BACKGROUND: The distribution of time across physical activity, sedentary behaviors, and sleep appears to be essential for the management of obesity. However, the impact of reallocating time among these behaviors, collectively known as 24-h movement behaviors, remains underexplored. OBJECTIVE: This study examines the theoretical effects of reallocating time between 24-h movement behaviors on obesity indicators across different age groups. METHODS: We performed a pooled data meta-analysis of 9818 participants from 11 observational and experimental studies. To estimate the time spent in movement behaviors, we reprocessed and harmonized individual-level raw accelerometer-derived data. Isotemporal substitution models estimated theoretical changes in body mass index (BMI) and waist circumference (WC) associated with time reallocation between movement behaviors. We performed the analysis separately for children, adolescents, adults, and older adults. RESULTS: Even minor reallocations of 10 min led to significant changes in obesity indicators, with pronounced effects observed when 30 min were reallocated. The most substantial adverse effects on BMI and WC occurred when moderate-to-vigorous physical activity (MVPA) was reallocated to other movement behaviors. For 30-min reallocations, the largest increase in BMI (or BMI z-score for children) occurred when MVPA was reallocated to light-intensity physical activity (LPA) in children (0.26 units, 95% confidence interval [CI] 0.15, 0.37) and to sedentary behavior (SB) in adults (0.72 kg/m2, 95% CI 0.47, 0.96) and older adults (0.73 kg/m2, 95% CI 0.59, 0.87). The largest increase in WC was observed when MVPA was substituted with LPA in adults (2.66 cm, 95% CI 1.42, 3.90) and with SB in older adults (2.43 cm, 95% CI 2.07, 2.79). Conversely, the highest magnitude of the decrease in obesity indicators was observed when SB was substituted with MVPA. Specifically, substituting 30 min of SB with MVPA was associated with a decrease in BMI z-score by - 0.15 units (95% CI - 0.21, - 0.10) in children and lower BMI by - 0.56 kg/m2 (95% CI - 0.74, - 0.39) in adults and by - 0.52 kg/m2 (95% CI - 0.61, - 0.43) in older adults. Reallocating time away from sleep and LPA showed several significant changes but lacked a consistent pattern. While the predicted changes in obesity indicators were generally consistent across age groups, inconsistent findings were observed in adolescents, particularly for reallocations between MVPA and other behaviors. CONCLUSIONS: This investigation emphasizes the crucial role of MVPA in mitigating obesity risk across the lifespan, and the benefit of substituting SB with low-intensity movement behaviors. The distinct patterns observed in adolescents suggest a need for age-specific lifestyle interventions to effectively address obesity. Emphasizing manageable shifts, such as 10-min reallocations, could have significant public health implications, promoting sustainable lifestyle changes that accommodate individuals with diverse needs, including those with severe obesity.

• MeSH
• akcelerometrie MeSH
• časové faktory MeSH
• cvičení * MeSH
• dítě MeSH
• dospělí MeSH
• index tělesné hmotnosti MeSH
• léčba obezity * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• obezita * MeSH
• obvod pasu MeSH
• sedavý životní styl * MeSH
• senioři MeSH
• spánek MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

OBJECTIVE: Previous retrospective studies have reported vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM), although clinical impact is unknown. We evaluated the association between vigabatrin and predefined brain magnetic resonance imaging (MRI) changes in a large homogenous tuberous sclerosis complex (TSC) cohort and assessed to what extent VABAM-related symptoms were reported in TSC infants. METHODS: The Dutch TSC Registry and the EPISTOP cohort provided retrospective and prospective data from 80 TSC patients treated with vigabatrin (VGB) before the age of 2 years and 23 TSC patients without VGB. Twenty-nine age-matched non-TSC epilepsy patients not receiving VGB were included as controls. VABAM, specified as T2/fluid-attenuated inversion recovery hyperintensity or diffusion restriction in predefined brain areas, were examined on brain MRI before, during, and after VGB, and once in the controls (at approximately age 2 years). Additionally, the presence of VABAM accompanying symptoms was evaluated. RESULTS: Prevalence of VABAM in VGB-treated TSC patients was 35.5%. VABAM-like abnormalities were observed in 13.5% of all patients without VGB. VGB was significantly associated with VABAM (risk ratio [RR] = 3.57, 95% confidence interval [CI] = 1.43-6.39), whereas TSC and refractory epilepsy were not. In all 13 VGB-treated patients with VABAM for whom posttreatment MRIs were available, VABAM entirely resolved after VGB discontinuation. The prevalence of symptoms was 11.7% in patients with VABAM or VABAM-like MRI abnormalities and 4.3% in those without, implicating no significant association (RR = 2.76, 95% CI = .68-8.77). SIGNIFICANCE: VABAM are common in VGB-treated TSC infants; however, VABAM-like abnormalities also occurred in children without either VGB or TSC. The cause of these MRI changes is unknown. Possible contributing factors are abnormal myelination, underlying etiology, recurrent seizures, and other antiseizure medication. Furthermore, the presence of VABAM (or VABAM-like abnormalities) did not appear to be associated with clinical symptoms. This study confirms that the well-known antiseizure effects of VGB outweigh the risk of VABAM and related symptoms.

• MeSH
• antikonvulziva * škodlivé účinky   terapeutické užití   MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek * diagnostické zobrazování   účinky léků   MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• registrace MeSH
• retrospektivní studie MeSH
• tuberózní skleróza * diagnostické zobrazování   komplikace   MeSH
• vigabatrin * terapeutické užití   škodlivé účinky   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The actions required to achieve higher-quality and harmonised global surveillance of child and adolescent movement behaviours (physical activity, sedentary behaviour including screen time, sleep) are unclear. OBJECTIVE: To identify how to improve surveillance of movement behaviours, from the perspective of experts. METHODS: This Delphi Study involved 62 experts from the SUNRISE International Study of Movement Behaviours in the Early Years and Active Healthy Kids Global Alliance (AHKGA). Two survey rounds were used, with items categorised under: (1) funding, (2) capacity building, (3) methods, and (4) other issues (e.g., policymaker awareness of relevant WHO Guidelines and Strategies). Expert participants ranked 40 items on a five-point Likert scale from 'extremely' to 'not at all' important. Consensus was defined as > 70% rating of 'extremely' or 'very' important. RESULTS: We received 62 responses to round 1 of the survey and 59 to round 2. There was consensus for most items. The two highest rated round 2 items in each category were the following; for funding (1) it was greater funding for surveillance and public funding of surveillance; for capacity building (2) it was increased human capacity for surveillance (e.g. knowledge, skills) and regional or global partnerships to support national surveillance; for methods (3) it was standard protocols for surveillance measures and improved measurement method for screen time; and for other issues (4) it was greater awareness of physical activity guidelines and strategies from WHO and greater awareness of the importance of surveillance for NCD prevention. We generally found no significant differences in priorities between low-middle-income (n = 29) and high-income countries (n = 30) or between SUNRISE (n = 20), AHKGA (n = 26) or both (n = 13) initiatives. There was a lack of agreement on using private funding for surveillance or surveillance research. CONCLUSIONS: This study provides a prioritised and international consensus list of actions required to improve surveillance of movement behaviours in children and adolescents globally.

• MeSH
• budování kapacit MeSH
• čas strávený před obrazovkou * MeSH
• celosvětové zdraví MeSH
• cvičení * MeSH
• delfská metoda * MeSH
• dítě MeSH
• konsensus MeSH
• lidé MeSH
• mladiství MeSH
• sedavý životní styl * MeSH
• spánek MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

During GABAergic synaptic transmission, G protein-coupled GABAB receptors (GBRs) activate K+ channels that prolong the duration of inhibitory postsynaptic potentials (IPSPs). We now show that KCTD16, an auxiliary GBR subunit, anchors hyperpolarization-activated cyclic nucleotide-gated (HCN) channels containing HCN2/HCN3 subunits to GBRs. In dopamine neurons of the VTA (DAVTA neurons), this interaction facilitates activation of HCN channels via hyperpolarization during IPSPs, counteracting the GBR-mediated late phase of these IPSPs. Consequently, disruption of the GBR/HCN complex in KCTD16-/- mice leads to prolonged optogenetic inhibition of DAVTA neuron firing. KCTD16-/- mice exhibit increased anxiety-like behavior in response to stress - a behavior replicated by CRISPR/Cas9-mediated KCTD16 ablation in DAVTA neurons or by intra-VTA infusion of an HCN antagonist in wild-type mice. Our findings support that the retention of HCN channels at GABAergic synapses by GBRs in DAVTA neurons provides a negative feedback mechanism that restricts IPSP duration and mitigates the development of anxiety.

• MeSH
• dopaminergní neurony * metabolismus   MeSH
• hyperpolarizační iontové kanály řízené cyklickými nukleotidy * metabolismus   genetika   MeSH
• inhibiční postsynaptické potenciály fyziologie   účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• receptory GABA-B * metabolismus   MeSH
• tegmentum mesencephali - area ventralis * metabolismus   MeSH
• úzkost * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.

• MeSH
• Asijci genetika   MeSH
• běloch MeSH
• běloši genetika   MeSH
• bipolární porucha * genetika   MeSH
• celogenomová asociační studie * MeSH
• černoši nebo Afroameričané genetika   MeSH
• fenotyp * MeSH
• GABAergní neurony metabolismus   MeSH
• genetická predispozice k nemoci MeSH
• genomika * MeSH
• Hispánci a Latinoameričané genetika   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Pathogenesis of epilepsy involves dysregulation of the neurotransmitter system contributing to hyper-excitability of neuronal cells. MicroRNA (miRNAs) are small non-coding RNAs known to play a crucial role in post-transcriptional regulation of gene expression. METHODS: The present review was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, employing a comprehensive search strategy to identify and extract data from published research articles. Keywords suchas epilepsy, micro RNA (micro RNAs, miRNA, miRNAs, miR), neurotransmitters (specific names), and neurotransmitter receptors (specific names) were used to construct the query. RESULTS: A total of 724 articles were identified using the keywords epilepsy, microRNA along with select neurotransmitter and neurotransmitter receptor names. After exclusions, the final selection consisted of 17 studies, most of which centered on glutamate and gamma-aminobutyric acid (GABA) receptors. Singular studies also investigated miRNAs affecting cholinergic, purinergic, and glycine receptors. CONCLUSION: This review offers a concise overview of the current knowledge on miRNA-mediated regulation of neurotransmitter receptors in epilepsy and highlights their potential for future clinical application.

• MeSH
• epilepsie * genetika   metabolismus   MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• receptory neurotransmiterů * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

BACKGROUND AND OBJECTIVES: Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. METHODS: This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. RESULTS: We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. DISCUSSION: Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.

• MeSH
• autoprotilátky * krev   MeSH
• dospělí MeSH
• encefalitida * imunologie   MeSH
• Hashimotova nemoc imunologie   krev   MeSH
• intracelulární signální peptidy a proteiny * imunologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny * imunologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• proteiny nervové tkáně * imunologie   MeSH
• proteiny imunologie   MeSH
• receptory GABA-B * imunologie   MeSH
• receptory N-methyl-D-aspartátu imunologie   MeSH
• recidiva * MeSH
• retrospektivní studie MeSH
• senioři MeSH
• záchvaty etiologie   imunologie   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
• multicentrická studie MeSH

GABAB receptors (GBRs) are G protein-coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. GBRs regulate fast synaptic transmission by gating Ca2+ and K+ channels via the Gβγ subunits of the activated G protein. It has been demonstrated that auxiliary GBR subunits, the KCTD proteins, shorten onset and rise time and increase desensitization of receptor-induced K+ currents. KCTD proteins increase desensitization of K+ currents by scavenging Gβγ from the channel, yet the mechanism responsible for the rapid activation of K+ currents has remained elusive. In this study, we demonstrate that KCTD proteins preassemble Gβγ at GBRs. The preassembly obviates the need for diffusion-limited G protein recruitment to the receptor, thereby accelerating G protein activation and, as a result, K+ channel activation. Preassembly of Gβγ at the receptor relies on the interaction of KCTD proteins with a loop protruding from the seven-bladed propeller of Gβ subunits. The binding site is shared between Gβ1 and Gβ2, limiting the interaction of KCTD proteins to these particular Gβ isoforms. Substituting residues in the KCTD binding site of Gβ1 with those from Gβ3 hinders the preassembly of Gβγ with GBRs, delays onset and prolongs rise time of receptor-activated K+ currents. The KCTD-Gβ interface, therefore, represents a target for pharmacological modulation of channel gating by GBRs.

• MeSH
• draslíkové kanály metabolismus   genetika   MeSH
• gating iontového kanálu * fyziologie   MeSH
• HEK293 buňky MeSH
• lidé MeSH
• proteiny vázající GTP - beta-podjednotky * metabolismus   genetika   MeSH
• proteiny vázající GTP - gama-podjednotky * metabolismus   genetika   MeSH
• receptory GABA-B * metabolismus   genetika   MeSH
• Xenopus laevis MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: National surveillance of physical activity (PA) is essential to establish public health policy actions for PA promotion and evaluation, thereby promoting accountability. The main goal of this study is to comprehensively analyse surveillance data on PA behaviours, outcomes, and influencing factors among Slovakian children and adolescents by using the methodology of the Active Healthy Kids Global Alliance Global Matrix (AHKGA-GM) project. Secondary goals are to provide comparisons with international data and the identification of surveillance gaps. METHODS: A comprehensive multilevel search strategy for data about 10 core indicators and 1 additional indicator published between 2015 and 2020 (solely pre-COVID-19-pandemic data) was used. The data were then synthesised, and a set of standardised benchmarks was used to assign grades according to The Global Matrix 4.0 Grading Rubric. RESULTS: A total of 552 potentially relevant data resources were retrieved, of which 34 were identified as eligible for data extraction. Grade B was assigned to four core indicators, grade C to five core indicators, and grade D to one core indicator. The additional Sleep indicator was graded a C-. Compared with the average grades from countries with high Human Development Index scores, Slovakia received higher grades in five core indicators (Overall Physical Activity, Active Transportation, Sedentary Behaviours, School, Government), and in the aggregate Behavioural average and Overall average. Compared with global averages, Slovakia had higher grades in the aforementioned core and aggregate indicators, and in the Community and Environment core indicator and aggregate Sources of Influence average indicator. Numerous surveillance gaps were identified. CONCLUSIONS: The overall grading of the available surveillance data suggests the need for improvement in all 10 surveilled core indicators, and in additional Sleep indicator. Despite the fact that numerous identified surveillance gaps limit the overall informative value of the current grade, they provide the important information needed to enhance surveillance of PA-related indicators in Slovakia. For instance, the focus should be put on younger children and parents, on obtaining the device-measured data on various movement behaviours, on the topic of outdoor physical activities, and policy evaluation.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Migraine and epilepsy are two paroxysmal chronic neurological disorders affecting a high number of individuals and being responsible for a high individual and socioeconomic burden. The link between these disorders has been of interest for decades and innovations concerning diagnosing and treatment enable new insights into their relationship. FINDINGS: Although appearing to be distinct at first glance, both diseases exhibit a noteworthy comorbidity, shared pathophysiological pathways, and significant overlaps in characteristics like clinical manifestation or prophylactic treatment. This review aims to explore the intricate relationship between these two conditions, shedding light on shared pathophysiological foundations, genetic interdependencies, common and distinct clinical features, clinically overlapping syndromes, and therapeutic similarities. There are several shared pathophysiological mechanisms, like CSD, the likely underlying cause of migraine aura, or neurotransmitters, mainly Glutamate and GABA, which represent important roles in triggering migraine attacks and seizures. The genetic interrelations between the two disorders can be observed by taking a closer look at the group of familial hemiplegic migraines, which are caused by mutations in genes like CACNA1A, ATP1A2, or SCN1A. The intricate relationship is further underlined by the high number of shared clinical features, which can be observed over the entire course of migraine attacks and epileptic seizures. While the variety of the clinical manifestation of an epileptic seizure is naturally higher than that of a migraine attack, a distinction can indeed be difficult in some cases, e.g. in occipital lobe epilepsy. Moreover, triggering factors like sleep deprivation or alcohol consumption play an important role in both diseases. In the period after the seizure or migraine attack, symptoms like speech difficulties, tiredness, and yawning occur. While the actual attack of the disease usually lasts for a limited time, research indicates that individuals suffering from migraine and/or epilepsy are highly affected in their daily life, especially regarding cognitive and social aspects, a burden that is even worsened using antiseizure medication. This medication allows us to reveal further connections, as certain antiepileptics are proven to have beneficial effects on the frequency and severity of migraine and have been used as a preventive drug for both diseases over many years. CONCLUSION: Migraine and epilepsy show a high number of similarities in their mechanisms and clinical presentation. A deeper understanding of the intricate relationship will positively advance patient-oriented research and clinical work.

• MeSH
• antikonvulziva terapeutické užití   MeSH
• epilepsie * etiologie   genetika   MeSH
• komorbidita MeSH
• lidé MeSH
• migréna s aurou * genetika   MeSH
• migréna * diagnóza   genetika   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH