Insertive condom-protected and condomless vaginal sex both have a profound impact on the penile immune correlates of HIV susceptibility

The penis is the primary site of HIV acquisition in heterosexual men. Elevated penile inflammatory cytokines increase sexual acquisition risk, and topically applied cytokines enhance foreskin HIV susceptibility in an explant model. However, the impact of penile-vaginal sex on these immune parameters is undefined. Heterosexual couples were recruited to the Sex, Couples and Science (SECS) Study, with the collection of penile swabs, semen, cervico-vaginal secretions, and blood after a period of abstinence, and repeated sampling up to 72 hours after either condomless (n = 30) or condom-protected (n = 8) penile-vaginal sex. Soluble immune parameters were quantified by multiplex immunoassay. Co-primary immune endpoints were penile levels of IL-8 and MIG, cytokines previously linked to penile HIV acquisition. One hour after sex there were dramatic increases in penile IL-8 and MIG levels, regardless of condom use, with a gradual return to baseline by 72 hours; similar patterns were observed for other chemoattractant chemokines. Penile cytokine changes were similar in circumcised and uncircumcised men, and repeated measures ANOVA and ANCOVA models demonstrated that the degree of change after condomless sex was explained by cytokine levels in their partners’ cervico-vaginal secretions. This may have important implications for the biology of penile HIV acquisition.

Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria

Antibiotic resistance is a global health threat. There are a few antibiotics under development, and even fewer with new modes of action and no cross-resistance to established antibiotics. Accordingly, reformulation of old antibiotics to overcome resistance is attractive. Nano-mupirocin is a PEGylated nano-liposomal formulation of mupirocin, potentially enabling parenteral use in deep infections, as previously demonstrated in several animal models. Here, we describe extensive in vitro profiling of mupirocin and Nano-mupirocin and correlate the resulting MIC data with the pharmacokinetic profiles seen for Nano-mupirocin in a rat model. Nano-mupirocin showed no cross-resistance with other antibiotics and retained full activity against vancomycin-, daptomycin-, linezolid- and methicillin- resistant Staphylococcus aureus, against vancomycin-resistant Enterococcus faecium, and cephalosporin-resistant Neisseria gonorrhoeae. Following Nano-mupirocin injection to rats, plasma levels greatly exceeded relevant MICs for >24 h, and a biodistribution study in mice showed that mupirocin concentrations in vaginal secretions greatly exceeded the MIC90 for N. gonorrhoeae (0.03 µg/mL) for >24 h. In summary, Nano-mupirocin has excellent potential for treatment of several infection types involving multiresistant bacteria. It has the concomitant benefits from utilizing an established antibiotic and liposomes of the same size and lipid composition as Doxil®, an anticancer drug product now used for the treatment of over 700,000 patients globally.

Human Anelloviruses: Prevalence and Clinical Significance During Pregnancy

Although the bacterial microbiota of various compartments (e.g. vagina, amniotic fluid, and placenta) have been studied in pregnancy, there has been far less emphasis on normal and pathological viral communities. Cumulative evidence shows the presence of a number of apathogenic viruses in various tissues of healthy people, including pregnant individuals. What role, if any, these viruses play in human physiology is unknown. Anelloviruses (family Anelloviridae) are circular, single-stranded DNA viruses commonly detected with high prevalence in vertebrate hosts, including primates. Humans are nearly always colonized with at least 1 of 3 anellovirus subtypes, namely Alphatorquevirus (torque teno virus, TTV), Betatorquevirus (torque teno midi virus, TTMDV), and Gammatorquevirus (torque teno mini virus, TTMV). In healthy pregnant people, the prototype anellovirus, TTV, has been found in maternal and (variably) fetal blood, amniotic fluid, cervical and vaginal secretions, breast milk, and saliva. Nonetheless, the relevance of human anelloviruses in pregnancy and labor is unclear. There is evidence suggesting a link between anellovirus colonization and preterm birth. In this review, we discuss what is known about this family of commensal viruses in health and disease, and specifically the roles they might play during pregnancy and in the timing of delivery.

IMMUNO-BIOLOGICAL PROPERTIES OF VAGINAL DISCHARGE IN HEALTHY AND MYCOPLASMOSIS-INFECTED COWS

Genital mycoplasmosis in cows is a disease accompanied by a latent course, which complicates its timely diagnosis and the appointment of adequate therapy. The nonspecific symptomatology of mycoplasmosis, combined with periods of asymptomatic course, leads to the development of functional and morphological changes in the organs of the reproductive system of cows, resulting in infertility. Monitoring studies of livestock farms in the North-West region of the Russian Federation have shown that infection of the genitals of cows with mycoplasmas can be from 20 to 40% of the livestock. Moreover, there is a clear relationship between the high infection rate of the livestock and low reproduction rates. In this regard, livestock enterprises incur significant economic damage. One of the important mechanisms preventing the introduction of various pathogens into the reproductive tract is the resistance of the vaginal mucosa. Among these factors, the most important role is assigned to vaginal autoflora, epithelial desquamation, phagocytosis, acidity of vaginal secretions, the content of immunoglobulins, lysozyme and a number of other nonspecific protective factors in it. We studied the changes in the immuno-biological characteristics of vaginal secretions in the subclinical course of genital mycoplasmosis. Healthy cows with a negative PCR test for Mycoplasma spp. were selected for the study. and infected with Mycoplasma spp., without clinical signs of vaginitis. In both groups of animals, the concentration of hydrogen ions, the activity of lysozyme and immunoglobulins of the classes IgG, IgM, IgA and sIgA were determined in the vaginal secretions. Despite the fact that the persistence of mycoplasmas in the vagina is not accompanied by pronounced clinical signs of vaginitis, but the state of protective factors the mucous membrane undergoes significant changes. The conducted studies made it possible to establish that the long-term presence of mycoplasmas in the vagina of cows is manifested by a significant increase in the concentration of hydrogen ions by 41% and a decrease in the lysozyme activity of vaginal secretions by 2 times, that is, inhibition of the main factors preventing the colonization of mucous pathogenic microflora is observed. In addition, there is a redistribution of classes of immunoglobulins in the vaginal secretion. This is manifested by a significant increase in the content of IgM and sIgA against the background of a tendency towards a decrease in IgA. The noted changes in aggregate create favorable conditions for the introduction of secondary microflora and the development of bacterial-mycoplasma vaginitis, aggravating morpho-functional changes in the reproductive tract and increasing the risk of infertility.

