INTRODUCTION: Mitochondrial dysfunction stands as a pivotal feature in neurodegenerative disorders, spurring the quest for targeted therapeutic interventions. This review examines Ubiquitin-Specific Protease 30 (USP30) as a master regulator of mitophagy with therapeutic promise in Alzheimer's disease (AD) and Parkinson's disease (PD). USP30's orchestration of mitophagy pathways, encompassing PINK1-dependent and PINK1-independent mechanisms, forms the crux of this exploration. METHOD: A systematic literature search was conducted in PubMed, Scopus, and Web of Science, selecting studies that investigated USP's function, inhibitor design, or therapeutic efficacy in AD and PD. Inclusion criteria encompassed mechanistic and preclinical/clinical data, while irrelevant or duplicate references were excluded. Extracted findings were synthesized narratively. RESULTS: USP30 modulates interactions with translocase of outer mitochondrial membrane (TOM) 20, mitochondrial E3 ubiquitin protein ligase 1 (MUL1), and Parkin, thus harmonizing mitochondrial quality control. Emerging novel USP30 inhibitors, racemic phenylalanine derivatives, N-cyano pyrrolidine, and notably, benzosulphonamide class compounds, restore mitophagy, and reduce neurodegenerative phenotypes across diverse models with minimal off-target effects. Modulation of other USPs also influences neurodegenerative disease pathways, offering additional therapeutic avenues. CONCLUSIONS: In highlighting the nuanced regulation of mitophagy by USP30, this work heralds a shift toward more precise and effective treatments, paving the way for a new era in the clinical management of neurodegenerative disorders.

• MeSH
• individualizovaná medicína metody   MeSH
• lidé MeSH
• mitochondriální proteiny MeSH
• mitofagie * fyziologie   účinky léků   MeSH
• neurodegenerativní nemoci * farmakoterapie   metabolismus   MeSH
• specifické proteázy ubikvitinu metabolismus   antagonisté a inhibitory   MeSH
• thiolesterhydrolasy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy 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
• jednofotonová emisní výpočetní tomografie * MeSH
• lidé MeSH
• mozek * diagnostické zobrazování   MeSH
• počítačové zpracování obrazu * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články 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
• algoritmy MeSH
• mikro RNA * genetika   metabolismus   MeSH
• modely nemocí na zvířatech * MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nealkoholová steatóza jater * genetika   metabolismus   patologie   MeSH
• nitrobřišní tuk * metabolismus   MeSH
• regulace genové exprese MeSH
• stanovení celkové genové exprese metody   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články 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
• betain * terapeutické užití   MeSH
• cystathionin-beta-synthasa nedostatek   MeSH
• dítě MeSH
• dospělí MeSH
• homocystein * krev   metabolismus   MeSH
• homocystinurie * farmakoterapie   MeSH
• kojenec MeSH
• lidé MeSH
• methionin * nedostatek   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• pyridoxin * terapeutické užití   MeSH
• registrace * MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články 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
• dospělí MeSH
• hráčství * psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• motivace MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• sociální média * 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
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika 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
• lidé MeSH
• přeprogramování buněk * genetika   MeSH
• regenerativní lékařství * MeSH
• vývojová biologie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy 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 2. typu * diagnostické zobrazování   patologie   MeSH
• diabetické neuropatie diagnostické zobrazování   patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mrtvola * MeSH
• nervus medianus diagnostické zobrazování   patologie   MeSH
• nervus suralis * diagnostické zobrazování   patologie   MeSH
• nervus tibialis diagnostické zobrazování   patologie   MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• zobrazování difuzních tenzorů * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články 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
• anastomóza chirurgická metody   MeSH
• anestezie metody   MeSH
• dexmedetomidin * farmakologie   MeSH
• fentanyl * farmakologie   MeSH
• kolorektální chirurgie metody   MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články 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
• afekt MeSH
• agrese * psychologie   MeSH
• chování mladistvých psychologie   MeSH
• dítě MeSH
• interpersonální vztahy * MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladiství MeSH
• oběti zločinu * psychologie   MeSH
• školy MeSH
• sociální normy MeSH
• sociální percepce * MeSH
• studenti psychologie   MeSH
• vyrovnaná skupina * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Prognostic significance of the timing in the cardiac cycle of the first (TP1) and second (TP2) systolic peak of the central aortic pulse wave is ill-defined. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of adverse health outcomes associated with TP1 and TP2, estimated by the SphygmoCor software, were assessed in the International Database of Central Arterial Properties for Risk Stratification (IDCARS) (n = 5529). Model refinement was assessed by the integrated discrimination (ID) and net reclassification (NR) improvement. Over 4.1 years (median), 201 participants died and 248 and 159 patients experienced cardiovascular or cardiac endpoints. Mean TP1 and TP2, standardized for cohort, sex, age, and heart rate, were 103 and 228 ms. Shorter TP1 and TP2 were associated with higher mortality and shorter TP1 with a higher risk of cardiovascular and cardiac endpoints (trend p ≤ 0.004). The HRs relating total mortality and cardiovascular endpoints to TP2 were 0.82 (95% confidence interval [CI]: 0.72-0.94) and 0.87 (0.77-0.98), respectively. The HR relating cardiac endpoints to TP1 was 0.81 (0.68-0.97). For total mortality and cardiovascular endpoints in relation to TP2, NRI was significant (p ≤ 0.010), but not for cardiac endpoints in relation to TP1. Integrated discrimination improvement (IDI) was not significant for any endpoint. The HRs relating total mortality to TP2 were smaller (p ≤ 0.026) in women than men (0.67 vs. 0.95) and in older (≥ 60 years) versus younger (< 60 years) participants (0.80 vs. 0.88). Our study adds to the evidence supporting risk stratification based on aortic pulse analysis by showing that TP2 and TP1 carry prognostic information.

• MeSH
• analýza pulzové vlny * metody   MeSH
• aorta patofyziologie   MeSH
• hodnocení rizik metody   statistika a číselné údaje   MeSH
• hypertenze epidemiologie   mortalita   patofyziologie   MeSH
• kardiovaskulární nemoci * mortalita   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční frekvence fyziologie   MeSH
• systola fyziologie   MeSH
• tuhost cévní stěny fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH