BACKGROUND: Negative symptoms (NS) represent a detrimental symptomatic domain in schizophrenia affecting social and occupational outcomes. AIMS: We aimed to identify factors from the baseline visit (V1) - with a mean illness duration of 0.47 years (SD = 0.45) - that predict the magnitude of NS at the follow-up visit (V3), occurring 4.4 years later (mean +/- 0.45). METHOD: Using longitudinal data from 77 first-episode schizophrenia spectrum patients, we analysed eight predictors of NS severity at V3: (1) the age at disease onset, (2) age at V1, (3) sex, (4) diagnosis, (5) NS severity at V1, (6) the dose of antipsychotic medication at V3, (7) hospitalisation days before V1 and; (8) the duration of untreated psychosis /DUP/). Secondly, using a multiple linear regression model, we studied the longitudinal relationship between such identified predictors and NS severity at V3 using a multiple linear regression model. RESULTS: DUP (Pearson's r = 0.37, p = 0.001) and NS severity at V1 (Pearson's r = 0.49, p < 0.001) survived correction for multiple comparisons. The logarithmic-like relationship between DUP and NS was responsible for the initial stunning incremental contribution of DUP to the severity of NS. For DUP < 6 months, with the sharpest DUP/NS correlation, prolonging DUP by five days resulted in a measurable one-point increase in the 6-item negative symptoms PANSS domain assessed 4.9 (+/- 0.6) years after the illness onset. Prolongation of DUP to 14.7 days doubled this NS gain, whereas 39 days longer DUP tripled NS increase. CONCLUSION: The results suggest the petrification of NS during the early stages of the schizophrenia spectrum and a crucial dependence of this symptom domain on DUP. These findings are clinically significant and highlight the need for primary preventive actions.

• MeSH
• antipsychotika * terapeutické užití   MeSH
• lidé MeSH
• multivariační analýza MeSH
• psychotické poruchy * diagnóza   farmakoterapie   MeSH
• schizofrenie * diagnóza   farmakoterapie   MeSH
• syndrom Nijmegen breakage * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Záměr: Cílem studie byla deskripce asociace počtu hodin strávených na internetu a symptomatologie „závislosti na internetu“ korigované sociodemografickými údaji, psychickou labilitou, užíváním alkoholu a konopí, hráčstvím a subjektivním odhadem tělesného i duševního zdraví na podkladě odpovědí českého reprezentativního souboru respondentů v době pandemie COVID-19. Soubor a procedura: Soubor tvořilo 2 602 osob (1 206 mužů, 1 396 žen), průměrný věk 44,61 roku, SD = 15,82, rozsah 15–85 let náhodně vybraných kvótním výběrem na podkladě věku, pohlaví, vzdělání a regionu. Data byla zpracována hierarchickou multivariační lineární regresní analýzou (OLS). Závisle proměnnou byly údaje z testu Excessive Internet Use. Nezávisle proměnnými byly věk, pohlaví, čistý příjem, rodinný stav, vzdělání, subjektivní odhad duševního a tělesného zdraví, údaje z nástrojů Mhi-5, caGe, cast a PGsi. výsledky: Výsledky jsou v souladu s předchozími výzkumy, které se shodují na tom, že rozvoj závislosti na internetu je podmíněn především časem stráveným na internetu, riziko je v inverzním vztahu k věku a mírně vyšší u mužů. Vliv dalších proměnných z oblasti látkových závislostí, hazardního hraní a duševního zdraví podporuje hypotézy o společné etiologii různých typů závislosti a jejich souvislost s duševním zdravím. Omezení studie: Studie je založena na autoreferenčních údajích, má deskriptivní, empirický charakter a neopírá se o předem formulovanou teorii.

Objectives: the aim of the study was description of the association between the number of hours spent on the internet and symptomatology of Internet addiction, corrected by sociodemographic data, mental instability, alcohol and cannabis use, gambling, and subjective estimation of physical and mental health using responses from a representative sample of Czech respondents during COVID-19 pandemic. Sample and setting: The group consisted of 2 602 people (1 206 men, 1 396 women), average age 44,61 years, SD = 15,8223, range 15–85 years randomly selected by quota selection based on age, gender, education and region. Data were processed by hierarchical multivariate linear regression analysis (OLS). The dependent variable was data from the Excessive Internet Use test. Independent variables were age, gender, net income, marital status, education, subjective estimation of mental and physical health, data from MHI-5, CAGE, cast and PGsi tools. Results: the results are in line with previous research, which indicates that the development of internet addiction is mainly due to time spent on the Internet, the risk is inversely related to age and slightly higher in men. The influence of other variables measuring substance use, gambling and mental health supports hypotheses about common etiology of various types of addiction and their association with mental health. Study limitation: the study is based on self-referential data, has a heuristic, empirical character and does not rely on a pre-formulated theory.

• MeSH
• internet * MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• závislost na technologiích * MeSH
• Check Tag
• lidé MeSH

Increases in beat-to-beat variability of electrocardiographic QT interval duration have repeatedly been associated with increased risk of cardiovascular events and complications. The measurements of QT variability are frequently normalized for the underlying RR interval variability. Such normalization supports the concept of the so-called immediate RR effect which relates each QT interval to the preceding RR interval. The validity of this concept was investigated in the present study together with the analysis of the influence of electrocardiographic morphological stability on QT variability measurements. The analyses involved QT and RR measurements in 6,114,562 individual beats of 642,708 separate 10-s ECG samples recorded in 523 healthy volunteers (259 females). Only beats with high morphology correlation (r > 0.99) with representative waveforms of the 10-s ECG samples were analyzed, assuring that only good quality recordings were included. In addition to these high correlations, SDs of the ECG signal difference between representative waveforms and individual beats expressed morphological instability and ECG noise. In the intra-subject analyses of both individual beats and of 10-s averages, QT interval variability was substantially more strongly related to the ECG noise than to the underlying RR variability. In approximately one-third of the analyzed ECG beats, the prolongation or shortening of the preceding RR interval was followed by the opposite change of the QT interval. In linear regression analyses, underlying RR variability within each 10-s ECG sample explained only 5.7 and 11.1% of QT interval variability in females and males, respectively. On the contrary, the underlying ECG noise contents of the 10-s samples explained 56.5 and 60.1% of the QT interval variability in females and males, respectively. The study concludes that the concept of stable and uniform immediate RR interval effect on the duration of subsequent QT interval duration is highly questionable. Even if only stable beat-to-beat measurements of QT interval are used, the QT interval variability is still substantially influenced by morphological variability and noise pollution of the source ECG recordings. Even when good quality recordings are used, noise contents of the electrocardiograms should be objectively examined in future studies of QT interval variability.

• Publikační typ
• časopisecké články MeSH

Genomic instability is a characteristic of a majority of human malignancies. Chromosomal instability is a common form of genomic instability that can be caused by defects in mitotic checkpoint genes. Chromosomal aberrations in peripheral blood are also indicative of genotoxic exposure and potential cancer risk. We evaluated associations between inherited genetic variants in 33 mitotic checkpoint genes and the frequency of chromosomal aberrations (CAs) in the presence and absence of environmental genotoxic exposure. Associations with both chromosome and chromatid type of aberrations were evaluated in two cohorts of healthy individuals, namely an exposed and a reference group consisting of 607 and 866 individuals, respectively. Binary logistic and linear regression analyses were performed for the association studies. Bonferroni-corrected significant p-value was 5 × 10-4 for 99 tests based on the number of analyzed genes and phenotypes. In the reference group the most prominent associations were found with variants in CCNB1, a master regulator of mitosis, and in genes involved in kinetochore function, including CENPH and TEX14, whereas in the exposed group the main association was found with variants in TTK, also an important gene in kinetochore function. How the identified variants may affect the fidelity of mitotic checkpoint remains to be investigated, however, the present study suggests that genetic variation may partly explain interindividual variation in the formation of CAs.

• MeSH
• chromozomální aberace * MeSH
• chromozomální proteiny, nehistonové genetika   MeSH
• cyklin B1 genetika   MeSH
• cyklin-dependentní kinasy genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• jednonukleotidový polymorfismus * MeSH
• kinetochory metabolismus   MeSH
• kohortové studie MeSH
• kontrolní body M fáze buněčného cyklu genetika   MeSH
• kultivované buňky MeSH
• lidé MeSH
• lineární modely MeSH
• odds ratio MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

The stability of α-bromophenylacetic acid (BPAA) in 50% aqueous methanol solution has been tested. CE in different running buffers was used to separate BPAA from the decomposition reaction products α-hydroxyphenylacetic (mandelic) acid and α-methoxyphenylacetic acid. Suitable CE separation of all three compounds and other product, bromide, was achieved in 60 mmol/L formate buffer (pH 3.0) at -30 kV in 50 μm (i.d.) poly(vinyl alcohol)-coated fused silica capillary (30 cm/24.5 cm) with UV detection at 200 nm. The CE method was applied to determine the reaction order of the decomposition of BPAA (0.47 mmol/L) via nucleophilic substitution in 50% aqueous methanol. The first-order reaction kinetics was confirmed by linear and non-linear regression, giving the rate constants 1.52 × 10-4 ± 2.76 × 10-5 s-1 and 7.89 × 10-5 ± 5.02 × 10-6 s-1, respectively. Additionally, the degradation products were identified by CE coupled to mass spectrometric (MS) detection. The CE-MS experiments carried out in 60 mmol/L formate buffer (pH 3.0) and in 60 mmol/L acetate buffer (pH 5.0) confirmed the results obtained by CE-UV. Furthermore, the stability of BPAA in polar solvents was tested by 1H NMR experiments. Our results provide strong evidence of the instability and fast degradation of BPAA in 50% aqueous methanol indicating that BPAA is not suitable as the model analyte for chiral separations.

• MeSH
• chemické modely * MeSH
• elektroforéza kapilární metody   normy   MeSH
• fenylacetáty chemie   izolace a purifikace   MeSH
• hmotnostní spektrometrie metody   MeSH
• reprodukovatelnost výsledků MeSH
• stabilita léku MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Non-specific structural chromosomal aberrations (CAs) observed in peripheral blood lymphocytes of healthy individuals can be either chromosome-type aberrations (CSAs) or chromatid-type aberrations (CTAs) depending on the stage of cell division they are induced in and mechanism of formation. It is important to study the genetic basis of chromosomal instability as it is a marker of genotoxic exposure and a predictor of cancer risk. For that purpose, we conducted two genome-wide association studies (GWASs) on healthy individuals in the presence and absence of apparent genotoxic exposure from the Czech Republic and Slovakia. The pre-GWAS cytogenetic analysis reported the frequencies of CSA, CTA and total CA (CAtot). We performed both linear and binary logistic regression analysis with an arbitrary cut-off point of 2% for CAtot and 1% for CSA and CTA. Using the statistical threshold of 1.0 × 10-5, we identified five loci with in silico predicted functionality in the reference group and four loci in the exposed group, with no overlap between the associated regions. A meta-analysis on the two GWASs identified further four loci with moderate associations in each of the studies. From the reference group mainly loci within genes related to DNA damage response/repair were identified. Other loci identified from both the reference and exposed groups were found to be involved in the segregation of chromosomes and chromatin modification. Some of the discovered regions in each group were implicated in tumourigenesis and autism.

• MeSH
• alely MeSH
• celogenomová asociační studie MeSH
• chromozomální aberace účinky léků   MeSH
• cytogenetické vyšetření MeSH
• dospělí MeSH
• frekvence genu * MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• mladý dospělý MeSH
• mutageny škodlivé účinky   MeSH
• odds ratio MeSH
• populační genetika * MeSH
• poškození DNA účinky léků   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• buňky * MeSH
• molekulární biologie MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• molekulární biologie, molekulární medicína
• NLK Publikační typ
• učebnice vysokých škol

• MeSH
• fyzikální jevy MeSH
• magnetická rezonanční tomografie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• radiologie, nukleární medicína a zobrazovací metody
• NLK Publikační typ
• kolektivní monografie

Cíl:Porovnání výsledků audiologických a otoneurologických testů před radiochirurgií Leksellovým gama nožem u pacientů s vestibulárním schwannomem a po ní. Výsledky byly hodnoceny v korelaci s MR mozku a PC volumometrií. Sledovali jsme změnu velikosti nádoru a vyhodnocovali efekt léčby. Zaměřili jsme se na záchyt komplikací léčby ve smyslu zhoršení sluchu, tinnitu, vertiga, instability, projevů neuropatie n. V, vzniku poruchy funkce n. VII, hypo­resorpčního hydrocefalu. Soubor a metodika: Dvacet sedm pacientů sledovaných v letech 1999–2009. Provedeno komplexní neurootologické vyšetření před léčbou a po ní. Follow-up po radiochirurgii byl 20–132 měsíců, průměr 50 měsíců. Výsledky: Úspěšnost léčby byla 81 %, u 5 (19 %) nemocných došlo ke zvětšení nádoru. Z toho byli tři pacienti úspěšně léčeni reiradiací, jedna pacientka byla léčena úspěšně mikrochirurgicky s pooperačními komplikacemi a jeden pacient léčen úspěšně kortikosteroidy. Zachytili jsme jednu pacientku s progresí hyporesorpčního hydrocefalu. Celkový záchyt komplikací tvořil 22 %. Závěr: Monitoring otoneurologického profilu přispěl k odhalení některých komplikací léčby Leksellovým gama nožem. Záchyt komplikací je pro další osud pacienta významný. Výsledky studie ukazují na potřebnou roli neurootologa ve sledování pacientů s vestibulárním schwannomem.

Purpose: The results of audiological-otoneurological tests before treatment of patients with vestibular schwannoma with the Leksell gamma knife were compared with findings after the treatment. The results were assessed in correlation with PC volumetry and brain MRI. Changes to the tumor size were monitored and the treatment effect evaluated. We focused on the detection of complications including deterioration of hearing, tinnitus, vertigo, instability, manifestation of neuropathy n. V, development of paresis n. VII, hyporesorptive hydrocephalus. Patients and methods: Between 1999 and 2009, 27 patients were fully neurootologically examined before the treatment and subsequently and repeatedly after the treatment. The follow-up after radiosurgery was 20–132 months, 50 months on average. Results: Treatment success rate was 81%; enlargement of the tumor was detected in 5 (19%) cases. Three of the five patients with enlarged tumors were successfully treated with reirradiation, one patient was treated using microsurgery (postoperative complications occurred), and one patient was successfully treated with corticosteroids. We detected one patient with hyporesorptive hydrocefalus progression. Total number of complications detected made up 22%. Conclusions: Monitoring of the otoneurological profile contributed to detection of some complications associated with the treatment with the Leksell gamma knife. Detection of complications is significant for the patient’s prognosis. The results testify to the significance of involving a neurootologist in the treatment and monitoring of patients with vestibular schwannoma.

• MeSH
• dospělí MeSH
• hydrocefalus komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek radiografie   MeSH
• neurootologie MeSH
• pooperační komplikace * diagnóza   epidemiologie   etiologie   MeSH
• radiochirurgie * metody   škodlivé účinky   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• sluchové testy MeSH
• statistika jako téma MeSH
• stupeň závažnosti nemoci MeSH
• vestibulární funkční testy MeSH
• vestibulární schwannom * chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Telomeres, as elaborate nucleo-protein complexes, ensure chromosomal stability. When impaired, the ends of linear chromosomes can be recognised by cellular repair mechanisms as double-strand DNA breaks and can be healed by non-homologous-end-joining activities to produce dicentric chromosomes. During cell divisions, particularly during anaphase, dicentrics can break, thus producing naked chromosome tips susceptible to additional unwanted chromosome fusion. Many telomere-building protein complexes are associated with telomeres to ensure their proper capping function. It has been found however, that a number of repair complexes also contribute to telomere stability. RESULTS: We used Arabidopsis thaliana to study the possible functions of the DNA repair subunit, NBS1, in telomere homeostasis using knockout nbs1 mutants. The results showed that although NBS1-deficient plants were viable, lacked any sign of developmental aberration and produced fertile seeds through many generations upon self-fertilisation, plants also missing the functional telomerase (double mutants), rapidly, within three generations, displayed severe developmental defects. Cytogenetic inspection of cycling somatic cells revealed a very early onset of massive genome instability. Molecular methods used for examining the length of telomeres in double homozygous mutants detected much faster telomere shortening than in plants deficient in telomerase gene alone. CONCLUSIONS: Our findings suggest that NBS1 acts in concert with telomerase and plays a profound role in plant telomere renewal.

• MeSH
• anafáze MeSH
• Arabidopsis cytologie   enzymologie   genetika   růst a vývoj   MeSH
• chromozomální nestabilita MeSH
• chromozomy rostlin genetika   metabolismus   MeSH
• cytogenetické vyšetření MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• homeostáza telomer MeSH
• hybridizace in situ fluorescenční MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• klíčení MeSH
• květy cytologie   genetika   metabolismus   MeSH
• mapování interakce mezi proteiny MeSH
• meióza MeSH
• oprava DNA MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• rostlinné buňky enzymologie   metabolismus   MeSH
• samooplození MeSH
• semena rostlinná genetika   růst a vývoj   metabolismus   MeSH
• telomerasa genetika   metabolismus   MeSH
• telomery genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH