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Flashcards in Precision Med Deck (29):

Types of Oral Samples

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



- 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


Why develop oral/salivary diagnostic tests?

- Safe
- User friendly
- Cost effective
-Field studies
-Home testing
-Special populations


Widely used Oral Tests

Kaposi's sacroma
Mononucleosis (EBV)
Strep throat


Preventing HIV

- Vaccine
- Microbicides
- Test and Treat
- PrepExposure Prophylaxis (PrEP)


PrepExposure Prophylaxis (PrEP)

Oral anti-retroviral provided 70-90% protection

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


HIV rapid testing

- 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


Rapid Screening + Confirmatory Test

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


4th Generation HIV Test

- 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


Dealing with the HIV pandemic

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


Target Analytes

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


Point of Care (POC) HIv Diagnosis

- 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)


Diagnosis of Malaria

- 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


Zika Overview

-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



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

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


Periodontal Disease

• Most common cause of tooth loss in the world
• More than 50% of Americans are affected


Periodontal Disease Progression

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


Personalized Medicine

• 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


Microbiome - Initiator Biomarkers

• 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


Host-Response Inflammatory Mediators/Tissue Degradation Enzymes

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


Tissue Degradation Enzyme/Microbiome Study

• 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


Microbiome/Host-Response Inflammatory
Mediators/Tissue Degradation Enzymes Study

• 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


Goal of Biomarker Research

• 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


Signature Metric Study

• 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


British Study (2017)

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


Salivary Diagnostics Conclusions

• 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


What to do about personalized medicine?

• 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


AXIN2 Gene

• 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?


Orr-Shelton Model of Resolving Clinical Ethical Dilemmas

• 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)