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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.
- Publikační typ
- časopisecké články 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.
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
- biokompatibilní materiály chemie MeSH
- myši MeSH
- polyestery * chemie MeSH
- poréznost MeSH
- testování materiálů MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury * chemie MeSH
- vstřebatelné implantáty MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články 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 * klasifikace genetika izolace a purifikace MeSH
- DNA bakterií genetika MeSH
- dysbióza mikrobiologie MeSH
- feces * mikrobiologie MeSH
- lidé MeSH
- metagenomika MeSH
- nekrotizující enterokolitida * mikrobiologie MeSH
- novorozenec nedonošený MeSH
- novorozenec MeSH
- RNA ribozomální 16S * genetika MeSH
- střevní mikroflóra * MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články 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.
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
- bipolární porucha * genetika MeSH
- dospělí MeSH
- fenotyp * MeSH
- hyperkinetická porucha genetika MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- multifaktoriální dědičnost genetika MeSH
- neurovývojové poruchy genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví 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
INTRODUCTION: Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD). METHODS: Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study. Clinical obstetrical information was collected by a standardized questionnaire. GBS strains were characterized by serological and molecular methods. RESULTS: Among GBS carriers included in this study after testing positive for GBS by vaginal or recto-vaginal sampling, 13.4% had at least one additional obstetrical risk factor for EOD. The five most common capsular types (i.e., Ia, Ib, II, III and V) comprised ~ 93% of GBS carried. Of the colonized women, 77.8% received any IAP, and in 49.5% the IAP was considered appropriate. In our cohort, nine neonates presented with GBS early-onset disease (EOD) with significant regional heterogeneity. CONCLUSIONS: Screening methods and IAP rates need to be harmonized across Europe in order to reduce the rates of EOD. The epidemiological data from eight different European countries provides important information for the development of a successful GBS vaccine.
- MeSH
- antibiotická profylaxe MeSH
- dospělí MeSH
- infekční komplikace v těhotenství * epidemiologie mikrobiologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- novorozenec MeSH
- přenašečství epidemiologie mikrobiologie MeSH
- Streptococcus agalactiae * izolace a purifikace klasifikace MeSH
- streptokokové infekce * epidemiologie mikrobiologie prevence a kontrola MeSH
- těhotenství MeSH
- vagina mikrobiologie MeSH
- vertikální přenos infekce statistika a číselné údaje prevence a kontrola MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
Eozinofilní ezofagitida je chronické zánětlivé, imunologicky podmíněné onemocnění, charakterizované patologickou infiltrací sliznice jícnu eozinofilními granulocyty. Na vzniku nemoci se podílí genetická predispozice a faktory vnějšího prostředí. Stanovení správné diagnózy se u dětí opírá o klinické příznaky dysfunkce jícnu, zvracení, neprospívání a typický histologický nález. Velmi častou komorbiditou jsou alergická onemocnění. Cílem léčby je odstranit klinické příznaky onemocnění, potlačit infiltraci jícnu eozinofilními granulocyty a zabránit komplikacím, zejména přestavbě stěny (remodelace) a zúžení jícnu. U dětí je nezbytné zajistit správný růst a vývoj. Léčba je komplexní a zahrnuje empirickou eliminační dietu nebo kombinovanou farmakoterapii inhibitorem protonové pumpy nebo topickým kortikosteroidem (budesonid jako suspenze nebo rozpustná tableta). U nejtěžších případů je indikována celková farmakoterapie prednisonem a biologická léčba (dupilumabem). Kazuistika u chlapce ukazuje na úskalí diagnostiky eozinofilní ezofagitidy v kojeneckém věku a na nutnost mezioborové spolupráce nejen při stanovení správné diagnózy a zahájení adekvátní komplexní léčby za nezbytné spolupráce rodičů nemocného dítěte, ale i při dispenzární péči a včasném rozpoznání recidivy onemocnění.
Eosinophilic esophagitis is a chronic inflammatory immune-mediated disease characterized by pathological eosinophilic infiltration of the esophageal wall. Genetic predisposition and environmental factors contribute to the development of this illnes. Establishing the correct diagnosis in children is based on clinical symptoms of esophageal dysfunction, vomiting, failure to thrive and typical histological findings. Allergic diseases are very common comorbidities. The treatment aims to remove the clinical symptoms of the disease, suppress the infiltration of the esophagus by eosinophilic granulocytes, and prevent complications, especially the remodeling of the esophagus wall with its subsequent narrowing. Ensuring proper children's growth and development is essential. Treatment of eosinophilic esophagitis is comprehensive and includes empiric elimination diet, or pharmacotherapy with proton pump inhibitors, or topical corticosteroids. In the most severe cases, systemic pharmacotherapy with prednisone and biological treatment is indicated dupilumab. The presented case report illustrates the difficulties in diagnosing in infancy and the necessity of an interdisciplinary approach (pediatrician-gastroenterologist-allergist) not only in establishing the correct diagnosis and starting adequate treatment necessitating the cooperation of the chilďs parents but also in long-term care and early recognition of the possible disease recurrence.
Potransplantačný diabetes mellitus (PTDM) ostáva naďalej jednou z najčastejších komplikácii po transplantácii solídnych orgánov. Dôležitá je hlavne včasná diagnostika a správne cielená liečba v rámci jednotlivých potransplantačných období. Najlepším diagnostickým mechanizmom je pravidelná realizácia orálneho glukózového tolerančného testu, ideálne už v období pred transplantáciou, tak aj potransplantačne. Rovnako dôležité je identifikovanie rizikových faktorov rozvoja PTDM a ich prípadný včasný manažment. Správna voľba imunosupresného protokolu a predovšetkým jeho personalizáciu na jednotlivých pacientov môže taktiež predchádzať PTDM prípadne spomaliť jeho rozvoj. Pokiaľ sa však už PTDM u pacienta rozvinie, je kľúčové zvoliť správny liečebný postup v závislosti od obdobia vo vzťahu ku transplantácii. V terapii PTDM sa objavujú aj nové preparáty s významným kardio a renoprotektívnym účinkom. V neposlednom rade je dôležitá multidisciplinárna spolupráca na rozvoji diagnostiky, predikcie a terapie PTDM, so zameraním sa na moderné metódy.
Post-transplant diabetes mellitus (PTDM) remains one of the most common complications after solid organ transplantation. Early diagnosis and properly targeted treatment within the individual post-transplant periods are especially important. The best diagnostic mechanism is regular implementation of an oral glucose tolerance test, ideally in the period before transplantation and also after transplantation. Equally important is the identification of risk factors for the development of PTDM and their possible early management. The correct choice of an immunosuppressive protocol and, above all, its personalization for individual patients can also prevent PTDM or slow down its development. However, if PTDM has already developed in a patient, it is crucial to choose the correct treatment procedure depending on the period in relation to transplantation. New preparations with significant cardio- and renoprotective effects are also appearing in PTDM therapy. Last but not least, multidisciplinary cooperation is important in the development of diagnostics, prediction and therapy of PTDM, focusing on modern methods.
