Goal: This study aims to discover the interest of foster parents in cooperating with the school social workers in elementary schools to support the children's school success during foster care. Methods: The quantitative survey was based on a non-standardised questionnaire validated for comprehensibility and relevance by professionals in non-profit organisations who conducted a pilot survey with cooperating foster parents. The research group was created by purposive sampling (n = 102). Descriptive statistics and exploratory analysis methods were used to evaluate the obtained data. Results: Foster parents are provided with expert advice by a non-profit organisation supporting foster families in social services, child rearing, education, and health. In schools, they use the entire spectrum of consulting services of pedagogical staff. They are somewhat satisfied with the support services provided, but show an interest in working with the school social worker to support the children's school success, health, and well-being. Conclusion: The need to institutionalise the profession of a school social worker in a Czech primary school appears to be a desirable prospective support of a child's school success and healthy growth, and a necessary help for parents regarding health and social counselling and services, especially when dealing with challenging life situations associated with school attendance. The social worker's global role has already been institutionalised in many countries around the world.
BACKGROUND: Heterogeneity in temperature-mortality relationships across locations may partly result from differences in the demographic structure of populations and their cause-specific vulnerabilities. Here we conduct the largest epidemiological study to date on the association between ambient temperature and mortality by age and cause using data from 532 cities in 33 countries. METHODS: We collected daily temperature and mortality data from each country. Mortality data was provided as daily death counts within age groups from all, cardiovascular, respiratory, or noncardiorespiratory causes. We first fit quasi-Poisson regression models to estimate location-specific associations for each age-by-cause group. For each cause, we then pooled location-specific results in a dose-response multivariate meta-regression model that enabled us to estimate overall temperature-mortality curves at any age. The age analysis was limited to adults. RESULTS: We observed high temperature effects on mortality from both cardiovascular and respiratory causes compared to noncardiorespiratory causes, with the highest cold-related risks from cardiovascular causes and the highest heat-related risks from respiratory causes. Risks generally increased with age, a pattern most consistent for cold and for nonrespiratory causes. For every cause group, risks at both temperature extremes were strongest at the oldest age (age 85 years). Excess mortality fractions were highest for cold at the oldest ages. CONCLUSIONS: There is a differential pattern of risk associated with heat and cold by cause and age; cardiorespiratory causes show stronger effects than noncardiorespiratory causes, and older adults have higher risks than younger adults.
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: The pathophysiology of haemophilic arthropathy (HA) is complex and largely undefined. Proteomic analyses provide insights into the intricate mechanisms of the HA.Our study aimed to identify differentially expressed proteins in relation to the severity of HA, explore their pathophysiological roles, and evaluate their potential as HA biomarkers. METHODS: Our cross-sectional observational study encompassed 30 HA patients and 15 healthy subjects. Plasma samples were pooled into three groups of 15 samples from those with severe haemophilic arthropathy (sHA), mild haemophilic arthropathy (mHA) and healthy controls. Proteomic analysis was performed using liquid chromatography-mass spectrometry. The severity of HA was assessed using the World Federation of Haemophilia Physical Examination Score and ultrasonography following the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) guidelines. RESULTS: A total of 788 proteins were identified, with 97% of the uniquely identified proteins being expressed in all analysed groups. We identified several up and downregulated proteins across the groups that were mainly related to inflammatory and immunity-modulating processes, as well as joint degeneration. We highlighted ten proteins relevant for the development of HA: cathepsin G, endoplasmic reticulum aminopeptidase 2, S100-A9, insulin-like growth factor I, apolipoprotein (a), osteopontin, pregnancy zone protein, cartilage oligomeric matrix protein, CD44, and cadherin-related family member 2. CONCLUSION: Our analysis identified several proteins that shed further light on the distinctive pathogenesis of HA and could serve for biomarker research. However, these results need to be validated on a larger patient group.
- Publikační typ
- časopisecké články MeSH
Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5-15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5-97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.
