Updates in Breast Cancer Screening and Diagnosis.

Breast cancer does not wait until a woman reaches her 50's to strike. One in six cases occurs in women between the ages of 40 and 49 and breast cancer is the most prevalent cancer and the leading cause of cancer-related deaths among women under 50 in the United States (10% of breast cancer deaths), emphasizing the urgency of early detection (American Society. 2024).

Obesity is associated with lower bacterial vaginosis prevalence in menopausal but not pre-menopausal women in a retrospective analysis of the Women's Interagency HIV Study.

The vaginal microbiota is known to impact women's health, but the biological factors that influence the composition of the microbiota are not fully understood. We previously observed that levels of glycogen in the lumen of the vagina were higher in women that had a high body mass index (BMI). Vaginal glycogen is thought to impact the composition of the vaginal microbiota.

Automated breast ultrasound: Supplemental screening for average-risk women with dense breasts.

Objective: We review ultrasound (US) options for supplemental breast cancer screening of average risk women with dense breasts.

Conclusion: Performance data of physician-performed handheld US (HHUS), technologist-performed HHUS, and automated breast ultrasound (AUS) indicate that all are appropriate for adjunctive screening. Volumetric 3D acquisitions, reduced operator dependence, protocol standardization, reliable comparison with previous studies, independence of performance and interpretation, and whole breast depiction on coronal view may favor selection of AUS.

Clinical accuracy of preoperative breast MRI for breast cancer.

Background: It is unclear if breast magnetic resonance imaging (MRI) is more accurate than mammography (MGM) and ultrasound (U/S) in aggregate for patients with invasive cancer.

Methods: We compared concordance of combined tumor size and tumor foci between MRI and MGM and U/S combined to pathological tumor size and foci as the gold standard from 2009 to 2015. Tumor size was nonconcordant if it differed from the pathologic size by ≥33% and tumor foci was nonconcordant if >1 foci were seen.

The Cervicovaginal Microbiota and Its Associations With Human Papillomavirus Detection in HIV-Infected and HIV-Uninfected Women.

Background:  Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus species, high pH, and immune cell infiltration and has been associated with an increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in human immunodeficiency virus (HIV)-infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status.

Methods:  16S ribosomal RNA gene amplicon pyrosequencing and HPV DNA testing were conducted annually in serial cervicovaginal lavage specimens obtained over 8-10 years from African American women from Chicago, of whom 22 were HIV uninfected, 22 were HIV infected with a stable CD4 T-cell count of > 500 cells/mm, and 20 were HIV infected with progressive immunosuppression.

Glycogen Levels in Undiluted Genital Fluid and Their Relationship to Vaginal pH, Estrogen, and Progesterone.

Background: Colonization of the female lower genital tract with Lactobacillus provides protection against STIs and adverse pregnancy outcomes. Growth of genital Lactobacillus is postulated to depend on epithelial cell-produced glycogen. However, the amount of cell-free glycogen in genital fluid available for utilization by Lactobacillus is not known.

Effect of pH on Cleavage of Glycogen by Vaginal Enzymes.

Glycogen expressed by the lower genital tract epithelium is believed to support Lactobacillus growth in vivo, although most genital isolates of Lactobacillus are not able to use glycogen as an energy source in vitro. We recently reported that α-amylase is present in the genital fluid of women and that it breaks down glycogen into small carbohydrates that support growth of lactobacilli. Since the pH of the lower genital tract can be very low, we determined how low pH affects glycogen processing by α-amylase.

T. vaginalis Infection Is Associated with Increased IL-8 and TNFr1 Levels but with the Absence of CD38 and HLADR Activation in the Cervix of ESN.

Introduction: Trichomonas vaginalis infection is associated with an increased risk of HIV infection in exposed-seronegative women (ESN) despite their unique immune quiescent profile. It is important to understand possible mechanisms, such as recruitment of activated T cells, by which T. vaginalis could facilitate HIV infection in this population.

The vaginal microbiota over an 8- to 10-year period in a cohort of HIV-infected and HIV-uninfected women.

Background: We identified predominant vaginal microbiota communities, changes over time, and how this varied by HIV status and other factors in a cohort of 64 women.

Methods: Bacterial DNA was extracted from reposited cervicovaginal lavage samples collected annually over an 8-10 year period from Chicago Women's Interagency HIV Study participants: 22 HIV-negative, 22 HIV-positive with stable infection, 20 HIV-positive with progressive infection. The vaginal microbiota was defined by pyrosequencing of the V1/V2 region of the 16S rRNA gene.

Cleavage/alteration of interleukin-8 by matrix metalloproteinase-9 in the female lower genital tract.

Objective: Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses at mucosal sites including in the lower genital tract. Since several types of bacteria produce proteases that cleave IL-8 and many types of bacteria can be present in lower genital tract microbiota, we assessed genital fluids for IL-8 cleavage/alteration.

Study Design: Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA.

Exploratory comparison of vaginal glycogen and Lactobacillus levels in premenopausal and postmenopausal women.

Objective: Previous studies have suggested that glycogen expression in the vaginal epithelium decreases during menopause, resulting in reduced levels of lactobacilli. However, free glycogen in genital fluids and its relationship with Lactobacillus levels have not been compared in premenopausal and postmenopausal women.

Methods: Eighty-two cervicovaginal lavage samples were collected at different phases of the menstrual cycle from 11 premenopausal (4 HIV-uninfected and 7 HIV-infected) and 12 postmenopausal (7 HIV-uninfected and 5 HIV-infected) women during a 1- to 3-month period.

Free glycogen in vaginal fluids is associated with Lactobacillus colonization and low vaginal pH.

Objective: Lactobacillus dominates the lower genital tract microbiota of many women, producing a low vaginal pH, and is important for healthy pregnancy outcomes and protection against several sexually transmitted pathogens. Yet, factors that promote Lactobacillus remain poorly understood. We hypothesized that the amount of free glycogen in the lumen of the lower genital tract is an important determinant of Lactobacillus colonization and a low vaginal pH.

Comparison of lower genital tract microbiota in HIV-infected and uninfected women from Rwanda and the US.

Introduction: Previous studies have shown that alterations of the bacterial microbiota in the lower female genital tract influence susceptibility to HIV infection and shedding. We assessed geographic differences in types of genital microbiota between HIV-infected and uninfected women from Rwanda and the United States.

Methods: Genera of lower genital tract bacterial microbiota were identified by high-throughput pyrosequencing of the 16S rRNA gene from 46 US women (36 HIV-infected, 10 HIV-uninfected) and 40 Rwandan women (18 HIV-infected, 22 HIV-uninfected) with similar proportions of low (0-3) Nugent scores.

Human α-amylase present in lower-genital-tract mucosal fluid processes glycogen to support vaginal colonization by Lactobacillus.

Lactobacillus colonization of the lower female genital tract provides protection from the acquisition of sexually transmitted diseases, including human immunodeficiency virus, and from adverse pregnancy outcomes. While glycogen in vaginal epithelium is thought to support Lactobacillus colonization in vivo, many Lactobacillus isolates cannot utilize glycogen in vitro. This study investigated how glycogen could be utilized by vaginal lactobacilli in the genital tract.

The barrier to HIV transmission provided by genital tract Lactobacillus colonization.

While resistance to HIV transmission is due to multiple mechanisms such as the epithelium, a lower genital tract microbiota dominated by Lactobacillus appears to play an important role. This article reviews selected recent research on genital tract microbiota in women including how microbiota impacts HIV resistance and factors affecting Lactobacillus colonization.

Effects of Succinic Acid and Other Microbial Fermentation Products on HIV Expression in Macrophages.

Bacterial vaginosis (BV), a common condition in women, is associated with increased shedding of HIV in the female genital tract. While the Lactobacillus species that comprise a healthy vaginal microbiota produce lactic acid, the bacteria common in BV produce high concentrations of short chain fatty acids (SCFAs) and succinic acid. Macrophages are abundant in the lower genital tract mucosa and are thought to play an important role in HIV infection.

Bovine papillomavirus-like particles presenting conserved epitopes from membrane-proximal external region of HIV-1 gp41 induced mucosal and systemic antibodies.

Two conserved epitopes, located in the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 (HIV-1) gp41, are recognized by two HIV-1 broadly neutralizing antibodies 2F5 and 4E10, and are promising targets for vaccine design in efforts to elicit anti-HIV-1 broadly neutralizing antibodies. Since most HIV-1 infections initiate at mucosal surfaces, induction of mucosal neutralizing antibodies is necessary and of utmost importance to counteract HIV-1 infection. Here, we utilized a mucosal vaccine vector, bovine papillomavirus (BPV) virus-like particles (VLPs), as a platform to present HIV-1 neutralizing epitopes by inserting the extended 2F5 or 4E10 epitope or the MPER domain into D-E loop of BPV L1 respectively.

Lectin-dependent enhancement of Ebola virus infection via soluble and transmembrane C-type lectin receptors.

Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances.

IL-22 levels are associated with Trichomonas vaginalis infection in the lower genital tract.

Problem: IL-22 has important functions at mucosal surfaces, including the induction of antimicrobial peptides and maintenance of epithelium. However, IL-22 has not been investigated in the genital tract during TV infection.

Methods Of Study: Women who visited an STD clinic and women from a cohort with frequent Trichomoniasis were studied.

In captive rhesus macaques, cervicovaginal inflammation is common but not associated with the stable polymicrobial microbiome.

Vaginal inoculation of rhesus macaques (RM) with simian immunodeficiency virus (SIV) has been used to study the biology of HIV transmission. Although the results of vaginal SIV transmission experiments could be affected by vaginal inflammation, studies to date have been conducted without regard to levels of pre-existing genital inflammation present in RM. We collected cevicovaginal secretions (CVS) from 33-36 RM during the mid menstrual cycle (day 10-20) at 2 time points approximately 8 months apart and characterized the mRNA and protein levels of inflammatory cytokines, chemokines and interferon-stimulated genes.

Microbial diversity of genital ulcer disease in men enrolled in a randomized trial of male circumcision in Kisumu, Kenya.

Background: Medical male circumcision (MMC) reduces the risk of genital ulcer disease (GUD) in men by 50%. In Ugandan and Kenyan trials, a sexually transmissible agent was not identified in 50-60% of GUD specimens by polymerase chain reaction (PCR) assay. We sought to better define the etiology of GUD in men participating in the Kenyan trial and examine how MMC affects GUD etiology.

Exploring a road map to counter misconceptions about the cervicovaginal microbiome and disease.

Urogenital diseases, especially infection and cancer, are major causes of death and morbidity in females. Yet, millions of women in the developing world have no access to basic urogynecological care, and the diagnosis and treatment of widespread aberrant bacterial conditions (bacterial vaginosis [BV] and aerobic vaginitis [AV]) remain suboptimal the world over. Samples from women living in resource-disadvantaged and developed countries have been analyzed by high-throughput sequencing to reveal the diversity of bacteria in the vagina, how rapidly the bacterial population fluctuates over time, and how rapidly the switch occurs between healthy and aberrant conditions.