Leveraging a Y. lipolytica naringenin chassis for biosynthesis of apigenin and associated glucoside.

Flavonoids are a diverse set of natural products with promising bioactivities including anti-inflammatory, anti-cancer, and neuroprotective properties. Previously, the oleaginous host Yarrowia lipolytica has been engineered to produce high titers of the base flavonoid naringenin. Here, we leverage this host along with a set of E. coli bioconversion strains to produce the flavone apigenin and its glycosylated derivative isovitexin, two potential nutraceutical and pharmaceutical candidates. Through downstream strain selection, co-culture optimization, media composition, and mutant isolation, we were able to produce168 mg/L of apigenin, representing a 46% conversion rate of 2-(R/S)-naringenin to apigenin. This apigenin platform was modularly extended to produce isovitexin by addition of a second bioconversion strain. Together, these results demonstrate the promise of microbial production and modular bioconversion to access diversified flavonoids.

Temporal sorting of microdroplets can identify productivity differences of itaconic acid from libraries of Yarrowia lipolytica.

Microdroplet screening of microorganisms can improve the rate of strain selection and characterization within the canonical design-build-test paradigm. However, a full analysis of the microdroplet environment and how well these conditions translate to culturing conditions and techniques is lacking in the field. Quantification of three different biosensor/analyte combinations at 12 hour timepoints reveals the potential for extended dose-response ranges as compared to traditional in vitro conditions. Using these dynamics, we present an application and analysis of microfluidic droplet screening utilizing whole-cell biosensors, ultimately identifying an altered productivity profile of itaconic acid in a Yarrowia lipolytica-based piggyBac transposon library. Specifically, we demonstrate that the timepoint for microdroplet selection can influence the outcome of the selection and thus shift the identified strain productivity and final titer. In this case, strains selected at earlier timepoints showed increased early productivity in flask scale, with the converse true as well. Differences in response indicate microdroplet assays require tailored development to more accurately sort for phenotypes that are scalable to larger incubation volumes. Likewise, these results further highlight that screening conditions are critical parameters for success in high-throughput applications.

Valorization of Caribbean Sargassum biomass as a source of alginate and sugars for de novo biodiesel production.

Since 2011, a massive influx of pelagic brown algae Sargassum has invaded coastlines causing environmental and economic disaster. Valorizing this plentiful macroalgae can present much needed economic relief to the areas affected. Here the production of biodiesel and a high-value alginate stream using Sargassum biomass collected from the coast of Quintana Roo, Mexico is reported. Biomass was pretreated via AEA (Alginate Extraction Autohydrolysis) and enzymatic saccharification via fungal Solid State Fermentation, releasing 7 g/L total sugars. The sugar mixture was fermented using engineered Yarrowia lipolytica resulting in 0.35 g/L total lipid titer at the lab tube scale. Additionally, the capability of extracting 0.3875 g/g DW of a high-value, purified alginate stream from this material is demonstrated. The findings presented here are promising and suggest an opportunity for the optimization and scale up of a biodiesel production biorefinery for utilization of Sargassum seaweeds during seasons of high invasion.

Cooperation During Orthodontic Treatment of Patients with I Phase and Phase Orthodontic Treatment

ABSTRACT: To evaluate differences in cooperation of adolescent patients in active orthodontic treatment between those who received one phased treatment (no prior interceptive or early treatment) and two phased treatment (prior interceptive or early treatment and subsequent corrective treatment). A prospective cohort study was carried out in 132 patients undergoing orthodontic treatment between 10 and 17 years old at CES University Dental Clinics and in 9 private practices in Medellín Colombia; two groups of 66 patients were defined; one that received two phased treatment and one that received one phased treatment. The Orthodontic Patient Cooperation Scale (OPCS) was applied to all individuals every three months during the first year of treatment in order to assess cooperation. Statistical differences between both groups were assessed using the SSPS® software program. Significantly greater cooperation (M = 4.6) was observed in patients who had received two phased treatment compared with those who were only subjected to one phased treatment (M = 2.3). Patient cooperation during orthodontic treatment does not seem to be affected by two phased treatment and to the contrary seems to have a positive impact when comparing it with individuals with one phased treatment. The most important factors found to influence cooperation were correlated with attitude, interest and commitment to treatment, patient and parental motivation. The OPCS scale proved to be useful for evaluating cooperation and making comparisons with other studies.

RESUMEN: Evaluar las diferencias en la cooperación de los pacientes adolescentes en el tratamiento de ortodoncia activa entre los que recibieron una fase de tratamiento (sin tratamiento interceptivo previo o temprano) y los que recibieron el tratamiento de dos fases (tratamiento interceptivo previo o temprano y tratamiento correctivo posterior). Se realizó un estudio de cohorte prospectivo en 132 pacientes sometidos a tratamiento de ortodoncia entre 10 y 17 años en la clínica odontológica de la Universidad CES y en 9 consultorios privados en Medellín Colombia; se definieron dos grupos de 66 pacientes; uno que recibió dos fases de tratamiento y otro que recibió una fase de tratamiento. La Escala de Cooperación del Paciente de Ortodoncia (OPCS) se aplicó a todas las personas cada tres meses durante el primer año de tratamiento para evaluar la cooperación. Las diferencias estadísticas entre ambos grupos se evaluaron utilizando el programa de software SSPS®. Se observó una cooperación significativamente mayor (M = 4.6) en pacientes que habían recibido tratamiento dos fases en comparación con aquellos que solo fueron sometidos a una fase de tratamiento. (M = 2.3). La cooperación del paciente durante el tratamiento de ortodoncia no parece verse afectada por el tratamiento en dos fases y, por el contrario, parece tener un impacto positivo cuando se compara con individuos con un tratamiento en una fase. Los factores más importantes que influyeron en la cooperación se correlacionaron con la actitud, el interés y el compromiso con el tratamiento, la motivación del paciente y de los padres. La escala OPCS demostró ser útil para evaluar la cooperación y hacer comparaciones con otros estudios.

Progress in the metabolic engineering of bio-based lactams and their ω-amino acids precursors.

Lactams, cyclic carboxamide acids, are important building blocks as monomers for the manufacture of polyamides (nylons), with a market of millions of tons per year. Likewise, their non-natural building blocks, straight chain ω-amino acids, also have a wide range of applications as pharmaceuticals, therapeutic agents, and precursors to other platform chemicals. Current industrial lactam production requires petrochemically-derived routes that involve the use of harsh chemicals and reaction conditions. Microbial production provides a more sustainable method for production, from cost effective renewable resources. This review provides an extensive overview of progress toward the microbial production of lactams, particularly 4C butyrolactam, 5C valerolactam and 6C caprolactam, and their ω-amino acid precursors. Additionally, recent advances in the field as well as proposed microbial production pathways will be discussed, as well as future perspectives for the production of these important bulk chemicals.

Análisis Rasch de la medida de cooperación del paciente ortodóncico en adolescentes de Medellín / Rasch Analysis of Cooperation Measure of the adolescent Orthodontic Patient in Medellin

Resumen Introducción: La cooperación es un elemento relevante para el éxito terapéutico en procesos de ortodoncia. En el caso particular de los adolescentes, conocer su grado de cooperación permite al ortodoncista considerar, en la planeación de la intervención, comportamientos y actitudes que contribuyan a los propósitos del tratamiento. Objetivo: Analizar las evidencias de validez de la medida de cooperación del paciente ortodóncico, propuesta por Slakter, Albino, Fox y Lewis, siguiendo los lineamientos de Wolfe y Smith. Métodos: Estudio de validación anidado en un diseño de cohortes en el cual se siguieron, entre enero del 2014 y noviembre del 2015, 132 adolescentes pacientes activos de tratamiento de ortodoncia correctiva residentes de la ciudad de Medellín. Se estimaron las locaciones y estadísticos de ajuste de los ítems, confiabilidad, unidimensionalidad y funcionamiento diferencial por características clínicas y demográficas de los participantes. Se presenta el mapa de Wright. Resultados: Cuatro ítems fueron eliminados de la escala. A partir de los seis restantes se obtuvo una medida con una confiabilidad de .74 y capacidad para explicar el 74.9% de la varianza. Se identificó funcionamiento diferencial de los ítems según tipo de maloclusión y según antecedente de ortodoncia interceptiva. Conclusión: La validez de la medida se ve afectada por limitaciones en la generalización del constructo según características clínicas relevantes de los adolescentes.

Abstract Introduction: Cooperation is a relevant therapeutic factor in achieving a successful orthodontic treatment result. In the case of adolescents, knowing cooperation level allows the orthodontist to consider behaviors and attitudes that contribute to treatment purposes. Objective: To Analyze the evidence of validity that measures collaboration in the orthodontic patient proposed by Slakter Albino, Fox and Lewis, in accordance with Wolfe and Smith guidelines. Methods: Validation study nested in a cohort study in which 132 adolescent patients under orthodontic treatment in Medellin Colombia were monitored between January 2014 and November 2015. It was estimated the locations and statistics for the adjustment of items, reliability, one-dimensionality and differential functioning by clinical and demographic characteristics of the participants Wright's map is presented. Results: Four items were removed from the scale. From the remaining six, a measure was obtained with a reliability of 0.74 and the capability to explain 74.9% of the variance. Differential Item Functioning was identified by type of malocclusion and by interceptive orthodontic history. Conclusion: The validity of the measure is affected by limitations in the generalization of the construct according to relevant clinical characteristics of adolescents.

Extraccion del primer molar permanente como una alternativa en el tratamiento de ortodoncia / Extractions of first permanent molars as a choice of the orthodontic treatment

La extracción de primeros molares permanentes es una alternativa de tratamiento en algunos casosde ortodoncia como aquellos que presentan apiñamiento moderado, biprotrusión, mordidas abiertas,clase II y III en casos en los cuales es necesario realizar exodoncias y en donde los primeros molaresestán en mal estado por caries extensas u otras alteraciones en su formación, lo que los hace maselegibles para ser extraidos evitando restauraciones extensas futuras o la necesidad de colocar implantespara remplazarlos . Este articulo describe tres casos con diferentes tipos de maloclusiones en los cualeslos primeros molares superiores y/o inferiores fueron elegidos para ser extraídos y así poder obtenerresultados clínicos óptimos tanto faciales como oclusales.

Extraction of First permanent molars is a treatment alternative in patients with moderate crowding, bimaxillaryprotrusion, open bites, class III, Class II, in cases of extensive caries or other developmental problems or to prevent the placement of implants to replace them. This article describes three different clinical cases in which first, upper and lower permanent molars were chosen to be extracted in order toobtain clinical, facial and oclusal good results.

Land- and water-based exercise intervention in women with fibromyalgia: the al-Andalus physical activity randomised controlled trial.

BACKGROUND: The al-Andalus physical activity intervention study is a randomised control trial to investigate the effectiveness of a land- and water-based exercise intervention for reducing the overall impact of fibromyalgia (primary outcome), and for improving tenderness and pain-related measures, body composition, functional capacity, physical activity and sedentary behaviour, fatigue, sleep quality, health-related quality of life, and cognitive function (secondary outcomes) in women with fibromyalgia. METHODS/DESIGN: One hundred eighty women with fibromyalgia (age range: 35-65 years) will be recruited from local associations of fibromyalgia patients in Andalucía (Southern Spain). Patients will be randomly assigned to a usual care (control) group (n = 60), a water-based exercise intervention group (n = 60) or a land-based exercise intervention group (n = 60). Participants in the usual care group will receive general physical activity guidelines and participants allocated in the intervention groups will attend three non-consecutive training sessions (60 min each) per week during 24 weeks. Both exercise interventions will consist of aerobic, muscular strength and flexibility exercises. We will also study the effect of a detraining period (i.e., 12 weeks with no exercise intervention) on the studied variables. DISCUSSION: Our study attempts to reduce the impact of fibromyalgia and improve patients' health status by implementing two types of exercise interventions. Results from this study will help to assess the efficacy of exercise interventions for the treatment of fibromyalgia. If the interventions would be effective, this study will provide low-cost and feasible alternatives for health professionals in the management of fibromyalgia. Results from the al-Andalus physical activity intervention will help to better understand the potential of regular physical activity for improving the well-being of women with fibromyalgia. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01490281.

Distalización de molares maxilares con aparatos intraorales de nueva generación que no necesitan colaboración del paciente / Maxillary molar distalization with new generation intraoral appliances that does not require patient cooperation

Las alternativas de tratamiento de las maloclusiones de clase II esqueléticas y dentales incluyen las extracciones de dientes permanentes y la distalización de los molares maxilares con aparatos extraorales e intraorales. Estos últimos, no necesitan la cooperación del paciente, además, en ellos se han hecho variaciones importantes en su mecánica y diseño a lo largo de los años. Con el uso de los minitornillos se ha podido eliminar, en gran parte, los efectos de reacción como la vestibularización de los incisivos y la mesialización de los premolares. Este artículo sintetiza una revisión de la literatura de los últimos 20 años de los diferentes diseños y sistemas mecánicos que se han usado con éxito en la distalización de los molares maxilares.

The alternatives of treatment of class II skeletal and dental maloclussions included the extractions of permanent teeth and the maxillary molars distalization by extraoral devices and intraoral devices. The above mentioned, does not need cooperation of the patient. In addition, important variations have been mechanics and design throughout the years. With the miniscrews one could have eliminated, largely, the effects of reaction as the vestibularization of the incisor teeth and the mesialization of the bicuspid. This article is a synthesis of a review of the literature of last 20 years of the different designs and mechanical systems that have been used successfully in the distalization of the maxillary molars.

Alternativa de tratamiento para la distalización de molares superiores con una barra traspalatina anclada a un mini-implante / An alternative for the upper molar distalization with a transpalatalbar anchored to mini-implant

La distalización es un tratamiento común en la corrección de las maloclusiones clase II, para lo cualse han diseñado dispositivos dento-soportados como el péndulo, pero con efectos colaterales como la mesialización de premolares y vestibularización de incisivos superiores, actualmente se utilizandiferentes sistemas oseo-soportados eliminando estas reacciones.

Distalization is a common treatment for the correction of class II malocclusion; several tooth supportedappliances such as the pendulum have been designed and used with side effects like mesializationof premolars and labialization of upper incisors; currently different bone supported systems arebeing used in order to eliminate this reaction.

Distalizador oseo-soportado sin minitornillos: c-dfd distalizer / Bone supported distalizer without miniscrews: C-DFD distalizer

La distalización es un tratamiento común en la corrección de las maloclusiones dentales clase II para lo cual se han diseñado aditamentos intraorales, como lo son el péndulo, el Dual Force Distalizer, entre otros. Estos aparatos han sido combinados con mini implantes temporales (TADs) para obtener máximo anclaje y así disminuir los efectos en la mesialización de premolares y vestibularización de incisivos superiores. Una modificación del dual forcé distalizer (DFD), Cortical – Dual Force Distalizer (C-DFD) es descrito en el presente artículo que consiste en la adición de barras puntiagudas en la parte anterior del aparato para evitar la necesidad de TADs como anclaje y eliminar el botón acrílico permiten una mejor higiene oral de la zona. La paciente tratada es una niña de 11 años, en estadio 3 de maduración cervical, con una maloclusión dental Clase ll , apiñamiento severo en el arco superior, canino superior derecho impactado, mordida profunda y un perfil no-favorable para el tratamiento con extracciones de premolares. El paciente recibió un distalizador óseo-soportado (C-DFD), hasta lograr una relación clase I y una resolución del apiñamiento. La aparatología fija fue utilizada para continuar con el tratamiento ortodóntico y el C-DFD se mantuvo pasivo como un aparato de anclaje durante la retracción de canino y premolar. Radiografías Cefálicas laterales y panorámicas fueron tomadas al principio y al final del movimiento para ver los cambios dentales y esqueléticos. La distalización fue lograda en 4.5 meses aproximadamente. Con un promedio de 4 mm por lado, con una resolución espontanea del apiñamiento anterior. No se observó ninguna pérdida de anclaje dental durante el movimiento distal, sugiriendo que esta modificación proporciona un anclaje absoluto.

Distalization is a common treatment in the correction of class II dental malocclusions for which several intraoral non-compliances appliances have been designed, such as the pendulum, Dual Force Distalizer, among others. This appliance has been combined with Mini-screws (TADs) to obtain maximum anchorage to decrease the side effects such as mesialization of premolars and labialization of upper incisors. A modification of the dual force distalizer (DFD), the cortical-DFD (C-DFD distalizer) is described in the present article that consisted in the inclusion of spikes in the anterior part of the appliance to avoid the need of TADs as anchorage and the acrylic button was eliminate for a better hygienic. The treated patient was a girl 11 years old, in stage 3 of the cervical vertebral maturation method, with a class ll dental malocclusion, severe crowding in the upper arch, upper right canine was impacted, deep bite and a non-favorable profile for premolar extraction treatment. The patient received a bone supported distalizer (C-DFD distalizer) until a super class l molar relationship was obtained and the crowding resolved. Fixed appliances was used to continue with the orthodontic treatment and the C-DFD was maintained passive as an anchorage device during the premolar and canine retraction. Lateral head plates and panoramic x-rays were taken at the beginning and at the end of the movement in order to see the dental and skeletal changes. It was found that the time of the distalization treatment was 4.5 months aprox. with an average distalization of 4 mm per side, with an spontaneously resolution of the anterior crowding. No loss of dental anchorage was observed during the distal movement, which shows that this modification provided absolute anchorage.

Relationship between personality traits and cooperation of adolescent orthodontic patients.

OBJECTIVE: To establish the relationship between the personality traits of the adolescent and his or her cooperation with the orthodontic treatment. MATERIALS AND METHODS: From a sample of 70 adolescent orthodontic patients (46 girls and 24 boys) between 12 and 15 years of age (average age, 13.4 +/- 1.1 years), the patients' personality traits were evaluated by using a personality questionnaire (16 Personality Factors-Adolescent Personal Questionnaire) and the degree of patient cooperation was assessed through the cooperation test (Orthodontic Patient Cooperation Scale [OPCS]). The cutting point for the assessment of cooperation on the OPCS questionnaire (noncooperation vs cooperation) was carried out through the receiver operating characteristic (ROC) analysis of curves. A chi2 test with Yates correction (P < or = .05) was applied to evaluate the associations between the degree of cooperation and the scales of personality, gender, or age. RESULTS: The cutting point for cooperation as assessed by the OPCS by means of ROC analysis was 380. No statistically significant relations were found between the degree of cooperation and the scales of personality, gender, or age. CONCLUSIONS: The results of the current study indicate that the personality traits alone of adolescents do not predict cooperation during treatment.