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During last decades, significant advances have been made in iron-based spin crossover (SCO) complexes, with a particular emphasis on achieving reversible and reproducible thermal hysteresis at room temperature (RT). This pursuit represents a pivotal goal within the field of molecular magnetism, aiming to create molecular devices capable of operating in ambient conditions. Here, we summarize the recent progress of iron complexes with spin transition near RT based on nitrogen ligands containing aromatic rings from molecular design to functional devices. Specifically, we discuss the various factors, including supramolecular interactions, crystal packing, guest molecules and pressure effects, that could influence its cooperativity and the spin transition temperature. Furthermore, the most recent advances in their implementation as mechanical actuators, switching/memories, sensors, and other devices, have been introduced as well. Finally, we give a perspective on current challenges and future directions in SCO community.
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We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
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COVID-19/imunologia , Biologia Computacional/métodos , Bases de Dados Factuais , SARS-CoV-2/imunologia , Software , Antivirais/uso terapêutico , COVID-19/genética , COVID-19/virologia , Gráficos por Computador , Citocinas/genética , Citocinas/imunologia , Mineração de Dados/estatística & dados numéricos , Regulação da Expressão Gênica , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/virologia , Redes e Vias Metabólicas/genética , Redes e Vias Metabólicas/imunologia , Células Mieloides/efeitos dos fármacos , Células Mieloides/imunologia , Células Mieloides/virologia , Mapeamento de Interação de Proteínas , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia , Tratamento Farmacológico da COVID-19RESUMO
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Proteínas , Software , Genes , Modelos MolecularesRESUMO
OBJECTIVES: Children with acquired brain injury (ABI) can present with disruptive behavior, which is often a consequence of injury and parent factors. Parent factors are associated with child disruptive behavior. Furthermore, disinhibition in the child also leads to disruptive behavior. However, it is unclear how these factors interact. We investigated whether parental factors influence child disruptive behavior following ABI and how these factors interact. METHODS: Parents of 77 children with ABI participated in the study. Parent factors (executive dysfunction, trait-anxiety), potential intervention targets (dysfunctional parenting practices, parental stress, child disinhibition), and child disruptive behavior were assessed. A hypothetical model based on the literature was tested using mediation and path analysis. RESULTS: Mediation analysis revealed that child disinhibition and dysfunctional parenting practices mediated the association of parent factors and child disruptive behavior. Parents' executive dysfunction mediated the association of dysfunctional parenting practices, parental stress and parent trait-anxiety. Parenting practices mediated the association of executive dysfunction and child disruptive behavior. Path analysis indices indicated good model adjustment. Comparative and Tucker-Lewis Index were >0.95, and the root mean square error of approximation was 0.059, with a chi-square of 0.25. CONCLUSIONS: A low level of parental trait-anxiety may be required to reduce dysfunctional parenting practices and child disinhibition. Impairments in child disinhibition can be exacerbated when parents present with high trait-anxiety. Child disinhibition is the major contributor of disruptive behavior reported by parents and teachers. The current study provides evidence of parent anxiety and child disinhibition as possible modifiable intervention targets for reducing child disruptive behavior. (JINS, 2019, 25, 237-248).
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Ansiedade/fisiopatologia , Lesões Encefálicas/fisiopatologia , Comportamento Infantil/fisiologia , Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Inibição Psicológica , Poder Familiar , Comportamento Problema , Adulto , Lesões Encefálicas/complicações , Criança , Disfunção Cognitiva/etiologia , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Modelos EstatísticosRESUMO
Two new heteroleptic complexes [Fe(1bppCOOH)(3bpp-bph)](ClO4)2·solv (1·solv, solv = various solvents; 1bppCOOH = 2,6-bis(1H-pyrazol-1-yl)isonicotinic acid; 3bpp-bph = 2,6-bis(5-([1,1'-biphenyl]-4-yl)-1H-pyrazol-3-yl)pyridine) and [Fe(1bppCOOH)(1bppCOOEt)](ClO4)2·0.5Me2CO (2·0.5Me2CO, 1bppCOOEt = ethyl 2,6-bis(1H-pyrazol-1-yl)isonicotinate) were designed and prepared. The heteroleptic compound 1·solv was obtained by the combination of stoichiometric amounts of Fe(ClO4)2, 1bppCOOH, and 3bpp-bph, and it was designed to fine-tune the spin crossover (SCO) properties with respect to the previously reported homoleptic compound [Fe(1bppCOOH)2](ClO4)2. Indeed, the introduction of a new substituted 3bpp ligand induces a weaker ligand field in addition to promoting the formation of π···π and C-H···π intermolecular interactions through the biphenyl groups. For the desolvated counterpart 1, this results in a shift of the SCO curve toward room temperature and the observation of a 13 K hysteresis width. Besides, compound 2·0.5Me2CO, which represents the first example of a heteroleptic complex containing two 1bpp tridentate ligands, stabilizes the LS state at room temperature confirming the same trend observed for the corresponding homoleptic compounds. Interestingly, both 1 and 2·0.5Me2CO heteroleptic complexes exhibit photoswitchable properties when irradiating with a 523 nm laser at 10 K. Preliminary characterization of the deposited complexes on native SiO2 by X-ray absorption measurements suggests oxidation and decomposition of the complexes.
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BACKGROUND/AIMS: One hallmark of chronic liver disease in patients with portal hypertension is the formation of portal-systemic collaterals in which angiogenesis has a fundamental role. We studied patients with chronic liver disease undergoing liver transplantation to correlate levels of circulating angiogenic factors in portal and peripheral circulation with portal pressure and portal-systemic collaterals. METHODS: Sixteen patients who underwent liver transplantation were enrolled. During transplant surgery, we determined portal venous pressure and portal-systemic collateral formation. We determined angiogenics mediator levels in systemic and portal plasma. Peripheral plasma from healthy donors was measured as controls. RESULTS: Vascular endothelial growth factor (VEGF)-R1 and 2, Ang-1 and 2, Tie2, FGF- 1 and 2, CD163, PDGFR-ß, PDGFsRα, PDGF-AB and BB, CD163, TGF-ß VASH-1 levels were significantly different in the controls in comparison to cases. Significantly decreased portal venous levels of Ang-1, FGF-1, PDGF-AB/BB, and CC were observed in patients with higher portal pressure. Peripheral VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation. While peripheral VEGF-R1 was higher in patients with severe collateral formation. For portal circulation, VEGF, Ang-1, -pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation Conclusions: Angiogenesis factors correlated with portal pressure and collateral formation and different patterns of circulating angiogenesis mediators were found in peripheral and portal blood of patients with chronic liver disease. These results support the importance of angiogenic pathways in cirrhosis and portal hypertension and highlight areas for further study to identify clinically useful noninvasive markers of portal pressure and collateral formation.
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Circulação Colateral , Hepatopatias/fisiopatologia , Neovascularização Patológica/patologia , Pressão na Veia Porta , Adulto , Idoso , Animais , Doença Crônica , Feminino , Humanos , Fígado/patologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/fisiopatologia , Doadores de TecidosRESUMO
Human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in children. The development of novel prophylactic and therapeutic antiviral drugs against hRSV is imperative to control the burden of disease in the susceptible population. In this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (HO-1) on hRSV replication and pathogenesis on lung inflammation induced by this virus. Our results show that after hRSV infection, HO-1 induction with metalloporphyrin cobalt protoporphyrin IX significantly reduces the loss of body weight due to hRSV-induced disease. Further, HO-1 induction also decreased viral replication and lung inflammation, as evidenced by a reduced neutrophil infiltration into the airways, with diminished cytokine and chemokine production and reduced T cell function. Concomitantly, upon cobalt protoporphyrin IX treatment, there is a significant upregulation in the production of IFN-α/ß mRNAs in the lungs. Furthermore, similar antiviral and protective effects occur by inducing the expression of human HO-1 in MHC class II+ cells in transgenic mice. Finally, in vitro data suggest that HO-1 induction can modulate the susceptibility of cells, especially the airway epithelial cells, to hRSV infection.
