Faculty Bibliography

gp340 is a member of the scavenger receptor cysteine-rich family of innate immune molecules and also functions as a tumor suppressor. This study describes a picogram level assay using electrochemiluminescent technology on the MesoScale Discovery (MSD) platform. Antibodies were evaluated and the best pair used to assay whole mouth stimulated saliva (WMSS) and cervical vaginal lavage (CVL). The assay was tested using specimens obtained from healthy volunteers in order to determine if gp340 concentration in saliva correlates with levels in vaginal lavage fluid. Interestingly, no correlation was determined between gp340 content in these two fluids.

In the present study, we have established a new methodology to analyze saliva proteins from HIV-1-seropositive patients before highly active antiretroviral therapy (HAART) and seronegative controls. A total of 593 and 601 proteins were identified in the pooled saliva samples from 5 HIV-1 subjects and 5 controls, respectively. Forty-one proteins were found to be differentially expressed. Bioinformatic analysis of differentially expressed salivary proteins showed an increase of antimicrobial proteins and decrease of protease inhibitors upon HIV-1 infection. To validate some of these differentially expressed proteins, a high-throughput quantitation method was established to determine concentrations of 10 salivary proteins in 40 individual saliva samples from 20 seropositive patients before HAART and 20 seronegative subjects. This method was based on limited protein separation within the zone of the stacking gel of the 1D SDS PAGE and using isotope-coded synthetic peptides as internal standards. The results demonstrated that a combination of protein profiling and targeted quantitation is an efficient method to identify and validate differentially expressed salivary proteins. Expression levels of members of the calcium-binding S100 protein family and deleted in malignant brain tumors 1 protein (DMBT1) were up-regulated while that of Mucin 5B was down-regulated in HIV-1 seropositive saliva samples, which may provide new perspectives for monitoring HIV-infection and understanding the mechanism of HIV-1 infectivity.

BACKGROUND: Diagnostics that involve the use of oral fluids have become increasingly available commercially in recent years and are of particular interest because of their relative ease of use, low cost and noninvasive collection of oral fluid for testing. TYPES OF STUDIES REVIEWED: The authors discuss the use of salivary diagnostics for virus detection with an emphasis on rapid detection of infection by using point-of-care devices. In particular, they review salivary diagnostics for human immunodeficiency virus, hepatitis C virus and human papillomavirus. Oral mucosal transudate contains secretory immunoglobulin (Ig) A, as well as IgM and IgG, which makes it a good source for immunodiagnostic-based devices. CLINICAL IMPLICATIONS: Because patients often visit a dentist more regularly than they do a physician, there is increased discussion in the dental community regarding the need for practitioners to be aware of salivary diagnostics and to be willing and able to administer these tests to their patients.

BACKGROUND: More than 1 million individuals in the U.S. are infected with HIV; approximately 20% of whom do not know they are infected. Early diagnosis of HIV infection results in earlier access to treatment and reductions in HIV transmission. In 2006, the CDC recommended that health care providers offer routine HIV screening to all adolescent and adult patients, regardless of community seroprevalence or patient lifestyle. Dental providers are uniquely positioned to implement these recommendations using rapid oral fluid HIV screening technology. However, thus far, uptake into dental practice has been very limited. METHODS: The study utilized a qualitative descriptive approach with convenience samples of dental faculty and students. Six in-depth one-on-one interviews were conducted with dental faculty and three focus groups were conducted with fifteen dental students. RESULTS: Results were fairly consistent and indicated relatively high levels of acceptability. Barriers and facilitators of oral fluid HIV screening were identified in four primary areas: scope of practice/practice enhancement, skills/knowledge/training, patient service/patient reactions and logistical issues. CONCLUSIONS: Oral fluid HIV screening was described as having benefits for patients, dental practitioners and the public good. Many of the barriers to implementation that were identified in the study could be addressed through training and interdisciplinary collaborations.

Transcranial direct current stimulation (tDCS) is a novel non-invasive neuromodulatory method that influences neuronal firing rates and excitability of neuronal circuits in the brain. tDCS has been shown to relieve Major Depressive Disorder (MDD) in the general population, suggesting its potential for other vulnerable populations with high MDD prevalence. Aims: This study evaluated the feasibility, safety, acceptability, and clinical outcomes of a 2-week tDCS antidepressant treatment in HIV-MDD co-diagnosed patients, and the feasibility of collecting serum and saliva for analysis of immunity biomarkers. Methods: Ten enrolled patients underwent baseline evaluation and started the tDCS treatment (Monday-Friday for 2 weeks) delivered with Phoresor II 850 PM for 20 min at 2 mA at each visit, using two saline-soaked sponge electrodes placed over the F3 position of EEG 10-20 system and the contralateral supraorbital region. Outcome measures were collected at baseline, after the last tDCS and 2 weeks later. A quantitative microarray (Ray Bio Tech Inc.) for TH1/TH2 cytokines was used for saliva and plasma analysis. Results: Analyzable outcome-data were obtained from eight subjects. Depression scores significantly decreased (p < 0.0005) after the treatment. No serious adverse events occurred. Several transient minor AEs and occasional changes of blood pressure and heart rate were noted. Mini-mental state examination scores remained unchanged or increased after the treatment. All subjects were highly satisfied with the protocol and treatment results and described the desire to find new treatments for HIV-MDD as motivating participation. Conclusion: Findings support feasibility and clinical potential of tDCS for HIV-MDD patients, and justify larger-sample, sham-controlled trials.

