Exploring the association between quality of life and survival in patients with transthyretin amyloidosis

BACKGROUND: Studies in various chronic diseases have correlated health-related quality of life (HRQOL) with disease state and treatment outcomes. Limited data exists on the association between HRQOL, survival, and clinical biomarkers of disease in wild-type and familial TTR amyloidosis (ATTRwt & ATTRm) patient populations. OBJECTIVES: To assess the association between HRQOL and survival, as well as HRQOL and clinical biomarkers of disease in transthyretin-mediated amyloidosis (ATTR) patient populations. METHODS: Using a retrospective cohort study design, HRQOL was assessed via SF-36 health surveys collected from patients with ATTRwt and ATTRm presenting for their initial evaluation at the BU Amyloidosis Center between 1985 and 2015. Kaplan-Meier curves and hazard ratios (HRs) calculated using Cox proportional hazards regression analysis were used to examine the association between physical (PCS) and mental (MCS) component scores derived from the SF-36 health surveys and survival follow-up. All analyses were adjusted for potential confounders such as age at presentation, gender, and co-morbidities including diabetes mellitus, hypertension and hyperlipidemia. Spearman’s rank correlations were calculated to assess the association between PCS, MCS and clinical biomarkers of disease (mBMI, troponin I and BNP) also collected at time of initial evaluation visit. Statistical significance was set at a two-sided alpha=0.05. RESULTS: In the ATTRwt cohort, 133 white males, aged 74.6 +/- 6.0 years (mean + SD) presented with mean MCS (45.7 +/- 12.3) and PCS (36.7 +/- 10.8) that were respectively, 0.5 and 1.5 SD below 50. Patients with PCS or MCS scores = 35 for PCS (HR=2.45; p=0.002) and for MCS (HR=3.38, p= 35 (HR=2.76; p= <0.0001). In contrast, MCS scores < 35 did not correlate with increased risk of death during follow-up (HR=1.38, p=0.13). BNP and troponin I most strongly associated with PCS (r= - 0.50; p<0.0001 and r= - 0.41; p<0.0001, respectively) and less with MCS (r= - 0.16; p=0.03 and r= - 0.24; p=0.007, respectively). mBMI did not associate with MCS or PCS in the ATTRwt and ATTRm cohorts. CONCLUSIONS: ATTR disease significantly decreased an individual’s physical and mental HRQOL. PCS and MCS were shown to be independent predictors of mortality but their ability to predict survival varied by cohort. Assessment of HRQOL may provide valuable prognostic information that could be of use in the management of ATTR disease

Tissue Specific Roles for the Ribosome Biogenesis Factor Wdr43 in Zebrafish Development

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome

The Second-Generation Guide Star Catalog: Description and Properties

The GSC-II is an all-sky database of objects derived from the uncompressed DSS that the STScI has created from the Palomar and UK Schmidt survey plates and made available to the community. Like its predecessor (GSC-I), the GSC-II was primarily created to provide guide star information and observation planning support for HST. This version, however, is already employed at some of the ground-based new-technology telescopes such as GEMINI, VLT, and TNG, and will also be used to provide support for the JWST and Gaia space missions as well as LAMOST, one of the major ongoing scientific projects in China. Two catalogs have already been extracted from the GSC-II database and released to the astronomical community. A magnitude-limited (R=18.0) version, GSC2.2, was distributed soon after its production in 2001, while the GSC2.3 release has been available for general access since 2007. The GSC2.3 catalog described in this paper contains astrometry, photometry, and classification for 945,592,683 objects down to the magnitude limit of the plates. Positions are tied to the ICRS; for stellar sources, the all-sky average absolute error per coordinate ranges from 0.2" to 0.28" depending on magnitude. When dealing with extended objects, astrometric errors are 20% worse in the case of galaxies and approximately a factor of 2 worse for blended images. Stellar photometry is determined to 0.13-0.22 mag as a function of magnitude and photographic passbands (B,R,I). Outside of the galactic plane, stellar classification is reliable to at least 90% confidence for magnitudes brighter than R=19.5, and the catalog is complete to R=20.Comment: 52 pages, 33 figures, to be published in AJ August 200

BMP Signaling Modulates Hepcidin Expression in Zebrafish Embryos Independent of Hemojuvelin

Hemojuvelin (Hjv), a member of the repulsive-guidance molecule (RGM) family, upregulates transcription of the iron regulatory hormone hepcidin by activating the bone morphogenetic protein (BMP) signaling pathway in mammalian cells. Mammalian models have identified furin, neogenin, and matriptase-2 as modifiers of Hjv's function. Using the zebrafish model, we evaluated the effects of hjv and its interacting proteins on hepcidin expression during embryonic development. We found that hjv is strongly expressed in the notochord and somites of the zebrafish embryo and that morpholino knockdown of hjv impaired the development of these structures. Knockdown of hjv or other hjv-related genes, including zebrafish orthologs of furin or neogenin, however, failed to decrease hepcidin expression relative to liver size. In contrast, overexpression of bmp2b or knockdown of matriptase-2 enhanced the intensity and extent of hepcidin expression in zebrafish embryos, but this occurred in an hjv-independent manner. Furthermore, we demonstrated that zebrafish hjv can activate the human hepcidin promoter and enhance BMP responsive gene expression in vitro, but is expressed at low levels in the zebrafish embryonic liver. Taken together, these data support an alternative mechanism for hepcidin regulation during zebrafish embryonic development, which is independent of hjv

Establishing Virtual Continuity of Care for a Patient with Long Covid Using a Multidisciplinary Approach

Our interprofessional team met virtually to address the concerns of a patient about their symptoms of Long Covid. We discuss the impacts of telehealth medicine and our goals for creating an effective treatment session based on our roles as individuals in our healthcare setting and as a team.https://dune.une.edu/cecespring2023/1002/thumbnail.jp

Arquitectura de la periferia y los bordes: Vivienda, trabajo y paisaje. Producción de hábitat para el trabajo, tejido residencial y paisaje para un convivir sustentable en un enfoque interdisciplinario. El caso Rosario y su área metropolitana

El presente Proyecto busca explorar una nueva ampliación de la ciudad de Rosario incorporando la dimensión socio ambiental de las nuevas urbanizaciones, el paisaje y las migraciones en el contexto rururbano. El tratamiento de los aspectos paisajísticos y ambientales sugieren la producción de hábitats sustentables en un enfoque interdisciplinario. Los valores cualitativos topográficos, sociales, culturales y económicos, y la red de relaciones existentes son puestos en valor en una estructura proyectual que pueda potencializarlos. El impacto del modelo de uso del suelo presionado por el crecimiento de la mancha urbana y las consecuencias que estas modificaciones de cobertura provocan en el tejido ecológico y social de la periferia son los ejes de intervención para generar reflexiones sobre nuevas metodologías de diseño que acompañen procesos de co-producción arquitectónica – espacial. El abordaje conceptual y metodológico se recuesta en la transdisciplinariedad, la trans- escalaridad y la multi-temporalidad, y atienden las modificaciones espontáneas del territorio producto de la migración como hecho social que reúne variadas dimensiones: espaciales, demográficas, sociológicas y políticas. La compilación de los resultados en la investigación, es editado en las siguientes publicaciones: MP vol. 14 ISBN 978-987-702-392-3 “50000 viviendas para Rosario”; MP vol. 16 ISBN 978-987-702-523-1 “Arquitectura, paisaje y mestizaje entre dos ríos” y MP vol. 17, “Rosario al sur” en elaboración en este momento. Dichos resultados incluyen mapeos de situación que se elaboran a partir del relevamiento físico y fenomenológico del sitio. A nivel epistemológico se avanzó en la construcción de cuestiones teórico metodológicas: la colisión de escalas entre lo urbano y lo rural, las instancias de valoración y diferencias de representaciones entre los actores de las poblaciones implicadas, y las consideraciones acerca del rol de la producción y del desarrollo local. Se produjo material gráfico, de diversa índole, que expresa los componentes de un sistema territorial complejo sobre el cual se instala el proyecto de la vivienda social y de mercado. Derivan de la investigación propuestas de vivienda que revisan los modos contemporáneos de habitar y los vínculos de las nuevas urbanizaciones con la ciudad, resultando de ello novedosas articulaciones entre espacios públicos, vivienda y equipamiento, estructuras productivas y áreas de uso y goce del paisaje natural

Póster: Arquitectura de los bordes y la periferia: vivienda, trabajo y paisaje

El presente Proyecto, continuidad de cuatro proyectos anteriores en los que se conceptualizaron la Periferia y los Bordes, busca afianzar la relación entre la instancia constructiva y el accionar popular en torno a tres dimensiones: a) La diseminación de tipologías y sistemas constructivos populares como una forma de expandir los medios mediante los cuales sectores populares aseguran su aparición y circulación en el medio urbano: desde infraestructuras sociales a vivienda; b) El uso de nuevas metodologías de diseño para acompañar procesos de co-producción.; y c) El desarrollo de materialidades alternativas reutilizando elementos de descarte y produciendo tecnologías que permitan replicabilidad y rapidez en la ejecución (ejemplo sistemas modulares, encofrados reutilizables, entre otros.Fil: Apellido, Nombre. Universidad Nacional de Rosario. Facultad de Arquitectura, Planeamiento y Diseño; Argentina.Fil: Secretaria de Ciencia y Tecnología - Universidad Nacional de Rosario. Facultad de Arquitectura, Planeamiento y Diseño; Argentina

Subcellular localization of nucleolar proteins in WDR43 depleted HeLa cells.

<p>IF analysis of nucleolar protein localization in control siRNA (A, C, E, G) and <i>WDR43</i> (B, D, F, H) siRNA treated HeLa cells. WDR43 depleted cells exhibited mislocalized expression of TCOF1 (B), Mpp10 (D), Nucleolin (F) and Fibrillarin (H) (arrows), as compared to their respective control GFP siRNA treated cells (see arrows). Scale bar = 10 µm.</p