An integrated care model for people living with Parkinson's disease (PD) offers the promise of meeting complex care needs in a person-centered way that addresses fragmentation and improves quality of life. The purpose of our research was to co-design a care delivery model that supports both social and medical care from the perspective of patients and care partners. In the first step of our co-design approach, participants from five countries were invited to share their experiences of living with PD during a narrative interview. A qualitative analysis of these narrative interviews based on the Corbin and Strauss model was done to map out patients' trajectories. Three typical trajectories were identified: (a) the "unpredictable" trajectory, (b) the "situated" trajectory, and (c) the "demanding" trajectory. Based on the analysis of these trajectories, we were able to integrate various patient experiences into the design of an integrated care network.

• MeSH
• integrované poskytování zdravotní péče * MeSH
• kvalita života MeSH
• lidé MeSH
• Parkinsonova nemoc * terapie   MeSH
• vyprávění MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• vytváření politiky MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Politika
• NLK Obory
• státní správa

• MeSH
• 2D gelová elektroforéza metody   využití   MeSH
• fosfopeptidy chemie   MeSH
• hmotnostní spektrometrie metody   využití   MeSH
• trypsin chemie   MeSH

• MeSH
• genetika MeSH
• molekulární biologie MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• genetika, lékařská genetika
• biologie

• MeSH
• hodnocení rizik MeSH
• monitorování životního prostředí * MeSH
• rozhodování MeSH
• znečištění životního prostředí MeSH
• Publikační typ
• periodika MeSH

• Konspekt
• Životní prostředí a jeho ochrana
• NLK Obory
• environmentální vědy

Uterine leiomyosarcomas (uLMS) are rare, aggressive malignancies for which limited treatment options are available. To gain novel molecular insights into uLMS and identify potential novel therapeutic targets, we characterized 84 uLMS samples for genome-wide somatic copy number alterations, mutations, gene fusions and gene expression and performed a data integration analysis. We found that alterations affecting TP53, RB1, PTEN, MED12, YWHAE and VIPR2 were present in the majority of uLMS. Pathway analyses additionally revealed that the PI3K/AKT/mTOR, estrogen-mediated S-phase entry and DNA damage response signaling pathways, for which inhibitors have already been developed and approved, frequently harbored genetic changes. Furthermore, a significant proportion of uLMS was characterized by amplifications and overexpression of known oncogenes (CCNE1, TDO2), as well as deletions and reduced expression of tumor suppressor genes (PTEN, PRDM16). Overall, it emerged that the most frequently affected gene in our uLMS samples was VIPR2 (96%). Interestingly, VIPR2 deletion also correlated with unfavorable survival in uLMS patients (multivariate analysis; HR = 4.5, CI = 1.4-14.3, p = 1.2E-02), while VIPR2 protein expression was reduced in uLMS vs. normal myometrium. Moreover, stimulation of VIPR2 with its natural agonist VIP decreased SK-UT-1 uLMS cell proliferation in a dose-dependent manner. These data suggest that VIPR2, which is a negative regulator of smooth muscle cell proliferation, might be a novel tumor suppressor gene in uLMS. Our work further highlights the importance of integrative molecular analyses, through which we were able to uncover the genes and pathways most frequently affected by somatic alterations in uLMS.

• MeSH
• dospělí MeSH
• genomika metody   MeSH
• Kaplanův-Meierův odhad MeSH
• karcinogeneze genetika   MeSH
• leiomyosarkom genetika   mortalita   patologie   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myometrium patologie   MeSH
• nádory dělohy genetika   mortalita   patologie   terapie   MeSH
• onkogeny genetika   MeSH
• proliferace buněk genetika   MeSH
• receptory vazoaktivního intestinálního peptidu typu II genetika   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• sekvenční analýza RNA metody   MeSH
• sekvenování celého genomu metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• signální transdukce genetika   MeSH
• tumor supresorové geny MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• obezita dětí a dospívajících MeSH
• vytváření politiky MeSH
• zdravotní politika MeSH
• Publikační typ
• učebnice MeSH
• Geografické názvy
• Spojené státy americké MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• veřejné zdravotnictví
• pediatrie

• MeSH
• časná detekce nádoru MeSH
• klinické zkoušky jako téma MeSH
• medicína založená na důkazech MeSH
• nádory diagnóza   terapie   MeSH
• náklady a analýza nákladů MeSH
• náklady na zdravotní péči MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• onkologie

Chronic lymphocytic leukemia (CLL) stereotyped subsets #6 and #8 include cases expressing unmutated B cell receptor immunoglobulin (BcR IG) (U-CLL). Subset #6 (IGHV1-69/IGKV3-20) is less aggressive compared to subset #8 (IGHV4-39/IGKV1(D)-39) which has the highest risk for Richter's transformation among all CLL. The underlying reasons for this divergent clinical behavior are not fully elucidated. To gain insight into this issue, here we focused on epigenomic signatures and their links with gene expression, particularly investigating genome-wide DNA methylation profiles in subsets #6 and #8 as well as other U-CLL cases not expressing stereotyped BcR IG. We found that subset #8 showed a distinctive DNA methylation profile compared to all other U-CLL cases, including subset #6. Integrated analysis of DNA methylation and gene expression revealed significant correlation for several genes, particularly highlighting a relevant role for the TP63 gene which was hypomethylated and overexpressed in subset #8. This observation was validated by quantitative PCR, which also revealed TP63 mRNA overexpression in additional nonsubset U-CLL cases. BcR stimulation had distinct effects on p63 protein expression, particularly leading to induction in subset #8, accompanied by increased CLL cell survival. This pro-survival effect was also supported by siRNA-mediated downregulation of p63 expression resulting in increased apoptosis. In conclusion, we report that DNA methylation profiles may vary even among CLL patients with similar somatic hypermutation status, supporting a compartmentalized approach to dissecting CLL biology. Furthermore, we highlight p63 as a novel prosurvival factor in CLL, thus identifying another piece of the complex puzzle of clinical aggressiveness.

• MeSH
• apoptóza genetika   MeSH
• chronická lymfatická leukemie krev   genetika   patologie   MeSH
• epigenomika metody   MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• metylace DNA genetika   MeSH
• nádorové buňky kultivované MeSH
• nádorové supresorové proteiny genetika   metabolismus   MeSH
• primární buněčná kultura MeSH
• promotorové oblasti (genetika) genetika   MeSH
• receptory antigenů B-buněk metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• sekvenční analýza RNA MeSH
• stanovení celkové genové exprese metody   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• up regulace MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

We present an integrated and low-cost microfluidic platform capable of extraction of nucleic acids from real biological samples. We demonstrate the application of this platform in pathogen detection and cancer screening. The integrated platform consists of three units including a pretreatment unit for separation of nucleic acids from lysates, a preconcentration unit for concentration of isolated nucleic acids and a sensing unit localized at a designated position on the chip for specific detection of the target nucleic acid. The platform is based on various electrokinetic phenomena exhibited by ion exchange membranes in a DC electrical field that allow them to serve as molecular filters, analyte preconcentrators and sensors. In this manuscript, we describe each unit of the integrated chip separately and show specific detection of a microRNA (miRNA 146a) biomarker associated with oral cancer as a proof-of-concept experiment. This platform technology can easily be extended to other targets of interest by optimizing the properties of the ion exchange membranes and the specific probes functionalized onto the sensors.

• MeSH
• elektrická vodivost * MeSH
• laboratoř na čipu * ekonomika   MeSH
• mikro RNA analýza   MeSH
• nádorové biomarkery analýza   MeSH
• nádory úst diagnóza   MeSH
• systémová integrace MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH