Sulodexide reduces glucose induced senescence in human retinal endothelial cells.

Chronic exposure of retinal endothelium cells to hyperglycemia is the leading cause of diabetic retinopathy. We evaluated the effect of high glucose concentration on senescence in human retinal endothelial cells (HREC) and modulation of that effect by Sulodexide. Experiments were performed on HREC undergoing in vitro replicative senescence in standard medium or medium supplemented with glucose 20 mmol/L (GLU) or mannitol 20 mnol/L (MAN). Effect of Sulodexide 0.5 LRU/mL (SUL) on the process of HREC senescence was studied. Glucose 20 mmol/L accelerates senescence of HREC: population doubling time (+ 58%, p < 0.001) ß-galactosidase activity (+ 60%, p < 0.002) intracellular oxidative stress (+ 65%, p < 0.01), expression of p53 gene (+ 118%, p < 0.001). Senescent HREC had also reduced transendothelial electrical resistance (TEER) (- 30%, p < 0.001). Mannitol 20 mmol/L used in the same scenario as glucose did not induce HREC senescence. In HREC exposed to GLU and SUL, the senescent changes were smaller. HREC, which became senescent in the presence of GLU, demonstrated higher expression of genes regulating the synthesis of Il6 and VEGF-A, which was reflected by increased secretion of these cytokines (IL6 + 125%, p < 0.001 vs control and VEGF-A + 124% p < 0.001 vs control). These effects were smaller in the presence of SUL, and additionally, an increase of TEER in the senescent HREC was observed. Chronic exposure of HREC to high glucose concentration in medium accelerates their senescence, and that process is reduced when the cells are simultaneously exposed to Sulodexide. Additionally, Sulodexide decreases the secretion of IL6 and VEGF-A from senescent HREC and increases their TEER.

Cortical regions supporting reading comprehension skill for single words and discourse.

A substantial amount of variation in reading comprehension skill is explained by listening comprehension skill, suggesting tight links between printed and spoken discourse processing. In addition, both word level (e.g., vocabulary) and discourse-level sub-skills (e.g., inference-making) support overall comprehension. However, while these contributions to variation in comprehension skill have been well-studied behaviorally, the underlying neurobiological basis of these relationships is less well understood. In order to examine the neural bases of individual differences in reading comprehension as a function of input modality and processing level, we examined functional neural activation to both spoken and printed single words and passages in adolescents with a range of comprehension skill. Data driven Partial Least Squares Correlation (PLSC) analyses revealed that comprehension skill was positively related to activation in a number of regions associated with discourse comprehension and negatively related to activation in regions associated with executive function and memory across processing levels and input modalities.

Bilingualism yields language-specific plasticity in left hemisphere's circuitry for learning to read in young children.

How does bilingual exposure impact children's neural circuitry for learning to read? Theories of bilingualism suggests that exposure to two languages may yield a functional and neuroanatomical adaptation to support the learning of two languages (Klein et al., 2014). To test the hypothesis that this neural adaptation may vary as a function of structural and orthographic characteristics of bilinguals' two languages, we compared Spanish-English and French-English bilingual children, and English monolingual children, using functional Near Infrared Spectroscopy neuroimaging (fNIRS, ages 6-10, N =26). Spanish offers consistent sound-to-print correspondences ("phonologically transparent" or "shallow"); such correspondences are more opaque in French and even more opaque in English (which has both transparent and "phonologically opaque" or "deep" correspondences). Consistent with our hypothesis, both French- and Spanish-English bilinguals showed hyperactivation in left posterior temporal regions associated with direct sound-to-print phonological analyses and hypoactivation in left frontal regions associated with assembled phonology analyses. Spanish, but not French, bilinguals showed a similar effect when reading Irregular words. The findings inform theories of bilingual and cross-linguistic literacy acquisition by suggesting that structural characteristics of bilinguals' two languages and their orthographies have a significant impact on children's neuro-cognitive architecture for learning to read.

Comparison of human metapneumovirus, respiratory syncytial virus and Rhinovirus respiratory tract infections in young children admitted to hospital.

Respiratory Syncytial Virus (RSV), Human metapneumovirus (HMPV), and Rhinoviruses (RV) are frequent causes of respiratory tract infections in young children. We compared laboratory and clinical findings in children with comparable age distribution and hospitalized due to RSV, HMPV or RV infections. Viral pathogens were detected by a quantitative real time PCR from nasopharyngeal aspirates. No significant differences in the admission diagnosis, laboratory parameters, patient demographics and treatment measures between the three viral causes of respiratory illness were found. No correlation between viral load and disease severity was observed however, there was a significantly lower concentration of the nasopharyngeal interleukin 8 (IL-8) in children with RV compared to HMPV and RSV, indicating a milder proinflammatory reaction. Moreover, RV-infected children had significantly lower body temperature, higher leucocyte counts in peripheral blood, and a tendency to have a shorter stay in hospital than children with either HMPV or RSV infection. Taken together, clinical presentation of the infections with RSV, HMPV, and RV is similar among children of the same age group and not clearly distinguishable by standard clinical or laboratory findings. Therefore, virus specific testing should be included regularly for routine diagnosis of children with respiratory tract infections.

Development of neural systems for reading in the monolingual and bilingual brain: new insights from functional near infrared spectroscopy neuroimaging.

What neural changes underlie reading development in monolingual and bilingual children? We examined neural activation patterns of younger (ages 6-8) and older (ages 8-10) children and adults to see whether early-life language experience influences the development of neural systems for reading. Using functional Near Infrared Spectroscopy, we observed an age-related shift in neural recruitment of language areas (left inferior frontal gyrus [LIFG], superior temporal gyrus [STG]). Bilinguals showed a greater extent and variability of neural activation in bilateral IFG and STG, and higher cognitive areas (dorsolateral prefrontal cortex, rostrolateral prefrontal cortex). This bilingual "neural signature" reveals the extent that neural systems underlying reading development can be modified through differences in early-life language experience.

How age of bilingual exposure can change the neural systems for language in the developing brain: a functional near infrared spectroscopy investigation of syntactic processing in monolingual and bilingual children.

Is the developing bilingual brain fundamentally similar to the monolingual brain (e.g., neural resources supporting language and cognition)? Or, does early-life bilingual language experience change the brain? If so, how does age of first bilingual exposure impact neural activation for language? We compared how typically-developing bilingual and monolingual children (ages 7-10) and adults recruit brain areas during sentence processing using functional Near Infrared Spectroscopy (fNIRS) brain imaging. Bilingual participants included early-exposed (bilingual exposure from birth) and later-exposed individuals (bilingual exposure between ages 4-6). Both bilingual children and adults showed greater neural activation in left-hemisphere classic language areas, and additionally, right-hemisphere homologues (Right Superior Temporal Gyrus, Right Inferior Frontal Gyrus). However, important differences were observed between early-exposed and later-exposed bilinguals in their earliest-exposed language. Early bilingual exposure imparts fundamental changes to classic language areas instead of alterations to brain regions governing higher cognitive executive functions. However, age of first bilingual exposure does matter. Later-exposed bilinguals showed greater recruitment of the prefrontal cortex relative to early-exposed bilinguals and monolinguals. The findings provide fascinating insight into the neural resources that facilitate bilingual language use and are discussed in terms of how early-life language experiences can modify the neural systems underlying human language processing.

Sulodexide modifies intravascular homeostasis what affects function of the endothelium.

PURPOSE: Sulodexide is a mixture of heparin and dermatan sulphate which has an antithrombotic action. It was shown that it has also direct effect on the endothelial cells. We tested the effect of sulodexide on the intravascular homeostasis in patients with peripheral vascular disease. METHODS: Sulodexide was infused iv. at a dose of 1200 Lipoprotein Lipase Releasing Units (LRU) in 10 patients with peripheral vascular disease. Blood samples were collected before the infusion and 1, 6 and 24 hours after the infusion. Inflammatory and fibrinolytic parameters were studied in the collected serum samples. Additionally, ex-vivo effect of the serum samples on in vitro function of the endothelial cells was studied. RESULTS: Infusion of sulodexide caused acute and transient peak of the Hepatocyte Growth Factor (HGF) concentration in blood and decrease of the Vascular Endothelial Growth Factor (VEGF) level, what, as we found in in vitro experiments, was due to adsorption of VEGF to endothelium. We found that HGF enhanced in vitro stimulating effect of VEGF on proliferation of the endothelial cells. Serum level of interleukin-6 was gradually decreased, whereas fibrinolytic activity of serum, reflected by t-PA/PAI-1 ratio, increased. Serum samples obtained from the studied patients suppressed oxidative stress and release of interleukin-6 in endothelial cells maintained in in vitro culture. CONCLUSION: Sulodexide reduces intravascular inflammation and suppresses inflammatory reaction in the endothelial cells; both effects are desirable in patients with peripheral vascular disease.

The "Perceptual Wedge Hypothesis" as the basis for bilingual babies' phonetic processing advantage: new insights from fNIRS brain imaging.

In a neuroimaging study focusing on young bilinguals, we explored the brains of bilingual and monolingual babies across two age groups (younger 4-6 months, older 10-12 months), using fNIRS in a new event-related design, as babies processed linguistic phonetic (Native English, Non-Native Hindi) and non-linguistic Tone stimuli. We found that phonetic processing in bilingual and monolingual babies is accomplished with the same language-specific brain areas classically observed in adults, including the left superior temporal gyrus (associated with phonetic processing) and the left inferior frontal cortex (associated with the search and retrieval of information about meanings, and syntactic and phonological patterning), with intriguing developmental timing differences: left superior temporal gyrus activation was observed early and remained stably active over time, while left inferior frontal cortex showed greater increase in neural activation in older babies notably at the precise age when babies' enter the universal first-word milestone, thus revealing a first-time focal brain correlate that may mediate a universal behavioral milestone in early human language acquisition. A difference was observed in the older bilingual babies' resilient neural and behavioral sensitivity to Non-Native phonetic contrasts at a time when monolingual babies can no longer make such discriminations. We advance the "Perceptual Wedge Hypothesis" as one possible explanation for how exposure to greater than one language may alter neural and language processing in ways that we suggest are advantageous to language users. The brains of bilinguals and multilinguals may provide the most powerful window into the full neural "extent and variability" that our human species' language processing brain areas could potentially achieve.

[Changes of selected immunological parameters after cardiopulmonary bypass in postop period]. / Wplyw krazenia pozaustrojowego na wybrane parametry odpowiedzi immunologicznej z uwzglednieniem przebiegu okresu pooperacyjnego.

The aim of the study was to evaluate the influence of changes of chosen immunological parameters on postoperative course patients after cardiopulmonary bypass operation. Complement components C3, C4 and immunoglobulins IgA, IgG, IgM were taken into account. The group consisted of 70 patients, 51 men at mean age 52.6 +/- 10.8 years and 19 women at mean age 50.7 +/- 11.0 years. All patients were operated in moderate hypothermia 26-32 degrees C with use of crystalloid cardioplegia. We used membrane oxygenators: Safe II (Polystan), Monolyth (Sorin), Maxima (Medtronic) and Bentley (Baxter). In 36 patients with multivessel coronary artery disease the internal thoracic artery and saphena vein grafts were performed. 27 patients underwent the valve prosthesis implantation procedure and 7 correction of the congenital heart dis-ease. The mean extracorporeal perfusion time was 127.5 +/- 51.0 min. The mean aortic cross-clamping time was 65.6 +/- 26.9 min. 6 blood samples were taken in the time periods called from 0 to 5: 0--before the operation, 1--right after the operation, 2--1 day after the operation, 3--3 days after the operation, 4--7 days after the operation, 5--14 days after the operation. All the immunological parameters were measured at the Technicon RA-1000 System device using plasma antibody serum of Behring Company. We compared two groups: 1) 21 patients extubated at operation day with 42 patients extubated at 1-th postoperative day, 2) 38 patients with postoperative organ failure with 32 patients without organ complications. The intubation time was shorter in patients with higher levels of C3 (to 7-th day) and C4 (at 1-th postoperative day). The postoperative organ failure were more frequently in patients with lower postoperative C3 (to 3-th day) and with lower C4 at 1-th postoperative day. The postoperative changes of immunoglobulins IgA, IgG, IgM were similar in patients with complicated and uncomplicated postoperative course.