In recent years, the existence of possible developmental pathways from childhood Attention-Deficit/Hyperactivity Disorder (ADHD) to adult Borderline Personality Disorder (BPD) has been suggested. The existence of common genetic factors has been described but there is little evidence on the role of environmental factors in the possible transition from one disorder to another throughout life. The main goal of this work is to review the literature about the existing evidence on childhood traumas as factors that mediate the risk of developing BPD in children with ADHD.A literature search was conducted using PubMed, Science Direct and PsychInfo databases. Criteria included studies of BPD and ADHD relationships and childhood traumas as environmental influences from epidemiological or clinical samples.The review only identified 4 studies that matched the search criteria. All studies retrospectively analyzed childhood traumas, and adult patients with BPD, with or without comorbid ADHD, were the most frequently mentioned. The analyzed evidence reinforces the relationship between the number of childhood traumas and higher clinical severity. Three of these analyzed studies describe an increased the risk of children with ADHD who report emotional and sexual traumatic experiences to develop BPD in adulthood.The experience of traumatic childhood events, especially those of an emotional type, may have a mediating effect of an increased risk of developing adult BPD in childhood ADHD patients. However, to consider them as risk factors, more studies, and especially longitudinal studies, are necessary to clarify the probable transactional process between the two disorders. Evidence from these studies may be helpful to develop early intervention programs to reduce the functional impairment associated with the two disorders. Borderline Personality Disorder (BPD) is characterized by an enduring pattern of instability in interpersonal relationships, self-image and affect, and marked impulsivity . DSM-5 aDifferent studies have highlighted the remarkable overlap of symptoms of BPD and ADHD in adulthood, as is the case of impulsiveness, which is considered a core component both of ADHD and BPD . EmotionHowever, although previous studies have described this significant association between BPD and ADHD, its nature has not yet been fully clarified. The evidence suggests that the high frequency with which the two disorders coexist should be interpreted not only as a coincidence of two disorders at a certain period of life . In thisTo study the transition of childhood ADHD to adult BPD, with or without comorbid ADHD, it is necessary to analyze the etiology of each disorder. From twins and twin family studies, ADHD heritability has been estimated to be between 60 and 80% , and aroThus, to analyze the factors that may have a mediating effect on the increase of the risk of developing BPD in childhood ADHD, it is advisable to study the variables that are more characteristic of the development of BPD than of ADHD. This would justify the main aim of this study, which is to analyze the literature about the existing evidence on the environmental factors involved in the developmental trajectory from childhood ADHD to adult BPD, namely traumatic experiences.In this paper, we performed a search for studies dealing with the association ADHD-BPD and environmental traumatic influences. For this purpose, the following bibliographic databases were searched: PubMed, Science Direct and PsychInfo. The following search terms were used: Borderline Personality Disorder AND Attention-Deficit/Hyperactivity Disorder AND childhood traumas or childhood maltreatment OR environmental vulnerability influences. Given the limited results, we added key terms by including emotional dysregulation, impulsivity, environmental, childhood, adolescence, in the association BPD and ADHD, and also in each of the disorders separately. As this is a review of recently published articles on the subject, the studies published before 2000, studies that were not published in English, unsystematic clinical case reports and treatment studies were excluded.We included studies that explicitly mentioned the key terms. The titles and abstracts were screened to eliminate non-relevant and duplicate studies. When a title or abstract seemed to describe a study suitable for inclusion, the full-text article was obtained and examined to evaluate its relevance for our work. A total of 11 articles were potentially relevant in relation to the involvement of traumatic environmental factors in the transition from ADHD in childhood to BPD in adulthood. However, only 4 of them specifically and directly analyzed the possible contribution of traumatic childhood experiences in the evolution of one disorder to the other , 23–25 (Differences in childhood trauma history between adult patients diagnosed with BPD, ADHD, and comorbid BPD-ADHD were assessed from the study of Prada et al., who analyzed the clinical differences between these disorders in adulthood . This stFerrer et al.’s study  analyzedA study conducted with a non-clinical sample of university students was also analyzed . DalbudaNot all analyzed studies have conducted analyses to estimate the effect of childhood traumas on the increased risk of developing a BPD in ADHD patients. At the clinical level, the study of Philipsen et al.  analyzedAlthough the importance of trauma in the subsequent development of BPD has been extensively studied, the available evidence so far of the potential mediating role of childhood maltreatment in the evolution from childhood ADHD to adult BPD is very scarce. While most of the identified studies analyze childhood traumas as a secondary objective, the authors end up highlighting the relevance of the outcome of this specific analysis in the interpretation of the relationship between childhood ADHD and adult BPD.Firstly, all the studies refer to the relationship between the experience of childhood trauma and the severity of psychopathology in adulthood. The study of Philipsen et al.  already Secondly, the descriptive analysis of the differences between the groups included in the studies of this review shows that most of the adult patients studied reported traumatic antecedents in their childhood, even those that did not reach the diagnostic threshold but suffered from functional impairment as a result of their psychopathology , 24. AltIn relation to the analysis of the traumatic childhood event as a risk factor for a subsequent development of BPD in ADHD patients, a history of childhood sexual and emotional abuse has been associated with adult BPD or BPD-ADHD diagnosis , especiaDespite the above-mentioned considerations, several limitations of the review should be noted. Despite the importance of these issues, to date, the studies carried out are limited, and we must be cautious when generalizing the results obtained. In addition, the type of studies from which this evidence comes have relevant methodological limitations, especially the fact that most of them are based on retrospective evaluations and there are no longitudinal studies. Therefore, the results may be conditioned by memory and recall bias and by patients’ subjective evaluations, with a high risk of overvaluing or undervaluing, and thereby reducing the reliability due to the type of designs. However, the fact that the different studies used the same diagnostic instrument, the CTQ, allows us to underline the results obtained. Nevertheless, future longitudinal studies would be necessary to assess the possible impact of trauma from childhood to adulthood from a developmental perspective for a better understanding of ADHD-BPD across the lifespan. Therefore, in the coming years, it is essential for studies to be carried out to define the biological and environmental risk factors to intervene early in childhood and adolescence, to improve their prognosis and to prevent the crystallization of these disorders.Although trauma has been extensively studied in relation to the development of BPD, in recent years, research has raised the question of its role in the ADHD-BPD association. This work reviews the studies published to date and notes that, although they are scarce, some conclusions can be drawn from the available evidence. They all agree that whether or not adult BPD develops from childhood ADHD could be conditioned by the differences in the environmental factors. Specifically, it can be hypothesized that exposure to childhood traumas, especially emotional trauma, which compromise the individual’s emotional maturation, could be one of the variables that increase the possibility of a child with ADHD developing BPD in adult life. The possibility of identifying the role of these variables can be highly beneficial for early diagnosis and intervention in these patients.


