Fatal cases of hemorrhagic fever with renal syndrome in Udmurtia,Russia, 2010 to 2019

European Journal of Clinical Microbiology & Infectious Diseases - Hemorrhagic fever with renal syndrome (HFRS) continues to be a cause of death in Europe. Our aim was to describe the clinical...     

Optical mapping of impulse propagation in engineered cardiac tissue

Cardiac tissue engineering has a potential to provide functional, synchronously contractile tissue constructs for heart repair, and for studies of development and disease using in vivo-like yet controllable in vitro settings. In both cases, the utilization of bioreactors capable of providing biomimetic culture environments is instrumental for supporting cell differentiation and functional assembly. In the present study, neonatal rat heart cells were cultured on highly porous collagen scaffolds in bioreactors with electrical field stimulation. A hallmark of excitable tissues such as myocardium is the ability to propagate electrical impulses. We utilized the method of optical mapping to measure the electrical impulse propagation. The average conduction velocity recorded for the stimulated constructs (14.4 +/- 4.1 cm/s) was significantly higher than that of the nonstimulated constructs (8.6 +/- 2.3 cm/s, p = 0.003). The measured electrical propagation properties correlated to the contractile behavior and the compositions of tissue constructs. Electrical stimulation during culture significantly improved amplitude of contractions, tissue morphology, and connexin-43 expression compared to the nonsimulated controls. These data provide evidence that electrical stimulation during bioreactor cultivation can improve electrical signal propagation in engineered cardiac constructs.     

Electroencephalogram asymmetry and spectral power during sleep in the northern fur seal

The fur seal (Callorhinus ursinus), a member of the Pinniped family, displays a highly expressed electroencephalogram (EEG) asymmetry during slow wave sleep (SWS), which is comparable with the unihemispheric sleep in cetaceans. In this study, we investigated the EEG asymmetry in the fur seal using spectral analysis. Four young (2-3 years old) seals were implanted with EEG electrodes for polygraphic sleep recording. In each animal, EEG spectral power in the frequency range of 1.2-16 Hz was computed in symmetrical cortical recordings over two consecutive nights. The degree of EEG asymmetry was measured by using the asymmetry index [AI = (L - R)/(L + R), where L and R are the spectral powers in the left and right hemispheres, respectively]. In fur seals, EEG asymmetry, as measured by the percent of 20-s epochs with absolute AI > 0.3 and >0.6, was expressed in the entire frequency range (1.2-16 Hz). The asymmetry was significantly greater during SWS (25.6-44.2% of all SWS epochs had an absolute AI > 0.3 and 2.1-12.2% of all epochs had AI > 0.6) than during quiet waking (11.0-20.3% and 0-1.9% of all waking epochs, respectively) and REM sleep (4.2-8.9% of all REM sleep epochs and no epochs, respectively). EEG asymmetry was recorded during both low- and high-voltage SWS, and was maximal in the range of 1.2-4 and 12-16 Hz. As shown in this study, the degree of EEG asymmetry and the frequency range in which it is expressed during SWS in fur seals are profoundly different from those of terrestrial mammals and birds.     

Fractal network dimension and viscoelastic powerlaw behavior: I. A modeling approach based on a coarse-graining procedure combined with shear oscillatory rheometry

Recent advances in dynamic elastography and biorheology have revealed that the complex shear modulus, G*, of various biological soft tissues obeys a frequency-dependent powerlaw. This viscoelastic powerlaw behavior implies that mechanical properties are communicated in tissue across the continuum of scales from microscopic to macroscopic. For deriving constitutive constants from the dispersion of G* in a biological tissue, a hierarchical fractal model is introduced that accounts for multiscale networks. Effective-media powerlaw constants are derived by a constitutive law based on cross-linked viscoelastic clusters embedded in a rigid environment. The spatial variation of G* is considered at each level of hierarchy by an iterative coarse-graining procedure. The establishment of cross-links in this model network is associated with an increasing fractal dimension and an increasing viscoelastic powerlaw exponent. This fundamental relationship between shear modulus dynamics and fractal dimension of the mechanical network in tissue is experimentally reproduced in phantoms by applying shear oscillatory rheometry to layers of tangled paper strips embedded in agarose gel. Both model and experiments demonstrate the sensitivity of G* to the density of the mechanical network in tissue, corroborating disease-related alterations of the viscoelastic powerlaw exponent in human parenchyma demonstrated by in vivo elastography.     

