Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease

<p>Abstract</p> <p>Background</p> <p>The emergence and continuing spread of Chronic Wasting Disease (CWD) in cervids has now reached 14 U.S. states, two Canadian provinces, and South Korea, producing a potential for transmission of CWD prions to humans and other animals globally. In 2005, CWD spread for the first time from the Midwest to more densely populated regions of the East Coast. As a result, a large cohort of individuals attending a wild game feast in upstate New York were exposed to a deer that was subsequently confirmed positive for CWD.</p> <p>Methods</p> <p>Eighty-one participants who ingested or otherwise were exposed to a deer with chronic wasting disease at a local New York State sportsman's feast were recruited for this study. Participants were administered an exposure questionnaire and agreed to follow-up health evaluations longitudinally over the next six years.</p> <p>Results</p> <p>Our results indicate two types of risks for those who attended the feast, a <it>Feast Risk </it>and a G<it>eneral Risk</it>. The larger the number of risk factors, the greater the risk to human health if CWD is transmissible to humans. Long-term surveillance of feast participants exposed to CWD is ongoing.</p> <p>Conclusion</p> <p>The risk data from this study provide a relative scale for cumulative exposure to CWD-infected tissues and surfaces, and those in the upper tiers of cumulative risk may be most at risk if CWD is transmissible to humans.</p

Mining Big Data for Tourist Hot Spots: Geographical Patterns of Online Footprints

Understanding the complex, and often unequal, spatiality of tourist demand in urban contexts requires other methodologies, among which the information base available online and in social networks has gained prominence. Innovation supported by Information and Communication Technologies in terms of data access and data exchange has emerged as a complementary supporting tool for the more traditional data collection techniques currently in use, particularly, in urban destinations where there is the need to more (near)real-time monitoring. The capacity to collect and analise massive amounts of data on individual and group behaviour is leading to new data-rich research approaches. This chapter addresses the potential for discovering geographical insights regarding tourists’ spatial patterns within a destination, based on the analysis of geotagged data available from two social networks. ·info:eu-repo/semantics/publishedVersio

The EYA Tyrosine Phosphatase Activity Is Pro-Angiogenic and Is Inhibited by Benzbromarone

Eyes Absents (EYA) are multifunctional proteins best known for their role in organogenesis. There is accumulating evidence that overexpression of EYAs in breast and ovarian cancers, and in malignant peripheral nerve sheath tumors, correlates with tumor growth and increased metastasis. The EYA protein is both a transcriptional activator and a tyrosine phosphatase, and the tyrosine phosphatase activity promotes single cell motility of mammary epithelial cells. Since EYAs are expressed in vascular endothelial cells and cell motility is a critical feature of angiogenesis we investigated the role of EYAs in this process. Using RNA interference techniques we show that EYA3 depletion in human umbilical vein endothelial cells inhibits transwell migration as well as Matrigel-induced tube formation. To specifically query the role of the EYA tyrosine phosphatase activity we employed a chemical biology approach. Through an experimental screen the uricosuric agents Benzbromarone and Benzarone were found to be potent EYA inhibitors, and Benzarone in particular exhibited selectivity towards EYA versus a representative classical protein tyrosine phosphatase, PTP1B. These compounds inhibit the motility of mammary epithelial cells over-expressing EYA2 as well as the motility of endothelial cells. Furthermore, they attenuate tubulogenesis in matrigel and sprouting angiogenesis in the ex vivo aortic ring assay in a dose-dependent fashion. The anti-angiogenic effect of the inhibitors was also demonstrated in vivo, as treatment of zebrafish embryos led to significant and dose-dependent defects in the developing vasculature. Taken together our results demonstrate that the EYA tyrosine phosphatase activity is pro-angiogenic and that Benzbromarone and Benzarone are attractive candidates for repurposing as drugs for the treatment of cancer metastasis, tumor angiogenesis, and vasculopathies

Prenatal exposure to mite and pet allergens and total serum IgE at birth in high-risk children.

Contains fulltext : 47898.pdf (publisher's version ) (Closed access)To examine the relationship between prenatal exposure to mite, cat and dog allergens and total serum IgE at birth in newborns at high risk of asthma. In the homes of 221 newborns with at least one first-degree relative with asthma, concentrations (ng/g dust) of allergens of house dust mite (mite), cat and dog were measured at the fourth to sixth month of pregnancy in dust samples from the maternal mattress and living room. At day 3-5 after birth, total IgE was measured in capillary heel blood. A total number of 174 blood samples were available (11 mothers refused newborn's blood sampling, and in 36 cases the blood sample was too small for analysis). In 24% of the newborns, total IgE was elevated (cut-off value 0.5 IU/ml). A significant dose response relationship was found between increasing mite allergen levels [divided in quartiles ng/g dust (qrt)] and the percentage of elevated IgE: first qrt (0-85 ng/g) 13%; second qrt (86-381) 19%; third qrt (382-2371) 26%; fourth qrt (> or =2372) 42%, respectively, p=0.01. This relationship remained significant after adjusting for passive smoking, maternal and paternal mite allergy, socio-demographic factors, birth characteristics and (breast) feeding practice in the first week of life. In high-risk newborns, prenatal exposure to mite allergens, but not to cat and dog allergens from dust of the living room and of the maternal mattress was associated with total serum IgE at birth

Compliance of asthmatic families with a primary prevention programme of asthma and effectiveness of measures to reduce inhalant allergens--a randomized trial.

Contains fulltext : 59248.pdf (publisher's version ) (Closed access)BACKGROUND: Compliance to and the effect of pre- and post-natal exposure reduction measures to prevent asthma in high-risk children from asthmatic families were studied. METHOD: Families were randomized to a special care group (n=222) and a control group (n=221). Educational advice on measures to reduce their newborn's exposure to allergens and smoke was provided to the special care group during three visits (two pre-natal and one post-natal). The control group (n=221) received usual care. RESULT: After the intervention, the special care group differed significantly (P<0.01) from the usual care group in: use of anti-mite encasings (parental: 88% vs. 14%; baby: 98% vs. 10%); keeping pets outside (51% vs. 19%); combined breast- and hypoallergenic formula feeding (55% vs. 22%); first solids postponement until after the sixth month (71% vs. 28%); maternal post-natal smoking (52% vs. 28%). Little or no compliance was found for other sanitary measures (cleaning habits, providing a smooth floor covering, ventilation/airing, pet removal), exclusive breastfeeding, pre-natal smoking and partner smoking. In spite of pre-existent low allergen levels in both groups, there was a significant reduction of mite, cat, and dog allergens on the mattresses and mite and cat allergens in the living room in the special care group and were significantly lower compared with the usual care group after 1 year. CONCLUSION: High compliance was found for the use of anti-mite encasings; substantial compliance for using hypoallergenic formula, solid food postponement, keeping pets outside and reported post-natal maternal smoking. There was no compliance for sanitary measures and the reduction of maternal pre-natal passive smoking. Mite and pet allergens on mattresses were strongly reduced by anti-mite encasings