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

Identifying the World's Most Climate Change Vulnerable Species: A Systematic Trait-Based Assessment of all Birds, Amphibians and Corals

Climate change will have far-reaching impacts on biodiversity, including increasing extinction rates. Current approaches to quantifying such impacts focus on measuring exposure to climatic change and largely ignore the biological differences between species that may significantly increase or reduce their vulnerability. To address this, we present a framework for assessing three dimensions of climate change vulnerability, namely sensitivity, exposure and adaptive capacity; this draws on species’ biological traits and their modeled exposure to projected climatic changes. In the largest such assessment to date, we applied this approach to each of the world’s birds, amphibians and corals (16,857 species). The resulting assessments identify the species with greatest relative vulnerability to climate change and the geographic areas in which they are concentrated, including the Amazon basin for amphibians and birds, and the central Indo-west Pacific (Coral Triangle) for corals. We found that high concentration areas for species with traits conferring highest sensitivity and lowest adaptive capacity differ from those of highly exposed species, and we identify areas where exposure-based assessments alone may over or under-estimate climate change impacts. We found that 608–851 bird (6–9%), 670–933 amphibian (11–15%), and 47–73 coral species (6–9%) are both highly climate change vulnerable and already threatened with extinction on the IUCN Red List. The remaining highly climate change vulnerable species represent new priorities for conservation. Fewer species are highly climate change vulnerable under lower IPCC SRES emissions scenarios, indicating that reducing greenhouse emissions will reduce climate change driven extinctions. Our study answers the growing call for a more biologically and ecologically inclusive approach to assessing climate change vulnerability. By facilitating independent assessment of the three dimensions of climate change vulnerability, our approach can be used to devise species and area-specific conservation interventions and indices. The priorities we identify will strengthen global strategies to mitigate climate change impacts

Effects of ambient air pollution on functional status in patients with chronic congestive heart failure: a repeated-measures study

<p>Abstract</p> <p>Background</p> <p>Studies using administrative data report a positive association between ambient air pollution and the risk of hospitalization for congestive heart failure (HF). Circulating levels of B-type natriuretic peptide (BNP) are directly associated with cardiac hemodynamics and symptom severity in patients with HF and, therefore, serves as a marker of functional status. We tested the hypothesis that BNP levels would be positively associated with short-term changes in ambient pollution levels among 28 patients with chronic stable HF and impaired systolic function.</p> <p>Methods</p> <p>BNP was measured in whole blood at 0, 6, and 12 weeks. We used linear mixed models to evaluate the association between fine particulate matter (PM_2.5), carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, and black carbon and log(BNP). Lags of 0 to 3 days were considered in separate models. We calculated the intraclass correlation coefficient and within-subject coefficient of variation as measures of reproducibility.</p> <p>Results</p> <p>We found no association between any pollutant and measures of BNP at any lag. For example, a 10 μg/m³increase in PM_2.5was associated with a 0.8% (95% CI: -16.4, 21.5; p = 0.94) increase in BNP on the same day. The within-subject coefficient of variation was 45% on the natural scale and 9% on the log scale.</p> <p>Conclusion</p> <p>These results suggest that serial BNP measurements are unlikely to be useful in a longitudinal study of air pollution-related acute health effects. The magnitude of expected ambient air pollution health effects appears small in relation to the considerable within-person variability in BNP levels in this population.</p

Serum CEA and CA 15-3 as prognostic factors in primary breast cancer

In the present study, we investigated the association of the serum levels of the tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free survival and death from disease in 1046 women with breast cancer without metastases at the time of primary diagnosis in relation to age and the established prognostic factors tumour size, lymph node status, histological grading and hormone receptor status. We found that elevated pre-operative serum marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003) and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001 both) in univariate analyses. By comparing pre- and post-operative values we found a decline in values post-surgery. In those patients where marker levels of carcinoembryonic antigen decreased more than 33%, a significantly higher risk for relapse and death from disease (both P=0.0001) in univariate analyses was observed. In multivariate analysis this decrease of carcinoembryonic antigen proved to be an independent prognostic factor. The results for cancer antigen 15-3 were comparable to carcinoembryonic antigen in univariate analyses but showed no significance in multivariate analysis. In this study the post-operative decrease of the serum tumour marker carcinoembryonic antigen was a strong independent prognostic factor for disease free survival and death from disease in breast cancer patients

Recent Asian origin of chytrid fungi causing global amphibian declines

Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of the most devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide