Transcutaneous vagus nerve stimulation and extinction of prepared fear: A conceptual non-replication

Stress-related psychiatric disorders across the life spa

Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair

Schwann cell development and peripheral nerve myelination require the serial expression of transcriptional activators, such as Sox10, Oct6 (also called Scip or Pou3f1) and Krox20 (also called Egr2). Here we show that transcriptional repression, mediated by the zinc-finger protein Zeb2 (also known as Sip1), is essential for differentiation and myelination. Mice lacking Zeb2 in Schwann cells develop a severe peripheral neuropathy, caused by failure of axonal sorting and virtual absence of myelin membranes. Zeb2-deficient Schwann cells continuously express repressors of lineage progression. Moreover, genes for negative regulators of maturation such as Sox2 and Ednrb emerge as Zeb2 target genes, supporting its function as an inhibitor of inhibitors in myelination control. When Zeb2 is deleted in adult mice, Schwann cells readily dedifferentiate following peripheral nerve injury and become repair cells. However, nerve regeneration and remyelination are both perturbed, demonstrating that Zeb2, although undetectable in adult Schwann cells, has a latent function throughout life

Patient reported outcome measures concerning urinary incontinence after robot assisted radical prostatectomy: development and validation of an online prediction model using clinical parameters, lower urinary tract symptoms and surgical experience

The prediction of post-prostatectomy incontinence (PPI) after robot-assisted radical prostatectomy (RARP) depends on multiple clinical, anatomical and surgical factors. There are only few risk formulas, tables or nomograms predicting PPI that may assist clinicians and their patients in adequate risk counseling on postoperative side-effects. Prospective data collection of 1814 patients who underwent RARP between 2009 and 2017 was done. Pre-operative parameters were age, body mass index (BMI), prostate volume, the American Society of Anesthesiologists (ASA) score, severity of Lower Urinary Tract Symptoms (LUTS), type of planned nerve-sparing surgery and surgical experience. The continence status was reported using Patient Reported Outcome Measurements (PROMs) using the validated pad-use questionnaire EPIC26. Continence was defined as either the use of zero pads or one safety pad. Multivariable logistic regression analysis was performed to identify predictors of PPI within one year after RARP. An online prediction tool was developed and validated. The median follow-up was 36 months (range 12–108). The response rate was high at 85.2%. A total of 85% (1537/1814) of patients was continent on follow-up. One-year continence rate was 80.1% (95% CI 78.3–81.9%) (1453/1814) and increased to 87.4% (95% CI 85.4–89.4%) after 5 years. On multivariable analysis, severity of LUTS (OR = 0.56 p = 0.004), higher age (OR = 0.73 p = 0.049), extend of nerve-sparing surgery (OR = 0.60 p = 0.001) and surgeon experience (OR = 1.48 p = 0.025) were significant independent predictors for PPI. The online prediction model performed well in predicting continence status with poor discrimination and good calibration. An intuitive online tool was developed to predict PPI after RARP that may assist clinicians and their patients in counseling of treatment

Functional assessment of TSC1 missense variants identified in individuals with tuberous sclerosis complex

Mechanisms of disease, diagnostics and therap

The expanding phenotype of COL4A1 and COL4A2 mutations : clinical data on 13 newly identified families and a review of the literature

Two proa1(IV) chains, encoded by COL4A1, form trimers that contain, in addition, a proa2(IV) chain encoded by COL4A2 and are the major component of the basement membrane in many tissues. Since 2005, COL4A1 mutations have been known as an autosomal dominant cause of hereditary porencephaly. COL4A1 and COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities, indicated as "COL4A1 mutation-related disorders." Genetic counseling is challenging because of broad phenotypic variation and reduced penetrance. At the Erasmus University Medical Center, diagnostic DNA analysis of both COL4A1 and COL4A2 in 183 index patients was performed between 2005 and 2013. In total, 21 COL4A1 and 3 COL4A2 mutations were identified, mostly in children with porencephaly or other patterns of parenchymal hemorrhage, with a high de novo mutation rate of 40% (10/24). The observations in 13 novel families harboring either COL4A1 or COL4A2 mutations prompted us to review the clinical spectrum. We observed recognizable phenotypic patterns and propose a screening protocol at diagnosis. Our data underscore the importance of COL4A1 and COL4A2 mutations in cerebrovascular disease, also in sporadic patients. Follow-up data on symptomatic and asymptomatic mutation carriers are needed for prognosis and appropriate surveillance