ALT-EJ genera rearreglos cromosómicos en respuesta a Etopósido en células humanas con los principales sistemas de reparación de rupturas de doble cadena comprometidos / ALT-EJ originates chromosomal rearrangements in response to Etoposide in human cells with the main DNA double-strand break repair systems compromised

RESUMEN La droga antitumoral Etopósido (ETO) induce rupturas de doble cadena en el ADN (RDC) y promueve el desarrollo de neoplasias secundarias en los pacientes tratados. Dos mecanismos principales, recombinación homóloga (HR) y reunión de extremos no-homólogos clásica (c-NHEJ) reparan las RDC. Cuando HR y c-NHEJ son defectuosas, la vía alternativa de reunión de extremos (alt-EJ) dependiente de PARP-1 está implicada. Se examinó la participación de alt-EJ en la progresión de las RDC inducidas por ETO en la fase G2 de células humanas. Se establecieron células HeLa deficientes en HR (inhibición de cohesina RAD21, HeLa RAD21kd) y su control no-silenciada (HeLa NS). Las células se trataron con ETO en presencia del inhibidor químico de DNA-PKcs (DNA-PKi, c-NHEJ). En ambas líneas celulares, la inducción de RDC (γH2AX+) por ETO en la fase G2 aumentó respecto a sus controles. La reparación incorrecta en células deficientes en DNA-PKcs y RAD21 originó un incremento sinérgico de intercambio de cromátidas y de cromosomas dicéntricos en la primera y segunda metafase, respectivamente. En cambio, la frecuencia de cromosomas dicéntricos se redujo en células deficientes en PARP-1 (HeLa PARP- 1kd) luego del tratamiento con ETO. En células binucleadas HeLa RAD21kd, DNA-PKi/ETO acrecentó el porcentaje de células con ≥20 focos γH2AX en la fase G1-posmitótica y de micronúcleos a las 96 h. Una mayor acumulación en G2/M se observó en HeLa NS tratadas con DNA-PKi/ETO en relación a HeLa RAD21kd a las 8 h. El ciclo celular se reanudó en HeLa NS a las 16 h, sin embargo, la acumulación se mantuvo en HeLa RAD21kd. Los rearreglos cromosómicos obtenidos con DNA-PKcs y RAD21 disfuncionales y su disminución en células HeLa PARP-1kd, sugieren que alt-EJ contribuye a su formación.

ABSTRACT The antitumor drug Etoposide (ETO) induces DNA double-strand breaks (DSB) and is associated with the development of secondary neoplasms in treated patients. DSB are repaired by two main mechanisms, homologous recombination (HR) and classical non-homologous end joining (c-NHEJ). When HR and c-NHEJ are defective, DSB are repaired by the PARP-1-dependent alternative end-joining (alt-EJ) pathway. The involvement of alt-EJ in the progression of DSB induced by ETO in the G2 phase of human cells was analyzed. HeLa cells deficient in HR (cohesin RAD21 inhibition, HeLa RAD21kd) and their nonsilencing control (HeLa NS) were established. Cells were treated with ETO in the presence of a chemical inhibitor of DNA-PKcs (DNA-PKi, c-NHEJ). In both cell lines, ETO-induced DSB (γH2AX+) in G2 phase were increased compared to their controls. The incorrect repair of DSB in DNA-PKcs- and RAD21-deficient cells caused a synergistic augment in chromatid exchanges and dicentric chromosomes in the first and second metaphase, respectively. In contrast, the frequency of dicentric chromosomes was reduced in PARP-1-deficient cells (HeLa PARP-1kd) following ETO treatment. In HeLa RAD21kd binucleated cells, DNA-PKi/ETO increased the percentage of cells with ≥20 γH2AX foci in the G1-postmitotic phase and of micronuclei at 96 h. A greater accumulation in G2/M was observed in HeLa NS treated with DNA-PKi/ ETO compared with HeLa RAD21kd at 8 h. The cell cycle restarted in HeLa NS at 16 h; however, the G2/M accumulation was maintained in HeLa RAD21kd. Chromosomal rearrangements obtained when DNAPKcs and RAD21 were absent and their decrease in HeLa PARP-1kd cells suggest that alt-EJ contributes to their formation.

Revisión del intervalo de referencia del recuento plaquetario: ¿son adecuados los valores que estamos utilizando? / Review of the platelet count reference range: are the values we are using appropriate?

