First episodes of norovirus and sapovirus gastroenteritis protect against subsequent episodes in a Nicaraguan birth cohort

alexandrossfakianakis shared this article with you from Inoreader First episodes of norovirus and sapovirus gastroenteritis protect against subsequent episodes in a Nicaraguan birth cohort via Epidemiology - Published Ahead-of-Print Background: Norovirus and sapovirus cause a large burden of acute gastroenteritis (AGE) in young children. We assessed protection conferred by norovirus and sapovirus AGE episodes against future episodes. Methods: Between June 2017-July 2018 we recruited 444 newborns in León, Nicaragua. Weekly household surveys identified AGE episodes over 36 months, and AGE stools were tested by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) for norovirus GI/GII and sapovirus. We used recurrent-event Cox models and negative control methods to estimate protection conferred by first episodes, controlling for observed and unobserved risk factors, respectively. Results: Sapovirus episodes conferred a 69% reduced hazard of subsequent episodes using the negative control method. Norovirus GI (HR: 0.67, 95% CI: 0.31, 1.3) and GII (HR: 0.20, 95% CI: 0.04, 0.44) episodes also appeared highly protective. Protection against norovirus GII was enhanced following two episodes. Conclusions: Evidence of natural immunity in early childhood provides optimism for the future success of pediatric norovirus and sapovirus vaccines. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. View on Web

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Prognostic Nutrıtıonal Index: Is It Assocıated wıth The Prognosıs of Crımean Congo Hemorrhagıc Fever?

alexandrossfakianakis shared this article with you from Inoreader Prognostic Nutrıtıonal Index: Is It Assocıated wıth The Prognosıs of Crımean Congo Hemorrhagıc Fever? via Journal of Medical Virology Abstract Introduction The prognostic nutritional index (PNI) is calculated using total serum lymphocyte counts and albumin levels. We aimed to analyze the role of PNI in predicting intensive care unit (ICU) referral and mortality in patients with Crimean Congo Hemorrhagic Fever (CCHF). Materials and Methods Our target population was adult (age>18) patients who presented between March 2015 and October 2021 within five days of symptom emergence and were diagnosed with CCHF. The predictive value of PNI was analyzed by the ROC analysis. The patients were categorized based on the severity grading scores (SGS) as mild, moderate, and severe. The relationship between PNI and ICU referral and mortality was analyzed by logistic regression analysis. Results Overall, 115 patients with the diagnosis of CCHF were included. 13,9% (n=16) of the patients were referred to ICU while 11,3% (n=13) died. A comparison of the patients with different SGS grades revealed that they were significantly different regarding PNI (p<0,001). There was a significant negative correlation between PNI and SGS (r=-0,662; p<0,001). PNI had a PV regarding ICU referral and mortality ((AUC=0,723 95% CI: 0,609-0,836, p=0,004, (AUC=0,738 95% CI: 0,613-0,863, p=0,005)). The PNI threshold was 36,1 for ICU referral and mortality. The rates of female patients, hospitalization periods longer than one week, platelet apheresis replacement, diabetes mellitus, bleeding history, ICU admission, and mortality were significantly higher in patients with a PNI of lower than 36,1 (p<0,05). Conclusion PNI can predict ICU referral and mortality in patients admitted due to CCHF. This article is protected by copyright. All rights reserved. View on Web

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A novel homozygous missense mutation in the FASTKD2 gene leads to Lennox-Gastaut syndrome

alexandrossfakianakis shared this article with you from Inoreader A novel homozygous missense mutation in the <i>FASTKD2</i> gene leads to Lennox-Gastaut syndrome via Journal of Human Genetics - Issue - nature.com science feeds Journal of Human Genetics, Published online: 21 June 2022; doi:10.1038/s10038-022-01056-7 A novel homozygous missense mutation in the FASTKD2 gene leads to Lennox-Gastaut syndrome View on Web

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PHAREO study: Perceived and observed accessibility to therapeutic drugs used for treating patients with inherited bleeding disorders

alexandrossfakianakis shared this article with you from Inoreader PHAREO study: Perceived and observed accessibility to therapeutic drugs used for treating patients with inherited bleeding disorders via Journal of Clinical Pharmacy and Therapeutics The PHAREO study provides subjective and objective data regarding satisfaction levels of persons with haemophilia and other coagulation deficiencies regarding treatment accessibility. The main determinants of dissatisfaction were parental burden and waiting time at the hospital pharmacy. Patients and hospital pharmacists pled for an evolution of the current dispensing circuit to improve access to treatment and reduce the burden for patients. Abstract What Is Known and Objective The dispensing of clotting factor concentrates in hospital pharmacies imposes accessibility constraints on patients and their caregivers, thereby increasing the disease burden. Very few studies have addressed these issues so far in terms of individual perceptions and actual difficulties. The PHAREO study aims to report patient's perception of treatment accessibility and evaluate spatial accessibility. Methods The PHAREO study is an observational survey based on a questionnaire specifically designed for the study purpose in collaboration with patients' representatives in the second demographic and economic French region. Results and Discussion We collected 293 responses (participation rate of 64.1%) which show that 89.8% of respondents were either very or rather satisfied with regard to access to treatment. However, respondents reported difficulties in accessing the hospital pharmacy. The data also showed that 79.2% of respondents tended to over-estimate travel time which was reported above their acceptable threshold for 39.2% of them. The main determinants of dissatisfaction were parental burden (OR 2.5 [1.3; 4.8], p = 0.008) and waiting time at the hospital pharmacy (OR 1.5 [1.1;2.0], p = 0.016, per 10 min increase). What Is New and Conclusion The PHAREO study provides subjective and objective data regarding satisfaction levels of persons with haemophilia and other coagulation deficiencies, with a high representativeness rate for patients on prophylaxis (87.5%). Both respondents and hospital pharmacists pled for an evolution of the current dispensing circuit to improve access to treatment and reduce the burden for patients. Currently, the community pharmacists are apart from the dispensing circuit. The authors propose improvements in the pathway of care for patients and their caregivers by including the community pharmacists alongside the hospital pharmacists in a centralized coordination scheme. View on Web

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FRK inhibits glioblastoma progression via phosphorylating YAP and inducing its ubiquitylation and degradation by Siah1

alexandrossfakianakis shared this article with you from Inoreader FRK inhibits glioblastoma progression via phosphorylating YAP and inducing its ubiquitylation and degradation by Siah1 via Neuro-Oncology Advance Access Abstract Background We previously report that yes-associated protein (YAP), the core downstream effector of Hippo pathway, promotes the malignant progression of glioblastoma (GBM). However, although classical regulatory mechanisms of YAP are well explored, how YAP is modulated by the Hippo-independent manner remains poorly understood. Meanwhile, the non-receptor tyrosine kinase Fyn-related kinase (FRK), which exhibits low expression and possesses tumor suppressor effects in GBM, is reported to be involved in regulation of protein phosphorylation. Here, we examined whether FRK could impede tumor progression by modulating YAP activities. Methods Human GBM cells and intracranial GBM model were used to assess the effects of FRK and YAP on the malignant biological behaviors of GBM. Immunoblotting and immunohistochemistry were used to detect the expression of core proteins in GBM tissues. Co-immunoprecipitation, proximity ligation assay, luci ferase assay and ubiquitination assay were utilized to determine the protein-protein interactions and related molecular mechanisms. Results The expression levels of FRK and YAP were inversely correlated with each other in glioma tissues. In addition, FRK promoted the ubiquitination and degradation of YAP, leading to tumor suppression in vitro and in vivo. Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP. Siah1 is required for YAP destabilization initiated by FRK. Conclusions We identify a novel mechanism by which FRK orchestrates tumor-suppression effect through phosphorylating YAP and inducing its ubiquitination by Siah1. FRK-Siah1-YAP signaling axis may serve as a potential therapeutic target for GBM treatment. View on Web

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Oct4A palmitoylation modulates tumorigenicity and stemness in human glioblastoma cells

alexandrossfakianakis shared this article with you from Inoreader Oct4A palmitoylation modulates tumorigenicity and stemness in human glioblastoma cells via Neuro-Oncology Advance Access Abstract Background Glioblastoma multiforme and other solid malignancies are heterogeneous, containing subpopulations of tumor cells that exhibit stem characteristics. Oct4, also known as POU5F1, is a key transcription factor in the self-renewal, proliferation, and differentiation of stem cells. Although it has been detected in advanced gliomas, the biological function of Oct4, and transcriptional machinery maintained by the stemness of Oct4 protein-mediated glioma stem cells (GSC), has not been fully determined. Methods The expression of Oct4 variants was evaluated in brain-cancer cell lines, and in brain-tumor tissues, by quantitative real-time PCR, western blotting, and immunohistochemical analysis. The palmitoylation level of Oct4A was determined by the acyl-biotin exchange method, and the effects of palmitoylation Oct4A on GSCs were investigated by a series of in vitro (neuro-sphere formation assay, double immunofluorescence, pharmacological treatment, luciferase assay, and coimmunoprecipitation) and in vivo (xenograft model) experiments. Results Here, we report that all three variants of Oct4 are expressed in different types of cerebral cancer, while Oct4A is important for maintaining tumorigenicity in GSCs. Palmitoylation mediated by ZDHHC17 was indispensable for preserving Oct4A from lysosome degradation to maintain its protein stability. Oct4A palmitoylation also helped to integrate Sox4 and Oct4A in the SOX2 enhancement subregion to maintain the stem performance of GSCs. We also designed Oct4A palmitoylation competitive inhibitors, inhibiting the self-renewal ability and tumorigenicity of GSCs. Conclusions These findings indicate that Oct4A acts on the tumorigenic activity of glioblastoma, and Oct4A palmitoylation is a candidate therapeutic target. View on Web

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circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis

alexandrossfakianakis shared this article with you from Inoreader circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 21 June 2022; doi:10.1038/s41368-022-00184-2 circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis View on Web

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Combination of fluorescence visualization and iodine solution-guided surgery for local control of early tongue cancer

alexandrossfakianakis shared this article with you from Inoreader Combination of fluorescence visualization and iodine solution-guided surgery for local control of early tongue cancer via International Journal of Oral and Maxillofacial Surgery via MedWorm.com The control of enclosed oral epithelial dysplasia is important for the control of oral cancer. Fluorescence visualization and iodine solution are able to detect oral epithelial dysplasia and surrounding oral cancer. The purpose of this study was to clarify the effectiveness of combining fluorescence visualization and iodine solution-guided surgery for early tongue cancer. Participants comprised 264 patients with primary early tongue cancer who underwent surgery. The surgical margin was set at 10  mm outside the clinical tumour, and 5 mm outside the area of fluorescence visualization loss, and 5mm outside the iodine unstained area. (Source: International Journal of Oral and Maxillofacial Surgery) View on Web

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