Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea

Background: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. Methods: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. Results: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. Conclusions: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.info:eu-repo/semantics/publishedVersio

Role and regulation of MKP-1 in airway inflammation

Mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a protein with anti-inflammatory properties and the archetypal member of the dual-specificity phosphatases (DUSPs) family that have emerged over the past decade as playing an instrumental role in the regulation of airway inflammation. Not only does MKP-1 serve a critical role as a negative feedback effector, controlling the extent and duration of pro-inflammatory MAPK signalling in airway cells, upregulation of this endogenous phosphatase has also emerged as being one of the key cellular mechanism responsible for the beneficial actions of clinically-used respiratory medicines, including beta(2)-agonists, phosphodiesterase inhibitors and corticosteroids. Herein, we review the role and regulation of MKP-1 in the context of airway inflammation. We initially outline the structure and biochemistry of MKP-1 and summarise the multi-layered molecular mechanisms responsible for MKP-1 production more generally. We then focus in on some of the key in vitro studies in cell types relevant to airway disease that explain how MKP-1 can be regulated in airway inflammation at the transcriptional, post-translation and post-translational level. And finally, we address some of the potential challenges with MKP-1 upregulation that need to be explored further to fully exploit the potential of MKP-1 to repress airway inflammation in chronic respiratory disease

Cerebellar anaplastic ganglioglioma in a septuagenarian

Ganglioglioma is a rare neoplasm most common in children and adolescents. It is typically located in the supratentorial compartment, with the temporal lobe being the most common tumor location. Anaplastic ganglioglioma is a WHO grade III ganglioglioma, a rare subtype accounting for a small minority of ganglioglioma cases. Posterior fossa anaplastic ganglioglioma in an adult is incredibly rare; only 3 prior cases have been reported. Only 1 adult anaplastic ganglioglioma in the cerebellum has been reported. We present the second reported adult cerebellar anaplastic ganglioglioma

Heart Rate Variability Biofeedback Improves Emotional and Physical Health and Performance: A Systematic Review and Meta Analysis.

We performed a systematic and meta analytic review of heart rate variability biofeedback (HRVB) for various symptoms and human functioning. We analyzed all problems addressed by HRVB and all outcome measures in all studies, whether or not relevant to the studied population, among randomly controlled studies. Targets included various biological and psychological problems and issues with athletic, cognitive, and artistic performance. Our initial review yielded 1868 papers, from which 58 met inclusion criteria. A significant small to moderate effect size was found favoring HRVB, which does not differ from that of other effective treatments. With a small number of studies for each, HRVB has the largest effect sizes for anxiety, depression, anger and athletic/artistic performance and the smallest effect sizes on PTSD, sleep and quality of life. We found no significant differences for number of treatment sessions or weeks between pretest and post-test, whether the outcome measure was targeted to the population, or year of publication. Effect sizes are larger in comparison to inactive than active control conditions although significant for both. HRVB improves symptoms and functioning in many areas, both in the normal and pathological ranges. It appears useful as a complementary treatment. Further research is needed to confirm its efficacy for particular applications