Neuronal Nsun2 deficiency produces tRNA epitranscriptomic alterations and proteomic shifts impacting synaptic signaling and behavior.

Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease in tRNA m5C levels, resulting in deficits in expression of 70% of tRNAGly isodecoders. Altogether, 1488/5820 proteins changed upon neuronal Nsun2-deficiency, in conjunction with glycine codon-specific defects in translational efficiencies. Loss of Gly-rich proteins critical for glutamatergic neurotransmission was associated with impaired synaptic signaling at PFC pyramidal neurons and defective contextual fear memory. Changes in the neuronal translatome were also associated with a 146% increase in glycine biosynthesis. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC. Furthermore, they link synaptic plasticity and complex behaviors to epitranscriptomic modifications of cognate tRNAs and the proteomic homeostasis associated with specific amino acids.

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico.

BACKGROUND: With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. METHODS: The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. RESULTS: The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. CONCLUSIONS: For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma.

Silvopastoral System Economical and Financial feasibility with Jatropha curcas L. in Manabí, Ecuador / Viabilidad económica y financiera de sistemas silvopastoriles con Jatropha curcas L. en Manabí, Ecuador

ABSTRACT Objective. To assess the economic and financial feasibility of traditional silvopastoral systems for the biofuels production as a contribution to the sustainability of "Piñón for Galapagos" project. Materials and methods. A survey was conducted to 450 small livestock producer in 10 cantons of the Manabí province in order to collect basic agronomic knowledge, management, establishment and costs involved in production of the Piñón ((Jatropha curcas L.)/Savoy (Megathyrsus maximus) silvopastoral systems. For Piñón CP041 production recording plantation in live fence were stablished and for the tradition Piñón, the production of 10 sites were recorded, both systems since 2009. With those data were calculated the following economic indicators: ratio benefit/cost, net present value (NPV), internal rate ratio (IRR) and land expectation value (LEV). Results. The study exhibited a production decrease of Piñón with the passage of time. The CP041 INIAP improved silvopastoral system Piñón showed a B/C 1.07, NPV of USD$ 404.11, LEV US$ 970.23 and IRR of 18%. Followed by silvopastoral system with a local Piñón with a B/C 1.06, NPV of USD$ 363.66, LEV USD$ 873.10 and IRR of 17% and finally silvopastoral system without harvesting Piñón with a B/C 1.05, NPV of USD$ 285.72, LEV USD$ 685.99 and IRR of 15%. Conclusions. The alternative biofuels production was the silvopastoral systems (INIAP CP041)/Savoya in Manabí and is economically feasible. This system does not compete for arable land for food production and would not affect food security.

RESUMEN Objetivo. Evaluar la viabilidad económica y financiera de los sistemas silvopastoriles tradicionales para la producción de Biocombustibles como aporte a la sostenibilidad del proyecto "Piñón para Galápagos". Materiales y Métodos. Se llevaron a cabo encuestas a 450 pequeños productores ganaderos de 10 cantones de la provincia de Manabí con la finalidad de colectar información agronómica, manejo, costos implicados en establecimiento y producción de los sistemas silvopastoriles vigentes de Piñón (Jatropha curcas L.)/Saboya (Megathyrsus maximus). Para recopilar datos de producción del Piñón establecido en cercas vivas de Piñón INIAP CP041 e igualmente se registró la producción de sistemas en 10 sitios, desde el año 2009. Con estos datos se calcularon los siguientes indicadores financieros radio beneficio/costo (B/C), valor actual neto (VAN), tasa interna de retorno (TIR) y valor de expectativa de la tierra (VET). Resultados. El estudio mostró una disminución de la producción del Piñón con el transcurso del tiempo. El sistema silvopastoril mejorado con Piñón INIAP CP041 mostró B/C 1.07, VAN de USD$ 404.11, VET USD$ 970.23 y TIR de 18%. Seguido del sistema silvopastoril con Piñón local con un B/C 1.06, VAN de USD$ 363.66, VET USD$ 873.10 y TIR de 17% y finalmente sistema silvopastoril sin cosecha del Piñón con un B/C 1.05, VAN de USD$ 285.72, VET USD$ 685.99 y TIR de 15%. Conclusiones. La alternativa de producción de biocombustibles con sistemas silvopastoriles Piñón (INIAP CP041)/Saboya en Manabí es el sistema de mayor rentabilidad y no competiría por superficies de cultivo para la producción de alimentos, sin afectar a la seguridad alimentaria.

Análisis de la evidencia disponible para el consumo de edulcorantes no calóricos. Documento de expertos / Analysis of the available evidence for the intake of non-caloric sweeteners. Expert document

Resumen Los edulcorantes no calóricos representan una buena alternativa para sustituir los sabores dulces sin la respuesta fisiológica que genera el consumo de azúcares. Por sí solos no son herramientas para el control de peso. Su consumo debe ir acompañado de una dieta correcta y un estilo de vida saludable que incluya actividad física. Su utilidad radica en proporcionar el agradable sabor dulce sin el aporte energético. La inocuidad de cada uno de los compuestos aprobados está comprobada y se reevalúa constantemente para tomar en cuenta los resultados de nuevos estudios. Debido a que no existe un edulcorante perfecto, la variedad ayuda a que se desarrollen productos cada vez más agradables para el consumidor. Este trabajo es fruto de una revisión exhaustiva de la bibliografía y de las discusiones de un panel de expertos de diversas especialidades: toxicología, ginecoobstetricia, pediatría, endocrinología, nutrición, medicina interna, salud pública y medicina preventiva, en el que se analizó extensamente la bibliografía se revisó una variedad de trabajos científicos que responden a las interrogantes que habitualmente se hacen los profesionales de la salud acerca de seguridad en diferentes grupos etáreos y con afecciones específicas, ingestión diaria admisible, etc.

Abstract Non-caloric sweeteners are a good alternative to replace the sweet flavors without the physiological response generated by the consumption of sugars. Alone they are not tools for weight control. Its intake must be accompanied by a proper diet and a healthy lifestyle that includes physical activity. Its usefulness lies in providing a pleasant sweet taste without the energy intake. The safety of each of the compounds is tested and approved and constantly reassessed to take into account the results of new studies. Since there is no perfect sweetener, variety helps that more and more pleasing to the consumer products are developed. This work is the result of a comprehensive review of the literature and discussions of a panel of experts from various specialties: toxicology, obstetrics and gynecology, pediatrics, endocrinology, nutrition, internal medicine, public health and preventive medicine, where literature was widely analyzed reviewing a variety of scientific papers that address the questions that usually are made by health professionals on safety in different age groups and with specific diseases, acceptable daily intake, etc.

Current Proteomic Methods to Investigate the Dynamics of Histone Turnover in the Central Nervous System.

Characterizing the dynamic behavior of nucleosomes in the central nervous system is vital to our understanding of brain-specific chromatin-templated processes and their roles in transcriptional plasticity. Histone turnover-the complete loss of old, and replacement by new, nucleosomal histones-is one such phenomenon that has recently been shown to be critical for cell-type-specific transcription in brain, synaptic plasticity, and cognition. Such revelations that histones, long believed to static proteins in postmitotic cells, are highly dynamic in neurons were only possible owing to significant advances in analytical chemistry-based techniques, which now provide a platform for investigations of histone dynamics in both healthy and diseased tissues. Here, we discuss both past and present proteomic methods (eg, mass spectrometry, human "bomb pulse labeling") for investigating histone turnover in brain with the hope that such information may stimulate future investigations of both adaptive and aberrant forms of "neuroepigenetic" plasticity.

Seasons and planting densities interaction on forage production of eight hybrids maize, Ecuador / Interacción época/densidad de siembra sobre la producción de ocho híbridos de maíz forrajeros, Ecuador

Objective. To assess the interaction effect of the season and planting densities on the production of eight INIAP corn hybrids. Materials and methods. A research process was conducted in 2013. It was applied a split - split plot design with three replication and Tukey test was used. It was evaluated two planting seasons (28 January and 8 April), they were placed in large plots. Two planting densities (65.500 y 125.000 plants/ha), that were located in the subplots and eight INIAP corn hybrids arranged in the sub- subplots. The evaluated variables were Fresh Matter, Dry Matter, Plant Height and Crude Protein Results. Fresh Matter and Crude Protein productions were influenced by planting seasons. Plant densities affected the production of Fresh Matter, Dry Matter and Plant Height, as well as the interaction season by corn INIAP hybrids. While INIAP corn hybrids showed statistical differences in the production of Fresh, Dry Matter, Plant Height and Crude Protein. The eight INIAP hybrids productions were: Fresh Matter (58.86 ton/ha ±5.19); Dry Matter (21.45 ton/ha ±4.71); Plant Height (2.46 m ±0.16) and Crude Protein (10.6±1.12). Conclusions. The performance showed by hybrids INIAP CML-172, INIAP 6021 and INIAP 551 were very acceptable forage material and could be used for silage purposes.

Objetivo. Evaluar el efecto de la interacción época y densidad de siembra en ocho híbridos de maíz para producción de forraje sobre la obtención de materia fresca MF, seca MS, altura de planta AP y proteína cruda PC. Materiales y métodos. Se empleó un diseño de parcela dos veces dividida con tres repeticiones. Se evaluó el efecto de dos épocas de siembra (28 de enero y el 8 de abril) que se dispusieron en la parcelas grandes, dos densidades de siembra (65.500 y 125.000 plantas/ha) que se ubicaron en las subparcelas y ocho híbridos de maíz INIAP dispuestas en las sub-subparcelas. Las variables evaluadas fueron producción de MF, MS, AP y PC. Resultados. La época de siembra tuvo su influencia sobre la producción de MF y contenido de PC. La densidad de cultivo y época de siembra afectó la producción de MF, MS y AP por híbridos de maíz. Mientras que los híbridos INIAP de maíz mostraron diferencias estadísticas (p<0.001) en la producción de MF, MS, AP y PC. La producción de los ocho híbridos INIAP fue de MF (58.86 Ton/ha ±5.19); MS (21.45 Ton/ha ±4.71); AP (2.46 m±0.16) y PC (10.6±1.12). Conclusiones. Los rendimientos mostrados por los híbridos INIAP CML 172, INIAP 6021 e INIAP 551 son materiales aceptables con relación a las variables evaluadas y pueden ser empleados especialmente para ensilaje.

Treatment considerations in hutchinson-gilford progeria syndrome: a case report.

Hutchinson-Guilford progeria syndrome is an extremely rare condition classified as one of the premature ageing syndromes. This case presents a 16-year-old Israeli female patient, suffering from a variant of Hutchinson-Guilford progeria with a history of treatment with oral biphosphnates. The patient presented with typical cranial and facial features of the syndrome including delayed teeth eruption and root development probably due to insufficient jaw growth and severs retrognatic position of the maxilla and mandible. Orthodontic treatment considerations are described along with those required in light of the previous treatment by oral biphosphonates.All primary teeth were extracted in three appointments while creating as minimal trauma as possible to the surrounding tissue and alveolar bone. For now, the patient refuses to begin the orthodontic treatment course. There are no limitations to conduct any dental procedures in progeria patients, however, extreme caution must be exercised during oral surgery due to the inelasticity of tissues and dermal atrophy. Orthodontic procedure commencement should be early enough to manage the delayed development and eruption of teeth. Patients taking oral biphosphonates should be advised of this potential complication. If orthodontic treatment is considered appropriate, plans should be assessed and modified to include compromises.

Periodontal cytokines profile under orthodontic force and extracorporeal shock wave stimuli in a rat model.

BACKGROUND AND OBJECTIVE: Extracorporeal shock wave therapy has been used in various clinical conditions as a result of its ability to stimulate healing processes in acute and chronic inflammatory states. Orthodontic force application triggers an inflammatory reaction in the periodontal tissue surrounding the involved teeth, resulting in tooth movement. Preliminary work revealed that extracorporeal shock wave therapy increased the expression of the inflammatory cytokines involved. Our aim was to investigate the expression of inflammatory cytokines in the periodontal tissues following orthodontic force induction, with and without shock wave therapy, in experimental rats. MATERIAL AND METHODS: An orthodontic appliance was fabricated and applied between the molars and the incisors of adult Wistar rats. In conjunction with orthodontic force commencement, the rats were treated with a single episode of 1000 shock waves. Every day, during the 3 d of the study, rats were killed and the immunolocalization of RANKL, interleukin (IL)-1ß, IL-6 and tumor necrosis factor-alpha was evaluated. RESULTS: The percentage of the area staining positively for all inflammatory cytokines during the first 2 d decreased statistically significantly more in the shock wave-treated group compared with the nontreated control group. On the first day, the percentage of the area staining positively for IL-1ß and RANKL on the compression side peaked in both groups, with a sequential rise in the number of TRAP-positive cells. CONCLUSION: The induction of shock wave therapy during orthodontic tooth movement influences the expression of different inflammatory cytokines in the tissue and might alter the expected periodontal remodeling rate.

The reverse quad helix expander: easy access for bone graft manipulation in the cleft maxilla.

Cleft-affected patients are characterized by a normal/almost normal posterior maxillary width and a severe anterior constriction of the maxilla in the mixed dentition period. The purposes of this paper were to present: two cases of unilateral cleft-affected patients treated with a reverse quad-helix appliance; and a new method for differential expansion of the premaxillary area of the palatal cleft using a reverse quad-helix expander, thus enabling improved access for the surgeons during secondary bone graft procedures. /// Orthodontic and Craniofacial Department, School of Graduate Dentistry, Rambam Health Care Campus and Bruce Rappaport Faculty of Medicine­Technion, Israel Institute of Technology, Haifa, Israel. aizenbud@ortho.co.il

A Verification Method for MASOES.

MASOES is a 3agent architecture for designing and modeling self-organizing and emergent systems. This architecture describes the elements, relationships, and mechanisms, both at the individual and the collective levels, that favor the analysis of the self-organizing and emergent phenomenon without mathematically modeling the system. In this paper, a method is proposed for verifying MASOES from the point of view of design in order to study the self-organizing and emergent behaviors of the modeled systems. The verification criteria are set according to what is proposed in MASOES for modeling self-organizing and emerging systems and the principles of the wisdom of crowd paradigm and the fuzzy cognitive map (FCM) theory. The verification method for MASOES has been implemented in a tool called FCM Designer and has been tested to model a community of free software developers that works under the bazaar style as well as a Wikipedia community in order to study their behavior and determine their self-organizing and emergent capacities.

3D vector control during alveolar ridge augmentation using distraction osteogenesis and temporary anchorage devices: a new technique.

This report describes a combined orthodontic surgical technique involving vertical alveolar distraction using temporary anchorage devices (TADs) in cases of massive alveolar ridge bone and teeth loss. A combined surgical orthodontic protocol included presurgical orthodontic preparation and a preimplantation surgical augmentation stage for insertion of a vertical distractor. During the active vertical alveolar distraction process TADs were inserted. Intraoral orthodontic elastics were attached to the main orthodontic archwire exerting multidirectional forces to control the vertical distraction vector. After 3 months of vector controlling and active bone moulding, the TADs were removed. Anterior alveolar ridge augmentation using distraction osteogenesis was achieved. The application of TADs for better anterior segment curvature enabled dental implant insertion, better positioning and restoration. A combined surgical orthodontic management protocol involving vertical alveolar distraction osteogenesis for augmentation purposes is an efficient treatment method to improve alveolar ridge volume for the preimplantation stage.

Relationship between inferior alveolar nerve imaging and neurosensory impairment following bilateral sagittal split osteotomy in skeletal Class III cases with mandibular prognathism.

Postoperative inferior alveolar nerve (IAN) neurosensory impairment was prospectively evaluated in 20 consecutive patients with mandibular prognathism who underwent bilateral sagittal split osteotomy. Routine presurgical imaging was obtained for all patients in study and control groups (10 patients each). Cone beam CT of the mandibular ramus and body was performed in 10 randomly selected patients (study group) and the precise location of the IAN was determined preoperatively and intraoperatively. Nerve sensation was evaluated by subjectively monitoring the physical feeling of the lower lip and the chin skin preoperatively and at different times postoperatively. Exact nerve location was successfully determined in all 10 cases in the study group. There were almost no significant differences between patients' sensation scores at the chin skin and lip sites. No significant differences were found between the two sides of the 20 patients. A significant increase in the score trend along the timeframes, in both groups, could be clearly seen together with a statistically significant difference (P≤0.004) between the study and the control groups. In conclusion, precisely locating the IAN using CT is a significant means for efficiently minimizing nerve damage during sagittal split osteotomy.

[Orthodontic tooth movement under extracorporeal shock wave therapy: the characteristics of the inflammatory reaction--a preliminary study].

Extracorporeal generated shock waves were introduced in medical therapy approximately 20 years ago in order to disintegrate kidney stones. Over the last 10 years, extracorporeal generated shock waves have been used to stimulate healing processes. No report to date has examined its influence on different inflammation mediators and growth factors in the periodontium. Orthodontic tooth movement is a model including the induction of an aseptic inflammation and its resolution. We conducted a preliminary study to investigate the periodontium cytokine concentration fluctuations after induction of orthodontic force with and without extracorporeal shock wave therapy (ESWT) in a rat model. An orthodontic appliance was fabricated and applied between the molars and the incisors of rats. The rats were treated by a single episode of 1000 shock waves and gingival crevicular fluid was collected for 3 days. The concentration of typical acute phase cytokines was evaluated by ELISA assay. Of the three tested cytokines, IL-1beta was the only detected cytokine along the study timeframe. IL-1beta concentration rose in both the treated and non treated shockwave groups on the first day, however it was statistically significantly higher in the treated group on day 2. On day 3, IL-1beta concentrations in both groups decreased and reached a lower level in the treated group, revealing a statistically significant difference than its level on the previous day. The application of ESWT during orthodontic force induction enhances IL-1beta production as part of mechanical forces transduction triggering a biologic response, which may contribute to accelerated periodontal remodeling and therefore foreshortening the orthodontic tooth movement period.