Bendermartinussen2007

Neuroendocrine carcinoma of small cell type (SCNEC) is a rare pathological subtype in cervical cancer, which has a worse prognosis than other histological cell types. Due to its low incidence and the lack of experimental platforms, the molecular characteristics of SCNEC in the cervix remain largely unknown. Using the cancer tissue-originated spheroid (CTOS) method-an ex vivo 3D culture system that preserves the differentiation status of the original tumors-we established a panel of CTOS lines of SCNEC. We demonstrated that xenograft tumors and CTOSs, respectively, exhibited substantial intra-tumor and intra-CTOS variation in the expression levels of chromogranin A (CHGA), a neuroendocrine tumor marker. Since hypoxia affects differentiation in various tumors and in stem cells, we also investigated how hypoxia affected neuroendocrine differentiation of SCNEC of the uterine cervix. In the CTOS line cerv21, hypoxia suppressed expression of the neuroendocrine markers CHGA and synaptophysin (SYP). Flow cytometry analysis using CD99 (a membrane protein marker of SCNEC) revealed decreased CD99 expression in a subset of cells under hypoxic conditions. These expression changes were attenuated by HIF-1α knockdown, and by a Notch inhibitor, suggesting that these molecules played a role in the regulation of neuroendocrine differentiation. The examined SCNEC markers were suppressed under hypoxia in multiple CTOS lines. Overall, our present results indicated that neuroendocrine differentiation in SCNEC of the uterus is a variable phenotype, and that hypoxia may be one of the factors regulating the differentiation status. TDP-43 inclusion is a pathological hallmark for ∼97% ALS and ∼45% FTD patients. So far, >50 ALS-causing mutations have been identified, most of which are hosted by the intrinsically-disordered prion-like domain. The D169G mutation is the only one within the well-folded RRM1 domain, which, however, induces no significant change of the crystal structure and even slightly enhances the thermodynamic stability. Therefore, the mechanism for D169G to enhance the cytotoxicity remains elusive. Here by NMR, we reveal for the first time 1) D169G does trigger significant dynamic changes for a cluster of residues. 2) Very unexpectedly, D169G disrupts the ATP-binding capacity of RRM1 although the ATP-binding pocket is on the back side of the mutation site. D609 clinical trial Taken together with our previous results, the current study provides a potential mechanism to rationalize enhancement of the TDP-43 cytotoxicity by D169G and highlights again the key roles of ATP in neurodegenerative diseases and ageing. STUDY OBJECTIVES To evaluate the diagnostic accuracy of a non-invasive technology based on image processing for the identification of obstructive sleep apnea (OSA) and its severity at patients' home. METHODS Observational, prospective, diagnostic accuracy study to evaluate the degree of measure agreement between Sleepwise (SW), in-laboratory attended polysomnography (PSG) and a home sleep apnea test (HSAT). 38 consecutive subjects with suspected OSA referred as outpatients to the sleep unit were recruited from September 2016 to September 2017. All patients underwent in-laboratory attended PSG and image processing with SW simultaneously overnight. Subsequently, a HSAT and image processing with SW were performed simultaneously overnight at patients' home, and the 2 nights after, patients underwent only image processing with SW consecutively. RESULTS In-laboratory polysomnography and SW had a Lin's concordance correlation coefficient of 0.933 and a κ of 0.930. Between HSAT and SW the Lin's concordance correlation coefficient was 0.842 and a κ of 0.571. Agreement between two consecutive nights with SW recording showed a Lin's concordance correlation coefficient of 0.923 and a κ of 0. 837. CONCLUSIONS SW was highly accurate for non-invasive and automatic diagnosis of OSA in outpatients compared to standard methods for OSA diagnosis either in-laboratory attended PSG or HSAT. SW proved to be a technique with repeatable and concordant results on different nights for the same patient. We conclude SW is a non-invasive, easy-to-use, portable, effective and highly accurate system for the in-home diagnosis of OSA. OBJECTIFS La présente directive clinique vise à diminuer la probabilité que la pratique de l'excision génitale féminine (EGF) se poursuive et à améliorer les soins prodigués aux filles et aux femmes qui ont subi une EGF ou qui risquent d'en subir une en fournissant (1) des renseignements destinés à améliorer les connaissances et la compréhension de la pratique, (2) des renseignements sur les enjeux juridiques liés à cette pratique, (3) des directives relatives au traitement des complications obstétricales et gynécologiques connexes et (4) des directives sur la compétence culturelle dans la prestation de soins aux filles et femmes touchées par l'EGF. OPTIONS Des stratégies de prévention primaire, secondaire et tertiaire de l'EGF et de ses complications. RéSULTATS Les conséquences à court et à long terme de l'EGF. UTILISATEURS CIBLES Les fournisseurs de soins de santé qui fournissent des soins obstétricaux et gynécologiques. POPULATION CIBLE Les femmes originaires de pays où l'EGF est couramment pratiquée ainsiiter les femmes ayant subi une EGF à solliciter rapidement des soins. DÉCLARATIONS SOMMAIRES RECOMMANDATIONS. OBJECTIVES To decrease the likelihood that the practice of female genital cutting (FGC) be continued in the future and to improve the care of girls and women who have been subjected to FGC or who are at risk by providing (1) information intended to strengthen knowledge and understanding of the practice, (2) information regarding the legal issues related to the practice, (3) guidance for the management of its obstetrical and gynaecological complications, and (4) guidance on the provision of culturally competent care to girls and women affected by FGC. OPTIONS Strategies for the primary, secondary, and tertiary prevention of FGC and its complications. OUTCOMES The short- and long-term consequences of FGC. INTENDED USERS Health care providers delivering obstetrical and gynaecological care. TARGET POPULATION Women from countries where FGC is commonly practised and Canadian girls and women from groups who may practise FGC for cultural or religious reasons. EVIDENCE Published literature was retrieved through searches of PubMed, CINAHL, and the Cochrane Library in September 2010 using appropriate controlled vocabulary (e.