AIM: Exposure to light at night and meal time misaligned with the light/dark (LD) cycle-typical features of daily life in modern 24/7 society-are associated with negative effects on health. To understand the mechanism, we developed a novel protocol of complex chronodisruption (CD) in which we exposed female rats to four weekly cycles consisting of 5-day intervals of constant light and 2-day intervals of food access restricted to the light phase of the 12:12 LD cycle. METHODS: We examined the effects of CD on behavior, estrous cycle, sleep patterns, glucose homeostasis and profiles of clock- and metabolism-related gene expression (using RT qPCR) and liver metabolome and lipidome (using untargeted metabolomic and lipidomic profiling). RESULTS: CD attenuated the rhythmic output of the central clock in the suprachiasmatic nucleus via Prok2 signaling, thereby disrupting locomotor activity, the estrous cycle, sleep patterns, and mutual phase relationship between the central and peripheral clocks. In the periphery, CD abolished Per1,2 expression rhythms in peripheral tissues (liver, pancreas, colon) and worsened glucose homeostasis. In the liver, it impaired the expression of NAD+, lipid, and cholesterol metabolism genes and abolished most of the high-amplitude rhythms of lipids and polar metabolites. Interestingly, CD abolished the circadian rhythm of Cpt1a expression and increased the levels of long-chain acylcarnitines (ACar 18:2, ACar 16:0), indicating enhanced fatty acid oxidation in mitochondria. CONCLUSION: Our data show the widespread effects of CD on metabolism and point to ACars as biomarkers for CD due to misaligned sleep and feeding patterns.
- MeSH
- Circadian Clocks physiology MeSH
- Circadian Rhythm * physiology MeSH
- Photoperiod MeSH
- Liver * metabolism MeSH
- Carnitine * analogs & derivatives metabolism MeSH
- Rats MeSH
- Metabolome * MeSH
- Suprachiasmatic Nucleus metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: This study aims to evaluate the feasibility of generating pseudo-normal single photon emission computed tomography (SPECT) data from potentially abnormal images. These pseudo-normal images are primarily intended for use in an on-the-fly data harmonization technique. MATERIAL AND METHODS: The methodology was tested on brain SPECT with [123I]Ioflupane. The proposed model for generating a pseudo-normal image was based on a variational autoencoder (VAE) designed to process 2D sinograms of the brain [123I]-FP-CIT SPECT, potentially exhibiting abnormal uptake. The model aimed to predict SPECT sinograms with corresponding normal uptake. Training, validation, and testing datasets were created by SPECT simulator from 45 brain masks segmented from real patient's magnetic resonance (MR) scans, using various uptake levels. The training and validation datasets each comprised 612 and 360 samples, respectively, drawn from 36 brain masks. The testing dataset contained 153 samples based on 9 brain masks. VAE performance was evaluated through brain dimensions, Dice similarity coefficient (DSC) and specific binding ratio. RESULTS: Mean DSC was 80% for left basal ganglia and 84% for right basal ganglia. The proposed VAE demonstrated excellent consistency in predicting basal ganglia shape, with a coefficient of variation of DSC being less than 1.1%. CONCLUSIONS: The study demonstrates that VAE can effectively estimate an individualized pseudo-normal distribution of the radiotracer [123I]-FP-CIT SPECT from abnormal SPECT images. The main limitations of this preliminary research are the limited availability of real brain MR data, used as input for the SPECT data simulator, and the simplified simulation setup employed to create the synthetic dataset.
- MeSH
- Tomography, Emission-Computed, Single-Photon * MeSH
- Humans MeSH
- Brain * diagnostic imaging MeSH
- Image Processing, Computer-Assisted * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The selection of proper reference genes and materials is critical in the design of PCR experiments, especially for differential expression studies. In this study, we propose a method to identify robust endogenous control miRNAs in the visceral adipose tissue of C57BL/6J mice with non-alcoholic fatty liver disease induced by alternating Western and control diets. This study outlines a comprehensive methodology for the analysis of microRNA endogenous controls using microfluidic cards in conjunction with miRNA profiling through small RNA sequencing and subsequent validation by quantitative PCR and the RefFinder algorithm. Criteria included were fold change, p-value, reads per million, and gene stability assessment. A set of six putative endogenous microRNAs was identified (miR-331-3p, let-7a-5p, miR-1839-5p, miR-151a-5p, let-7d-5p, and let-7c-5p). Subsequent validation and analysis using the RefFinder algorithm assessed the stability of the selected genes, and a combination of the three most stable endogenous miRNA controls (miR-331-3p, let-7a- 5p, and miR-1839-5p) exhibiting consistent expression patterns with minimal variability was set. Given the absence of universal endogenous controls, individual evaluation of normalizers for each experiment is imperative for accurate miRNA expression measurements. This approach, which combines multiple techniques and assessments, provides a reliable strategy for identifying and validating endogenous controls in miRNA studies.
- MeSH
- Algorithms MeSH
- MicroRNAs * genetics metabolism MeSH
- Disease Models, Animal * MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Non-alcoholic Fatty Liver Disease * genetics metabolism pathology MeSH
- Intra-Abdominal Fat * metabolism MeSH
- Gene Expression Regulation MeSH
- Gene Expression Profiling methods MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Cystathionine β-synthase (CBS) deficiency (classical homocystinuria) has a wide range of severity. Mildly affected patients typically present as adults with thromboembolism and respond to treatment with pyridoxine. Severely affected patients usually present during childhood with learning difficulties, ectopia lentis and skeletal abnormalities; they are pyridoxine non-responders (NR) or partial responders (PR) and require treatment with a low-methionine diet and/or betaine. The European network and registry for Homocystinurias and methylation Defects (E-HOD) has published management guidelines for CBS deficiency and recommended keeping plasma total homocysteine (tHcy) concentrations below 100 μmol/L. We have now analysed data from 311 patients in the registry to see how closely treatment follows the guidelines. Pyridoxine-responsive patients generally achieved tHcy concentrations below 50 μmol/L, but many NRs and PRs had a mean tHcy considerably above 100 μmol/L. Most NRs were managed with betaine and a special diet. This usually involved severe protein restriction and a methionine-free amino acid mixture, but some patients had a natural protein intake substantially above the WHO safe minimum. Work is needed on the methionine content of dietary protein as estimates vary widely. Contrary to the guidelines, most NRs were on pyridoxine, sometimes at dangerously high doses. tHcy concentrations were similar in groups prescribed high or low betaine doses and natural protein intakes. High tHcy levels were probably often due to poor compliance. Comparing time-to-event graphs for NR patients detected by newborn screening and those ascertained clinically showed that treatment could prevent thromboembolism (risk ratio 0.073) and lens dislocation (risk ratio 0.069).
- MeSH
- Betaine * therapeutic use MeSH
- Cystathionine beta-Synthase deficiency MeSH
- Child MeSH
- Adult MeSH
- Homocysteine * blood metabolism MeSH
- Homocystinuria * drug therapy MeSH
- Infant MeSH
- Humans MeSH
- Methionine * deficiency MeSH
- Adolescent MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Pyridoxine * therapeutic use MeSH
- Registries * MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The evolving gambling environment, marked by increased accessibility and innovative promotions, has led to rising expenditures globally. Despite this, the relationship between social media use and problem gambling in the Czech Republic remains underexplored. To investigate the association between social media use and problem gambling severity among Czech adults using the Problem Gambling Severity Index (PGSI). Is there a difference in gambling severity based on demographic characteristics? (1); Is there a relationship between social media news consumption and gambling severity? (2); Is there a connection between negative motives for social media use and problematic usage? (3); Is there a link between problematic social media use and gambling severity? (4). Primary research, designed as a cross-sectional study, was conducted in the Czech Republic in November 2024 on a sample of 3093 respondents (48.4% male). All participants were aged 16 years or older. The sample was selected using quota sampling based on multiple identifying quota variables, with minimal differences in the proportions of quota indicators compared to the general population. Non-parametric tests and ordinal logistic regression analyzed relationships between demographics, social media use, and PGSI scores. Higher PGSI scores were found among males, younger participants, those with lower education, and the unemployed or students. Greater social media news consumption correlated with increased gambling severity. Disruptive social media behaviors, such as waking up to check notifications and interrupting activities, were significantly associated with higher PGSI scores. Problematic social media use involving deceit and family conflict substantially heightened the risk of severe gambling problems. These findings highlight the need for targeted prevention initiatives, regulatory policies, and enhanced digital literacy to safeguard vulnerable groups from the risks posed by digital gambling platforms. Addressing both gambling behaviors and problematic social media use is crucial in mitigating potential harms.
- MeSH
- Adult MeSH
- Gambling * psychology MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Motivation MeSH
- Cross-Sectional Studies MeSH
- Surveys and Questionnaires MeSH
- Aged MeSH
- Social Media * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
The authors of the article titled "Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine" (Dhanjal DS, Singh R, Sharma V, Nepovimova E, Adam V, Kuca K, Chopra C. Curr Med Chem. 2024; 31(13): 1646-1690. DOI: 10.2174/0929867330666230503144619. PMID: 37138422) [1] have made revisions to the references in the text and the reference section. These updates have been made to ensure the integrity of the article. The updated reference list can be found in the latest version of the article. The authors apologize for any confusion or inconvenience caused. The original article can be found online at: https://www.eurekaselect.com/article/131443.
- MeSH
- Humans MeSH
- Cellular Reprogramming * genetics MeSH
- Regenerative Medicine * MeSH
- Developmental Biology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND AND PURPOSE: The primary objective was to compare diffusion tensor imaging (DTI) scalar parameters of peripheral nerves between subjects with type 2 diabetes mellitus (T2DM) and those without diabetes. Secondarily, we aimed to correlate DTI scalar parameters with nerve morphometric properties. METHODS: Median, tibial, and sural nerves were harvested from 34 male cadavers (17 T2DM, 17 nondiabetic). Each nerve was divided into three segments. The initial segment was scanned using 9.4 Tesla MRI system (three-dimensional pulsed-gradient spin-echo sequence). DTI scalars were calculated from region-average diffusion-weighted signals. Second segment was optically cleared, acquired with optical projection tomography (OPT), and analyzed for morphometrical properties. Toluidine-stained sections were prepared from last segment, and axon- and myelin-related properties were evaluated. RESULTS: DTI scalar parameters of median and tibial nerves were comparable between the groups, while sural nerves of T2DM exhibited on average 41% higher mean diffusivity (MD) (p = 0.03), 38% higher radial diffusivity (RD) (p = 0.03), and 27% lower fractional anisotropy (FA) (p = 0.005). Significant differences in toluidine-evaluated parameters of sural nerves were observed between the groups, with a positive correlation between FA with fiber density (p = 0.0001) and with myelin proportion (p < 0.0001) and an inverse correlation between RD and myelin proportion (p = 0.003). OPT-measured morphometric properties did not correlate with DTI scalar parameters. CONCLUSIONS: High-field DTI shows promise as an imaging technique for detecting axonal and myelin-related changes in small sural nerves ex vivo. The reduced fiber density and decreased myelin content, which can be observed in T2DM, likely contribute to observed FA reduction and increased MD/RD.
- MeSH
- Diabetes Mellitus, Type 2 * diagnostic imaging pathology MeSH
- Diabetic Neuropathies diagnostic imaging pathology MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Cadaver * MeSH
- Median Nerve diagnostic imaging pathology MeSH
- Sural Nerve * diagnostic imaging pathology MeSH
- Tibial Nerve diagnostic imaging pathology MeSH
- Reproducibility of Results MeSH
- Aged MeSH
- Sensitivity and Specificity MeSH
- Diffusion Tensor Imaging * methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The effect of dexmedetomidine on regional splanchnic blood flow remain unclear. OBJECTIVES: We hypothesized, that there is no difference in regional rectal perianastomotic perfusion and oxygenation when using non-opioid dexmedetomidine-isoflurane anesthesia when compared to fentanyl-isoflurane anesthesia. METHODS: Ten female pigs were randomly divided into two groups (Dexmedetomidine, DEX, Fentanyl, FNT). Analgesia was provided by either dexmedetomidine (0.7-1.0 μg/kg/h) or fentanyl (6-10 μg/kg/h). The model of rectosigmoid resection in pigs was used. Two combined Laser Doppler flowmetry (LDF) and oxymetry probes were fixed on the antimesenterial site of the rectosigmoid, one orally and the second distally to resection zone. At the end of the experiment all animals were woken up and extubated. The healing of the anastomosis was controlled seven days after the operation. RESULTS: All experimental animals were hemodynamically stable throughout the experiment. No anastomotic leakage was detected. All animals survived until the seventh postoperative day. In the DEX group the median of the LDF signal on aboral site at the end of experiment was 35% (23-49%), in FNT group the median of the LDF signal was 19% (12-28%), which was statistically significantly lower (p < 0,05). CONCLUSIONS: This study has shown some protective effects of dexmedetomidine-isoflurane based anesthesia on perianastomotic microcirculation when compared to fentanyl-isoflurane based anesthesia.
- MeSH
- Anastomosis, Surgical methods MeSH
- Anesthesia methods MeSH
- Dexmedetomidine * pharmacology MeSH
- Fentanyl * pharmacology MeSH
- Colorectal Surgery methods MeSH
- Swine MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Reputational peer nominations are a common method for measuring involvement in aggression-related behaviors, encompassing the roles of aggressor, victim, and defender, but may be influenced by students' affective (dis)liking relationships. This social network study investigated whether dyad- and group-level (dis)liking relationships affect perceptions of classmates' involvement in physical aggression and explored the moderating roles of classroom moral disengagement and defending norms. The study employed a longitudinal design with two time points 6 months apart, encompassing 27 classrooms and 632 early adolescents. Using multiplex stochastic actor-oriented modeling, we found that liking, but not disliking, significantly influenced perceptions. Liking a classmate increased the likelihood of perceiving them as a defender. Moreover, students' own perceptions (aggressor, victim, and defender nominations) were shaped by the perceptions of classmates they liked, while classroom moral disengagement reduced this influence for defender nominations. Results on classroom defending norms were mixed. Our findings underscore the importance of accounting for students' liking relationships and classroom-level norms to reduce bias in peer nominations and improve the accuracy of assessments of aggression-related behaviors.
- MeSH
- Affect MeSH
- Aggression * psychology MeSH
- Adolescent Behavior psychology MeSH
- Child MeSH
- Interpersonal Relations * MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Adolescent MeSH
- Crime Victims * psychology MeSH
- Schools MeSH
- Social Norms MeSH
- Social Perception * MeSH
- Students psychology MeSH
- Peer Group * MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Good brain health plays a significant role in an individual's well-being and profoundly impacts the collective economy and society. Brain development does not stop at birth, and some aspects continue throughout childhood and adolescence, allowing the full development of cognitive functions. Different determinants related to physical health, healthy environments, safety and security, life-long learning and social connection as well as access to quality services influence the way our brains develop, adapt and respond to stress and adversity. Ongoing progress in neurobiology and cognitive neuroscience allows the design of better prevention and intervention strategies to help avoid brain deficits and/or limit their impact and maintain brain health. The European Brain Council (EBC) convened an expert meeting during the Federation of European Neuroscience Societies (FENS) Forum 2024 to address youth brain health challenges. In recent years, the importance of brain health has garnered significant attention across scientific, medical and policy-making communities. Although much focus has traditionally been on neurodegenerative conditions affecting the elderly, a paradigm shift towards prioritizing brain health in youth is both timely and necessary. This shift can profoundly impact individual lives and society, necessitating an interdisciplinary approach that brings neuroscience to the forefront of public health and informs evidence-based policy. The topic is of utmost importance as EBC launched this year a new campaign on No Health Without Brain Health rallying support with its member organizations and the wider brain community for the increased prioritization of brain health on EU health and research agendas.
- MeSH
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Brain * physiology MeSH
- Neurosciences * MeSH
- Societies, Scientific MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Publication type
- Editorial MeSH
- Geographicals
- Europe MeSH