Improving the quality of the most basic health behavior among youth may contribute to short-term body composition management with long-term implications for noncommunicable disease regression. This investigation aimed to assess the impact of primary school physical activity (PA), dietary, or dual approach interventions on pupils' body weight (BW) and body mass index (BMI). A systematic review and meta-analysis was completed following a study protocol and a trial registration (PROSPERO: CRD4202347770) with the PRISMA approach. Publications in English or German were included with school-based randomized controlled trials on diet and/or PA. Pupils of primary schools (aged 5-10) with no major nutritional deficiency or unstable health condition were included. The Boolean search strategy revealed a total of 9479 articles, qualifying 39 studies with 20 462 pupils (including 10 211 girls and 10 251 boys) for quantitative synthesis. The interventions were mostly PA (n = 31), several were dietary (n = 6), and some were dual approach (n = 5). Random effects meta-analyses revealed PA intervention (n = 20) to have an effect size of +0.07 kg (95% CI: -0.01 to 0.15) and -0.12 kg/m2 (95% CI: -0.23 to -0.01). Low statistical heterogeneity was found for BW (I2 = 0%; P = 1.000) and BMI (I2 = 0%; P = .9688), respectively. The findings indicate a scarcity of top-quality scientific research performed on healthy diet for body weight management in primary schools. PA intervention for elementary school pupils provides support for a healthier body composition profile amidst the current world health crisis.

• MeSH
• Exercise * MeSH
• Diet * MeSH
• Child MeSH
• Body Mass Index MeSH
• Humans MeSH
• Health Promotion * methods   MeSH
• Child, Preschool MeSH
• Randomized Controlled Trials as Topic MeSH
• School Health Services MeSH
• Schools MeSH
• Students * statistics & numerical data   MeSH
• Body Weight * MeSH
• Public Health * MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH

Well-defined gold nanoparticles (AuNPs) are accessible via simple synthetic methods, and their surface chemistry stands as a key factor in determining applications in the biomedical field. While macromolecules featuring amino groups are already known to successfully mediate the formation of stable gold colloids in one-pot, two-reactant, no workup reactions in aqueous media, we herein report the discovery that, under mild reaction temperatures, polymers of outstanding biomedical interest not only can play the simultaneous role of reducing and capping agent but also lead to particulate systems with unique features. From a library of samples that included branched polyethylenimine (BPEI), poly-(l-lysine) (PLL), bovine serum albumin (BSA), poly-(2-methyl-2-oxazoline) (PMeOx), poly-(N-(2-hydroxypropyl) methacrylamide) (PHPMA), and amine-functionalized poly-(N-(2-hydroxypropyl)-methacrylamide-co-N-(3-aminopropyl)-methacrylamide) P-(HPMA-co-APMA), we found that PHPMA end-functionalized with nitrile motifs generate spherical and stable AuNPs@PHPMA of very small size (diameter of ∼2.4 nm), as underlined by imaging experiments. Cell viability experiments indicated exceptionally good biocompatibility up to very high numerical particle concentrations as compared to the other systems. The reduced size imparted to the AuNPs@PHPMA outstanding catalytic properties (no induction time and high reaction rate constant for the hydrogenation of p-nitrophenol) and antimicrobial activity (total antibacterial activity against Escherichia coli and dose-dependent antibacterial activity against Staphylococcus aureus). The introduction of primary amine groups (13.4 mol %) of higher nucleophilicity known to work better for AuNP synthesis makes these unique features disappear, as evidenced for P-(HPMA-co-APMA). The other systems yielded 6-28 nm particles whose properties reflected both the size of the metallic core and chemical nature and conformation of the capping agent. These findings point to novel applications of PHPMA polymers worthy of further development, especially in light of their excellent water solubility and biocompatibility.

• Publication type
• Journal Article MeSH

INTRODUCTION: The objective of this systematic review is to evaluate the efficacy and safety of antigen-specific tolerance-inducing therapeutic approaches (products based on peptides, DNA and T cells) versus placebo or other comparators, where possible, in adult multiple sclerosis (MS) patients. METHODS: PubMed, CINAHL, Web of Science, Cochrane and International Clinical Trials Registry Platform, ClinicalTrials.gov were searched for published and unpublished studies. Screening, critical appraisal, and data extraction for included studies were carried out by two independent reviewers. For efficacy, phase I, II and III clinical trials (randomized/non-randomized; double blind/single blind/unblinded; single-center/multicenter; single-arm/two-arm) and for safety, phase I, II and III clinical trials (randomized/non-randomized; double blind/single blind/unblinded; controlled/uncontrolled; single-center/multicenter; single-arm/two-arm) were included. Observational studies (cross-sectional studies, cohort studies, case studies/reports etc), review articles, systematic reviews, meta-analysis, preclinical and pilot studies were excluded. All included studies were critically appraised using standardized JBI tools, with no exclusions based on methodological quality. Where possible, studies were pooled in statistical meta-analysis, presented in tabular format, and accompanied by narrative synthesis. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for grading the certainty of evidence. RESULTS: Search yielded 2644 results and in total 26 studies were included in the final analysis. Twelve studies were RCTs and 14 were quasi-experimental. In total, there were 1427 subjects from the RCTs, and 314 from non-RCTs. Sample size of studies ranged from 10 to 612 patients. All studies included adult patients, principally aged 18-55/65 years. Critical appraisal scores for the RCTs were in the range 31% to 92%. For quasi-experimental studies, critical appraisal scores were in the range 45% to 78%. Due to high heterogeneity of the studies, efficacy of all antigen-specific treatment remained ambiguous. For all three types of treatment, there was no statistical difference in occurrence of adverse effects (AEs) between the treatment- and placebo-related AEs (for DNA-based treatment RR was 1.06 (0.94-1.10), p = 0.334; for peptides-base treatments RR was 1.04 (0.90-1.08), p = 0.115; for T-cells-based treatments RR was 1.31 (0.97-1.76), p = 0.08). There were no differences in RR for serious AEs (SAEs) between the treatments either for DNA-based treatment (RR was 0.63 (0.25-1.58), p = 0.322) or peptide-based treatment (RR was 0.86 (0.62-1.19), p = 0.361). There were no reported SAEs for T cell-based treatments, so meta-analysis for these therapies was not performed. The most frequent AEs were local reactions to injection, such as redness, erythema, pain. DISCUSSION: Antigen-specific tolerance-inducing therapeutic approaches appeared to be safe. However, the certainty for these results was very low for SAEs in peptide- and DNA-based therapies, whereas it was low for AEs in DNA- and T cells-based therapies and moderate for AEs in peptide-based therapies. The efficacy of antigen-specific therapies remains ambiguous. Larger, well-designed studies with high level quality are needed to ensure ultimate conclusions. REGISTRATION: The registration number provided following registration of the protocol in PROSPERO is 'CRD42021236776'.

• MeSH
• Antigens * immunology   therapeutic use   MeSH
• Humans MeSH
• Multiple Sclerosis * therapy   immunology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Systematic Review MeSH

BACKGROUND: Psychological distress is recognized as an independent risk factor for cardiovascular diseases (CVDs), contributing to increased morbidity and mortality. While eHealth is increasingly used to deliver psychological interventions, their effectiveness for patients with CVDs remains unclear. OBJECTIVE: This meta-analysis aimed to evaluate the effects of eHealth psychological interventions for patients with CVDs. METHODS: Eligible studies were retrieved from 5 databases (Embase, Medline, PubMed, CINAHL, and Cochrane Library), covering the period from database inception to December 2024. Randomized controlled trials (RCTs) investigating the effect of evidence-based psychological eHealth interventions to improve psychosocial well-being and cardiovascular outcomes for people with CVDs were included. The Cochrane Risk of Bias tool (version 2) was used to judge the methodological quality of reviewed studies. RevMan (version 5.3) was used for meta-analysis. RESULTS: A total of 12 RCTs, comprising 2319 participants from 10 countries, were included in the review. The results demonstrated significant alleviation of depressive symptoms for patients receiving psychological eHealth intervention compared to controls (number of paper included in that particular analysis, n=7; standardized mean difference=-0.30, 95% CI -0.47 to -0.14; I2=57%; P<.001). More specifically, in 6 trials where internet-based cognitive behavioral therapy was delivered, a significant alleviation of depressive symptoms was achieved (standardized mean difference=-0.39, 95% CI -0.56 to -0.21; I2=53%; P<.001). There was no significant change in anxiety or quality of life. Synthesis without meta-analysis regarding stress, adverse events, and cardiovascular events showed inconclusive findings. CONCLUSIONS: Psychological eHealth interventions, particularly internet-based cognitive behavioral therapy, can significantly reduce depressive symptoms among patients with CVDs. A multidisciplinary approach is crucial for comprehensively improving psychological and cardiovascular outcomes. Future studies should explore integrating persuasive design features into eHealth and involving mental health professionals for intervention delivery. TRIAL REGISTRATION: PROSPERO CRD42023452276; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023452276.

• MeSH
• Depression therapy   MeSH
• Cardiovascular Diseases * psychology   therapy   MeSH
• Cognitive Behavioral Therapy MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Telemedicine * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Review MeSH
• Systematic Review MeSH

BACKGROUND AND OBJECTIVES: Gingivitis and periodontitis are common periodontal diseases that can significantly harm overall oral health, affecting the teeth and their supporting tissues, along with the surrounding anatomical structures, and if left untreated, leading to the total destruction of the alveolar bone and the connective tissues, tooth loss, and other more serious systemic health issues. Numerous studies have shown that propolis can help reduce gum inflammation, inhibit the growth of pathogenic bacteria, and promote tissue regeneration, but with varying degrees of success reported. For this reason, this comprehensive systematic review aims at finding out the truth concerning the efficacy of propolis mouthwashes in treating gingivitis and periodontitis, as its main objective. DATA SOURCES: Research findings from 6 different databases: China National Knowledge Infrastructure (CNKI), PubMed®, Europe PMC, Cochrane Central Register of Controlled Trials (CENTRAL), BioMed Central, and Google Scholar, were retrieved and examined in addition to a manual search in the references lists. STUDY SELECTION AND SYNTHESIS: The PICOS framework was used to select and exclude studies. The focus was on clinical randomized controlled trials (RCTs) that examined the effectiveness of propolis-containing mouthwashes in comparison with propolis-free ones for the treatment of gingivitis and periodontitis, employing related periodontal indices. Animal studies, microbiological studies, in-vitro studies, retrospective studies, case-control studies, cohorts, case reports, case series, reviews, letters, editorials, meta-analyses, and non-clinical randomized controlled trials (non-RCTs), all were excluded. A meta-analysis was not performed and data were only studied qualitatively due to the obvious heterogeneity amongst the studies. Data from the selected studies were extracted, and then the revised Cochrane's risk of bias tool (RoB 2.0) was utilised by two of the authors, independently, to evaluate the risk of bias in each study. RESULTS: At first, 151 results were reached, but then after removing duplicates, 99 records remained, and were later screened, assessed, and studied in full details based on the set PICOS criteria. Out of these 99 articles, ten studies were included in this systematic review, encompassing a total of 453 patients with an age range of (13-70) years old. Propolis mouthwashes with different protocols of application were the intervention whereas placebo or the rest of the tested mouthwashes such as, chlorhexidine, sodium fluoride with cetylpyridinium chloride, sterile distilled water, hydrogen peroxide, were the ones to which propolis mouthwashes were compared. Treatment duration extended from 14 days to 3 months and the follow-up period differed from 14 days to 3 months. In general, propolis mouthwashes decreased plaque accumulations and gingival inflammation in gingivitis patients based on the employed indices. On the other hand, the aforementioned tested mouthwashes other than propolis were deemed equally effective or even superior to propolis in some studies. As an overall assessment for the risk of bias, four studies were assigned as having a low risk of bias. Two studies were deemed to have some concerns, while four studies were identified as having a high risk of bias. CONCLUSIONS: Despite the fact that propolis has shown positive effects in terms of controlling gingival and periodontal inflammation especially when used with mechanical methods, studies lack certainty and their power of evidence is low with no agreed gold standards. These conclusions come, for sure, within the limitations of this review, like having substantial variability amongst the included studies and the presence of studies with a high risk of bias. The findings demonstrate that propolis-based mouthwashes showed promising clinical outcomes in reducing plaque and gingival inflammation. However, it is highly recommended to conduct more rigorous trials with patient-reported outcome measures, extended follow-up periods, larger samples sizes, better-designed methodologies, typified propolis use, and with the implementation of similar indices in order to obtain more reliable, conclusive, and generalisable results. PROSPERO REGISTRATION NUMBER: CRD42024524523.

• Publication type
• Journal Article MeSH

Public transport represents a potential site for the transmission of resistant pathogens due to the rapid movement of large numbers of people. This study aimed to investigate the bacterial contamination of frequently touched surfaces in the public transport system operating in the proximity of the biggest Czech hospital during the coronavirus pandemic despite extensive cleaning and disinfection efforts. In June and September 2020, samples from the metro trains, ground transport and stationary objects were collected, enriched and cultured. The antimicrobial susceptibility was tested by broth microdilution. Staphylococcus aureus isolates exhibiting inconclusive results of vancomycin susceptibility testing were retested by broth macrodilution and subjected to whole genome sequencing. All S. aureus isolates were tested for vancomycin heteroresistance (hVISA). A total of 513/542 (94.6 %) samples were culture-positive with higher frequency in September (p = 0.004). S. aureus was the most frequent opportunistic bacterial pathogen found (3.7 %, 20/542) followed by Enterobacterales spp. (1.8 %, 10/542). No methicillin-resistant S. aureus (MRSA), extended-spectrum beta-lactamase producers (ESBL) or carbapenemase-producing bacteria were detected. Resistance to clinically relevant drugs was rare except for resistance to ampicillin (67 %, 8/12), cefuroxime (42 %, 5/12) in Enterobacterales and chloramphenicol (90 %, 18/20), penicillin (45 %, 9/20), and erythromycin (20 %, 4/20) in S. aureus. One S. aureus isolate was shown to be resistant to vancomycin (8 mg/L) by forming large visible cell aggregates. Population analysis profile-area under the curve ratio (PAP-AUC) testing did not confirm the hVISA phenotype, but mutations in the hVISA phenotype-related gene vraR and other genes related to cell wall synthesis (fmtB) and intercellular adhesion (sasC) were found. Our study shows that in the COVID-19 pandemic, despite the intensive use of disinfectants, public transport was a source of opportunistic bacterial pathogens including S. aureus with unusual vancomycin resistance phenotype that could be easily missed by standard susceptibility testing.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• COVID-19 * MeSH
• Transportation MeSH
• Humans MeSH
• Microbial Sensitivity Tests * MeSH
• Pandemics MeSH
• Vancomycin Resistance MeSH
• SARS-CoV-2 * MeSH
• Staphylococcus aureus * drug effects   genetics   MeSH
• Vancomycin * pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

We report the first total synthesis of the natural product selaginpulvilin X, a selaginellaceae polyphenol class of compounds. Our synthetic strategy employs cross-coupling reactions and an organolithium addition to construct the carbon framework. Subsequently, the functional group modifications and deprotection yield the natural product. Spectral analysis confirms the proposed structure by comparing natural and synthetic samples.

• Publication type
• Journal Article MeSH

Human cytoplasmic tRNAs contain dihydrouridine modifications at positions 16 and 17 (D16/D17). The enzyme responsible for D16/D17 formation and its cellular roles remain elusive. Here, we identify DUS1L as the human tRNA D16/D17 writer. DUS1L knockout in the glioblastoma cell lines LNZ308 and U87 causes loss of D16/D17. D formation is reconstituted in vitro using recombinant DUS1L in the presence of NADPH or NADH. DUS1L knockout/overexpression in LNZ308 cells shows that DUS1L supports cell growth. Moreover, higher DUS1L expression in glioma patients is associated with poorer prognosis. Upon vector-mediated DUS1L overexpression in LNZ308 cells, 5' and 3' processing of precursor tRNATyr(GUA) is inhibited, resulting in a reduced mature tRNATyr(GUA) level, reduced translation of the tyrosine codons UAC and UAU, and reduced translational readthrough of the near-cognate stop codons UAA and UAG. Moreover, DUS1L overexpression increases the amounts of several D16/D17-containing tRNAs and total cellular translation. Our study identifies a human dihydrouridine writer, providing the foundation to study its roles in health and disease.

• MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Protein Biosynthesis * MeSH
• RNA, Transfer * metabolism   genetics   MeSH
• Uridine metabolism   analogs & derivatives   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Upregulation of MYC is a hallmark of cancer, wherein MYC drives oncogenic gene expression and elevates total RNA synthesis across cancer cell transcriptomes. Although this transcriptional anabolism fuels cancer growth and survival, the consequences and metabolic stresses induced by excess cellular RNA are poorly understood. Herein, we discover that RNA degradation and downstream ribonucleotide catabolism is a novel mechanism of MYC-induced cancer cell death. Combining genetics and metabolomics, we find that MYC increases RNA decay through the cytoplasmic exosome, resulting in the accumulation of cytotoxic RNA catabolites and reactive oxygen species. Notably, tumor-derived exosome mutations abrogate MYC-induced cell death, suggesting excess RNA decay may be toxic to human cancers. In agreement, purine salvage acts as a compensatory pathway that mitigates MYC-induced ribonucleotide catabolism, and inhibitors of purine salvage impair MYC+ tumor progression. Together, these data suggest that MYC-induced RNA decay is an oncogenic stress that can be exploited therapeutically. Significance: MYC is the most common oncogenic driver of poor-prognosis cancers but has been recalcitrant to therapeutic inhibition. We discovered a new vulnerability in MYC+ cancer where MYC induces cell death through excess RNA decay. Therapeutics that exacerbate downstream ribonucleotide catabolism provide a therapeutically tractable approach to TNBC (Triple-negative Breast Cancer) and other MYC-driven cancers.

• MeSH
• Humans MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Breast Neoplasms * metabolism   genetics   pathology   MeSH
• Proto-Oncogene Proteins c-myc * metabolism   genetics   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Ribonucleotides * pharmacology   MeSH
• RNA Stability * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

STUDY QUESTION: Which actively translated maternal transcripts are differentially regulated between clinically relevant in vitro and in vivo maturation (IVM) conditions in mouse oocytes and zygotes? SUMMARY ANSWER: Our findings uncovered significant differences in the global transcriptome as well as alterations in the translation of specific transcripts encoding components of energy production, cell cycle regulation, and protein synthesis in oocytes and RNA metabolism in zygotes. WHAT IS KNOWN ALREADY: Properly regulated translation of stored maternal transcripts is a crucial factor for successful development of oocytes and early embryos, particularly due to the transcriptionally silent phase of meiosis. STUDY DESIGN, SIZE, DURATION: This is a basic science study utilizing an ICR mouse model, best suited for studying in vivo maturation. In the treatment group, fully grown germinal vesicle oocytes from stimulated ovaries were in vitro matured to the metaphase II (MII) stage either as denuded without gonadotropins (IVM DO), or as cumulus-oocyte complexes (IVM COC) in the presence of 0.075 IU/ml recombinant FSH (rFSH) and 0.075 IU/ml recombinant hCG (rhCG). To account for changes in developmental competence, IVM COC from non-stimulated ovaries (IVM COC-) were included. In vivo matured MII oocytes (IVO) from stimulated ovaries were used as a control after ovulation triggering with rhCG. To simulate standard IVM conditions, we supplemented media with amino acids, vitamins, and bovine serum albumin. Accordingly, in vitro pronuclear zygotes (IMZ) were generated by IVF from IVM DO, and were compared to in vivo pronuclear zygotes (IVZ). All experiments were performed in quadruplicates with samples collected for both polyribosome fractionation and total transcriptome analysis. Samples were collected over three consecutive months. PARTICIPANTS/MATERIALS, SETTING, METHODS: All ICR mice were bred under legal permission for animal experimentation (no. MZE-24154/2021-18134) obtained from the Ministry of Agriculture of the Czech Republic. Actively translated (polyribosome occupied) maternal transcripts were detected in in vitro and in vivo matured mouse oocytes and zygotes by density gradient ultracentrifugation, followed by RNA isolation and high-throughput RNA sequencing. Bioinformatic analysis was performed and subsequent data validation was done by western blotting, radioactive isotope, and mitotracker dye labelling. MAIN RESULTS AND THE ROLE OF CHANCE: Gene expression analysis of acquired polysome-derived high-throughput RNA sequencing data revealed significant changes (RPKM ≥ 0.2; P ≤ 0.005) in translation between in vitro and in vivo matured oocytes and respectively produced pronuclear zygotes. Surprisingly, the comparison between IVM DO and IVM COC RNA-seq data of both fractionated and total transcriptome showed very few transcripts with more than a 2-fold difference. Data validation by radioactive isotope labelling revealed a decrease in global translation bof20% in IVM DO and COC samples in comparison to IVO samples. Moreover, IVM conditions compromised oocyte energy metabolism, which was demonstrated by both changes in polysome recruitment of each of 13 mt-protein-coding transcripts as well as by validation using mitotracker red staining. LARGE SCALE DATA: The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE241633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE241633). LIMITATIONS, REASONS FOR CAUTION: It is extremely complicated to achieve in vivo consistency in animal model systems such as porcine or bovine. To achieve a high reproducibility of in vivo stimulations, the ICR mouse model was selected. However, careful interpretation of our findings with regard to assisted reproductive techniques has to be made by taking into consideration intra-species differences between the mouse model and humans. Also, the sole effect of the cumulus cells' contribution could not be adequately addressed by comparing IVM COC and IVM DO, because the IVM DO were matured without gonadotropin supplementation. WIDER IMPLICATIONS OF THE FINDINGS: Our findings confirmed the inferiority of standard IVM technology compared with the in vivo approach. It also pointed at compromised biological processes employed in the critical translational regulation of in vitro matured MII oocytes and pronuclear zygotes. By highlighting the importance of proper translational regulation during in vitro oocyte maturation, this study should prompt further clinical investigations in the context of translation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Czech Grant Agency (22-27301S), Charles University Grant Agency (372621), Ministry of Education, Youth and Sports (EXCELLENCE CZ.02.1.01/0.0/0.0/15_003/0000460 OP RDE), and Institutional Research Concept RVO67985904. No competing interest is declared.

• MeSH
• Chorionic Gonadotropin pharmacology   MeSH
• Embryonic Development * physiology   MeSH
• In Vitro Oocyte Maturation Techniques * MeSH
• Cumulus Cells * metabolism   MeSH
• Mice, Inbred ICR * MeSH
• Mice MeSH
• Oocytes * metabolism   MeSH
• Protein Biosynthesis MeSH
• Transcriptome MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Zygote metabolism   MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH