Tina D. Cunningham

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

The relationship between exogenous contraceptive hormones and permissiveness of the female genital tract to human immunodeficiency virus type 1 (HIV-1) is the subject of renewed debate. To better characterize the effect of depot medroxyprogesterone acetate (DMPA) on HIV-1 cellular targets and epithelial integrity in the vagina, we compared leukocyte populations, markers of activation and proliferation, and the density of intercellular junctional proteins in the vaginal epithelium of women during the follicular and luteal phases of the menstrual cycle and approximately 12 weeks after receiving a DMPA injection. This prospective cohort study involved 15 healthy women. Vaginal biopsies were obtained in the follicular and luteal phases of the menstrual cycle, and approximately 12 weeks following a 150-mg intramuscular injection of DMPA. Leukocyte populations, activation phenotype, and epithelial tight junction and adherens proteins were evaluated by immunohistochemistry. After receiving DMPA, the numbers of CD45, CD3, CD8, CD68, HLA-DR, and CCR5 bearing immune cells were significantly (p<0.05) increased in vaginal tissues, compared to the follicular and/or luteal phases of untreated cycles. There were no significant differences in immune cell populations between the follicular and luteal phases of the control cycle. There were also no statistically significant differences in epithelial thickness and density of epithelial tight junction and adherens proteins among the follicular, luteal, and post-DMPA treatment sampling points. In this pilot study, vaginal immune cell populations were significantly altered by exogenous progesterone, resulting in increased numbers of T cells, macrophages, and HLA-DR- and CCR5-positive cells.

Long-Term Treatment Outcomes for Parent-Assisted Social Skills Training for Adolescents With Autism Spectrum Disorders: The UCLA PEERS Program

Social deficits are a hallmark characteristic among adolescents with autism spectrum disorders (ASD), yet few evidence-based interventions exist aimed at improving social skills for this population, and none have examined the maintenance of treatment gains years after the intervention has ended. This study examines the durability of the Program for the Education and Enrichment of Relational Skills (PEERS), a manualized, parent-assisted social skills intervention for high-functioning adolescents with ASD. Targeted skills related to the development and maintenance of friendships were assessed 1–5 years following treatment for 53 adolescent participants and their parents. Results indicate that adolescents receiving PEERS maintained treatment gains at long-term follow-up on standardized measures of social functioning including the Social Skills Rating System and the Social Responsiveness Scale as well as in frequency of peer interactions and social skills knowledge. Perhaps due to parent involvement in treatment, results reveal additional improvements in social functioning at follow-up assessment.

Deletion of 12/15-Lipoxygenase Alters Macrophage and Islet Function in NOD-Alox15null Mice, Leading to Protection against Type 1 Diabetes Development

Aims Type 1 diabetes (T1D) is characterized by autoimmune depletion of insulin-producing pancreatic beta cells. We showed previously that deletion of the 12/15-lipoxygenase enzyme (12/15-LO, Alox15 gene) in NOD mice leads to nearly 100 percent protection from T1D. In this study, we test the hypothesis that cytokines involved in the IL-12/12/15-LO axis affect both macrophage and islet function, which contributes to the development of T1D. Methods 12/15-LO expression was clarified in immune cells by qRT-PCR, and timing of expression was tested in islets using qRT-PCR and Western blotting. Expression of key proinflammatory cytokines and pancreatic transcription factors was studied in NOD and NOD-Alox15null macrophages and islets using qRT-PCR. The two mouse strains were also assessed for the ability of splenocytes to transfer diabetes in an adoptive transfer model, and beta cell mass. Results 12/15-LO is expressed in macrophages, but not B and T cells of NOD mice. In macrophages, 12/15-LO deletion leads to decreased proinflammatory cytokine mRNA and protein levels. Furthermore, splenocytes from NOD-Alox15null mice are unable to transfer diabetes in an adoptive transfer model. In islets, expression of 12/15-LO in NOD mice peaks at a crucial time during insulitis development. The absence of 12/15-LO results in maintenance of islet health with respect to measurements of islet-specific transcription factors, markers of islet health, proinflammatory cytokines, and beta cell mass. Conclusions These results suggest that 12/15-LO affects islet and macrophage function, causing inflammation, and leading to autoimmunity and reduced beta cell mass.

