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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)
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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.
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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:
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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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An HIV Post-Exposure Prophylaxis Pilot Program Implemented in Public Health Settings in Los Angeles
1. An HIV Post-Exposure Prophylaxis
Pilot Program
Implemented in Public Health
Settings in Los Angeles
Jennifer N Sayles, MD, MPH, Gary P García,
MPH, Rosemary C Veniegas, PhD, Robert K
Bolan, MD, Wilbert C Jordan, MD, and Raphael
J Landovitz, MD, MsC
2. Estimated
Population
HIV/AIDS Cases
9,848,011 61,700
Overall, Race/Ethnicity
13.3% 0.5% 8.8%
30.1%
47.3%
HIV/AIDS Cases
3.0% 1.0%
Black
21.0% Latino
35.0%
White
40.0% Asian/PI
NA/AI
Data Source: U.S. Department of Commerce, 2010; Los Angeles County Department of Public Health, HIV
Surveillance, 2010
3. A Case for nPEP?
A 26 year old man presents to an outpatient clinic,
reporting that the night before last (36 hours ago) he
had receptive anal intercourse without the use of a
condom with a new male partner, who he just
learned from a mutual acquaintance is infected with
the Human Immunodeficiency Virus (HIV). The
patient is known to the clinic and has had several
negative HIV tests (most recently 6 months ago), and
he recently lost his job and health insurance. He
wants to know if there is anything he can do to help
prevent transmission of HIV from this recent
exposure.
3
5. OAPP
LAC
PPC
STD
Commission
Providers P-QUAD on HIV
Behavior/SA
Specialists CBO/CHCs
Academics
5
6.
7. The nPEP Pilot: Comprehensive
Biomedical HIV Prevention for LAC
• 2 demonstration sites; 28 days of ART
• IRB and FDA regulatory oversight
• Structured Protocol and Manual of Procedures
• Demonstration site preparation and training
• Safety labs and serial HIV and STI testing
• Sexual/substance use risk-reduction counseling
• Planned transition to Public Health Service Model
9. nPEP Pilot Components
Baseline Week 2 Visit Week 4-6 Visit Week 12 Visit Week 24
(Day 0) (Day 10-14) Visit
ART Dispensed X X
HIV ELISAc X X X X
Urine GC/CT X Xb Xb Xb Xb
Rectal GC/CT
Pharynx GC
Serum RPR X X
Urine HCGa X Xb Xb Xb Xb
HBsAg X
CB, Cr, LFTs, X Xb
HIV Viral Load
HIV Genotype
Stored Plasmad X X X X
Adherence Cnsl X X
Drug and Alc Assess X
Risk Assess X X X X
Risk Red (Standard) X X Xb Xb Xb
Referral to Behavioral X
Programming (Expanded)
aFemales of childbearing potential only
bIfclinical signs and symptoms direct, not routine
cPositive or indeterminate rapid HIV ELISA testing will be confirmed with a
serum Western Blot
dPlasma will be drawn and stored at indicated time points. If HIV
seroconversion occurs, these samples will be run for HIV RNA (viral load)
and genotyping
10. Inclusion Criteria
1. 18 yrs of age and ability to provide consent
2. High-risk exposure (unprotected or with failed condom):
• Receptive/Insertive anal intercourse
• Receptive/Insertive vaginal intercourse
• Receptive oral intercourse w/ejaculation with HIV+ source
• Sharing intravascular injection drug works
3. High-risk source (one or more):
• Known HIV+, MSM, MSM/W, IDU, CSW, sexual perpetrator,
history of incarceration, from an endemic country (prevalence
>1%), partner of one of the above
4. Exposure within 72-hrs of presentation
5. Not known to be HIV+
6. No countermanding concomitant medications or allergies
11. Medication Regimens
Standard ART Regimen for high-risk
exposures:
• Truvada
• Combivir – for intolerance to Truvada
Expanded ART Regimen:
• For highest-risk exposures or suspected
source drug resistance; added to the
above medication administration
• Kaletra or Raltegravir
12. Preliminary Findings
Presentation data as of July 1, 2011
• Screened 303, Enrolled 283
• Data to follow N=163 (151 at Site 1, 12 at Site 2)
• N=38 had already initiated PEP at another
location (ED, Primary Care, HIV clinic)
Site 1: LAGLC – Los Angeles Gay and Lesbian Ctr
• Screened 271, enrolled 260
Site 2: OASIS
• Screened 32, enrolled 23
13. nPEP Sites, HIV/STI Clusters, 2009
Legend
nPEP sites
HIV/STI Disease Clusters
HIV Cases, 2009
1.3%
6.6%
9.2%
18.4%
46.3%
Los Angeles County Boundary
LAGLC
Source: Semi-Annual Surveillance Report,
2008, HIV Epidemiology Program
Data Source: HIV Testing Services Data, Oasis Clinic
CY2009; Zip Codes with <100 tests not
included in analysis
23. Seroconversions N=4
PID Date Exposure Time to Med STIs Repeat
Seroconversion PEP Adherence Exposures
identified Self-Report Self-Report
1016 12-week URAI and UIAI 64hrs 100% None None
w/recently
seroconverted Source
1064 12-week URAI and UIAI 41hrs 100% + GC at Yes
w/recently baseline
seroconverted Source
1101 12-week UIAI with known HIV+ 26hrs 95% None Yes
Source; Source
reported to be
undetectable on meds
1155 12-week RAI with failed condom 62hrs 100% Positive RPR 3 Yes
w/known HIV+ Source month
24. nPEP Pilot: Summary
• Demonstrated feasible implementation of nPEP
in clinical care settings for high risk population
• Real life example of how to develop and
implement comprehensive biomedical and
behavioral HIV prevention interventions
• Cost of ART is significant and can be an
obstacle to scaling up service delivery
• Education for primary care (non HIV specialty)
needed to support providers to deliver nPEP
more broadly
25. Next Steps: Sustained nPEP Program
Public health program premised on the findings from
pilot with few modifications:
• 2 drug regimen (Truvada) except in cases of
documented drug resistance from source patient
(3rd drug Raltegravir/Kaletra)
• Integrated hepatitis screening and vaccination
• Streamlined data reporting
• PEP coordinator to do follow up visits
• Full 28 day ART dispensed at intake
• Integrated risk-reduction counseling via OAPP
funded behavioral programs
26. Acknowledgements
• Gilead Sciences • LA County OAPP
– Jim Rooney – Mario Perez
– Alexia Exarchos • LA County STD
• Abbott Laboratories Program
– Ashwaq Hermes – Sarah Guerry
– Judith Kruse – Peter Kerndt
• Merck Laboratories • LAC Public Health Lab
– Kathleen Bailey – Debbie Emlien
– Michael Harbour – Ramiro Garate
• GSK/Viiv
– Gary Pakes • LAGLC Site Staff
– Sue Pippin • OASIS Clinic Site Staff
27. Contact Information
Jennifer N. Sayles, MD, MPH
Medical Director
Office of AIDS Programs and Policy
600 South Commonwealth Avenue, 10th Floor
Los Angeles, California 90005-4001
Phone: (213) 351-8264
E-mail: jsayles@ph.lacounty.gov
27