Children With Autism Spectrum Disorder With Regression Exhibit a Different Profile in Plasma Cytokines and Adhesion Molecules Compared to Children Without Such Regression.

Background: In the etiopathogenesis of autism spectrum disorder (ASD), it has been suggested that a proinflammatory condition, as well as an alteration in adhesion molecules in the early stages of neurodevelopment, may play a role in the pathophysiology of the disorder. This study set out to evaluate the plasma levels of certain inflammatory cytokines, adhesion molecules, and growth factors in a sample of pediatric patients with ASD and compare them to the levels in a control group of healthy children. Methods: Fifty-four children (45 males and nine females) aged 2-6, who were diagnosed with ASD, and a control group of 54 typically-developing children of similar ages were selected. The diagnosis of ASD was carried out in accordance with the DSM-5 criteria and the data obtained from a developmental semi-structured clinical interview and the ADOS evaluation test. Additional testing was carried out to identify the children's developmental level and severity of ASD symptomatology. Patients with ASD were further divided into two subgroups based on developmental parameters: ASD children with neurodevelopmental regression (AMR) and ASD children without neurodevelopmental regression (ANMR). Analyses of plasma molecules, such as cathepsin, IL1ß, IL6, IL8, MPO, RANTES, MCP, BDNF, PAI NCAM, sICAM, sVCAM and NGF, were performed. Results: Higher levels of NGF were observed in the ASD group compared with the levels in the control group (p < 0.05). However, in the analysis of the ASD subgroups, lower plasma levels of NCAM and higher levels of NGF were found in the group of ASD children without developmental regression compared to the levels in the group of typically-developing children. Conclusions: These results suggest differences that could be related to different pathophysiological mechanisms in ASD. There is not a specific profile for the expression of relevant plasma cytokines, adhesion molecules or growth factors in children with ASD compared with that in typically-developing children. However, in the ANMR and AMR subgroups, some of the adhesion molecules and neuronal growth factors show differences that may be related to synaptogenesis.

Lung recruitment manoeuvres do not cause haemodynamic instability or oxidative stress but improve oxygenation and lung mechanics in a newborn animal model: an observational study.

BACKGROUND: Lung recruitment manoeuvres in neonates during anaesthesia are not performed routinely due to concerns about causing barotrauma, haemodynamic instability and oxidative stress. OBJECTIVE: To assess the influence of recruitment manoeuvres and positive end-expiratory pressure (PEEP) on haemodynamics, oxidative stress, oxygenation and lung mechanics. DESIGN: A prospective experimental study. SETTING: Experimental Unit, La Paz University Hospital, Madrid, Spain. ANIMALS: Eight newborn piglets (<48 h) with healthy lungs under general anaesthesia. INTERVENTIONS: The recruitment manoeuvres in pressure-controlled ventilation (PCV) were performed along with a constant driving pressure of 15 cmH2O. After the recruitment manoeuvres, PEEP was reduced in a stepwise fashion to find the maximal dynamic compliance step (maxCDyn-PEEP). Blood oxidative stress biomarkers (lipid peroxidation products, protein carbonyls, total glutathione, oxidised glutathione, reduced glutathione and activity of glutathione peroxidase) were analysed. MAIN OUTCOME MEASURES: Haemodynamic parameters, arterial partial pressure of oxygen (paO2), tidal volume (Vt), dynamic compliance (Cdyn) and oxidative stress biomarkers were measured. RESULTS: The recruitment manoeuvres did not induce barotrauma. Haemodynamic instability was not detected either in the maximum pressure step (overdistension step 5) or during the entire process. No substantial differences were observed in blood oxidative stress parameters analysed as compared with their baseline values (with 0 PEEP) or the values obtained 180 min after the onset of the recruitment manoeuvres (optimal PEEP). Significant maximal values were achieved in step 14 with an increase in paO2 (32.43 ±â€Š8.48 vs. 40.39 ±â€Š15.66 kPa; P = 0.037), Vt (47.75 ±â€Š13.59 vs. 73.87 ±â€Š13.56 ml; P = 0.006) and Cdyn (2.50 ±â€Š0.64 vs. 4.75 ±â€Š0.88 ml cmH2O; P < 0.001). Maximal dynamic compliance step (maxCdyn-PEEP) was 2 cmH2O. CONCLUSION: Recruitment manoeuvres in PCV with a constant driving pressure are a well tolerated open-lung strategy in a healthy-lung neonatal animal model under general anaesthesia. The recruitment manoeuvres improve oxygenation parameters and lung mechanics and do not cause barotrauma, haemodynamic instability or oxidative stress.