Rivasfitzsimmons2584
Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results indicated that the purified PPV-VP2 protein self-assembled into VLPs. Immunogenicity assays in guinea pigs and pigs indicated that the ISA-201 VG adjuvanted PPV-VP2 VLP vaccine elicited hemagglutination inhibition (HI) and virus neutralization (VN) antibody titers comparable with PPV commercial inactivated vaccines, whereas viral loads in the spleen and liver of challenged guinea pigs were significantly reduced. In conclusion, our study provides a method for producing the PPV-VLP vaccine against PPV infection in E. coli and may offer a novel strategy for the soluble expression of other vaccine antigens.Staphylocoagulase (Coa) is a virulence factor of Staphylococcus aureus (S. aureus) that promotes blood coagulation by activating prothrombin to convert fibrinogen to fibrin. Coa plays a crucial role in disease pathogenesis and is a promising target for the treatment of S. aureus infections. Here, we identified that isoquercitrin, a natural flavonol compound, can markedly reduce the activity of Coa at concentrations that have no effect on bacterial growth. Mechanistic studies employing molecular dynamics simulation revealed that isoquercitrin binds to Coa by interacting with Asp-181 and Tyr-188, thereby affecting the binding of Coa to prothrombin. Importantly, in vivo studies showed that isoquercitrin treatment significantly reduced the bacterial burden, pathological damage, and inflammation of lung tissue and improved the percentage of survival of mice infected with S. aureus Newman strain. These data suggest that isoquercitrin is a promising inhibitor of Coa that can be used for the development of therapeutic drugs to combat S. aureus infections.Key Points• Staphylocoagulase plays a key role in the pathogenesis of S. aureus infection.• We identified that isoquercitrin is a direct inhibitor of staphylocoagulase.• Isoquercitrin treatment can significantly attenuate S. aureus virulence in vivo.INTRODUCTION AND HYPOTHESIS Faecal incontinence (FI) is prevalent in postmenopausal women. Oestrogen receptors have been identified in the anal sphincter and have been implicated in the pathogenesis and potential treatment. We sought to evaluate the literature regarding the impact of local and systemic oestrogen therapy on FI in postmenopausal women. METHODS A systematic review of all studies in postmenopausal women was performed to establish how oestrogen therapy affects FI. Eight articles were deemed eligible for inclusion following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Their quality was assessed using the Cochrane risk-of-bias tool (RoB-2) and Newcastle-Ottawa quality assessment scale. RESULTS One randomised controlled trial (RCT), two cohort studies, one observational and four cross-sectional studies were identified. The RCT showed an improvement in FI with anal oestrogen (p = 0.002), but this improvement was also observed in the placebo arm (p = 0.013) and no difference was seen between these groups. A prospective observational study demonstrated significant improvement with an oestrogen patch (p = 0.004), but had no control group. Conversely, a large prospective cohort study demonstrated an increased hazard ratio of FI with current (1.32; 95% CI, 1.20-1.45) and previous oestrogen use (1.26; 95% CI, 1.18-1.34) compared with non-users. CONCLUSION All studies had a high risk of bias and had conflicting views on the effects of oestrogen on FI in postmenopausal women. This review has identified the need for further research in this area by highlighting the paucity of good research for evidence-based practice. We believe that a further RCT of local oestrogen is mandated to draw a valid conclusion.INTRODUCTION The aims of the present study were to report longitudinal data on the prevalence of urinary incontinence (UI) in a fitness club setting and to investigate whether gym members are educated about and exercise their pelvic floor muscles. METHODS New members (125 women) from 25 fitness clubs in Oslo, Norway, filled in a 25-min online questionnaire (SurveyXact) at four time points (onset, 3, 6 and 12 months of fitness club membership). The questionnaire covered background/health information, membership dropout and exercise habits, including pelvic floor muscle training (PFMT). A modified Subjective Health Complaints Inventory (SHC Inventory) and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) were used to gather repeated measures of UI. RESULTS At onset, 3, 6 and 12 months of fitness club membership, 16.8%, 13.8%, 19.6% and 18.7% reported UI, respectively (p = 0.11). Of these, 57.1% to 76.2% reported leakage during exercise and perceived the UI to be slight. Less than 8% had received information about PFMT by the fitness club staff. Adherence to regular exercise and PFMT throughout the follow-up period (minimum two sessions/week) did not show any association with absent or present UI at 12 months (p = 0.48 and p = 0.63) and was reported by 30% and 22.2% of the participants, respectively. CONCLUSIONS About 17% reported UI at onset of fitness club membership, with no changes in proportions throughout the first year. Adherence to regular exercise and PFMT did not show any association with absent or present UI at 12 months. Few had been taught PFMT.INTRODUCTION AND HYPOTHESIS To determine whether prior prolapse repair has an impact on operative time, surgical complications, and prolapse recurrence with minimally invasive sacral colpopexy (MISC). METHODS This was a retrospective study of all laparoscopic and robotic MISC procedures performed from January 2009 to July 2014 at the University of Pittsburgh Medical Center. Patient demographics, clinical and surgical data were compared in women who underwent MISC for initial repair versus those undergoing MISC for recurrence after prior prolapse surgery. Our primary outcome was operating room (OR) time (skin incision to closure) using linear regression. Logistic regression compared complications (a composite variable considered present if any major complication occurred) and prolapse recurrence (any POP-Q point ≥0 or retreatment). RESULTS Of 816 subjects, the mean age was 59.6 ± 8.7, with mean BMI 27.0 ± 3.0 in a primarily Caucasian population (97.8%). https://www.selleckchem.com/products/Roscovitine.html Subjects had predominantly POP-Q stage III prolapse (69.9%), and 21.