Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree, leading to significant liver function impairment over time. There is a strong association with inflammatory bowel diseases (IBD), together representing a distinct and complex medical condition. Patients with PSC-IBD face a heightened risk of various cancers, particularly colorectal carcinoma (CRC) and cholangiocarcinoma (CCA) as the most common types. In this review, we aim to characterize the distinctive features of PSC-IBD-associated carcinomas. Cancer pathogenesis in PSC-IBD is shaped by various factors including dysregulated bile acid metabolism, gut dysbiosis, and unique immune responses. PSC-IBD-associated CRC is often right-sided and warrants vigilant monitoring due to its higher incidence and unique morphological features compared to CRC arising in the terrain of IBD alone. CCA shares substantial genetic similarities with extrahepatic CCA and poses diagnostic challenges since it is frequently detected at advanced stages due to symptom overlap with PSC. Besides, reliable predictive biomarkers for targeted therapy remain largely unexplored. The distinct molecular, genetic, and histopathological profiles of CRC and CCA in PSC-IBD underscore the complexity of these malignancies and highlight the need for continued research to develop precise therapeutic strategies.

• MeSH
• Cholangiocarcinoma * pathology   etiology   genetics   MeSH
• Inflammatory Bowel Diseases * complications   pathology   MeSH
• Colorectal Neoplasms * pathology   etiology   genetics   MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Bile Duct Neoplasms * pathology   etiology   genetics   MeSH
• Cholangitis, Sclerosing * complications   pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Evidence suggests that brain-computer interface (BCI)-based rehabilitation strategies show promise in overcoming the limited recovery potential in the chronic phase of stroke. However, the specific mechanisms driving motor function improvements are not fully understood. OBJECTIVE: We aimed at elucidating the potential functional brain connectivity changes induced by BCI training in participants with chronic stroke. METHODS: A longitudinal crossover design was employed with two groups of participants over the span of 4 weeks to allow for within-subject (n = 21) and cross-group comparisons. Group 1 (n = 11) underwent a 6-day motor imagery-based BCI training during the second week, whereas Group 2 (n = 10) received the same training during the third week. Before and after each week, both groups underwent resting state functional MRI scans (4 for Group 1 and 5 for Group 2) to establish a baseline and monitor the effects of BCI training. RESULTS: Following BCI training, an increased functional connectivity was observed between the medial prefrontal cortex of the default mode network (DMN) and motor-related areas, including the premotor cortex, superior parietal cortex, SMA, and precuneus. Moreover, these changes were correlated with the increased motor function as confirmed with upper-extremity Fugl-Meyer assessment scores, measured before and after the training. CONCLUSIONS: Our findings suggest that BCI training can enhance brain connectivity, underlying the observed improvements in motor function. They provide a basis for developing novel rehabilitation approaches using non-invasive brain stimulation for targeting functionally relevant brain regions, thereby augmenting BCI-induced neuroplasticity and enhancing motor recovery.

• MeSH
• Stroke * physiopathology   diagnostic imaging   MeSH
• Chronic Disease MeSH
• Default Mode Network * physiopathology   diagnostic imaging   MeSH
• Adult MeSH
• Cross-Over Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Magnetic Resonance Imaging MeSH
• Brain * physiopathology   diagnostic imaging   MeSH
• Nerve Net * physiopathology   diagnostic imaging   MeSH
• Stroke Rehabilitation * methods   MeSH
• Brain-Computer Interfaces * MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Publikace se zaměřuje na dezinformace, propagandu, politiku a farmaceutické společnosti a jejich vztah k nedávným pandemiím. Určeno široké veřejnosti.; Strach ohrožuje zdraví. Znalosti posilují naši obranu - proti virům, nebezpečné propagandě a lžím. Farmaceutické společnosti a virologové se již pokusili oklamat miliony lidí falešnými poplašnými zprávami o pandemii během epidemií prasečí a ptačí chřipky. Lékař, politik a bývalý poslanec Spolkového sněmu Wolfgang Wodarg se tehdy zasloužil o zmaření těchto plánů a dnes opět zaujímá jednoznačný postoj: „V současné době zažíváme obrovský zločin proti lidskosti. Je zřejmé, že korona-spekulanty nevede starost o životní prostředí a naše zdraví, ani emancipace či ochrana před globálním oteplováním. Jejich hnací silou je, stejně jako již dlouho, jejich chorobná chamtivost po bohatství, monopolech a moci.“ Wolfgang Wodarg odhaluje pandemii jako puč shora, řízený očkovací mafií a techno-elitou. Jeho kniha je nepostradatelným průvodcem - k opravdové solidaritě, skutečné demokracii a zdravotnickému systému, který slouží lidem, a ne zájmům nemocného kapitálu.

• MeSH
• History, 21st Century MeSH
• Disinformation MeSH
• Drug Industry MeSH
• Communications Media MeSH
• Pandemics MeSH
• Politics MeSH
• Fear MeSH
• Vaccination MeSH
• Check Tag
• History, 21st Century MeSH
• Publication type
• Monograph MeSH
• Popular Work MeSH

• Conspectus
• Sociální procesy
• NML Fields
• sociologie

Příručka, která se zaměřuje na sportovní aktivitu u pacientů s diabetem mellitus. Obsahuje i kazuistiky. Určeno odborné veřejnosti.; Diabetes u dětí a mladistvých byl tradičně považován za překážku větší sportovní aktivity. Dramatické zlepšení kvality života diabetiků 1. typu – v důsledku nových technických i farmakologických možností inzulinové terapie – umožňuje mnohým z nich život téměř srovnatelný s jejich zdravými vrstevníky. Přirozeným zájmem se tak mezi diabetiky 1. typu stává sport, včetně jeho závodního provozování. Diabetolog dnes musí být schopen pečovat o aktivně sportujícího diabetika. Riziko hypoglykemie i další nebezpečí spojená se sportem nelze podceňovat, na druhou stranu se lékař dostává do nepříjemného světla, když mladému pacientovi sport zakáže, když on sám zná další diabetiky, kteří se sportu věnovat mohou, a to někdy i vrcholovému. Třetí vydání úspěšné publikace obsahuje i nejmodernější metody léčby a kontroly glykemie, tedy aplikaci inzulinových pump a okamžitého měření glukózy (CGM). Knížka kolektivu autorů vedených jedním z nejuznávanějších českých odborníků v oblasti diabetologie a výživy, prof. MUDr. Zdeňkem Rušavým, Ph.D., je koncipována jako praktický návod pro diabetologa, resp. ošetřujícího lékaře, který se stará o sportující diabetiky 1. typu.

• MeSH
• Diabetes Mellitus MeSH
• Blood Glucose Self-Monitoring MeSH
• Athletes MeSH
• Sports MeSH
• Physical Exertion MeSH
• Physical Fitness MeSH
• Publication type
• Case Reports MeSH
• Handbook MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• diabetologie
• tělovýchovné lékařství
• NML Publication type
• kolektivní monografie

Publikace obsahuje komentář českých zákonů, které se týkají odpovědnosti za přestupky. Určeno odborné veřejnosti.

• MeSH
• Liability, Legal MeSH
• Social Control Policies legislation & jurisprudence   MeSH
• Criminal Law MeSH
• Publication type
• Comment MeSH
• Geographicals
• Czech Republic MeSH

• Conspectus
• Ústavní právo. Správní právo
• NML Fields
• právo, zákonodárství
• NML Publication type
• zákony

BACKGROUND: Despite extensive research on physical activity behaviour (PAB), consensus is lacking on related terms and definitions, thereby hindering the ability to compare findings between studies and to develop reliable assessment tools. This study therefore aimed to establish consensus on the definitions of key PAB determinants. METHODS: First, an international expert steering committee was established, comprising members of the European Cooperation in Science and Technology (COST) action "DEterminants of Physical ActivitieS in Settings" (DE-PASS). Recently published review-level studies were used to identify key determinants of PAB. Two independent reviewers systematically reviewed the literature to catalogue the range of definitions used for key determinants of PAB (steps 1-2). A two-round modified Delphi survey was conducted online from February to September 2023, to determine the optimal definition for each determinant. In round 1, experts selected the most suitable definition for each of the 41 initially identified determinants. In round 2, experts ranked the appropriateness of the definition selected from round 1 on a 5-point Likert scale. Consensus was defined a priori as ≥ 75% agreement on the definition (i.e., ratings of ≥ 4 points). A professional English language expert ensured concise, coherent wording and high-quality editing of the definitions (steps 3-6). RESULTS: Eighty-five experts in PAB research participated in round 1, and sixty-nine experts in round 2. Consensus of definitions was achieved for 39 of the 41 determinants (88.4%-98.6% agreement). The consensus threshold was not achieved for two determinants: genetic profile and regulation (69.6%) and backyard access/size (73.9%). CONCLUSIONS: The findings of this study offer a consensus-based set of definitions for 39 key determinants of PAB. These definitions can be used homogenously in academic research on physical activity.

