Deshidrogenasa láctica sérica en preeclámpticas y embarazadas normotensas

Avelin Vargas García; Eduardo Reyna Villasmil; Jorly Mejia Montilla; Nadia Reyna Villasmil; Joel Santos Bolívar; Andreina Fernández Ramírez

Adolescents with perinatally acquired HIV: emerging behavioral and health needs forCompu4aa202016-09-17T23:48:00Z2016-09-20T01:22:00Z2016-09-20T01:22:00Z6473926070IDIC217613074814

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Deshidrogenasa láctica sérica en preeclámpticas y embarazadas normotensas

(

Serum lactic dehydrogenase in preeclamptic patients and normotensive pregnant women

)

Avelin Vargas-García

, Eduardo Reyna-Villasmil



, Jorly Mejia-Montilla

, Nadia Reyna-Villasmil

, Joel Santos-Bolívar

, Andreina Fernández-Ramírez

1 Servicio de Obstetricia y Ginecología - Maternidad "Dr. Nerio Belloso" Hospital Central "Dr. Urquinaona". Maracaibo, Estado Zulia. Venezuela.

Recibido

Abril

201

Aceptado

Septiembre

2016

Publicación online:

Septiembre

2016

[TRABAJO ORIGINAL]

Resumen (español)

El objetivo de la investigación fue comparar las concentraciones séricas de deshidrogenasa láctica en pacientes con preeclampsia y embarazadas normotensas sanas. Se seleccionó un total de 180 pacientes. Se incluyeron 90 preeclámpticas como grupo de estudio (grupo A) y un grupo de control seleccionado por tener edad e índice de masa corporal similares al grupo de estudio que consistió en 90 embarazadas normotensas sanas (grupo B). Las muestras de sangre se recolectaron en todas las pacientes antes del parto e inmediatamente después del diagnóstico en el grupo A para determinar las concentraciones de deshidrogenasa láctica. Se encontraron diferencias estadísticamente significativas en las concentraciones séricas de deshidrogenasa láctica entre las pacientes del grupo de estudio (grupo A: 523,9 +/- 131,7 UI/L) y las pacientes del grupo de control (grupo B: 241,0 +/- 76,3 UI/L; p < 0,001). No se observaron correlaciones significativas con los valores de presión arterial sistólica y diastólica (p = ns). Un valor de corte de 350 UI/L presentó un valor por debajo de la curva de 0,98, sensibilidad del 92,2%, especificidad del 86,6%, valor predictivo positivo del 87,7% y valor predictivo negativo del 91,7%, con una exactitud diagnóstica del 89,4%. Se concluye que las preeclámpticas presentaron concentraciones séricas significativamente más altas de deshidrogenasa láctica al compararlo con embarazadas normotensas sanas

Palabras clave

(español)

Deshidrogenasa láctica, preeclampsia; embarazo

Abstract (english)

The objective of research was to compare serum lactic dehydrogenase in preeclamptic patients and healthy normotensive pregnant women. A total of 180 patients were selected. Ninety preeclamptic patients were selected as the study group (group A) and 90 healthy normotensive pregnant women with the same age and body mass index as the study group were selected as controls (group B). Blood samples were extracted from all patients before labor and immediately after diagnosis in group A to determine serum lactic dehydrogenase concentrations. There was statistically significant difference in serum lactic dehydrogenase concentrations between group A (523.9 +/- 131.7 UI/L) and group B (241.0 +/- 76.3 UI/L; p < 0.001). There were not significant correlation with systolic and diastolic blood pressure values (P = ns). A cutoff value of 350 UI/L had an area under the curve of 0.98, sensitivity of 92.2%, specificity of 86.6%, a positive predictive value of 87.7% and a negative predictive value of 91.7%, with a diagnostic accuracy of 89.4%. It is concluded that preeclamptic patients have significantly higher concentrations of serum lactic dehydrogenase compared with healthy normotensive pregnant women

Keywords

(english)

Lactic dehydrogenase; preeclampsia, pregnancy

DHL

sérica en preeclámpticas

Vargas-García

A y col

Vargas-García

y col.

