INTRODUCTION: The use of signal dogs for cancer detection is not yet routinely performed,but dogs and their powerful olfactory system have proven to be a unique and valuable tool for many lineages and are beginning to be incorporated into medical practice. This method has great advantages; the dog can detect a tumour in the human body already in preclinical stages, when the patient has no symptoms yet. The identification of cancer biomarkers to enable early diagnosis is a need for many types of cancer, whose prognosis is strongly dependent on the stage of the disease. However, this method also has its various pitfalls that must be taken into account. AIM: The aim of the study was to identify and highlight the factors that affect the level of detection accuracy, but also the conditions associated with olfactometric diagnosis. METHODS: The study included 48 dogs and 48 handlers, that were part of the training between 2016 and 2023.All those who started olfactometry training and remained in training for at least one year were included in the study. The dogs ranged in age from 8 months to 12 years and were of different races and sexes. After long-term observation, a qualitative analysis was performed and factors that may play a role in the early detection of the disease were listed. RESULTS: The results of the search for the different factors have been compiled into two groups, focussing on the actual handling of the patient biological sample from collection, processing, storage until transport, preparation of the sample,and detection. Focus on the actual work and behaviour of the dog and handler. CONCLUSION: There are many factors; however, it is worth addressing them because the canine sense of smell is one of the possible uses as a diagnostic method.

• Publication type
• Journal Article MeSH

Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6 . The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.

• MeSH
• Adult MeSH
• Epigenesis, Genetic MeSH
• Epigenomics MeSH
• Gene Fusion * MeSH
• Genetic Predisposition to Disease MeSH
• Genomics MeSH
• Immunohistochemistry MeSH
• Polymorphism, Single Nucleotide MeSH
• Juxtaglomerular Apparatus pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Methylation MeSH
• Biomarkers, Tumor * genetics   MeSH
• Kidney Neoplasms * genetics   pathology   chemistry   MeSH
• Whole Genome Sequencing MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

The prevalence of centenarians, people who lived 100 years and longer, is steadily growing in the last decades. This exceptional longevity is based on multifaceted processes influenced by a combination of intrinsic and extrinsic factors such as sex, (epi-)genetic factors, gut microbiota, cellular metabolism, exposure to oxidative stress, immune status, cardiovascular risk factors, environmental factors, and lifestyle behavior. Epidemiologically, the incidence rate of cardiovascular diseases is reduced in healthy centenarians along with late onset of age-related diseases compared with the general aged population. Understanding the mechanisms that affect vascular ageing in centenarians and the underlying factors could offer valuable insights for developing strategies to improve overall healthy life span in the elderly. This review discusses these key factors influencing vascular ageing and how their modulation could foster healthy longevity.

• MeSH
• Longevity * physiology   MeSH
• Cardiovascular Diseases physiopathology   epidemiology   MeSH
• Humans MeSH
• Oxidative Stress physiology   MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aging * physiology   MeSH
• Gastrointestinal Microbiome physiology   MeSH
• Healthy Aging physiology   MeSH
• Life Style MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

INTRODUCTION AND OBJECTIVES: With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options. MATERIALS AND METHODS: This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months. RESULTS: Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009). CONCLUSIONS: Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis. GOV REGISTRATION: NCT04895943.

• MeSH
• Bariatric Surgery * MeSH
• Time Factors MeSH
• Equipment Design MeSH
• Adult MeSH
• Elasticity Imaging Techniques MeSH
• Weight Loss MeSH
• Liver Cirrhosis * etiology   diagnostic imaging   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Non-alcoholic Fatty Liver Disease * diagnostic imaging   diagnosis   etiology   MeSH
• Obesity * complications   surgery   diagnosis   MeSH
• Pilot Projects MeSH
• Prospective Studies MeSH
• Treatment Outcome MeSH
• Gastric Balloon * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH

A double primary colorectal cancer (CRC) in a familial setting signals a high risk of CRC. In order to identify novel CRC susceptibility genes, we whole-exome sequenced germline DNA from nine persons with a double primary CRC and a family history of CRC. The detected variants were processed by bioinformatics filtering and prioritization, including STRING protein-protein interaction and pathway analysis. A total of 150 missense, 19 stop-gain, 22 frameshift and 13 canonical splice site variants fulfilled our filtering criteria. The STRING analysis identified 20 DNA repair/cell cycle proteins as the main cluster, related to genes CHEK2, EXO1, FAAP24, FANCI, MCPH1, POLL, PRC1, RECQL, RECQL5, RRM2, SHCBP1, SMC2, XRCC1, in addition to CDK18, ENDOV, ZW10 and the known mismatch repair genes. Another STRING network included extracellular matrix genes and TGFβ signaling genes. In the nine whole-exome sequenced patients, eight harbored at least two candidate DNA repair/cell cycle/TGFβ signaling gene variants. The number of families is too small to provide evidence for individual variants but, considering the known role of DNA repair/cell cycle genes in CRC, the clustering of multiple deleterious variants in the present families suggests that these, perhaps jointly, contributed to CRC development in these families.

• MeSH
• Adult MeSH
• Genetic Predisposition to Disease * MeSH
• Colorectal Neoplasms * genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Repair genetics   MeSH
• Pedigree MeSH
• Exome Sequencing * methods   MeSH
• Aged MeSH
• Germ-Line Mutation * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. METHODS: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. RESULTS: When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. CONCLUSIONS: This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.

• MeSH
• Adult MeSH
• Interoception * physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain Mapping MeSH
• Young Adult MeSH
• Brain * physiopathology   diagnostic imaging   MeSH
• Nervous System Diseases * physiopathology   diagnostic imaging   MeSH
• Attention physiology   MeSH
• Heart Rate physiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients. METHODS: A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method. RESULTS: We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma. CONCLUSIONS: In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.

• MeSH
• Diffuse Intrinsic Pontine Glioma genetics   diagnosis   blood   MeSH
• Child MeSH
• Epigenesis, Genetic MeSH
• Glioma genetics   diagnosis   blood   pathology   diagnostic imaging   MeSH
• Histones * genetics   metabolism   blood   MeSH
• Humans MeSH
• Adolescent MeSH
• Mutation MeSH
• Biomarkers, Tumor blood   MeSH
• Brain Stem Neoplasms genetics   diagnosis   blood   diagnostic imaging   pathology   metabolism   MeSH
• Child, Preschool MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The COVID-19 Pandemic contributed to accelerating the process of using information and communication technologies and digital technologies in healthcare management and delivery within healthcare systems. At that time, the Czech healthcare system faced the same problems as other European systems and struggled with a temporary limitation of direct provision of healthcare services. It was solved by switching to telemedicine. The Czech healthcare system used telemedicine to a minimal extent until then. Despite adopting the law on healthcare digitisation, it is still one of the countries with a lower level of digitisation of healthcare processes. The article presents the results of an exploratory expert investigation focused on the implementation and development of telemedicine in the Czech Republic. The conducted research aimed to identify problems related to the implementation of telemedicine in practice, place them in the broader framework of the healthcare system and structure them, propose possible solutions, and identify the future challenges of telemedicine in the Czech Republic. We based our study on the results of a three-phase QUAL-QUAN-QUAL research. Data collection in the first phase took the form of individual semi-structured interviews with patients (25) with practical experience in the field of telemedicine, followed by the second quantitative phase of the questionnaire survey with patients (650). The third qualitative phase included semi-structured interviews with experts (17) with practical experience in telemedicine. The introduction and expansion of telemedicine require several fundamental changes. These include adjustments to the legislative environment and changes to the technological infrastructure, organisation of care and work. Several barriers have been identified at the healthcare system level, healthcare providers, healthcare professionals and patients.

• MeSH
• COVID-19 * epidemiology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Pandemics * MeSH
• Delivery of Health Care organization & administration   MeSH
• Surveys and Questionnaires MeSH
• Interviews as Topic MeSH
• SARS-CoV-2 MeSH
• Aged MeSH
• Telemedicine * organization & administration   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: Despite secondary prevention with aspirin, patients with stable cardiovascular disease (CVD) remain at elevated long-term risk of major adverse cardiovascular events. The Cardiovascular Outcomes in People Using Anticoagulant Strategies (COMPASS) double-blind, randomized clinical trial demonstrated that aspirin plus low-dose rivaroxaban (COMPASS regime) significantly decreased the incidence of major adverse cardiovascular events by 24% compared with aspirin alone. However, the mechanisms underlying these potential synergistic/nonantithrombotic effects remain elusive. Extracellular vesicles (EVs) are crucial messengers regulating a myriad of biological/pathological processes and are highly implicated in CVD. OBJECTIVES: We hypothesized that circulating EV profiles reflect the cardioprotective properties of the COMPASS regime. METHODS: A cohort of stable CVD patients (N = 40) who participated in the COMPASS trial and were previously randomized to receive aspirin were prospectively recruited and assigned a revised regimen of open-label aspirin plus rivaroxaban. Blood samples were obtained at baseline (aspirin only) and 6-month follow-up. Plasma EV concentration, size, and origin were analyzed by nanoparticle tracking analysis and flow cytometry. EVs were enriched by ultracentrifugation for proteomic analysis. RESULTS: The COMPASS regime fundamentally altered small (<200 nm) and large (200-1000 nm) EV concentration and size compared with aspirin alone. Crucially, levels of platelet-derived and myeloperoxidase-positive EVs became significantly decreased at follow-up. Comparative proteomic characterization further revealed a significant decrease in highly proinflammatory protein expression at follow-up. CONCLUSION: The observed changes in EV subpopulations, together with the differential protein expression profiles, suggest amelioration of an underlying proinflammatory and prothrombotic state upon dual therapy, which may be of clinical relevance toward understanding the fundamental mechanism underlying the reported superior cardiovascular outcomes associated with this antithrombotic regimen.

• MeSH
• Aspirin * administration & dosage   therapeutic use   adverse effects   MeSH
• Double-Blind Method MeSH
• Extracellular Vesicles * metabolism   drug effects   MeSH
• Platelet Aggregation Inhibitors * administration & dosage   adverse effects   therapeutic use   MeSH
• Factor Xa Inhibitors * administration & dosage   adverse effects   therapeutic use   MeSH
• Cardiovascular Diseases * blood   prevention & control   drug therapy   MeSH
• Drug Therapy, Combination * MeSH
• Middle Aged MeSH
• Humans MeSH
• Inflammation Mediators blood   MeSH
• Prospective Studies MeSH
• Proteomics methods   MeSH
• Rivaroxaban * administration & dosage   MeSH
• Aged MeSH
• Thrombosis blood   prevention & control   drug therapy   MeSH
• Treatment Outcome MeSH
• Inflammation blood   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

Our aim is to determine the number of leukocytes, T lymphocytes and B lymphocytes and the expression of activation markers CD200 and CD23 on B lymphocytes in atopic dermatitis (AD) patients (treated and not treated with dupilumab) during the pollen season. We examined 29 patients not treated with dupilumab, 24 patients treated with dupilumab and 40 healthy subjects as a control group. The count of T and B lymphocytes and their subsets were assessed by flow cytometry. The non-parametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni's modification was used for statistical processing. Although there was a significant improvement in skin findings in patients treated with dupilumab, the changes in immunological profile show a persistent altered immune response characterized by dysregulation and overactivation of B lymphocytes. Dupilumab therapy leads to normalization of relative T regulatory lymphocytes and total memory B lymphocytes and to decreased count of absolute CD8+ T lymphocytes. Why carry out this study?Studies investigating the immunological profile of atopic dermatitis (AD) patients during the pollen season are rare. There are no studies investigating the count of B lymphocytes (CD5+, CD22+ and CD73+ B lymphocytes) and the expression of activation markers CD23 and CD200 on B lymphocytes and on their subsets during pollen season in AD patients treated and non-treated with dupilumab therapy.What was learned from the study?In atopic dermatitis (AD) patients with and without dupilumab therapy, we confirmed the significantly higher count of absolute neutrophils, absolute monocytes, absolute eosinophils, absolute basophils, non-switched B lymphocytes, transitional B lymphocytes, CD23 memory, naive, non-switched, switched and total CD23 B lymphocytes, the relative count of CD200 memory and CD200 switched B lymphocytes.In dupilumab treated patients, we confirmed the significantly higher count of relative eosinophils, relative CD16+ eosinophils, relative CD200 non-switched B lymphocytes and lower count of absolute CD8+ T lymphocytes. Further studies should focus on investigating the effect of dupilumab on CD8+ T lymphocytes and their subpopulations.In patients without dupilumab therapy, we confirmed the significantly higher count of relative neutrophils, relative T regulatory lymphocytes and total memory B lymphocytes.The changes in the count of CD5+, CD22+ and CD73+ B lymphocytes were not observed during pollen season in both groups of AD patients.

• MeSH
• Dermatitis, Atopic * drug therapy   immunology   MeSH
• B-Lymphocytes immunology   MeSH
• Antigens, CD MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Pollen immunology   MeSH
• Receptors, IgE MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH