INTRODUCTION: A variable proportion of non-responders to cardiac resynchronization therapy (CRT) warrants the search for new approaches to optimize the position of the left ventricular (LV) lead and the CRT device programming. CineECG is a novel ECG modality proposed for the spatial visualization and quantification of myocardial depolarization and repolarization sequences. OBJECTIVE: The present study aimed to evaluate CineECG-derived parameters in different pacing modes and to test their associations with acute hemodynamic responses in CRT patients. METHODS AND RESULTS: CineECG was used to construct the average electrical path within the cardiac anatomy from the 12-lead ECG. CineECG and LV dP/dt max were tested in 15 patients with nonischemic dilated cardiomyopathy and left bundle branch block (QRS: 170 ± 17 ms; LVEF: 26 ± 5.5%) under pacing protocols with different LV lead localizations. The CineECG-derived path directions were computed for the QRS and ST-T intervals for the anteroposterior (Xh), interventricular (Yh), and apicobasal (Zh) axes. In a multivariate linear regression analysis with adjustment for the pacing protocol type, the ST-T path direction Yh was independently associated with the increase in dP/dt max during CRT, [regression coefficient 639.4 (95% confidence interval: 187.9-1090.9), p = 0.006]. In ROC curve analysis, the ST-T path direction Yh was associated with the achievement of a 10% increase in dP/dt max (AUC: 0.779, p = 0.002) with the optimal cut-off > 0.084 (left-to-right direction) with sensitivity 0.67 and specificity 0.92. CONCLUSION: The acute hemodynamic response in CRT patients was associated with specific CineECG repolarization sequence parameters, warranting their further testing as potential predictors of clinical outcomes.

• MeSH
• akční potenciály MeSH
• blokáda Tawarova raménka * patofyziologie   terapie   diagnóza   MeSH
• časové faktory MeSH
• dilatační kardiomyopatie patofyziologie   terapie   diagnóza   MeSH
• elektrokardiografie * MeSH
• funkce levé komory srdeční * MeSH
• hemodynamika * MeSH
• lidé středního věku MeSH
• lidé MeSH
• prediktivní hodnota testů * MeSH
• prostředky srdeční resynchronizační terapie MeSH
• senioři MeSH
• srdeční frekvence MeSH
• srdeční resynchronizační terapie * MeSH
• srdeční selhání patofyziologie   terapie   diagnóza   MeSH
• tepový objem MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

G protein-coupled receptors (GPCRs) play a crucial role in cell function by transducing signals from the extracellular environment to the inside of the cell. They mediate the effects of various stimuli, including hormones, neurotransmitters, ions, photons, food tastants and odorants, and are renowned drug targets. Advancements in structural biology techniques, including X-ray crystallography and cryo-electron microscopy (cryo-EM), have driven the elucidation of an increasing number of GPCR structures. These structures reveal novel features that shed light on receptor activation, dimerization and oligomerization, dichotomy between orthosteric and allosteric modulation, and the intricate interactions underlying signal transduction, providing insights into diverse ligand-binding modes and signalling pathways. However, a substantial portion of the GPCR repertoire and their activation states remain structurally unexplored. Future efforts should prioritize capturing the full structural diversity of GPCRs across multiple dimensions. To do so, the integration of structural biology with biophysical and computational techniques will be essential. We describe in this review the progress of nuclear magnetic resonance (NMR) to examine GPCR plasticity and conformational dynamics, of atomic force microscopy (AFM) to explore the spatial-temporal dynamics and kinetic aspects of GPCRs, and the recent breakthroughs in artificial intelligence for protein structure prediction to characterize the structures of the entire GPCRome. In summary, the journey through GPCR structural biology provided in this review illustrates how far we have come in decoding these essential proteins architecture and function. Looking ahead, integrating cutting-edge biophysics and computational tools offers a path to navigating the GPCR structural landscape, ultimately advancing GPCR-based applications. LINKED ARTICLES: This article is part of a themed issue Complexity of GPCR Modulation and Signaling (ERNST). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.14/issuetoc.

• MeSH
• konformace proteinů MeSH
• lidé MeSH
• receptory spřažené s G-proteiny * chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The disease currently known as frontotemporal dementia (FTD) has undergone a complex evolution from its first description by Arnold Pick and later by Alois Alzheimer, through the first clinicopathological criteria introduced by David Neary and David Mann, to its current nomenclatural perception as a complex clinicopathological entity. Currently, Frontotemporal lobar degeneration is viewed as a heterogeneous syndrome caused by progressive degeneration of the frontal and temporal lobes of the brain. Clinically, it can manifest as three syndromes of frontotemporal dementia (behavioral variant of FTD, progressive non-fluent aphasia and semantic dementia) but also as so-called "overlap" syndromes involving corticobasal degeneration and progressive supranuclear palsy. Its prevalence is about 10 % among all dementias and 40 % among dementias with onset between 45 and 65 years of age. The clinical manifestation of the different subtypes varies, the common denominator being behavioral disturbances and impairment of fatic, gnostic and executive functions. Mnestic and visuo-spatial functions, although preserved for a relatively long time, are superimposed by personality disintegration, fatic, gnostic and executive dysfunction. Compared with Alzheimer's disease, it generally has an earlier age of onset, a more rapid course and more devastating impairment of individual cognitive domains. FTD has a heritability of more than 30 % according to current knowledge. The main genes involved are MAPT, C9orf72 and GRN. More rarely affected genes are VCP, TDP-43, FUS and CHMP2B. In our article, we focus on the genetics of FTD and the clinic-genetic-pathological correlations. We also aim to provide a plastic picture of how individual mutations affect the molecular mechanisms of neurodegeneration.

• MeSH
• epigeneze genetická genetika   MeSH
• frontotemporální demence * diagnóza   genetika   klasifikace   MeSH
• genetické testování metody   MeSH
• lidé MeSH
• primární progresivní nonfluentní afázie diagnóza   genetika   MeSH
• progranuliny genetika   MeSH
• proteiny tau genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Space and time are fundamental attributes of the external world. Deciphering the brain mechanisms involved in processing the surrounding environment is one of the main challenges in neuroscience. This is particularly defiant when situations change rapidly over time because of the intertwining of spatial and temporal information. However, understanding the cognitive processes that allow coping with dynamic environments is critical, as the nervous system evolved in them due to the pressure for survival. Recent experiments have revealed a new cognitive mechanism called time compaction. According to it, a dynamic situation is represented internally by a static map of the future interactions between the perceived elements (including the subject itself). The salience of predicted interactions (e.g. collisions) over other spatiotemporal and dynamic attributes during the processing of time-changing situations has been shown in humans, rats, and bats. Motivated by this ubiquity, we study an artificial neural network to explore its minimal conditions necessary to represent a dynamic stimulus through the future interactions present in it. We show that, under general and simple conditions, the neural activity linked to the predicted interactions emerges to encode the perceived dynamic stimulus. Our results show that this encoding improves learning, memorization and decision making when dealing with stimuli with impending interactions compared to no-interaction stimuli. These findings are in agreement with theoretical and experimental results that have supported time compaction as a novel and ubiquitous cognitive process.

• MeSH
• lidé MeSH
• mozek fyziologie   MeSH
• neuronové sítě * MeSH
• paměť fyziologie   MeSH
• rozhodování fyziologie   MeSH
• učení fyziologie   MeSH
• vnímání času fyziologie   MeSH
• vnímání prostoru fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Animals and humans receive the most critical information from parts of the environment that are immediately inaccessible and highly dynamic. The brain must effectively process potential interactions between elements in such an environment to make appropriate decisions in critical situations. We trained male Long-Evans rats to discriminate static and dynamic spatial stimuli and to generalize novel dynamic spatial stimuli displayed on an inaccessible computer screen. We provide behavioral evidence indicating that rats encode dynamic visuospatial situations by constructing internal static representations that capture meaningful future interactions between objects. These observations support previous findings in humans that such internal static representations can encapsulate relevant spatiotemporal information of dynamic environments. This mechanism would allow animals and humans to process complex time-changing situations neatly.

• MeSH
• chování zvířat fyziologie   MeSH
• krysa rodu rattus MeSH
• potkani Long-Evans * MeSH
• vnímání prostoru * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Úvod: 3D tisk, koncept starý přes 40 let, nachází díky technologickému pokroku stále širší uplatnění v klinické praxi. Ve FN Ostrava je využíván k vytváření anatomických modelů konkrétních pacientů před chirurgickými výkony na základě dat ze zobrazovacích vyšetření. Kazuistiky: 3D tisk nachází uplatnění jako doplněk ke konvenčním zobrazovacím metodám s cílem zhotovit morfologicky přesné modely anatomických struktur konkrétních pacientů. Tyto modely slouží především pro předoperační přípravu v elektivní břišní, cévní a hrudní chirurgii. Využívají se rovněž při plánování osteosyntéz složitých zlomenin a korekčních osteotomií. Vícebarevný tisk, přestože zvyšuje časovou náročnost procesu, umožňuje lepší přehlednost a diferenciaci jednotlivých anatomických struktur v rámci jednoho modelu. Diskuze: 3D modely poskytují lepší prostorovou orientaci a rozpoznání operovaných struktur než 2D obrazy, což přispívá k lepším výsledkům zákroků. Jejich přínos je potvrzen studiemi napříč obory, od kardiochirurgie po traumatologii. Závěr: Po odstranění počátečních překážek se 3D tisk stal spolehlivou součástí arzenálu Chirurgické kliniky FN Ostrava pro elektivní chirurgii. I když 3D tisk nepředstavuje univerzální odpověď na všechny výzvy, kterým v medicíně čelíme, jeho role je v řadě indikovaných případů velmi přínosná a perspektivní.

