An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean.

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region's continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the "need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics". Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%-99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.

Preclinical Efficacy and Toxicology Evaluation of RAC1 Inhibitor 1A-116 in Human Glioblastoma Models.

Malignant gliomas are the most common primary central nervous system tumor in adults. Despite current therapeutics, these tumors are associated with poor prognosis and a median survival of 16 to 19 months. This highlights the need for innovative treatments for this incurable disease. Rac1 has long been associated with tumor progression and plays a key role in glioma's infiltrative and invasive nature. The aim of this study is to evaluate the 1A-116 molecule, a Rac1 inhibitor, as targeted therapy for this aggressive disease. We found that targeting Rac1 inhibits cell proliferation and cell cycle progression using different in vitro human glioblastoma models. Additionally, we evaluated 1A-116 in vivo, showing a favorable toxicological profile. Using in silico tools, 1A-116 is also predicted to penetrate the blood-brain barrier and present a favorable metabolic fate. In line with these results, 1A-116 i.p daily treatment resulted in a dose-dependent antitumor effect in an orthotopic IDH-wt glioma model. Altogether, our study provides a strong potential for clinical translation of 1A-116 as a signal transduction-based precision therapy for glioma and also increases the evidence of Rac1 as a key molecular target.

Molecular biomarkers and integrated pathological diagnosis in the reclassification of gliomas.

The present study aimed to evaluate the impact caused by the 2016 World Health Organization (WHO) diagnostic classification of gliomas in 139 patients studied in Argentina. Formalin-fixed paraffin-embedded tissues were used for histological and immunohistochemical analysis [glial fibrillary acidic protein, KI67, synaptophysin and isocitrate dehydrogenase (IDH)1-R132H]. DNA from formalin-fixed paraffin-embedded tissues was used for molecular analysis: 1p/19q co-deletion and mutation status of the IDH gene. These experiments were performed by direct Sanger sequencing and multiplex ligation-dependent probe amplification. According to the new classification, diagnoses included oligodendroglioma IDH-mutant and 1p/19q co-deletion (4.20%), anaplastic oligodendroglioma IDH-mutant and 1p/19q co-deletion (2.52%), diffuse astrocytoma IDH-mutant (6.72%), diffuse astrocytoma IDH-wild type (1.68%), anaplastic astrocytoma IDH-mutant (5.04%), anaplastic astrocytoma IDH-wild type (8.40%), glioblastoma IDH-mutant (5.88%) and glioblastoma IDH-wild type (65.56%). Regarding tumor histology, 60% of oligodendrogliomas, 35% of astrocytoma and 100% of unclassified gliomas were re-classified, while glioblastomas maintained their initial classification. Additionally, the present study evaluated the prognostic value of the histological grade for the 2007 and 2016 WHO classifications of gliomas. The histological subgroup associated with longer overall survival (OS) was grade II glioma (OS-2007WHO, 35.6 months; and OS-2016WHO, 47.7 months). Glioblastoma was the subgroup associated with a poor outcome (OS-2007WHO, 10.4 months; and OS-2016WHO, 11.1 months). The present study evaluated the OS of tumor grade subgroups with respect to their IDH status. For all subgroups, IDH-mutant tumors were associated with an improved prognosis compared with IDH-wild type tumors. The results suggested that the incorporation of molecular biomarkers in the new WHO classification improves tumor characterization and prognostic value of the subgroups.

Mayten Tree Seed Oil: Nutritional Value Evaluation According to Antioxidant Capacity and Bioactive Properties.

The Mayten tree (Maytenus boaria Mol.), a native plant of Chile that grows under environmentally limiting conditions, was historically harvested to extract an edible oil, and may represent an opportunity to expand current vegetable oil production. Seeds were collected from Mayten trees in north-central Chile, and seed oil was extracted by solvent extraction. The seed oil showed a reddish coloration, with quality parameters similar to those of other vegetable oils. The fatty acid composition revealed high levels of monounsaturated and polyunsaturated fatty acids. Oleic and linoleic acids, which are relevant to the human diet, were well represented in the extracted Mayten tree seed oil. The oil displayed an antioxidant capacity due to the high contents of antioxidant compounds (polyphenols and carotenoids) and may have potential health benefits for diseases associated with oxidative stress.

Guias carcinoma de celulas renales (SCU-2020) / Guidelines renal cell carcinoma (SCU-2020)

La guía que se presenta actualmente es una adaptación de la guía de cáncer renal de la Asociación Europea de Urología en su versión más reciente 2020. Se eligió con la metodología ADOLOPMENT tras una evaluación con el instrumento AGREE II

The guideline currently presented is an adaptation of the renal cancer guideline of the European Association of Urology in its most recent version 2020. It was chosen using the ADOLOPMENT methodology after evaluation with the AGREE II instrument.

Recomendaciones y consideraciones del Comité Vascular de la Asociación Colombiana de Neurología para el manejo del ataque cerebrovascular isquémico durante la pandemia por covid-19 / Considerations and recommendations from the Stroke Committee of the Colombian Neurological Association for the management of Acute Ischemic Stroke during the pandemic for COVID-19

RESUMEN PROPÓSITO: En marzo 11 del 2020 la Organización Mundial de la Salud declara la pandemia por Covid-19. El clínico se va enfrentar a pacientes con ataque cerebrovascular (ACV) y sospecha o presencia de la infección. Miembros participantes del comité vascular de la Asociación Colombiana de Neurología basados en la experticia y la literatura amplían las primeras recomendaciones en el manejo de los pacientes con ACV isquémico agudo durante la actual pandemia. MÉTODOS: Mediante reuniones virtuales y por consenso de los participantes se escogieron tres ejes de trabajo: Tamización para Covid-19, Medidas de bioseguridad y Aspectos relevantes del ACV isquémico en época de pandemia por Covid-19. Se desarrollaron los ejes por grupos de trabajo mediante la modalidad de pregunta-respuesta pretendiendo generar en cada una de ellas recomendaciones sobre el tema. La versión final del documento conto con la revisión y el aval de todos los participantes. RESULTADOS: El documento cuenta con tres secciones correspondientes a los ejes de trabajo. En el primer eje se responden 3 preguntas y se dan recomendaciones sobre la tamización de la infección por Covid-19 en ACV agudo. En el segundo se responden 8 preguntas y se dan recomendaciones sobre las medidas de bioseguridad en la atención de pacientes con ACV durante la pandemia. En el tercero se tratan 13 aspectos relevantes del ACV durante la pandemia, según criterio de los participantes, y se dan recomendaciones pertinentes. CONCLUSIÓN: Las recomendaciones son basadas en la literatura y consenso de los participantes para el cuidado de pacientes con ACV isquémico agudo con sospecha o infección por Covid-19. No pretenden reemplazar las guías o protocolos establecidos sino ampliar las primeras recomendaciones del comité y apoyar al clínico en la atención de pacientes con ACV isquémico durante la pandemia.

SUMMARY PURPOSE: The World Health Organization declared the COVID-19 pandemic on March 11th 2020. Clinicians will face patients with stroke and confirmed or suspected infection. Members of the Stroke Committee of the Colombian Neurological Association based on their expertise and literature review extend on the first recommendations on acute ischemic stroke management during the pandemic. METHODS: Through virtual meetings and by consensus of participants three topics were selected: COVID-19 screening, biosafety measures and relevant aspects of acute ischemic stroke care during the pandemic. A question and answer format was used to develop recommendations for each topic. RESULTS: The manuscript is divided into three sections. The first includes three questions and recommendations on screening for COVID-19 in stroke patients. The second includes 8 questions and recommendations on biosafety measures on stroke patients during the pandemic. The last section includes 13 relevant stroke topics during COVID-19 pandemic, as deemed by the authors, and their recommendations. CONCLUSIONS: Recommendations on stroke care and COVID-19 are based on literature review and expert consensus. The aim of the manuscript is to extend on the first recommendations forwarded by the Committee, not to replace current guidelines, and to support the clinician caring for stroke patients during the pandemic.

New Poly(imide)s Bearing Alkyl Side-Chains: A Study on the Impact of Size and Shape of Lateral Groups on Thermal, Mechanical, and Gas Transport Properties.

A set of five new aromatic poly(imide)s (PIs) incorporating pendant acyclic alkyl moieties were synthesized. The difference among them was the length and bulkiness of the pendant group, which comprises of linear alkyl chains from three to six carbon atoms, and a tert-butyl moiety. The effect of the side group length on the physical, thermal, mechanical, and gas transport properties was analyzed. All PIs exhibited low to moderate molecular weights (Mn ranged between 27.930-58.970 Da, and Mw ranged between 41.760-81.310 Da), good solubility in aprotic polar solvents, except for PI-t-4, which had a tert-butyl moiety and was soluble even in chloroform. This behaviour was probably due to the most significant bulkiness of the side group that increased the interchain distance, which was corroborated by the X-ray technique (PI-t-4 showed two d-spacing values: 5.1 and 14.3 Å). Pure gas permeabilities for several gases were reported (PI-3 (Barrer): He(52); H2(46); O2(5.4); N2(1.2); CH4(1.1); CO2(23); PI-t-4 (Barrer): He(139); H2(136); O2(16.7); N2(3.3); CH4(2.3); CO2(75); PI-5 (Barrer): He(44); H2(42); O2(5.9); N2(1.4); CH4(1.2); CO2(27); PI-6 (Barrer): He(45); H2(43); O2(6.7); N2(1.7); CH4(1.7); CO2(32)). Consistent higher volume in the side group was shown to yield the highest gas permeability. All poly(imide)s exhibited high thermal stability with 10% weight loss degradation temperature between 448-468 °C and glass transition temperature between 240-270 °C. The values associated to the tensile strength (45-87 MPa), elongation at break (3.2-11.98%), and tensile modulus (1.43-2.19 GPa) were those expected for aromatic poly(imide)s.

Variables Associated with a Urinary MicroRNAs Excretion Profile Indicative of Renal Fibrosis in Fabry Disease Patients.

INTRODUCTION: In advanced Fabry nephropathy stages, enzyme replacement theraphy (ERT) efficacy decreases, due to its impossibility to reverse renal fibrosis. Therefore, the finding of early kidney fibrosis biomarkers in affected patients is of interest. During renal fibrosis miR-21, miR-192 and miR-433 (fibrosis promotors) are activated by transforming growth factor-ß (TGF-ß), and miR-29 and miR-200 family (fibrosis supressors) are inhibited by TGF-ß. The aim of this study is to analyze the probability that Fabry disease (FD) patients with some clinical variables can present an urinary microRNAs excretion profile indicative of renal fibrosis through a logistic regression analysis. RESULTS: A population of 34 participants was included: 24 FD patients and 10 controls. 16/24 (66.66%) FD patients presented microRNAs urinary excretion profile indicative of renal fibrosis. This profile was observed by decrease of fibrosis suppresors miR-29 and miR-200 and not by increase of fibrosis promotors miR-21, miR192, and miR-433. Hypohidrosis, angiokeratomas, neuropathic pain, hearing loss, cardiac involvement, male gender, reduced αGalA activity, and renin-angiotensin-aldosterone system inhibitors treatment are associated with the appearance of amicroRNAs urinary excretion profile indicative of renal fibrosis. A probable beneficial effect on urinary microRNAs excretion profile was observed in patients receiving ERT with agalsidase beta. The correlation between parameters of renal function with each family of microRNAs was studied. The only association with statistical significance was found between miR-21 and urine albumin-creatinine ratio (p =0.021). CONCLUSIONS: A probable microRNAs regulation not mediated by TGF-ß should be considered or TGF-ß has a different effect in FD than in other nephropathies on microRNAs regulation. Typical clinical manifestations of classic FD are associated with appearance of urinary microRNAs profile indicative of renal fibrosis. FD patients express renal fibrosis biomarkers in urine prior to onset of pathological albuminuria. A direct correlation between urinary miR-21 and degree of albuminuria was observed.

Synthesis and Properties of Poly(imides) and Poly(imides)/Ionic Liquid Composites Bearing a Benzimidazole Moiety.

Three new aromatic poly(imides) containing benzimidazole units in the backbone were synthesized and characterized by several spectroscopic techniques. Flexible spacer groups were incorporated into the poly(imides) structure to improve their solubility in organic solvents and their oxidative stabilization. All poly(imides) were thermally stable (Td5% > 512 °C) and had the ability to form dense flexible films. Novel composite films were successfully prepared by loading poly(imide) with ionic liquid ([Bmim]Br) at different concentrations up to 25 wt.%. The resulting materials were characterized according to their morphology and elemental composition (SEM-EDX), water uptake capability, contact angle, and oxidative degradation resistance. Results suggested that poly(imide)/ionic liquid composites would be excellent candidates for future proton conductivity measurements.

