Publications by authors named "Darville T"

Objective: To study the impact of preconception Chlamydia trachomatis seropositivity on fecundability, live birth, and pregnancy loss and to assess the effect of low-dose aspirin therapy (81 mg/day) on live birth and pregnancy loss.

Design: Preconception cohort study conducted using data and specimens from the Effects of Aspirin in Gestation and Reproduction study-a randomized placebo-controlled trial.

Patients: A total of 1,228 individuals with proven fecundity and a history of 1-2 pregnancy losses.

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Introduction: Chlamydia trachomatis (CT) infection can lead to pelvic inflammatory disease, infertility and other reproductive sequelae when it ascends to the upper genital tract. Factors including chlamydial burden, co-infection with other sexually-transmitted bacterial pathogens and oral contraceptive use influence risk for upper genital tract spread. Cervicovaginal microbiome composition influences CT susceptibility and we investigated if it contributes to spread by analyzing amplicon sequence variants (ASVs) derived from the V4 region of 16S rRNA genes in vaginal samples collected from women at high risk for CT infection and for whom endometrial infection had been determined.

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Background: Performance of a 16S rRNA analysis of the cervicovaginal microbiome of 220 participants recruited into the T Cell Response against Chlamydia (TRAC) cohort between February 2011 and August 2014 in Allegheny County, Pennsylvania USA detected DNA encoding chlamydial 16S rRNA in samples from seven participants whose tests were negative for Chlamydia trachomatis (CT) and DNA encoding gonococcal 16S rRNA from five participants whose tests were negative for Neisseria gonorrhoeae (NG) infection with the Aptima Combo2 assay (Hologic).

Methods: We used targeted PCR amplification followed by sequencing to characterize the chlamydial 23S rRNA locus and qPCR to detect gonococcal DNA in residual diagnostic swab eluates or DNA used to generate 16S rRNA libraries.

Results: Discrepant specimens that contained chlamydial DNA carried a diagnostic-avoidant, G1526A variant in the 23S rRNA locus identical to variants previously detected in Finland, Denmark, and the UK.

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Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection globally, and a vaccine is urgently needed to stop transmission and disease. Chlamydial Protease Activity Factor (CPAF) is an immunoprevalent and immunodominant antigen for CD4 T cells and B cells, which makes it a strong vaccine candidate. Due to the tolerogenic nature of the female genital tract (FGT) and its lack of secondary lymphoid tissue, effective induction of protective cell-mediated immunity will likely require potent and safe mucosal adjuvants.

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Article Synopsis
  • Chlamydia trachomatis (Ct) is the most prevalent bacterial STI worldwide, highlighting the urgent need for an effective vaccine.
  • The study focuses on Chlamydial Protease Activity Factor (CPAF), identified as a promising antigen for vaccine development due to its strong immune response in T and B cells.
  • Researchers tested different mucosal adjuvants, finding that intranasal vaccination with CPAF and a specific adjuvant (CDA) was safe and effective in reducing infection in mice, indicating potential for a new Chlamydia vaccine.
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Background: Chlamydia trachomatis (CT) is a globally prevalent sexually transmitted infection (STI) that can result in pelvic inflammatory disease, ectopic pregnancy and infertility in women. Currently, there is no prophylactic vaccine.

Methods: This study examined T cell immunity in a cohort of women recently infected with CT.

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Article Synopsis
  • - STIs caused by bacterial pathogens pose serious challenges to public health, impacting reproductive health and increasing risks of complications like pelvic inflammatory disease and infertility.
  • - Preventative measures are complicated due to the asymptomatic nature of these infections, the necessity for continuous screening, and rising antibiotic resistance, particularly for gonorrhea and limited penicillin availability for syphilis.
  • - Although vaccines are available for some viral STIs, there are no current vaccines for bacterial STIs, prompting research into the immune responses in the female genital tract to help in vaccine development.
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A vaccine is needed to combat the Chlamydia epidemic. Replication-deficient viral vectors are safe and induce antigen-specific T-cell memory. We tested the ability of intramuscular immunization with modified vaccinia Ankara (MVA) virus or chimpanzee adenovirus (ChAd) expressing chlamydial outer membrane protein (OmcB) or the secreted protein, chlamydial protease-like activating factor (CPAF), to enhance T-cell immunity and protection in mice previously infected with plasmid-deficient Chlamydia muridarum CM972 and elicit protection in naïve mice.

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() infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for , undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as () in pigs.

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infection of ocular conjunctiva can lead to blindness, while infection of the female genital tract can lead to chronic pelvic pain, ectopic pregnancy, and/or infertility. Conjunctival and fallopian tube inflammation and the resulting disease sequelae are attributed to immune responses induced by chlamydial infection at these mucosal sites. The conserved chlamydial plasmid has been implicated in enhancing infection, via improved host cell entry and exit, and accelerating innate inflammatory responses that lead to tissue damage.

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(CT) is the most common bacterial sexually transmitted infection globally. Understanding natural immunity to CT will inform vaccine design. This study aimed to profile immune cells and associated functional features in CT-infected women, and determine immune profiles associated with reduced risk of ascended endometrial CT infection and CT reinfection.

