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Global warming is linked to progressive soil salinisation, which reduces crop yields, especially in irrigated farmland on arid and semiarid regions. Therefore, it is necessary to apply sustainable and effective solutions that contribute to enhanced crop salt tolerance. In the present study, we tested the effects of a commercial biostimulant (BALOX®) containing glycine betaine (GB) and polyphenols on the activation of salinity defense mechanisms in tomato. The evaluation of different biometric parameters and the quantification of biochemical markers related to particular stress responses (osmolytes, cations, anions, oxidative stress indicators, and antioxidant enzymes and compounds) was carried out at two phenological stages (vegetative growth and the beginning of reproductive development) and under different salinity conditions (saline and non-saline soil, and irrigation water), using two formulations (different GB concentrations) and two doses of the biostimulant. Once the experiments were completed, the statistical analysis revealed that both formulations and doses of the biostimulant produced very similar effects. The application of BALOX® improved plant growth and photosynthesis and assisted osmotic adjustment in root and leaf cells. The biostimulant effects are mediated by the control of ion transport, reducing the uptake of toxic Na+ and Cl- ions and favoring the accumulation of beneficial K+ and Ca2+ cations, and a significant increase in leaf sugar and GB contents. BALOX® significantly reduced salt-induced oxidative stress and its harmful effects, as evidenced by a decrease in the concentration of oxidative stress biomarkers, such as malondialdehyde and oxygen peroxide, which was accompanied by the reduction of proline and antioxidant compound contents and the specific activity of antioxidant enzymes with respect to the non-treated plants.
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OBJECTIVES: The objective of this study was to assess the diagnostic performance of combined computerised tomography (CT) and positron emission tomography (PET) in mediastinal staging of surgical lung cancer based on data obtained from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS). METHODS: A total of 2782 patients underwent surgery for primary lung carcinoma. We analysed diagnostic success in mediastinal lymph node staging (cN2) using CT and PET. Bivariate and multivariate analyses were performed of the factors involved in this success. The risk of unexpected pN2 disease was analysed for cases in which an invasive testing is recommended: cN1, the tumour centrally located or the tumour diameter >3 cm. RESULTS: The overall success of CT together with PET was 82.9% with a positive predictive value of 0.21 and negative predictive value of 0.93. If the tumour was larger than 3 cm and for each unit increase in mediastinal SUVmax, the probability of success was lower with OR 0.59 (0.44-0.79) and 0.71 (0.66-0.75), respectively. In the video-assisted thoracic surgery (VATS) approach, the probability of success was higher with OR 2.04 (1.52-2.73). The risk of unexpected pN2 increased with the risk factors cN1, the tumour centrally located or the tumour diameter >3 cm: from 4.5% (0 factors) to 18.8% (3 factors) but did not differ significantly as a function of whether invasive testing was performed. CONCLUSIONS: CT and PET together have a high negative predictive value. The overall success of the staging is lower in the case of tumours >3 cm and high mediastinal SUVmax, and it is higher when VATS is performed. The risk of unexpected pN2 is higher if the disease is cN1, the tumour centrally located or the tumour diameter >3 cm but does not vary significantly as a function of whether patients have undergone invasive testing.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Cirurgia Torácica Vídeoassistida , Estudos Prospectivos , Estadiamento de Neoplasias , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologiaRESUMO
Metastatic estrogen receptor α (ERα)-positive breast cancer is presently incurable. Seeking to target these drug-resistant cancers, we report the discovery of a compound, called ErSO, that activates the anticipatory unfolded protein response (a-UPR) and induces rapid and selective necrosis of ERα-positive breast cancer cell lines in vitro. We then tested ErSO in vivo in several preclinical orthotopic and metastasis mouse models carrying different xenografts of human breast cancer lines or patient-derived breast tumors. In multiple orthotopic models, ErSO treatment given either orally or intraperitoneally for 14 to 21 days induced tumor regression without recurrence. In a cell line tail vein metastasis model, ErSO was also effective at inducing regression of most lung, bone, and liver metastases. ErSO treatment induced almost complete regression of brain metastases in mice carrying intracranial human breast cancer cell line xenografts. Tumors that did not undergo complete regression and regrew remained sensitive to retreatment with ErSO. ErSO was well tolerated in mice, rats, and dogs at doses above those needed for therapeutic responses and had little or no effect on normal ERα-expressing murine tissues. ErSO mediated its anticancer effects through activation of the a-UPR, suggesting that activation of a tumor protective pathway could induce tumor regression.
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Neoplasias da Mama , Recidiva Local de Neoplasia , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular , Linhagem Celular Tumoral , Cães , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Camundongos , Ratos , Resposta a Proteínas não DobradasRESUMO
A fast PCR-assisted impedimetric biosensor was developed for the selective detection of the clbN gene from the polyketide synthase (pks) genomic island in real Escherichia coli samples. This genomic island is responsible for the production of colibactin, a harmful genotoxin that has been associated with colorectal cancer. The experimental protocol consisted of immobilizing the designated forward primer onto an Au electrode surface to create the sensing probe, followed by PCR temperature cycling in blank, positive, and negative DNA controls. Target DNA identification was possible by monitoring changes in the system's charge transfer resistance values (Rct) before and after PCR treatment through electrochemical impedance spectroscopy (EIS) analysis. Custom-made, flexible gold electrodes were fabricated using chemical etching optical lithography. A PCR cycle study determined the optimum conditions to be at 6 cycles providing fast results while maintaining a good sensitivity. EIS data for the DNA recognition process demonstrated the successful distinction between target interaction resulting in an increase in resistance to charge transfer (Rct) percentage change of 176% for the positive DNA control vs. 21% and 20% for the negative and non-DNA-containing controls, respectively. Results showed effective fabrication of a fast, PCR-based electrochemical biosensor for the detection of pks genomic island with a calculated limit of detection of 17 ng/µL.
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Técnicas Biossensoriais/métodos , Espectroscopia Dielétrica/métodos , Escherichia coli/genética , Genoma Bacteriano , Peptídeos/genética , Policetídeo Sintases/genética , Reação em Cadeia da Polimerase/métodos , Limite de Detecção , PolicetídeosRESUMO
The gut microbiota has been implicated in a number of normal and disease biological processes. Recent studies have identified a subset of gut bacterial genes as potentially involved in inflammatory processes. In this work, we explore the sequence variability for some of these bacterial genes using a combination of deep sequencing and oligotyping, a data analysis application that identifies mutational hotspots in short stretches of DNA. The genes for pks island, tcpC and usp, all harbored by certain strains of E. coli and all implicated in inflammation, were amplified by PCR directly from stool samples and subjected to deep amplicon sequencing. For comparison, the same genes were amplified from individual bacterial clones. The amplicons for pks island and tcpC from stool samples showed minimal levels of heterogeneity comparable with the individual clones. The amplicons for usp from stool samples, by contrast, revealed the presence of five distinct oligotypes in two different regions. Of these, the oligotype GT was found to be present in the control uropathogenic clinical isolate and also detected in stool samples from individuals with colorectal cancer (CRC). Mutational hotspots were mapped onto the USP protein, revealing possible substitutions around Leu110, Glu114, and Arg115 in the middle of the pyocin domain (Gln110, Gln114, and Thr115 in most healthy samples), and also Arg218 in the middle of the nuclease domain (His218 in the uropathogenic strain). All of these results suggest that a level of variability within bacterial pro-inflammatory genes could explain differences in bacterial virulence and phenotype.
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Gut bacterial toxins are thought to contribute to the development of colorectal cancer (CRC). This study examines the presence of specific gut bacterial toxin genes in stool samples from individuals with colorectal neoplasia (adenomas and/or CRC). The presence of bacterial genes encoding genotoxic or pro-inflammatory factors (pks, tcpC, gelE, cnf-1, AMmurB, and usp) was established by PCR of stool samples from individuals from mainland US (n = 30; controls = 10, adenoma = 10, CRC = 10) and from Puerto Rico (PR) (n = 33; controls = 13; adenomas = 8; CRC = 12). Logistic regression models and multinomial logistic regression models were used to estimate the magnitude of association. Distinct bacterial gene profiles were observed in each sample cohort. In individuals with CRC, AMmurB was detected more frequently in samples from the US and gelE in samples from PR. In samples from PR, individuals with ≥2 gut bacterial toxin genes in stool had higher odds of having colorectal neoplasia (OR = 11.0, 95%: CI 1.0â»637.1): however, no significant association between bacterial genes and colorectal neoplasia was observed in the US cohort. Further analyses are warranted in a larger cohort to validate these preliminary findings, but these encouraging results highlight the importance of developing bacterial markers as tools for CRC diagnosis or risk stratification.
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PURPOSE: Medial patellofemoral ligament (MPFL) reconstruction offers good clinical results with a very low rate of instability recurrence. However, its in vivo effect on patellar tracking is not clearly known. The aim of this study is to investigate the effects of MPFL reconstruction on patellar tracking using dynamic 320-detector-row CT. METHODS: Ten patients with patellofemoral instability referred to isolated MPFL reconstruction surgery were selected and subjected to dynamic CT before and ≥6 months after surgery. Patellar tilt angles and shift distance were analysed using computer software specifically designed for this purpose. Kujala and Tegner scores were applied, and the radiation of the CTs was recorded. Two protocols for imaging acquisition were compared: a tube potential of 80 kV and 50 mA versus a tube potential of 120 kV and 100 mA, both with a slice thickness of 0.5 mm and an acquisition duration of 10 s. RESULTS: There were no changes in patellar tracking after MPFL reconstruction. There was no instability relapse. Clinical scores improved from a mean of 51.9 (±15.6)-74.2 (±20.9) on the Kujala scale (p = 0.011) and from a median of 2 (range 0-4) to 4 (range 1-6) on the Tegner scale (p = 0.017). The imaging protocols produced a dose-length product (DLP) of 254 versus 1617 mGycm and a radiation effective estimated dose of 0.2 versus 1.3 mSv, respectively. Both protocols allowed the analysis of the studied parameters without loss of precision. CONCLUSIONS: Reconstruction of the MPFL produced no improvement in patellar tilt or shift in the population studied. The low-radiation protocol was equally effective in measuring changes in patellar tracking and is recommended. Although the procedure successfully stabilized the patella, knee surgeons should not expect patellar shift and tilt correction when performing isolated patellofemoral ligament reconstruction in patients with recurrent patellar instability. LEVEL OF EVIDENCE: IV.
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Instabilidade Articular/cirurgia , Ligamentos Articulares/cirurgia , Tomografia Computadorizada Multidetectores , Patela/diagnóstico por imagem , Patela/fisiopatologia , Luxação Patelar/cirurgia , Articulação Patelofemoral/cirurgia , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/fisiopatologia , Ligamentos Articulares/fisiopatologia , Masculino , Procedimentos Ortopédicos , Patela/cirurgia , Luxação Patelar/diagnóstico por imagem , Luxação Patelar/fisiopatologia , Articulação Patelofemoral/diagnóstico por imagem , Articulação Patelofemoral/fisiopatologia , Procedimentos de Cirurgia Plástica , Recidiva , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Quick diagnosis units (QDUs) are a promising alternative to conventional hospitalization for the diagnosis of suspected serious diseases, most commonly cancer and severe anemia. Although QDUs are as effective as hospitalization in reaching a timely diagnosis, a full economic evaluation comparing both approaches has not been reported. AIMS: To evaluate the costs of QDU vs. conventional hospitalization for the diagnosis of cancer and anemia using a cost-minimization analysis on the proven assumption that health outcomes of both approaches were equivalent. METHODS: Patients referred to the QDU of Bellvitge University Hospital of Barcelona over 51 months with a final diagnosis of severe anemia (unrelated to malignancy), lymphoma, and lung cancer were compared with patients hospitalized for workup with the same diagnoses. The total cost per patient until diagnosis was analyzed. Direct and non-direct costs of QDU and hospitalization were compared. RESULTS: Time to diagnosis in QDU patients (n=195) and length-of-stay in hospitalized patients (n=237) were equivalent. There were considerable costs savings from hospitalization. Highest savings for the three groups were related to fixed direct costs of hospital stays (66% of total savings). Savings related to fixed non-direct costs of structural and general functioning were 33% of total savings. Savings related to variable direct costs of investigations were 1% of total savings. Overall savings from hospitalization of all patients were 867,719.31. CONCLUSION: QDUs appear to be a cost-effective resource for avoiding unnecessary hospitalization in patients with anemia and cancer. Internists, hospital executives, and healthcare authorities should consider establishing this model elsewhere.
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Anemia/diagnóstico , Custos e Análise de Custo , Custos de Cuidados de Saúde , Hospitais Universitários/organização & administração , Tempo de Internação/economia , Neoplasias/diagnóstico , Humanos , Pacientes Internados , Tempo de Internação/estatística & dados numéricos , Pacientes Ambulatoriais , Satisfação do Paciente , EspanhaRESUMO
OBJETIVOS: desenvolver solução para integração de monitores de beira de leito ao Sistema de Informações Hospitalares (SIH). MÉTODOS: Desenvolvimento e implementação de troca de mensagens no padrão Health Level 7, Admit Discharge Transfer (ADT) e Observation (OBX), utilizando a biblioteca HAPI, para cadastro do paciente e coletados parâmetros de monitoramento. Criação de base de dados para seleção e armazenamento dos parâmetros desejados. RESULTADOS: cadastro integrado com o SIH e captura em banco de dados dos parâmetros dos monitores de beira de leito além de interface de teste para visualização dos dados. CONCLUSÃO: Desenvolvido e implementado um sistema para a integração com monitores beira de leito, permitindo uma visão mais abrangente dos dados dos pacientes.
OBJECTIVES: develop solution for integration of bedside monitors to the Hospital Information System (HIS). METHODS: Development and implementation of the exchange of messages using the standard Health Level 7, Admit Discharge Transfer (ADT) and Observation (OBX), using the HAPI library in order to register the patient and to collect parameters from the monitors. It was also created a database in order to support the selection and storage of the desired parameters. RESULTS: registration integrated with HIS and saving of bedside monitors' parameters in database plus test interface for data visualization. CONCLUSION: Developed and implemented a system to integrate with bedside monitors, allowing a more comprehensive view of patient data.
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Humanos , Integração de Sistemas , Monitoramento Ambiental , Nível Sete de Saúde , Congressos como AssuntoRESUMO
The objectives of this study were to estimate global uncertainty for patients with thoracic tumors treated in our center using the CyberKnife VSI after placement of fiducial markers and to compare our findings with the standard CTV to PTV margins used to date. Datasets for 16 patients (54 fractions) treated with the CyberKnife and the Synchrony Respiratory Tracking System were analyzed retrospectively based on CT planning, tracking information, and movement data generated and saved in the logs files by the system. For each patient, we analyzed all the main uncertainty sources and assigned a value. We also calculated an expanded global uncertainty to ensure a robust estimation of global uncertainty and to enable us to determine the position of 95% of the CTV points with a 95% confidence level during treatment. Based on our estimation of global uncertainty and compared with our general mar- gin criterion (5 mm in all three directions: superior/inferior [SI], anterior/posterior [AP], and lateral [LAT]), 100% were adequately covered in the LAT direction, as were 94% and 94% in the SI and AP directions. We retrospectively analyzed the main sources of uncertainty in the CyberKnife process patient by patient. This individualized approach enabled us to estimate margins for patients with thoracic tumors treated in our unit and compare the results with our standard 5 mm margin.
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Radiocirurgia/normas , Neoplasias Torácicas/radioterapia , Marcadores Fiduciais , Humanos , Margens de Excisão , Modelos Teóricos , Planejamento da Radioterapia Assistida por Computador/normas , Estudos Retrospectivos , IncertezaRESUMO
BACKGROUND: The influence of age on rotator cuff function and muscle structure remains poorly understood. We hypothesize that normal aging influences rotator cuff function, muscle structure, and regulatory protein expression in an established rat model of aging. METHODS: Seventeen rats were obtained from the National Institute on Aging. The supraspinatus muscles in 11 middle-aged (12 months old) and 6 old (28 months old) rats were studied for age-related changes in rotator cuff neuromuscular function by in vivo muscle force testing and electromyography (EMG). Changes in muscle structure and molecular changes were assessed with quantitative immunohistochemistry for myogenic determination factor 1 (MyoD) and myogenic factor 5 (Myf5) expression. RESULTS: Old animals revealed significantly decreased peak tetanic muscle force at 0.5 N and 0.7 N preload tension (P < .05). The age of the animal accounted for 20.9% of variance and significantly influenced muscle force (P = .026). Preload tension significantly influenced muscle force production (P < .001) and accounted for 12.7% of total variance. There was regional heterogeneity in maximal compound motor action potential (CMAP) amplitude in the supraspinatus muscle; the proximal portion had a significantly higher CMAP than the middle and distal portions (P < .05). The expression of muscle regulatory factors MyoD and Myf5 was significantly decreased in old animals compared with middle-aged animals (P < .05). CONCLUSIONS: The normal aging process in this rat model significantly influenced contractile strength of the supraspinatus muscle and led to decreased expression of muscle regulatory factors. High preload tensions led to a significant decrease in force production in both middle-aged and old animals.
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Envelhecimento/fisiologia , Manguito Rotador/metabolismo , Manguito Rotador/fisiopatologia , Envelhecimento/metabolismo , Animais , Eletromiografia , Imuno-Histoquímica , Masculino , Modelos Animais , Contração Muscular/fisiologia , Proteína MyoD/biossíntese , Fator Regulador Miogênico 5/biossíntese , Ratos , Manguito Rotador/patologiaRESUMO
The enzyme telomerase is present in about 85% of human cancers which makes it not only a good target for cancer treatment but also an excellent marker for cancer detection. Using a single stranded DNA probe specific for telomerase binding and reverse transcription tethered to an interdigital gold electrode array surface, the chromosome protection provided by the telomerase was replicated and followed by Electrochemical Impedance Spectroscopy as an unlabeled biosensor. Using this system designed in-house, easy and affordable, impedance measurements were taken while incubating at 37 °C and promoting the probe elongation. This resulted in up to 14-fold increase in the charge transfer resistance when testing a telomerase-positive nuclear extract from Jurkat cells compared to the heat-inactivated telomerase-negative nuclear extract. The electron transfer process at the Au electrodes was studied before the elongation, at different times after the elongation, and after desorption of non-specific binding.
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Although predominantly associated with health benefits, the gut microbiota has also been shown to harbor genes that promote inflammation. In this work, we report a method for the direct detection and quantification of these pro-inflammatory bacterial genes by PCR and qPCR in DNA extracted from human stool samples. PCR reactions were performed to detect (i) the pks island genes, (ii) tcpC, which is present in some strains of Escherichia coli and (iii) gelE presented in some strains of Enterococcus faecalis. Additionally, we screened for the presence of the following genes encoding cyclomodulins that disrupted mammalian cell division: (iv) cdt (which encodes the cytolethal distending toxin) and (v) cnf-1 (which encodes the cytotoxic necrotizing factor-1). Our results show that 20% of the samples (N = 41) tested positive for detectable amounts of pks island genes, whereas 10% of individuals were positive for tcpC or gelE and only one individual was found to harbor the cnf-1 gene. Of the 13 individuals that were positive for at least one of the pro-inflammatory genes, 5 were found to harbor more than one. A quantitative version of the assay, which used real-time PCR, revealed the pro-inflammatory genes to be in high copy numbers: up to 1.3 million copies per mg of feces for the pks island genes. Direct detection of specific genes in stool could prove useful toward screening for the presence of pro-inflammatory bacterial genes in individuals with inflammatory bowel diseases or colorectal cancer.
