Interferon-Gamma Responses to Chlamydia trachomatis Vaccine Candidate Proteins in Chlamydia-Infected Women with Different Chlamydia Outcomes.

BACKGROUND: Chlamydia trachomatis (CT) testing and treatment strategies have not decreased infection rates, justifying need for a CT vaccine. A murine study showed that a vaccine consisting of MOMP and 4 polymorphic membrane proteins (Pmps E, F, G, H) elicited protective immunity; studies on human cellular immune responses to Pmps are sparse. METHODS: Interferon gamma (IFN-γ) responses to these 5 CT proteins were measured by ELISPOT in PBMCs from women returning for treatment of a positive CT screening test. Responses were compared in those with spontaneous CT clearance vs. persisting infection at baseline and no reinfection vs. reinfection at a 3-month follow-up visit. RESULTS: IFN-γ response to one or more proteins was detected in 39% at baseline and 51.5% at follow-up; PmpE and MOMP most often elicited positive responses. IFN-γ responses to MOMP were detected less often at follow-up vs. baseline in women with reinfection, but were maintained in those without reinfection. Women with spontaneous clearance had a higher magnitude of IFN-γ response to PmpE and MOMP. CONCLUSIONS: IFN-γ responses to these 5 CT vaccine candidate proteins were heterogenous and primarily directed against MOMP and PmpE. Spontaneous clearance of infection and absence of reinfection may be clinical correlates of protection.

Antibody responses to Chlamydia trachomatis vaccine candidate antigens in Chlamydia-infected women and correlation with antibody-mediated phagocytosis of elementary bodies.

Murine research has revealed a significant role for antibody responses in protection against Chlamydia reinfection. To explore potential humoral immune markers of protection elicited by Chlamydia trachomatis (CT) antigens in humans in the context of presumed clinical correlates of protection, we used both an IgG1-based ELISA and a conventional total IgG ELISA to evaluate antibody responses. We evaluated responses to five CT outer membrane proteins (PmpE, PmpF, PmpG, PmpH, and MOMP), along with other promising CT antigens (Pgp3 and HSP60), negative control antigens (RecO and AtpE), and CT elementary bodies (EBs) in sera from a well-characterized cohort of 60 women with different CT infection outcomes, including two outcomes that are likely clinical correlates of protective immunity: spontaneous resolution of infection and absence of reinfection after treatment. Furthermore, we used a flow cytometry-based assay to measure antibody-mediated phagocytosis by neutrophils in these sera. Results demonstrated that IgG1 ELISA displayed higher sensitivity than conventional total IgG ELISA in assessing antibody responses to CT EBs and antigens. Pgp3 IgG1 ELISA exhibited the highest sensitivity compared to IgG1 ELISA incorporating CT EBs or other antigens, confirming Pgp3 IgG1 ELISA as an ideal assay for CT antibody detection. Most (95%) sera from women with CT infection outcomes exhibited antibody-mediated phagocytosis of CT EBs, which was significantly correlated with IgG1 antibody responses to MOMP, Pgp3, HSP60, and PmpF. However, neither IgG1 responses to CT antigens and EBs nor antibody-mediated phagocytosis were associated with clinical correlates of protection. These findings suggest that neither CT IgG1 antibody detection nor antibody-mediated phagocytosis will be useful as immune correlates of protection against CT infection in humans.

HLA-DQB1*06 and Select Neighboring HLA Variants Predict Chlamydia Reinfection Risk.

Associations of HLA class II alleles with genital chlamydial infection outcomes have been reported, especially HLA DQB1*06. However, the potential role of DQB1*06 in influencing reinfection risk has still not been established. The purpose of this study was to determine whether the association of DQB1*06 with chlamydia reinfection was impacted by any other nearby HLA class II variants that were also associated with reinfection. We used next-generation sequencing to map HLA class II variants spanning the HLA-DQ and -DR loci. DQB1*06 as well as DQB1*04 were confirmed as significant predictors of chlamydia reinfection, when controlling for age and percent African ancestry. SKAT analysis revealed one region each in DRB1, DRB5, DQA2, and three intergenic regions that had variants associated with reinfection. Further analyses of these variants revealed that rs112651494 within DRB5 and an intergenic SNP rs617058 in DRB1:DQA1 were significantly associated with reinfection, but this did not impact the significance of the association of DQB1*06 or DQB1*04 with reinfection.

Chlamydia trachomatis -Specific Antibody Responses in Women in Cameroon With Secondary Infertility.

ABSTRACT: The contribution of chlamydia to secondary infertility in women is poorly understood. Among 404 female participants enrolled in a previous study in Cameroon, 142 had secondary infertility (cases) and 262 were pregnant with no history of infertility (controls) , Chlamydia trachomatis seropositivity was 92%. Seropositivity did not significantly differ by case/control status.

Natural Clearance of Chlamydia trachomatis Infection Is Associated With Distinct Differences in Cervicovaginal Metabolites.

BACKGROUND: Natural clearance of Chlamydia trachomatis in women occurs in the interval between screening and treatment. In vitro, interferon-γ (IFN-γ)-mediated tryptophan depletion results in C. trachomatis clearance, but whether this mechanism occurs in vivo remains unclear. We previously found that women who naturally cleared C. trachomatis had lower cervicovaginal levels of tryptophan and IFN-γ compared to women with persisting infection, suggesting IFN-γ-independent pathways may promote C. trachomatis clearance. METHODS: Cervicovaginal lavages from 34 women who did (n = 17) or did not (n = 17) naturally clear C. trachomatis were subjected to untargeted high-performance liquid chromatography mass-spectrometry to identify metabolites and metabolic pathways associated with natural clearance. RESULTS: In total, 375 positively charged metabolites and 149 negatively charged metabolites were annotated. Compared to women with persisting infection, C. trachomatis natural clearance was associated with increased levels of oligosaccharides trehalose, sucrose, melezitose, and maltotriose, and lower levels of indoline and various amino acids. Metabolites were associated with valine, leucine, and isoleucine biosynthesis pathways. CONCLUSIONS: The cervicovaginal metabolome in women who did or did not naturally clear C. trachomatis is distinct. In women who cleared C. trachomatis, depletion of various amino acids, especially valine, leucine, and isoleucine, suggests that amino acids other than tryptophan impact C. trachomatis survival in vivo.

Immunohistochemical expression of Ki-67 and Glypican-3 to distinguish aggressive from nonaggressive benign odontogenic tumors.

Background: The benign neoplasms are normally slow growing, indolent with no invasive potential. However, there exist a few locally aggressive benign odontogenic tumors that have a tendency to invade and deform the surrounding structures. The exact reason for the aggressiveness of these benign neoplasms remained an enigma. Their biology and clinical expression can often be destructive and ominous. An appropriate treatment protocol needs to be followed to combat the high recurrence rate and aggressiveness of these entities. Aggressive and noniaggressive epithelial odontogenic tumors were analyzed immunohistochemically with Ki-67 and glypican 3 (GPC3). Materials and Methods: Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, four unicystic ameloblastoma, and 28 keratocystic odontogenic tumors) and nonaggressive odontogenic tumors (five adenomatoid odontogenic tumors and two calcifying cystic odontogenic itumors). Results: Statistical analysis using Pearson correlation showed Ki-67 to be a better marker for differentiating aggressive from nonaggressive odontogenic tumor as compared to GPC3 (P < 0.001, highly significant), whereas among aggressive tumors, GPC3 turned out to be more useful as compared to Ki-67 (P < 0.001, highly significant). Conclusion: The present study provides an insight into the different biological behavior of odontogenic tumors, which can thus be helpful in determining the therapy strategies for more aggressive odontogenic tumors.

Chlamydia trachomatis Infection and Seropositivity in Women Reporting Sexual Contact to a Chlamydia-Infected Partner.

ABSTRACT: Among 73 women presenting to a sexually transmitted infection (STI) clinic in Birmingham, Alabama for reported sexual contact to a chlamydia-infected partner, Chlamydia trachomatis was detected in genital specimens in 24 (32.8%), less often in women reporting prior chlamydial infection ( P = 0.001). Most women (93.2%) were C. trachomatis seropositive.

Association of Bacterial Vaginosis With Higher Vaginal Indole Levels.

ABSTRACT: We adapted a simple hydroxylamine-based indole assay to detect indole from stored vaginal swab specimens from women with and without bacterial vaginosis (BV). Women with BV had significantly higher vaginal indole levels compared with women without BV (6451.5 vs 5632.4 µM; P = 0.01), suggesting that indole-producing bacteria are a component of BV.

Mycoplasma genitalium infection in women reporting dysuria: A pilot study and review of the literature.

