Using the remarkable overlap between brain circuits affected in Parkinson's disease (PD) and those underlying motor sequence learning, we may improve the effectiveness of motor rehabilitation interventions by identifying motor learning facilitators in PD. For instance, additional sensory stimulation and task cueing enhanced motor learning in people with PD, whereas exercising using musical rhythms or console computer games improved gait and balance, and reduced some motor symptoms, in addition to increasing task enjoyment. Yet, despite these advances, important knowledge gaps remain. Most studies investigating motor learning in PD used laboratory-specific tasks and equipment, with little resemblance to real life situations. Thus, it is unknown whether similar results could be achieved in more ecological setups and whether individual's task engagement could further improve motor learning capacity. Moreover, the role of social interaction in motor skill learning process has not yet been investigated in PD and the role of mind-set and self-regulatory mechanisms have been sporadically examined. Here, we review evidence suggesting that these psychosocial factors may be important modulators of motor learning in PD. We propose their incorporation in future research, given that it could lead to development of improved non-pharmacological interventions aimed to preserve or restore motor function in PD.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Abdominal obesity is a strong cardiometabolic risk factor that often occurs as early as in childhood. The negative effect of abdominal obesity on the metabolism is partially mediated by changes to the production of the major adipocyte hormones leptin and adiponectin. Leptin/adiponectin imbalance is associated with increased risk of developing obesity and type 2 diabetes mellitus. AIM: To determine whether leptin, adiponectin and the leptin/adiponectin ratio are significant predictors of body weight loss in intensively treated children/adolescents. METHODS: 183 paediatric overweight or obese patients (71 boys and 112 girls), aged 7-16 years, were enrolled in a one-month intensive lifestyle intervention programme. Participants reduced their energy intake and engaged in a supervised exercise programme consisting of 5 physical activity units per day. The subjects were examined both before and after the intervention. RESULTS: The mean BMI decrease achieved was-2.38±0.07 kg/m² (P<0.01). The decrease in plasma leptin concentration was-16.59±0.84 ng/mL (P<0.001) and CRP-0.38±0.04 mg/L (P<0.001). Changes in adiponectin concentrations were not statistically significant. The baseline leptin/adiponectin ratio was a significant predictor of decreases in body weight (P<0.005), BMI (P<0.0001) and waist circumference (P<0.05). CONCLUSION: The leptin/adiponectin ratio at baseline may be a useful predictor of results from interventions focused on decreasing BMIs in children/adolescents.

• MeSH
• abdominální obezita * krev   patologie   terapie   MeSH
• adiponektin krev   MeSH
• behaviorální terapie * MeSH
• cvičení * MeSH
• dítě MeSH
• index tělesné hmotnosti * MeSH
• leptin krev   MeSH
• lidé MeSH
• mladiství MeSH
• obezita dětí a dospívajících * krev   patologie   terapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH

BACKGROUND: Ovarian cancer (OC) is mostly diagnosed in advanced stages with high incidence-to-mortality rate. Nevertheless, some patients achieve long-term disease-free survival. However, the prognostic markers have not been well established. OBJECTIVE: The primary objective of this study was to analyse the association of the suggested prognostic marker rs2185379 in PRDM1 with long-term survival in a large independent cohort of advanced OC patients. METHODS: We genotyped 545 well-characterized advanced OC patients. All patients were tested for OC predisposition. The effect of PRDM1 rs2185379 and other monitored clinicopathological and genetic variables on survival were analysed. RESULTS: The univariate analysis revealed no significant effect of PRDM1 rs2185379 on survival whereas significantly worse prognosis was observed in postmenopausal patients (HR = 2.49; 95%CI 1.90-3.26; p= 4.14 × 10 - 11) with mortality linearly increasing with age (HR = 1.05 per year; 95%CI 1.04-1.07; p= 2 × 10 - 6), in patients diagnosed with non-high-grade serous OC (HR = 0.44; 95%CI 0.32-0.60; p= 1.95 × 10 - 7) and in patients carrying a gBRCA1 pathogenic variant (HR = 0.65; 95%CI 0.48-0.87; p= 4.53 × 10 - 3). The multivariate analysis interrogating the effect of PRDM1 rs2185379 with other significant prognostic factors revealed marginal association of PRDM1 rs2185379 with worse survival in postmenopausal women (HR = 1.54; 95%CI 1.01-2.38; p= 0.046). CONCLUSIONS: Unlike age at diagnosis, OC histology or gBRCA1 status, rs2185379 in PRDM1 is unlikely a marker of long-term survival in patients with advance OC.

• MeSH
• dospělí MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery * genetika   MeSH
• nádory vaječníků * genetika   mortalita   patologie   MeSH
• prognóza MeSH
• protein BRCA1 * genetika   MeSH
• protein PRDI-BF1 * genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů 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

Germline alterations in many genes coding for proteins regulating DNA repair and DNA damage response (DDR) to DNA double-strand breaks (DDSB) have been recognized as pathogenic factors in hereditary cancer predisposition. The ATM-CHEK2-p53 axis has been documented as a backbone for DDR and hypothesized as a barrier against cancer initiation. However, although CHK2 kinase coded by the CHEK2 gene expedites the DDR signal, its function in activation of p53-dependent cell cycle arrest is dispensable. CHEK2 mutations rank among the most frequent germline alterations revealed by germline genetic testing for various hereditary cancer predispositions, but their interpretation is not trivial. From the perspective of interpretation of germline CHEK2 variants, we review the current knowledge related to the structure of the CHEK2 gene, the function of CHK2 kinase, and the clinical significance of CHEK2 germline mutations in patients with hereditary breast, prostate, kidney, thyroid, and colon cancers.

• MeSH
• checkpoint kinasa 2 chemie   genetika   metabolismus   MeSH
• genetická predispozice k nemoci * MeSH
• lidé MeSH
• mutační rychlost MeSH
• nádory enzymologie   genetika   MeSH
• substrátová specifita MeSH
• zárodečné mutace genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

OBJECTIVES: This study aimed to retrospectively assess using computed tomography pulmonary angiography (CTPA) for predicting residual pulmonary hypertension (RPH) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy (PEA). METHODS: We retrospectively analyzed data of 131 patients with CTEPH who underwent PEA in our center (2008-2015). We measured several diameters of the pulmonary artery and thoracic aorta preoperatively. We evaluated the relationship between these measurements (and their indices) and signs of RPH represented by pulmonary artery systolic pressure (PASP) estimated by echocardiography. RESULTS: Significant correlations were observed between the aortopulmonary index and prediction of any residual hypertension and moderate/severe hypertension 1 year after PEA, and any residual hypertension and severe hypertension 2 years after PEA. The aortopulmonary index was significantly related to a reduction in PASP 1 year after the operation. A lower aortopulmonary index (≤0.88 for the ascending aorta and ≤0.64 for the descending aorta) predicted lower RPH. CONCLUSIONS: Preoperative CTPA parameters can be used to assess the risk of RPH after PEA. The aortopulmonary index has significant predictive value for RPH and a reduction in PASP after PEA. Lower values of the aortopulmonary index suggest a better outcome after PEA.

• MeSH
• angiografie MeSH
• arteria pulmonalis diagnostické zobrazování   chirurgie   MeSH
• chronická nemoc MeSH
• endarterektomie MeSH
• lidé MeSH
• plicní embolie * diagnostické zobrazování   chirurgie   MeSH
• plicní hypertenze * diagnostické zobrazování   chirurgie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Movement sequencing difficulties are part of the neurological soft signs (NSS), they have high clinical value because they are not always present in schizophrenia. We investigated the neuronal correlates of movement sequencing in 24 healthy controls and 24 schizophrenia patients, with (SZP SQ+) or without (SZP SQ-) sequencing difficulties. We characterized simultaneous and lagged functional connectivity between brain regions involved in movement sequencing using psychophysiological interaction (PPI) and the Granger causality modeling (GCM), respectively. Left premotor cortex (PMC) and superior parietal lobule (SPL) were specifically activated during sequential movements in all participants. Right PMC and precuneus, ipsilateral to the hand executing the task, activated during sequential movements only in healthy controls and SZP SQ-. SZP SQ+ showed hyperactivation in contralateral PMC, as compared to the other groups. PPI analysis revealed a deficit in inhibitory connections within this fronto-parietal network in SZP SQ+ during sequential task. GCM showed a significant lagged effective connectivity from right PMC to left SPL during task and rest periods in all groups and from right PMC to right precuneus in SZP SQ+ group only. Both SZP groups had a significant lagged connectivity from right to left PMC, during sequential task. Our results indicate that aberrant fronto-parietal network connectivity with cortical inhibition deficit and abnormal reliance on previous network activity are related to movement sequencing in SZP. The overactivation of motor cortex seems to be a good compensating strategy, the hyperactivation of parietal cortex is linked to motor deficit symptoms.

• MeSH
• dospělí MeSH
• funkční lateralita MeSH
• lidé MeSH
• lineární modely MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku * MeSH
• mladý dospělý MeSH
• mozek MeSH
• nervové dráhy MeSH
• počítačové zpracování obrazu MeSH
• pohybové poruchy etiologie   patologie   MeSH
• progrese nemoci MeSH
• psychomotorický výkon fyziologie   MeSH
• psychosomatické poruchy etiologie   MeSH
• schizofrenie komplikace   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• lidé MeSH
• nádory vaječníků * genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Renal cell carcinoma (RCC) is one of the most prevalent cancers in kidney transplant recipients (KTR). The hereditary background of RCC in native kidneys has been determined, implicating its clinical importance. MATERIALS AND METHODS: This retrospective single-center pilot study aimed to identify a potential genetic predisposition to RCC of the transplanted kidney and outcome in KTR who underwent single kidney transplantation between January 2000 and December 2020 and manifested RCC of the transplanted kidney. Next-generation sequencing (NGS) based germline genetic analysis from peripheral blood-derived genomic DNA (gDNA) was performed in both the recipient and donor using a gene panel targeting 226 cancer predisposition genes. RESULTS: The calculated incidence of RCC of the transplanted kidney among 4146 KTR was 0.43%. In fifteen KTR and donors, NGS was performed. The mean KTR age at transplantation and the diagnosis of RCC was 50.3 years (median 54; 5-67 years) and 66 years (median 66; 24-79 years), respectively. The mean donor age at transplantation and graft age at RCC diagnosis was 39.7 years (median 42; 7-68 years) and 50.2 years (median 46; 20-83 years), respectively. The mean follow-up after RCC diagnosis was 47 months (median 39.1; 0-112 months). Papillary RCC was the most prevalent (n = 8), followed by clear cell RCC (n = 6) and unspecified RCC (n = 1). Thirteen RCCs were low-stage (pT1a/b) diseases, one was pT3, and one was of unknown stage. Most RCC was higher graded. No germline pathogenic cancer-predisposition variant was found in either KTR or donors except for several variants of uncertain significance. CONCLUSION: RCC of the transplanted kidney is very rare. Germline cancer-predisposition testing has identified several variants of uncertain significance, but no germline genetic predisposition to graft RCC in KTR. Further research is needed to assess the clinical relevance of genetic testing for cancer risk in KTR.

• MeSH
• dárci tkání MeSH
• dítě MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• karcinom z renálních buněk * genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory ledvin * genetika   MeSH
• pilotní projekty MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Alternative pre-mRNA splicing increases transcriptome plasticity by forming naturally-occurring alternative splicing variants (ASVs). Alterations of splicing processes, caused by DNA mutations, result in aberrant splicing and the formation of aberrant mRNA isoforms. Analyses of hereditary cancer predisposition genes reveal many DNA variants with unknown clinical significance (VUS) that potentially affect pre-mRNA splicing. Therefore, a comprehensive description of ASVs is an essential prerequisite for the interpretation of germline VUS in high-risk individuals. To identify ASVs in a gene of interest, we have proposed an approach based on multiplex PCR (mPCR) amplification of all theoretically possible exon-exon junctions and subsequent characterization of size-selected and pooled mPCR products by next-generation sequencing (NGS). The efficiency of this method is illustrated by a comprehensive analysis of BRCA1 ASVs in human leukocytes, normal mammary, and adipose tissues and stable cell lines. We revealed 94 BRCA1 ASVs, including 29 variants present in all tested samples. While differences in the qualitative expression of BRCA1 ASVs among the analyzed human tissues were minor, larger differences were detected between tissue and cell line samples. Compared with other ASV analysis methods, this approach represents a highly sensitive and rapid alternative for the identification of ASVs in any gene of interest.

• MeSH
• alternativní sestřih * MeSH
• izoformy RNA MeSH
• lidé MeSH
• multiplexová polymerázová řetězová reakce metody   MeSH
• mutace * MeSH
• nádory prsu genetika   MeSH
• protein BRCA1 genetika   MeSH
• výpočetní biologie MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Cutaneous melanoma is the deadliest skin malignity with a rising prevalence worldwide. Patients carrying germline mutations in melanoma-susceptibility genes face an increased risk of melanoma and other cancers. To assess the spectrum of germline variants, we analyzed 264 Czech melanoma patients indicated for testing due to early melanoma (at <25 years) or the presence of multiple primary melanoma/melanoma and other cancer in their personal and/or family history. All patients were analyzed by panel next-generation sequencing targeting 217 genes in four groups: high-to-moderate melanoma risk genes, low melanoma risk genes, cancer syndrome genes, and other genes with an uncertain melanoma risk. Population frequencies were assessed in 1479 population-matched controls. Selected POT1 and CHEK2 variants were characterized by functional assays. Mutations in clinically relevant genes were significantly more frequent in melanoma patients than in controls (31/264; 11.7% vs. 58/1479; 3.9%; p = 2.0 × 10-6). A total of 9 patients (3.4%) carried mutations in high-to-moderate melanoma risk genes (CDKN2A, POT1, ACD) and 22 (8.3%) patients in other cancer syndrome genes (NBN, BRCA1/2, CHEK2, ATM, WRN, RB1). Mutations in high-to-moderate melanoma risk genes (OR = 52.2; 95%CI 6.6-413.1; p = 3.2 × 10-7) and in other cancer syndrome genes (OR = 2.3; 95%CI 1.4-3.8; p = 0.003) were significantly associated with melanoma risk. We found an increased potential to carry these mutations (OR = 2.9; 95%CI 1.2-6.8) in patients with double primary melanoma, melanoma and other primary cancer, but not in patients with early age at onset. The analysis revealed affected genes in Czech melanoma patients and identified individuals who may benefit from genetic testing and future surveillance management of mutation carriers.

• Publikační typ
• časopisecké články MeSH