Vaginal Epithelium Research Articles

Studi Literatur: Disfungsi Seksual pada Pasien dengan Penyakit Ginjal Kronik Yang Menjalani Hemodialysis

One of the effects of chronic kidney disease is a decrease in sexual function due to long hemodialysis, where patients who undergo hemodialysis for a long time will experience an inability to enjoy sexual activity so that it has an impact on fulfilling their needs. sexuality and change the patient's sexuality pattern. Sexual dysfunction in female hemodialysis patients causes increased pain in women (dyspareunia) and difficulty in vaginal mucus, whereas in men it includes disorders of sexual desire, erectile dysfunction and premature ejaculation. The aim of this study was to review the extent of sexual function in chronic kidney disease patients undergoing hemodialysis. This type of research uses a Literature Review (LR) with a population of 69 journals, with a sample of 2 national journals and 13 international journals according to the inclusion criteria of international or national journals related to sexual dysfunction in hemodialysis patients, journals published in a span of 10 years (2010 - 2020) ) and the journal must be in full text. Evaluation of the feasibility of the data using the Joanna Brigs Institute (JBI) by filling in the critical appraisal tool checklist sheet. The results showed sexual dysfunction that occurs in men is found; dissatisfaction, avoidance, loss of energy, premature ejaculation and erectile dysfunction, impotence, does not last long during sexual activity, lack of excitement, and the condition of sperm mixed with blood. Whereas in women it is found; dissatisfaction, orgasm, decreased desire, lubrication, pain during intercourse, reluctance to engage in sexual activity, decreased desire and libido. It is hoped that this research will serve as a theoretical basis in the nursing process both applied and theoretically.

Miconazole-loaded nanoparticles coated with hyaluronic acid to treat vulvovaginal candidiasis

Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy of the vulvovaginal candidiasis (VVC). They were synthesized by emulsification and solvent evaporation techniques, characterized by diameter, polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy (AFM), evaluated in terms of efficacy against C. albicans in vitro, and tested in a murine VVC model. Nanoparticles showed 211nm of diameter with a 0.32 polydispersity index, -53mV of zeta potential, and 90% miconazole encapsulation efficiency. AFM evidenced nanoparticles with a spherical shape. They inhibited the proliferation of C. albicans in vitro and in vivo after a single administration. Nanoparticles released the miconazole directly in the site of action at low therapeutic doses, which was enough to eliminate the fungal burden in the murine VVC model. These systems were rationally designed since the existence of the HA induces their adhesion on the vaginal mucus and their internalization via CD44 receptors, inhibiting the C. albicans. Therefore, miconazole-loaded nanoparticles/HA represent an innovative non-conventional pharmaceutical dosage form to treat the VVC and recurrent VVC.

GD07 The role of the dermatologist in the fight against female genital mutilation

Abstract Female genital mutilation (FGM) is a practice that the World Health Organization (WHO) estimates to affect 200 million women globally. The practice of FGM is often attributed to the Middle East, sub-Saharan Africa, North Africa and, to a lesser extent, Asia; however, it is now being witnessed in cities worldwide with high numbers of FGM-practising communities. The WHO defines FGM as ‘all procedures that involve partial or total removal of the external female genitalia or other injury to the female genital organs for non-medical reason’. While FGM has no health benefits, in certain cultures, the practice confers upon women full social acceptability and integration into the community and serves as a rite of passage to womanhood and marriage (Mpinga EK, Marcias A, Hasselgard-Rowe J et al. Female genital mutilation: a systematic review of research on its economic and social impacts across four decades. Glob Health Action 2016; 4:9). This systematic review aimed to assess the dermatological impact of FGM on women and the role dermatologists can play in the fight against the practice. A systematic review was carried out in accordance with the PRISMA guidelines. PubMed (n = 98), Cochrane (n = 1), CINAHL (n = 8) and Embase (n = 38) were searched for articles published between January 1990 and January 2023 with the phrase ‘female genital mutilation and skin or dermatology’. A total of 148 studies were initially identified; following screening, 21 articles were deemed suitable for inclusion and analysed. The literature highlighted that the main dermatological consequences of FGM were severe keloid formation, hypertrophic scars, vitiligo lesions, clitoral neuromas and, most commonly, epidermal inclusion cysts (Dave AJ, Sethi A, Morrone A. Female genital mutilation: what every American dermatologist needs to know. Dermatol Clin 2011; 29:103–9). A study of women in Somalia who had been admitted to the hospital following complications due to FGM noted that 55.1% of women (n = 65/118) had developed epidermal inclusion cysts. The literature suggests women often feel shame approaching clinicians for help; however, without support, these women can experience years of dyspareunia, dysuria, pruritus, pelvic pain and obstetric complications, as well as increased transmission of sexually transmitted infections and HIV following damage to the vaginal epithelium. By analysing the literature, it is clear further research into the dermatological consequences of FGM is necessary so that a conversation can be had about the ways in which dermatologists can effectively support survivors of FGM. It is important that each woman is recognized as an individual with her own story to tell, her own lived experience and her own humanity.