Los intervalos de referencia (IR) dependen de la población y de las características metrológicas del procedimiento de medida utilizado. A pesar de las recomendaciones internacionales, son pocos los laboratorios que establecen sus propios IR para cada magnitud por la dificultad para conseguir voluntarios de referencia y el elevado costo económico asociado. La International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) acepta la adopción de IR bibliográficos o su cálculo por métodos indirectos dado su bajo costo y fácil obtención. Existen varias fuentes confiables de IR bibliográficos para el hemograma. No obstante, para el recuento plaquetario, es una práctica común de los laboratorios emplear el rango de valores de 150-450.109 /L independiente de la metodología utilizada y grupo etario. El objetivo de este trabajo fue revisar los IR bibliográficos disponibles para el recuento plaquetario y estimarlo empleando el método indirecto de Hoffmann a partir de nuestra población. Los métodos indirectos se basan en aplicar criterios de exclusión y cálculos matemáticos sobre los resultados de una base de datos de laboratorio. Nuestros IR para el recuento plaquetario se comparan con los bibliográficos, que han sido establecidos por técnicas de muestreo directo. Por este motivo y dado que no existen estudios poblacionales que lo avalen, sería apropiado reemplazar el rango de 150-450.109 / L. Estos límites podrían seguir empleándose como puntos de corte o niveles de decisión médica para definir, según la clínica y otros resultados de laboratorio, los pacientes que ameritan un seguimiento posterior (AU)

Reference ranges (RR) depend on the population and the metrological characteristics of the measurement procedure used. Despite international recommendations, few laboratories establish their own RRs for each magnitude because of the difficulty in obtaining reference volunteers and the associated high economic cost. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) accepts the use of literaturebased RRs or RRs calculated by indirect methods because of their low cost and easy collection. There are several reliable sources of literature-based RRs for the Cell Blood Count. However, for platelet count, it is common laboratory practice to use the range of 150-450,109 /L regardless of the methodology used and age group. The aim of this study was to review the available literature regarding RRs for platelet count and to establish it using the indirect Hoffmann method in our population. Indirect methods are based on applying exclusion criteria and mathematical calculations on the results of a laboratory database. Our RRs for platelet counts are compared with those in the literature, which have been established by direct sampling techniques. Therefore, and given that there are no population studies to support these findings, it would be appropriate to replace the 150-450,109 /L range. These limits may continue to be used as cut-off points or medical decision levels to define, according to clinical manifestations and other laboratory results, patients who warrant further follow-up (AU)

Cost of lost productivity from acute respiratory infections in South America.

Objectives: To estimate the burden of permanent productivity losses caused by acute respiratory infections in South American countries in 2019. Methods: Mortality data from the Global Burden of Disease Study 2019 were analyzed to estimate the burden of disease attributable to acute respiratory infections. An approach based on the human capital method was used to estimate the cost of permanent productivity losses associated with respiratory diseases. To calculate this cost, the sum of the years of productive life lost for each death was multiplied by the proportion in the workforce and the employment rate, and then by the annual minimum wage or purchasing power parity in United States dollars (US$) for each country in the economically active age groups. Separate calculations were done for men and women. Results: The total number of deaths from acute respiratory infections in 2019 was 30 684 and the years of productive life lost were 465 211 years. The total cost of permanent productivity loss was about US$ 835 million based on annual minimum wage and US$ 2 billion in purchasing power parity, representing 0.024% of the region's gross domestic product. The cost per death was US$ 33 226. The cost of productivity losses differed substantially between countries and by sex. Conclusion: Acute respiratory infections impose a significant economic burden on South America in terms of health and productivity. Characterization of the economic costs of these infections can support governments in the allocation of resources to develop policies and interventions to reduce the burden of acute respiratory infections.

Cost of lost productivity from acute respiratory infections in South America

[ABSTRACT]. Objectives. To estimate the burden of permanent productivity losses caused by acute respiratory infections in South American countries in 2019. Methods. Mortality data from the Global Burden of Disease Study 2019 were analyzed to estimate the burden of disease attributable to acute respiratory infections. An approach based on the human capital method was used to estimate the cost of permanent productivity losses associated with respiratory diseases. To calculate this cost, the sum of the years of productive life lost for each death was multiplied by the proportion in the work- force and the employment rate, and then by the annual minimum wage or purchasing power parity in United States dollars (US$) for each country in the economically active age groups. Separate calculations were done for men and women. Results. The total number of deaths from acute respiratory infections in 2019 was 30 684 and the years of productive life lost were 465 211 years. The total cost of permanent productivity loss was about US$ 835 mil- lion based on annual minimum wage and US$ 2 billion in purchasing power parity, representing 0.024% of the region’s gross domestic product. The cost per death was US$ 33 226. The cost of productivity losses differed substantially between countries and by sex. Conclusion. Acute respiratory infections impose a significant economic burden on South America in terms of health and productivity. Characterization of the economic costs of these infections can support governments in the allocation of resources to develop policies and interventions to reduce the burden of acute respiratory infections.