High Lyso-Gb3 Plasma Levels Associated with Decreased miR-29 and miR-200 Urinary Excretion in Young Non-Albuminuric Male Patient with Classic Fabry Disease.

Renal involvement is associated with a greater morbidity and mortality in Fabry disease. Pathological albuminuria, the first Fabry nephropathy clinical manifestation, can occur from early childhood, although histological lesions such as tubulo-interstitial fibrosis and glomerulosclerosis are present or may precede the onset of pathological albuminuria. In renal cells, exposure to Lyso-Gb3 is correlated with increased expression of Transforming Growth Factor-ßeta (TGF-ß). miR-21, miR-192, and miR-433 that promote fibrosis are activated by TGF-ß, and miR-29 and miR-200 that suppress fibrosis are inhibited by TGF-ß. A 23-year-old male was diagnosed with FD. αGalA decreased enzyme activity: 0.1 nmol/hour/liter; genotype: [c.317T>G (p.L106R)]; GFR: 104.4 mL/min/m2; urinary albumin excretion: 6.00 mg/day; plasma Lyso-Gb3: 124.5 nmol/L. A decrease urinary excretion of miR-29 and miR-200 was found (p <0.005) compared to controls. In addition to its usefulness as a phenotype marker, Lyso-Gb3 has been proposed as an indicator of therapeutic response. We detect an association of high Lyso-Gb3 plasma values with decreased urinary excretion of miRNAs with known antifibrotic effect (miR-29 and miR-200). Although the present work is a case report, it could be hypothesized that one of the harmful Lyso-Gb3 effects could be the miRNAs regulation through changes in TGF-ß expression.

Rara presentación de polineuropatía distal hipoglicémica causada por un insulinoma en el contexto de una neoplasia endocrinamúltiple tipo 1 / An unusual presentation of hypoglycemic distal polyneuropathy caused by an insulinoma in the context of multiple endocrine neoplasia 1

La neoplasia endocrina múltiple tipo 1 es una enfermedad de rara presentación. Se caracteriza por el compromiso tumoral neuroendocrino, de paratiroides, hipófisis y enteropancreático. Presentamos el caso de una paciente de 19 años con síntomas de cefalea, convulsiones y debilidad de las cuatro extremidades. Se confirmó la presencia de hipoglicemia 33mg/dL. El estudio elecromiográfico evidenció polineuropatía sensitivo motora en las cuatro extremidades. La resonancia magnética abdominal mostró un tumor en la cola del páncreas que luego de la pancreatectomía se confirmó como insulinoma. La glicemia se normalizó. Además, presentó un macroadenoma hipofisario, hiperparatiroidismo primario y tumor adrenal no funcionante. A los 25 años presentó cefalea intensa y amaurosis de ojo derecho, en la tomografía axial se evidenció tumoración hipofisaria gigante y en estudio de patología se diagnosticó neoplasia maligna condroide (cordoma).

Multiple endocrine neoplasia type 1 is a rare disease. It is characterized by the neuroendocrine, parathyroid, pituitary, and enteropancreatic tumor involvement. We present the case of a 19 year old patient with symptoms of headache, convulsions and weakness of the four extremities. The presence of hypoglycemia 33mg/dL was confirmed. The electromyographic study showed motor sensory polyneuropathy in all four extremities. The abdominal magnetic resonance showed a tumor in the tail of the pancreas that after the pancreatectomy was confirmed as insulinoma. The glycemia was normalized. In addition, he presented a pituitary macroadenoma, primary hyperparathyroidism and non-functioning adrenal tumor. At 25 years of age, he presented severe headache and amaurosis of the right eye. Axial tomography showed a giant pituitary tumor and in the study of pathology chondroid malignancy (chordoma) was diagnosed.

Guía de práctica clínica de infección de vías urinarias en el adulto / Clinical Practice Guideline for Urinary Tract Infection in Adults

Las IVU son las infecciones más frecuentes en el ámbito de infecciones adquiridas en la comunidad. Se estima que el 40% de las mujeres y el 12% de los hombres, presentaran por lo menos, un episodio de IVU en su vida adulta.1 Aproximadamente el 40% de las infecciones nosocomiales son IVU, de las cuales la mayoría están relacionadas con el uso de dispositivos médicos. El microorganismo más frecuentemente aislado es la Escherichia coli que causa del 79% al 95% de las IVU adquiridas en la comunidad.

UTIs are the most common infections in the context of community-acquired infections. It is estimated that 40% of women and 12% of men will have at least one episode of UTI in adulthood.1 Approximately 40% of nosocomial infections are UTIs, most of which are related to the use of medical devices. The most frequently isolated microorganism is Escherichia coli, which causes 79% to 95% of community-acquired UTIs.

A novel approach to approximate order preserving matching / Una nueva aproximación al emparejamiento con preservación de orden / Uma nova abordagem al emparelhamento com preservação de ordem

Abstract A problem with important applications in stock market analysis and music information retrieval is order-preserving matching. This problem is a recently introduced variant of the string matching problem that searches for substrings in the text whose natural representation matches the natural representation of the pattern. The natural representation of a string X is a string that contains the rankings of the characters occurring at each position of X. Then, order-preserving matching regardsthe internal structure of the strings rather than their absolute values. But both stock market analysis and music information retrieval require more flexibility: not only the substrings with exactly the same structure are of interest, but also the ones that are similar. In this paper, we propose an approximate version of order-preserving matching based on the δγ- distances that permit an individual error between the ranking of corresponding symbols (bounded by δ) and a global error of all the positions (bounded by γ). We present an algorithm that solves this problem in O(nm+m log m). Experimental results verify the efficiency of the proposed algorithm.

Resumen Un problema importante en el análisis de mercado de valores y la recuperación de información musical es el empareja- miento con preservación de orden. Este problema es una variante recientemente introducida del problema de empareja- miento de cadenas en el que busca subcadenas en el texto cuya representación natural coincide con la representación natural del patrón. La representación natural de una cadena X es una cadena que contiene los rankings de los caracteres que ocurren en cada posición de X. Entonces, el emparejamiento con preservación de orden considera la estructura inter- na de las cadenas en lugar de sus valores absolutos. Pero tanto en el análisis de mercado de valores como en la recuperación de información musical, se requiere más flexibilidad: no sólo las subcadenas con exactamente la misma estructura son de interés, sino también las que son similares. En este artículo se propone una versión aproximada del problema de emparejamiento con preservación de orden basada en las distancias δγ que permiten un error individual entre el ranking de los símbolos correspondientes (delimitada por δ) y un error global de todas los rankings (delimitadas por γ). Se presenta un algoritmo que resuelve este problema en O(nm+m log m). Los resultados experimentales verifican la eficiencia del algoritmo propuesto.

Resumo Um grande problema na análise do mercado de ações e na recuperação de informações musicais é o emparelhamento com a preservação de ordem. Esse problema é uma variante recentemente introduzida do problema de correspondência de cordas que procura por substrings no texto cuja representação natural corresponde à representação natural do padrão. A representação natural de uma corda X é uma corda que contém as classificações dos caracteres que ocorrem em cada posição de X. Então, a correspondência de preservação de ordem considera a estrutura interna das cordas em vez de seus valores absolutos. Mas na análise do mercado de ações, bem como na recuperação da informação musical, é necessária mais flexibilidade: não são apenas as sub-cordas com exatamente a mesma estrutura que interessam, mas também as que são semelhantes. Neste artigo, propomos uma versão aproximada da emparelhamento com preservação de ordem com base nas distâncias δγ- que permitem um erro individual entre a classificação de símbolos correspondentes (delimitada por δ) e um erro global de Todas as posições (delimitadas por γ). Apresentamos um algoritmo que resolve este problema em O(nm+m log m). Os resultados experimentais verificaram a eficiência do algoritmo proposto.

Cardiac abnormalities in Trypanosoma cruzi seropositive patients in the State of Querétaro, México / Alteraciones cardiacas en una población seropositiva a Trypanosoma cruzi en Querétaro, México

Abstract: Background: Chagas disease is an endemic illness in the Americas and therefore constitutes a public health problem. An estimated 8 million people are infected and over 20 million live in areas at risk. In Mexico, the problem is under reported and no epidemiological data by the different States indicating true prevalence for this infection is available. During the chronic phase, 30% of infected patients may develop chagasic cardiomyopathy (CCM), characterized by different types of alterations of cardiac function. Objective: To describe cardiac abnormalities in Trypanosoma cruzi seropositive subjects in the endemic areas. Material and methods: This is a descriptive cross-sectional study with non-random sampling. In our project the endemic area was considered for Trypanosoma cruzi using the Epi Info statistical program (Stat Calc) to calculate the number of subjects to study by means of a sample of 1 033 subjects aged 2-90 years. Prior informed consent or parental consent, implementation of a survey, a 5 mL of blood sample free from anticoagulant was taken from the cubital vein to detect anti-Trypanosoma cruzi by ELISA, recombinant ELISA, hemagglutination indirect (HAI), indirect immunofluorescence (IFI) and Western blot (using the enzyme superoxide dismutase iron as antigen). Those subjects who were positive in two or more tests were chosen for electrocardiogram (EKG) and an echocardiogram (ECO) with portable devices. Results: Of the 1 033 participants, 84 between 6 and 88 years tested positive for Trypanosoma cruzi. In the analysis of data with echocardiograms and electrocardiograms, 47 subjects over 26 years (56%), presented right bundle branch block or left bundle block (RBBB/LBBB), changes in the diameters of the right ventricle or left ejection fraction accounting of 70%. In subjects under 26 years there were electrocardiographic changes (RBBB/LBBB). Conclusion: 8.13% were seropositive for Trypanosoma cruzi with ventricular conduction system and morphological alterations.

Resumen: Antecedentes: La enfermedad de Chagas es una patología endémica en las Américas, donde representa un problema de salud pública. Se estima que aproximadamente 8 millones de personas están infectadas y 20 millones viven en áreas de riesgo de infectarse. En México el problema está subestimado y se carece de datos epidemiológicos por estado del país que indiquen una prevalencia real de este padecimiento. Durante la fase crónica, el 30% de los pacientes infectados pueden desarrollar miocardiopatía chagásica (MCC), que se caracteriza por presentar diferentes alteraciones de la función cardiaca. Objetivo: Describir las alteraciones cardiacas en sujetos seropositivos para Trypanosoma cruzi de áreas endémicas. Material y métodos: Es un estudio con diseño transversal descriptivo, con muestra no probabilística. En nuestro proyecto, se consideró una zona endémica a Trypanosoma cruzi, mediante el programa estadístico Epi Info (Stat Calc), para estimar el número de sujetos a estudiar, obteniéndose una muestra de 1 033 sujetos de edades entre 2 a 90 años. Previo consentimiento informado, y aplicación de una encuesta, se puncionó la vena cubital, obteniéndose una muestra sanguínea de 5 mL, sin anticoagulante, para buscar anticuerpos anti-Trypanosoma cruzi mediante, ELISA, ELISA recombinante, hemaglutinación indirecta (HAI), inmunofluorescencia indirecta (IFI) y Western-Blot (usando la enzima superóxido dismutasa de hierro como antígeno). Los sujetos reactivos a dos o más pruebas fueron seleccionados para la realización de un electrocardiograma (EKG) y un ecocardiograma (ECO) con equipos portátiles Resultados: De los 1 033 participantes, 84 entre 6 a 88 años resultaron positivos para Trypanosoma cruzi. En el análisis de los hallazgos ecocardiográficos y electrocardiográficos en los 47 sujetos mayores de 26 años (56%) presentaron bloqueo de rama derecha o izquierda del haz de His (BRDHH/BRIHH). Conclusión: El 8.13% fueron seropositivos para Trypanosoma cruzi con cambios morfológicos ventriculares y del sistema de conducción del haz de His.

Osmotic stress alters UV-based oxidative damage tolerance in a heterocyst forming cyanobacterium.

Cyanobacteria are successful in diverse habitats due to their adaptation strategies. Their mechanisms to cope with individual stresses have been studied. However, the response to combined stress conditions as found in nature remains unclear. With this aim, we studied the dual effect of 24h-osmotic and 3h-UV irradiation on the cyanobacterium Calothrix BI22. Our approach included the study of redox homeostasis, oxidative damage, reactive oxygen species production-consumption processes and photosynthetic activity. Superoxide in vivo determination with confocal image processing showed the highest accumulation under UV. However, no lipoperoxidation occurred due to a high SOD activity. This cyanobacterium was less prepared to cope with the osmotic stress assayed. Under this condition, O2 photoevolution decreased abruptly and oxidative damage was produced by reactive species other than superoxide. In this situation the cellular control of the amount of ROS failed to prevent oxidative damage and photosynthesis was seriously disturbed in spite of maximum quantum photosynthetic efficiency remained unchanged. Calothrix BI22 presented the more severe oxidative damage when both stressors were applied. The osmotic stress disentangled the mechanisms developed by this cyanobacterium to deal with 3h-UV irradiation alone.

Integrating sampling techniques and inverse virtual screening: toward the discovery of artificial peptide-based receptors for ligands.

A novel heuristic using an iterative select-and-purge strategy is proposed. It combines statistical techniques for sampling and classification by rigid molecular docking through an inverse virtual screening scheme. This approach aims to the de novo discovery of short peptides that may act as docking receptors for small target molecules when there are no data available about known association complexes between them. The algorithm performs an unbiased stochastic exploration of the sample space, acting as a binary classifier when analyzing the entire peptides population. It uses a novel and effective criterion for weighting the likelihood of a given peptide to form an association complex with a particular ligand molecule based on amino acid sequences. The exploratory analysis relies on chemical information of peptides composition, sequence patterns, and association free energies (docking scores) in order to converge to those peptides forming the association complexes with higher affinities. Statistical estimations support these results providing an association probability by improving predictions accuracy even in cases where only a fraction of all possible combinations are sampled. False positives/false negatives ratio was also improved with this method. A simple rigid-body docking approach together with the proper information about amino acid sequences was used. The methodology was applied in a retrospective docking study to all 8000 possible tripeptide combinations using the 20 natural amino acids, screened against a training set of 77 different ligands with diverse functional groups. Afterward, all tripeptides were screened against a test set of 82 ligands, also containing different functional groups. Results show that our integrated methodology is capable of finding a representative group of the top-scoring tripeptides. The associated probability of identifying the best receptor or a group of the top-ranked receptors is more than double and about 10 times higher, respectively, when compared to classical random sampling methods.

Evidence for homologous recombination in Chikungunya Virus.

Chikungunya Virus (CHIKV), a mosquito-transmitted alphavirus, causes acute fever and joint pain in humans. Recently, endemic CHIKV infection outbreaks have jeopardized public health in wider geographical regions. Here, we analyze the phylogenetic associations of CHIKV and explore the potential recombination events on 152 genomic isolates deposited in GenBank database. The CHIKV genotypes [West African, Asian, East/Central/South African (ECSA)], and a clear division of ECSA clade into three sub-groups (I-II-III), were defined by Bayesian analysis; similar results were obtained using E1 gene sequences. A nucleotide identity-based approach is provided to facilitate CHIKV classification within ECSA clade. Using seven methods to detect recombination, we found a statistically significant event (p-values range: 1.14×10(-7)-4.45×10(-24)) located within the nsP3 coding region. This finding was further confirmed by phylogenetic networks (PHI Test, p=0.004) and phylogenetic tree incongruence analysis. The recombinant strain, KJ679578/India/2011 (ECSA III), derives from viruses of ECSA III and ECSA I. Our study demonstrates that recombination is an additional mechanism of genetic diversity in CHIKV that might assist in the cross-species transmission process.

Anotaciones para una historia de Acta Neurológica Colombiana / Annotations for a History of Acta Neurologica Colombiana

La aparición de una publicación científica seriedad, reconocida como órgano oficial de una asociación de médicos especialista, consolida el ciclo de profesionalización de un saber o conocimiento y afianza su imagen social en la comunidad en general y en la comunidad científica en particular. Estas anotaciones para una historia de Acta Neurológica Colombiana cubren ese período inicial y establecen las condiciones profesionales y educativas en las cuales se creó y desarrolló la publicación oficial de la Asociación Colombiana de Neurología. Muestran, de forma paralela, cómo la comunidad científica y el país diseñaron y pusieron en marcha un sistema de ciencia y tecnología que entre sus primeras acciones adoptó un sistema de clasificación para las revista científicas que privilegió los criterios numéricos de la bibliometría como indicadores de visibilidad.

The appearance of a scientific publication, recognized as the official organ of an medical specialist association, strengthens the professionalization cycle of a field of knowledge or one career, and reinforces its social image in the general community and specifically in the scientific community. These annotations for a history of Acta Neurológica Colombiana, covering the initial period establish the professional and educational conditions in which it was created and developed as the official publication of the Asociación Colombiana de Neurología. Additionally it shows, in parallel, how in the scientific community and the Country a system of science and technology was designed and implemented having among its first actions the adoption of a classification system for scientific journals that favored the numerical criteria of bibliometrics as an indicator of visibility.

Conocimientos de los estudiantes de último año del pregrado de medicina en el uso de estudios imaginológicos frecuentes, Cartagena 2014. Estudio ATENEA / Knowledge of Students from Last Year of Undergraduate Medical Studies on the Use of Frequent Imaging Modalities, Cartagena 2014. Atenea Study

Introducción: El uso inadecuado de estudios imaginológicos es un grave problema en todo el mundo. Una de las principales causas es la ausencia de competencias de los médicos en el tema. Objetivos: Determinar el nivel de conocimientos de los estudiantes cartageneros de último año del pregrado de medicina en el uso de estudios imaginológicos frecuentes. Métodos: Estudio observacional, descriptivo, de corte transversal. Participaron los estudiantes de último año del pregrado de medicina de dos universidades cartageneras. Se aplicó a los estudiantes un cuestionario de 17 preguntas con el que se determinaron sus conocimientos sobre indicaciones, costos y riesgos de estudios radiológicos frecuentes. Se describieron todas las variables estudiadas. Resultados: Se analizaron los datos de 194 estudiantes. Ninguno respondió las 17 preguntas en forma correcta. El promedio de preguntas buenas contestadas fue 8,14, lo que equivale a menos de la mitad de las preguntas. El 42,27 % tuvo un desempeño aceptable en al menos un subtema de la prueba de conocimientos (solo el 7,73 % en dos subtemas). Y el 57,73 % no tuvo un desempeño aceptable en ninguno de los subtemas. El área con mejor desempeño fue "costos" y la de peor desempeño fue "riesgos". Conclusiones: Los estudiantes de último año de pregrado de medicina de dos universidades de Cartagena tuvieron, en términos generales, un mal desempeño en la prueba de conocimientos sobre uso de estudios imaginológicos frecuentes.

Introduction: The inappropriate use of imaging studies is a serious global problem. One of the main reasons is a lack of competence of doctors in the topic. Objectives: To determine the level of knowledge of Cartagena students from last year of undergraduate medical studies on the use of frequent imaging modalities. Methods: Observational, descriptive, cross-sectional study. Students of two universities of Cartagena were included in this study. A questionnaire with 17 questions was applied to students, where their knowledge on indications, costs, and risks of frequent radiological studies was determined. All studied variables were described. Results: Data from 194 students were analyzed. No student answered 17 questions correctly. The average number of correctly answered questions was 8.14, equivalent to less than half of the questions. 42.27% had an acceptable performance in at least one of the subthemes in the knowledge test (only 7.73% in two sub-themes). 57.73% did not have an acceptable performance in any of the subtopics. The best performing area was "costs" and worst performing area was "risks". Conclusions: In general, students in final year of undergraduate medical of two universities in Cartagena, had poor performance on the knowledge test regarding the use of frequent imaging studies.

Comparative serology techniques for the diagnosis of Trypanosoma cruzi infection in a rural population from the state of Querétaro, Mexico.

Immunological diagnostic methods for Trypanosoma cruzi depend specifically on the presence of antibodies and parasitological methods lack sensitivity during the chronic and "indeterminate" stages of the disease. This study performed a serological survey of 1,033 subjects from 52 rural communities in 12 of the 18 municipalities in the state of Querétaro, Mexico. We detected anti-T. cruzi antibodies using the following tests: indirect haemagglutination assay (IHA), indirect immunofluorescence assay (IFA), ELISA and recombinant ELISA (rELISA). We also performed Western blot (WB) analysis using iron superoxide dismutase (FeSOD), a detoxifying enzyme excreted by the parasite, as the antigen. Positive test results were distributed as follows: ELISA 8%, rELISA 6.2%, IFA and IHA 5.4% in both cases and FeSOD 8%. A comparative study of the five tests was undertaken. Sensitivity levels, specificity, positive and negative predictive values, concordance percentage and kappa index were considered. Living with animals, trips to other communities, gender, age, type of housing and symptomatology at the time of the survey were statistically analysed using SPSS software v.11.5. Detection of the FeSOD enzyme that was secreted by the parasite and used as an antigenic fraction in WBs showed a 100% correlation with traditional ELISA tests.