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INTRODUCTION: Finding a goal of time in range (%TIR) that defines good glycemic control is necessary. Previous retrospective studies suggest good concordance between HbA1c ≤7% with a TIR >70%; however, the studies that included the largest number of patients used blood glucose measurement data with a follow-up time of less than 90 days. This study defined the TIR value that best discriminates HbA1c ≤7%. METHODS: We performed a prospective study of diagnostic tests based on a cohort of patients with type 1 diabetes (T1D) treated with a hybrid closed loop (HCL) followed for three months. The ability of %TIR to distinguish patients with HbA1c ≤7% was evaluated through receiver operating characteristic curve analysis. We determined the %TIR cutoff point with the best operating characteristics. RESULTS: A total of 118 patients were included (58.1% women, 47% overweight or obese, and 33% with high glycemic variability). A moderate negative correlation (R = -.54, P < .001) was found between %TIR and HBA1c. The discrimination ability was moderate, with an area under the curve of 0.7485 (95% confidence interval = 0.6608-0.8363). The cutoff point that best predicted HbA1c ≤7% was %TIR ≥75.5 (sensitivity 70%, specificity 67%). The findings were similar among those with a coefficient of variation (CV%) ≥36%. CONCLUSIONS: Our data suggest that the %TIR adequately identifies patients with HbA1c ≤7%. A target of TIR ≥75%, rather than the currently recommended TIR ≥70%, may be a more suitable value for optimal glycemic control.
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In this work, we have developed numerical simulations and weakly nonlinear analysis based on the multiple-scales perturbation technique for a coated microbubble that performs radial pulsations subject to an acoustic pressure disturbance in the far-field and whose encapsulated hyperelastic material obeys the Mooney-Rivlin equation. Departing from an elastic coating as a hyperelastic shell of finite thickness, we assume eventually that the shell is of very small thickness in comparison with the microbubble radius. Under this condition, we then perform weakly nonlinear analysis, to identify resonance conditions for small pressure disturbances of the acoustic field. In parallel and also for the limit of small thickness, we have carried out numerical simulations of the radial motion of the microbubble, identifying the onset of limit cycles via the construction of Poincare maps. Under both schemes, we have recognized the importance of two dimensionless hyperelastic parameters that dictate the main behavior of the oscillations: α∗ and ß∗. Decreasing the values of these parameters, the resonance conditions are drastically amplified, which is an expected result because of the weak rigidity of the hyperelastic solid, prevails. In this manner, we suggest that moderate values for these previous parameters can be widely advisable when, in medical diagnostic applications, we are applying microbubbles as contrast agents. Therefore, we recommend widely the use of shell softens, because in this case the amplitude of radial pulsation is always amplified.
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BACKGROUND: We identified a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America, which we term El Bagre-EPF, and observed reactivity to arrector pili muscle (APM), thus we tested for autoimmunity to APM. METHODS: We took skin biopsies from 30 patients with El Bagre-EPF and 30 healthy controls (HCs) matched by age, sex and occupation, who were all from the endemic area, and tested these using direct immunofluorescence (DIF), confocal microscopy, immunohistochemistry and immunoblotting (IB). RESULTS: Of the 30 patients with El Bagre-EPF, 27 had autoantibodies to APM that colocalized with commercial antibodies to myocardium-enriched zonula occludens-1-associated protein (MYZAP), desmoplakin (DP)1 and DP2, plakophilin 4, and Armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) (P < 0.001, Fisher exact test). The positive staining also colocalized with Junctional Adhesion Molecule 1 (JAM-A), a control antibody for gap cell junctions. No HC samples were positive. In 27 of the 30 patients, serum that was APM-positive also displayed IB colocalization of their autoantibody molecular weights with the Progen antibodies (P < 0.001, Fisher exact test). CONCLUSIONS: Patients affected by El Bagre-EPF have autoantibodies to APM, colocalizing with the antibodies MYZAP, ARVCF, p0071, DP1 and DP2, suggesting that these molecules are El Bagre-EPF antigens. Further, all of these antigens represent components of cell junctions, indicating that the immune response is directed, at least partially, against cell junctions. The immune response in patients affected by El Bagre-EPF is polyclonal, and it includes B and T lymphocytes, mast cells, IgG, IgA, IgM, IgD, IgE, fibrinogen, albumin, complement/C1q, C3c and C4.
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Autoanticorpos/sangue , Autoimunidade , Doenças Endêmicas , Músculo Liso/imunologia , Pênfigo/imunologia , Proteínas do Domínio Armadillo/imunologia , Moléculas de Adesão Celular/imunologia , Colômbia , Desmoplaquinas/imunologia , Humanos , Immunoblotting , Imuno-Histoquímica , Pênfigo/patologia , Fosfoproteínas/imunologia , Placofilinas/imunologia , Receptores de Superfície Celular/imunologia , Proteína da Zônula de Oclusão-1/imunologiaRESUMO
BACKGROUND: Induction therapies in kidney transplantation have led to prescriptions of lower doses of maintenance immunosuppression and fewer acute rejection episodes. We sought to assess the use of an affordable monoclonal antibody in terms of the incidences of rejection episodes as well as graft and patient survivals and cytomegalovirus (CMV) and opportunistic infections among our kidney transplant recipients between August 2005 and December 2010. Data were obtained for patients who had more than 20 months' follow-up. MATERIALS AND METHODS: We retrospectively analyzed data from kidney recipients between August 2005 and December 2010, using descriptive statistics and Kaplan-Meier survival analysis. We performed a multivariate analysis with logistic regression for the dependent variables of rejection episodes and death. RESULTS: Among 425 transplant patients graft survival was 89.2% and patient survival was 94.1% after 76.2% of patients received alemtuzumab, 10.7% daclizumab, 3.6% basiliximab, 2.4% thymoglobulin, and 7%, no induction therapy. Rejection incidence in general in the first year was 10.8% and CMV incidence 10%. There was an increased risk of rejection among subjects without any us with alemtuzumab induction therapy. CONCLUSION: Induction therapies show an important reduction in kidney transplant rejection incidence during the first year, allowing low doses of maintenance immunosuppressants, thereby diminishing long-term adverse effects. Alemtuzumab seemed to be a safe alternative with similar results to those obtained with standard immunosuppression.
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Transplante de Rim/métodos , Insuficiência Renal/terapia , Adulto , Alemtuzumab , Anticorpos Monoclonais/química , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Basiliximab , Colômbia , Infecções por Citomegalovirus , Daclizumabe , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Hospitais , Humanos , Imunoglobulina G/uso terapêutico , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Recombinantes de Fusão/uso terapêutico , Análise de Regressão , Insuficiência Renal/mortalidade , Estudos Retrospectivos , Risco , Resultado do TratamentoRESUMO
Este estudio describe la evaluación de las actividades citotóxica y leishmanicida del aceite esencial de Matricaria chamomilla, una planta conocida como manzanilla a la que se le atribuye una variedad de usos en la medicina tradicional. La actividad del aceite esencial se evaluó in vitro contra amastigotes axénicos de L. (V) braziliensis, a concentraciones menores o iguales que 250μg/ml, y amastigotes intracelulares de L. (V) braziliensis y L. (V) panamensis, a concentraciones menores o iguales que 30μg/ml. Por su parte, la actividad citotóxica se evaluó contra células mamíferas de la línea promonocítica humana U-937, a concentraciones por debajo de 1,0 mg/ml. El aceite esencial de manzanilla mostró ser activo contra amastigotes intracelulares de L. (V) panamensis y L. (V) braziliensis (CE50 de 2,87 y 10,30μg /ml, respectivamente). Aunque el aceite esencial de manzanilla también mostró ser potencialmente tóxico para las células mamíferas (CL50 de 30,21μg /ml), esta toxicidad fue similar a la mostrada por la Anfotericina B (CL50 de 31,39μg /ml). El aceite esencial de manzanilla no mostró actividad contra las formas axénicas de L. (V) braziliensis, demostrando la importancia del metabolismo del compuesto en el interior de la célula para que se produzca el metabolito activo contra el parásito. Estos resultados aportan bases para sugerir que el aceite esencial de manzanilla tiene potencial para el desarrollo de medicamentos contra Leishmania, el cual debe ser validado en estudios futuros in vivo en modelos animales.
This study describes the evaluation of cytotoxic and leishmanicidal activities for Matricaria chamomilla essential oil. M. chamomilla is a plant commonly named manzanilla that has many uses in traditional medicine. The activity of essential oil was evaluated in vitro against axenic amastigotes of L. (V) braziliensis at concentrations lower than or equal to 250μg/ml and intracellular amastigotes of L. (V) braziliensis and L. (V) panamensis at concentrations lower than or equal to 30μg/ml. On other hand, the cytotoxic activity was assessed against mammalian cells of the promonocytic human cell line U937 at concentrations below 1.0mg/ml. The essential oil of M. chamomilla showed activity against intracellular amastigotes of L. (V) panamensis and L. (V) braziliensis (EC50 of 2.87 and 10.30μg/ml, respectively). Although the essential oil of M. chamomilla also shown to be potentially toxic to mammalian cells LC50 of 30.21μg ml) this toxicity was similar to that shown by Amphotericin B (LC50 of 31.39μg/ml). This essential oil showed no activity against axenic forms of L. (V) braziliensis suggesting the importance of the compound metabolism inside cells to produce the metabolite that would be active against parasites. These results suggest that the essential oil of M. chamomilla has potential for development of drugs anti- Leishmania that must be validated in future studies in vivo using animal models.
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Camomila , Leishmania braziliensis , Leishmania guyanensis , Matricaria , Produtos Biológicos , Citotoxicidade Imunológica , Leishmaniose/terapiaRESUMO
Objetivos: (1) diseñar y evaluar una técnica de angiorresonancia 3D contrastada (ARM 3D) para el diagnóstico de la estenosis carotídea y compararla con la ecografía triplex (eco triplex) y la arteriografía por sustracción digital (ASD), esta última como estándar de referencia. (2) Evaluar la factibilidad de adicionar a la técnica anterior secuencias anatómicas y angiográficas del cerebro. Materiales y métodos: en 39 pacientes (78 carótidas) se estudió la bifurcación carotídea con ASD, angiorresonancia 3D con doble inyección y eco triplex. Se utilizó el método descrito en el estudio NASCET para cuantificar el grado de estenosis. Cada examen fue evaluado por observadores diferentes que no conocían el resultado de los otros métodos. Adicionalmente, se obtuvieron imágenes del cerebro y se describieron dichos hallazgos. Resultados: la angiorresonancia 3D con técnica de doble inyección detectó el 98 por ciento del grupo de carótidas clasificadas como normal-leves, el 83 por ciento de las estenosis moderadas, el 88 por ciento de las estenosis graves y el 100 por ciento de las oclusiones. Adicionalmente, dos errores diagnósticos (oclusiones falsas) de la ASD fueron identificados efectivamente por la ARM 3D. La eco triplex detectó el 92 por ciento del grupo normal-leve, el 33 por ciento de las estenosis moderadas, el 86 por ciento de las graves y todas las oclusiones encontradas con la ASD, pero la ecografía sobrestimó una estenosis leve a oclusión (falsa oclusión). La correlación estadística entre el estándar de referencia ASD y la ARM 3D fue buena a excelente, para los diferentes grados de estenosis (K>0,7 y K>0,9, respectivamente). En todos los pacientes se logró una evaluación adecuada del cerebro con resonancia. Conclusión: esta investigación sugiere que la ARM 3D con técnica de doble inyección tiene el potencial para remplazar la ASD en el diagnóstico y seguimiento de la enfermedad carotídea