The effect of CO2 laser therapy on vaginal microcirculatory parameters in an animal model for genitourinary syndrome of menopause.

Vaginal laser therapy for the treatment of genitourinary syndrome of menopause (GSM) has been introduced to the market with limited (pre)clinical and experimental evidence supporting its efficacy. It is suggested that vaginal laser therapy increases epithelial thickness and improves vascularization, but the underlying biological working mechanism has not been substantiated yet. To evaluate the effects of CO2 laser therapy on vaginal atrophy using noninvasive incident dark field (IDF) imaging in a large animal model for GSM. An animal study was conducted between 2018 and 2019 and included 25 Dohne Merino ewes, of which 20 underwent bilateral ovariectomy (OVX) to induce iatrogenic menopause, and 5 did not. The total study duration was 10 months. Five months after OVX, ovariectomized ewes received monthly applications of CO2 laser (n = 7), vaginal estrogen (n = 7), or no treatment (n = 6) for 3 months. IDF imaging was performed monthly in all animals. The primary outcome was the proportion of image sequences containing capillary loops (angioarchitecture). Secondary outcomes included focal depth (epithelial thickness), and quantitative measures of vessel density and perfusion. Treatment effects were evaluated using ANCOVA and binary logistic regression. Compared to OVX-only, ewes treated with estrogen demonstrated a higher capillary loops proportion (4% vs. 75%, p < 0.01), and higher focal depth (60 (IQR 60-80) vs. 80 (IQR 80-80) p < 0.05). CO2 laser therapy did not change microcirculatory parameters. As the ewes' vaginal epithelium is thinner than that of humans, it may demand different laser settings. In a large animal model for GSM, CO2 laser therapy does not affect microcirculatory outcomes related to GSM, whereas vaginal estrogen treatment does. Until more homogeneous and objective evidence about its efficacy is available, CO2 laser therapy should not be adopted into widespread practice for treating GSM.

Safety of multiple administrations of spermicidal LL-37 antimicrobial peptide into the mouse female reproductive tract.

We have previously demonstrated spermicidal activity of LL-37 antimicrobial peptide on mouse/human sperm and its contraceptive effects in female mice. With its microbicidal action against Neisseria gonorrhoeae, LL-37 warrants development into a multipurpose prevention technology (MPT) agent for administering into the female reproductive tract (FRT). However, it is important to verify that multiple administrations of LL-37 do not lead to damage of FRT tissues and/or irreversible loss of fecundity. Herein, we transcervically injected LL-37 (36 µM-10× spermicidal dose) into female mice in estrus in three consecutive estrous cycles. A set of mice were sacrificed for histological assessment of the vagina/cervix/uterus 24 h after the last injection, while the second set were artificially inseminated with sperm from fertile males 1week afterwards, and then monitored for pregnancy. Mice injected with PBS in parallel were regarded as negative controls, whereas those injected with vaginal contraceptive foam (VCF, available over the counter), containing 12.5% nonoxynol-9, served as positive controls for vaginal epithelium disruption. We demonstrated that the vagina/cervix/uterus remained normal in both LL-37-injected and PBS-injected mice, which also showed 100% resumption of fecundity. In contrast, VCF-injected mice showed histological abnormalities in the vagina/cervix/uterus and only 50% of them resumed fecundity. Similarly, LL-37 multiply administered intravaginally caused no damage to FRT tissues. While our results indicate the safety of multiple treatments of LL-37 in the mouse model, similar studies have to be conducted in non-human primates and then humans. Regardless, our study provides an experimental model for studying in vivo safety of other vaginal MPT/spermicide candidates.