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BACKGROUND: Endoscopic ultrasonography (EUS) and Endoscopic Retrograde Cholangiopancreatography (ERCP) are often required in patients with pancreaticobiliary disorders. AIMS: To assess the clinical impact and costs savings of a single session EUS-ERCP. METHODS: Patient and intervention data from April 2009 to March 2012 were prospectively recruited and retrospectively analyzed from a database at a tertiary hospital. Indications, diagnostic yield, procedure details, complications and costs were evaluated. RESULTS: Fifty-five scheduled combined procedures were done in 53 patients. The accuracy of EUS-fine needle aspiration for malignancy was 90%. The main clinical indication was a malignant obstructing lesion (66%). The ERCP cannulation was successful in 67%, and in 11/15 failed ERCP (73%), drainage was completed thanks to an EUS-guided biliary drainage: 6 transmurals, 5 rendezvous. Eight patients (14%) had related complications: bacteremia (n = 3), pancreatitis (n = 2), bleeding (n = 2) and perforation (n = 1). The mean duration was 65 ± 22.2 min. The mean estimated cost for a single session was 3437, and 4095 for two separate sessions. The estimated cost savings using a single-session strategy was 658 per patient, representing a total savings of 36,189. CONCLUSION: Combined EUS and ERCP is safe, technically feasible and cost beneficial. Furthermore, in failed ERCP cases, the endoscopic biliary drainage can be completed with EUS-guided biliary access in the same procedure.
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Doenças Biliares/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica/economia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/economia , Endossonografia/economia , Custos de Cuidados de Saúde , Pancreatopatias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Biliares/complicações , Biópsia por Agulha Fina/economia , Biópsia por Agulha Fina/normas , Biópsia por Agulha Fina/estatística & dados numéricos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangiopancreatografia Retrógrada Endoscópica/estatística & dados numéricos , Análise Custo-Benefício , Drenagem/economia , Drenagem/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Endossonografia/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatopatias/complicações , Estudos Prospectivos , Estudos Retrospectivos , Centros de Atenção Terciária , Fatores de TempoRESUMO
Neste artigo é apresentada uma arquitetura para a integração do Sistema de Informação hospitalar (SIH) com uma ferramenta colaborativa. Também se descreve o desenvolvimento de seu protótipo, denominado MedCast, realizado em parceria entre o CPqD e o Instituto do Coração (InCor) - HCFMUSP. O MedCast, em sua versão atual, permite a inclusão de casos clínicos por meio de Web services e a discussão de casos com utilização de ferramentas multimídia. O protótipo demonstra que a utilização cuidadosa dessas informações permite o enriquecimento da discussão.
This article presents an architecture for the integration of the Hospital Information System (HIS) with a collaborative tool. It is also described the development of its prototype, called MedCast, as result of a partnership between CPqD and Heart Institute (InCor) - FMUSP. The MedCast, in its current version, allows the inclusion of clinical cases by means of Web services and the discussion of cases with use of multimedia tools. The prototype demonstrates that the careful use of this information is useful to enrich the discussion.
Este artículo presenta una arquitectura para la integración del Sistema de Información Hospitalario (SIH) con una herramienta de colaboración. También se describe el desarrollo de su prototipo, llamado MedCast, hecho en colaboración entre CPqD y el Instituto del Corazón (InCor) - FMUSP. El MedCast, en su versión actual, permite la inclusión de casos clínicos por medio de servicios Web y la discusión de casos con el uso de herramientas multimedia. El prototipo demuestra que el uso cuidadoso de esta información permite enriquecer el debate.
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Comportamento Cooperativo , Sistemas Computadorizados de Registros Médicos , Sistemas de Informação Hospitalar , Disseminação de Informação , Visitas de PreceptoriaRESUMO
We reviewed the major issues in thoracic surgery relating to the advances made in our specialty in 2010. To do this, the 43(rd) Congress of the Spanish Society of Pneumology and Thoracic Surgery held in La Coruña and the articles published in the Society's journal, Archivos de Bronconeumología, were reviewed. The main areas of interest were related to the development of video-assisted thoracic surgery, lung transplantation and descending mediastinitis. The new tumor-node-metastasis (TNM) classification (7(th) edition), presented last year, was still a topical issue this year. The First Forum of Thoracic Surgeons and the Update in Thoracic Surgery together with the Nurses' Area have constituted an excellent teaching program.
