Polynitroxylated Pegylated Hemoglobin: A Novel Neuroprotective Hemoglobin for Acute Volume-Limited Fluid Resuscitation After Combined Traumatic Brain Injury and Hemorrhagic Hypotension in Mice

Objective: Resuscitation of hemorrhagic hypotension after traumatic brain injury is challenging. A hemoglobin-based oxygen carrier may offer advantages. The novel therapeutic hemoglobin-based oxygen carrier, polynitroxylated pegylated hemoglobin (PNPH), may represent a neuroprotective hemoglobin-based oxygen carrier for traumatic brain injury resuscitation.Hypotheses: 1) PNPH is a unique non-neurotoxic hemoglobin-based oxygen carrier in neuronal culture and is neuroprotective in in vitro neuronal injury models. 2) Resuscitation with PNPH would require less volume to restore mean arterial blood pressure than lactated Ringer\u27s or Hextend and confer neuroprotection in a mouse model of traumatic brain injury plus hemorrhagic hypotension.Design: Prospective randomized, controlled experimental study.Setting: University center.Measurements and Main Results: In rat primary cortical neuron cultures, control bovine hemoglobin was neurotoxic (lactate dehydrogenase release; 3-[4,5-dimethylthiazol-2-yl-]-2,5-diphenyltetrazolium bromide assay) at concentrations from 12.5 to 0.625 [mu]M, whereas polyethylene glycol-conjugated hemoglobin showed intermediate toxicity. PNPH was not neurotoxic (p \u3c .05 vs. bovine hemoglobin and polyethylene glycol hemoglobin; all concentrations). PNPH conferred neuroprotection in in vitro neuronal injury (glutamate/glycine exposure and neuronal stretch), as assessed via lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl-]-2,5-diphenyltetrazolium bromide (all p \u3c .05 vs. control). C57BL6 mice received controlled cortical impact followed by hemorrhagic hypotension (2 mL/100 g, mean arterial blood pressure ~35-40 mm Hg) for 90 min. Mice were resuscitated (mean arterial blood pressure \u3e50 mm Hg for 30 min) with lactated Ringer\u27s, Hextend, or PNPH, and then shed blood was reinfused. Mean arterial blood pressures, resuscitation volumes, blood gasses, glucose, and lactate were recorded. Brain sections at 7 days were examined via hematoxylin and eosin and Fluoro-Jade C (identifying dying neurons) staining in CA1 and CA3 hippocampus. Resuscitation with PNPH or Hextend required less volume than lactated Ringer\u27s (both p \u3c .05). PNPH but not Hextend improved mean arterial blood pressure vs. lactated Ringer\u27s (p \u3c .05). Mice resuscitated with PNPH had fewer Fluoro-Jade C positive neurons in CA1 vs. Hextend and lactated Ringer\u27s, and CA3 vs. Hextend (p \u3c .05).Conclusions: PNPH is a novel neuroprotective hemoglobin-based oxygen carrier in vitro and in vivo that may offer unique advantages for traumatic brain injury resuscitation

Use of Machine Learning to Investigate the Quantitative Checklist for Autism in Toddlers (Q-CHAT) towards Early Autism Screening.

In the past two decades, several screening instruments were developed to detect toddlers who may be autistic both in clinical and unselected samples. Among others, the Quantitative CHecklist for Autism in Toddlers (Q-CHAT) is a quantitative and normally distributed measure of autistic traits that demonstrates good psychometric properties in different settings and cultures. Recently, machine learning (ML) has been applied to behavioral science to improve the classification performance of autism screening and diagnostic tools, but mainly in children, adolescents, and adults. In this study, we used ML to investigate the accuracy and reliability of the Q-CHAT in discriminating young autistic children from those without. Five different ML algorithms (random forest (RF), naïve Bayes (NB), support vector machine (SVM), logistic regression (LR), and K-nearest neighbors (KNN)) were applied to investigate the complete set of Q-CHAT items. Our results showed that ML achieved an overall accuracy of 90%, and the SVM was the most effective, being able to classify autism with 95% accuracy. Furthermore, using the SVM-recursive feature elimination (RFE) approach, we selected a subset of 14 items ensuring 91% accuracy, while 83% accuracy was obtained from the 3 best discriminating items in common to ours and the previously reported Q-CHAT-10. This evidence confirms the high performance and cross-cultural validity of the Q-CHAT, and supports the application of ML to create shorter and faster versions of the instrument, maintaining high classification accuracy, to be used as a quick, easy, and high-performance tool in primary-care settings

