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The Cochrane Database of Systematic... Jul 2023Apical vaginal prolapse is the descent of the uterus or vaginal vault (post-hysterectomy). Various surgical treatments are available, but there are no guidelines to... (Review)
Review
BACKGROUND
Apical vaginal prolapse is the descent of the uterus or vaginal vault (post-hysterectomy). Various surgical treatments are available, but there are no guidelines to recommend which is the best.
OBJECTIVES
To evaluate the safety and efficacy of any surgical intervention compared to another intervention for the management of apical vaginal prolapse.
SEARCH METHODS
We searched the Cochrane Incontinence Group's Specialised Register of controlled trials, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings and ClinicalTrials.gov (searched 14 March 2022).
SELECTION CRITERIA
We included randomised controlled trials (RCTs).
DATA COLLECTION AND ANALYSIS
We used Cochrane methods. Our primary outcomes were awareness of prolapse, repeat surgery and recurrent prolapse (any site).
MAIN RESULTS
We included 59 RCTs (6705 women) comparing surgical procedures for apical vaginal prolapse. Evidence certainty ranged from very low to moderate. Limitations included imprecision, poor methodology, and inconsistency. Vaginal procedures compared to sacral colpopexy for vault prolapse (seven RCTs, n=613; six months to f four-year review) Awareness of prolapse was more common after vaginal procedures (risk ratio (RR) 2.31, 95% confidence interval (CI) 1.27 to 4.21, 4 RCTs, n = 346, I = 0%, moderate-certainty evidence). If 8% of women are aware of prolapse after sacral colpopexy, 18% (10% to 32%) are likely to be aware after vaginal procedures. Surgery for recurrent prolapse was more common after vaginal procedures (RR 2.33, 95% CI 1.34 to 4.04; 6 RCTs, n = 497, I = 0%, moderate-certainty evidence). The confidence interval suggests that if 6% of women require repeat prolapse surgery after sacral colpopexy, 14% (8% to 25%) are likely to require it after vaginal procedures. Prolapse on examination is probably more common after vaginal procedures (RR 1.87, 95% CI 1.32 to 2.65; 5 RCTs, n = 422; I = 24%, moderate-certainty evidence). If 18% of women have recurrent prolapse after sacral colpopexy, between 23% and 47% are likely to do so after vaginal procedures. Other outcomes: Stress urinary incontinence (SUI) was more common after vaginal procedures (RR 1.86, 95% CI 1.17 to 2.94; 3 RCTs, n = 263; I = 0%, moderate-certainty evidence). The effect of vaginal procedures on dyspareunia was uncertain (RR 3.44, 95% CI 0.61 to 19.53; 3 RCTs, n = 106, I = 65%, low-certainty evidence). Vaginal hysterectomy compared to sacral hysteropexy/cervicopexy (six RCTS, 554 women, one to seven year review) Awareness of prolapse - There may be little or no difference between the groups for this outcome (RR 1.01 95% CI 0.10 to 9.98; 2 RCTs, n = 200, very low-certainty evidence). Surgery for recurrent prolapse - There may be little or no difference between the groups for this outcome (RR 0.85, 95% CI 0.47 to 1.54; 5 RCTs, n = 403; I = 9%, low-certainty evidence). Prolapse on examination- there was little or no difference between the groups for this outcome (RR 0.78, 95% CI 0.54 to 1.11; 2 RCTs n = 230; I = 9%, moderate-certainty evidence). Vaginal hysteropexy compared to sacral hysteropexy/cervicopexy (two RCTs, n = 388, 1-four-year review) Awareness of prolapse - No difference between the groups for this outcome (RR 0.55 95% CI 0.21 to 1.44; 1 RCT n = 257, low-certainty evidence). Surgery for recurrent prolapse - No difference between the groups for this outcome (RR 1.34, 95% CI 0.52 to 3.44; 2 RCTs, n = 345; I = 0%, moderate-certainty evidence). Prolapse on examination- There were little or no difference between the groups for this outcome (RR 0.99, 95% CI 0.83 to 1.19; 2 RCTs n =367; I =9%, moderate-certainty evidence). Vaginal hysterectomy compared to vaginal hysteropexy (four RCTs, n = 620, 6 months to five-year review) Awareness of prolapse - There may be little or no difference between the groups for this outcome (RR 1.0 95% CI 0.44 to 2.24; 2 RCTs, n = 365, I = 0% moderate-quality certainty evidence). Surgery for recurrent prolapse - There may be little or no difference between the groups for this outcome (RR 1.32, 95% CI 0.67 to 2.60; 3 RCTs, n = 443; I = 0%, moderate-certainty evidence). Prolapse on examination- There were little or no difference between the groups for this outcome (RR 1.44, 95% CI 0.79 to 2.61; 2 RCTs n =361; I =74%, low-certainty evidence). Other outcomes: Total vaginal length (TVL) was shorter after vaginal hysterectomy (mean difference (MD) 0.89cm 95% CI 0.49 to 1.28cm shorter; 3 RCTs, n=413, low-certainty evidence). There is probably little or no difference between the groups in terms of operating time, dyspareunia and stress urinary incontinence. Other analyses There were no differences identified for any of our primary review outcomes between different types of vaginal native tissue repair (4 RCTs), comparisons of graft materials for vaginal support (3 RCTs), pectopexy versus other apical suspensions (5 RCTs), continuous versus interrupted sutures at sacral colpopexy (2 RCTs), absorbable versus permanent sutures at apical suspensions (5 RCTs) or different routes of sacral colpopexy. Laparoscopic sacral colpopexy is associated with shorter admission time than open approach (3 RCTs) and quicker operating time than robotic approach (3 RCTs). Transvaginal mesh does not confer any advantage over native tissue repair, however is associated with a 17.5% rate of mesh exposure (7 RCTs).
AUTHORS' CONCLUSIONS
Sacral colpopexy is associated with lower risk of awareness of prolapse, recurrent prolapse on examination, repeat surgery for prolapse, and postoperative SUI than a variety of vaginal interventions. The limited evidence does not support the use of transvaginal mesh compared to native tissue repair for apical vaginal prolapse. There were no differences in primary outcomes for different routes of sacral colpopexy. However, the laparoscopic approach is associated with a shorter operating time than robotic approach, and shorter admission than open approach. There were no significant differences between vaginal hysteropexy and vaginal hysterectomy for uterine prolapse nor between vaginal hysteropexy and abdominal hysteropexy/cervicopexy. There were no differences detected between absorbable and non absorbable sutures however, the certainty of evidence for mesh exposure and dyspareunia was low.
Topics: Female; Humans; Dyspareunia; Suspensions; Urinary Incontinence, Stress; Uterine Prolapse
PubMed: 37493538
DOI: 10.1002/14651858.CD012376.pub2 -
Current Protocols Nov 2023Neuroscience research greatly benefits from single-cell sequencing technologies, which can reveal transcriptional alterations on a cellular level. However, preparing...
Neuroscience research greatly benefits from single-cell sequencing technologies, which can reveal transcriptional alterations on a cellular level. However, preparing single-cell suspensions is technically challenging, requires experience, and has several limitations that can influence the transcriptional readout. Performing sequencing of single nuclei instead of single cells alleviates several of the challenges of sample preparation and highlights acute nuclear transcription. Here, we provide a protocol to prepare a nuclei suspension for single-nucleus RNA-sequencing for cell type-specific transcriptional profiling of brain tissue using the 10x Genomics single-cell gene expression assay. Furthermore, we highlight important aspects to consider during experimental design and data analysis. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparation of single-nucleus suspension Basic Protocol 2: Preparation and sequencing of single-nucleus libraries for RNA-seq.
Topics: Gene Expression Profiling; Sequence Analysis, RNA; RNA-Seq; Solitary Nucleus; RNA
PubMed: 37987152
DOI: 10.1002/cpz1.919 -
Journal of Pediatric Gastroenterology... Dec 2023The objective of this study was to evaluate the efficacy and safety of budesonide oral suspension (BOS) in adolescents with eosinophilic esophagitis (EoE).
OBJECTIVES
The objective of this study was to evaluate the efficacy and safety of budesonide oral suspension (BOS) in adolescents with eosinophilic esophagitis (EoE).
METHODS
This post hoc analysis pooled data from two 12-week, randomized, double-blind, placebo-controlled studies of BOS 2.0 mg twice daily (b.i.d.) (phase 2, NCT01642212; phase 3, NCT02605837) in patients aged 11-17 years with EoE and dysphagia. Efficacy endpoints included histologic (≤6, ≤1, and <15 eosinophils per high-power field [eos/hpf]), dysphagia symptom (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] scores from baseline), and clinicopathologic (≤6 eos/hpf and ≥30% reduction in DSQ scores from baseline) responses at week 12. Change from baseline to week 12 in peak eosinophil counts, DSQ scores, EoE Histology Scoring System (EoEHSS) grade (severity) and stage (extent) total score ratios (TSRs), and total EoE Endoscopic Reference Scores (EREFS) were assessed. Safety outcomes were also examined.
RESULTS
Overall, 76 adolescents were included (BOS, n = 45; placebo, n = 31). Significantly more patients who received BOS than placebo achieved histologic responses (≤6 eos/hpf: 46.7% vs 6.5%; ≤1 eos/hpf: 42.2% vs 0.0%; <15 eos/hpf: 53.3% vs 9.7%; P < 0.001) and a clinicopathologic response (31.1% vs 3.2%; P = 0.003) at week 12. More BOS-treated than placebo-treated patients achieved a dysphagia symptom response at week 12 (68.9% vs 58.1%; not statistically significant P = 0.314). BOS-treated patients had significantly greater reductions in EoEHSS grade and stage TSRs ( P < 0.001) and total EREFS ( P = 0.021) from baseline to week 12 than placebo-treated patients. BOS was well tolerated, with no clinically meaningful differences in adverse events versus placebo.
CONCLUSIONS
BOS 2.0 mg b.i.d. significantly improved most efficacy outcomes in adolescents with EoE versus placebo.
Topics: Adolescent; Humans; Budesonide; Deglutition Disorders; Eosinophilic Esophagitis; Esophagoscopy; Suspensions; Treatment Outcome; Child; Randomized Controlled Trials as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic
PubMed: 37718471
DOI: 10.1097/MPG.0000000000003948 -
Journal of Colloid and Interface Science Nov 2023Foam is not only an industrially important form of matter, but also one of soft jammed system such as colloidal suspensions and emulsion suspensions. Since foams are...
HYPOTHESIS
Foam is not only an industrially important form of matter, but also one of soft jammed system such as colloidal suspensions and emulsion suspensions. Since foams are composed of gas bubbles and liquid, it is expected that the coupling of bubbles and liquid strongly affects rheology of foams, which is different from simple liquids. To reveal this coupling effect and considering the importance of foam applications, we studied the scraping of foam by a rigid plate on a substrate.
EXPERIMENT
We mainly used 5.0 wt% solution of ionic surfactant TTAB (tetradecyltrimethylammonium bromide). We systematically investigate the scraping behaviors by the rigid plate as a function of scraping velocity, gap height, confinement length, amount of foam and wettability of the substrate.
FINDINGS
The results show that there are three distinguishable scraping patterns: homogeneous scraping, no scraping, and slendered scraping. These behaviors are clearly different from those of simple liquid systems. Of these, the upper limit of homogeneous scraping could be explained theoretically by the competition between dewetting and shear, which is not previously discussed. Furthermore, the theory is applicable to the scraping of other soft jammed systems such as colloidal and emulsion suspensions.
