-
Mucosal Immunology Jun 2024Regulatory T cells (Treg) are well-known to mediate peripheral tolerance at homeostasis, and there is growing appreciation for their role in modulating infectious...
Regulatory T cells (Treg) are well-known to mediate peripheral tolerance at homeostasis, and there is growing appreciation for their role in modulating infectious disease immunity. Following acute and chronic infections, Tregs can restrict pathogen-specific T cell responses to limit immunopathology. However, it is unclear if Tregs mediate control of pathology and immunity in distal tissue sites during localized infections. We investigated a role for Tregs in immunity and disease in various tissue compartments in the context of "mild" vaginal Zika virus (ZIKV) infection. We found that Tregs are critical to generate robust virus-specific CD8 T cell responses in the initial infection site. Further, Tregs limit inflammatory cytokines and immunopathology during localized infection; a dysregulated immune response in Treg-depleted mice leads to increased T cell infiltrates and immunopathology in both the vagina and the central nervous system (CNS). Importantly, these CNS infiltrates are not present at the same magnitude during infection of Treg sufficient mice, in which there is not CNS immunopathology. Our data suggest that Tregs are necessary to generate a robust virus-specific response at the mucosal site of infection, while Treg-mediated restriction of bystander inflammation limits immunopathology both at the site of infection as well as distal tissue sites.
PubMed: 38908483
DOI: 10.1016/j.mucimm.2024.06.007 -
Journal of Biomechanics Jun 2024The perineum is a layered soft tissue structure with mechanical properties that maintain the integrity of the pelvic floor. During childbirth, the perineum undergoes...
The perineum is a layered soft tissue structure with mechanical properties that maintain the integrity of the pelvic floor. During childbirth, the perineum undergoes significant deformation that often results in tears of various degrees of severity. To better understand the mechanisms underlying perineal tears, it is crucial to consider the mechanical properties of the different tissues that make up the perineum. Unfortunately, there is a lack of data on the mechanical properties of the perineum in the literature. The objective of this study is to partly fill these gaps. Hence sow perineums were dissected and the five perineal tissues involved in tears were characterized by uniaxial tension tests: Skin, Vagina, External Anal Sphincter, Internal Anal Sphincter and Anal Mucosa. From our knowledge, this study is the first to investigate all these tissues and to design a testing protocol to characterize their material properties. Six material models were used to fit the experimental data and the correlation between experimental and predicted data was evaluated for comparison. As a result, even if the tissues are of different nature, the best correlation was obtained with the Yeoh and Martins material models for all tissues. Moreover, these preliminary results show the difference in stiffness between the tissues which indicates that they might have different roles in the structure. These obtained results will serve as a basis to design an improved experimental protocol for a more robust structural model of the porcine perineum that can be used for the human perineum to predict perineal tears.
Topics: Animals; Perineum; Swine; Female; Biomechanical Phenomena; Models, Biological; Anal Canal; Vagina; Stress, Mechanical
PubMed: 38908107
DOI: 10.1016/j.jbiomech.2024.112175 -
Microbiome Jun 2024Bacterial vaginosis (BV) increases HIV acquisition risk, potentially by eliciting genital inflammation. After BV treatment, the vaginal administration of LACTIN-V, a...
BACKGROUND
Bacterial vaginosis (BV) increases HIV acquisition risk, potentially by eliciting genital inflammation. After BV treatment, the vaginal administration of LACTIN-V, a live biotherapeutic containing the Lactobacillus crispatus strain CTV-05, reduced BV recurrence and vaginal inflammation; however, 3 months after product cessation, CTV-05 colonization was only sustained in 48% of participants.
RESULTS
This nested sub-study in 32 participants receiving LACTIN-V finds that 72% (23/32) demonstrate clinically relevant colonization (CTV-05 absolute abundance > 10 CFU/mL) during at least one visit while 28% (9/32) of women demonstrate colonization resistance, even during product administration. Immediately prior to LACTIN-V administration, the colonization-resistant group exhibited elevated vaginal microbiota diversity. During LACTIN-V administration, colonization resistance was associated with elevated vaginal markers of epithelial disruption and reduced chemokines, possibly due to elevated absolute abundance of BV-associated species and reduced L. crispatus. Colonization permissive women were stratified into sustained and transient colonization groups (31% and 41% of participants, respectively) based on CTV-05 colonization after cessation of product administration. These groups also exhibited distinct genital immune profiles during LACTIN-V administration.
CONCLUSIONS
The genital immune impact of LACTIN-V may be contingent on the CTV-05 colonization phenotype, which is in turn partially dependent on the success of BV clearance prior to LACTIN-V administration.
Topics: Humans; Female; Vaginosis, Bacterial; Vagina; Lactobacillus crispatus; Adult; Probiotics; Administration, Intravaginal; Microbiota; Young Adult; Phenotype
PubMed: 38907268
DOI: 10.1186/s40168-024-01828-7 -
Techniques in Coloproctology Jun 2024Four patients with rectal cancer required reconstruction of a defect of the posterior vaginal wall. All patients received neoadjuvant (chemo)radiotherapy, followed by an...
Four patients with rectal cancer required reconstruction of a defect of the posterior vaginal wall. All patients received neoadjuvant (chemo)radiotherapy, followed by an en bloc (abdomino)perineal resection of the rectum and posterior vaginal wall. The extent of the vaginal defect necessitated closure using a tissue flap with skin island. The gluteal turnover flap was used for this purpose as an alternative to conventional more invasive myocutaneous flaps (gracilis, gluteus, or rectus abdominis). The gluteal turnover flap was created through a curved incision at a maximum width of 2.5 cm from the edge of the perineal wound, thereby creating a half-moon shape skin island. The subcutaneous fat was dissected toward the gluteal muscle, and the gluteal fascia was incised. Thereafter, the flap was rotated into the defect and the skin island was sutured into the vaginal wall defect. The contralateral subcutaneous fat was mobilized for perineal closure in the midline, after which no donor site was visible.The duration of surgery varied from 77 to 392 min, and the hospital stay ranged between 3 and 16 days. A perineal wound dehiscence occurred in two patients, requiring an additional VY gluteal plasty in one patient. Complete vaginal and perineal wound healing was achieved in all patients. The gluteal turnover flap is a promising least invasive technique to reconstruct posterior vaginal wall defects after abdominoperineal resection for rectal cancer.
Topics: Humans; Female; Vagina; Buttocks; Rectal Neoplasms; Middle Aged; Plastic Surgery Procedures; Surgical Flaps; Aged; Perineum; Operative Time; Treatment Outcome
PubMed: 38907171
DOI: 10.1007/s10151-024-02941-3 -
Reproductive Sciences (Thousand Oaks,... Jun 2024Pelvic organ prolapse (POP), a downward descent of the vagina and/or uterus through the vaginal canal, is a prevalent condition affecting up to 40% of women. Several...
Pelvic organ prolapse (POP), a downward descent of the vagina and/or uterus through the vaginal canal, is a prevalent condition affecting up to 40% of women. Several risk factors of POP have been identified, including childbirth, connective tissue defects, and chronic intra-abdominal pressure; however, the underlying etiologies of POP development are not fully understood, leading to a high burden on patients and the healthcare systems. The uterosacral ligaments are key support structures of the uterus and upper vagina. Our previous work describes observed histopathological changes in uterosacral ligament (USL) tissue and demonstrates the presence of neutrophils in a subgroup of POP individuals. This presence of neutrophils prompted an examination for the presence of a broader spectrum of inflammatory cell types in the USL. Immunohistochemical staining was performed to identify neutrophils, lymphocytes, macrophages, and mast cells outside of the vasculature. All 4 inflammatory cell types were increased in the POP-HQ system-defined POP-Inflammatory (POP-I) phenotype USL tissue relative to the USL tissues of control or other POP-HQ phenotypes. Focal T-lymphocyte and macrophage co-accumulations were observed in the arterial walls from some patients of the POP-vascular (POP-V) phenotype suggesting previous arterial injury. In addition, 1 control and 2 POP-V subjects' USLs contained arterial wall foamy macrophages, evidence of atherosclerosis. These findings further support a complex etiology for POP and indicate that personalized approaches to preventing and treating the condition may be warranted.
PubMed: 38907126
DOI: 10.1007/s43032-024-01618-4 -
Nature Microbiology Jun 2024The human vagina harbours diverse microorganisms-bacteria, viruses and fungi-with profound implications for women's health. Genome-level analysis of the vaginal...
The human vagina harbours diverse microorganisms-bacteria, viruses and fungi-with profound implications for women's health. Genome-level analysis of the vaginal microbiome across multiple kingdoms remains limited. Here we utilize metagenomic sequencing data and fungal cultivation to establish the Vaginal Microbial Genome Collection (VMGC), comprising 33,804 microbial genomes spanning 786 prokaryotic species, 11 fungal species and 4,263 viral operational taxonomic units. Notably, over 25% of prokaryotic species and 85% of viral operational taxonomic units remain uncultured. This collection significantly enriches genomic diversity, especially for prevalent vaginal pathogens such as BVAB1 (an uncultured bacterial vaginosis-associated bacterium) and Amygdalobacter spp. (BVAB2 and related species). Leveraging VMGC, we characterize functional traits of prokaryotes, notably Saccharofermentanales (an underexplored yet prevalent order), along with prokaryotic and eukaryotic viruses, offering insights into their niche adaptation and potential roles in the vagina. VMGC serves as a valuable resource for studying vaginal microbiota and its impact on vaginal health.
PubMed: 38907008
DOI: 10.1038/s41564-024-01751-5 -
Pathology May 2024Vulvar and vaginal melanomas (VVMs) are rare and aggressive malignancies with limited prognostic models available and there is no standard reporting protocol. VVMs were...
Vulvar and vaginal melanomas (VVMs) are rare and aggressive malignancies with limited prognostic models available and there is no standard reporting protocol. VVMs were selected from six tertiary Canadian hospitals from 2000-2021, resected from patients aged ≥18 years, with 6 months or longer follow-up data, and confirmation of melanocytic differentiation by at least two immunohistochemical markers. Cases were reviewed by pathologists to identify histological biomarkers. Survival outcomes were tested with Kaplan-Meier log-rank, univariate Cox, and multivariate Cox regression. There were 79 VVMs with median follow-up at 26 months. Univariate analysis revealed that tumour necrosis, tumour ulceration, positive lymph nodes, and metastasis at diagnosis were significantly associated with disease-specific mortality, progression, and metastasis. Multivariate analysis identified tumour necrosis as an independent prognostic factor for disease-specific mortality (HR 4.803, 95% CI 1.954-11.803, p<0.001), progression (HR 2.676, 95% CI 1.403-5.102, p=0.003), and time-to-metastasis for non-metastatic patients at diagnosis (HR 3.761, 95%CI 1.678-8.431, p=0.001). Kaplan-Meier survival analyses demonstrated that tumour necrosis was a poor prognostic factor for disease-specific, progression-free, and metastasis-free survival (p<0.001 for all comparisons). Vaginal melanomas displayed decreased survival compared to vulvar or clitoral melanomas. This study identifies tumour necrosis as an independent prognostic factor for VVMs. Vaginal melanomas specifically showed worse survival outcomes compared to vulvar or clitoral melanomas, consistent with previously reported findings in the literature, emphasising the importance of differentiating between these primary tumour epicentres for prognostication and treatment planning in the care of genital melanoma patients.
PubMed: 38906758
DOI: 10.1016/j.pathol.2024.03.008 -
Journal of Robotic Surgery Jun 2024The Da Vinci single port® (SP) robotic platform heralds a new era of minimally invasive surgery (MIS). The primary objective of this study was to assess short-term...
The Da Vinci single port® (SP) robotic platform heralds a new era of minimally invasive surgery (MIS). The primary objective of this study was to assess short-term outcomes in patients undergoing SP robotic hysterectomy with concomitant sacrocolpopexy for pelvic organ prolapse (POP). We performed a retrospective case series at two tertiary care centers between January 2021 and August 2023. Patients with POP electing to undergo SP robotic hysterectomy with concomitant sacrocolpopexy were included. Chart abstraction was used to collect patient demographics and clinical outcomes. Recurrent POP was defined as new bothersome vaginal bulge symptoms and evidence of POP beyond the hymen on postoperative examination. 69 patients were included. Median operative time was 209 min (135-312) and estimated blood loss was 100 mL (20-2000). 1 (1.4%) patient sustained a major vascular injury resulting in laparotomy. Median pain score and morphine equivalents administered in PACU were low at 3 (0-7) and 3.2 (0-27) respectively. At 3 months, 60 (86.9%) patients were seen either in person or via telemedicine for their follow up appointment. 59/60 (98.3%) reported no vaginal bulge symptoms and 50/51 (98.0%) had stage 0 or 1 prolapse on exam. One (1.4%) patient had recurrent prolapse and underwent an additional repair. Postoperative complications included 2 (2.9%) cases of ileus/small bowel obstruction, 1 (1.4%) pelvic hematoma requiring a blood transfusion, and 1 (1.4%) umbilical hernia. The SP robotic platform is a safe and feasible platform for MIS hysterectomy and sacrocolpopexy with good short term anatomic and symptomatic outcomes.
Topics: Humans; Robotic Surgical Procedures; Female; Pelvic Organ Prolapse; Hysterectomy; Middle Aged; Retrospective Studies; Treatment Outcome; Aged; Operative Time; Vagina; Postoperative Complications; Sacrum; Time Factors; Gynecologic Surgical Procedures; Blood Loss, Surgical
PubMed: 38904835
DOI: 10.1007/s11701-024-02029-y -
Frontiers in Microbiology 2024The concept of a sterile uterus was challenged by recent studies that have described the microbiome of the virgin and pregnant uterus for species including humans and...
INTRODUCTION
The concept of a sterile uterus was challenged by recent studies that have described the microbiome of the virgin and pregnant uterus for species including humans and cattle. We designed two studies that tested whether the microbiome is introduced into the uterus when the virgin heifer is first inseminated and whether the origin of the microbiome is the vagina/cervix.
METHODS
The uterine microbiome was measured immediately before and after an artificial insemination (AI; Study 1; = 7 AI and = 6 control) and 14 d after insemination (Study 2; = 12 AI and = 12 control) in AI and non-AI (control) Holstein heifers. A third study (Study 3; = 5 Holstein heifers) that included additional negative controls was subsequently conducted to support the presence of a unique microbiome within the uterus despite the low microbial biomass and regardless of insemination. Traditional bacteriological culture was performed in addition to 16S rRNA gene sequencing on the same samples to determine whether there were viable organisms in addition to those detected based on DNA sequencing (16S rRNA gene sequence).
RESULTS AND DISCUSSION
Inseminating a heifer did not lead to a large change in the microbiome when assessed by traditional methods of bacterial culture or metataxonomic (16S rRNA gene) sequencing (results of Studies 1 and 2). Very few bacteria were cultured from the body or horn of the uterus regardless of whether an AI was or was not (negative control) performed. The cultured bacterial genera (e.g., , and ) were typical of those found in the soil, environment, skin, mucous membranes, and urogenital tract of animals. Metataxonomic sequencing of 16S rRNA gene generated a large number of amplicon sequence variants (ASV), but these larger datasets that were based on DNA sequencing did not consistently demonstrate an effect of AI on the abundance of ASVs across all uterine locations compared with the external surface of the tract (e.g., perimetrium; positive control samples for environment contamination during slaughter and collection). Major genera identified by 16S rRNA gene sequencing overlapped with those identified with bacterial culture and included , and .
PubMed: 38903779
DOI: 10.3389/fmicb.2024.1385505 -
Regenerative Biomaterials 2024Pelvic organ prolapse (POP) afflicts millions of women globally. In POP, the weakened support of the pelvic floor results in the descent of pelvic organs into the...
Promoting cell proliferation and collagen production with ascorbic acid 2-phosphate-releasing poly(l-lactide-co-ε-caprolactone) membranes for treating pelvic organ prolapse.
Pelvic organ prolapse (POP) afflicts millions of women globally. In POP, the weakened support of the pelvic floor results in the descent of pelvic organs into the vagina, causing a feeling of bulging, problems in urination, defaecation and/or sexual function. However, the existing surgical repair methods for relapsed POP remain insufficient, highlighting the urgent need for more effective alternatives. Collagen is an essential component in pelvic floor tissues, providing structural support, and its production is controlled by ascorbic acid. Therefore, we investigated novel ascorbic acid 2-phosphate (A2P)-releasing poly(l-lactide-co-ε-caprolactone) (PLCL) membranes to promote cell proliferation and extracellular matrix protein production to strengthen the natural support of the pelvic fascia for POP applications. We analysed the mechanical properties and the impact of PLCL on cellular responses through cell culture analysis using human vaginal fibroblasts (hVFs) and human adipose-derived stem/stromal cells (hASCs) compared to PLCL. In addition, the A2P release from PLCL membranes was assessed . The PLCL demonstrated slightly lower tensile strength (2.2 ± 0.4 MPa) compared to PLCL (3.7 ± 0.6 MPa) for the first 4 weeks . The A2P was most rapidly released during the first 48 h of incubation. Our findings demonstrated significantly increased proliferation and collagen production of both hVFs and hASCs on A2P-releasing PLCL compared to PLCL. In addition, extracellular collagen Type I fibres were detected in hVFs, suggesting enhanced collagen maturation on PLCL. Moreover, increased extracellular matrix protein expression was detected on PLCL in both hVFs and hASCs compared to plain PLCL. In conclusion, these findings highlight the potential of PLCL as a promising candidate for promoting tissue regeneration in applications aimed for POP tissue engineering applications.
PubMed: 38903561
DOI: 10.1093/rb/rbae060