This article reports and discusses how quantitative (physiological and behavioral) and qualitative methods are being combined in an open-label pilot feasibility study. The study evaluates safety, tolerability, and acceptability of a protocol to treat depression in HIV-infected individuals, using a 2-week block of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex. Major depressive disorder (MDD) is the second most prevalent psychiatric disorder after substance abuse among HIV-positive adults, and novel antidepressant treatments are needed for this vulnerable population. The authors describe the challenges and contributions derived from different research perspectives and methodological approaches and provide a philosophical framework for combining quantitative and qualitative measurements for a fuller examination of the disorder. Four methodological points are presented: (1) the value of combining quantitative and qualitative approaches; (2) the need for context-specific measures when studying patients with medical and psychiatric comorbidities; (3) the importance of research designs that integrate physiological, behavioral, and qualitative approaches when evaluating novel treatments; and (4) the need to explore the relationships between biomarkers, clinical symptom assessments, patient self-evaluations, and patient experiences when developing new, patient-centered protocols. The authors conclude that the complexity of studying novel treatments in complex and new patient populations requires complex research designs to capture the richness of data that inform translational research.

In 2006, the Centers for Disease Control and Prevention (CDC) recommended routine HIV screening in health care settings regardless of the patient's level of risk. This pilot study was developed in response to the suggestion by some health care professionals that dental settings would be appropriate for expansion of HIV testing. This project consisted of two parts: oral fluid HIV testing of patients in the clinic of a dental school and a survey of the clinical dental faculty members' attitudes about acceptability of routine HIV testing in the dental clinic. When patients' agreement to participate in oral fluid HIV testing was examined, 8.2 percent of the patients contacted by the clinic administration staff completed testing. When approached by a faculty member or student during the dental visit admission and tested during the dental visit, however, 88.2 percent completed testing. Of the faculty members who took the survey, 27.4 percent were neutral, 26.4 percent were somewhat in agreement, and 32.1 percent were willing to incorporate HIV testing into routine dental care. In this pilot study, HIV testing of dental patients was most successful when a dental care provider approached patients about testing. If consent was given, the testing was performed during the visit. For the faculty members, the major barrier to testing was a lack of protocol familiarity.

We report a clinical study that examines whether HIV infection affects Streptococcus mutans colonization in the oral cavity. Whole stimulated saliva samples were collected from 46 HIV-seropositive individuals and 69 HIV-seronegative control individuals. The level of S. mutans colonization was determined by conventional culture methods. The genotype of S. mutans was compared between 10 HIV-positive individuals before and after highly active antiretroviral therapy (HAART) and 10 non-HIV-infected control individuals. The results were analyzed against viral load, CD4+ and CD8+ T-cell counts, salivary flow rate, and caries status. We observed that S. mutans levels were higher in HIV-infected individuals than in the non-HIV-infected control individuals (p = 0.013). No significant differences in S. mutans genotypes were found between the two groups over the six-month study period, even after HAART. There was a bivariate linear relationship between S. mutans levels and CD8+ counts (r = 0.412; p = 0.007), but not between S. mutans levels and either CD4+ counts or viral load. Furthermore, compared with non-HIV-infected control individuals, HIV-infected individuals experienced lower salivary secretion (p = 0.009) and a positive trend toward more decayed tooth surfaces (p = 0.027). These findings suggest that HIV infection can have a significant effect on the level of S. mutans, but not genotypes.

An estimated 1.1 million people in the USA are living with HIV/AIDS. Nearly 200,000 of these individuals do not know that they are infected. In 2006, the CDC recommended that all healthcare providers routinely offer HIV screening to adolescent and adult patients. Nurse-dentist collaborations present unique opportunities to provide rapid oral HIV screening to patients in dental clinic settings and reach the many adults who lack primary medical providers. However, little is known about the feasibility and acceptability of this type of innovative practice. Thus, elicitation research was undertaken with dental providers, students, and patients. This paper reports the results of qualitative interviews with 19 adults attending a university-based dental clinic in New York City. Overall, patients held very positive attitudes and beliefs toward HIV screening in dental sites and identified important factors that should be incorporated into the design of nurse-dentist collaborative HIV screening programs.