DHL

sérica en preeclámpticas

Avan Biomed

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Avances en Biomedicina

Publicación Oficial del Instituto de Inmunología Clínica

Mérida-Venezuela

Volumen 5(

Agosto

2016, p

Depósito Legal:

PPI201102ME3935

ISSN:

2477-9369

Autor de correspondencia: Dr. Eduardo Reyna-Villasmil, Hospital Central "Dr. Urquinaona" Final Av. El Milagro. Maracaibo, Estado Zulia. Venezuela. Teléfono: 584162605233. Email: sippenbauch@gmail.com

Introducción

La preeclampsia es un desorden propio del embarazo humano y es la principal causa de muertes maternas y morbilidad del feto en crecimiento. Está caracterizada por amplia disfunción endotelial materna que produce hipertensión secundaria a vasoconstricción generalizada, proteinuria debida a lesión glomerular y edema causado por aumento de la permeabilidad vascular (1,2).

El embarazo normal está asociado con activación de los leucocitos sanguíneos periféricos. Los factores específicos que inducen daño endotelial en la preeclampsia son desconocidos, aunque se ha reportado activación del sistema de coagulación, de las plaquetas y de los neutrófilos y se localizan en el sitio de lesión vascular (3). Se ha sugerido que todo esto es atribuible a una respuesta inflamatoria materna excesiva al embarazo secundario a la combinación de factores placentarios y maternos relacionados con el fenotipo y el genotipo (4,5).

Se ha propuesto que los perfiles enzimáticos varían de acuerdo con las necesidades metabólicas particulares de los diferentes tejidos y que esta variación puede producirse en respuesta a isquemia, inflamación, necrosis o neoplasias malignas (6). Los valores enzimáticos considerados como normales obedecen a la renovación celular, por lo que un aumento de sus valores séricos responde siempre a un daño celular o a necrosis (7). La afección multi-orgánica que se observa en la preeclampsia puede ser evaluada por la determinación de las enzimas séricas para determinar el grado de gravedad y afección de distintos sistemas (8).

Diferentes pruebas de laboratorio que se han utilizado en busca de un indicador para el diagnóstico de la preeclampsia. Entre los indicadores de laboratorio destaca la deshidrogenasa láctica (DHL). Esta es una enzima del metabolismo intermedio, presente en todas las células. Los distintos tejidos contienen diferentes cantidades e isoenzimas. El corazón, riñón, cerebro y hematíes muestran un predominio de la iso-enzima 1, la iso-enzima 2, 3 y 4 destacan en pulmón, bazo, glándulas endocrinas, ganglios linfáticos y plaquetas. La iso-enzima 5 se encuentra fundamentalmente en hígado y músculo esquelético (9).

Las concentraciones de DHL pueden ser utilizadas para determinar la extensión de la muerte

celular y por lo tanto la severidad de la enfermedad (10-12). También puede ser útil para el diagnóstico y la toma de decisiones con relación a las estrategias de manejo del síndrome hipertensivo del embarazo. El objetivo de la investigación fue comparar las concentraciones séricas de deshidrogenasa láctica sérica en preeclámpticas y embarazadas normotensas sanas.

Materiales y métodos

Se realizó un estudio de casos y controles entre enero del 2014 y febrero del 2016 que incluyó mujeres con embarazos simples que fueron atendidas en el Hospital Central “Dr. Urquinaona”, Maracaibo, Venezuela. La investigación fue aprobada por el Comité de Ética e Investigación del hospital y se obtuvo consentimiento por escrito de todas las pacientes.

Selección de pacientes

. Se seleccionó un total de 180 embarazadas de las cuales 90 preeclámpticas fueron seleccionadas como casos (grupo A) y un grupo control que fue seleccionado por tener edad materna e índice de masa corporal al momento de la selección similar al grupo de estudio, y consistió en 90 embarazadas normotensas sanas (grupo B).

