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This observation was characterized by prolonged lag phase and increased critical and inactive concentration of tubulin. In addition, the GTPase activity in samples from AD brains was significantly higher than in both normal young and normal aged samples, concurrent with profound conformational changes and contracted intermolecular MT-tau distances as revealed by FRET. These alterations were partially restored in the presence of microtubule stabilizer, paclitaxel. We proposed that alterations of both tubulin function and GTPase activity may be involved in the molecular neuropathogenesis of AD, thus providing new avenues for therapeutic approaches. This article is protected by copyright. All rights reserved.BACKGROUND Young people in out-of-home care are substantially more likely to meet criteria for PTSD than their peers, while their early maltreatment exposure may also place them at greater risk of developing the newly proposed complex PTSD. Yet, there remains limited empirical evidence for the mechanisms that might drive either PTSD or complex features in this group, and ongoing debate about the suitability of existing cognitive behavioural models and their related NICE-recommended treatments. In a prospective study of young people in out-of-home care, we sought to identify demographic and cognitive processes that may contribute to the maintenance of both PTSD symptom and complex features. METHODS We assessed 120 10- to 18-year-olds in out-of-home care and their primary carer at two assessments an initial assessment and 12-month follow-up. Participants completed questionnaires on trauma history, PTSD symptoms and complex features, while young people only also self-reported on trauma-related (a) maladaptive appraisals, (b) memory quality and (c) coping. Social workers reported on maltreatment severity. RESULTS Young people's maltreatment severity was not a robust predictor of either PTSD symptoms or complex features. All three cognitive processes were moderately-to-strongly correlated with baseline and 12-month PTSD symptoms and complex features, with maladaptive appraisals the most robust unique driver of both, even when controlling for initial PTSD symptom severity. CONCLUSIONS Existing cognitive models of PTSD are applicable in this more complex sample of young people. The model was also found to be applicable to the additional features of complex PTSD, with the same processes driving both outcomes at both time points. Clinical implications are discussed. © 2020 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.OBJECTIVE To compare safety, efficacy, and impact on quality of life (QoL) between ischial spine fascia fixation (ISFF) and sacrospinous ligament fixation (SSLF) for stage 2-3 pelvic organ prolapse (POP). METHOD A prospective cohort study among women with POP attending a national referral university hospital in Beijing, China, between May 2007 and May 2015. Women underwent either ISFF or SSLF. Primary end point was objective success rates at 3 months after surgery. Tanespimycin manufacturer Exploratory outcomes included perioperative parameters, complications, subjective satisfaction rates and QoL at 1 year. RESULTS There was no difference in baseline characteristics between the groups (all P>0.05). After ISFF and SSLF, the objective success rate at 3 months was 100% and 98.1% (P>0.99), the recurrence rate at 1 year was 5.3% and 8.3% (P=0.266), and the subjective satisfaction rate at 1 year was 97.8% and 97.9%, respectively. Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 scores improved significantly after ISFF. De novo urinary incontinence occurred for 5.3% and 6.3% of women, respectively, and de novo dyspareunia for approximately 14% of women in both groups. CONCLUSION ISFF was found to be a safe and effective alternative to SSLF for women with symptomatic stage 2 and 3 POP. This article is protected by copyright. All rights reserved.Epidemiological evidence for the association between postdiagnostic metformin use and survival in patients with colorectal cancer (CRC) remains limited. Using the Taiwan Cancer Registry database, a cohort of 16,676 diabetic patients newly diagnosed with CRC from January 1, 2004 through December 31, 2014, followed until December 31, 2016, was identified. Postdiagnostic use of metformin (two or more prescriptions after CRC diagnosis) was defined as a time-dependent covariate with 6-month lag. Multivariate Cox regression model and stabilized inverse probability of treatment weighting (IPTW) were used to estimate adjusted effects of metformin on all-cause mortality and CRC-specific mortality during follow-up. 11,438 (69%) received metformin after CRC diagnosis. Overall, 7,393 deaths, including 4,845 CRC-specific deaths, were observed during 64,322 person-years of follow-up. After adjustment for demographic and clinical covariates, metformin users had lower all-cause mortality than did nonusers (hazard ratio [HR], 0.42; 95% CI, 0.40-0.44) and lower CRC-specific mortality (HR, 0.41; 95% CI, 0.39-0.44). Similar but somewhat attenuated effects were observed after stabilized IPTW (HR for all-cause mortality, 0.56; 95% CI, 0.53-0.59; HR for CRC-specific mortality, 0.58; 95% CI, 0.55-0.61). Similar results were observed in stratified analyses of 2,112 patients with no prediagnostic metformin use and 14,564 patients with prediagnostic metformin use. Findings for both outcomes were consistent in multiple sensitivity analyses. Use of postdiagnostic metformin was associated with significantly lower all-cause mortality and CRC-specific mortality, regardless of prior metformin use. These findings support the use of metformin as an adjunct to standard care of diabetic patients with CRC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.OBJECTIVE To determine the association between Medicaid expansion and infant mortality rate (IMR) in the United States. DATA SOURCES State-level aggregate data on US IMR, race, and sex were abstracted from the US Center for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research. STUDY DESIGN The association between Medicaid expansion and IMR adjusted for race and sex was assessed with multiple linear regression models using difference-in-differences estimation and Huber-White robust standard errors. PRINCIPAL FINDINGS Difference-in-differences regression found no association between Medicaid expansion status and change in national IMR from 2010 to 2017 (Coef. = 0.04; 95% CI -0.39, 0.46). However, among Hispanics, the program was found to be associated with reduction in IMR (Diff-in-Diff Coef. = -0.53; 95% CI -1.02, -0.03). CONCLUSIONS Overall, the Affordable Care Act-induced Medicaid expansion was not associated with IMR reduction in expansion states relative to nonexpansion states.