Framework for Adoption of Next-Generation Sequencing (NGS) Globally in the Oncology Area.

Radical new possibilities of improved treatment of cancer are on offer from an advanced medical technology already demonstrating its significance: next-generation sequencing (NGS). This refined testing provides unprecedentedly precise diagnoses and permits the use of focused and highly personalized treatments. However, across regions globally, many cancer patients will continue to be denied the benefits of NGS as long as some of the yawning gaps in its implementation remain unattended. The challenges at the regional and national levels are linked because putting the solutions into effect is highly dependent on cooperation between regional- and national-level cooperation, which could be hindered by shortfalls in interpretation or understanding. The aim of the paper was to define and explore the necessary conditions for NGS and make recommendations for effective implementation based on extensive exchanges with policy makers and stakeholders. As a result, the European Alliance for Personalised Medicine (EAPM) developed a maturity framework structured around demand-side and supply-side issues to enable interested stakeholders in different countries to self-evaluate according to a common matrix. A questionnaire was designed to identify the current status of NGS implementation, and it was submitted to different experts in different institutions globally. This revealed significant variability in the different aspects of NGS uptake. Within different regions globally, to ensure those conditions are right, this can be improved by linking efforts made at the national level, where patients have needs and where care is delivered, and at the global level, where major policy initiatives in the health field are underway or in preparation, many of which offer direct or indirect pathways for building those conditions. In addition, in a period when consensus is still incomplete and catching up is needed at a political level to ensure rational allocation of resources-even within individual countries-to enable the best ways to make the necessary provisions for NGS, a key recommendation is to examine where closer links between national and regional actions could complement, support, and mutually reinforce efforts to improve the situation for patients.

Empowering quality data - the Gordian knot of bringing real innovation into healthcare system.

OBJECTIVES: The introduction of Personalised Medicine (PM) into healthcare systems could benefit from a clearer understanding of the distinct national and regional frameworks around the world. Recent engagement by international regulators on maximising the use of real-world evidence (RWE) has highlighted the scope for improving the exploitation of the treasure-trove of health data that is currently largely neglected in many countries. The European Alliance for Personalised Medicine (EAPM) led an international study aimed at identifying the current status of conditions. METHODS: A literature review examined how far such frameworks exist, with a view to identifying conducive factors - and crucial gaps. This extensive review of key factors across 22 countries and 5 regions revealed a wide variety of attitudes, approaches, provisions and conditions, and permitted the construction of a comprehensive overview of the current status of PM. Based on seven key pillars identified from the literature review and expert panels, the data was quantified, and on the basis of further analysis, an index was developed to allow comparison country by country and region by region. RESULTS: The results show that United States of America is leading according to overall outcome whereas Kenya scored the least in the overall outcome. CONCLUSIONS: Still, common approaches exist that could help accelerate take-up of opportunities even in the less prosperous parts of the world.

Acute effect of different loads on muscle performance and perceived exertion in young women / Efecto agudo de distintas cargas sobre el desempeño muscular y el esfuerzo percibido en mujeres jóvenes / Efeito agudo de diferentes cargas no desempenho muscular e esforço percebido em mulheres jovens

ABSTRACT Introduction: Load reduction using the repetition maximum (RM) method may be necessary to promote higher numbers of repetitions, and consequently, higher total volume, time under tension, and perceived exertion ratings. Objective: To compare the effects of different leg press exercise loads on number of repetitions, total volume, time under tension, and perceived exertion. Methods: Eighteen women university students (23.9 ± 3.8 years) performed two experimental sessions with 90% and 100% of 10-12 RM in a balanced crossover design. Results: The number of repetitions of the second and third sets, the total volume, and time under tension at 90% of 10-12 RM was statistically higher than at 100% of 10-12 RM ( p < 0.05). The perceived exertion of the first and second sets and the training load (perceived exertion x duration of sessions) were higher at 100% of the 10-12 RM session ( p < 0.05). Conclusion: A small reduction in load results in a greater number of repetitions, total volume, and time under tension. The session with the higher load appeared to induce higher perceived exertion and training load. Thus, scientists and coaches might consider lower loads to maximize the number of repetitions, total volume, and time under tension, which may cause greater long-term muscular adaptations. Level of evidence II; Comparative prospective study.

RESUMEN Introducción: La reducción de la carga por el método de las repeticiones máximas (RM) puede ser necesaria para promover un mayor número de repeticiones y, consecuentemente, un mayor volumen total, tiempo bajo tensión y calificaciones del esfuerzo percibido. Objetivo: Comparar los efectos de diferentes cargas del ejercicio de prensa de piernas sobre el número de repeticiones, volumen, tiempo bajo tensión y esfuerzo percibido. Métodos: Dieciocho estudiantes universitarios (23,9 ± 3,8 años) realizaron dos sesiones experimentales con el 90% y el 100% de 10-12 RM en un diseño trasversal equilibrado. Resultados: El número de repeticiones de la segunda y tercera serie, el volumen total y el tiempo bajo tensión al 90% de 10-12 RM fue estadísticamente mayor que al 100% de 10-12 RM (p < 0,05). El esfuerzo percibido de la primera y segunda serie y la carga de entrenamiento (esfuerzo percibido x duración de las sesiones) fueron superiores en la sesión realizada al 100% de 10-12 RM (p < 0,05). Conclusión: Una pequeña reducción de la carga da lugar a un mayor número de repeticiones, volumen total y tiempo bajo tensión. La sesión con mayor carga indujo un mayor esfuerzo percibido y carga de entrenamiento. Por lo tanto, los científicos y entrenadores pueden considerar cargas más bajas para maximizar el número de repeticiones, el volumen total y el tiempo bajo tensión, lo que puede causar mayores adaptaciones musculares a largo plazo. Nivel de evidencia II; Estudio prospectivo comparativo.

RESUMO Introdução: A redução da carga pelo método das repetições máximas (RM) pode ser necessária para promover maior número de repetições e, consequentemente, maior volume total, tempo sob tensão e classificações do esforço percebido. Objetivo: Comparar os efeitos de diferentes cargas do exercício leg press no número de repetições, volume total, tempo sob tensão e percepção de esforço. Métodos: Dezoito universitárias (23,9 ± 3,8 anos) realizaram duas sessões experimentais com 90% e 100% de 10-12 RM em desenho transversal balanceado. Resultados: O número de repetições da segunda e terceira séries, volume total e tempo sob tensão a 90% de 10-12 RM foi estatisticamente maior do que a 100% de 10-12 RM (p < 0,05). A percepção do esforço da primeira e segunda séries e a carga de treinamento (percepção do esforço x duração das sessões) foram maiores na sessão realizada com 100% de 10-12 RM (p < 0,05). Conclusão: Uma pequena redução da carga resulta em maior número de repetições, volume total e tempo sob tensão. A sessão com maior carga induziu maior percepção do esforço e carga de treinamento. Assim, cientistas e treinadores podem considerar cargas menores para maximizar o número de repetições, o volume total e o tempo sob tensão, o que pode causar maiores adaptações musculares a longo prazo. Nível de evidência II; Estudo prospectivo comparativo.

Zoonotic RVA: State of the Art and Distribution in the Animal World.

Rotavirus species A (RVA) is a pathogen mainly affecting children under five years old and young animals. The infection produces acute diarrhea in its hosts and, in intensively reared livestock animals, can cause severe economic losses. In this study, we analyzed all RVA genomic constellations described in animal hosts. This review included animal RVA strains in humans. We compiled detection methods, hosts, genotypes and complete genomes. RVA was described in 86 animal species, with 52% (45/86) described by serology, microscopy or the hybridization method; however, strain sequences were not described. All of these reports were carried out between 1980 and 1990. In 48% (41/86) of them, 9251 strain sequences were reported, with 28% being porcine, 27% bovine, 12% equine and 33% from several other animal species. Genomic constellations were performed in 80% (32/40) of hosts. Typical constellation patterns were observed in groups such as birds, domestic animals and artiodactyls. The analysis of the constellations showed RVA's capacity to infect a broad range of species, because there are RVA genotypes (even entire constellations) from animal species which were described in other studies. This suggests that this virus could generate highly virulent variants through gene reassortments and that these strains could be transmitted to humans as a zoonotic disease, making future surveillance necessary for the prevention of future outbreaks.

Fighting Cancer around the World: A Framework for Action.

Tackling cancer is a major challenge right on the global level. Europe is only the tip of an iceberg of cancer around the world. Prosperous developed countries share the same problems besetting Europe-and the countries and regions with fewer resources and less propitious conditions are in many cases struggling often heroically against a growing tide of disease. This paper offers a view on these geographically wider, but essentially similar, challenges, and on the prospects for and barriers to better results in this ceaseless battle. A series of panels have been organized by the European Alliance for Personalised Medicine (EAPM) to identify different aspects of cancer care around the globe. There is significant diversity in key issues such as NGS, RWE, molecular diagnostics, and reimbursement in different regions. In all, it leads to disparities in access and diagnostics, patients' engagement, and efforts for a better understanding of cancer.

How the COVID-19 pandemic affects specialty training: An analysis of a nationwide survey among otolaryngology residents in Chile. / How the COVID-19 pandemic affects specialty training: An analysis of a nationwide survey among otolaryngology residents in Chile.

INTRODUCTION: Coronavirus disease 2019, or COVID-19, has become a global pandemic. Given that the highest viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in the airway, otolaryngologists are at high risk of infection. As a result, multiple recommendations have emerged regarding protective measures for surgical teams, including suspending non-urgent procedures and surgeries. OBJECTIVES: To evaluate the impact of the COVID-19 pandemic on otolaryngology residency training programs nationwide. METHODS: A cross-sectional survey-based study was completed in April 2020. The participants were recruited through an online survey, sent by email to all Chilean otolaryngology residents. Demographics, clinical activities, on-call shifts, COVID-19 infection status, exposure to COVID-19 patients, deployment to other specialties, diagnostic/therapeutic procedures, and surgeries performed were analyzed. Self-reported surgical data logs from previous years were used to compare results. RESULTS: Forty-seven residents completed the survey (84% response rate); 64% of residents refer seeing patients ten days or less during April 2020. Commonly performed procedures such as flexible nasolaryngoscopy, rigid nasal endoscopy, and peritonsillar abscess drainage were not performed by over 40% of the residents in that month. Only 38% participated in surgeries, with an average of 0.6 surgeries as a first surgeon, a dramatic decrease in surgical exposure when comparing the data logs from previous years. Most residents refer the following measures taken by their residency program to improve residency training: bibliographic videoconferences (87%), online clinical case seminars (60%), weekly journal clubs (38%), among others. CONCLUSIONS: Clinical and surgical opportunities decreased dramatically during April 2020. Adjustments to the regular academic curricula should be considered to decrease the negative impact of this pandemic on residency training.

INTRODUCCIÓN: La enfermedad por coronavirus 2019, o COVID-19, se ha convertido en una pandemia. Dada que la mayor carga viral de coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SARS-CoV-2) se encuentra en la vía aérea, los otorrinolaringólogos tienen un elevado riesgo de infección. Múltiples recomendaciones han surgido con respecto a las medidas de protección, incluidos la suspensión de procedimientos y cirugías electivas. OBJETIVOS: Evaluar el impacto de la pandemia de COVID-19 en los programas de formación de otorrinolaringología a nivel nacional. MÉTODOS: Estudio transversal de encuesta en línea a residentes de otorrinolaringología realizado durante abril de 2020. Se analizaron datos demográficos, actividades clínicas, turnos de llamado, infección por COVID-19, exposición a pacientes COVID-19 positivos, despliegue a otras especialidades, procedimientos y cirugías realizadas. Se utilizaron los portafolios quirúrgicos de años previos para comparar los resultados. RESULTADOS: Completaron la encuesta 47 residentes, con 84% de tasa de respuesta; el 64% refirió haber acudido a su centro asistencial 10 días o menos durante el mes de abril de 2020. Con relación a procedimientos frecuentes tales como nasofibroscopía, endoscopia nasal rígida y drenaje de absceso periamigdalino, no fueron realizados por más del 40% de los residentes en el mes. Solo el 38% participó en cirugías, con un promedio de 0,6 procedimientos como primer cirujano; se constata una drástica disminución al comparar los registros de años anteriores. La mayoría de los residentes refieren estas medidas educativas complementarias: videoconferencias bibliográficas (87%), seminarios de casos clínicos en línea (60%), revisión de artículos (38%), entre otros. CONCLUSIONES: La formación clínica y quirúrgica disminuyó drásticamente durante abril de 2020. Se deben considerar ajustes a los planes de estudio para disminuir el impacto negativo de la pandemia en la formación de los residentes.

Impacto de pandemia COVID-19 en la formación de residentes: análisis de una encuesta nacional a residentes de otorrinolaringología en Chile / How the COVID-19 pandemic affects specialty training: An analysis of a nationwide survey among otolaryngology residents in Chile

Introducción La enfermedad por coronavirus 2019, o COVID-19, se ha convertido en una pandemia. Dada que la mayor carga viral de coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SARS-CoV-2) se encuentra en la vía aérea, los otorrinolaringólogos tienen un elevado riesgo de infección. Múltiples recomendaciones han surgido con respecto a las medidas de protección, incluidos la suspensión de procedimientos y cirugías electivas. Objetivos Evaluar el impacto de la pandemia de COVID-19 en los programas de formación de otorrinolaringología a nivel nacional. Métodos Estudio transversal de encuesta en línea a residentes de otorrinolaringología realizado durante abril de 2020. Se analizaron datos demográficos, actividades clínicas, turnos de llamado, infección por COVID-19, exposición a pacientes COVID-19 positivos, despliegue a otras especialidades, procedimientos y cirugías realizadas. Se utilizaron los portafolios quirúrgicos de años previos para comparar los resultados. Resultados Completaron la encuesta 47 residentes, con 84% de tasa de respuesta; el 64% refirió haber acudido a su centro asistencial 10 días o menos durante el mes de abril de 2020. Con relación a procedimientos frecuentes tales como nasofibroscopía, endoscopia nasal rígida y drenaje de absceso periamigdalino, no fueron realizados por más del 40% de los residentes en el mes. Solo el 38% participó en cirugías, con un promedio de 0,6 procedimientos como primer cirujano; se constata una drástica disminución al comparar los registros de años anteriores. La mayoría de los residentes refieren estas medidas educativas complementarias: videoconferencias bibliográficas (87%), seminarios de casos clínicos en línea (60%), revisión de artículos (38%), entre otros. Conclusiones La formación clínica y quirúrgica disminuyó drásticamente durante abril de 2020. Se deben considerar ajustes a los planes de estudio para disminuir el impacto negativo de la pandemia en la formación de los residentes.

Introduction Coronavirus disease 2019, or COVID-19, has become a global pandemic. Given that the highest viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in the airway, otolaryngologists are at high risk of infection. As a result, multiple recommendations have emerged regarding protective measures for surgical teams, including suspending non-urgent procedures and surgeries. Objectives To evaluate the impact of the COVID-19 pandemic on otolaryngology residency training programs nationwide. Methods A cross-sectional survey-based study was completed in April 2020. The participants were recruited through an online survey, sent by email to all Chilean otolaryngology residents. Demographics, clinical activities, on-call shifts, COVID-19 infection status, exposure to COVID-19 patients, deployment to other specialties, diagnostic/therapeutic procedures, and surgeries performed were analyzed. Self-reported surgical data logs from previous years were used to compare results. Results Forty-seven residents completed the survey (84% response rate); 64% of residents refer seeing patients ten days or less during April 2020. Commonly performed procedures such as flexible nasolaryngoscopy, rigid nasal endoscopy, and peritonsillar abscess drainage were not performed by over 40% of the residents in that month. Only 38% participated in surgeries, with an average of 0.6 surgeries as a first surgeon, a dramatic decrease in surgical exposure when comparing the data logs from previous years. Most residents refer the following measures taken by their residency program to improve residency training: bibliographic videoconferences (87%), online clinical case seminars (60%), weekly journal clubs (38%), among others. Conclusions Clinical and surgical opportunities decreased dramatically during April 2020. Adjustments to the regular academic curricula should be considered to decrease the negative impact of this pandemic on residency training.

