Large TRAPPC11 gene deletions as a cause of muscular dystrophy and their estimated genesis.

BACKGROUND: Transport protein particle (TRAPP) is a multiprotein complex that functions in localising proteins to the Golgi compartment. The TRAPPC11 subunit has been implicated in diseases affecting muscle, brain, eye and to some extent liver. We present three patients who are compound heterozygotes for a missense variant and a structural variant in the TRAPPC11 gene. TRAPPC11 structural variants have not yet been described in association with a disease. In order to reveal the estimated genesis of identified structural variants, we performed sequencing of individual breakpoint junctions and analysed the extent of homology and the presence of repetitive elements in and around the breakpoints. METHODS: Biochemical methods including isoelectric focusing on serum transferrin and apolipoprotein C-III, as well as mitochondrial respiratory chain complex activity measurements, were used. Muscle biopsy samples underwent histochemical analysis. Next-generation sequencing was employed for identifying sequence variants associated with neuromuscular disorders, and Sanger sequencing was used to confirm findings. RESULTS: We suppose that non-homologous end joining is a possible mechanism of deletion origin in two patients and non-allelic homologous recombination in one patient. Analyses of mitochondrial function performed in patients' skeletal muscles revealed an imbalance of mitochondrial metabolism, which worsens with age and disease progression. CONCLUSION: Our results contribute to further knowledge in the field of neuromuscular diseases and mutational mechanisms. This knowledge is important for understanding the molecular nature of human diseases and allows us to improve strategies for identifying disease-causing mutations.

Prevalence of ADHD Symptomatology in Adult Population in the Czech Republic: A National Study.

BACKGROUND: ADHD is a common neurodevelopmental disorder frequently diagnosed between the ages 7 and 10 years. We measured ADHD symptomatology in a representative sample of the Czech population. MATERIAL AND METHODS: Data collection was performed in January 2019 through the European National Panel. The respondents completed a demographic questionnaire focusing on ADHD history and a standardized questionnaire, the Adult ADHD Self-Report Scale (ASRS) screener for ADHD symptomatology in adulthood. RESULTS: From the sample of 1,518 respondents, 3% of the respondents reported having been diagnosed with ADHD/hyperkinetic disorder in their lifetime. According to ASRS scoring, 119 respondents were classified as suspected ADHD. Overall, more males than females reported ADHD symptomatology. Age was also significantly associated with ASRS. Education status yielded no significant results. CONCLUSION: Our study documents that the prevalence of ADHD symptomatology in adults is comparable with that in Western countries despite the different historical and health care backgrounds.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Time Perception in Adults: Do Adults with Different ADHD Symptomatology Severity Perceive Time Differently? Findings from the National Czech Study.

BACKGROUND Studies show neurological differences between patients with attention-deficit/hyperactivity disorder (ADHD) and healthy controls. Furthermore, it is possible that poor timing is linked with impairments in neural circuitry. This study aimed to test the hypothesis that there is a difference in time perception between adults with severe ADHD symptomatology and adults with no ADHD symptomatology. MATERIAL AND METHODS Previously, we collected data from a more extensive set of participants (n=1518) concerning the prevalence of ADHD in adulthood. We recruited participants from 3 groups defined by increasing ADHD severity out of this participant pool. Each participant was presented with 2 experimental tasks (in counterbalanced order): duration estimation and duration discrimination. RESULTS In general, we did not find any specific differences in time perception related to the severity of ADHD. Regarding duration estimation, we found that the difference between the actual and estimated durations increased with the actual duration (F(1, 7028.00)=2685.38, P<0.001). Although the differences between groups were not significant, the group×duration interaction was (F[1, 7028.00]=10.86, P<0.001), with a very small effect size (ηp²<0.001, 95% CI [0.00, 0.01]). CONCLUSIONS The results suggest that although individuals may demonstrate increased ADHD symptomatology, they may not have objectively more significant difficulties in time perception tasks than their counterparts with mild symptomatology. Nonetheless, time perception should be further studied because, as qualitative research suggests, participants with more severe ADHD symptomatology subjectively perceive more significant differences in time management in real life.

Cognitive and Socioemotional Development at 5 and 9 Years of Age of Children Born with Very Low Birth Weight and Extremely Low Birth Weight in the Czech Republic.

BACKGROUND There is a high prevalence of cognitive and socioemotional dysfunction in very low birth weight (VLBW <1500 g) and extremely low birth weight (ELBW <1000 g) children. This study from the Czech Republic aimed to compare the cognitive and socioemotional development at 5 and 9 years of age of children born with VLBW/ELBW with children born with normal birth weight (NBW ≥2500 g). MATERIAL AND METHODS The clinical group consisted of 118 VLBW/ELBW children and the control group consisted of 101 children with NBW at ages 5 to 9 years. The research battery included selected subscales from the Intelligence and Development Scales (IDS), A Developmental Neuropsychological Assessment - second edition (NEPSY-II), and the Behavior Rating Inventory of Executive Function (BRIEF). Data were analyzed using STATA IC v. 15 software and G*Power (descriptive statistic, analysis of variance (ANOVA), correlations, multivariate analysis of variance - MANOVA, post hoc power analysis). RESULTS We found a statistically significant difference in cognitive and socioemotional development between children with VLBW/ELBW and those with NBW. The average intelligence quotient (IQ) of VLBW/ELBW children was 96.38, while that of NBW children was 12.98 points higher (P<0.001). NBW children achieved better results on all subtests of the IDS (P<0.001) as well as in affect recognition (P<0.001). All results for both groups were within normal range. Parents of VLBW/ELBW children did not recognize impaired executive functioning (P=0.494). CONCLUSIONS This study has shown significant cognitive and socioemotional deficit in children born with VLBW and ELBW when evaluated at 5 and 9 years of age.

Selective Neuronal Mitochondrial Targeting in SARS-CoV-2 Infection Affects Cognitive Processes to Induce 'Brain Fog' and Results in Behavioral Changes that Favor Viral Survival.

Alterations in brain functioning, especially in regions associated with cognition, can result from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and are predicted to result in various psychiatric diseases. Recent studies have shown that SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) can directly or indirectly affect the central nervous system (CNS). Therefore, diseases associated with sequelae of COVID-19, or 'long COVID', also include serious long-term mental and cognitive changes, including the condition recently termed 'brain fog'. Hypoxia in the microenvironment of select brain areas may benefit the reproductive capacity of the virus. It is possible that in areas of cerebral hypoxia, neuronal cell energy metabolism may become compromised after integration of the viral genome, resulting in mitochondrial dysfunction. Because of their need for constant high metabolism, cerebral tissues require an immediate and constant supply of oxygen. In hypoxic conditions, neurons with the highest oxygen demand become dysfunctional. The resulting cognitive impairment benefits viral spread, as infected individuals exhibit behaviors that reduce protection against infection. The effects of compromised mitochondrial function may also be an evolutionary advantage for SARS-CoV-2 in terms of host interaction. A high viral load in patients with COVID-19 that involves the CNS results in the compromise of neurons with high-level energy metabolism. Therefore, we propose that selective neuronal mitochondrial targeting in SARS-CoV-2 infection affects cognitive processes to induce 'brain fog' and results in behavioral changes that favor viral propagation. Cognitive changes associated with COVID-19 will have increasing significance for patient diagnosis, prognosis, and long-term care.

Prevalence of ADHD Symptomatology in Adult Population in the Czech Republic-A National Study.

Background: Attention deficit/hyperactivity disorder is a common neurodevelopmental disorder frequently diagnosed between the ages 7 and 10 years. We measured ADHD symptomatology in a representative sample of the Czech population. Material and Methods: Data collection was performed in January 2019 through the European National Panel. The respondents completed a demographic questionnaire focusing on ADHD history and a standardized questionnaire, the Adult ADHD Self-Report Scale (ASRS) screener for ADHD symptomatology in adulthood. Results: From the sample of 1,518 respondents, 3% of the respondents reported having been diagnosed with ADHD/hyperkinetic disorder in their lifetime. According to ASRS scoring, 119 respondents were classified as suspected ADHD. Overall, more males than females reported ADHD symptomatology. Age was also significantly associated with ASRS. Education status yielded no significant results. Conclusion: Our study documents that the prevalence of ADHD symptomatology in adults is comparable with that in Western countries despite the different historical and health care backgrounds.

Psychiatric Manifestations of COVID-19 and Their Social Significance.

Alterations in complex behavioral patterns during the extended period of the COVID-19 pandemic are predicted to promote a variety of psychiatric disease symptoms due to enforced social isolation and self-quarantine. Accordingly, multifaceted mental health problems will continue to increase, thereby creating a challenge for society and the health care system in general. Recent studies show that COVID-19 can directly or indirectly influence the central nervous system, potentially causing neurological pathologies such as Alzheimer disease and Parkinson disease. Thus, chronic COVID-19-related disease processes have the potential to cause serious mental illnesses, including depression, anxiety, and sleep disorders. Importantly, mental health problems can foster systemic changes in functionally-linked neuroendocrine conditions that heighten a person's susceptibility to COVID-19 infection. These altered defense mechanisms may include compromised "self-control" and "self-care", as well as a "lack of insight" into the danger posed by the virus. These consequences may have serious social impacts on the future of COVID-19 survivors. Compounding the functionally related issues of altered mental health parameters and viral susceptibility are the potential effects of compromised immunity on the establishment of functional herd immunity. Within this context, mental health takes on added importance, particularly in terms of the need to increase support for mental health research and community-based initiatives. Thus, COVID-19 infections continue to reveal mental health targets, a process we must now be prepared to deal with.

BMI and Odds of Endometrial Adenocarcinoma in Czech Women - a Case Control Study.

INTRODUCTION: The incidence of malignant tumors of the uterine body is increasing in the Czech Republic. Endometrial adenocarcinoma is one of the most frequent morphological types. Obesity or even overweight is a risk factor for the development of this disease. More accurate stratification of risk relative to body mass index (BMI) has not yet been determined in the Czech Republic, although the risk of overweight (BMI 25-29.9) has been reported in one study as comparable to that of first or second degree obesity (BMI 30-30.9). PATIENTS AND METHODS: The study population included 376 women of Caucasian race diagnosed with endometrial adenocarcinoma, with BMI measured simultaneously, in 2005-2017. A control group consisted of an equal number of age-matched women not diagnosed with any oncological or gynecological disease. These two files were statistically processed. RESULTS: Odds (OR, 95% CI) relative to normal weight women, overweight women were at 2.26-times higher odds of endometrial adenocarcinoma, and women with obesity were at 5.18-8.67-, and 24.70-times higher odds, depending on the severity of obesity. CONCLUSION: The hypothesis that overweight represents same risk for the development of endometrial adenocarcinoma, as lower degrees of obesity was not verified. However overweight is serious risk for endometrial adenocarcinoma development. The odds of endometrial adenocarcinoma is correlated with increasing BMI and in the population studied is higher than reported previously for all endometrial carcinoma subtypes. This work was carried out with the support of an internal grant of Krajská zdravotní, a.s., for the years 2017-2019: IGA217129002. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 29. 4. 2019 Accepted: 22. 7. 2019.