BACKGROUND: Quantitative sensory testing (QST) assesses the functional integrity of small and large nerve fibre afferents and central somatosensory pathways; QST was assumed to provide insight into the mechanisms of neuropathy. We analysed QST profiles and phenotypes in patients with diabetes mellitus to study whether these could differentiate patients with and without pain and neuropathy. METHODS: A standardized QST protocol was performed and 'loss and gain of function' abnormalities were analysed in four groups of subjects: diabetic patients with painful (pDSPN; n = 220) and non-painful distal symmetric polyneuropathy (nDSPN; n = 219), diabetic patients without neuropathy (DM; n = 23) and healthy non-diabetic subjects (n = 37). Based on the QST findings, diabetic subjects were further stratified into four predefined prototypic phenotypes: sensory loss (SL), thermal hyperalgesia (TH), mechanical hyperalgesia (MH) and healthy individuals. RESULTS: Patients in the pDSPN group showed the greatest hyposensitivity ('loss of function'), and DM patients showed the lowest, with statistically significant increases in thermal, thermal pain, mechanical and mechanical pain sensory thresholds. Accordingly, the frequency of the SL phenotype was significantly higher in the pDSPN subgroup (41.8%), than expected (p < 0.0042). The proportion of 'gain of function' abnormalities was low in both pDSPN and nDSPN patients without significant differences. CONCLUSIONS: There is a continuum in the sensory profiles of diabetic patients, with a more pronounced sensory loss in pDSPN group probably reflecting somatosensory nerve fibre degeneration. An analysis of 'gain of function' abnormalities (allodynia, hyperalgesia) did not offer a key to understanding the pathophysiology of spontaneous diabetic peripheral neuropathic pain. SIGNIFICANCE: This article, using quantitative sensory testing profiles in large cohorts of diabetic patients with and without polyneuropathy and pain, presents a continuum in the sensory profiles of diabetic patients, with more pronounced 'loss of function' abnormalities in painful polyneuropathy patients. Painful diabetic polyneuropathy probably represents a 'more progressed' type of neuropathy with more pronounced somatosensory nerve fibre degeneration. The proportion of 'gain of function' sensory abnormalities was low, and these offer limited understanding of pathophysiological mechanisms of spontaneous neuropathic pain.

• MeSH
• diabetes mellitus * MeSH
• diabetické neuropatie * MeSH
• hyperalgezie etiologie   MeSH
• lidé MeSH
• měření bolesti metody   MeSH
• neuralgie * MeSH
• polyneuropatie * MeSH
• práh bolesti fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The increasing global incidence of obesity and type 2 diabetes mellitus (T2D) underscores the urgency of addressing these interconnected health challenges. Obesity enhances genetic and environmental influences on T2D, being not only a primary risk factor but also exacerbating its severity. The complex mechanisms linking obesity and T2D involve adiposity-driven changes in β-cell function, adipose tissue functioning, and multi-organ insulin resistance (IR). Early detection and tailored treatment of T2D and obesity are crucial to mitigate future complications. Moreover, personalized and early intensified therapy considering the presence of comorbidities can delay disease progression and diminish the risk of cardiorenal complications. Employing combination therapies and embracing a disease-modifying strategy are paramount. Clinical trials provide evidence confirming the efficacy and safety of glucagon-like peptide 1 receptor agonists (GLP-1 RAs). Their use is associated with substantial and durable body weight reduction, exceeding 15%, and improved glucose control which further translate into T2D prevention, possible disease remission, and improvement of cardiometabolic risk factors and associated complications. Therefore, on the basis of clinical experience and current evidence, the Eastern and Southern Europe Diabetes and Obesity Expert Group recommends a personalized, polymodal approach (comprising GLP-1 RAs) tailored to individual patient's disease phenotype to optimize diabetes and obesity therapy. We also expect that the increasing availability of dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists will significantly contribute to the modern management of the cardiometabolic continuum.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• biomechanika MeSH
• femur anatomie a histologie   MeSH
• mechanický stres MeSH
• počítačová simulace MeSH
• teoretické modely MeSH