• MeSH
• Exercise * MeSH
• Delphi Technique * MeSH
• Consensus * MeSH
• Humans MeSH
• Health Behavior MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Epitranscriptomics, the study of RNA modifications such as N6-methyladenosine (m6A), provides a novel layer of gene expression regulation with implications for numerous biological processes, including cellular adaptation to hypoxia. Hypoxia-inducible factor-1 (HIF-1), a master regulator of the cellular response to low oxygen, plays a critical role in adaptive and pathological processes, including cancer, ischemic heart disease, and metabolic disorders. Recent discoveries accent the dynamic interplay between m6A modifications and HIF-1 signaling, revealing a complex bidirectional regulatory network. While the roles of other RNA modifications in HIF-1 regulation remain largely unexplored, emerging evidence suggests their potential significance. MAIN BODY: This review examines the reciprocal regulation between HIF-1 and epitranscriptomic machinery, including m6A writers, readers, and erasers. HIF-1 modulates the expression of key m6A components, while its own mRNA is regulated by m6A modifications, positioning HIF-1 as both a regulator and a target in this system. This interaction enhances our understanding of cellular hypoxic responses and opens avenues for clinical applications in treating conditions like cancer and ischemic heart disease. Promising progress has been made in developing selective inhibitors targeting the m6A-HIF-1 regulatory axis. However, challenges such as off-target effects and the complexity of RNA modification dynamics remain significant barriers to clinical translation. CONCLUSION: The intricate interplay between m6A and HIF-1 highlights the critical role of epitranscriptomics in hypoxia-driven processes. Further research into these regulatory networks could drive therapeutic innovation in cancer, ischemic heart disease, and other hypoxia-related conditions. Overcoming challenges in specificity and off-target effects will be essential for realizing the potential of these emerging therapies.

• MeSH
• Adenosine analogs & derivatives   metabolism   MeSH
• Epigenesis, Genetic * MeSH
• Hypoxia-Inducible Factor 1 * metabolism   genetics   MeSH
• Humans MeSH
• RNA Processing, Post-Transcriptional MeSH
• Gene Expression Regulation MeSH
• Signal Transduction MeSH
• Transcriptome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Malignant lymphoma survivors are at increased risk for anthracycline and/or radiotherapy-induced chronic cardiotoxicity. Proper long-term follow-up is essential for malignant lymphoma survivors after-care. This study aimed to assess TTE parameters of potential subclinical cardiotoxicity and to examine their utility in diagnosing chronic cardiotoxicity. Improvement of the diagnostic process may precede the manifestation of cardiac adverse events. Main objective of the study was to improve the identification of cancer survivors in increased risk of treatment cardiotoxicity. To achieve this goal, utility of various echocardiography parameters was examined.In this retrospective study we analysed TTE of 167 subjects with speckle tracking according to the European Society of Echocardiography guidelines during the follow-up period. 88 of them were long-term lymphoma survivors diagnosed with malignant lymphoma between the years 1994-2015. Minimum follow up period was 5 years with the median of 10 years after anti-cancer treatment cessation. TTE were performed between the years 2017-2022 at cardio-oncology outpatient office during regular follow-up period. A total of 79 volunteers with no history of chronic heart failure (CHF) or decline in LVEF, 51 (64.6%) of whom were males, with the median age of 46 (16-58) years were included in the analysis as control group. Control subjects had various indications for TTE (e.g. preoperative examination, benign palpitations, or with well controlled arterial hypertension taking two antihypertensives at most). Ischemic heart disease was ruled out by stress test. None of the control subjects had history of stroke or chronic lower limb ischemia. All control subjects were considered clinically stable with no sign of cardiac impairment caused by primary disease. Both cancer survivors and control group were divided into subgroups based on LVEF: lower normal LVEF (53-61%), and higher normal LVEF (> 61%). Survivors with lower normal LVEF (53-61%) had a statistically significant decline in GLS compared to those with higher normal LVEF (> 61%). This phenomenon was not observed in control group indicating a possible additional diagnostic value of this parameter. Inclusion of GLS assessment in follow-up TTE examination of subjects with lower normal LVEF may improve the sensitivity of detection of chronic cardiotoxicity. Patients with declined GLS and lower normal LVEF are candidates for intensified follow-up to precede manifestation of cardiac adverse events.

• MeSH
• Anthracyclines adverse effects   MeSH
• Adult MeSH
• Echocardiography * MeSH
• Ventricular Function, Left drug effects   MeSH
• Global Longitudinal Strain MeSH
• Cardiotoxicity * etiology   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphoma * drug therapy   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Cancer Survivors * MeSH
• Retrospective Studies MeSH
• Stroke Volume drug effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The precise and unambiguous detection and quantification of internal RNA modifications represents a critical step for understanding their physiological functions. The methods of direct RNA sequencing are quickly developing allowing for the precise location of internal RNA marks. This detection is, however, not quantitative and still presents detection limits. One of the biggest remaining challenges in the field is still the detection and quantification of m6A, m6Am, inosine, and m1A modifications of adenosine. The second intriguing and timely question remaining to be addressed is the extent to which individual marks are coregulated or potentially can affect each other. Here, we present a methodological approach to detect and quantify several key mRNA modifications in human total RNA and in mRNA, which is difficult to purify away from contaminating tRNA. We show that the adenosine demethylase FTO primarily targets m6Am marks in noncoding RNAs in HEK293T cells. Surprisingly, we observe little effect of FTO or ALKBH5 depletion on the m6A mRNA levels. Interestingly, the upregulation of ALKBH5 is accompanied by an increase in inosine level in overall mRNA.

• MeSH
• Adenosine * analogs & derivatives   metabolism   genetics   analysis   MeSH
• AlkB Homolog 5, RNA Demethylase * metabolism   genetics   MeSH
• Chromatography, Liquid methods   MeSH
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO * metabolism   genetics   MeSH
• HEK293 Cells MeSH
• Inosine * metabolism   genetics   MeSH
• Liquid Chromatography-Mass Spectrometry MeSH
• Humans MeSH
• RNA, Messenger * genetics   metabolism   MeSH
• RNA Processing, Post-Transcriptional MeSH
• Tandem Mass Spectrometry * methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

AIMS: This study aimed to examine changes in the repertoire of functional T-cells specific for six leukemia-associated antigens (LAA), including WT1, PRAME, MUC1, CCNA1, NPM1, and NPM1c, during immune reconstitution following allogeneic transplantation of hematopoietic stem cells (HSCT) in patients with acute myeloid leukemia. PATIENTS & METHODS: LAA-specific T cell response was measured by ELISPOT- IFNγ and intracellular cytokine staining in 47 patients before starting conditioning therapy (baseline) and 7 months after HSCT. RESULTS: The positive cumulative LAA-specific T cell response before HSCT was associated with a decreased risk of relapse after HSCT. The prevalent genetic aberration - an internal tandem duplication of Fms 3 - related receptor tyrosine kinase, which has been previously implicated in immune escape mechanisms, is presented here for the first time as a factor associated with the absence of an adaptive T cell response against multiple LAAs. T-cell specific responses against wild-type and mutated NPM1 antigens were less frequent in the study cohort and did not correlate with mutations in the NPM1 gene. CONCLUSIONS: Our results showed that the T-cell response to LAA can be reconstituted after HSCT. Measurement of functional pre-transplant T-cell responses against multiple LAAs could help to find patients with an increased risk of relapse.

• MeSH
• Leukemia, Myeloid, Acute * therapy   immunology   genetics   MeSH
• Antigens, Neoplasm immunology   MeSH
• Adult MeSH
• Transplantation, Homologous MeSH
• Nuclear Proteins genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Mucin-1 genetics   immunology   MeSH
• Mutation * MeSH
• Nucleophosmin * MeSH
• WT1 Proteins immunology   genetics   MeSH
• Recurrence MeSH
• Aged MeSH
• T-Lymphocytes * immunology   MeSH
• Hematopoietic Stem Cell Transplantation * MeSH
• fms-Like Tyrosine Kinase 3 * genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH