Depot medroxyprogesterone acetate administration increases cervical CCR5+CD4+ T cells and induces immunosuppressive milieu at the cervicovaginal mucosa.

OBJECTIVES: Depot medroxyprogesterone acetate (Depo-Provera) is the most commonly used injectable hormone contraceptive in Sub-Saharan Africa where HIV incidence is high. We determined the impact of Depo-Provera on cervical immune cells and mediators in healthy women. METHODS: In this longitudinal study, vaginal, endocervical, and rectal swabs were collected at baseline (visit 1), 1 month (visit 2), and 3 months (visit 3) after Depo-Provera injection. Cervical cells were collected by cytobrush and immune markers on cervical CD4 T cells were analyzed by multicolor flow cytometry at three different visits. The levels of immune mediators in cytobrush supernatants as well as vaginal, cervical, and rectal secretions from swabs were analyzed by multiplex assays and ELISA. RESULTS: Compared with baseline levels, we found a significant increase in the frequency of cervical CCR5CD4 T cells and a significant decrease in the frequency of cervical central memory CD4 T cells. Depo-Provera treatment had little effect on expression of immune mediators in rectal mucosa but significantly suppressed numerous immune mediators at cervicovaginal mucosa. Levels of MCP-1, G-CSF, IL-6, IL-10, GM-CSF, and IP-10 were significantly decreased in both vaginal and cervical secretions after Depo-Provera injection. In cervical samples collected by cytobrush, we found reduced levels of 22 of 25 immune mediators after Depo-Provera injection. Changes in immune mediators differed between vaginal and cervical mucosa, demonstrating compartment-specific responses. CONCLUSION: Depo-Provera altered immune profiles of cervical CD4 T cells and suppressed host immune response at cervicovaginal mucosa, suggesting its likely effect on transmission of sexually transmitted infections including HIV.

Differential effects of depot medroxyprogesterone acetate administration on vaginal microbiome in Hispanic White and Black women.

The use of depot medroxyprogesterone acetate (DMPA), a 3-monthly injectable hormonal contraceptive, is associated with an increased risk of HIV acquisition possibly through alteration of the vaginal microbiome. In this longitudinal interventional study, we investigated the impact of DMPA administration on the vaginal microbiome in Hispanic White and Black women at the baseline (visit 1), 1 month (visit 2), and 3 months (visit 3) following DMPA treatment by using 16S rRNA gene sequencing. No significant changes in the vaginal microbiome were observed after DMPA treatment when Hispanic White and Black women were analysed as a combined group. However, DMPA treatment enriched total vaginosis-associated bacteria (VNAB) and Prevotella at visit 2, and simplified the correlational network in the vaginal microbiome in Black women, while increasing the network size in Hispanic White women. The microbiome in Black women became more diversified and contained more VNAB than Hispanic White women after DMPA treatment. While the Firmicutes to Bacteroidetes (F/B) ratio and Lactobacillus to Prevotella (L/P) ratio were comparable between Black and Hispanic White women at visit 1, both ratios were lower in Black women than in Hispanic White women at visit 2. In conclusion, DMPA treatment altered the community network and enriched VNAB in Black women but not in Hispanic White women. The Lactobacillus deficiency and enrichment of VNAB may contribute to the increased risk of HIV acquisition in Black women. Future studies on the impact of racial differences on the risk of HIV acquisition will offer insights into developing effective strategies for HIV prevention. Abbreviations: DMPA: depot medroxyprogesterone acetate; PCR: polymerase chain reaction; OTU: operational taxonomic unit; STI: sexually transmitted infections; VNAB: vaginosis-associated bacteria.

Telomere length dynamics in early life: the blood-and-muscle model.

Telomere length (TL) trajectories in somatic tissues during human growth and development are poorly understood. We examined a blood-and-muscle model during early life, focusing on TL trajectories in leukocytes, representing the highly proliferative hematopoietic system, and skeletal muscle, a minimally proliferative tissue. Leukocyte TL (LTL) and skeletal muscle TL (MTL) were measured in 28 fetuses and 73 children. LTL and MTL were highly variable across individuals (sd: fetal LTL = 0.72 kb, MTL = 0.72 kb; children LTL = 0.81 kb, MTL = 0.82 kb) but were highly correlated within individuals (fetuses, r = 0.76, P < 0.0001; children, r = 0.87, P < 0.0001). LTL was shorter than MTL in fetuses (10.63 vs. 11.01 kb; P = 0.0004) and children (8.46 vs. 9.40 kb; <0.0001). The LTL-MTL gap was smaller in fetuses than children. TL in children was inversely correlated with body mass index (BMI) (LTL: -0.047 ± 0.016 kb/BMI, P < 0.005; MTL: -0.037 ± 0.017 kb/BMI, P = 0.03). We conclude that variations in TL across adults and differences in TL between somatic tissues are largely established in early life. Because TL plays a significant role in aging-related diseases, insight into the factors that fashion TL in somatic tissues during early development should contribute to an understanding of the relationship of TL with these disease and longevity in humans.-Sabharwal, S., Verhulst, S., Guirguis, G., Kark, J. D., Labat, C., Roche, N. E., Martimucci, K., Patel, K., Heller, D. S., Kimura, M., Chuang, D., Chuang, A., Benetos, A., Aviv, A. Telomere length dynamics in early life: the blood-and-muscle model.

Depot medroxyprogesterone acetate administration alters immune markers for HIV preference and increases susceptibility of peripheral CD4+ T cells to HIV infection.

Depot medroxyprogesterone acetate (Depo-Provera) has been associated with an increased risk of HIV acquisition. In a longitudinal study, we investigated the impact of Depo-Provera use by healthy women on expression of immune markers for HIV preference and on HIV infection ex vivo at baseline (visit 1), one month (visit 2) and three months (visit 3) after Depo-Provera treatment. We found a significant increase in the frequency and expression of integrin α4ß7 on CD4+ T cells at visit 2. Interestingly, Hispanic but not black women exhibited a significant increase in integrin α4ß7 cell numbers and expression levels at visit 2, whereas, black but not Hispanic women exhibited a significant change in CCR5 and CD38 expression levels between visit 2 and visit 3. The frequency of terminal effector memory CD4+ T cells decreased significantly in black women from visit 1 to visit 3. Virus production following ex vivo HIV infection of PBMCs was increased at visit 3 compared to visit 1. In black women, the frequency of HIV p24+CD4+ T cells was higher at visit 3 than at visit 1. Expression of integrin α4ß7 on HIV p24+CD4+ T cells following ex vivo infection at visit 2 was significantly less than at visit 1. These results demonstrate that Depo-Provera alters the immune profile of peripheral CD4+ T cells and increases susceptibility to HIV infection ex vivo. The observation that these effects differed between women of different ethnicities has implications for developing effective and targeted strategies for HIV prevention.

The Epidemiology of Infant Mortality in the Greater Newark, New Jersey Area: A New Look at an Old Problem.

REVIEW: This research had institutional review board approval from the University of Medicine and Dentistry of New Jersey and the State of New Jersey Department of Health and Senior Services. IRB #0120110286 BACKGROUND: The death rate during the first year of life, or infant mortality rate (IMR), is a key indicator of a nation's health. Many factors affect IMR in the United States, including race and ethnicity. The 2020 U.S. Healthy People IMR target goal has been revised to 6.0 deaths per 1,000 births. In 2006, the IMR in New Jersey was 5.5 deaths per 1,000 births, ranging from 4.4 for Caucasians, to 11.5 for African Americans. OBJECTIVE: This study is designed to determine whether IMRs vary by zip code in the greater Newark region and identify maternal/infant characteristics associated with elevated IMRs. METHODS: A descriptive study was conducted using New Jersey Department of Health (NJDOH) birth certificate data and U.S. Census data by zip code in the greater Newark area. IMRs were analyzed by zip code and by characteristics of mothers and infants. RESULTS: IMRs vary by zip code of residence. The lowest and highest IMRs were in zip codes 07105 and 07102, respectively, both located within the city of Newark. Maternal characteristics associated with high IMR, in multivariable analysis, include: lack of prenatal care, single marital status, and non-Hispanic black race. Demographic characteristics associated with high IMRs were: low mean household income and a large percentage of the population living below poverty level. CONCLUSIONS: Race/ethnicity, marital status, and zip code of residence show significant impact upon infant mortality. Poverty and race/ethnicity are associated with increased IMRs and track to ZIP code.

The effect of perioperative ketorolac on pain control in pregnancy termination.

BACKGROUND: The study was conducted to evaluate the effect of perioperative ketorolac on pain associated with first-trimester aspiration abortion. STUDY DESIGN: A double-blind, randomized, placebo-controlled trial was performed involving pregnant women up to 14 weeks' gestation who desired pregnancy termination. Subjects were randomized to receive ketorolac 30 mg intravenously (n=31) or placebo (n=45) at the time of induction of anesthesia. Postoperative pain was assessed using a visual analog scale (VAS). The primary outcome was pain control as determined by VAS score. Secondary measures of patient use of supplemental postoperative pain medications and patient satisfaction were assessed. RESULTS: Subjects in the ketorolac group had lower postoperative pain scores on the VAS at all time points compared to the placebo group, but the difference was not statistically significant. The ketorolac group used less postoperative acetaminophen compared to the placebo group (6.5% versus 35.6%), respectively. Subjects in the placebo group and the ketorolac group had similar requirements for postoperative narcotics in the recovery room (22.2% versus 19.4%). Patient satisfaction with pain level was equivalent between the groups at all postoperative end points. There was no observed difference in perioperative blood loss observed between the two groups. CONCLUSION: Perioperative ketorolac has the same effect on postoperative pain as determined by VAS as placebo. The use of ketorolac at the 30-mg dose cannot be recommended for better pain control for patients undergoing first-trimester pregnancy termination by suction curettage. The only positive effect of the use of ketorolac compared to placebo was a reduction in the use of acetaminophen. Ketorolac use does not appear to change blood loss in the operating room or through postoperative day 1 compared to placebo.

Epidemiology of injuries by needles and other sharp instruments: minimizing sharp injuries in Gynecologic and Obstetric Operations

Surgical and obstetric HCWs and epidemiologists will benefit from working together to describe the frequency and circumstances of percutaneous injuries in operating and delivery rooms. Rates of percutaneous injury vary among institutions, and attending and resident surgeons are among those at greatest risk for injury. Gynecologic surgery appears to have one of the highest rates of injury of the surgical specialties, and rates of injury vary by procedure within a given specialty. Suture needles cause the majority of injuries. Certain actions such as holding tissue while suturing or cutting are associated with a higer risk of injury. Many percutaneous injuries appear to be preventable. Epidemiologic data can be used to develop strategies based on the industrial hygiene model to reduce the incidence of percutaneous injury ant to collect and disseminate data on the efficacy of new preventive measures. Potentially safer instruments and suture needles, technique modification strategies, and personal protective equipment such as cut-resistant gloves and finger protective strips are now available. Scientific assessment is needed of these and other new measures to determine whether they will decrease the risk of percutaneous injury, be acceptable to users, be cost effective, and avoid adverse consequenmces to patients or HCWs