OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. METHODS: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. RESULTS: When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. CONCLUSIONS: This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.

• MeSH
• dospělí MeSH
• interocepce * fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mladý dospělý MeSH
• mozek * patofyziologie   diagnostické zobrazování   MeSH
• nemoci nervového systému * patofyziologie   diagnostické zobrazování   MeSH
• pozornost fyziologie   MeSH
• srdeční frekvence fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses. METHODS: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications. RESULTS: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.

• MeSH
• bipolární porucha * genetika   MeSH
• dospělí MeSH
• fenotyp * MeSH
• hyperkinetická porucha genetika   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• multifaktoriální dědičnost genetika   MeSH
• neurovývojové poruchy genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Present study was aimed to develop an efficient microbial consortium for combating Alternaria blight disease in cumin. The research involved isolating biocontrol agents against Alternaria burnsii, characterizing their biocontrol and growth promotion traits, and assessing compatibility. A pot experiment was conducted during rabi season of 2022-2023 to evaluate the bioefficacy of four biocontrol agents (1F, 16B, 31B, and 223B) individually and in consortium, focusing on disease severity, plant growth promotion, and defense responses in cumin challenged with A. burnsii. Microbial isolates 1F, 16B, 31B, and 223B significantly inhibited A. burnsii growth in dual plate assays (~ 86%), displaying promising biocontrol and plant growth promotion activities. They were identified as Trichoderma afroharzianum 1F, Aneurinibacillus aneurinilyticus 16B, Pseudomonas lalkuanensis 31B, and Bacillus licheniformis 223B, respectively. The excellent compatibility was observed among all selected biocontrol agents. Cumin plants treated with consortia of 1F + 16B + 31B + 223B showed least percent disease index (32.47%) and highest percent disease control (64.87%). Consortia of biocontrol agents significantly enhanced production of secondary metabolites (total phenol, flavonoids, antioxidant, and tannin) and activation of antioxidant-defense enzymes (POX, PPOX, CAT, SOD, PAL, and TAL) compared to individual biocontrol treatment and infected control. Moreover, consortium treatments effectively reduced electrolyte leakage over the individual biocontrol agent and infected control treatment. The four-microbe consortium significantly enhanced chlorophyll (154%), carotenoid content (88%), plant height (78.77%), dry weight (72.81%), and seed yield (104%) compared to infected control. Based on these findings, this environmentally friendly four-microbe consortium may be recommended for managing Alternaria blight in cumin.

• MeSH
• Alternaria * růst a vývoj   fyziologie   MeSH
• biologická ochrana MeSH
• Cuminum * mikrobiologie   imunologie   růst a vývoj   MeSH
• mikrobiální společenstva * MeSH
• nemoci rostlin * mikrobiologie   prevence a kontrola   imunologie   MeSH
• odolnost vůči nemocem MeSH
• Publikační typ
• časopisecké články MeSH

The perception of a voice in the absence of an external auditory source-an auditory verbal hallucination-is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address this with a locally adapted MEGA-PRESS sequence incorporating interleaved unsuppressed water acquisitions, allowing concurrent assessment of behaviour, blood-oxygenation-level-dependent (BOLD) functional changes, Glutamate + Glutamine (Glx), and GABA, synchronised with a cognitive (flanker) task. We acquired data from the anterior cingulate cortex (ACC) of 51 patients with psychosis (predominantly schizophrenia spectrum disorder) and hallucinations, matched to healthy controls. Consistent with the notion of an excitatory/inhibitory imbalance, we hypothesized differential effects for Glx and GABA between groups, and aberrant dynamics in response to task. Results showed impaired task performance, lower baseline Glx and positive association between Glx and BOLD in patients, contrasting a negative correlation in healthy controls. Task-related increases in Glx were observed in both groups, with no significant difference between groups. No significant effects were observed for GABA. These findings suggest that a putative excitatory/inhibitory imbalance affecting inhibitory control in the ACC is primarily observed as tonic, baseline glutamate differences, rather than GABAergic effects or aberrant dynamics in relation to a task.

• MeSH
• cingulární gyrus metabolismus   patofyziologie   MeSH
• dospělí MeSH
• GABA * metabolismus   MeSH
• glutamin metabolismus   MeSH
• halucinace * metabolismus   patofyziologie   MeSH
• kognice * fyziologie   MeSH
• kyselina glutamová * metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladý dospělý MeSH
• psychotické poruchy * metabolismus   patofyziologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Pancreatic cancer (PC) is becoming one of the most serious health problems at present, but its causes and risk factors are still unclear. One of the drivers in pancreatic carcinogenesis is altered genomic (DNA) integrity with subsequent genomic instability in cancer cells. The latter comprises a) DNA damage response and DNA repair mechanisms, b) DNA replication and mitosis, c) epigenetic regulation, and d) telomere maintenance. In our review we addressed the above aspects in relation to the most abundant and severe form of PC, pancreatic ductal adenocarcinoma (PDAC). In summary, the interactions between the DNA damage response, telomere homeostasis and mitotic regulation are not comprehensively understood at present, including the epigenetic factors entering the trait of genomic stability maintenance. In addition, the complexity of telomere homeostasis in relation to PDAC risk, prognosis and prediction also warrants further investigations.

• MeSH
• duktální karcinom slinivky břišní * genetika   patologie   MeSH
• epigeneze genetická MeSH
• homeostáza telomer * genetika   MeSH
• lidé MeSH
• nádory slinivky břišní * genetika   patologie   MeSH
• nestabilita genomu * MeSH
• oprava DNA MeSH
• poškození DNA * MeSH
• telomery * genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• muzea MeSH
• politika MeSH
• postižení MeSH
• skupiny lidí MeSH
• sociologické faktory MeSH
• výstavy jako téma MeSH
• Publikační typ
• katalogy MeSH
• výstavy MeSH

• Konspekt
• Muzea. Muzeologie. Muzejnictví. Výstavy
• NLK Obory
• patologie
• sociologie
• politologie, politika, zdravotní politika

• O autorovi
• Würtz, Hans, 1875-1958 Autorita

DNA damage is a common event in cells, resulting from both internal and external factors. The maintenance of genomic integrity is vital for cellular function and physiological processes. The inadequate repair of DNA damage results in the genomic instability, which has been associated with the development and progression of various human diseases. Accumulation of DNA damage can lead to multiple diseases, such as neurodegenerative disorders, cancers, immune deficiencies, infertility, and ageing. This comprehensive review delves the impact of alterations in DNA damage response genes (DDR) and tries to elucidate how and to what extent the same traits modulate diverse major human diseases, such as cancer, neurodegenerative diseases, and immunological disorders. DDR is apparently the trait connecting important complex disorders in humans. However, the pathogenesis of the above disorders and diseases are different and lead to divergent consequences. It is important to discover the switch(es) that direct further the pathogenic process either to proliferative, or degenerative diseases. Our understanding of the influence of DNA damage on diverse human disorders may enable the development of the strategies to prevent, diagnose, and treat these diseases. In our article, we analysed publicly available GWAS summary statistics from the NHGRI-EBI GWAS Catalog and identified 12 009 single-nucleotide polymorphisms (SNPs) associated with cancer. Among these, 119 SNPs were found in DDR pathways, exhibiting significant P-values. Additionally, we identified 44 SNPs linked to various cancer types and neurodegenerative diseases (NDDs), including four located in DDR-related genes: ATM, CUX2, and WNT3. Furthermore, 402 SNPs were associated with both cancer and immunological disorders, with two found in the DDR gene RAD51B. This highlights the versatility of the DDR pathway in multifactorial diseases. However, the specific mechanisms that regulate DDR to initiate distinct pathogenic processes remain to be elucidated.

• MeSH
• celogenomová asociační studie MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• nádory * genetika   MeSH
• nemoci imunitního systému * genetika   MeSH
• nestabilita genomu genetika   MeSH
• neurodegenerativní nemoci * genetika   MeSH
• oprava DNA * genetika   MeSH
• poškození DNA * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Nonspecific structural chromosomal aberrations (CAs) are found in around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. CAs have been used in the monitoring of persons exposed to genotoxic agents and radiation. Previous studies on occupationally exposed individuals have shown associations between the frequency of CAs in peripheral blood lymphocytes and subsequent cancer risk. The cause for CA formation is believed to be unrepaired or insufficiently repaired DNA double-strand breaks or other DNA damage, and additionally telomere shortening. CAs include chromosome (CSAs) and chromatid type aberrations (CTAs). In the present review, we first describe the types of CAs, the conventional techniques used for their detection and some aspects of interpreting the results. We then focus on germline genetic variation in the frequency and type of CAs measured in a genome-wide association study in healthy individuals in relation to occupational and smoking-related exposure compared to nonexposed referents. The associations (at P < 10-5) on 1473 healthy individuals were broadly classified in candidate genes from functional pathways related to DNA damage response/repair, including PSMA1, UBR5, RRM2B, PMS2P4, STAG3L4, BOD1, COPRS, and FTO; another group included genes related to apoptosis, cell proliferation, angiogenesis, and tumorigenesis, COPB1, NR2C1, COPRS, RHOT1, ITGB3, SYK, and SEMA6A; a third small group mapped to genes KLF7, SEMA5A and ITGB3 which were related to autistic traits, known to manifest frequent CAs. Dedicated studies on 153 DNA repair genes showed associations for some 30 genes, the expression of which could be modified by the implicated variants. We finally point out that monitoring of CAs is so far the only method of assessing cancer risk in healthy human populations, and the use of the technology should be made more attractive by developing automated performance steps and incorporating artificial intelligence methods into the scoring.

• MeSH
• celogenomová asociační studie * MeSH
• chromozomální aberace * MeSH
• interakce genů a prostředí MeSH
• lidé MeSH
• lymfocyty metabolismus   MeSH
• nádory genetika   MeSH
• oprava DNA genetika   MeSH
• poškození DNA MeSH
• pracovní expozice škodlivé účinky   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PROBLEM: Disgust contributes to anxiety-based psychopathology, and in turn, anxiety increases disgust proneness. BACKGROUND: Disgust and anxiety undergo significant changes in pregnancy, but no previous study has examined their longitudinal associations in this time period. AIM: This prospective longitudinal study aimed to identify longitudinal associations between disgust sensitivity and state anxiety across the three trimesters of pregnancy, while exploring the directionality of the effect between those two variables. METHODS: At each trimester of pregnancy, the pregnant women (n = 261) completed the Disgust Scale-Revised (DS-R), the Pathogen disgust domain of the Three Domains of Disgust Scale (TDDS), and the State-Trait Anxiety Inventory. A path analysis (structural equation model) was used to assess cross-lagged effects between disgust sensitivity and state anxiety across the three pregnancy trimesters. FINDINGS: We found significant cross-lagged associations between disgust and anxiety such that higher disgust (overall DS-R score, Core disgust subscale of DS-R and Pathogen disgust domain of TDDS) in the first trimester predicted greater anxiety in the third. No significant cross-lagged associations were found between Animal-reminder or Contamination disgust subscales of DS-R and state anxiety. State anxiety did not predict disgust sensitivity at any time point. DISCUSSION: Our results indicate a unidirectional association between disgust sensitivity and state anxiety in pregnant women such that disgust sensitivity in early pregnancy predicts state anxiety in late pregnancy, but anxiety does not predict disgust sensitivity at any time point. CONCLUSION: Assessing disgust in early pregnancy could help to identify women at risk of higher anxiety levels in advanced pregnancy.

• MeSH
• dospělí MeSH
• lidé MeSH
• longitudinální studie MeSH
• odpor * MeSH
• prospektivní studie MeSH
• průzkumy a dotazníky MeSH
• první trimestr těhotenství * psychologie   MeSH
• psychometrie přístrojové vybavení   metody   MeSH
• těhotenství MeSH
• těhotné ženy * psychologie   MeSH
• úzkost * psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The human mind, trying to perceive events coherently, creates the illusion of continuous time passage. Empirical evidence suggests distortions in subjectively perceived time flow associated with well-studied neural responses to sensory stimuli. This study aimed to investigate whether visually uncomfortable patterns, causing exceptionally strong brain activation, affect short time estimates and whether these estimates vary based on the overall reported sensory sensitivity and cortical excitability of individuals. Two experiments in virtual reality testing our assumptions at different levels of complexity of timed stimuli provided initial insight into the studied processes in highly controlled and realistic conditions. Data analysis results did not support our hypotheses, but showed that subjectively most visually uncomfortable simple patterns, i.e., achromatic gratings, cause more variable temporal judgments. Supposedly, this inaccuracy depends on the currently perceived visual comfort and thus the current visual system sensitivity, which cannot be satisfactorily derived from trait-based measures. The exploration of the effect of complex stimuli, i.e., virtual exteriors, suggested that their visual comfort does not affect time perception at all. Biological sex was an important variable across experiments, as males experienced temporal compression of stimuli compared to females. Neuroimaging research is needed for a deeper investigation of the origin of these results.Protocol registration: The Stage 1 manuscript associated with this Registered Report was in-principle accepted on 4 March 2024 prior to data collection for hypothesis testing. The accepted version of the manuscript can be found in the publicly available OSF repository at https://doi.org/ https://doi.org/10.17605/OSF.IO/K3YZE .

• MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mozek fyziologie   diagnostické zobrazování   MeSH
• světelná stimulace metody   MeSH
• virtuální realita MeSH
• vnímání času * fyziologie   MeSH
• zraková percepce * fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH