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

Cancer immunotherapy is increasingly used in clinical practice, but its success rate is reduced by tumor escape from the immune system. This may be due to the genetic instability of tumor cells, which allows them to adapt to the immune response and leads to intratumoral immune heterogeneity. The study investigated spatial immune heterogeneity in the tumor microenvironment and its possible drivers in a mouse model of tumors induced by human papillomaviruses (HPV) following immunotherapy. Gene expression was determined by RNA sequencing and mutations by whole exome sequencing. A comparison of different tumor areas revealed heterogeneity in immune cell infiltration, gene expression, and mutation composition. While the mean numbers of mutations with every impact on gene expression or protein function were comparable in treated and control tumors, mutations with high or moderate impact were increased after immunotherapy. The genes mutated in treated tumors were significantly enriched in genes associated with ECM metabolism, degradation, and interactions, HPV infection and carcinogenesis, and immune processes such as antigen processing and presentation, Toll-like receptor signaling, and cytokine production. Gene expression analysis of DNA damage and repair factors revealed that immunotherapy upregulated Apobec1 and Apobec3 genes and downregulated genes related to homologous recombination and translesion synthesis. In conclusion, this study describes the intratumoral immune heterogeneity, that could lead to tumor immune escape, and suggests the potential mechanisms involved.

• MeSH
• imunoterapie * metody   MeSH
• infekce papilomavirem imunologie   virologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• mutace * MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové mikroprostředí * imunologie   MeSH
• regulace genové exprese u nádorů MeSH
• sekvenování exomu MeSH
• únik nádoru z imunitní kontroly genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Respirační syncytiální virus (rsV) patří mezi nejčastější původce infekcí dolních cest dýchacích u kojenců a malých dětí. každoročně celosvětově způsobuje miliony případů bronchiolitidy a pneumonie a je jednou z vedoucích příčin hospitalizace kojenců v zimních měsících, kdy působí výraznou zátěž zdravotnickému systému. Vzhledem k absenci specifické antivirové terapie zůstávala klíčovým opatřením prevence. tradiční možností ochrany bylo podávání palivizumabu (synagis) – monoklonálních protilátek určených k ochraně vysoce rizikových kojenců. nové možnosti prevence nyní přinášejí dva zásadní průlomy – dlouhodobě působící monoklonální protilátku nirsevimab pro novorozence a kojence a vakcínu abrysvo. ta je určena pro těhotné ženy mezi 24. a 36. týdnem těhotenství a zajišťuje pasivní ochranu novorozenců přenosem mateřských protilátek placentou. Imunitní systém novorozence není po narození plně vyvinutý, což zvyšuje jeho zranitelnost vůči infekcím, zejména v prvních měsících života. Během prvního roku dochází k postupnému zrání vrozené i adaptivní imunity, přičemž klíčovou roli v ochraně hraje pasivní imunita přenášená z matky. Vakcinace těhotných žen je proto považována za jednu z nejúčinnějších strategií ochrany novorozenců před závažnými infekcemi. Díky rozvoji nových technologií lze očekávat, že prevence rsV se stane běžnou součástí pediatrické péče, což povede ke snížení nemocnosti a úmrtnosti spojené s tímto virem. Cílem tohoto článku je poskytnout komplexní přehled o rsV infekci u kojenců a možnostech prevence pasivní imunizací.

The respiratory syncytial virus (rsV) is one of the most common causes of lower respiratory tract infections in infants and young children. each year, it causes millions of cases of bronchiolitis and pneumonia and is one of the leading causes of infant hospitalisation during the winter months, placing a significant burden on the healthcare system. Due to the lack of specific antiviral therapy, prevention remained the key measure. the traditional approach to protection has been the administration of palivizumab (synagis), a monoclonal antibody intended for high-risk infants. However, new prevention strategies have brought two breakthroughs: the long-acting monoclonal antibody nirsevimab for neonates and infants and the abrysvo vaccine. abrysvo is designed for pregnant women between 24 and 36 weeks of gestation, providing passive protection to newborns by transferring maternal antibodies via the placenta. The immune system of a newborn is not fully developed at birth, making infants particularly vulnerable to infections, especially during the first months of life. throughout the first year, both innate and adaptive immunity gradually mature, with passive immunity transferred from the mother playing a key protective role — which is why maternal vaccination is considered one of the most effective strategies to protect newborns from severe infections. With the advancement of new technologies, rsV prevention is expected to become a routine part of pediatric care, leading to a reduction in morbidity and mortality associated with this virus. This article aims to provide a comprehensive overview of rsV infection in infants and prevention strategies through vaccination.

• Klíčová slova
• vakcína Abrysvo, studie MATISSE,
• MeSH
• humanizované monoklonální protilátky farmakologie   terapeutické užití   MeSH
• infekce respiračními syncytiálními viry * diagnóza   epidemiologie   farmakoterapie   prevence a kontrola   MeSH
• kojenec MeSH
• lidé MeSH
• pasivní imunizace metody   MeSH
• randomizované kontrolované studie jako téma MeSH
• respirační syncytiální viry imunologie   patogenita   MeSH
• těhotné ženy MeSH
• vakcíny proti respiračnímu syncyciálnímu viru aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH

Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.

• MeSH
• biopsie MeSH
• dospělí MeSH
• hodnoty glomerulární filtrace MeSH
• isoprotilátky imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• přežívání štěpu imunologie   MeSH
• prognóza MeSH
• rejekce štěpu * patologie   imunologie   etiologie   MeSH
• rizikové faktory MeSH
• T-lymfocyty imunologie   MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• vyšetření funkce ledvin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

There is growing interest in the role of extracellular vesicles (EVs) in neonatal pathology. This study aimed to characterise circulating EVs following preterm birth. This single-centre prospective observational study included cord and postnatal plasma from preterm (n = 101) and full-term infants (n = 66). EVs were analysed using nanoparticle tracking analysis, flow cytometry, proteomics and procoagulant activity assay. We found changes in the concentration, size, cellular origin and proteomic content of circulating EVs in preterm infants during perinatal adaptation. To understand if these changes were related to prematurity or normal adaptation to extrauterine life, they were also investigated in term infants. There was a dramatic increase in the concentration of small and large EVs on Day 3 in the preterm group; specific subsets of platelet (CD42b+ and CD62P+), endothelial (VEGFR2) and tissue factor EVs were elevated. Differentially expressed proteins relating to haemostasis, pulmonary physiology and immunity were identified between Day 1 and 3 in preterm infants. These changes have never previously been described in a large cohort of preterm infants and differ from healthy term infants. These findings have major implications for future neonatal EV studies, particularly the timing of sample collection. Further work is required to understand the clinical implications of this unique EV profile following preterm birth.

• MeSH
• extracelulární vezikuly * metabolismus   MeSH
• fyziologická adaptace * MeSH
• lidé MeSH
• novorozenec nedonošený * krev   MeSH
• novorozenec MeSH
• prospektivní studie MeSH
• proteomika metody   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND: Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. CONCLUSION: Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.

• MeSH
• dysbióza metabolismus   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• lidé MeSH
• mozek * metabolismus   MeSH
• neurodegenerativní nemoci * mikrobiologie   metabolismus   MeSH
• osa mozek-střevo * fyziologie   MeSH
• probiotika MeSH
• stárnutí * MeSH
• střevní mikroflóra * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Introduction: The topic of work-life harmony of Child Protection Authority (OSPOD) workers is crucial, not only for their personal well-being, but also for the long-term sustainability of this demanding profession. This article focuses on developing a deeper understanding of the strategies that workers use to maintain work-life harmony, and provides insights into the role of organizational support in this process. Methods: The research was conducted through interpretive phenomenological analysis (IPA) and qualitative semi-structured interviews. Results: The results show that employees use a variety of individual strategies such as self-development, mindset, networking, time management and personal space for relaxation. They perceive support from the organization mainly through supervision, flexible working hours, professional training, and employee benefits. An interesting finding was that workers did not pay attention to the development of spiritual needs, which are an important aspect of wellbeing. Conclusion: The study highlights the importance of systematic organizational support in the field of work-life harmony and recommends measures that can contribute to the development of wellbeing of workers and their sustainability in the profession.

• MeSH
• adaptace psychologická MeSH
• lidé MeSH
• organizace a řízení MeSH
• psychická odolnost MeSH
• rovnováha mezi pracovním a osobním životem * klasifikace   metody   MeSH
• rozhovory jako téma MeSH
• sociální péče o dítě psychologie   MeSH
• sociální pracovníci * psychologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

In this manuscript, we highlight the evolutionary origins of mitochondria from bacterial endosymbionts and explore their contributions to health, energy metabolism, and neural-immune communication. Mitochondrial adaptability and the roles played by these organelles in promoting oxygen-dependent ATP production provide critical regulation of cognition, motivation, and inflammation. Hypoxia has been identified as an important initiator of inflammation, neurodegeneration, and mitochondrial dysfunction, emphasizing the overall importance of oxygen homeostasis to health and well-being. The Behavior, Exercise, Relaxation, and Nutrition framework highlights these observations as tools that can be used to optimize mitochondrial efficiency. Interestingly, mitochondrial dysfunction may also be linked to psychiatric disorders (e.g., schizophrenia), a hypothesis that focuses on energy dynamics, a proposal that may extend our understanding of these disorders beyond traditional neurotransmitter-focused concepts. Collectively, these perspectives underscore the critical contributions of mitochondria to health and disease and offer a novel framework that may help to explain the connections featured in mind-body medicine.

• MeSH
• biologická evoluce MeSH
• bolest * metabolismus   patofyziologie   MeSH
• cvičení * fyziologie   MeSH
• energetický metabolismus * MeSH
• kognice * fyziologie   MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• motivace * MeSH
• radost * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS), characterized by inflammation and neurodegeneration. The pathophysiology of MS, especially its progressive forms, involves various cellular components, including microglia, the primary resident immune cells of the CNS. This review discusses the role of microglia in neuroinflammation, tissue repair, and neural homeostasis, as well as their involvement in MS and explores potential therapeutic strategies targeting microglial function. METHODS: A literature search conducted in August 2023 and updated in March 2025, using the PubMed database, focused on articles relating to microglia and MS published in 2018-2025. Additionally, ongoing clinical trials of Bruton's tyrosine kinase (BTK) inhibitors were identified through the ClinicalTrials.gov website in November 2023 and updated in March 2025. RESULTS: Microglia are highly adaptive and exhibit various functional states throughout different life stages and play critical roles in neuroinflammation, tissue repair, and neural homeostasis. Their altered activity is a prominent feature of MS, contributing to its pathogenesis. Imaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) provide insights into microglial activity in MS. BTK inhibitors and other novel treatments for MS, including masitinib and frexalimab, show promise in modulating microglial function and influencing the disease progression rate. CONCLUSIONS: The multifaceted roles of microglia in CNS development, immune surveillance, and particularly in the pathogenesis of MS highlight the potential of targeting microglial functions in MS treatment. Emerging research on the involvement of microglia in MS pathophysiology offers promising avenues for developing novel therapies, especially for progressive MS, potentially improving patient outcomes in this debilitating disease.

• MeSH
• inhibitory proteinkinas * terapeutické užití   farmakologie   MeSH
• inhibitory tyrosinkinasy MeSH
• lidé MeSH
• mikroglie * účinky léků   imunologie   metabolismus   MeSH
• proteinkinasa BTK * antagonisté a inhibitory   metabolismus   MeSH
• roztroušená skleróza * farmakoterapie   imunologie   etiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

We estimated the effectiveness of the adapted monovalent XBB.1.5 COVID-19 vaccines against PCR-confirmed SARS-CoV-2 hospitalisation during the BA.2.86/JN.1 lineage-predominant period using a multicentre test-negative case-control study in Europe. We included older adults (≥ 65 years) hospitalised with severe acute respiratory infection from November 2023 to May 2024. Vaccine effectiveness was 46% at 14-59 days and 34% at 60-119 days, with no effect thereafter. The XBB.1.5 COVID-19 vaccines conferred protection against BA.2.86 lineage hospitalisation in the first 4 months post-vaccination.

• MeSH
• COVID-19 * prevence a kontrola   epidemiologie   imunologie   MeSH
• hospitalizace * statistika a číselné údaje   MeSH
• lidé MeSH
• SARS-CoV-2 * imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• účinnost vakcíny * MeSH
• vakcinace statistika a číselné údaje   MeSH
• vakcíny proti COVID-19 * imunologie   aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH