Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Teste para COVID-19 , América Latina , Espanha , Equador/epidemiologia , Carga ViralRESUMO
During the second year of the COVID-19 pandemic, the use of Rapid Diagnosis Antigen Tests (RDAgTs) for SARS-CoV-2 detection has substantially increased as some of the brands available in the market were certified for clinical use by international regulatory agencies. RDAgTs are a fast and cheap tool for SARS-CoV-2 surveillance with great potential to improve testing capacities in middle- and low-income countries compared to the gold standard RT-qPCR. However, as the clinical performance of RDAgTs has been shown to vary greatly between the commercial brands available, evaluation studies are necessary. Moreover, the available evaluation has been done in high-income countries while SARS-CoV-2 transmission is also actively happening in developing countries, many of which are located in tropical latitudes where cross-reactivity with other infectious agents is highly prevalent, which could compromise RDAgT specificity. Moreover, unreported mutations and/or new SARS-CoV-2 variants may compromise RDAgT sensitivity as genomic surveillance is limited in these settings. Here we describe a multicenter and manufacturer-independent evaluation of the clinical performance and analytical sensitivity of three different RDAgTs brands available in South America from three companies, Rapigen (South Korea), SD-Biosensor (South Korea), and Certest (Spain), compared to the gold standard RT-qPCR. A total number of 1,646 nasopharyngeal swabs from community-dwelling individuals were included in the study, and 379 of them were SARS-CoV-2 positive by RT-qPCR. The overall sensitivity for each RDAgT was 79% (IC95%: 72 - 86.2), 64.2% (IC95%: 56.7 - 71.6), and 45.8% (IC95%: 35.8 - 55.8) for SD-Biosensor, Certest, and Rapigen, respectively. The overall specificity for each RDAgT was 100%, 97.7% (IC95%: 96.8 - 98.6), and 100% for SD-Biosensor, Certest, and Rapigen, respectively. However, the limit of detection (LoD) to achieve a sensitivity over 90% was substantially lower for Certest RDAgT (102 copies/uL) compared to SD-Biosensor (103 copies/uL) or Rapigen (106 copies/uL) RDAgTs, considering that the gold standard RT-qPCR method used in this study has a high sensitivity of 97.7% and low LoD of 5 copies/uL. Additionally, the Certest RDAgT also showed an improved sensitivity up to 79.7% (IC95%: 70.2 - 89.2) for symptomatic individuals. Finally, the slight reduction in specificity for Certest RDAgTs was only associated with one of the laboratories performing this study, pointing out the need for locally assessed evaluation for RDAgTs like this one carried out in Ecuador. In conclusion, two of the three the RDAgTs tested in this study are a fast, cheap, and point of care tool for SARS-CoV-2 surveillance and reliable enough to detect SARS-CoV-2 infectious individuals.
Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Humanos , Vida Independente , Pandemias , SARS-CoV-2/genética , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Dozens of commercial RT-qPCR kits for SARS-CoV-2 detection are available with or without Emergency Use Authorization (EUA) by FDA or other regulatory agencies. OBJECTIVE: We evaluated the clinical performance of two SARS-CoV-2 RT-PCR kits designed and produced in South America, "COVID-19 RT-PCR Real TM FAST (CY5)" (ATGen, Uruguay) and "ECUGEN SARS-CoV-2 RT-qPCR" (UDLA-STARNEWCORP, Ecuador), for RT-qPCR SARS-CoV2 detection using "TaqMan 2019-nCoV Assay Kit v1" (Thermofisher, USA) as a gold standard technique. RESULTS: We report a great clinical performance and analytical sensitivity for the two South American kits with sensitivity values of 96.4 and 100%, specificity of 100% and limit of detection in the range of 10 copies/uL of RNA extraction. CONCLUSIONS: "COVID-19 RT-PCR Real TM FAST (CY5)" and "ECUGEN SARS-CoV-2 RT-qPCR" kits are reliable SARS-CoV-2 tests made in South America that have been extensively used in Uruguay, Argentina, Brazil, Bolivia and Ecuador. These locally produced SARS-CoV-2 tests have contributed to overcome supply shortages and reduce diagnosis cost, while maintaining the high quality standards of FDA EUA commercially available kits. This approach could be extended for other diagnostic products to improve infectious diseases surveillance at middle and low income countries beyond COVID-19 pandemic.
Assuntos
COVID-19 , SARS-CoV-2 , Brasil , COVID-19/diagnóstico , Carbocianinas , Equador/epidemiologia , Humanos , Pandemias , RNA Viral/análise , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , Sensibilidade e Especificidade , UruguaiRESUMO
BACKGROUND: Several RT-qPCR kits are available for SARS-CoV-2 diagnosis, some of them with Emergency Use Authorization (EUA) by FDA, but most of them lacking of proper evaluation studies due to covid19 emergency. OBJECTIVE: We evaluated Viasure RT-qPCR kit (CerTest Biotec, Spain) for SARS-CoV-2 diagnosis using FDA EUA 2019-nCoV CDC kit (IDT, USA) as a gold standard. RESULTS: Although we found the lack of RNA quality control probe as the main limitation for the Viasure kit, the sensitivity was 91.9% and the specificity was 100%. The limit of detection (LOD) was 2000 copies/mL and 1000 copies/mL for Viasure and IDT kits, respectively. CONCLUSIONS: Viasure RT-qPCR kit is a reliable tool for SARS-CoV-2 diagnosis but improvement of an alternative RT-qPCR reaction for RNA extraction quality control as RNaseP is recommended.
Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Kit de Reagentes para Diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , SARS-CoV-2 , COVID-19/virologia , Humanos , Limite de Detecção , Carga ViralRESUMO
Members of the fibroblast growth factor (FGF) family have been associated with tumor progression and angiogenesis, though the mechanism through which they affect the progression of breast cancer remains elusive. We recently showed that progestins increase the production of the potent angiogenic factor VEGF in an in vivo BT-474 human breast cancer cell-derived xenograft model. In this study we sought to determine the effect of progesterone (P) on regulation of specific FGF family members (FGF-2, FGF-4 and FGF-8) in the same model. Using immunohistochemistry we found that treatment with P significantly reduced FGF-2 and FGF-8 levels, while modestly increasing the levels of FGF-4 in tumors collected at the termination of the study or soon after P treatment began. The in vivo observations with FGF-2 were confirmed in cultured BT-474 cells, though the P-mediated reduction in FGF-2 was not blocked by the anti-progestin RU-486, suggesting that classical progesterone receptors (PR) are not involved in FGF-2 down-regulation. Also, P did not affect levels of FGF-2 mRNA in BT-474 cells, indicating that P exerts its effects on FGF-2 post-transcriptionally. Our observations suggest that the in vivo stimulation of BT-474 cell growth by P is associated with down-regulation of FGF-2 and FGF-8. Furthermore, since FGF-4 levels increased during P-treatment, FGF-4 may be required for tumor growth and maintenance and might therefore be a potential therapeutic target through which to suppress P-dependent tumor growth.
Assuntos
Neoplasias da Mama/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Progesterona/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator 4 de Crescimento de Fibroblastos/metabolismo , Fator 8 de Crescimento de Fibroblasto/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Humanos , Imuno-Histoquímica , Camundongos , RNA Mensageiro/metabolismo , Fatores de Tempo , Transplante Heterólogo , Carga TumoralRESUMO
The use of progestins as a component of hormone replacement therapy has been linked to an increase in breast cancer risk in postmenopausal women. We have previously shown that medroxyprogesterone acetate (MPA), a commonly administered synthetic progestin, increases production of the potent angiogenic factor vascular endothelial growth factor (VEGF) by tumor cells, leading to the development of new blood vessels and tumor growth. We sought to identify nontoxic chemicals that would inhibit progestin-induced tumorigenesis. We used a recently developed progestin-dependent mammary cancer model in which tumors are induced in Sprague-Dawley rats by 7,12-dimethylbenz(a)anthracene (DMBA) treatment. The flavonoid apigenin, which we previously found to inhibit progestin-dependent VEGF synthesis in human breast cancer cells in vitro, significantly delayed the development of, and decreased the incidence and multiplicity of, MPA-accelerated DMBA-induced mammary tumors in this animal model. Whereas apigenin decreased the occurrence of such tumors, it did not block MPA-induced intraductal and lobular epithelial cell hyperplasia in the mammary tissue. Apigenin blocked MPA-dependent increases in VEGF, and suppressed VEGF receptor-2 (VEGFR-2) but not VEGFR-1 in regions of hyperplasia. No differences were observed in estrogen or progesterone receptor (ER/PR) levels, or the number of estrogen receptor-positive cells, within the mammary gland of MPA-treated animals administered apigenin, MPA-treated animals, and placebo treated animals. However, the number of progesterone receptor-positive cells was reduced in animals treated with MPA or MPA and apigenin compared with those treated with placebo. These findings suggest that apigenin has important chemopreventive properties for those breast cancers that develop in response to progestins.
Assuntos
9,10-Dimetil-1,2-benzantraceno/farmacologia , Apigenina/farmacologia , Neoplasias Mamárias Animais/tratamento farmacológico , Acetato de Medroxiprogesterona/metabolismo , Animais , Apigenina/metabolismo , Relação Dose-Resposta a Droga , Feminino , Imuno-Histoquímica/métodos , Neovascularização Patológica , Placebos , Ratos , Ratos Sprague-Dawley , Receptores de Progesterona/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
We report on the data mining of publicly available Litopenaeus vannamei expressed sequence tags (ESTs) to generate simple sequence repeat (SSRs) markers and on their transferability between related Penaeid shrimp species. Repeat motifs were found in 3.8% of the evaluated ESTs at a frequency of one repeat every 7.8 kb of sequence data. A total of 206 primer pairs were designed, and 112 loci were amplified with the highest success in L. vannamei. A high percentage (69%) of EST-SSRs were transferable within the genus Litopenaeus. More than half of the amplified products were polymorphic in a small testing panel of L. vannamei. Evaluation of those primers in a larger testing panel showed that 72% of the markers fit Hardy-Weinberg equilibrium, which shows their utility for population genetic analysis. Additionally, a set of 26 of the EST-SSRs were evaluated for Mendelian segregation. A high percentage of monomorphic markers (46%) proved to be polymorphic by singles-stranded conformational polymorphism analysis. Because of the high number of ESTs available in public databases, a data mining approach similar to the one outlined here might yield high numbers of SSR markers in many animal taxa.
Assuntos
Bases de Dados de Ácidos Nucleicos , Etiquetas de Sequências Expressas/química , Marcadores Genéticos , Repetições de Microssatélites/genética , Penaeidae/genética , Animais , Mapeamento Cromossômico , Primers do DNA/genética , Variação Genética , Genética Populacional , Modelos Biológicos , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
En nuestro estudio revisamos los expedientes de 20 pacientes sometidos a pericardietomía en el Instituto Nacional de Cardiología "Ignacio Chávez" en un periodo entre los meses de agosto de 1987 y septiembre de 1992. Se trata de 9 hombres y 11 mujeres, con edades comprendidas entre 18 y 57 años (promedio 35.8). Las causas incluyeron: derrame recidivante 5 casos, pericarditis constrictiva 4, urémica 2, síndrome pospericardiectomía 2 y otras con menor frecuencia: neoplasia 1, postraumática 1 y secundaria a radioterapia 1. El diagnóstico se realizó en base a: cuadro clínico, radiografía torácica, ecocardiografía bidimensional y cateterismo cardiaco. Todos los pacientes se sometieron a esternotomía y las resección del pericardio fue ampliada hasta el borde anterior de ambos nervios frénicos. La monitorización incluyó catéter venoso central y línea arterial en todos los casos y en 12 (60 por ciento) catéter de flotación pulmonar. Todas las intervenciones contaron con equipo de circulación extracorpórea en standby. La mortalidad operatoria fue de 1 caso, como consecuencia de bajo gasto cardiaco progresivo y falla multiorgánica en un paciente urémico. La mortalidad a 1 año se incrementó a 2 casos (10 por ciento) con la inclusión de un paciente con neoplasia cardiaca que correspondía a un rabdomiosarcoma del ventrículo izquierdo. Las complicaciones postoperatorias incluyeron: arritmias supraventriculares (10 por ciento), bloqueo incompleto de la rama derecha del haz de His 1 caso (5 por ciento), sangrado postoperatorio 1 caso (5 por ciento) y mediastinitis 1 caso (5 por ciento). El estudio anatomopatológico de 17 piezas quirúrgicas demostró: pericarditis crónica inespecífica en 6 casos (35 por ciento), fibrosis e infiltración cálcica en 3 (17 por ciento), perivasculitis crónica en 3 (17 por ciento), granulomatosis crónica en 2 (11 por ciento), pericarditis fibrinopurulenta en 2 (11 por ciento) y fibrosis hialina en uno (5 por ciento). El seguimiento a 25 meses, promedio, demostró una mejoría en la clase funcional: clase I 72 por ciento y clase II 27 por ciento. Los resultados de este estudio se correlacionan bien con los reportados en otras series. La pericarditis más común en nuestro medio sigue siendo la idiopática
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Cateterismo Cardíaco/métodos , Derrame Pericárdico/terapia , Ecocardiografia , Neoplasias Cardíacas/terapia , Pericardiectomia , Pericardite Constritiva/terapia , Tamponamento Cardíaco/terapia , Uremia/complicaçõesRESUMO
Los inconvenientes técnicos y la morbi-mortalidad relacionada con dos operaciones en la reparación clásica en dos tiempos ha conducido a varios grupos de cirujanos a corregir esta enfermedad de etapas tempranas. Nosotros presentamos 19 niños con tetralogía de Fallot (T.F.) operados entre julio de 1988 y agosto de 1992: 11 hombres y 8 mujeres con edades entre 11 meses y 11 años sin cirugía previa. El cateterismo preoperatorio reveló un gradiente en resección a través de la aurícula derecha, en combinación con una arteriotomía pulmonar, con cierre de comunicación interventricular por este mismo medio. Un paciente falleció con hipertensión pulmonar severa. El resto se encontraba en buenas condiciones, en clase funcional I-II de la NYHA, sin necesidad de medicamentos, a 23.1 meses de seguimiento en promedio, con gradiente transinfundibular menor de 21 mm Hg. El ecocardiograma bidimensional demostró regurgitación pulmonar en 44.9 por ciento de los casos: sólo en 3 de ellos moderada y en ninguno severa. La reparación transatrial-transpulmonar de la T.F. evita las consecuencias hemodinámicas secundarias a la corrección transanular y ventriculotomía, preserva la función ventricular y reduce la posibilidad de falla derecha en el postoperatorio temprano. Es aplicable a muchos de estos casos incluyendo además aquellos con origen anómalo de las arterias coronarias, en especial la descendente anterior que cruza la cara anterior del ventrículo derecho
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Angiocardiografia , Ecocardiografia , Tetralogia de Fallot/cirurgiaRESUMO
Se presenta una revisión retrospectiva de 44 pacientes con heridas por arma de fuego y arma blanca que ingresaron al Servicio de Emergencia del Hospital Dr. "Luis Salazar Dominguez" IVSS, Guarenas (Estado Miranda), en un período de 4 años (abril 1988-mayo 1992). Se detérmino cual fue el sexo grupo etario más afectado, así como las lesiones más frecuentes y tratamiento quirúrgico realizado. Se hace referencia sobre la morbimortalidad obtenida. Nuestro objetivo fue el de realizar una comparación estadística de nuestros casos