Ultrasound-mediated targeted microbubble sonoporation of endothelial cells

Molecular imaging using ultrasound makes use of targeted microbubbles. In this study we investigated whether these microbubbles could also be used to induce drug uptake in endothelial cells. CD31-targeted microbubbles insonified at 1 MHz induced sonoporation when they were larger than 3.0 μm or when their relative vibration amplitude was larger than 0.5. No relationship was found between the position of the microbubble on the cell and the induction of sonoporation

The determination of integral closures and geometric applications

We express explicitly the integral closures of some ring extensions; this is done for all Bring-Jerrard extensions of any degree as well as for all general extensions of degree < 6; so far such an explicit expression is known only for degree < 4 extensions. As a geometric application we present explicitly the structure sheaf of every Bring-Jerrard covering space in terms of coefficients of the equation defining the covering; in particular, we show that a degree-3 morphism f : Y --> X is quasi-etale if and only if the first Chern class of the sheaf f_*(O_Y) is trivial (details in Theorem 5.3). We also try to get a geometric Galoisness criterion for an arbitrary degree-n finite morphism; this is successfully done when n = 3 and less satifactorily done when n = 5.Comment: Advances in Mathematics, to appear (no changes, just add this info

Biofilm formation behaviour of marine filamentous cyanobacterial strains in controlled hydrodynamic conditions

Marine biofouling has severe economic impacts and cyanobacteria play a significant role as early surface colonizers. Despite this fact, cyanobacterial biofilm formation studies in controlled hydrodynamic conditions are scarce. In this work, computational fluid dynamics was used to determine the shear rate field on coupons that were placed inside the wells of agitated 12-well microtiter plates. Biofilm formation by three different cyanobacterial strains was assessed at two different shear rates (4 and 40 s-1 ) which can be found in natural ecosystems and using different surfaces (glass and perspex). Biofilm formation was higher under low shear conditions, and differences obtained between surfaces were not always statistically significant. The hydrodynamic effect was more noticeable during the biofilm maturation phase rather than during initial cell adhesion and optical coherence tomography showed that different shear rates can affect biofilm architecture. This study is particularly relevant given the cosmopolitan distribution of these cyanobacterial strains and the biofouling potential of these organisms.This work was financially supported by project UID/EQU/ 00511/2019 – Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE funded by national funds through FCT/MCTES (PIDDAC) and by the CVMAR+i – Industrial Innovation and Marine Biotechnology Valorisation, funded by INTERREG V A Espanha Portugal (POCTEP) [0302_CVMAR_I_1_P]. The authors also acknowledge support from the EU COST Actions iPROMEDAI (TD1305) and ENBA (CA15216), and M.J.R. acknowledges a PhD grant from FCT (SFRH/BD/140080/2018)

Подарунок Сталіна радянському електорату. (До 70-річчя «великого терору»)

The article is dedicated to mass terror of Soviet period as the tool of state policy

The impact of late treatment-toxicity on generic health-related quality of life in head and neck cancer patients after radiotherapy

SummaryTo examine the impact of late treatment-related xerostomia and dysphagia on health-related quality of life (HRQOL) in head and neck cancer (HNC) patients after radiotherapy. A multi-center cross-sectional survey was performed. Patients with a follow-up of at least 6months after curative radiotherapy, without evidence of recurrent disease were eligible for inclusion. The Euroqol-5D questionnaire (EQ-5D) was filled out and toxicity was scored and converted to the RTOG scale. The EQ-5D measures generic HRQOL in terms of utility and visual analogue scale (VAS) scores. Missing data on the EQ-5D were imputed using multiple imputation. HRQOL was compared between subgroups of patients with and without toxicity. Subsequently, the impact of xerostomia and dysphagia on HRQOL was analyzed using multivariate regression analyses. Both analyses were performed separately for utility scores and VAS scores. The study population was composed of 396 HNC patients. The average utility and VAS scores were 0.85 (scale 0–1) and 75 (scale 0–100). Subgroups of patients with xerostomia and/or dysphagia showed statistically significantly lower utility and VAS scores (P=0.000–0.022). The multivariate regression model showed that xerostomia and dysphagia were negative predictors of both utility and VAS scores. Other factors which influenced HRQOL in at least one of the two regression models were: sex, tumor location and the addition of surgery to radiotherapy. Xerostomia and dysphagia diminish generic HRQOL. Moreover dysphagia affects patients’ HRQOL stronger than xerostomia

Fatal cerebral edema associated with serine deficiency in CSF

Two young girls without a notable medical history except for asthma presented with an acute toxic encephalopathy with very low serine concentrations both in plasma and cerebrospinal fluid (CSF) comparable to patients with 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency. Clinical symptoms and enzyme measurement (in one patient) excluded 3-PGDH deficiency. Deficiencies in other serine biosynthesis enzymes were highly unlikely on clinical grounds. On basis of the fasting state, ketone bodies and lactate in plasma, urine and CSF, we speculate that reduced serine levels were due to its use as gluconeogenic substrate, conversion to pyruvate by brain serine racemase or decreased L-serine production because of a lack of glucose. These are the first strikingly similar cases of patients with a clear secondary serine deficiency associated with a toxic encephalopathy

Anionic metabolic profiling of urine from antibiotic-treated rats by capillary electrophoresis-mass spectrometry

Abstract A recently developed capillary electrophoresis (CE)-negative-ionisation mass spectrometry (MS) method was used to profile anionic metabolites in a microbial-host co-metabolism study. Urine samples from rats receiving antibiotics (penicillin G and streptomycin sulfate) for 0, 4, or 8 days were analysed. A quality control sample was measured repeatedly to monitor the performance of the applied CE-MS method. After peak alignment, relative standard deviations (RSDs) for migration time of five representative compounds were below 0.4 %, whereas RSDs for peak area were 7.9-13.5 %. Using univariate and principal component analysis of obtained urinary metabolic profiles, groups of rats receiving different antibiotic treatment could be distinguished based on 17 discriminatory compounds, of which 15 were downregulated and 2 were upregulated upon treatment. Eleven compounds remained down-or upregulated after discontinuation of the antibiotics administration, whereas a recovery effect was observed for others. Based on accurate mass, nine compounds were putatively identified; these included the microbialmammalian co-metabolites hippuric acid and indoxyl sulfate. Some discriminatory compounds were also observed by other analytical techniques, but CE-MS uniquely revealed ten metabolites modulated by antibiotic exposure, including aconitic acid and an oxocholic acid. This clearly demonstrates the added value of CE-MS for nontargeted profiling of small anionic metabolites in biological samples

White Matter Connectivity Abnormalities in Prediabetes and Type 2 Diabetes:The Maastricht Study

OBJECTIVE: Prediabetes and type 2 diabetes are associated with structural brain abnormalities, often observed in cognitive disorders. Besides visible lesions, (pre)diabetes might also be associated with alterations of the intrinsic organization of the white matter. In this population-based cohort study, the association of prediabetes and type 2 diabetes with white matter network organization was assessed. RESEARCH DESIGN AND METHODS: In the Maastricht Study, a type 2 diabetes-enriched population-based cohort study (1,361 normal glucose metabolism, 348 prediabetes, and 510 type 2 diabetes assessed by oral glucose tolerance test; 52% men; aged 59 ± 8 years), 3 Tesla structural and diffusion MRI was performed. Whole-brain white matter tractography was used to assess the number of connections (node degree) between 94 brain regions and the topology (graph measures). Multivariable linear regression analyses were used to investigate the associations of glucose metabolism status with network measures. Associations were adjusted for age, sex, education, and cardiovascular risk factors. RESULTS: Prediabetes and type 2 diabetes were associated with lower node degree after full adjustment (standardized [st]βPrediabetes = -0.055 [95% CI -0.172, -0.062], stβType2diabetes = -0.256 [-0.379, -0.133], Ptrend < 0.001). Prediabetes was associated with lower local efficiency (stβ = -0.084 [95% CI -0.159, -0.008], P = 0.033) and lower clustering coefficient (stβ = -0.097 [95% CI -0.189, -0.005], P = 0.049), whereas type 2 diabetes was not. Type 2 diabetes was associated with higher communicability (stβ = 0.148 [95% CI 0.042, 0.253], P = 0.008). CONCLUSIONS: These findings indicate that prediabetes and type 2 diabetes are associated with fewer white matter connections and weaker organization of white matter networks. Type 2 diabetes was associated with higher communicability, which was not yet observed in prediabetes and may reflect the use of alternative white matter connections