INTRODUCTION: Currently, limited data are available on long-term use of dupilumab to treat atopic dermatitis (AD) in a multinational real-world setting. The aim of this analysis was to report the interim 1-year data for patients with AD enrolled in the GLOBOSTAD registry, including treatment patterns, dupilumab effectiveness and safety, and healthcare burden. METHODS: GLOBOSTAD is an ongoing, 5-year, multinational, prospective, observational study of adult/adolescent (aged ≥ 12 years at baseline) patients with AD who initiated dupilumab in real-world settings according to their local country-specific prescribing guidelines. Outcomes were evaluated at baseline and at 3, 6 and 12 months and included Eczema Area and Severity Index (EASI) total score, SCORing Atopic Dermatitis (SCORAD) total score, percent body surface area (BSA) affected, Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI) total score for adults or Children's Dermatology Life Quality Index (CDLQI) total score for adolescents and pruritus Numeric Rating Scale (NRS) total score. RESULTS: At the interim 1-year cut-off (March 2023), 955 patients were enrolled in GLOBOSTAD, and follow-up data were obtained from 903 patients. After dupilumab initiation, mean improvements in effectiveness outcome measures from baseline to month 3 were EASI from 25.1 to 6.1, SCORAD 59.3 to 25.3, POEM 19.7 to 8.7, DLQI 13.7 to 5.3, CDLQI 12.2 to 2.7 and pruritus NRS 6.3 to 2.5, with each measure exceeding the minimal clinically important difference. These positive changes in effectiveness outcomes were maintained or further improved through 12 months since treatment initiation. AD-related hospitalizations and emergency room or urgent care facility visits decreased from 11.1% to 1.7% from baseline to month 12. CONCLUSIONS: In a multinational real-world setting, dupilumab demonstrated rapid, robust and sustained effectiveness in patients with moderate-to-severe AD across multiple disease domains, including AD signs, symptoms, quality of life and emergency/urgent care visits. Safety was consistent with the known dupilumab safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03992417.

• MeSH
• atopická dermatitida * farmakoterapie   MeSH
• dítě MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• kvalita života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prospektivní studie MeSH
• registrace MeSH
• stupeň závažnosti nemoci * MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

PURPOSE: MRI-only adaptive brachytherapy (MRI-ABT) is the state-of-the-art for treating locally advanced cervical cancer (LACC) in combination with concurrent chemoradiotherapy. We aimed to evaluate the pattern of pelvic recurrence after the treatment. MATERIAL AND METHODS: A total of one hundred LACC patients were treated between January 2017 and December 2023 with concurrent chemoradiotherapy of 45 Gy in 25 fractions ± boost to lymphadenopathy (up to a maximum dose of 60 Gy in 25 fractions) with concurrent weekly cisplatin chemotherapy at the dose of 40 mg/m2/week, and MR-ABT. RESULTS: At a median follow-up of 30.2 months, there were 2 local recurrences (2%) and 9 regional pelvic recurrences (9%). The median time to local/regional recurrence was 11 months (range 6-21). For all stages, the 3-year local control was 97.66%, and the 3-year pelvic control was 89.45%. Twenty-four patients died during follow-up; the 3-year overall survival was 75.11%, and the 3-year disease-free survival was 70.97%. CONCLUSION: MRI-ABT combined with external beam radiotherapy and concurrent chemotherapy for LACC demonstrates excellent local and regional pelvic control. Most local/regional recurrences occur inside or at the edge of the external-beam irradiated field. Recurrences inside the field of brachytherapy are rare. Distant recurrences are the predominant cause of death in LACC patients treated with definitive CRT and MRI-ABT.

• MeSH
• brachyterapie * metody   MeSH
• chemoradioterapie * MeSH
• cisplatina terapeutické užití   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * radioterapie   MeSH
• magnetická rezonanční tomografie * MeSH
• nádory děložního čípku * radioterapie   diagnostické zobrazování   patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Sinonasal adenosquamous carcinoma (ASC) is a rare tumour classified as a variant of squamous cell carcinoma, exhibiting both squamous and glandular differentiation. ASC has a poorer prognosis compared to sinonasal mucoepidermoid carcinoma (MEC), another uncommon tumour in this region. ASC is believed to originate from metaplastic squamous epithelium, though it may also arise from respiratory epithelium in respiratory epithelial adenomatoid hamartoma (REAH) or seromucinous glands in seromucinous hamartoma (SH). METHODS AND RESULTS: Five cases of sinonasal ASC were retrieved from our registry. Initially, they were classified as sinonasal MEC (n = 3), ASC (n = 2), and carcinoma ex REAH (n = 1). All cases showed adenosquamous malignant proliferation beneath the surface respiratory epithelium with occasional squamous metaplasia, except for one case that showed dysplasia. The respiratory epithelium exhibited an inverted growth pattern consistent with REAH/SH, and displayed atypical sinonasal glands (ASGSH) arising within seromucinous hamartoma. Next-generation sequencing (NGS) revealed multiple pathogenic mutations in two cases, and in case 4 GGA2::PRKCB and EYA2::SERINC3 gene fusions. One case was positive for high-risk HPV. None of the cases exhibited CRTC1/3::MAML2 gene fusion. CONCLUSION: The connection between ASGSH and ASC has not been described in the literature. There is a growing need for additional studies on the morphological, immunohistochemical, and genetic aspects of these tumours. SH/REAH may serve as precursor lesions in the progression of atypical sinonasal glands to malignancy, and their role in tumour development deserves further investigation.

• MeSH
• adenoskvamózní karcinom * patologie   genetika   MeSH
• dospělí MeSH
• hamartom * patologie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory vedlejších dutin nosních patologie   genetika   MeSH
• respirační sliznice patologie   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

Glioblastomas are aggressive brain tumors for which effective therapy is still lacking, resulting in dismal survival rates. These tumors display significant phenotypic plasticity, harboring diverse cell populations ranging from tumor core cells to dispersed, highly invasive cells. Neuron navigator 3 (NAV3), a microtubule-associated protein affecting microtubule growth and dynamics, is downregulated in various cancers, including glioblastoma, and has thus been considered a tumor suppressor. In this study, we challenge this designation and unveil distinct expression patterns of NAV3 across different invasion phenotypes. Using glioblastoma cell lines and patient-derived glioma stem-like cell cultures, we disclose an upregulation of NAV3 in invading glioblastoma cells, contrasting with its lower expression in cells residing in tumor spheroid cores. Furthermore, we establish an association between low and high NAV3 expression and the amoeboid and mesenchymal invasive phenotype, respectively, and demonstrate that overexpression of NAV3 directly stimulates glioblastoma invasive behavior in both 2D and 3D environments. Consistently, we observed increased NAV3 expression in cells migrating along blood vessels in mouse xenografts. Overall, our results shed light on the role of NAV3 in glioblastoma invasion, providing insights into this lethal aspect of glioblastoma behavior.

• MeSH
• fenotyp * MeSH
• glioblastom * patologie   genetika   metabolismus   MeSH
• invazivní růst nádoru * genetika   MeSH
• lidé MeSH
• membránové proteiny MeSH
• mikrotubuly metabolismus   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory mozku * patologie   genetika   metabolismus   MeSH
• pohyb buněk genetika   fyziologie   MeSH
• proteiny nervové tkáně metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Starting point: Cervical dystonia is a common form of focal dystonia, resulting in neck pain and the development of asymmetric neck and head postures. These abnormal postures contribute to muscular impairment, muscle imbalances, and, as a result, alteration in movement patterns. This study aimed to compare the asymmetry of cervical muscle activation pattern during cervical flexion movements between individuals with cervical dystonia and healthy young subjects. Methods: Eight individuals with cervical dystonia and eight healthy participants participated in this study. We recorded muscle activation from five pairs of cervical muscles (sternocleidomastoid, scalene, trapezius, suprahyoid, and infrahyoid) using surface electromyography. Normalized cross-correlation was used to analyze the symmetry of bilateral muscle activation. Results: The results showed significant differences in muscle activation symmetry between the cervical dystonia group and healthy subjects. Notably, patients with cervical dystonia exhibited less symmetric activation in the trapezius and sternocleidomastoid muscles compared to healthy controls (p < 0.01 and p < 0.05, respectively). Additionally, the trapezius muscle on the dystonic side lacked coordination with other cervical muscles, unlike in healthy individuals who displayed better coordination. Conclusions: These findings underline the challenges faced by individuals with cervical dystonia in achieving symmetric activation and coordination of cervical muscles. Evaluating cervical muscle activation symmetry may be a valuable approach for assessing motor impairments in these patients.

BACKGROUND: The acromion projects laterally in a curving orientation. When a fracture of the acromion occurs, despite being rare, matching the best-fit fixation plate is challenging due to few options and limited availability of fixation plate types. Alternative fixation methods can carry risk of nonunion complications. PURPOSE: The objective of this study was to investigate the morphological curvature pattern of the acromion to assess the level of the fixation plates fitness and provide the suitable imaging modalities for evaluating the acromion curvature. BASIC PROCEDURES: The correlation between the acromion curvature and five fixation plates were calculated and their fitness level was evaluated statistically. The curvature of acromion and the five available fixation plates were photographed and assessed digitally by software (FIJI ImageJ and Microsoft Excel). The method entails plotting seven points along the curving surface and margins of the acromion, while the Excel Solver function calculates the regression, ultimately giving curvature values. First, the acromion parameters were studied on 180 paired healthy dry scapulae. Then, the acromion curvature values were compared to the fixation plates curvatures. Likewise, the acromion curvature was assessed as applicable on 153 (100 AP- views, 50 Y- views, and 3 superior-views) retrospective plain X-rays and 40 3D-CT scapula reconstructions of healthy acromia. MAIN FINDINGS: The mean length of the acromion was 48.70 ± 5.29 mm, mean thickness was 8.51 ± 1.67 mm, and mean width was 25.97 ± 5.97 mm. The calculated values of the mean curvatures were 0.050 ± 0.015 mm-1 for the mean acromion surface, 0.042 ± 0.027 mm-1 for the internal margin, and 0.055 ± 0.010 mm-1 for the external margin. The curved geometry of the acromion was plotted on a graph giving a spectrum of curvature patterns with distribution values revealing fixation plates fitness represented by area under the curve with frequencies of 4.32 % for the acromion-specific fixation plate, 14.28 % for the large clavicle fixation plate, 0.26 % for the small clavicle fixation plate, 53.38 % for the flexible universal fixation plate, and none for the rigid universal fixation plate. PRINCIPAL CONCLUSIONS: Approximately 27.76 % of the acromion surface curvatures distribution does not overlap with any of our measured fixation plates. Evaluating the acromion surface curvature was possible on plain X-rays in the Y-view only.

• MeSH
• akromion * diagnostické zobrazování   zranění   anatomie a histologie   chirurgie   MeSH
• fraktury kostí * chirurgie   diagnostické zobrazování   MeSH
• kostní destičky * MeSH
• lidé MeSH
• lopatka * diagnostické zobrazování   anatomie a histologie   MeSH
• radiografie MeSH
• vnitřní fixace fraktury * metody   přístrojové vybavení   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: This study analyzed the kinematics and muscle activity during the stand-up paddleboarding (SUP) under different visual focus points in three conditions: i) eyes on the board nose, ii) looking at the turn buoy, and iii) free choice. METHODS: Fourteen male paddleboarders (24.2 ± 7.1 years) performed three trials covering 65 m, and the electromyographic (EMG) activation patterns and kinematic parameters in four cycle strokes for the left and right sides were analyzed. Surface EMG of the upper trapezius, biceps brachii, triceps brachii, tibialis anterior, and gastrocnemius medialis were recorded. The data were processed according to the percentage of maximum voluntary contraction (%MVC). Speed, stroke frequency (SF), stroke length, and stroke index (SI) were analyzed. RESULTS: The speed, SF, and SI (p < 0.01, η2 ≥ 0.42) showed significant variance between conditions, with the free condition achieving the highest speed (1.20 ± 0.21 m/s), SF (0.65 ± 0.13 Hz) and SI (2.25 ± 0.67 m2/s). This condition showed greater neuromuscular activity, particularly in the triceps brachii during both the left (42.25 ± 18.76 %MVC) and right recoveries (32.93 ± 16.06 %MVC). During the pull phase, the free choice presented higher biceps brachii activity (8.51 ± 2.80 %MVC) compared to the eyes on the board nose (6.22 ± 2.41 %MVC; p < 0.01), while showing lower activity in the triceps brachii (10.02 ± 4.50 %MVC vs. 16.52 ± 8.45 %MVC; p < 0.01) and tibialis anterior (12.24 ± 7.70 %MVC vs. 17.09 ± 7.73 %MVC; p < 0.01) compared to looking at the turn buoy. CONCLUSION: These results suggest that a free visual focus allows paddleboarders to enhance their kinematics and muscle activation, highlighting the significance of visual focus strategies in improving both competitive and recreational SUP performance.

