Although our knowledge regarding oocyte quality and development has improved significantly, the molecular mechanisms that regulate and determine oocyte developmental competence are still unclear. Therefore, the objective of this study was to identify and analyze the transcriptome profiles of porcine oocytes derived from large or small follicles using RNA high-throughput sequencing technology. RNA libraries were constructed from oocytes of large (LO; 3-6 mm) or small (SO; 1.5-1.9 mm) ovarian follicles and then sequenced in an Illumina HiSeq4000. Transcriptome analysis showed a total of 14,557 genes were commonly detected in both oocyte groups. Genes related to the cell cycle, oocyte meiosis, and quality were among the top highly expressed genes in both groups. Differential expression analysis revealed 60 up- and 262 downregulated genes in the LO compared with the SO group. BRCA2, GPLD1, ZP3, ND3, and ND4L were among the highly abundant and highly significant differentially expressed genes (DEGs). The ontological classification of DEGs indicated that protein processing in endoplasmic reticulum was the top enriched pathway. In addition, biological processes related to cell growth and signaling, gene expression regulations, cytoskeleton, and extracellular matrix organization were among the highly enriched processes. In conclusion, this study provides new insights into the global transcriptome changes and the abundance of specific transcripts in porcine oocytes in correlation with follicle size.

• MeSH
• Gene Regulatory Networks physiology   MeSH
• Oocytes metabolism   MeSH
• Oogenesis genetics   MeSH
• Ovarian Follicle cytology   MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Swine genetics   growth & development   MeSH
• Signal Transduction genetics   MeSH
• Gene Expression Profiling MeSH
• Transcriptome * MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Gene Expression Regulation, Developmental physiology   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Aims: the presented study is aimed at the evaluation of correlation of free light chains serum levels – kappa, lambdaand their relation (K/L ratio) and serum levels of selected biological markers in a group of patients with multiplemyeloma examined at the time of the diagnosis. Methods: 102 patients with multiple myeloma were included in this prospective study. Free light chains serumlevels were determined by FreeliteTM Binding Site system, for determination of serum levels of selected parameters thefollowing methods were used: REA thymidinekinase (TK), RIA (ß2microglobulin (ß2m), ICTP, PINP), enzymoimmunoassay(sIL-6R, sVCAM-1, sICAM-1, sOPG) and quantitative enzymatic immunoassay (sHGF, sVEGF, sSyndecan-1(sSyn-1) a sFas). Results: There was found a correlation in the kappa-group of the dominant kappa chain and serum readings of ß2m(r = 0.344, p = 0.005), TK (r = 0.263, p = 0.035), ICTP (r = 0.402, p = 0.001), PINP (r = 0.264, p = 0.039), sOPG (r =0.328, p = 0.028), sSyn-1 (r = 0.255, p = 0.046) and sFas (r = 0.418, p = 0.001). In case of K/L ratio there was found astatistically signifi cant association of levels of ß2m (r = 0.316, p = 0.01), TK (r = 0.274, p = 0.027), ICTP (r = 0.346, p =0.006), PINP (r = 0.261, p = 0.042), sSyn-1 (r = 0.283, p = 0.026) and sFas (r = 0.377, p = 0.002). In the lambda-groupthe analysis confi rmed mutual dependence of the dominant lambda chain levels on ß2m (r = 0.476, p = 0.003), ICTP(r = 0.375, p = 0.022), sVCAM-1 (r = 0.383, p = 0.019), sHGF (r = 0.441, p = 0.006) and sFas (r = 0.334, p = 0.040).In addition we ascertained a correlation of L/K ratio and levels of ß2m (r = –0.473, p = 0.003), TK (r = –0.412, p =0.011), ICTP (r = –0.331, p = 0.045), PINP (r = –0.409, p = 0.012), sHGF (r = –0.357, p = 0.028), sSyn-1 (r = –0.449,p = 0.005) a sFas (r = – 0.371, p = 0.022). Conclusions: The study confi rmed mutual correlation of FLC serum levels and the levels of several selected biologicalmarkers, in particular ß2m, TK, ICTP, PINP, sSyn-1 a sFas at time of the diagnosis. It referred to the mutualrelation of bone marrow microenvironment, biological qualities of clonal plasmocytes and the intensity of the freelight chains production by the tumour cell population.

• MeSH
• Biomarkers blood   MeSH
• Diagnosis, Differential MeSH
• Financing, Organized MeSH
• Immunoassay methods   utilization   MeSH
• Immunoenzyme Techniques methods   utilization   MeSH
• Immunoglobulin kappa-Chains isolation & purification   MeSH
• Immunoglobulin lambda-Chains isolation & purification   MeSH
• Immunoglobulin Light Chains isolation & purification   MeSH
• Humans MeSH
• Multiple Myeloma diagnosis   etiology   MeSH
• Monoclonal Gammopathy of Undetermined Significance diagnosis   MeSH
• Disease Progression MeSH
• Prospective Studies MeSH
• Radioimmunoassay methods   utilization   MeSH
• Statistics as Topic MeSH
• Check Tag
• Humans MeSH

Cíl: Moderní zdravotnictví interaktivně zapojuje pacienta do léčebného procesu. Se zaváděním nových medicínských a ošetřovatelských postupů je nutné věnovat dostatek času edukaci pacientů. Dobře zvládnutý edukační proces je přínosem pro pacienta i ošetřující personál a může snížit možné komplikace zdravotní péče. Cílem práce je zhodnocení vlivu metody edukace na incidenci komplikací čisté intermitentní katetrizace (ČIK) u pacientů po spinálním poranění. Metodika: Provedli jsme prospektivní randomizovanou studii. Soubor tvořilo 53 pacientů s neurogenní dysfunkcí močení po spinálním traumatu, u kterých bylo indikované vyprazdňování moči technikou čisté intermitentní katetrizace. Po randomizaci jsme pacienty eduko-vali v ČIK. V první skupině byla provedena edukace s použitím vytvořeného obrazového materiálu, ve druhé skupině standardní metodou - verbálně. Ve studii jsme sledovali dobu do výskytu první močové infekce, dobu do výskytu asymptomatické bakteriurie, celkovou dobu trvání močové infekce ve studii a výskyt poranění uretry Pacientům jsme během studie v pravidelných týdenních intervalech prováděli kultivační vyšetření moči a pacienti si vedli mikční deník. Výsledky: Ve skupině pacientů s obrazovou edukací byla signifikantně delší doba do první epizody močové infekce, než u pacientů s verbální edukací (p < 0,000). Při vyhodnocení doby do výskytu asymptomatické bakteriurie a době trvání močové infekce ve studii jsme statisticky signifikantní rozdíl mezi oběma skupinami neprokázali. Zaznamenali jsme jedno poranění uretry u skupiny pacientů s obrazovou edukací. Závěr: Ve studii jsme prokázali, že obrazová edukace intermitentní katetrizace vede na 5% hladině významnosti ke statisticky signifikantnímu prodloužení doby do vzniku první močové infekce. Při porovnání ostatních sledovaných parametrů jsme neprokázali statisticky signifikantní rozdíl v době, kdy dochází k výskytu asymptomatické bakteriurie a době trvání močové infekce.

Aim: Modern health care relies on the involvement of the patient in the treatment process. Implementation of new medical and nursing practices necessitates that sufficient time is devoted to patient education. Well managed educational process is beneficial for both the patients and their caregivers and may lead to a reduction in the incidence of treatment-induced complications. The aim of this study was to evaluate the effect of the method of education on the incidence of complications associated with clean intermittent catheterization (CIC) in patients after spinal injury. Methods: This is a prospective randomized study. The study group consisted of 53 patients with neurogenic voiding dysfunction after spinal trauma, in whom bladder emptying using CIC was indicated. Following randomization, the patients in the first group were educated in CIC using a detailed demonstration with pictures. The second group was instructed using the standard method of education - verbal instruction. In addition to a voiding diary, weekly urine culture was performed in patients in both study groups. We monitored the time to the first occurrence of urinary tract infection, time to the occurrence of asymptomatic bac-teriuria, the total duration of urinary tract infection and the incidence of urethral injury. Results: In the group of patients with the detailed picture education, the time to first episode of urinary infection was significantly longer than in patients who received verbal education (p < 0.000). We did not find a statistically significant difference between the two groups in the time to onset of asymptomatic bacteriuria and total duration of urinary tract infection. One urethral injury occurred in the picture education group. Conclusions: We have demonstrated that detailed education, using pictures, leads to a significant increase in the time to the first occurrence of urinary infection. We did not find a statistically significant difference in the time of onset of asymptomatic bacteriuria or in total duration of urinary tract infection.

• MeSH
• Cystitis prevention & control   MeSH
• Adult MeSH
• Urinary Tract Infections prevention & control   MeSH
• Intermittent Urethral Catheterization * adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Urinary Bladder, Neurogenic nursing   MeSH
• Spinal Injuries MeSH
• Prospective Studies MeSH
• Aged MeSH
• Statistics as Topic MeSH
• Patient Education as Topic * methods   statistics & numerical data   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Aged MeSH

Distal hereditary motor neuropathy (HMN) is a clinically and genetically heterogeneous group of disorders affecting spinal alpha-motor neurons. Since 2001, mutations in six different genes have been identified for autosomal dominant distal HMN; glycyl-tRNA synthetase (GARS), dynactin 1 (DCTN1), small heat shock 27 kDa protein 1 (HSPB1), small heat shock 22 kDa protein 8 (HSPB8), Berardinelli-Seip congenital lipodystrophy (BSCL2) and senataxin (SETX). In addition a mutation in the (VAMP)-associated protein B and C (VAPB) was found in several Brazilian families with complex and atypical forms of autosomal dominantly inherited motor neuron disease. We have investigated the distribution of mutations in these seven genes in a cohort of 112 familial and isolated patients with a diagnosis of distal motor neuropathy and found nine different disease-causing mutations in HSPB8, HSPB1, BSCL2 and SETX in 17 patients of whom 10 have been previously reported. No mutations were found in GARS, DCTN1 and VAPB. The phenotypic features of patients with mutations in HSPB8, HSPB1, BSCL2 and SETX fit within the distal HMN classification, with only one exception; a C-terminal HSPB1-mutation was associated with upper motor neuron signs. Furthermore, we provide evidence for a genetic mosaicism in transmitting an HSPB1 mutation. This study, performed in a large cohort of familial and isolated distal HMN patients, clearly confirms the genetic and phenotypic heterogeneity of distal HMN and provides a basis for the development of algorithms for diagnostic mutation screening in this group of disorders.

• MeSH
• Electrophysiology MeSH
• Phenotype MeSH
• Genotype MeSH
• Haplotypes MeSH
• Hereditary Sensory and Motor Neuropathy * genetics   physiopathology   MeSH
• Humans MeSH
• Chromosomes, Human, Pair 11 genetics   MeSH
• Mutation, Missense * MeSH
• Mosaicism MeSH
• Neoplasm Proteins genetics   MeSH
• Protein Serine-Threonine Kinases genetics   MeSH
• HSP27 Heat-Shock Proteins MeSH
• Heat-Shock Proteins genetics   MeSH
• GTP-Binding Protein gamma Subunits genetics   MeSH
• RNA Helicases genetics   MeSH
• Pedigree MeSH
• Base Sequence MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Cieľ. Cieľom štúdie bolo overiť faktorovú štruktúru, reliabilitu a validitu slovenskej verzie dotazníka EPOCH na meranie well-beingu u adolescentov. Dotazník vychádza z teoretickej koncepcie optimálneho prospievania Seligmana a meria päť pozitívnych indikátorov (zaujatie činnosťou, vytrvalosť, optimizmus, zapojenie do vzťahov, šťastie), ktoré môžu predikovať optimálne prospievanie v dospelosti. Vzorka a metódy. Faktorová validita a reliabilta bola testovaná na súbore 1009 respondentov (M = 16,79, SD = 2,10) a na čiastkových súboroch chlapcov a dievčat a respondentov v ranej + strednej a neskorej adolescencii. Validita bola testovaná na štyroch podsúboroch získaných postupne v priebehu jedného akademického roka ako súčasť riešenia čiastkových cieľov výskumného projektu. Štatistické analýzy. Na overenie faktorovej štruktúry bola realizovaná konfirmačná faktorová analýza (WLSVM), na overenie reliability bol vypočítaný Cronbachov koeficient alfa a Pearsonov koeficient na koreláciu meraní s 6-mesačným odstupom, rovnako na testovanie konvergentnej a divergentnej validity. Výsledky. Zistenia ukázali vysokú validitu a reliabilitu slovenskej verzie dotazníka EPOCH na vzorke žiakov základných, stredných a vysokých škôl. Výsledky podporili 5-faktorovú štruktúru metodiky navrhovanú autormi, ktorá platí rovnako u oboch pohlaví aj u vekových skupín. Limity. Zistenia je potrebné ďalej overiť na reprezentatívnej vzorke žiakov ZŠ, ŠS a VŠ, rovnako ako prediktívnu validitu metodiky.

Objectives. The aim of the study was to verify factor structure, reliability and validity of the Slovak version of the EPOCH measure of adolescent well-being. The questionnaire is grounded in Seligman´s theory of human flourishing and assesses 5 positive psychological characteristics (Engagement, Perseverance, Optimism, Connectedness, and Happiness) that might foster optimal functioning in adulthood. Sample and settings. Factorial validity and reliability was evaluated within the sample of 1009 respondents (M=16.79, SD=2.10) and also in partial samples of boys and girls and respondents in early+middle and late adolescence. Validity was tested in four partial samples, gathered during one academic year as a part of a research project. Statistical analysis. To verify factor structure the confirmatory factor analysis (WLSVM) was conducted, to evaluate reliability and validity Cronbach coefficient alpha and Pearson correlation coefficients were calculated. Results. The Slovak version of the EPOCH measure demonstrated adequate levels of validity and reliability in primary, high school and university students. The five-factor structure reported by the author fit the data well and was equivalent for both genders and age groups. Limits. Additional studies with representative samples of primary, high, and university students, and verifying predictive validity are needed to further validate the measure.

• MeSH
• Factor Analysis, Statistical MeSH
• Correlation of Data MeSH
• Humans MeSH
• Adolescent MeSH
• Surveys and Questionnaires * MeSH
• Reproducibility of Results MeSH
• Students psychology   statistics & numerical data   MeSH
• Adolescent Health * MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Geographicals
• Slovakia MeSH

Several pathophysiological mechanisms have been proposed in the development of pregnancy complications, including endothelial dysfunction, an inflammatory pathway and oxidative stress. The aim of the present study was to evaluate the correlation between proinflammatory cytokines TNF-alpha, IL-6 and dual cytokine IL-10 in the mother's peripheral blood and systolic blood pressure, risk of preeclampsia and low birth weight in gestational diabetes (GDM). We observed 40 women with GDM divided into a gestational hypertension group (n=20) and comparison group (n=20) with normal blood pressure. We found a significant positive correlation between TNF-alpha; IL-6; IL-10 levels and systolic blood pressure (SBP) in the second trimester (p<0.001; p<0.001; p<0.001); the third trimester (p<0.001; p<0.001; p<0.05). We also proved correlations for diastolic blood pressure (DBP) during the second; third trimester (p<0.001; p<0.001; p<0.001); (p<0.001; p<0.001; p<0.0015). We demonstrated a statistically significant positive association between high TNF-alpha group and preeclampsia risk in the third trimester (p=0.04). We also determined the negative correlation in the second trimester between birth weight and TNF-alpha; IL-6, IL-10 levels (p<0.05; p<0.001; p<0.001). To conclude, our data highlight the importance of cytokines TNF-alpha, IL-6 and IL-10 in blood pressure regulation. In addition, high levels of TNF-alpha have been associated with increased risk of preeclampsia. We found a significant negative correlation between levels of TNF-alpha, IL-6, IL-10 and birth weight.

• MeSH
• Biomarkers blood   MeSH
• Adult MeSH
• Diabetes, Gestational blood   diagnosis   MeSH
• Interleukin-10 blood   MeSH
• Interleukin-6 blood   MeSH
• Blood Pressure physiology   MeSH
• Humans MeSH
• Infant, Low Birth Weight blood   MeSH
• Infant, Newborn MeSH
• Pre-Eclampsia blood   diagnosis   MeSH
• Risk Factors MeSH
• Pregnancy MeSH
• Tumor Necrosis Factor-alpha blood   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVES: The association between obesity and atrial fibrillation (AF) is well-established. We aimed to evaluate the impact of index body mass index (BMI) on AF recurrence at 12 months following catheter ablation using propensity-weighted analysis. In addition, periprocedural complications and fluoroscopy details were examined to assess overall safety in relationship to increasing BMI ranges. METHODS: Baseline, periprocedural and follow-up data were collected on consecutive patients scheduled for AF ablation. There were no specific exclusion criteria. Patients were categorised according to baseline BMI in order to assess the outcomes for each category. RESULTS: Among 3333 patients, 728 (21.8%) were classified as normal (BMI <25.0 kg/m2), 1537 (46.1%) as overweight (BMI 25.5-29.0 kg/m2) and 1068 (32.0%) as obese (BMI ≥30.0 kg/m2). Procedural duration and radiation dose were higher for overweight and obese patients compared with those with a normal BMI (p=0.002 and p<0.001, respectively). An index BMI ≥30 kg/m2 led to a 1.2-fold increased likelihood of experiencing recurrent AF at 12-months follow-up as compared with overweight patients (HR 1.223; 95% CI 1.047 to 1.429; p=0.011), while no significant correlation was found between overweight and normal BMI groups (HR 0.954; 95% CI 0.798 to 1.140; p=0.605) and obese versus normal BMI (HR 1.16; 95% CI 0.965 to 1.412; p=0.112). CONCLUSIONS: Patients with a baseline BMI ≥30 kg/m2 have a higher recurrence rate of AF following catheter ablation and therefore lifestyle modification to target obesity preprocedure should be considered in these patients.

• MeSH
• Risk Reduction Behavior MeSH
• Radiation Dosage MeSH
• Atrial Fibrillation * epidemiology   therapy   MeSH
• Fluoroscopy * methods   statistics & numerical data   MeSH
• Risk Assessment MeSH
• Body Mass Index MeSH
• Catheter Ablation * adverse effects   methods   MeSH
• Comorbidity MeSH
• Correlation of Data MeSH
• Middle Aged MeSH
• Humans MeSH
• Overweight * diagnosis   epidemiology   MeSH
• Follow-Up Studies MeSH
• Obesity * diagnosis   epidemiology   psychology   MeSH
• Recurrence MeSH
• Registries statistics & numerical data   MeSH
• Risk Factors MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

BACKGROUND: Varicella vaccination confers high and long-lasting protection against chickenpox and induces robust immune responses, but an absolute correlate of protection (CoP) against varicella has not been established. This study models the relationship between varicella humoral response and protection against varicella. METHODS: This was a post-hoc analysis of data from a Phase IIIb, multicenter, randomized trial (NCT00226499) conducted in ten varicella-endemic European countries. Healthy children aged 12-22 months were randomized 3:3:1 to receive one dose of measles-mumps-rubella and one dose of varicella vaccine (one-dose group) or two doses of measles-mumps-rubella-varicella vaccine (two-dose group) or two doses of measles-mumps-rubella vaccine (control group) six weeks apart. The study remained observer-blind until completion, except in countries with obligatory additional immunizations. The objective was to correlate varicella-specific antibody concentrations with protection against varicella and probability of varicella breakthrough, using Cox proportional hazards and Dunning and accelerated failure time statistical models. The analysis was guided by the Prentice framework to explore a CoP against varicella. RESULTS: The trial included 5803 participants, 5289 in the efficacy (2266: one-dose group, 2279: two-dose group and 744: control group) and 5235 (2248, 2245 and 742 in the same groups) in the immunogenicity cohort. The trial ended in 2016 with a median follow-up time of 9.8 years. Six weeks after vaccination with one- or two-dose varicella-containing vaccine, more than 93.0% of vaccinees were seropositive for varicella-specific antibodies. Estimated vaccine efficacy correlated positively with antibody concentrations. The fourth Prentice CoP criterion was not met, due to predicted positive vaccine efficacy in seronegative participants. Further modelling showed decreased probability of moderate to severe varicella breakthrough with increasing varicella-specific antibody concentrations (ten-year probability <0.1 for antibody concentrations ≥2-fold above the seropositivity cut-off). CONCLUSIONS: Varicella-specific antibody concentrations are a good predictor of protection, given their inverse correlation with varicella occurrence. CLINICAL TRIAL: NCT00226499.

• MeSH
• Child MeSH
• Infant MeSH
• Vaccines, Combined MeSH
• Humans MeSH
• Chickenpox * prevention & control   MeSH
• Antibodies, Viral MeSH
• Measles * MeSH
• Chickenpox Vaccine MeSH
• Measles-Mumps-Rubella Vaccine MeSH
• Herpesvirus 3, Human MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• Europe MeSH

Východiska: Karcinom prsu je celosvětově nejčastější ženskou malignitou. Pro ženy premenopauzální, obzvláště ve velmi nízkém věku do 35 let, přináší toto onemocnění velké riziko – mívá agresivnější chování a horší prognózu. Soubor pa cientů a metody: Skupinu pa cientek v naší retrospektivní studii tvořilo 356 žen do 35 let věku, kterým byl v letech 2006– 2015 diagnostikován invazivní karcinom prsu. Z této základní kohorty jsme vybrali 92 nemocných, které byly léčeny na Onkologické a radioterapeutické klinice FN Plzeň. Kontrolní skupinu tvořilo 100 postmenopauzálních žen nad 65 let v době stanovení dia gnózy invazivního karcinomu prsu. Srovnali jsme prognostické a prediktivní indikátory, léčbu a průběh onemocnění v obou skupinách. Výsledky: U mladých pa cientek byla častěji přítomna overexprese proteinu HER2/ neu, nádory měly častěji triple negativní imunoprofi l a bazaloidní fenotyp, byly hůře diferencované. Naopak prognosticky příznivější typy karcinomu nebyly v této skupině tak časté. Co se týče průběhu onemocnění, i zde výsledky hovoří v neprospěch pa cientek nízkého věku – méně pa cientek dosáhlo remise onemocnění, více bylo zaznamenáno případů generalizace nemoci i počtu úmrtí. Závěr: Incidence invazivního karcinomu prsu u mladých žen je nízká, představuje kolem 2 % ze všech případů, tato skupina nemocných je však prognosticky velmi významná. Karcinomy v takto mladém věku bývají agresivnější a častěji bývají zastoupeny prognosticky nepříznivější typy karcinomu, jako triple negativní nebo bazaloidní. Výsledky naší retrospektivní studie tento předpoklad potvrzují. Karcinomy prsu u mladých žen navíc bývají častěji způsobeny genetickou predispozicí (vrozené mutace v genech BRCA1 a BRCA2 a v dalších).

Background: Worldwide, breast cancer is the leading type of malignancy in women. For premenopausal women, the disease brings much higher risk as it is usually more aggressive with worse prognosis. Patients and Methods: In this retrospective study, 92 women treated at the Department of Oncology and Radiotherapy in Pilsen were selected from a basic cohort of 356 women under 35 years of age with breast cancer who were diag - nosed between 2006 and 2015. The control group comprised 100 postmenopausal women over 65 years of age who were treated for invasive breast cancer. Results: Overexpression of HER2/ neu protein and a triple-negative immunoprofi le and basal-like phenotype of cancer were more frequently seen in the women under 35 years of age. In addition, malignant cells were poorly diff erentiated and more aggressive, and prognostically favourable types were not often seen, in these women. In terms of the course of disease, the outcome was worse for the younger patients, and complete remission was reached less frequently and more cases of advanced disease and death due to the malignancy were detected. Conclusion: The incidence of invasive breast cancer in young women is low, representing around 2% of all cases of the disease, but this group of patients is prognostically very important. The cancers at such a young age are usually more aggressive (higher mitotic activity and higher grade), and prognostically worse types, such as triple-negative or basal-like, are seen signifi cantly more often in younger patients. This retrospective study confi rmed this premise. Moreover, breast cancer in young women is more often associated with genetic predisposition (e. g., hereditary mutations in BRCA1 and BRCA2 genes) than in older women .

• MeSH
• Adult MeSH
• Genes, BRCA1 MeSH
• Genes, BRCA2 MeSH
• Immunohistochemistry utilization   MeSH
• Humans MeSH
• Young Adult MeSH
• Breast Neoplasms * epidemiology   mortality   pathology   MeSH
• Retrospective Studies MeSH
• Triple Negative Breast Neoplasms MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Female MeSH

OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are a group of severe, early-onset epilepsies characterised by refractory seizures, developmental delay, or regression and generally poor prognosis. DEE are now known to have an identifiable molecular genetic basis and are usually examined using a gene panel. However, for many patients, the genetic cause has still not been identified. The aims of this study were to identify causal variants for DEE in patients for whom the previous examination with a gene panel did not determine their genetic diagnosis. It also aims for a detailed description and broadening of the phenotypic spectrum of several rare DEEs. METHODS: In the last five years (2015-2020), 141 patients from all over the Czech Republic were referred to our department for genetic testing in association with their diagnosis of epilepsy. All patients underwent custom-designed gene panel testing prior to enrolment into the study, and their results were inconclusive. We opted for whole exome sequencing (WES) to identify the cause of their disorder. If a causal or potentially causal variant was identified, we performed a detailed clinical evaluation and phenotype-genotype correlation study to better describe the specific rare subtypes. RESULTS: Explanatory causative variants were detected in 20 patients (14%), likely pathogenic variants that explain the epilepsy in 5 patients (3.5%) and likely pathogenic variants that do not fully explain the epilepsy in 11 patients (7.5%), and variants in candidate genes in 4 patients (3%). Variants were mostly de novo 29/40 (72.5%). SIGNIFICANCE: WES enables us to identify the cause of the disease in additional patients, even after gene panel testing. It is very important to perform a WES in DEE patients as soon as possible, since it will spare the patients and their families many years of a diagnostic odyssey. In particular, patients with rare epilepsies might significantly benefit from this approach, and we propose using WES as a new standard in the diagnosis of DEE instead of targeted gene panel testing.

• MeSH
• Epilepsy, Generalized * genetics   MeSH
• Epilepsy * diagnosis   genetics   MeSH
• Phenotype MeSH
• Genetic Association Studies MeSH
• Genetic Testing MeSH
• Humans MeSH
• Exome Sequencing MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH