Generation, establishment and characterization of a pluripotent stem cell line (CVTTHi001-A) from primary fibroblasts isolated from a patient with activated PI3 kinase delta syndrome (APDS2).

APDS2 is caused by mutations in PIK3R1 gene resulting in constitutive PI3Kδ activation. PI3Kδ is predominantly expressed in leukocytes and plays critical roles in regulating immune responses. Here we first derived fibroblast primary cells from a skin biopsy of a patient carrying a heterozygous single T deletion in intron 11 of the PIK3R1 gene. We next present the derivation of an induced pluripotent stem cell (iPS) line using a non-integrative reprogramming technology. Pluripotent-related hallmarks are further shown, including: iPSCs self-renewal and expression of pluripotent and differentiation markers after in vitro differentiation towards embryonic germ layers, assessed by RT-PCR and immunofluorescence.

Publisher Correction: Dimensionally and environmentally ultra-stable polymer composites reinforced with carbon fibres.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Publisher Correction: Dimensionally and environmentally ultra-stable polymer composites reinforced with carbon fibres.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Dimensionally and environmentally ultra-stable polymer composites reinforced with carbon fibres.

The quest to develop materials that enable the manufacture of dimensionally ultra-stable structures for critical-dimension components in spacecraft has led to much research over many decades and the evolution of carbon fibre reinforced polymer materials. This has resulted in structural designs that feature a near-zero coefficient of thermal expansion. However, the dimensional instabilities that result from moisture ingression and release remain the fundamental vulnerability of the matrix, which restricts many applications. Here, we address this challenge by developing a space-qualifiable physical surface barrier that blends within the mechanical properties of the composite, thus becoming part of the composite itself. The resulting enhanced composite features mechanical integrity and a strength that is superior to the underlying composite, while remaining impervious to moisture and outgassing. We demonstrate production capability for a model-sized component for the Sentinel-5 mission and demonstrate such capability for future European Space Agency (ESA) and National Aeronautics and Space Administration (NASA) programmes such as Copernicus Extension, Earth Explorer and Science Cosmic Visions.

Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells.

Among hematological cancers, Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL) are the most common leukemia in children and elderly people respectively. Some patients do not respond to chemotherapy treatments and it is necessary to complement it with immunotherapy-based treatments such as chimeric antigen receptor (CAR) therapy, which is one of the newest and more effective treatments against these cancers and B-cell lymphoma. Although complete remission results are promising, CAR T cell therapy presents still some risks for the patients, including cytokine release syndrome (CRS) and neurotoxicity. We proposed a different immune cell source for CAR therapy that might prevent these side effects while efficiently targeting malignant cells. NK cells from different sources are a promising vehicle for CAR therapy, as they do not cause graft versus host disease (GvHD) in allogenic therapies and they are prompt to attack cancer cells without prior sensitization. We studied the efficacy of NK cells from adult peripheral blood (AB) and umbilical cord blood (CB) against different target cells in order to determine the best source for CAR therapy. AB CAR-NK cells are slightly better at killing CD19 presenting target cells and CB NK cells are easier to stimulate and they have more stable number from donor to donor. We conclude that CAR-NK cells from both sources have their advantages to be an alternative and safer candidate for CAR therapy.

Haplo-Cord transplantation compared to haploidentical transplantation with post-transplant cyclophosphamide in patients with AML.

For patients with AML, the best alternative donor remains to be defined. We analyze outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide (PTCY-haplo) between 2012 and 2014 in GETH centers. The Haplo-Cord cohort included a higher proportion of patients with high disease risk index and use of TBI in the conditioning regimen, and hematopoietic cell transplantation-age Comorbidity Age Index was higher in PTCY-haplo patients. Cumulative incidence of neutrophil engraftment was 97% in the Haplo-Cord and 100% in the PTCY-haplo group, achieved in a median of 12 and 17 days, respectively (P=0.01). Grade II-IV acute GvHD rate was significantly higher in the PTCY-haplo group (9.8% vs 29%, P=0.02) as well as chronic GvHD rates (20% vs 38%, P=0.03). With a median follow-up of 61 months for the Haplo-Cord group and 26 months for the PTCY-haplo cohort, overall survival at 2 years was 55% and 59% (P=0.66), event-free survival was 45% vs 56% (P=0.46), relapse rate was 27% vs 21% (P=0.79), and non-relapse mortality was 17% vs 23% (P=0.54), respectively. In this multicenter experience, Haplo-Cord and PTCY-haplo HSCT offer valid alternatives for patients with AML. Neutrophil engraftment was faster in the Haplo-Cord cohort, with similar survival rates, with higher GvHD rates after haploidentical HSCT.

Multi-Functional Carbon Fibre Composites using Carbon Nanotubes as an Alternative to Polymer Sizing.

Carbon fibre reinforced polymers (CFRP) were introduced to the aerospace, automobile and civil engineering industries for their high strength and low weight. A key feature of CFRP is the polymer sizing - a coating applied to the surface of the carbon fibres to assist handling, improve the interfacial adhesion between fibre and polymer matrix and allow this matrix to wet-out the carbon fibres. In this paper, we introduce an alternative material to the polymer sizing, namely carbon nanotubes (CNTs) on the carbon fibres, which in addition imparts electrical and thermal functionality. High quality CNTs are grown at a high density as a result of a 35 nm aluminium interlayer which has previously been shown to minimise diffusion of the catalyst in the carbon fibre substrate. A CNT modified-CFRP show 300%, 450% and 230% improvements in the electrical conductivity on the 'surface', 'through-thickness' and 'volume' directions, respectively. Furthermore, through-thickness thermal conductivity calculations reveal a 107% increase. These improvements suggest the potential of a direct replacement for lightning strike solutions and to enhance the efficiency of current de-icing solutions employed in the aerospace industry.

Plasmocytoma of C1 in a child. Case report.

BACKGROUND AND AIM: Vertebral involvement is a common occurrence in myelomas, but isolated involvement of the high cervical spine is exceptionally rare. This factor, together with the pediatric age of our patient, makes this case the first report of a plasmocytoma involving C1. CASE REPORT: A 14-year-old boy, without neurological involvement, presented with cervical pain and a palpable posterior neck mass. Cervical spine radiographs showed an osteolytic lesion at C1 compressing the cervical spinal canal and instability of the craniocervical junction. After a complete study, the patient was diagnosed with solitary plasmocytoma. A sequential treatment was instituted that consisted of radiotherapy after craniocervical junction stabilization with an halo-jacket, followed by occipitocervical stabilization with instrumented arthrodesis that was accompanied by resection of the residual C1 tumor and, finally, with consolidation of the oncological treatment with further radiotherapy. CONCLUSION: The treatment of choice for a cervical solitary plasmocytoma consists of a combination of chemotherapy, corticosteroids, radiotherapy, and immunotherapy, but the main neurosurgical problem is the craniocervical instability as occurred in other tumor of the cervical column.

Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells.

Single-unit umbilical cord blood (CB) SCT is limited by low total nucleated cell (TNC) dose. Co-infusion of CD34+ cells from a third party HLA-mismatched donor, known as dual or haplo-cord transplant, reduces the period of post-transplant neutropenia and related complications. The aim of this study was to analyze the value of early post-transplant peripheral blood (PB) and T cell chimerism after 28 dual transplants regarding CB engraftment. Cumulative incidence of myeloid engraftment at 30 days was 93% with a median time to engraftment of 14 days (10-29). Patients who developed CB graft failure (n=5) showed very low percentages of CB cells on days +14, +21 and +28 with decreasing dynamics. On the other hand, percentages of CB cells in patients who achieved CB engraftment increased over time. Interestingly, such patients showed two distinct chimerism dynamics in PB, but all of them showed a predominance of CB T cells early after SCT with increasing dynamics over time. Early post-transplant chimerism dynamics in PB and T cells predicts CB graft failure enabling rapid therapeutic measures to be applied. On the other hand, early increasing percentages of CB T cells correlates with ultimate CB engraftment.

Nanostructuring of ultra-thin HfO2 layers for high-k/III-V device application.

We report on the nanopatterning by electron beam lithography (EBL) and reactive ion etching (RIE) in a SF6/Ar+ plasma of ultra-thin HfO2 films deposited on GaAs (001) substrates for gate oxide application in next generation III-V metal-oxide-semiconductor field effect transistors (MOSFETs). Characterization of the HfO2/GaAs nanostructured samples by atomic force microscopy (AFM), high-resolution scanning electron microscopy (HRSEM), energy-dispersive X-ray spectroscopy microanalysis (EDX) and transmission electron microscopy (TEM) has shown the formation of well defined HfO2 patterns with nanometre-scale linewidth control and anisotropic profiles. In addition, atomically smooth, stoichiometric and residue-free bottom GaAs etched lines with a lateral dimension of approximately 50 nm have been demonstrated.

The growth of silica and silica-clad nanowires using a solid-state reaction mechanism on Ti, Ni and SiO(2) layers.

A large area compatible and solid-state process for growing silica nanowires is reported using nickel, titanium and silicon dioxide layers on silicon. The silica nanowires also contain silicon, as indicated by Raman spectroscopy. The phonon confinement model is employed to measure the diameter of the Si rich tail for our samples. The measured Raman peak shift and full width at half-maximum variation with the nanowire diameter qualitatively match with data available in the literature. We have investigated the effect of the seedbed structure on the nanowires, and the effect of using different gas conditions in the growth stages. From this, we have obtained the growth mechanism, and deduced the role of each individual substrate seedbed layer in the growth of the nanowires. We report a combined growth mechanism, where the growth is initiated by a solid-liquid-solid process, which is then followed by a vapour-liquid-solid process. We also report on the formation of two distinct structures of nanowires (type I and type II). The growth of these can be controlled by the use of titanium in the seedbed. We also observe that the diameter of the nanowires exhibits an inverse relation with the catalyst thickness.

Rocking ratchets in nanostructured superconducting-magnetic hybrids.

Two rectification mechanisms in vortex lattice dynamics in Nb films have been studied. These two effects are based on ratchet effects, that is, an ac driving force induces a net dc vortex flow. In our case, an input ac current applied to the Nb films, grown on top of arrays of Ni nanotriangles, yields an output dc voltage. These two rectification effects occur when the vortex lattice moves in periodic asymmetric potentials. These pinning potentials are induced by the array of Ni triangles. In one configuration (longitudinal effect) the driven force is applied perpendicular to the triangle reflection symmetry axis; in the second one (transverse effect) the input current is injected parallel to the triangle reflection symmetry axis. In the framework of the rocking ratchet mechanism, the appropriate Langevin equation allows us to model the experimental data, taking into account the vortex-vortex interaction.

Crossed-ratchet effects for magnetic domain wall motion.

We study both experimentally and theoretically the driven motion of domain walls in extended amorphous magnetic films patterned with a periodic array of asymmetric holes. We find two crossed-ratchet effects of opposite sign that change the preferred sense for domain wall propagation, depending on whether a flat or a kinked wall is moving. By solving numerically a simple phi(4) model we show that the essential physical ingredients for this effect are quite generic and could be realized in other experimental systems involving elastic interfaces moving in multidimensional ratchet potentials.

[Percutaneous sacroplasty for relieving pain caused by sacral metastases]. / Sacroplastia como tratamiento del dolor en metástasis sacra.

Percutaneous injection of polymethyl-metacrylate is an increasingly popular treatment for spine metastatic tumors. We present a case of sacral breast carcinoma treated successfully by percutaneous sacroplasty with injection of bone cement, resulting in pain relief.

Challenge-based clinical patterns of 223 Spanish patients with nonsteroidal anti-inflammatory-drug-induced-reactions.

BACKGROUND: The single-blind, placebo controlled oral challenge (SBPCOC) is the definitive way to diagnosis nonsteroidal anti-inflammatory drug (NSAID)-induced reactions. OBJECTIVE: To evaluate 223 NSAID-sensitive patients by means of SBPCOC, and to describe the main clinical patterns found. METHODS: A prospective study was carried out, including 2 patient groups with case histories consistent with NSAID-induced reactions. Of the 223 patients, 174 were diagnosed on the basis of a positive SBPCOC. The second group consisted of 49 patients who were referred because of a documented history of anaphylaxis after taking NSAIDs, and these underwent SBPCOC with potent cyclooxygenase (COX)-1/COX-2 inhibitors, except those reported as being responsible for the reaction. The type of SBPCOC reaction, the NSAID reactivity pattern, and the associated diseases were the main classification criteria. RESULTS: Two broad categories of NSAID-induced reactions were identified: the cross-reactive and selective syndromes. The 150 patients who showed cross-reactive syndromes included 3 types of diseases: type 1, patients with rhinitis and/or asthma who developed nasoocular and/or asthmatic reactions (n=40); type 2, patients with or without chronic urticaria who presented urticaria/angioedema (n=59); and type 3, atopic patients with isolated periorbital angioedema (n=51). In contrast, the selective syndromes, or type 4, included 50 patients who developed anaphylaxis, as well as 11 patients with urticaria during SBPCOC. Finally, a miscellaneous group of reactions not matching any of the above types was identified (n=1 2). CONCLUSIONS: NSAID-sensitive patients can be classified into 4 different groups of reactors, each with well-defined clinical characteristics. Thus, a clinical classification of this NSAID-induced reaction complex is proposed.

Sacroplastia como tratamiento del dolor en metástasis sacra / Percutaneous sacroplasty for relieving pain caused by sacral metastases

La inyección o cementación percutánea de polimetil-metacrilato es un tratamiento cada vez de uso másfrecuente en el tratamiento del dolor en los pacientescon metástasis vertebrales.Se presenta el caso de una paciente de 43 años querefería un cuadro de dolor sacro a punta de dedo muyinvalidante, secundario a infiltración metastásica decarcinoma de mama a nivel del sacro, con una inmediatay drástica mejoría del dolor tras la cementaciónpercutánea

Percutaneous injection of polymethyl-metacrylate isan increasingly popular treatment for spine metastatictumors. We present a case of sacral breast carcinomatreated successfully by percutaneous sacroplasty withinjection of bone cement, resulting in pain relief

An occupational respiratory allergy caused by Sinapis alba pollen in olive farmers.

BACKGROUND: Sinapis alba (white mustard) is a entomophilic species included in the Brassicaceae family. To date it has not been related to allergic sensitization or clinical respiratory disease. METHODS: Twelve olive orchard workers had a history of rhinitis and/or bronchial asthma that occurred during control weed management and/or harvest, from January to March. They underwent skin prick tests (SPT) with S. alba pollen extract and a standard battery of aeroallergens. Sinapis alba pollen extract was prepared for performing quantitative skin tests, enzyme allergosorbent test and nasal challenge test (NCT). A portable monitoring station and an urban volumetric Hirst-type spore trap were used for the aerobiological study. RESULTS: Eleven patients suffered from rhinitis and bronchial asthma and one had only from rhinitis. All patients were sensitized to S. alba pollen extract, and they showed a positive NCT response. In the urban aerobiologic monitoring station the amount of S. alba pollen only exceptionally reached peaks of 21 grains/m(3), whereas in the work environment peaks of 1801 grains/m(3) were detected between 15 February and 7 April. CONCLUSIONS: We demonstrate the existence of a new occupational allergen for olive farmers: S. alba pollen. We point out the importance of perform aerobiological sampling within the occupational environment for the detection and quantification of the allergenic source.

Impaired anti-pneumococcal polysaccharide antibody production and invasive pneumococcal infection following heart transplantation.

An increased risk of invasive pneumococcal infection has been described among adult heart transplant (HT) recipients. Vaccination has been recommended before HT but the appropriate time for revaccination is not known. In a preliminary analysis of a prospective study involving a cohort of 32 HT recipients receiving daclizumab and triple immunosuppresion therapy, a progressive decline in pneumococcal polysaccharide antibody (anti-PPS) levels was observed during the first year after HT. One of the patients who was found to have a decrease in the levels of anti-PPS developed severe pneumococcal meningitis 20 months after HT. Before HT he had received non-conjugated 23-valent pneumococcal vaccine and showed a normal post-immunization anti-PPS production. The data suggest that long-term immunologic monitoring might be useful to recognize impairment of antibody responses under immunosuppressive therapy in HT.

[Evidence of occult systemic hypoperfussion in head injured patients. Preliminary study]. / Existencia de hipoperfusión oculta sistémica en el traumatismo craneoecefálico. Estudio preliminar

OBJECTIVES: To determine the correlation between blood lactic acid levels in the first 48 hours and outcome, in hemodynamically stable patients, with moderate or severe head injury (HI), and to investigate the risk factors associated with abnormal lactate levels. MATERIAL AND METHODS: A prospective observational study, in 210 adults patients with moderate or severe head injury. When the patients were hemodynamically stable, blood lactate concentrations were measured once on admission, twice daily during the first 2 days and once daily until lactate levels were normalized. The whole group 210 patients were divided into 2 groups. Group 1: (LA < 2.2 mmol/L) patients without occult hypoperfussion (OH), and group 2: (LA >or= 2.2 mmol/L) patients with OH. RESULTS: One hundred and fifteen patients (57.76%) were categorized as group 1, and 95 patients (45.24%) as group 2. In the univariate analysis of risk factors for blood lactate >or=2.2 mmol/L the following variables showed statistical significance: severity of the head injury measured by several scales [Glasgow Coma Scale (GCS), Injury Severity Score (ISS), Revised Trauma Score (RTS) and Acute Physiology and Chronic Health Evaluation (APACHE) II], arterial hypotension, hypoxemia, anaemia, hyperglucemia, hypothermia, a greater incidence of norepinephrine infusion, and the higher percentage of type II lesions in the head computerized tomography at admission showed in the group 1 (53.91% vs. 38.94%) (p<0.03). In the multiple logistic regression analysis only two variables were risk independently associated with elevated blood lactate concentration: APACHE II in the first 24 hours: OR 1.12 (95% IC 1.06--1.196; p<0.0001) and the first 48-hours total fluid infusion volumes: OR 1.09 (95% IC 1.021,16; p < 0.0001). The infection rate (63.2% vs 47.8%, p=0.026), and length of ICU stay [mediana (percentil 25--75)] [13.29 (7.11--21.22) days vs. 8.78 (4.40--16.72) days; p<0.018] were significantly higher in patients with blood lactate >or=2.2 mmol/L (group 2). Although, the percentage of intracranial hypertension and mortality was higher in the group 2, there was no significant difference. In the multivariate analysis, the increase of blood lactate concentration, was not independently associated as a risk factor with studied complications. CONCLUSIONS: The presence of OH in patients with moderate or severe head injury, with postres uscitation arterial pressure, according to present recommendations, is associated with a more severe head injury, showed by APACHE II and the total fluid infusion volumes in the first 48 hours. OH in head injury increases the infection rate and length of ICU stay.