Longitudinal Study of the Dynamics of Vaginal Microflora during Two Consecutive Menstrual Cycles

Although the vaginal microflora (VMF) has been well studied, information on the fluctuation of the different bacterial species throughout the menstrual cycle and the information on events preceding the presence of disturbed VMF is still very limited. Documenting the dynamics of the VMF during the menstrual cycle might provide better insights. In this study, we assessed the presence of different Lactobacillus species in relation to the BV associated species during the menstrual cycle, assessed the influence of the menstrual cycle on the different categories of vaginal microflora and assessed possible causes, such as menstruation and sexual intercourse, of VMF disturbance. To our knowledge, this is the first longitudinal study in which swabs and Gram stains were available for each day of two consecutive menstrual cycles, whereby 8 grades of VMF were distinguished by Gram stain analysis, and whereby the swabs were cultured every 7(th) day and identification of the bacterial isolates was carried out with a molecular technique.status: publishe

Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT

Development of a Composite Measure of Product Adherence, Protocol Compliance, and Semen Exposure Using DNA and Protein Biomarkers for Topical HIV Prevention Studies

Poor and inconsistent use of study products has hindered clinical HIV prevention studies. It is important to be able to monitor product adherence and protocol compliance in order to determine microbicide efficacy and safety more accurately. Current methods for monitoring adherence are subjective, non-specific, or invasive. Herein, we present a composite, objective measure of product adherence and protocol compliance to assess vaginal insertion, semen exposure and drug expulsion utilizing DNA, protein, and drug isolated directly from returned, vaginally used gel applicators.DNA, vaginal cells, and residual tenofovir were isolated from vaginally inserted applicators. Vaginal and semen biomarkers were amplified using a multiplex PCR to determine vaginal insertion. Vaginal cells were fixed followed by cytokeratin 4 immunocytochemistry to confirm DNA assessment of vaginal insertion. Tenofovir was extracted and quantitated through LC-MS/MS.DNA isolated from vaginally inserted applicators were positive for vaginal bacteria DNA and the control eukaryotic gene, amelogenin, while manually handled, "sham", applicators were negative for both. Semen exposure was independently determined by simultaneous amplification of one or both Y-chromosomal genes, SRY and TSPY4. Vaginal insertion determination by DNA analysis was further confirmed by positive cytokeratin 4 (CK4) immunocytochemistry of vaginal cells remaining on the gel applicators. On the contrary, sham applicators provided very few cells when swabbed, and they were all negative for CK4. CK4 was not found in epidermal cells from the hand. Drug expulsion was detected through quantitation of residual gel present on the surface of returned applicators. Sham applicators had no detectable tenofovir.Utilizing a composite, triple marker based panel of DNA, protein, and drug present on the surface of returned vaginal gel applicators, it is possible to determine, objectively and non-invasively, product adherence, protocol compliance, and semen exposure in microbicide trials

Exploring the association of care fragmentation and patient ratings of care quality: A mediation analysis of women Veterans’ experience with VA care

ObjectiveTo examine the relationship between care fragmentation and patient ratings of care quality and identify potentially actionable mediators.Data sources/study setting2015 telephone survey of 1395 women Veterans with three or more visits in primary care and/or women's health care in the prior year at 12 Veterans Affairs (VA) medical centers.Study designCross-sectional analysis.Data collection/extraction methodsWe operationalized lower care fragmentation as receiving VA-only care versus dual use of VA/non-VA care. Participants rated VA care quality (overall care, women's health care (WH), and primary care (PC)) and three aspects of their patient experience (ease of access to services, provider communication, and gender sensitivity of VA environments). We examined associations between care fragmentation and care ratings and applied the Karlson-Holm-Breen decomposition method to test for mediation by aspects of patients' experience.Principal findingsLower care fragmentation was associated with higher ratings of care quality (odds ratios [95% CI] for overall care: 1.57 [1.14;2.17]; WH: 1.65 [1.20;2.27]; PC: 1.41 [1.10;1.82]). Relationships were mediated by patient-rated provider communication and gender sensitivity (26-54 percent and 14-15 percent of total effects, respectively). Ease of access was associated with higher care ratings (odds ratios [95% CI] for overall care: 2.93 [2.25;3.81]; WH: 2.81 [2.15;3.68]; PC: 2.33 [1.63;3.33], in models with the three types of patient care experiences included), but did not mediate the association of care fragmentation and care ratings.ConclusionsPotential negative effects of care fragmentation on care quality ratings could be mitigated by attention to quality of patient-provider communication and gender sensitivity of VA environments