Posterior reversible leukoencephalopathy syndrome (PRES) clinically presents with seizures, severe headaches, and mental and visual changes. Our goal was to describe the clinical features, triggering factors, neuro-imaging findings, and electroencephalogram (EEG) findings in a pediatric cohort with renal disease. We retrospectively analyzed the records of 18 children with the diagnosis of PRES between January 2001 and June 2006 at the University of Miami/Holtz Children's Hospital, USA. There were 22 PRES episodes. The most common clinical presentation was generalized tonic-clonic seizures in 59% (13/22). The most common identified trigger of PRES was hypertensive crisis in 59% (13/22). Almost half of the children had no evidence of on-going uncontrolled hypertension; 44% (8/18) had normal funduscopic examination findings, and 50% (9/18) had no or mild left ventricular hypertrophy. Two of the 18 patients had recurrent PRES episodes, three episodes each. Diffuse slowing was the most common finding on the EEGs. Atypical magnetic resonance imaging (MRI) findings were more prevalent in the imaged cases (62% vs 25%, P < 0.05). All the computerized tomography (CT) scans were normal, despite the positive MRI findings in four cases when both types of imaging was used. All the episodes had total clinical resolution. In conclusion, despite the diverse initial trigger, acute hypertension seems to be the common pathogenic pathway for pediatric PRES. MRI seems superior to CT, with better sensitivity due to its high resolution and diffusion-weighted imaging. The lesions do not necessarily have to be in the posterior white matter and may not be totally reversible.

autoimmunity ͉ regulatory T cell ͉ inflammation ͉ knock-out ͉ multiple sclerosis M ultiple sclerosis (MS) afflicts over 2.5 million people worldwide, with women affected 3 times more frequently than men. Although its precise etiology is unknown, MS has been characterized as a Th1-and/or Th17-mediated autoimmune disease (1). Experimental autoimmune encephalomyelitis (EAE), commonly induced by immunizing with various myelin autoantigens, is an experimental model of MS that allows investigators to study the pathogenesis of this disease and to test new therapeutic strategies (2). Indeed EAE is an acute or chronic-relapsing inflammatory and demyelinating autoimmune disease with resemblance to MS in humans. The major features shared are the autoimmune destruction of the myelin sheaths of the nerve fibers, the presence of multiple CNS lesions with a predominantly perivascular location, and a temporal maturation of lesions from inflammation through demyelination, and finally axonal destruction.Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a 38-amino-acid neuropeptide identified by Arimura and colleagues in 1989 from ovine hypothalamus (3) and belongs to the secretin family. Its closest family member is vasoactive intestinal peptide (VIP), to which it is 68% identical. The actions of PACAP and VIP are mediated by 3 heterotrimeric G protein-coupled receptors, 1 (PAC1), which is highly specific for PACAP except for 1 splice variant (4), and 2 (VPAC1 and VPAC2) which interact with PACAP and VIP with equally high affinity (5). Although PACAP is widely distributed in the CNS and peripheral nervous system and is classically viewed as a neurotransmitter, it is capable of eliciting a broad spectrum of biological actions (5). Numerous results indicate that it exerts growth factor-like activities in the brain during development, regeneration, and tumorigenesis (6-10). Indeed, considerable data indicate that PACAP, mainly via PAC1, regulates neural cell proliferation, survival, axon regeneration and oligodendrocyte progenitor proliferation and maturation (6-9, 11-13).A series of studies beginning in the early 1980s implicated VIP as a regulator of immune function (14). These studies revealed that VIP can modulate both innate and adaptive immunity, showing a predominant anti-inflammatory action on macrophages, promoting a positive Th2/Th1 cytokine balance, and enhancing the production of regulatory T cells (Tregs) (15). Later it was found that PACAP could mimic many of these actions, suggesting the involvement of VPAC receptors. Moreover, it was determined that both VIP and PACAP are expressed in lymphocytes and other immune cell types (16-18), indicating that modulation of inflammation could result from either neurogenic or immunogenic neuropeptide expression. Finally, in the last decade, an increasing body of in vivo data indicates that VPAC receptors may be promising targets for the treatment of inflammatory diseases, and in particular, Th1-associated pathologies such as MS and rheumatoid arthritis. Indeed, adminis...

Exclusive enteral nutrition involves the use of a complete liquid diet, with the exclusion of normal dietary components for a defined period of time, as a therapeutic measure to induce remission in active Crohn's disease (CD). This very efficacious approach leads to high rates of remission, especially in children and adolescents newly diagnosed with CD. This intervention also results in mucosal healing, nutritional improvements and enhanced bone health. Whilst several recent studies have provided further elaboration of the roles of exclusive enteral nutrition in the management of CD, other reports have provided new understanding of the mechanisms by which this intervention acts.

The bone marrow microenvironment influences malignant hematopoiesis but how it promotes leukemogenesis has not been elucidated. Additionally, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands. Stroma derived from 5-azacytidine-treated patients lacked aberrant methylation and DNMTi treatment of primary MDS stroma enhanced its ability to support erythroid differentiation. An integrative expression analysis revealed that the WNT pathway antagonist FRZB was aberrantly hypermethylated and underexpressed in MDS stroma. This result was confirmed in an independent set of sorted, primary MDS-derived mesenchymal cells. We documented a WNT/β-catenin activation signature in CD34+ cells from advanced cases of MDS where it associated with adverse prognosis. Constitutive activation of β-catenin in hematopoietic cells yielded lethal myeloid disease in a NUP98-HOXD13 mouse model of MDS, confirming its role in disease progression. Our results define novel epigenetic changes in the bone marrow microenvironment which lead to β-catenin activation and disease progression of MDS.

The incidence of paediatric IBD in Canterbury has increased dramatically during the last 2 decades. Some of the observed incidence rates are among the highest documented anywhere in the world. The preponderance of CD over UC in the present study is the highest published.

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Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, these non-invasive markers of inflammation have significant clinical utility in the management of inflammatory bowel disease. Their use informs the decision to perform endoscopy before diagnosis is made right through to influencing therapeutic choices and the need for interval endoscopic assessment. In this review, the roles of two S100 proteins, calprotectin, and S100A12 are described along with that of lactoferrin, in the context of inflammatory bowel disease.

Edited by Alex Toker