PRRGO: A Tool for Visualizing and Mapping Globally Expressed Genes in Public Gene Expression Omnibus RNA-Sequencing Studies to PageRank-scored Gene Ontology Terms.

We herein report PageRankeR Gene Ontology (PRRGO), a downloadable web application that can integrate differentially expressed gene (DEG) data from the gene expression omnibus (GEO) GEO2R web tool with the gene ontology (GO) database [1]. Unlike existing tools, PRRGO computes the PageRank for the entire GO network and can generate both interactive GO networks on the web interface and comma-separated values (CSV) files containing the DEG statistics categorized by GO term. These hierarchical and tabular GO-DEG data are especially conducive to hypothesis generation and overlap studies with the use of PageRank data, which can provide a metric of GO term centrality. We verified the tool for accuracy and reliability across nine independent heat shock (HS) studies for which the RNA-seq data was publicly available on GEO and found that the tool produced increasing concordance between study DEGs, GO terms, and select HS-specific GO terms.

IoT System Based on Artificial Intelligence for Hot Spot Detection in Photovoltaic Modules for a Wide Range of Irradiances.

Infrared thermography (IRT) is a technique used to diagnose Photovoltaic (PV) installations to detect sub-optimal conditions. The increase of PV installations in smart cities has generated the search for technology that improves the use of IRT, which requires irradiance conditions to be greater than 700 W/m2, making it impossible to use at times when irradiance goes under that value. This project presents an IoT platform working on artificial intelligence (AI) which automatically detects hot spots in PV modules by analyzing the temperature differentials between modules exposed to irradiances greater than 300 W/m2. For this purpose, two AI (Deep learning and machine learning) were trained and tested in a real PV installation where hot spots were induced. The system was able to detect hot spots with a sensitivity of 0.995 and an accuracy of 0.923 under dirty, short-circuited, and partially shaded conditions. This project differs from others because it proposes an alternative to facilitate the implementation of diagnostics with IRT and evaluates the real temperatures of PV modules, which represents a potential economic saving for PV installation managers and inspectors.

Predator response to the coloured eyespots and defensive posture of Colombian four-eyed frogs.

Deimatic displays, where sudden changes in prey appearance elicit aversive predator reactions, have been suggested to occur in many taxa. These (often only putative) displays frequently involve different components that may also serve antipredator functions via other mechanisms (e.g., mimicry, warning signalling, body inflation). The Colombian four-eyed frog, Pleurodema brachyops, has been suggested to gain protection against predation through putative deimatic displays where they inflate and elevate the posterior part of their body revealing eye-like colour markings. We exposed stationary artificial frogs to wild predators to test whether the two components (eyespot/colour markings, defensive posture) of their putative deimatic display, and their combination, provide protection from predation without the sudden change in appearance. We did not detect any obvious additive effect of defensive posture and eyespots/colour markings on predation risk, but found a marginally significant trend for model frogs in the resting posture to be less attacked when displaying eyespots/colour markings than when they were not, suggesting that the presence of colour markings/eyespots may provide some protection on its own. Additionally, we found that models in a resting posture were overall more frequently attacked on the head than models in a defensive posture, indicating that a defensive posture alone could help redirect predator attacks to non-vital parts of the body. The trends found in our study suggest that the different components of P. brachyops' coloration may serve different functions during a deimatic display, but further research is needed to elucidate the role of each component when accompanied by sudden prey movement.

The Burden of Gastric Cancer Disease from 2010 to 2019 in Tunja, Boyacá, Colombia

Introduction: Gastric cancer (GC) is the first cause of death by neoplasm in Colombia, with 6,451 deaths in 2020. This pathology and its chronic manifestations pose a public health challenge. The objective is to estimate the disease burden of GC in Tunja, Boyacá, from 2010 to 2019. Materials and methods: An exploratory ecological study was conducted using disability-adjusted life years (DALYs) as the unit of measurement. The National Administrative Department of Statistics (DANE) mortality databases and prevalence information from the Integrated Social Protection Information System (SISPRO) records were used. Deaths and GC cases were pooled and then adjusted to control for bias. Results: In 2010-2019, 34.2 DALYs were lost for every 1,000 people secondary to GC in Tunja, 30.5 were due to years lost due to premature death, and 3.72 were due to years lived with disability. DALYs due to premature death were found to exceed DALYs due to disability. Conclusion: The morbidity burden of GC from 2010 to 2019 for Tunja was similar to that of other cancers because of years of life lost due to premature death, so public health efforts should be made to increase early detection.

Introducción: el cáncer gástrico (CG) es la primera causa de muerte por neoplasia en Colombia, con 6451 muertes durante el 2020. Esta patología y sus manifestaciones crónicas plantean un desafío en la salud pública. El objetivo fue estimar la carga de enfermedad por CG en Tunja, Boyacá, durante los años 2010 a 2019. Metodología: se realizó un estudio ecológico exploratorio en el que se utilizó como unidad de medida los años de vida ajustados por discapacidad (AVAD). Se emplearon las bases de datos de mortalidad del Departamento Administrativo Nacional de Estadística (DANE) e información de la prevalencia desde los registros del Sistema Integrado de Información de la Protección Social (SISPRO). Las muertes y los casos de CG se agruparon y luego se ajustaron para controlar sesgos. Resultados: en el período 2010-2019 se perdieron 34,2 AVAD por cada 1000 personas secundarios a CG en Tunja, de los cuales 30,5 fueron debido a años perdidos por muerte prematura y 3,72 por años vividos con discapacidad. Se encontró que los AVAD por muerte prematura superan a los AVAD por discapacidad. Conclusión: la carga de morbilidad por CG en el período 2010 a 2019 para la ciudad de Tunja fue similar a la carga de otros cánceres y fue debido a años de vida perdidos por muerte prematura, motivo por el cual se deben realizar esfuerzos de salud pública para aumentar la detección temprana.

Advertisement call of the Colombian Horned Frog Ceratophrys calcarata (Anura, Ceratophryidae).

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Study of the Interaction of Ti-Zn as a Mixed Oxide at Different pH Values Synthesized by the Sol-Gel Method and Its Antibacterial Properties.

TiO2, ZnO, and their combination (TiO2−ZnO) at different molar ratios and pH values (Ti−Zn A and B 3:1, 1:1, and 1:3) via the sol−gel method were characterized by SEM, XRD, UV-Vis, and FT-IR. Moreover, antibacterial tests of the nanoparticles were conducted against Escherichia coli (E. coli), Salmonella paratyphi (S. paratyphi), Staphylococcus aureus (S. aureus), and Listeria monocytogenes (L. monocytogenes). The indirect bandgap of the Ti−Zn binary oxide synthesized in the basic process at molar ratios of 3:1, 1:1, and 1:3 exhibited a higher eV (3.31, 3.30, and 3.19 eV, respectively) compared to pure TiO2 (3.2 eV) and synthesized in the acid process (3.22, 3.29, and 3.19 eV at same molar ratio, respectively); in addition, the results of the indirect bandgap were interesting due to a difference found by other authors. Moreover, the sol−gel method promoted the formation of a spherical, semi-sphere, and semi-hexagonal shape (TiO2, Ti−Zn 1:1, and Ti−Zn 1:3) with a size ≤ 150 nm synthesized during the acid process, with a crystallite size of ~71, ~12, ~34, and ~21 nm, respectively, while ZnO NPs developed a hexagonal and large size (200−800 nm) under the same synthesis process (acid). Samples were classified as TiO2 anatase phase (basic synthesis); however, the presented changes developed in the rutile phase (24% rutile phase) at an acid pH during the synthesis process. Moreover, Ti−Zn maintained the anatase phase even with a molar ratio of 1:3. The most interesting assessment was the antibacterial test; the Ti−Zn A (1:3) demonstrated a bacteriostatic effect compared with all treatments except ZnO, which showed a similar effect in dark conditions, and only Gram-positive bacteria were susceptible (Listeria monocytogenes > Staphylococcus aureus). Therefore, the Ti−Zn characteristic suggests that the results have potential in treating wastewater as well as in pharmaceutical (as drug carriers) and medical applications.

Giant pancreatic pseudocyst drainage by endoscopic cystogastrostomy: Case report / Drenaje de pseudoquiste pancreático gigante mediante cistogastrostomía endoscópica: reporte de caso

Abstract Introduction: The pancreatic pseudocyst is one of the late local complications of acute pancreatitis. For managing a giant pancreatic pseudocyst, there are multiple strategies. Aim: To present the case of a patient with a giant pancreatic pseudocyst managed by endoscopic cystogastrostomy. Clinical case: A 41-year-old woman developed a giant pancreatic pseudocyst as a complication of acute pancreatitis that was managed by endoscopic cystogastrostomy without endoscopic ultrasound guidance, with good evolution. Conclusions: Endoscopic cystogastrostomy, with or without the help of ultrasound endoscopy or lumen-apposing metal stent (LAMS), is a viable, safe, effective, and economical therapeutic option for selected patients with a giant pancreatic pseudocyst.

Resumen Introducción: el pseudoquiste pancreático es una de las complicaciones locales tardías de la pancreatitis aguda. Para el manejo del pseudoquiste pancreático gigante existen múltiples estrategias. Objetivo: presentar el caso de una paciente con pseudoquiste pancreático gigante manejado mediante cistogastrostomía endoscópica. Caso clínico: mujer de 41 años que desarrolló un pseudoquiste pancreático gigante como complicación de una pancreatitis aguda y se manejó mediante cistogastrostomía endoscópica sin guía ecoendoscópica, con una adecuada evolución. Conclusiones: la cistogastrostomía endoscópica, con la ayuda o no de ecoendoscopia ni stent de aposición luminal (LAMS), es una opción terapéutica viable, segura, efectiva y económica para pacientes seleccionados con pseudoquiste pancreático gigante.

Effects of SPTA1 Gene Variants on the Hematological Phenotype of Mexican Patients with Hereditary Spherocytosis.

Introduction: Hereditary spherocytosis (HS) is a common hereditary hemolytic anemia characterized by chronic hemolysis, increased indirect serum bilirubin, the presence of reticulocytes and spherocytes in blood smears, and great heterogeneity at the clinical, biochemical, and molecular levels. The molecular pathology of HS includes genetic variants at five genes: ANK1, EPB42, SLC4A1, SPTA1, and SPTB. Alpha spectrin (SPTA1) deficiency is the second leading cause of HS in Mexican patients. Aim: To assess the effects of five SPTA1 variants on the hematological phenotype of Mexican patients with HS. Materials and Methods: This study included a retrospective cohort of 227 biologically unrelated patients with HS. Variants c.4339-99C>T and c.6531-12C>T in SPTA1 were identified by the amplification-refractory mutation system polymerase chain reaction (ARMS-PCR), and variants c.5572C>T, c.5992C>G, and c.6794T>C were identified by quantitive Real Time-Polymerase Chain Reaction (qRT-PCR) allelic discrimination. Risk tests were performed for each variant with respect to HS clinical severity. Results: The SPTA1 c.5992C>G variant showed association with moderately severe HS (p = 0.006, odds ratio = 5.67, confidence interval95% = 1.6-19.9); the risk increased when the variant was in compound heterozygosity with αLELY and c.6794T>C. Lower hematological levels were observed in simple αLely (c.5572C>T and c.6531-12C>T), and c.5992C>G heterozygotes (red blood cell [RBC] p = 0.028 and 0.010; hemoglobin [Hb] p = 0.030 and 0.002; packed cell volume [PCV] p = 0.034 and 0.002 respectively), and in c.5992C>G+c.6794T>C compound heterozygotes (RBC p = 0.043; Hb p = 0.033; PCV p = 0.043). Additional genetic traits were observed: 15% had HS+Gilbert syndrome and 13% HS+thalassemia. Conclusion: Although most of the studied variants are considered benign, we observed significant associations with phenotypic severity. Therefore, we recommend the inclusion of these variants in molecular screening for HS.

Causas del hidrops fetal: experiencia en un hospital obstétrico del Occidente de México / Etiology of fetal hydrops: experience in an obstetric hospital in western Mexico

Resumen OBJETIVO: Identificar las causas de hidrops fetal no inmunitario en un hospital obstétrico de referencia del Occidente de México. MATERIALES Y MÉTODOS: Estudio de serie de casos, con un muestreo no probabilístico por conveniencia, llevado a cabo de octubre de 2014 a septiembre de 2015 al que se incluyeron pacientes (entre las 15 y 38 semanas de embarazo), mayores de edad (en casos de menores de edad se solicitó consentimiento informado a los padres o tutores), con diagnóstico de hidrops fetal por ultrasonido obstétrico. Para el análisis estadístico se generó una base de datos en Excel y se aplicó estadística descriptiva. RESULTADOS: Se reunieron 33 embarazadas en quienes el hidrops fetal no inmunitario fue el más frecuente (n = 31) y la causa idiopática más común (n = 10) seguida por errores innatos del metabolismo, alteraciones cromosómicas y cardiacas (n = 6 de cada una). Posteriormente, las causas hematológicas (n = 4), linfáticas y sindrómicas (n = 3 de cada una), y las infecciosas y tumorales (n = 1 de cada una). En este estudio los errores innatos del metabolismo (específicamente síndrome Sly) tuvieron una frecuencia superior a la referida en la bibliografía. CONCLUSIONES: Los errores innatos del metabolismo, las anomalías cromosómicas y cardiacas fueron la segunda causa más frecuente de hidrops fetal no inmunitario. Se sugiere tener en cuenta las causas metabólicas en el enfoque diagnóstico del hidrops fetal, sobre todo para el establecimiento del tratamiento temprano.

Abstract OBJECTIVE: To identify the causes of nonimmune fetal hydrops fetalis in an obstetric referral hospital in Western Mexico. MATERIALS AND METHODS: Case series study, with non-probabilistic sampling by convenience, carried out from October 2014 to September 2015 which included patients (between 15 and 38 weeks of pregnancy), of legal age (in cases of minors, informed consent was requested from parents or guardians), with a diagnosis of fetal hydrops fetalis by obstetric ultrasound. For statistical analysis, an Excel database was generated and descriptive statistics were applied. RESULTS: Thirty-three pregnant women were included, in whom non-immune fetal hydrops fetalis was the most frequent (94%) and idiopathic was the most common cause (n = 10), followed by inborn errors of metabolism, chromosomal and cardiac alterations (n = 6 each). This was followed by hematologic (n = 4), lymphatic and syndromic causes (n = 3 each), and infectious and tumor causes (n = 1 each). In this study, inborn errors of metabolism (specifically Sly syndrome) had a higher frequency than that reported in the literature. CONCLUSIONS: Inborn errors of metabolism, chromosomal and cardiac abnormalities were the second most frequent cause of nonimmune fetal hydrops. It is suggested that metabolic causes be taken into account in the diagnostic approach to fetal hydrops, especially for the establishment of early treatment.

Biopsia de próstata, acceso transperineal bajo anestesia local / Prostate Biopsy, Transperineal Access under Local Anesthesia

Objetivo La biopsia de próstata es una ayuda esencial en el diagnóstico de cáncer, siendo el método más utilizado la biopsia transrectal guiada por ultrasonido (TRUS), con una tasa diagnóstica entre el 37% y el 45%, aunque no exenta de complicaciones como infecciones, dolor o sangrado. El enfoque alternativo y seguro a las biopsias TRUS se encuentra en la biopsia transperineal (BTP), realizada comúnmente bajo anestesia regional o general. El objetivo de este estudio fue determinar la efectividad de la BTP bajo anestesia local y guía ultrasonográfica transrectal, con el impacto sobre la sensibilidad del estudio y la tasa de readmisión hospitalaria por infección. Métodos Estudio de cohorte retrospectiva en el que se evaluaron 83 pacientes sometidos a BTP con anestesia local y guía ultrasonográfica transrectal de enero de 2017 a agosto de 2018 en una ciudad intermedia de Colombia. La muestea incluyó todos los hombres mayores de 18 años con datos de historia clínica disponibles para su análisis, así como los reportes histopatológicos de las biopsias. Se excluyeron casos de rebiopsia o con datos insuficientes. El análisis de datos nominales se realizó mediante la prueba de chi cuadrado, y el de los datos numéricos, con las prubas t de Student o de Mann-Whitney. Resultados Un total de 83 pacientes, con media de edad de 65 ± 7.9 años fueron sometidos al análisis del estudio histopatológico. Se excluyeron nueve pacientes que no tenían información disponible en el registro clínico sistematizado, ni en historia clínica de formato físico. Se encontró una proporción de positividad y diagnóstico de cáncer de prostata en el 39.7% (33) de los pacientes, distribuidos así: grado de grupo 1 (69.7%; 23); grado de grupo 2 )15.2%; 5); grados de grupos 3 y 4 (3% cada uno de ellos; 2); y grado de grupo 5 (9%; 3). En total, 60% (50) fueron negativos para malignidad y, de estos el 54% (27) tuvo hiperplasia. El antibiótico profiláctico indicado en el 96.7% (80) de los casos fue una cefalosporina de primera generación, administrada en el 15% (12) por vía parenteral preoperatoria. En esta serie de casos, no se documentaron ingresos hospitalarios asociados a infección después del procedimiento. Conclusiones La biopsia de próstata por vía transperineal es una técnica con rendimiento diagnostico similar al del abordaje transrectal: es segura, rápida, de fácil acceso, con bajo costo y, sobre todo, con un riesgo insignificante de infección y sepsis. Sus beneficios son altamente representativos en un sistema de salud como el de nuestro país, y la BTP facilita el acceso de la población vulnerable del área rural y de ciudades intermedias, en las que no se dispone de un urólogo experto.

Objective Prostate biopsy is an essencial aid in cancer diagnosis, and the the most widely-used method is known as transrectal ultrasound-guided (TRUS) biopsy, with a diagnostic rate ranging from 37% to 45%; however, it is not free of complications such as infections, pain, or bleeding. The alternative and safe approach lies in the transpineal biopsy (TPB), commonly performed under regional or general anesthesia. The objetive of the present study was to determine the effectiveness of TPBunder local anesthesia and transrectal ultrasound guidance, with the impact of the sensitiviy of the study and the rate of hospital readmission due to infection. Methods Retrospective cohort study in which 83 patients underwent TPB with local anesthesia and transrectal ultrasound guidance from january 2017 and august 2018 in an intermediate city in Colombia. The sample included all male subjects older than 18 years of age with medical history data available for analysis, as well as the histopathological reports of the biopsies. Cases of rebiopsy or with insufficient data were excluded. The analysis of the nominal data was performed using the chi-squared test, and that of the numerical data, with the Student t or the Mann-Whitney test. Results A total of 83 patientswith an average age was of 65 ± + 7.9 years, had their histopathological studies analyzed. We excluded nine patients who did not have information available in the systematized clinical registry nor in the medical history in physical format. Positivity and a diagnosis of prostate cancer was found in 39.7% (33) of the patients, who were distributed like this: grade group 1 (69.7%; 23); grade group 2 (15.2%; 5); grade groups 3 and 4 (each with 3%; 2); and grade group 5 (9%; 3). In total, 60% (50) were negative for malignancy, and, of these, 54% (27) had glandulostromal hyperplasia. The indicated prophylactic antibiotic in 96.7% (80) of the cases was a first generation cephalosporin and, in 15% (12) of the cases it was administered through a preoperative parenteral route. Hospital admissions after the procedure associated with infection were not documented in the present series of cases. Conclusions Transperineal prostate biopsy is a technique with diagnostic performance similar to that of the transrectal approach: it is safe, fast, easy to access, has a low cost and, above all, presents a minimum risk of infection and sepsis. Its benefits are highly representative in a health system like that of our country, and TPB facilitates the access of the vulnerable population of the rural area and of intermediate cities in which there is no availability of an expert urologist.

Histology and structure of the testicles in three species of Atelopus frogs (Anura: Bufonidae) endemic to the Sierra Nevada de Santa Marta, Colombia / Histología y estructura de los testículos en tres especies de ranas Atelopus (Anura: Bufonidae) endémicas de la Sierra Nevada de Santa Marta, Colombia

Abstract Introduction: Testicular histology constitutes one of the least explored aspects in frogs of the genus Atelopus. This taxonomic group shows an alarming population decline; therefore, its reproductive biology is one of the greatest topics of interest for its conservation. Objective: To describe the testicular morphology and the spermatogenetic lineage cells in adult males of Atelopus laetissimus, Atelopus nahumae, and Atelopus carrikeri in the Sierra Nevada de Santa Marta, Colombia. Methods: During June - July 2017 and 2018, sampling was conducted in the localities of San Lorenzo and Páramo Cebolletas, Sierra Nevada de Santa Marta (SNSM), to collect 15 adult males, 5 per species. Testes samples were fixed in Bouin to be processed by the standard paraffin-embedding technique. Histological sections (3 μm) were stained with Hematoxylin-eosin and Mallory-Heidenhain-Azan-Gomori's. For the description and photographic register of the germ cells, the photonic microscopy technique was used with the differential interference contrast system. Results: The testes are oval organs, compact, light yellow color, and with little vascularization. Externally, they are surrounded by a thin albuginea tunic constituted by regular dense connective tissue. Inside this layer, they are composed of numerous seminiferous tubules of hexagonal contour, in which germ cell cysts are distinguished at different stages of spermatogenesis (spermatogonia I and II, spermatocyte I and II, and early and late spermatids) and spermiogenesis (spermatozoa in fascicles and free spermatozoa). Separating the seminiferous structures is the interstitial tissue in which Leydig cells and blood vessels stand out. Additionally, in the cranial part of the testis, the Bidder's organ was found, formed by two distinguishable regions, the cortex and the medulla. In the cortex, there are previtellogénic oocytes of different sizes surrounded by a monolayer of flat follicular cells. For its part, the medullary region is the connective tissue that nourishes the oocytes and is constituted by blood capillaries. Conclusions: The gonads of the three species analyzed present a cystic cellular organization similar to other anurans, where all stages of spermatogenesis and spermiogenesis were identified, possibly indicating a continuous reproductive activity. Likewise, the Bidder's organ is reported for the first time in the three Atelopus species, which allows suggesting a possible sexual reversion in case of a population decrease of females as a reproductive strategy.

Resumen Introducción: La histología testicular constituye uno de los aspectos menos explorados en las ranas del género Atelopus. Este grupo taxonómico ostenta un declive poblacional alarmarte, es por ello, que su biología reproductiva resulta uno de los temas de mayor interés para su conservación. Objetivo: Describir la morfología testicular y las células del linaje espermatogénico en machos adultos de Atelopus laetissimus, Atelopus nahumae y Atelopus carrikeri en la Sierra Nevada de Santa Marta, Colombia. Métodos: Durante Junio - Julio de 2017 y 2018 se realizaron muestreos en las localidades de San Lorenzo y Páramo Cebolletas, Sierra Nevada de Santa Marta (SNSM), para recolectar 15 machos adultos, 5 por especie. Las muestras de testículo se fijaron en Bouin para ser procesadas mediante la técnica estándar de inclusión en parafina. Las secciones histológicas (3 μm) se tiñeron con Hematoxilina-eosina y Mallory-Heidenhain-Azan-Gomori's. Para la descripción y registro fotográfico de las células germinales, se utilizó la técnica de microscopía fotónica con el sistema de contraste diferencial de interferencia. Resultados: Los testículos son órganos ovalados, compactos, de color amarillo claro y con poca vascularización. Externamente, están rodeados por una delgada túnica albugínea constituida por tejido conectivo denso regular. Al interior de esta capa se componen por numerosos túbulos seminíferos de contorno hexagonal, en los que se distinguen quistes de células germinativas en diferentes etapas de la espermatogénesis (espermatogonia I y II, espermatocito I y II y espermátidas tempranas y tardías) y espermiogénesis (espermatozoides en fascículos y espermatozoides libres). Separando las estructuras seminíferas se halla el tejido intersticial en el que se destacan las células de Leydig y los vasos sanguíneos. Adicionalmente, en la parte craneal del testículo se encontró el órgano de bidder formado por dos regiones diferenciables, la corteza y la medula. En la corteza se aprecian ovocitos previtelogénicos en diferente tamaño rodeados por una monocapa de células foliculares planas. Por su parte, la región medular es el tejido conectivo que nutre los ovocitos y está constituido por capilares sanguíneos. Conclusiones: Las gónadas de las tres especies analizadas presentan una organización celular quística de manera similar con otros anuros, donde se identificó todos los estadios de la espermatogénesis y espermiogénesis indicando posiblemente una actividad reproductiva continua. Así mismo, se reporta por primera vez el órgano de bidder en las tres especies de Atelopus, lo cual permite sugerir una posible reversión sexual en caso de una disminución poblacional de las hembras como una estrategia reproductiva.