PubMed: 37494858
DOI: 10.1016/j.jcis.2023.07.023 -
Sensors (Basel, Switzerland) Aug 2023Compact Michelson interferometers are well positioned to replace existing displacement sensors in the readout of seismometers and suspension systems, such as those used...
Compact Michelson interferometers are well positioned to replace existing displacement sensors in the readout of seismometers and suspension systems, such as those used in contemporary gravitational-wave detectors. Here, we continue our previous investigation of a customised compact displacement sensor built by SmarAct that operates on the principle of deep frequency modulation. The focus of this paper is the linearity of this device and its subsequent impact on sensitivity. We show the three primary sources of nonlinearity that arise in the sensor: residual ellipticity, intrinsic distortion of the Lissajous figure, and distortion caused by exceeding the velocity limit imposed by the demodulation algorithm. We verify the theoretical models through an experimental demonstration, where we show the detrimental impact that these nonlinear effects have on device sensitivity. Finally, we simulate the effect that these nonlinearities are likely to have if implemented in the readout of the Advanced LIGO suspensions and show that the noise from nonlinearities should not dominate across the key sub-10 Hz frequency band.
PubMed: 37687983
DOI: 10.3390/s23177526 -
Antimicrobial Agents and Chemotherapy Jul 2023Invasive fungal infections are a major cause of morbidity and mortality for immunocompromised patients. Posaconazole is approved for treatment and prophylaxis of...
Model Based Estimation of Posaconazole Tablet and Suspension Bioavailability in Hospitalized Children Using Real-World Therapeutic Drug Monitoring Data in Patients Receiving Intravenous and Oral Dosing.
Invasive fungal infections are a major cause of morbidity and mortality for immunocompromised patients. Posaconazole is approved for treatment and prophylaxis of invasive fungal infection in adult patients, with intravenous, oral suspension, and gastroresistant/delayed-released tablet formulations available. In Europe, until very recently, posaconazole was used off-label in children, although a new delayed-release suspension approved for pediatric use is expected to become available soon. A population pharmacokinetic model was developed which uses posaconazole therapeutic drug monitoring data following intravenous and oral dosing in hospitalized children, thus enabling estimation of pediatric suspension and tablet oral bioavailability. In total, 297 therapeutic drug monitoring plasma levels from 104 children were included in this analysis. The final model was a one-compartment model with first-order absorption and nonlinear elimination. Allometric scaling on clearance and volume of distribution was included . Tablet bioavailability was estimated to be 66%. Suspension bioavailability was estimated to decrease with increasing doses, ranging from 3.8% to 32.2% in this study population. Additionally, concomitant use of proton pump-inhibitors was detected as a significant covariate, reducing suspension bioavailability by 41.0%. This is the first population pharmacokinetic study to model posaconazole data from hospitalized children following intravenous, tablet, and suspension dosing simultaneously. The incorporation of saturable posaconazole clearance into the model has been key to the credible joint estimation of tablet and suspension bioavailability. To aid rational posaconazole dosing in children, this model was used alongside published pharmacodynamic targets to predict the probability of target attainment using typical pediatric dosing regimen.
Topics: Adult; Humans; Child; Antifungal Agents; Child, Hospitalized; Biological Availability; Drug Monitoring; Administration, Oral; Invasive Fungal Infections; Tablets; Suspensions
PubMed: 37260401
DOI: 10.1128/aac.00077-23 -
Journal of Visualized Experiments : JoVE Sep 2023Kidney organoids can be generated from induced pluripotent stem cells (iPSCs) through various approaches. These organoids hold great promise for disease modeling, drug...
Kidney organoids can be generated from induced pluripotent stem cells (iPSCs) through various approaches. These organoids hold great promise for disease modeling, drug screening, and potential therapeutic applications. This article presents a step-by-step procedure to create kidney organoids from iPSCs, starting from the posterior primitive streak (PS) to the intermediate mesoderm (IM). The approach relies on the APEL 2 medium, which is a defined, animal component-free medium. It is supplemented with a high concentration of WNT agonist (CHIR99021) for a duration of 4 days, followed by fibroblast growth factor 9 (FGF9)/heparin and a low concentration of CHIR99021 for an additional 3 days. During this process, emphasis is given to selecting the optimal cell density and CHIR99021 concentration at the start of iPSCs, as these factors are critical for successful kidney organoid generation. An important aspect of this protocol is the suspension culture in a low adherent plate, allowing the IM to gradually develop into nephron structures, encompassing glomerular, proximal tubular, and distal tubular structures, all presented in a visually comprehensible format. Overall, this detailed protocol offers an efficient and specific technique to produce kidney organoids from diverse iPSCs, ensuring successful and consistent results.
Topics: Animals; Induced Pluripotent Stem Cells; Kidney; Nephrons; Kidney Glomerulus; Suspensions; Organoids
PubMed: 37677041
DOI: 10.3791/65698 -
PNAS Nexus Sep 2023Bacteria form human and animal microbiota. They are the leading causes of many infections and constitute an important class of active matter. Concentrated bacterial...
Bacteria form human and animal microbiota. They are the leading causes of many infections and constitute an important class of active matter. Concentrated bacterial suspensions exhibit large-scale turbulent-like locomotion and swarming. While the collective behavior of bacteria in Newtonian fluids is relatively well understood, many fundamental questions remain open for complex fluids. Here, we report on the collective bacterial motion in a representative biological non-Newtonian viscoelastic environment exemplified by mucus. Experiments are performed with synthetic porcine gastric mucus, natural cow cervical mucus, and a Newtonian-like polymer solution. We have found that an increase in mucin concentration and, correspondingly, an increase in the suspension's elasticity monotonously increases the length scale of collective bacterial locomotion. On the contrary, this length remains practically unchanged in Newtonian polymer solution in a wide range of concentrations. The experimental observations are supported by computational modeling. Our results provide insight into how viscoelasticity affects the spatiotemporal organization of bacterial active matter. They also expand our understanding of bacterial colonization of mucosal surfaces and the onset of antibiotic resistance due to swarming.
PubMed: 37719751
DOI: 10.1093/pnasnexus/pgad291 -
Environmental Science and Pollution... May 2024Sediment re-suspension plays a crucial role in releasing endogenous nitrogen and greenhouse gases in shallow urban waters. However, the impacts of repeated re-suspension...
Sediment re-suspension plays a crucial role in releasing endogenous nitrogen and greenhouse gases in shallow urban waters. However, the impacts of repeated re-suspension and photo-induced processes on migration and transformation from endogenous nitrogen, as well as the emission of greenhouse gases, remain unclear. This study simulated three conditions: re-suspension (Rs), re-suspension combined with ultravioletirradiation (Rs + UV), and ultraviolet irradiation (UV). The findings revealed that both repeated sediment re-suspension and exposure to UV light altered the characteristics of surface sediments. Decrease of convertible nitrogen in sediments, leading to the release of ion-exchangeable nitrogen (IEF-N) into NH-N and NO-N, influenced greenhouse gas production differently under various conditions. The study observed the highest concentration of dissolved NO in under UV irradiation, positively correlated with NO-N and NO-N. Re-suspension increased the turbidity of the overlying water and accelerated nitrification, resulting in the highest NO-N concentration and the lowest dissolved NO concentration. Additionally, in the Rs + UV dissolved NO maintained the higher concentrations than in Rs, with greatest amount of N conversion in surface sediments, and a 59.45% reduction in IEF-N. The production of NO during re-suspension was mainly positively correlated with NH-N in the overlying water. Therefore, this study suggest that repeated re-suspension and light exposure significantly influence nitrogen migration and transformation processes in sediment, providing a theoretical explanation for the eutrophication of water and greenhouse gas emissions.
Topics: Nitrogen; Ultraviolet Rays; Water Pollutants, Chemical
PubMed: 38771537
DOI: 10.1007/s11356-024-33672-5