Effects of palatal augmentation prosthesis in oropharyngeal dysphagia in Chilean patients with tongue cancer: Cases report

ABSTRACT: Therapy of malignant neoplasms of the tongue or oropharynx may cause dysphagia. Dysphagia in patients has negative significant social and psychological consequences. The six cases reports describe the effect of palatal augmentation prosthesis (PAP) on the management of dysphagia in patients with oral-pharyngeal cancer and as consequence of its treatment. The study also assesses PAP's effects on the quality of life of such patients.

Diagnóstico molecular de síndrome de Smith-Magenis por MLPA (Multiplex Ligation-dependent Probe Amplification) / Molecular diagnosis of Smith-Magenis syndrome using MLPA (Multiplex Ligationdependent Probe Amplification)

La genética médica avanza rápidamente gracias a las tecnologías que definen con precisión el aporte de los genes en el desarrollo de enfermedades. Algunos síndromes se presentan en la población general, y su diagnóstico y manejo son importantes para brindar al paciente cuidados y pronósticos de vida adecuados. Presentamos el caso de una niña dismórfica nacida a las 33 semanas de gestación por cesárea por preemclampsia materna. El análisis citogenético reveló una deleción heterocigota en el brazo corto del cromosoma 17 (46, XX, del 17p11.2) en el estudio cromosómico. El diagnóstico se complementó con el análisis de MLPA, que mide la presencia/ausencia de ciertos genes definidos en algunos síndromes, y confirmó la deleción de 2.1 megabases que incluyen el gen RAI1, responsable del Síndrome de Smith-Magenis.

Medical genetics is rapidly advancing thanks to technologies that accurately define which genes are involved in the development of diseases. Some syndromes occur in the general population, and their diagnosis and treatment are important to provide patients with an adequate care and prognosis. We present the case of a dysmorphic child who was born at 33 weeks of pregnancy by caesarean delivery due to preeclampsia. Cytogenetic analysis showed a heterozygous deletion on the short arm of chromosome 17 (46, XX, del 17p11.2). The diagnosis was complemented by MLPA analysis, which measures the presence/absence of certain genes defined in some syndromes, and confirmed the deletion of 2.1 megabases of DNA, including the RAS1 gene, responsible for the Smith-Magenis syndrome.

Nontraumatic Laryngeal Fractures: Report of Two Cases and Review of the Literature.

Laryngeal fractures occur mainly in the context of cervical trauma, hanging, or strangulation. Nontraumatic laryngeal fractures are rare and there are few reports in the literature. We present two cases of nontraumatic laryngeal fractures evaluated in our service.

Biochemical effect of a histidine phosphatase acid (phytase) of Aspergillus japonicus var. Saito on performance and bony characteristics of broiler.

Phytases are enzymes that hydrolyze the ester linkage of phytic acid, releasing inositol and inorganic phosphate. The phytic acid (phytate) is a major form of phosphorus in plant foods. Knowing that diet for animal of production has the cereal base (corn and soybean), primarily, broilers need for an alternative to use of the phosphate present in these ingredients, since it does not naturally produce the enzyme phytase, which makes it available. The aims of this work was studding the safe supplementation of Aspergillus japonicus var. Saito crude phytase in feeding broilers and check the biochemical effect on performance and bones of these animals. The enzymatic extract did not have aflatoxins B1, B2, G2 and G1 and zearalenone and ochratoxin, and low concentrations of this extract did not have cytotoxic effects on cells derived from lung tissue. The in vivo experiments showed that the phytase supplied the available phosphate reduction in the broiler feed formulation, with a live weight, weight gain, feed intake, feed conversion, viability, productive efficiency index and carcass yield similar to the control test. Furthermore, the phytase supplementation favored the formation of bone structure and performance of the broilers. The results show the high biotechnological potential of A. japonicus phytase on broiler food supplementation to reduce phosphorus addition in the food formulation. So, this enzyme could be used as a commercial alternative to animal diet supplementation.

Cis-regulatory elements are harbored in Intron5 of the RUNX1 gene.

BACKGROUND: Human RUNX1 gene is one of the most frequent target for chromosomal translocations associated with acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). The highest prevalence in AML is noted with (8; 21) translocation; which represents 12 to 15% of all AML cases. Interestingly, all the breakpoints mapped to date in t(8;21) are clustered in intron 5 of the RUNX1 gene and intron 1 of the ETO gene. No homologous sequences have been found at the recombination regions; but DNase I hypersensitive sites (DHS) have been mapped to the areas of the genes involved in t(8;21). Presence of DHS sites is commonly associated with regulatory elements such as promoters, enhancers and silencers, among others. RESULTS: In this study we used a combination of comparative genomics, cloning and transfection assays to evaluate potential regulatory elements located in intron 5 of the RUNX1 gene. Our genomic analysis identified nine conserved non-coding sequences that are evolutionarily conserved among rat, mouse and human. We cloned two of these regions in pGL-3 Promoter plasmid in order to analyze their transcriptional regulatory activity. Our results demonstrate that the identified regions can indeed regulate transcription of a reporter gene in a distance and position independent manner; moreover, their transcriptional effect is cell type specific. CONCLUSIONS: We have identified nine conserved non coding sequence that are harbored in intron 5 of the RUNX1 gene. We have also demonstrated that two of these regions can regulate transcriptional activity in vitro. Taken together our results suggest that intron 5 of the RUNX1 gene contains multiple potential cis-regulatory elements.

Skull base clear cell carcinoma, metastasis of renal primary tumor: a case report and literature review.

We report on a patient who presented with cranial nerve VI bilateral paresis, absence of pharyngeal reflex, dysarthria, right tongue deviation, and right facial paralysis. Imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging studies revealed a mass in the right kidney. Consequently, radiotherapy was performed, and the patient was enrolled in a palliative care and pain control program.

Antiphospholipid syndrome in Mexican children.

BACKGROUND: Data on pediatric antiphospholipid syndrome (APS) are very sparse. OBJECTIVES: To describe the main clinical characteristics, laboratory data and complications of pediatric APS patients, and to analyze the differences between primary APS and APS associated with systemic lupus erythematosus (SLE). METHODS: We retrospectively reviewed clinical and laboratory data of 32 children at the Federico Gomez children's hospital in Mexico. Nineteen patients had SLE, 12 (37.5%) had primary APS and 1 (3%) had immune thrombocytopenic purpura. We collected information on sociodemographic variables, vaccinations, age at onset, and family history of rheumatic disease, hematological disorders, skin disorders and non-thrombotic neurological disorders. Immunological features included immunoglobulin (Ig) G and IgM anticardiolipin antibodies, IgG and IgM anti-beta2 glycoprotein I antibodies, lupus anticoagulant, and anti-dsDNA and antinuclear antibodies. RESULTS: The patients included 24 females and 8 males. The most common thrombotic events were small vessel thrombosis (44%), venous thrombosis (28%) mainly deep venous thrombosis (DVT) in lower extremities, and arterial thrombosis (25%). The most common clinical non-thrombotic manifestations were hematological (53%) and neurological disorders (22%). There were no significant differences between groups with regard to the site of thrombosis, nonthrombotic clinical manifestations or laboratory features. CONCLUSIONS: There were some important differences between the clinical manifestations of APS in children compared with adults, but we found no significant differences between patients with primary and APS associated with SLE. Larger studies in Latin American APS children are necessary to determine whether there are differences between ethnic groups.

Long-term reading performance in patients with bilateral dual-optic accommodating intraocular lenses.