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Bibliometria , Transplante de Pulmão , Mediastinite/cirurgia , Cirurgia Torácica Vídeoassistida , Cirurgia Torácica/tendências , Congressos como Assunto , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Publicações Periódicas como Assunto , Pneumologia , Sociedades Médicas , Espanha , Cirurgia Torácica Vídeoassistida/tendênciasRESUMO
Perforin-mediated lymphocyte cytotoxicity is critical for pathogen elimination and immune homeostasis. Perforin disruption of target cell membranes is hypothesized to require binding of a calcium-dependent, lipid-inserting, C2 domain. In a family affected by hemophagocytic lymphohistiocytosis, a severe inflammatory disorder caused by perforin deficiency, we identified 2 amino acid substitutions in the perforin C2 domain: T435M, a previously identified mutant with disputed pathogenicity, and Y438C, a novel substitution. Using biophysical modeling, we predicted that the T435M substitution, but not Y438C, would interfere with calcium binding and thus cytotoxic function. The capacity for cytotoxic function was tested after expression of the variant perforins in rat basophilic leukemia cells and murine cytotoxic T lymphocytes. As predicted, cells transduced with perforin-T435M lacked cytotoxicity, but those expressing perforin-Y438C displayed intact cytotoxic function. Using novel antibody-capture and liposome-binding assays, we found that both mutant perforins were secreted; however, only nonmutated and Y438C-substituted perforins were capable of calcium-dependent lipid binding. In addition, we found that perforin-Y438C was capable of mediating cytotoxicity without apparent proteolytic maturation. This study clearly demonstrates the pathogenicity of the T435M mutation and illustrates, for the first time, the critical role of the human perforin C2 domain for calcium-dependent, cytotoxic function.
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Cálcio/imunologia , Membrana Celular/imunologia , Lipídeos de Membrana/imunologia , Mutação de Sentido Incorreto/imunologia , Perforina/imunologia , Linfócitos T Citotóxicos/imunologia , Substituição de Aminoácidos/imunologia , Animais , Linhagem Celular Tumoral , Membrana Celular/genética , Homeostase/imunologia , Humanos , Imunidade Celular/genética , Imunidade Celular/imunologia , Camundongos , Perforina/genética , Estrutura Terciária de Proteína/genética , RatosRESUMO
Perforin gene (PRF1) mutations have been reported in 20-30% of patients with familial hemophagocytic lymphohistiocytosis (FHL), an autosomal recessive disorder of infancy and early childhood that impairs or abolishes lymphocyte cytotoxicity. We report the first case of FHL in an adult patient homozygous for A91V in PRF1 with tuberculosis. The monozygotic twin of the patient is healthy. A91V confers genetic susceptibility for the development of FHL, but is not enough to trigger the disease on its own. We discuss the role of the A91V change together with M. tuberculosis infection as synergistic factors in the late onset of FHL.
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Linfo-Histiocitose Hemofagocítica/etiologia , Glicoproteínas de Membrana/genética , Mutação de Sentido Incorreto , Tuberculose/complicações , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Perforina , Proteínas Citotóxicas Formadoras de Poros , Gêmeos MonozigóticosRESUMO
PURPOSE: To describe the first pediatric report of systemic inflammatory response syndrome, shock, and multiple organ dysfunction syndrome associated with Sweet's syndrome. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENTS: A patient with Sweet's syndrome and multiple organ dysfunction syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We report the case of a 7-yr-old female child with an acute nonlymphoblastic leukemia in complete remission after an autologous bone marrow transplantation, with a clinical picture of skin lesions and fever that met the criteria of Sweet's syndrome and developing systemic inflammatory response syndrome, septic shock, and multiple organ dysfunction syndrome. Her clinical condition worsened despite broad-spectrum antimicrobial therapy and standard measures of cardiovascular support. An infectious site could not be identified, and all culture results were negative. Her condition improved dramatically once steroid therapy was administered, and she made a full recovery. CONCLUSION: Although it is a rare condition, the diagnosis of Sweet's syndrome must be considered in a patient with the typical skin lesions and systemic inflammatory response syndrome. The correct diagnosis is of great clinical importance, because therapy with systemic steroids results in a fast and remarkable improvement.