Plasmin as a proinflammatory cell activator

The serine protease plasmin generated from its zymogen plasminogen is best known for its function as a key enzyme of the fibrinolytic cascade. However, beyond fibrinolysis, plasmin has a number of crucial functions in a variety of processes, including inflammation. Various cells can bind plasminogen and plasmin via plasminogen-binding sites exposing a C-terminal lysine. Plasmin, generated as a result of plasminogen activation at the cell surface, is protected from its physiological inhibitors. Apart from its ability to facilitate cell migration in tissues, plasmin is capable of triggering signaling, which depends on cellular binding via its lysine-binding sites and its proteolytic activity. Plasmin-induced signaling affects various functions of monocytes, macrophages, DCs, and others, with the list of affected cells still growing. In vitro and in vivo studies have demonstrated the ability of plasmin to stimulate the production of cytokines, ROS, and other mediators, thereby contributing to inflammation. Plasmin-induced chemotaxis of monocytes and DCs indicates that it is also a potent chemoattractant for immune cells. Therefore, excessive activation of plasmin in chronic inflammatory or autoimmune diseases might exacerbate the activation of inflammatory cells and the pathogenesis of the disease. This review focuses on the available evidence for physiological and pathophysiological roles the serine protease plasmin in inflammatory processes.     

Surface charge impact in low-magnesium model of seizure in rat hippocampus

Putative mechanisms of induction and maintenance of seizure-like activity (SLA) in the low Mg(2+) model of seizures are: facilitation of NMDA receptors and decreased surface charge screening near voltage-gated channels. We have estimated the role of such screening in the early stages of SLA development at both physiological and room temperatures. External Ca(2+) and Mg(2+) promote a depolarization shift of the sodium channel voltage sensitivity; when examined in hippocampal pyramidal neurons, the effect of Ca(2+) was 1.4 times stronger than of Mg(2+). Removing Mg(2+) from the extracellular solution containing 2 mM Ca(2+) induced recurrent SLA in hippocampal CA1 pyramidal layer in 67% of slices. Reduction of [Ca(2+)](o) to 1 mM resulted in 100% appearance of recurrent SLA or continuous SLA. Both delay before seizure activity and the inter-SLA time were significantly reduced. Characteristics of seizures evoked in low Mg(2+)/1 mM Ca(2+)/3.5 K(+) were similar to those obtained in low Mg(2+)/2 Ca(2+)/5mM K(+), suggesting that reduction of [Ca(2+)](o) to 1 mM is identical to the increase in [K(+)](o) to 5 mM in terms of changes in cellular excitability and seizure threshold. An increase of [Ca(2+)](o) to 3 mM completely abolished SLA generation even in the presence of 5 mM [K(+)](o). A large variation in the ability of [Ca(2+)](o) to stop epileptic discharges in initial stage of SLA was found. Our results indicate that surface charge of the neuronal membrane plays a crucial role in the initiation of low Mg(2+)-induced seizures. Furthermore, our study suggests that Ca(2+) and Mg(2+), through screening of surface charge, have important anti-seizure and antiepileptic properties.     

The neuromuscular system in continuously swimming cercariae from Belarus. II Echinostomata, Gymnocephala and Amphistomata

The neuromuscular system in cercariae of Moliniella anceps, Echinostoma revolutum, Cathaemasia hians, Psilochasmus oxyurus, Sphaeridiotrema globulus, Paramphistomum cervi and Diplodiscus subclavatus was studied with immunocytochemical methods and confocal scanning laser microscopy. The patterns of F-actin in the musculature, 5-HT immunoreactive (IR), FMRFamide-IR neuronal elements and ??-tubulin-IR sensory receptors were investigated. The general patterns of musculature, 5-HT- and FMRFamide-IR neuronal elements in the 12 species studied here and in paper I are similar to those observed in other cercariae and reflect the morphology of the groups. The musculature of the tail shows variations which are related to the different strategies of host finding. In the Echinostomatoidea and Paramphistomoidea, the striated musculature of the tail is well developed compared to that in the Xiphidiocercariae. Specialized muscle fibres were found in S. globulus, which are able to change the shape of the tail. Nine of the species studied have seven paired 5-HT-IR neurons in the body, and two species have eight. No correlation between the body size and the number of 5-HT-IR neurons was observed. However, the size of the neurons followed the body size. The number of 5-HT-IR neurons in the brain ganglia increased from the primitive to the advanced forms. The number of FMRFamide-IR transverse commissures in the body correlates with the size of the cercariae. Regardless of the differences in the second intermediate host, the distribution of ??-tubulin-IR sensory receptors shows a high degree of conformity in all species except in P. cervi, which encysts on plants.     

Duplication of chromosome band 12q24.11q24.23 results in apparent Noonan syndrome

Noonan syndrome is an autosomal dominant disorder with an estimated incidence of 1 in 1,000 to 1 in 2,500 live births. It is characterized by postnatal-onset short stature, characteristic facial changes, webbed neck, pectus carinatum, or excavatum, congenital heart defects, and bleeding abnormalities. Gain-of-function mutations in the PTPN11, KRAS, SOS1, and RAF1 genes that are components of the RAS/MEPK signaling pathway are identified in about 70-85% of individuals with Noonan syndrome. We report here a case of duplication of chromosome region 12q24.11q24.23 identified by array comparative genomic hybridization (aCGH) that includes the PTPN11 gene in a 3-year-old girl with apparent Noonan syndrome. The patient presented with postnatal-onset failure-to-thrive, developmental delay, microcephaly, velopalatal incompetence, pectus excavatum, coarctation of aorta, atrial and ventricular septal defects, decreased muscle tone, and minor facial anomalies consistent with Noonan syndrome. At 3 years of age her speech, gross and fine motor development were at the level of a 12-18 month old child. This degree of developmental delay was atypical for an individual with Noonan syndrome, raising concerns for a chromosomal abnormality. Array-CGH showed an interstitial duplication of 10 Mb including the PTPN11 gene. Sequencing of PTPN11, KRAS, SOS1 and the coding region of RAF1 did not identify mutations. The increased gene dosage of the PTPN11 gene in the form of duplication is expected to have the same consequence as gain-of-function mutations seen in Noonan syndrome. We propose that at least some of the 15-30% of individuals with Noonan syndrome who do not have a mutation by sequencing may have a gain in copy number of PTPN11 and recommend that comprehensive testing for Noonan syndrome should include analysis for copy number changes of PTPN11.     

Inorganic coatings for cardiovascular stents: In vitro and in vivo studies

The in-vitro and in-vivo biocompatibility of two oxides (TiO and ZrO) and diamond-like carbon (D) coated stents has been assessed and compared with uncoated stainless steel (St) stents. In vitro studies demonstrated that both fibrinogen adsorption and platelet adhesion were significantly higher on D coating compared to those on oxide coatings and uncoated stainless steel. In addition TiO and ZrO coatings showed evidence of a minor inflammatory response and more complete endothelialization of the aorta than that seen around D coated and uncoated St stents. The resulting neointimal growth in the aorta with TiO, ZrO, and D coated and uncoated St stents, measured 8 weeks after stenting (the ratio of the neointima in the stented artery to the non-stented artery) was 1.03 + 0.28, 0.85 + 0.36, 1.78 + 1.26, and 1.15 + 0.56, accordingly. From the data obtained it could be concluded that the increased neointima measured around D-coated stents, may be due to both, the inferior haemocompatibility of the diamond-like carbon coating and mechanical instability of D coating observed in an in vivo environment.