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DOD > Precision Med > Flashcards

Precision Med Flashcards

1
Q

Types of Oral Samples

A 
Whole Saliva (stimulated/unstimulated) 
     > Stimulated - spit into a tube after chewing non flavored gum to stimulae salivation from mainly the parotid glands 
    > Unstimulated - is pretty much just drooling and comes from parotid and sub mandibular

Duct Saliva - from salivary ducts

Gingival Crevicular Fluid - Not a lot of it - taken from a paper point and only end up with 1 micrometer (closely related to blood - more so than saliva)

Mucosal Transudate - Moist and slimy texture of cheeks; mixture of saliva and vascular fluid from small capillaries (take in substances or out from the blood)

Buccal Swabs for DNA testing

Plaque - toxins can reside in dental plaque (fun fact)

Volatiles - volatile molecules present in for example, with cancer or other systemic diseases

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2
Q

Transmission/Diagnostics

A
  • HIV (though proven its not in saliva although a series of proteins in saliva are anti HIV active - one identified and they made a drug out (DMDT-1 protein) HIV in hypotonic solution, it will lyse RBCs AND the virus
  • Strep Throat
  • Flu
  • Herpes
  • Zika
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3
Q

Why develop oral/salivary diagnostic tests?

A
  • Non-invasive
  • Safe
  • User friendly
  • Cost effective
  • Field studies
  • Home testing
  • Special populations
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4
Q

Widely used Oral Tests

A 
HIV
Herpes
Candidiasis
HPV 
Kaposi's sacroma 
Mononucleosis (EBV) 
Flu 
Strep throat
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5
Q

Preventing HIV

A
  • Education
  • Behavior
  • Vaccine
  • Microbicides
  • Test and Treat
  • PrepExposure Prophylaxis (PrEP)
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6
Q

PrepExposure Prophylaxis (PrEP)

A

Oral anti-retroviral provided 70-90% protection

  • approved for high risk MSM populations
  • long-active vaginal rings and injectable products being developed
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7
Q

HIV rapid testing

A
  • Currently excellent screening tests available for antibodies to HIV-1 and HIV-2
  • test results in 20 minutes
  • positive test results require a confirmatory test
  • ideally want a combined screening and confirmatory test
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8
Q

Rapid Screening + Confirmatory Test

A
  • Ideally, want to detect:
    1. anti- HIV antibodies
    2. HIV antigen
    3. HIV RNA
  • Combine screening test with a confirmatory test
  • narrow the seroconversion window
  • less stress on subject with immediate access to care/treatment
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9
Q

4th Generation HIV Test

A
  • Measures antibodies to HIV and p24, a viral antigen
  • First FDA approved test was the Abbotts Architect HIV Ag/ Ab
  • Decreases the seroconversion window to ~12 days
  • important because individuals are 10-20 times more infectious during the early infection
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10
Q

Dealing with the HIV pandemic

A
  • Theurapeutics - HAART
  • Vaccines/microbicides/ PrEP
  • Treatment of opportunistic infections
  • Identification of reservoirs
  • Behavior modification
  • Natural Defenses: Exposed uninfected elite controllers long term non-progressors
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11
Q

Target Analytes

A

HIV- antigen or antibody plus RNA
Malaria - DNA
Zika - Antibody plus RNA

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12
Q

Point of Care (POC) HIv Diagnosis

A
  • Current POC tests are screening which detect antibodies to HIV but require a confirmatory test which takes days-weeks
  • goal is to create a combined screening and confirmatory test using blood or saliva with results in less than 1 hours
  • confirmatory tests use PCR or isothermal amplication (LAMP)
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13
Q

Diagnosis of Malaria

A
  • currently tests rely on blood smears
  • time consuming and requires trained personnel
  • existing POC tests for antigen are insensitive and signal persists
  • POC “Test and Treat” using blood/saliva to detect P. falciparium/P vivax followed by treating all positives
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14
Q

Zika Overview

A
  • A member of the flavivirus genus
  • First isolated from a monkey in 1946 in the Zika forest in Uganda
  • Generally infection is asymptomatic
  • Transmitted by mosquitos and sexual transmission (virus persists in semen)
  • Zika disappears from blood in 7-10 days
  • Persists longer in saliva and urine
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15
Q

Saliva

A 
• Facilitates physiologic functions of: 
    - tasting and swallowing food 
    - antibacterial and antiviral protection of oral 
      structures 
    - tissue lubrication

• Contains enzyme, hormones, antibodies, cytokines, antimicrobial, and other biomarkers

