Polyethylene Glycol Treatment for Peripheral Nerve Repair in Preclinical Models

Introduction: Peripheral nerve injuries commonly result from trauma and can lead to devastating loss of sensory and motor function. A novel strategy to improve peripheral nerve regeneration is a chemical fusogen known as polyethylene glycol (PEG). Several animal studies have illustrated PEG’s potential to help prevent axon loss after peripheral nerve injury. However, the relative rate of success and potential complications of these studies have not been definitively shown in the literature. The purpose of this systematic review is to evaluate the literature regarding the success of PEG adjunct treatment after peripheral nerve injury in preclinical models. Materials and Methods: The MEDLINE database was queried using the PubMed search engine with the following keywords and phrases: “polyethylene glycol” OR “PEG” AND “nerve” AND “fusion”. All resulting articles were screened by two reviewers. Animal type, nerve type, injury type, type(s) of analyses, and overall superiority of outcomes were assessed. Results: One-hundred and seventy-nine articles were identified, and thirteen studies remained after the application of inclusion and exclusion criteria. Twelve of the thirteen studies utilized rats as the preclinical model, while one utilized a guinea pig. Superiority of peripheral nerve repair outcomes with adjunct PEG treatment compared to a control group was reported in eleven of thirteen studies. Conclusions: The majority of studies reported positive outcomes when using PEG; this indicates that PEG treatment has the potential to enhance peripheral nerve regeneration after injury. However, the results of some of these studies indicated several uncertainties that need to be addressed in future studies. These preclinical models may help guide clinicians regarding the use of PEG treatment in peripheral nerve repair.

Classification of Trauma-Related Outcomes in US Veterans Using Magnetoencephalography (MEG)

Previous research has demonstrated highly accurate classification of veterans with posttraumatic stress disorder (PTSD) and controls based on synchronous neural interactions (SNI), highlighting the utility of SNI as a biomarker of PTSD. Here we extend that research to classify additional trauma-related outcomes including subthreshold PTSD, partial recovery, and full recovery according to SNI. A total of 219 U.S. veterans completed diagnostic interviews and underwent a magnetoencephalography (MEG) scan from which SNI was computed. Linear discriminant analysis was used to classify the PTSD and control brains, achieving 100% accuracy. That discriminant function was then used to classify each brain in the subthreshold PTSD, partial recovery, and full recovery diagnostic groups as PTSD or Control. All of the subthreshold PTSD diagnostic group were classified as PTSD, as were three-quarters of the partial recovery group. Findings regarding the full recovery group were mixed, documenting variability in the functional brain status of PTSD recovery. The results of the present study add to the literature supporting the discriminatory power of MEG SNI and demonstrate the utility of SNI as a biomarker of various PTSD-related trajectories.

Emotional, Behavioral, and Cognitive Correlates of Attention Deficit and Hyperactive Disorder (ADHD) Screening and Diagnosis History: Sex/Gender Differences

Background: While clinical studies have documented sex differences in emotional, behavioral, and cognitive function of children with Attention Deficit and Hyperactive Disorder (ADHD), it is unknown if these sex differences are due to differences in referral and diagnosis or if they can be also seen when we screen a community sample for ADHD. If these sex differences exist in populations with a diagnosis history but cannot be seen in screening, then they are unfair, preventable, and due to gender (social processes in referral and diagnosis) rather than sex. Aim:Using the data from a community sample of 9-10-year-old healthy developing children, we explored sex differences in the associations between cognitive, emotional, behavioral, and health status with positive screening vs. history of diagnosed ADHD. Methods: The Adolescent Brain Cognitive Development (ABCD) study included a national sample of 10,171 American children between ages 9 and 10 years old. This sample included 1,488 children with a history of psychiatric diagnosis and 8,683 children without a diagnosis. The two independent variables were screening and history of ADHD. The following variables were outcomes: symptom severity, cognitive function, body mass index (BMI), internalizing, externalizing, and total behavioral disorders. Sex was the moderator, and age, race, ethnicity, education, household income, and family structure were covariates. Mixed-effects regression models were used to adjust for the nested nature of the data. Results: Positive screening for ADHD and a history of diagnosis were both associated with worse cognitive function, higher internalizing, externalizing, total problem behaviors, higher inattention (ADHD symptoms), and lower BMI. Sex altered the association between history of diagnosis but not positive screening for ADHD with externalizing, and total behavioral problems as well as cognitive function. Sex did not affect the associations between positive screening for ADHD or a history of diagnosis with BMI or ADHD symptoms. Both history of diagnosis and positive screening for ADHD were associated with higher internalizing for boys than girls. Conclusion: History of diagnosis, but not positive screening for ADHD, is differently associated with behavioral and cognitive performance of males and females. As sex differences are seen in correlates of history of diagnosis but not positive screening, some of the observed sex differences are due to differential referral and diagnosis rather than differential presentation of ADHD in the community. This finding suggests that some of the so-called “sex differences” that are believed to be due to biology and heritable may be “gender differences” and modifiable. This is important because while gender differences are preventable and modifiable, sex differences are not.