[RESUMEN]. Objetivos. Estimar la carga de la pérdida permanente de productividad causada por infecciones respiratorias agudas en países sudamericanos en el 2019. Métodos. Se analizaron los datos de mortalidad del estudio sobre carga mundial de enfermedad del 2019 para estimar la carga de enfermedad atribuible a las infecciones respiratorias agudas. Se empleó un enfoque basado en el método del capital humano para estimar el costo de las pérdidas permanentes de productividad relacionadas con las enfermedades respiratorias. Para ello, la suma de los años perdidos de vida productiva por cada muerte se multiplicó por la proporción de la fuerza de trabajo y la tasa de empleo y, a continuación, por el salario mínimo anual o la paridad del poder adquisitivo en dólares estadounidenses en los grupos etarios económicamente activos de cada país. Se realizaron cálculos separados para hombres y mujeres. Resultados. El número total de muertes por infecciones respiratorias agudas en el 2019 fue de 30 684 y se perdieron 465 211 años de vida productiva. El costo total de la pérdida permanente de productividad fue de aproximadamente US$ 835 millones según el salario mínimo anual y de US$ 2000 millones en cuanto a la paridad de poder adquisitivo, lo que representa el 0,024% del producto interno bruto de la región. El costo por muerte fue de US$ 33 226. El costo de la pérdida de productividad difirió sustancialmente entre los países y según el sexo. Conclusión. Las infecciones respiratorias agudas suponen una carga económica significativa para América del Sur en términos de salud y productividad. La caracterización de los costos económicos de estas infecciones puede ayudar a los gobiernos en la asignación de recursos para elaborar políticas e intervenciones que permitan reducir la carga de las infecciones respiratorias agudas.

[RESUMO]. Objetivos. Estimar a carga de perdas permanentes de produtividade causadas por infecções respiratórias agudas em países da América do Sul em 2019. Métodos. Dados de mortalidade do estudo Carga Global de Doença 2019 foram analisados para estimar a carga de doença atribuível a infecções respiratórias agudas. Utilizou-se uma abordagem baseada no método do capital humano para estimar o custo das perdas permanentes de produtividade associadas às doenças respiratórias. Para calcular esse custo, a soma dos anos de vida produtiva perdidos devido a cada morte foi multiplicada pela proporção da força de trabalho e da taxa de emprego. Em seguida, esse valor foi multiplicado pelo salário mínimo anual ou pela paridade do poder de compra, em dólares dos Estados Unidos (US$), de cada país nas faixas etárias economicamente ativas. Foram feitos cálculos separados para homens e mulheres. Resultados. O número total de mortes por infecções respiratórias agudas em 2019 foi de 30 684, com 465 211 anos de vida produtiva perdidos. O custo total da perda permanente de produtividade foi de cerca de US$ 835 milhões com base no salário mínimo anual e US$ 2 bilhões em paridade de poder de compra, o que representa 0,024% do produto interno bruto da região. O custo por morte foi US$ 33 226. O custo da perda de produtividade diferiu substancialmente entre os países e por sexo. Conclusão. As infecções respiratórias agudas impõem uma carga econômica significativa à América do Sul em termos de saúde e produtividade. A caracterização dos custos econômicos dessas infecções pode fundamentar as decisões de alocação de recursos tomadas pelos governos para desenvolver políticas e intervenções com o intuito de reduzir a carga das infecções respiratórias agudas.

Cost of lost productivity from acute respiratory infections in South America / Costo de la pérdida de productividad por infecciones respiratorias agudas en América del Sur / Custo da perda de produtividade devido a infecções respiratórias agudas na América do Sul

ABSTRACT Objectives. To estimate the burden of permanent productivity losses caused by acute respiratory infections in South American countries in 2019. Methods. Mortality data from the Global Burden of Disease Study 2019 were analyzed to estimate the burden of disease attributable to acute respiratory infections. An approach based on the human capital method was used to estimate the cost of permanent productivity losses associated with respiratory diseases. To calculate this cost, the sum of the years of productive life lost for each death was multiplied by the proportion in the workforce and the employment rate, and then by the annual minimum wage or purchasing power parity in United States dollars (US$) for each country in the economically active age groups. Separate calculations were done for men and women. Results. The total number of deaths from acute respiratory infections in 2019 was 30 684 and the years of productive life lost were 465 211 years. The total cost of permanent productivity loss was about US$ 835 million based on annual minimum wage and US$ 2 billion in purchasing power parity, representing 0.024% of the region's gross domestic product. The cost per death was US$ 33 226. The cost of productivity losses differed substantially between countries and by sex. Conclusion. Acute respiratory infections impose a significant economic burden on South America in terms of health and productivity. Characterization of the economic costs of these infections can support governments in the allocation of resources to develop policies and interventions to reduce the burden of acute respiratory infections.