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Heme Oxigenase-1/metabolismo , Pulmão/imunologia , Infecções por Vírus Respiratório Sincicial/fisiopatologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/fisiologia , Animais , Linhagem Celular , Citocinas/biossíntese , Citocinas/imunologia , Replicação do DNA , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Heme Oxigenase-1/genética , Humanos , Interferon-alfa/biossíntese , Interferon-alfa/imunologia , Interferon beta/imunologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Camundongos , Protoporfirinas/administração & dosagem , Protoporfirinas/farmacologia , Infecções por Vírus Respiratório Sincicial/imunologia , Linfócitos T/imunologia , Ligação Viral , Internalização do Vírus , Replicação ViralRESUMO
OBJECTIVE: Lung cancer is one the leading causes of mortality worldwide. Symptomatic manifestations of the disease generally occur in the advanced-stage setting, and therefore an important number of patients have advanced or metastatic disease by the time they are diagnosed. This situation contributes to a poor prognosis in the treatment of lung cancer. Evidencebased clinical recommendations are of great value to support decision-making for daily practice, and thus improving health care quality and patient outcomes. MATERIALS AND METHODS: This document was an initiative of the Mexican Society of Oncology (SMEO) in collaboration with Mexican Center of Clinical Excellence (Cenetec) according to Interna- tional Standards. Such standards included those described by the IOM, NICE, SIGN and GI-N. An interdisciplinary Guideline Development Group (GDG) was put together which included medical oncologists, surgical oncologistsc, radiation therapists, and methodologists with expertise in critical appraisal, sys- tematic reviews and clinical practice guidelines development. RESULTS: 62 clinical questions were agreed among members of the GDG. With the evidence identified from systematic reviews, the GDG developed clinical recommendations using a Modified Delphi Panel technique. Patients' representatives validated them. CONCLUSIONS: These Clinical Practice Guideline aims to support the shared decision-making process for patients with different stages of non-small cell lung cancer. Our goal is to improve health-care quality on these patients.
OBJETIVO: El cáncer de pulmón es una de las principales causas de mortalidad alrededor del mundo. Su historia natural, con la manifestación de síntomas en etapas avanzadas y el retraso en su diagnóstico hacen que una gran proporción de pacientes se diagnostiquen en estadios tardíos de la enfermedad, lo que hace muy complicado el tratamiento exitoso de la misma. De esto deriva la importancia de dar origen a recomendaciones basadas en evidencia para soportar la toma de decisiones clínicas por parte de los grupos interdisicplinarios que se encargan del manejo de este padecimiento. MATERIAL Y MÉTODOS: Este documento se desarrolló por parte de la Sociedad Mexicana de Oncología en colaboración con el Centro Nacional de Excelencia Tec- nológica de México (Cenetec) a través de la dirección de integración de Guías de Práctica Clínica en cumplimiento a estándares internacionales como los descritos por el Ins- tituto de Medicina de EUA (IOM, por sus siglas en inglés), el Instituto de Excelencia Clínica de Gran Bretaña (NICE, por sus siglas en inglés), la Red Colegiada para el Desarrollo de Guías de Escocia (SIGN, por sus siglas en inglés), la Red Internacional de Guías (G-I-N, por sus siglas en inglés); entre otros. Se integró en representación de la Sociedad Mexicana de Oncología un Grupo de Desarrollo de la Guía (GDG) de manera interdisciplinaria, considerando oncólogos médicos, cirujanos oncólogos, cirujanos de tórax, radio-oncólogos, y metodólogos con experiencia en revisiones sistemáticas de la literatura y guías de práctica clínica. RESULTADOS: Se consensuaron 62 preguntas cllínicas que abarcaron lo establecido previamente por el GDG en el documento de alcances de la Guía. Se identificó la evidencia científica que responde a cada una de estas preguntas clínicas y se evaluó críticamente la misma, antes de ser incorporada en el cuerpo de evidencia de la Guía. El GDG acordó mediante la técnica de consenso formal de expertos Panel Delphi la redacción final de las recomendaciones clínicas. C. CONCLUSIONES: Esta Guía de Práctica Clínica pretende proveer recomendaciones clínicas para el manejo de los distintos estadios de la enfermedad y que asistan en el proceso de toma de decisiones compartida. El GDG espera que esta guía contribuya a mejorar la calidad de la atención clínica en las pacientes con cáncer de pulmón de células no pequeñas.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Algoritmos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Intervenção Médica Precoce , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de NeoplasiasRESUMO
BACKGROUND AIMS: Recently, clinical studies show that cell therapy with mesenchymal stromal cells (MSCs) improves the sequelae chronically established in paraplegic patients, being necessary to know which of them can obtain better benefit. METHODS: We present here a phase 2 clinical trial that includes six paraplegic patients with post-traumatic syringomyelia who received 300 million MSCs inside the syrinx and who were followed up for 6 months. Clinical scales, urodynamic, neurophysiological, magnetic resonance (MR) and studies of ano-rectal manometry were performed to assess possible improvements. RESULTS: In all the cases, MR at the end of the study showed a clear reduction of the syrinx, and, at this time, signs of improvement in the urodynamic studies were found. Moreover, four patients improved in ano-rectal manometry. Four patients improved in neurophysiological studies, with signs of improvement in evoked potentials in three patients. In the American Spinal Injury Association (ASIA) assessment, only two patients improved in sensitivity, but clinical improvement in neurogenic bowel dysfunction was observed in four patients and three patients described improvement in bladder dysfunction. Spasms reduced in two of the five patients who had them previous to cell therapy, and spasticity was improved in the other two patients. Three patients had neuropathic pain before treatment, and it was reduced or disappeared completely during the study. Only two adverse events ocurred, without relation to the cell therapy. CONCLUSIONS: Cell therapy can be considered as a new alternative to the treatment of post-traumatic syringomyelia, achieving reduction of syrinx and clinical improvements in individual patients.
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Terapia Baseada em Transplante de Células e Tecidos/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Traumatismos da Medula Espinal/terapia , Siringomielia/terapia , Adulto , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Humanos , Imageamento por Ressonância Magnética , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Neuralgia/diagnóstico , Neuralgia/etiologia , Neuralgia/terapia , Paraplegia/diagnóstico , Paraplegia/etiologia , Paraplegia/terapia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico , Siringomielia/diagnóstico , Siringomielia/etiologia , Resultado do TratamentoRESUMO
Objective: We investigated interventions, which aimed to improve cold and hot executive functions (EFs) in children and adolescents with a diagnosis of acquired brain injury (ABI). Methods: The following electronic databases were searched: Medline, CINAHL, PsycINFO, and Pubmed. The database filters limited the search to articles published between 1990 and July 2017 in English or Spanish, including children and adolescents. Articles were read and classified according to the levels of evidence of the Australian National Health and Medical Research Council and the Downs and Black checklist was used for Measuring Study Quality. Results: Thirty studies are reported in this systematic review. Level of evidence, quality of the studies, characteristics of the participants, interventions implemented, and outcomes are described. Conclusions: The study of rehabilitation for executive dysfunction in children with ABI is emerging. Although few high-quality intervention studies exist in this area, which limits conclusions regarding intervention efficacy, results of existing studies suggest that education for parents may be an important component of intervention. Moreover, caregiver involvement may improve the effectiveness of hot EFs rehabilitation interventions, while high intervention session frequency may be important in improving cold EFs. Positive behavior supports and specific training based on a cognitive model provided some promising findings, which require further evaluation.
