Metformin-induced suppression of Nemo-like kinase improves erythropoiesis in preclinical models of Diamond-Blackfan anemia through induction of miR-26a.

Diamond-Blackfan anemia (DBA) results from haploinsufficiency of ribosomal protein subunits in hematopoietic progenitors in the earliest stages of committed erythropoiesis. Nemo-like kinase (NLK) is chronically hyperactivated in committed erythroid progenitors and precursors in multiple human and murine models of DBA. Inhibition of NLK activity and suppression of NLK expression both improve erythroid expansion in these models. Metformin is a well-tolerated drug for type 2 diabetes with multiple cellular targets. Here we demonstrate that metformin improves erythropoiesis in human and zebrafish models of DBA. Our data indicate that the effects of metformin on erythroid proliferation and differentiation are mediated by suppression of NLK expression through induction of miR-26a, which recognizes a binding site within the NLK 3' untranslated region (3'UTR) to facilitate transcript degradation. We propose that induction of miR-26a is a potentially novel approach to treatment of DBA and could improve anemia in DBA patients without the potentially adverse side effects of metformin in a DBA patient population.

Advertising of tobacco products at point of sale: who are more exposed in Brazil?

OBJECTIVE:: To describe the adult population perception of cigarette advertising at point of sale, according their tobacco-use status and socio-demographic characteristics such as sex, age, race/color, region, household location and schooling. MATERIALS AND METHODS:: A multivariable analysis was carried out using data from the Global Adult Tobacco Survey in 2008 and the National Health Survey in 2013. RESULTS:: Both surveys showed that among nonsmokers: women, young adults and those who had over 10 years of schooling had more frequently noticed advertising of cigarettes at point of sale. It was also observed that among the population with fewer years of schooling these proportions increased significantly. CONCLUSION:: A measure that completely bans tobacco advertising would be more effective to protect the vulnerable groups from tobacco consumption.

Comparison of Conflicts of Interest among Published Hernia Researchers Self-Reported with the Centers for Medicare and Medicaid Services Open Payments Database.

BACKGROUND: Many healthcare providers have financial interests and relationships with healthcare companies. To maintain transparency, investigators are expected to disclose their conflicts of interest (COIs). Recently, the Centers for Medicare and Medicaid Services developed the Open Payment database of COIs reported by industry. We hypothesize that there is discordance between industry-reported and physician self-reported COIs in ventral hernia publications. STUDY DESIGN: PubMed was searched for ventral hernia studies accepted for publication between June 2013 and October 2015 and published by authors from the US. Conflicts of interest were defined as payments received as honoraria, consulting fees, compensation for serving as faculty or as a speaker at a venue, research funding payments, or having ownerships/partnerships in companies. Conflicts of interest disclosed on the published articles were compared with the financial relationships in the Open Payments database. RESULTS: A total of 100 studies were selected with 497 participating authors. Information was available from the Open Payments database for 245 (49.2%) authors, of which 134 (26.9%) met the definition for COI. When comparing COIs disclosed by authors and data in the Open Payments database, 81 (16.3%) authors had at least 1 COI but did not declare any, 35 (7.0%) authors had COIs other than what they declared, and 20 (4.0%) declared a COI not listed in the Open Payments database, for a combined discordance rate of 27.3%. CONCLUSIONS: There is substantial discordance between self-reported COI in published articles compared with those in the Centers for Medicare and Medicaid Services Open Payments database. Additional studies are needed to determine the reasons for these differences, as COI can influence the validity of the design, conduct, and results of a study.

Advertising of tobacco products at point of sale: who are more exposed in Brazil? / Publicidad de productos de tabaco en el punto de venta: ¿quiénes están más expuestos en Brasil?

Abstract: Objective: To describe the adult population perception of cigarette advertising at point of sale, according their tobacco-use status and socio-demographic characteristics such as sex, age, race/color, region, household location and schooling. Materials and methods: A multivariable analysis was carried out using data from the Global Adult Tobacco Survey in 2008 and the National Health Survey in 2013. Results: Both surveys showed that among nonsmokers: women, young adults and those who had over 10 years of schooling had more frequently noticed advertising of cigarettes at point of sale. It was also observed that among the population with fewer years of schooling these proportions increased significantly. Conclusion: A measure that completely bans tobacco advertising would be more effective to protect the vulnerable groups from tobacco consumption.

Resumen: Objetivo: Describir a la población adulta en relación con la percepción de la publicidad de cigarrillos en los puntos de venta, según el estado de consumo de tabaco y características sociodemográficas como sexo, edad, raza/color, región, ubicación del hogar y escolaridad. Material y métodos: Se realizó un análisis multivariado con los datos de la Encuesta Global de Tabaquismo en Adultos de 2008 y la Encuesta Nacional de Salud de 2013. Resultados. Ambas encuestas mostraron que entre los no fumadores: las mujeres, los adultos jóvenes y los que tenían más de 10 años de escolaridad notaron con más frecuencia la publicidad de cigarrillos en puntos de venta. También se observó que estas proporciones aumentaron significativamente entre la población con menos años de escolaridad. Conclusión. Una política que prohíba completamente la publicidad de cigarrillos sería más efectiva para proteger a los grupos vulnerables del consumo de tabaco.

Bulk adhesive strength of recombinant hybrid mussel adhesive protein.

Mussel adhesive proteins (MAPs) have received increased attention as potential biomedical and environmental friendly adhesives. However, practical application of MAPs has been severely limited by uneconomical extraction and unsuccessful genetic production. Developing new adhesives requires access to large quantities of material and demonstrations of bulk mechanical properties. Previously, the authors designed fp-151, a fusion protein comprised of six MAP type 1 (fp-1) decapeptide repeats at each MAP type 5 (fp-5) terminus and successfully expressed it in Escherichia coli. This recombinant hybrid protein exhibited high-level expression, a simple purification and high biocompatibility as well as strong adhesive ability on a micro-scale. In the present work, investigations on the bulk adhesive properties of semi-purified ( approximately 90% purity) fusion fp-151 were performed in air. The unmodified recombinant fp-151, as expressed, contains tyrosine residues and showed significant shear-adhesive forces ( approximately 0.33 MPa). Adhesion strength increased ( approximately 0.45 MPa) after enzymatic oxidation of tyrosine residues to l-3,4-dihydroxyphenylalanine (DOPA) groups. Addition of cross-linkers such as iron(III), manganese(III) and periodate (IO(4)(-)) generally enhanced adhesion, although too much addition decreased adhesion. Among the three cross-linking reagents examined, the non-metallic oxidant periodate showed the highest shear-adhesive forces ( approximately 0.86 MPa). In addition, it was found that adhesive strengths could be increased by adding weights to the samples. The highest adhesion strength found was that of DOPA-containing fp-151 cross-linked with periodate and having weights applied to the samples ( approximately 1.06 MPa). Taken together, the first bulk-scale adhesive force measurements are presented for an expressed recombinant hybrid mussel adhesive protein.