007). Prolonged osteogenesis and RMP treatment at 21 days significantly improved the ECM mineralization level. Ultrastructural images of the mineralized RMP-treated infected osteoblasts revealed viable osteoblasts and densely distributed calcium crystal deposits within the extracellular organic matrix. The expression levels of prominent bone formation genes were comparable to the RMP-treated uninfected osteoblasts.

Intracellular

infection impaired osteoblast metabolism and function. However, treatment with low dosage of RMP eradicated the intracellular

, enabling extracellular organic matrix formation and mineralization of osteoblasts at later stage. Cite this article

2022;11(5)327-341.

Intracellular S. aureus infection impaired osteoblast metabolism and function. However, treatment with low dosage of RMP eradicated the intracellular S. aureus, enabling extracellular organic matrix formation and mineralization of osteoblasts at later stage. Cite this article Bone Joint Res 2022;11(5)327-341.

The current terminology used to describe cosmetic gynecologic procedures includes many nondescriptive, trademarked, or informal names, which contributes to substantial ambiguity about their aims and specific techniques. The development of clear, uniform descriptive terminology for cosmetic gynecology is needed for patients, researchers, and practitioners across multiple specialties.

This document was developed from a collaboration of selected members from the International Urogynecological Association (IUGA) and the American Urogynecologic Society (AUGS). Wide-ranging literature reviews were performed to identify the breadth of currently used terms and tools for measuring efficacy and safety. After extensive internal review the adoption of each definition was ratified by group consensus.

A terminology report for elective cosmetic gynecology procedures, anatomical classification, outcome metrics, and reporting of complications has been developed. This document seeks to provide clear descriptive guidance for patients, researchers, and practitioners across multiple specialties. This document will be subject to internal review by IUGA and AUGS to incorporate and adopt evidence-based changes in the field.

A consensus-based document establishing clear terminology for cosmetic gynecology procedures has been created. Use of these terms should be encouraged to provide clarity to patients seeking these procedures and to facilitate future research to establish the safety and efficacy of these procedures.

A consensus-based document establishing clear terminology for cosmetic gynecology procedures has been created. Use of these terms should be encouraged to provide clarity to patients seeking these procedures and to facilitate future research to establish the safety and efficacy of these procedures.

The aim was to demonstrate our minimally invasive technique for excision of eroded transvaginal cervical cerclage suture through the bladder mucosa using a suprapubic-assisted transurethral approach. Transvaginal cervical cerclage is a common treatment for cervical insufficiency in pregnancy. Complications such as erosion are rare, as the duration of treatment is typically several months, with cerclage placement in the second trimester and complete removal prior to the onset of labor. Retained suture can lead to erosion through the vaginal epithelium and into other organs, as seen in our case. Our technique offers a minimally invasive approach to the excision of eroded transvaginal cervical cerclage suture through the bladder mucosa.

A narrated, stepwise video demonstration for removal of eroded cervical cerclage through bladder epithelium with suprapubic-assisted transurethral technique in a single patient was carried out. Key strategies for a successful outcome include use of a Carter-Thomason device for suprapubic assistance in lieu of suprapubic trocar or suprapubic incision, use of rigid biopsy forceps for improved traction on the eroded suture, performing a methylene blue test for evaluation of vesicovaginal fistula after excision procedure.

At her 2-week postoperative evaluation, the patient reported resolution of all symptoms. The Carter-Thomason incision was well healed, and postoperative urinalysis was negative for hematuria.

A suprapubic-assisted transurethral approach can be used as a minimally invasive technique for excision of eroded transvaginal cervical cerclage suture through the bladder mucosa.

A suprapubic-assisted transurethral approach can be used as a minimally invasive technique for excision of eroded transvaginal cervical cerclage suture through the bladder mucosa.

Obstructed defecation (OD) is often associated with trauma to pelvic connective tissue and nerves sustained during pregnancy and childbirth. Although there are multiple potential etiologies of defecatory dysfunction, the pathophysiology of this symptom complex is not well understood. The purpose of this study is to determine the role of parity in the development of obstructed defecatory symptoms in women with normal anorectal anatomy in a search for evidence of a presumptive neuropathic effect of pregnancy and childbirth.

This study retrospectively evaluated the records of 754 women presenting at a tertiary urogynecology unit for pelvic floor dysfunction with no anatomical abnormalities of the anorectum on imaging. They were stratified according to parity. The authors determined the prevalence of obstructed defecation symptoms in these groups. Chi-squared test was performed for statistical analysis.

Median age was 51 (range 16-88) years, and median vaginal parity was 2 (0-8); 399 (53%) women reported symptoms of OD. When anatomical abnormalities of the anorectum were excluded, parity did not seem to have a major effect on the prevalence of symptoms of OD.

In this cohort, parity is unlikely to be a cause of OD in women with normal anorectal anatomy.

In this cohort, parity is unlikely to be a cause of OD in women with normal anorectal anatomy.New approach methodologies predicting human cardiotoxicity are of interest to support or even replace in vivo-based drug safety testing. The present study presents an in vitro-in silico approach to predict the effect of inter-individual and inter-ethnic kinetic variations in the cardiotoxicity of R- and S-methadone in the Caucasian and the Chinese population. In vitro cardiotoxicity data, and metabolic data obtained from two approaches, using either individual human liver microsomes or recombinant cytochrome P450 enzymes (rCYPs), were integrated with physiologically based kinetic (PBK) models and Monte Carlo simulations to predict inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. Chemical specific adjustment factors were defined and used to derive dose-response curves for the sensitive individuals. Our simulations indicated that Chinese are more sensitive towards methadone-induced cardiotoxicity with Margin of Safety values being generally two-fold lower than those for Caucasians for both methadone enantiomers. Individual PBK models using microsomes and PBK models using rCYPs combined with Monte Carlo simulations predicted similar inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. The present study illustrates how inter-individual and inter-ethnic variations in cardiotoxicity can be predicted by combining in vitro toxicity and metabolic data, PBK modelling and Monte Carlo simulations. The novel methodology can be used to enhance cardiac safety evaluations and risk assessment of chemicals.Approximately 50 million people are suffering from epilepsy worldwide. Corals have been used for treating epilepsy in traditional Chinese medicine, but the mechanism of this treatment is unknown. In this study, we analyzed the transcriptome of the branching coral Acropora digitifera and obtained its Kyoto Encyclopedia of Genes and Genomes (KEGG), EuKaryotic Orthologous Groups (KOG) and Gene Ontology (GO) annotation. Combined with multiple sequence alignment and phylogenetic analysis, we discovered three polypeptides, we named them AdKuz1, AdKuz2 and AdKuz3, from A. digitifera that showed a close relationship to Kunitz-type peptides. Molecular docking and molecular dynamics simulation indicated that AdKuz1 to 3 could interact with GABAA receptor but AdKuz2-GABAA remained more stable than others. The biological experiments showed that AdKuz1 and AdKuz2 exhibited an anti-inflammatory effect by decreasing the aberrant level of nitric oxide (NO), IL-6, TNF-α and IL-1β induced by LPS in BV-2 cells. In addition, the pentylenetetrazol (PTZ)-induced epileptic effect on zebrafish was remarkably suppressed by AdKuz1 and AdKuz2. AdKuz2 particularly showed superior anti-epileptic effects compared to the other two peptides. Furthermore, AdKuz2 significantly decreased the expression of c-fos and npas4a, which were up-regulated by PTZ treatment. In addition, AdKuz2 reduced the synthesis of glutamate and enhanced the biosynthesis of gamma-aminobutyric acid (GABA). In conclusion, the results indicated that AdKuz2 may affect the synthesis of glutamate and GABA and enhance the activity of the GABAA receptor to inhibit the symptoms of epilepsy. We believe, AdKuz2 could be a promising anti-epileptic agent and its mechanism of action should be further investigated.

This study aimed to evaluate the effect of dapagliflozin on 1 and 3-month maximal functional capacity in patients with stable heart failure with reduced ejection fraction (HFrEF).

In this multicentre, randomized, double-blind clinical trial, 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin (n=45) or placebo (n=45). The primary outcome was a change in peak oxygen consumption (peakVO

) at 1 and 3 months. Secondary endpoints were changes at 1 and 3 months in 6-min walk test (6MWT) distance, quality of life (Minnesota Living with Heart Failure Questionnaire [MLHFQ]), and echocardiographic parameters (diastolic function, left chamber volumes, and left ventricular ejection fraction). We used linear mixed regression analysis to compare endpoint changes. Estimates were adjusted for multiple comparisons. The mean age was 67.1 ± 10.7 years, 69 (76.7%) were men, 29 (32.2%) had type 2 diabetes, and 80 (88.9%) were in New York Heart Association class II. Baseline means of peakVO

, 6MWT and MLHFQ were 13.2 ± 3.5ml/kg/min, 363 ± 110 m, and 23.1 ± 16.2, respectively. The median (25th-75th percentile) of N-terminal pro-brain natriuretic peptide was 1221 pg/ml (889-2100). Most patients were on treatment with sacubitril/valsartan (88.9%), beta-blockers (91.1%), and mineralocorticoid receptor antagonists (74.4%). PeakVO

significantly increased in patients on treatment with dapagliflozin (1 month +Δ 1.09 ml/kg/min, 95% confidence interval [CI] 0.14-2.04; p=0.021, and 3 months +Δ 1.06 ml/kg/min, 95% CI 0.07-2.04; p=0.032). Similar positive findings were found when evaluating changes from baseline. No significant differences were observed in secondary endpoints.

Among patients with stable HFrEF, dapagliflozin resulted in a significant improvement in peakVO

at 1 and 3 months.

ClinicalTrials.gov Identifier NCT04197635.

ClinicalTrials.gov Identifier NCT04197635.