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

IFN-λ3, not IFN-λ4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis

Genetic variation in the IFNL3-IFNL4 (interferon-λ3-interferon-λ4) region is associated with hepatic inflammation and fibrosis. Whether IFN-λ3 or IFN-λ4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-λ3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3-IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-λ4 protein and reduces IFN-λ4 activity, or between patients encoding functionally defective IFN-λ4 (IFN-λ4-Ser70) and those encoding fully active IFN-λ4-Pro70. The two proposed functional variants (rs368234815 and rs4803217) were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-λ3 rather than IFN-λ4 likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis

Analisis Kekuatan Massa Batugamping Dengan Menggunakan Kaidah Hoek-Brown Failure Criterion-Roclab Di Daerah Gunung Sudo Kabupaten Gunung Kidul YOGYAKARTA

The research area is a limestone quarry region prospect, located in Gunung Sudo, Gunung Kidul Regency, Special Region of Yogyakarta Province. Safety factor of bench in limestone quarry is extremely determined by rock mass quality. The aim of this research is analyzing of rock mass strength of limestone in the quarry prospect using the Hoek-Brown failure criterion. The research used quantitative method. To obtain rock mass strength analysis of limestone needs some parameters. The main parameters are uniaxial compressive strength of intact rock, GSI, lithology, disturbance factor, unit weight and application for slope (height).To solve this analysis is assisted by Roclab software. The Roclab is a software program for determining rock mass strength parameters based on the generalized Hoek-Brown failure criterion. Final result of the research will be used for safely mine design of the limestone quarry

Transcriptional Analysis of Murine Macrophages Infected with Different Toxoplasma Strains Identifies Novel Regulation of Host Signaling Pathways

Most isolates of Toxoplasma from Europe and North America fall into one of three genetically distinct clonal lineages, the type I, II and III lineages. However, in South America these strains are rarely isolated and instead a great variety of other strains are found. T. gondii strains differ widely in a number of phenotypes in mice, such as virulence, persistence, oral infectivity, migratory capacity, induction of cytokine expression and modulation of host gene expression. The outcome of toxoplasmosis in patients is also variable and we hypothesize that, besides host and environmental factors, the genotype of the parasite strain plays a major role. The molecular basis for these differences in pathogenesis, especially in strains other than the clonal lineages, remains largely unexplored. Macrophages play an essential role in the early immune response against T. gondii and are also the cell type preferentially infected in vivo. To determine if non-canonical Toxoplasma strains have unique interactions with the host cell, we infected murine macrophages with 29 different Toxoplasma strains, representing global diversity, and used RNA-sequencing to determine host and parasite transcriptomes. We identified large differences between strains in the expression level of known parasite effectors and large chromosomal structural variation in some strains. We also identified novel strain-specifically regulated host pathways, including the regulation of the type I interferon response by some atypical strains. IFNβ production by infected cells was associated with parasite killing, independent of interferon gamma activation, and dependent on endosomal Toll-like receptors in macrophages and the cytoplasmic receptor retinoic acid-inducible gene 1 (RIG-I) in fibroblasts.National Institutes of Health (U.S.) (R01-AI080621)New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (Developmental Grant AIO57159)Pew Charitable Trusts (Biomedical Scholars Program)Robert A. Swanson Career Development awardThe Knights Templar Eye Foundation, Inc.Pre-Doctoral Grant in the Biological Sciences (5-T32-GM007287-33)Cleo and Paul Schimmel Foundatio

The stranding anomaly as population indicator: the case of Harbour Porpoise <i>Phocoena phocoena</i> in North-Western Europe

Ecological indicators for monitoring strategies are expected to combine three major characteristics: ecological significance, statistical credibility, and cost-effectiveness. Strategies based on stranding networks rank highly in cost-effectiveness, but their ecological significance and statistical credibility are disputed. Our present goal is to improve the value of stranding data as population indicator as part of monitoring strategies by constructing the spatial and temporal null hypothesis for strandings. The null hypothesis is defined as: small cetacean distribution and mortality are uniform in space and constant in time. We used a drift model to map stranding probabilities and predict stranding patterns of cetacean carcasses under H-0 across the North Sea, the Channel and the Bay of Biscay, for the period 1990-2009. As the most common cetacean occurring in this area, we chose the harbour porpoise <i>Phocoena phocoena</i> for our modelling. The difference between these strandings expected under H-0 and observed strandings is defined as the stranding anomaly. It constituted the stranding data series corrected for drift conditions. Seasonal decomposition of stranding anomaly suggested that drift conditions did not explain observed seasonal variations of porpoise strandings. Long-term stranding anomalies increased first in the southern North Sea, the Channel and Bay of Biscay coasts, and finally the eastern North Sea. The hypothesis of changes in porpoise distribution was consistent with local visual surveys, mostly SCANS surveys (1994 and 2005). This new indicator could be applied to cetacean populations across the world and more widely to marine megafauna

Buses, cars, bicycles and walkers the influence of the type of human transport on the flight responses of waterbirds

One way to manage disturbance to waterbirds in natural areas where humans require access is to promote the occurrence of stimuli for which birds tolerate closer approaches, and so cause fewer responses. We conducted 730 experimental approaches to 39 species of waterbird, using five stimulus types (single walker, three walkers, bicycle, car and bus) selected to mimic different human management options available for a controlled access, Ramsar-listed wetland. Across species, where differences existed (56% of 25 cases), motor vehicles always evoked shorter flight-initiation distances (FID) than humans on foot. The influence of stimulus type on FID varied across four species for which enough data were available for complete cross-stimulus analysis. All four varied FID in relation to stimuli, differing in 4 to 7 of 10 possible comparisons. Where differences occurred, the effect size was generally modest, suggesting that managing stimulus type (e.g. by requiring people to use vehicles) may have species-specific, modest benefits, at least for the waterbirds we studied. However, different stimulus types have different capacities to reduce the frequency of disturbance (i.e. by carrying more people) and vary in their capacity to travel around important habita

Maternal Serologic Screening to Prevent Congenital Toxoplasmosis: A Decision-Analytic Economic Model

We constructed a decision-analytic and cost-minimization model to compare monthly maternal serological screening for congenital toxoplasmosis, prenatal treatment, and post-natal follow-up and treatment according to the current French protocol, versus no systematic screening or perinatal treatment. Costs are based on published estimates of lifetime societal costs of developmental disabilities and current diagnostic and treatment costs. Probabilities are based on published results and clinical practice in the United States and France. We use sensitivity analysis to evaluate robustness of results. We find that universal monthly maternal screening for congenital toxoplasmosis with follow-up and treatment, following the French (Paris) protocol, leads to savings of $620 per child screened. Results are robust to changes in test costs, value of statistical life, seroprevalence in women of childbearing age, fetal loss due to amniocentesis, incidence of primary T. gondii infection during pregnancy, and to bivariate analysis of test costs and incidence of primary T. gondii infection. Given the parameters in this model and a maternal screening test cost of$12, screening is cost-saving for rates of congenital infection above 1 per 10,000 live births. Universal screening according to the French protocol is cost saving for the US population within broad parameters for costs and probabilities

Clinical undergraduate training and assessment in primary health care: Experiences gained from Crete, Greece

BACKGROUND: Primary Health Care (PHC) is increasingly being introduced into undergraduate medical education. In Greece, the Faculty of Medicine of the University of Crete was the first to introduce a 4-week long training in primary health care. This paper presents the experiences gained from the initial implementation of the teaching of practice-based primary care in rural Crete and reports on the assessment scale that was developed. METHODS: 284 students' case write-ups from the 6 primary care units (PCUs) where they were allocated for the period 1990 to 1994 were analysed. The demographic data of the students and patients and the number of home visits were studied. Content analysis of the students' write-ups was carried out, using an assessment scale consisting of 10 dichotomous variables, in order to quantify eight (8) primary qualitative criteria. RESULTS: Internal reliability was estimated by the index KR20 = 0.67. Face and content validity was found to conform to the standards set for the course, while logistic linear regression analysis showed that the quality criteria could be used as an assessment scale. The number of home visits carried out varied between the various different PCUs (p < 0.001) and more were reported in the write-ups that fulfilled criteria related to the biopsychosocial approach (p < 0.05). Nine quantitative criteria were fulfilled in more than 90% of case reports, but laboratory investigations were reported only in 69.0% of case reports. Statistically significant differences between the PCUs were observed in the fulfilment of criteria related to the community approach, patient assessment and information related to the patient's perception of the illness, but not to those related to aspects of clinical patient management. Differences in reporting laboratory investigations (p < 0.001) are explained by the lack of such facilities in some PCUs. Demographic characteristics of the patients or the students' do not affect the criteria. CONCLUSION: The primary health care course achieved the objectives of introducing students to comprehensive, community oriented care, although there was variation between the PCUs. The assessment scale that was developed to analyse the case-write ups of the students provided data that can be used to evaluate the course

A surveillance sector review applied to infectious diseases at a country level

<p>Abstract</p> <p>Background</p> <p>The new International Health Regulations (IHR) require World Health Organization (WHO) member states to assess their core capacity for surveillance. Such reviews also have the potential to identify important surveillance gaps, improve the organisation of disparate surveillance systems and to focus attention on <it>upstream </it>hazards, determinants and interventions.</p> <p>Methods</p> <p>We developed a <it>surveillance sector review </it>method for evaluating all of the surveillance systems and related activities across a sector, in this case those concerned with infectious diseases in New Zealand. The first stage was a systematic description of these surveillance systems using a newly developed framework and classification system. Key informant interviews were conducted to validate the available information on the systems identified.</p> <p>Results</p> <p>We identified 91 surveillance systems and related activities in the 12 coherent categories of infectious diseases examined. The majority (n = 40 or 44%) of these were disease surveillance systems. They covered all categories, particularly for more severe outcomes including those resulting in death or hospitalisations. Except for some notifiable diseases and influenza, surveillance of less severe, but important infectious diseases occurring in the community was largely absent. There were 31 systems (34%) for surveillance of <it>upstream </it>infectious disease hazards, including risk and protective factors. This area tended to have many potential gaps and lack integration, partly because such systems were operated by a range of different agencies, often outside the health sector. There were fewer surveillance systems for determinants, including population size and characteristics (n = 9), and interventions (n = 11).</p> <p>Conclusions</p> <p>It was possible to create and populate a workable framework for describing all the infectious diseases surveillance systems and related activities in a single developed country and to identify potential surveillance sector gaps. This is the first stage in a review process that will lead to identification of priorities for surveillance sector development.</p