Vulvo-vaginal aging

Age produces changes in the vulva and vagina, but the key moment is the decrease in estrogen, the main cause of vulvovaginal atrophy (VVA). The main consequence of a hypoestrogenic environment are signs and symptoms that can adversely affect tissues as the labia majora, labia minora, vestibule, clitoris, vagina, urethra, urethral meatus, bladder, pelvic floor muscles, and periurethral anterior vaginal wall.After menopause, the vaginal epithelium loses its rugae, and tissues grow thin and pale. Elastic fibers are fragmented and connective tissue increases. Elasticity is reduced, and the vagina is shortened and narrowed and has reduced distensibility. As vaginal secretions decrease, lubrication is reduced.

A study of the objective benefits and safety of Er-YAG laser in the treatment of genitourinary syndrome of menopause

The aim of this study is to evaluate changes in vaginal pH and epithelium maturation after erbium-doped yttrium aluminum garnet (Er-YAG) laser treatment, and to assess its safety and efficacy on the symptoms of genitourinary syndrome of menopause (GSM). This was a retrospective study conducted between November 2019 and April 2022 and included 32 women diagnosed with GSM who had not benefitted from lubrication treatment and could not or would not use estrogen. Patients received three sessions of Er- YAG laser. All patient data before and after treatment were obtained from computer records. Vaginal maturation index (VMI), maturation value (MV) and vaginal pH values of the patients before and after laser treatment were compared. We also evaluated post-procedural complications and symptoms. Mean age was 59.72 ± 5.66years. After laser therapy, there was a significant decrease in vaginal pH (p < 0.001) and the proportion of parabasal cells in VMI (p < 0.001), while there was a significant increase in MV (p < 0.001) and the proportion of superficial cells in VMI (p < 0.001). In 84.4% of the patients, GSM-related symptoms regressed completely or decreased to a tolerable level. Patients in which symptoms disappeared completely had significantly lower mean age (p = 0.002) and duration of menopause (p = 0.009). The laser procedure resulted in complications including mucosal injury in 5 (15.6%) patients (all recovered spontaneously) and vaginal burning sensation in 2 (6.3%) patients. Vaginal Er-YAG laser treatment may be a safe and effective alternative treatment method in a population of women with GSM who do not want to or cannot use estrogen therapy.

Coxiella burnetii shedding and serological status in pregnant and postpartum ewes

This study aimed to evaluate the occurence C. burnetii-DNA shedding by pregnant (vaginal mucus and feces) and postpartum (vaginal mucus, feces and milk) meat breed ewes from Saint Kitts. Additionally, antibodies anti-C. burnetii were detected in serum, and milk. Barbados Blackbelly ewes (n=187) were sampled using stratified convenience cross-sectional sampling. There were two animal groups: pregnant (n=96) and postpartum (n=91). Vaginal mucus (n=187), feces (n=177) and milk (n=83) samples were subjected to a TaqMan real time qPCR assay for C. burnetii based on the IS1111 multi copy element. IgG antibodies against C. burnetii were tested in blood serum (n=187) and milk (n=61) samples, via indirect ELISA. McNemar and Fischer exact tests were used to compare occurrence between routes and between groups, respectively. Overall, 86.6% of all the animals (162/187) were shedding C. burnetti DNA through at least one route (vaginal and/or fecal and/or milk). The DNA shedding occurrence via vaginal (73% vs 51%, p-value=0.003) and fecal routes (64% vs 47%, p-value=0.001) was higher in the pregnant compared to the postpartum animals. There was no prevalent shedding route among vaginal, fecal or milk in all ewes. Overall, 38% of the ewes were seropositive for C. burnetii IgG and a total of 19.7% of the tested postpartum ewes had IgG antibodies in milk. The vaginal and fecal DNA shedding were not associated with the blood serology, nor was milk DNA shedding related to the milk serology status, thus there was no association between C. burnetii seropositivity and bacterial DNA shedding. In short, high occurrence of C. burnetii DNA shedding was observed within ewes in St. Kitts, and represents the first detection of the Q fever agent within the Caribbean islands. Bacterial shedding was more prevalent in pregnant ewes, highlighting the importance of gestating animals as a source of C. burnetii.

