OBJECTIVE: The insulin/IGF superfamily is conserved across vertebrates and invertebrates. Our team has identified five viruses containing genes encoding viral insulin/IGF-1 like peptides (VILPs) closely resembling human insulin and IGF-1. This study aims to characterize the impact of Mandarin fish ranavirus (MFRV) and Lymphocystis disease virus-Sa (LCDV-Sa) VILPs on the insulin/IGF system for the first time. METHODS: We chemically synthesized single chain (sc, IGF-1 like) and double chain (dc, insulin like) forms of MFRV and LCDV-Sa VILPs. Using cell lines overexpressing either human insulin receptor isoform A (IR-A), isoform B (IR-B) or IGF-1 receptor (IGF1R), and AML12 murine hepatocytes, we characterized receptor binding, insulin/IGF signaling. We further characterized the VILPs' effects of proliferation and IGF1R and IR gene expression, and compared them to native ligands. Additionally, we performed insulin tolerance test in CB57BL/6 J mice to examine in vivo effects of VILPs on blood glucose levels. Finally, we employed cryo-electron microscopy (cryoEM) to analyze the structure of scMFRV-VILP in complex with the IGF1R ectodomain. RESULTS: VILPs can bind to human IR and IGF1R, stimulate receptor autophosphorylation and downstream signaling pathways. Notably, scMFRV-VILP exhibited a particularly strong affinity for IGF1R, with a mere 10-fold decrease compared to human IGF-1. At high concentrations, scMFRV-VILP selectively reduced IGF-1 stimulated IGF1R autophosphorylation and Erk phosphorylation (Ras/MAPK pathway), while leaving Akt phosphorylation (PI3K/Akt pathway) unaffected, indicating a potential biased inhibitory function. Prolonged exposure to MFRV-VILP led to a significant decrease in IGF1R gene expression in IGF1R overexpressing cells and AML12 hepatocytes. Furthermore, insulin tolerance test revealed scMFRV-VILP's sustained glucose-lowering effect compared to insulin and IGF-1. Finally, cryo-EM analysis revealed that scMFRV-VILP engages with IGF1R in a manner closely resembling IGF-1 binding, resulting in a highly analogous structure. CONCLUSIONS: This study introduces MFRV and LCDV-Sa VILPs as novel members of the insulin/IGF superfamily. Particularly, scMFRV-VILP exhibits a biased inhibitory effect on IGF1R signaling at high concentrations, selectively inhibiting IGF-1 stimulated IGF1R autophosphorylation and Erk phosphorylation, without affecting Akt phosphorylation. In addition, MFRV-VILP specifically regulates IGF-1R gene expression and IGF1R protein levels without affecting IR. CryoEM analysis confirms that scMFRV-VILP' binding to IGF1R is mirroring the interaction pattern observed with IGF-1. These findings offer valuable insights into IGF1R action and inhibition, suggesting potential applications in development of IGF1R specific inhibitors and advancing long-lasting insulins.

• MeSH
• elektronová kryomikroskopie MeSH
• exprese genu MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• fosforylace MeSH
• insulinu podobný růstový faktor I * genetika   metabolismus   MeSH
• inzulin metabolismus   MeSH
• lidé MeSH
• myši MeSH
• protein - isoformy metabolismus   MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• receptor IGF typ 1 * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Different biomarkers are investigated to detect the causes of severe complications in preterm infants. Extracellular vesicles (EVs) are recognized as an important part of cell-to-cell communication, and their increased levels were reported in numerous pathological states. We aimed to increase our knowledge about the incidence of platelet and endothelial EVs in cord blood of preterm newborns using conventional flow cytometry. The presence of platelet (CD36+CD41+), activated platelet (CD41+CD62+), and endothelial (CD31+CD105+) EVs was analyzed. Immune electron microscopy was used to confirm the presence of EVs and the specificity of their labeling. The size of detected extracellular vesicles was in the range 400-2000 nm. The differences in the counts of EVs between the preterm and control group were not significant and no correlation of EVs count with gestation age was recorded. Cord blood plasma samples with free hemoglobin level > 1 mg/mL had more than threefold higher counts of CD36+CD41+ and CD41+CD62+ EVs (p < 0.001), while the count of CD31+CD105+ EVs was only moderately increased (p < 0.05). Further studies utilizing cytometers with improved sensitivity are needed to confirm that the analysis of large platelet and endothelial EVs mirrors the quantitative situation of their whole plasma assemblage.

• Publikační typ
• časopisecké články MeSH

In contrast to varied therapy approaches, mirror therapy (MT) can be used even in completely plegic stroke survivors, as it uses visual stimuli for producing a desired response in the affected limb. MT has been studied to have effects not just on motor impairments but also on sensations, visuospatial neglect, and pain after stroke. This paper attempts to systematically review and present the current perspectives on mirror therapy and its application in stroke rehabilitation, and dosage, feasibility and acceptability in stroke rehabilitation. An electronic database search across Google, PubMed, Web of Science, etc., generated 3871 results. After screening them based on the inclusion and exclusion criteria, we included 28 studies in this review. The data collected were divided on the basis of application in stroke rehabilitation, modes of intervention delivery, and types of control and outcome assessment. We found that most studies intervened for upper limb motor impairments post stroke. Studies were equally distributed between intervention in chronic and acute phases post stroke with therapy durations lasting between 1 and 8 weeks. MT showed definitive motor and sensory improvements although the extent of improvements in sensory impairments and hemineglect is limited. MT proves to be an effective and feasible approach to rehabilitate post-stroke survivors in the acute, sub-acute, and chronic phases of stroke, although its long-term effects and impact on activities of daily living need to be analysed extensively.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE OF THE STUDY: The aim of the study was to describe a novel Omega plate and the procedure for obtaining an accurate pelvic inlet view, the mode of pre-operative plate contouring, the surgical procedure used and the evaluation of results in the first 15 patients treated using this method. MATERIAL AND METHODS: In the period 2009-2011, a total of 232 patients underwent osteosynthesis for pelvic fractures. Out of them, 52 were treated by the modified Stoppa approach and 12 with the original Omega plate. Between July 2010 and January 2014, a novel 3.5-mm Omega plate was used in 12 men and 3 women. The average duration of follow-up was 8.5 months in 11 patients; four were shortly after surgery. The multi-functional Omega plate is described in detail. An exact pelvic inlet projection, named the "computer tomography-defined (CTD) view", was based on pre-operative CT examination. It facilitates pre-operative contouring of the plate according to a mirror image of the uninjured half of the pelvis. The surgical procedure enables us to apply the contoured plate to the correct position; the plate completes reduction, restores normal pelvic anatomy and makes operative time shorter. The radiographic evaluation of post-operative results was done using the Matta classification and functional outcome was assessed by the Harris Hip Score. RESULTS: Surgery using the isolated Stoppa approach was carried out in 11 patients and a procedure combining the Stoppa approach with another method was used in four patients. All operations were successfully completed, during two of them the external iliac vein was injured and treated by vascular suturing. No other vascular or nerve injury occurred. One deep wound infection successfully healed was recorded. The post-operative radiographic results were excellent or satisfactory in 12 and poor in three patients. At follow-ups of 6 to 12 months, no failure of fracture reduction or osteosynthesis was recorded in 11 patients. Neither avascular necrosis of the femoral head nor heterotopic ossification was found. One patient showed signs of post-injury arthritis at 6 months after surgery. The functional result assessed by the Harris Hip Score was excellent in seven patients, good in two (one of them with gonarthrosis), satisfactory in one patient with contralateral total hip replacement and ipsilateral gonarthrosis, and poor in one patient with hemiparesis after a stroke. DISCUSSION: Shape and size variability in CTD pelvic inlet views do not allow us to create a unified anatomically correct implant. Contouring during the operative procedure may not be accurate enough and significantly prolongs the time of surgery. Therefore, a custom-made plate for each patient seems to be an optimal method. It has been demonstrated on a group of 50 patients that CTD images of the right and left halves of the pelvis are identical in 68% and very similar (variation in length up to 5 mm and in curvature up to 3 mm) in 18%. At present plate contouring according to a mirror image of the acetabulum, which will be obtained by 3D printing, is prepared. CONCLUSIONS: Pre-operative contouring of an Omega plate based on a post-injury CT scan of the uninjured half of the pelvis is over 80% accurate or almost accurate. The multi-functional 3.5-mm pelvic plate Omega allows us to stabilise complicated fractures of the superior ramus of the pubic bone, anterior acetabular column or quadrilateral plate as well as fractures above the linea arcuata or uncomplicated fractures of the posterior column. The stabilisation of all fragments of the anterior column and quadrilateral plate is very firm and the Omega plate is resistant to fragment redisplacement. Also, it is its advantage that it can remain in situ if total hip arthroplasty is required later.

