BACKGROUND: Person-centred care (PCC) is a fundamental principle in general practice, emphasising practices tailored to individual patient preferences, needs, and values. Despite the importance of PCC, general practitioners (GPs) face obstacles in effectively implementing it, with associated factors remaining unclear. OBJECTIVES: The PACE GP/FP study aims to explore GPs' attitudes towards PCC and the factors facilitating or hindering its implementation in daily practice across European countries. This paper outlines the PACE GP/FP study protocol. METHODS: The cross-sectional design with data collection via an online survey distribution to GPs in 24 European countries. Study instruments include two validated questionnaires (Perceived Stress Scale (PSS) and Patient Physician Orientation Scale (PPOS)) and additional items covering general information about the doctor and their practice, as well as facilitators and barriers to PCC. These additional items were specifically developed for the study, translated using the forward-backward method, evaluated through cognitive debriefing, and integrated into the REDCap platform to create language and country-specific survey links. The STROBE checklist guides the reporting of the manuscript. CONCLUSION: The PACE GP/FP study will provide a comprehensive exploration of GPs' attitudes towards PCC and the factors shaping its practice in Europe. The findings from the PACE GP/FP study will provide evidence for designing future implementation strategies and guide targeted interventions to promote PCC in primary care across Europe.

• MeSH
• lidé MeSH
• péče orientovaná na pacienta * MeSH
• postoj zdravotnického personálu * MeSH
• praktické lékařství organizace a řízení   MeSH
• praktičtí lékaři * psychologie   MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

Papillary renal neoplasm with reversed polarity (PRNRP) is a recently described rare renal neoplasm. Traditionally, it was considered a variant of papillary renal cell carcinoma (PRCC). However, several studies reported significant differences between PRNRP and PRCC in terms of clinical, morphological, immunohistochemical and molecular features. Nonetheless, PRNRP remains a poorly understood entity. We used microarray analysis to elucidate the non-coding RNA (ncRNA) and gene expression profiles of 10 PRNRP cases and compared them with other renal neoplasms. Unsupervised cluster analysis showed that PRNRP had distinct expression profiles from either clear cell renal cell carcinoma (ccRCC) or PRCC cases at the level of ncRNA but were less distinct at the level of gene expression. An integrated omic approach determined miRNA:gene interactions that distinguished PRNRP from PRCC and we validated 10 differentially expressed miRNAs and six genes by quantitative RT-PCR. We found that levels of the miRNAs, miR-148a, miR-375 and miR-429, were up-regulated in PRNRP cases compared to ccRCC and PRCC. miRNA target genes, including KRAS and VEGFA oncogenes, and CXCL8, which regulates VEGFA, were also differentially expressed between renal neoplasms. Gene set enrichment analysis (GSEA) determined different activation of metabolic pathways between PRNRP and PRCC cases. Overall, this study is by far the largest molecular study of PRNRP cases and the first to investigate either ncRNA expression or their gene expression by microarray assays.

• MeSH
• dospělí MeSH
• karcinom z renálních buněk * genetika   patologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory ledvin * genetika   patologie   metabolismus   MeSH
• nekódující RNA * genetika   MeSH
• papilární karcinom patologie   genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Borrelia burgdorferi sensu lato, the causative agents of Lyme borreliosis, are transmitted by Ixodes ticks. Tick saliva proteins are instrumental for survival of both the vector and spirochete and have been investigated as targets for vaccine targeting the vector. In Europe, the main vector for Lyme borreliosis is Ixodes ricinus, which predominantly transmits Borrelia afzelii. We here investigated the differential production of I. ricinus tick saliva proteins in response to feeding and B. afzelii infection. METHOD: Label-free Quantitative Proteomics and Progenesis QI software was used to identify, compare, and select tick salivary gland proteins differentially produced during tick feeding and in response to B. afzelii infection. Tick saliva proteins were selected for validation, recombinantly expressed and used in both mouse and guinea pig vaccination and tick-challenge studies. RESULTS: We identified 870 I. ricinus proteins from which 68 were overrepresented upon 24-hours of feeding and B. afzelii infection. Selected tick proteins were successfully validated by confirming their expression at the RNA and native protein level in independent tick pools. When used in a recombinant vaccine formulation, these tick proteins significantly reduced the post-engorgement weights of I. ricinus nymphs in two experimental animal models. Despite the reduced ability of ticks to feed on vaccinated animals, we observed efficient transmission of B. afzelii to the murine host. CONCLUSION: Using quantitative proteomics, we identified differential protein production in I. ricinus salivary glands in response to B. afzelii infection and different feeding conditions. These results provide novel insights into the process of I. ricinus feeding and B. afzelii transmission and revealed novel candidates for an anti-tick vaccine.

• MeSH
• arachnida jako vektory MeSH
• klíště * MeSH
• lymeská nemoc * prevence a kontrola   MeSH
• morčata MeSH
• myši MeSH
• proteiny členovců MeSH
• proteom MeSH
• slinné žlázy MeSH
• vakcíny * MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• tisková chyba MeSH

Cellular proteins begin to fold as they emerge from the ribosome. The folding landscape of nascent chains is not only shaped by their amino acid sequence but also by the interactions with the ribosome. Here, we combine biophysical methods with cryo-EM structure determination to show that folding of a β-barrel protein begins with formation of a dynamic α-helix inside the ribosome. As the growing peptide reaches the end of the tunnel, the N-terminal part of the nascent chain refolds to a β-hairpin structure that remains dynamic until its release from the ribosome. Contacts with the ribosome and structure of the peptidyl transferase center depend on nascent chain conformation. These results indicate that proteins may start out as α-helices inside the tunnel and switch into their native folds only as they emerge from the ribosome. Moreover, the correlation of nascent chain conformations with reorientation of key residues of the ribosomal peptidyl-transferase center suggest that protein folding could modulate ribosome activity.

• MeSH
• cirkulární dichroismus MeSH
• elektronová kryomikroskopie MeSH
• Escherichia coli genetika   metabolismus   MeSH
• konformace proteinů, alfa-helix MeSH
• konformace proteinů, beta-řetězec MeSH
• molekulární modely MeSH
• posttranslační úpravy proteinů MeSH
• proteiny a peptidy chladového šoku chemie   genetika   metabolismus   MeSH
• proteiny z Escherichia coli chemie   genetika   metabolismus   MeSH
• proteosyntéza MeSH
• ribozomy genetika   metabolismus   MeSH
• sbalování proteinů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Poly(hydroxyalkanoates) are biodegradable and biocompatible polymers suitable for tissue engineering. Fused deposition modeling (FDM) belongs to modern rapid prototyping techniques for the fabrication of scaffolds. In this work, poly(3-hydroxybutyrate (PHB), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH) were tested for FDM. Thermal and rheological properties of industrial PHAs were compared with poly(lactic acid) (PLA), which is a biodegradable polymer commonly used for FDM. The massive decrease in viscosity and loss of molecular weight of PHB and PHBV precluded their use for FDM. On the other hand, the thermal stability of PHBH was comparable to that of PLA. PHBH scaffolds prepared by FDM exhibited excellent mechanical properties, no cytotoxicity and large proliferation of mouse embryonic fibroblast cells within 96 h. The hydrolytic degradation of PHBH and PLA scaffolds tested in synthetic gastric juice for 52 days confirmed a faster degradation of PHBH than PLA. The decrease in molecular weight confirmed the first-order kinetics with a slightly higher (0.0169 day-1) degradation rate constant for PHBH as compared to the value (0.0107 day-1) obtained for PLA. These results indicate that PHBH could be used to produce scaffolds by FDM with application in tissue engineering.

• MeSH
• biokompatibilní materiály chemie   MeSH
• kapronáty chemie   MeSH
• kyselina 3-hydroxymáselná chemie   MeSH
• lidé MeSH
• mechanické jevy MeSH
• molekulární struktura MeSH
• molekulová hmotnost MeSH
• myši MeSH
• polymery chemie   MeSH
• reologie MeSH
• teplota MeSH
• termogravimetrie MeSH
• tkáňové podpůrné struktury chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Gene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkb1 alone in the murine prostate epithelium was inconsequential for tumorigenesis, its combination with an oncogenic insult, illustrated by Pten heterozygosity, elicited lethal metastatic prostate cancer. Despite the low frequency of LKB1 deletion in patients, this event was significantly enriched in lung metastasis. Modeling the role of LKB1 in cellular systems revealed that the residual activity retained in a reported kinase-dead form, LKB1K78I, was sufficient to hamper tumor aggressiveness and metastatic dissemination. Our data suggest that prostate cells can function normally with low activity of LKB1, whereas its complete absence influences prostate cancer pathogenesis and dissemination.

• MeSH
• epitel enzymologie   patologie   MeSH
• fosfohydroláza PTEN metabolismus   MeSH
• HEK293 buňky MeSH
• heterozygot MeSH
• lidé MeSH
• metastázy nádorů MeSH
• mutantní proteiny metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši nahé MeSH
• nádorové buněčné linie MeSH
• nádory prostaty enzymologie   MeSH
• progrese nemoci MeSH
• prostata enzymologie   patologie   MeSH
• protein-serin-threoninkinasy nedostatek   genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Tubulocystic renal cell carcinoma (TC-RCC) is a rare recently described renal neoplasm characterized by gross, microscopic, and immunohistochemical differences from other renal tumor types and was recently classified as a distinct entity. However, this distinction remains controversial particularly because some genetic studies suggest a close relationship with papillary RCC (PRCC). The molecular basis of this disease remains largely unexplored. We therefore performed noncoding (nc) RNA/miRNA expression analysis and targeted next-generation sequencing mutational profiling on 13 TC-RCC cases (11 pure, two mixed TC-RCC/PRCC) and compared with other renal neoplasms. The expression profile of miRNAs and other ncRNAs in TC-RCC was distinct and validated 10 differentially expressed miRNAs by quantitative RT-PCR, including miR-155 and miR-34a, that were significantly down-regulated compared with PRCC cases (n = 22). With the use of targeted next-generation sequencing we identified mutations in 14 different genes, most frequently (>60% of TC-RCC cases) in ABL1 and PDFGRA genes. These mutations were present in <5% of clear cell RCC, PRCC, or chromophobe RCC cases (n > 600) of The Cancer Genome Atlas database. In summary, this study is by far the largest molecular study of TC-RCC cases and the first to investigate either ncRNA expression or their genomic profile. These results add molecular evidence that TC-RCC is indeed a distinct entity from PRCC and other renal neoplasms.

• MeSH
• diferenciální diagnóza MeSH
• karcinom z renálních buněk diagnóza   genetika   patologie   MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• mutace genetika   MeSH
• nádory ledvin diagnóza   genetika   patologie   MeSH
• nekódující RNA genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• reprodukovatelnost výsledků MeSH
• stanovení celkové genové exprese MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Clear cell tubulopapillary renal cell carcinoma (CCPRCC) is a recently described rare renal malignancy that displays characteristic gross, microscopic and immunohistochemical differences from other renal tumour types. However, CCPRCC remains a very poorly understood entity. We therefore sought to elucidate some of the molecular mechanisms involved in this neoplasm by carrying out targeted next-generation sequencing (NGS) to identify associated mutations, and in addition examined the expression of non-coding (nc) RNAs. We identified multiple somatic mutations in CCPRCC cases, including a recurrent [3/14 cases (21%)] non-synonymous T992I mutation in the MET proto-oncogene, a gene associated with epithelial-to-mesenchymal transition (EMT). Using a microarray approach, we found that the expression of mature (n = 1105) and pre-miRNAs (n = 1105), as well as snoRNA and scaRNAs (n = 2214), in CCPRCC cases differed from that of clear cell renal cell carcinoma (CCRCC) or papillary renal cell carcinoma (PRCC) tumours. Surprisingly, and unlike other renal tumour subtypes, we found that all five members of the miR-200 family were over-expressed in CCPRCC cases. As these miRNAs are intimately involved with EMT, we stained CCPRCC cases for E-cadherin, vimentin and β-catenin and found that the tumour cells of all cases were positive for all three markers, a combination rarely reported in other renal tumours that could have diagnostic implications. Taken together with the mutational analysis, these data suggest that EMT in CCPRCC tumour cells is incomplete or blocked, consistent with the indolent clinical course typical of this malignancy. In summary, as well as describing a novel pathological mechanism in renal carcinomas, this study adds to the mounting evidence that CCPRCC should be formally considered a distinct entity. Microarray data have been deposited in the GEO database [GEO accession number (GSE51554)].

• MeSH
• DNA nádorová chemie   genetika   MeSH
• epitelo-mezenchymální tranzice MeSH
• karcinom z renálních buněk genetika   patologie   MeSH
• lidé MeSH
• mikro RNA chemie   genetika   izolace a purifikace   MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery genetika   MeSH
• nádory ledvin genetika   patologie   MeSH
• následné studie MeSH
• nekódující RNA chemie   genetika   MeSH
• přežití bez známek nemoci MeSH
• retrospektivní studie MeSH
• RNA nádorová genetika   izolace a purifikace   MeSH
• sekvenční analýza DNA MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• shluková analýza MeSH
• stanovení celkové genové exprese MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH