Apical Compartment Research Articles

Gangrenous Small Bowel Due to Reposition of Procidentia in an Elderly Woman

Gynecologists are familiar with procidentia, a severe form of pelvic organ prolapse (POP) that includes herniation of the anterior, posterior, and apical compartments of the vagina, through the introitus. Usually, women with POP present with concerns of something coming out of the vagina, heaviness, discharge through the vagina, urinary complaints, and, rarely bowel, complaints. Intestinal obstruction secondary to procidentia is a rare complication and is seldom reported in the literature. We report one such case where an elderly woman presented with the primary concerns of constipation, retention of urine, and multiple episodes of vomiting. Clinical history revealed that herniated tissue protruding outside the vaginal introitus was reposited inside the vagina two days ago. Clinical examination and investigations were suggestive of intestinal obstruction, secondary to the reposition of procidentia. Exploratory laparotomy revealed gangrene of the terminal ileum. Right hemicolectomy with ileo-colic anastomosis was done, which saved the woman’s life. Reposition of the prolapsed uterus was thought to be the probable reason, leading to obstructed and gangrenous small bowel. As this case illustrates, the chronology of symptoms and signs and progression of disease should be appropriately interpreted to diagnose and manage such potentially life-threatening conditions.

Qiangjing tablets repair of blood-testis barrier dysfunction in rats via regulating oxidative stress and p38 MAPK pathway

BackgroundThe blood-testis barrier (BTB) is a physical barrier of the testis to prevent various exogenous substrates from entering apical compartments and provides immune privilege for spermatogenesis, which is essential for normal spermatogenic function of testis. It has been shown that oxidative stress can damage BTB by activating the p38 MAPK pathway. In Traditional Chinese Medicine, Qiangjing tablets (QJT) improve spermatogenesis and increase pregnancy rates. Previous studies have confirmed that QJT can improve sperm quality and have obvious antioxidant effects. In this study, we explore whether QJT contributes to recovery from BTB dysfunction in rats.MethodsBTB dysfunction was induced in rats by 1% Cyclophosphamide (CP). The CP-induced rats in the treatment group were given a dose of QJT (0.45 g/kg·d) by gavage. Testis tissues were collected for histopathological and biochemical analysis, and the testis weight was estimated. Levels of BTB-related proteins and antioxidant enzyme were analyzed in the testis tissues.ResultsQJT resolved the pathological injury of rats testis induced by CP. Furthermore, MDA levels were significantly reduced, and the levels of SOD markedly increased in the testicular tissue after QJT treatment. In addition, QJT down-regulated the expression of p38 protein in rat testis and up-regulated the expressions of key proteins ZO-1, occludin and F-actin in BTB.ConclusionThese results demonstrate that QJT exerts protective effects on CP-induced rats with BTB dysfunction, likely by regulating the oxidative stress-mediated p38 MAPK pathway.

PD36-08 BLOOD TESTIS BARRIER-MIMETIC DROPLET INTERFACE BILAYERS (DIBS) FOR PASSIVE PERMEABILITY PREDICTION

You have accessJournal of UrologyCME1 May 2022PD36-08 BLOOD TESTIS BARRIER-MIMETIC DROPLET INTERFACE BILAYERS (DIBS) FOR PASSIVE PERMEABILITY PREDICTION Jaime Korner, Meghan Robinson, Katherine Elvira, Ryan Flannigan, and Stephanie Willerth Jaime KornerJaime Korner More articles by this author , Meghan RobinsonMeghan Robinson More articles by this author , Katherine ElviraKatherine Elvira More articles by this author , Ryan FlanniganRyan Flannigan More articles by this author , and Stephanie WillerthStephanie Willerth More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002594.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The blood testis barrier (BTB) serves as a “gatekeeper” for the apical compartment of the seminiferous epithelium where spermatogenesis takes place. Tight junctions between adjacent Sertoli cells create the BTB, regulate transport of molecules, and protect the luminal compartment from toxins and pathogens. Investigating the impact of toxins and drugs, and the regulation of human spermatogenesis requires realistic in vitro models. The purpose of this study was to develop an artificial cellular membrane to mimic the BTB using droplet interface bilayers (DIBs) derived from human Sertoli cell lipid extracts. METHODS: Human Sertoli cells were collected from a dissociated human testicular biopsy using magnetic activated sorting for Follicle-Stimulating Hormone Receptor (FSHR). Sertoli cells were expanded in vitro and lipids were extracted using a Lipid Extraction Kit (Cell Biolabs). Permeability experiments were conducted using a poly(dimethylsiloxane) (PDMS) microfluidic device which allows for the controlled formation of pairs of differing droplet compartments connected by a phospholipid bilayer. A solution of Sertoli lipids in squalene (10 mg/mL) was used as the outer phase. Donor droplets contained fluorophore (100 µM in buffer) and acceptor droplets contained only buffer (both pH 7.4). The DIB-connected droplet pairs were formed at 50 °C and the temperature was decreased to 37 °C for observation. RESULTS: These results represent the first DIBs to be made using human lipid extracts and the first use of DIBs to model permeability of the BTB. We found that the BTB-mimetic DIBs were impermeable to both fluorophores tested: fluorescein and calcein. Calcein is normally membrane-impermeable and serves as a control experiment to confirm the presence of an intact phospholipid bilayer. Fluorescein has been observed to permeate DIBs made using single, synthetic lipids and intestine-mimetic DIBs but not most blood-brain barrier-mimetic DIBs. CONCLUSIONS: DIBs can be made from human Sertoli cell lipid extracts and show great potential to more accurately model BTB permeability. Source of Funding: Collaborative Healthy Grant © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e635 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jaime Korner More articles by this author Meghan Robinson More articles by this author Katherine Elvira More articles by this author Ryan Flannigan More articles by this author Stephanie Willerth More articles by this author Expand All Advertisement PDF DownloadLoading ...

Laparoscopic sacrohysteropexy versus vaginal sacrospinous hysteropexy as treatment for uterine descent: comparison of long-term outcomes

Introduction and hypothesisPelvic organ prolapse (POP) is a frequent occurring health issue, especially concerning elderly women. The objective of this study is to examine the long-term outcomes of laparoscopic sacrohysteropexy (LSH) and vaginal sacrospinous hysteropexy (SSHP) for treatment of uterine prolapse.MethodsA retrospective study of patients who underwent a LSH or SSHP. Validated questionnaires and an outpatient examination visit were used to investigate the effects of both surgical treatments. The primary outcome was the composite outcome of success for the apical compartment, defined as no recurrence of uterine prolapse (POP-Q measurement C ≤ 0), no subjective recurrence of POP, and/or not requiring therapy for recurrent prolapse. Secondary outcomes were peri- and postoperative data, anatomical failure, prolapse beyond hymen, subjective outcomes, and disease-specific quality of life.ResultsWe included 105 patients, 53 in the LSH group and 52 in the SSHP group. The overall response rate of the questionnaires was 83% (n = 87) after a mean follow-up time of 4.5 years (54.2 months; 95% CI 44.8–64.2 months) in the LSH group and 2.5 years (30.1 months; 95% CI 29.3–31.5 months) in the SSHP group. There were no clinically relevant differences between the study groups in composite outcome of success (p = 0.073), anatomical failure of the apical compartment (p = 0.711), vaginal bulge symptoms for which patients consulted professionals (p = 0.126), and patient satisfaction (p = 0.741). The operative time was longer in the LSH group (117 min; interquartile range (IQR) 110–123) compared to the SSHP group (67 minutes; IQR 60–73) (p < 0.001). The duration of hospital stay was also longer in the LSH group (4 days) than in the SSHP group (3 days) (p = 0.006).ConclusionsLSH and SSHP seem to be equally effective after long-term follow-up in treating uterine prolapse in terms of objective and subjective recurrence.

Stasis ulcer and hydronephrosis after severe genital prolapse: a case report\xa0

Introduction and importanceThe most common complication of pelvic organ prolapse is stress urinary incontinence, whereas hydronephrosis or stasis ulcers are quite rare and typical of severe stages. The best treatment for this unusual presentation is still controversial. Here we present our approach.Case presentationHere we present the case of a 70-year-old White/Caucasian woman who presented to our hospital with genital procidentia lasting for 10 years that was associated with both hydronephrosis and stasis ulcers.Clinical findings and investigationsThe Pelvic Organ Prolapse Quantitation system was used to assess the severity of the prolapse, being evaluated as stage IV with the apical compartment leading. A thorough search of the literature was conducted to find any similar cases and evaluate the best evidence treatment.Interventions and outcomesA no-mesh procedure comprising vaginal hysterectomy, axial apex suspension, and anterior and posterior repair with ulcerated skin removal resulted in complete resolution of both mechanical and functional symptoms. At 3- and 6-month follow-up visits, a satisfying vaginal profile without hydronephrosis was seen. The Pelvic Organ Prolapse Quantitation at 6 months follow-up was as follows: Aa -3, Ba -3, C -7; gh 2, pb 3, tvt 9; Ap -3, Bp -3.Relevance and impactPelvic organ prolapse involves many organs and causes further complications, leading seldom to renal insufficiency and stasis ulcers. A temporary solution to the obstruction can be achieved by utilizing a pessary, but this device cannot be applied when a stasis ulcer has been previously established. The use of mesh for pelvic floor repair is controversial, but a previous vaginal ulcer may represent a contraindication. A complete evaluation and a challenging surgery may allow the recovery of complicated and severe pelvic organ prolapse. Native tissue pelvic repair gives no erosion postsurgical risk, which is the typical complication of the prosthesis.

Preclinical In Vitro Model to Assess the Changes in Permeability and Cytotoxicity of Polarized Intestinal Epithelial Cells during Exposure Mimicking Oral or Intravenous Routes: An Example of Arsenite Exposure.

The gastrointestinal tract (GIT) is exposed to xenobiotics, including drugs, through both: local (oral) and systemic routes. Despite the advances in drug discovery and in vitro pre-clinical models, there is a lack of appropriate translational models to distinguish the impact of these routes of exposure. Changes in intestinal permeability has been observed in different gastrointestinal and systemic diseases. This study utilized one such xenobiotic, arsenic, to which more than 200 million people around the globe are exposed via their food, drinking water, work environment, soil, and air. The purpose of this study was to establish an in vitro model to mimic gastrointestinal tract exposure to xenobiotics via oral or intravenous routes. To achieve this, we compared the route (mimicking oral and intravenous exposure to GIT and the dose response (using threshold approach) of trivalent and pentavalent inorganic arsenic species on the permeability of in vitro cultured polarized T84 cells, an example of intestinal epithelial cells. Arsenic treatment to polarized T84 cells via the apical and basolateral compartment of the trans-well system reflected oral or intravenous routes of exposure in vivo, respectively. Sodium arsenite, sodium arsenate, dimethyl arsenic acid sodium salt (DMAV), and disodium methyl arsonate hydrate (MMAV) were assessed for their effects on intestinal permeability by measuring the change in trans-epithelial electrical resistance (TEER) of T-84 cells. Polarized T-84 cells exposed to 12.8 µM of sodium arsenite from the basolateral side showed a marked reduction in TEER. Cytotoxicity of sodium arsenite, as measured by release of lactate dehydrogenase (LDH), was increased when cells were exposed via the basolateral side. The mRNA expression of genes related to cell junctions in T-84 cells was analyzed after exposure with sodium arsenite for 72 h. Changes in TEER correlated with mRNA expression of focal-adhesion-, tight-junction- and gap-junction-related genes (upregulation of Jam2, Itgb3 and Notch4 genes and downregulation of Cldn2, Cldn3, Gjb1, and Gjb2). Overall, exposure to sodium arsenite from the basolateral side was found to have a differential effect on monolayer permeability and on cell-junction-related genes as compared to apical exposure. Most importantly, this study established a preclinical human-relevant in vitro translational model to assess the changes in permeability and cytotoxicity during exposure, mimicking oral or intravenous routes.

Risk factors for pelvic organ prolapse recurrence after sacrospinous hysteropexy or vaginal hysterectomy with uterosacral ligament suspension

Given that the number of surgeries for pelvic organ prolapse is expected to increase worldwide, knowledge on risk factors for prolapse recurrence is of importance for developing preventive strategies and shared decision-making. To identify risk factors for subjective and objective failure after either sacrospinous hysteropexy or vaginal hysterectomy with uterosacral ligament suspension over a period of 5 years after surgery. This was a secondary analysis of the 5-year follow-up of the SAVE-U trial. The SAVE-U trial was conducted in 4 Dutch hospitals. A total of 208 women with uterine prolapse stage ≥2 were randomized to sacrospinous hysteropexy or vaginal hysterectomy with uterosacral ligament suspension. For the current analysis, available annual 5-year follow-up data of 207 women were analyzed. Without missing values this analysis would have included 1035 measurements in total over the 5-year follow-up. Recurrences were analyzed as "events" using generalized linear mixed models because recurrences of anatomic failure and bothersome vaginal bulge symptoms fluctuated over time. The primary outcome was the composite outcome of failure defined as prolapse beyond the hymen, bothersome bulge symptoms, repeated surgery, or pessary use for recurrent prolapse. Secondary outcome measures were bothersome vaginal bulge symptoms, overall anatomic failure (Pelvic Organ Prolapse Quantification stage ≥2 in any compartment), apical compartment recurrence (Pelvic Organ Prolapse Quantification stage ≥2), anterior compartment recurrence (Pelvic Organ Prolapse Quantification stage ≥2), and posterior compartment recurrence (Pelvic Organ Prolapse Quantification stage ≥2). For the composite outcome of failure (164 events in 66 different women), statistically significant risk factors were: body mass index (odds ratio, 1.10 [per 1 kg/m2]; 95% confidence interval, 1.02-1.19; P=.02), smoking (odds ratio, 2.88; 95% confidence interval, 1.12-7.40; P=.03), and preoperative Pelvic Organ Prolapse Quantification point Ba (odds ratio, 1.23 [per 1 cm]; 95% confidence interval, 1.01-1.50; P=.04). When analyzing each surgical outcome measure separately, body mass index and Pelvic Organ Prolapse Quantification point Ba were risk factors for overall anatomic failure (462 events in 147 women; odds ratio, 1.15; 95% confidence interval, 1.07-1.25; P<.01 and odds ratio, 1.14; 95% confidence interval, 1.00-1.30; P=.05, respectively) and anterior compartment recurrence (385 events in 128 women; odds ratio, 1.11; 95% confidence interval, 1.02-1.22; P=.02 and odds ratio, 1.17; 95% confidence interval, 1.02-1.34; P=.02, respectively). Vaginal hysterectomy was a risk factor for posterior compartment recurrence when compared with sacrospinous hysteropexy (93 events in 40 women; odds ratio, 5.21; 95% confidence interval, 2.05-13.27; P<.01). Smoking was a risk factor for bothersome vaginal bulge symptoms (70 events in 41 women; odds ratio, 3.80; 95% confidence interval, 1.48-9.75; P=.01), and preoperative Pelvic Organ Prolapse Quantification stage 3 or 4 was significantly protective against bothersome bulge symptoms (odds ratio, 0.32; 95% confidence interval, 0.11-0.89; P=.03). Body mass index, smoking, and Pelvic Organ Prolapse Quantification point Ba were statistically significant risk factors for the composite outcome of failure (prolapse beyond the hymen, bothersome bulge symptoms, repeated surgery, or pessary use for recurrent prolapse) in the period of 5 years after surgery.

Toxicity of different biodiesel exhausts in primary human airway epithelial cells grown at air-liquid interface

Biodiesel is created through the transesterification of fats/oils and its usage is increasing worldwide as global warming concerns increase. Biodiesel fuel properties change depending on the feedstock used to create it. The aim of this study was to assess the different toxicological properties of biodiesel exhausts created from different feedstocks using a complex 3D air-liquid interface (ALI) model that mimics the human airway. Primary human airway epithelial cells were grown at ALI until full differentiation was achieved. Cells were then exposed to 1/20 diluted exhaust from an engine running on Diesel (ULSD), pure or 20% blended Canola biodiesel and pure or 20% blended Tallow biodiesel, or Air for control. Exhaust was analysed for various physio-chemical properties and 24-h after exposure, ALI cultures were assessed for permeability, protein release and mediator response. All measured exhaust components were within industry safety standards. ULSD contained the highest concentrations of various combustion gases. We found no differences in terms of particle characteristics for any of the tested exhausts, likely due to the high dilution used.Exposure to Tallow B100 and B20 induced increased permeability in the ALI culture and the greatest increase in mediator response in both the apical and basal compartments. In contrast, Canola B100 and B20 did not impact permeability and induced the smallest mediator response. All exhausts but Canola B20 induced increased protein release, indicating epithelial damage.Despite the concentrations of all exhausts used in this study meeting industry safety regulations, we found significant toxic effects. Tallow biodiesel was found to be the most toxic of the tested fuels and Canola the least, both for blended and pure biodiesel fuels. This suggests that the feedstock biodiesel is made from is crucial for the resulting health effects of exhaust exposure, even when not comprising the majority of fuel composition.

Outcomes of the anterior approach versus posterior sacrospinous ligament fixation for pelvic organ prolapse.

This study aimed to compare anterior sacrospinous ligament fixation (SSLF) with the standard posterior SSLF concerning complications and outcomes in patients with apical compartment pelvic organ prolapse (POP). This is an observational descriptive study using prospective data collected from two referral urogynecological centers. The study cohort represents all 135 women in our prospective study who underwent anterior approach bilateral anterior or unilateral posterior meshless SSLF from January 2018 to December 2020 using the PFDI-20 questionnaire and the POP quantification (POP-Q) system pre- and postoperatively. The objective success rate was assessed by the number of POP recurrence cases and total vaginal length (TVL) postoperatively. Patients were followed up for at least 6 months (range, 6 to 18 months). Data were analyzed using SPSS version 21. P < 0.05 was considered statistically significant. Sixty-seven (49.6%) patients underwent posterior SSLF, and 68 (50.4%) underwent anterior SSLF. The mean age of patients was 58.2 ± 9.7 and 64.9 ± 11.6, respectively (P < 0.001). Most patients who underwent the posterior approach had stage III apical prolapse (74.6%), while 65.5% of those who underwent anterior SSLF had stage II apical prolapse (P < 0.001). Following the treatment, no significant difference was detected between these two vaginal approaches in terms of women's satisfaction rate (P > 0.05). One case of postoperative recurrence was found in the posterior group, which ultimately led to surgical retreatment. There were no major intra- or postoperative complications in the groups. Postoperative TVL was higher in the anterior SSLF group (P < 0.001). The postoperative POPDI-6, CRADI-8, UDI-6, and PFDI-20 decreased significantly compared to preoperative status in both groups (P < 0.001). It appears that the anterior SSLF approach can be regarded as effective as the posterior approach in the management of apical POP. Therefore, the proper surgical technique can be chosen according to the surgeon's expertise and other compartment's prolapse status.

A novel bilateral anterior sacrospinous hysteropexy technique for apical pelvic organ prolapse repair via the vaginal route: a cohort study

BackgroundUterine-preserving techniques are becoming increasingly popular in the last decade. This investigation evaluates a novel hysteropexy technique using a mesh in sling-alike configuration [Splentis (Promedon, Argentina)] which is attached anteriorly to the cervix and suspended to the sacrospinous ligaments bilaterally via the vaginal route in women undergoing surgery for uterine prolapse.MethodsThis was a single-center cohort study, evaluating women who underwent transvaginal hysteropexy with Splentis for primary uterine descent. Data have been collected prospectively as part of the quality assurance system. Primary endpoint was treatment success, defined as a combined endpoint including the absence of a vaginal bulge symptom and no retreatment of apical prolapse. A validated questionnaire to evaluate quality-of-life and prolapse symptoms was utilized. Descriptive analysis was applied. Wilcoxon signed-rank test was performed to compare paired samples. The significance level was set at 5%.ResultsA total of 103 women with a median age of 68.0 [IQR 11.5] years with a median apical POP-Q stage of 3 were included. The median surgery time was 22 [IQR 12] minutes and no intraoperative complication occurred. After a median follow-up time of 17 months, treatment success was achieved in 91 (89.2%) patients and quality of life and patient report outcomes improved significantly (p < 0.001). Mesh exposure occurred in 3 (2.9%) patients. Of these, two patients required surgical revision, and one patient was treated conservatively. One patient required partial mesh removal due to dyspareunia.ConclusionBilateral sacrospinous hysteropexy with Splentis offers an efficacious and safe alternative for apical compartment repair, incorporating the advantages of pelvic floor reconstruction via the vaginal route.

Human Multi-Compartment Airways-on-Chip Platform for Emulating Respiratory Airborne Transmission: From Nose to Pulmonary Acini.

The past decade has witnessed tremendous endeavors to deliver novel preclinical in vitro lung models for pulmonary research endpoints, including foremost with the advent of organ- and lung-on-chips. With growing interest in aerosol transmission and infection of respiratory viruses within a host, most notably the SARS-CoV-2 virus amidst the global COVID-19 pandemic, the importance of crosstalk between the different lung regions (i.e., extra-thoracic, conductive and respiratory), with distinct cellular makeups and physiology, are acknowledged to play an important role in the progression of the disease from the initial onset of infection. In the present Methods article, we designed and fabricated to the best of our knowledge the first multi-compartment human airway-on-chip platform to serve as a preclinical in vitro benchmark underlining regional lung crosstalk for viral infection pathways. Combining microfabrication and 3D printing techniques, our platform mimics key elements of the respiratory system spanning (i) nasal passages that serve as the alleged origin of infections, (ii) the mid-bronchial airway region and (iii) the deep acinar region, distinct with alveolated airways. Crosstalk between the three components was exemplified in various assays. First, viral-load (including SARS-CoV-2) injected into the apical partition of the nasal compartment was detected in distal bronchial and acinar components upon applying physiological airflow across the connected compartment models. Secondly, nebulized viral-like dsRNA, poly I:C aerosols were administered to the nasal apical compartment, transmitted to downstream compartments via respiratory airflows and leading to an elevation in inflammatory cytokine levels secreted by distinct epithelial cells in each respective compartment. Overall, our assays establish an in vitro methodology that supports the hypothesis for viral-laden airflow mediated transmission through the respiratory system cellular landscape. With a keen eye for broader end user applications, we share detailed methodologies for fabricating, assembling, calibrating, and using our multi-compartment platform, including open-source fabrication files. Our platform serves as an early proof-of-concept that can be readily designed and adapted to specific preclinical pulmonary research endpoints.

Functional interplay between CFTR and pendrin: physiological and pathophysiological relevance.

The transport of chloride and bicarbonate across epithelia controls the pH and volume of the intracellular and luminal fluids, as well as the systemic pH and vascular volume. The anion exchanger pendrin (SLC26A4) and the cystic fibrosis transmembrane conductance regulator (CFTR) channel are expressed in the apical membrane of epithelial cells of various organs and tissues, including the airways, kidney, thyroid, and inner ear. While pendrin drives chloride reabsorption and bicarbonate, thiocyanate or iodide secretion within the apical compartment, CFTR represents a pathway for the apical efflux of chloride, bicarbonate, and possibly iodide. In the airways, pendrin and CFTR seems to be involved in alkalinization of the apical fluid via bicarbonate secretion, especially during inflammation, while CFTR also controls the volume of the apical fluid via a cAMP-dependent chloride secretion, which is stimulated by pendrin. In the kidney, pendrin is expressed in the cortical collecting duct and connecting tubule and co-localizes with CFTR in the apical membrane of β intercalated cells. Bicarbonate secretion occurs via pendrin, which also drives chloride reabsorption. A functional CFTR is required for pendrin activity. Whether CFTR stimulates pendrin via a direct molecular interaction or other mechanisms, or simply provides a pathway for chloride recycling across the apical membrane remains to be established. In the thyroid, CFTR and pendrin might have overlapping functions in driving the apical flux of iodide within the follicular lumen. In other organs, including the inner ear, the possible functional interplay between pendrin and CFTR needs to be explored.

Complications After Vaginal Vault Suspension Versus Minimally Invasive Sacrocolpopexy in Women With Elevated Body Mass Index: A Retrospective Cohort Study Using Data From the National Surgical Quality Improvement Program Database.

Overweight and obese women represent a growing share of pelvic floor reconstruction surgeons' practices. Determining perioperative risk specific to this population is essential to inform decision making regarding operative approach in this population. The aim of the study was to compare surgical complications among overweight and obese women undergoing apical compartment prolapse surgery by either minimally invasive abdominal or vaginal approach. The American College of Surgeons National Surgical Quality Improvement Database was used to identify overweight and obese patients (body mass index ≥ 25) undergoing either minimally invasive sacrocolpopexy (MISC) or vaginal vault suspension (VVS) in the form of a sacrospinous vault fixation or uterosacral ligament fixation for pelvic organ prolapse from 2012 to 2019. Odds ratios for surgical complications, readmission, and reoperation were estimated using multivariable logistic regression. Of 8,990 eligible patients, 5,851 underwent a VVS and 3,139 patients underwent MISC. There was a greater odds of any complication in the first 30 days following VVS (n = 608 [10.4%]) compared with MISC (n = 247 [7.9%]; odds ratio, 1.27; 95% confidence interval, 1.08-1.48) on multivariable analysis. Urinary tract infections (UTIs) were the most common complication and were more likely following VVS (112 (3.6%) versus 350 (6.0%), P < 0.001). When UTIs were excluded, there was no difference in complications between approaches (1.00; 95% CI, 0.82-1.22). There were no statistically significant odds of readmission, reoperation, or serious complications between approaches. Vaginal vault suspension may be associated with a higher odds of any complication compared with MISC in overweight and obese women, but the rate of serious complications, readmission, and reoperation are low, and approaches were comparable when considering complications other than UTI.

Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction-Lesson from the Toxicant/Pharmaceutical Models.

Emerging evidence has shown that cell-cell interactions between testicular cells, in particular at the Sertoli cell-cell and Sertoli-germ cell interface, are crucial to support spermatogenesis. The unique ultrastructures that support cell-cell interactions in the testis are the basal ES (ectoplasmic specialization) and the apical ES. The basal ES is found between adjacent Sertoli cells near the basement membrane that also constitute the blood-testis barrier (BTB). The apical ES is restrictively expressed at the Sertoli-spermatid contact site in the apical (adluminal) compartment of the seminiferous epithelium. These ultrastructures are present in both rodent and human testes, but the majority of studies found in the literature were done in rodent testes. As such, our discussion herein, unless otherwise specified, is focused on studies in testes of adult rats. Studies have shown that the testicular cell-cell interactions crucial to support spermatogenesis are mediated through distinctive signaling proteins and pathways, most notably involving FAK, Akt1/2 and Cdc42 GTPase. Thus, manipulation of some of these signaling proteins, such as FAK, through the use of phosphomimetic mutants for overexpression in Sertoli cell epithelium in vitro or in the testis in vivo, making FAK either constitutively active or inactive, we can modify the outcome of spermatogenesis. For instance, using the toxicant-induced Sertoli cell or testis injury in rats as study models, we can either block or rescue toxicant-induced infertility through overexpression of p-FAK-Y397 or p-FAK-Y407 (and their mutants), including the use of specific activator(s) of the involved signaling proteins against pAkt1/2. These findings thus illustrate that a potential therapeutic approach can be developed to manage toxicant-induced male reproductive dysfunction. In this review, we critically evaluate these recent findings, highlighting the direction for future investigations by bringing the laboratory-based research through a translation path to clinical investigations.

Composition and sorting of polarized cell plasma membrane compartments

Epithelial cell polarization is an essential biological process, serving many physiological roles including tissue morphogenesis and wound healing. A defining feature of polarization is the separation of cell plasma membrane lipids and proteins into apical and basolateral compartments between which molecular exchange is restricted. Decades ago, the apical membrane was found to be enriched in saturated lipids, glycolipids, and cholesterol. Mechanistic hypotheses to explain the biogenesis and unique composition of the apical membrane include self-assembling membrane domains (i.e., lipid rafts), specific protein sorting motifs, and post-translational modifications mediating protein sorting.

The effects of citrus flavonoids and their metabolites on immune-mediated intestinal barrier disruption using an in vitro co-culture model.

Hesperidin and naringin are citrus flavonoids with known anti-oxidative and anti-inflammatory properties. Evidence from previous studies indicates that both these compounds and the metabolites that are formed during intestinal metabolism are able to exert beneficial effects on intestinal barrier function and inflammation. However, so far, studies investigating the relative contributions of the various compounds are lacking. Therefore, we assessed the effect of citrus flavonoids and their intestinal metabolites on immune-mediated barrier disruption in an in vitro co-culture model. Caco-2 cell monolayers were placed in co-culture with phorbol 12-myristate 13-acetate-stimulated THP-1-Blue™ NF-κB cells for 30 h. At baseline, the citrus flavonoids and their metabolites were added to the apical compartment (50 or 100 µM per compound). After 24 h, THP-1 cells were incubated with lipopolysaccharide (LPS) in the basolateral compartment for 6 h. Incubation with citrus flavonoids and their metabolites did not induce changes in transepithelial electrical resistance, fluorescein isothiocyanate-dextran 4 kDa permeation or gene expression of barrier-related genes for any of the compounds tested. After LPS stimulation, NF-κB activity was significantly inhibited by all compounds (100 µM) except for one metabolite (all P ≤ 0·03). LPS-induced production of the cytokines IL-8, TNF-α and IL-6 was inhibited by most compounds (all P < 0·05). However, levels of IL-1β were increased, which may contribute to the lack of an improved barrier effect. Overall, these results suggest that citrus flavonoids may decrease intestinal inflammation via reduction of NF-κB activity and that the parent compounds and their metabolites formed during intestinal metabolism are able to exert comparable effects.

Rhinovirus C replication is associated with the endoplasmic reticulum and triggers cytopathic effects in an in vitro model of human airway epithelium.

The clinical impact of rhinovirus C (RV-C) is well-documented; yet, the viral life cycle remains poorly defined. Thus, we characterized RV-C15 replication at the single-cell level and its impact on the human airway epithelium (HAE) using a physiologically-relevant in vitro model. RV-C15 replication was restricted to ciliated cells where viral RNA levels peaked at 12 hours post-infection (hpi), correlating with elevated titers in the apical compartment at 24hpi. Notably, infection was associated with a loss of polarized expression of the RV-C receptor, cadherin-related family member 3. Visualization of double-stranded RNA (dsRNA) during RV-C15 replication revealed two distinct replication complex arrangements within the cell, likely corresponding to different time points in infection. To further define RV-C15 replication sites, we analyzed the expression and colocalization of giantin, phosphatidylinositol-4-phosphate, and calnexin with dsRNA. Despite observing Golgi fragmentation by immunofluorescence during RV-C15 infection as previously reported for other RVs, a high ratio of calnexin-dsRNA colocalization implicated the endoplasmic reticulum as the primary site for RV-C15 replication in HAE. RV-C15 infection was also associated with elevated stimulator of interferon genes (STING) expression and the induction of incomplete autophagy, a mechanism used by other RVs to facilitate non-lytic release of progeny virions. Notably, genetic depletion of STING in HAE attenuated RV-C15 and -A16 (but not -B14) replication, corroborating a previously proposed proviral role for STING in some RV infections. Finally, RV-C15 infection resulted in a temporary loss in epithelial barrier integrity and the translocation of tight junction proteins while a reduction in mucociliary clearance indicated cytopathic effects on epithelial function. Together, our findings identify both shared and unique features of RV-C replication compared to related rhinoviruses and define the impact of RV-C on both epithelial cell organization and tissue functionality–aspects of infection that may contribute to pathogenesis in vivo.

Robot-assisted sacro(hystero)colpopexy with anterior and posterior mesh placement: impact on lower bowel tract function and clinical outcomes at mid-term follow-up.