Insertive vaginal sex has a profound impact on the penile immune correlates of HIV susceptibility

ABSTRACTThe penis is the primary site of HIV acquisition in heterosexual men. Elevated penile inflammatory cytokines increase sexual acquisition risk, and topically applied cytokines enhance foreskin HIV susceptibility in an explant model. However, the impact of penile-vaginal sex on these immune parameters is undefined. Heterosexual couples were recruited to the Sex, Couples and Science (SECS) Study, with the collection of penile swabs, semen, cervico-vaginal secretions, and blood after a period of abstinence, and repeated sampling up to 72 hours after either condomless (n=30) or condom-protected (n=8) penile-vaginal sex. Soluble immune parameters were quantified by multiplex immunoassay. Co-primary immune endpoints were penile levels of IL-8 and MIG, cytokines previously linked to penile HIV acquisition. One hour after sex there were dramatic increases in penile IL-8 and MIG levels, regardless of condom use, with a gradual return to baseline by 72 hours; similar patterns were observed for other chemoattractant chemokines. Penile cytokine changes were similar in circumcised and uncircumcised men, and repeated measures ANOVA and ANCOVA models demonstrated that the degree of change after condomless sex was explained by cytokine levels in their partners’ cervico-vaginal secretions. This may have important implications for the biology of penile HIV acquisition.Author summaryIn heterosexual men, the penis is the primary site of Human Immunodeficiency Virus (HIV) acquisition. Levels of inflammatory cytokines in the coronal sulcus are associated with an increased HIV risk, and we hypothesized that these may be altered after insertive penile sex. Therefore, we designed the Sex, Couples and Science Study (SECS study) to define the impact of penile-vaginal sex on the penile immune correlates of HIV susceptibility. We found that multiple coronal sulcus cytokines increased dramatically and rapidly after sex, regardless of condom use, with a return to baseline levels by 72 hours. The changes observed after condomless sex were strongly predicted by cytokine concentrations in the vaginal secretions of the female partner, and were similar in circumcised and uncircumcised men. We believe that these findings have important implications for understanding the immunopathogenesis of penile HIV acquisition; in addition, they have important implications for the design of clinical studies of penile HIV acquisition and prevention.

Contrasting Vaginal Bacterial Communities Between Estrus and Non-estrus of Giant Pandas (Ailuropoda melanoleuca)

Bacterial infection and imbalance of bacterial community in the genitourinary system of giant panda could affect the reproductive health. In severe cases, it can also lead to abortion. In this study, 13 of vaginal secretions in the estrue (E) group and seven of vaginal secretions in the non-estrue (NE) group were used to study the composition and diversity of vaginal bacterial communities between estrus and non-estrus by 16S rRNA gene sequencing analysis. The results showed that the vaginal microbiome in giant pandas shared the same top five abundant species between estrus and non-estrus at the phylum level. However, the vaginal microbiome changed significantly during estrus at the genus level. In top 10 genera, the abundance of Escherichia, Streptococcus, and Bacteroides in the E group was significantly higher than that in the NE group (p<0.05); Azomonas, Porphyromonas, Prevotella, Campylobacter, and Peptoniphilus in the NE group was significantly higher than that in the E group (p<0.05). The richness and diversity of vaginal microbiome in giant panda on estrus were significantly lower than those on non-estrus (p<0.05). It is noteworthy that the abundance of Streptococcus, Escherichia, and Bacteroides of vagina in giant pandas maintained low abundance in the daily. Whereas, they increased significantly during estrus period, which may play an important role in female giant pandas during estrus period. It was hypothesized that hormones may be responsible for the changes in the vaginal microbiome of giant pandas between estrus and no-estrus stages.

The prognostic value of the degree of purity of vaginal secretions in pregnant women is analyzed by Neumann (Zeit. F. G. u. G., Bd. 89, 1925)

The predictive value of the degree of purity of vaginal secretions in pregnant women is analyzed by Neumann (Zeit. F. G. u. G., Bd. 89, 1925) on the basis of 400 cases.

Modern Concepts of Diagnosis and Prediction of Preterm Birth

The article presents modern methods of diagnosing and predicting preterm birth in the practice of an obstetrician-gynecologist. Early prediction and diagnosis of preterm birth, based on the determination of placental alpha macroglobulin 1 in vaginal secretions, will make it possible to reduce the incidence of preterm birth, as well as reduce the number of unnecessary hospitalizations and unnecessary medical interventions.