Perianal Pediatric Crohn Disease Is Associated With a Distinct Phenotype and Greater Inflammatory Burden

Objectives: Data on the outcomes of children with perianal Crohn disease (pCD) are limited, although its presence is often used for justifying early use of biologics. We aimed to assess whether pCD in children is associated with more severe outcomes as found in adults. Methods: Data were extracted from the ImageKids database, a prospective, multicenter, longitudinal cohort study. The study enrolled 246 children at disease onset or thereafter. All patients underwent comprehensive clinical, endoscopic, and radiologic evaluation at enrollment;98 children had repeat evaluation at 18 months. Results: Of the 234 included patients (mean age 14.2 +/- 2.4 years;131 [56%] boys), 57 (24%) had perianal findings, whereas only 21 (9%) had fistulizing perianal disease. Children with pCD had reduced weight and height z scores compared with non-pCD patients (-0.9 vs -0.35, P = 0.03 and -0.68 vs -0.23, respectively;P = 0.04), higher weighted pediatric CD activity index (32 [interquartile range 16-50] vs 20 [8-37];P = 0.004), lower serum albumin (3.6 +/- 0.7 vs 4.5 +/- 0.8, P = 0.016), and higher magnetic resonance enterography global inflammatory score (P = 0.04). Children with pCD had more rectal (57% vs 38%, P = 0.04), and jejunal involvement (31% vs 11% P = 0.003) and a higher prevalence of granulomas (64% vs 23%, P = 0.0001). Magnetic resonance enterography-based damage scores did not differ between groups. Patients with skin tags/fissures only, had similar clinical, endoscopic, and radiologic characteristics as patients with no perianal findings. Conclusions: Pediatric patients with pCD with fistulizing disease have distinct phenotypic features and a predisposition to a greater inflammatory burden

The cyclic-di-GMP signaling pathway in the Lyme disease spirochete,

In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any) c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease

Cognitive and neuroimaging findings in developmental coordination disorder: New insights from a systematic review of recent research

Contains fulltext : 178215.pdf (publisher's version ) (Open Access)Aim: To better understand the neural and performance factors that may underlie developmental coordination disorder (DCD), and implications for a multi-component account. Method: A systematic review of the experimental literature published between June 2011 and September 2016 was conducted using a modified PICOS (population, intervention, comparison, outcomes, and study type) framework. A total of 106 studies were included. Results: Behavioural data from 91 studies showed a broad cluster of deficits in the anticipatory control of movement, basic processes of motor learning, and cognitive control. Importantly, however, performance issues in DCD were often shown to be moderated by task type and difficulty. As well, we saw new evidence of compensatory processes and strategies in several studies. Neuroimaging data (15 studies, including electroencephalography) showed reduced cortical thickness in the right medial orbitofrontal cortex and altered brain activation patterns across functional networks involving prefrontal, parietal, and cerebellar regions in children with DCD than those in comparison groups. Data from diffusion-weighted magnetic resonance imaging suggested reduced white matter organization involving sensorimotor structures and altered structural connectivity across the whole brain network. Interpretation: Taken together, results support the hypothesis that children with DCD show differences in brain structure and function compared with typically developing children. Behaviourally, these differences may affect anticipatory planning and reduce automatization of movement skill, prompting greater reliance on slower feedback-based control and compensatory strategies. Implications for future research, theory development, and clinical practice are discussed.13 p