PURPOSE: To evaluate reading ability in patients who had cataract surgery with binocular implantation of a dual-optic accommodating intraocular lens (IOL) over a 2-year period. SETTING: Department of Ophthalmology, Cataract and Refractive Surgery, Salucoop EPS-ServiOftalmos, Bogota, Colombia. DESIGN: Prospective case series. METHODS: This study assessed reading ability 1 year and 2 years after bilateral implantation of the Synchrony IOL accommodating IOL using standardized Spanish reading charts based on MNRead charts. Testing was performed with distance correction and without near addition (40 cm). Patients read aloud sentences with a print size ranging from 1.0 to 0.0 logMAR. Responses were audio taped and analyzed offline to obtain reading speed (words per minute [wpm]), reading acuity (logMAR), and critical print size (logMAR). RESULTS: Mixed-model analysis of variance with time (1 year and 2 years) and print size (1.0 to 0.0 logMAR; 11 levels) as factors showed statistically significantly better reading speed at 2 years, with significant differences at print sizes from 0.3 to 0.1 logMAR (P<.01). Mean reading acuity (0.07 logMAR versus 0.15 logMAR) (P<.01, paired t test) and critical print size (0.28 logMAR versus 0.48 logMAR) were also statistically significantly better at 2 years than at 1 year (both P<.01, paired t test). There was no significant difference in reading speed at 0.4 logMAR (newspaper print or 20/50 Snellen equivalent) between 1 year (180.5 wpm) and 2 years (184.2 wpm) (P = .90, paired t test). CONCLUSION: The dual-optic accommodating IOL provided stable or improved reading ability over a 2-year period.

Poblamiento del continente americano y del Perú sugerido de un análisis filogeográfico de haplogrupos del mtDNA en etnias nativas I: inferencias primarias / Peopling of the American continent and Peru as suggested from a phylogeographic mtDNA haplogroups analysis in native ethnoses. I: preliminary inferences

OBJETIVOS: Precisar el origen de las poblaciones peruanas en un contexto filogeográfico, global y temporal. METODOS: Análisis comparativo de los resultados obtenidos a partir del procesamiento del mtDNA, de cinco poblaciones peruanas nativas sitas en Pucallpa, Taquile, Anapia, Amantani y Los Uros, con los resultados obtenidos por diferentes autores en la misma molécula (reciente y antigua) de 91 etnias–localidades, que incluyen varias del continente americano y algunas de nuestro país, y 13 del SE del continente asiático. Realizamos un análisis filogeográfico a partir de las frecuencias de los haplogrupos hallados por RFLPs y una secINDEL del mtDNA. Los datos fueron procesados por el programa PHYLIP 3.65 opción Distancias de Reynolds, para determinar los valores F de Diferenciación Genética o Coalescencia. El algoritmo UPGMA usó los valores de F entre pares de ST STetnias–localidades, para construir un árbol de distancias que permita el análisis de sus principales grupamientos(clusters). RESULTADOS: El árbol obtenido exhibe 7 clusters. El cluster 1 comprende a la etnia Han ubicada al SEde Asia, en tanto que las americanas se ubican entre los clusters 2 al 7. Las etnias menos diversas fueron dos: la Quechua (Taquile, Puno-Perú) – 100 por ciento haplotipo B - y la de los Kuna (Panamá) – 100 por ciento haplotipo A-.CONCLUSIONES: Los mayores valores encontrados de diferenciación genética, corresponden a los Yanomami, con un F de 0.23741, mientras que en el Perú fueron los Quechua de Taquile con un valor F de 0.16673. En ambos casos los resultados indican, según la tabla de calificación de valores F , una Divergencia Genética Alta.

OBJETIVES: To determine the origins of Peruvian populations in a more global and temporal phylogeographic context. METHODS: mtDNA results obtained in our laboratories from the analysis of the mtDNA from 5 native Peruvian populations that inhabit Pucallpa, Taquile, Anapia, Amantani and Los Uros, were compared with the results obtained different authors on the same molecule from 91 ethnoses-localities that include some of our country, others from the American continent, as well as 13 of the SE of the Asian continent. Phylogeographic analysis was done from the haplogroups frequencies found from the RFLPs and an INDEL sequence of mtDNA, and the data were processed by the program PHYLIP 3.65, option Distances of Reynolds to find F values of Genetic ST Differentiation or Coalescency. The UPGMA algorithm allowed us to express the values F between pairs of ST ethnoses-localities and to carry out the analysis of the main clusters, by means of a tree. RESULTS: The tree exhibit 7 main clusters. Cluster I comprised only the ethnos located to SE of Asia. The American ethnoses are located along the clusters 2 to 7. The less diverse ones were two: the Quechua from Taquile, (Puno-Peru) - 100 per cent B haplotype, and the Kuna from Panama, – 100 per cent A haplotype. CONCLUSIONS: Genetic differentiation larger values were in the Yanomami (0.23741) group. For Peru, they were in the Aymara ethnos from Taquile with F values of 0.16673. Both correspond to a High Genetic Divergence respect to the near closest ones.

Variantes del gen Mannose Binding Lectin (MBL) en pobladores amazónicos de Andoas - Loreto y su posible implicancia en la salud / Variants of gene MBL in native amazonians from Andoas - Loreto, and its possible implications in health

El gen MBL (Mannose Binding Lectin) codifica una proteína de la inmunidad innata que activa el sistema del complemento, así como recluta macrófagos y quimioquinas proinflamatorias. Estudios realizados en otras latitudes han asociado susceptibilidad o resistencia a enfermedades infecciosas, autoinmunes y cardiovasculares con alelos deficientes de MBL. Sin embargo, muchos estudios no son concluyentes debido a la rareza de estos alelos en las poblaciones estudiadas. Previamente hemos demostrado que en las islas del Lago Titicaca, el alelo deficiente B tiene la más alta prevalencia del mundo. Por ello, queremos corroborar su presencia en zonas más cálidas que son más propicias a enfermedades infecciosas. Para ello se analizó el genotipo de 94 individuos procedentes de la región amazónica de Andoas-Loreto. Aunque en menor proporción que en las islas del Lago Titicaca, la frecuencia de la variante deficiente B en Andoas es más alta que en otras poblaciones del mundo. Esta frecuencia y su gran exposición a enfermedades tropicales, hacen de Andoas una población interesante para estudiar el rol de las variantes de MBL en el desarrollo de las mismas.

The gene MBL codifies for a protein that has a role in innate immunity by activating the complement system as well as recruiting macrophages and proinflammatory chemokines. Studies performed around the world have associated susceptibility/resistance to infectious, autoimmune and cardiovascular diseases, with deficient alleles of MBL. However, many of these studies remain inconclusive because of the rarity of these alleles. We have previously shown that the frequency of defective allele B in the islands of Lake Titicaca is the highest in the world. Now, we want to evaluate the frequency of this allele in Amazonian areas that are more prone to infectious diseases. We have genotyped 94 individuals from Andoas-Loreto and found a higher frequency of the defective allele B compared to other populations (but lower than that from Lake Titicaca). This frequency and the high exposure to tropical diseases make the population of Andoas interesting to study the role of the MBL variants in the development these diseases.

Mutational analysis of substrate recognition by human arginase type I--agmatinase activity of the N130D variant.

Upon mutation of Asn130 to aspartate, the catalytic activity of human arginase I was reduced to approximately 17% of wild-type activity, the Km value for arginine was increased approximately 9-fold, and the kcat/Km value was reduced approximately 50-fold. The kinetic properties were much less affected by replacement of Asn130 with glutamine. In contrast with the wild-type and N130Q enzymes, the N130D variant was active not only on arginine but also on its decarboxylated derivative, agmatine. Moreover, it exhibited no preferential substrate specificity for arginine over agmatine (kcat/Km values of 2.48 x 10(3) M(-1) x s(-1) and 2.14 x 10(3) M(-1) x s(-1), respectively). After dialysis against EDTA and assay in the absence of added Mn2+, the N130D mutant enzyme was inactive, whereas about 50% full activity was expressed by the wild-type and N130Q variants. Mutations were not accompanied by changes in the tryptophan fluorescence properties, thermal stability or chromatographic behavior of the enzyme. An active site conformational change is proposed as an explanation for the altered substrate specificity and low catalytic efficiency of the N130D variant.