Background:Robotic sacrocolpopexy (RSCP) is an established option for the treatment of apical, anterior, and proximal posterior compartment pelvic organ prolapses (POP). However, there is lack of evidence investigating how lower bowel tract symptoms (LBTS) may change after RSCP.Methods:Data from consecutive patients treated with RSCP for stage 3 or higher POP from 2012 to 2019 at a single tertiary referral center with at least 1 year of follow-up were prospectively collected and retrospectively analyzed. RSCP was performed following a standardized technique which always employed both anterior and posterior hand-shaped meshes. Outcomes were collected at follow-up and analyzed. LBTS were evaluated through the Wexner questionnaire.Results:Overall, 114 women underwent RSCP. Eleven were excluded for missing data, whereas 12 had insufficient follow-up. Thus, 91 (79.8%) patients were included in this cohort. Median follow-up was 42 [interquartile range (IQR), 19–62] months. Mean age was 65 ± 10 years. In our series, RSCP was mainly performed for anterior and apical/medium stage 3 POP (in 95.6% of patients). Anatomic success rate of RSCP was 97.8%, with 89 patients with POP stage 0–1 at 12-month follow-up. Two patients (2.2%) experienced POP recurrence and were treated with redo-SCP. No patient experienced clinically significant posterior vaginal wall prolapse after RSCP. When analyzing LBTS, there was no significant change in postoperative total Wexner’s score as compared to the preoperative value (p > 0.05). However, the manual assistance subscore was statistically significantly lower within the first-year follow-up (p = 0.04), but it spontaneously improved during the follow-up (p = 0.12).Conclusion:RSCP with simultaneous placement of both anterior and posterior mesh is safe and successful to treat high-stage POP in carefully selected patients. Of note, LBTS appear unaffected by posterior mesh placement, supporting its routine use to prevent posterior POP recurrence. Larger prospective studies are needed to confirm our results.

Short‑term outcomes of patients undergoing laparoscopic sacrocolpopexy without mesh for the treatment of pelvic organ prolapse with apical compartment defect

The present study aimed to investigate the clinical efficacy and safety of laparoscopic sacrocolpopexy (LSC) without mesh in the treatment of female pelvic organ prolapse (POP) with an apical compartment defect (a‑POP). For this purpose, a total of 24 patients with POP [POP quantification (POP‑Q) ≥II] who underwent LSC without mesh between January, 2019 and August, 2020 were analyze retrospectively. The duration of the surgery, intraoperative blood loss, post‑operative hospital stay, catheter removal time, post‑operative pain and post‑operative complications were recorded and evaluated. The changes in the POP‑Q scores at 3 months post‑surgery were then analyzed. The pelvic floor distress inventory short form 20 (PFDI‑20) was used to evaluate the post‑operative systemic improvement and subjective satisfaction rate of the patients. All surgeries were successfully completed. The mean duration of the surgery 135.3±31.5 min. The mean loss of blood was 22.9±15.1 ml. No injuries to the great vessels, nerves, rectum, urethra or bladder occurred. The catheter was retained for 2 days and all patients were able to micturate following extubation. The mean observation time following surgery in hospital was 7 days. The average follow‑up time was 9.4±4.0 months. According to POP‑Q scores, the anatomic cure rate of the LSC without mesh was 100%. The PFDI‑20 scores decreased from 90.6±24.6 to 55.8±18.5 (P&lt;0.0001), and the subjective satisfaction rate was 100% (24/24).

Morphology of the Cutaneous Poison and Mucous Glands in Amphibians with Particular Emphasis on Caecilians (Siphonops annulatus).

Caecilians (order Gymnophiona) are apodan, snake-like amphibians, usually with fossorial habits, constituting one of the most unknown groups of terrestrial vertebrates. As in orders Anura (frogs, tree frogs and toads) and Caudata (salamanders and newts), the caecilian skin is rich in mucous glands, responsible for body lubrication, and poison glands, producing varied toxins used in defence against predators and microorganisms. Whereas in anurans and caudatans skin gland morphology has been well studied, caecilian poison glands remain poorly elucidated. Here we characterised the skin gland morphology of the caecilian Siphonops annulatus, emphasising the poison glands in comparison to those of anurans and salamanders. We showed that S. annulatus glands are similar to those of salamanders, consisting of several syncytial compartments full of granules composed of protein material but showing some differentiated apical compartments containing mucus. An unusual structure resembling a mucous gland is frequently observed in lateral/apical position, apparently connected to the main duct. We conclude that the morphology of skin poison glands in caecilians is more similar to salamander glands when compared to anuran glands that show a much-simplified structure.