Variables Affecting CA15.3 Tumor Antigen Expression and Antibodies against It in Female National Health and Nutritional Survey Participants.

Background: Cancers of ductal origin often express glycoprotein mucin 1 (MUC1), also known as CA15.3, with higher levels leading to poor prognosis. Conversely, anti-MUC1 antibodies develop in some patients, leading to better prognosis.

Cervical and systemic innate immunity predictors of HIV risk linked to genital herpes acquisition and time from HSV-2 seroconversion.

Objectives: To examine innate immunity predictors of HIV-1 acquisition as biomarkers of HSV-2 risk and biological basis for epidemiologically established HIV-1 predisposition in HSV-2 infected women.

Methods: We analysed longitudinal samples from HIV-1 negative visits of 1019 women before and after HSV-2 acquisition. We measured cervical and serum biomarkers of inflammation and immune activation previously linked to HIV-1 risk.

Intestinal Inflammation is Significantly Associated With Length Faltering in Preterm Infants at Neonatal Intensive Care Unit Discharge.

Objective: The aim of the study was to assess intestinal inflammatory measures, urinary intestinal fatty acid-binding protein (IFABP), and fecal calprotectin (FC) by gestational age (GA) and postmenstrual age (PMA) and determine the association between intestinal inflammation and growth in preterm infants from birth to hospital discharge. We hypothesized that intestinal inflammation is associated with adverse growth in preterm infants.

Methods: We assayed repeated measures of IFABP and FC in 72 hospitalized preterm infants (<34 weeks' gestation).

Protozoan-Viral-Bacterial Co-Infections Alter Galectin Levels and Associated Immunity Mediators in the Female Genital Tract.

Co-infections with sexually transmittable pathogens are common and more likely in women with disturbed vaginal bacteriome. Among those pathogens, the protozoan parasite (TV) is most common after accounting for the highly persistent DNA viruses human papillomavirus (HPV) and genital herpes. The parasitic infection often concurs with the dysbiotic syndrome diagnosed as bacterial vaginosis (BV) and both are associated with risks of superimposed viral infections.

Elevated Intestinal Inflammation in Preterm Infants With Signs and Symptoms of Gastroesophageal Reflux Disease.

Objectives: Reflux is common in infancy; however, persistent signs and symptoms of gastrointestinal distress are often attributed to gastroesophageal reflux disease (GERD). In this pilot study, we aimed to characterize associations between signs and symptoms of suspected GERD and noninvasive markers of intestinal inflammation in preterm infants.

Methods: We reviewed Electronic Medical Record (EMR) data to identify clinical signs and symptoms among case patients (n = 16).

Epidemiologic and biologic correlates of serum HE4 and CA125 in women from the National Health and Nutritional Survey (NHANES).

Objectives: In women with ovarian cancer, tumor features largely determine serum HE4 and CA125 levels, but non-tumor factors may also influence levels and be better understood by studying determinants in a well-characterized sample of women without cancer.

Methods: Serum HE4 and CA125 were measured in 2302 women from the 2001-2002 cohort of the National Heath and Nutritional Survey (NHANES). Publicly-available data on this cohort included demographic/reproductive variables, blood counts, and measurements of C-reactive protein (CRP), total homocysteine (tHcy), cotinine, and creatinine which were examined as predictors of HE4 and CA125 using multivariate models and correlational analyses.

Racial/ethnic differences in average CA125 and CA15.3 values and its correlates among postmenopausal women in the USA.

Purpose: Among healthy postmenopausal women, levels of CA125 and CA15.3 are influenced by demographic and reproductive factors, including race/ethnicity. In this study, we sought to examine the interaction between race/ethnicity and other correlates of these biomarkers and whether the racial differences observed are simply determined by other correlates with racial differences.

The Role of Small Extracellular Vesicles in Viral-Protozoan Symbiosis: Lessons From in an Isogenic Host Parasite Model.

The protozoan parasite (TV), exclusively adapted to the human genital tract, is one of the most common sexually transmitted pathogens. Adding to the complexity of the host-pathogen interactions, the parasite harbors TV-specific endosymbiont viruses (, TVV). It was reported that small extracellular vesicles (sEVs) released by TV play a role in host immunity; however, the role of the viral endosymbiosis in this process remained unknown.

Concomitant Imbalances of Systemic and Mucosal Immunity Increase HIV Acquisition Risk.

Background: We previously reported association of increased cervical RANTES and decreased secretory leukocyte protease inhibitor (SLPI) with higher risk of HIV acquisition in reproductive-age women. We now examine the interaction of concomitantly altered systemic and cervical immunity on such risk.

Methods: We measured immune biomarkers in 4390 cervical and 2390 paired serum specimens at quarterly visits in 218 HIV seroconverters and 784 seronegative women.

Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age.

Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data.

Development and validation of circulating CA125 prediction models in postmenopausal women.

Background: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker.

[Urine Protein/Creatinine Ratio Measurement Is Useful to Continue Anti-Angiogenic Agent Treatment].

Background: Aside effect of anti-angiogenic agent treatment is proteinuria. Evaluation of the severity of adverse effects and the decision to discontinue treatment is based on the qualitative analysis of urinary proteins. However, a qualitative analysis result may not be indicative of the actual amounts of protein excreted.

Surfactant Protein D Reverses the Gene Signature of Transepithelial HIV-1 Passage and Restricts the Viral Transfer Across the Vaginal Barrier.

Effective prophylactic strategy against the current epidemic of sexually transmitted HIV-1 infection requires understanding of the innate gatekeeping mechanisms at the genital mucosa. Surfactant protein D (SP-D), a member of the collectin family of proteins naturally present in the vaginal tract, is a potential HIV-1 entry inhibitor at the cellular level. Human EpiVaginal tissues compartmentalized in culture inserts were apically exposed to HIV-1 and/or a recombinant fragment of human SP-D (rfhSP-D) and viral passage was assessed in the basal chamber containing mononuclear leukocytes.

Predicting Circulating CA125 Levels among Healthy Premenopausal Women.

Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women.

A Longitudinal Assessment of Cervical Inflammation and Immunity Associated with HIV-1 Infection, Hormonal Contraception, and Pregnancy.

Hormonal contraception (HC), particularly injectable depot-medroxyprogesterone acetate (DMPA), has been associated with increased HIV acquisition and higher levels of cervical regulated upon activation, normal T-cell expressed, and secreted (RANTES), also associated with HIV seroconversion. Longitudinal changes in cervical immunity associated with DMPA and combined oral contraceptives (COCs) have not been studied. Cervical samples from 216 HIV seroconverters in Uganda and Zimbabwe with matched samples from 727 HIV-uninfected controls were collected at two quarterly visits before (t - 2, t - 1), at (t0), and two visits following (t + 1, t + 2) HIV seroconversion and corresponding visits for HIV-negative controls.

Anti-CA15.3 and Anti-CA125 Antibodies and Ovarian Cancer Risk: Results from the EPIC Cohort.

Neoplastic and non-neoplastic events may raise levels of mucins, CA15.3, and CA125, and generate antibodies against them, but their impact on epithelial ovarian cancer (EOC) risk has not been fully defined. CA15.

Antecedents and correlates of blood concentrations of neurotrophic growth factors in very preterm newborns.

Aim: To identify the antecedents and very early correlates of low concentrations of neurotrophic growth factors in the blood of extremely preterm newborns during the first postnatal month.

Methods: Using an immunobead assay, we measured the concentrations of neurotrophin 4 (NT4), brain-derived neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF) in blood spots collected on postnatal days 1 (N=1062), 7 (N=1087), 14 (N=989), 21 (N=940) and 28 (N=880) from infants born before the 28th week of gestation. We then sought the correlates of measurements in the top and bottom quartiles for gestational age and day the specimen was collected.

Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models: results from the EPIC cohort.

Background: Ovarian cancer early detection markers CA125, CA15.3, HE4, and CA72.4 vary between healthy women, limiting their utility for screening.

A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort.

Purpose: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers.

Trichomonas vaginalis Lipophosphoglycan Exploits Binding to Galectin-1 and -3 to Modulate Epithelial Immunity.

Trichomoniasis is the most common non-viral sexually transmitted infection caused by the vaginotropic extracellular protozoan parasite Trichomonas vaginalis. The infection is recurrent, with no lasting immunity, often asymptomatic, and linked to pregnancy complications and risk of viral infection. The molecular mechanisms of immune evasion by the parasite are poorly understood.

Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics.

Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes.

Gene Expression Profiling of Human Vaginal Cells In Vitro Discriminates Compounds with Pro-Inflammatory and Mucosa-Altering Properties: Novel Biomarkers for Preclinical Testing of HIV Microbicide Candidates.

Background: Inflammation and immune activation of the cervicovaginal mucosa are considered factors that increase susceptibility to HIV infection. Therefore, it is essential to screen candidate anti-HIV microbicides for potential mucosal immunomodulatory/inflammatory effects prior to further clinical development. The goal of this study was to develop an in vitro method for preclinical evaluation of the inflammatory potential of new candidate microbicides using a microarray gene expression profiling strategy.

Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract.

Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and found that the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity.

A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation.

Any vaginal product that alters the mucosal environment and impairs the immune barrier increases the risk of sexually transmitted infections, especially HIV infection, which thrives on mucosal damage and inflammation. The FDA-recommended rabbit vaginal irritation (RVI) model serves as a first line selection tool for vaginal products; however, for decades it has been limited to histopathology scoring, insufficient to select safe anti-HIV microbicides. In this study we incorporate to the RVI model a novel quantitative nuclease protection assay (qNPA) to quantify mRNA levels of 25 genes representing leukocyte differentiation markers, toll-like receptors (TLR), cytokines, chemokines, epithelial repair, microbicidal and vascular markers, by designing two multiplex arrays.