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16
Q

Periodontal Disease

A
  • Most common cause of tooth loss in the world
  • More than 50% of Americans are affected
  • Associated with such systemic diseases such as DIABETES, CARDIOVASCULAR DISEASES, OSTEOPOROSIS, ARTHRITIS, ALZHEIMER’S DISEASE, GASTRIC CANCER
17
Q

Periodontal Disease Progression

A

1) Genetic predisposition
2) Infection
3) Inflammation with tissue degradation
4) Clinical findings of peridontal pockets and alveolar bone loss

18
Q

Personalized Medicine

A
  • Salivary diagnostics is a rapidly evolving discipline with conflicting data and challenges of statistical sensitivity and specificity
  • As research is translated into clinical application, clinicians will use this technology to provide patients with personalized care
19
Q

Microbiome - Initiator Biomarkers

A 
• Bacterial initiators for Periodontal Disease Progression include: 
    - the "RED COMPLEX" pathogens: 
          > Treponema denticola 
          > Porphyromonas gingivalis 
          > Tannerella forsythia

• Other pathogens able to predict PDP:

- Fusobacterium nucleatum 
- Campylobacter rectus 
- Prevotella intermedia
20
Q

Host-Response Inflammatory Mediators/Tissue Degradation Enzymes

A
  • IL-1B
  • MMP-8
  • MMP-9
  • ALT (alanine aminotransferase)
21
Q

Tissue Degradation Enzyme/Microbiome Study

A
  • 18 month longitudinal study
  • P. Gingivalis and P. Intermedia – likely to predict loss of attachment and loss of bone
  • Combination of ALT and P. gingivalis – most likely to predict loss of attachment
22
Q

Microbiome/Host-Response Inflammatory

Mediators/Tissue Degradation Enzymes Study

A

• 100 patients followed for 12 months
• 6 months disease monitoring phase: OHI & prophy
• SRP intervention to test group
• 6 months recovery phase post-SRP
• During recovery phase, they found:
o Decreased MMP-8, MMP-9, IL-1B
o Decreased all bacterial pathogens

23
Q

Goal of Biomarker Research

A
  • Find a combination, a panel/signature, of biomarkers that can predict periodontal tissue destruction prior to the destruction occurring
  • This panel would be used by clinicians to guide them in choosing an intervention that is both timely and appropriate in magnitude
24
Q

Signature Metric Study

A

• Cross-sectional study aimed at finding a metric of active periodontal disease

• Looked at a “signature” of P, gingivalis, IL-1B, and MMP-8 to see if there was a correlation between this signature and traditional measures of
periodontal disease

  • Found that this signature was strongly associated with periodontal disease
  • This was only done on Scandinavian patients
25
Q

British Study (2017)

A

Longitudinal study of 77 British patients

Looked at a signature of two host responder degradation enzymes (MMP-8 and elastase) and one red complex bacterial produced enzyme (sialidase) and the red complex microbiome

26
Q

Salivary Diagnostics Conclusions

A
  • ONE biomarker does NOT diagnose periodontal disease
  • PANELS of biomarkers needed to predict PDP

• DIFFERENT biomarker signatures connote different periodontal disease
o Examples of different disease signatures:
(A) MMP-9, IL-1B, P. gingivalis
(B) MMP-9, IL-1B, P. gingivalis, diabetes
(C) MMP-9, IL-1B, P. gingivalis, diabetes, smoker

27
Q

What to do about personalized medicine?

A
  • Conduct pre-test counseling to educate patients about gene penetrance, biomarker sensitivity and specificity, obligations to relatives, privacy and confidentiality
  • Provide patients with informed consents explaining these concepts
  • With informed consent, provide post-test counseling on the findings, like carrier status, that would affect reproductive decision-making
  • With informed consent, provide post-test counseling on findings that would motivate actionable changes in behavior
28
Q

AXIN2 Gene

A
  • SNP of this gene is linked to tooth agenesis
  • It is also linked to breast, ovarian, and colorectal cancer

• Ex: see a patient missing both maxillary lateral incisors
o Congenitally missing and had implants placed
o Patient has 1 sister and 1 brother and 1 daughter
o How much information about cancer risk should the dentist share with the patient about the AXIN2 gene? What about the siblings and child? What is your ethical/legal obligation?

29
Q

Orr-Shelton Model of Resolving Clinical Ethical Dilemmas

A
  • Gather demographic data (name, DOB, etc.)
  • Formulating ethics question (capture ethical dilemma in question form)
  • Assessment (of clinical and ethical situation)
  • Discussion (identify ethical principles relevant and apply them to the dilemma)
  • Recommendations (provide coherent path for moving forward and identify boundaries for appropriate clinical action)

DOD (2 decks)

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