Effects of preoperative intravaginal estrogen on pelvic floor disorder symptoms in postmenopausal women with pelvic organ prolapse

Menopause and the decline in systemic estrogen are associated with the development of pelvic floor disorders, such as prolapse, urinary incontinence, overactive bladder, and vulvovaginal atrophy symptoms. Past evidence suggests that postmenopausal women with symptomatic prolapse gain benefit from the preoperative application of intravaginal estrogen, but it is unknown whether they would experience improvement in other pelvic floor symptoms when treated with intravaginal estrogen. This study aimed to determine the effects of intravaginal estrogen (compared with placebo) on stress and urgency urinary incontinence, urinary frequency, sexual function and dyspareunia, and vaginal atrophy symptoms and signs in postmenopausal women with symptomatic prolapse. This was a planned ancillary analysis of a randomized, double-blind trial, "Investigation to Minimize Prolapse Recurrence Of the Vagina using Estrogen," which included participants with ≥stage 2 apical and/or anterior prolapse scheduled for transvaginal native tissue apical repair at 3 US sites. The intervention was 1 g conjugated estrogen intravaginal cream (0.625 mg/g) or identical placebo (1:1), inserted nightly for 2 weeks and then twice weekly for ≥5 weeks total before surgery and continued twice weekly for 1 year postoperatively. For this analysis, question responses were compared from participants' baseline and preoperative visits: lower urinary tract symptoms (Urogenital Distress Inventory-6 Questionnaire); sexual health questions, including dyspareunia (Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised); and atrophy-related symptoms (dryness, soreness, dyspareunia, discharge, and itching; each scored 1-4, 4 being quite a bit bothersome). Masked examiners assessed vaginal color, dryness, and petechiae (each scored 1-3, total range 3-9, with 9 being the most estrogenized appearing). Data were analyzed by intent to treat and "per protocol" (ie, those adherent with ≥50% of expected intravaginal cream use, per objective tube before and after weights). Of 199 participants randomized (mean age of 65 years) and contributing baseline data, 191 had preoperative data. The characteristics were similar between groups. Total Urogenital Distress Inventory-6 Questionnaire scores showed minimal change during this median time of 7 weeks between baseline and preoperative visits, but for those with at least moderately bothersome baseline stress urinary incontinence (32 in the estrogen group and 21 in the placebo group), 16 (50%) in the estrogen group and 9 (43%) in the placebo group showed improvement (P=.78). In addition, 43% of participants in the estrogen group and 31% of participants in the placebo group showed improvement in urgency urinary incontinence (P=.41), and 41% of participants in the estrogen group and 26% of participants in the placebo group showed improvement in urinary frequency (P=.18). There was minimal change in the Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised scores among sexually active women; dyspareunia rates did not differ between intravaginal estrogen and placebo at the preoperative assessment: 42% and 48%, respectively (P=.49). The maximum score for most bothersome atrophy symptom (among those with baseline symptoms and adherent to study cream) improved slightly more with intravaginal estrogen (adjusted mean difference,-0.33 points; 95% confidence interval,-0.98 to 0.31), but this was not statistically significant (P=.19). However, on examination, among adherent participants, objective signs of atrophy were more improved with intravaginal estrogen treatment (+1.54 vs+0.69; mean difference, 0.85; 95% confidence interval, 0.05-1.65; P=.01). Despite objective changes in the vaginal epithelium consistent with increased estrogenization among drug-adherent participants, the results were inconclusive regarding whether 7 weeks of preoperative intravaginal estrogen cream in postmenopausal women with symptomatic pelvic organ prolapse was associated with improved urinary function, sexual function, dyspareunia symptoms, and other symptoms commonly attributed to atrophy. Additional study is needed.

(104) Immunohistochemical Staining Reveals Estrogen, Androgen and Progesterone Receptors in the Vestibule

