Increase of Mutant Clones Is Common within Nonmalignant Urothelium

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Mechanisms of the upper esophageal sphincter (UES) when exposed to acid are still incompletely understood. The presented work investigated the reaction of the UES to acid exposure during swallowing. Ten healthy individuals swallowed ten 2 ml neutral water boli of pH 7, followed by 10 swallows each of different levels of acidity (pH 1.8, pH 3 and pH 5). Effects were analyzed by high-resolution manometry (HRM) for the primary parameter Restitution Time, as well as Resting Pressures, maximal, minimal pressures and time intervals. Restitution Times measured mean values of 12.67 s (SD ± 7.03 s) for pH 1.8, pH 7 = 8.69 s (SD ± 2.72 s), pH 3 = 7.56 s (SD ± 2.23 s) and pH 5 = 7.29 s (SD ± 2.55 s), showing prolonged Restitution Times in the UES when exposed to strong bolus acidity. This difference was significant towards the neutral bolus, but also to less acidic boli (pH 5 p = 0.006, pH 3 p = 0.009, pH 7 p = 0.038). Considerable differences of mean values were found for Post-Swallow Maximum and Period of Sphincter Activity. Also, Pre-Swallow Maximum values were found to be highest with the strongest acid. Relaxation Times showed a slight trend of prolongation for the highest bolus acidity. Prolonged Restitution Times may represent a reflexive protective mechanism triggered by receptors in the pharyngeal mucosa or the UES preventing regurgitation of acid into the pharynx and larynx, besides representing ongoing attempts of acid clearance. Exposure to high levels of acidity by a swallowed bolus does influence UES functions during swallowing.Severe brain damage associated with Zika-related microcephaly (ZRM) have been reported to result in oropharyngeal dysphagia (OPD); however, it is unknown if OPD presents in children with prenatal Zika virus (ZIKV) exposure but only mild or undetectable abnormalities. The aims of this study were to compare the frequency and characteristics of OPD in children with ZRM and in children without microcephaly born to mothers who tested polymerase chain reaction positive (PCR+) for ZIKV during pregnancy; and to investigate the concordance of caregiver reports of OPD with the diagnosis from the clinical swallowing assessment (CSA). Between Mar/2017 and May/2018, we evaluated 116 children (n = 58 with microcephaly, n = 58 children without microcephaly born to ZIKV PCR + mothers) participating in the Microcephaly Epidemic Research Group (MERG) cohort of children born during the 2015-2016 ZIKV epidemic in Pernambuco, Brazil. To assess OPD we used a CSA; a clinical assessment of the stomatognathic system; and a questionnaire administered to caregivers. The frequency of OPD was markedly higher in children with ZRM (79.3%) than in the exposed but normocephalic group (8.6%). The children with microcephaly also presented more frequently with anatomic and functional abnormalities in the stomatognathic system. click here There was a high degree of agreement between the caregiver reports of OPD and the CSA (κ = 0.92). In conclusion, our findings confirm that OPD is a feature of Congenital Zika Syndrome that primarily occurs in children with microcephaly and provide support for policies in which children are referred for rehabilitation with an OPD diagnosis based on caregiver report.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder associated with motor, psychiatric and cognitive deterioration over time. To date, Continuous Electrical Neuromodulation (CEN) of the globus pallidus internus (GPi) has been reported to improve chorea but little is known about cognitive progression in these patients. We propose to examine CEN impact on expected cognitive decline throughout long-term neuropsychological assessment of a cohort of HD patients.
13 consecutive HD patients underwent GPi neuromodulation between January 2008 and February 2019. Over a 5-year follow-up period, they received systematic pre- and post-operative assessment according to the existing protocol in our unit. The main outcome measure was the total score obtained on the Mattis Dementia Rating Scale (MDRS) as an indicator of global cognitive function.
Chorea decreased in all patients postoperatively with a mean improvement of 56% despite disease progression over time, according to previous studies. decline in HD patients operated at an early stage of the disease.Amyotrophic lateral sclerosis (ALS) is an inexorably progressive neurodegenerative condition with no effective disease-modifying therapy at present. Given the striking clinical heterogeneity of the condition, the development and validation of reliable prognostic models is a recognised research priority. We present a prognostic model for functional decline in ALS where outcome uncertainty is taken into account. Patient data were reduced and projected onto a 2D space using Uniform Manifold Approximation and Projection (UMAP), a novel non-linear dimension reduction technique. Information from 3756 patients was included. Development data were sourced from past clinical trials. Real-world population data were used as validation data. Predictors included age, gender, region of onset, symptom duration, weight at baseline, functional impairment, and estimated rate of functional loss. UMAP projection of patients showed an informative 2D data distribution. As limited data availability precluded complex model designs, the projection was divided into three zones defined by a functional impairment range probability. Zone membership allowed individual patient prediction. Patients belonging to the first zone had a probability of [Formula see text] (± [Formula see text]) to have an ALSFRS score over 20 at 1-year follow-up. Patients within the second zone had a probability of [Formula see text] (± [Formula see text]) to have an ALSFRS score between 10 and 30 at 1 year follow-up. Finally, patients within the third zone had a probability of [Formula see text] (± [Formula see text]) to have an ALSFRS score lower than 20 at 1 year follow-up. This approach requires a limited set of features, is easily updated, improves with additional patient data, and accounts for results uncertainty. This method could therefore be used in a clinical setting for patient stratification and outcome projection.