Hickmansaleh3204

Background and aims Almost all patients with familial adenomatous polyposis (FAP) develop duodenal adenomas, with a 4% to 18% risk of progression into duodenal cancer. Prophylactic endoscopic resection of duodenal adenomas may prevent cancer and is considered safer than surgical alternatives; however, data are limited. Therefore, the aim of this study was to assess safety and effectiveness of endoscopic duodenal interventions in patients with FAP. Methods We have performed a historical cohort study including patients with FAP that underwent an endoscopic duodenal intervention between 2002 and 2018. Safety was defined as adverse event rate per intervention and effectiveness as duodenal surgery free and duodenal cancer free survival. Cisplatinum order Change in Spigelman stage was assessed as secondary outcome. Results In 68 endoscopy sessions, 139 duodenal polypectomies were performed in 49 (20 male, median age 43) patients. Twenty-nine patients (14 male, median age 49) underwent a papillectomy. After polypectomy, 9 (13%) bleedings and 1 (2%) perforation occurred, all managed endoscopically. Six (21%) bleedings (endoscopically managed), 4 (14%) cases of pancreatitis and 1 (3%) perforation (conservatively treated) occurred after papillectomy. Duodenal surgery free survival was 74% at 89 months after polypectomy and 71% at 71 months after papillectomy; no duodenal cancers were observed. After median 18 (IQR 10-40, range 3-121) months after polypectomy, Spigelman stages were significantly lower (p less then 0.01). Conclusions In our FAP patients, prophylactic duodenal polypectomies were relatively safe. Papillectomies showed substantial adverse events, suggesting its benefits and risk should be carefully weighted. Both were however effective as surgical interventions were limited and none developed duodenal cancer.Background National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited. Methods All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated. Results Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed median age was 65 (IQR 56-75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5-11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60-99), with median PaO2/FiO2 ratio, 267 (IQR 184-314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4-16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality. Conclusion In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.Learning a second language (L2) at a young age is a driving factor of functional neuroplasticity in the auditory brainstem. To date, it remains unclear whether these effects remain stable until adulthood and to what degree the amount of exposure to the L2 in early childhood might affect their outcome. We compared three groups of adult English-French bilinguals in their ability to categorize English vowels in relation to their frequency following responses (FFR) evoked by the same vowels. At the time of testing, cognitive abilities as well as fluency in both languages were matched between the (1) simultaneous bilinguals (SIM, N = 18); (2) sequential bilinguals with L1-English (N = 14); and (3) sequential bilinguals with L1-French (N = 11). Our results show that the L1-English group show sharper category boundaries in identification of the vowels compared to the L1-French group. Furthermore, the same pattern was reflected in the FFRs (i.e., larger FFR responses in L1-English > SIM > L1-French), while again onlyneuroplastic effect in the brainstem remains stable until young adulthood and that the amount of L2 exposure does not influence behavioral or brainstem plasticity. Our study provides novel insights into low-level auditory plasticity as a function of varying bilingual experience.Background Many studies that aim to identify gene biomarkers using statistical methods and translate them into FDA-approved drugs have faced challenges due to lack of clinical validity and methodological reproducibility. Since genomic data analysis relies heavily on these statistical learning tools more than before, it is vital to address the limitations of these computational techniques. Methods Our study demonstrates these methodological gaps among most common statistical learning techniques used in gene expression analysis. To assess the classification ability and reproducibility of statistical learning tools for gene biomarker detection, six state-of-the-art machine learning models were trained on four different cancer data retrieved from The Cancer Genome Atlas (TCGA). Standard performance metrics including specificity, sensitivity, precision, and F1 score were evaluated to investigate the classification ability. For analysis of reproducibility, the identifiability of gene classifiers was examined by quantifying the consistency of the chosen classifier genes. Results Among the six state-of-the-art machine learning methods, the random forest had the best classification ability overall. Very few genes were selected by multiple methods, which suggests poor identifiability and reproducibility of statistical learning methods for gene expression data. Our results demonstrated the challenges of reproducing discoveries from gene expression analysis due to the inherent differences that exist in statistical machine learning methods. Conclusion Since statistical machine learning models can have large variations in high-dimensional settings such as analysis of gene expression data, transparent analysis procedures including data preprocessing, model parameterization, and evaluation and choice of interpretable models are required for clinical validity and utility.Background To maintain vascular tone and blood flow when tissue oxygenation is reduced, nitrite anions are reduced to nitric oxide (NO). From a practical perspective, it is unclear how the application of a tourniquet during blood collection might influence measurement of NO metabolites. Accordingly, this study evaluated the effect of venous occlusion on plasma nitrite and nitrate during venous blood collection. Methods Fifteen healthy participants completed two trials that were preceded by the ingestion of nitrate-rich beetroot juice (BRJ; total of ~8.4 mmol nitrate) or no supplementation (control). In both trials, blood was collected using a venepuncture needle while a tourniquet was applied to the upper arm and using an indwelling intravenous cannula, from the opposing arm. The venepuncture samples were collected at 35 s post occlusion. link2 Changes in the oxygenation of forearm flexor muscles were assessed using near-infrared spectroscopy. Plasma nitrite and nitrate were analysed using gas-phase chemiluminescence. Results In the control trial, plasma nitrite was significantly elevated when collected via the cannula (179 ± 67 nM) compared to venepuncture (112 ± 51 nM, P = 0.03). The ingestion of BRJ increased plasma nitrite and values remained higher when sampled from the cannula (473 ± 164 nM) compared to venepuncture (387 ± 136 nM, P 0.05). link3 The delta changes in total-, deoxy-, and oxy-haemoglobin were all significantly greater during venepuncture sample compared to the cannula sample at the point of blood collection (all P less then 0.05). Conclusions Venous occlusion during venepuncture blood collection lowers plasma nitrite concentration, potentially due to localised changes in haemoglobin concentration and/or a suppression of endogenous NO synthesis. Accordingly, the method of blood collection to enable measurements of NO metabolites should be carefully considered and consistently reported by researchers.According to preclinical and clinical studies, the antidepressant-induced increase in the activity of atypical antipsychotics may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. In the present study, we aimed to evaluate the effects of the antidepressants escitalopram and mirtazapine and the atypical antipsychotic drug aripiprazole, administered separately or in combination, on the MK-801-induced deficits in the recognition memory test and on the extracellular levels of monoamines and their metabolites in the rat frontal cortex. Based on the results of the behavioral tests, co-treatment with an ineffective dose of aripiprazole (0.1 mg/kg) and escitalopram (2.5 and 5 mg/kg) or mirtazapine (5 mg/kg) abolished the deficits evoked by MK-801 in the novel object recognition test, and those effects were blocked by the 5-HT1A receptor antagonist (WAY 100,635) or the dopamine D1 receptor antagonist (SCH 23,390). Moreover, co-treatment with aripiprazole (0.3 mg/kg) and escitalopram (5 mg/kg) significantly increased the levels of noradrenaline and serotonin, decreased the level of its metabolite, and did not alter level of dopamine, but decreased the levels of its metabolites. In addition, co-treatment with aripiprazole (0.3 mg/kg) and mirtazapine (10 mg/kg) significantly increased the level of noradrenaline, did not change the levels of dopamine and serotonin, but increased the levels of their metabolites. Based on these results, the increase in the extracellular levels of noradrenaline or serotonin in the cortex induced by co-treatment with an antidepressant and aripiprazole may be very important for the pharmacotherapy of negative and some cognitive symptoms of schizophrenia.Background Early psycho-social experiences influence the developing brain and possible onset of various neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD). ASD is characterized by a variety of brain abnormalities, including alteration of oxytocin receptors in the brain. Recently, early life adverse experiences, such as maternal separation (MS), have been shown to constitute risk factors for ASD in preclinical studies. Therefore, the main aims of the current study were to i) explore the association between onset of autistic-like behaviours and molecular/structural changes in the brain following MS, and ii) evaluate the possible beneficial effects of oxytocin treatment on the same parameters. Method and material Male rats were exposed to the maternal separation from post-natal day (PND) 1 to PND14. After weaning, daily injections of oxytocin (1 mg/kg, ip) were administered (PND 22-30), followed by examination of autism-related behaviours at adolescence (PND 42-50). Brain structural plasticity was examined using stereological methods, and the plasma level of brain derived neurotrophic factor (BDNF) was analysed using ELISA.