Even though speciation involving multiple interacting partners, such as plants and their pollinators, has attracted much research, most studies focus on isolated phases of the process. This currently precludes an integrated understanding of the mechanisms leading to cospeciation. Here, we examine population genetic structure across six species-pairs of figs and their pollinating wasps along an elevational gradient in New Guinea. Specifically, we test three hypotheses on the genetic structure within the examined species-pairs and find that the hypothesized genetic structures represent different phases of a single continuum, from incipient cospeciation to the full formation of new species. Our results also illuminate the mechanisms governing cospeciation, namely that fig wasps tend to accumulate population genetic differences faster than their figs, which initially decouples the speciation dynamics between the two interacting partners and breaks down their one-to-one matching. This intermediate phase is followed by genetic divergence of both partners, which may eventually restore the one-to-one matching among the fully formed species. Together, these findings integrate current knowledge on the mechanisms operating during different phases of the cospeciation process. They also reveal that the increasingly reported breakdowns in one-to-one matching may be an inherent part of the cospeciation process. Mechanistic understanding of this process is needed to explain how the extraordinary diversity of species, especially in the tropics, has emerged. Knowing which breakdowns in species interactions are a natural phase of cospeciation and which may endanger further generation of diversity seems critical in a constantly changing world.

• MeSH
• druhová specificita MeSH
• Ficus genetika   parazitologie   MeSH
• fylogeneze MeSH
• interakce hostitele a patogenu genetika   MeSH
• sršňovití genetika   MeSH
• vznik druhů (genetika) * MeSH
• zeměpis MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Podľa dimenzionálneho modelu psychických porúch predstavuje paranoja konštrukt ležiaci na kontinuu od normy až po identifikovateľnú patológiu. Perzekučné bludy ako symptóm prítomný pri viacerých psychických poruchách môžu byť považované za extrémne vyjadrený koniec paranoidného kontinua. Literatúra vo všeobecnosti poskytuje niekoľko teórií, ktoré v rôznej miere zdôrazňujú psychické a neurobiologické mechanizmy zodpovedné za vznik a udržiavanie paranoidnej symptomatiky a perzekučných bludov. Cieľom príspevku je popis a vysvetlenie súčasných teoretických koncepcií paranoje a perzekučných bludov, s dôrazom na psychické mechanizmy, ktoré prispievajú k ich vzniku a udržiavaniu. Základom Bentallovej koncepcie je nazeranie na paranoju ako na psychickú obranu pred nízkou sebaúctou. Kognitívny model Freemana a Garetyovej naopak považuje nízku sebaúctu len za jeden z mnohých faktorov, ktoré sa podieľajú na výskyte paranoje. Modely sú vzájomné porovnávané a konfrontované so súčasnou empirickou evidenciou. Implikácie pre klinickú prax sú diskutované.

According to dimensional model of mental disorders paranoia represents a construct across the normal – pathological continuum. Persecutory delusions, as a symptom of many mental disorders, can be considered an extremely expressed end of the paranoid continuum. In general, the literature provides several theories which, to different degrees, emphasize the psychological and neurobiological mechanisms responsible for the formation and maintenance of paranoid symptomatology and persecutory delusions. The aim of the paper is to describe and explain the current theoretical concepts of paranoia and persecutory delusions, with an emphasis on psychological mechanisms contributing to their formation and maintenance. In Bentall’s concept, it is proposed that paranoia is a psychological defense against low self-esteem. Cognitive model of Freeman and Garety, however, suggested low self-esteem to be just one of many factors involved in the occurrence of paranoia. Models are compared and confronted with current empirical evidence. Implications for clinical practice are discussed.

• MeSH
• kognitivně behaviorální terapie MeSH
• lidé MeSH
• paranoidní poruchy diagnóza   etiologie   klasifikace   terapie   MeSH
• psychologické modely MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Sepse je dominující příčinou morbidity a mortality pacientů hospitalizovaných na jednotkách intenzivní péče. Je definována jako systémová zánětlivá odpověď organizmu na přítomnost infekce. Dysfunkce myokardu jako součást multiorgánového selhání postihuje až 2/ 3 pacientů v těžké sepsi. Škála funkčních změn je kontinuální od izolované a lehké poruchy relaxace komor až po kombinovanou těžkou biventrikulární dysfunkci, imitující až obraz kardiogenního šoku. Typickým nálezem při hodnocení septické myokardiální dysfunkce (SMD) echokardiografickými metodami je pokles ejekční frakce (EF) s dilatací komor, tedy zvýšením end-diastolického objemu (EDV). Důležitým prognostickým znamením je dynamika dysfunkce myokardu v prvních dnech rozvoje sepse. U přeživších pacientů dochází obvykle 7.- 10. den od manifestace septického šoku k normalizaci kardiálních funkcí. Lze tedy spekulovat, že rozvoj určitého typu SMD, jako dočasného ochranného kompenzačního mechanizmu, může být pro organizmus z hlediska přežití výhodný. V patogenezi SMD byla popsána řada mechanizmů. Předpokládá se dysfunkce endotelu s navazující poruchou mikrocirkulace a mitochondriální dysfunkcí, významnou roli hraje kardiodepresivní vliv cirkulujících faktorů, především endotoxinu, TNF, interleukinů.

Sepsis is considered to be the major cause of morbidity and mortality of patients hospitalised in intensive care. It's defined as a systemic inflammatory response of organism to infection. Incidence of myocardial dysfunction in studies with severe sepsis patients is up to two thirds of patients. Cardiac dysfunction shows a continuum from isolated and mild diastolic dysfunction to combined severe diastolic and systolic failure of both ventricles mimicking even cardiogenic shock in some patients. Typical features of septic myocardial dysfunction (SMD) are decrease in ejection fraction (EF) with dilatation ofventricles, e.g. increase in end-diastolic volume (EDV). Reversibility of myocardial dysfunction during a period from 7 to 10 days in survivors is other typical manifestation of SMD. Hence, one can speculate that development of such a type ofSMD as a temporary protective compensatory mechanism could be advantageous for of an individual patient. A large body ofevidence about mechanisms ofSMD was described; endothelial dysfunction with consequent microcirculatory and mitochondrial dysfunction and role of circulating factors are considered to be the most important.

• MeSH
• autonomní nervový systém patofyziologie   MeSH
• cytokiny fyziologie   MeSH
• endotoxiny fyziologie   MeSH
• kardiomyopatie etiologie   patofyziologie   MeSH
• koronární cirkulace MeSH
• lidé MeSH
• myofibrily fyziologie   MeSH
• myokard metabolismus   MeSH
• oxid dusnatý fyziologie   MeSH
• sepse komplikace   MeSH
• srdeční mitochondrie fyziologie   MeSH
• TNF-alfa fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• biomechanika MeSH
• muskuloskeletální nemoci MeSH
• muskuloskeletální vývoj MeSH
• regenerace MeSH
• stárnutí MeSH
• vývojová biologie MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• fyziologie
• biologie

Objectives: A significant portion of care related to cardiorespiratory diseases is provided at home, usually but not exclusively, after the discharge of a patient from hospital. It is the purpose of the present study to present the technical means which we have developed, in order to support the adaptation of the continuity of care of cardiorespiratory diseases at home. Methods: We have developed an integrated system that includes: first, a prototype laptop-based portable monitoring system that comprises low-cost commercially available components, which enable the periodical or continuous monitoring of vital signs at home; second, software supporting medical decision-making related to tachycardia and ventricular fibrillation, as well as fuzzy-rules-based software supporting home-ventilation optimization; third, a typical continuity of care record (CCR) adapted to support also the creation of a homecare plan; and finally, a prototype ontology, based upon the HL7 clinical document architecture (CDA), serving as basis for the development of semantically annotated web services that allow for the exchange and retrieval of homecare information. Results: The flexible design and the adaptable data-exchange mechanism of the developed system result in a useful and standard-compliant tool, for cardiorespiratory disease-related homecare. Conclusions: The ongoing laboratory testing of the system shows that it is able to contribute to an effective and low-cost package solution, supporting patient supervision and treatment. Furthermore, semantic web technologies prove to be the perfect solution for both the conceptualization of a continuity of care data exchange procedure and for the integration of the structured medical data.

• MeSH
• informační systémy normy   MeSH
• internet MeSH
• kardiovaskulární nemoci MeSH
• kontinuita péče o pacienty MeSH
• lidé MeSH
• sémantika MeSH
• služby domácí péče MeSH
• systémová integrace MeSH
• telemetrie metody   přístrojové vybavení   MeSH
• ukládání a vyhledávání informací metody   MeSH
• zajištění kvality zdravotní péče metody   MeSH
• Check Tag
• lidé MeSH

Image registration methods play a crucial role in computational neuroanatomy. This paper mainly contributes to the field of image registration with the use of nonlinear spatial transformations. Particularly, problems connected to matching magnetic resonance imaging (MRI) brain image data obtained from various subjects and with various imaging conditions are solved here. Registration is driven by local forces derived from multimodal point similarity measures which are estimated with the use of joint intensity histogram and tissue probability maps. A spatial deformation model imitating principles of continuum mechanics is used. Five similarity measures are tested in an experiment with image data obtained from the Simulated Brain Database and a quantitative evaluation of the algorithm is presented. Results of application of the method in automated spatial detection of anatomical abnormalities in first-episode schizophrenia are presented.

• MeSH
• algoritmy MeSH
• financování organizované MeSH
• interpretace obrazu počítačem metody   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• modely neurologické MeSH
• mozek anatomie a histologie   fyziologie   MeSH
• neuroanatomie metody   MeSH
• neurologie metody   MeSH
• počítačová simulace MeSH
• pružnost MeSH
• psychiatrie metody   MeSH
• reprodukovatelnost výsledků MeSH
• rozpoznávání automatizované metody   MeSH
• senzitivita a specificita MeSH
• subtrakční technika MeSH
• umělá inteligence MeSH
• vylepšení obrazu metody   MeSH
• zobrazování trojrozměrné metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• hodnotící studie MeSH

A semiempirical quantum mechanical PM6-DH2 method accurately covering the dispersion interaction and H-bonding was used to score fifteen structurally diverse CDK2 inhibitors. The geometries of all the complexes were taken from the X-ray structures and were reoptimised by the PM6-DH2 method in continuum water. The total scoring function was constructed as an estimate of the binding free energy, i.e., as a sum of the interaction enthalpy, interaction entropy and the corrections for the inhibitor desolvation and deformation energies. The applied scoring function contains a clear thermodynamical terms and does not involve any adjustable empirical parameter. The best correlations with the experimental inhibition constants (ln K (i)) were found for bare interaction enthalpy (r (2) = 0.87) and interaction enthalpy corrected for ligand desolvation and deformation energies (r (2) = 0.77); when the entropic term was considered, however, the correlation becomes worse but still acceptable (r (2) = 0.52). The resulting correlation based on the PM6-DH2 scoring function is better than previously published function based on various docking/scoring, SAR studies or advanced QM/MM approach, however, the robustness is limited by number of available experimental data used in the correlation. Since a very similar correlation between the experimental and theoretical results was found also for a different system of the HIV-1 protease, the suggested scoring function based on the PM6-DH2 method seems to be applicable in drug design, even if diverse protein-ligand complexes have to be ranked.

• MeSH
• cyklin-dependentní kinasa 2 antagonisté a inhibitory   metabolismus   MeSH
• inhibitory proteinkinas chemie   farmakologie   MeSH
• kvantová teorie MeSH
• lidé MeSH
• ligandy MeSH
• molekulární modely MeSH
• racionální návrh léčiv MeSH
• termodynamika MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH