Comparing Pandemic to Seasonal Influenza Mortality: Moderate Impact Overall but High Mortality in Young Children

Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality. Methods and Findings: We used data on all-cause mortality (1999-2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266-958) influenza-attributed deaths; for seasonal influen

A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function

Peer reviewe

CuII Binding to Various Forms of Amyloid-β Peptides: Are They Friends or Foes?

In the present microreview, we describe CuII binding to several forms of amyloid-β peptides, the peptides involved in Alzheimer's disease. It has indeed been shown that in addition to the “full-length” peptide that originates from the precursor protein after cleavage at the 1-position, several other shorter peptides do exist in large proportion and might be involved in the disease as well. CuII binding to amyloid-β peptides is one of the key interactions that impact both the aggregating properties of the amyloid peptides and the production of reactive oxygen species (ROS), two events that are linked to the etiology of the disease. Binding sites and affinity are described in correlation with CuII-induced ROS formation and CuII-altered aggregation for amyloid peptides starting at the 1-, 3-, 4-, and 11-positions, and for the corresponding pyroglutamate forms when they could be obtained (i.e., for peptides cleaved at the 3- and 11-positions). It appears that the current paradigm, which points to a toxic role of the CuII–amyloid-β interaction, might well be shifted towards a possible protective role when the peptides considered are the N-terminally truncated ones

CuII Binding to Various Forms of Amyloid-β Peptides: Are They Friends or Foes?

Invited for the cover of this issue are Christelle Hureau from Laboratoire de Chimie de Coordination (LCC), Toulouse, France, and co-workers. The cover image shows the two kinds of interaction between CuII and the amyloid-β peptides involved in Alzheimer's disease

Mutations of Histidine 13 to Arginine and Arginine 5 to Glycine Are Responsible for Different Coordination Sites of Zinc(II) to Human and Murine Peptides

Because mice and rats do not naturally develop Alzheimer's disease, genetically modified animals are required to study this pathology. This striking difference in terms of disease onset could be due to three alterations in the murine sequence (R5G, Y10F and H13R) of the amyloid-β peptide with respect to the human counterpart. Whether the metal-ion binding properties of the murine peptide are at the origin of such different amyloidogenicity of the two peptides is still an open question. Herein, the main zinc binding site to the murine amyloid-β at physiological pH has been determined through the combination of several spectroscopic and analytical methods applied to a series of six peptides with one or two of the key mutations. These results have been compared with the zinc binding site encountered in the human peptide. A coordination mechanism that demonstrates the importance of the H13R and R5G mutations in the different zinc environments present in the murine and human peptides is proposed. The nature of the minor zinc species present at physiological pH is also suggested for both peptides. Finally, the biological relevance and fallouts of the differences determined in zinc binding to human versus murine amyloid-β are also discussed

The flock-to-flock force of infection for scrapie in Britain.

A postal survey of British sheep farmers provided information on the proportion of farms that experienced their first case of scrapie in each year between 1962 and 1998. We found no evidence of a large increase in the proportion of scrapie-affected farms prior to, during or following the epidemic of BSE in British cattle. After correcting for between-farm heterogeneity in the probability of acquiring scrapie, we estimated the yearly between-flock force of infection since 1962. The current force of infection is estimated at approximately 0.0045 per farm per year and combined with a simple model of scrapie spread provides an estimate of the average duration of a scrapie outbreak on an individual farm. Considering all farms, the average outbreak lasts for five years, but if only those farms that have cases in animals born on the farm are considered, it lasts 15 years. We use these parameter estimates to compare the proportion of farms with scrapie in time periods of different lengths. In the survey, 2.7% of farms had a case in 1998. The 5.3% of farms reporting having a case between 1993 and 1997 is consistent with the hypothesis that the scrapie force of infection remained constant over this period