The Gut Microbiota and Irritable Bowel Syndrome: Friend or Foe?

Progress in the understanding of the pathophysiology of irritable bowel syndrome (IBS), once thought to be a purely psychosomatic disease, has advanced considerably and low-grade inflammation and changes in the gut microbiota now feature as potentially important. The human gut harbours a huge microbial ecosystem, which is equipped to perform a variety of functions such as digestion of food, metabolism of drugs, detoxification of toxic compounds, production of essential vitamins, prevention of attachment of pathogenic bacteria to the gut wall, and maintenance of homeostasis in the gastrointestinal tract. A subset of patients with IBS may have a quantitative increase in bacteria in the small bowel (small intestinal bacterial overgrowth). Qualitative changes in gut microbiota have also been associated with IBS. Targeting the gut microbiota using probiotics and antibiotics has emerged as a potentially effective approach to the treatment of this, hitherto enigmatic, functional bowel disorder. The gut microbiota in health, quantitative and qualitative microbiota changes, and therapeutic manipulations targeting the microbiota in patients with IBS are reviewed in this paper

Standard Cosmology Delayed

The introduction of a delay in the Friedmann equation of cosmological evolution is shown to result in the very early universe undergoing the necessary accelerated expansion in the usual radiation (or matter) dominated phase. Occurring even without a violation of the strong energy condition, this expansion slows down naturally to go over to the decelerated phase, namely the standard Hubble expansion. This may obviate the need for a scalar field driven inflationary epoch.Comment: 12 pages, 3 figures, Revised with more elaborate discussions. Accepted for publication in JCA

Integrable Impurity Model with Spin and Flavour: Model Inspired by Resonant Tunneling in Quantum Dot

We introduce an integrable impurity model in which both electrons and impurity have spin and flavour degrees of freedom. This model is a generalization of the multi-channel Kondo model and closely related with resonant tunneling through quantum dot. The Hamiltonian is exactly diagonalized by means of the Bethe ansatz.Comment: 1 reference is adde

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Magnetization and dimerization profiles of the cut two-leg spin ladder and spin-1 chain

The physical properties of the edge states of the cut two-leg spin ladder are investigated by means of the bosonization approach. By carefully treating boundary conditions, we derive the existence of spin-1/2 edge states in the spin ladder with a ferromagnetic rung exchange and for the open spin-1 Heisenberg chain. In contrast, such states are absent in the antiferromagnetic rung coupling case. The approach, based on a mapping onto decoupled semi-infinite off-critical Ising models, allows us to compute several physical quantities of interest. In particular, we determine the magnetization and dimerization profiles of the cut two-leg spin ladder and of the open biquadratic spin-1 chain in the vicinity of the SU(2)$_2$ WZNW critical point.Comment: RevTeX 4, no figure, 26 page

Mice with Different Susceptibility to Japanese Encephalitis Virus Infection Show Selective Neutralizing Antibody Response and Myeloid Cell Infectivity

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes public health problems in Asian countries. Only a limited number of JEV-infected individuals show symptoms and develop severe encephalitis, indicating host-dependent susceptibilities.C3H/HeN and DBA/2 mice, which exhibit different mortalities when infected by intraperitoneal inoculation with JEV, were used as experimental models to compare viral pathogenesis and host responses. One hundred infectious virus particles killed 95% of C3H/HeN mice whereas only 40% of DBA/2 mice died. JEV RNA was detected with similar low levels in peripheral lymphoid organs and in the sera of both mouse strains. High levels of viral and cytokine RNA were observed simultaneously in the brains of C3H/HeN and DBA/2 mice starting on days 6 and 9 post-infection, respectively. The kinetics of the cytokines in sera correlated with the viral replication in the brain. Significantly earlier and higher titers of neutralizing antibodies were detected in the DBA/2 strain. Primary embryonic fibroblasts, bone marrow-derived dendritic cells and macrophages from the two mouse strains were cultured. Fibroblasts displayed similar JEV replication abilities, whereas DBA/2-derived myeloid antigen-presenting cells had lower viral infectivity and production compared to the C3H/HeN–derived cells. may be elements associated with late and decreased mouse neuroinvasion

A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal

BACKGROUND: Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial. METHODOLOGY/PRINCIPAL FINDINGS: We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group. CONCLUSIONS/SIGNIFICANCE: A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01856205

Tobacco industry globalization and global health governance: : towards an interdisciplinary research agenda

Shifting patterns of tobacco production and consumption, and the resultant disease burden worldwide since the late twentieth century prompted efforts to strengthen global health governance through adoption of the Framework Convention on Tobacco Control. While the treaty is rightfully considered an important achievement, to address a neglected public health issue through collective action, evidence suggests that tobacco industry globalization continues apace. In this article we provide a systematic review of the public health literature and reveal definitional and measurement imprecision, ahistorical timeframes, transnational tobacco companies and the state as the primary units and levels of analysis, and a strong emphasis on agency as opposed to structural power. Drawing on the study of globalization in international political economy and business studies, we identify opportunities to expand analysis along each of these dimensions. We conclude that this expanded and interdisciplinary research agenda provides the potential for fuller understanding of the dual and dynamic relationship between the tobacco industry and globalization. Deeper analysis of how the industry has adapted to globalization over time, as well as how the industry has influenced the nature and trajectory of globalization, is essential for building effective global governance responses

Age at symptom onset and death and disease duration in genetic frontotemporal dementia : an international retrospective cohort study

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49\ub75 years (SD 10\ub70; onset) and 58\ub75 years (11\ub73; death) in the MAPT group, 58\ub72 years (9\ub78; onset) and 65\ub73 years (10\ub79; death) in the C9orf72 group, and 61\ub73 years (8\ub78; onset) and 68\ub78 years (9\ub77; death) in the GRN group. Mean disease duration was 6\ub74 years (SD 4\ub79) in the C9orf72 group, 7\ub71 years (3\ub79) in the GRN group, and 9\ub73 years (6\ub74) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0\ub745 between individual and parental age at onset, r=0\ub763 between individual and mean family age at onset, r=0\ub758 between individual and parental age at death, and r=0\ub769 between individual and mean family age at death) than in either the C9orf72 group (r=0\ub732 individual and parental age at onset, r=0\ub736 individual and mean family age at onset, r=0\ub738 individual and parental age at death, and r=0\ub740 individual and mean family age at death) or the GRN group (r=0\ub722 individual and parental age at onset, r=0\ub718 individual and mean family age at onset, r=0\ub722 individual and parental age at death, and r=0\ub732 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35\u201362, for age at onset; 61%, 47\u201373, for age at death), and even more by family membership (66%, 56\u201375, for age at onset; 74%, 65\u201382, for age at death). In the GRN group, only 2% (0\u201310) of the variability of age at onset and 9% (3\u201321) of that of age of death was explained by the specific mutation, whereas 14% (9\u201322) of the variability of age at onset and 20% (12\u201330) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11\u201326) of the variability of age at onset and 19% (12\u201329) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society