Correlation between Lactobacillus and expression of E-cadherin, ß-catenin, N-cadherin, and Vimentin in postmenopausal cervical lesions.

BACKGROUND: To detect the correlation between Lactobacillus vaginalis and the expression of epithelial-mesenchymal transition (EMT)-related factors, E-cadherin, ß-catenin, N-cadherin, and Vimentin, in postmenopausal cervical squamous intraepithelial lesions (SILs) and cervical squamous cell carcinoma (SCC), and to explore the possible mechanism. METHODS: From January 2016 to January 2020, 30 postmenopausal patients with low-grade SIL (LSIL), 18 patients with high-grade SIL (HSIL), and 30 patients with SCC who underwent colposcopy biopsy in the Outpatient Department of the First Affiliated Hospital of Inner Mongolia Medical University were selected as the experimental group, and 30 postmenopausal normal women were selected as the control group. The expression of 16SrRNA of Lactobacillus vaginalis in each group was determined by the 16S third-generation full-length amplification sequencing technique. The mRNA expression levels of E-cadherin, ß-catenin, N-cadherin, and Vimentin were detected by quantitative real-time polymerase chain reaction (qPCR). The correlation between the 16SrRNA expression level of Lactobacillus vaginalis and the mRNA expression level of the EMT-related proteins was compared among all groups. RESULTS: (I) The progression of postmenopausal cervical SILs to cervical SCC was significantly positively correlated with age, number of pregnancies, smoking, pH value, positive rate of HPV16, and negatively correlated with total Lactobacillus 16SrRNA expression (P<0.0001). (II) The level of vaginal microbiota in postmenopausal women showed that Lactobacillus iners was dominant. With the progression of the disease, the expression levels of 16SrRNA in Lactobacillus iners and Lactobacillus total vagina decreased gradually, and the differences were statistically significant (P<0.05). (III) With the disease progresses. The expression of total Lactobacillus 16SrRNA was positively correlated with the mRNA expression of ß-catenin and E-cadherin (r>0; P<0.05), and negatively correlated with the mRNA expression of Vimentin and N-cadherin (r<0; P<0.05). CONCLUSIONS: In postmenopausal women, Lactobacillus vaginalis interacts with HPV and is associated with the occurrence of EMT, promoting the development of cervical lesions.

Uterine cervical ulceration caused by group C streptococcal infection during pregnancy: A case report.

Causes of cervical ulceration include infection, collagen disease, malignant tumors and external stimuli. Cervical ulceration during pregnancy is rare. We present a case of cervical ulceration caused by group C streptococcal infection during pregnancy. A 36-year-old woman (gravida 1, para 0) complained of metrorrhagia, and a circular cervical ulcer of about 1.5 cm in diameter was detected on her cervix at 37 weeks' gestation. A biopsy and a cultivation test of the ulcer were performed, and pathological diagnosis was made as suppurative inflammation, and group C streptococcal infection was detected by the cultivation test. The ulcer had expanded to about 3 cm in diameter at the onset of labor at 40 weeks' gestation. An emergency cesarean section was performed because of failed induction of labor, and she was delivered of a male baby. The ulcer became gradually smaller after delivery, and completely disappeared on the 35th day after delivery.

HPV/Chlamydia trachomatis co-infection: metagenomic analysis of cervical microbiota in asymptomatic women.

HPV and Chlamydia trachomatis are the most common causes of sexually transmitted diseases worldwide. Most infections are asymptomatic and left untreated lead to severe reproductive tract sequelae such as cervical cancer and infertility. Interestingly, C. trachomatis may also increase the susceptibility to HPV infection as well as contribute to viral persistence. Recently, a growing body of evidence has suggested that the composition of the cervico-vaginal microbiota plays a key role in the susceptibility and outcome of genital infections caused by several pathogens, including HPV and C. trachomatis. The aim of our study was to undertake a metagenomic analysis of sequenced 16s rRNA gene amplicons to characterize the cervical microbiota from asymptomatic women with HPV/C. trachomatis co-infection. The composition of the cervical microbiota from HPV-positive or C. trachomatis-positive women was also analysed. The main finding of our study showed that the cervical microbiota in HPV/C. trachomatis co-infected women had a higher microbial diversity than the cervical microbiota in healthy controls (p<0.05). In addition, Aerococcus christensenii was associated with C. trachomatis infection. In conclusion, the increased cervical microbial diversity observed in HPV/C. trachomatis co-infected women and the detection of potential microbiological biomarkers of C. trachomatis infection will open the way to innovative approaches that may be helpful to identify women at risk of co-infection.

Tuberculosis in Pap samples with emphasis on LBC: Caught only when thought.

Despite being a commonly encountered infection, the clinical diagnosis of tuberculosis of the uterine cervix is elusive. Though a straightforward diagnosis on tissue sections, identification of typical features of tubercular infection on cervical Pap samples is challenging. In our experience, the infrequent pale staining collections of epithelioid cells are difficult to pick up on Pap stained smears, particularly LBC samples. In this series, 2 of the three samples were reported as atypical squamous cells of undetermined significance while 1 was reported as inflammatory at the initial diagnosis. Scattered Langhans' type giant cells may be seen as a subtle clue which should prompt the search for epithelioid cell granulomas. These cases may have a mass lesion clinically while no obvious signs of malignancy on the cervical samples.

Co-infection of sexually transmitted pathogens and Human Papillomavirus in cervical samples of women of Brazil.

BACKGROUND: Some sexually transmitted infectious agents, such as Chlamydia trachomatis and Herpes simplex, cause local inflammation, and could contribute to Human Papillomavirus (HPV) and cervical lesion progression. Thus, the aim of this study was to determine any association between the presence of microorganisms of gynecological importance, sexual behavior, clinical and demographical variables to the development and progress of cervical lesions. METHODS: One hundred and thirty-two women between 14 and 78 years and living at Vitória da Conquista, Bahia, Brazil, were included (62 individuals with cervical lesions and 70 without lesions). They answered a questionnaire to provide data for a socioeconomic and sexual activity profile. Samples of cervical swabs were collected and analyzed by PCR to detect genital microorganisms and HPV. Quantitative PCR was used to detect and quantify Ureaplasma urealyticum and Ureaplasma parvum. Univariate and multiple logistic regression were performed to measure the association with the cervical lesions, and an odds ratio (OR) with 95% confidence intervals (95%CI) were calculated. The Mann-Whitney U test was also used to compare the microorganism load in the case and control groups. The significance level was 5% in all hypotheses tested. RESULTS: Cervical lesions were associated with: women in a stable sexual relationship (OR = 14.21, 95%CI = 3.67-55.018), positive PCR for HPV (OR = 16.81, 95%CI = 4.19-67.42), Trichomonas vaginalis (OR = 8.566, 95%CI = 2.04-35.94) and Gardnerella vaginalis (OR = 6.13, 95%CI = 1.53-24.61), adjusted by age and qPCR for U. parvum. U. parvum load showed a statistical difference between the case and control groups (p-value = 0.002). CONCLUSION: Variables such as stable relationship, HPV, T. vaginalis, G. vaginalis were associated with cervical lesions in epidemiological studies. U. parvum load was higher in woman with cervical lesions compared with women without lesions. Additional studies are needed to better understand the role of these factors in cervical lesion development.

Intra-abdominal fungal pseudomycetoma in two cats.

BACKGROUND: Pseudomycetomas are deep cutaneous to subcutaneous lesions caused by Microsporum canis mainly described in Persian cats, with few reports of intra-abdominal location. This report describes the clinical signs and lesions of intra-abdominal pseudomycetomas caused by M. canis in two Persian cats. CASE REPORT: Two Persian cats with a history of previous laparotomy (ovariohysterectomy and nephrostomy) and fecal impaction were examined. Cat #1 was euthanized and subjected to necropsy, histopathology and mycological evaluation. Cat #2 presented with chronic dermatophytosis, and an intra-abdominal mass, that was subjected to histopathology evaluation. Cat #1 presented at necropsy a white-grayish, firm mass (6cm×3.5cm×2.8cm) in the uterine cervix. Cat #2 presented a firm whitish mass (6.5cm×1.5cm×0.5cm) located close to the left kidney. Histologically, both masses contained multifocal granules with hyphae and spores surrounded by Splendore-Hoeppli reaction, with a pyogranulomatous inflammatory infiltrate and fibrous connective tissue proliferation in the periphery. Hyphae and spores exhibited marked Grocott and periodic acid-Schiff staining. M. canis was identified by fungal isolation in cat #1. CONCLUSIONS: Pseudomycetoma should be considered as a differential diagnosis in cats, especially in Persian cats presenting with an intra-abdominal mass. Entrance of the agent into the cavity can occur during laparotomy.

[FREQUENCY OF PRETERM BIRTH IN WOMEN WITH CERVICAL VAGINAL INFECTIONS.]

Premature birth (PB) occurs in 5% to 18% of births in the world. Children born prematurely are at increased risk of death, major neonatal complications, long-term adverse consequences for health and development. The cause of spontaneous preterm birth is often unknown, but it is believed that intrauterine infection is implicated in 40% of cases. The most likely route to intrauterine infection is ascending infection of the genital tract. Infection of the genital tract is more common in women with spontaneous preterm births in lower ge. tational age. s performed a retrospective research of 70 pregnant women and their newborns. In the group with preterm birth was reported high percentage of CVI - 37.14%, while in the control group this percentage is 17.14%. The results showed the increase in the incidence of CVI group of PB more than twice. There is a need an effective prevention and treatment of CVI during pregnancy. The timely detection of deviations from normal vaginal microflora and the correct therapeutic approach would reduce the risks of PB and infectious complications in newborns.

Microbiological Infections in Women With Cervical Cytological Reports of Atypical Squamous Cells of Undetermined Significance.

OBJECTIVE: To study the role of cervicovaginal infections in women with cytological reports of atypical squamous cells of undetermined significance (ASC-US). MATERIALS AND METHODS: The study included 220 women admitted to the Clinic of Microscopy, Cervicovaginal and Vulvar Pathology of the Department of Gynecology and Obstetrics of the Tor Vergata University Hospital, Rome, Italy, enrolled between October 2012 and July 2013. RESULTS: Among the enrolled women, 105 women (47.7%) had ASC-US cytology, whereas 115 women (52.3%) had negative cytology. Microscopy showed infections more frequently in women with ASC-US than in those with negative cytology: 70.5% (74/105) vs 36% (41/115); p < .001. Cocci were present in 73.3% (77/105) of the women with ASC-US and in 43.5% (50/115) of those with negative cytology; p < .001. According to Ison score, 84% (88/105) of ASC-US was grade 0 vs 22% (25/115) of negative cytology, p < .001. Human papillomavirus was detected in 35% of the women with ASC-US. A statistically significant correlation between high pH and vaginal infections was found in women aged 20 to 29 (p = .003) and those 50 years or older in both cytological report groups; p < .001. CONCLUSIONS: Cervicovaginal infections are associated with a cytological report of ASC-US. Direct microscopy of vaginal specimens allowing immediate evaluation of the vaginal microflora and infectious agents may be a useful tool in managing women with cytological reports of ASC-US.

Autoimmune neutropenia of infancy with recurrent urinary tract infections: a case report.

Autoimmune neutropenia of infancy is characterized by minor intercurrent infections despite severe neutropenia; severe bacterial infections are uncommon. An infant developed recurrent urinary tract infections at 9 and 11 months of age. The identified uropathogens were Escherichia coli and Enterococcus faecalis, respectively. Empirical treatment with carbapenems, as broad-spectrum antibiotics, promptly resolved the infection without sequelae. Febrile neutropenic children with cancer and autoimmune neutropenia can develop urinary tract infections; therefore, in such infants, urine culture should be obtained through catheterization. In febrile neutropenic infants with no apparent fever source, cephalosporin monotherapy should not be selected empirically because Enterococci can be the involved pathogens.

Whole Slide Imaging of Pap Cell Block Preparations versus Liquid-Based Thin-Layer Cervical Cytology: A Comparative Study Evaluating the Detection of Organisms and Nonneoplastic Findings.

OBJECTIVE: Cervical cancer is one of the most common malignancies worldwide, yet it is preventable by population screening. In a previous study, we confirmed the feasibility of utilizing whole slide imaging (WSI) of cell block (CB) preparations to overcome the limitations of digitizing cytologic samples. In this study, we evaluated the accuracy of WSI in identifying various organisms and nonneoplastic findings. STUDY DESIGN: A total of 335 WS images from Pap CB preparations were analyzed using the Aperio system. The test performance characteristics of ThinPrep (TP) and WSI samples were compared for adequacy, for the presence of bacterial vaginosis (BV), fungi, Trichomonas vaginalis (TV) and herpes simplex virus (HSV) and for nonneoplastic findings. RESULTS: The WSI samples contained optimal material from all preparations. BV was diagnosed in 33 WSI versus 36 TP samples. Budding yeasts and/or pseudohyphal forms were noted in 18 WSI versus 19 TP samples. TV organisms (10 of 11 samples) and 1 HSV case were accurately identified in the WSI and TP samples. Squamous metaplasia, keratosis and reactive/reparative and inflammatory changes were easily identified by WSI. CONCLUSIONS: The concept of WSI from Pap CB preparations is potentially feasible for adoption. Digital remote web-based technology eliminates the need for an individual on site, saving time and resources.

Clinicopathological study of Papanicolaou (Pap) smears for diagnosing of cervical infections.

Cervical infections are not uncommon in our population especially in young and sexually active women. One thousand samples of married women, aged between 20 and 70 years, were studied by conventional Papanicolaou smears. These samples were examined in the Department of Pathology, King Edward Medical University, Lahore from January 2007 to June 2009. Only cases without (pre)neoplastic cytology were included. Six types of infections were diagnosed cytologically. The overall frequency of normal, inadequate, neoplastic, and infective smears was 50%, 1.8%, 10.2%, and 38.3%, respectively. Most of the patients (67%) were in the reproductive age group with mean age 34.7 ± 2.6 years. The commonest clinical sign seen in 354/383 (92%) cases and symptom in (349/383; 91%) cases were vaginal discharge and pruritis vulvae. Among the infective smears, 290 cases (75.7%), the cytologic diagnosis was nonspecific inflammation. Most of these 290 smears contained clue cells (indicating Gardnerella infection) and a lack of lactobacilli. Such smears are predominant in patients suffering from bacterial vaginosis (BV). Twenty-eight smears (7.3%) were positive for Trichomonas vaginalis, 27 cases (7%) were smears with koilocytic change pathognomonic of human papilloma virus infection. Twenty-five smears (6.5%) were positive for fungal infection. Seven cases (1.8%) were diagnosed as herpes simplex virus infection. Finally, there were six cases (1.5%) with atrophic vaginitis. We conclude that the cervical smear is well suited for diagnosing cervical infections. It is clear that Gardnerella, known to be associated with bacterial vaginosis, is a major problem in our Pakistani population.

Altered protein secretion of Chlamydia trachomatis in persistently infected human endocervical epithelial cells.

Chlamydia trachomatis is the most common bacterial infection of the human reproductive tract globally; however, the mechanisms underlying the adaptation of the organism to its natural target cells, human endocervical epithelial cells, are not clearly understood. To secure its intracellular niche, C. trachomatis must modulate the host cellular machinery by secreting virulence factors into the host cytosol to facilitate bacterial growth and survival. Here we used primary human endocervical epithelial cells and HeLa cells infected with C. trachomatis to examine the secretion of bacterial proteins during productive growth and persistent growth induced by ampicillin. Specifically, we observed a decrease in secretable chlamydial protease-like activity factor (CPAF) in the cytosol of host epithelial cells exposed to ampicillin with no evident reduction of CPAF product by C. trachomatis. In contrast, the expression of CopN and Tarp was downregulated, suggesting that C. trachomatis responds to ampicillin exposure by selectively altering the expression of secretable proteins. In addition, we observed a greater accumulation of outer-membrane vesicles from C. trachomatis in persistently infected cells. Taken together, these results suggest that the regulation of both gene expression and the secretion of chlamydial virulence proteins is involved in the adaptation of the bacteria to a persistent infection state in human genital epithelial cells.

Development of a pigtail macaque model of sexually transmitted infection/HIV coinfection using Chlamydia trachomatis, Trichomonas vaginalis, and SHIV(SF162P3).

BACKGROUND: Sexually transmitted infections (STIs) are associated with an increased risk of HIV infection. To model the interaction between STIs and HIV infection, we evaluated the capacity of the pigtail macaque model to sustain triple infection with Trichomonas vaginalis, Chlamydia trachomatis, and SHIV(SF162P3). METHODS: Seven SHIV(SF162P3) -infected pigtail macaques were inoculated with T. vaginalis only (n = 2), C. trachomatis only (n = 1), both T. vaginalis and C. trachomatis (n = 2), or control media (no STI; n = 2). Infections were confirmed by culture and/or nucleic acid testing. Genital mucosa was visualized by colposcopy. RESULTS: Characteristic gynecologic signs were observed for both STIs, but not in control animals. Manifestations were most prominent at days 7-10 post-infection. STIs persisted between 4 and 6 weeks and were cleared with antibiotics. CONCLUSIONS: These pilot studies demonstrate the first successful STI-SHIV triple infection of pigtail macaques, with clinical presentation of genital STI symptoms similar to those observed in humans.

[The study of expression of apoptosis receptors (CD95+) on the surface of neutrophils from cervical secretion of women with chlamydial infection and the possibility of its correction by magnetic laser radiation].

The present work was designed to study the expression of CD95 antigen (Fas/APO-1) at the surface of neutrophil granulocytes from the cervical secretion. Sixty five female patients with Chlamydia infection available for observation exhibited enhanced CD95+ expression following basic therapy. It was found that combined treatment with the use of magnetic laser radiation normalized the level of CD95+ surface receptors on neutrophils.

Tuberculosis of uterine cervix: a report of two cases with variable clinical presentation.

Tuberculosis (TB) of the cervix is a rare disease. We describe two cases of tuberculous cervicitis with variable clinical presentation. In one case, a young woman presented with primary infertility and secondary amenorrhoea. The other is a perimenopausal woman with irregular vaginal bleeding and postcoital blood-stained discharge. The diagnosis was confirmed on histopathological examination of the endocervical curettings and a cervical biopsy. The patients were given six months of anti-tuberculous therapy and responded well.

Risk factors and algorithms for chlamydial and gonococcal cervical infections in women attending family planning clinics in Thailand.

AIM: To identify risk factors associated with and evaluate algorithms for predicting Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) cervical infections in women attending family planning clinics in Thailand. METHODS: Eligible women were recruited from family planning clinics from all regions in Thailand. The women were followed at 3-month intervals for 15-24 months. At each visit, the women were interviewed for interval sexually transmitted infection (STI) history in the past 3 months, recent sexual behavior, and contraceptive use. Pelvic examinations were performed and endocervical specimens were collected to test for CT and NG using polymerase chain reaction. RESULTS: Factors associated with incident CT/NG cervical infections in multivariate analyses included region of country other than the north, age

Inflammatory events as detected in cervical smears and squamous intraepithelial lesions.

The Dutch cytological coding system, KOPAC, enables to code for eight inflammatory events, that is koilocytosis (related to human papillomavirus (HPV)), Trichomonas, dysbacteriosis [related to bacterial vaginosis (BV)], Candida, Gardnerella, Actinomyces, Chlamydia, and non-specific inflammation (leucocytosis). This study presents an analysis of 1,008,879 smears. Of each smear, the age of the woman and the reason for smear taking (screening or indication) was available. The cytoscores (per mille) for these codes were calculated. For the screening smears, the cytoscores were for koilocytosis (HPV) 2.6, for Trichomonas vaginalis 1.9, for dysbacteriosis 31.4, for Candida albicans 9.8, for Gardnerella vaginalis 0.7, for Actinomyces 6.9, for Chlamydia 0.8, and for non-specific inflammatory changes 66.4. For the calculation of the Odds Ratio (OR), normal smears were used as a reference. The cytoscores for Chlamydia and Gardnerella covaried with high grade SIL (HSIL), with an OR of 7 and 12, respectively. In addition, the OR for Trichomonas vaginalis, for dysbacteriosis, and for leucocytosis proved to be significantly high in the indication smears. This study provides an oversight of HSIL and the full range of cervical infections as detected by cytology, proving that this infectious byproduct of screening can be very valuable.

Cervical epithelial cells from Chlamydia trachomatis-infected sites coexpress higher levels of chlamydial heat shock proteins 60 and 10 in infertile women than in fertile women.

BACKGROUND/AIMS: The objective of the present study was to examine the possible relationship between the chlamydial heat shock proteins (cHSP) 60 and 10 expression and the damaging sequelae of a Chlamydia trachomatis infection, such as infertility. METHODS: Seven fertile and 7 infertile female patients infected with C. trachomatis attending the gynecology outpatient department of Safdarjung hospital (New Delhi, India) were enrolled. The relative transcript levels and intracellular expression of cHSP60 and cHSP10 in cervical cells were assessed using real-time RT-PCR and flow cytometry, respectively. RESULTS: Quantitative real-time RT-PCR analysis showed that transcript levels of both cHSP60 (p = 0.007) and cHSP10 (p = 0.0006) were higher in infertile women than in fertile women. Flow cytometric analysis showed significantly higher intracellular levels of cHSP60 (p = 0.0006) and cHSP10 (p = 0.0041) in fertile women infected with Chlamydia than in infertile women. However, the percentage of double-positive cells (both cHSP60- and cHSP10-expressing cells) were higher (p = 0.0006) in infertile women than in fertile women. CONCLUSION: Our results suggest that cHSP60 and cHSP10 have a different pattern of expression in infertile women compared to fertile women reflecting a probable difference in the metabolic state of Chlamydia with the presence of an abnormal cryptic form of C. trachomatis in infertile women.

Chlamydia infection in patients with and without cervical intra-epithelial lesions tested by real-time PCR vs. direct immunofluorescence

This study compares the detection rates of Chlamydia trachomatis by two techniques, direct immunofluorescence (IMF) and real time polymerase chain reaction (PCR), in patients with and without intra-epithelial cervical lesions (SIL) in Recife. We conducted a transversal study involving 35 women with SIL and 35 without SIL attended at Ambulatório Especializado da Mulher, Recife, Brazil. They were tested for Chlamydia trachomatis using two techniques, direct IMF or real time PCR. The rates of Chlamydia trachomatis detection were compared and the association with intra-epithelial cervical lesions was determined using the chi-square test at a 5 percent level of significance. Concordance between the tests was evaluated using kappa. The global prevalence of Chlamydia infection was 47.1 percent by direct IMF and 58.6 percent by real time PCR. A significant association was observed between Chlamydia diagnosis and presence of intra-epithelial cervical lesions, with about 80 percent positive results by direct IMF and 77.1 percent by real time PCR. However, the detected rate of infection with Chlamydia trachomatis was significantly greater in patients without intra-epithelial cervical lesions tested by real time PCR (40 percent) when compared to direct IMF (14.3 percent). The concordance between the tests was weak, with a kappa coefficient of 0.4. Both real time PCR and direct IMF detected elevated rates of Chlamydia infection in patients with intra-epithelial cervical lesions (80 percent) but the tests were discordant when patients without cervical lesions were tested, possibly because sensitivity of real time PCR is greater.