangaster
Fruit fly with 65% genetic homology to human
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Why would drispholia melangaster be used in neuropharmacy research
Life cycle and development are very sensitive to environmental conditions Can be Used in neuropharmacy research to study the effects of drugs and alcohol
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Laboratory rats
Animal models Very social and intelligent Often used to study lifestyle effects on metabolism (diets, exercise, drugs) Tend to take a more severe approach than with humans ex 50% fat diets, 10hrs/week except code Not good model for human infant nutrition and metabolism
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Laboratory mice
Many different strains Used to study lifestyle effects on metabolism, results may differ from rats Can’t assume one model = another
37
Why are mice a popular animal model for research?
Due to ease of applying recombinant DNA technology (knockout a gene, overexpress a gene) Can test importance of a single protein
38
Why can’t we assume rats = mice
Results may differ Takes longer to make a mouse insulin resistant on a high fat diet than rats Muscle metabolism can differ(less impairments of glucose uptake with mice with high fat diet vs rats Mitochondria adapt less robustly with exercise in mice vs rats
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Laboratory swine
animal models Piglets are the Best primative models for human infant development and metabolism Used to study organ transplant (xenografts)
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Laboratory primates
Closest model you will get to represent the human BUT Ethics? Cost? Very little primate research in Canada more in USA
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TYPE of research done on laboratory primates
Human pathologies (AIDS etc) drug abuse Transplantation
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Basic experimental design of humans and healthcare research
Non-clinical studies (non intervention) Clinical studies (intervention)
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Non clinical studies
No intervention No medicinal / lifestyle treatment given Cannot predict or prove cause and effect of a medicinal substance Only predicts associations/correlations
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What are most common type of non clinical study
Epidemiological (diseases)
45
Clinical studies
Intervention Any investigation involving participants that evaluates the effects of one or more health related interventional health outcomes A medicinal or lifestyle treatment and or control substance and placebo are given
46
What are the gold standard for human healthcare research
Double-blind, placebo controlled clinical trials
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Who reviews research for human clinical trials
Institutional ethics review boards
48
Tests performed to test a new drug’s safety
1. Preclinical 2. Phase I clinical trial 3. Phase II clinal trial 4. Phase III clinical trial 5. After approval
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Preclinical
Animal studies before testing on human
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Phase I clinical trial
Is the drug safe for humans? Small group of people (10s)
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Phase II clinical trial
Does the drug work for its intended purpose? Uses larger group (100s) Check safety, figure out dose
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Phase III clinical trial
How does the drug compare to other available treatments? Even larger group (1000s)
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After approval
Ongoing assessment of long term use, benefits and risks
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Cochrane reviews
A database of systemic reviews and meta-analyses which summarize and interpret results of medical research
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RCTs
Randomized controlled trials Gold standard of human medicine research Interventions Should be blinded
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Lowest to highest relevance to clinical setting types of research
Insilico research (lowest) In vitro Animal model Case control studies (no intervention) Cohort survey studies Randomized control trials Critically appraised papers “. “. Topics Systematic reviews
57
Evidence based medicine outcome
Takes into account Patient values Clinical data Research evidence To formulate the optimal decision
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New dimensions in medical and healthcare practice
A. Evolutionary medecine B. Integrative medecine C. Collective medicine D. Enhancement medicine
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Evolutionary medicine
Aka Darwinian medicine The application of modern evolutionary theory to understanding healthcare and disease
60
Examples of evolutionary medecine
Paleo diet- is our modern diet unhealthy? We get little physical activity- is this a sign we’re injured and need to slow down our metabolism We all have fight or flight response but what if it’s always on
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Integrative medicine
Treats the whole person, including all aspects of lifestyle, not just the symptoms Holistic medecine Emphasizes therapeutic relationship between practitioner and patient, is informed by evidence and makes use of all appropriate therapies Ex acupuncture, aromatherapy
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Collective medicine
Recognises human and animal health and mental health are inextricably linked
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One health
Term applied to connections among the health of humans animals and the environment
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Enhancement medicine
Botox, liposuction, fertility drugs, laser vision, steroids
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Nootropics
Type of enhancement medicine (Brain enhancers) Dopaminergenics Cholinergic stimulants Natural compounds (omega 3s?)