Mindfulness-Based Interventions for Physical and Psychological Wellbeing in Cardiovascular Diseases: A Systematic Review and Meta-Analysis

Background: Recently, there has been an increased interest in the efficacy of mindfulness-based interventions (MBI) for people with cardiovascular diseases (CVD), although the exact beneficial effects remain unclear. Methods: This review aims to establish the role of MBI in the management of wellbeing for patients with CVD. Seventeen articles have been included in this systematic synthesis of the literature and eleven in the meta-analysis. Results: Considering physical (i.e., heart rate, blood pressure) and psychological outcomes (i.e., depression, anxiety, stress, styles of coping), the vast majority of studies confirmed that MBI has a positive influence on coping with psychological risk factors, also improving physiological fitness. Random-effects meta-analysis models suggested a moderate-to-large effect size in reducing anxiety, depression, stress, and systolic blood pressure. Conclusions: Although a high heterogeneity was observed in the methodological approaches, scientific literature confirmed that MBI can now be translated into a first-line intervention tool for improving physical and psychological wellbeing in CVD patients

Information and communication technologies-based interventions for children with autism spectrum conditions: a systematic review of randomized control trials from a positive technology perspective

Information and communication technologies (ICTs) have become more widely used in the past years to help people with autism spectrum conditions (ASC). Serious games embedded into computers or tablets, as well as social robots, are the most employed ICT-related tools that are appealing to and appropriate for autistic children. The goal of ICT applications is to enhance behavioral abnormalities associated with ASC while also creating an interactive link between one person and one computer. Comparatively, to human-based therapy, ICT tools aid to inspire autistic children by providing predictability and regularity of tasks. Regaining social skills is the primary behavioral goal for which ICT tools have been designed and implemented. In the past several years, many studies have been created to show how effective it is at improving targeted behaviors. However, only a small number of researchers have used an RCT approach to evaluate its effectiveness. In this systematic review, we only included RCT studies where ICT technologies were used to help children with ASC in improving their social skills. Only 14 RCT studies satisfied the criteria and 12 described significant improvements, showing how the use of technology in educational contexts produced better improvement in developing several social skill facets with respect to the traditional face-to-face approach. Some studies used interventions and outcome measures focused on the core ASC symptoms, but many others addressed neurocognitive functions directly, like social cognition or emotional regulation, while other more general functions such as language or adaptive behaviors. We propose a classification based on processes and outcome measures to foster future research in this specific area of research. The behavioral intervention mediated by technological tools such as computer-based, tablet, and social robotics, undoubtedly provides a comfortable environment that promotes constant learning for people with ASC. Evidence provided in this review highlights the translational potential of this field of study in primary care practice and educational settings

The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report.

In an era of mass migration, social scientists, populist parties and social movements raise concerns over the future of immigration-destination societies. What impacts does this have on policy and social solidarity? Comparative cross-national research, relying mostly on secondary data, has findings in different directions. There is a threat of selective model reporting and lack of replicability. The heterogeneity of countries obscures attempts to clearly define data-generating models. P-hacking and HARKing lurk among standard research practices in this area.This project employs crowdsourcing to address these issues. It draws on replication, deliberation, meta-analysis and harnessing the power of many minds at once. The Crowdsourced Replication Initiative carries two main goals, (a) to better investigate the linkage between immigration and social policy preferences across countries, and (b) to develop crowdsourcing as a social science method. The Executive Report provides short reviews of the area of social policy preferences and immigration, and the methods and impetus behind crowdsourcing plus a description of the entire project. Three main areas of findings will appear in three papers, that are registered as PAPs or in process

Working memory and decision making in children with ADHD: an analysis of delay discounting with the use of the dual-task paradigm

Abstract Background Deficits in working memory tasks have been widely documented in Attention Deficit Hyperactivity Disorder (ADHD) studies. The aim of this study is to evaluate the effects of working memory load in impulsivity during decision-making processes. A delayed discounting (DD) paradigm was used, comparing children with ADHD and age-matched controls. Method Thirty-two children equally divided between typically developing and ADHD, from 8 to 10 years of age were assigned to sessions of a dual-task paradigm. In the primary task the child has to choose between two different amounts of money at different time delays, while in the secondary task the child has to repeat a random series of digits with different lengths. The experiment was conducted in a school setting. Results Compared to peers with typical development, delayed discounting was significantly stronger in children with ADHD and discounting rates increased in both groups for heavier memory loads. Furthermore, the memory load impact on frequency of immediate rewards was stronger in children with ADHD compared to typically developing children. Discussion Results are discussed in terms of the relation between working memory load and decision-making processes, their impact on impulsive behaviour in ADHD and the need for future research to understand possible neurocognitive correlates and use that information to develop better inclusive policies. </jats:sec

Tele-Assisted Behavioral Intervention for Families with Children with Autism Spectrum Disorders: A Randomized Control Trial

Background: Telehealth is useful for both autism spectrum disorder (ASD) diagnosis and treatment, but studies with a direct comparison between teletherapy and traditional in-person therapy are limited. Methods: This randomized control trial&mdash;ISRCTN (International Standard Randomised Controlled Trial Number) primary clinical trial registry ID ISRCTN15312724&mdash;was aimed at comparing the effect of a tele-assisted and in-person intervention based on a behavioral intervention protocol for families with children affected by ASDs. Forty-two parents with children with autism (30 months to 10 years old) were randomly assigned to 12 sessions of an applied behavioral analysis (ABA) intervention implemented in an individual and group setting, either with or without the inclusion of tele-assistance. Pre- and postintervention assessments were conducted using the Home Situation Questionnaire (HSQ-ASD) and the Parental Stress Index (PSI/SF). Results: Substantial improvements in the perception and management of children&rsquo;s behavior by parents, as well as in the influence of a reduction in parent stress levels on said children&rsquo;s behavior through the use of a tele-assisted intervention, were obtained. Conclusions: This randomized controlled trial demonstrates the evidence-based potential for telehealth to improve treatment of ASDs

TeleRehabilitation of Social-Pragmatic Skills in Children with Autism Spectrum Disorder: A Principal Component Analysis

In many therapeutic settings, remote health services are becoming increasingly a viable strategy for behavior management interventions in children with autism spectrum disorder (ASD). However, there is a paucity of tools for recovering social-pragmatic skills. In this study, we sought to demonstrate the effectiveness of a new online behavioral training, comparing the performance of an ASD group carrying out an online treatment (n°8) with respect to a control group of demographically-/clinically matched ASD children (n°8) engaged in a traditional in-presence intervention (face-to-face). After a 4-month behavioral treatment, the pragmatic skills language (APL test) abilities detected in the experimental group were almost similar to the control group. However, principal component analysis (PCA) demonstrated that the overall improvement in socio-pragmatic skills was higher for ASD children who underwent in-presence training. In fact, dimensions defined by merging APL subscale scores are clearly separated in ASD children who underwent in-presence training with respect to those performing the online approach. Our findings support the effectiveness of remote healthcare systems in managing the social skills of children with ASD, but more approaches and resources are required to enhance remote services

Alexithymia Profile in Relation to Negative Affect in Parents of Autistic and Typically Developing Young Children

In our study, we explored the construct of alexithymia in parents of children with and without ASD using a multi-method approach based on self-rated and external rater assessment. We also assessed the level of self-report measures of negative affect states such as trait anxiety and depression, and investigated the correlation between the alexithymia construct, trait anxiety, and depression within the broader autism phenotype (BAP). A total sample of 100 parents (25 mothers and 25 fathers in each group) were administered the TAS-20 and the TSIA to measure self-reported and observer-rated alexithymia traits, as well as self-report measures of anxiety and depression. Study results showed that the TSIA but not the TAS-20 was able to detect significant group differences in alexithymia traits among parents of children with and without ASD, with parents of ASD children displaying significantly higher levels of alexithymia. Furthermore, differently from the TAS-20, no significant correlations between the TSIA and measures of anxiety and depression were detected. Taken together, our results suggest the importance of using multi-method approaches to control for potential measurement bias and to detect psychological constructs such as alexithymia in subclinical samples such as parents of children with ASD