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We developed a reusable and open-source machine learning (ML) pipeline that can provide an analytical framework for rigorous biomarker discovery. We implemented the ML pipeline to determine the predictive potential of clinical and immunoproteome antibody data for outcomes associated with Chlamydia trachomatis () infection collected from 222 cis-gender females with high exposure. We compared the predictive performance of 4 ML algorithms (naive Bayes, random forest, extreme gradient boosting with linear booster [xgbLinear], and -nearest neighbors [KNN]), screened from 215 ML methods, in combination with two different feature selection strategies, Boruta and recursive feature elimination.

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Electronic cigarette, or vaping, product use-associated lung injury (EVALI) is an increasingly recognized entity with the potential for severe pulmonary toxicity. We present the case of a young man first evaluated at a tertiary care center in the United States in 2019 with newly diagnosed testicular cancer with acute respiratory failure, which was initially attributed to possible metastatic disease but eventually determined to be related to EVALI. This case highlights the clinical features of EVALI, the potential diagnostic dilemma that can arise with EVALI when occurring in the setting of malignancy and the importance of inquiring about vaping use among patients with malignancy, especially in adolescents and young adults.

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Chlamydia trachomatis is the most common cause of infectious blindness and sexually transmitted bacterial infection globally. C. trachomatis contains a conserved chlamydial plasmid with eight coding sequences.

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Objectives: Identify genetic loci of enhanced susceptibility to upper genital tract infection in women.

Methods: We performed an integrated analysis of DNA genotypes and blood-derived mRNA profiles from 200 exposed women to identify expression quantitative trait loci (eQTL) and determine their association with endometrial chlamydial infection using a mediation test. We further evaluated the effect of a lead eQTL on the expression of by immune cells from women with genotypes associated with low and high whole blood expression of , respectively.

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To prepare for the development of the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections treatment guidelines, the CDC convened a committee of expert consultants in June 2019 to discuss recent abstracts and published literature on the epidemiology, diagnosis, and management of sexually transmitted infections.This paper summarizes the key questions, evidence, and recommendations for the diagnosis and management of uncomplicated Chlamydia trachomatis (CT) infections in adolescents and adults that were reviewed and discussed for consideration in developing the guidelines. The evidence reviewed mostly focused on efficacy of doxycycline and azithromycin for urogenital, rectal, and oropharyngeal CT infection, CT risk factors in women, performance of CT nucleic acid amplification tests on self-collected meatal specimens in men, and performance of newer CT point-of-care tests.

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Many biomedical studies collect data of mixed types of variables from multiple groups of subjects. Some of these studies aim to find the group-specific and the common variation among all these variables. Even though similar problems have been studied by some previous works, their methods mainly rely on the Pearson correlation, which cannot handle mixed data.

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() causes the most prevalent bacterial sexually transmitted disease leading to ectopic pregnancy and infertility. Swine not only have many similarities to humans, but they are also susceptible to . Despite these benefits and the ease of access to primary tissue from this food animal, in vitro research in swine has been underutilized.

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Background: Previous research revealed antibodies targeting Chlamydia trachomatis elementary bodies was not associated with reduced endometrial or incident infection in C. trachomatis-exposed women. However, data on the role of C.

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Pelvic inflammatory disease (PID) results from ascension of sexually transmitted pathogens from the lower genital tract to the uterus and/or fallopian tubes in women, with potential spread to neighboring pelvic organs. Patients may present acutely with lower abdominal or pelvic pain and pelvic organ tenderness. Many have subtle symptoms or are asymptomatic and present later with tubal factor infertility, ectopic pregnancy, or chronic pelvic pain.

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Background: Chlamydia trachomatis (Ct) infection ascending to the upper genital tract can cause infertility. Direct association of genetic variants as contributors is challenging because infertility may not be diagnosed until years after infection. Investigating the intermediate trait of ascension bridges this gap.

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Genital infections with Chlamydia trachomatis can lead to uterine and oviduct tissue damage in the female reproductive tract. Neutrophils are strongly associated with tissue damage during chlamydial infection, while an adaptive CD4 T cell response is necessary to combat infection. Activation of triggering receptor expressed on myeloid cells-1 (TREM-1) on neutrophils has previously been shown to induce and/or enhance degranulation synergistically with Toll-like receptor (TLR) signaling.

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Introduction: is the most common sexually transmitted bacterial pathogen in the world. Antibiotic treatment does not prevent against reinfection and a vaccine is not yet available.

Areas Covered: We focus the review on the progress made of our understanding of the immunological responses required for a vaccine to elicit protection, and on the antigens, adjuvants, routes of immunization and delivery systems that have been tested in animal models.

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To elucidate the molecular mechanisms underlying genetic variants identified from genome-wide association studies (GWAS) for a variety of phenotypic traits encompassing binary, continuous, count, and survival outcomes, we propose a novel and flexible method to test for mediation that can simultaneously accommodate multiple genetic variants and different types of outcome variables. Specifically, we employ the intersection-union test approach combined with the likelihood ratio test to detect mediation effect of multiple genetic variants via some mediator (e.g.

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infection of the female genital tract can lead to irreversible fallopian tube scarring. In the mouse model of genital infection using IL-1R signaling plays a critical role in oviduct tissue damage. In this study, we investigated the pathologic role of IL-1α, one of the two proinflammatory cytokines that bind to IL-1R.

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