Introduction: 3D printing, a concept over 40 years old, is finding broader application in clinical practice thanks to technological advancements. At University Hospital Ostrava, 3D printing is utilized to create anatomically accurate models of specific patients before surgical procedures based on imaging data. Case series: 3D printing is employed as a complement to conventional imaging methods to produce morphologically precise models of anatomical structures of individual patients. These models primarily serve for preoperative planning in elective abdominal, vascular, and thoracic surgery. They are also used in planning osteosynthesis of complex fractures and corrective osteotomies. Multicolor printing, although increasing the process‘s time demands, allows better clarity and differentiation of individual anatomical structures within a single model. Discussion: Compared to 2D images, 3D models provide better spatial orientation and awareness of the operated structures, contributing to improved surgical outcomes. The benefits of 3D printing in preoperative planning and patient education are confirmed by studies across the fields ranging from cardiac surgery to traumatology. Conclusion: After overcoming initial challenges, 3D printing has become a reliable component of the surgical arsenal at University Hospital Ostrava for elective surgery. While 3D printing does not represent a universal answer to all medical challenges, its role is highly beneficial and promising in many indicated cases.

• MeSH
• 3D tisk MeSH
• anatomické modely * MeSH
• chirurgie operační MeSH
• individualizovaná medicína MeSH
• lidé MeSH
• předoperační péče * MeSH
• Check Tag
• lidé MeSH

Charakter proudění krve může být důležitý faktor při formování cévní patologie. Komplexní chaotické proudění a turbulence v kritických místech jako jsou bifurkace, může vést k iritaci cévní stěny a nakonec ke stenóze či poškození stěny. Kritická místa mohou vzniknout i při endovaskulárních zákrocích (např. při stentování) nebo v oblasti anastomózy po transplantaci orgánů. Rychlost proudění krve a jeho charakter lze efektivně a neinvazivně měřit pomocí magnetické rezonance. Metoda fázového kontrastu (PC) je dobře etablovanou technikou, která umožňuje měřit rychlost relativně přesně. Tato metoda má však i své limitace (např. omezené prostorové rozlišení s ohledem na rozměr některých cév). Navíc v případě použití stentu je MR signál silně ovlivněn až potlačen v jeho nejbližším okolí a vnitřním lumen. Proto nemůže být rychlost relevantně měřena ve stentu nebo na jeho hranicích. Avšak pomocí matematického modelování proudění s hraničními hodnotami získanými mimo problematickou oblast (stent, oblast silných turbulencí) a se znalostí anatomické geometrie by mohla informace o charakteru proudění ve zmíněných kritických oblastech přispět k predikci vývoje cévní patologie.; Character of the blood flow can be important factor in for the formation of vessel pathology. Complex chaotic flow and turbulences in critical places like bifurcation can lead to vessel wall irritation and finally to stenosis or wall damage. Such critical places can also be created by endovascular treatment (e.g. by means of stenting) or in case of vessel anastomosis after organs transplantation (e.g. connection of the renal artery to iliac artery during kidney transplantation). Flow velocity and character can be efficiently and non-invasively measured using magnetic resonance imaging (MRI). Phase contrast (PC) MRI is well established method where flow velocity is coded into the MR signal phase and so the velocity can be measured relatively precisely. However, there are several limitations when using PC for “in-vivo” quantification (e.g. low spatial resolution in respect to vessel diameter). Moreover, in case when stent was used for the treatment, the MR signal is strongly influence or even suppressed by the presence of metallic net of the stent wall creating RF shielded volume inside the stent. Therefore, the flow cannot be measured directly in the stent or very close to its border. But proper mathematical model of the flow character based on initial conditions provided by MRI outside the stent could help to predict the impact of the flow phenomena on the future vessel disease development.

• Klíčová slova
• MRI, MRI, stent, stenóza, kvantifikace průtoku, matematické modelování toku, endovaskulární zákrok, flow quantification, mathematical model of the flow, stenosis, stent, endovascular treatment,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.

• MeSH
• depresivní porucha unipolární * MeSH
• dospělí MeSH
• konsensus MeSH
• kvalita života MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozeček patologie   MeSH
• průřezové studie MeSH
• senioři MeSH
• stárnutí MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The regional disparity of heatwave-related mortality over a long period has not been sufficiently assessed across the globe, impeding the localisation of adaptation planning and risk management towards climate change. We quantified the global mortality burden associated with heatwaves at a spatial resolution of 0.5°×0.5° and the temporal change from 1990 to 2019. METHODS AND FINDINGS: We collected data on daily deaths and temperature from 750 locations of 43 countries or regions, and 5 meta-predictors in 0.5°×0.5° resolution across the world. Heatwaves were defined as location-specific daily mean temperature ≥95th percentiles of year-round temperature range with duration ≥2 days. We first estimated the location-specific heatwave-mortality association. Secondly, a multivariate meta-regression was fitted between location-specific associations and 5 meta-predictors, which was in the third stage used with grid cell-specific meta-predictors to predict grid cell-specific association. Heatwave-related excess deaths were calculated for each grid and aggregated. During 1990 to 2019, 0.94% (95% CI: 0.68-1.19) of deaths [i.e., 153,078 cases (95% eCI: 109,950-194,227)] per warm season were estimated to be from heatwaves, accounting for 236 (95% eCI: 170-300) deaths per 10 million residents. The ratio between heatwave-related excess deaths and all premature deaths per warm season remained relatively unchanged over the 30 years, while the number of heatwave-related excess deaths per 10 million residents per warm season declined by 7.2% per decade in comparison to the 30-year average. Locations with the highest heatwave-related death ratio and rate were in Southern and Eastern Europe or areas had polar and alpine climates, and/or their residents had high incomes. The temporal change of heatwave-related mortality burden showed geographic disparities, such that locations with tropical climate or low incomes were observed with the greatest decline. The main limitation of this study was the lack of data from certain regions, e.g., Arabian Peninsula and South Asia. CONCLUSIONS: Heatwaves were associated with substantial mortality burden that varied spatiotemporally over the globe in the past 30 years. The findings indicate the potential benefit of governmental actions to enhance health sector adaptation and resilience, accounting for inequalities across communities.

• MeSH
• celosvětové zdraví trendy   MeSH
• extrémní horko * škodlivé účinky   MeSH
• klimatické změny * MeSH
• lidé MeSH
• mortalita trendy   MeSH
• roční období MeSH
• vysoká teplota škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Vaccine efficacy (VE) assessed in a randomized controlled clinical trial can be affected by demographic, clinical, and other subject-specific characteristics evaluated as baseline covariates. Understanding the effect of covariates on efficacy is key to decisions by vaccine developers and public health authorities. METHODS: This work evaluates the impact of including correlate of protection (CoP) data in logistic regression on its performance in identifying statistically and clinically significant covariates in settings typical for a vaccine phase 3 trial. The proposed approach uses CoP data and covariate data as predictors of clinical outcome (diseased versus non-diseased) and is compared to logistic regression (without CoP data) to relate vaccination status and covariate data to clinical outcome. RESULTS: Clinical trial simulations, in which the true relationship between CoP data and clinical outcome probability is a sigmoid function, show that use of CoP data increases the positive predictive value for detection of a covariate effect. If the true relationship is characterized by a decreasing convex function, use of CoP data does not substantially change positive or negative predictive value. In either scenario, vaccine efficacy is estimated more precisely (i.e., confidence intervals are narrower) in covariate-defined subgroups if CoP data are used, implying that using CoP data increases the ability to determine clinical significance of baseline covariate effects on efficacy. CONCLUSIONS: This study proposes and evaluates a novel approach for assessing baseline demographic covariates potentially affecting VE. Results show that the proposed approach can sensitively and specifically identify potentially important covariates and provides a method for evaluating their likely clinical significance in terms of predicted impact on vaccine efficacy. It shows further that inclusion of CoP data can enable more precise VE estimation, thus enhancing study power and/or efficiency and providing even better information to support health policy and development decisions.

• MeSH
• demografie statistika a číselné údaje   MeSH
• klinické zkoušky, fáze III jako téma statistika a číselné údaje   metody   MeSH
• lidé MeSH
• logistické modely MeSH
• počítačová simulace MeSH
• randomizované kontrolované studie jako téma statistika a číselné údaje   metody   MeSH
• účinnost vakcíny * statistika a číselné údaje   MeSH
• vakcinace statistika a číselné údaje   metody   MeSH
• vakcíny terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH