The Gut-Brain Axis in Autism Spectrum Disorder: A Focus on the Metalloproteases ADAM10 and ADAM17

Autism Spectrum Disorder (ASD) is a spectrum of disorders that are characterized by problems in social interaction and repetitive behavior. The disease is thought to develop from changes in brain development at an early age, although the exact mechanisms are not known yet. In addition, a significant number of people with ASD develop problems in the intestinal tract. A Disintegrin And Metalloproteases (ADAMs) include a group of enzymes that are able to cleave membrane-bound proteins. ADAM10 and ADAM17 are two members of this family that are able to cleave protein substrates involved in ASD pathogenesis, such as specific proteins important for synapse formation, axon signaling and neuroinflammation. All these pathological mechanisms are involved in ASD. Besides the brain, ADAM10 and ADAM17 are also highly expressed in the intes-tines. ADAM10 and ADAM17 have implications in pathways that regulate gut permeability, home-ostasis and inflammation. These metalloproteases might be involved in microbiota-gut–brain axis interactions in ASD through the regulation of immune and inflammatory responses in the intestinal tract. In this review, the potential roles of ADAM10 and ADAM17 in the pathology of ASD and as targets for new therapies will be discussed, with a focus on the gut–brain axis

Comparison of Rupture Risk of Intracranial Aneurysms Between Familial and Sporadic Patients

Background and Purpose A much higher rupture rate for patients with familial intracranial aneurysms (IA) compared with patients with sporadic IA has been reported in a study with highly selected familial aneurysms using sporadic patients from other populations a controls. We aimed to validate these findings in a large independent series of Dutch patients with familial and sporadic IA. Methods We conducted a secondary analysis of our institutional cohort of patients who were screened for IAs between 1994 and 2016. We assessed the incidence of aneurysmal subarachnoid hemorrhage between familial, defined as ≥2 affected first-degree relatives with aneurysmal subarachnoid hemorrhage and unruptured IA (UIA), and sporadic patients with UIA with Cox regression analysis. Results We identified 62 familial IA patients with 91 UIA and 412 sporadic IA patients with 542 UIA. Despite familial aneurysms being smaller and more often located at low risk sites than sporadic IA, 3 familial patients had aneurysmal subarachnoid hemorrhage (0.77 ruptures per 100 aneurysm-years [95% CI, 0.20-2.09]) compared with 7 sporadic patients (0.51 ruptures per 100 aneurysm-years [95% CI, 0.22-1.01]). As compared to sporadic UIA, familial UIA seems to have a 3-fold higher risk of rupture (hazard ratio, 2.9 [95% CI, 0.6-14]). Conclusions Our results suggest a slightly increased risk of aneurysm rupture for familial compared with sporadic IA, although we were not able to demonstrate this with statistical significance. However, the rupture risk seems less strongly increased than found in a previous study. Based on our results, we recommend to treat familial UIA more aggressively

The Gut-Brain Axis in Autism Spectrum Disorder: A Focus on the Metalloproteases ADAM10 and ADAM17

Autism Spectrum Disorder (ASD) is a spectrum of disorders that are characterized by problems in social interaction and repetitive behavior. The disease is thought to develop from changes in brain development at an early age, although the exact mechanisms are not known yet. In addition, a significant number of people with ASD develop problems in the intestinal tract. A Disintegrin And Metalloproteases (ADAMs) include a group of enzymes that are able to cleave membrane-bound proteins. ADAM10 and ADAM17 are two members of this family that are able to cleave protein substrates involved in ASD pathogenesis, such as specific proteins important for synapse formation, axon signaling and neuroinflammation. All these pathological mechanisms are involved in ASD. Besides the brain, ADAM10 and ADAM17 are also highly expressed in the intes-tines. ADAM10 and ADAM17 have implications in pathways that regulate gut permeability, home-ostasis and inflammation. These metalloproteases might be involved in microbiota-gut–brain axis interactions in ASD through the regulation of immune and inflammatory responses in the intestinal tract. In this review, the potential roles of ADAM10 and ADAM17 in the pathology of ASD and as targets for new therapies will be discussed, with a focus on the gut–brain axis

A cross-sectional analysis of facial palsy-related quality of life in 125 patients: Comparing linear, quadratic and cubic regression analyses

Introduction: Facial function correlates with quality of life in facial palsy. Previous studies have examined a linear relationship; based on clinical experience, we hypothesize a curved regression (i.e. quadratic or cubic) will be more fitting to show the correlation between quality of life and facial function. Methods: We compared the fit of a linear regression model between Sunnybrook scores (facial function) and FaCE and FDI scores (quality of life) to a quadratic and cubic regression model in 125 patients cross-sectionally. Results: A total of 125 patients were included, 53.6% female with a mean (standard deviation) age of 56.6 (16.7) and a median (interquartile range) duration of palsy of 6.6 (1.5; 18.3) years. The quadratic regression proved a significant improvement over a linear regression analysis in the model using the FaCE total score (linear R2 =.346, quadratic R2 = .378, p = .033) and the FDI physical score (linear R2 = .245, quadratic R2 =.276, p = .034). The cubic regression analysis was no significant improvement over a quadratic regression. Discussion: The relationship between facial function and quality of life in facial palsy is not linear meaning that there is a lot of variation in QoL in cases with severe and moderate facial impairment. This is most applicable to patients suffering from post-paralysis synkinesis, proving the highly individually experienced burden of synkinesis. As the relationship is not linear it should not be included as such in future research studies