Hunter disease eClinic: interactive, computer-assisted, problem-based approach to independent learning about a rare genetic disease

<p>Abstract</p> <p>Background</p> <p>Computer-based teaching (CBT) is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II).</p> <p>Aim</p> <p>To develop interactive teaching software functioning as a virtual clinic for the management of MPS II.</p> <p>Implementation and Results</p> <p>The <it>Hunter disease eClinic</it>, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (<url>http://www.lysosomalstorageresearch.ca</url>), was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The <it>Hunter disease eClinic </it>consists of an <it>eBook </it>and an <it>eClinic</it>. The <it>eClinic </it>is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The <it>eBook </it>provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the <it>eClinic</it>, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available.</p> <p>Conclusions</p> <p>The Hunter disease <it>eClinic </it>employs a CBT model providing the trainee with realistic clinical problems, coupled with comprehensive basic and clinical reference information by instantaneous access to an electronic textbook, the <it>eBook</it>. The program was rated highly by attendees at national and international presentations. It provides a potential model for use as an educational approach to other rare genetic diseases.</p

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

A survey of the pain experienced by males and females with Fabry disease

BACKGROUND: The clinical onset of Fabry disease, a rare, X-linked, multisystemic disorder, is marked by neuropathic pain. Males suffer extensively from this disease. Females, as genetic ‘carriers’, have traditionally been viewed as either asymptomatic or mildly afflicted with this disease

Initial report from the Hunter Outcome Survey

Purpose:Hunter syndrome (Mucopolysaccharidosis II) is a rare, X-linked disorder of glycosaminoglycan metabo-lism. It is caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase, and in affected patients glycosaminoglycan accumulates in lysosomes of various tissues and organs and contributes to the pathophysiol-ogy of Hunter syndrome. The Hunter Outcome Survey (HOS) was established to better describe the natural history of this disorder and to evaluate the long-term effect of enzyme replacement therapy.Methods:HOS is an international, multicenter, long-term observational survey that will collect data on participating patients with a confirmed diagnosis of Hunter syndrome. Data will be collected during regular physician examinations and entered into an electronic database. Examples of observations include vital signs, laboratory values, signs and symptoms of organ involvement, and the results of selected functional tests (e.g., audiometry, echocardiogram, joint mobility, etc.).Results:As of May 15, 2007, 263 patients from 16 countries have enrolled in HOS; 24% of these patients were currently being treated with enzyme replacement therapy. The median age at enrollment was 12.2 years. The median age of onset of symptoms and diagnosis of Hunter syndrome were 1.5 and 3.5 years, respectively. Otitis media and abdominal hernia were the earliest presenting symptoms. Facial dysmorphismand hepatosplenomegaly were demonstrated by 95% and 89% of patients, respectively.Conclusions:HOS will be a valuable resource for enhancing the understanding of Hunter syndrome and will provide important information about the natural history of the disease and the role of enzyme replacement therapy in its treatment. Patients and their physicians should be encouraged to participate

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field