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Trajectory
Growth, development and aging (Years, decades)
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Rhythms
Maintenance/repair, other processes (Days weeks months)
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Homeostasis or balance (time)
Maintenance of steady state (Seconds minutes, hours)
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Energy and information flow (time)
Action potentials, enzymatic reactions (Milliseconds, microseconds)
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Lifespan
How long we live
71
Healthspan
How long we live healthily, independent lifestyle
72
Average lifespan factors
Weight, build, exercise, stress, sleep, education level, blood, total cholesterol, blood pressure, smoking, age of parents/grandparents
73
Bio markers
Things to measure objectively Then we can track aging/disease process Indicates the biological state of an organism
74
Sarcopenia
Age related muscle mass loss Up to 1% after age 40
75
Requirements of a bio marker
Reflect the normal healthy function or disease process or predict the risk of future development of disease Have a predictable range across an identifiable category of individuals or must be routinely monitored over time within each individual Have methods available for accurate and precise measurement
76
How to use bio markers to diagnose?
Most markers have normal ranges and if patients value is too high or low it can be used to assess a risk for a disease or diagnose one When you are outside of a reference range
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Chronobiology
The study of timescales and cycles in biology Branch of biology concerned with natural physical rhythms
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The 3 Biological rhythms
Ultradian Circadian Infradian
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Ultradian rhythm
Less than 24 hours Ex. Appetite ghrelin, cortisol
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Circadian
24 hour biological rhythm Ex. Sleep, cortisol lowest at midnight, peak in the morning
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Infradian rhythm
Biological rhythm More than 24 hours Ex. Menstrul cycle
82
Diurnal variation/circadian rhythms
Based on 24 hour cycle Involved in all phsiological processes Controlled by peripheral clocks that are governed by a master or central clock Controls gene expression, regulation of enzyme activities, neural function, hormone secretion
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What do circadian rhythms coordinate
Sleep, nutrient supply, activity patterns. With metabolic patterns required at different stages of the day
84
Disruption of circadian rhythms outcomes
Leads to a wide spectrum of health problems and premature aging Elevated inflammatory cytokines Gastrointestinal function Obesity Metabolic syndrome
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When is wound healing fastest and why
In the morning because our cells evolved to be able to heal wounds more effectively at the biological time they are most likely to occur
86
Suprachiasmatic nucleus
The master or central clock which keeps time based on light signals from the retina Nearly every cell in the body has a subsidiary (peripheral) clock that coordinates its metabolism with the rest of the body (slave to central clock)
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What controls the molecular clock
Not very understood Entrained by light and dark cycles Still intact in most blind individuals Chemical signals involved are not clear (prob melatonin)
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Health implications of f disruptions of circadian rhythms
Shift workers tend to experience a greater incidence of Heart attacks Obesity, diabetes, cardiovascular complications Cancer Alzheimer’s disease
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Late chronotypes risks
Night owls More likely to suffer from mental stress than smokers
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Examples of circadian rhythm relevant to health
1. Heart attack risk is greater mid morning no clear answer yet (Could be protein Klf15) affect the K+ efflux in heart or caffeine, stress, combination of factors 2. There is a two centimetre diurnal/daily variation in height
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Limitation of using height as a bio marker for osteoporosis
It varies Timing of measurements need to be standardized Needs to be measured over time in each Individual Doesn’t change much during disease Can’t directly predict the disease state
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What is best bio marker for osteoporosis
DEXA Dual energy X-ray absorptionometry determines bone mineral density as a more definite approach
93
When we need calcium for our non bone tissues where do we get it
We obtain it from dissolution of the minerals in bone
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When we have excess calcium in the blood stream where does it go
we deposit calcium in the bone Bone acts as a buffer for calcium levels
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Age of peak bone mass
20-30
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When we measure bone density with dexa what are we estimating
The amount of x-ray absorbing dense material, hydroxyapatite that is packed in the extracellular space of the bone
97
Hydroappetite
The amount of x-ray absorbing dense material that is packed in the extracellular space of the bone

BIOL1080 (3 decks)

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