Genital Disease Research Articles

Boron neutron capture therapy for urological cancers.

Boron neutron capture therapy is based on a nuclear reaction between the nonradioactive isotope boron-10 and either low-energy thermal neutrons or high-energy epithermal neutrons, which generate high linear energy transfer α particles and a recoiled lithium nucleus (7 Li) that selectively destroys the DNA helix in tumor cells. Boron neutron capture therapy is an emerging procedure aimed at improving the therapeutic ratio for the traditional treatment of various malignancies, which has been studied clinically in a variety of diseases, including glioblastoma, head and neck cancer, cutaneous melanoma, hepatocellular carcinoma, lung cancer, and extramammary Paget's disease. However, boron neutron capture therapy has not been clinically performed for urological cancers, excluding genital extramammary Paget's disease that appeared at the scrotum to penis area. In this review, we aimed to provide an updated summary of the current clinical literature of patients treated with boron neutron capture therapy and to focus on the future prospects of boron neutron capture therapy for urological cancers.

Neutralizing Antibody Kinetics and Immune Protection Against Herpes Simplex Virus 1 Genital Disease in Vaccinated Women.

Previously, our group conducted the Herpevac Trial for Women, a randomized efficacy field trial of type 2 glycoprotein D (gD2) herpes simplex virus (HSV) vaccine adjuvanted with ASO4 in 8323 women. Study participants were selected to be seronegative for HSV-1 and HSV-2. We found that the vaccine was 82% protective against culture-positive HSV-1 genital disease but offered no significant protection against HSV-2 genital disease. Efficacy against HSV-1 was associated with higher levels of antibody to gD2 at enzyme-linked immunosorbent assay (ELISA). To better understand the results of the efficacy study, we measured postvaccination concentrations of neutralizing antibody (nAb) to either HSV-1 and HSV-2 from HSV-infected study participants and matched uninfected controls. Statistical modeling was used to determine whether these responses were correlated with protection against HSV. nAbs to either HSV-1 or HSV-2 were correlated with ELISA binding antibodies to gD2. HSV-1 or HSV-2 nAb findings support the observation of protection by higher levels of antibody against HSV-1 infection, but the lack of protection against HSV-2 remains unexplained. The protection against HSV-1 infection observed in the Herpevac Trial for Women was associated with nAbs directed against the virus, although the power to assess this was lower in the nAb study compared with the ELISA results owing to smaller sample size. NCT00057330.

Sexual and Emotional Health after Allogeneic Hematopoietic Cell Transplantation: A Comprehensive Review and Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

A person’s sexual and emotional life is greatly impacted after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This topic is not addressed very much by patients and caregivers. Physical, endocrine and genital chronic graft versus host disease (cGVHD)-related disorders are multiple and intertwined with psychological disorders. The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) has issued recommendations for a better gynecological monitoring of female recipients after allo-HCT. A patient booklet was also offered to patients in the form of questions and answers to facilitate discussions between patients and caregivers and to improve the management of sexual and emotional life after transplant.

Pharmacognostical Study and Biological Potential of Nerium Oleander Linn

Medicinal plants are used all over the world in traditional and ethnological medicine. Medicinal plants include various types of plants used in herbal medicine, some of which have medicinal properties. These medicinal plants are rich source of materials that can be used in drug development and synthesis. Sushruta Samhita and Charaka Samhita form the basis of the Ayurvedic medical system, in which thousands of plants are used therapeutically. Nerium oleander is an important medicinal plant in traditional Indian medicine. It is commonly known as Kanner. In Sanskrit medical literature, the plant is described as spicy and poisonous. Two powerful cardiac glycosides, oleanderin and nerinium, are toxic compounds isolated from all parts of the plant. The leaves, stems, bark, roots and flowers of the oleander plant are used to treat various ailments such as heart disease and asthma, corns, epilepsy, cancer, painful catamenial periods, leprosy, malaria, ringworm, upset stomach, and genital disease; and to cause abortions. Nerium Oleander has many secondary metabolites with important pharmacological uses such as flavonoids, alkaloids, steroids, cardiac glycosides, etc., which have significant pharmacological applications. This review describes the pharmacognostic study, phytochemical screening and biological potential of Nerium oleander.

Provider preferences for anal cancer prevention screening: Results of the International Anal Neoplasia Society survey

ObjectiveThis study explores provider preferences regarding anal cancer screening indications, initiation age, tools, and referral threshold to high resolution anoscopy (HRA). MethodsInternational Anal Neoplasia Society affiliates were invited to complete an online survey. Options for initiation age and tools were delineated by sub-groups. HRA referral thresholds separately queried recommendations by patient immune status. ResultsOne hundred forty respondents participated. Although consensus was lacking with regard to specific screening initiation age, more respondents recommended younger initiation ages for men who have sex with men (MSM) living with HIV (LWH) compared with MSM not LWH (p < 0.01). “No age threshold” ranged 44-55% among sub-groups with lower genital tract disease. Cytology and digital anorectal exam (DARE) were the most frequently selected tools for all sub-groups (ranges 77-90% and 74-86%, respectively). HRA was recommended significantly more frequently for MSM LWH (58%) and patients with vulvar cancer (52%) compared to others (p < 0.01). “Any [test] abnormality” was more often selected as indication for HRA for immunocompromised (56%) and immunocompetent (46%) patients than a specific cytology test result (29%, 36% respectively). ConclusionCytology and DARE were preferred screening tools; screening initiation age and HRA referral threshold showed less consensus. Evidence-based guidelines are needed and may lead to more consistent screening practices.

Desires and attitudes of outpatients and physicians regarding the use of teleurology during the pandemic: a prospective survey study.

It is not known to date how many patients admitted to urology outpatient clinics are willing to use telemedicine. We aimed to investigate knowledge levels and attitudes concerning the utilization of teleurology by patients applying to urology outpatient clinics. This prospective multicentre survey study included 334 patients aged 18-65 years who applied to an urology outpatient clinics. The patients were asked questions about their attitudes and expectations regarding teleurology. Diseases were divided into seven subgroups due to the broad spectrum of diagnoses. Physicians' and patients' opinions on whether it was possible to manage the current medical condition via teleurology were recorded. 69.5% of patients stated that they had sufficient technical skills to use teleurology by themselves for medical examination. 55.4% of patients and 78.4% of physicians responded that the existing complaints were suitable for teleurology. Both patients and physicians deemed genital system diseases and urinary tract infections suitable for teleurology (p<0.001, p<0.001 for physicians, and p<0.001, p<0.001 for patients), whereas urine transport, storage and emptying disorders (p=0.003) and benign prostatic hyperplasia (p=0.029) were deemed to be suitable for teleurology only by the physicians. Our study shows that (i) the majority of our patient population has a telecommunications infrastructure suitable for teleurology, (ii) teleurology has aroused interest among patients, particularly during the pandemic period, and (iii) physicians and patients have high expectations that the problem can be solved with teleurology in suitable patients.

A Review of the Diversity of the Genital Tract Microbiome and Implications for Fertility of Cattle.

Simple SummaryReproductive systems of cattle contain multiple microbes resident in the female from a young age. Sometimes other harmful microbes can invade the genital tract and cause diseases that impair fertility. Normally, commensal microbes facilitate genital tract homeostasis and produce factors that stimulate male sexual response. For this reason, the type and number of microbes present in the genital tract are important for reproductive tract health, and any disruption of this microbial balance leads to genital diseases. Interestingly, these microbes frequently populate the genital tract of cows, leading to reproductive diseases that perturb fertility. However, a microbiome composed of commensal microbes will likely result in the restoration of uterine health and improved fertility of the cows.Cattle have a genital microbiome that is established early in life, even before calving. Microbial influx into the reproductive system of cows, during calving or mating, is unavoidable and is likely to alter the commensal microflora composition. It is now well established that a commensal endometrial flora is largely responsible for the overall fertility of cows. These microbes are important for maintenance of structural integrity of the genital mucosal barrier, immunomodulation, and protection against pathogens. Further, the genital microbiome functions in the semiochemical communication between a male and female. An optimal balance between the abundance and diversity of the microbiome is essential to promote female genital tract health. Disruption of this balance leads to dysbiosis and genital diseases and perturbed fertility. As part of the global strategy of One World, One Health, there is a need to reduce antibiotic use in animals. This area of research has the potential to expand the knowledge about the nexus between the endometrial microbiome and fertility including being probiotic in different species.

MICROSURGICAL AND VARICOCELECTOMY COMPERSION WITH AND WITHOUT TESTICULAR DELIVERY FOR TREATMENT OF VARICOCELE: A RANDOMIZE CONTROL TRIAL

Purpose: Varicocele is a common type of male genital disease and can occur in men of any age, especially young people. Clinically venous enlargement or varicocele are found in about 15% of the general male population, up to 35% of men with primary fertility, and 75% of men with secondary fertility dysfunction. Varicoceles are known to be the most common cause of male infertility and can be corrected surgically, but the exact mechanism of sperm formation caused by varicocele-induced impairment remains controversial. Most men with varicocele are asymptomatic and infertile, with only 15% – 20% suffering from physical discomfort or other fertility-related problems. With therefore systematically evaluated the RCTs published together and summarized evidence evaluating the benefits of testicular delivery and ligation of gubernacular vein in microsurgical varicocelectomy.&#x0D; Methodology: Comprehensive electronic search using the keywords "microsurgical varicocelectomy", "gubernacular vein", "testicular delivery", "infertility" and "varicocele" was done in databases of Cochrane, PubMed, Embase, CINAHL and Web of Science databases. English language used to search databases. Some studies were taken from studies references.&#x0D; Result: Two studies reported grade II and III of varicoceles in patients that participated in the study. Overall sperm count in microsurgical resection with testicular delivery compared to microsurgical resection without testicular delivery, increased significantly (SMD = 0.23, 95% CI = 0.07-0.39, p =&lt;.05), but sperm motility, sperm concentration and gradual increase have no difference in between the two microsurgical methods (p&gt; 0.05).&#x0D; Conclusion: In conclusion, as a result of this systematic review and meta-analysis, compared with microsurgical varicocelectomy without testicular delivery, delivery of the testicles during microsurgical varicocelectomy to further to further ligate the gonadal veins leads to epidydemo orchitis and oedema, and longer surgery. In addition, testicular delivery may not improve parameters of sperm, serum testosterone, and incidence of varicose veins, wound inflammation and spontaneous pregnancy compared to non-delivered testicles. However, a higher level of research is needed to determine if testicular delivery is an important surgery in microsurgical venous ligation.

Nonsquamous Lesions of the Vulvar Skin and Subcutaneous Tissue: A Review (Part 2).

The aim of this second article was to complete part 1 review of nonsquamous lesions of the vulvar skin and subcutaneous tissue (Journal of Lower Genital Tract Disease, 2021), clinically and pathologically, based on the fifth edition of the World Health Organization tumor classification. A database search of PubMed and Google Scholar was performed between 1970 and 2021, using the search terms "vulva," "lower genital tract," and "non-squamous lesions." The search was limited to "human gynecological pathology." Full article texts were reviewed, and reference lists were screened for additional articles. We excluded abstracts and articles written in the non-English language. An initial list of 400 articles was identified. Thirty-seven articles discussed clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue. Clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue as categorized by the updated World Health Organization classification are presented.

Exploring the role of gut microbiome in male reproduction.

The impact of the gut microbiome on the organism has become a growing research focus with the development of 16S rRNA sequencing. However, the effect of the gut microbiome in male reproduction has yet to be investigated. To overview on possible mechanisms by which the gut microbiome could affect male reproduction and therapeutic opportunities related to the gut microbiome METHODS: Authors searched PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library for medical subject headings terms and free text words referred to "male infertility" "testis" "gut microbiome" "insulin resistance" "erectile dysfunction" "therapy" "sex hormones" and "genital diseases" until December 2, 2021. Evidence suggests that immune system activation caused by the gut microbiome translocation not only leads to testicular and epididymal inflammation but can also induce insulin resistance together with gastrointestinal hormones such as leptin and ghrelin, which in turn affects the secretion of various sex hormones such as LH, FSH, and T to regulate spermatogenesis. In addition, the gut microbiome can influence spermatogenesis by controlling and metabolizing androgens as well as affecting the blood-testis barrier. It also promotes vascular inflammation by raising trimethylamine-N-oxide (TMAO) levels in the blood, which causes erectile dysfunction. The testicular microbiome and gut microbiome can interact to influence male reproductive function. This study discusses therapeutic options such as probiotics, prebiotics, and fecal microbiota transplantation, as well as the challenges and opportunities behind ongoing research, and emphasizes the need for additional research in the future to demonstrate the links and underlying mechanisms between the gut microbiome and male reproduction. Therapeutic options such as probiotics, prebiotics, and fecal microbiota transplantation are potential treatments for male infertility. Gut microbiota may have a causal role in male reproduction health, therapeutic strategies such as supplementation with appropriate probiotics could be undertaken as a complementary treatment. In the future, additional research is needed to demonstrate the links and underlying mechanisms between the gut microbiome and male reproduction.

Prevalence and Antimicrobial Resistance of Ureaplasma urealyticum and Mycoplasma hominis in Patients with Genital Tract Infection in Jiangsu, China.

The aim of this study was to investigate the infection and antimicrobial resistance of Ureaplasma urealyticum (U. urealyticum) and Mycoplasma hominis (M. hominis) in patients with genital tract diseases in Jiangsu, China. A total of 3,321 patients suspected with genital tract infectious diseases were enrolled in this study from September 2017 to September 2020. The Mycoplasma detection and antimicrobial susceptibility were tested using the commercially available Mycoplasma kit. Among the 3,321 specimens tested, 1,503 (45.3%) were positive for Mycoplasmas, and the proportion of mono-infection of U. urealyticum is highest (79.5%). The overall infection rate has been increasing in the past 3 years. The positive rate in females (68.7%) was higher than in males (25.0%), and the main infection age group was 20 - 39 (81.2%). Besides, U. urealyticum and M. hominis displayed relative lower resistance rates to gatifloxacin, josamycin, minocycline, and doxycycline (6.0%, 6.5%, 3.1%, and 3.2%, respectively). However, the antimicrobial resistance rates to azithromycin, clindamycin, roxithromycin, sparfloxacin, and ofloxacin were relatively high (45.4%, 42.1%, 34.9, 36.0, and 65.5%, respectively). Antimicrobial resistance of U. urealyticum and M. hominis to these 14 drugs have been changing in the past 3 years. In total, these preliminary data showed the prevalence and antimicrobial resistance status of U. urealyticum and M. hominis in patients suspected with genital tract infectious diseases, which has use for reference on both prevention and treatment of diseases caused by them.

Lower Genital Tract Microbiome—A Work in Progress

The lower genital tract microbiome is composed of millions upon millions of microbes colonizing this unique anatomical niche reflecting the influence of genetic, biologic, and behavioral factors. Over the last decade, as a result of ever advancing technology and research investment, our knowledge of this complex microbiome ecosystem has grown enormously. All too often such progress remains invisible to practitioners. In this special issue, clinical scientists, in a unique contribution, have bridged the ever-increasing distance between vaginal microbiota science and clinical disease. Approaching a myriad of pathologic entities, authors describe the clinical application of recent molecular laboratory findings encouraging diagnostic, prognostic, and therapeutic advances. Nevertheless, challenges are recognized and the authors outline vulvovaginal disease management opportunities. Above all, exposing the dynamism of vaginal microbiota affords a better understanding of pathogenesis of lower genital tract disease.

Intrinsic Antiviral Activity of Optineurin Prevents Hyperproliferation of a Primary Herpes Simplex Virus Type 2 Infection.

Very little knowledge exists on virus-specific host cell intrinsic mechanisms that prevent hyperproliferation of primary HSV type 2 (HSV-2) genital infections. In this study, we provide evidence that the Nemo-related protein, optineurin (OPTN), plays a key role in restricting HSV-2 infection both in vitro and in vivo. Contrary to previous reports regarding the proviral role of OPTN during Sendai virus infection, we demonstrate that lack of OPTN in cells causes enhanced virus production. OPTN deficiency negatively affects the host autophagy response and results in a marked reduction of CCL5 induction. OPTN knockout (OPTN-/-) mice display exacerbated genital disease and dysregulated T cell frequencies in infected tissues and lymph nodes. A human transcriptomic profile dataset provides further credence that a strong positive correlation exists between CCL5 upregulation and OPTN expression during HSV-2 genital infection. Our findings underscore a previously unknown OPTN/CCL5 nexus that restricts hyperproliferative spread of primary HSV-2 infection, which may constitute an intrinsic host defense mechanism against herpesviruses in general.

A Comparative Study of the Levels of Heat Shock Protein 70, Some Biochemical and Hormonal in the Blood of Cows Suffering from Follicular Cystic Ovarian and Endometritis

Twenty- four reproductive systems of Frisian cross breed cows, aged between (3-5years) were obtained from Basrah abattoir during the period of (2nd March 2020 - 30th June, 2020). They were divided into 3 groups of cows with ovarian follicular cystic (n=8), cows with endometritis (n = 8), and healthy cows (n=8) depending on clinical signs. The main gall of this paper compare and report the different values of heat shock protein 70 (HSP70), some biochemical and hormonal levels in those cows in the native Basrah climate. Samples of blood were collected from all cows subjected to this study and serum was harvested from each individual sample by centrifugation. Heat shock protein 70 (Hsp70), total protein (TP), albumin(Alb), globulin, total cholesterol (Cho), triglyceride (TG), low density lipo-protein(LDL), aspartate aminotransferase (AST), cortisol, testosterone, thyroid stimulation hormone (TSH), thyroxin (T4) and triiodothyronine hormones(T3) were measured in serum samples. Results revealed a significant increase (p≤0.05) in the level of Hsp70, and thyroid stimulation hormones (TSH) of cows with two pathological cases (endometritis and follicular cysts) compared with those healthy cow. Significant decrease (p≤0.05) in the measurement of total protein, albumin, globulin, thyroxin (T4), triiodothyronine (T3) hormones, cholesterol, triglyceride, and low density lipoprotein (LDL) in cows having those two genital diseases compared with normal cows. The results also were revealed a significant increase (p≤0.05) in the level of testosterone hormone in cows with follicular cystic ovarian case compared with endometritis case and control ones. Finally, significant increase (p≤0.05) in cortisol hormone level and aspartate aminotransferase (AST) activity in cows with endometritis case compared with the control one and follicular cystic ovarian cases.

An analysis of the pathological states of pregnant women in ante-intranatal fetal death in kharkov during 2016-2019

Background. In Ukraine among perinatal losses, a high proportion of stillbirth remains, the level of which depends on many factors, including the presence of somatic and genital pathology in a woman, pathological conditions during pregnancy, including eclampsia (PE), iron deficiency anemia of pregnant women (IDA), chorioamnionitis (CA). These conditions can be combined with each other, which increases the risk of fetal death during pregnancy or childbirth. Objective. To conduct a somatic and gynecological diseases, complications of pregnancy in pregnant women with preeclampsia (PE), iron deficiency anemia (IDA) and chorioamnionitis (CA), whose pregnancy ended in ante-intrapartum fetal death at 30-40 weeks of gestation. Methods. We investigated 58 cases of stillbirth at 30-40 weeks of gestation from pregnant women with PE (n = 16), IDA (n = 16), CA (n = 26) on the basis of the Communal non-profit enterprise "City Perinatal Center "Kharkov. The clinical data of the mothers, the protocols of the pathological examination of the placenta were studied. Results. Based on the study, it was found that in women whose pregnancy was complicated by PE and IDA, the most frequent types of somatic pathology were hypertensive disorders (32% and 12.5%, respectively) and chronic diseases of the digestive system. (25% and 12.5%, respectively), among gynecological diseases, uterine leiomyoma and endocervicosis were more common, among complications of pregnancy and childbirth - premature birth (50% each, respectively) pathology of the placenta (50% and 68.8%, respectively) and disorders of the content amniotic fluid (31.3% and 18.8%, respectively).The extragenital pathology in pregnant women with CA was presented with the infectious diseases (30.7%), an acute respiratory viral infections (19.2%), the cardiovascular pathology (11.5%), and the chronic inflammatory diseases of various localization (7.6%). The most frequency gynecological pathology were inflammatory genital diseases (23.21%). The pregnancy and labor were often complicated with the placental pathology (50%), premature birth (38.5%), preeclampsia (19.2%), and anemia (19.2%). During pregnancy, placental dysfunction diagnosed only in 31.3% of cases with PE, 25% with IDA and 3.8% with CA, but in pathological examination, morphological signs of placental insufficiency recorded in almost every case of all groups. Conclusion. In pregnancy, aggravated by PE, IDA or CA, the presence of extragenital pathology, gynecological diseases, and other complications of pregnancy were additional factors that increased the severity of placental insufficiency and fetal hypoxia, which was the cause of its death. Timely diagnosis of placental dysfunction and the implementation of therapeutic measures aimed at reducing the associated negative impact on the fetus can help reduce perinatal mortality.

Chlamydia trachomatis induces lncRNA MIAT upregulation to regulate mitochondria-mediated host cell apoptosis and chlamydial development.

Chlamydia trachomatis persistent infection is the leading cause of male prostatitis and female genital tract diseases. Inhibition of host cell apoptosis is the key to maintaining Chlamydia survival in vivo, and long noncoding RNAs (lncRNAs) play important roles in its developmental cycle and pathogenesis. However, it is not clear how lncRNAs regulate persistent Chlamydia infection. Here, using a microarray method, we identified 1718 lncRNAs and 1741 mRNAs differentially expressed in IFN‐γ‐induced persistent C. trachomatis infection. Subsequently, 10 upregulated and 5 downregulated differentially expressed lncRNAs were verified by qRT–PCR to confirm the reliability of the chip data. The GO and KEGG analyses revealed that differentially regulated transcripts were predominantly involved in various signalling pathways related to host immunity and apoptosis response. Targeted silencing of three lncRNAs (MIAT, ZEB1‐AS1 and IRF1) resulted in increased apoptosis rates. Furthermore, interference with lncRNA MIAT caused not only an obvious downregulation of the Bcl‐2/Bax ratio but also a marked release of cytochrome c, resulting in a significantly elevated level of caspase‐3 activation. Meanwhile, MIAT was involved in the regulation of chlamydial development during the persistent infection. Collectively, these observations shed light on the enormous complex lncRNA regulatory networks involved in mitochondria‐mediated host cell apoptosis and the growth and development of C. trachomatis.

Characterization of Candida species isolated from vulvovaginal candidiasis by MALDI-TOF with in vitro antifungal susceptibility profiles.

Background and Purpose: Vulvovaginal candidiasis (VVC) is an opportunistic infection due to Candida species, one of the most common genital tract diseases among reproductive-age women. The present study aimed to investigate the prevalence of VVC among non-pregnant women and identify the epidemiology of the involved Candida species with the evaluation of antifungal susceptibilities.Materials and Methods: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed to identify Candida species isolated from the genital tract of 350 non-pregnant women. Moreover, antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute broth microdilution method guidelines (M27-A3 and M27-S4).Results: Vaginal swab cultures of 119 (34%) women yielded Candida species. Candida albicans was the most frequently isolated species (68%), followed by Candida glabrata (19.2%). Voriconazole was the most active drug against all tested isolates showing an MIC50/MIC90 corresponding to 0.016/0.25 µg/mL, followed by posaconazole (0.031/1 µg/mL). Overall, resistance rates to fluconazole, itraconazole, and voriconazole were 2.4%, 4.8% and, 0.8% respectively. However, posaconazole showed potent in vitro activity against all tested isolates.Conclusion: Results of the current study showed that for the effectual therapeutic outcome of candidiasis, accurate identification of species, appropriate source control, suitable antifungal regimens, and improved antifungal stewardship are highly recommended for the management and treatment of infection with Candida, like VVC.

Guinea Pig and Mouse Models for Genital Herpes Infection.

This article describes procedures for two preclinical animal models for genital herpes infection. The guinea pig model shares many features of genital herpes in humans, including a natural route of inoculation, self-limiting primary vulvovaginitis, spontaneous recurrences, symptomatic and subclinical shedding of HSV-2, and latent infection of the associated sensory ganglia (lumbosacral dorsal root ganglia, DRG). Many humoral and cytokine responses to HSV-2 infection in the guinea pig have been characterized; however, due to the limited availability of immunological reagents, assessments of cellular immune responses are lacking. In contrast, the mouse model has been important in assessing cellular immune responses to herpes infection. Both the mouse and guinea pig models have been extremely useful for evaluating preventative and immunotherapeutic approaches for controlling HSV infection and recurrent disease. In this article, we describe procedures for infecting guinea pigs and mice with HSV-2, scoring subsequent genital disease, and measuring replicating virus to confirm infection. We also provide detailed protocols for dissecting and isolating DRG (the site of HSV-2 latency), quantifying HSV-2 genomic copies in DRG, and assessing symptomatic and subclinical shedding of HSV-2 in the vagina. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Primary and recurrent genital herpes infection in the guinea pig model Support Protocol 1: Blood collection via lateral saphenous vein or by cardiac puncture after euthanasia Support Protocol 2: Dissection and isolation of dorsal root ganglia from guinea pigs Support Protocol 3: PCR amplification and quantification of HSV-2 genomic DNA from samples Basic Protocol 2: Primary genital herpes infection in the mouse model Alternate Protocol: Flank infection with HSV-2 in the mouse model Support Protocol 4: Dissection and isolation of mouse dorsal root ganglia.

Human genetic diversity regulating the TLR10/TLR1/TLR6 locus confers increased cytokines in response to Chlamydia trachomatis.

SummaryHuman genetic diversity can have profound effects on health outcomes upon exposure to infectious agents. For infections with Chlamydia trachomatis (C. trachomatis), the wide range of genital and ocular disease manifestations are likely influenced by human genetic differences that regulate interactions between C. trachomatis and host cells. We leveraged this diversity in cellular responses to demonstrate the importance of variation at the Toll-like receptor 1 (TLR1), TLR6, and TLR10 locus to cytokine production in response to C. trachomatis. We determined that a single-nucleotide polymorphism (SNP) (rs1057807), located in a region that forms a loop with the TLR6 promoter, is associated with increased expression of TLR1, TLR6, and TLR10 and secreted levels of ten C. trachomatis-induced cytokines. Production of these C. trachomatis-induced cytokines is primarily dependent on MyD88 and TLR6 based on experiments using inhibitors, blocking antibodies, RNAi, and protein overexpression. Population genetic analyses further demonstrated that the mean IL-6 response of cells from two European populations were higher than the mean response of cells from three African populations and that this difference was partially attributable to variation in rs1057807 allele frequency. In contrast, a SNP associated with a different pro-inflammatory cytokine (rs2869462 associated with the chemokine CXCL10) exhibited an opposite response, underscoring the complexity of how different genetic variants contribute to an individual’s immune response. This multidisciplinary study has identified a long-range chromatin interaction and genetic variation that regulates TLR6 to broaden our understanding of how human genetic variation affects the C. trachomatis-induced immune response.

Vaginal microbiome: community characteristics and disease intervention

The application of high-throughput sequencing technologies has greatly enhanced our understanding to the human microbiome. The causal relations between human microbiome and diseases have become a critical issue to elucidate disease development and develop precision medicine. Recently, the study about vaginal microbiome (the microbial flora that inhabits the female vagina) has received wide interests. It has been shown that dysbiosis of vaginal microbiome was closely related to the development of genital tract diseases. This article summarizes the interaction between vaginal microbiome and disease and the treatment for the dysbiosis of vaginal microbiome. The culturomics of virginal microbiome, engineered probiotics and synthetic microbiome were also proposed.