RESUMO
Flaviviruses are positive, single-stranded, enveloped cytoplasmic sense RNA viruses that cause a variety of important diseases worldwide. Among them, Zika virus, West Nile virus, Japanese encephalitis virus, and Dengue virus have the potential to cause severe disease. Extensive studies have been performed to elucidate the structure and replication strategies of flaviviruses, and current studies are aiming to unravel the complex molecular interactions between the virus and host during the very early stages of infection. The outcomes of viral infection and rapid establishment of the antiviral state, depends on viral detection by pathogen recognition receptors and rapid initiation of signalling cascades to induce an effective innate immune response. Extracellular and intracellular pathogen recognition receptors play a crucial role in detecting flavivirus infection and inducing a robust antiviral response. One of the main hallmarks of flaviviral nonstructural proteins is their multiple strategies to antagonise the interferon system. In this chapter, we summarize the molecular characteristics of flaviviral proteins and discuss how viral proteins target different components of the interferon signalling pathway by blocking phosphorylation, enhancing degradation, and downregulating the expression of major components of the Janus kinase/signal transducer and activator of transcription pathway. We also discuss how the interactions of viral proteins with host proteins facilitate viral pathogenesis. Due to the lack of antivirals or prophylactic treatments for many flaviviral infections, it is necessary to fully elucidate how these viruses disrupt cellular processes to influence pathogenesis and disease outcomes.
Assuntos
Infecções por Flavivirus/imunologia , Flavivirus/imunologia , Imunidade Inata , Interferons/imunologia , Transdução de Sinais/imunologia , Proteínas não Estruturais Virais/imunologia , Animais , Flavivirus/patogenicidade , Infecções por Flavivirus/patologia , Humanos , Janus Quinases/imunologiaRESUMO
We study the tunneling of optical vibrational modes with transverse horizontal polarization that impinge, at a given angle, on a semiconductor heterostructure. We find a large influence of the Goos-Hänchen shift on tunneling times. In particular, a Goos-Hänchen shift larger than the barrier thickness is reported for the first time. The relation between Goos-Hänchen and Hartman effects is also discussed. The identity that equals the dwell time to the sum of transmission and interference times, previously derived for one-dimensional tunneling problems, is extended to the two-dimensional case. Closed-form expressions are developed for the relevant quantities. Instead of using the standard approach, the interference time is computed from the vibrational energy density. The present study could be useful for the design of semiconductor devices.
RESUMO
The anterior (A) and posterior (P) cruciate ligaments (CL) of the knee, located inside the joint, connect the femur and the tibia and thus provide stability in the anteroposterior axis of one bone over the other. The anterior cruciate ligament (ACL) may be injured as a result of rotation when practicing a sport involving turning with the foot on the ground. ACL injuries are diagnosed with maneuvers like the Lachman, drawer and pivot. Accelerometers were used to plot the pivot maneuver in patients seeing the orthopedist surgeon using the KT1000 test as gold standard. This case-control descriptive study was approved by the Hospital's Ethics Committee. Results: 92 patients accepted to participate through an informed consent; nine cases were KT1000 positive, and nine age- and gender-matched controls were selected among KT1000 negative patients. KT1000 alterations were greater among females (78%) and in 67% of cases the right leg was affected. Mean KT1000 results were 5.44 mm in cases and 0.66 mm in controls. Accelerometers allowed plotting the pivot maneuver and the resulting charts for cases and controls were similar. Remarkable differences were seen only in one male patient with a 15 mm KT1000, who underwent repair of the left ACL; the maneuver was performed under sedation. We concluded that conscious patients oppose the maneuver, unlike anesthetized patients, and that the use of accelerometers helps document the pivot maneuver which, in turn, helps detect differences between a normal ACL and an injured one.
Assuntos
Acelerometria/métodos , Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho/diagnóstico , Procedimentos Ortopédicos/métodos , Adolescente , Adulto , Idoso , Ligamento Cruzado Anterior/patologia , Estudos de Casos e Controles , Feminino , Humanos , Traumatismos do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Our study aimed to evaluate metallothionein and p53 expression in colorectal cancer and to correlate their combined expression with selected clinical and pathologic variables of the disease, to define their prognostic significance. Colorectal cancer specimens from 99 patients were retrospectively analyzed by immunohistochemistry for metallothionein and p53 expression. Survival curves were generated according to the Kaplan-Meier method, and univariate survival distributions were compared with the use of the log-rank test. Multivariate models were computed using Cox proportional hazards regression. This research was approved by the institutional review boards of all centers. Tumors showing concomitant high metallothionein expression and negative p53 (metallothionein(H)/p53(-)) were significantly inversely related to depth of invasion, frequency of nodal metastasis, and Dukes stage (P < .01). In univariate analysis, patients with metallothionein(H)/p53(-) phenotype showed a better overall survival (hazard ratio [HR], 2.83; P < .05) and disease-free survival (HR, 2.03; P < .05). In multivariate analysis, considering staging, metallothionein, and metallothionein + p53 variables, in 83 patients with Dukes stages B and C, metallothionein(H)/p53(-) combination was the sole factor showing an independent prognostic value for overall survival (HR, 3.88; P < .1) and disease-free survival (HR, 2.56; P < .1). In conclusion, the combined analysis of metallothionein and p53 may enhance the prognostic power of each individual marker by predicting the progression of the disease and contributing to a better identification of patients at low risk for mortality, especially for those with Dukes stage B and C colorectal cancer.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/metabolismo , Metalotioneína/análise , Proteína Supressora de Tumor p53/análise , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metalotioneína/biossíntese , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Proteína Supressora de Tumor p53/biossínteseRESUMO
Triple negative breast cancer (TNBC) patients are not likely to benefit from anti-estrogen or anti-HER2 therapy and this phenotype is associated with a more aggressive clinical course and worse clinical outcome. Taking into account the limited treatment possibilities in TNBC, the aim of the present work was to study a potential therapy based on Cetuximab-mediated immune activity by natural killer (NK) cells. We performed in vitro studies on human breast cancer (BC) cell lines, IIB-BR-G, and the in vivo metastatic variant IIB-BR-G MT. The immunohistochemical analysis showed a TNBC phenotype with high but different levels of EGFR expression on each cell line, measured by flow cytometry. DNA sequencing showed that both cell lines have a mutated K-RAS status, 38 G > A at codon 13. Consequently, Cetuximab did not inhibit cellular proliferation or induce apoptosis. We investigated if Cetuximab could trigger immune mechanisms, and we determined that both cell lines treated with 1 µg/ml Cetuximab were susceptible to antibody dependent cellular cytotoxicity (ADCC), mediated by peripheral blood mononuclear cells (PBMC). At 50:1 effector:target ratio, lytic activity was 34 ± 2% against IIB-BR-G and 27 ± 6% against IIB-BR-G MT cells. PBMC pretreatment with IL-2 allowed reaching 65 ± 3% of Cetuximab-mediated ADCC against IIB-BR-G and 63 ± 6.5% against IIB-BR-G MT. Furthermore, IL-15 pretreatment increased the ADCC up to 71 ± 3% in IIB-BR-G and 79 ± 3.5% in IIB-BR-G MT. We suggest that NK cells are the effectors present in PBMC since they were able to induce ADCC at lower effector:target ratios. Besides, IL-2- and mainly IL-15-induced upregulation of NK activating receptors CD16 and NKG2D and enhanced IFN-γ production. EGFR-expressing TNBC could be killed by Cetuximab-mediated ADCC at clinically achievable concentrations. IL-15 could advantageously replace IL-2 in most of its immunologic activities, stimulating the ability to produce IFN-γ, and paralleling the up-regulation of activating receptors.
Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Receptores ErbB/metabolismo , Interleucina-15/farmacologia , Interleucina-2/farmacologia , Anticorpos Monoclonais Humanizados , Apoptose/efeitos dos fármacos , Sequência de Bases , Neoplasias da Mama , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cetuximab , Técnicas de Cocultura , Análise Mutacional de DNA , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Humanos , Interferon gama/metabolismo , Interleucina-15/fisiologia , Interleucina-2/fisiologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Mutação Puntual , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de IgG/genética , Receptores de IgG/metabolismo , Receptores de Progesterona/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteínas ras/genéticaRESUMO
Concepts presented to explain social learning, observational learning and imitation were analyzed. Hogans (1994) model for behavioral development was used to organize them and to show that those concepts refer to different sources of stimulus control, rather than to different processes. Valence change and potentiation were named as associative factors that determine observational learning. The relation between observational learning and occasion setting was underlined. It is suggested that these three terms are variants of the conditional discrimination paradigm.
En este trabajo se analizaron los conceptos que se han presentado para explicar lo que ocurre en situaciones de aprendizaje social, aprendizaje observacional e imitación. Con el uso del modelo de desarrollo del comportamiento presentado por Hogan (1994b) para organizarlos se señaló que los conceptos analizados se refieren a diferentes fuentes de control del estímulo. Se revisaron, asimismo, los factores asociativos que determinan tanto el aprendizaje social como el cambio de valencia y la potenciación; se indicó, también, la relación del aprendizaje social con la disposición de la ocasión. Se sugiere que estos tres términos equivalen a un paradigma de discriminación condicional.
RESUMO
The Mexico City Metropolitan Zone (ZMCM) population's exposure to benzene, toluene and xylene was measured at different microenvironments to establish basic indicators of the presence and effects of these characteristic volatile organic compounds (VOC). In particular, VOC personal exposures were measured in different microenvironments during a 5-day working week, with 12-h daily periods. We have found a good agreement of our results with the registered VOC levels of the Metropolitan Automated Monitor System (RAMA) for the corresponding period. From our results, we expect to generate useful information to evaluate the health effects of these VOCs on exposed people.
Assuntos
Benzeno/análise , Exposição Ambiental , Monitoramento Ambiental , Poluentes Ambientais/análise , Tolueno/análise , Xilenos/análise , Automação , Humanos , México , Periodicidade , Saúde Pública , População Urbana , VolatilizaçãoRESUMO
Ambient air VOC samples were collected at surface air quality monitoring sites, near sources of interest, and aloft on the US (El Paso) and Mexican (Ciudad Juárez) side of the border during a six-week period of the 1996 Paso del Norte Ozone Study. Samples were collected at five sites, three on the US side and two on the Mexican side, during nine intensive operation days when high ozone levels were forecast for the area. Six other sites were sampled to characterize up-wind, down-wind and other emission sources. Samples for determining source profiles were collected for rush hour traffic, propane-powered bus exhaust, automobile paint shop emissions, propane fuels, and industrial manufacturing in Cd. Juárez and a refinery in El Paso. Most samples were collected in electro-polished stainless steel canisters for determination of C2 to C(10+) hydrocarbons by GC-FID. Carbonyl samples were collected on DNPH impregnated cartridges at three surface sites during aircraft flights and analyzed by HPLC. This paper presents the spatial and temporal characteristics of VOC species concentrations and compositions to examine the differences and similarities of the various locations and time periods. Overall surface, total non-methane hydrocarbon values ranged from 0.1 to 3.4 ppmC with the highest concentrations being recorded in the morning and evening at five vehicle-dominated sites, three in Cd. Juárez and two in El Paso. Toluene in El Paso samples and propane, which is used as a cooking and transportation fuel in Cd. Juárez, were the most abundant hydrocarbons. The most abundant carbonyls were acetaldehyde, acetone and formaldehyde.
Assuntos
Poluição do Ar/análise , Monitoramento Ambiental , Hidrocarbonetos/análise , Movimentos do Ar , Culinária , Humanos , Indústrias , México , Compostos Orgânicos/análise , Centrais Elétricas , Estados Unidos , Emissões de Veículos , VolatilizaçãoAssuntos
Atitude Frente a Saúde/etnologia , Defesa da Criança e do Adolescente/legislação & jurisprudência , Cristianismo , Diversidade Cultural , Liberdade , Testemunhas de Jeová , Pais , Defesa do Paciente/legislação & jurisprudência , Religião e Medicina , Recusa do Paciente ao Tratamento , Criança , Ética Médica , Humanos , MéxicoRESUMO
The efficacy of a florfenicol premix was studied in weaning pigs experimentally inoculated with Actinobacillus pleuropneumoniae. Twenty five clinically healthy pigs were distributed into 3 groups; group A non-medicated, groups B and C orally medicated with 20 and 40 ppm of florfenicol respectively. The pigs were fed during 12 consecutive days and on day 5 all the groups were challenged with A. pleuropneumoniae serotype 1. All the animals in Group A developed clinical signs. Most of the pigs in the medicated groups maintained a good health status. Postmortem examination revealed severe pleuropneumonia in pigs from the control group and pneumonic lesions in 40% of the animals treated with 20 ppm of florfenicol. Development of pleuropneumonia was prevented in all the pigs medicated with 40 ppm of florfenicol. Actinobacillus pleuropneumoniae was recovered from the lungs of all control animals and from one pig of each of the medicated groups, however, the avidin biotin peroxidase (ABC-P) method detected the presence of the microorganism in all the animals. We demonstrated that medication with feed containing 40 ppm of florfenicol blocked efficiently the signs and lesions caused by A. pleuropneumoniae and increased the daily body weight gain.
Assuntos
Actinobacillus pleuropneumoniae/efeitos dos fármacos , Ração Animal , Antibacterianos/uso terapêutico , Aditivos Alimentares/uso terapêutico , Pleuropneumonia/veterinária , Doenças dos Suínos/prevenção & controle , Tianfenicol/análogos & derivados , Actinobacillus pleuropneumoniae/isolamento & purificação , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Avaliação de Medicamentos/veterinária , Aditivos Alimentares/administração & dosagem , Aditivos Alimentares/farmacologia , Pulmão/microbiologia , Pulmão/patologia , Pleuropneumonia/tratamento farmacológico , Pleuropneumonia/microbiologia , Pleuropneumonia/patologia , Pleuropneumonia/prevenção & controle , Método Simples-Cego , Suínos , Doenças dos Suínos/tratamento farmacológico , Doenças dos Suínos/microbiologia , Doenças dos Suínos/patologia , Tianfenicol/administração & dosagem , Tianfenicol/farmacologia , Tianfenicol/uso terapêuticoRESUMO
Measurements of hydrocarbon (HC) emissions generated by the use of liquefied petroleum gas (LPG) in the metropolitan area of Guadalajara City (MAG) are presented in this work. Based on measurements in the course of distribution, handling, and consumption, an estimated 4407 tons/yr are released into the atmosphere. The three most important contributors to LPG emissions were refilling of LPG-fueled vehicles and commercial and domestic consumption. The MAG shows a different contribution pattern of LPG emission sources compared with that of the metropolitan area of Mexico City (MAMC). These results show that each megacity has different sources of emissions, which provides more accurate strategies in the handling procedures for LPG to decrease the impact in O3 levels. This work represents the first evaluation performed in Guadalajara City, based on current measurements, of the LPG contribution to polluting emissions.