- MeSH
- autoprotilátky * imunologie MeSH
- dospělí MeSH
- interferon typ I * imunologie MeSH
- klíšťová encefalitida * imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- neutralizující protilátky * imunologie MeSH
- senioři MeSH
- viry klíšťové encefalitidy imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Rakousko MeSH
We explored how a simple retrovirus, Mason-Pfizer monkey virus (M-PMV) to facilitate its replication process, utilizes DHX15, a cellular RNA helicase, typically engaged in RNA processing. Through advanced genetic engineering techniques, we showed that M-PMV recruits DHX15 by mimicking cellular mechanisms, relocating it from the nucleus to the cytoplasm to aid in viral assembly. This interaction is essential for the correct packaging of the viral genome and critical for its infectivity. Our findings offer unique insights into the mechanisms of viral manipulation of host cellular processes, highlighting a sophisticated strategy that viruses employ to leverage cellular machinery for their replication. This study adds valuable knowledge to the understanding of viral-host interactions but also suggests a common evolutionary history between cellular processes and viral mechanisms. This finding opens a unique perspective on the export mechanism of intron-retaining mRNAs in the packaging of viral genetic information and potentially develop ways to stop it.
- MeSH
- buněčné jádro metabolismus virologie MeSH
- DEAD-box RNA-helikasy metabolismus genetika MeSH
- genom virový MeSH
- HEK293 buňky MeSH
- lidé MeSH
- Masonův-Pfizerův opičí virus * genetika metabolismus fyziologie MeSH
- replikace viru genetika fyziologie MeSH
- RNA virová * metabolismus genetika MeSH
- RNA-helikasy metabolismus genetika MeSH
- sestavení viru * genetika fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: To evaluate biopsy-related complications and detection rates of any PCa and clinically significant PCa (csPCa, intended as grade group ≥ 2) between MRI-targeted TP fusion biopsies (TPBx) and TR ones (TRBx). METHODS: We performed a multicentric study on 4841 patients who underwent fusion biopsy between 2016 and 2023. A case-control matching was performed to find comparable cohorts of 646 TPBx and 646 TRBx. Mean T test and Pearson chi-square tests were used to compare continuous and categorical variables. RESULTS: Baseline characteristics were comparable between the cohorts, except for target location with a higher rate of anterior lesions in TPBx group. Complications were rare and no difference was found between the groups, with similar rates of infections after TRBx and TPBx (N = 5 (0.8%) vs N = 2 (0.3%), p 0.45). All patients in TRBx and 90.1% in TPBx group received antibiotic prophylaxis. A higher csPCa detection rate was found in TPBx over the group (50.5% vs 36.2%, p < 0.001). On average, positive targeted cores were increased in TPBx group, for any PCa (1.6 vs 1.4, p 0.04) and csPCa (1.0 vs 0.8, p 0.02). Among the limitations of study, we acknowledge the retrospective design and the possible under-reporting of complications. CONCLUSIONS: MRI-targeted fusion TPBx achieves a significantly higher csPCa detection than TRBx, with a diagnostic advantage for apical and anterior lesions. No significant differences were found in terms of complications that were rare in both groups, considering a widespread adoption of antibiotic prophylaxis.
- MeSH
- analýza párové shody MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nádory prostaty * patologie MeSH
- perineum MeSH
- pooperační komplikace epidemiologie MeSH
- prostata * patologie MeSH
- rektum MeSH
- reprodukovatelnost výsledků MeSH
- retrospektivní studie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- ultrazvukem navigovaná biopsie * metody škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- srovnávací studie MeSH
PURPOSE: Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous (SC) compared to intravenous (IV) IFX. However, it is unknown whether re-exposure to IFX SC after secondary loss of response and immunogenicity to its intravenous formulation is safe and effective. METHODS: In a retrospective cohort study conducted at two medical centers, patients with clinically (Harvey-Bradshaw Index ≥ 5) and/or biochemically (fecal calprotectin > 250 μg/g) active Crohn's disease (CD) and previous immunogenic failure of IFX IV underwent exposure to IFX SC. Harvey-Bradshaw Index, fecal calprotectin, IFX serum concentration, and anti-drug antibodies were assessed until month 12. RESULTS: Twenty CD patients were included. The majority of patients (90%) had previous treatment with three or more biologics. Fifteen (75%) and ten (50%) of 20 patients continued IFX SC treatment until months 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients discontinued IFX SC treatment because of delayed hypersensitivity at week 2 and week 4. IFX serum concentrations increased from baseline to month 12, while anti-drug antibody levels decreased. Combined clinical and biochemical remission at month 12 was observed in seven of 20 patients (35%). CONCLUSION: Subcutaneous infliximab treatment of Crohn's disease patients with previous immunogenic failure of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn's disease.
