- MeSH
- chirurgická rána terapie MeSH
- dopravní nehody MeSH
- dospělí MeSH
- hojení ran * MeSH
- infekce v ráně terapie MeSH
- kongresy jako téma MeSH
- lidé MeSH
- terapie ran pomocí řízeného podtlaku * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- novinové články MeSH
- zprávy MeSH
- Klíčová slova
- atogepant,
- MeSH
- bolesti hlavy * farmakoterapie prevence a kontrola MeSH
- kongresy jako téma MeSH
- lidé MeSH
- migréna farmakoterapie prevence a kontrola MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
- zprávy MeSH
INTRODUCTION: Initial evidence suggests that engaging with accepting communities on social media such as Instagram may inform sexual minority youths' sense of stigma and well-being. However, as existing research has predominately drawn upon cross-sectional or qualitative designs, it is currently unclear whether the positive experiences identified in previous research accumulate, endure, or evolve over time. We also know relatively little about whether engagement with accepting online communities is primarily a compensatory or enhancing behavior. Thus, drawing upon minority stress theory and broaden-and-build theory, this study explores the longitudinal reciprocal relationships between perceived stigma, well-being, and engagement with accepting Instagram communities. METHOD: Three-wave panel data were collected from 460 sexual minority youth in the United States and Poland (M age = 18.58, SD = 1.64), and data were analyzed using a random intercept cross-lagged panel model. RESULTS: At the between-person level, engagement with accepting Instagram communities was positively associated with perceived stigma and negatively associated with well-being. No significant within-person associations emerged between perceived stigma and engagement with accepting Instagram networks. However, a positive reciprocal relationship was found between well-being and engagement with accepting Instagram communities. Cultural context had no moderating effect on the hypothesized model. CONCLUSIONS: Results suggest that whilst the interrelations between perceived stigma and engaging with accepting online networks may be short-lived, engaging with supportive Instagram communities may contribute to an upward spiral of positive emotions. Findings therefore extend the existing literature regarding the potential benefits of social media use amongst sexual minority youth.
- MeSH
- lidé MeSH
- longitudinální studie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- sexuální a genderové menšiny * psychologie MeSH
- sociální média * MeSH
- společenské stigma * MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Polsko MeSH
- Spojené státy americké MeSH
Metastases of the articular process, temporomandibular joint (TMJ), are rare findings. Their frequency is around 5% of patients with metastatic involvement of the mandible. The most common primary tumor is adenocarcinoma of the lung in women and adenocarcinoma of the prostate in men. The authors present 3 patients with TMJ metastasis. These were metastasis of breast adenocarcinoma, prostate adenocarcinoma, and lung adenocarcinoma. TMJ metastases are rare but complicated to diagnose because their presence may be accompanied by symptoms typical of other TMJ diseases (discopathy, arthritis, osteoarthritis). However, the authors recommend the unequivocal exclusion of a metastatic process in cases where the patient has a positive cancer history and their complaints do not respond to usual therapy.
- MeSH
- adenokarcinom * sekundární patologie MeSH
- diferenciální diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nádory mandibuly * sekundární MeSH
- nádory plic * patologie MeSH
- nádory prostaty * patologie MeSH
- nádory prsu * patologie MeSH
- nemoci temporomandibulárního kloubu MeSH
- počítačová rentgenová tomografie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
OBJECTIVE: The objective of this study is to evaluate whether adding oral glucocorticoids to immunosuppressive therapy improves skin scores and ensures safety in patients with early diffuse cutaneous systemic sclerosis (dcSSc). METHODS: We performed an emulated randomized trial comparing the changes from baseline to 12 ± 3 months of the modified Rodnan skin score (mRSS: primary outcome) in patients with early dcSSc receiving either oral glucocorticoids (≤20 mg/day prednisone equivalent) combined with immunosuppression (treated) or immunosuppression alone (controls), using data from the European Scleroderma Trials and Research Group. Secondary end points were the difference occurrence of progressive skin or lung fibrosis and scleroderma renal crisis. Matching propensity score was used to adjust for baseline imbalance between groups. RESULTS: We matched 208 patients (mean age 49 years; 33% male; 59% anti-Scl70), 104 in each treatment group, obtaining comparable characteristics at baseline. In the treated group, patients received a median prednisone dose of 5 mg/day. Mean mRSS change at 12 ± 3 months was similar in the two groups (decrease of 2.7 [95% confidence interval {95% CI} 1.4-4.0] in treated vs 3.1 [95% CI 1.9-4.4] in control, P = 0.64). Similar results were observed in patients with shorter disease duration (≤ 24 months) or with mRSS ≤22. There was no between-group difference for all prespecified secondary outcomes. A case of scleroderma renal crisis occurred in both groups. CONCLUSION: We did not find any significant benefit of adding low-dose oral glucocorticoids to immunosuppression for skin fibrosis, and at this dosage, glucocorticoid did not increase the risk of scleroderma renal crisis.
- MeSH
- aplikace orální MeSH
- databáze faktografické MeSH
- difuzní sklerodermie * farmakoterapie patologie diagnóza MeSH
- dospělí MeSH
- fibróza MeSH
- glukokortikoidy * aplikace a dávkování škodlivé účinky MeSH
- imunosupresiva * aplikace a dávkování škodlivé účinky MeSH
- kombinovaná farmakoterapie MeSH
- kůže * patologie účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- prednison * aplikace a dávkování škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND AND AIMS: Myocardial infarction (MI) in multivessel disease (MVD) and chronic total occlusion (CTO) is associated with high mortality. However, all-cause mortality of matched cohort without a CTO is unclear. Our aim was to analyse clinical characteristics, presenting symptoms, and survival of patients with MI in MVD and the possible impact of CTO on 1-year mortality. METHODS: All MI patients with MVD (two or three vessel disease) hospitalized in our center from January 2020 to September 2022 (1309 patients) were selected. We conducted a propensity score matching (PSM) analysis based on age, gender, type of MI, and compared patients with CTO (CTO group, n = 90) and without CTO (Control group, n = 90). RESULTS: We observed no difference in presenting clinical symptoms and initial heart rhythm between the groups. 1-year follow-up shows all-cause mortality rate of 23.3 % (n = 21) in the CTO group (Mean survival [MS] = 292.1 days, 95 % CI = 263.8 to 320.4) and 18.9 % (n = 17) in the Control group (MS = 310.2 days, 95 % CI = 285.3 to 335.2), p = 0.44. PCI alone was performed in 64.4 % (n = 58) in both groups, CABG in 18.8 % (n = 17) and 24.4 % (n = 22) (CTO vs. Control group respectively). Combination of PCI and CABG occurred in 8.8 % (n = 8) in both groups. Conservative treatment was chosen for 7 CTO and 2 Control group patients. CONCLUSION: We observed no 1-year mortality difference in patients with MI, MVD and a CTO compared to a matched cohort of patients with MI, MVD without CTO. Excellent 1-year survival was observed in patients treated by CABG, irrespective of CTO presence.
- MeSH
- chronická nemoc MeSH
- infarkt myokardu * mortalita diagnóza MeSH
- kohortové studie MeSH
- koronární angioplastika metody MeSH
- koronární okluze * diagnóza mortalita chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití trendy MeSH
- následné studie MeSH
- nemoci koronárních tepen mortalita diagnóza chirurgie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- tendenční skóre MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Neoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, providing new strategies for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannan-BAM, Toll-like receptor ligands, and anti-CD40 antibody (MBTA therapy) followed by surgery in murine models of MTT pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas. In the MTT pheochromocytoma model, it was found that neoadjuvant MBTA therapy followed by surgery could prevent the development of distant metastases in 100% of treated animals, compared to a 60% mortality rate in the control group due to metastatic disease after surgery. These outcomes were achieved even in tumors three times larger than those in the control group. In the aggressive 4T1 model, neoadjuvant MBTA therapy resulted in slower tumor progression and a significant prolongation of survival. In the B16-F10 and E0771.lmb models, neoadjuvant MBTA therapy also protected animals from metastases development and tumor recurrence upon rechallenge with tumor cells after surgery. Transcriptomic analysis revealed enhanced effector immune cell infiltration, cytotoxicity, and antigen presentation in retransplanted tumors from MBTA-treated mice, indicating robust immune memory. Notably, the exclusion of the anti-CD40 antibody from the neoadjuvant MBTA therapy (MBT therapy) yielded comparable outcomes in protection against metastases development. These findings advocate for further investigation of intratumoral neoadjuvant MBTA therapy for immunologically "cold" tumors, including those at high risk of metastases or recurrence.
- MeSH
- antigeny CD40 imunologie antagonisté a inhibitory MeSH
- imunoterapie * metody MeSH
- lokální recidiva nádoru * prevence a kontrola MeSH
- mannany farmakologie MeSH
- melanom experimentální * imunologie terapie patologie MeSH
- metastázy nádorů MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- neoadjuvantní terapie * metody MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The choroid plexus (ChP) is the secretory epithelial structure located in the brain ventricles. Choroid plexus tumors (CPTs) are rare neoplasms predominantly occurring in young patients with intensified malignancy in children. CPT treatment is hindered by insufficient knowledge of tumor pathology and the limited availability of valid models. METHODS: Genomic and transcriptomic data from CPT patients were analyzed to identify the putative pathological pathway. Cellular and molecular techniques were employed to validate bioinformatic results in CPT patient samples. Pharmacologic inhibition of Wnt/β-catenin signaling was assessed in CPT cells. Cell-based assays of ChP cell lines were performed following CRISPR-Cas9-derived knockout and overexpression of Wnt/β-catenin pathway genes. A 3D CPT model was generated through CRISPR-Cas9-derived knockout of APC. RESULTS: We discovered that Wnt/β-catenin signaling is activated in human CPTs, likely as a consequence of large-scale chromosomal instability events of the CPT genomes. We demonstrated that CPT-derived cells depend on autocrine Wnt/β-catenin signaling for survival. Constitutive Wnt/β-catenin pathway activation, either through knockout of the negative regulator APC or overexpression of the ligand WNT3A, induced tumorigenic properties in ChP 2D in vitro models. Increased activation of the Wnt/β-catenin pathway in ChP organoids, through treatment with a potent GSK3β inhibitor, reduced the differentiation of mature ChP epithelial cells. Remarkably, the depletion of APC was sufficient to induce the oncogenic transformation of ChP organoids. CONCLUSIONS: Our research identifies Wnt/β-catenin signaling as a critical driver of CPT tumorigenesis and provides the first 3D in vitro model for future pathological and therapeutic studies of CPT.
- MeSH
- beta-katenin metabolismus genetika MeSH
- karcinogeneze metabolismus MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- nádory plexus chorioideus * patologie metabolismus genetika MeSH
- plexus chorioideus metabolismus patologie MeSH
- proliferace buněk MeSH
- regulace genové exprese u nádorů MeSH
- signální dráha Wnt * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Protein synthesis (translation) consumes a substantial proportion of cellular resources, prompting specialized mechanisms to reduce translation under adverse conditions. Ribosome inactivation often involves ribosome-interacting proteins. In both bacteria and eukaryotes, various ribosome-interacting proteins facilitate ribosome dimerization or hibernation, and/or prevent ribosomal subunits from associating, enabling the organisms to adapt to stress. Despite extensive studies on bacteria and eukaryotes, understanding factor-mediated ribosome dimerization or anti-association in archaea remains elusive. Here, we present cryo-electron microscopy structures of an archaeal 30S dimer complexed with an archaeal ribosome dimerization factor (designated aRDF), from Pyrococcus furiosus, resolved at a resolution of 3.2 Å. The complex features two 30S subunits stabilized by aRDF homodimers in a unique head-to-body architecture, which differs from the disome architecture observed during hibernation in bacteria and eukaryotes. aRDF interacts directly with eS32 ribosomal protein, which is essential for subunit association. The binding mode of aRDF elucidates its anti-association properties, which prevent the assembly of archaeal 70S ribosomes.
- MeSH
- archeální proteiny * chemie metabolismus ultrastruktura MeSH
- dimerizace MeSH
- elektronová kryomikroskopie * MeSH
- malé podjednotky ribozomu archebakteriální chemie metabolismus MeSH
- molekulární modely MeSH
- multimerizace proteinu MeSH
- Pyrococcus furiosus * metabolismus MeSH
- ribozomální proteiny * chemie metabolismus MeSH
- ribozomy metabolismus ultrastruktura chemie MeSH
- vazba proteinů MeSH
- Publikační typ
- časopisecké články MeSH