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Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/reabilitação , Função Executiva/fisiologia , Adolescente , Afeto , Criança , Humanos , Matemática , LeituraRESUMO
BACKGROUND: Acquired brain injury (ABI) during childhood typically causes behaviour problems in the child and high levels of stress in the family. OBJECTIVES: (1) To investigate the feasibility and effectiveness of a parenting programme to: improve behaviour and self-regulation (SR) in Mexican children with ABI, enhance parenting skills, and decrease parental stress in parents of children with ABI; (2) to explore the impact of parent SR on child. METHODS: Case study design with four participants post-ABI, aged 7-12 years, recruited in Mexico City. A parenting programme (Signposts for Building Better Behaviour) was delivered and provided parents with strategies to manage child behaviour. Child behaviour, child self-regulation, parental stress and parenting practices were measured before, immediately post-intervention, and three months post-intervention. RESULTS: At immediate and three months post-intervention improvements in parenting skills, reduction in parental stress, and improvement in child behaviour were identified. CONCLUSIONS: The programme is feasible in a Mexican population and was effective in improving parenting skills and reducing stress in parents of children with ABI, as well as improving child behaviour and behavioural SR. These domains continue improving three months after the intervention. The improvements in challenging behaviour at home did not transfer to the school environment.
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Lesões Encefálicas , Transtornos do Comportamento Infantil/etiologia , Relações Pais-Filho , Poder Familiar/psicologia , Adulto , Lesões Encefálicas/complicações , Lesões Encefálicas/enfermagem , Lesões Encefálicas/psicologia , Criança , Transtornos do Comportamento Infantil/enfermagem , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , México , Testes Neuropsicológicos , Avaliação de Resultados em Cuidados de Saúde , Inquéritos e QuestionáriosRESUMO
The syntheses, structures, magnetic, and proton conductivity properties of a family of bimetallic anilate-based compounds with inserted alkylammonium cations are presented. The structures of (Me2NH2)[MnIICrIII(Br2An)3]·2H2O (1), (Et2NH2)[MnIICrIII(Br2An)3] (2), (Et3NH)[MnIICrIII(Cl2An)3] (3), and [(Et)(i-Pr)2NH][MnIICrIII(Br2An)3]·(CHCl3)0.5·(H2O) (4) contain a 2D anionic network formed by Mn(II) and Cr(III) ions linked through anilate ligands. In 1, 2, and 3, the hexagonal holes of this network are occupied by Me2NH2+, Et2NH2+, or Et3NH+ cations. Interestingly, the small increase of size of the templating cation in 4 ([(Et)(i-Pr)2NH]+ in the place of Me2NH2+, Et2NH2+ or Et3NH+), gives rise to a different structure with half of the cations placed within the layers and the other one in the space between the layers. This leads to bilayers with an interlayer separation similar to those of 1, 2, and 3 separated by larger interbilayer distances. Compounds 1, 2, and 3 show a ferrimagnetic ordering with a Tc of 8.0 K (1), 8.9 K (2), and 8.0 K (3). In 4, the presence of different interlayer distances leads to a metamagnetic behavior when the sample is measured in contact with the mother liquor. The behavior changes in the dry sample, which shows a ferrimagnetic ordering as that of 1, 2, and 3 due to collapse of the structure as confirmed by powder X-ray diffraction. Interestingly, the metamagnetic behavior is recovered after reimmersing the crystals in the mother liquor proving the reversibility of the process. All solids are Grotthuss-type proton conductors with conductivity values ranging between 2.3 × 10-6 S·cm-1 for 3 and 2.4 × 10-5 S·cm-1 for 1 measured at 70 °C and 95% relative humidity and activation energies of â¼0.2 eV.
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INTRODUCTION: Failure to eradicate Helicobacter pylori despite antibiotic treatment is generally attributed to increasing clarithromycin resistance conferred by point mutations in the 23S-rRNA gene or metronidazole resistance attributed to rdxA gene (HP0954) deletion in patients. Scarce data for pediatric population are available from developing countries. OBJECTIVES: The aim of the present study was to determine the presence of A2142G/C and A2143G mutations in the 23S-rRNA gene and/or rdxA gene (HP0954) deletion in a group of symptomatic H pylori-infected children recruited from an area with high infection rate and risk of gastric cancer. PATIENTS AND METHODS: We recruited 118 patients referred for upper endoscopy for gastrointestinal symptoms. The presence of H pylori was determined by urease test and histological staining. The rdxA gene (HP0954) deletion, and 2142G/C and A2143G mutations were determined by polymerase chain reaction-restriction fragment length polymorphism. A subgroup of infected patients received a 14-day regimen of omeprazole, amoxicillin, and clarithromycin. The effectiveness of this regime was determined by stool antigen determination 8 weeks after treatment. RESULTS: About 21% of the analyzed infected patients showed mutation in the 23S-rRNA gene, with the A2143G transition as the more frequent mutation, and 2% of the patients showed rdxA gene (HP0954) deletion. After treatment, 25% of the patients continued to harbor the bacteria; of these, 67% carried the A2143G mutation. CONCLUSIONS: H pylori-infected pediatric patients from Chile show high prevalence of the mutation responsible for clarithromycin resistance. The failure to eradicate H pylori can be attributed to the presence of the A2143G mutation.
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Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Claritromicina/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Nitrorredutases/genética , RNA Ribossômico 23S/genética , Adolescente , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Antibacterianos/uso terapêutico , Sequência de Bases , Criança , Pré-Escolar , Chile/epidemiologia , Claritromicina/uso terapêutico , Países em Desenvolvimento , Feminino , Seguimentos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/genética , Humanos , Masculino , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Mutação Puntual , Polimorfismo de Fragmento de Restrição , Prevalência , Deleção de Sequência , Resultado do TratamentoRESUMO
Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L(+) CD11b(+) DCs. Mice lacking the TSLP receptor deficient mice (tslpr(-/-) ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4(+) and CD8(+) T cells was found in tslpr(-/-) mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr(-/-) mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication.
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Citocinas/metabolismo , Metapneumovirus/fisiologia , Infecções por Paramyxoviridae/metabolismo , Infecções por Paramyxoviridae/virologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Transdução de Sinais , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Linhagem Celular , Citocinas/genética , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Expressão Gênica , Humanos , Interleucina-33 , Interleucina-8/genética , Interleucina-8/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Metapneumovirus/efeitos dos fármacos , Camundongos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Ligante OX40/antagonistas & inibidores , Ligante OX40/genética , Ligante OX40/metabolismo , Infecções por Paramyxoviridae/tratamento farmacológico , Infecções por Paramyxoviridae/genética , Infecções por Paramyxoviridae/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/genética , Pneumonia Viral/patologia , Receptores de Citocinas/antagonistas & inibidores , Receptores de Citocinas/deficiência , Transdução de Sinais/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Replicação Viral , Linfopoietina do Estroma do TimoRESUMO
Reductive genome evolution is a universal phenomenon observed in endosymbiotic bacteria in insects. As the genome reduces its size and irreversibly losses coding genes, the functionalities of the cell system, including the energetics processes, are more restricted. Several energetic pathways can also be lost. How do these reduced metabolic networks sustain the energy needs of the system? Among the bacteria with reduced genomes Candidatus Portiera aleyrodidarum, obligate endosymbiont of whiteflies, represents an extreme case since lacks several key mechanisms for ATP generation. Thus, to analyze the cell energetics in this system, a genome-scale metabolic model of this endosymbiont was constructed, and its energy production capabilities dissected using stoichiometric analysis. Our results suggest that energy generation is coupled to the synthesis of essential amino acids and carotenoids, crucial metabolites in the symbiotic association. A deeper insight showed that ATP production via carotenoid synthesis is also connected with amino acid production. This unusual association of energy production with anabolism suggests that, although minimized, endosymbiont metabolic networks maintain a remarkable biosynthetic potential.
Assuntos
Aminoácidos/metabolismo , Metabolismo Energético , Halomonadaceae/metabolismo , Hemípteros/microbiologia , Simbiose , Animais , Genoma Bacteriano , Halomonadaceae/genética , Análise do Fluxo Metabólico , Redes e Vias Metabólicas , Modelos Biológicos , beta Caroteno/metabolismoRESUMO
The synthesis and magnetostructural characterization of [Fe(III)3(µ3-O)(H2O)3[Fe(II)(bppCOOH)(bppCOO)]6](ClO4)13·(CH3)2CO)6·(solvate) (2) are reported. This compound is obtained as a secondary product during synthesis of the mononuclear complex [Fe(II)(bppCOOH)2](ClO4)2 (1). The single-crystal X-ray diffraction structure of 2 shows that it contains the nonanuclear cluster of the formula [Fe(III)3(µ3-O)(H2O)3[Fe(II)(bppCOOH)(bppCOO)]6](13+), which is formed by a central Fe(III)3O core coordinated to six partially deprotonated [Fe(II)(bppCOOH)(bppCOO)](+) complexes. Raman spectroscopy studies on single crystals of 1 and 2 have been performed to elucidate the spin and oxidation states of iron in 2. These studies and magnetic characterization indicate that most of the iron(II) complexes of 2 remain in the low-spin (LS) state and present a gradual and incomplete spin crossover above 300 K. On the other hand, the Fe(III) trimer shows the expected antiferromagnetic behavior. From the structural point of view, 2 represents the first example in which bppCOO(-) acts as a bridging ligand, thus forming a polynuclear magnetic complex.
RESUMO
OBJECTIVE: To evaluate if the application of a negative-pressure therapy system (Prevena Incision Management System, Kinetics Concepts Inc, [KCI] an Acelity Company, San Antonio, Texas) on ileostomy-closure surgical wounds would reduce surgical site infections (SSIs) in comparison with conventional closure and dressing. DESIGN: Prospective interventional pilot study. SETTING: La Paz University Hospital, tertiary care academic hospital in Madrid, Spain. PATIENTS: The Prevena device was applied on the wounds of 17 consecutive patients undergoing ileostomy reversal. Control subjects were 43 patients undergoing the same procedure, in which conventional dressings were used for the wound. INTERVENTION: The device was applied on the wound immediately after surgery (under sterile conditions) and maintained for 5 to 7 days. Patients were evaluated daily, and on the seventh postoperative day, the device was removed and wounds carefully inspected. Another evaluation was performed a month after the surgical intervention in the outpatient clinic. MAIN OUTCOME MEASURE: The primary end point of the study was the detection of SSI (defined according to the Centers for Disease Control and Prevention definitions). Other intervention-related complications were also registered. MAIN RESULTS: There were no significant differences in demographic variables between groups. In the control group, 9 patients (21%) presented SSI, with statistical significance (P < .038) when compared with the intervention group (0%). There were no complications associated with the application of the Prevena device. Other complications (for example, ileus or obstruction) occurred in 30% of patients. CONCLUSIONS: The negative-pressure Prevena System was safe and easy to use and may prevent SSIs in dirty wounds, such as those from ileostomy closure.
Assuntos
Ileostomia/efeitos adversos , Tratamento de Ferimentos com Pressão Negativa/métodos , Infecções Relacionadas à Prótese/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Humanos , Obstrução Intestinal/cirurgia , Projetos Piloto , Estudos Prospectivos , Infecções Relacionadas à Prótese/microbiologia , Fatores de Risco , Espanha , Infecção da Ferida Cirúrgica/microbiologia , Resultado do TratamentoRESUMO
Respiratory Syncytial Virus (RSV) is the first cause of hospitalization due to bronchiolitis in infants. RSV bronchiolitis has been linked to asthma and recurrent wheezing, however the mechanisms behind this association have not been elucidated. Here, we evaluated the cytokine and chemokine profiles in the airways in infants with RSV bronchiolitis. Nasopharyngeal Aspirates (NPA) and Bronchoalveolar Lavage Fluids (BALF) from infants hospitalized due to RSV bronchiolitis and healthy controls were analyzed for cytokine and chemokine production. We observed elevated levels of Th2 cytokines (IL-3, IL-4, IL-10 and IL-13), pro-inflammatory cytokines and chemokines (IL-1ß, IL-6, TNF-ß, MCP-1/CCL2, MIP-1α/CCL3 and IL-8/CXCL8) in BALF from infants with RSV bronchiolitis, as compared to controls. We found a direct correlation of IL-3 and IL-12p40 levels with the development of recurrent wheezing later in life. These results suggest that IL-3 and IL-12p40 could be considered as molecular predictors for recurrent wheezing due to RSV infection.