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.

Abstract: Botulism is caused by a potent neurotoxin that blocks neuromuscular transmission, resulting in death by asphyxiation. Currently, the therapeutic options are limited and there is no antidote. Here, we harness the structural and trafficking properties of an atoxic derivative of botulinum neurotoxin (BoNT) to transport a function-blocking single-domain antibody into the neuronal cytosol where it can inhibit BoNT serotype A (BoNT/A1) molecular toxicity. Post-symptomatic treatment relieved toxic signs of botulism and rescued mice, guinea pigs, and nonhuman primates after lethal BoNT/A1 challenge. This platform might enable delivery of antibodies and other protein-based therapeutics to previously inaccessible intraneuronal targets. Resumen: El botulismo es causado por una potente neurotoxina que bloquea la transmisión neuromuscular, provocando la muerte por asfixiamiento. Actualmente, las opciones de tratamiento son limitadas y no existe un antídoto. En este artículo aprovechamos las propiedades estructurales y de tráfico neuronal de un derivado atóxico de la neurotoxina botulínica (BoNT) para transportar un anticuerpo que bloquea la función al citosol neuronal, donde puede inhibir la toxicidad molecular del serotipo A de la BoNT (BoNT /A1). El tratamiento post-sintomático alivió los signos tóxicos del botulismo y rescató de la muerte a ratones, conejillos de indias y primates no humanos después de la exposición letal a BoNT / A1. Esta plataforma podría permitir la administración de anticuerpos y otros terapéuticos basados en proteínas a blancos intraneuronales que previamente eran inaccesibles.

Abstract: Mixed microbial cultures have become a preferred choice of biocatalyst for chain elongation systems due to their ability to convert complex substrates into medium chain carboxylates. However, the complexity of the effects of process parameters on the microbial metabolic networks is a drawback that makes the task of optimizing product selectivity challenging. Here, we studied the effects of small air contaminations on the microbial community dynamics and the product formation in anaerobic bioreactors fed with lactate, acetate and H2/CO2. Two stirred tank reactors and two bubble column reactors were operated with H2/CO2 gas recirculation for 139 and 116 days, respectively, at pH 6.0 and 32°C with a hydraulic retention time of 14 days. One reactor of each type had periods with air contamination (between 97 ± 28 and 474 ± 33 mL O2 L−1 d−1, lasting from 4 to 32 days), while the control reactors were kept anoxic. During air contamination, production of n-caproate and CH4 was strongly inhibited, whereas no clear effect on nbutyrate production was observed. In a period with detectable O2 concentrations that went up to 18%, facultative anaerobes of the genus Rummeliibacillus became predominant and only n-butyrate was produced. However, at low air contamination rates and with O2 below the detection level, Coriobacteriia and Actinobacteria gained a competitive advantage over Clostridia and Methanobacteria, and propionate production rates increased to 0.8–1.8 mmol L−1 d−1 depending on the reactor (control reactors 0.1–0.8 mmol L−1 d−1). Moreover, i-butyrate production was observed, but only when Methanobacteria abundances were low and, consequently, H2 availability was high. After air contamination stopped completely, production of n-caproate and CH4 recovered, with n-caproate production rates of 1.4–1.8 mmol L−1 d−1 (control 0.7–2.1 mmol L−1 d−1). The results underline the importance of keeping strictly anaerobic conditions in fermenters when consistent n-caproate production is the goal. Beyond that, micro-aeration should be further tested as a controllable process parameter to shape the reactor microbiome. When odd-chain carboxylates are desired, further studies can develop strategies for their targeted production by applying micro-aerobic conditions.

Abstract: Objective: To evaluate the effect of post-curing method, printing layer thickness, and water storage on the me chanical properties and degree of conversion of a light-curing methacrylate based resin material (IMPRIMO® LC Splint), used for the fabrication of 3D printed occlusal splints and surgical guides. Methods: 96 bar-shaped specimens were 3D printed (Asiga MAX), half of them with a layer thickness of 100 ? m (Group A), and half with 50 ? m (Group B). Each group was divided in three subgroups based on the post-curing method used: post-curing with light emitting diode (LED) and nitrogen gas; post-curing with only LED; and non- post-curing. Half of the specimens from each subgroup were water-stored for 30 days while the other half was dry-stored (n = 8). Flexural strength and flexural modulus were evaluated. Additional specimens were prepared and divided in the same way for surface hardness (n = 96), fracture toughness, and work of fracture (n = 96). Five specimens were selected from each subgroup for evaluating the degree of conversion (DC). Data were collected and statistically analyzed with 1-way, 2-way ANOVA, and Tukey post-hoc analysis (? = 0.05). Results: The 2-way ANOVA showed that the post-curing method and water storage significantly affected the investigated mechanical properties (P < 0.001). The 1-way ANOVA revealed a statistically significant difference among the tested groups on the investigated properties (P < 0.001). After water storage, the 100 ? m subgroup post-cured with only LED showed higher flexural strength (51 ± 9) than the 50 ? m and 100 ? m subgroups that were post-cured with LED in addition to nitrogen gas atmosphere (38 ± 5, 30 ± 3) (p < 0.05). The 50 ? m subgroup post-cured with only LED showed the highest significant flexural modulus values (1.7 ± 0.08) (p < 0.05). However, the 50 ? m subgroup post-cured with LED plus nitrogen showed significantly higher surface hardness values (p < 0.05) among the investigated groups. The non-post-cured subgroups showed the lowest values, which were significantly different from the other subgroups (p < 0.05). Conclusion: The post-curing method, water storage, and printing layer thickness play a role in the mechanical properties of the investigated 3D Printed occlusal splints material. The combination of heat and light within the post-curing unit can enhance the mechanical properties and degree of conversion of 3D printed occlusal splints. Flexural strength and surface hardness can increase when decreasing printing layer thickness. Resumen: Objetivo: Evaluar el efecto del método de poscurado, el espesor de la capa de impresión y el almacenamiento de agua en el tiempo. Propiedades mecánicas y grado de conversión de un material de resina fotopolimerizable a base de metacrilato (IMPRIMO® LC Splint), utilizado para la fabricación de férulas oclusales y guías quirúrgicas impresas en 3D. Métodos: Se imprimieron en 3D (Asiga MAX) 96 muestras en forma de barra, la mitad de ellas con un espesor de capa de 100 ? m. (Grupo A), y la mitad con 50 ? m (Grupo B). Cada grupo se dividió en tres subgrupos según el poscurado. método utilizado: postcurado con diodo emisor de luz (LED) y gas nitrógeno; postcurado solo con LED; y no- después de curado. La mitad de los especímenes de cada subgrupo se almacenaron en agua durante 30 días mientras que la otra mitad se almacenó en agua. almacenado en seco (n = 8). Se evaluaron la resistencia a la flexión y el módulo de flexión. Se prepararon muestras adicionales. y dividido de la misma manera para dureza de la superficie (n = 96), tenacidad a la fractura y trabajo de fractura (n = 96). Se seleccionaron cinco ejemplares de cada subgrupo para evaluar el grado de conversión (DC). Los datos fueron recopilados y analizados estadísticamente con ANOVA de 1 vía, 2 vías y análisis posthoc de Tukey (? = 0,05).

Abstract: The purpose of this in vitro study was to evaluate the mechanical properties of 3 prepolymerized polymethyl methacrylate (PMMA) resins used in the fabrication of computer- aided design and computer-aided manufacturing (CAD-CAM) milled complete dentures (CDs), as well as 2 denture base polymers used for conventionally fabricated CDs. Material and methods. Three CAD-CAM materials were evaluated: Degos Dental L-Temp, IvoBase CAD, and Zirkonzahn Temp Basic Tissue. Two materials used for conventionally manufactured dentures were also included as controls (Palapress and Paladon 65). Each material type was sectioned into bars for flexural strength, nanohardness, elastic modulus, and surface microhardness evaluation (n=8/material). Half of the specimens were stored in water for 30 days, while the other half was dry-stored. A 2-way ANOVA was conducted to detect the effect of material and storage on the evaluated properties (a =.05). Linear contrasts were conducted to compare the differences among the 3 types of CAD-CAM material and the conventional ones. Results. Material type and storage had a significant influence on the flexural strength, nanohardness, elastic modulus, and surface hardness of the materials investigated (P<.001). The post hoc Scheffé test for flexural strength revealed a nonsignificant difference in the interaction between Degos L-Temp and Paladon (P=1.000). In terms of nanohardness, no difference was found when comparing Palapress with Paladon, as well as IvoBase CAD with Zirkonzahn Temp Basic (P=1.000). A nonsignificant interaction in terms of surface hardness was also found between IvoBase CAD and Palapress (P=.575). Resumen: El propósito de este estudio in vitro fue evaluar las propiedades mecánicas de 3 resinas prepolimerizadas de polimetilmetacrilato (PMMA) utilizadas en la fabricación de computadoras Diseño asistido y fabricación asistida por ordenador (CAD-CAM) de prótesis dentales completas fresadas (CD), así como así como 2 polímeros de base para dentaduras postizas utilizados para los CD fabricados de forma convencional. Material y métodos. Se evaluaron tres materiales CAD-CAM: Degos Dental L-Temp, IvoBase CAD y Zirkonzahn Temp Basic Tissue. Dos materiales utilizados de forma convencional. Las dentaduras postizas fabricadas también se incluyeron como controles (Palapress y Paladon 65). Cada El tipo de material se seccionó en barras para determinar la resistencia a la flexión, la nanodureza, el módulo elástico, y evaluación de microdureza superficial (n=8/material). La mitad de los especímenes fueron almacenados en agua durante 30 días, mientras que la otra mitad se almacenó en seco. Se realizó un ANOVA de 2 vías para detectar el efecto del material y el almacenamiento sobre las propiedades evaluadas (a =.05). Lineal Se realizaron contrastes para comparar las diferencias entre los 3 tipos de CAD-CAM. materiales y los convencionales. Resultados. El tipo de material y el almacenamiento tuvieron una influencia significativa en la resistencia a la flexión, nanodureza, módulo elástico y dureza superficial de los materiales investigados (P<0,001). El La prueba post hoc de Scheffé para la resistencia a la flexión reveló una diferencia no significativa en la interacción entre Degos L-Temp y Paladon (P=1.000). En términos de nanodureza, no se encontraron diferencias. Encontrado al comparar Palapress con Paladon, así como IvoBase CAD con Zirkonzahn Temp Básico (P=1.000). También se encontró una interacción no significativa en términos de dureza superficial. entre IvoBase CAD y Palapress (p=0,575).

Abstract: The research aimed to determine the tensile bond strength (TBS) between polymerized intact and ground fiber-reinforced composite (FRC) surfaces. FRC prepregs (a reinforcing fiber pre-impregnated with a semi-interpenetrating polymer network (semi-IPN) resin system; everStick C&B) were divided into two groups: intact FRCs (with a highly PMMA-enriched surface) and ground FRCs (with a low PMMA gradient). Each FRC group was treated with: StickRESIN and G-Multi PRIMER. These groups were further divided into four subgroups based on the application time of the treatment agents: 0.5, 1, 2, and 5 min. Next, a resin luting cement was applied to the FRC substrates on the top of the photo polymerized treating agent. Thereafter, weight loss, surface microhardness, and TBS were evaluated. Three-factor analysis of variance (p ? 0.05) revealed significant differences in the TBS among the FRC groups. The highest TBS was recorded for the intact FRC surface treated with G-Multi PRIMER for 2 min (13.0 ± 1.2 MPa). The monomers and solvents of G-Multi PRIMER showed a time-dependent relationship between treatment time and TBS. They could diffuse into the FRC surface that has a higher PMMA gradient, further resulting in a high TBS between the FRC and resin luting cement. Resumen: La investigación tuvo como objetivo determinar la resistencia a la tracción (TBS) entre polimerizados Superficies compuestas reforzadas con fibra (FRC) intactas y rectificadas. Prepregs de FRC (una fibra de refuerzo preimpregnado con un sistema de resina de red polimérica semiinterpenetrante (semi-IPN); siempreStick C&B) se dividieron en dos grupos: FRC intactos (con una superficie altamente enriquecida en PMMA) y molidos. FRC (con un gradiente bajo de PMMA). Cada grupo de FRC fue tratado con: StickRESIN y G-Multi CEBADOR. Estos grupos se dividieron en cuatro subgrupos según el tiempo de aplicación del agentes de tratamiento: 0,5, 1, 2 y 5 min. A continuación, se aplicó un cemento de resina a los sustratos de FRC. en la parte superior del agente de tratamiento fotopolimerizado. Posteriormente, pérdida de peso, microdureza superficial, y TBS fueron evaluados. El análisis de varianza de tres factores (p ? 0,05) reveló diferencias significativas en el TBS entre los grupos del FRC. El TBS más alto se registró para la superficie intacta de FRC tratada con G-Multi PRIMER durante 2 min (13,0 ± 1,2 MPa). Los monómeros y disolventes de G-Multi PRIMER mostró una relación dependiente del tiempo entre el tiempo de tratamiento y TBS. Podrían difundirse hacia el Superficie de FRC que tiene un gradiente de PMMA más alto, lo que resulta además en un TBS alto entre el FRC y Cemento de fijación de resina.

Abstract: Statement of problem: The fracture incidence of implant-supported overdentures is more frequent in the area of attachment because of stress concentration and denture deformation in this area. How Eglass fiber reinforcement can address this problem is unclear. Purpose: The purpose of this in vitro study was to evaluate the influence of unidirectional E-glass fiber reinforcement on the mid-line denture base strains of single implant-supported overdentures. Material and methods. An experimental acrylic resin cast was constructed with a single implant placed in the mid-line area and a ball attachment screwed to the implant. Twenty-four experimental overdentures were constructed and divided into 4 groups: group AP fabricated from autopolymerizing acrylic resin without fiber reinforcement, group APF fabricated from autopolymerizing acrylic resin with unidirectional E-glass fiber reinforcement running over the residual ridge and the ball matrix, group HP fabricated from heatpolymerized acrylic resin without fiber reinforcement, and group HPF fabricated from heat-polymerized acrylic resin with unidirectional E-glass fiber reinforcement running over the residual ridge and the ball matrix. A biaxial rosette strain gauge was attached to the incisor areas of each overdenture above the attachment level (Ch1, Ch2) and to a multichannel digital strain meter. A static vertical load of 100 N was applied to the first molar area bilaterally by using a universal testing device during strain measurement procedures. The differences in the mean strain and deflection values among the investigated groups were evaluated for statistical significance using 1-way analysis of variance (ANOVA) with the Tukey post hoc multiple comparison (a =.05). Results. The type of acrylic resin did not have a statistically significant effect on the mean strain values among groups (P=.350), while the reinforcement did significantly affect them (P<.001). The interaction between reinforcement and acrylic resin was not statistically significant (P=.552). Both strain gauge channels in group APF and group HPF recorded significantly lower strain values by almost 50% than those of group AP and group HP (P<.05). Conclusions. Unidirectional E-glass fiber reinforcement placed over the residual ridge and implant attachment significantly reduced denture base strains and deformation of single implantsupported overdentures. Resumen: Declaración del problema. La incidencia de fracturas de las sobredentaduras implantosoportadas es más frecuente en el área de inserción debido a la concentración de tensiones y la deformación de la dentadura postiza en esta área. No está claro cómo el refuerzo de fibra de vidrio E puede abordar este problema. Objetivo. El propósito de este estudio in vitro fue evaluar la influencia de unidireccional Refuerzo de fibra de vidrio E en la línea media de la base de la dentadura postiza de un solo implante. Material y métodos. Se construyó un modelo experimental de resina acrílica con un solo implante. colocado en la zona de la línea media y un accesorio de bola atornillado al implante. Veinticuatro se construyeron sobredentaduras experimentales y se dividieron en 4 grupos: grupo AP fabricado de resina acrílica autopolimerizable sin refuerzo de fibra, grupo APF fabricado con resina acrílica autopolimerizable con refuerzo de fibra de vidrio E unidireccional que recorre el cresta residual y matriz de bolas, grupo HP fabricados con resina acrílica termopolimerizada sin refuerzo de fibra, y grupo HPF fabricado a partir de resina acrílica termopolimerizada con Refuerzo unidireccional de fibra de vidrio E que recorre la cresta residual y la matriz de bolas. Se adjuntó un medidor de tensión de roseta biaxial a las áreas de los incisivos de cada sobredentadura por encima del nivel de conexión (Ch1, Ch2) y a un medidor de tensión digital multicanal.