• MeSH
• biomechanika MeSH
• dospělí MeSH
• elektromyografie MeSH
• kosterní svaly * fyziologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• svalová kontrakce fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The clinical diversity of schizophrenia is reflected by structural brain variability. It remains unclear how this variability manifests across different gray and white matter features. In this meta- and mega-analysis, the authors investigated how brain heterogeneity in schizophrenia is distributed across multimodal structural indicators. METHODS: The authors used the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6,037 individuals for a given brain measure. Variability and mean values of cortical thickness, cortical surface area, cortical folding index, subcortical volume, and fractional anisotropy were examined in individuals with schizophrenia and healthy control subjects. RESULTS: Individuals with schizophrenia showed greater variability in cortical thickness, cortical surface area, subcortical volume, and fractional anisotropy within the frontotemporal and subcortical network. This increased structural variability was mainly associated with psychopathological symptom domains, and the schizophrenia group frequently displayed lower mean values in the respective structural measures. Unexpectedly, folding patterns were more uniform in individuals with schizophrenia, particularly in the right caudal anterior cingulate region. The mean folding values of the right caudal anterior cingulate region did not differ between the schizophrenia and healthy control groups, and folding patterns in this region were not associated with disease-related parameters. CONCLUSIONS: In patients with schizophrenia, uniform folding patterns in the right caudal anterior cingulate region contrasted with the multimodal variability in the frontotemporal and subcortical network. While variability in the frontotemporal and subcortical network was associated with disease-related diversity, uniform folding may indicate a less flexible interplay between genetic and environmental factors during neurodevelopment.

• MeSH
• anizotropie MeSH
• bílá hmota patologie   diagnostické zobrazování   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek * patologie   diagnostické zobrazování   MeSH
• schizofrenie * patologie   diagnostické zobrazování   MeSH
• šedá hmota patologie   diagnostické zobrazování   MeSH
• zobrazování difuzních tenzorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

Perflorochemicals (PFCs), among which are the most commonly detected perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), are persistent emergent contaminants of concern in recent times. These compounds have been reported for their cytotoxicity, genotoxicity, carcinogenicity, immunotoxicity, and developmental toxicities. Meanwhile, they have been detected in diverse matrices such as soil, sediment, and, surprisingly, in serum and even breastmilk. Worrisomely, these compounds are detected in drinking water across the globe, aquaculture water, and other surface waters. Thus, it was important to appraise the studies conducted on PFOS and PFOA to provide an overview of the environmental status of contamination regarding them. The present review article sought to provide insights into the occurrence patterns and ecotoxic effects of both pollutants in the water ecosystems within five continents of the world. Based on the information gathered in this article, the ∑PFOS concentration (ng/L) within the five continents is in the order Europe > Asia > Africa > North America > South America, while the ∑PFOA level (ng/L) is in the order Europe > Asia > South America > Africa > North America. The study also investigated the previous works that have been conducted regarding the diverse elimination technologies employed for the removal of these pollutants from the aqueous environments, with plasma combined with surfactant process being the most efficient. Generally, studies on PFOS/PFOA are still scanty when compared to those on pharmaceuticals and personal care products (PPCPs), especially in North America. The information gathered in this study could be useful in establishing thresholds of PFOA and PFOS environmental levels and be adopted by appropriate authorities as safety guidelines.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The RNA chaperone Hfq plays crucial roles in bacterial gene expression and is a major facilitator of small regulatory RNA (sRNA) action. The toroidal architecture of the Hfq hexamer presents three well-characterized surfaces that allow it to bind sRNAs to stabilize them and engage target transcripts. Hfq-interacting sRNAs are categorized into two classes based on the surfaces they use to bind Hfq. By characterizing a systematic alanine mutant library of Hfq to identify amino acid residues that impact survival of Escherichia coli experiencing nitrogen (N) starvation, we corroborated the important role of the three RNA-binding surfaces for Hfq function. We uncovered two, previously uncharacterized, conserved residues, V22 and G34, in the hydrophobic core of Hfq, to have a profound impact on Hfq's RNA-binding activity in vivo. Transcriptome-scale analysis revealed that V22A and G34A Hfq mutants cause widespread destabilization of both sRNA classes, to the same extent as seen in bacteria devoid of Hfq. However, the alanine substitutions at these residues resulted in only modest alteration in stability and structure of Hfq. We propose that V22 and G34 have impact on Hfq function, especially critical under cellular conditions when there is an increased demand for Hfq, such as N starvation.

• MeSH
• bakteriální RNA * metabolismus   genetika   chemie   MeSH
• dusík metabolismus   MeSH
• Escherichia coli * genetika   metabolismus   MeSH
• hydrofobní a hydrofilní interakce * MeSH
• konzervovaná sekvence MeSH
• malá nekódující RNA * metabolismus   genetika   chemie   MeSH
• mutace MeSH
• protein hostitelského faktoru 1 * metabolismus   genetika   chemie   MeSH
• proteiny z Escherichia coli * metabolismus   genetika   chemie   MeSH
• regulace genové exprese u bakterií MeSH
• stabilita RNA * genetika   MeSH
• stanovení celkové genové exprese MeSH
• transkriptom genetika   MeSH
• vazba proteinů MeSH
• Publikační typ
• časopisecké články MeSH