BACKGROUND AND AIMS The intestinal microbiomes of healthy children and pediatric patients with irritable bowel syndrome (IBS) are not well defined. Studies in adults have indicated that the gastrointestinal microbiota could be involved in IBS. METHODS We analyzed 71 samples from 22 children with IBS (pediatric Rome III criteria) and 22 healthy children, ages 7–12 years, by 16S rRNA gene sequencing, with an average of 54,287 reads/stool sample (average 454 read length = 503 bases). Data were analyzed using phylogenetic-based clustering (Unifrac), or an operational taxonomic unit (OTU) approach using a supervised machine learning tool (randomForest). Most samples were also hybridized to a microarray that can detect 8,741 bacterial taxa (16S rRNA PhyloChip). RESULTS Microbiomes associated with pediatric IBS were characterized by a significantly greater percentage of the class Gammaproteobacteria (0.07% vs 0.89% of total bacteria; P <.05); one prominent component of this group was Haemophilus parainfluenzae. Differences highlighted by 454 sequencing were confirmed by high-resolution PhyloChip analysis. Using supervised learning techniques, we were able to classify different subtypes of IBS with a success rate of 98.5%, using limited sets of discriminant bacterial species. A novel Ruminococcus-like microbe was associated with IBS, indicating the potential utility of microbe discovery for gastrointestinal disorders. A greater frequency of pain correlated with an increased abundance of several bacterial taxa from the genus Alistipes. CONCLUSIONS Using16S metagenomics by Phylochip DNA hybridization and deep 454 pyrosequencing, we associated specific microbiome signatures with pediatric IBS. These findings indicate the important association between gastrointestinal microbes and IBS in children; these approaches might be used in diagnosis of functional bowel disorders in pediatric patients.

In the classic view interleukin-13 (IL-13) binds to a heterodimer protein complex of the IL-13Rα1 and IL-4Rα chains and signals through a janus kinase 1 (JAK1)-signal transducer and activator of transcription 6 (STAT6) mechanism. We recently reported that IL-13 also signals through the IL-13Rα2 chain initiating all three mitogen activated protein kinase (MAPK) pathways, and the relative expression of IL-13Rα1 and IL-13Rα2 modulates one another's transduction pathway. Therefore we investigated whether generation of reactive oxygen species (ROS) as second messengers may serve as a common nexus between these two pathways emanating from the individual IL-13 receptor chains in intestinal epithelial cells (IEC). IL-13 stimulates intracellular ROS synthesis within 5 min via IL-13Rα1-JAK1-STAT6-and IL-13Rα2-MEK1/2-ERK1/2-dependent activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 (NOX-1). IL-13-induced ROS generation in turn positively regulates phosphorylation of ERK1/2 and STAT6, yielding a feed forward amplification loop. IL-13 also stimulates the stable, longterm gene expression of two other NADPH oxidases, NOX-4 and DUOX-2, which along with constitutive NOX-1, might facilitate elevated, continuous production of ROS in IL-13-activated IEC. The contribution of each signal transduction pathway initiated by IL-13 engagement to such biological functions as wound healing, inflammation, and apoptosis was mapped for representative, responsive genes. Distinct usage patterns were observed, demonstrating that not only is IL-13 signal transduction through STAT6, MAPK, and ROS regulated in both an antagonistic and cyclic fashion, but each pathway also plays a specific role in modulating the wound healing and anti-apoptotic capabilities of the intestinal epithelium.

Although conception was spontaneous in all these pregnancies, antenatal and intrapartum control of blood pressure played a pivotal role in pregnancy outcome. High rate of operative interference was present. All subsequent pregnancies had similar outcome due to slow progression of the disease. Although pregnancy was complicated by hypertension and its sequelae, successful outcome could be achieved with timely admission, judicious medication and multidisciplinary approach.

Subsequent pregnancies should be discouraged as it increases the risk of recurrence of left ventricular dysfunction. Anticoagulation may be considered as a primary prevention of thromboembolism in pregnant mothers with peripartum cardiomyopathy.

Chronic inflammation in ulcerative colitis (UC) is a sizeable risk factor for colorectal cancer (CRC). Interleukin-13 (IL-13) is elevated in the UC mucosa and may induce dysregulated signaling in neighboring intestinal epithelial cells (IEC) and thus function as a tumorogenic cytokine. Expression of IL-13 receptor chains on IEC obtained from control or chronically inflamed mucosa and colonic tumors was quantified by flow cytometry and immunoblot. IL-13Rα1 and IL-13Rα2 expression is significantly increased on IEC from UC and CRC patients compared to control and CD subjects. Purified IEC from these subjects and cell lines expressing varying ratios of IL-13Rα1 and α2 chains were stimulated with IL-13 in vitro to investigate by immunoblot the activation of the STAT6 and MAPK signaling pathways. Despite similarly elevated receptor expression in UC and CRC, IL-13 does not activate the STAT6 or MAPK pathways in UC, while in colonic tumors only the STAT6 pathway is activated. Using neutralizing antibodies and cell lines expressing a range of surface densities for IL-13Rα1 and IL-3Rα2, we demonstrate that IL-13Rα2 serves a dual role, initiating MAPK signaling at low concentrations and as an inhibitory, decoy receptor at high IL-13Rα2 to IL-13Rα1 ratios. Thus IL-13Rα2 is both a decoy receptor and induces MAPK signal transduction, depending on its relative expression and the local concentration of IL-13, which together modulate the balance and intensity of the signaling pathways initiated in UC and CRC.

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We studied the roles of vitamin D and its receptor, VDR, in the progression of leprosy. The majority of individuals with leprosy from Kolkata, India, with a type 1 or type 2 reaction have low levels of vitamin D3 in serum samples. Interestingly, individuals with a type 2 reaction associated with neuritis/erythema nodosum leprosum had very low VDR mRNA expression levels, ranging from 5% to 10%, compared to that of healthy control subjects; these patients also had a high bacilli index, ranging from 3+ to 5+. This is the first report to indicate that VDR expression levels may determine the complexity and severity of the progression of leprosy.

It can be completely idiopathic and can also be a result of passive autoimmunity with cardiac ailment in response to active transport of maternal IgG autoantibodies to fetal circulation, as in SLE. The history of CHB begins in utero and there is a tendency for female preponderance [2-4]. One study group followed up 102 subjects with CHB during adulthood and observed in lifelong perspective and explained it to be a life threatening disease with significant morbidity and risk of Stokes Adams (SA) attacks and sudden death at any age could be anticipated even in the absence of poor prognostic signs [5]. Patients with isolated CHB, who survive infancy are usually asymptomatic and achieve normal growth and development although mortality in this period is 8% [2]. Thus cases associated with pregnancy may be observed. CHB is rare and relatively serious problem in pregnancy as feto-maternal outcome is concerned. A normal physiologic response to pregnancy creates an increased cardiac output by 30 to 50% by increased heart rate and blood volume. These alterations pose a substantial challenge in the setting of fixed maternal heart rate. As pregnancy and CHB is a rare association and reported in the literature as small series or isolated case reports, there are no established guidelines regarding management. Here we are sharing our experience of 21 women with CHB during pregnancy and analyzed the pregnancy outcome in terms foeto-maternal morbidity and mortality and discussed the management issues. Materials and Methods This was a prospective cohort study of consecutive CHB patients hospitalized to the