- MeSH
- Crohnova nemoc * farmakoterapie imunologie MeSH
- dospělí MeSH
- feces chemie MeSH
- infliximab * terapeutické užití imunologie aplikace a dávkování MeSH
- injekce subkutánní MeSH
- intravenózní podání MeSH
- leukocytární L1-antigenní komplex analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- retrospektivní studie MeSH
- terapie neúspěšná 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
AIMS: In a recent meta-analysis of randomized controlled trials, routine use of veno-arterial ECMO (VA-ECMO) did not improve outcomes in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS), while a microaxial flow pump reduced mortality in a selected group of patients with AMI-CS in the DanGer-Shock trial. METHODS AND RESULTS: Individual patient data of patients included in four randomized clinical trials investigating the routine use of VA-ECMO in AMI-CS were centrally analysed. For the purpose of this sub-analysis, DanGer-Shock-like patients were analysed (STEMI only, presumed low likelihood of brain injury). The primary endpoint was 180-day all-cause mortality. A total of 202 patients (106 randomized to VA-ECMO and 96 to control) were included. There were no differences in baseline characteristics, angiographic and interventional features between the two groups. Mortality after 6 months was numerically lower with VA-ECMO between the groups [45% in VA-ECMO group vs. 51% in control group; hazard ratio, 0.84; 95% confidence interval (CI), 0.56-1.26], while major bleeding (OR, 2.24; 95% CI, 1.08-4.64) and peripheral vascular complications (OR, 3.65; 95% CI, 1.15-11.56) were increased with the use of VA-ECMO. CONCLUSION: In this exploratory subgroup analysis in patients with CS, STEMI, and a low likelihood of brain injury, there was no mortality benefit with the routine use of VA-ECMO. However, as indicated by the large confidence intervals, the statistical power was limited to draw definite conclusions.
- MeSH
- infarkt myokardu * komplikace terapie mortalita MeSH
- kardiogenní šok * terapie mortalita etiologie MeSH
- lidé MeSH
- mimotělní membránová oxygenace * metody MeSH
- randomizované kontrolované studie jako téma MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Progress in cytokine engineering is driving therapeutic translation by overcoming these proteins' limitations as drugs. The IL-2 cytokine is a promising immune stimulant for cancer treatment but is limited by its concurrent activation of both pro-inflammatory immune effector cells and antiinflammatory regulatory T cells, toxicity at high doses, and short serum half-life. One approach to improve the selectivity, safety, and longevity of IL-2 is complexing with anti-IL-2 antibodies that bias the cytokine toward immune effector cell activation. Although this strategy shows potential in preclinical models, clinical translation of a cytokine/antibody complex is complicated by challenges in formulating a multiprotein drug and concerns regarding complex stability. Here, we introduced a versatile approach to designing intramolecularly assembled single-agent fusion proteins (immunocytokines, ICs) comprising IL-2 and a biasing anti-IL-2 antibody that directs the cytokine toward immune effector cells. We optimized IC construction and engineered the cytokine/antibody affinity to improve immune bias. We demonstrated that our IC preferentially activates and expands immune effector cells, leading to superior antitumor activity compared with natural IL-2, both alone and combined with immune checkpoint inhibitors. Moreover, therapeutic efficacy was observed without inducing toxicity. This work presents a roadmap for the design and translation of cytokine/antibody fusion proteins.
- MeSH
- cytokiny metabolismus MeSH
- interleukin-2 * imunologie MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory imunologie terapie farmakoterapie MeSH
- proteinové inženýrství metody MeSH
- regulační T-lymfocyty imunologie účinky léků MeSH
- rekombinantní fúzní proteiny * farmakologie imunologie aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
