Background: Treatment abandonment is a leading cause of treatment failure and poor survival in children with cancer in low- and middle-income countries. It compromises the outcome of 1 in 7 children with cancer globally, it has an estimated prevalence of about 15%. In Mexico, Prior to the creation of medical insurance in 2005, the rate of treatment abandonment was reported as >20% (data from 2000-2004), more recently, the rate of treatment abandonment has been reported at 15.5% (data from 2008 -2017). Methods: Case and control study was performed. We retrospectively reviewed the sociodemographic and clinical data of children with a diagnosis with cancer in the Hospital Civil of Guadalajara- Mexico, between January 2006 and December 2018, this a reference in childhood cancer for western of Mexico. The definition of treatment abandonment followed the International Society of Paediatric Oncology. Results: Data from 1812 patients diagnosed with cancer were analyzed, of which 183 (10%) abandoned treatment. Bivariate logistic regression analysis showed significantly higher abandonment rates in children level of education of the parents; basic education (OR 0.36; p 0.058), Time to travel to hospital > 3 hr. (OR 11.95; p 0.001), single parent (OR 2.50; p 0.003), rural area (OR 0.597; p 0.040), Primary Caregiver Age < 20 years old (OR 4.04; p 0.023). Conclusion: Treatment abandonment prevalence in Hospital Civil of Guadalajara Mexico is high and closely related to socio-demographic factors. This study will create a risk score for the abandonment of treatment in our population, validating it and managing to reduce the percentage of this problem. Resumen. Antecedentes: el abandono del tratamiento es una de las principales causas de fracaso del tratamiento y una pobre supervivencia en niños con cáncer en países de bajos y medianos ingresos. Actualmente 1 de cada 7 niños con cáncer a nivel mundial, tiene una prevalencia estimada de aproximadamente el 15% de abandono. En México, antes de la creación del seguro médico en 2005, la tasa de abandono del tratamiento se informó como> 20% (datos de 2000-2004), más recientemente, la tasa de abandono del tratamiento se reportó en 15.5% (datos de 2008 -2017). Métodos: se realizó un estudio de casos y controles. Revisamos retrospectivamente los datos sociodemográficos y clínicos de niños con diagnóstico de cáncer en el Hospital Civil de Guadalajara- México, entre enero de 2006 y diciembre de 2018, este es un hospital de referencia en cáncer infantil para el oeste de México. La definición de abandono del tratamiento se baso en el de la Sociedad Internacional de Oncología Pediátrica. Resultados: Se analizaron datos de 1812 pacientes diagnosticados con cáncer, de los cuales 183 (10%) abandonaron el tratamiento. El análisis de regresión logística bivariada mostró tasas de abandono significativamente más altas en el nivel de educación de los padres de los niños; educación básica (OR 0.36; p 0.058), Tiempo para viajar al hospital> 3 h (OR 11.95; p 0.001), familia monoparental (OR 2.50; p 0.003), área rural (OR 0.597; p 0.040), Edad del cuidador primario < 20 años (OR 4.04; p 0.023). Conclusión: La prevalencia del abandono del tratamiento en el Hospital Civil de Guadalajara México es alta y está estrechamente relacionada con factores sociodemográficos. Este estudio creará una puntuación de riesgo para el abandono del tratamiento en nuestra población, validándolo y logrando reducir el porcentaje de este problema.

