This study explored how the human cortical folding pattern composed of convex gyri and concave sulci affected single-subject morphological brain networks, which are becoming an important method for studying the human brain connectome. We found that gyri-gyri networks exhibited higher morphological similarity, lower small-world parameters, and lower long-term test-retest reliability than sulci-sulci networks for cortical thickness- and gyrification index-based networks, while opposite patterns were observed for fractal dimension-based networks. Further behavioral association analysis revealed that gyri-gyri networks and connections between gyral and sulcal regions significantly explained inter-individual variance in Cognition and Motor domains for fractal dimension- and sulcal depth-based networks. Finally, the clinical application showed that only sulci-sulci networks exhibited morphological similarity reductions in major depressive disorder for cortical thickness-, fractal dimension-, and gyrification index-based networks. Taken together, these findings provide novel insights into the constraint of the cortical folding pattern to the network organization of the human brain.

• MeSH
• depresivní porucha unipolární patologie   diagnostické zobrazování   MeSH
• dospělí MeSH
• konektom * MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mladý dospělý MeSH
• mozková kůra * diagnostické zobrazování   anatomie a histologie   MeSH
• nervová síť * diagnostické zobrazování   anatomie a histologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské 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

INTRODUCTION: Upper limb (UL) impairment is common in people with multiple sclerosis (pwMS), and functional recovery of the UL is a key rehabilitation goal. Technology-based approaches, like virtual reality (VR), are increasingly promising. While most VR environments are task-oriented, our clinical approach integrates neuroproprioceptive 'facilitation and inhibition' (NFI) principles. To advance this, we developed immersive VR software based on NFI principles targeting UL function and sit-to-stand ability. This study aims to evaluate the effectiveness of this VR therapy compared with conventional NFI-based physical therapy in pwMS. Our study uniquely applies advanced imaging techniques, along with biological molecular assessments, to explore adaptive processes induced by VR rehabilitation. METHODS AND ANALYSIS: This double-arm, randomised, assessor-blinded, controlled trial runs over 2 months (1 hour, 2 times per week). PwMS with mild to severe disability will receive either VR therapy or real-world physical therapy. Primary outcomes include the nine-hole peg test, box and block test, handgrip strength, tremor and five times sit-to-stand test. Secondary measures include the Multiple Sclerosis Impact Scale, the 5-level EQ-5D questionnaire and kinematic analysis. Adaptive processes will be monitored using imaging techniques (functional MRI and tractography), molecular genetic methods (long non-coding RNAs) and immune system markers (leukocytes, dendritic cells). The International Classification of Functioning, Disability and Health brief set for MS will map the bio-psycho-social context of participants. ETHICS AND DISSEMINATION: This project and its amendments were approved by the Ethics Committee of the Institute for Clinical and Experimental Medicine and Thomayer Hospital (1983/21+4772/21 (G-21-02) and the Ethics Committee of Kralovske Vinohrady University Hospital (EK-VP/38/0/2021) in Prague, Czechia (with single enrolment). The findings of this project will be disseminated through scientific publications, conferences, professional networks, public engagement, educational materials and stakeholder briefings to ensure a broad impact across clinical, academic and public domains. TRIAL REGISTRATION NUMBER: clinicaltrials.gov (NCT04807738).

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• horní končetina * patofyziologie   MeSH
• kvalita života * MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• postura těla MeSH
• randomizované kontrolované studie jako téma MeSH
• roztroušená skleróza * diagnostické zobrazování   MeSH
• síla ruky MeSH
• techniky fyzikální terapie * MeSH
• terapie pomocí virtuální reality metody   MeSH
• virtuální realita MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

BACKGROUND: Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model. METHODS: We evaluated a cohort of patients with PZS (n = 9) for HNPGL by positron emission tomography, magnetic resonance imaging, and computed tomography and measured carotid body size compared to literature reference values. Resected tumors were evaluated by histologic sectioning and staining. We evaluated the corresponding mouse model at multiple developmental stages (P8 and adult) for lesions of the head and neck by high resolution ex vivo imaging and performed immunohistochemical staining on histologic sections of the identified lesions. RESULTS: hree patients had imaging consistent with HNPGL, one of which warranted resection and was confirmed on histology. Three additional patients had carotid body enlargement (Z-score > 2.0), and 3 had carotid artery malformations. We found that 9 of 10 adult variant mice had carotid body tumors and 6 of 8 had a paraganglioma on the cranio-caval vein, the murine homologue of the superior vena cava; these were also found in 4 of 5 variant mice at post-natal day 8. These tumors and the one resected from a patient were positive for tyrosine hydroxylase, synaptophysin, and chromogranin A. Brown fat in a resected patient tumor carried the EPAS1 pathogenic variant. CONCLUSIONS: These findings (1) suggest HNPGL as a feature of PZS and (2) show that these pathogenic variants are sufficient to cause the development of these tumors, which we believe represents a continuous spectrum of disease starting from hyperplasia.

• MeSH
• dospělí MeSH
• hyperplazie MeSH
• karotická tělíska * patologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mladý dospělý MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nádory hlavy a krku * genetika   patologie   diagnostické zobrazování   MeSH
• paragangliom * genetika   diagnostické zobrazování   patologie   MeSH
• počítačová rentgenová tomografie MeSH
• pozitronová emisní tomografie MeSH
• transkripční faktory bHLH * genetika   analýza   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Behavioral variant frontotemporal dementia (bvFTD) is characterized by profound and early deficits in social cognition (SC) and executive functions (EF). To date it remains unclear whether deficits of the respective cognitive domains are based on the degeneration of distinct brain regions. In 103 patients with a diagnosis of bvFTD (possible/probable/definite: N = 40/58/5) from the frontotemporal lobar degeneration (FTLD) consortium Germany cohort (age 62.5±9.4 years, gender 38 female/65 male) we applied multimodal structural imaging, i.e. voxel-based morphometry, cortical thickness (CTH) and networks of structural covariance via source based morphometry. We cross-sectionally investigated associations with performance in a modified Reading the Mind in the Eyes Test (RMET; reflective of theory of mind - ToM) and five different tests reflective of EF (i.e. Hamasch-Five-Point Test, semantic and phonemic Fluency, Trail Making Test, Stroop interference). Finally, we investigated the conjunction of RMET correlates with functional networks commonly associated with SC respectively ToM and EF as extracted meta-analytically within the Neurosynth database. RMET performance was mainly associated with gray matter volume (GMV) and CTH within temporal and insular cortical regions and less within the prefrontal cortex (PFC), whereas EF performance was mainly associated with prefrontal regions (GMV and CTH). Overlap of RMET and EF associations was primarily located within the insula, adjacent subcortical structures (i.e. putamen) and the dorsolateral PFC (dlPFC). These patterns were more pronounced after adjustment for the respective other cognitive domain. Corroborative results were obtained in analyses of structural covariance networks. Overlap of RMET with meta-analytically extracted functional networks commonly associated with SC, ToM and EF was again primarily located within the temporal and insular region and the dlPFC. In addition, on a meta-analytical level, strong associations were found for temporal cortical RMET correlates with SC and ToM in particular. These data indicate a temporo-frontal dissociation of bvFTD related disturbances of ToM and EF, with atrophy of the anterior temporal lobe being critically involved in ToM deficits. The consistent overlap within the insular cortex may be attributable to the multimodal and integrative role of this region in socioemotional and cognitive processing.

• MeSH
• exekutivní funkce * fyziologie   MeSH
• frontotemporální demence * patologie   diagnostické zobrazování   patofyziologie   psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• neuropsychologické testy * MeSH
• průřezové studie MeSH
• senioři MeSH
• sociální kognice MeSH
• teorie mysli * fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Quercetin is a promising phytochemical in treating abnormalities associated with metabolic syndrome (MetS). This study aimed to explore the morphometric, metabolic, transcriptomic, and nutrigenetic responses to quercetin supplementation using two genetically distinct MetS models that only differ in the variant of the MetS-related Zbtb16 gene (Zinc Finger And BTB Domain Containing 16). RESULTS: Quercetin supplementation led to a significant reduction in the relative weight of retroperitoneal adipose tissue in both investigated strains. A decrease in visceral (epididymal) fat mass, accompanied by an increase in brown fat mass after quercetin treatment, was observed exclusively in the SHR strain. While the levels of serum triglycerides decreased within both strains, the free fatty acids levels decreased in SHR-Zbtb16-Q rats only. The total serum cholesterol levels were not affected by quercetin in either of the two tested strains. While there were no significant changes in brown adipose tissue transcriptome, quercetin supplementation led to a pronounced gene expression shift in white retroperitoneal adipose tissue, particularly in SHR-Zbtb16-Q. CONCLUSION: Quercetin administration ameliorates certain MetS-related features; however, the efficacy of the treatment exhibits subtle variations depending on the specific variant of the Zbtb16 gene.

• Publikační typ
• časopisecké články MeSH

Quantitative maps of rotating frame relaxation (RFR) time constants are sensitive and useful magnetic resonance imaging tools with which to evaluate tissue integrity in vivo. However, to date, only moderate image resolutions of 1.6 x 1.6 x 3.6 mm3 have been used for whole-brain coverage RFR mapping in humans at 3 T. For more precise morphometrical examinations, higher spatial resolutions are desirable. Towards achieving the long-term goal of increasing the spatial resolution of RFR mapping without increasing scan times, we explore the use of the recently introduced Transform domain NOise Reduction with DIstribution Corrected principal component analysis (T-NORDIC) algorithm for thermal noise reduction. RFR acquisitions at 3 T were obtained from eight healthy participants (seven males and one female) aged 52 ± 20 years, including adiabatic T1ρ, T2ρ, and nonadiabatic Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n = 4 (RAFF4) with both 1.6 x 1.6 x 3.6 mm3 and 1.25 x 1.25 x 2 mm3 image resolutions. We compared RFR values and their confidence intervals (CIs) obtained from fitting the denoised versus nondenoised images, at both voxel and regional levels separately for each resolution and RFR metric. The comparison of metrics obtained from denoised versus nondenoised images was performed with a two-sample paired t-test and statistical significance was set at p less than 0.05 after Bonferroni correction for multiple comparisons. The use of T-NORDIC on the RFR images prior to the fitting procedure decreases the uncertainty of parameter estimation (lower CIs) at both spatial resolutions. The effect was particularly prominent at high-spatial resolution for RAFF4. Moreover, T-NORDIC did not degrade map quality, and it had minimal impact on the RFR values. Denoising RFR images with T-NORDIC improves parameter estimation while preserving the image quality and accuracy of all RFR maps, ultimately enabling high-resolution RFR mapping in scan times that are suitable for clinical settings.

• MeSH
• algoritmy MeSH
• analýza hlavních komponent MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mapování mozku MeSH
• mozek * diagnostické zobrazování   MeSH
• poměr signál - šum * MeSH
• rotace 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

INTRODUCTION: The ongoing conflict in Ukraine from Russian invasion presents a critical challenge to medical planning in the context of multi-domain battle against a peer adversary deploying conventional weapon systems. The potential escalation of preventable morbidity and mortality, reaching a scale unprecedented since World War II, underscores the paramount importance of effective phases of care from Point of Injury (PoI)/Point of Wounding (PoW) or Point of Exposure (PoE) to Role 1 (R1) and Role 2 (R2) echelons of care.The NATO Vigorous Warrior (VW) Live Exercise (LIVEX) serves as a strategic platform for NATO and its partners, providing an opportunity to challenge operational concepts, experiment, innovate life-saving systems, and foster best practices across the Alliance. MATERIALS AND METHODS: This study delineates the strategic application of the VW LIVEX platform for the adaptation of the computational simulation software Simulation for the Assessment and Optimization of Medical Disaster Management (SIMEDIS) within the context of Large-Scale Combat Operations (LSCO). The SIMEDIS computer simulator plays a pivotal role by furnishing real-time insights into the evolving injury patterns of patients, employing an all-hazards approach. This simulator facilitates the examination of temporal shifts in medical timelines and the ramifications of resource scarcity against both morbidity and mortality outcomes. The VW LIVEX provides a unique opportunity for systematic validation to evaluate the results of the computer simulator in a realistic setting and identify gaps for future concepts of operations. RESULTS: We report the process and methodologies to be evaluated at the VW LIVEX in far forward and retrospective medical support operations. Using the SIMEDIS simulator, we can define battlefield scenarios for varied situations including artillery, drone strikes, and Chemical, Biological, Radiological, Nuclear, and explosive (CBRNe) attacks. Casualty health progressions versus time are dependent on each threat. Mortality is computed based on the concepts found in Tactical Combat Casualty Care (TCCC) of "self-aid"/"buddy-aid" factoring in the application or absence of definitive traumatic hemorrhage control and on the distribution policy of victims to medical treatment facilities through appropriate Command and Control (C2) ("Scoop and Run" versus "Stay and Play"). The number of medical supplies available along with the number of transport resources and personnel are set and are scalable, with their effect on both morbidity and mortality quantified.Concept of Medical Operations can be optimized and interoperability enhanced when shared data are provided to C2 for prospective medical planning with retrospective data. The SIMEDIS simulator determines best practices of medical management for a myriad of injury types and tactical/operational situations relevant to policy making and battlefield medical planning for LSCO. CONCLUSIONS: The VW LIVEX provides a Concept Development and Experimentation platform for SIMEDIS refinement and conclusive insights into medical planning to reduce preventable morbidity and mortality. Recommending further iterations of similar methodologies at other NATO LIVEXs for validation is crucial, as is information sharing across the Alliance and partners to ensure best practice standards are met.

• MeSH
• lidé MeSH
• počítačová simulace * trendy   normy   statistika a číselné údaje   MeSH
• vedení války statistika a číselné údaje   MeSH
• vojenské lékařství metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Ukrajina MeSH

Juvenile hormone (JH) signaling is realized at the gene regulatory level by receptors of the bHLH-PAS transcription factor family. The sesquiterpenoid hormones and their synthetic mimics are agonist ligands of a unique JH receptor (JHR) protein, methoprene-tolerant (MET). Upon binding an agonist to its PAS-B cavity, MET dissociates from a cytoplasmic chaperone complex including HSP83 and concomitantly switches to a bHLH-PAS partner taiman, forming a nuclear, transcriptionally active JHR heterodimer. This course of events resembles the vertebrate aryl hydrocarbon receptor (AHR), activated by a plethora of endogenous and synthetic compounds. Like in AHR, the pliable PAS-B cavity of MET adjusts to diverse ligands and binds them through similar mechanisms. Despite recent progress, we only begin to discern agonist-induced conformational shifts within the PAS-B domain, with the ultimate goal of understanding how these localized changes stimulate the assembly of the active JHR complex and, thus, fully grasp the mechanism of JHR signaling.

• MeSH
• juvenilní hormony * metabolismus   MeSH
• signální transdukce MeSH
• transkripční faktory bHLH metabolismus   genetika   chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• Klíčová slova
• Mýtus jedné miliardy,
• MeSH
• alokace nákladů * metody   trendy   MeSH
• farmaceutický výzkum * MeSH
• lidé MeSH
• partnerství veřejného a soukromého sektoru trendy   MeSH
• veřejný sektor organizace a řízení   MeSH
• výdaje na zdravotnictví MeSH
• vyvíjení léků ekonomika   zákonodárství a právo   MeSH
• Check Tag
• lidé MeSH