RESUMEN Objetivos. Estimar la carga de la pérdida permanente de productividad causada por infecciones respiratorias agudas en países sudamericanos en el 2019. Métodos. Se analizaron los datos de mortalidad del estudio sobre carga mundial de enfermedad del 2019 para estimar la carga de enfermedad atribuible a las infecciones respiratorias agudas. Se empleó un enfoque basado en el método del capital humano para estimar el costo de las pérdidas permanentes de productividad relacionadas con las enfermedades respiratorias. Para ello, la suma de los años perdidos de vida productiva por cada muerte se multiplicó por la proporción de la fuerza de trabajo y la tasa de empleo y, a continuación, por el salario mínimo anual o la paridad del poder adquisitivo en dólares estadounidenses en los grupos etarios económicamente activos de cada país. Se realizaron cálculos separados para hombres y mujeres. Resultados. El número total de muertes por infecciones respiratorias agudas en el 2019 fue de 30 684 y se perdieron 465 211 años de vida productiva. El costo total de la pérdida permanente de productividad fue de aproximadamente US$ 835 millones según el salario mínimo anual y de US$ 2000 millones en cuanto a la paridad de poder adquisitivo, lo que representa el 0,024% del producto interno bruto de la región. El costo por muerte fue de US$ 33 226. El costo de la pérdida de productividad difirió sustancialmente entre los países y según el sexo. Conclusión. Las infecciones respiratorias agudas suponen una carga económica significativa para América del Sur en términos de salud y productividad. La caracterización de los costos económicos de estas infecciones puede ayudar a los gobiernos en la asignación de recursos para elaborar políticas e intervenciones que permitan reducir la carga de las infecciones respiratorias agudas.

RESUMO Objetivos. Estimar a carga de perdas permanentes de produtividade causadas por infecções respiratórias agudas em países da América do Sul em 2019. Métodos. Dados de mortalidade do estudo Carga Global de Doença 2019 foram analisados para estimar a carga de doença atribuível a infecções respiratórias agudas. Utilizou-se uma abordagem baseada no método do capital humano para estimar o custo das perdas permanentes de produtividade associadas às doenças respiratórias. Para calcular esse custo, a soma dos anos de vida produtiva perdidos devido a cada morte foi multiplicada pela proporção da força de trabalho e da taxa de emprego. Em seguida, esse valor foi multiplicado pelo salário mínimo anual ou pela paridade do poder de compra, em dólares dos Estados Unidos (US$), de cada país nas faixas etárias economicamente ativas. Foram feitos cálculos separados para homens e mulheres. Resultados. O número total de mortes por infecções respiratórias agudas em 2019 foi de 30 684, com 465 211 anos de vida produtiva perdidos. O custo total da perda permanente de produtividade foi de cerca de US$ 835 milhões com base no salário mínimo anual e US$ 2 bilhões em paridade de poder de compra, o que representa 0,024% do produto interno bruto da região. O custo por morte foi US$ 33 226. O custo da perda de produtividade diferiu substancialmente entre os países e por sexo. Conclusão. As infecções respiratórias agudas impõem uma carga econômica significativa à América do Sul em termos de saúde e produtividade. A caracterização dos custos econômicos dessas infecções pode fundamentar as decisões de alocação de recursos tomadas pelos governos para desenvolver políticas e intervenções com o intuito de reduzir a carga das infecções respiratórias agudas.

Association between vitamin D deficiency and common variants of Vitamin D binding protein gene among Mexican Mestizo and indigenous postmenopausal women.

PURPOSE: Vitamin D deficiency (VDD) and polymorphisms in the group-specific component (GC) gene are known to be associated in different populations. However, the effects of such genetic variants may vary across different populations. Thus, the objective of this study was to estimate the association between Vitamin D-Binding Protein (VDBP) haplotypes and VDD in mestizo postmenopausal women and Mexican Amerindian ethnic groups. METHODS: This was a cross-sectional study of 726 postmenopausal Mexican women from the Health Workers Cohort Study (HWCS) and 166 postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort in Mexico. GC polymorphisms (rs7045 and rs4588) were analyzed by TaqMan probes. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by Chemiluminescent Microparticle Immuno Assay. RESULTS: The prevalence of VDD serum 25(OH)D < 20 ng/mL was 43.7% in mestizo women and 44.6% in indigenous women. In HWCS, the single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were associated with VDD. In addition, women from the HWCS, carrying the haplotypes GC2/2 and GC1f/2 had higher odds of VDD (OR = 2.83, 95% CI 1.14, 7.02; and OR = 2.30, 95% CI 1.40, 3.78, respectively) compared to women with haplotype 1f/1 s. These associations were not statistically significant in the MAIS cohort. CONCLUSIONS: Our results show genetic association of the analyzed SNPs and related haplotypes, on the GC gene, with VDD in mestizo Mexican postmenopausal women. Moreover, a high prevalence of VDD with high genetic variability within the country was observed. Our results support the need for national policies for preventing VDD.

Cost-effectiveness analysis of oral rehydration therapy compared to intravenous rehydration for acute gastroenteritis without severe dehydration treatment.

BACKGROUND: Diarrhea causes, annually, approximately 1.7 billion cases and 760,000 deaths worldwide among children under 5 years of age, although these are preventable and treatable. This study aim to assess the cost-effectiveness for the treatment of diarrhea in emergency services in the management of children of acute gastroenteritis with non-severe dehydration. METHODS: A stochastic decision tree model considering the perspective of the Brazilian public health system was used to calculate the cost-effectiveness of the 5 interventions: oral rehydration therapy (ORT) at home, and if it fails supervised ORT; they would receive; ORT at home, and if it fails intravenous rehydration therapy (IVT). ORT at home and if it fails, the half of them will receive supervised ORT, and the other half would receive IVT; Patient receives supervised oral treatment; Patient receives IVT. Quality-adjusted life year (QALY) was used to measure the clinical outcomes. RESULTS: The strategy of initiating oral rehydration in children younger than 5 is the most efficient practice with a cost of $14.28 and effectiveness of 0.89 QALYs. CONCLUSION: ORT is an underutilized resource for the management of children with non-severe dehydration in emergency services. The overprescribed IVT increases cost without a corresponding significant increase in effectiveness.

Cost-effectiveness analysis of the treatment of mild and moderate Alzheimer's disease in Brazil

Objective: To perform a cost-effectiveness analysis of donepezil and rivastigmine therapy for mild and moderate Alzheimer's disease (AD) from the perspective of the Brazilian Unified Health System. Method: A hypothetical cohort of 1,000 individuals of both sexes, aged >65 years, and diagnosed with AD was simulated using a Markov model. The time horizon was 10 years, with 1-year cycles. A deterministic and probabilistic sensitivity analysis was performed. Results: For mild AD, the study showed an increase in quality-adjusted life years (QALYs) of 0.61 QALY/21,907.38 Brazilian reais (BRL) for patients treated with donepezil and 0.58 QALY/BRL 24,683.33 for patients treated with rivastigmine. In the moderate AD group, QALY increases of 0.05/BRL 27,414.96 were observed for patients treated with donepezil and 0.06/BRL 34,222.96 for patients treated with rivastigmine. Conclusions: The findings of this study contradict the standard of care for mild and moderate AD in Brazil, which is based on rivastigmine. A pharmacological treatment option based on current Brazilian clinical practice guidelines for AD suggests that rivastigmine is less cost-effective (0.39 QALY/BRL 32,685.77) than donepezil. Probabilistic analysis indicates that donepezil is the most cost-effective treatment for mild and moderate AD.

Cost-effectiveness analysis of the treatment of mild and moderate Alzheimer's disease in Brazil.

OBJECTIVE: To perform a cost-effectiveness analysis of donepezil and rivastigmine therapy for mild and moderate Alzheimer's disease (AD) from the perspective of the Brazilian Unified Health System. METHOD: A hypothetical cohort of 1,000 individuals of both sexes, aged >65 years, and diagnosed with AD was simulated using a Markov model. The time horizon was 10 years, with 1-year cycles. A deterministic and probabilistic sensitivity analysis was performed. RESULTS: For mild AD, the study showed an increase in quality-adjusted life years (QALYs) of 0.61 QALY/21,907.38 Brazilian reais (BRL) for patients treated with donepezil and 0.58 QALY/BRL 24,683.33 for patients treated with rivastigmine. In the moderate AD group, QALY increases of 0.05/BRL 27,414.96 were observed for patients treated with donepezil and 0.06/BRL 34,222.96 for patients treated with rivastigmine. CONCLUSIONS: The findings of this study contradict the standard of care for mild and moderate AD in Brazil, which is based on rivastigmine. A pharmacological treatment option based on current Brazilian clinical practice guidelines for AD suggests that rivastigmine is less cost-effective (0.39 QALY/BRL 32,685.77) than donepezil. Probabilistic analysis indicates that donepezil is the most cost-effective treatment for mild and moderate AD.

Eficacia de terapia fotodinámica como complemento de terapia convencional periodontal versus terapia convencional en el tratamiento de pacientes adultos con periodontitis crónica: una revisión sistemática con metaanálisis / Effectiveness photodynamic therapy complementing conventional periodontal therapy versus conventional therapy in the treatment of adult patients with chronic periodontitis: a systematic review with meta-analyses

Se evaluó la eficacia de la terapia fotodinámica como complemento de terapia periodontal convencional comparándola con la terapia convencional en el tratamiento de sacos periodontales en pacientes adultos con periodontitis crónica basándose en ensayos clínicos comprendidos entre los años 2010 y 2015, para determinar si su uso otorga mejores resultados para el tratamiento de esta enfermedad. Se seleccionaron ensayos clínicos aleatorios prospectivos, aleatorizados o no aleatorizados, controlados y no controlados que permitieron la comparación entre el tratamiento convencional y la terapia fotodinámica, con un grupo en el cual se utilizó sólo la terapia convencional. Los datos de los ensayos clínicos fueron ingresados al software Review Manager®. Se realizaron tres metaanálisis para las variables: Nivel de inserción clínica (NIC) y profundidad de sondaje (PS), el test de I2 fue utilizado para medir la heterogeneidad del estudio y posteriormente un análisis de sensibilidad para determinar los estudios heterogéneos. Se pudieron analizar 7 estudios, con un total de 186 pacientes, quienes fueron controlados 3 meses post tratamiento. Se utilizó la diferencia de medias, un intervalo de confianza de 95 % para medir el NIC y PS. A los 3 meses, no se encontró diferencias significativas en NIC (p= 0,93) y PS (p= 0,71). Conclusión: La terapia fotodinámica en complementación a la terapia convencional no otorga mejor resultado clínico ni estadístico comparado con la terapia convencional al evaluar el nivel de inserción clínica. Al evaluar la profundidad de sondaje es recomendable la utilización de terapia convencional sola.

The efficacy of photodynamic therapy as an adjunct to conventional periodontal therapy evaluated by comparing with conventional therapy alone in the treatment of periodontal pockets in adult patients with chronic periodontitis based on clinical trials between 2010 and 2015, to determine if its use can provide better results for treating this disease. Prospective randomized clinical trials and randomized clinical trials or non-randomized, controlled and uncontrolled that allowed comparison between a group which was applied to conventional therapy and photodynamic therapy, a similar group was selected to which you He applied only conventional therapy. Data from clinical trials entered into Review Manager®. Three meta-analyzes for the variables analyzed were performed: Level clinical attachment (NIC) and probing depth (PS), the test of I2 was used to measure the heterogeneity of the study and then a sensitivity analysis to determine which studies awardedheterogeneity. As results, seven studies analyzed in 186 patients who underwent treatment at least controlled within 3 months post treatment. The mean difference was used, a confidence interval of 95 % to measure the NIC and PS. At 3 months, no significant differences in NIC (p= 0.93) and PS (p= 0.71). In conclusion, the photodynamic therapy complementary to conventional therapy does not provide better clinical or statistical results compared with conventional therapy to evaluate the clinical attachment level. In assessing probing depth, is advisable to use conventional therapy alone.

[Resection of an aneurysmal bone cyst in the proximal humerus with a non-vascularized fibular graft. Case report]. / Resección de quiste óseo aneurismático en húmero proximal con aplicación de injerto peroneo no vascularizado. Presentación de un caso.

An aneurysmal bone cyst is a benign lesion involving the marrow of long bones; it accounts for 6% of primary bone lesions and may occur as a secondary lesion with other benign or malignant bone tumors. We describe herein the case of a seven year-old female with an aneurysmal bone cyst which was diagnosed clinically, radiographically and with a CAT scan, and confirmed with histopathology. Resection was performed using the eggshell technique and a non-vascularized left fibular bone graft. The patient did well up to the fourth postoperative year, which is consistent with what has been reported in world literature.

Central α- and ß-thujone: similar anxiogenic-like effects and differential modulation on GABAA receptors in neonatal chicks.

The convulsant effects of α-thujone are attributed to inhibitory actions on the GABAA receptor. We investigated, for the first time, the effects of α-thujone or ß-thujone administrated centrally on the fear/anxiety behaviour of 3-day-old chicks in an Open Field and their modulation on the GABAA receptor. Higher doses were convulsant by eliciting a toxic and excitatory action, with the results showing that a dose of 78 nmol of either of the two diastereoisomers had an anxiogenic-like effect observed as an increased latency to ambulate and a reduced locomotor activity in an Open Field. Nevertheless, only the central administration of α-thujone reversed the increase induced by acute stress in the flunitrazepam-sensitive GABAA receptor recruitment. These findings demonstrated that α-thujone, when intracerebroventricularly administered, suppressed the GABAA receptor recruitment induced by acute stress, maybe due to α-thujone blocking the benzodiazepine binding site or another site of the GABAA complex. However, it should not be discarded that acute stress associated with novelty may have induced the recruitment of a subpopulation of GABAA receptors more sensitive to α-thujone than to the constitutive receptors, or that this monoterpene could have inhibited any protein or enzyme trafficking that modulated the phosphorylation of the receptor involved in the turnover of GABAA receptor. ß-Thujone showed behavioural effects similar to its diastereoisomer α-thujone. However, its action mechanism may have been mediated by other neurotransmitter systems, such as the serotonergic one or by a different biological effectiveness due to a distinct stereochemistry at the specific site of the GABAA receptor.

[Cervical arthrodesis by means of interbody fusion with autologous bone and/or interbody spacer for cervical disc disease]. / Artrodesis cervical mediante fusión intersomática con hueso autólogo versus espaciador intersomático en discopatía cervical.

UNLABELLED: The purpose of this study was to compare the results of cervical arthrodesis performed through interbody fusion with autologous bone and/or interbody spacer for cervical disc disease. MATERIAL AND METHODS: Comparative cross-sectional study that included 49 patients who underwent surgery for anterior arthrodesis between January and December 2011, whose clinical records were reviewed. RESULTS: We included 49 patients: 20 (40.8%) males and 29 (59.2%) females. All of them were diagnosed with disc disease (cervical disc herniation) involving one or two levels. Mean operative time was 69.12, with a minimum of 53 and a maximum of 110 +/- 19.61 minutes for cervical arthrodesis with a graft. Mean operative time was 61.18 with a minimum of 50 and a maximum of 96.00 +/- 11.38 minutes for cer vical arthrodesis with an interbody spacer (p = 0.00, Student t test). Patient sociodemographic and clinical characteristics and complications are shown. Patients in whom both surgical techniques were used had appropriate radiological integration, with p = 0.015, considering p < or = a 0.05 as significant, chi2. CONCLUSIONS: In patients with cervical disc disease bone integration is appropriate with the use of either an interbody cage or an autologous iliac crest graft.

Pharmacological alterations that could underlie radiation-induced changes in associative memory and anxiety.

It is widely known that ionizing radiation is a physical agent broadly used to kill tumor cells during human cancer therapy. Unfortunately, adjacent normal tissues can concurrently undergo undesirable cell injury. Previous data of our laboratory demonstrated that exposure of developing rats to ionizing radiations induced a variety of behavioral differences respect to controls, including changes in associative memory and in anxiety state. However, there is a lack of data concerning modifications in different related pharmacological intermediaries. Therefore, the aim of the present study was to investigate whether the behavioral differences observed in young animals irradiated at birth might be underlain by early changes in PKCß1 levels which, in turn, could lead to changes in hippocampal GABAergic neurotransmission. Male Wistar rats were irradiated with 5Gy of X rays between 24 and 48 h after birth. Different pharmacological markers related to the affected behavioral tasks were assessed in control and irradiated hippocampus at 15 and 30 days, namely GABAA receptor, GAD65-67, ROS and PKCß1. Results showed that all measured parameters were increased in the hippocampus of 30-days-old irradiated animals. In contrast, in the hippocampus of 15-days-old irradiated animals only the levels of PKCß1 were decreased. These data suggest that PKCß1 might constitute a primary target for neonatal radiation damage on the hippocampus. Therefore, it could be hypothesized that an initial decrease in the levels of this protein can trigger a subsequent compensatory increase that, in turn, could be responsible for the plethora of biochemical changes that might underlie the previously observed behavioral alterations.

Fatal Wedelia glauca intoxication in calves following natural exposure.

A group of 342 beef calves, corralled in the Patagonia region of Argentina, were fed alfalfa hay that had been inadvertently contaminated with Wedelia glauca. A total of 147 (43%) calves died within 4 days. Pathologic findings in 2 calves were diffuse centrilobular hepatic necrosis and hemorrhage with edema in the gallbladder, common bile duct, and choledochoduodenal junction. Epidermal fragments of W. glauca were identified in rumen contents by microscopy. Intact W. glauca plants and leaf fragments were found in the hay. Patches of defoliated W. glauca were also identified in the alfalfa pasture from which the hay had been baled.

Participation of the GABAergic system on the glutamate release of frontal cortex synaptosomes from Wistar rats with experimental autoimmune encephalomyelitis.

We previously found that the glutamate release was decreased in synaptosomes from rat cerebral cortex during the development of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. Various other reports have shown a deficit in the expression of proteins associated with GABAergic neurotransmission in the neocortex of patients with multiple sclerosis and it was also demonstrated that the activation of GABAA receptors leads to an inhibition of glutamate release. Now, in order to evaluate the events that may affect the neuronal function in EAE synaptosomes, we analyzed the participation of the GABAergic system in glutamate release and in the flunitrazepam-sensitive GABAA receptor density. This revealed alterations in the GABAergic system of the frontal cortex synaptosomes from EAE animals. GABA induced a decrease in the 4-aminopyridine-evoked glutamate release in control synaptosomes which was abolished by picrotoxin, a GABAA receptor antagonist. In contrast, synaptosomes from EAE rats showed a loss in the inhibition of glutamate release mediated by GABA. Furthermore, the flunitrazepam-sensitive GABAA receptor density was decreased during the acute stage of the disease in synaptosomes from EAE rats. We also observed a loss of inhibition in the Ca2+-dependent phosphorylation of synapsin I mediated by GABA in nerve terminals from EAE animals, which could explain the loss of GABAergic regulation on evoked glutamate release. The changes observed in the GABAA receptor density as well as the loss of GABAergic inhibition of glutamate release were partially reverted in cortical synaptosomes from recovered EAE animals. These results suggest that the decrease in the flunitrazepam-sensitive GABAA receptor density may explain the observed failure of GABAergic regulation in the glutamate release of synaptosomes from EAE rats, which might contribute to the appearance of clinical symptoms and disease progression.

Genotoxicity of AMPA, the environmental metabolite of glyphosate, assessed by the Comet assay and cytogenetic tests.

Formulations containing glyphosate are the most widely used herbicides in the world. AMPA is the major environmental breakdown product of glyphosate. The purpose of this study is to evaluate the in vitro genotoxicity of AMPA using the Comet assay in Hep-2 cells after 4h of incubation and the chromosome aberration (CA) test in human lymphocytes after 48h of exposition. Potential in vivo genotoxicity was evaluated through the micronucleus test in mice. In the Comet assay, the level of DNA damage in exposed cells at 2.5-7.5mM showed a significant increase compared with the control group. In human lymphocytes we found statistically significant clastogenic effect AMPA at 1.8mM compared with the control group. In vivo, the micronucleus test rendered significant statistical increases at 200-400mg/kg. AMPA was genotoxic in the three performed tests. Very scarce data are available about AMPA potential genotoxicity.

Super-oxidized solution inhibits IgE-antigen-induced degranulation and cytokine release in mast cells.

Activation of the high affinity IgE receptor (Fc epsilonRI) through IgE-antigen complexes induces mast cell degranulation, synthesis of lipid mediators and cytokine production. These effects are involved in Type I hypersensitivity reactions and controlling them has been the main objective of many anti-allergic therapies. Here we report that pretreatment of murine bone marrow derived mast cells (BMMC) with super-oxidized solution (SOS) inhibits Fc epsilonRI dependent-beta hexosaminidase and cytokine release. This effect is exerted without altering total protein tyrosine phosphorylation, MAPK activation, cytokine mRNA accumulation or calcium mobilization after Fc epsilonRI triggering. Our data suggest that this neutral pH-SOS acts like a mast cell-membrane stabilizer inhibiting the cell machinery for granule secretion without altering the signal transduction pathways induced by IgE-antigen receptor crosslinking.

Linfangioma cervical cavernoso en un gemelo: analísis crítico del diagnóstico y manejo perinatal / Cervical lymphangioma in a twin: prenatal diagnosis and perinatal management

Los tumores fetales son hallazgos infrecuentes y muchas veces no diagnosticados prenatalmente. El objetivo de este trabajo es presentar y discutir en forma critica el diagnostico y manejo prenatal de un gemelo portador en un linfangioma cervical cavernoso, incluyendo el procedimiento EXIT.

Fetal cervical tumors are uncommon, and not always prenataly diagnosticated. We describe the prenatal findings and prenatal management in a case of cervical cavernous lymphangioma in one twin, including EXIT procedure.