Abstract Introduction The introitus has three embryologic tissue types: ectoderm (vulva), endoderm (vestibule), and mesoderm (vagina). The vulva and vagina have been shown previously to have estrogen receptors (ER), androgen receptors (AR) and progesterone receptors (PR). ER and AR have been demonstrated in vaginal epithelial cells, as well as in fibroblasts and smooth muscle of underlying stroma. Vulvar ER and AR were demonstrated in epidermal keratinocytes and dermal fibroblasts of hair and non-hair bearing skin. AR were also seen in vulvar sebaceous glands, sweat glands, and hair follicles. PR was seen in vaginal epithelium, fibroblasts, and smooth muscle but not in the vulva. Despite the importance of the vestibule to sexual health, there is limited information regarding vestibular hormone receptors. Objective To better understand vestibular hormonal physiology, immunohistochemical (IHC) studies of ER, AR, and PR was performed on excised vestibulectomy tissue specimen. Methods IHC was performed on 7 vestibular specimen from eugonadal individuals with confirmed diagnosis of neuroproliferative vestibulodynia based on positive CD117 and PGP9.5 staining, consistent with excess mast cells and nerve endings, respectively. Specimen were also studied with primary antibodies (Anti-ERα, Ab 32063; Anti-AR, MI 06680; Anti-PR, Dako PGR636). Finally, sections were lightly counterstained with Gill-modified hematoxylin. Results ER and AR were richly expressed in tissue samples from all 7 patients. Dense labeling of both receptor types (AR on left, on ER right) was identified in the germinal layer of the epithelium (Fig. 1) with comparatively sparse expression in the subepithelial stroma. AR, but not ER, were noted in mucinous vestibular glands (Fig. 2). While labeling of PR was highly variable (Fig. 3), all samples showed evidence of moderate PR labeling in the subepithelial stroma. Variability may be due to menstrual cycle phase during which samples were obtained, however this information was not collected. Conclusions This preliminary study provides evidence of dense ER and AR expression in the vestibule, consistent with it being in part an androgenic organ. This supports the concept that the vestibule may be more effectively treated with combined testosterone and estradiol cream than with topical estradiol alone in patients with entrance dyspareunia from hormonally mediated vestibulodynia or genitourinary syndrome of menopause. Also consistent with these findings is that treatment with intravaginal DHEA, which converts to testosterone and estradiol intracrinologically and spreads to the vestibule, successfully resolves entrance dyspareunia, as shown in a previous clinical trial. While the significance of variable vestibular progesterone receptor expression is unclear, the addition of topical progesterone in patients with entrance dyspareunia may be considered. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endoceutics, Inc

(100) The Effect of Oral Contraceptive Pill Type on Vulvovaginal Atrophy

Abstract Introduction Oral contraceptive pills (OCPs), which are used by over a quarter of reproductive-age women in the United States (Daniels et al., 2015; Jones et al., 2013), contain either both ethinylestradiol and a synthetic progestin, or solely a synthetic progestin. Through progestin-induced hepatic increases in sex hormone binding globulin (SHBG), OCPs have been found to reduce the number of bioavailable androgens within women’s bodies (Zimmerman et al., 2014). Given that androgens are essential for the maintenance of healthy vaginal tissue (I. Goldstein, 2009), reduced androgen levels may adversely impact the vaginal epithelium in OCP users. While OCPs are indeed associated with symptoms of vulvovaginal atrophy (VVA), such as vaginal pain and vaginal dryness (Battaglia et al., 2012), little is known about how these symptoms may vary based on the androgenicity of OCPs. Objective The aim of the present study was to compare rates of VVA among three groups of women: (1) women using OCPs containing low doses (i.e., ≤25 μg) of ethinylestradiol coupled with an androgenic progestin, (2) women using OCPs containing low doses (i.e., ≤25 μg) of ethinylestradiol coupled with an antiandrogenic progestin, and (3) naturally-cycling women (i.e., women with no history of oral contraceptive pill use). Methods Participants rated the severity of the following symptoms of VVA on a 4-point Likert-type scale ranging from 0 (mild) to 3 (severe): vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, and vaginal pain associated with sexual activity. Participants also dichotomously rated the presence or absence of vaginal bleeding associated with sexual activity. Results Women taking androgenic OCPs (n = 50) were significantly more likely to report vaginal bleeding associated with sexual activity than were women in the control group (n = 59), χ2(2, 130) = 9.759, p = .007. One participant (1.69%) in the control reported vaginal bleeding, compared to ten women (20%) in the androgenic group. Three participants (14.28%) in the antiandrogenic group endorsed vaginal bleeding, however this result was not significant. A MANOVA indicated no significant between-group differences for any of the remaining VVA items (i.e., dryness, itching/irritation, dysuria, or pain), F(2, 250) = 1.098, p = .365, and an ANOVA confirmed there were no differences between groups in the total VVA score, F(2) = 2.093, p = .127. Conclusions There were elevated rates of vaginal bleeding among OCP users compared to non-OCP users in this sample. This finding could be attributable a range of factors which have previously linked OCP use to vaginal bleeding, such as thinning of the vaginal tissue (Kagan &amp; Rivera, 2018), cervical ectopy (Patil &amp; Sharma, 2017), and thinning of the endometrium (Bright et al., 2011). Disclosure No

Vaginal Epithelial Cell Membrane-Based Phototherapeutic Decoy Confers a "Three-in-One" Strategy to Treat against Intravaginal Infection of Candida albicans.

Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.

Vaginal epithelial histology before and after fractional CO2 laser in postmenopausal women: a double-blind, sham-controlled randomized trial

Postmenopausal vaginal symptoms affect over 60% of women and may substantially impact a woman's quality of life. Since 2012, fractional CO2 laser has been suggested as a treatment for this indication. Structural assessment of vaginal epithelium using microscopic biopsy examination has been used as a primary outcome measure and surrogate determinant of success of vaginal laser in previous clinical studies. This study aimed to report the effects of laser compared with sham treatment on human vaginal epithelium from postmenopausal women using microscopic examination of tissue biopsies. This single-center double-blind, sham-controlled randomized controlled trial was performed in a tertiary hospital in Sydney, Australia. A total of 49 postmenopausal women who were symptomatic of at least 1 vaginal symptom (vaginal dryness, burning, itching; dyspareunia; or dryness) were randomized to either laser or sham treatment. For this nested histologic study, participants had a pre- and post-treatment vaginal wall biopsy collected. Biopsy samples were analyzed by 3 independent specialist gynecologic pathologists and categorized as Type 1 (well-estrogenized), 2 (poorly estrogenized), or 3 (combination) mucosae. Other outcomes assessed included symptom severity (visual analog scale for symptoms including most bothersome symptom, and Vulvovaginal Symptom Questionnaire) and Vaginal Health Index. Prespecified secondary analyses of data were performed. Categorical data were analyzed using the Pearson chi-square test (or Fisher exact test if <5 in any category) or related-samples McNemar test for paired nonparametric data. Nonparametric, continuous variables were assessed using Wilcoxon signed-rank test or Mann-Whitney U test, and parametric variables with t test or 1-way analysis of variance as appropriate. All analyses were performed using SPSS software version 26.0 (IBM Corp, Armonk, NY). There was no significant difference in microscopic features of vaginal epithelium following laser or sham treatment (P=.20). Further subgroup analyses of age, menopause type, duration of reproductive life, time since menopause and BMI, still demonstrated no significant difference between laser and sham groups in histological category of vaginal epithelium. Microscopic features at pre-treatment vaginal biopsy were Type 1 in 27% (13/49). There was no significant difference in VAS score for overall vaginal symptom between those classified as Type 1 vs. Type 2/3 (VAS score overall: Type 1 vs. Type 2/3, (48.1 [95% CI 27.0, 69.2] vs. 61.5 [95% CI 49.8, 73.3]; P=.166). Data from this double-blind, sham-controlled randomized controlled trial demonstrate that fractional CO2 laser and sham treatment have a comparable histologic effect on vaginal tissue that is not significantly different. Fractional CO2 laser is not significantly different from sham treatment and should not be recommended for clinical use for postmenopausal vaginal symptoms.

Small intestinal submucosa promotes angiogenesis via the Hippo pathway to improve vaginal repair.

Vaginal reconstruction has incorporated the use of gastrointestinal segments for decades, but the technique is inevitably associated with complications. Tissue-engineering techniques, however, have brought great hope for vaginal reconstruction. This study aimed to evaluate the utility of small intestinal submucosa (SIS) in reconstructing clinically significant large vaginal defects in a porcine model and to investigate the role of the Hippo pathway in the vascular remodeling process. The composition and mechanical properties of SIS were characterized. Full-thickness vaginal defects were established in 10 minipig donors, with 4 cm lengths removed and replaced by an equal sized SIS scaffolds. The neovaginas were subjected to macroscopic, histological, immunohistochemical and molecular evaluations at 4 and 12 weeks after the surgery. Four weeks after the operation, extracellular matrix reorganization and complete coverage the surface of the luminal matrix by vaginal epithelium were observed, accompanied by the formation of a microvascular network and the regeneration of smooth muscles, albeit disorderly arranged. Twelve weeks after implantation, enhacements were seen in the formation of the multi-layered squamous epithelium, angiogenesis, and large muscle bundle formation in the vagina. Aditionally, the expression levels of angiogenesis-related proteins, proliferation-related proteins and Hippo pathway-related proteins in the neovagina were significantly increased. These results indicate that SIS could be used to reconstruct large vaginal defects and that the vascular remodeling process is potentially regulated by the Hippo pathway.

Repurposing Disulfiram as an Antifungal Agent: Development of a New Disulfiram Vaginal Mucoadhesive Gel.

Alternative formulations need to be developed to improve the efficacy of treatments administered via the vaginal route. Mucoadhesive gels with disulfiram, a molecule that was originally approved as an antialcoholism drug, offer an attractive alternative to treat vaginal candidiasis. The aim of the current study was to develop and optimize a mucoadhesive drug delivery system for the local administration of disulfiram. Such formulations were composed of polyethylene glycol and carrageenan to improve the mucoadhesive and mechanical properties and to prolong the residence time in the vaginal cavity. Microdilution susceptibility testing showed that these gels had antifungal activity against Candida albicans, Candida parapsilosis, and Nakaseomyces glabratus. The physicochemical properties of the gels were characterized, and the in vitro release and permeation profiles were investigated with vertical diffusion Franz cells. After quantification, it was determined that the amount of the drug retained in the pig vaginal epithelium was sufficient to treat candidiasis infection. Together, our findings suggest that mucoadhesive disulfiram gels have the potential to be an effective alternative treatment for vaginal candidiasis.

Establishment of a vaginal organoid system to study local resident memory T cell differentiation

Abstract Over a million sexually transmitted diseases (STDs) are acquired every day worldwide, many of which preferentially target the female reproductive tract (FRT). Resident memory T cells (TRM) in the vaginal mucosa have proven protective roles against these STDs. Accordingly, a crucial objective of STD vaccinations is to establish a higher quantity and quality of TRM in the FRT. The vaginal epithelium has been implicated in regulation of local TRM differentiation and function, but the biological nature of this interaction has not been investigated. Here, we established a murine three dimensional (3D) vaginal organoid-CD8 coculture system to examine epithelial-T cell interactions at the molecular level. Differentiation of single epithelial stem cells led to the formation of 3D epithelial organoids. These organoids can be maintained long-term through serial passage and structurally resembled vaginal epithelium with a multilayer specialized epithelium. After culturing activated CD8 T cells with the organoids, we assessed the transcriptional and phenotypic composition of the T cells. We found that cocultured CD8 T cells were integrated into the extracellular matrix and acquired phenotypic and functional traits of in vivo TRM. This TRM-biased differentiation could be suppressed by a small molecule inhibitor of the cytokine TGF-β. Overall, the vaginal organoid coculture model recapitulates the in vivo environment far better than traditional 2D cell culture, while retaining high-throughput abilities. Importantly, it will enable highly reductionist experiments to examine the complex epithelial cell-T cell crosstalk to devise targeted approaches for improving CD8 T cell mediated immunosurveillance in the FRT. Supported by grants from NIH (2P20GM109035 &amp; P20GM121298) and by the Searle Scholars award.

Measuring the effects of estrus on rumen temperature and environment, behavior and physiological attributes in Korean Native breeding cattle.

In this study, rumen temperature and environment in estral and non-estral Korean Native breeding cattle were evaluated by using a bolus sensor. Behavioral and physiological changes in study animals were also assessed. To assess the rumen temperature and environment, we inserted bolus sensors into 12 Korean Native cattle with an average age of 35.5 months, then measured temperature and activity within the rumen using the wireless bolus sensor. Drinking, feeding and mounting behavior, and measured vaginal temperature and levels of intravaginal mucus resistance were recorded. We found that cattle in estrus exhibited more acts of mounting (37.4 vs. 0 times/day), increased vaginal temperature (39.0°C vs. 38.4°C), and decreased vaginal mucus resistance (136.3 Ω vs 197.4 Ω), compared with non-estral animals. Furthermore, increased levels of rumen activity were most significant in estrus cattle at the highest activity levels (p < 0.01). Overall, the estrus group exhibited increased rumen temperature (p = 0.01), compared with the non-estrus group. In conclusion, the results of this study not only provide basic physiological data related to estrus in improved Korean Native breeding cattle, but also suggest that monitoring of rumen temperature and activity might be used as an effective smart device for estrus detection.

Megaloblastic anemia at the Mohamed VI University Hospital of Marrakech: About 132 cases

Megaloblastic anemia is a common form of anemia that may be related to a vitamin B12 or B9 deficiency. It results from an abnormality of DNA synthesis and is diagnosed on the myelogram by a cellular gigantism of the medullary erythroblasts called megaloblasts but also in all cells with rapid renewal (oral, intestinal, vaginal epithelium...). Megaloblastic anemias are predominantly found in subjects over 60 years of age, with a male predominance. The clinical signs are dominated by digestive and neurological disorders. The diagnosis of megaloblastic anemia, guided by the hemogram, is classically confirmed by vitamin assays and the myelogram, which reveals a medullary megaloblastosis. However, for some authors, the myelogram is no longer systematic when the epidemiological, anamnestic and clinical data make it possible to eliminate other causes of macrocytic anemia and to retain a vitamin deficiency. Confirmation of this deficiency is done by vitamin assays. Megaloblastic anemias are generally of deficiency origin, in which case their management is based on vitamin supplementation for curative or preventive purposes.

Efficacy of Fractional CO2 Laser Treatment for Genitourinary Syndrome of Menopause in Short-Term Evaluation-Preliminary Study.

The postmenopausal state covers 40% of modern women's lives and 50-70% of postmenopausal women report GSM symptoms such as vaginal dryness, itching, frequent inflammations, lack of elasticity, or dyspareunia. Consequently, a safe and effective method of treatment is crucial. In a group of 125 patients, a prospective observational study was performed. The aim was to evaluate the clinical effectiveness of fractional CO2 laser in the treatment of GSM symptoms using a protocol of three procedures in 6-week intervals. The vaginal pH, VHIS, VMI, FSFI, and treatment satisfaction questionnaire were used. The fractional CO2 laser treatment was effective in improving all the objective forms of evaluation: vaginal pH (from 5.61 ± 0.50 at the baseline up to 4.69 ± 0.21 in the 6-week follow-up after the third procedure); VHIS (12.02 ± 1.89 at the baseline vs. 21.50 ± 1.76); VMI (21.5 ± 5.66 vs. 48.4 ± 4.46). Similar results were obtained for FSFI: 12.79 ± 5.351 vs. 24.39 ± 2.733, where 79.77% of patients were highly satisfied. Fractional CO2 laser therapy increases the quality of life by having a beneficial effect on the sexual function of women with GSM symptoms. This effect is obtained by restoring the correct structure and proportions of the cellular composition of the vaginal epithelium. This positive effect was confirmed by both objective and subjective forms of evaluating GSM symptom severity.

Prevalence and risk factors of Q fever (Coxiella burnetii) in cattle on farms of Limpopo province, South Africa.

Q fever in animals and humans and its economic and public health significance has been widely reported worldwide but in South Africa. There are few studies on the prevalence of this zoonosis and its associated risk factors in South African livestock. Therefore, a cross-sectional study was conducted to determine the seroprevalence, molecular prevalence, and risk factors associated with C. burnetii in cattle on farms in South Africa's Limpopo province. Out of 383 cattle tested for antibodies, the overall seroprevalence was 24.28%. Herd size of >150 (OR: 9.88; 95%CI: 3.92-24.89; p < 0.01) remained associated with C. burnetii seropositivity in cattle. For PCR detection, targeting IS1111 fragment, cattle with no abortion history (OR: 0.37; 95%CI: 0.18-0.77; p < 0.01) and herd size of >150 (OR: 3.52; 95%CI: 1.34-9.24; p < 0.01) remained associated with C. burnetii positivity. The molecular prevalence in sheath scrapings and vaginal swabs by IS1111 PCR was 15.67%. Cohen's kappa agreement test revealed a fair agreement between the PCR and ELISA results (k = 0.40). Sequence analysis revealed that the amplicons had similarities to the C. burnetii transposase gene fragment, confirming the presence of the pathogen. The higher seroprevalence than molecular prevalence indicated a past C. burnetii infection, no bacterial shedding through vaginal mucus in cows, or preputial discharge in bulls. Similarly, the detection of C. burnetii by PCR in the absence of antibodies could be partly explained by recent infections in which antibodies have not yet been produced against the bacteria, or the level of these antibodies was below the detectability threshold. The presence of the pathogen in cattle and the evidence of exposure, as shown by both PCR and ELISA suggests an active circulation of the pathogen. This study demonstrated that C. burnetii is widespread in the study area and that a herd size of >150 is associated with C. burnetii seroprevalence and molecular prevalence.