Se excluyó a las embarazadas con polihidramnios, hemorragia del tercer trimestre (desprendimiento prematuro de placenta, placenta previa), sospecha de restricción del crecimiento intrauterino del feto (circunferencia cefálica, circunferencia abdominal y longitud del fémur menor del percentil 10 de referencia con confirmación posnatal de peso menor al percentil 10 de referencia), síndrome de HELLP, alteraciones de la frecuencia cardiaca fetal, gestaciones múltiples, presencia de infección intrauterina o materna activa, enfermedad hipertensiva crónica (hipertensión antes de las 20 semanas de embarazo), enfermedad cardiaca, hematológicas, hepática, renal o sistémica crónica, diabetes mellitus pre o gestacional, hábito tabáquico, aquellas embarazadas en las cuales no se pudo obtener muestras de sangre y en las que hayan utilizado medicamentos que alteren la concentración de DHL (por ejemplo, antihipertensivos, expansores plasmáticos). También se excluyó a las pacientes que se negaron a participar en la investigación.

La preeclampsia se definió como presión arterial sistólica de 140 mm de Hg o más, o presión

arterial diastólica de 90 mm de Hg o más, confirmada por 6 h o más de diferencia, mientras que la proteinuria se definió como 300 mg o más de proteína en una muestra de 24 h, o 1-2 cruces de proteinuria en un examen cualitativo después de las 20 semanas de gestación. La presión sanguínea se midió en posición sentada después de 15 min de descanso usando un esfigmógrafo de mercurio estándar con un manguito de 14 cm. La presión arterial sistólica y diastólica (tomada en relación con el quinto ruido de Korotkoff) se ubicó con relación al punto de 2 mm de Hg más cercano. El método palpatorio se utilizó para verificar las lecturas auscultatorias de la presión arterial sistólica. Las presiones arteriales sistólica y diastólica se calcularon del promedio de la presión arterial de cada brazo.

Recolección de muestras y determinación de DHL sérica

Se recolectaron 10 ml de sangre de la vena antecubital en todas las pacientes antes del parto e inmediatamente después del diagnóstico en las embarazadas del grupo de casos y antes de la administración de cualquier medicamento. Estas muestras se colocaron en un tubo de vidrio seco, estéril y almacenado a temperatura ambiente y protegidos de la luz ultravioleta. Posteriormente fueron centrifugados a 1600 rpm por 10 minutos y separados en alícuotas y se almacenaron a -70º C hasta el momento del análisis.

Las mediciones de hemoglobina y plaquetas se realizaron utilizando un analizador cuantitativo automático de hematología LH75 (Beckman Coulter Inc®., EE.UU.). Las concentraciones séricas de ácido úrico y creatinina también se determinaron por espectrofotometría con un kit comercial (DiaSys Diagnostic Systems®, Alemania) con una sensibilidad de 0,01 mg/dL y 0,1 mg/dL, respectivamente. La proteinuria se determinó en una muestra de orina de 24 h y se almacenó a −20ºC. Los valores se determinaron por medio de una prueba turbidimétrica (Raichem®, EE.UU.). Los coeficientes de variación inter e intraensayo fueron menores del 5 y el 7%, respectivamente.

Tabla 1.

Características generales

GRUPO ACasos(n = 90)

GRUPO BControles(n = 90)pEdad, años21,9 +/- 2,422,4 +/- 2,3nsEdad gestacional al momento del parto, semanas38,8 +/- 1,038,9 +/- 1,1nsÍndice de masa corporal, Kg/m230,0 +/- 1,229,7 +/- 1,2nsPresión arterial sistólica, mm de Hg150,2 +/- 12,6104,5 +/- 6,1< 0,001Presión arterial diastólica, mm de Hg106,2 +/- 8,374,3 +/- 8,0< 0,001Peso del recién nacido, g2929 +/- 3443645 +/- 390< 0,001