Clinical Exome Sequencing Enables Congenital Sialidosis Type II Diagnosis in Two Siblings Presenting with Unreported Clinical Features from a Rare Homozygous Sequence Variant p.(Tyr370Cys) in NEU1.

Sialidosis is a rare autosomal recessive disease that presents with progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by homozygous or compound heterozygous sequence variants in the neuraminidase 1 (NEU1) gene. These sequence variants can lead to sialidosis type I and II; the latter is the most severe and presents prenatally or at early age. However, sialidosis diagnosis is challenging, especially in those health systems with limited resources of developing countries. Consequently, it is necessary to dip into high-throughput molecular diagnostic tools to allow for an accurate diagnosis with better cost-effectiveness and turnaround time. We report a 4-member pedigree segregating an ultrarare missense variant, c.1109A>G; p.Tyr370Cys, in NEU1 as detected by whole-exome sequencing. Two short-lived siblings, who presented with previously unreported clinical features from such a homozygous sequence variant, were diagnosed with sialidosis type II. Additionally, we present a novel molecular model exhibiting the consequences of the variant in the sialidase-1 tridimensional structure. This study allowed us to provide a definitive diagnosis for our patients, increase our understanding of this pathogenic variant, and improve genetic counseling.

Microcephaly, an etiopathogenic vision.

Microcephaly is defined by an occipital-frontal head circumference (OFD) 2 standard deviations (SD) smaller than the average expected for age, gender and population. Its incidence has been reported between 1.3 and 150 cases per 100,000 births. Currently, new clinical characteristics, causes and pathophysiological mechanisms related to microcephaly continue to be identified. Its etiology is varied and heterogeneous, with genetic and non-genetic factors that produce alterations in differentiation, proliferation, migration, repair of damage to deoxyribonucleic acid and neuronal apoptosis. It requires a multidisciplinary diagnostic approach that includes a medical history, detailed prenatal and postnatal clinical evaluation, cerebral magnetic resonance imaging, neuropsychological evaluation, and in some cases complementary tests such as metabolic screening, tests to rule out infectious processes and genetic testing. There is no specific treatment or intervention to increase cerebral growth; however, timely intervention strategies and programs can be established to improve motor and neurocognitive development, as well as to provide genetic counseling. The objective of this work is to review the available information and reinforce the proposal to carry out an etiopathogenic approach for microcephaly diagnosis and management.

Histatin-1 is a novel osteogenic factor that promotes bone cell adhesion, migration, and differentiation.

Histatin-1 is a salivary antimicrobial peptide involved in the maintenance of enamel and oral mucosal homeostasis. Moreover, Histatin-1 has been shown to promote re-epithelialization in soft tissues, by stimulating cell adhesion and migration in oral and dermal keratinocytes, gingival and skin fibroblasts, endothelial cells and corneal epithelial cells. The broad-spectrum activity of Histatin-1 suggests that it behaves as a universal wound healing promoter, although this is far from being clear yet. Here, we report that Histatin-1 is a novel osteogenic factor that promotes bone cell adhesion, migration, and differentiation. Specifically, Histatin-1 promoted cell adhesion, spreading, and migration of SAOS-2 cells and MC3T3-E1 preosteoblasts in vitro, when placed on a fibronectin matrix. Besides, Histatin-1 induced the expression of osteogenic genes, including osteocalcin, osteopontin, and Runx2, and increased both activity and protein levels of alkaline phosphatase. Furthermore, Histatin-1 promoted mineralization in vitro, as it augmented the formation of calcium deposits in both SAOS-2 and MC3T3-E1 cells. Mechanistically, although Histatin-1 failed to activate ERK1/2, FAK, and Akt, which are signaling proteins associated with osteogenic differentiation or cell migration, it triggered nuclear relocalization of ß-catenin. Strikingly, the effects of Histatin-1 were recapitulated in cells that are nonosteogenically committed, since it promoted surface adhesion, migration, and the acquisition of osteogenic markers in primary mesenchymal cells derived from the apical papilla and dental pulp. Collectively, these observations indicate that Histatin-1 is a novel osteogenic factor that promotes bone cell differentiation, surface adhesion and migration, as crucial events required for bone tissue regeneration.

The RabGEF ALS2 is a hypoxia inducible target associated with the acquisition of aggressive traits in tumor cells.

Tumor hypoxia and the hypoxia inducible factor-1, HIF-1, play critical roles in cancer progression and metastasis. We previously showed that hypoxia activates the endosomal GTPase Rab5, leading to tumor cell migration and invasion, and that these events do not involve changes in Rab protein expression, suggesting the participation of intermediate activators. Here, we identified ALS2, a guanine nucleotide exchange factor that is upregulated in cancer, as responsible for increased Rab5-GTP loading, cell migration and metastasis in hypoxia. Specifically, hypoxia augmented ALS2 mRNA and protein levels, and these events involved HIF-1α-dependent transcription, as shown by RNAi, pharmacological inhibition, chromatin immunoprecipitation and bioinformatics analyses, which identified a functional HIF-1α-binding site in the proximal promoter region of ALS2. Moreover, ALS2 and Rab5 activity were elevated both in a model of endogenous HIF-1α stabilization (renal cell carcinoma) and by following expression of stable non-hydroxylatable HIF-1α. Strikingly, ALS2 upregulation in hypoxia was required for Rab5 activation, tumor cell migration and invasion, as well as experimental metastasis in C57BL/6 mice. Finally, immunohistochemical analyses in patient biopsies with renal cell carcinoma showed that elevated HIF-1α correlates with increased ALS2 expression. Hence, this study identifies ALS2 as a novel hypoxia-inducible gene associated with tumor progression and metastasis.

Trasplante de microbiota fecal: una revisión / Fecal Microbial Transplantation: A Review

Resumen La microbiota intestinal sana se define a partir de la presencia de grupos de microorganismos que potencian el metabolismo del huésped. Estos microorganismos le confieren resistencia ante las infecciones, así como ante procesos inflamatorios y frente al desarrollo de neoplasias o autoinmunidad. Además, favorecen las funciones endocrinas y colaboran con la función neurológica a través del eje intestino-cerebro. Por otro lado, el trasplante de microbiota fecal consiste en la introducción de una suspensión de materia fecal de un donante sano en el tracto gastrointestinal de otra persona, que generalmente es un paciente que presenta una patología concreta. Esto se realiza con el fin de manipular la composición de la microbiota del destinatario y contribuir al tratamiento de su problema. El concepto de trasplante de microbiota fecal rompe con la consideración tradicional de las bacterias como elementos dañinos y presta atención a las que, probablemente, son las más subvaloradas de las excretas del cuerpo humano: las heces. En efecto, se ha evidenciado su alta eficacia y el procedimiento es reconocido por el número de pacientes a los que ha ayudado, que se puede ya cifrar en miles. El objetivo de esta revisión de literatura fue describir aspectos básicos para comprender el trasplante de microbiota fecal enfocado al tratamiento de infecciones producidas por Clostridioides difficile.

Abstract Gut microbiota is defined as healthy when there are groups of microorganisms that enhance the host's metabolism, confer resistance to infections, inflammatory processes, the development of malignancies or autoimmunity, promote endocrine functions and support neurological function through the so-called gut-brain axis. Fecal microbial transplantation is the transfer of fecal matter from a healthy donor into the gastrointestinal tract of another person, usually a patient with a specific pathology, to manipulate the composition of the recipient's microbiota and contribute to the treatment of his or her condition. The concept of fecal microbial transplantation breaks with the traditional thought of bacteria as harmful elements and draws attention to what is probably the most undervalued of the human body's excreta: feces. Its high efficiency has been demonstrated and the procedure is recognized by the many patients it has helped, which can already be counted in thousands. The objective of this literature review was to describe the basics of fecal microbial transplantation for the treatment of Clostridioides difficile infections.

Whole-exome sequencing in three children with sporadic Blau syndrome, one of them co-presenting with recurrent polyserositis.

Blau syndrome (BS) is a rare, chronic autoinflammatory disease with onset before age 4 and mainly characterised by granulomatous arthritis, recurrent uveitis, and skin rash. Sporadic (also known as early-onset sarcoidosis) or familial BS is caused by gain-of-function mutations in the NOD2 gene, which encodes for a multi-task protein that plays a crucial role in the innate immune defense. We report on three Mexican patients clinically diagnosed with BS who exhibited a likely pathogenic variant in NOD2 as revealed by whole-exome sequencing (WES) and Sanger sequencing: two variants (c.1000 C > T/p.Arg334Trp and c.1538 T > C/p.Met513Thr) lie in the ATP/Mg2+ binding site, whereas the other (c.3019dupC/p.Leu1007ProfsTer2) introduces a premature stop codon disrupting the last LRR domain (LRR9) formation; all three variants are consistent with gain-of-function changes. Interestingly, all these patients presented concomitant likely pathogenic variants in other inflammatory disease-related genes, i.e. TLR10, PRR12, MEFV and/or SLC22A5. Although the clinical presentation in these patients included the BS diagnostic triad, overall it was rather heterogeneous. It is plausible that this clinical variability depends partly on the patients' genetic background as suggested by our WES results. After this molecular diagnosis and given the absence of NOD2 mutations (demonstrated in two trios) and related symptoms in the respective parents (confirmed in all trios), patients 1 and 2 were considered to have sporadic BS, while patient 3, a sporadic BS-recurrent polyserositis compound phenotype. Altogether, our observations and findings underscore the overlapping among inflammatory diseases and the importance of determining the underlying genetic cause by high-throughput methods. Likewise, this study further reinforces a pathogenic link between the here found NOD2 variants and BS and envisages potential additive effects from other loci in these, and probably other patients.

Revisión: Factores asociados a cáncer colorrectal / Review: Associated factors with colorectal cancer

Resumen Introducción: El cáncer colorrectal (CCR) es la neoplasia de mayor frecuencia en vías digestivas, constituyendo del 9 al 10% de todos los cánceres en el mundo. Se considera que es multicausal, pues abarca factores intrínsecos del huésped como mutaciones genéticas, hormonales y condiciones inmunológicas; además de factores externos como dietas poco saludables, consumo de alcohol, obesidad, sedentarismo, tabaquismo y la exposición ambiental a carcinógenos. Las manifestaciones clínicas son poco específicas, razón por la cual el diagnóstico está enfocado en grupos de riesgo relacionados con la edad e historia familiar demostrada. Objetivo: Identificar los factores genéticos y de estilos de vida predisponentes al desarrollo de CCR. Metodología: Se realizó una búsqueda de la bibliografía respectiva en las bases de datos ScienceDirect, Google académico, Redalyc, Scielo, Proquest publicada durante el período 2004- 2019, mediante las palabras clave: Colorrectal cancer, risk factors, epidemiology, mortality, mutation, incidence. Resultados: Se observaron factores genéticos predisponentes entre un 20% a 25% de las personas con CCR asociados principalmente con la mutación de gen APC. En relación al cáncer esporádico, se identifica hasta en un 80% de los casos, relacionado con el consumo no controlado de alimentos como carnes rojas, embutidos, café, además de hábitos como el consumo de cigarrillo y alcohol conjuntamente con el estrés y comorbilidades como la obesidad y la diabetes. Conclusión: La multicausalidad del CCR está centrada en factores tanto internos como externos siendo de relevancia el seguimiento para personas genéticamente predispuestas y la implementación de estilos de vida saludables que reduzcan la mortalidad por esta causa.

Abstract Introduction: Colorectal cancer (CRC) is the most frequent neoplasm in the digestive tract; it constitutes 9 of 10% of all cancer cases in the world. This type of cancer is considered multicausal since it is associated with intrinsic and extrinsic factors. Among the internal factors, there are genetic, hormonal mutations, and immunological conditions. On the other hand, the external factors are composed of unhealthy diets, alcohol consumption, obesity, sedentary lifestyle, smoking habits, and environmental exposure to carcinogens. The clinical symptoms are not very specific; that is why the diagnosis is focused on risk groups related to age and proven family medical history. Objective: To identify genetic factors and lifestyle factors related to the development of Colorectal cancer (CRC). Methodology: A literature search was carried out in databases such as ScienceDirect, Google Scholar, Redalyc, Scielo, Proquest, in a range of time between 2004 and 2019. The keywords: colorectal cancer, risk factors, epidemiology, mortality, mutation, and incidence were used as helpers for the search. Results: Predisposing genetic factors were observed in about 20% to 25% of people with CRC associated primarily with the APC gene mutation. In terms of sporadic cancer, the results showed that 80% of the cases were related to the uncontrolled consumption of red meat, sausages, and coffee. Additionally, smoking and alcoholic behaviors, stress, and comorbidities, such as obesity and diabetes, were also the cause of the development of this issue. Conclusion: CRC could be caused by internal and external factors. Based on this, the people with a genetic predisposition to this issue should monitor themselves frequently and implement a healthy lifestyle that reduces the probability of suffering from this type of cancer.

Description of a transitions of care and telemedicine simulation lab activity.

BACKGROUND AND PURPOSE: Transitions of Care (ToC) is an important clinical practice area requiring trained health care professionals, but there is limited literature describing ToC in the didactic curriculum. The purpose of this study was to describe and evaluate a ToC telemedicine simulation activity in a doctor of pharmacy curriculum. EDUCATIONAL ACTIVITY AND SETTING: A one-hour lecture and simulation activity was incorporated into a second-year course. Student teams participated in discharge and telemedicine encounters with standardized patients (SPs). Six medication-related problems (MRPs) were incorporated into the activity. Activity documents were collected to identify student competency. FINDINGS: Fifty-nine student pharmacists in 16 teams participated. All teams accurately identified five of the six MRPs. Fourteen teams (87.5%) accurately identified the sixth MRP after completion of the telemedicine encounter. Six teams (62.5%) completed the discharge medication list accurately and completely. All teams provided medication education, and 93.8% (n = 15) of teams identified follow-up was needed. Ten teams utilized effective interview sequence and structure during both encounters. Activity challenges included resources, financial support and SP training. SUMMARY: Case-based learning and the use of simulation has good evidence supporting its use in education. Utilizing these techniques to reinforce concepts may be a beneficial way for students to be trained effectively to deliver impactful ToC services.