Mycoplasma genitalium (MG) infection, a sexually transmitted infection (STI), causes cervicitis and may cause reproductive sequelae and adverse pregnancy outcomes. Some MG-infected women report dysuria, a symptom frequently attributed to urinary tract infection (UTI). Given potential MG-associated morbidity and the likelihood that UTI treatment would be ineffective in eradicating MG, an improved understanding of MG infection frequency and clinical significance in young women reporting dysuria is needed. We conducted MG testing on stored urogenital specimens collected in a pilot study on frequency of STIs in young women presenting to an emergency department for dysuria evaluation and performed a literature review on MG infection frequency in women reporting dysuria. Among 25 women presenting for dysuria evaluation in our pilot study, 6 (24.0%) had MG detected and one-third had co-infection with chlamydia and one-third with trichomoniasis; half with MG detected did not receive an antibiotic with known efficacy against MG, while the other half received azithromycin. In five studies identified in the literature review, dysuria was reported by 7%-19% of women and MG detected in 5%-22%. MG infection is common in young women with dysuria and empiric UTI treatment may not be effective against MG. Studies evaluating the clinical significance of MG infection in women reporting dysuria are needed.

Prevalence of Chlamydia trachomatis Infection in Young Women and Associated Predictors.

BACKGROUND: Chlamydia trachomatis (CT) infection remains highly prevalent, and young women are disproportionately affected. Most CT-infected women are asymptomatic, and their infection often goes unrecognized and untreated. We hypothesized that testing for active CT infection with molecular diagnostics and obtaining a reported history of CT infection underestimate the prevalence of current and past CT infection, and incorporating serum CT antibody testing in addition to these other prevalence measures would generate more accurate estimates of the prevalence of CT infection in asymptomatic young women. METHODS: We enrolled 362 asymptomatic women aged 16 to 29 years at 4 different clinical settings in Birmingham, AL, between August 2016 and January 2020 and determined the prevalence of CT infection based on having 1 or more of the following prevalence measures: an active urogenital CT infection based on molecular testing, reported prior CT infection, and/or being CT seropositive. Multivariable regression analysis was used to determine predictors of the prevalence of CT infection after adjustment for participant characteristics. RESULTS: The prevalence of CT infection was 67.7% (95% confidence interval, 62.6%-72.5%). Addition of CT antibody testing to the other individual prevalence measures more than doubled the CT infection prevalence. Non-Hispanic Black race, reported prior gonorrhea, and reported prior trichomoniasis predicted a higher prevalence of CT infection. CONCLUSIONS: More than half of women were unaware of ever having CT infection, suggesting many were at risk for CT-associated reproductive complications. These data reinforce the need to adhere to chlamydia screening guidelines and to increase screening coverage in those at risk.

Predicting the Probability of Chlamydia Reinfection in African American Women Using Immunologic and Genetic Determinants in a Bayesian Model.

BACKGROUND: African Americans have the highest rates of Chlamydia trachomatis (CT) infection in the United States and also high reinfection rates. The primary objective of this study was to develop a Bayesian model to predict the probability of CT reinfection in African American women using immunogenetic data. METHODS: We analyzed data from a cohort of CT-infected African American women enrolled at the time they returned to a clinic in Birmingham, AL, for the treatment of a positive routine CT test result. We modeled the probability of CT reinfection within 6 months after treatment using logistic regression in a Bayesian framework. Predictors of interest were presence or absence of an HLA-DQB1*06 allele and CT-specific CD4+ IFN-γ response, both of which we had previously reported were independently associated with CT reinfection risk. RESULTS: Among 99 participants evaluated, the probability of reinfection for those with a CT-specific CD4+ IFN-γ response and no HLA-DQB1*06 alleles was 14.1% (95% credible interval [CI], 3.0%-45.0%), whereas the probability of reinfection for those without a CT-specific CD4+ IFN-γ response and at least one HLA-DQB1*06 allele was 61.5% (95% CI, 23.1%-89.7%). CONCLUSIONS: Our model demonstrated that presence or absence of an HLA-DQB1*06 allele and CT-specific CD4+ IFN-γ response can have an impact on the predictive probability of CT reinfection in African American women.

Mycoplasma genitalium Infection in Young Women Without Urogenital Symptoms Presenting to a Community-Based Emergency Department in Birmingham, Alabama.

ABSTRACT: We used the Food and Drug Administration-cleared Aptima Mycoplasma genitalium assay to evaluate for M. genitalium infection among young women without urogenital symptoms presenting to a community-based emergency department in Birmingham, Alabama, between August 2016 to August 2019 for evaluation of nongynecological concerns. M. genitalium was detected in 23 (14.8%) of 155 women.

Current Conceptual Understanding of the Epileptogenic Network From Stereoelectroencephalography-Based Connectivity Inferences.

Localization of the epileptogenic zone (EZ) is crucial in the surgical treatment of focal epilepsy. Recently, EEG studies have revealed that the EZ exhibits abnormal connectivity, which has led investigators to now consider connectivity as a biomarker to localize the EZ. Further, abnormal connectivity of the EZ may provide an explanation for the impact of focal epilepsy on more widespread brain networks involved in typical cognition and development. Stereo-electroencephalography (sEEG) is a well-established method for localizing the EZ that has recently been applied to examine altered brain connectivity in epilepsy. In this manuscript, we review recent computational methods for identifying the EZ using sEEG connectivity. Findings from previous sEEG studies indicate that during interictal periods, the EZ is prone to seizure generation but concurrently receives inward connectivity preventing seizures. At seizure onset, this control is lost, allowing seizure activity to spread from the EZ. Regulatory areas within the EZ may be important for subsequently ending the seizure. After the seizure, the EZ appears to regain its influence on the network, which may be how it is able to regenerate epileptiform activity. However, more research is needed on the dynamic connectivity of the EZ in order to build a biomarker for EZ localization. Such a biomarker would allow for patients undergoing sEEG to have electrode implantation, localization of the EZ, and resection in a fraction of the time currently needed, preventing patients from having to endure long hospital stays and induced seizures.

Seizure-onset regions demonstrate high inward directed connectivity during resting-state: An SEEG study in focal epilepsy.

OBJECTIVE: In patients with medically refractory focal epilepsy, stereotactic-electroencephalography (SEEG) can aid in localizing epileptogenic regions for surgical treatment. SEEG, however, requires long hospitalizations to record seizures, and ictal interpretation can be incomplete or inaccurate. Our recent work showed that non-directed resting-state analyses may identify brain regions as epileptogenic or uninvolved. Our present objective is to map epileptogenic networks in greater detail and more accurately identify seizure-onset regions using directed resting-state SEEG connectivity. METHODS: In 25 patients with focal epilepsy who underwent SEEG, 2 minutes of resting-state, artifact-free, SEEG data were selected and functional connectivity was estimated. Using standard clinical interpretation, brain regions were classified into four categories: ictogenic, early propagation, irritative, or uninvolved. Three non-directed connectivity measures (mutual information [MI] strength, and imaginary coherence between and within regions) and four directed measures (partial directed coherence [PDC] and directed transfer function [DTF], inward and outward strength) were calculated. Logistic regression was used to generate a predictive model of ictogenicity. RESULTS: Ictogenic regions had the highest and uninvolved regions had the lowest MI strength. Although both PDC and DTF inward strengths were highest in ictogenic regions, outward strengths did not differ among categories. A model incorporating directed and nondirected connectivity measures demonstrated an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.88 in predicting ictogenicity of individual regions. The AUC of this model was 0.93 when restricted to patients with favorable postsurgical seizure outcomes. SIGNIFICANCE: Directed connectivity measures may help identify epileptogenic networks without requiring ictal recordings. Greater inward but not outward connectivity in ictogenic regions at rest may represent broad inhibitory input to prevent seizure generation.

Exophytic gingival growth of the maxillary canine region in a young individual: Extremely rare case report of peripheral dentinogenic ghost cell tumor.

The present case report is a case of peripheral dentinogenic ghost cell tumor (PDGCT), an extremely rare solid benign neoplastic variant of calcifying cystic odontogenic tumor of the gingiva mimicking clinically as pyogenic granuloma, fibroma, peripheral ossifying fibroma, and peripheral giant-cell granuloma. A 24-year-old male reported with painless, firm, solitary, sessile, smooth-surfaced, nonulcerative, nonpulsatile, well-defined swelling measuring ≈12 mm × 9 mm in the interdental gingiva of the teeth #13 and #14 extending to the mucogingival junction. Intraoral periapical radiographic showed a normal trabecular pattern with mild radiolucency without bony expansion, periapical lesion, and resorption of the adjacent teeth. The diagnosis was established by histopathologic examination. Very few cases of this entity have been documented in the literature. The present case report aims to document this rare entity and emphasizes on the fact that histopathological examination of every localized gingival growth should be included in the treatment planning to differentiate with other commonly found lesions.

Emerging indications for stereotactic laser interstitial thermal therapy in pediatric neurosurgery.

Surgical treatment of deep or difficult to access lesions represents a unique and significant challenge for pediatric neurosurgeons. The introduction of stereotactic magnetic resonance-guided laser interstitial thermal therapy (LITT) over the last decade has had a dramatic impact on the landscape of pediatric neurosurgery. LITT provides a safe and effective option for children with epilepsy from hypothalamic hamartoma that represents a ground-breaking new therapy for a condition which was historically very difficult to treat with previous neurosurgical techniques. LITT has also been used as an alternative surgical technique for mesial temporal sclerosis, focal cortical dysplasia, MR-negative epilepsy, cavernoma-related epilepsy, insular epilepsy, and corpus callosotomy among other epilepsy etiologies. In some cases, LITT has been associated with improved cognitive outcomes compared to standard techniques, as in mesial temporal lobe epilepsy. Initial experiences with LITT for neuro-oncologic processes are also promising. LITT is often attractive to patients and providers as a minimally invasive approach, but the differences in safety and clinical outcome between LITT and traditional approaches are still being studied. In this review, we examine the emerging indications and clinical evidence for LITT in pediatric neurosurgery.

Resting-State SEEG May Help Localize Epileptogenic Brain Regions.

BACKGROUND: Stereotactic electroencephalography (SEEG) is a minimally invasive neurosurgical method to localize epileptogenic brain regions in epilepsy but requires days in the hospital with interventions to trigger several seizures. OBJECTIVE: To make initial progress in the development of network analysis methods to identify epileptogenic brain regions using brief, resting-state SEEG data segments, without requiring seizure recordings. METHODS: In a cohort of 15 adult focal epilepsy patients undergoing SEEG, we evaluated functional connectivity (alpha-band imaginary coherence) across sampled regions using brief (2 min) resting-state data segments. Bootstrapped logistic regression was used to generate a model to predict epileptogenicity of individual regions. RESULTS: Compared to nonepileptogenic structures, we found increased functional connectivity within epileptogenic regions (P < .05) and between epileptogenic areas and other structures (P < .01, paired t-tests, corrected). Epileptogenic areas also demonstrated higher clustering coefficient (P < .01) and betweenness centrality (P < .01), and greater decay of functional connectivity with distance (P < .05, paired t-tests, corrected). Our functional connectivity model to predict epileptogenicity of individual regions demonstrated an area under the curve of 0.78 and accuracy of 80.4%. CONCLUSION: Our study represents a preliminary step towards defining resting-state SEEG functional connectivity patterns to help localize epileptogenic brain regions ahead of neurosurgical treatment without requiring seizure recordings.

Comparison of different stains in exfoliated oral mucosal cell micronucleus of potentially malignant disorders of oral cavity.

BACKGROUND: Micronucleus (MN) has been proved to be an important biomarker of genomic damage. Leishman Giemsa (LG) cocktail, being a relatively new staining technique, has not been used in exfoliative cytology. The aim of this study is to observe and compare the micronuclei (MN) frequency in potentially malignant disorders (PMDs) and also to compare the staining efficacy of May-Grünwald Giemsa (MGG), LG cocktail, and Papanicolaou (PAP) for micronuclei in exfoliated oral mucosal cells. MATERIALS AND METHODS: Three smears were prepared from each 30 controls (buccal mucosa) and 120 patients (40 oral submucous fibrosis, 40 lichen planus, and 40 leukoplakia) clinically diagnosed with having one of the PMDs of the oral cavity stained with PAP, MGG, and LG cocktail stains. MN frequency (No. of MN/1000 cells) was evaluated and compared between the cases and the controls. Comparison between the three different stained smears was also made to determine the clarity and efficacy of the stains. RESULTS: LG cocktail gave comparatively better results followed by PAP and MGG. Statistically significant results (P < 0.05) were obtained, using Mann-Whitney test for comparison of MN frequency between cases and controls. CONCLUSION: LG cocktail is an easy, cost- effective, and one step technique comparable to PAP staining; however, it warrants further study in its potential application in screening of oral cancer.

Nonkeratinizing squamous cell carcinoma: A rare case report with oral involvement.

Transitional cell carcinoma also known as nonkeratinizing carcinoma (NKCa) of sinonasal tract comprises 15%-20% of malignant sinonasal carcinoma. We are reporting the case of 48-year-old male with a history of tooth extraction. A computed tomography was done which showed opacity in the right nasal cavity. Incisional biopsy was taken which revealed NKCa (transitional type). Very few reported cases of this type of malignancy were found. A possible reason could be multiple synonyms such as cylindrical cell carcinoma, Schneiderian carcinoma, and transitional cell carcinoma.