Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.

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Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases.

There is now an abundance of evidence to show that short-chain fatty acids (SCFAs) play an important role in the maintenance of health and the development of disease. SCFAs are a subset of fatty acids that are produced by the gut microbiota during the fermentation of partially and nondigestible polysaccharides. The highest levels of SCFAs are found in the proximal colon, where they are used locally by enterocytes or transported across the gut epithelium into the bloodstream. Two major SCFA signaling mechanisms have been identified, inhibition of histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs). Since HDACs regulate gene expression, inhibition of HDACs has a vast array of downstream consequences. Our understanding of SCFA-mediated inhibition of HDACs is still in its infancy. GPCRs, particularly GPR43, GPR41, and GPR109A, have been identified as receptors for SCFAs. Studies have implicated a major role for these GPCRs in the regulation of metabolism, inflammation, and disease. SCFAs have been shown to alter chemotaxis and phagocytosis; induce reactive oxygen species (ROS); change cell proliferation and function; have anti-inflammatory, antitumorigenic, and antimicrobial effects; and alter gut integrity. These findings highlight the role of SCFAs as a major player in maintenance of gut and immune homeostasis. Given the vast effects of SCFAs, and that their levels are regulated by diet, they provide a new basis to explain the increased prevalence of inflammatory disease in Westernized countries, as highlighted in this chapter.

The role of short-chain fatty acids in health and disease.

Structure–function relationships of immunostimulatory polysaccharides: A review

Butyrate: A Double-Edged Sword for Health?

Introduction Japanese encephalitis (JE) is among the most important viral encephalitides in Asia, especially in rural and suburban areas where rice culture and pig farming coexist. (1-3) It has also occurred rarely and sporadically in northern Australia and parts of the Western Pacific. (4-6) JE is due to infection with the JE virus (JEV), a mosquito-borne flavivirus. The main JEV transmission cycle involves Culex tritaeniorhynchus mosquitoes and similar species that lay eggs in rice paddies and other open water sources, with pigs and aquatic birds as principal vertebrate amplifying hosts. (1,2,7) Humans are generally thought to be dead-end JEV hosts, i.e. they seldom develop enough viremia to infect feeding mosquitoes. Fewer than 1% of human JEV infections result in JE. Approximately 20-30% of JE cases are fatal and 30-50% of survivors have significant neurologic sequelae. (8) JE is primarily a disease of children and most adults in endemic countries have natural immunity after childhood infection, but all age groups are affected. In most temperate areas of Asia, JEV is transmitted mainly during the warm season, when large epidemics can occur. In the tropics and subtropics, transmission can occur year-round but often intensifes during the rainy season. (1-3) The global incidence of JE is unknown because the intensity and quality of JE surveillance and the availability of diagnostic laboratory testing vary throughout the world. Countries that have implemented high-quality childhood JE vaccination programmes have seen a dramatic decline in JE incidence. Although JE is reportable to the World Health Organization (WHO) by its Member States, reporting is highly variable and incomplete. In the late 1980s, Burke and Leake estimated that 50 000 new cases of JE occurred annually among the 2.4 billion people living in the 16 Asian countries considered endemic at the time (approximate overall annual incidence: 2 per 100 000). (2) In the intervening two decades, despite major population growth, urbanization, changes in agricultural practices and increased use of the JE vaccine in many countries, this figure has been widely quoted, including very recently. (9-13) In 2000, assuming an annual, age-group-specific incidence of 25 cases per 100 000, Tsai estimated that in the absence of vaccination 175 000 cases of JE would occur annually among Asian children aged 0-14 years living in rural areas. (14) The current study used more recent, published, local or national incidence estimates and current population data to produce an updated estimate of the annual global incidence of JE. Methods We approximated the JE-affected territory of each of the 24 countries endemic for JE using a recent update (15) of an earlier approximation by Tsai (16) with some modifications (Table 1, available at: http://www.who.int/bulletin/ volumes/89/10/10-085233). Based on these same approximations, (15,16) we then stratified the JE-affected territory of some countries (e.g. China excluding Taiwan, India and Nepal) into two or more incidence strata. Because suitable studies of JE incidence were not available for every endemic country or incidence stratum, we sorted JE-endemic countries and incidence strata into 10 incidence groups (A, B, C1, C2 and D through I) based primarily on geographic proximity, ecologic similarity, vaccine programme similarity. Table 1 briefly describes the status of each endemic country's JE vaccination programme as of 2009, according to recent publications and unpublished sources. (8,17-20) Incidence data We identified studies that contained potentially useful data on the incidence of JE in Asia in a manner similar to the one used in a recent study of global typhoid fever incidence. (21) Whenever possible, this review followed the relevant guidelines for Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). (22) The review process is described as follows and no protocol is available. …

Estimated Global Incidence of Japanese Encephalitis: A Systematic review/Estimation De L'incidence Mondiale De L'encephalite Japonaise: Une Evaluation Systematique/ Incidencia Global Estimada De la Encefalitis Japonesa: Una Revision Sistematica

Su1578: FETAL INTESTINAL MARKERS LYMPHOCYTE 6 ANTIGEN COMPLEXES LY6A AND LY6C ARE ELEVATED IN HIGHLY PROLIFERATIVE SLC26A3 DEFICIENT COLON

Tu1535: ESTABLISHMENT OF A NOVEL HUMANIZED MOUSE MODEL OF GULF WAR ILLNESS

Providing quality service is an integral part of any airline’s efforts to increase profitability and cope with the growing aggressive competition that has emerged after the deregulation. To do this, the airlines must understand the requirements of their passengers and try to meet their expectations. This study tried to develop a scale consisting of the dimensions of service quality in the domestic airline industry in India, which has been experiencing a boom owing to the increasing number of passengers traveling by air. An extensive literature review was done, followed by empirical research conducted with the help of 384 questionnaires consisting of 28 items. The validity and reliability of the items were checked with KMO’s Bartlett’s test. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used for the study. The research established five dimensions of service quality known as EATRC (i.e., Employees, Assurance, Tangibles, Reliability, and Check-in) along with 23 sub-dimensions that depicted passengers’ perception of service quality. CFA was used to confirm the overall fitness of the model and validate the hypothesized relationships. 

Structural Equation Modeling of Airlines Service Quality: A Study of Airlines Industry in India

Most antihypertensive drugs have impaired dissolution rate and result from poorly aqueous solubility, polymorphic modifications, structure-based H-bond donor or acceptor anamolies. These physical attributes would have detrimental effects and may cause an entity out of the race from efficacious candidates. Nevertheless, compliance with the dissolution rate must be fulfilled under the regulatory mandate and serve as an assessment tool for product performance. The present reviews the niche technologies like electrospinning, spraying, or mesoporous methods that led to the generation of more dissolvable antihypertensives.  Several drug delivery systems design allows the incorporation of surfactants, microenvironment dissolution rate modifiers, acidifiers that could improve the dissolution rate of antihypertensives are reviewed.

Anoop Kumar

Papers

Su1578: FETAL INTESTINAL MARKERS LYMPHOCYTE 6 ANTIGEN COMPLEXES LY6A AND LY6C ARE ELEVATED IN HIGHLY PROLIFERATIVE SLC26A3 DEFICIENT COLON

Tu1535: ESTABLISHMENT OF A NOVEL HUMANIZED MOUSE MODEL OF GULF WAR ILLNESS

Structural Equation Modeling of Airlines Service Quality: A Study of Airlines Industry in India

Developing new treatment modalities from poorly dissolvable antihypertensive: courtesy delivery system design &niche technologies

Tu1515: DYSREGULATION OF INTESTINAL EPITHELIAL TRANSPORTERS AND JUNCTIONAL PROTEINS IN A MOUSE MODEL OF ANTI-CD40 COLITIS