Las concentraciones de aspartato aminotransferasa y alanino aminotransferasa se midieron por el método de espectofotometría usando kits comerciales (DiaSys Diagnostic Systems®, Alemania) con sensibilidad de 4 UI/L y 2 UI/L, respectivamente. Las determinaciones de las concentraciones séricas de DHL se realizaron con una prueba comercial cuantitativa, usando una prueba enzimática de lactato a piruvato (Roche Diagnostics Corp®, EE.UU.) con coeficientes de variación intra e inter ensayo de 8,7% y 7%, respectivamente. Los valores de referencia para cada prueba fue: aspartato aminotransferasa 10 - 40 UI/L, alanino aminotransferasa: 10 - 45 UI/L y LDH: 300 - 600 U/L. Los coeficientes de variación inter e intra-ensayo fueron menores del 8% y 10%, respectivamente.

Análisis estadístico

Los datos se presenta como valores promedios +/- desviación estándar. El análisis estadístico entre los dos grupos se realizó una prueba t de Student para datos no relacionados para comparar las características demográficas y las concentraciones séricas de DHL. Se utilizó la prueba de Pearson para establecer la correlación entre la presión arterial, datos de laboratorio y peso del recién nacido con las concentraciones séricas de DHL. La precisión de la DHL para el diagnóstico de preeclampsia se presentó en función de sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo. Se utilizó el análisis operador-receptor para determinar el mejor valor de corte. Se consideró p < 0,05 como estadísticamente significativa.

Resultados

Las características de las preeclámpticas (grupo A) y las embarazadas normotensas (grupo B) se muestran en la tabla 1. No se encontraron diferencias estadísticamente significativas con relación a la edad materna, edad gestacional al momento del parto e índice de masa corporal materno (p = ns), pero si encontraron diferencias estadísticamente significativas en los valores de la presión arterial sistólica, presión

arterial diastólica y peso del recién nacido (p < 0,001).

Tabla

Características de laboratorio

GRUPO ACasos(n = 90)

GRUPO BControles(n = 90)pHemoglobina, g/dL11,1 +/- 1,510,3 +/- 1,3< 0,001Plaquetas, x103/mm3174,6 +/- 40,1252,1 +/- 30,3< 0,001Aspartato aminotransferasa, UI/L90,0 +/- 29,022,7 +/- 7,7< 0,001Alanino aminotransferasa, UI/l107,6 +/- 34,627,9 +/- 5,4< 0,001Creatinina, mg/dL0,9 +/- 0,10,7 +/- 0,1< 0,001Ácido úrico, mg/dL5,0 +/- 0,63,4 +/- 0,3< 0,001Proteinuria en 24 horas, g3,95 +/- 0,590,15 +/- 0,02< 0,001Deshidrogenasa láctica, UI/L523,9 +/- 131,7241,0 +/- 76,3< 0,001

En la tabla 2 se muestran los valores de laboratorio de cada uno de los grupos. Las concentraciones de hemoglobina, plaquetas, transaminasas, creatinina, ácido úrico y proteinuria fueron significativamente más altas en las pacientes del grupo A comparado con las pacientes del grupo B (p < 0,001). Las pacientes del grupo A presentaron valores significativamente más altas de DHL (523,9 +/- 131,7 UI/L) comparado con las pacientes del grupo B (241,0 +/- 76,3 UI/L; figura 1; p < 0,001).

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Figura 1.

Concentraciones séricas de deshidrogenasa láctica en cada uno de los grupos de estudio

Al correlacionar las concentraciones séricas de DHL con los valores de presión arterial, se observaron correlaciones significativas entre los valores de DHL y los valores de presión arterial sistólica y diastólica en las pacientes de ambos grupos (p < 0,05). En las embarazadas controles solo se observó correlación débil, positiva y significativa entre las concentraciones séricas de DHL y los valores de presión arterial diastólica (r = 0,270; p < 0,05). No se encontró correlación entre las concentraciones de DHL y la presión arterial en las pacientes del grupo de casos (p = ns). Las concentraciones de DHL solo mostraron una correlación débil, negativa y significativa con los valores de alanino aminotransferasa en las preeclámpticas (r = -0,254; p < 0,05). Tampoco se encontraron correlaciones significativas con el peso del recién nacido en ninguno de los dos grupos (para el grupo de casos r = -0,029 y para el grupo control r = 0,066; p = ns para ambos).

Al analizar la capacidad del valor de corte de 350 UI/L de DHL en el diagnóstico de preeclampsia (figura 2) se observó que el área bajo la curva fue de 0,98 (intervalo de confianza [IC] del 95%; 0,97 - 0,99)

con sensibilidad del 92,2 (IC del 95%; 84,6 – 96,8), especificidad del 86,6% (IC del 95%; 77,8 – 92,9), valor predictivo positivo del 87,7% (IC del 95%; 78,9 – 93,3%) y valor predictivo negativo del 91,7% (IC del 95%; 83,7 – 96,6%). La relación de probabilidad positiva fue de 6,91. La exactitud diagnóstica de la prueba fue de 89,4%.

Discusión

Los resultados de la investigación confirman las alteraciones en las concentraciones séricas de DHL de las pacientes con preeclampsia comparado con las embarazadas normotensas sanas y demuestran que puede ser utilizada como una prueba útil para confirmar el diagnóstico de preeclampsia.

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AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAD//Z

Figura 1.

Curva operador-receptor de las concentraciones séricas de deshidrogenasa láctica para el diagnóstico de preeclampsia

La DHL es una enzima citoplasmática que contiene zinc y se encuentra en diferentes ubicaciones en los mamíferos. Es un tetrámero que tiene un peso molecular de cerca de 140 kDa. Para que una molécula de tal tamaño sea liberada al espacio extracelular a través de la membrana citoplasmática, se debe al intercambio celular normal como la apoptosis o a destrucción celular como el infarto agudo de miocardio. Cuando se desarrollaron las técnicas de separación de isoenzimas de DHL, muchos investigadores intentaron relacionar las alteraciones en el patrón iso-enzimático con el daño a ciertos

tejidos como el hígado o músculo estriado (13). En el miocardio, la iso-enzima 1 contribuye con cerca del 60% de la actividad total de la deshidrogenasa lactina; en el eritrocito la contribución es cerca del 40% (14). La iso-enzima 1 predomina en tejidos ricos en aporte de oxigeno que sufren metabolismo oxidativo, mientras la 5 es la principal forma hallada en el músculo esquelético, al tratarse de un tejido que experimenta glucólisis anaerobia con acumulación de lactato y piruvato (15).

La preeclampsia es considerada un desorden multi-sistémico con un complejo mecanismo endocrinológico responsable de la disfunción endotelial (16,17). Se ha sugerido que la disfunción vascular sistémica como causa patogénica central de la preeclampsia (17-20). Esta disfunción incrementa la sensibilidad de la vasculatura a las sustancias vasoactivas, con una posterior reducción de la perfusión y perdida de líquido desde el compartimiento intravascular (21). Estos cambios hemodinámicos junto con la activación de la cascada de coagulación con formación de micro-trombos secundarios al daño endotelial producirá las diferentes complicaciones clínicas asociadas a la preeclampsia (17,19).

Varios potenciales marcadores bioquímicos han sido propuestos en el diagnóstico del síndrome hipertensivo del embarazo. Entre estos está la DHL.

(22,23). Existen estudios que han confirmado la asociación entre la elevación de las concentraciones y la preeclampsia (11,12) y otro que no logró demostrar tal asociación (10). La elevación de las concentraciones séricas de DHL en la preeclampsia está asociada con el aumento de la actividad de la iso-enzima 1 comparado con las otras isoenzimas. Aunque los resultados de esta investigación demuestran que las concentraciones séricas de DHL son significativamente más elevadas en las pacientes con preeclampsia que en las embarazadas normotensas, no se observaron correlaciones significativas con los valores de presión arterial. La única correlación significativa fue con alanino aminotransferasa.

La elevación de las transaminasas y de DHL son manifestaciones de la preeclampsia y puede ser la causa de hematoma hepático sub-capsular, función hepática anormal en el síndrome de HELLP debido a necrosis hemorrágica peri-portal o puede ser un indicador de eclampsia inminente. En la mayoría de los casos los síntomas asociados son epigastralgia, cefalea, alteraciones de la agudeza visual o vómitos. Por lo que las elevaciones marcadas de DHL (superiores a 800 UI/L) pueden ser indicativas de daño celular hepático (24).

En esta investigación se observó que la exactitud diagnóstica de la determinación de deshidrogenasa para el diagnóstico de preeclampsia es cercana al 90% cuando los valores sobrepasan las 350 UI/L. Se desconoce si alguna investigación previa ha demostrado estos valores. Estos hallazgos podrían sugerir que la disfunción multi-orgánica que se observa en la preeclampsia causada por el daño vascular de los tejidos hepático, renal, pulmonar, nervioso, sanguíneo y del sistema de coagulación podría llevar a un exceso en la producción de DHL que lleva a elevación de las concentraciones séricas secundarias (10-12).

Los hallazgos de esta investigación tampoco demostraron correlación entre las concentraciones séricas de DHL y el peso del recién nacido en el grupo de preeclámpticas. Este hallazgo es similar a lo reportado por Qublan y col. (25). Sin embargo, He y col. (26) encontraron una asociación significativa de ambos parámetros, lo cual puede ser explicado por la incidencia de partos pretérminos en las pacientes con preeclampsia.

Se ha considerado que la elevación de DHL es una respuesta reactiva hacia la alteración inmunológica que se observa en la preeclampsia (27). La respuesta de fase aguda involucra citocinas liberadas de las células inflamatorias las cuales es una reacción de defensa contra el agente causal para proteger las funciones vitales. El incremento de las concentraciones de la iso-enzima 1 se origina de los eritrocitos y diferentes tejidos corporales. El aumento de las concentraciones séricas de DHL se ha propuesto como resultado de la destrucción tisular masiva por la hiperactividad inmune (28). Se ha demostrado que el aumento de las concentraciones de citocinas y quimocinas con elevación significativas de interferón gamma, interleucina 1, interleucina 6, interleucina 12, proteína 1 quimioatrayente de neutrófilos y la proteína 10 inducible por el interferón gamma (29). La elevación de las concentraciones séricas de DHL es común en muchas enfermedades y puede ser inducido por diferentes factores.

La elevación de las concentraciones séricas de DHL puede reflejar, en parte, la severidad de la respuesta de la fase aguda, la cual a su vez refleja la severidad del daño tisular (29). Establecer el diagnóstico y realizar un manejo y tratamiento adecuado resulta, en algunas ocasiones, una tarea complicada. Se debe determinar si la elevación de DHL y otras enzimas pueden servir como marcador para predecir los resultados clínicos en pacientes con diagnóstico de preeclampsia.

Se concluye que las preeclámpticas presentaron concentraciones séricas significativamente más altas de deshidrogenasa láctica al compararlo con embarazadas normotensas sanas. Los hallazgos sugieren que la determinación de la DHL sérica en la preeclampsia puede ser un marcador bioquímico útil para determinar la severidad de la enfermedad materna.

Conflicto de Interés

Los autores declaran no tener ningún conflicto de interés

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Como citar este artículo:

Vargas-García A, Reyna-Villasmil E, Mejia-Montilla Y, Reyna-Villasmil N, Santos-Bolívar J, Fernández-Ramírez A

Deshidrogenasa láctica sérica en preeclámpticas y embarazadas normotensas

Avan Biomed

2016; 5:

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