This study elucidates the genotypic and phenotypic spectrum and histopathological findings related to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in Japan. For this single-center retrospective observational study, we enrolled 215 patients who were clinically suspected of having CADASIL and were examined at Kumamoto University from 1997 to 2014, and we diagnosed CADASIL in 70 patients. We found 19 different NOTCH3 mutations in the patients, with the NOTCH3 Arg133Cys mutation being found most frequently. We also found the Arg75Pro mutation, a cysteine-sparing NOTCH3 mutation. CADASIL patients with this Arg75Pro mutation were frequently found throughout Japan, and fewer patients with the Arg75Pro mutation showed MRI hyperintensity in the anterior temporal pole compared with patients with other NOTCH3 mutations. Significantly more CADASIL patients with the NOTCH3 Arg133Cys mutation had hyperintensity in the external capsule compared with CADASIL patients with the other mutations not including the NOTCH3 Arg75Pro mutation. We also showed postmortem pathological findings of the first Japanese CADASIL case with the NOTCH3 Arg133Cys mutation, and histopathological findings of fresh frozen skin biopsy specimens of CADASIL patients. In conclusions, the spectrum of NOTCH3 mutations in Japanese CADASIL patients may be partially explained by founder effects. Genotype-phenotype correlations may exist in CADASIL, which should be considered so as to make an accurate diagnosis of CADASIL in each population. Fresh frozen skin biopsy specimens may aid detection of Notch3 deposits on vascular walls for an improved diagnosis of CADASIL.

A substantial amount of evidence indicates that news coverage of suicide deaths by celebrities is followed by an increase in suicide rates, suggesting a copycat behavior. However, the underlying process by which celebrity status and media coverage leads to increases in subsequent suicides is still unclear. This study collected over 1 million individual messages ("tweets") posted on Twitter that were related to 26 prominent figures in Japan who died by suicide between 2010 and 2014 and investigated whether media reports on suicide deaths that generated a greater level of reactions by the public are likely to be followed by a larger increase in actual suicides. We also compared the number of Twitter posts and the number of media reports in newspaper and on television to understand whether the number of messages on Twitter in response to the deaths corresponds to the amount of coverage in the traditional media. Using daily data from Japan's national death registry between 2010 and 2014, our analysis found an increase in actual suicides only when suicide deaths generated a large reaction from Twitter users. In contrast, no discernible increase in suicide counts was observed when the analysis included suicide deaths to which Twitter users did not show much interest, even when these deaths were covered considerably by the traditional media. This study also found suicides by relatively young entertainers generated a large number of posts on Twitter. This sharply contrasts with the relatively smaller volume of reaction to them generated by traditional forms of media, which focuses more on the deaths of non-entertainers. The results of this study strongly suggest that it is not sufficient to examine only traditional news media when investigating the impact of media reports on actual suicides.

Beta-1 blocker therapy improves outcome in sepsis possibly through modulation of gut mucosal integrity and local inflammatory response.

This study presents evidence that media reports on celebrity suicides have an immediate impact on the number of suicides in the general population. Our findings also highlight the importance of responsible and cautious media reporting on suicide.