Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening infections and inflammatory complications. Allogeneic hematopoietic cell transplantation (allo-HCT) can ...cure the disease, but the indication to transplant remains controversial. We performed a retrospective multicenter study of 712 patients with CGD who underwent allo-HCT transplantation from March 1993 through December 2018. We studied 635 children (aged <18 years) and 77 adults. Median follow-up was 45 months. Median age at transplantation was 7 years (range, 0.1-48.6). Kaplan-Meier estimates of overall survival (OS) and event-free survival (EFS) at 3 years were 85.7% and 75.8%, respectively. In multivariate analysis, older age was associated with reduced survival and increased chronic graft-versus-host disease. Nevertheless, OS and EFS at 3 years for patients ≥18 years were 76% and 69%, respectively. Use of 1-antigen-mismatched donors was associated with reduced OS and EFS . No significant difference was found in OS, but a significantly reduced EFS was noted in the small group of patients who received a transplant from a donor with a >1 antigen mismatch. Choice of conditioning regimen did not influence OS or EFS. In summary, we report an excellent outcome after allo-HCT in CGD, with low incidence of graft failure and mortality in all ages. Older patients and recipients of 1-antigen-mismatched grafts had a less favorable outcome. Transplantation should be strongly considered at a younger age and particularly in the presence of a well-matched donor.
•An excellent outcome was obtained after allo-HCT in 712 patients with CGD, with a low incidence of graft failure and mortality.•HCT for CGD should be strongly considered in young patients, particularly in the presence of a well-matched donor.
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One of the most severe traumatic brain injuries, the subdural haematoma, is related to damage and rupture of the bridging veins, generating an abnormal collection of blood between the dura mater and ...arachnoid mater. Current numerical models of these vessels rely on very simple geometries and material laws, limiting its accuracy and bio-fidelity.
In this work, departing from an existing human head numerical model, a realistic geometry for the bridging veins was developed, devoting special attention to the finite elements type employed. A novel and adequate constitutive model including damage behavior was also successfully implemented.
Results attest that vessel tearing onset was correctly captured, after comparison against experiments on cadavers.
Doing so, the model allow to precisely predict the individual influence of kinematic parameters such as the pulse duration, linear and rotational accelerations in promoting vessel tearing.
•Detailed numerical modeling of the superior sagittal sinus and 9 pairs of bridging veins•Constitutive modeling including elasto-plasticity and ductile damage•Integration into a finite element head model and validation against experiments on cadavers
Hybrid polymer/lipid large unilamellar vesicles (LUVs) were studied by small angle neutron scattering (SANS), time-resolved Förster resonance energy transfer (TR-FRET), and cryo-transmission ...electron microscopy (cryo-TEM). For the first time in hybrid vesicles, evidence for phase separation at the nanoscale was obtained, leading to the formation of stable nanodomains enriched either in lipid or polymer. This stability was allowed by using vesicle-forming copolymer with a membrane thickness close to the lipid bilayer thickness, thereby minimizing the hydrophobic mismatch at the domain periphery. Hybrid giant unilamellar vesicles (GUVs) with the same composition have been previously shown to be unstable and susceptible to fission, suggesting a role of curvature in the stabilization of nanodomains in these structures.
Hybrids, i.e., intimately mixed polymer/phospholipid vesicles, can potentially marry in a single membrane the best characteristics of the two separate components. The ability of amphiphilic ...copolymers and phospholipids to self-assemble into hybrid membranes has been studied until now on the submicrometer scale using optical microscopy on giant hybrid unilamellar vesicles (GHUVs), but limited information is available on large hybrid unilamellar vesicles (LHUVs). In this work, copolymers based on poly(dimethylsiloxane) and poly(ethylene oxide) with different molar masses and architectures (graft, triblock) were associated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Classical protocols of LUV formation were used to obtain nanosized self-assembled structures. Using small-angle neutron scattering (SANS), time-resolved Förster resonance energy transfer (TR-FRET), and cryo-transmission electron microscopy (cryo-TEM), we show that copolymer architecture and molar mass have direct influences on the formation of hybrid nanostructures that can range from wormlike hybrid micelles to hybrid vesicles presenting small lipid nanodomains.
Evidence has shown that hospital surfaces are one of the major vehicles of nosocomial infections caused by drug-resistant pathogens. Smart surface coatings presenting multiple antimicrobial activity ...mechanisms have emerged as an advanced approach to safely prevent this type of infection. In this work, industrial waterborne polyurethane varnish formulations containing for the first time cationic polymeric biocides (SPBs) combined with photosensitizer curcumin were developed to afford contact-active and light-responsive antimicrobial surfaces. SPBs were prepared by atom transfer radical polymerization, which allows control over the polymer features that influence antimicrobial efficiency (e.g., molecular weight), while natural curcumin was employed to impart photodynamic activity to the surface. Antibacterial testing against Gram-negative Escherichia coli revealed that glass surfaces coated with the new formulations displayed photokilling effect under white-light (42 mW/cm2) irradiation within only 15 min of exposure. In addition, it was observed a combined antimicrobial effect between the two biocides (cationic SPB and curcumin), with a higher reduction in the number of viable bacteria observed for the surfaces containing cationic SPB/curcumin mixtures in comparison with the one obtained for surfaces only with polymer or without biocides. The waterborne industrial varnish formulations allowed the formation of homogeneous films without the need for addition of a coalescing agent, which can be potentially applied in diverse surface substrates to reduce bacterial transmission infections in healthcare environments.
Recently, highly stretchable and tough hydrogels that are photodegradable on‐demand have been reported. Unfortunately, the preparation procedure is complex due to the hydrophobic nature of the ...photocrosslinkers. Herein, a simple method is reported to prepare photodegradable double‐network (DN) hydrogels that exhibit high stretchability, toughness, and biocompatibility. Hydrophilic ortho‐nitrobenzyl (ONB) crosslinkers incorporating different poly(ethylene glycol) (PEG) backbones (600, 1000, and 2000 g mol−1) are synthesized. These photodegradable DN hydrogels are prepared by the irreversible crosslinking of chains by using such ONB crosslinkers, and the reversible ionic crosslinking between sodium alginate and divalent cations (Ca2+). Remarkable mechanical properties are obtained by combining ionic and covalent crosslinking and their synergistic effect, and by reducing the length of the PEG backbone. The rapid on‐demand degradation of these hydrogels is also demonstrated by using cytocompatible light wavelength (λ = 365 nm) that degrades the photosensitive ONB units. The authors have successfully used these hydrogels as skin‐worn sensors for monitoring human respiration and physical activities. A combination of excellent mechanical properties, facile fabrication, and on‐demand degradation holds promise for their application as the next generation of substrates or active sensors eco‐friendly for bioelectronics, biosensors, wearable computing, and stretchable electronics.
A simple method for preparing highly stretchable, tough, and photodegradable double‐network (DN) hydrogels using ortho‐nitrobenzyl (ONB) crosslinkers with different poly(ethylene glycol) sizes is reported. The stringent design of the ONB structures allows to control the degradation time. The properties of these hydrogels open the way for a new generation of environmentally friendly substrates that can be used for bioelectronics.
Overexpression of human epidermal growth factor receptor-2 (HER-2) occurs in 20% of all breast cancer subtypes, especially those that present the worst prognostic outcome through a very invasive and ...aggressive tumour. HCC-1954 (HER-2+) is a highly invasive, metastatic cell line, whereas MCF-7 is mildly aggressive and non-invasive. We investigated membrane proteins from both cell lines that could have a pivotal biological significance in metastasis. Membrane protein enrichment for HCC-1954 and MCF-7 proteomic analysis was performed. The samples were analysed and quantified by mass spectrometry. High abundance membrane proteins were confirmed by Western blot, immunofluorescence, and flow cytometry. Protein interaction prediction and correlations with the Cancer Genome Atlas (TCGA) patient data were conducted by bioinformatic analysis. In addition, β1 integrin expression was analysed by Western blot in cells upon trastuzumab treatment. The comparison between HCC-1954 and MCF-7 membrane-enriched proteins revealed that proteins involved in cytoskeleton organisation, such as HER-2, αv and β1 integrins, E-cadherin, and CD166 were more abundant in HCC-1954. β1 integrin membrane expression was higher in the HCC-1954 cell line resistant after trastuzumab treatment. TCGA data analysis showed a trend toward a positive correlation between HER-2 and β1 integrin in HER-2+ breast cancer patients. Differences in protein profile and abundance reflected distinctive capabilities for aggressiveness and invasiveness between HCC-1954 and MCF-7 cell line phenotypes. The higher membrane β1 integrin expression after trastuzumab treatment in the HCC-1954 cell line emphasised the need for investigating the contribution of β1 integrin modulation and its effect on the mechanism of trastuzumab resistance.
This paper describes the preparation of a biomimetic Langmuir–Blodgett film of tyrosinase incorporated in a lipidic layer and the use of lutetium bisphthalocyanine as an electron mediator for the ...voltammetric detection of phenol derivatives, which include one monophenol (vanillic acid), two diphenols (catechol and caffeic acid) and two triphenols (gallic acid and pyrogallol). The first redox process of the voltammetric responses is associated with the reduction of the enzymatically formed
o-quinone and is favoured by the lutetium bisphthalocyanine because significant signal amplification is observed, while the second is associated with the electrochemical oxidation of the antioxidant and occurs at lower potentials in the presence of an electron mediator. The biosensor shows low detection limit (1.98
×
10
−6–27.49
×
10
−6
M), good reproducibility, and high affinity to antioxidants (
K
M in the range of 62.31–144.87
μM).
The excellent functionality of the enzyme obtained using a biomimetic immobilisation method, the selectivity afforded by enzyme catalysis, the signal enhancement caused by the lutetium bisphthalocyanine mediator and the increased selectivity of the curves due to the occurrence of two redox processes make these sensors exceptionally suitable for the detection of phenolic compounds.
The present work is a comparative study of different combinations of microcrystalline (MCD) and nanocrystalline diamond (NCD) varieties (monolayers, bi-, tri- and fourfold layers) grown by hot ...filament CVD technique on silicon nitride ceramic substrates. The Hertzian stress states under static indentation are estimated and compared on the basis of the von Mises stress parameter. The diamond multilayer morphology and the structural quality were evaluated step-by-step by SEM, AFM and UV-Raman spectroscopy. By using the multilayer strategy, starting with a MCD adherent layer on Si3N4 ceramic substrates and finishing with a NCD smooth layer at the top, it was possible to keep the surface roughness at a lower RMS level, of around 90nm. The fourfold multilayer configuration allowed obtaining 10μm thick diamond coatings that endure an indentation load of 800N with a Brale cone, before film spalling-off. This behaviour is determined by the high bonding strength of the initial MCD layer grown on the Si3N4 ceramic substrate, where the von Mises stress (J21/2) is estimated as 27GPa.
•Multilayer strategy is ideal to keep low RMS values with high CVD diamond thickness.•A first microcrystalline diamond gives the best adhesion to CVD diamond multilayers.•A top nanocrystalline diamond provides low RMS values to CVD diamond multilayers.•Adhesion strength values of 27GPa are estimated from von Mises stress distribution.
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