Accurate preoperative diagnosis of a Rathke cleft cyst with the aid of a novel classification for sellar cystic lesions and a diagnostic algorithm decision: Tools for differentiating cystic sellar lesions with a representative case.

Background: Rathke's cleft cyst (RCC) is a benign lesion in the sellar and suprasellar compartments. Similarly, pituitary adenomas can present with cystic morphology, making it a differential diagnosis when evaluating a patient with a cystic lesion in the sellar region. Surgical goals differ between RCCs and pituitary adenomas as the first can achieve remission of symptoms with cyst decompression in contrast to pituitary adenomas where complete resection would be the main goal. Imaging analysis alone may not be sufficient to define a preoperative surgical plan. The combination of imaging and conjoined use of validated tools may provide valuable insights to the clinician when defining a surgical approach. Case Description: We present a case of a 27-year-old male with a 3-month history of visual disturbances and headaches. Magnetic resonance imaging showed a cystic lesion in the sellar compartment with compression of nearby structures. The authors were able to accurately diagnose this sellar lesion as an RCC with the conjoined aid of two classifications proposed in the literature. Cyst evacuation was performed with relief of symptoms and improved visual outcomes at follow-up. Conclusion: While cystic adenomas can require total resection for cure, RCCs can show marked improvement with partial resection and evacuation of its contents. An accurate preoperative diagnosis can lead the surgeon to opt for the best surgical approach.

Effects of a Low Dose of Orally Administered Creatine Monohydrate on Post-Fatigue Muscle Power in Young Soccer Players.

The use of creatine monohydrate (Cr) in professional soccer is widely documented. However, the effect of low doses of Cr on the physical performance of young soccer players is unknown. This study determined the effect of a low dose of orally administered Cr on muscle power after acute intra-session fatigue in young soccer players. Twenty-eight young soccer players (mean age = 17.1 ± 0.9 years) were randomly assigned to either a Cr (n = 14, 0.3 g·kg-1·day-1 for 14 days) or placebo group (n = 14), using a two-group matched, double-blind, placebo-controlled design. Before and after supplementation, participants performed 21 repetitions of 30 m (fatigue induction), and then, to measure muscle power, they performed four repetitions in half back squat (HBS) at 65% of 1RM. Statistical analysis included a two-factor ANOVA (p ˂ 0.05). Bar velocity at HBS, time: p = 0.0006, ŋp2 = 0.22; group: p = 0.0431, ŋp2 = 0.12, time × group p = 0.0744, ŋp2 = 0.02. Power at HBS, time: p = 0.0006, ŋp2 = 0.12; group: p = 0.16, ŋp2 = 0.06, time × group: p = 0.17, ŋp2 = 0.009. At the end of the study, it was found that, after the induction of acute intra-session fatigue, a low dose of Cr administered orally increases muscle power in young soccer players.

CD8+ T-cell Exhaustion Phenotype in Human Asymptomatic and Ocular Toxoplasmosis.

This work analyzed exhaustion markers in CD8+ T-cell subpopulations in 21 samples of peripheral blood mononuclear cells (PBMCs) from individuals with ocular toxoplasmosis (n = 9), chronic asymptomatic toxoplasmosis (n = 7), and non-infected people (n = 5) by using RT-qPCR and flow cytometry techniques. The study found that gene expression of PD-1 and CD244, but not LAG-3, was higher in individuals with ocular toxoplasmosis versus individuals with asymptomatic infection or uninfected. Expression of PD1 in CD8+ central memory (CM) cells was higher in nine individuals with toxoplasmosis versus five uninfected individuals (p = .003). After ex vivo stimulation, an inverse correlation was found between the exhaustion markers and quantitative clinical characteristics (lesion size, recurrence index, and number of lesions). A total exhaustion phenotype was found in 55.5% (5/9) of individuals with ocular toxoplasmosis. Our results suggest that the CD8+ exhaustion phenotype is involved in the pathogenesis of ocular toxoplasmosis.

Preclinical evaluation of oncolytic potential human rotavirus Wt 1-5 in gastric adenocarcinoma.

Despite advances in biomedical research, gastric cancer remains the leading cause of morbidity and mortality worldwide due to the limited efficacy of conventional therapies. In recent decades, oncolytic viruses have emerged as a biological therapeutic alternative to cancer due to their selectivity, effectiveness, and low toxicity. However, clinical trials have shown that developing a virus with selectivity for multiple tumor receptors and the ability to penetrate and diffuse through the tumor microenvironment to reactivate the immune system remains challenging. This study aimed to examine the oncolytic potential of tumor cell-adapted rotavirus Wt1-5 in gastric adenocarcinoma samples. This study focused on determining the propagation capacity of the RV Wt1-5 through the tumor and the importance of the expression of cell surface co-receptors, including integrin ß3, protein disulfide isomerase (PDI), and heat shock proteins (Hsp-90, -70, -60, -40, and Hsc 70), during infection of tumor cells. These proteins were found to be differentially expressed in tumor cells compared to adjacent non-tumor cells. Preincubation of gastric tumor cells with antibodies against these proteins decreased rotavirus infections, validating their importance in the binding and entry of RV Wt1-5 into tumor cells, as previously reported. Upon RV infection, apoptosis was one of the types of death that was observed. This was evidenced by evaluating the expression of CASP-3, -9, PARP, cytochrome C, Bax, Bid, p53, and Bcl-2, as well as observing morphological changes such as chromatin margination, nuclear condensation, and fragmentation. Finally, at 60 h.p.i, histological analysis revealed that oncolysis compromised the entire thickness of the tumor. Therefore, the results suggest that RV Wt1-5 could be a novel therapeutic agent co-adjuvant agent for conventional and targeted therapies in managing GC. Ex vivo infection of the tumor tissue model showed characteristics of an immune response that could be explored in future studies.

Status of breast cancer in Latin American: Results of the breast cancer revealed initiative.

The Breast Cancer Revealed initiative was designed and conducted to know the status of breast cancer at each point of breast cancer care, through i) prevention, ii) detection, iii) diagnosis, iv) treatment, and iv) the capacity of our health systems. The expert panel from 11 Latin American countries identified several strategies and proposed high impact priorities, including implementation of prevention policies, improve primary healthcare capacity for breast cancer screening, have adequate infrastructure to make effective and timely diagnoses, have a multidisciplinary team in the treatment process, access to a variety of treatments for all types of patients, have a coordinated and articulated system from primary care to specialized hospital. In a region with limited resources, prioritization in high-impact strategies for breast cancer control could lead to improved clinical outcomes and quality of life for our patients.

Performance of Colombian Silk Fibroin Hydrogels for Hyaline Cartilage Tissue Engineering.

The development and evaluation of scaffolds play a crucial role in the engineering of hyaline cartilage tissue. This work aims to evaluate the performance of silk fibroin hydrogels fabricated from the cocoons of the Colombian hybrid in the in vitro regeneration of hyaline cartilage. The scaffolds were physicochemically characterized, and their performance was evaluated in a cellular model. The results showed that the scaffolds were rich in random coils and ß-sheets in their structure and susceptible to various serine proteases with different degradation profiles. Furthermore, they showed a significant increase in ACAN, COL10A1, and COL2A1 expression compared to pellet culture alone and allowed GAG deposition. The soluble portion of the scaffold did not affect chondrogenesis. Furthermore, they promoted the increase in COL1A2, showing a slight tendency to differentiate towards fibrous cartilage. The results also showed that Colombian silk could be used as a source of biomedical devices, paving the way for sericulture to become a more diverse economic activity in emerging countries.

Tamizaje para cáncer de mama con resonancia magnética en mujeres portadoras de mutaciones BRCA y no-BRCA / Magnetic resonance imaging breast cancer screening in women who are carriers of BRCA and non-BRCA gene mutations / Rastreamento de câncer de mama com ressonância magnética em mulheres com mutações BRCA e não BRCA

Introducción: la predisposición hereditaria causada por mutaciones patogénicas de la línea germinal (MPG) explica hasta el 10% de los cánceres de mama. Para reducir su impacto en mujeres mutadas se han propuesto diferentes estrategias, tales como las cirugías reductoras de riesgo o el screening con resonancia magnética (RM) de mamas. Métodos: en este estudio observacional retrospectivo se analizaron los registros de mujeres portadoras de MPG para evaluar las diferentes acciones tomadas luego del test genético. A las pacientes no mastectomizadas se les recomendó ingresar a un programa anual de cribado con RM y se evaluó el porcentaje de adherencia al plan, el número de biopsias efectuadas y el número de cánceres de mama detectados. Resultados: se incluyeron 134 mujeres con MPG, con una distribución en tercios iguales de los genes BRCA1, BRCA2 y genes no-BRCA. Entre las mutadas con indicación de seguimiento, 64% ingresaron al programa de cribado con RM. Las razones que llevaron a las mujeres a no ingresar al programa de seguimiento fueron: la oposición del médico tratante (53%), oposición de la paciente (38%), y falta de recursos (9%). Se realizaron seis biopsias por hallazgos en la RM entre las cuales se detectó un cáncer de mama. La incidencia de cáncer fue de 11 cada 1.000 mujeres-años de riesgo. Conclusiones: nuestro programa de seguimiento con RM de pacientes mutadas logró captar un porcentaje alto de candidatas. Una proporción significativa de las mujeres no ingresó debido la desaprobación del médico tratante o de la propia paciente. La evidencia obtenida revela una necesidad imperiosa de reforzar los programas educativos que destaquen la importancia del seguimiento con RM de las pacientes de alto riesgo en nuestro país.

Summary: Introduction: genetic propensity caused by germline pathogenic mutations explain up to 10% of breast cancer cases. Different strategies have been proposed to reduce its impact on women who are carriers of mutations, such as risk-reducing surgeries or breast magnetic resonance screening. Method: observational, retrospective study analyzing the medical records of women who are carriers of germline pathogenic mutations to assess the different measures taken after the genetic test. Non-mastectomized patients were advised to join an annual MRI screening program and the percentage of adherence to plan was evaluated, along with biopsies performed and the number of breast cancer cases detected. Results: 134 women carriers of germline pathogenic mutations were included in the study, with equal distributions in thirds for BRCA1, BRCA2 and non-BRCA genes. 64% of carriers of mutations who were subject to follow-up checkups joined the RMI screening program. The reasons why women failed to join the follow-up program were: the treating physician objected to the program (53%), the patients opposed to program (38%) and lack of resources (9%). Six biopsies were performed as a consequence of findings in the RMI, and one case of breast cancer was detected. Cancer incidence was 11 out of 1000 women - risk years. Conclusions: our RMI follow-up program for women who are carriers of mutations managed to attract a high percentage of candidates. A significant amount of women failed to join the program because of their treating physician's or their own disapproval. Evidence obtained reveals the dramatic need to reinforce educational programs that emphasize on the importance of RMI follow-up of high risk patients in our country.

Introdução: a predisposição hereditária causada por mutações germinativas patogênicas (GMP) explica até 10% dos cânceres de mama. Para reduzir seu impacto em mulheres com mutações, diferentes estratégias têm sido propostas, como cirurgias de redução de risco ou ressonância magnética (RM) das mamas. Métodos: neste estudo observacional retrospectivo, os registros de mulheres portadoras de MPG foram analisados para avaliar as diferentes ações tomadas após o teste genético. Pacientes não mastectomizadas foram recomendadas a entrar em um programa anual de triagem por ressonância magnética e foram avaliados o percentual de adesão ao plano, o número de biópsias realizadas e o número de cânceres de mama detectados. Resultados: foram incluídas 134 mulheres com MPG, com uma distribuição de terços iguais dos genes BRCA1, BRCA2 e não-BRCA. Entre as mulheres com mutações com indicação de acompanhamento, 64% entraram no programa de triagem por ressonância magnética. Os motivos que levaram as mulheres a não ingressarem ao programa de acompanhamento foram: oposição do médico assistente (53%), oposição da paciente (38%) e falta de recursos (9%). Seis biópsias foram realizadas devido a achados de ressonância magnética, entre os quais foi detectado um câncer de mama. A incidência de câncer foi de 11 por 1.000 mulheres-ano de risco. Conclusões: nosso programa de acompanhamento de ressonância magnética para pacientes com mutação conseguiu capturar uma alta porcentagem de candidatas. Uma proporção significativa de mulheres não entrou devido à falta de aprovação do médico assistente ou da própria paciente. As evidências obtidas revelam a necessidade urgente de reforçar programas educacionais que destaquem a importância do acompanhamento por RM de pacientes de alto risco no Uruguai.

Evaluating the Impact of Dropout and Genotyping Error on SNP-Based Kinship Analysis With Forensic Samples.

Technological advances in sequencing and single nucleotide polymorphism (SNP) genotyping microarray technology have facilitated advances in forensic analysis beyond short tandem repeat (STR) profiling, enabling the identification of unknown DNA samples and distant relationships. Forensic genetic genealogy (FGG) has facilitated the identification of distant relatives of both unidentified remains and unknown donors of crime scene DNA, invigorating the use of biological samples to resolve open cases. Forensic samples are often degraded or contain only trace amounts of DNA. In this study, the accuracy of genome-wide relatedness methods and identity by descent (IBD) segment approaches was evaluated in the presence of challenges commonly encountered with forensic data: missing data and genotyping error. Pedigree whole-genome simulations were used to estimate the genotypes of thousands of individuals with known relationships using multiple populations with different biogeographic ancestral origins. Simulations were also performed with varying error rates and types. Using these data, the performance of different methods for quantifying relatedness was benchmarked across these scenarios. When the genotyping error was low (<1%), IBD segment methods outperformed genome-wide relatedness methods for close relationships and are more accurate at distant relationship inference. However, with an increasing genotyping error (1-5%), methods that do not rely on IBD segment detection are more robust and outperform IBD segment methods. The reduced call rate had little impact on either class of methods. These results have implications for the use of dense SNP data in forensic genomics for distant kinship analysis and FGG, especially when the sample quality is low.

skater: an R package for SNP-based kinship analysis, testing, and evaluation.

