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.

Neutrophil gelatinase-associated lipocalin protein accompanied by apparent bacteriostatic action accumulated in the intestinal wall and streamed into the mucosal layer during critically ill state, thereby possibly shaping microbiota homeostasis in the gut.

When the brain tries to acquire an elaborate model of the world, multisensory integration should contribute to building predictions based on the various pieces of information, and deviance detection should repeatedly update these predictions by detecting “errors” from the actual sensory inputs. Accumulating evidence such as a hierarchical organization of the deviance-detection system indicates that the deviance-detection system can be interpreted in the predictive coding framework. Herein, we targeted mismatch negativity (MMN) as a type of prediction-error signal and investigated the relationship between multisensory integration and MMN. In particular, we studied whether and how cross-modal information processing affected MMN in rodents. We designed a new surface microelectrode array and simultaneously recorded visual and auditory evoked potentials from the visual and auditory cortices of rats under anesthesia. Then, we mapped MMNs for five types of deviant stimuli: single-modal deviants in (i) the visual oddball and (ii) auditory oddball paradigms, eliciting single-modal MMN; (iii) congruent audio-visual deviants, (iv) incongruent visual deviants, and (v) incongruent auditory deviants in the audio-visual oddball paradigm, eliciting cross-modal MMN. First, we demonstrated that visual MMN exhibited deviance detection properties and that the first-generation focus of visual MMN was localized in the visual cortex, as previously reported in human studies. Second, a comparison of MMN amplitudes revealed a non-linear relationship between single-modal and cross-modal MMNs. Moreover, congruent audio-visual MMN exhibited characteristics of both visual and auditory MMNs—its latency was similar to that of auditory MMN, whereas local blockage of N-methyl-D-aspartic acid receptors in the visual cortex diminished it as well as visual MMN. These results indicate that cross-modal information processing affects MMN without involving strong top-down effects, such as those of prior knowledge and attention. The present study is the first electrophysiological evidence of cross-modal MMN in animal models, and future studies on the neural mechanisms combining multisensory integration and deviance detection are expected to provide electrophysiological evidence to confirm the links between MMN and predictive coding theory.

No abstract

BackgroundSince hyperglycemia-induced cellular dysfunction could be associated with alterations of the immune system, we tested the hypothesis that hyperglycemia augments the aberrant immune responses such as inflammation and differentiation of CD4+ T lymphocytes in the mesenteric lymph nodes (MLNs), and induces alterations of microbiota both under physiological and pathological conditions.MethodsMale Wistar rats were randomly allocated into 4 groups: Control and Endotoxemia (lipopolysaccharide, LPS 1 mg/kg) with or without hyperglycemia. The hyperglycemia groups were administered glucose solution (10-40 %), while the normoglycemia groups were administered saline. Alterations of the mRNA expressions of inflammatory cytokines and CD4+ T lymphocyte transcriptional factor expressions in the MLNs, and those of the intestinal microbiota were analyzed at 24 hr.ResultsHyperglycemia was kept approximately 250–350 mg/dL during the 24 hr study period. At the end of 24 hr, hyperglycemia augmented the mRNA expressions of interleukin (IL)-1β and IL-6 in the MLNs, while both the helper T (Th) 2 and regulatory-T (Treg) transcriptional factors were simultaneously up-regulated under non-endotoxemic condition. LPS injection significantly modulated the obligate anaerobe bacterial populations of the Bacteroidetes class, and altered the population sizes of the Clostridium perfringens and the Bacteroides fragilis subgroup. Hyperglycemia did not enhance these alterations of the microbiota evoked by LPS, although it did modify the bacterial populations of the L. reuteri subgroup and staphylococci in healthy condition without endotoxemia.ConclusionsThe present study indicates that both gut immune function and microbiota are significantly modulated by persistent hyperglycemia.Electronic supplementary materialThe online version of this article (doi:10.1186/s40560-015-0101-8) contains supplementary material, which is available to authorized users.