Bacterial Vaginosis and Subclinical Markers of Genital Tract Inflammation and Mucosal Immunity

Bacterial vaginosis (BV) has been linked to an increased risk of human immunodeficiency virus (HIV) acquisition and transmission in observational studies, but the underlying biological mechanisms are unknown. We measured biomarkers of subclinical vaginal inflammation, endogenous antimicrobial activity, and vaginal flora in women with BV and repeated sampling 1 week and 1 month after completion of metronidazole therapy. We also compared this cohort of women with BV to a healthy control cohort without BV. A longitudinal, open label study of 33 women with a Nugent score of 4 or higher was conducted. All women had genital swabs, cervicovaginal lavage (CVL) fluid, and cervicovaginal biopsies obtained at enrollment and received 7 days of metronidazole treatment. Repeat sampling was performed approximately 1 week and 1 month after completion of therapy. Participants baseline samples were compared to a healthy, racially matched control group (n=13) without BV. The CVL from women with resolved BV (Nugent 0-3) had significantly higher anti-HIV activity, secretory leukocyte protease inhibitor (SLPI), and growth-related oncogene alpha (GRO-α) levels and their ectocervical tissues had significantly more CD8 cells in the epithelium. Women with persistent BV after treatment had significantly higher levels of interleukin-1β, tumor necrosis factor alpha (TNF-α), and intercellular adhesion molecule 1 (ICAM-1) in the CVL. At study entry, participants had significantly greater numbers of CCR5(+) immune cells and a higher CD4/CD8 ratio in ectocervical tissues prior to metronidazole treatment, compared to a racially matched cohort of women with a Nugent score of 0-3. These data indicate that BV is associated with changes in select soluble immune mediators, an increase in HIV target cells, and a reduction in endogenous antimicrobial activity, which may contribute to the increased risk of HIV acquisition.

Is Self-Reported Sleep Duration Associated with Osteoporosis? Data from a 4-Year Aggregated Analysis from the National Health and Nutrition Examination Survey

To examine the association between self‐reported sleep duration and osteoporosis in a national sample of the U.S. elderly population.

Long-term outcomes of parent-assisted social skills intervention for high-functioning children with autism spectrum disorders

This study aims to evaluate the long-term outcome of Children’s Friendship Training, a parent-assisted social skills intervention for children. Prior research has shown Children’s Friendship Training to be superior to wait-list control with maintenance of gains at 3-month follow-up. Participants were families of children diagnosed with autism spectrum disorder who completed Children’s Friendship Training 1–5 years earlier. They were recruited through mail, phone, and email. Information collected included parent and child completed questionnaires and a phone interview. Data were collected on 24 of 52 potential participants (46%). With an average of 35-month follow-up, participants had a mean age of 12.6 years. Results indicated that participants at follow-up were invited on significantly more play dates, showed less play date conflict, improved significantly in parent-reported social skills and problem behaviors, and demonstrated marginally significant decreases in loneliness when compared to pre–Children’s Friendship Training.

Frequency and clinical relevance of PET/CT incidentalomas

Rationale and objectivesTo assess the frequency of clinically significant incidental CT findings on PET/CT.Materials and methodsReports of 345 cases of baseline standard skull base to thighs PET/CT exams done over the course of a 6 month period at an outpatient facility affiliated with a large tertiary care level 1 trauma medical center were retrospectively reviewed. Incidental CT findings were assigned a level of clinical significance on a scale of 1–5, from doubtful significance to very significant. CT findings already known from prior CT reports were not included. CT findings corresponding to PET findings were also excluded. A score of 3 or greater was considered significant and reportable.ResultsOut of 345 cases, 171 (50%) had a least one CT finding rated at or above a score of 3 on our scale of significance, while 96 (28%) were found to have at least one CT finding with score at or above 4, and 25 cases (7%) showed at least one CT finding rated 5.ConclusionA substantial percentage of baseline PET/CT studies contain previously undiagnosed, significant incidental findings on the CT images.

Design effects for sample size computation in three-level designs

Experiments with multiple nested levels where randomization can take place at any level bring challenges to the computation of sample sizes. Formulas derived under simple single-level experiments must be adjusted using multiplicative factors or design effects. In this work, we take a unified approach to finding the design effects in terms of intracluster correlations and present formulas to compute sample sizes of different levels. Equal cluster sample sizes and homogeneous within cluster variances are assumed.

Interleukin‐9 and interleukin‐17C in chronic rhinosinusitis

Interleukin (IL)‐9 and IL‐17C have been known to play a role in allergic inflammation, yet, their roles in chronic rhinosinusitis (CRS) are not well defined. IL‐9 induces changes in epithelial cell gene expression leading to goblet cell metaplasia, whereas IL‐17C is functionally distinct in that its expression can be induced by bacterial challenge and inflammatory stimuli. This study aimed to compare levels of IL‐9 and IL‐17C in CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) as well as atopy.

Effectiveness of a Screening and Brief Intervention protocol for heavy drinkers in dental practice: A cluster-randomized trial

Results of a cluster-randomized trial of a Screening and Brief Intervention for heavy drinkers in dental practice are reported. Data were obtained from 103 heavy drinking patients recruited from randomized intervention (7; n = 50) and control (6; n = 53) practices. Analysis of data revealed that 6-month decreases in total drinks per week were significantly (p < .05) greater for heavy drinking intervention (43%) than control patients (21%)—a 4 drink per week difference. Similar decreases were obtained for quantity and frequency among intervention patients compared to control patients. Despite power limitations, the 6-month results support the effectiveness of the Screening and Brief Intervention.