PURPOSE: Missense de novo variants in CACNA1G, which encodes the Cav3.1 T-type calcium channel, have been associated with a severe, early-onset form of cerebellar disorder with neurodevelopmental deficits (SCA42ND). We explored a large series of pediatric cases carrying heterozygous variants in CACNA1G to further characterize genotype-phenotype correlations in SCA42ND. METHODS: We describe 19 patients with congenital CACNA1G-variants, including 6 new heterozygotes of the recurrent SCA42ND variants, p.(Ala961Thr) and p.(Met1531Val), and 8 unreported variants, including 7 missense variants, mainly de novo. We carried out genetic and structural analyses of all variants. Patch-clamp recordings were performed to measure their channel activity. RESULTS: We provide a consolidated clinical description for the patients carrying p.(Ala961Thr) and p.(Met1531Val). The new variants associated with the more severe phenotypes are found in the Cav3.1 channel intracellular gate. Calcium currents of these Cav3.1 variants showed slow inactivation and deactivation kinetics and an increase in window current, supporting a gain of channel activity. On the contrary, the p.(Met197Arg) variant (IS4-S5 loop) resulted in a loss of channel activity. CONCLUSION: This detailed description of several de novo missense pathogenic variants in CACNA1G, including 13 previously reported cases, supports a clinical spectrum of congenital CACNA1G syndrome beyond spinocerebellar ataxia.

• MeSH
• dítě MeSH
• fenotyp * MeSH
• genetické asociační studie MeSH
• heterozygot MeSH
• kojenec MeSH
• lidé MeSH
• missense mutace * genetika   MeSH
• mladiství MeSH
• neurovývojové poruchy * genetika   patologie   MeSH
• předškolní dítě MeSH
• vápníkové kanály - typ T * genetika   metabolismus   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Several studies have demonstrated the positive effects of mindfulness and self-compassion on employee well-being, mental health, and resilience. The objective of this observational study was to explore the mutual relationships among the dimensions of self-compassion and particular characteristics of work-related well-being: work engagement, workaholism (excessive and compulsive work), and job boredom in a population of early career workers. In this quantitative cross-sectional study, 286 master's students with proper working experience were examined; results from 244 respondents were suitable for further data analysis. The Self-compassion Scale, Utrecht Work Engagement Scale, Dutch Work Addiction Scale, and Dutch Boredom Scale were administered. Spearman's rank correlation analysis found a positive relationship between work engagement and excessive work and a negative relationship between work engagement and job boredom. Furthermore, a positive correlation was identified between compulsive work and negative subscales of the Self-compassion Scale. Structural equation modeling indicated that workaholism was a mediator between the negative scales of self-compassion and work engagement with job boredom. In conclusion, the negative aspects of self-compassion (isolation, self-judgment, and over-identification) are related to the symptoms of workaholism in young workers. Self-compassion-based interventions could help prevent the negative effects of compulsive and excessive work. Possible age-related explanations for the positive relationship between work engagement and workaholism (i.e., excessive work) are discussed. Future longitudinal research could identify the dynamics of the connection between self-compassion and work-related well-being from a long-term perspective.

• Publikační typ
• časopisecké články MeSH

Penile squamous cell carcinoma (pSCC) represents an uncommon malignancy characterized by stagnant mortality, psychosexual distress, and a highly variable prognosis. Currently, the World Health Organization distinguishes between human papillomavirus (HPV)-related and HPV-independent pSCC. Recently, there has been an evolving line of research documenting the enrichment of HPV-independent pSCC with a high tumor mutational burden (TMB) and programmed death ligand-1 expression, as well as clusters of genes associated with HPV status. In this study, we conducted comprehensive next-generation sequencing DNA profiling of 146 pSCC samples using a panel consisting of 355 genes associated with tumors. This profiling was correlated with immunohistochemical markers and prognostic clinical data. A survival analysis of recurrent genomic events (found in ≥10 cases) was performed. TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR alterations were associated with significantly shortened overall survival in univariate and multivariate analysis. HPV positivity, diagnosed through both p16 immunohistochemistry and HPV DNA analysis, displayed no impact on survival but was associated with high-grade, lymphatic invasion, programmed death ligand-1 negativity/weak expression, and low TMB. FAT1, TP53, CDKN2A, CASP8, and HRAS were more often mutated in HPV-independent pSCC. In contrast, HPV-associated pSCCs were enriched by EPHA7, ATM, GRIN2A, and CHEK1 mutations. PIK3CA, FAT1, FBXW7, and KMT2D mutations were associated with high TMB. NOTCH1, TP53, CDKN2A, POT1, KMT2D, ATM, CHEK1, EPHA3, and EGFR alterations were related to adverse clinicopathologic signs, such as advanced stage, high tumor budding, and lymphovascular invasion. We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination repair pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular pathologic, clinical, and prognostic analysis correlating with prognosis.

• MeSH
• ATM protein genetika   MeSH
• dospělí MeSH
• erbB receptory genetika   MeSH
• infekce papilomavirem MeSH
• inhibitor p16 cyklin-dependentní kinasy genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory penisu * genetika   mortalita   patologie   virologie   MeSH
• prognóza MeSH
• proteiny vázající telomery MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• shelterinový komplex MeSH
• spinocelulární karcinom * genetika   mortalita   patologie   virologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: This study aimed to evaluate local control (LC) of tumors, patient overall survival (OS), and the safety of stereotactic radiosurgery (SRS) for esophageal cancer brain metastases (EBMs). METHODS: This retrospective cohort study used data from 15 International Radiosurgery Research Foundation facilities encompassing 67 patients with 185 EBMs managed using SRS between January 2000 and May 2022. The median patient age was 63 years, with a male predominance (92.5%). Most patients (64.2%) had a single brain metastasis, while 7.5% had more than 5 metastases. The median tumor volume was 0.9 cm3, and the median margin dose delivered to the tumor was 20 Gy. RESULTS: The median OS post-SRS was 15.2 months, with 1- and 2-year OS rates of 65.7% and 32.3%, respectively. A significant inverse correlation was found between the number of EBMs and OS in the univariable analysis. LC rates at 1 and 2 years were 89% and 76%, respectively. Adverse radiation effects (AREs) were observed in 17.9% of patients, with 13.4% being mild and transient and 4.5% severely symptomatic (Common Terminology Criteria for Adverse Events grade 3). New intracranial disease developed in 58.2% of patients, with 1- and 2-year rates of 58% and 73%, respectively. CONCLUSIONS: SRS for EBMs demonstrated high survival rates and effective tumor control, with a low incidence of severe AREs. These findings highlight the potential role of SRS in the multidisciplinary multimodality management paradigm of EBM.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory jícnu * patologie   mortalita   MeSH
• nádory mozku * sekundární   radioterapie   mortalita   MeSH
• radiochirurgie * metody   škodlivé účinky   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Cardiac involvement (CI) in phosphomannomutase 2-congenital disorders of glycosylation (PMM2-CDG) is part of the multisystemic presentation contributing to high mortality rates. The most common cardiac manifestations are pericardial effusion, cardiomyopathy, and structural heart defects. A genotype-phenotype correlation with organ involvement has not yet been described. We analyzed clinical, biochemical, and molecular genetic data of 222 patients from eight European centers and characterized the natural course of patients with CI. Fifty-seven patients (45 children) presented with CI, of whom 24 died (median age 21 months, standard deviation 49.8). Pericardial effusion was the most frequent manifestation (55.4%), occurring mostly within the first 6 months of life. The most common pathogenic variants in patients with CI were p.(Arg141His) in 74%, followed by p.(Val231Met) in 36%, which is 3.5 times higher than in PMM2-CDG patients without CI (p < 0.0001). Twenty-one out of 36 patients with p.(Val231Met) had CI; among them, 15 died, compared to 33 out of 166 patients without p.(Val231Met) who had CI (p < 0.0001). Nine out of 33 patients died (p = 0.0015), indicating greater clinical severity. Furthermore, the p.(Val231Met) variant is predominant in Eastern Europe, suggesting a founder effect. Cardiac complications in PMM2-CDG patients are common and serious. The variant p.(Val231Met) profoundly influences the extent of CI and mortality rates. Therefore, we recommend cardiac surveillance be included in the follow-up protocols for PMM2-CDG.

• MeSH
• dítě MeSH
• fenotyp * MeSH
• fosfotransferasy (fosfomutasy) * genetika   nedostatek   MeSH
• genetické asociační studie MeSH
• kardiomyopatie genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mutace MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• stupeň závažnosti nemoci MeSH
• vrozené poruchy glykosylace * genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: The current requirement is to establish the preoperative diagnosis accurately as possible and to achieve an adequate extent of surgery. The aim of this study was to define the preoperative clinical and molecular genetic risks of malignancy in indeterminate thyroid nodules (Bethesda III and IV) and to determine their impact on the surgical strategy. METHODS: Prospectively retrospective analysis of 287 patients provided the basis of preoperative laboratory examination, sonographic stratification of malignancy risks and cytological findings. Molecular tests focused on pathogenic variants of genes associated with thyroid oncogenesis in cytologically indeterminate nodules (Bethesda III and IV). The evaluation included clinical risk factors: positive family history, radiation exposure and growth in size and/or number of nodules. RESULTS: Preoperative FNAB detected 52 cytologically indeterminate nodules (28.7%) out of 181 patients. Postoperative histopathological examination revealed malignancy in 12 cases (23.7%) and there was no significant difference between Bethesda III and IV categories (P=0.517). Clinical risk factors for malignancy were found in 32 patients (61.5%) and the presence of at least one of them resulted in a clearly higher incidence of malignancy than their absence (31.3% vs. 10.0%, respectively). Pathogenic variants of genes were detected in 12/49 patients in Bethesda III and IV, and in 4 cases (33.3%) thyroid carcinoma was revealed. The rate of malignancies was substantially higher in patients with pathogenic variants than in those without (33.3% vs. 16.2%, respectively). CONCLUSIONS: Our experience implies that molecular genetic testing is one of several decision factors. We will continue to monitor and enlarge our patient cohort to obtain long-term follow-up data.

• MeSH
• dospělí MeSH
• genetické testování MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory štítné žlázy * genetika   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• tenkojehlová biopsie MeSH
• uzly štítné žlázy * genetika   patologie   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: Plantar fasciitis (PF) is one of the most common running-related injuries. PURPOSE: The aim of this prospective study was to determine the incidence of PF and identify potential risk or protective factors for PF in runners and non-runners. METHODS: Data from 1206 participants from the 4HAIE cohort study (563 females/643 males; 715 runners/491 non-runners; 18-65 yr of age) were included in the analysis. We collected biomechanical data during overground running using a three-dimensional motion capture system at the baseline and running distance data via retrospective questionnaires and followed the participants for 12 months following the baseline data collection. Participants were asked weekly about any sports-related injury (including PF). A binary logistic regression was performed to reveal potential associations between running distance and biomechanical risk factors and PF while controlling for running distance, sex, and age. RESULTS: The total incidence of PF was 2.3% (28 PF from 1206 participants), 2.5% in runners and 2.0% in non-runners ( P = 0.248). Runners who ran more than 40 km·wk -1 had six times higher odds of suffering PF than individuals who ran 6-20 km·wk -1 ( P = 0.009). There was a significant association between maximal ankle adduction and PF; that is, runners with a lower abduction angle during the stance period had higher risk of PF ( P = 0.024). No other biomechanical variables indicated significant associations with PF. CONCLUSIONS: Regular running with a moderate weekly volume and more toeing out of the foot relative to the shank may reduce the risk against PF in runners, which may be useful for researchers, runners, coaches, and health professionals to minimize PF injury risk.

• MeSH
• běh * fyziologie   zranění   MeSH
• biomechanika MeSH
• dospělí MeSH
• fasciitida plantární * epidemiologie   patofyziologie   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE AND BACKGROUND: The 10-item Edinburgh Postnatal Depression Scale (EPDS) is a widely-used screening measure for postnatal depression. Factor analysis studies have suggested an embedded sub-scale could be used for screening for anxiety disorders. The current investigation sought to replicate and extend a recent study supporting this assertion. METHODS: A cross-sectional design. EPDS data were collected at up to two years postpartum. Confirmatory factor analysis, correlational and distributional characteristics of the measure were examined. Participants were a large sample (N = 985) of postpartum women in the Czech Republic. RESULTS: Factor structure findings substantially replicated the models evaluated by Della Vedova et al. (2022). Bifactor models, however, offered a better fit to data. A general factor of depression explained most of the variance in data in most models compared to embedded sub-scales across models. CONCLUSION: The model proposed by Della Vedova et al. (2022) offered an excellent fit to data. However, the findings from the bifactor modelling suggest the dominance of a general factor of depression which indicates the potential application of an embedded anxiety sub-scale for screening may be overstated.

• MeSH
• dospělí MeSH
• faktorová analýza statistická MeSH
• lidé MeSH
• mladý dospělý MeSH
• poporodní deprese * diagnóza   psychologie   MeSH
• průřezové studie MeSH
• psychiatrické posuzovací škály * normy   MeSH
• psychometrie MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVES: This study aims to identify factors possibly contributing to complications in children with acute leukaemia. Despite diverse etiological causes, similar processes trigger the process of cell malignancy. Genomic instability has received considerable attention in this context. METHOD: We conducted chromosomal analysis of bone marrow cells and measured the micronuclei (Mn) level in buccal cells over time. Statistical reliability assessment was performed using Analysis of variance (ANOVA), and the data were analyzed and visualized using the SPSS 12 statistical analysis software package. RESULTS: On the 15th day of treatment, our findings confirmed a statistically significant correlation (χ2=3.88, P=0.04) between the number of blasts in the bone marrow and unfavourable outcome in patients with a near-tetraploid chromosome clone. Additionally, on the 33rd day of treatment, we observed a correlation between an elevated number of Mn and relapses. DISCUSSION: While it is commonly believed that a hyperdiploid clone with >50 chromosomes in childhood acute lymphoblastic leukaemia confers favorable outcome, our study revealed partially heterogeneous results and poor prognosis in patients with a near-tetraploid clone. We have also identified a correlation between the Mn level on the 33rd day of treatment and the development of complications. It is possible that the increased Mn values and the occurrence of relapses were influenced by the individual patient's sensitivity to the genotoxic effect of the medication.

• MeSH
• akutní lymfatická leukemie * genetika   MeSH
• buňky kostní dřeně patologie   MeSH
• dítě MeSH
• lidé MeSH
• mikrojaderné testy MeSH
• mikrojádra chromozomálně defektní * MeSH
• mladiství MeSH
• předškolní dítě MeSH
• prognóza MeSH
• tetraploidie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Postoperative nausea and vomiting (PONV) in pediatric patients is a common and clinically significant postoperative complication. The incidence of PONV has not been extensively studied in large pediatric cohorts. Furthermore, in 2020, the Fourth Consensus Guidelines for the management of PONV were published. However, the association between perioperative factors and adherence to these guidelines remains unclear. This study aims to assess both the incidence of PONV and guideline adherence within a large and diverse pediatric population. METHODS: We conducted a retrospective observational study at a large tertiary medical center, including pediatric patients (≤18 years) who underwent surgery between September 2020 and March 2023. We conducted a retrospective analysis of data from our electronic health records, focusing on patient demographics, surgical details, anesthesia details, and prophylaxis for PONV. We calculated the incidence of PONV and used multivariable logistic regression to identify the predictors of guideline adherence. RESULTS: The cohort included 3772 patients with a median (interquartile range [IQR]) age of 9.21 (3.55-14.68) years. The incidence (95% confidence intervals) of early PONV was 1.0% (0.7-1.4) and 3.8% (3.2-4.5) for delayed PONV. Adherence to the fourth consensus guidelines for PONV management was observed in 32.5% (31.0-34.0) of cases. A high risk of PONV was identified in 55.9% (54.3-57.5) of the patients. The most common number of PONV risk factors was 3, observed in 1151 patients (30.5% [29.1-32.0]). Significant predictors of guideline adherence included the intraoperative use of long-acting opioids (odds ratio [OR], 2.711, P < .001) and age ≥3 years (OR, 2.074, P < .001). Nonadherence was associated with a higher incidence of PONV at 24 hours postsurgery (4.4% (3.6-5.2) vs 2.7% (1.9-3.8), P = .012). Factors such as specific high PONV risk surgeries ( P = .001), maintenance with inhalational agents solely ( P = .017), and neostigmine use ( P < .001) were also all statistically significant. CONCLUSIONS: Our study revealed a lower-than-expected incidence of PONV in pediatric patients, highlighting the need for standardized definitions and improved reporting. Adherence to PONV guidelines was suboptimal, emphasizing the need for better implementation strategies.

• MeSH
• antiemetika terapeutické užití   MeSH
• dítě MeSH
• dodržování směrnic * normy   MeSH
• incidence MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• pooperační nevolnost a zvracení * epidemiologie   diagnóza   prevence a kontrola   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• směrnice pro lékařskou praxi jako téma normy   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH