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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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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.
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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.
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Neoplasias Ósseas/terapia , Plasmocitoma/terapia , Adolescente , Vértebras Cervicais , Quimiorradioterapia/métodos , Terapia Combinada , Humanos , Masculino , Fusão VertebralRESUMO
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.
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Interleukin (IL)-4 is the most potent factor that causes naive CD4+ T cells to differentiate to the T helper cell (Th) 2 phenotype, while IL-12 and interferon gamma trigger the differentiation of Th1 cells. However, the source of the initial polarizing IL-4 remains unclear. Here, we show that IL-6, probably secreted by antigen-presenting cells, is able to polarize naive CD4+ T cells to effector Th2 cells by inducing the initial production of IL-4 in CD4+ T cells. These results show that the nature of the cytokine (IL-12 or IL-6), which is produced by antigen-presenting cells in response to a particular pathogen, is a key factor in determining the nature of the immune response.
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Linfócitos T CD4-Positivos/efeitos dos fármacos , Interleucina-4/biossíntese , Interleucina-6/farmacologia , Animais , Células Apresentadoras de Antígenos/fisiologia , Linfócitos T CD4-Positivos/fisiologia , Diferenciação Celular/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
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.
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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.
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Linhagem Celular , Células-Tronco Pluripotentes Induzidas , Doenças da Imunodeficiência Primária/genética , Diferenciação Celular , Classe I de Fosfatidilinositol 3-Quinases/genética , Fibroblastos , Humanos , MutaçãoRESUMO
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.
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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.
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Imunoterapia Adotiva/métodos , Células Matadoras Naturais/transplante , Leucemia/terapia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD19/imunologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Feminino , Sangue Fetal/imunologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Células Matadoras Naturais/imunologia , Leucemia/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Indução de RemissãoRESUMO
The effect of anti-interleukin (IL-12 treatment on Lyme borreliosis in C3H/HeN (C3H) mice was assessed because other studies have implicated CD4+ T cell helper (Th) type 1 responses in the genesis of disease caused by Borrelia burgdorferi. Infection of inbred mice with B. burgdorferi results in varying degrees of arthritis: BALB/c mice develop mild disease and C3H mice develop severe arthritis that is most pronounced 2-4 wk after infection. Since IL-12 is a major inducer of Th1 responses, we blocked this cytokine in vivo in B. burgdorferi infected C3H mice, and evaluated the effects of treatment on the development of arthritis at the peak of acute joint inflammation (14 d) and in the resolution phase (60 d) of disease. As expected, intraperitoneal administration of an anti-IL-12 monoclonal antibody (mAb) to C3H mice resulted in a decrease in both IFN-gamma and B. burgdorferi-specific IgG2a in serum, indicative of diminished Th1 responses. No IL-4 production was detected in serum of anti-IL-12 mAb treated or control mice. IgG1 and IgG2b levels did not increase in B. burgdorferi infected mice treated with anti-IL-12 mAb compared with controls suggesting that Th2 responses were not affected. Nevertheless, CD4+ T cells from both control and anti-IL-12 mAb treated mice had similar in vitro responses to B. burgdorferi antigens. Treatment with anti-IL-12 mAb produced a significant reduction in peak arthritis severity, and an increase in the number of spirochetes in ear tissue. These data show that treatment of B. burgdorferi infected mice with anti-IL-12 mAb results in a reduction of the Th1 and/or innate immune responses in vivo and a reduction in the severity of acute murine Lyme arthritis.
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Interleucina-12/uso terapêutico , Doença de Lyme/terapia , Animais , Borrelia/crescimento & desenvolvimento , Linfócitos T CD4-Positivos/imunologia , Feminino , Imunoglobulina G/imunologia , Interferon gama/fisiologia , Doença de Lyme/microbiologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C3H , Células Th1/imunologiaRESUMO
Borrelia burgdorferi outer surface protein (Osp) A has been used as a Lyme disease vaccine that blocks transmission: OspA antibodies of immune hosts enter ticks during blood feeding and destroy spirochetes before transmission to the host can occur. B. burgdorferi produce OspA in the gut of unfed Ixodes scapularis ticks, and many spirochetes repress OspA production during the feeding process. This preferential expression suggests that OspA may have an important function in the vector. Here we show that OspA mediates spirochete attachment to the tick gut by binding to an I. scapularis protein. The binding domains reside in the central region and COOH-terminus of OspA. OspA also binds to itself, suggesting that spirochete-spirochete interactions may further facilitate adherence in the gut. OspA-mediated attachment in the tick provides a possible mechanism for how stage-specific protein expression can contribute to pathogenesis during the B. burgdorferi natural cycle.
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Antígenos de Superfície/fisiologia , Proteínas da Membrana Bacteriana Externa/fisiologia , Grupo Borrelia Burgdorferi/fisiologia , Grupo Borrelia Burgdorferi/patogenicidade , Ixodes/microbiologia , Lipoproteínas , Sequência de Aminoácidos , Animais , Antígenos de Superfície/genética , Antígenos de Superfície/imunologia , Vetores Aracnídeos , Aderência Bacteriana/genética , Aderência Bacteriana/imunologia , Aderência Bacteriana/fisiologia , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas , Sequência de Bases , Grupo Borrelia Burgdorferi/genética , Primers do DNA/genética , Sistema Digestório/microbiologia , Humanos , Doença de Lyme/etiologia , Doença de Lyme/prevenção & controle , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Ligação ProteicaRESUMO
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.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Hipersensibilidade a Drogas/classificação , Administração Oral , Adolescente , Adulto , Idoso , Anafilaxia/induzido quimicamente , Angioedema/induzido quimicamente , Anti-Inflamatórios não Esteroides/administração & dosagem , Asma/induzido quimicamente , Criança , Pré-Escolar , Reações Cruzadas , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Hipersensibilidade a Drogas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rinite/induzido quimicamente , Método Simples-Cego , Espanha , Urticária/induzido quimicamenteRESUMO
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.
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Cimentos Ósseos/uso terapêutico , Injeções Intralesionais , Sacro/patologia , Neoplasias da Coluna Vertebral , Adulto , Neoplasias da Mama/patologia , Vias de Administração de Medicamentos , Feminino , Humanos , Cuidados Paliativos , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/terapiaRESUMO
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.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Ciclofosfamida/uso terapêutico , Leucemia Mieloide Aguda/terapia , Transplante Haploidêntico/métodos , Adolescente , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/mortalidade , Adulto JovemRESUMO
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.
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Formação de Anticorpos/efeitos dos fármacos , Transplante de Coração , Infecções Pneumocócicas/imunologia , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/imunologia , Formação de Anticorpos/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Meningites Bacterianas/induzido quimicamente , Meningites Bacterianas/imunologia , Pessoa de Meia-Idade , Monitorização Imunológica , Infecções Pneumocócicas/induzido quimicamente , Vacinas Pneumocócicas/uso terapêutico , Streptococcus pneumoniae/isolamento & purificação , Fatores de Tempo , Condicionamento Pré-Transplante , VacinaçãoRESUMO
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.
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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.
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Lesões Encefálicas/fisiopatologia , Encéfalo/irrigação sanguínea , Adolescente , Adulto , Idoso , Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Estudos de Coortes , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , Estudos Prospectivos , Fatores de RiscoRESUMO
Epstein-Barr virus-associated smooth muscle proliferations have been reported in immunosuppressed patients with acquired immunodeficiency syndrome and after organ transplantation. We report here a case of a histologically benign case arising in a 48-year-old male who had received immunosuppressive therapy 4 years earlier, after cardiac transplantation. In the necropsy performed for unrelated reasons, an incidental left intramyocardial tumor was discovered. The presence of Epstein-Barr virus was confirmed by EBER-1 in situ hybridization and polymerase chain reaction. To the best of our knowledge, this is the first case of an Epstein-Barr virus-associated smooth muscle proliferation arising in the heart after cardiac transplantation and should be added to the potential complications of this kind of procedure.