Waterborne diseases are transmitted by the faecal-oral route when water contaminated with faeces is ingested. Cryptosporidiosis is one of these diseases and is caused by one of the most widespread enteric parasites in the world; Cryptosporidium. To reduce the waterborne diseases, domestic wastewater needs to be treated sufficiently to reduce its pathogenic content. One of the recently introduced technologies for wastewater treatment is Aerobic Granular Sludge (AGS). AGS has proven to produce effluents with high chemical quality standards. However, little is known regarding the pathogen removal efficiencies or their removal mechanisms. In addition, there is a worldwide need to treat domestic wastewater appropriately to reduce pathogens causing waterborne diseases. The removal efficiencies and fate of some pathogens, such as Cryptosporidium, have not been studied in detail within wastewater treatment processes. Indicator microorganisms such as Escherichia coli (E. coli), have been used to understand the removal mechanisms and fate of pathogens in wastewater. However, it was found there is a miscorrelation between indicators and pathogens, and therefore there is a need for studies with pathogens themselves. Due to these reasons, this research aimed to develop a fluorescent staining method for E. coli and Cryptosporidium parvum (C. parvum) oocysts to allow their detection in AGS batch reactors, and evaluate the fate of fluorescently stained E. coli and C. parvum in these reactors. Pre-staining of E. coli and C. parvum was carried out using two fluorescent stains: dsGreen and SYBR. Experiments were carried out to test different pre-staining conditions. The stains were serial diluted, TWEEN was used to determine if it improved the staining, and the prestained microorganisms were incubated at 4 ºC, room temperature and 37 ºC. Two different batch reactors, 250 mL and 2 mL, were set up with AGS and were spiked with pre-stained microorganisms. Both reactors were run for 120 mins and sludge samples were collected and analysed using fluorescent microscopy. The filtered supernatant samples from the 250 mL were also analysed using the fluorescent microscope and the fluorescent cell count method. The best staining conditions for E. coli and C. parvum oocysts with dsGreen proved to be: 1,000x dilution of dye, incubation of stained microorganisms at room temperature for 15 mins and no need of TWEEN. SYBR photobleached rapidly and was therefore not an appropriate stain for this research. With the experiments in batch reactors, the fluorescent cell count method proved to be a generic and faster quantitative alternative to estimate E. coli concentrations in filtered supernatant samples than the E. coli agar plate method. In addition, it was qualitatively confirmed that fluorescently stained E. coli was removed by the predation of different species of protozoa. However, no conclusive results regarding protozoan predation of C. parvum oocysts were observed. Resumen: Las enfermedades transmitidas por el agua se transmiten por la ruta fecal-oral cuando se ingiere agua contaminada con heces. La criptosporidiosis es una de estas enfermedades y es causada por uno de los parásitos entéricos más extendidos del mundo; Cryptosporidium. Para reducir las enfermedades transmitidas por el agua, las aguas residuales domésticas deben tratarse lo suficiente como para reducir su contenido patógeno. Una de las tecnologías recientemente introducidas para el tratamiento de aguas residuales es el lodo granular aeróbico (AGS por sus siglas en inglés). AGS ha demostrado producir efluentes con altos estándares de calidad química. Sin embargo, se sabe poco sobre las eficiencias de eliminación de patógenos o sus mecanismos de eliminación. Además, existe una necesidad mundial de tratar las aguas residuales domésticas de manera adecuada para reducir los patógenos que causan enfermedades transmitidas por el agua. Las eficiencias de eliminación y el destino de algunos patógenos, como el Cryptosporidium, no se han estudiado en detalle en los procesos de tratamiento de aguas residuales. Se han utilizado microorganismos indicadores como Escherichia coli (E. coli) para comprender los mecanismos de eliminación y el destino de los patógenos en las aguas residuales. Sin embargo, se descubrió que existe una mala correlación entre los indicadores y los agentes patógenos y, por lo tanto, es necesario realizar estudios con los mismos agentes patógenos. Debido a estas razones, esta investigación tuvo como objetivo desarrollar un método de tinción fluorescente para E. coli y ooquistes de Cryptosporidium parvum (C. parvum) para permitir su detección en reactores discontinuos de AGS, y evaluar el destino de E. coli y C. parvum teñidos con fluorescencia en estos reactores. La tinción previa de E. coli y C. parvum se llevó a cabo utilizando dos tinciones fluorescentes: dsGreen y SYBR. Se llevaron a cabo experimentos para probar diferentes condiciones de pre-tinción. Las tintas se diluyeron en serie, se utilizó TWEEN para determinar si mejoraba la tinción, y los microorganismos pre-teñidos se incubaron a 4 ºC, temperatura ambiente y 37 ºC. Se prepararon dos reactores discontinuos diferentes, 250 ml y 2 ml, con AGS y se añadieron microorganismos previamente teñidos. Ambos reactores funcionaron durante 120 minutos y las muestras de lodo se recogieron y analizaron usando microscopía fluorescente. Las muestras de sobrenadante filtradas de 250 ml también se analizaron utilizando el microscopio fluorescente y el método de recuento de células fluorescentes. Las mejores condiciones de tinción para la E. coli y los ooquistes de C. parvum con dsGreen demostraron ser: dilución de colorante a 1,000x, incubación de microorganismos teñidos a temperatura ambiente durante 15 minutos y sin necesidad de TWEEN. SYBR se blanqueó rápidamente y, por lo tanto, no fue una tinta adecuada para esta investigación. Con los experimentos en reactores discontinuos, el método de recuento de células fluorescentes demostró ser una alternativa cuantitativa genérica y más rápida para estimar las concentraciones de E. coli en muestras de sobrenadante filtradas que el método de la placa de agar de E. coli. Además, se confirmó cualitativamente que E. coli teñida con fluorescencia se removió por la predación de diferentes especies de protozoos. Sin embargo, no se observaron resultados concluyentes con respecto a la predación de protozoos de los ooquistes de C. parvum.