• MeSH
• acetabulum zranění   radiografie   MeSH
• design vybavení MeSH
• fraktury kostí radiografie   chirurgie   MeSH
• kostní destičky * MeSH
• lidé MeSH
• počítačová rentgenová tomografie MeSH
• předoperační období * MeSH
• vnitřní fixace fraktury přístrojové vybavení   metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

• MeSH
• elektrodiagnostika metody   MeSH
• elektromyografie MeSH
• nemoci míchy diagnóza   MeSH
• nervové vedení fyziologie   MeSH
• nervový přenos fyziologie   MeSH
• neuromuskulární nemoci diagnóza   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• diagnostika
• NLK Publikační typ
• kolektivní monografie

• MeSH
• chemie MeSH

• Konspekt
• Organická chemie
• NLK Obory
• chemie, klinická chemie
• NLK Publikační typ
• učebnice vysokých škol

• MeSH
• biofyzika MeSH
• technologie lékařská MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• fyzika, biofyzika
• NLK Publikační typ
• učebnice vysokých škol

Pozitronová emisní tomografie je moderní vyšetřovací metoda detekující distribuci intravenózně podané glukózy, která je pro tento účel označena pozitronovým zářičem F18. V onkologii se využívá skutečnosti, že nádorové buňky glukózu zvýšeně utilizují, zvýšená konsumpce ale není specifická jen pro nádory, ale také pro záněty. K upřesnění lokalizace vyšší kumulace radionuklidu slouží společné zobrazení s CT nebo jejich dodatečná fúze. Cíl: Práce shrnuje 10leté zkušenosti s PET u pacientů léčených na Klinice ORL a chirurgie hlavy a krku FN u sv. Anny v Brně. V letech 2000 - 2009 bylo u 67 onkologických pacientů provedeno celkem 97 PET vyšetření v Masarykově onkologickém ústavu. Výsledky: Z 97 provedených vyšetření byl v 67 případech PET pozitivní a u 63 pacientů CT pozitivní. Výsledky se shodovaly v 77 případech (55 oba pozitivní, 22 oba negativní), což činí 79 %. U pacientů s rozdílným výsledkem jsme výsledky porovnali s klinickým, popř. histologickým nálezem. Uvedené výsledky odpovídají hodnotě senzitivity pro CT 89% a specifity 87%, pro PET senzitivita 91%, specifita 87%. Detailnější analýzu jsme provedli v minulosti při hodnocení významu PET pro diagnostiku perzistence krčních metastáz po CHRT v rámci záchovného protokolu. U 17 pacientů po léčbě CHRT byly nálezy zobrazení PET a CT korelovány s histopatologickým nálezem po 32 provedených blokových krčních disekcích. Senzitivita PET byla nízká - 45% , podobně i negativní prognostická hodnota 78%, na rozdíl od vysoké 96% specifity. Závěr: Hodnoty senzitivity a specifity PET a CT vyšetření jsou v celém našem souboru přibližně srovnatelné a poměrně vysoké. Jde ale o relativně nehomogenní soubor co se týká lokalizace tumorů a důvodů indikace PET. Nízká senzitivita a negativní prediktivní hodnota při hodnocení perzistujících krčních metastáz v souboru nemocných po CHRT nás neopravňuje k eliminaci blokové disekce. Uvedené skutečnosti spolu s poměrně vysokou finanční náročností jsou důvodem prozatímního, spíše výběrového, nestandardního využívání PET u našich onkologicky nemocných.

Positron emission tomography is a modern diagnostic method based on monitoring of intravenously applied glucose distribution marked with radionuclide F18. Increased glucose consumption of malign cells enables their detection, which is unfortunately not exclusively specific for tumor tissues but generally mirrors an increased metabolic cell activity. Better anatomic resolution is provided by PET/CT fusion. Aims: We have summarised our 10 year experience with PET diagnostics in patients treated in ENT clinic of St. Anne’s university hospital in Brno. From 2000 to 2009 in 67 oncologic patients 97 PET scanning were undertaken. Results: 67 of all 97 PET studies were positive, while CT scans were positive in 63 patients. Both studies were in accordance in 77 patients (55 both positive, 22 both negative), which makes 79%. In patients with any discrepancy were radiodiagnostic results compared with histopathology. The estimated CT sensitivity was 89% and specificity 87%, PET sensitivity 91% and specificity 87%. Further we analyzed PET benefit for diagnostics of lymph node metastases persistence after CHRT in organ preserving protocol. In 17 patients CT and PET results were histopathologically confirmed after neck dissection. Sensitivity in this indication was 45% in contrast to high specificity 96%, negative predictive value was 78%. Conclusion: PET and CT sensitivity and specificity are mutually comparable and relatively high. Group of patients in our study is non - homogeneous in respect to tumor locality and PET indication. Low sensitivity and negative predictive value for persistent lymph node metastases wouldn’t justify regarding PET as a tool suitable for elimination of neck dissection. All above mentioned facts and its high financial demands are our reasons for the selective and nonstandard PET indication in the oncological patients.

• Klíčová slova
• specifika, senzitivita, CT, PET,
• MeSH
• falešně negativní reakce MeSH
• falešně pozitivní reakce MeSH
• fluorodeoxyglukosa F18 diagnostické užití   MeSH
• konformní radioterapie využití   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory hlavy a krku radiografie   radioterapie   MeSH
• nádory neznámé primární lokalizace MeSH
• plánování radioterapie pomocí počítače MeSH
• počítačová rentgenová tomografie využití   MeSH
• pozitronová emisní tomografie využití   MeSH
• retrospektivní studie MeSH
• reziduální nádor MeSH
• senzitivita a specificita MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH

Advanced metal deposition and microfabrication techniques enable preparation of metal surfaces with high precision and excellent control over their size and shape with subnanometer resolution. Thin metal films of different types and functions can be found in many analytical instruments. Surfaces with high optical quality serve as mirrors, beam splitters, antireflective coatings etc. Smooth metal coating is crucial in electron microscopy. Unique properties of the thin metal films are widely used in optical systems, as tools for sample manipulation but also for chemical sensing and detection. While some of the applications are widespread and belong to the basic curriculum in analytical chemistry, the newer or less common uses of thin metal films are well known only to the experts in the field. The purpose of this critical review is to highlight the role of thin metal films in bioanalysis and summarize some of their main applications in current bioanalytical instrumentation.

• MeSH
• biosenzitivní techniky přístrojové vybavení   metody   MeSH
• elektrochemické techniky přístrojové vybavení   metody   MeSH
• kovy chemie   MeSH
• lidé MeSH
• mikrofluidika přístrojové vybavení   metody   MeSH
• nukleové kyseliny analýza   MeSH
• proteiny analýza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• Klíčová slova
• systém R, R software,
• MeSH
• automatizované zpracování dat MeSH
• software MeSH
• statistika jako téma MeSH
• Publikační typ
• monografie MeSH
• příručky MeSH

• Konspekt
• Kombinatorika. Teorie grafů. Matematická statistika. Operační výzkum. Matematické modelování
• NLK Obory
• statistika, zdravotnická statistika