Propiconazole is a triazole fungicide previously shown to induce triglyceride accumulation in human liver HepaRG cells, potentially via activation of the Pregnane X Receptor (PXR). However, whether propiconazole can disrupt hepatic and whole-body metabolism in vivo is currently unknown. Therefore, we aimed to examine the metabolic effects of propiconazole in the context of metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, and insulin resistance. To this end, male C57BL/6J mice were fed a high-fat diet for 20 weeks. During the last 10 weeks, mice additionally received vehicle, 0.04, 30, or 100 mg/kg body weight (bw)/day propiconazole via oral gavage. High-dose propiconazole, but not low or intermediate dose, reduced body weight gain and adipose tissue weight in obese mice. Mice receiving high-dose propiconazole displayed improved glucose tolerance and reduced levels of plasma triglycerides and cholesterol. Propiconazole dose-dependently increased liver weight and triglyceride levels and at high dose caused signs of hepatic inflammation. RNA sequencing on the liver revealed that propiconazole mainly induced PXR target genes. At intermediate and high dose, propiconazole induced pathways related to cell-cell interactions and inflammation, while oxidative phosphorylation was repressed by propiconazole. Comparison of gene regulation in wildtype and PXR knockout primary hepatocytes as well as gene reporter assays confirmed the activation of PXR by propiconazole. All in all, our data underscore the capacity of propiconazole to activate PXR in the liver and thereby promote the development of hepatic steatosis in vivo.

• MeSH
• dieta s vysokým obsahem tuků * MeSH
• inzulinová rezistence MeSH
• játra účinky léků   metabolismus   patologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL * MeSH
• myši MeSH
• obezita * chemicky indukované   MeSH
• pregnanový X receptor * metabolismus   genetika   MeSH
• průmyslové fungicidy * toxicita   MeSH
• triazoly * toxicita   MeSH
• triglyceridy krev   metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• ztučnělá játra * chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: It is hypothesized that systemically administered antibiotics penetrate wound sites more effectively during negative pressure wound therapy (NPWT). However, there is a lack of clinical data from patients who receive NPWT for deep sternal wound infection (DSWI) after open-heart surgery. Here, we evaluated vancomycin penetration into exudate in this patient group. PATIENTS AND METHODS: For this prospective observational study, we enrolled 10 consecutive patients treated with NPWT for post-sternotomy DSWI. On the first sampling day, serum and exudate samples were synchronously collected at 0 (pre-dose), 0.5, 1, 2, 3 and 6 h after vancomycin administration. On the following three consecutive days, additional samples were collected, only before vancomycin administration. RESULTS: The ratio of average vancomycin concentration in wound exudate to in serum was higher for free (unbound) (1.51 ± 0.53) than for total (bound + unbound) (0.91 ± 0.29) concentration (p = 0.049). The percentage of free vancomycin was higher in wound exudate than serum (0.79 ± 0.19 vs. 0.46 ± 0.16; p = 0.04). Good vancomycin wound penetration was maintained on the following three days (vancomycin trough exudate-to-serum concentration ratio > 1). The total hospital stay was significantly longer in patients with DSWI (46 ± 11.6 days) versus without DSWI (14 ± 11.7 days) (p < 0.001). There was no in-hospital or 90-day mortality. Two patients experienced late DSWI recurrence. All-cause mortality was 4.8% during a median follow-up of 2.5 years. CONCLUSION: Vancomycin effectively penetrates wound exudate in patients receiving NPWT for DSWI after open-heart surgery.The protocol for this study was registered at ClinicalTrials.gov on July 16, 2024 (NCT06506032).

• MeSH
• antibakteriální látky * farmakokinetika   aplikace a dávkování   MeSH
• exsudáty a transsudáty metabolismus   mikrobiologie   MeSH
• infekce chirurgické rány * MeSH
• kardiochirurgické výkony * škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• sternotomie * škodlivé účinky   MeSH
• sternum chirurgie   MeSH
• terapie ran pomocí řízeného podtlaku * metody   MeSH
• vankomycin * aplikace a dávkování   farmakokinetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Community-acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large-scale, real-world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA-EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023-2024 autumn-winter season. The study assessed epidemiology, clinical characteristics, risk factors, and outcomes. The study examined 1312 patients with HM diagnosed with CARV during the 2023-2024 autumn-winter season. Of these, 59.5% required hospitalization, with 13.5% needing ICU admission. The overall mortality rate was 10.6%, varying by virus: parainfluenza (21.3%), influenza (8.8%), metapneumovirus (7.1%), RSV (5.9%), or SARS-CoV-2 (5.0%). Poor outcomes were significantly associated with smoking history, severe lymphopenia, secondary bacterial infections, and ICU admission. This study highlights the severe risk CARV poses to patients with HM, especially those undergoing active treatment. The high rates of hospitalization and mortality stress the need for better prevention, early diagnosis, and targeted therapies. Given the severe outcomes with certain viruses like parainfluenza, tailored strategies are crucial to improving patient outcomes in future CARV seasons.

• MeSH
• chřipka lidská epidemiologie   mortalita   komplikace   MeSH
• COVID-19 * epidemiologie   mortalita   komplikace   MeSH
• dospělí MeSH
• hematologické nádory * mortalita   epidemiologie   MeSH
• hospitalizace MeSH
• infekce dýchací soustavy * epidemiologie   virologie   MeSH
• infekce respiračními syncytiálními viry epidemiologie   mortalita   komplikace   MeSH
• infekce získané v komunitě epidemiologie   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Metapneumovirus izolace a purifikace   MeSH
• registrace MeSH
• rizikové faktory MeSH
• roční období * MeSH
• SARS-CoV-2 MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This review describes our experience with native tissue repair of the visceral pelvic fascia, the perineum, and anal sphincters in women. We propose that complex repair of the pelvic floor should consider vaginal support in all three anatomical Delancey's levels, together with more caudal structures-the external and internal anal sphincters. Original illustrations were created to facilitate the understanding of the complex anatomy of common multi-level defects. As the integrity of connective tissue adds to various aspects of the delicate function of the female pelvic floor, it is complete and as perfect as possible repair is a common goal of both gynecologists and colorectal specialists.

• MeSH
• anální kanál * chirurgie   MeSH
• fascie MeSH
• gynekologické chirurgické výkony * metody   MeSH
• lidé MeSH
• onemocnění dna pánevního * chirurgie   MeSH
• pánevní dno * chirurgie   MeSH
• perineum chirurgie   MeSH
• prolaps pánevních orgánů * chirurgie   MeSH
• vagina chirurgie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The distribution of time across physical activity, sedentary behaviors, and sleep appears to be essential for the management of obesity. However, the impact of reallocating time among these behaviors, collectively known as 24-h movement behaviors, remains underexplored. OBJECTIVE: This study examines the theoretical effects of reallocating time between 24-h movement behaviors on obesity indicators across different age groups. METHODS: We performed a pooled data meta-analysis of 9818 participants from 11 observational and experimental studies. To estimate the time spent in movement behaviors, we reprocessed and harmonized individual-level raw accelerometer-derived data. Isotemporal substitution models estimated theoretical changes in body mass index (BMI) and waist circumference (WC) associated with time reallocation between movement behaviors. We performed the analysis separately for children, adolescents, adults, and older adults. RESULTS: Even minor reallocations of 10 min led to significant changes in obesity indicators, with pronounced effects observed when 30 min were reallocated. The most substantial adverse effects on BMI and WC occurred when moderate-to-vigorous physical activity (MVPA) was reallocated to other movement behaviors. For 30-min reallocations, the largest increase in BMI (or BMI z-score for children) occurred when MVPA was reallocated to light-intensity physical activity (LPA) in children (0.26 units, 95% confidence interval [CI] 0.15, 0.37) and to sedentary behavior (SB) in adults (0.72 kg/m2, 95% CI 0.47, 0.96) and older adults (0.73 kg/m2, 95% CI 0.59, 0.87). The largest increase in WC was observed when MVPA was substituted with LPA in adults (2.66 cm, 95% CI 1.42, 3.90) and with SB in older adults (2.43 cm, 95% CI 2.07, 2.79). Conversely, the highest magnitude of the decrease in obesity indicators was observed when SB was substituted with MVPA. Specifically, substituting 30 min of SB with MVPA was associated with a decrease in BMI z-score by - 0.15 units (95% CI - 0.21, - 0.10) in children and lower BMI by - 0.56 kg/m2 (95% CI - 0.74, - 0.39) in adults and by - 0.52 kg/m2 (95% CI - 0.61, - 0.43) in older adults. Reallocating time away from sleep and LPA showed several significant changes but lacked a consistent pattern. While the predicted changes in obesity indicators were generally consistent across age groups, inconsistent findings were observed in adolescents, particularly for reallocations between MVPA and other behaviors. CONCLUSIONS: This investigation emphasizes the crucial role of MVPA in mitigating obesity risk across the lifespan, and the benefit of substituting SB with low-intensity movement behaviors. The distinct patterns observed in adolescents suggest a need for age-specific lifestyle interventions to effectively address obesity. Emphasizing manageable shifts, such as 10-min reallocations, could have significant public health implications, promoting sustainable lifestyle changes that accommodate individuals with diverse needs, including those with severe obesity.

• MeSH
• akcelerometrie MeSH
• časové faktory MeSH
• cvičení * MeSH
• dítě MeSH
• dospělí MeSH
• index tělesné hmotnosti MeSH
• léčba obezity * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• obezita * MeSH
• obvod pasu MeSH
• sedavý životní styl * MeSH
• senioři MeSH
• spánek MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

AIMS: Ossifying fibromyxoid tumour is a rare mesenchymal neoplasm predominantly affecting adults characterised by a multinodular growth pattern and the presence of a fibrous pseudocapsule with areas of ossification. Prompted by the recognition of a non-ossifying ossifying fibromyxoid tumour with lipomatous differentiation which caused diagnostic difficulty, we sought to further explore cases of ossifying fibromyxoid tumour with non-osseous heterologous elements. METHODS AND RESULTS: A search of our institutional and consultation archives revealed three additional cases that demonstrated lipomatous components and two cases with cartilaginous differentiation. RNA-sequencing revealed fusions involving PHF1 (n = 4) or EPC1 (n = 1) in all (five of five) cases tested, including EPC1::PHC1 and JAZF1::PHF1 fusions, which have not been reported before in ossifying fibromyxoid tumour. CONCLUSION: These six cases expand the histomorphological spectrum of ossifying fibromyxoid tumour, introducing lipomatous differentiation as a hitherto undocumented feature. Awareness of these rare variants will ensure appropriate diagnosis and clinical management.

• MeSH
• buněčná diferenciace MeSH
• chrupavka patologie   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipom * patologie   diagnóza   genetika   MeSH
• nádory měkkých tkání * patologie   diagnóza   genetika   MeSH
• osifikující kostní fibrom * patologie   diagnóza   genetika   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Microbiology reference laboratories perform a crucial role within public health systems. This role was especially evident during the COVID-19 pandemic. In this Viewpoint, we emphasise the importance of microbiology reference laboratories and highlight the types of digital data and expertise they provide, which benefit national and international public health. We also highlight the value of surveillance initiatives among collaborative international partners, who work together to share, analyse, and interpret data, and then disseminate their findings in a timely manner. Microbiology reference laboratories have substantial impact at regional, national, and international levels, and sustained support for these laboratories is essential for public health in both pandemic and non-pandemic times.

• MeSH
• COVID-19 * epidemiologie   MeSH
• infekční nemoci MeSH
• laboratoře * ekonomika   MeSH
• lidé MeSH
• mikrobiologie MeSH
• pandemie MeSH
• SARS-CoV-2 MeSH
• veřejné zdravotnictví MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: Missense de novo variants in CACNA1G, which encodes the Cav3.1 T-type calcium channel, have been associated with a severe, early-onset form of cerebellar disorder with neurodevelopmental deficits (SCA42ND). We explored a large series of pediatric cases carrying heterozygous variants in CACNA1G to further characterize genotype-phenotype correlations in SCA42ND. METHODS: We describe 19 patients with congenital CACNA1G-variants, including 6 new heterozygotes of the recurrent SCA42ND variants, p.(Ala961Thr) and p.(Met1531Val), and 8 unreported variants, including 7 missense variants, mainly de novo. We carried out genetic and structural analyses of all variants. Patch-clamp recordings were performed to measure their channel activity. RESULTS: We provide a consolidated clinical description for the patients carrying p.(Ala961Thr) and p.(Met1531Val). The new variants associated with the more severe phenotypes are found in the Cav3.1 channel intracellular gate. Calcium currents of these Cav3.1 variants showed slow inactivation and deactivation kinetics and an increase in window current, supporting a gain of channel activity. On the contrary, the p.(Met197Arg) variant (IS4-S5 loop) resulted in a loss of channel activity. CONCLUSION: This detailed description of several de novo missense pathogenic variants in CACNA1G, including 13 previously reported cases, supports a clinical spectrum of congenital CACNA1G syndrome beyond spinocerebellar ataxia.

• MeSH
• dítě MeSH
• fenotyp * MeSH
• genetické asociační studie MeSH
• heterozygot MeSH
• kojenec MeSH
• lidé MeSH
• missense mutace * genetika   MeSH
• mladiství MeSH
• neurovývojové poruchy * genetika   patologie   MeSH
• předškolní dítě MeSH
• vápníkové kanály - typ T * genetika   metabolismus   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Categorization systems for tick-borne encephalitis virus (TBEV) infection lack consistency in classifying disease severity. To evaluate the need for a standard, consensus-based categorisation system for TBEV infection across subtypes, we gathered an expert panel of clinicians and scientists with diverse expertise in TBEV infection. Consensus was sought using the Delphi technique, which consisted of 2 web-based survey questionnaires and a final, virtual, consensus-building exercise. Ten panellists representing 8 European countries participated in the Delphi exercise, with specialities in neurology, infectious disease, paediatrics, immunology, virology, and epidemiology. Panellists reached unanimous consensus on the need for a standardised, international categorisation system to capture both clinical presentation and severity of TBEV infection. Ideally, such a system should be feasible for use at bedside, be clear and easy to understand, and capture both the acute and follow-up phases of TBEV infection. Areas requiring further discussion were (1) the timepoints at which assessments should be made and (2) whether there should be a separate system for children. This Delphi panel study found that a critical gap persists in the absence of a feasible and practical classification system for TBEV infection. Specifically, the findings of our Delphi exercise highlight the need for the development of a user-friendly classification system that captures the acute and follow-up (i.e., outcome) phases of TBEV infection and optimally reflects both clinical presentation and severity. Development of a clinical categorisation system will enhance patient care and foster comparability among studies, thereby supporting treatment development, refining vaccine strategies, and fortifying public health surveillance.

• MeSH
• delfská metoda * MeSH
• klíšťová encefalitida * epidemiologie   virologie   diagnóza   MeSH
• konsensus MeSH
• lidé MeSH
• viry klíšťové encefalitidy * klasifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Despite increasing interest, prospective data on the use of degradable starch microsphere-transarterial chemoembolization (DSM-TACE) in the management of patients with unresectable HCC are still scarce. The objective of the HepaStar study was to collect prospective safety and effectiveness data in a prospective multicenter observational study. MATERIALS AND METHODS: Between January 2017 and December 2022, consecutive participants with unresectable or recurrent HCC treated with DSM-TACE as standard of care at 6 participating centers in Europe were enrolled. Tumor response was evaluated according to the mRECIST criteria. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were assessed by using Kaplan-Meier analysis and Common Terminology Criteria for Adverse Events, version 5. Liver function deterioration was assessed by monitoring changes in liver blood tests during the follow-up. RESULTS: Seventy-nine participants (median age, 69 years (IQR, 51-87 years); 67 men (85%)) were enrolled and treated. The median follow-up time was 18 months (IQR 9.5-38.0 months). The estimated median OS and PFS for the entire cohort was 32 months (CI, 95% 21-NaN) and 9 months (CI, 95% 7-NaN), respectively. Eleven (13.9%) participants experienced at least one grade 3 or 4 AE. The most frequent grade 3-4 AE was elevated bilirubin (2.2%, 5 of 79). Deterioration of bilirubin, AST, ALT, and albumin were observed in 24.1%, 23.7%, 19%, and 24% of participants, respectively. CONCLUSION: DSM-TACE achieves promising survival in patients with unresectable or recurrent HCC. This technique shows a favorable safety profile both in terms of treatment-related AEs and liver function deterioration. KEY POINTS: Question Although degradable starch microspheres transarterial chemoembolization is widely used in clinical practice across Europe, prospective data on its application in hepatocellular carcinoma patients remains limited. Findings Degradable starch microspheres transarterial chemoembolization results in promising survival rates, good tumor response rates, and low rates of treatment-related adverse events. Clinical relevance In patients with unresectable hepatocellular carcinoma, degradable starch microspheres transarterial chemoembolization represents a safe and effective alternative to more well-established chemoembolization techniques like conventional transarterial chemoembolization and drug-eluting beads transarterial chemoembolization.

• MeSH
• chemoembolizace * metody   MeSH
• hepatocelulární karcinom * terapie   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrosféry MeSH
• nádory jater * terapie   mortalita   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• škrob * aplikace a dávkování   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH