Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma.

Metabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the von Hippel Lindau (VHL) gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner. Importantly, the concurrent inhibition of MYC signaling and glutamine metabolism prevented LD accumulation and reduced tumor burden in vivo. Furthermore, we identified the hypoxia-inducible lipid droplet-associated protein (HILPDA) as the key driver for induction of MYC-driven LD accumulation and demonstrated that conversely, proliferation, LD formation, and tumor growth are impaired upon its downregulation. Finally, analysis of ccRCC tissue as well as healthy renal control samples postulated HILPDA as a specific ccRCC biomarker. Together, these results provide an attractive approach for development of alternative therapeutic interventions for the treatment of this type of renal cancer.

Targeting mitochondrial metabolism for precision medicine in cancer.

During decades, the research field of cancer metabolism was based on the Warburg effect, described almost one century ago. Lately, the key role of mitochondria in cancer development has been demonstrated. Many mitochondrial pathways including oxidative phosphorylation, fatty acid, glutamine, and one carbon metabolism are altered in tumors, due to mutations in oncogenes and tumor suppressor genes, as well as in metabolic enzymes. This results in metabolic reprogramming that sustains rapid cell proliferation and can lead to an increase in reactive oxygen species used by cancer cells to maintain pro-tumorigenic signaling pathways while avoiding cellular death. The knowledge acquired on the importance of mitochondrial cancer metabolism is now being translated into clinical practice. Detailed genomic, transcriptomic, and metabolomic analysis of tumors are necessary to develop more precise treatments. The successful use of drugs targeting metabolic mitochondrial enzymes has highlighted the potential for their use in precision medicine and many therapeutic candidates are in clinical trials. However, development of efficient personalized drugs has proved challenging and the combination with other strategies such as chemocytotoxic drugs, immunotherapy, and ketogenic or calorie restriction diets is likely necessary to boost their potential. In this review, we summarize the main mitochondrial features, metabolic pathways, and their alterations in different cancer types. We also present an overview of current inhibitors, highlight enzymes that are attractive targets, and discuss challenges with translation of these approaches into clinical practice. The role of mitochondria in cancer is indisputable and presents several attractive targets for both tailored and personalized cancer therapy.

Expression and activation of nuclear hormone receptors result in neuronal differentiation and favorable prognosis in neuroblastoma.

BACKGROUND: Neuroblastoma (NB), a childhood tumor derived from the sympathetic nervous system, presents with heterogeneous clinical behavior. While some tumors regress spontaneously without medical intervention, others are resistant to therapy, associated with an aggressive phenotype. MYCN-amplification, frequently occurring in high-risk NB, is correlated with an undifferentiated phenotype and poor prognosis. Differentiation induction has been proposed as a therapeutic approach for high-risk NB. We have previously shown that MYCN maintains an undifferentiated state via regulation of the miR-17 ~ 92 microRNA cluster, repressing the nuclear hormone receptors (NHRs) estrogen receptor alpha (ERα) and the glucocorticoid receptor (GR). METHODS: Cell viability was determined by WST-1. Expression of differentiation markers was analyzed by Western blot, RT-qPCR, and immunofluorescence analysis. Metabolic phenotypes were studied using Agilent Extracellular Flux Analyzer, and accumulation of lipid droplets by Nile Red staining. Expression of angiogenesis, proliferation, and neuronal differentiation markers, and tumor sections were assessed by immunohistochemistry. Gene expression from NB patient as well as adrenal gland cohorts were analyzed using GraphPad Prism software (v.8) and GSEA (v4.0.3), while pseudo-time progression on post-natal adrenal gland cells from single-nuclei transcriptome data was computed using scVelo. RESULTS: Here, we show that simultaneous activation of GR and ERα potentiated induction of neuronal differentiation, reduced NB cell viability in vitro, and decreased tumor burden in vivo. This was accompanied by a metabolic reprogramming manifested by changes in the glycolytic and mitochondrial functions and in lipid droplet accumulation. Activation of the retinoic acid receptor alpha (RARα) with all-trans retinoic acid (ATRA) further enhanced the differentiated phenotype as well as the metabolic switch. Single-cell nuclei transcriptome analysis of human adrenal glands indicated a sequential expression of ERα, GR, and RARα during development from progenitor to differentiated chromaffin cells. Further, in silico analysis revealed that patients with higher combined expression of GR, ERα, and RARα mRNA levels had elevated expression of neuronal differentiation markers and a favorable outcome. CONCLUSION: Together, our findings suggest that combination therapy involving activation of several NHRs could be a promising pharmacological approach for differentiation treatment of NB patients.

The role of pre-treatment paraaortic surgical staging for cervical cancer in the EMBRACE criteria.

Background: The State-of-the-Art Treatment for Locally Advanced Cervical Cancer (LACC) is Definite Radio-Chemotherapy based on the Image-guided intensity modulated External beam radiochemotherapy and MRI-based adaptive BRAchytherapy (EMBRACE) trial, according to the FIGO staging. This staging is based on clinical examination and imaging studies; however, there are limitations of imaging techniques which may result in adverse events or death due to insufficient or overtreatment. The aim of the study was to evaluate the feasibility and outcomes of surgical staging in LACC prior to radiotherapy (RT) to personalise target volumes for radiotherapy. Methods: From 2008 to 2018, 138 patients with FIGO 2018 stages IB3-IIIC2 cervical cancer underwent a pretherapeutic laparoscopic staging procedure. The pathological diagnosis was compared with the results of preoperative CT scan. Patients were treated with chemoradiotherapy tailored according to the staging results. Results: The mean patient age was 43 years, the mean body mass index was 27 kg/m2; most lesions were squamous cervical cancer (92%). Staging CT scan had a 77% concordance with the histological findings. Sensitivity was 29%, specificity 85%, positive predictive value 21% and negative predictive value 89%. Surgical staging led to change of stage in 24% of cases. Para -aortic dissection led to change the initially planned radiotherapy fields in 47% of the cases. Major complications included involuntary section of the inferior mesenteric artery (IMA) without clinical repercussion, an infected retroperitoneal haematoma and a symptomatic lymphocele requiring laparoscopic drainage. Conclusion: Laparoscopic staging before primary chemoradiation in patients with LACC was feasible, safe and reproducible, allowing reduction of the radiotherapy treatment volumes of patients.

Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma.

Many metabolic pathways, including lipid metabolism, are rewired in tumors to support energy and biomass production and to allow adaptation to stressful environments. Neuroblastoma is the second deadliest solid tumor in children. Genetic aberrations, as the amplification of the MYCN-oncogene, correlate strongly with disease progression. Yet, there are only a few molecular targets successfully exploited in the clinic. Here we show that inhibition of fatty acid synthesis led to increased neural differentiation and reduced tumor burden in neuroblastoma xenograft experiments independently of MYCN-status. This was accompanied by reduced levels of the MYCN or c-MYC oncoproteins and activation of ERK signaling. Importantly, the expression levels of genes involved in de novo fatty acid synthesis showed prognostic value for neuroblastoma patients. Our findings demonstrate that inhibition of de novo fatty acid synthesis is a promising pharmacological intervention strategy for the treatment of neuroblastoma independently of MYCN-status.

Does the Use of Social Media Tools in Classrooms Increase Student Commitment to Corporate Social Responsibility?

There is an increasing demand for ethical and Corporate Social Responsibility (CSR) practices by companies. This competence has to be introduced in students' training in business degree programs, and a check must then be done to determine if the students have come to appreciate the importance of CSR commitments. Using the framework of Stakeholders Theory, this work aims to examine students' perceptions of ethical and CSR practices and commitment to different stakeholders, as well as the factors that lead students to act in a socially responsible way. Furthermore, we hope to identify how the perception of CSR can be improved when Web 2.0 and social media tools that have proven effective in transmitting emotions and values are used in classrooms to teach these ideas. To this end, a survey was carried out in the year 2019 with 1,030 first-year students; it was administered at the beginning of the semester and also at the end of the semester after the training activities had been carried out. The main finding of the research is that students start with the belief that ethics and CSR are developed for reasons of image and legitimacy; however, after receiving training on these topics through tools that take into account emotions and values, they start to value the importance of the company as an agent of social change. The main practical and managerial implication is that methods based on Web 2.0 and social media tools are useful to teach ethics and CSR; the theoretical contribution is that students take into account the welfare of others. This finding contributes to Stakeholder Theory in a higher education context.

MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma.

In pediatric neuroblastoma, MYCN-amplification correlates to poor clinical outcome and new treatment options are needed for these patients. Identifying the metabolic adaptations crucial for tumor progression may be a promising strategy to discover novel therapeutic targets. Here, we have combined proteomics, gene expression profiling, functional analysis, and metabolic tracing to decipher the impact of MYCN on neuroblastoma cell metabolism. We found that high MYCN levels are correlated with altered expression of proteins involved in multiple metabolic processes, including enhanced glycolysis and increased oxidative phosphorylation. Unexpectedly, we discovered that MYCN-amplified cells showed de novo glutamine synthesis. Furthermore, inhibition of ß-oxidation reduced the viability of MYCN-amplified cells in vitro and decreased tumor burden in vivo, while not affecting non-MYCN-amplified tumors. Our data provide information on metabolic processes in MYCN expressing tumors, which could be exploited for the development of novel targeted therapies.

Time Series Genome-Centric Analysis Unveils Bacterial Response to Operational Disturbance in Activated Sludge.

Understanding ecosystem response to disturbances and identifying the most critical traits for the maintenance of ecosystem functioning are important goals for microbial community ecology. In this study, we used 16S rRNA amplicon sequencing and metagenomics to investigate the assembly of bacterial populations in a full-scale municipal activated sludge wastewater treatment plant over a period of 3 years, including a 9-month period of disturbance characterized by short-term plant shutdowns. Following the reconstruction of 173 metagenome-assembled genomes, we assessed the functional potential, the number of rRNA gene operons, and the in situ growth rate of microorganisms present throughout the time series. Operational disturbances caused a significant decrease in bacteria with a single copy of the rRNA (rrn) operon. Despite moderate differences in resource availability, replication rates were distributed uniformly throughout time, with no differences between disturbed and stable periods. We suggest that the length of the growth lag phase, rather than the growth rate, is the primary driver of selection under disturbed conditions. Thus, the system could maintain its function in the face of disturbance by recruiting bacteria with the capacity to rapidly resume growth under unsteady operating conditions.IMPORTANCE Disturbance is a key determinant of community assembly and dynamics in natural and engineered ecosystems. Microbiome response to disturbance is thought to be influenced by bacterial growth traits and life history strategies. In this time series observational study, the response to disturbance of microbial communities in a full-scale activated sludge wastewater treatment plant was assessed by computing specific cellular traits of genomes retrieved from metagenomes. It was found that the genomes observed in disturbed periods have more copies of the rRNA operon than genomes observed in stable periods, whereas the in situ mean relative growth rates of bacteria present during stable and disturbed periods were indistinguishable. From these intriguing observations, we infer that the length of the lag phase might be a growth trait that affects the microbial response to disturbance. Further exploration of this hypothesis could contribute to better understanding of the adaptive response of microbiomes to unsteady environmental conditions.

Una mirada a las raíces, evolución y desarrollo de la Facultad de Cultura Física «Nancy Uranga Romagoza¼ de la Universidad de Pinar del Río «Hermanos Saíz Montes de Oca¼ / A view to the origin, evolution and development of the Faculty of Physical Culture «Nancy Uranga Romagoza at the University of Pinar del Rio «Hermanos Saíz Montes de Oca¼

RESUMEN Esta obra es el resultado del trabajo sistemático de quienes acumulan una larga trayectoria en el quehacer de la Facultad de Cultura Física "Nancy Uranga Romagoza" y en el ejercicio de la labor universitaria. En ella, se puede encontrar el proceso histórico de gestación, consolidación y afirmación de la Facultad de Cultura Física de Pinar del Río, expresado por los propios hacedores fundamentales. La investigación tiene como objetivo fundamental preservar la historia de la institución docente, así como también mostrar a las presentes y futuras generaciones el origen y decursar de la Facultad de Cultura Física "Nancy Uranga Romagoza" de la Universidad de Pinar del Río "Hermanos Saíz Montes de Oca", para así contribuir con la elevación del sentido de pertenencia hacia la carrera y el plantel. Para llevar a cabo este estudio, se realizó una revisión documental que incluyó una consulta a las resoluciones sobre la constitución de la Facultad de Cultura Física "Nancy Uranga Romagoza" en sus diferentes etapas, así como entrevistas a personalidades del deporte que han mantenido relación con las escuelas deportivas y, principalmente, con la Facultad de Cultura Física "Nancy Uranga Romagoza" en estudio.

ABSTRACT This work is the outcome of a systematic work coming from people who have saved deep and experienced records about the Faculty of Physical Culture"Nancy Uranga Romagoza", University of Pinar del Río "Hermanos Saíz Montes de Oca", Cuba. Throughout this article you can find the process of establishment and evolution of the Sport Faculty of Physical Culture "Nancy Uranga Romagoza" in Pinar del Río, taking in to consideration the critics and opinions of experts. The objective of the research is to preserve the historical background of the Faculty of Physical Culture "Nancy Uranga Romagoza" and the show the compiled work to the present and future generations. In this way it can be reinforced the sense of identity and positive moral values in the institution. To carry out this study it was necessary to apply some interviews and to consult some documents about the constitution of the Faculty of Physical Culture "Nancy Uranga Romagoza" attending to the different stages of evolution.

Population-based Study of First Hospitalizations for Heart Failure and the Interaction Between Readmissions and Survival.

INTRODUCTION AND OBJECTIVES: Disease progression in patients after a first hospitalization for heart failure (HF), in particular the interaction between survival and rehospitalizations, is not well established. METHODS: We studied all patients with a first hospitalization and main diagnosis of HF from 2009 to 2013 by analyzing the Minimum Data Set of the Region of Murcia. Both incident and recurrent patients were studied, and the trend in hospitalization rates was calculated by joinpoint regression. Patients were followed-up through their health cards until the end of 2015. Mortality and readmissions, including causes and chronology in relation to the time of death, were assessed. RESULTS: A total of 8258 incident patients were identified, with annual rates increasing (+2.3%, P <.05) up to 1.24 patients per 1000 inhabitants, representing 71% of hospitalized individuals and 57% of total discharges due to HF. In the first year, 22% were readmitted due to HF, 31% due to cardiovascular causes, and 54% due to any cause. Five-year survival was 40%, which was significantly lower than age- and sex-adjusted expected survival for the general population (76%) (P <.001). Among patients who died during follow-up, readmissions (1.5 per patient/y, 0.4 due to HF) showed a "J" pattern, with 48% of rehospitalizations being concentrated in the last 3 deciles of survival prior to death. CONCLUSIONS: Rates of first hospitalization due to HF continue to increase, with high mortality and rehospitalizations during follow-up, which are concentrated mainly in the period prior to death.

Hematoma subcapsular hepático asociado a síndrome de HELLP en el puerperio / Hepatic subcapsular hematoma associated with HELLP syndrome in the puerperium

El hematoma subcapsular hepático es una complicación grave del embarazo, asociada a preeclampsia severa o síndrome de HELLP. Al ser poco frecuente se requiere un alto índice de sospecha para realizar el diagnóstico precozmente, lo que determinará su pronóstico. A pesar de los avances en cirugía y medicina intensiva es una patología que sigue teniendo una elevada morbimortalidad materno fetal. Damos a conocer el caso de una paciente que cursó un embarazo sin incidentes hasta el parto, posterior a lo cual presenta síndrome de HELLP y un hematoma subcapsular hepático, que evolucionó favorablemente con tratamiento conservador.(AU)

A hepatic subcapsular hematoma is a serious complication of pregnancy, associated with severe preeclampsia or HELLP syndrome. Due to the low frequency of this presentation, a high suspicion index is required for early diagnosis, which it will determine its prognosis. Despite the advances in surgery and intensive medicine, it still has high maternal-fetal morbidity and mortality. In the present work, we report the case of a patient who had a physiological pregnancy until labor. Subsequently, the patient developed HELLP syndrome and hepatic subcapsular hematoma, which evolved favorably with conservative treatment. (AU)

Ángel Florencio Duque Pérez, microbiólogo colombino / Ángel Florencio Duque Pérez, a Colombinan microbiologist

Muchos han sido los médicos cubanos que se han dedicado al estudio de la microbiología médica, entre ellos algunos muy conocidos como el matancero Juan Guiteras Gener. Con este trabajo los autores pretendieron resaltar la figura del microbiólogo colombino Ángel Florencio Duque Pérez, primer microbiólogo matancero formado por la revolución y con una esmerada labor. Fallecido hace varios años, este excelente profesional es poco conocido y prácticamente ha quedado en el olvido. Para todos aquellos que lo conocieron y para los que no tuvieron ese enorme placer se les hace llegar esta síntesis biográfica (AU).

There have been many Cuban doctors who have devoted themselves to the study of Medical Microbiology, including well-known ones as the Matanzasan Juan Guiteras Gener. With this work the authors pretended to highlight the figure of the Colombinan microbiologist Florencio Angel Duque Pérez, the first microbiologist trained after the Revolution, with an important work. Deceased several years ago, this excellent professional is scarcely known and has been virtually forgotten. This biography is intended to all those who knew him and to all those who did not have that great pleasure (AU).

Ten years of clinical experience with biosimilar human growth hormone: a review of safety data.

Safety concerns for recombinant human growth hormone (rhGH) treatments include impact on cancer risk, impact on glucose homeostasis, and the formation of antibodies to endogenous/exogenous GH. Omnitrope® (biosimilar rhGH) was approved by the European Medicines Agency in 2006, with approval granted on the basis of comparable quality, safety, and efficacy to the reference medicine (Genotropin®). Additional concerns that may exist in relation to biosimilar rhGH include safety in indications granted on the basis of extrapolation and the impact of changing to biosimilar rhGH from other rhGH treatments. A substantial data set is available to fully understand the safety profile of biosimilar rhGH, which includes data from its clinical development studies and 10 years of post-approval experience. As of June 2016, 106,941,419 patient days (292,790 patient-years) experience has been gathered for biosimilar rhGH. Based on the available data, there have been no unexpected or unique adverse events related to biosimilar rhGH treatment. There is no increased risk of cancer, adverse glucose homeostasis, or immunogenic response with biosimilar rhGH compared with the reference medicine and other rhGH products. The immunogenicity of biosimilar rhGH is also similar to that of the reference and other rhGH products. Physicians should be reassured that rhGH products have a good safety record when used for approved indications and at recommended doses, and that the safety profile of biosimilar rhGH is in keeping with that of other rhGH products.

Evaluación de la Intervención Educativa "Tu sonrisa" en niños discapacitados / Evaluation of the Educative Intervention "Your smile" in disabled children

Introducción: los niños retrasados mentales presentan un desarrollo anormal de los procesos psíquicos, fundamentalmente los cognitivos superiores, los procesos voluntarios de la memoria, el pensamiento lógico verbal, y el lenguaje entre otros, todos como consecuencia de una lesión orgánica cerebral. Objetivo: para dar curso a la investigación se trazó como objetivo evaluar la aplicación de una intervención educativa con temas relacionados con higiene bucal, prevención y caries dental a niños con el propósito de mejorar el estado de salud bucal de los mismos, dadas por supuesto por sus características especiales. Materiales y métodos: para cumplimentar la investigación se evaluó la efectividad de la intervención propuesta en los niños retrasados mentales de 5 a 12 años de edad que pertenecen a esta área de salud sumando un total de 23 niños. Resultados: de los niños estudiados el mayor porciento eran del sexo masculino y tenían entre 8 y 10 años de edad; antes de la intervención educativa existía un gran numero de niños que tenían una higiene bucal inadecuada, desconocían los factores de riesgo de la caries dental y los métodos sobre prevención en Estomatología; mientras que después de aplicada la intervención mejoraron notablemente en estos aspectos. Conclusiones: según los resultados obtenidos se puede concluir que esta estrategia educativa preventiva permitió dar respuesta a los principales problemas identificados y alcanzar un mayor nivel de salud bucal en los niños con retraso mental en la etapa escolar al prevenir la formación de caries dental en dientes temporales y permanentes, pues al finalizar la intervención los resultados fueron evaluados de buenos (AU).

Introduction: children with mental retardation have an abnormal development of the psychical processes, mainly the superior cognitive ones, the voluntary processes of the memory, the logic verbal thought and language, among others, all of them as the result of a brain organic lesion. Objective: the aim of the research was evaluating the application of an educative intervention with themes related with oral hygiene, prevention and dental caries in children with the purpose of improving their oral health status, given the special characteristics of them. Materials and Methods: it was evaluated the effectiveness of the proposed intervention in children with mental retardation aged 5-12 years who belong to this health area, being 23 children in total. Results: the higher percent of the studied children were male, aged 8 and 10 years; before the educative intervention a great number of children had an inadequate oral hygiene, did not know dental caries risk factors and the preventive methods in Odontology, while after applying the intervention these aspects remarkably improved. Conclusions: according to the obtained results it could be concluded that this educative preventive strategy allowed answering to the main identified problems and reaching a higher level of oral health in children with mental retardation in scholar age, because it prevented the oral caries formation in deciduous and permanent teeth, since at the end of the intervention the achieved results were evaluated as good (AU).

The MYCN Protein in Health and Disease.

MYCN is a member of the MYC family of proto-oncogenes. It encodes a transcription factor, MYCN, involved in the control of fundamental processes during embryonal development. The MYCN protein is situated downstream of several signaling pathways promoting cell growth, proliferation and metabolism of progenitor cells in different developing organs and tissues. Conversely, deregulated MYCN signaling supports the development of several different tumors, mainly with a childhood onset, including neuroblastoma, medulloblastoma, rhabdomyosarcoma and Wilms' tumor, but it is also associated with some cancers occurring during adulthood such as prostate and lung cancer. In neuroblastoma, MYCN-amplification is the most consistent genetic aberration associated with poor prognosis and treatment failure. Targeting MYCN has been proposed as a therapeutic strategy for the treatment of these tumors and great efforts have allowed the development of direct and indirect MYCN inhibitors with potential clinical use.

Nivel de conocimientos en pacientes con traumatismo dental / Level of knowledge in patients with dental trauma

Introducción: el traumatismo de los dientes es uno de los accidentes más dramáticos que le suceden a una persona y su frecuencia en la clínica odontológica es cada día mayor, por lo que se requieren conocimientos en la población para su manejo inmediato y adecuado. Objetivo: determinar el nivel de conocimientos de pacientes con traumatismos dentales. Materiales y Métodos: se realizó un estudio descriptivo y transversal en la población del Área de Salud Pueblo Nuevo, Policlínico Docente “Carlos Verdugo” en el período comprendido del 2009 al 2014. La población estudiada fueron los pacientes que acudieron a consulta de urgencia, con traumatismos en dientes anteriores (215 pacientes), previo consentimiento informado. Resultados: mayor afectación del sexo masculino (65,1 %), así como mayor frecuencia de traumatismos en dientes permanentes que en dientes temporales. La escuela y el estomatólogo fueron las principales fuentes de información acerca del tema (7 % en ambos casos). El nivel de conocimientos que predominó fue el bajo (83,7 %), la población considera que se puede esperar días, como el criterio de actuación ante un trauma dentario. Conclusiones: predominó el sexo masculino, el traumatismo dental fue más frecuente en edades de 4 hasta 11 años y en dientes permanentes. Las fuentes de información reconocidas fueron el estomatólogo y la escuela. Se apreció un desconocimiento general, sobre todo en el manejo inmediato de esta afección (AU).

Introduction: dental trauma is one of the most dramatic accidents a person can suffer and its frequency in dental clinic is higher and higher; therefore it is required the population knowledge on its immediately and adequate handling. Aim: to determine the knowledge level of patients with dental trauma. Materials and methods: a descriptive, cross-sectional study was carried out in the population of Pueblo Nuevo Health Area, Teaching Policlinic "Carlos Verdugo", in the period from 2009 to 2014. Results: male sex was the most affected one (65.1 %), and the frequency of trauma in permanent teeth was higher than in deciduous ones. School and dentist were the main information sources on the theme (7 % in both cases). The predominant knowledge level was low (83.7 %). Population considers that waiting several days could be the behavioural criteria in the case of dental trauma. Conclusions: male sex was the predominant one; dental trauma was more frequent in 4-11 years age. The recognized information sources were the dentist and school. A general lack of knowledge was appreciated, above all in the immediate handling of the affection (AU).

Metabolic restructuring and cell fate conversion.

Accumulating evidence implicates mitochondrial and metabolic pathways in the establishment of pluripotency, as well as in the control of proliferation and differentiation programs. From classic studies in mouse embryos to the latest findings in adult stem cells, human embryonic and induced pluripotent stem cells, an increasing number of evidence suggests that mitochondrial and metabolic-related processes might intertwine with signaling networks and epigenetic rewiring, thereby modulating cell fate decisions. This review summarizes the progresses in this exciting field of research. Dissecting these complex mitochondrial and metabolic mechanisms may lead to a more comprehensive understanding of stemness biology and to potential improvements in stem cell applications for biomedicine, cell therapy, and disease modeling.

Nascent histamine induces α-synuclein and caspase-3 on human cells.

Histamine (Hia) is the most multifunctional biogenic amine. It is synthetized by histidine decarboxylase (HDC) in a reduced set of mammalian cell types. Mast cells and histaminergic neurons store Hia in specialized organelles until the amine is extruded by exocytosis; however, other immune and cancer cells are able to produce but not store Hia. The intracellular effects of Hia are still not well characterized, in spite of its physiopathological relevance. Multiple functional relationships exist among Hia metabolism/signaling elements and those of other biogenic amines, including growth-related polyamines. Previously, we obtained the first insights for an inhibitory effect of newly synthetized Hia on both growth-related polyamine biosynthesis and cell cycle progression of non-fully differentiated mammalian cells. In this work, we describe progress in this line. HEK293 cells were transfected to express active and inactive versions of GFP-human HDC fusion proteins and, after cell sorting by flow cytometry, the relative expression of a large number of proteins associated with cell signaling were measured using an antibody microarray. Experimental results were analyzed in terms of protein-protein and functional interaction networks. Expression of active HDC induced a cell cycle arrest through the alteration of the levels of several proteins such as cyclin D1, cdk6, cdk7 and cyclin A. Regulation of α-synuclein and caspase-3 was also observed. The analyses provide new clues on the molecular mechanisms underlying the regulatory effects of intracellular newly synthetized Hia on cell proliferation/survival, cell trafficking and protein turnover. This information is especially interesting for emergent and orphan immune and neuroinflammatory diseases.

The bias associated with amplicon sequencing does not affect the quantitative assessment of bacterial community dynamics.

The performance of two sets of primers targeting variable regions of the 16S rRNA gene V1-V3 and V4 was compared in their ability to describe changes of bacterial diversity and temporal turnover in full-scale activated sludge. Duplicate sets of high-throughput amplicon sequencing data of the two 16S rRNA regions shared a collection of core taxa that were observed across a series of twelve monthly samples, although the relative abundance of each taxon was substantially different between regions. A case in point was the changes in the relative abundance of filamentous bacteria Thiothrix, which caused a large effect on diversity indices, but only in the V1-V3 data set. Yet the relative abundance of Thiothrix in the amplicon sequencing data from both regions correlated with the estimation of its abundance determined using fluorescence in situ hybridization. In nonmetric multidimensional analysis samples were distributed along the first ordination axis according to the sequenced region rather than according to sample identities. The dynamics of microbial communities indicated that V1-V3 and the V4 regions of the 16S rRNA gene yielded comparable patterns of: 1) the changes occurring within the communities along fixed time intervals, 2) the slow turnover of activated sludge communities and 3) the rate of species replacement calculated from the taxa-time relationships. The temperature was the only operational variable that showed significant correlation with the composition of bacterial communities over time for the sets of data obtained with both pairs of primers. In conclusion, we show that despite the bias introduced by amplicon sequencing, the variable regions V1-V3 and V4 can be confidently used for the quantitative assessment of bacterial community dynamics, and provide a proper qualitative account of general taxa in the community, especially when the data are obtained over a convenient time window rather than at a single time point.