Hospital-diagnosed infections before age 20 and risk of a subsequent multiple sclerosis diagnosis

The involvement of specific viral and bacterial infections as risk factors for multiple sclerosis has been studied extensively. However, whether this extends to infections in a broader sense is less clear and little is known about whether risk of a multiple sclerosis diagnosis is associated with other types and sites of infections, such as of the CNS. This study aims to assess if hospital-diagnosed infections by type and site before age 20 years are associated with risk of a subsequent multiple sclerosis diagnosis and whether this association is explained entirely by infectious mononucleosis, pneumonia, and CNS infections. Individuals born in Sweden between 1970-1994 were identified using the Swedish Total Population Register (n = 2,422,969). Multiple sclerosis diagnoses from age 20 years and hospital-diagnosed infections before age 20 years were identified using the Swedish National Patient Register. Risk of a multiple sclerosis diagnosis associated with various infections in adolescence (11-19 years) and earlier childhood (birth-10 years) was estimated using Cox regression, with adjustment for sex, parental socioeconomic position, and infection type. None of the infections by age 10 years were associated with risk of a multiple sclerosis diagnosis. Any infection in adolescence increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.33, 95% confidence interval 1.21-1.46) and remained statistically significant after exclusion of infectious mononucleosis, pneumonia, and CNS infection (hazard ratio 1.17, 95% confidence interval 1.06-1.30). CNS infection in adolescence (excluding encephalomyelitis to avoid including acute disseminated encephalitis) increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.85, 95% confidence interval 1.11-3.07). The increased risk of a multiple sclerosis diagnosis associated with viral infection in adolescence was largely explained by infectious mononucleosis. Bacterial infections in adolescence increased risk of a multiple sclerosis diagnosis, but the magnitude of risk reduced after excluding infectious mononucleosis, pneumonia and CNS infection (hazard ratio 1.31, 95% confidence interval 1.13-1.51). Respiratory infection in adolescence also increased risk of a multiple sclerosis diagnosis (hazard ratio 1.51, 95% confidence interval 1.30-1.75), but was not statistically significant after excluding infectious mononucleosis and pneumonia. These findings suggest that a variety of serious infections in adolescence, including novel evidence for CNS infections, are risk factors for a subsequent multiple sclerosis diagnosis, further demonstrating adolescence is a critical period of susceptibility to environmental exposures that raise the risk of a multiple sclerosis diagnosis. Importantly, this increased risk cannot be entirely explained by infectious mononucleosis, pneumonia, or CNS infections

Field-induced magnetic structures in the chiral polar antiferromagnet Ni2_2InSbO6_6

We have performed $^{115}$In-NMR spectroscopy for Ni$_{2}$InSbO$_6$ with corundum-related crystal structure to reveal magnetic structures that develop in high magnetic fields. At low fields Ni$_{2}$InSbO$_6$ shows a helical magnetic order with a long wavelength because of its chiral and polar crystal structure. The field-induced magnetic state was not investigated by microscopic experiment because an extremely high magnetic field is required to modify the antiferromagnetically coupled helical structure. From the analysis of our $^{115}$In-NMR spectra obtained at high magnetic fields, we confirm that the canted antiferromagnetic structure appears in fields applied in the $[110]$ direction and the propagation vector of magnetic helix is rotated toward the field direction for fields in the $[001]$ direction. We discuss the effect of magnetic field that modifies the magnetic structure of an antiferromagnetic chiral magnet.Comment: 9 pages, 8 figures, accepted for publication from Phys. Rev.

Trends in health and health inequality during the Japanese economic stagnation: Implications for a healthy planet

Introduction: Human health and wellbeing may depend on economic growth, the implication being that policymakers need to choose between population health and the health of ecosystems. Over two decades of low economic growth, Japan's life expectancy grew. Here we assess the temporal changes of subjective health and health inequality during the long-term low economic growth period. Methods: Eight triennial cross-sectional nationally representative surveys in Japan over the period of economic stagnation from 1992 to 2013 were used (n = 625,262). Health is defined positively as wellbeing, and negatively as poor health, based on self-rated health. We used Slope and Relative Indices of Inequality to model inequalities in self-rated health based on household income. Temporal changes in health and health inequalities over time were examined separately for children/adolescents, working-age adults, young-old and old-old. Results: At the end of the period of economic stagnation (2013), compared to the beginning (1992), the overall prevalence of wellbeing declined slightly in all age groups. However, poor health was stable or declined in the young-old and old-old, respectively, and increased only in working-age adults (Prevalence ratio: 1.14, 95% CI 1.08, 1.20, <0.001). Over time, inequality in wellbeing and poor self-rated health were observed in adults but less consistently for children, but the inequalities did not widen in any age group between the start and end of the stagnation period. Conclusions: Although this study was a case study of one country, Japan, and inference to other countries cannot be made with certainty, the findings provide evidence that low economic growth over two decades did not inevitably translate to unfavourable population health. Japanese health inequalities according to income were stable during the study period. Therefore, this study highlighted the possibility that for high-income countries, low economic growth may be compatible with good population health

Increased MicroRNA-34b and -34c Predominantly Expressed in Stromal Tissues Is Associated with Poor Prognosis in Human Colon Cancer

published_or_final_versio

Latent heat in the chiral phase transition

The chiral phase transition at finite temperature and density is discussed in the framework of the QCD-like gauge field theory. The thermodynamical potential is investigated using a variational approach. Latent heat generated in the first-order phase transition is calculated. It is found that the latent heat is enhanced near the tricritical point and is more than several hundred MeV per quark.Comment: 6 pages, 3 figure

Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells

<p>Abstract</p> <p>Background</p> <p>Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells.</p> <p>Methods</p> <p>HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed.</p> <p>Results</p> <p>5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21^Cip1and p27^Kip1and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU.</p> <p>Conclusion</p> <p>Our findings suggest that the combination therapy with CQ should be a novel therapeutic modality to improve efficacy of 5-FU-based chemotherapy, possibly by inhibiting autophagy-dependent resistance to chemotherapy.</p

Bile Acid-Induced Virulence Gene Expression of Vibrio parahaemolyticus Reveals a Novel Therapeutic Potential for Bile Acid Sequestrants

Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2) encoded in pathogenicity island (Vp-PAI) is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections