Efectividad y seguridad de tocilizumab en 2 casos de orbitopatía tiroidea grave refractaria a corticosteroides. Hospital San José, Bogotá

La orbitopatía tiroidea es la manifestación extratiroidea más frecuente del hipertiroidismo autoinmune; más del 90 % de los casos se asocian con enfermedad de Graves (EG). Es un trastorno complejo que puede provocar deformidad orbitaria, visión doble e incluso pérdida visual permanente, con gran impacto en la calidad de vida. Aproximadamente, el 2 % de los pacientes que desarrollan orbitopatía de Graves desarrolla enfermedad moderada a grave. Existe una creciente conciencia de la necesidad de un diagnóstico precoz y un manejo oportuno para disminuir las secuelas irreversibles. Su manejo inicial es con glucocorticoides; sin embargo, la recurrencia ocurre con frecuencia una vez que se retiran. En más del 60 % de los casos, la anatomía orbitaria normal no se restaura y se requiere cirugía de rehabilitación. En casos de refractariedad, las terapias biológicas son una alternativa, las cuales han demostrado ser efectivas. Dentro de estas están el teprotumumab, que reduce la proptosis, recientemente aprobado por la Food and Drug Administration (FDA); el rituximab, que reduce la inflamación; y el tocilizumab, que potencialmente beneficia ambos parámetros. A continuación, se describe el efecto del tocilizumab en 2 pacientes con orbitopatía tiroidea en el Hospital San José, en Bogotá

‘All hands-on deck’, working together to develop UK standards for public involvement in research

Background: Public involvement in research is an established part of the research process in the UK, however there remain questions about what good public involvement in research looks and feels like. Until now public involvement practitioners, researchers and members of the public have looked for answers in examples shared across networks, published case studies, guidance and research articles. Pulling these strands together, the UK Standards for Public Involvement provides six statements (standards) about public involvement in research. They were produced by a partnership of organisations from Scotland, Northern Ireland, Wales and England with contributions from involvement practitioners, public partners, researchers and research funders. Main body: Each standard has reflective questions, which are designed to encourage standard users to use approaches and behaviours that improve involvement, over time. The standards are designed to be used as a practical tool, and reflect the agreed hallmarks of good public involvement in research for example, flexibility in approaches used, shared learning, and mutual respect. The standards development process is described from the initial idea and scoping, via the appraisal of existing standard sets and integration of values and principles in public involvement in research. The collaborative writing process of and consultation on the draft standard set is described, together with what changed as a result of feedback. The initiation of a year-long testing programme with forty participating research organisations, the experiential feedback and the resulting changes to the standards is summarised. Conclusion: This commentary paper describes, in some detail, a process to develop a set of six standards for public involvement in research in the UK. Producing a complex, national public involvement initiative is not without its challenges, and in supplementary material partnership members reflect on and share their experiences of standards development. The next phase of integration and implementation is explored with concluding comments from those that tested and helped improve the standards

Quantitative assessment of airborne exposures generated during common cleaning tasks: a pilot study

Background: A growing body of epidemiologic evidence suggests an association between exposure to cleaning products with asthma and other respiratory disorders. Thus far, these studies have conducted only limited quantitative exposure assessments. Exposures from cleaning products are difficult to measure because they are complex mixtures of chemicals with a range of physicochemical properties, thus requiring multiple measurement techniques. We conducted a pilot exposure assessment study to identify methods for assessing short term, task-based airborne exposures and to quantitatively evaluate airborne exposures associated with cleaning tasks simulated under controlled work environment conditions. Methods: Sink, mirror, and toilet bowl cleaning tasks were simulated in a large ventilated bathroom and a small unventilated bathroom using a general purpose, a glass, and a bathroom cleaner. All tasks were performed for 10 minutes. Airborne total volatile organic compounds (TVOC) generated during the tasks were measured using a direct reading instrument (DRI) with a photo ionization detector. Volatile organic ingredients of the cleaning mixtures were assessed utilizing an integrated sampling and analytic method, EPA TO-17. Ammonia air concentrations were also measured with an electrochemical sensor embedded in the DRI. Results: Average TVOC concentrations calculated for 10 minute tasks ranged 0.02 - 6.49 ppm and the highest peak concentrations observed ranged 0.14-11 ppm. TVOC time concentration profiles indicated that exposures above background level remained present for about 20 minutes after cessation of the tasks. Among several targeted VOC compounds from cleaning mixtures, only 2-BE was detectable with the EPA method. The ten minute average 2- BE concentrations ranged 0.30 -21 ppm between tasks. The DRI underestimated 2-BE exposures compared to the results from the integrated method. The highest concentration of ammonia of 2.8 ppm occurred during mirror cleaning. Conclusions: Our results indicate that airborne exposures from short-term cleaning tasks can remain in the air even after tasks' cessation, suggesting potential exposures to anyone entering the room shortly after cleaning. Additionally, 2-BE concentrations from cleaning could approach occupational exposure limits and warrant further investigation. Measurement methods applied in this study can be useful for workplace assessment of airborne exposures during cleaning, if the limitations identified here are addressed

Development of Sensory, Motor and Behavioral Deficits in the Murine Model of Sanfilippo Syndrome Type B

BACKGROUND: Mucopolysaccharidosis (MPS) IIIB (Sanfilippo Syndrome type B) is caused by a deficiency in the lysosomal enzyme N-acetyl-glucosaminidase (Naglu). Children with MPS IIIB develop disturbances of sleep, activity levels, coordination, vision, hearing, and mental functioning culminating in early death. The murine model of MPS IIIB demonstrates lysosomal distention in multiple tissues, a shortened life span, and behavioral changes. PRINCIPAL FINDINGS: To more thoroughly assess MPS IIIB in mice, alterations in circadian rhythm, activity level, motor function, vision, and hearing were tested. The suprachiasmatic nucleus (SCN) developed pathologic changes and locomotor analysis showed that MPS IIIB mice start their daily activity later and have a lower proportion of activity during the night than wild-type controls. Rotarod assessment of motor function revealed a progressive inability to coordinate movement in a rocking paradigm. Purkinje cell counts were significantly reduced in the MPS IIIB animals compared to age matched controls. By electroretinography (ERG), MPS IIIB mice had a progressive decrease in the amplitude of the dark-adapted b-wave response. Corresponding pathology revealed shortening of the outer segments, thinning of the outer nuclear layer, and inclusions in the retinal pigmented epithelium. Auditory-evoked brainstem responses (ABR) demonstrated progressive hearing deficits consistent with the observed loss of hair cells in the inner ear and histologic abnormalities in the middle ear. CONCLUSIONS/SIGNIFICANCE: The mouse model of MPS IIIB has several quantifiable phenotypic alterations and is similar to the human disease. These physiologic and histologic changes provide insights into the progression of this disease and will serve as important parameters when evaluating various therapies

Proteomic Analysis of Fusarium solani Isolated from the Asian Longhorned Beetle, Anoplophora glabripennis

Wood is a highly intractable food source, yet many insects successfully colonize and thrive in this challenging niche. Overcoming the lignin barrier of wood is a key challenge in nutrient acquisition, but full depolymerization of intact lignin polymers has only been conclusively demonstrated in fungi and is not known to occur by enzymes produced by insects or bacteria. Previous research validated that lignocellulose and hemicellulose degradation occur within the gut of the wood boring insect, Anoplophora glabripennis (Asian longhorned beetle), and that a fungal species, Fusarium solani (ATCC MYA 4552), is consistently associated with the larval stage. While the nature of this relationship is unresolved, we sought to assess this fungal isolate's ability to degrade lignocellulose and cell wall polysaccharides and to extract nutrients from woody tissue. This gut-derived fungal isolate was inoculated onto a wood-based substrate and shotgun proteomics using Multidimensional Protein Identification Technology (MudPIT) was employed to identify 400 expressed proteins. Through this approach, we detected proteins responsible for plant cell wall polysaccharide degradation, including proteins belonging to 28 glycosyl hydrolase families and several cutinases, esterases, lipases, pectate lyases, and polysaccharide deacetylases. Proteinases with broad substrate specificities and ureases were observed, indicating that this isolate has the capability to digest plant cell wall proteins and recycle nitrogenous waste under periods of nutrient limitation. Additionally, several laccases, peroxidases, and enzymes involved in extracellular hydrogen peroxide production previously implicated in lignin depolymerization were detected. In vitro biochemical assays were conducted to corroborate MudPIT results and confirmed that cellulases, glycosyl hydrolases, xylanases, laccases, and Mn- independent peroxidases were active in culture; however, lignin- and Mn- dependent peroxidase activities were not detected While little is known about the role of filamentous fungi and their associations with insects, these findings suggest that this isolate has the endogenous potential to degrade lignocellulose and extract nutrients from woody tissue

Mosquitoes LTR Retrotransposons: A Deeper View into the Genomic Sequence of Culex quinquefasciatus

A set of 67 novel LTR-retrotransposon has been identified by in silico analyses of the Culex quinquefasciatus genome using the LTR_STRUC program. The phylogenetic analysis shows that 29 novel and putatively functional LTR-retrotransposons detected belong to the Ty3/gypsy group. Our results demonstrate that, by considering only families containing potentially autonomous LTR-retrotransposons, they account for about 1% of the genome of C. quinquefasciatus. In previous studies it has been estimated that 29% of the genome of C. quinquefasciatus is occupied by mobile genetic elements

More than just child’s play?: An experimental investigation of the impact of an appearance-focused internet game on body image and career aspirations of young girls

© 2017, The Author(s). In recent years, elements of the modern environment (such as television, Internet, toys and clothes) have been criticized for having an increasingly sexualized or appearance focus, which has been suggested to be detrimental to girls’ development. The current study examined the impact of an appearance-focused Internet game on young girls’ body image and career cognitions and aspirations. Eighty British girls aged 8–9 years were randomly assigned to play an appearance-focused or a non-appearance focused game for 10 minutes. Girls in the appearance-focused game condition displayed greater body dissatisfaction compared to the control condition. Type of game did not impact girls’ perceived capacity to do various jobs. However, girls who played the appearance-focused game reported a greater preference for feminine careers compared to the control group. This provides preliminary evidence that appearance-focused Internet games may be detrimental to young girls’ body image and aspirations. Internet games should be included in our consideration of influential messages for young girls