El síndrome de Treacher Collins o disostosis mandibulofacial, es un desorden congénito craneofacial poco frecuente y se caracteriza por tener malformaciones en cabeza y cuello. Presentan vía aérea difícil predicha, alta incidencia de síndrome de apnea obstructiva del sueño; así como; pueden debutar con edema faríngeo y laríngeo transoperatorio, ocasionando distrés respiratorio y muerte súbita. La planificación de la vía aérea en estos pacientes es muy importante para el abordaje de la vía aérea por el anestesiólogo. Objetivo general: Determinar la frecuencia y manejo de la vía aérea difícil en los pacientes con síndrome de Treacher Collins intervenidos en el Hospital Dr. Manuel Gea González entre 1998 al 2018. Material y métodos: Se llevó a cabo un estudio observacional descriptivo, transversal y retrolectivo. El tamaño de la muestra fue de 134 eventos anestésicos con una población de 25 pacientes con síndrome de Treacher Collins que fueron atendidos entre 1998 al 2018 en el Hospital General “Dr. Manuel Gea González”. Resultados: De un total de 41 pacientes con síndrome de Treacher Collins atendidos en el hospital, sólo 25 requirieron de alguna intervención con manejo anestésico. En esta población se contabilizó un total de 134 eventos anestésicos, principalmente cirugías reconstructivas craneofaciales. Dentro de las características de la población el 52% fueron hombres; la media del número de cirugías por paciente fue de 5.36. La media de edad en la que fueron intervenidos fue de 12.36 años. La frecuencia de vía aérea difícil fue de 93.3% (125/134). La laringoscopia directa fue la principal técnica definitiva de abordaje de la vía aérea 42.5%, seguido del fibroscopio 35.1%, mascarilla laríngea 4.5%, tubo laríngeo 0.7% y traqueostomía 0.7%. La escala de Cormack-Lehane se reportó en el 34.3% de los eventos anestésicos, predominando el grado 4 (19.4%). Se realizó intubación exitosa en el 87.3% de los casos y los principales eventos adversos fueron sangrado de la vía aérea, edema de glotis y laringoespasmo. Se cancelaron 5 cirugías relacionado al manejo de la vía aérea, ningún paciente falleció y el uso del fibroscopio se asoció a menores complicaciones. Conclusiones: En esta población de estudio donde se realizaron 134 eventos anestésicos, en 125 se presentó vía área difícil, lo que corresponde a un 93.3%, así mismo un 59.5% (80/134) fue intubación difícil. Sin embargo, en el 87.3%, se logró una intubación exitosa (117/134). En relación a eventos adversos el más frecuente fue el sangrado con un 20.1% (27/134). De los 47 pacientes intubados con fibroscopio en 25 se resolvió con el plan A y al primer intento. Con base a esta información, observamos que en estos pacientes hay una alta frecuencia de vía aérea difícil, por lo que se tiene que tener presente que la preparación anticipada es esencial para ser abordados, contemplando dispositivos avanzados de vía aérea y personal experto en el manejo de esta situación. A mayor número de laringoscopias y utilización de diferentes aditamentos, aumenta el riesgo de eventos adversos. El fibroscopio según nuestros hallazgos es una opción ideal como plan A en el aseguramiento de la vía aérea de estos pacientes. Nuestra serie de casos es la más grande actualmente en México y Latinoamérica y es un preámbulo para realización de guías de vía aérea difícil en los pacientes con Síndrome de Treacher Collins en el futuro.

Insulin hormone is produced by pancreatic beta-cells and its biosynthesis, secretion, and intracellular degradation is tightly regulated. Newly formed SGs are preferentially released upon glucose stimulation while aged SGs are less competitive to be released and are more prompt to degradation mainly within lysosomes. The most assumed mechanism leading aged SGs to lysosome is autophagy, a degradation system for altered proteins and damaged organelles. The autophagic marker LC3 has facilitated the detection of autophagy through LC3-based biochemical and microscopic assays, as well as the possibility to experimentally manipulate the autophagy pathway. Here, we intended to establish a model for the further study of mechanism that target aged Ins-SNAPTMR-Star+ SGs to GFP-LC3+ autophagosomes in INS-1 cells by using three different approaches. Our results show that in INS-1 cells, modulation of autophagy with chemical agents can be detected by western blot. Likewise, TIRF Microscopy allowed for the detection of positive GFP-LC3+ aged Ins-SNAPTMR-Star+ objects in the cortical region of INS-1 cells. Additionally, we implemented SIM microscopy to gain more detail in the morphological aspect of autophagosomes vesicles. Despite some hints about the autophagosomal structures were uncovered through these approaches, further experiments should be performed to complement and confirm our findings. Thus, establishment of a suitable model for the study of autophagy, will allow us to further study the mechanisms behind the targeting process of aged SGs and to better understand how impairment of autophagy contributes to deterioration of pancreatic beta-cell function and subsequent onset of type 2 diabetes.

Abstract: Background: Seasonal Influenza is considered to be a cyclic and ordered sequence of values, influenced by external factors that can be predicted and used to detect disease outbreaks and monitoring. In machine learning, the key challenges that limit these analyses are in model explainability and limitations associated with ecological bias. Aim: Determine the best environmental variable selection method to predict Seasonal Influenza in Norway, using an environmental medicine approach combined with machine learning techniques. Methods: This is a quasi-experimental study that compares three approaches (non-variable selection, isolate component, and multipollutant mixture), represented in five methods (univariable, bivariable, multivariable AME, multivariable PCA, multivariable LDA). Per method, the best co-variable combination will be performed, following the internal rules of each method. The best covariable combination is the result of three components: variable selection, validation data set and lag. The first one involves 13 environmental variables (temperature, relative humidity, specific humidity, air pressure, wind speed, precipitation, CO, NO, NO2, O3, PM10, PM2,5 and SO2); second one compares a test dataset compiled from the data from 2019, last year (2018) and a synthetic environmental (avg. 2013-2018) data set in the validation process; and the third one compares a combination of lag from 0 to 12. All the predictions are made using ARIMA algorithm. The evaluation is given in terms of MAE, MSE, RMSE, OR. The training set is from 2 Jun 2013 (week 22/2013) to 28 May 2018 (week 21/2018), and test set is from (week 22/2018) to (week 21/2019) with a window of predictions of 52 weeks. Results: The increment of dimensionality in the environmental variable selection introduce different noise levels and optimize the prediction. Considerations that impact the explainability, usability, ecological bias and performance will be described. Conclusion: The increment of dimensionality in the variable selection has a better impact on performance than using complex algorithms.

Abstract: Objective: To analyze the population prevalence and birth prevalence of oral clefts in Colombia from 2009 to 2017. Methods: A cross-sectional study using information from the National Administrative Records of Colombia. The data came from 2 types of administrative records (Surveillance System and the Individual Registry of Service Provision) and the oral health national survey. Population prevalence and birth prevalence by type of cleft lip and/or cleft (CL/P) ratios were calculated using Poisson distribution for count data and to assess stationary tests on time series (Dickey-Fuller) and (Phillips-Perron) was used. Results: Population prevalence in Colombia was 3.27 per 10 000 inhabitants (95% confidence interval [CI], 3.21-3.32) and birth prevalence was 6.0 per 10 000 live births (95% CI, 5.67-6.35). Bogot´a have the highest population prevalence with CL/P. In the analysis of trends for the prevalence proportion by type of clefts in newborn babies with cleft, it was observed that the highest proportion was for babies with CLP. Cleft lip (CL) has increased from 17.4% in 2014 to 34.2% in 2017, cleft palate (CP) has decreased from 32.9% to 20.2%; and CLP changed from 49.6% to 45.5% in the same period. Conclusions: The population prevalence was 3.27 per 10 000 inhabitants. Births prevalence was 6.0 per 10 000 live births, and Orinoquia and Amazonia have higher rates than the national average. The administrative registers are adequate systems to know the behavior of oral clefts. The CL/P had a nonstationary trend during the period 2014 to 2017.

Abstract: Objective: Determine the population prevalence and trends of cleft lip and / or palate (CL/P) by department for Colombia in the period 2009 - 2015. Methods: Prevalence study based on Individual Registry of Health Services in general population from 2009 to 2015. All people diagnosed with CL/P were included for all ages, type of diagnosis and any type of health services in the mentioned period. The prevalence rate was calculated by period and point for each year, for each department and according to the type of cleft. Stationarity on time series was evaluated using (Dickey-Fuller) and (Phillips-Perron), the trends and prevalence ratios were calculated using Poisson regression. Results: 15,225 people with CL/P were identified, where 53.3% were men. The national period prevalence of CL/P is 3.37 per 10 000 (IC95%: 3.3-3.4) with upward trend (PR = 1.34 95% CI: 1.0 - 1.8 p = 0.05) and non-stationary behavior. The national period prevalence of CL is 0.93 per 10 000, CP 1.17 per 10 000 and CLP 1.26 per 10 000, where CLP is sub classify into CLPu (0.83 per 10 000), and CLPb (0.43 per 10 000). At the departmental level, the highest CL/P prevalence is Guaviare (11.2 95% CI: 8.6 – 14.2), followed by Guainía (8.4 95% CI:5.4 – 12.2) and the lowest Quindío (0.49 95% CI: 0.3 – 0.7) Conclusions: In Colombia, the national period prevalence of CL/P is 3.37 per 10 000 with upward trend at national level indicates an increase on prevalence from 2009 to 2015.

Abstract: Seasonal influenza is an infectious disease of multi-causal etiology and a major cause of mortality worldwide that has been associated with environmental factors. In the attempt to model and predict future outbreaks of seasonal influenza with multiple environmental factors, we face the challenge of increased dimensionality that makes the models more complex and unstable. In this paper, we propose a nowcasting and forecasting framework that compares the theoretical approaches of Single Environmental Factor and Multiple Environmental Factors. We introduce seven solutions to minimize the weaknesses associated with the increased dimensionality when predicting seasonal influenza activity levels using multiple environmental factors as external proxies. Our work provides evidence that using dimensionality reduction techniques as a strategy to combine multiple datasets improves seasonal influenza forecasting without the penalization of increased dimensionality.

Abstract: Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or Xlinked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.

Abstract: The disorders caused by mutations in genes encoding subunits and accessory proteins of cohesin complex are collectively termed as cohesinopathies. The best known cohesinopathy is Cornelia de Lange Syndrome (CdLS), which is a multisystem developmental disorder characterized by facial dysmorphism, limb malformations, growth and cognitive impairment. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), are responsible for ∼70% of CdLS cases. We describe a 16-year-old boy with facial dysmorphism, growth retardation, intellectual disability, hirsutism and small hands, who has a small Supernumerary Marker Chromosome (sSMC) present in mosaic form. sSMC is composed of two duplicated segments encompassing 17 genes including SMC1A gene, at the regions Xp11.22 and Xp11.21q11.1. Clinical comparison between our patient with a previously reported individual with a SMC1A duplication and four male carriers of similar sSMC reported in databases, suggest that they all share clinical features related to cohesinopathies. Although our patient does not have the classical CdLS craniofacial phenotype, he has pre and postnatal growth retardation, intellectual disability and mild musculoskeletal anomalies, features commonly seen in patients with cohesinopathies.