Motivation: SNP-based kinship analysis with genome-wide relationship estimation and IBD segment analysis methods produces results that often require further downstream process- ing and manipulation. A dedicated software package that consistently and intuitively imple- ments this analysis functionality is needed. Results: Here we present the skater R package for SNP-based kinship analysis, testing, and evaluation with R. The skater package contains a suite of well-documented tools for importing, parsing, and analyzing pedigree data, performing relationship degree inference, benchmarking relationship degree classification, and summarizing IBD segment data. Availability: The skater package is implemented as an R package and is released under the MIT license at https://github.com/signaturescience/skater. Documentation is available at https://signaturescience.github.io/skater.

Relación del índice nutricional pronóstico con complicaciones y mortalidad en los pacientes con cáncer gástrico sometidos a gastrectomía en un hospital de tercer nivel de Bogotá, Colombia / Relationship of the prognostic nutritional index with complications and mortality in patients with gastric cancer who underwent gastrectomy in a tertiary hospital in Bogotá, Colombia

Introducción. El cáncer gástrico es el quinto cáncer diagnosticado con mayor frecuencia y la tercera causa de muerte por cáncer en el mundo. En el tratamiento quirúrgico, la evidencia actual apoya las medidas preoperatorias e índices pronósticos para mejorar la supervivencia. El índice nutricional pronóstico, que une los valores de los linfocitos circulantes en sangre periférica con los de la albúmina sérica, ha presentado características de ser un marcador nutricional e inmunológico con valor predictivo sobre complicaciones y mortalidad. El objetivo de este estudio fue determinar la relación entre el índice nutricional pronóstico con las complicaciones y mortalidad en pacientes con cáncer gástrico sometidos a gastrectomía. Métodos. Se llevó a cabo un estudio observacional descriptivo, de corte transversal, con componente analítico, mediante la revisión retrospectiva de las historias clínicas. Resultados. Se analizaron 113 pacientes sometidos a gastrectomía total o subtotal. Se encontró asociación entre el índice nutricional pronóstico y la mortalidad; todos los pacientes que murieron tenían un índice menor o igual a 46. También se encontró asociación inversa entre el valor del índice y la presentación de complicaciones posoperatorias, como sepsis, peritonitis, fuga de la anastomosis y sangrado. Discusión. Similar a nuestro análisis, varios estudios plantean que un índice nutricional pronóstico bajo podría tener un valor predictivo sobre la frecuencia de complicaciones y supervivencia global en pacientes con cáncer gástrico llevados a cirugía. Conclusión. El índice nutricional pronóstico se asocia con la mortalidad y complicaciones posoperatorias en pacientes sometidos a gastrectomía por cáncer gástrico.

Introduction. Gastric cancer is the fifth most frequently diagnosed cancer and the third cause of cancer death in the world. In surgical treatment, current evidence supports preoperative measures and prognostic index to improve survival. The prognostic nutritional index, which unites the values of circulating lymphocytes in peripheral blood with those of serum albumin, has presented characteristics of being a nutritional and immunological marker with predictive value on complications and mortality. The objective of this study was to determine the relationship between the prognostic nutritional index with complications and mortality in patients with gastric cancer undergoing gastrectomy.Methods. A descriptive, cross-sectional, observational study with an analytical component was carried out by a retrospective review of medical records. Results. A total of 113 patients who underwent total or subtotal gastrectomy were analyzed. An association was found between mortality and the prognostic nutritional index and mortality; all patients who died had an index ≤ 46. An inverse association was also found between the value of the index and the presentation of postoperative complications, such as sepsis, peritonitis, anastomotic leak, and bleeding.Discussion. Similar to our analysis, several studies suggest that a low prognostic nutritional index could have a predictive value on the frequency of complications and overall survival in patients with gastric cancer undergoing surgery.Conclusion. The prognostic nutritional index is associated with mortality and postoperative complications in patients undergoing gastrectomy for gastric cancer.

Simulating transmission of ESKAPE pathogens plus C. difficile in relevant clinical scenarios.

BACKGROUND: The prevalence of healthcare-acquired infections (HAI) and rising levels of antimicrobial resistance places significant economic and public health burdens on modern healthcare systems. A group of highly drug resistant pathogens known as the ESKAPE pathogens, along with C. difficile, are the leading causes of HAIs. Interactions between patients, healthcare workers, and environmental conditions impact disease transmission. Studying pathogen transfer under varying contact scenarios in a controlled manner is critical for understanding transmission and disinfectant strategies. In lieu of human subject research, this method has the potential to contribute to modeling the routes of pathogen transmission in healthcare settings. METHODS: To overcome these challenges, we have developed a method that utilizes a synthetic skin surrogate to model both direct (skin-to-skin) and indirect (skin-to fomite-to skin) pathogen transfer between infected patients and healthy healthcare workers. This surrogate material includes a background microbiome community simulating typical human skin flora to more accurately mimic the effects of natural flora during transmission events. RESULTS: We demonstrate the ability to modulate individual bacterial concentrations within this microbial community to mimic bacterial concentrations previously reported on the hands of human subjects. We also explore the effect of various decontamination approaches on pathogen transfer between human subjects, such as the use of handwashing or surface disinfectants. Using this method, we identify a potential outlier, S. aureus, that may persist and retain viability in specific transfer conditions better than the overall microbial community during decontamination events. CONCLUSIONS: Our work describes the development of an in vitro method that uses a synthetic skin surrogate with a defined background microbiota to simulate skin-to-skin and skin-to fomite-to skin contact scenarios. These results illustrate the value of simulating a holistic microbial community for transfer studies by elucidating differences in different pathogen transmission rates and resistance to common decontamination practices. We believe this method will contribute to improvements in pathogen transmission modeling in healthcare settings and increase our ability to assess the risk associated with HAIs, although additional research is required to establish the degree of correlation of pathogen transmission by skin or synthetic alternatives.

Páramos Neotropicales como unidades biogeográficas

Introducción: El Páramo se ha definido desde diversos acercamientos, teniendo en cuenta factores de fácil reconocimiento o medición. A nivel biogeográfico se ha evaluado con métodos ampliamente criticados para la identificación de áreas de endemismo. El análisis de endemicidad, pese a su importancia y amplio reconocimiento, no se ha utilizado como herramienta para evaluar el Páramo. Objetivo: Determinar si los páramos neotropicales es una o varias unidades biogeográficas. Métodos: Incluimos registros de Aves, Amphibia, Mammalia, Reptilia, Marchantiophyta y Spermatophyta, para los que encontramos 7 025 especies con 193 250 presencias viables obtenidas desde GBIF (Global Biodiversity Information Facility) [a septiembre de 2018]. Usamos cada grupo taxonómico como una partición independiente, y generamos particiones adicionales como plantas totales (Plantas-T: Marchantiophyta + Spermatophyta), animales totales (Animales-T: Aves + Amphibia + Mammalia + Reptilia) y evidencia total (Plantas-T + Animales-T). Utilizamos el criterio de optimalidad para identificar áreas de endemismo. Realizamos el análisis usando dos tamaños de cuadrícula 0.5 y 0.25°. Con las áreas obtenidas, calculamos la intersección con los polígonos que representan las definiciones de páramo generadas por otros autores. Resultados: Con los dos tamaños de cuadrícula identificamos áreas de endemismo en diferentes sectores; sin embargo, el tamaño de 0.25° nos permitió mayor resolución al identificar los sectores en alta montaña. Estos sectores corresponden a ocho zonas que denominamos subprovincias: Santa Marta-Perijá, Mérida, Santanderes-Boyacá, Cundinamarca, Cordillera Central-Occidental, Norte de Ecuador, Centro-Sur de Ecuador y Talamanca, las cuales fueron congruentes entre un 4 y un 66 % con las definiciones previas. Conclusiones: Páramo se ha planteado como una sola unidad biogeográfica; sin embargo, dado nuestros análisis, lo identificamos como ocho subprovincias biogeográficas, congruentes con estudios previamente publicados.

Neotropical páramos as biogeographic units. Introduction: Páramo has been defined from various points of view, which take into account different factors that are easy to recognize or measure, nevertheless at the biogeographic level it has been evaluated with criticized methods used to identify historical units. The analysis of endemicity, despite its importance and wide recognition, has not been used as a tool to evaluate Páramo. Objective: Determine whether the neotropical Páramo is one or several biogeographic units. Methods: We included distributional records from Aves, Amphibia, Mammalia, Reptilia, Marchantiophyta, and Spermatophyta. We found 7 025 species with 193 250 suitable occurrences obtained from the GBIF. We used each taxonomic group as an independent partition or as a component of a larger partition, such as total plants (Plants-T: Marchantiophyta + Spermatophyta), or total animals (Animals-T: Aves + Amphibia + Mammalia + Reptilia), or total evidence (Plants-T + Animals-T). In order to identify areas of endemism, we used the optimality criterion (NDM/VNDM) with grids of 0.5° or 0.25°. We calculated the intersection among polygons of previous definitions and the areas recovered in our analyses. Results: Both grid sizes, 0.25° and 0.5°, identified areas of endemism in different sectors along the Andean and Central American cordilleras, but only the 0.25° size allowed us to recognize areas/sectors with a higher resolution. We recovered eight areas, which were considered as subprovinces (Santa Marta-Perijá, Mérida, Santanderes-Boyacá, Cundinamarca, Central-Western Cordillera, Northern Ecuador, Central-South Ecuador, and Talamanca). These areas were between 4 and 66 % consistent with previous definitions. Conclusions: Páramo has been considered a single biogeographic unit, however, given our analyses we identified it as a unit composed of eight biogeographic subprovinces, which is consistent with some published studies.

Effect of Synthetic Fibers and Hydrated Lime in Porous Asphalt Mixture Using Multi-Criteria Decision-Making Techniques.

Porous asphalt is a type of mixture characterized by having high air void percentages that offers multiple benefits when used in wearing courses in terms of driving safety, water flow management, and noise reduction. However, the durability of porous asphalt (PA) mixtures is significantly shorter when compared to dense-graded asphalt mixtures. This study investigated the impact of polyolefin-aramid fibers and hydrated lime in the functional and mechanical performance of porous asphalt mixtures. A parametric study based on the concept of design of experiments was carried out through the Taguchi methodology. Accordingly, an experimental design was conducted based on the L18 full factorial orthogonal array. Three control factors-fiber content, binder content, and filler type-were included at various levels, and multiple responses including total air voids, interconnected air voids, particle loss in dry conditions, particle loss in wet conditions, and binder drainage were assessed experimentally. Signal-to-noise ratios were calculated to determine the optimal solution levels for each control factor for the multiple responses. In the second phase of the research, multi-criteria decision-making techniques-namely, criteria importance through inter-criteria correlation and weighted aggregated sum product assessment-were used to transform the multiple-response optimization problem into a single-unique optimization problem and to elaborate a preference ranking among all the mixture designs. The most significant levels for acquiring the optimum overall response value were found to be 0.05% for fiber content and 5.00% for binder content and mixed filler with hydrated lime.

Multi-Response Optimization of Porous Asphalt Mixtures Reinforced with Aramid and Polyolefin Fibers Employing the CRITIC-TOPSIS Based on Taguchi Methodology.

For the optimum design of a Porous Asphalt (PA) mixture, different requirements in terms of functionality and durability have to be fulfilled. In this research, the influence of different control factors such as binder type, fiber content, and binder content were statistically investigated in terms of multiple responses such as total air voids, interconnected air voids, particle loss in dry conditions, particle loss in wet conditions, and binder drainage. The experiments were conducted based on a Taguchi L18 orthogonal array. The best parametric combination per each response was analyzed through signal to noise ratio values. Multiple regression models were employed to predict the responses of the experiments. As more than one response is obtained, a multi-objective optimization was performed by employing Criteria Importance through Criteria Inter-Correlation (CRITIC) and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) methodologies. The weights for the selection of the functional and mechanical performance criteria were derived from the CRITIC approach, whereas the ranking of the different experiments was obtained through the TOPSIS technique. According to the CRITIC-TOPSIS based Taguchi methodology, the optimal multiple-response was obtained for a polymer modified binder (PMB) with fiber and binder contents of 0.15% and 5.0%, respectively. In addition, good results were obtained when using a conventional 50/70 penetration grade binder with a 5.0% binder content and 0.05% fiber content.

Caracterización del dolor en las pacientes con cáncer de mama que sisten a la Unidad de Oncología del Hospital San José / Characterization of pain in patients with breast cancer attending the Oncology Unit of the San José Hospital

Introducción: El cáncer de mama ocupa el segundo lugar en el mundo y es el más frecuente en mujeres con presencia de 1,67 millones de casos nuevos. En 2012 supuso el 25 % de todos los cánceres, y se proyectan para 2030 más de 596.000 nuevos casos y un aumento de 142.100 muertes por cáncer de mama. Uno de los síntomas más frecuentes que experimentan estas pacientes es el dolor agudo o crónico, el cual puede ocurrir en cualquier momento de la enfermedad (diagnóstico, tratamiento, remisión o recaída); por esto debe evaluarse y diagnosticarse, evitando la cronicidad tanto como sea posible. En Colombia no existen estudios referentes al tema. Objetivos: Determinar la presencia de dolor en pacientes con cáncer de mama sometidas a tratamiento oncológico (quimioterapia, radioterapia, cirugía y/o tratamiento hormonal) y describir sus características. Métodos: Estudio observacional descriptivo de corte transversal en pacientes atendidas en el servicio de oncología de un hospital de cuarto nivel en Bogotá (Colombia), con diagnóstico de cáncer de mama y en tratamiento oncológico. Las variables cualitativas fueron descritas con frecuencias absolutas y relativas y las cuantitativas con medias. Resultados: Se recolectaron los datos de 93 pacientes, de las que el 56,9 % presentaron dolor, con mayor prevalencia de dolor crónico en un 52,8 %; el 54,7 % clasificaron su dolor como nociceptivo y el 45,2 % como dolor neuropático con dolor intenso en el 49,0 %. El dolor fue tratado en el 52,8 % con acetaminofeno, y un 22,6 % no tenían ningún tratamiento

Introduction: Breast cancer ranks second in the world and is the most frequent in women with 1.67 million new cases In 2012, it was 25% of all cancers, it is projected for 2030 more than 596,000 new cases and an increase of 142,100 deaths from breast cancer. One of the most frequent symptoms experienced by these patients is acute or chronic pain, which can occur at any time of the disease (Diagnosis, treatment, remission or relapse), should be evaluated and diagnosed, avoiding chronicity as much as possible. confers a degree of greater diffi culty for its control. Objectives: To determine the presence of pain in breast cancer patients undergoing cancer treatment (chemotherapy, radiotherapy, surgery, and / or hormonal treatment), and to describe the characteristics thereof. Methods: Descriptive cross-sectional study in patients attending the oncology service of San José Hospital with a diagnosis of breast cancer and who are undergoing oncological treatment through a personal survey. Results: Data were collected from 93 patients, of which 56.9% presented pain, with a higher prevalence of chronic pain in 52.8 %; 54.7 % classified their pain as nociceptive and 45.2 % as neuropathic pain with intense pain in 49.0 %. The pain was treated in 52.8 % with acetaminophen, and 22.6% had no treatment

TALLER I: La ley y las epilepsias en Latinoamérica / Workshop I: The Law and Epilepsies in Latin America

En relación al Taller "La Ley y las Epilepsias en Latinoamérica" realizado en el 9° Congreso Latinoamericano de Epilepsia en Cancún, México, el 21 de agosto de 2016, uno de los compromisos fue editar dicho taller con el objetivo de informar y discutir la realidad en nuestra región sobre las Leyes y Epilepsias con énfasis en los Derechos Humanos de las personas con epilepsia. A continuación, se presentan las exposiciones, discusión y conclusiones de dicho taller. Esperando que de este documento surjan iniciativas y acciones positivas, les saludan atentamente, los editores.

One of the commitments made in the workshop "The law and Epilepsies in Latin America" in the 9th Latin American Congress on epilepsy in Cancun on August 21st, 2016, was to edit this workshop in order to inform and discuss in regard to the reality in our region on the laws and epilepsies, with an emphasis on the human rights of people with epilepsy. The exhibitions, discussions and conclusions of the workshop are presented below. We hope that this document will help develop initiatives and positive actions, sincerely, the editors

Down Modulation of Host Immune Response by Amino Acid Repeats Present in a Trypanosoma cruzi Ribosomal Antigen.

Several antigens from Trypanosoma cruzi, the causative agent of Chagas disease (CD), contain amino acid repeats identified as targets of the host immune response. Ribosomal proteins containing an Ala, Lys, Pro-rich repeat domain are among the T. cruzi antigens that are strongly recognized by antibodies from CD patients. Here we investigated the role of amino acid repeats present in the T. cruzi ribosomal protein L7a, by immunizing mice with recombinant versions of the full-length protein (TcRpL7a), as well as with truncated versions containing only the repetitive (TcRpL7aRep) or the non-repetitive domains (TcRpL7aΔRep). Mice immunized with full-length TcRpL7a produced high levels of IgG antibodies against the complete protein as well as against the repeat domain, whereas mice immunized with TcRpL7aΔRep or TcRpL7aRep produced very low levels or did not produce IgG antibodies against this antigen. Also in contrast to mice immunized with the full-length TcRpL7a, which produced high levels of IFN-γ, only low levels of IFN-γ or no IFN-γ were detected in cultures of splenocytes derived from mice immunized with truncated versions of the protein. After challenging with trypomastigotes, mice immunized with the TcRpL7a were partially protected against the infection whereas immunization with TcRpL7aΔRep did not alter parasitemia levels compared to controls. Strikingly, mice immunized with TcRpL7aRep displayed an exacerbated parasitemia compared to the other groups and 100% mortality after infection. Analyses of antibody production in mice that were immunized with TcRpL7aRep prior to infection showed a reduced humoral response to parasite antigens as well as against an heterologous antigen. In vitro proliferation assays with mice splenocytes incubated with different mitogens in the presence of TcRpL7aRep resulted in a drastic inhibition of B-cell proliferation and antibody production. Taken together, these results indicate that the repeat domain of TcRpL7a acts as an immunosuppressive factor that down regulates the host B-cell response against parasite antigens favoring parasite multiplication in the mammalian host.

Cáncer de mama y ovario hereditario en Uruguay: resultados del screening para mutaciones en genes de susceptibilidad por secuenciación de nueva generación / Hereditary breast and ovary cancer in Uruguay: screening results for mutations in susceptibility genes by new generation sequencing

Introducción: el cáncer de mama representa la primera causa de muerte por cáncer en mujeres de Uruguay. Se estima que cerca de 7% son causados por mutaciones en el ácido desoxirribonucleico germinal. Los costos de la secuenciación genética han descendido dramáticamente gracias a la aparición de la secuenciación de nueva generación (NGS). El cambio tecnológico abrió una nueva etapa en el estudio del cáncer hereditario en nuestro país. Objetivo: comunicar los resultados de la utilización de tecnología NGS y paneles multigénicos en familias uruguayas con alto riesgo de cáncer de mama hereditario. Pacientes y método: se secuenciaron 135 familias de alto riesgo que provenían de la consulta de consejería genética que funciona en el Grupo Colaborativo Uruguayo: Investigación de afecciones oncológicas hereditarias. Cuando la historia familiar sugería claramente un síndrome de cáncer de mama y ovario hereditario se efectuó secuenciación NGS exclusiva de los genes BRCA1 y 2; cuando el patrón familiar no configuraba claramente se utilizó un panel multigénico. Resultados: se efectuó NGS exclusiva de genes BRCA1 y 2 en 62 familias y un panel multigénico en 73 familias. Se identificaron en total 29 mutaciones patógenas (21 en genes BRCA y 8 en otros genes). Dos de ellas fueron noveles y tres pueden considerarse recurrentes en la población uruguaya. Conclusiones: este trabajo es el primero en Uruguay en reportar el resultado de esta nueva tecnología en el cáncer de mama hereditario. El hallazgo de 29 mutaciones patógenas nos ayuda a delinear el perfil mutacional de nuestro país.

Introduction: breast cancer is women's first cause of death in Uruguay. According to estimations, around 7% of cases result from germinal mutations by deoxyribonucleic acid. The cost of genetic sequencing has dramatically dropped thanks to the arrival of next-generation sequencing (NGS). This technological change opened a new era in the study of hereditary cancer in our country. Objective:to communicate the results of using NGS technology and multigenic panels in Uruguayan families with high risk of hereditary breast cancer. Method: 135 high risk families referred by the genetic counselling consultation that is provided at the Uruguayan Collaborative Group (Hereditary Oncological Conditions Research) were sequenced. When the family history clearly suggested hereditary breast and ovary cancer was a possibility, exclusive NGS sequencing was done for BRCA1 and BRCA2 genes; when the family pattern was not clear to this respect, multigenic panels were used. Results: exclusive NGS sequencing for BRCA1 and BRCA2 genes was done in 62 families, and multigenic panels were used in 73 families. 29 pathogenic mutations were identified (21 in BRCA genes and 8 in other genes). Two of them were new to the disease and three could be considered recurrent in the Uruguayan population. Conclusions:this study is the first one in Uruguay to report the results of this new technology in hereditary breast cancer. The finding of 29 pathogenic mutations contributes to outlining the mutational profile of our country.

Introdução: o câncer de mama é a primeira causa de morte por câncer em mulheres no Uruguai. Estima-se que aproximadamente 7% sejam causados por mutações no ácido desoxirribonucleico germinal. Os custos da sequenciação genética diminuíram dramaticamente graças ao aparecimento da sequenciação de nova geração (NGS). Esta nova tecnologia deu inicio a uma nueva etapa no estudo do câncer hereditário no nosso país. Objetivo: comunicar os resultados da utilização de tecnologia NGS e painéis mutagênicos em famílias uruguaias com alto risco de câncer de mama hereditário. Pacientes e método: 135 famílias de alto risco originárias do aconselhamento genético que funciona no Grupo Colaborativo Uruguaio: Pesquisa de afecções oncológicas hereditárias foram sequenciadas. Quando a história familiar sugeria uma síndrome de câncer de mama e ovário hereditários fez-se a secuenciacao NGS exclusivamente dos genes BRCA1 e 2; quando o padrão familiar não era claro foi utilizado um painel multigênico. Resultados: realizou-se NGS exclusivamente de genes BRCA1 e 2 em 62 famílias e um painel multigênico em 73 famílias. Foram identificadas 29 mutações patogênicas (21 em genes BRCA e 8 em outros genes). Duas eram novas e três podem ser consideradas como recorrentes na população uruguaia. Conclusões: este trabalho é o primeiro que apresenta os resultados desta nova tecnologia aplicada ao câncer de mama hereditário no Uruguai. O achado de 29 mutações patogênicas ajuda a definir o perfil mutacional do nosso país.