Structure-stiffness relation of live mouse brain tissue determined by depth-controlled indentation mapping

The mechanical properties of brain tissue play a pivotal role in neurodevelopment and neurological disorders. Yet, at present, there is no consensus on how the different structural parts of the tissue contribute to its stiffness variations. Here, we have gathered depth-controlled indentation viscoelasticity maps of the hippocampus of isolated horizontal live mouse brain sections. Our results confirm the highly viscoelestic nature of the material and clearly show that the mechanical properties correlate with the different morphological layers of the samples investigated. Interestingly, the relative cell nuclei area seems to negatively correlate with the stiffness observed

Surface Grafting of Poly(L-glutamates). 3. Block Copolymerization

This paper describes for the first time the synthesis of surface-grafted AB-block copolypeptides, consisting of poly(γ-benzyl L-glutamate) (PBLG) as the A-block and poly(γ-methyl L-glutamate) (PMLG) as the B-block. Immobilized primary amine groups of (γ-aminopropyl)triethoxysilane (APS) on silicon wafers initiated the ring-opening polymerization of N-carboxyanhydrides of glutamic acid esters (NCAs). After removal of the BLG-NCA monomer solution after a certain reaction time, the amine end groups of the formed PBLG blocks acted as initiators for the second monomers. This method provides the possibility of making layered structures of surface-grafted block copolymers with tuned properties. Ellipsometry and small-angle X-ray reflection (SAXR) measurements revealed the thickness of the polypeptide layers ranging from 45-100 Å of the first block to 140-270 Å for the total block copolypeptides. The chemical composition of the blocks was determined by X-ray photoelectron spectroscopy (XPS). In addition, Fourier transform infrared transmission spectroscopy (FT-IR) revealed that the polypeptide main chains of both blocks consisted of pure R-helices. The average orientation of the helices ranging from 22-42° with respect to the substrate within the first block to 31-35° in the second block could be derived with FT-IR as well.

An assessment of validity and responsiveness of generic measures of health-related quality of life in hearing impairment

This article is made available through the Brunel Open Access Publishing Fund. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Purpose: This review examines psychometric performance of three widely used generic preference-based measures, that is, EuroQol 5 dimensions (EQ-5D), Health Utility Index 3 (HUI3) and Short-form 6 dimensions (SF-6D) in patients with hearing impairments. Methods: A systematic search was undertaken to identify studies of patients with hearing impairments where health state utility values were measured and reported. Data were extracted and analysed to assess the reliability, validity (known group differences and convergent validity) and responsiveness of the measures across hearing impairments. Results: Fourteen studies (18 papers) were included in the review. HUI3 was the most commonly used utility measures in hearing impairment. In all six studies, the HUI3 detected difference between groups defined by the severity of impairment, and four out of five studies detected statistically significant changes as a result of intervention. The only study available suggested that EQ-5D only had weak ability to discriminate difference between severity groups, and in four out of five studies, EQ-5D failed to detected changes. Only one study involved the SF-6D; thus, the information is too limited to conclude on its performance. Also evidence for the reliability of these measures was not found. Conclusion: Overall, the validity and responsiveness of the HUI3 in hearing impairment was good. The responsiveness of EQ-5D was relatively poor and weak validity was suggested by limited evidence. The evidence on SF-6D was too limited to make any judgment. More head-to-head comparisons of these and other preference measures of health are required.Medical Research Counci

Colony-Stimulating Factor 1 Receptor (CSF1R) Regulates Microglia Density and Distribution, but Not Microglia Differentiation In Vivo

Microglia are brain-resident macrophages with trophic and phagocytic functions. Dominant loss-of-function mutations in a key microglia regulator, colony-stimulating factor 1 receptor (CSF1R), cause adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a progressive white matter disorder. Because it remains unclear precisely how CSF1R mutations affect microglia, we generated an allelic series of csf1r mutants in zebrafish to identify csf1r-dependent microglia changes. We found that csf1r mutations led to aberrant microglia density and distribution and regional loss of microglia. The remaining microglia still had a microglia-specific gene expression signature, indicating that they had differentiated normally. Strikingly, we also observed lower microglia numbers and widespread microglia depletion in postmortem brain tissue of ALSP patients. Both in zebrafish and in human disease, local microglia loss also presented in regions without obvious pathology. Together, this implies that CSF1R mainly regulates microglia density and that early loss of microglia may contribute to ALSP pathogenesis. Oosterhof et al. show that colony-stimulating factor 1 receptor (CSF1R) primarily regulates microglia density and not their normal differentiation. In addition, they find widespread depletion of microglia in CSF1R-haploinsufficient zebrafish and leukodystrophy patients, also in the absence of pathology, indicating that microglia depletion may contribute to loss of white matter

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

Differential cargo mobilisation within Weibel-Palade bodies after transient fusion with the plasma membrane.

Inflammatory chemokines can be selectively released from Weibel-Palade bodies (WPBs) during kiss-and-run exocytosis. Such selectivity may arise from molecular size filtering by the fusion pore, however differential intra-WPB cargo re-mobilisation following fusion-induced structural changes within the WPB may also contribute to this process. To determine whether WPB cargo molecules are differentially re-mobilised, we applied FRAP to residual post-fusion WPB structures formed after transient exocytosis in which some or all of the fluorescent cargo was retained. Transient fusion resulted in WPB collapse from a rod to a spheroid shape accompanied by substantial swelling (>2 times by surface area) and membrane mixing between the WPB and plasma membranes. Post-fusion WPBs supported cumulative WPB exocytosis. To quantify diffusion inside rounded organelles we developed a method of FRAP analysis based on image moments. FRAP analysis showed that von Willebrand factor-EGFP (VWF-EGFP) and the VWF-propolypeptide-EGFP (Pro-EGFP) were immobile in post-fusion WPBs. Because Eotaxin-3-EGFP and ssEGFP (small soluble cargo proteins) were largely depleted from post-fusion WPBs, we studied these molecules in cells preincubated in the weak base NH4Cl which caused WPB alkalinisation and rounding similar to that produced by plasma membrane fusion. In these cells we found a dramatic increase in mobilities of Eotaxin-3-EGFP and ssEGFP that exceeded the resolution of our method (∼ 2.4 µm2/s mean). In contrast, the membrane mobilities of EGFP-CD63 and EGFP-Rab27A in post-fusion WPBs were unchanged, while P-selectin-EGFP acquired mobility. Our data suggest that selective re-mobilisation of chemokines during transient fusion contributes to selective chemokine secretion during transient WPB exocytosis. Selective secretion provides a mechanism to regulate intravascular inflammatory processes with reduced risk of thrombosis

Testing the paradox of enrichment along a land use gradient in a multitrophic aboveground and belowground community

In the light of ongoing land use changes, it is important to understand how multitrophic communities perform at different land use intensities. The paradox of enrichment predicts that fertilization leads to destabilization and extinction of predator-prey systems. We tested this prediction for a land use intensity gradient from natural to highly fertilized agricultural ecosystems. We included multiple aboveground and belowground trophic levels and land use-dependent searching efficiencies of insects. To overcome logistic constraints of field experiments, we used a successfully validated simulation model to investigate plant responses to removal of herbivores and their enemies. Consistent with our predictions, instability measured by herbivore-induced plant mortality increased with increasing land use intensity. Simultaneously, the balance between herbivores and natural enemies turned increasingly towards herbivore dominance and natural enemy failure. Under natural conditions, there were more frequently significant effects of belowground herbivores and their natural enemies on plant performance, whereas there were more aboveground effects in agroecosystems. This result was partly due to the “boom-bust” behavior of the shoot herbivore population. Plant responses to herbivore or natural enemy removal were much more abrupt than the imposed smooth land use intensity gradient. This may be due to the presence of multiple trophic levels aboveground and belowground. Our model suggests that destabilization and extinction are more likely to occur in agroecosystems than in natural communities, but the shape of the relationship is nonlinear under the influence of multiple trophic interactions.

Температурное поле в кристалле иттрий-алюминиевого граната при двухстадийном выращивании

Установлено существование оптимального значения теплопроводности, при котором достигается наиболее равномерное распределение модуля температурного градиента на фронте кристаллизации

Критерии оценки когнитивных нарушений после инсульта

Резюмированы определенные современные вопросы, с которыми сталкиваются неврологи и семейные врачи при выявлении и оказании помощи больным, у которых наблюдается ухудшение неврологического состояния в виде прогрессирования когнитивной дисфункции после развития инсульта.Резюмовано окремі сучасні питання, з якими стикаються неврологи і сімейні лікарі при виявленні та наданні допомоги хворим, у яких спостерігається погіршення неврологічного стану у вигляді прогресування когнітивної дисфункції після розвитку інсульту.Some urgent issues faced by neurologists and general practitioners when revealing and rendering medical aid to the patients with aggravation of the neurological state in the form of progression of post−stroke cognitive dysfunction are summarized