BACKGROUND: Presensitized patients with circulating donor-specific antibodies (DSAs) before transplantation are at risk for antibody-mediated rejection (AMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold AMR activity undetected by histology could be operating in some early biopsies. METHODS: Transcriptome of kidney allograft biopsies performed within the first month in presensitized patients (DSA+) who had received desensitization and did not develop active/probable AMR by histology (R-) was compared with biopsies showing active/probable AMR (R+/DSA+). As negative controls, biopsies without rejection by histology in patients without DSA at transplantation were used (R-/DSA-). RNA sequencing from biopsies selected from the biobank was used in cohort 1 (n = 32) and microarray, including the molecular microscope (Molecular Microscope Diagnostic System [MMDx]) algorithm, in recent cohort 2 (n = 30). RESULTS: The transcriptome of R-/DSA+ was similar to R+/DSA+ as these groups differed in 14 transcripts only. Contrarily, large differences were found between both DSA+ groups and negative controls. Fast gene set enrichment analyses showed upregulation of the immune system in both DSA+ groups (gene ontology terms: adaptive immune response, humoral immune response, antigen receptor-mediated signaling, and B-cell receptor signaling or complement activation) when compared with negative controls. MMDx assessment in cohort 2 classified 50% of R-/DSA+ samples as AMR and found no differences in AMR molecular scores between R+ and R- DSA+ groups. In imlifidase desensitization, MMDx series showed a gradual increase in AMR scores over time. CONCLUSIONS: Presensitized kidney transplant recipients exhibited frequent molecular calls of AMR in biopsy-based transcript diagnostics despite desensitization therapy and negative histology.

• Publication type
• Journal Article MeSH

MicroRNAs (miRNAs) have emerged as important regulators of gene expression in various biological processes, including cancer. miR-182-5p has gained attention for its potential implications in gynecologic cancers, including breast, ovarian, endometrial, and cervical cancers. miR-182-5p dysregulation has been associated with multiple facets of tumor biology in gynecologic cancers, including tumor initiation, progression, metastasis, and therapeutic response. Studies have highlighted its involvement in key signaling pathways and cellular processes that contribute to cancer development and progression. In addition, miR-182-5p has shown potential as a diagnostic and prognostic biomarker, with studies demonstrating its correlation with clinicopathological features and patient outcomes. Furthermore, the therapeutic potential of miR-182-5p is being explored in gynecologic cancers. Strategies such as miRNA mimics or inhibitors targeting miR-182-5p have shown promise in preclinical and early clinical studies. These approaches aim to modulate miR-182-5p expression, restoring normal cellular functions and potentially enhancing treatment responses. Understanding the biologic and clinical implications of miR-182-5p in gynecologic cancers is crucial for the development of targeted therapeutic strategies and personalized medicine approaches. Further investigations are needed to unravel the specific target genes and pathways regulated by miR-182-5p. It is important to consider the emerging biologic and clinical implications of miR-182-5p in gynecologic cancers.

• MeSH
• Humans MeSH
• MicroRNAs * genetics   MeSH
• Biomarkers, Tumor genetics   MeSH
• Genital Neoplasms, Female * genetics   therapy   MeSH
• Prognosis MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Poly(ɛ-caprolactone) (PCL) is a biocompatible, biodegradable, and highly mechanically resilient FDA-approved material (for specific biomedical applications, e.g. as drug delivery devices, in sutures, or as an adhesion barrier), rendering it a promising candidate to serve bone tissue engineering. However, in vivo monitoring of PCL-based implants, as well as biodegradable implants in general, and their degradation profiles pose a significant challenge, hindering further development in the tissue engineering field and subsequent clinical adoption. To address this, photo-cross-linkable mechanically resilient PCL networks are developed and functionalized with a radiopaque monomer, 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), to enable non-destructive in vivo monitoring of PCL-based implants. The covalent incorporation of AATIPA into the crosslinked PCL networks does not significantly affect their crosslinking kinetics, mechanical properties, or thermal properties, but it increases their hydrolysis rate and radiopacity. Complex and porous 3D designs of radiopaque PCL networks can be effectively monitored in vivo. This work paves the way toward non-invasive monitoring of in vivo degradation profiles and early detection of potential implant malfunctions.

• MeSH
• Biocompatible Materials chemistry   MeSH
• Mice MeSH
• Polyesters * chemistry   MeSH
• Porosity MeSH
• Materials Testing MeSH
• Tissue Engineering methods   MeSH
• Tissue Scaffolds * chemistry   MeSH
• Absorbable Implants MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Necrotizing enterocolitis (NEC) is one of the most devastating intestinal diseases observed in preterm in the first days of life. Researchers have recently focused on potential predictive biomarkers for early and concomitant diagnoses. Thus, we inquired about the linkage of intestinal dysbiosis, one of the most important factors in NEC development to the gut microbiota. In this study, the systematic differences in the bacterial composition between neonates affected by NEC and healthy newborns were highlighted by metagenomic analysis. The next-generation sequencing of the V3-V4 variable region of the 16S rRNA gene and gene-specific qPCR analyzed the untargeted gut microbiota. Total bacteria, total and fecal coliform loads in stool samples with NEC were higher than control. OTU-level relative abundances of NEC infant was characterized by Firmicutes and Bacteroidetes at phylum levels. At the genus level, NEC stool was identified by the lack of Klebsiella and the presence of Roseburia, Blautia, and Parasutterella. Finally, Clostridium fessum was the predominant species of Clostridium genus in disease and healthy specimens at the species level, whereas Clostridium jeddahitimonense was at NEC diagnosis. Despite a strong relationship between pathophysiology and characterization of gut microbiota at a clinical diagnosis of NEC, our results emphasize the broad difficulty in identifying potential biomarkers.

• MeSH
• Bacteria * classification   genetics   isolation & purification   MeSH
• DNA, Bacterial genetics   MeSH
• Dysbiosis microbiology   MeSH
• Feces * microbiology   MeSH
• Humans MeSH
• Metagenomics MeSH
• Enterocolitis, Necrotizing * microbiology   MeSH
• Infant, Premature MeSH
• Infant, Newborn MeSH
• RNA, Ribosomal, 16S * genetics   MeSH
• Gastrointestinal Microbiome * MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Acute kidney injury (AKI) due to gentamicin nephrotoxicity is a significant concern in clinical medicine, particularly in patients receiving prolonged or high-dose gentamicin therapy. Gentamicin is an aminoglycoside antibiotic frequently used in the treatment of a range of bacterial infections. However, its use is associated with nephrotoxicity which can manifest as AKI. Due to this, it is crucial to diagnose promptly and manage treatment effectively. Ongoing studies are therefore focusing on non-protein-coding RNAs as potential biomarkers for AKI. Numerous microRNAs (miRNAs) have been implicated in gentamicin-induced nephrotoxicity and AKI. They participate in pathways associated with inflammation, cell death, and oxidative stress and each of these factors play critical roles in the development of gentamicin-induced kidney injury. Research studies have demonstrated changes in the expression levels of these miRNAs in response to gentamicin exposure both in vitro and in in vivo models, as well as in human clinical trials involving patients receiving gentamicin therapy. The dysregulation of these miRNAs correlates with the severity of kidney injury and may serve as sensitive biomarkers for early detection and monitoring of AKI induced by gentamicin.

• MeSH
• Acute Kidney Injury * chemically induced   diagnosis   MeSH
• Anti-Bacterial Agents * adverse effects   MeSH
• Biomarkers * MeSH
• Gentamicins * adverse effects   MeSH
• Humans MeSH
• MicroRNAs * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses. METHODS: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications. RESULTS: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.

• MeSH
• Bipolar Disorder * genetics   MeSH
• Adult MeSH
• Phenotype * MeSH
• Attention Deficit Disorder with Hyperactivity genetics   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Multifactorial Inheritance genetics   MeSH
• Neurodevelopmental Disorders genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article 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
• Capacity Building MeSH
• Screen Time * MeSH
• Global Health MeSH
• Exercise * MeSH
• Delphi Technique * MeSH
• Child MeSH
• Consensus MeSH
• Humans MeSH
• Adolescent MeSH
• Sedentary Behavior * MeSH
• Sleep MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Srdeční selhání patří mezi nejzávažnější zdravotní problémy současnosti. I přesto, že celoživotní riziko srdečního selhání je u mužů a žen podobné, existují výrazné rozdíly mezi oběma pohlavími. Muži jsou predisponováni k srdečnímu selhání se sníženou ejekční frakcí, zatímco u žen převažuje srdeční selhání se zachovanou ejekční frakcí (HFpEF). HFpEF je velmi heterogenní skupinou poruch a pochopení rozdílů mezi muži a ženy může přinést užitečné informace o možnostech prevence a léčby tohoto onemocnění. Například v etiologii a progresi HFpEF mohou hrát výraznou úlohu ženské pohlavní hormony, jmenovitě estradiol. Dalším faktorem může být fakt, že u žen může být cévní systém, a to především poruchy mikrocirkulace, predisponujícím faktorem k HFpEF. Proto včasný záchyt a léčba poruch periferní cirkulace může výrazně přispět i k prevenci HFpEF, především u žen.

Heart failure is one of the most serious problems of recent medicine. Despite the lifetime risk of heart failure is similar in men and women, significant sex differences were described. Men are more predisposed to heart failure with reduced ejection fraction, while women are predisposed to heart failure with preserved ejection fraction (HFpEF). HFpEF is a very heterogeneous group of disorders, and the research of sex differences might substantially improve preventive and treatment approaches. For example, female sex hormones, namely estradiol, might play prominent role in development and progression of HFpEF. Very common factor associated with HFpEF is vascular and microvascular system, which is more pronounced in women and might be cause and accelerating factor for HFpEF. Therefore, also early detection and manage- ment of disorders of vascular system might substantially add to prevention of HFpEF, especially in women.

Východiska.| Výzkum rizikového chování a duševního zdraví žáků druhého stupně základních škol a středních škol v Praze se od roku 2016 zaměřuje na identifikaci trendů v oblasti rizikového chování, užívání návykových látek, užívání digitálních technologií, duševních potíží apod. Cíle. Cílem tohoto šetření bylo zjistit aktuální stav a vývoj rizikového chování adolescentů včetně negativních dopadů nadměrného a rizikového užívání digitálních technologií. Centrum sociálních služeb Praha realizuje tento výzkum s cílem poskytnout relevantní data pro prevenci a podporu duševního zdraví žáků na školách. Metody. Data byla shromažďována pomocí anonymního dotazníkového šetření mezi žáky pražských škol. V rámci dotazníku byly využity Škála excesivního užívání internetu (EIU) a Test herní poruchy (GDT). Výzkumný soubor byl vážen, aby odpovídal aktuálnímu rozložení věku a pohlaví vybrané populace žáků v Praze. Soubor | V roce 2023 šetření zahrnovalo 10 097 žáků základních a středních škol a víceletých gymnázií (věk 11–21 let). Výsledky. Závěry analýzy dat ukázaly, že pokračuje trend zvyšujícího se počtu dětí, které ve svém životě zažívají problémy v důsledku nadměrného a problémového užívání digitálních technologií, a to z důvodů sledování internetového obsahu, aktivity na sociálních sítích i hraní digitálních her. Diskuze a závěry. Interpretace dat podtrhuje nutnost pokračovat v preventivních opatřeních zaměřených na podporu digitálního wellbeingu a duševního zdraví i na rozvoj kompetencí pro práci s technologiemi bezpečným způsobem. Zvýšená pozornost by měla být věnována včasné identifikaci závislostního chování na technologiích, předcházení tomuto chování i rozvoji dovedností k poskytování včasné podpory u osob, které s dětmi přicházejí do pravidelného styku (učitelé, vedoucí volnočasových aktivit, lékaři).

Background. Since 2016, research on risk behaviour and mental health among lower and upper secondary school students in Prague has focused on identifying trends in areas such as risk-taking behaviours, substance use, digital technology use, and mental health difficulties. Aims. The aim of this survey was to determine the current status and development of risky behaviour among adolescents, including the negative effects of excessive and risky use of digital technologies. The Centre for Social Services Prague conducts this research with the aim of providing relevant data for the prevention and support of mental health among students in schools. Methods. Data was collected using an anonymous questionnaire survey among students in Prague schools. The questionnaire used the Excessive Internet Use Scale (EIU) and the Gaming Disorder Test (GDT). The research sample was weighted to correspond to the current age and gender distribution of the selected population of students in Prague. Sample | In 2023, the survey included 10,097 pupils from lower and upper secondary schools (aged 11–21). Results. The conclusions of the data analysis showed that there is a continuing trend of an increasing number of children experiencing problems in their lives as a result of excessive and problematic use of digital technologies, due to viewing internet content, activity on social networks, and playing digital games. Discussion and conclusions. The interpretation of the data underscores the need to continue prevention aimed at promoting digital wellbeing and mental health, as well as developing skills for working with technology in a safe manner. Increased attention should be paid to the early identification of addictive behaviour toward technology, the prevention of such behaviour, and the development of skills to provide timely support to people who come into regular contact with children (teachers, leisure activity leaders, medial practitioners).

Psoriáza je chronické zánětlivé onemocnění kůže s možným systémovým dopadem. Až 30 % pacientů s psoriázou vyvine psoriatickou artritidu (PsA), která může vést k ireverzibilnímu poškození kloubů, zhoršení kvality života a invaliditě. Včasná diagnostika a účinná léčba psoriázy mohou výrazně přispět k prevenci PsA.

Psoriasis is a chronic inflammatory skin disease with potential systemic involvement. Up to 30% of patients with psoriasis develop psoriatic arthritis (PsA), which can result in irreversible joint damage, decreased quality of life, and disability. Early diagnosis and effective treatment of psoriasis can significantly contribute to the prevention of PsA.