Homozygosity for the E526V Mutation in Fibrinogen A Alpha-Chain Amyloidosis: The First Report

Systemic hereditary amyloidoses are autosomal dominant diseases associated with mutations in genes encoding ten different proteins. The clinical phenotype has implications on therapeutic approach, but it is commonly variable and largely dependent on the type of mutation. Except for rare cases involving gelsolin or transthyretin, patients are heterozygous for the amyloidogenic variants. Here we describe the first patient identified worldwide as homozygous for a nephropathic amyloidosis, involving the fibrinogen variant associated with the fibrinogen alpha-chain E526V (p.Glu545Val) mutation. In 1989, a 44-year-old woman presented with hypertension, hepatosplenomegaly, nephrotic syndrome, and renal failure. She started hemodialysis in 1990 and 6 years later underwent isolated kidney transplantation from a deceased donor. Graft function and clinical status were unremarkable for 16 years, despite progressively increased left ventricular mass on echocardiography. In 2012, 4 months before death, she deteriorated rapidly with severe heart failure, precipitated by Clostridium difficile colitis and urosepsis. Affected family members developed nephropathy, on average, nearly three decades later, which may be explained by the gene dosage effects on the phenotype of E526V (p.Glu545Val) fibrinogen A alpha-chain amyloidosis.

Laryngeal amyloidosis: An uncommon cause of dysphonia

Introduction: Amyloidosis is used to describe a range of disorders deined by extracellular deposition of abnormal protein ibrils. The larynx is the most common site of localized amyloidosis in the head and neck region and constitutes less than 1% of benign laryngeal lesions. Hoarseness is the most common symptom. Objective: Prospective clinical evaluation of patients with localized laryngeal amyloidosis. Clinical cases: Presented are 4 cases of patients with localized laryngeal amyloidosis who were treated at the Otolaryngology and Head and Neck Surgery Department at the “Dr. José Eleuterio González” University Hospital in Monterrey, Mexico. Three patients underwent phonomicrosurgery by direct microlaryngoscopy with the removal of the amyloid implantation using a cold knife excision with great results. In each patient the major site of involvement was the supraglottis with a small focus on the false vocal cord. A medical work-up, including a complete blood count (CBC), a basic metabolic panel, urinalysis, liver function test, chest X-ray and physical examination were performed to rule out the presence of systemic disease; no amyloidosis or signs of systemic disease were found. Congo red staining conirms the diagnosis of amyloidosis in all surgical specimens. Conclusions: In laryngeal amyloidosis, the treatment should be directed toward the improvement of the voice and the maintenance of the airway.

Marco y práctica institucional en el estudio de la comunicación intercultural: El caso del estilo de crianza "chino" de Amy Chua en los Estado Unidos

Este trabajo aspira a proporcionar herramientas adicionales en el ámbito de la comunicación y la pragmática intercultural mediante la propuesta de dos constructos: “Marco Institucional” y “Práctica Institucional”. Estos dos constructos se apoyan sobre las ideas desarrolladas por el filósofo John Searle en su teoría de la realidad institucional (1995, 2010) que se basa en el supuesto de que la asignación de significado es un fenómeno intrínsecamente humano. Por lo tanto, la realidad social es una construcción social: es ontológicamente subjetiva. Según Searle, un atributo clave que capacita a los seres humanos para crear la realidad social es el lenguaje, lo que implica que la realidad social es esencialmente lingüística: Constituida por representaciones basadas en estados intencionales intrínsecamente humanos, impuestas de manera colectiva sobre acciones, objetos y situaciones. La realidad social es lingüística en el sentido de que existe en tanto que nuestra capacidad humana lingüística nos permite crear y representar entidades de cosas como teniendo significado y funciones que no tendrían si no fuera por nosotros. ¿De qué manera es esto relevante ayudar a para comprender mejor la comunicación y la pragmática intercultural? Pretendemos justificar que nuestro campo de estudio comprenda análisis que vayan más allá de aquello se dice o se pronuncia (beyond utterances). Para responder a esta necesidad, tendremos que, en primer lugar, abordar la cuestión de qué es la cultura y explorar lo que significa cultura dentro del alcance de este trabajo. Según el antropólogo Clifford Geertz, "el hombre es un animal suspendido en redes de significación que él mismo ha tejido" y él asume que "la cultura es esas redes" (1973: 5). Esta definición es relevante en el ámbito de esta investigación porque con ella podemos empezar a juntar piezas, y comprender que la cultura –siendo redes de significación hiladas por el hombre– corresponde con la noción, mencionada anteriormente, de la intervención humana en la constitución de la realidad social. Cultura, con todas sus redes de significación y simbología, viene a ser un componente fundamental de la realidad social que creamos y habitamos. Así, un análisis que va más allá de lo pronunciado (utterances) cobra sentido al intentar comprender aspectos de la interacción en la comunicación intercultural. La cultura y la sociedad, al estar constituidas por un conjunto de convenciones de significado y representaciones simbólicas vienen a ser un tipo de lenguaje, por así decirlo, y llegan a tener grados de inteligibilidad. En lingüística "cuando los hablantes de diferentes entidades lingüísticas pueden entenderse unos a otros" (Campbell 2004:191) se dice que sus lenguas son mutuamente inteligibles: Sin embargo, "las entidades que son totalmente incomprensible para los hablantes de otras entidades claramente son mutuamente ininteligibles" (2004: 217)...

Through the clock's workings

Through the Clock’s Workings is a world first: a remixed and remixable anthology of literature.----- Prominent Australian authors have written new short stories and released them under a Creative Commons Attribution Non-Commercial ShareAlike licence. What that means is you can remix the stories, but only if you acknowledge the author, the remix is not for commercial use, and your new work is available for others to remix. The authors’ stories were made available on our website and new and emerging writers were invited to create their own remixes to be posted on the website and considered for publication in the print anthology alongside the original stories.----- The result is a world first: a remixed and remixable anthology of literature. Buy your copy now from the Sydney University Press eStore or download the electronic version.----- So how do you use a remixable anthology? Simple.----- Step 1 - Read. Thumb your way through the pages at will. Find the stories you love, the ones you hate, the ones that could be better.----- Step 2 - Re/create. Each story is yours to share and to remix. Use only one paragraph or character or just make subtle changes. Change the genre, alter its formal or stylistic characteristics, or revise its message. Use as little or as much as you like - as long as it works.----- Step 3 - Share. Be part of a growing community of literature remixing. Email your remix to us and start sharing. The entire anthology can be remixed - the original stories, the remixes, and even the fonts.----- Through the Clock’s Workings is Read&Write!

Implication of 3D culture system for study of prostate cancer (CaP) mediated bone metastasis

Introduction : For the past decade, three dimensional (3D) culture has served as a foundation for regenerative medicine study. With an increasing awareness of the importance of cell-cell and cell-extracellular matrix interactions which are lacking in 2D culture system, 3D culture system has been employed for many other applications namely cancer research. Through development of various biomaterials and utilization of tissue engineering technology, many in vivo physiological responses are now better understood. The cellular and molecular communication of cancer cells and their microenvironment, for instance can be studied in vitro in 3D culture system without relying on animal models alone. Predilection of prostate cancer (CaP) to bone remains obscure due to the complexity of the mechanisms and lack of proper model for the studies. In this study, we aim to investigate the interaction between CaP cells and osteoblasts simulating the natural bone metastasis. We also further investigate the invasiveness of CaP cells and response of androgen sensitve CaP cells, LNCaP to synthetic androgen.----- Method : Human osteoblast (hOB) scaffolds were prepared by seeding hOB on medical grade polycaprolactone-tricalcium phosphate (mPLC-TCP) scaffolds and induced to produce bone matrix. CaP cell lines namely wild type PC3 (PC3-N), overexpressed prostate specific antigen PC3 (PC3k3s5) and LNCaP were seeded on hOB scaffolds as co-cultures. Morphology of cells was examined by Phalloidin-DAPI and SEM imaging. Gelatin zymography was performed on the 48 hours conditioned media (CM) from co-cultures to determine matrix metalloproteinase (MMP) activity. Gene expression of hOB/LNCaP co-cultures which were treated for 48 hours with 1nM synthetic androgen R1881 were analysed by quantitative real time PCR (qRT-PCR).----- Results : Co-culture of PCC/hOB revealed that the morphology of PCCs on the tissue engineered bone matrix varied from homogenous to heterogenous clusters. Enzymatically inactive pro-MMP2 was detected in CM from hOBs and PCCs cultured on scaffolds. Elevation in MMP9 activity was found only in hOB/PC3N co-culture. hOB/LNCaP co-culture showed increase in expression of key enzymes associated with steroid production which also corresponded to an increase in prostate specific antigen (PSA) and MMP9.----- Conclusions : Upregulation of MMP9 indicates involvement of ECM degradation during cancer invasion and bone metastases. Expression of enzymes involved in CaP progression, PSA, which is not expressed in osteoblasts, demonstrates that crosstalk between PCCs and osteoblasts may play a part in the aggressiveness of CaP. The presence of steroidogenic enzymes, particularly, RDH5, in osteoblasts and stimulated expression in co-culture, may indicate osteoblast production of potent androgens, fuelling cancer cell proliferation. Based on these results, this practical 3D culture system may provide greater understanding into CaP mediated bone metastasis. This allows the role of the CaP/hOB interaction with regards to invasive property and steroidogenesis to be further explored.

Transfer of learning across the globe : pre-service teachers taking the initiative

A continuing challenge for pre-service teacher education is the learning transfer between the university based components and the practical school based components of their training. It is not clear how easily pre-service teachers can transfer university learnings into ‘in school’ practice. Similarly, it is not clear how easily knowledge learned in the school context can be disembedded from this particular context and understood more generally by the pre-service teacher. This paper examines the effect of a community of practice formed specifically to explore learning transfer via collaboration and professional enquiry, in ‘real time’, across the globe. “Activity Theory” (Engestrom, 1999) provided the theoretical framework through which the cognitive, physical and social processes involved could be understood. For the study, three activity systems formed community of practice network. The first activity system involved pre-service teachers at a large university in Queensland, Australia. The second activity system was introduced by the pre-service teachers and involved Year 12 students and teachers at a private secondary school also in Queensland, Australia. The third activity system involved university staff engineers at a large university in Pennsylvania, USA. The common object among the three activity systems was to explore the principles and applications of nanotechnology. The participants in the two Queensland activity systems, controlled laboratory equipment (a high powered Atomic Force Microscope – CPII) in Pennsylvania, USA, with the aim of investigating surface topography and the properties of nano particles. The pre-service teachers were to develop their remote ‘real time’ experience into school classroom tasks, implement these tasks, and later report their findings to other pre-service teachers in the university activity system. As an extension to the project, the pre-service teachers were invited to co-author papers relating to the project. Data were collected from (a) reflective journals; (b) participant field notes – a pre-service teacher initiative; (c) surveys – a pre-service teacher initiative; (d) lesson reflections and digital recordings – a pre-service teacher initiative; and (e) interviews with participants. The findings are reported in terms of the major themes: boundary crossing, the philosophy of teaching, and professional relationships The findings have implications for teacher education. The researchers feel that deliberate planning for networking between activity systems may well be a solution to the apparent theory/practice gap. Proximity of activity systems need not be a hindering issue.

The effect of road lane width on cyclist safety in urban areas

Research has shown that road lane width impacts on driver behaviour. This literature review provides guidelines to assist in the design, construction and retrofitting of urban roads to accommodate road users' safety requirements. It focuses on the impacts of lane widths on cyclists and motor vehicle safety behaviour. The literature review commenced with a search of library databases. Peer reviewed articles and road authority (local, state and national) reports were reviewed. The majority of studies investigating the effects of lane width on driver behaviour were simulator based, while research into cycling safety involved data collected from actual traffic environments. Results show that marked road lane width influences perceived task difficulty, risk perception and possibly speed choice. The positioning of cyclists in traffic lanes is influenced by the presence of on-road cycling facilities and the total roadway width. The lateral displacement between bicycle and vehicle is smallest when a bicycle facility is present. Lower, or reduced, vehicle speeds play a significant role in improving bicyclist and pedestrian safety. It is also shown that if road lane widths in urban areas were reduced, to a functional width that was less than the current guidelines of 3.5m, it could result in a safer road environment for all road users.