Assuntos
Poluição do Ar/análise , Monitoramento Ambiental , Petróleo , Emissões de Veículos/análise , Gases , Humanos , México , Sensibilidade e Especificidade , População UrbanaRESUMO
PM10, PM25, precursor gas, and upper-air meteorological measurements were taken in Mexico City, Mexico, from February 23 to March 22, 1997, to understand concentrations and chemical compositions of the city's particulate matter (PM). Average 24-hr PM10 concentrations over the period of study at the core sites in the city were 75 H g/m3. The 24-hr standard of 150 µ g/m3 was exceeded for seven samples taken during the study period; the maximum 24-hr concentration measured was 542 µ g/m3. Nearly half of the PM10 was composed of fugitive dust from roadways, construction, and bare land. About 50% of the PM10 consisted of PM2.5, with higher percentages during the morning hours. Organic and black carbon constituted up to half of the PM2.5. PM concentrations were highest during the early morning and after sunset, when the mixed layers were shallow. Meteorological measurements taken during the field campaign show that on most days air was transported out of the Mexico City basin during the afternoon with little day-to-day carryover.
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OBJECTIVE: To explore the opinion of physicians about euthanasia and the treatment of dying patients. DESIGN: A comparative survey. MATERIAL AND METHODS: We interviewed 38 family physicians (FP), 38 specialty physicians (SP) and 38 medical students (MS). The survey had 30 items, five of them about experience with terminal patients which were not used for the students. ANALYSIS: Descriptive statistics and chi 2 or Fisher test to compare proportions between groups. RESULTS: One hundred and two (89%) of the interviewed had a correct concept of euthanasia; 105 (92%) thought that life is holy and untouchable; 29 (25%) agreed there are persons more valuable than others, and four (4%) consider that some should die in certain situations. In relation to patients with brain death, 79 (69%) believed they should not receive futile treatment, but 42 (37%) said they should be attended until cardiac arrest occurred. All agreed with the need of the patients to receive comfort and peace, but only 49/76 (64%) of the physicians and 28 (74%) of the students were in favor of sending dying patients to their home. Nine FP (23%) and 14 SP (36%) stated that in many occasions they lacked elements to solve ethical dilemmas. Thirty six (32%) agreed with the use of passive euthanasia and 21 (18%) with active euthanasia; the latter was more frequent among students. Nine FP (24%) and 13 SP (34%) said they had exceeded therapy sometimes and 23 (61%) of the FP and 19 (50%) of the SP considered they had stopped treatment too early in some cases. We found no differences in regard to euthanasia between physicians and students (chi 2 = 0.32, p = 0.71) nor between the physicians with frequent vs occasional contact with terminal patients (Fisher = 0.13). CONCLUSIONS: A third of the physicians agreed with some form of euthanasia but this frequency is smaller than that in other countries.
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Atitude do Pessoal de Saúde , Atitude Frente a Morte , Ética Médica , Eutanásia , Médicos/psicologia , Tomada de Decisões , Humanos , Medicina , México , Médicos de Família/psicologia , Especialização , Estudantes de Medicina/psicologiaRESUMO
The acute systemic complications of perinatal asphyxia, defined as an umbilical artery pH at birth of 7.10 or less, were evaluated in fifty full-term newborn infants. We also investigated the prenatal complications that lead to asphyxia, and the relationship between Apgar score and cord pH. Asphyxia or fetal distress was not identified in 56% of the cases. The most common condition associated with asphyxia was prolonged labor followed by abruptio placentae. About half of the babies studied, suffered some degree of renal and brain dysfunction; 24% had severe respiratory disease. Myocardial failure was present in 24%. Regarding metabolic complications, the most frequent was hypocalcemia, present in 44%. On the other hand, there was no correlation between Apgar score and cord pH. Mortality was 22%. The main cause of death was Persistent Pulmonary Hypertension.
Assuntos
Asfixia Neonatal/mortalidade , Hipertensão Pulmonar/mortalidade , Mortalidade Infantil , Descolamento Prematuro da Placenta/complicações , Índice de Apgar , Asfixia Neonatal/etiologia , Feminino , Idade Gestacional , Humanos , Hipertensão Pulmonar/complicações , Recém-Nascido , Idade Materna , GravidezRESUMO
We decided to undergo a study looking for normal liver size in relation with other anthropometric measures. Fifty healthy, appropriate for gestational age term-babies, born at the Hospital de Ginecopediatría Número 48, Centro Médico Nacional del IMSS, León, Guanajuato, México, were examined by hepatic ultrasound. The vertical diameter was 6.0 +/- 0.75 cm, transverse 8.26 +/- 0.72 cm, AP 5.44 +/- 0.5 cm. The longitudinal cross section area was 16.21 +/- 2.5 cm2, and the transverse cross section area 22.53 +/- 3.4 cm2. We found most important correlation between vertical diameter and longitudinal cross section area with the anthropometric measures. The hepatic measures correlate better with the weight. Ultrasound provides a rapid, accurate and convenient method for study the liver size and morphology in the neonate.
Assuntos
Fígado/diagnóstico por imagem , Antropometria , Peso ao Nascer , Idade Gestacional , Humanos , Recém-Nascido , Fígado/anatomia & histologia , Valores de Referência , UltrassonografiaRESUMO
A case of large bowel perforation at sigmoides level, secondary to application of a "medicated" intrauterine contraceptive device (IUD), Copper-7, is presented. This variety of IUD translocated to peritoneal cavity may provoke peritoneal or omental adhesions, volvulus, uterocutaneous fistula and bowel perforation, which involves a significant morbidity. The diagnosis is often delayed and difficult to establish, but, once knowing the exact location of ectopic IUD, it is justified the immediate removal from the peritoneal cavity by either laparoscopy or laparotomy with the utilization of prophylactic antimicrobials for colon preparation before elective surgery.
Assuntos
Colo Sigmoide/lesões , Perfuração Intestinal/etiologia , Dispositivos Intrauterinos/efeitos adversos , Adulto , Colo Sigmoide/diagnóstico por imagem , Colo Sigmoide/cirurgia , Feminino , Migração de Corpo Estranho/diagnóstico por imagem , Migração de Corpo Estranho/cirurgia , Humanos , Perfuração Intestinal/diagnóstico por imagem , Perfuração Intestinal/cirurgia , Paridade , Gravidez , Complicações na Gravidez/etiologia , Resultado da Gravidez , RadiografiaRESUMO
Ultrasound is the best non-invasive study to evaluate renal morphology in the neonate; so we decided to undergo a study looking for normal renal size in relation with other anthropometric measures. We performed renal ultrasounds in 50 healthy, appropriate for gestational age, term-babies. We found correlation between several anthropometric measures, but the most significant were weight and height. In most cases the left similar to others. It is important to know normal renal dimensions in newborns, since there are diseases that not only are associated with an increased incidence of renal malformations, but also with a reduced renal size such as Down syndrome, or increased renal size such as Beckwith-Wiedemann syndrome. Renal sonogram; term newborn babies; anthropometric correlation.
Assuntos
Antropometria , Rim/anatomia & histologia , Rim/diagnóstico por imagem , Humanos , Recém-Nascido , Valores de Referência , UltrassonografiaRESUMO
From June 1st, 1989 to May 31st, 1990, 16,987 consecutive newborns were examined at the No. 48 Gynecological Pediatric Hospital of the IMSS National Medical Center, looking for external congenital malformations including esophageal atresias, anorectal malformations and congenital hip luxations, all easily detected during a routine exploration. Each deformed newborn assigned two control patients the following two newborn babies showing no birth defects. 308 deformed newborns were detected, an incidence of 1.81%. Among the most frequent defects were midline flat hemangiomas, polyotia, Down syndrome, congenital hip luxation and myelomeningocele. The only significant statistical difference found with respect to the control group was a greater family history of defects in the case group (P less than 0.0001). When comparing our results with those from other studies, including a study done locally 15 years ago, we found differences among specific malformations: congenital hip malformation, polydactylia, foot deformities, flat hemangiomas, nevus and polyotias. Yet, the overall frequency of defects found was similar.