N = 55) and patients with ADHD treated with MPH (N = 31) with a healthy control group (N = 80). A neuropsychological test battery assessing basic processes and higher order functions was administered. Hierarchical logistic regression analyses were performed to evaluate the contribution of basic processes to impairments in higher order functions. Patients with ADHD not treated with MPH showed impairments in basic processes and higher order functions compared to controls. The impairments in basic processes explained 41–43% of impairments in executive functions, 27–29% in memory, and 56–74% in complex attention. In patients with ADHD treated with MPH, basic processes were not impaired and did not contribute significantly to impairments of higher order functions. Basic processes may constitute part of the foundation of cognitive impairments in adult ADHD. MPH may improve cognitive performance, presumably through improving basic processes. Applying this information could optimize neuropsychological assessments and inform treatment strategies by targeting basic processes.Attention deficit hyperactivity disorder (ADHD) in adulthood is associated with impairment of multiple aspects of cognition which adversely affect the individual’s everyday functioning. However, little is known about how these impairments are intertwined. This study explores whether impairments in basic processes (processing speed and distractibility) in adults with ADHD explain impairments in higher order functions, namely executive functions, memory, and complex attention. Furthermore, it is explored whether pharmacological treatment with methylphenidate (MPH) affects basic processes and higher order functions. A between-subjects design compared patients with ADHD without stimulant drug treatment ( Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that in many cases persists into adulthood and that is associated with various impairments in everyday life, especially in the social and occupational realm  are among the most robust findings and widely reported in the ADHD literature  is the first-line pharmacological treatment in adult ADHD and may reduce ADHD symptomatology and increase patients’ quality of life Wigal . In prevThe central focus of this study was to explore whether deficits in basic processes (distractibility and processing speed) may affect higher order functions  of adults with ADHD. To do so, several expectations were formulated: In line with previous findings, patients with ADHD without MPH were (1) expected to show impairments in higher order functions, namely complex attention, executive functioning, and memory. Furthermore, this study aimed to explore whether (2) a significant proportion of the impairment in these higher order functions can be explained by impairment of basic processes such as processing speed and distractibility. Moreover, we expect (3) an improvement in some cognitive domains in patients with ADHD treated with MPH compared to patients not treated with MPH. Improvements are expected in some but not all functions, as previous research found that although MPH improves a variety of functions, it does not normalize functioning  participated in this study. Recruitment occurred through self-referral or referral by local psychiatrists or neurologists to the Department of Psychiatry and Psychotherapy, SRH Hospital, Karlsbad-Langensteinbach, Germany. Qualified clinicians from the department performed the diagnostic assessment, which included a clinical psychiatric interview focusing on childhood and current symptomatology. The interview was conducted according to the Diagnostic and Statistical Manual of Mental Disorders criteria , as well as their willingness to participate in the study. The 31 patients treated with stimulant medication were assigned to the ADHD-ON group, while the remaining 55 patients formed the ADHD-OFF group. For all patients, the exclusion criteria were as follows: (a) chronic medical conditions, (b) current or past psychosis, (c) substance abuse in the past 6 months, (d) history of neurological disorders including head injury and (e) verbal IQ estimate lower than 85. Due to these criteria, two patients of the ADHD-OFF group were excluded, as one had a neurological disorder and the other psychosis. Diagnostic subtypes of ADHD and comorbid psychiatric disorders are displayed in Table Controls To form the control group (CG), a total of 80 individuals were included in the study. Recruitment occurred through public announcements, word of mouth and contacts of the researchers. At the clinical assessment, none of controls indicated any history of neurological or psychiatric disease or usage of medications affecting the central nervous system. To control for ADHD symptomatology, all control participants completed the same self-report scales for current and retrospective symptoms as patients. In addition, verbal IQ was estimated through a Multiple Choice Vocabulary Test (Lehrl F (2) = .131; p = .877, gender, χ2 (2)= 1.044; p = .593 and intellectual functions, F (2) = 1.63; p = .199. Patients scored significantly higher than controls on current symptoms  and retrospective symptoms , which corroborated their diagnostic status.st Lehrl . DescripIntellectual functions were assessed with the Multiple Choice Vocabulary Test  was measured with the Logical Memory subtest of the Wechsler Memory scale Wechsler . In thisImmediate recognition (encoding) and delayed recognition (retention) were assessed with the Immediate and Delayed Recognition Tests  in the delay between the study phase and the recognition phase of the delayed recognition test. In the second part of the assessment, participants completed the remaining cognitive tests, including the story recall . In the delay between the first part of the story recall test and the delayed story recall, participants performed nonverbal tests assessing executive functions and attention. Afterwards, participants were debriefed and thanked for their participation at the end of the study. In total, the duration of the assessment was about 2.5 h per participant.The ethics committee of the medical faculty of the University of Heidelberg, Germany, approved the study and its adherence to ethical standards. This research project was conducted in accordance with the Helsinki Declaration.z-score for each set of predictors , the z-scores for each variable of each set were calculated. Variables for which a positive z-score indicated impairment were recoded to ensure that for all variables, a negative z-score indicated impairment as compared to the control group. Next, the average of all z-transformed variables per set of predictors was calculated to represent the composite score per domain. Spearman’s correlation coefficients  of the composite scores and ASRS scores were computed to explore the association with ADHD symptom severity. Furthermore, boxplots were created to display the heterogeneity of cognitive performance within the two patient groups.Firstly, test scores of cognitive functions were compared between the groups. To yield a composite p < .01 in order to control for alpha error inflation due to multiple testing. Dunn’s tests with an alpha correction for multiple comparisons were employed as a follow-up pairwise analysis. This allowed the direct comparison of groups on individual test measures of cognitive performance. Furthermore, effect sizes (Cohen’s r) of all significant group differences were computed. Cohen’s r was chosen as it does not rely on the normality assumption. Based on Cohen’s criteria for r, .1 indicates a small effect, .3 indicates a medium effect, and .5 indicates a large effect , memory (R2 = .582), and complex attention (R2 = .150). In order to delineate to what extent impairments in basic processes account for impairments in higher order functions, hierarchical logistic regression models were employed. Whereas a model including processing speed revealed an impairment of R2 = .305, a hierarchical model including both processing speed and executive functions demonstrated an effect size of cognitive impairment of R2 = .579, indicating that executive functions increased the size of impairment by R2 = .274 in addition to impairments in processing speed. Compared to a model that only includes executive functions (R2 = .467), it can be concluded that processing speed accounted for about 41% (drop of R2 from .467 to .274) of the impairment in executive functions of patients with ADHD. Following this approach, impairments in distractibility (R2 = .318) accounted for R2 = .201  of the impairment in executive functions. With regard to memory, processing speed (R2 = .304) explained 29% (R2 = .582–.414) and distractibility (R2 = .308) explained 27% (R2 = .582–.425) of the impairments in memory functions of adults with ADHD. In complex attention, processing speed (R2 = .300) explained 56% (R2 = .150–.066) and distractibility (R2 = .297) explained 74% (R2 = .150–.039) of the impairment.To investigate the contribution of impairment in basic processes to impairment in higher order functions in the two patient groups, five sets of predictors were distinguished, namely processing speed and distractibility as sets of basic processes and executive functions, memory, and complex attention as sets of higher order functions. Hierarchical regression models were computed in which step 1 included basic cognitive functions (processing speed or distractibility) and in step 2 complex cognitive functions , with patient status (CG vs ADHD-OFF or ADHD-ON) as the outcome variable (Tables R2 = .233) and memory (R2 = .663), but not in complex attention . Whereas impairment was substantially lower in the ADHD-ON group than the ADHD-OFF group in executive function (R2 = .233 vs. .467) and complex attention (R2 = .094 vs. .150), impairments in memory showed a mild increase (R2 = .663 vs. .582). Regarding the effect of impairment in basic cognitive functions on impairment in higher order functions, processing speed did not explain any impairment in executive functions. The level of impairment in executive functions changed only marginally (R2 = .233–.237) when processing speed was already included in the model. Similarly, distractibility did not explain any impairment in executive functions, as the impairment in executive functions changed only slightly with distractibility included in the model (R2 = .233–.239). Processing speed influenced the impairment in memory only marginally (R2 = .663–.661) and distractibility (R2 = .663–.595) explained 10% of the memory impairment of the ADHD-ON group. Finally, no significant models were obtained for complex attention, indicating that the ADHD-ON group did not show any significant impairments in complex attention when compared to theCG (Table Logistic regression models of cognitive impairment with group status (ADHD-ON versus CG) as dependent variable are presented in Table The aim of this study was to investigate whether impairments in basic cognitive processes can explain impairments in higher order functions in adults with ADHD. The results confirmed this prediction as impairments in processing speed and distractibility (basic processes) accounted for a considerable part of the impairment of the higher order processes . Thus, the current evidence adds to previous literature  and distractibility . This is in line with a large body of research indicating slower reaction times and greater reaction time variability in adults with ADHD , memory , and complex attention , as compared to controls. With regard to individual tests, large differences were found between patients with ADHD and controls concerning planning, immediate and delayed recall as well as prospective memory . The author found that executive functioning as well as other neuropsychological measures (e.g. vocabulary ability) were closely related to reasoning but also perceptual speed. It is especially noteworthy that this relationship between perceptual speed and higher order processes was found in a sample of healthy participants and not in a clinical population. It follows from the evidence enumerated above, that processing speed represents a basic process that may underlie a variety of higher order functions, and maybe this holds true not just for adults with ADHD but represents a more general cognitive mechanism that is also applicable to other populations.After establishing the level of impairment in both basic processes and higher order functions, the next step underpinned the central question of this study, namely whether a part of the impairment in these higher order functions can be attributed to impairment in the basic processes. Indeed, we found that impairment in basic processes explained a considerable proportion of impairment in the higher order functions . Although no previous studies have explicitly investigated the link between impairments in basic processes and higher order functions in adults which ADHD, a few studies have investigated related elements. Fair et al.  conducteRecently, evidence for the pervasiveness of impairments in RTV and processing speed in ADHD has been growing (Cross-Villasana et al. The investigation of the effects of pharmacological treatment with MPH on cognitive functions provided converging evidence to the role of basic processes. Salum et al.  noted anThese findings are in line with previous research indicating that MPH improves but does not normalize cognitive functioning in adults with ADHD (Fuermaier et al. In future research, it is worth exploring exactly how this foundation is composed, to identify which basic processes constitute this foundation, which of them are functioning well and which are impaired in adults with ADHD. This information could be used to inform treatment strategies, as specifically targeting basic processes may lead to improvements in other cognitive domains. Thus, the implications for clinical practice are twofold. Firstly, the information that basic cognitive functions may constitute the foundation of cognitive impairment would allow clinicians to optimize the clinical assessment of adults with ADHD. Currently, large test batteries are commonly being used and there is little consensus as to which tests need to be included (Fuermaier et al. Several limitations of the present study must be noted. As this study did not employ a within subjects design on patients treated and not treated with MPH, the findings regarding the pharmacological treatment with MPH should be interpreted with caution. There may be qualitative differences between the two groups with regard to symptom presentations and comorbidities. This may partly be explained by the context that MPH is not randomly administered but depending on the clinical characteristics of the individual patient. Thus, no causal relationship regarding the effects of MPH on cognition can be established. It would be interesting for future research to replicate the study by employing a within subjects design and also to explore whether basic processes are differentially affected in the different symptom presentations of ADHD. For example, one may speculate that processing speed plays a larger role in the inattentive versus the hyperactive symptom presentation. Furthermore, the results of the study may be affected by the selection of the neuropsychological tests. In addition, considerable overlap may exist between tests (Salthouse In conclusion, the present findings highlight the importance of basic processes in the cognitive functioning of adults with ADHD. Basic processes seem to constitute at least part of the foundation upon which higher order functions are built upon. Consequently, impairments in these basic processes may have repercussions for a variety of higher order functions. This is also supported by the finding that a pharmacological treatment with MPH appears to improve basic processes and it could be argued that the improvements in basic processes partially account for improvements in higher order functions. Accordingly, utilizing this information in clinical settings could allow us to optimize the assessment of ADHD in adulthood. Basic processes may constitute a good target for treatment interventions, as improving basic processes may result in improvements in other cognitive functions as well. Designing and administering cognitive training interventions or medications that directly target processing speed and distractibility could generalize to improvements across a number of higher cognitive domains.


Secale cereale L.) is a cereal grass that is an important food crop in Central and Eastern Europe. In contrast to its close relatives wheat and barley, it was not a founder crop of Neolithic agriculture, but is considered a secondary domesticate that may have become a crop plant only after a transitory phase as a weed. As a minor crop of only local importance, genomic resources in rye are underdeveloped, and few population genetic studies using genomewide markers have been published to date. We collected genotyping‐by‐sequencing data for 603 individuals from 101 genebank accessions of domesticated rye and its wild progenitor S. cereale subsp. vavilovii and related species in the genus Secale. Variant detection in the context of a recently published draft sequence assembly of cultivated rye yielded 55,744 single nucleotide polymorphisms with present genotype calls in 90% of samples. Analysis of population structure recapitulated the taxonomy of the genus Secale. We found only weak genetic differentiation between wild and domesticated rye with likely gene flow between the two groups. Moreover, incomplete lineage sorting was frequent between Secale species because of either ongoing gene flow or recent speciation. Our study highlights the necessity of gauging the representativeness of ex situ germplasm collections for domestication studies and motivates a more in‐depth analysis of the interplay between sequence divergence and reproductive isolation in the genus Secale.Rye ( It is a diploid (2n = 14) grass of the Triticeae tribe, which also includes wheat (Triticum spp.) and barley (Hordeum vulgare L.). The major rye‐growing regions of the world are Central and Eastern Europe (http://www.fao.org/faostat), whose colder climate favors the high frost tolerance of rye and its ability to thrive on poor soils. Under such adverse growth conditions, rye is higher yielding than wheat. The closely related cereal crops wheat, barley, and rye share many characteristics: (i) The center of diversity of the wild progenitors of these three crops is the Fertile Crescent and neighboring regions , and two other wild species S. strictum and S. sylvestre , and morphological characters such as hairiness of leaf sheath of spike brittleness  data of rye and its wild relatives obtained through genotyping‐by‐sequencing  were selected based on passport information  available in the genebank information system of the German Federal ex situ Genebank at IPK Gatersleben . Variant calling was performed with SAMtools and BCFtools version 1.3 , SNPRelate . DOIs were registered with e!DAL  were calculated on previously defined groups using the modified Hudson estimator  tree  corroborated the clear separation between Secale species and the weak differentiation between S. cereale subsp. vavilovii and the other S. cereale subtaxa  than had S. sylvestre (51.1%), indicating that S. sylvestre split first from the lineage leading to S. strictum and S. cereale in agreement with AFLP phylogeny of Chikmawati, Skovmand, and Gustafson . The first four components together explained only 6.7% of the variance, indicating low genetic differentiation between populations. A Mantel test on genetic distances based on pairwise identity‐by‐state analysis and the geographic origin given in the passport data revealed a weak (r = .09), albeit significant (p = .01), correlation.Studies in wild and domesticated barley have shown (i) a clear separation of the crop and its wild progenitor and (ii) a good correlation between geographic and genetic distance in the crop and, independently, the wild relative  was intermediate between R1003 and the remaining samples. We used D‐statistics  from Armenia that also shared significantly more derived alleles with both R1003 and R2859 than with other S. cereale accessions . This shared ancestry could be caused by recent interspecific gene flow or shared ancestral variation. An improved, physically ordered reference genome sequence would enable the inspection of haplotype lengths to date hybridization events  had shattering ears, supporting their wild‐growing status.In the past, several taxa included in our study such as d et al.  who founSecale is not unexpected: Previous studies have examined the crossability of different Secale species and have identified chromosomal rearrangements as likely causes for frequent hybrid sterility  and wild rye   Figure  provide ) Figure . In prinBona fide wild accessions cluster closely together in the PCA plot  of rye.In contrast to the situation in barley To summarize, our data are consistent with the notion that the domestication history of rye is more complex than that of the Neolithic founder crops wheat and barley. We believe that a more comprehensive assessment of the rye genetic diversity maintained in ex situ collections and, subsequently, a targeted effort toward broader sampling of wild and weedy populations are necessary to better understand the population structure in domesticated rye and its wild relatives.https://doi.org/10.5447/ipk/2018/1.Data for this study are available at the European Nucleotide Archive under accession number PRJEB22681 at the Plant Genomics and Phenomics Research Data Repository under the Digital Object Identifier None declared. Click here for additional data file. Click here for additional data file. Click here for additional data file.


Objective: The aim of this study was to examine how attention-deficit hyperactivity disorder (ADHD) symptoms play an interaction effect on the association between psychosocial work environments and health  among workers.Methods: This is a cross-sectional study of 2,693 employees at a pharmaceutical company using a self-administered questionnaire evaluating ADHD symptoms , psychosocial work environments , and health outcomes . Multiple regression analyses were applied to assess the interaction between ADHD symptoms and psychosocial work environments on health outcomes.Results: The prevalence of workers with ADHD symptoms was 5.9% (n = 159). Significant interaction effects of ADHD symptoms × job control and ADHD symptoms × social support were observed  on psychological distress after adjustment of age, sex, occupation and education. The interaction effect of ADHD symptoms × each psychosocial work environment was not observed on work engagement.Conclusions: Job control and social support were more influential factors that were related to psychological distress in accordance with ADHD symptoms. This study also found no difference of the interaction between psychosocial work environments and ADHD symptoms on work engagement. To the best of our knowledge, this study was first to clarify the effect of ADHD symptoms on the association between psychosocial work environments and health outcomes . These findings can aid employers how to arrange better work environments for workers with ADHD symptoms. Attention-deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder characterized by inattention, excessive motor activity, and impulsivity. ADHD starts in childhood and can persist into adolescence and adulthood , 2. AdulIndividuals with ADHD are common in the workplace. An estimated 1.9–4.2% of workers are reported to have adult ADHD in the United States, and an average of 3.5% was found among workers in 10 countries  . MoreoveThe mental health of workers is associated with the psychosocial work environments. The past study indicated that unfavorable psychosocial work environments, such as high job demands, low job control and low social support are associated with psychological distress of workers . It was The purpose of this study was to investigate how ADHD symptoms modify the relationship psychosocial work environments and negative/positive aspects of mental health  for workers.We have two hypotheses.Hypothesis 1. ADHD symptoms enhance the association between low job control and psychological distress.Workers with ADHD symptoms have the difficulty to follow the instructions of others , and theHypothesis 2. ADHD symptoms enhance the association between high job control and work engagement.Adults with ADHD tend to be resilient and creative, to have foresight, and to generate ideas . WorkersIn addition to two hypotheses, we conducted the exploratory analyses to investigate how ADHD symptoms modify the relationship other psychosocial work environments  and health for workers.n = 4,738; male = 3,361, female = 1,377) to inform them about the study and encourage them to complete the questionnaire. The questionnaire included psychosocial work environments, psychological distress, work engagement, and the Adult ADHD Self-Report Scale short version (ASRS screener)  . Only thThe research protocol was approved by the Ethics Committee of Medical Research, University of Occupational and Environmental Health, Japan.The short-form ASRS Screener is available in many languages and comprises a checklist of six questions about ADHD symptoms based on the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision . RespondWe used the Brief Job Stress Questionnaire (BJSQ) to measure job stressors . The BJSJob demands include qualitative job overload (three items) and quantitative job overload (three items). Total possible score ranges from 6 to 24. Job control consists of three items, and the total possible score for job control ranges from 3 to 12. Social support at the workplace includes supervisor support (three items) and coworker support (three items), with total possible scores ranging from 6 to 24. Cronbach's alpha coefficient of job demands, job controls, and social support were 0.79, 0.83, and 0.88, respectively.Psychological distress was measured using the Japanese version of the K6 scale, which has demonstrated acceptable internal consistency, reliability, and validity . The K6 Work engagement was assessed using the nine-item Japanese version of the Utrecht Work Engagement Scale (UWES-9) . The UWEThe questionnaire also measured the following demographic characteristics: sex, age, education, and occupation. Age was used as a continuous variable. Education was categorized into four groups . Occupation was categorized into six groups based on the categories established in the International Standard Classification of Occupation: supervisory, clerical, blue collar, sales, research, and technical. Dummy variables were created using the clerical category as a reference.post-hoc simple slope analyses at one standard deviation above/below the mean score of ASRS scores. In a series of analyses, R2, adjusted R2, and ΔR2 were calculated in each step to assess model fit. In addition, residual analyses were conducted to estimate the amount of autocorrelation in the residuals using the Durbin-Watson statistic . The level of significance was 0.05. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 24 .We calculated means and standard deviations, or proportion of the demographic characteristics of participants. To assess for interaction between the severity of ADHD symptoms and psychosocial work environments, we conducted multiple regression analyses using ASRS totals as continuous variables among all participants. Prior to testing, the total ASRS, job demands, job control, and social support scores were mean-centered. ASRS scores, job demands × ASRS, job control × ASRS, and social support × ASRS were included as independent variables. Psychological distress and work engagement were used as dependent variables. We first conducted a crude model (Model 1), then adjusted for age and sex to generate a second model (Model 2). Psychosocial work environments differ depending on occupation, and health outcomes differ depending on socioeconomic status such as education. To confirm the consistency of results, we created additional models adjusted for occupation (Model 3), and education (Model 4). When significant interaction effects of psychosocial work environments × ASRS were observed, we conducted n = 159). The respondents were 2,791 workers out of all employees (response rate = 59.8%). The proportion of women and mean age of respondents and all employees were 28.1%, 42.7 and 29.1%, 42.5, respectively. After excluding cases with missing data, 2,693 cases were analyzed as complete cases. In this sample, the prevalence of workers with ADHD symptoms was 5.9% (p < 0.01), as well as a significant interaction effect of social support × ASRS on psychological distress . However, no significant interaction of job demands × ASRS on psychological distress was seen. Because we observed significant interactions of job control × ASRS, and social support × ASRS, we conducted post-hoc simple slope analyses at one standard deviation above/below the mean ASRS score. The post-hoc simple slope analyses showed that the simple slopes of job control and social support were greater at higher levels of ASRS compared to the lower levels of ASRS.For residual analyses, the Durbin-Watson statistic ranged from 1.988 to 2.041 , which indicated there was almost no autocorrelation in the residuals see , 3.This study demonstrated that there was a significant interaction effect of job control × ADHD symptoms and social support × ADHD symptoms on psychological distress. This study also found there was no interaction effect of psychosocial work environments × ADHD symptoms on work engagement.Multiple regression analysis showed an interaction effect of job control × ASRS severity on psychological distress. Greater job control was associated with lower psychological distress, and ADHD symptoms strengthened the association. These findings suggest that greater levels of job control are important to maintain mental health for workers with ADHD symptoms. However, past studies have shown that in workers with Autism Spectrum Disorder (ASD), greater job control is associated with poor health quality . ADHD anMultiple regression analysis showed no interaction effect of job demands × ASRS severity on psychological distress. Workers with ADHD often have the entrepreneurship and professionalism . These cWe found that there was no significant interaction effect of job demands × ADHD symptoms and job control × ADHD symptoms on work engagement. Workers who interpret high job demands and high job control as a challenge may show improved work engagement. Although motivational themes identified by individuals with ADHD symptoms are similar to those identified by workers without ADHD symptoms, past research has shown that the details of the motivational factors differ, and that individuals with ADHD symptoms do not prefer predictable and familiar tasks . It may Multiple regression analysis also did not show a significant interaction effect of social support × ADHD symptoms on work engagement. Bozionelos reported that incremental feedback on individual tasks resulted in greater improvements in work efficiency in workers with ADHD than in those without ADHD . It is dThe prevalence of workers with ADHD symptoms in this study was 5.6%, a slightly higher than the prevalence rate by structured interview [3.5%  and 6.0%The mental health status of workers with ADHD symptoms was poorer than that of workers without ADHD symptoms, which supports past findings . Among wSeveral limitations of our study warrant mention. First, all participants were from a single pharmaceutical company, and work engagement levels were higher than among other Japanese workers . This maDespite these limitations, this study is to our knowledge the first to investigate the role of ADHD symptoms on the relationship between psychosocial work environments and negative/positive health. This work may serve as a basis for future discussion of the preferred psychosocial work environments for workers with ADHD symptoms.MN, TN, and KM conceived and coordinated the project. MN, TN, and AI completed the analysis. MN and TN drafted the initial manuscript. MN, TN, AI, KM, and SM revised the manuscript, and commented on drafts of the report.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The physico-chemical properties of CSAC and CSAC modified by H2O plasma (HCSAC) were revealed by automated surface area and pore size analysis, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and Raman spectroscopy. Electrochemical work was applied to investigate the electrochemical properties of CSAC and HCSAC. The results obtained showed that plasma modification improved the specific capacitance of CSAC by 64.8%  within 100 s. This result is ascribed to the oxygen functional groups introduced to the surface of CSAC. It can also improve the hydrophilicity and wettability of the carbon surface leading to an increase from 76.7% to 84.6% in specific capacitance retention. Furthermore, H2O plasma modification can introduce oxygen functional groups without destroying the initial pore structures of CSAC. In summary, we provide a simple, fast, environment-friendly modification method to enhance the electrochemical properties of CSAC.Commercial coconut shell-based activated carbon (CSAC) has low specific capacitance and specific capacitance retention owing to its undeveloped pore structure and low proportion of heteroatoms. In this study, dielectric barrier discharge plasma was used to enhance the specific capacitance and rate capability of CSAC. H Coconet al. have performed water vapour plasma modification on wheat straw to improve bonding property. Higher wettability and surface polarity were achieved by introducing massive oxygen-containing groups [To date, a variety of modifications, including wet or gas oxidation, supercritical fluids, electrochemical oxidation, ion or cluster bombardment and plasma modification and activated carbon modification, have been applied to achieve higher electrochemical capacitance by changing the specific surface, porous structure and the type, content and bonding mode of heteroatoms on the surface of activated carbon ,7. In geg groups . In this2O as an excitable medium in the fast modification of commercial CSAC, which has never been discussed. A variety of methods were used to reveal the changes in the chemical and physical structures of CSAC after plasma modification. The characterizations were significant in the use of industrial by-product by the addition of value and the application of coconut shell in the supercapacitor electrode material.In the current study, DBD plasma was applied using H2.2.1.The precursor material used in this study is commercial CSAC, supplied by Nanjing Wood Linsen Carbon Company. Acetone, ethanol, hydrochloric acid (HCl), potassium hydroxide (KOH), and carbon black, used as a conductive agent, and polytetrafluoroethylene (PTFE) latex (60 wt.%), used as a binder, were purchased from Nanjing Chemical Reagent Co., Ltd . All mentioned agents were used as received. The nickel foam  was first immersed in acetone solution with an ultrasonic bath for 1 h then dipped in HCl (5%) for 1 h after ethanol cleaning. Finally, it was cleaned in ethanol again and dried in a vacuum oven at 40°C for 12 h.2.2.−1 HCl, adjusted to neutrality by deionized water and dried at 110°C for 12 h before use. The diagram of the experimental device for the H2O plasma modification is shown in 2O to 70°C and a vacuum pump was applied, keeping the pressure of the reactor chamber at 30 kPa. A number of preliminary experiments were carried out and the experimental conditions  can achieve better electrochemical performance.CSAC was rinsed repeatedly to remove the ash content and soaked for 24 h with deionized water. Then CSAC was adequately washed with 1 mol l2.3.−1. Transmission electron microscopy  was used to observe the morphology of the samples. The carbon samples were added into propanol and sonicated before dispersing on copper grid film before testing. X-ray photoelectron spectroscopy  was applied to investigate the surface atomic compositions and chemical functional groups of activated carbon. The C 1 s was deconvoluted into several components using XPSPEAK Software (v. 4.0). The composition of C, N, O elements was determined by the low-resolution spectra (0–1200 eV). The relative proportion of surface oxygen, nitrogen and carbon elements was calculated by the integrated area of each element divided by the integrate area of all the elements , respectively (XPS spectra of CSAC and CSAC modified by H2O plasma (HCSAC) are available in the electronic supplementary material, figure S1). Raman spectra of activated carbon were recorded by Raman spectroscopy  with laser radiation at a wavelength of 532 nm.Automated surface area and porosity analysis  was employed in recording the nitrogen adsorption–desorption isotherms at 77 K. Brunauer–Emmett–Teller (BET) and density functional theory (DFT) were used to reveal the specific surface area and the pore size distribution, respectively . The tem2.4.2 and dried at 60°C for 12 h. The resulting nickel foam was pressed under a pressure of 15 MPa to assemble the working electrodes. All electrochemical measurements were carried out on an electrochemical workstation . For a three-electrode system in 6.0 M KOH aqueous solution electrode, CSAC and HCSAC were used as the working electrodes, and the Hg/HgO electrode and the platinum foil were selected as the reference and counter electrode, respectively. Cyclic voltammetry (CV) and galvanostatic charge–discharge (GCD) measurements were performed over a potential range from −1 to 0 V. The electrochemical impedance spectroscopy (EIS) measurements were recorded in a frequency range from 100 kHz to 10 mHz with an amplitude of 5 mV at open circuit potential. The specific capacitance of the electrodes (C) was calculated by the following equation:C is the specific capacitance (F g−1), I is the constant charge–discharge current (A), t is the discharge time (s), V is the total change in voltage (V), and m is the mass of the active material in an electrode (g).Activated carbon, carbon black and PTFE were mixed with a weight ratio of 8 : 1 : 1 in an agate mortar to obtain a homogeneous slurry. The slurry was pressed onto a piece of nickel foam with an apparent area of 1 cm3.3.1.2 adsorption–desorption isotherms and the DFT pore size distributions of CSAC and HCSAC. Both the CSAC and HCSAC exhibit similar combined type I and IV isotherms with small H4 type hysteresis according to the IUPAC classification [2 g−1). The size of micropores for the samples displays a multimodal distribution with three peaks at 1.5, 1.7 and 2 nm, and the ratio of micropores has a slight increment after plasma modification, which leads to the increase in BET surface area. It is observed that DBD plasma modification hardly damages the hierarchically pore structures to CSAC.fication ,16. An afication . Furtherfication . The coefication . It can 3.2.−1) and D-band (1320–1370 cm−1) of CSAC and HCSAC. Based on previous studies, the G-band represents graphite in-plane vibrations, while the D-band is attributed to the breathing vibrations of sp2 rings or the double-resonance Raman process in disordered carbon structure [ID/IG) has been calculated because the ID/IG represents the graphitic degree of the carbon materials. It can be observed that the ID/IG value increases from 0.95 to 0.98; the slight increment means DBD plasma modification hardly destroys the graphitic order. The morphology of CSAC and HCSAC was further studied by TEM, as shown in tructure . The brotructure . The rel3.3.−1 is associated with the –OH stretching vibration due to the surface adsorbed moisture [−1 is attributed to CH3 bands which are consistent with the C–H stretching appearing at 1382 cm−1 in fingerprints. Another peak located at 1575 cm−1 reveals the presence of C = C aromatic bonds among samples [−1 is designed to be the C–O bond from esters and ethers [−1 indicates that alkyl groups are included in samples after plasma modification [FTIR was used in this study shown in  to invesmoisture . The pea samples . The band ethers . The enhfication .Figure a,b, the C 1 s spectrum can be resolved into four individual peaks based on the previous literature ; 289.1 eV, carboxyl peak) [figure 6c,d, the O 1 s spectrum of CSAC and HCSAC can be resolved into three individual peaks based on the previous literature  [figure 6e,f, the N 1 s spectrum can be fitted by three peaks  [2O molecule. It has been reported that the increase in the content of carbonyl (–C = O) is beneficial to the electrochemical properties of activated carbon [The surface elemental compositions of CSAC and HCSAC were further investigated by XPS, as shown in figure 6yl peak) –28. As sr water) . As showitrogen) . The nit3.4.2O plasma has the ability to improve the electrochemical performance of CSAC within a short time . Figure 8a shows the CV plots of the CSAC and HCSAC electrodes at a sweep rate of 10 mV s−1. The CV plots of the foam nickel (current collector) are known beforehand, which produces less capacitance than other samples. As for the carbon electrodes, all the CV diagrams display a quasi-rectangular shape, which could be mainly ascribed to EDLC and supplemented by pseudo-capacitance owing to oxygen functional groups on the carbon surface. The additional pseudo-capacitance is attributed to oxygen functional groups. Previous studies demonstrate that some oxygen functional groups can directly participate in faradaic reactions not only in acidic medium, but also in alkaline medium [b) of CSAC and HCSAC at a current density of 1 A g−1 show typical triangular shapes. Owing to the oxygen functional groups in HSCAC, the GCD curves are imperfectly symmetrical but slightly distorted, which was consistent with the CV graphs. A high specific capacitance of 155.2 F g−1 higher than CSAC by 64.8% is attained at the current of 1 A g−1. To further comprehend the capacitive behaviour of SCAC and HSCAC, EIS was performed over a frequency range from 10 kHz to 10 mHz (c). The Nyquist plots of CSAC and HSCAC electrodes exhibit similar shapes, in which short x-intercept, small diameter of an inconspicuous semicircle and high slope of the straight line are indicative of an ideal capacitive performance. In the low-frequency region, the line with a slope of 45° accorded with the Warburg resistance of electrolyte ions to the electrode surface. The more vertical and short line of HCSAC over CSAC electrode illustrates electrolyte ions transferring to the pore of activated carbon through a short diffusion path because of higher hydrophilicity and developed pore structures after modification. The intercept on the real axis is related to the internal resistance (iR), including the resistance of bulk electrolyte, intrinsic active material resistance and their contact resistance with the foam nickel [Ri of samples was below 0.4 Ω, demonstrating good electrical conductivity of materials. The increased internal resistance of the HCSAC electrode can be ascribed to the presence of surface oxides and thus increase the ohmic resistance along the axial direction of micropores, which show more quantity in HCSAC than in CSAC [Rct) between the interface of electrolyte and electrode. The smaller diameter in the semicircle of HCSAC electrodes illustrated the lower Rct at HCSAC–electrolyte interfaces mainly due to the higher hydrophilicity after the introduction of oxygen functional groups that enabled rapid ion diffusion and ideal capacitive behaviours. As shown in figure 8d, an increase from 76.7% to 84.6% in capacitance retention was observed when the current density increased from 0.5 to 10 A g−1 after plasma modification. This result is attributed to a higher microporous utilization rate at high current density after plasma modification. The life cycles of HCSAC at different current densities for 1000 cycles to prove the reusability of HCSAC can be seen in The electrochemical properties of CSAC and HCSAC electrodes are studied by CV measurement . 6.0 M KOH aqueous electrolyte is selected due to its high ionic conductivities . It can e medium ,35. The e medium ,37. In ce medium ,39. The e medium . Generale medium –40. The o 10 mHz c. The Nym nickel . The Ri  in CSAC . With th4.2 g−1) of HCSAC shows an unremarkable change in comparison with the initial material. A 60.4% higher surface oxygen content is observed compared with the untreated materials, indicating massive free radicals are generated and introduced to the carbon surface during H2O plasma modification. Quinolyl (–C = O) exhibits a 74.5% increment after modification, which is capable of facilitating electrochemical redox activity and improving the hydrophilicity and wettability of the material surface. H2O plasma modification improves the specific capacitance of CSAC by 64.8% at a current density of 1 A g−1. A higher specific capacitance retention of 84.6% is also achieved. Massive free radicals were generated and introduced to the carbon surface during H2O plasma modification; in particular, quinonyl (−C = O) was successfully incorporated after plasma modification. Furthermore, H2O plasma modification can introduce oxygen functional groups without destroying the initial porous structure of CSAC.A simple, fast and environment-friendly method was provided to enhance the specific capacitance and capacitance retention of CSAC. The BET surface area (846.0 m


CM-Dil-labeled hUC-MSCs were found to engraft within the recipient liver, whereas the homing of cells to the recipient liver in the P10 hUC-MSCs group was less effective compared to the P5 hUC-MSCs group. Previous studies have shown that the concentration of hepatocyte growth factor (HGF) in the injured liver was significantly increased. HGF is commonly known as the ligand of c-Met. The level of c-Met in hUC-MSCs as detected by Western blotting indicated that at a higher passage number, there is a decrease in c-Met. These data suggest that direct transplantation of P5 hUC-MSCs can more efficiently home to an injured liver. Subsequently, the P5 hUC-MSCs can rescue ALF and repopulate the livers of rats through the stimulation of endogenous liver regeneration and inhibition of hepatocellular apoptosis for compensated liver function, which is dependent on the higher level of c-Met than P10 hUC-MSCs.Recent studies have described beneficial effects of an infusion of mesenchymal stem cells (MSCs) derived from Wharton's jelly tissue, for the treatment of acute liver failure (ALF). However, data on the therapeutic potential of culture-expanded MSCs are lacking. We examined the therapeutic potential of passage five (P5) and ten (P10) human umbilical cord- (hUC-) MSCs via their transplantation into Sprague-Dawley (SD) rats with D-galactosamine  and LPS-induced acute liver failure (ALF). SD rats were randomly divided into three groups: control group, P5 hUC-MSCs group, and P10 hUC-MSCs group. After transplantation, P5 hUC-MSCs provided a significant survival benefit. The analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) levels showed that transplantation with P5 hUC-MSCs was more effective than treatment with P10 hUC-MSCs. P5 hUC-MSCs also successfully downregulated the hepatic activity index (HAI) scores. Compared to P10 hUC-MSCs  Liver failure is a clinical syndrome characterized by jaundice, ascites, hepatic encephalopathy, and a bleeding tendency due to the impaired liver function. The syndrome can be caused by a variety of factors such as viral hepatitis, autoimmune hepatitis, drug-induced liver injuries, metabolic diseases, and circulatory disturbances .To date, the only therapeutic option for liver failure is orthotopic liver transplantation. Reasons for failure to receive transplantation have included lack of available organs, high expense, and the requirement for lifelong immunosuppressive medication. Other treatment strategies include bioartificial livers that are short of liver cells and medical management . ConsequRecently, several studies reported that human umbilical cord mesenchymal stem cells (hUC-MSCs) are another promising source, as they are free from aging and are unlimited in their supply. They are also characterized by lower immunogenic potency, higher proliferative activity, and multipotency . GholamrHepatocyte growth factor (HGF), which is the most effective mitogen for hepatocytes, functions via a receptor termed the cellular mesenchymal to epithelial transition factor (c-Met) . The HGFIn this study, we aimed to investigate the effect of CM-Dil-labeled hUC-MSCs on liver failure and the underlying mechanism of homing among various passages in hUC-MSCs.Male Sprague-Dawley rats weighing 220 to 250 g were purchased from the Animal Laboratory Center of Nanjing Medical University . All procedures were performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Nanjing Medical University. All experimental protocols were approved by the Animal Ethical and Welfare Committee of Nanjing Medical University .P2 hUC-MSCs were purchased from Cyagen. The cell pellet was cultured in an expansion medium composed of the human umbilical cord mesenchymal stem cell basal medium , supplemented with 10% human umbilical cord mesenchymal stem cell cell-qualified fetal bovine serum, 1% glutamine, and 1% penicillin-streptomycin (Cyagen), at 37°C, with 5% carbon dioxide in a fully humidified environment.6 cells/mL, washed twice in phosphate-buffered saline (PBS), and then incubated for 30 min at 4°C in the dark with the following anti-human antibodies conjugated with fluorescein isothiocyanate (FITC) or phycoerythrin (PE): anti-CD31-PE (303105), anti-CD45-PE (368509), anti-CD34-PE (343605), anti-CD44-FITC (338803), anti-CD90-FITC (328107), and anti-CD105-FITC . After 30 min, cells were washed and resuspended in 300 mL Cell Fix (BD). PE-conjugated IgG1 and FITC-conjugated IgG1 were used as isotype controls (R&D Systems Inc. and Santa Cruz Biotechnology Inc.). Immunophenotyping of hUC-MSCs was performed by flow cytometry.Native hUC-MSCs (at P5) were suspended at a concentration of 1 × 10μg/kg body weight; Sigma) were dissolved in PBS and simultaneously administered to animals intraperitoneally. Cells were transplanted under 10% chloral hydrate injection anesthesia, 24 h after the administration of D-GalN/LPS. SD rats were randomly divided into three groups: group A, rats that received 1 mL of normal saline via tail vein as the control (n = 12); group B, rats that received 1 mL of P5 hUC-MSCs (1 × 107 cells/kg) via tail vein (n = 12); and group C, rats that received P10 hUC-MSCs (1 × 107 cells/kg) via tail vein (n = 12). Blood samples were collected at 24 h, 48 h, and 72 h after the injection of D-GalN/LPS, and finally, entire livers were collected, fixed, then prepared for further analysis.The animal model used was described in a previous study . D-galacSerum samples were stored at −80°C until the time of analysis. Serum aspartate aminotransferase (AST), total bilirubin (TBil), and alanine aminotransferase (ALT) levels in the rat blood were measured according to the manufacturer's directions with a kit from the Nanjing Jiancheng Bioengineering Institute .μm and stained with hematoxylin & eosin (H&E). Histological assessment was performed using the hepatic activity index (HAI) and was graded following guidelines previously described [Formalin-fixed, paraffin-embedded liver samples were sectioned at a thickness of 4 escribed .μg/mL) for 5 minutes at 37°C, and then for an additional 15 minutes at 4°C. Following labeling, the medium was discarded, and the cells were washed three times with PBS to eliminate residual fluorescent-conjugated antibodies. At 24 h after the injection of D-GalN/LPS, the labeled P5 and P10 hUC-MSCs  were transplanted into the rats, and the control rats received 1 mL of normal saline. After an additional 24 h, the rats were killed so the livers could be removed. The frozen sections were examined by fluorescence microscope and analyzed by Image-Pro Plus.Before labeling, the P5 and P10 hUC-MSCs in plates were trypsinized for cell counting. CM-Dil  was then directly added to the culture medium to label cells in the working solution  immunohistochemistry, sections were blocked with 1.5% bovine serum albumin (BSA) for 30 minutes and incubated with anti-mouse PCNA  overnight at 4°C. Sections were washed and incubated with a rabbit anti-human IgG secondary antibody  for 50 minutes at room temperature. The sections were then added to a newly prepared DAB kit . The positive nucleus is indicated with brown and yellow colors. Sections were counterstained with hematoxylin for 3 minutes and 1% of hydrochloric acid for several seconds. Finally, the sections were observed under a Nikon light microscope after being dehydrated. For terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) staining, we used the In Situ Cell Death Detection Kit  according to the vendor's instructions.To detect the level of c-Met, the total protein samples in the same quantity for P3, P5, P8, and P10 hUC-MSCs were extracted. Proteins were identified based on instructions provided with the BCA Kit  and then separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred onto nitrocellulose membranes. The membranes were incubated with mouse monoclonal anti-c-Met antibody  at a 1 : 500 dilution overnight at 4°C and then incubated with a sheep anti-mouse immunoglobulin G secondary antibody  for 60 minutes at room temperature. The results were detected using an enhanced chemiluminescence (ECL) kit  and visualized under an imaging system.P value of <0.05 was considered to be statistically significant.The data are expressed as mean ± standard deviation (SD) using SPSS version 16.0 . Statistical significance was determined via a one-way analysis of the variance (ANOVA) and the log-rank test for survival analysis among the three groups. A in vitro, without significant changes in morphology. Flow cytometry revealed that these cells were negative for the expression of hematopoietic markers such as CD45, CD34, and CD31. However, they were positive for CD105, CD90, and CD44, which are generally considered to be markers of MSCs. This indicated that these cells were hUC-MSCs , while the liver function of the P10 hUC-MSCs group still increased . 48 h after transplantation, the serum levels in the P10 hUC-MSCs group were also dramatically decreased , with indicators of liver injury that were still lower than those of the rats that received the P5 hUC-MSCs . Moreover, significant differences in serum levels of ALT, AST, and TBil between the P5 hUC-MSCs group and P10 hUC-MSCs group were observed at 48 h and 72 h post-D-GalN/LPS injection (P < 0.01). No significant differences were observed at 24 h after the D-GalN/LPS coinjection.As shown in Figures P < 0.05; To evaluate whether treatment with P5 hUC-MSCs regenerated the injured liver to a greater extent than with P10 hUC-MSCs, we further assessed the liver histology with H&E staining. H&E-stained sections revealed massive necrosis and hepatic lobule damage in the control group at 72 h, but hepatocyte necrosis was suppressed in both the P5 hUC-MSC and P10 hUC-MSC groups . While mTo determine whether different passages of hUC-MSCs have an impact on hepatocellular apoptosis, the number of TUNEL-reactive hepatocyte nuclei in liver sections was determined. Four 400x fields were randomly selected from the three groups, and the number of accumulated apoptotic cells was counted using Image-Pro Plus software. Many apoptotic hepatocytes were observed in the control samples (NS: 24.0 ± 4.8), while a significant reduction was present with hUC-MSC treatment  were engrafted via tail vein 24 h after the injection with D-GalN/LPS. As shown in The administration of P5 hUC-MSCs to rats with injured livers is more effective than P10 hUC-MSCs. Importantly, primary MSCs lose ligands or receptors that respond to migratory signals during xpansion . TherefoOur primary experiment found that levels of HGF in the liver significantly increased and peaked at 24 h and 48 h, respectively, post-D-GalN/LPS injection. In addition, overexpressed c-Met in BM-MSCs improved the homing efficacy to injured livers and improved liver function. Furthermore, freshly isolated MSCs lose ligands or receptors that respond to migratory signals during expansion , 16. TheWith the capacity of self-renewal and multipotency, MSCs have been increasingly used in tissue engineering and regenerative medicine . BM-MSCsIn a previous study, UC-MSCs were successfully isolated and cultivated . Due to in vivo, the proportion of hepatocytes derived from hUC-MSCs was <1% of the total hepatocytes. The data suggested that the differentiated hepatocytes may not compensate for the recovery of liver function [in vivo [ALF is typically associated with progressive, massive hepatocellular necrosis . Althougfunction . Stimulafunction . Our resfunction , 29. In [in vivo . It is g[in vivo . Recentl[in vivo . Tan et [in vivo . Moreove[in vivo . In addi[in vivo .Most reports describe cell transplantation as the primary mode of MSC therapy, but the therapeutic effect of MSCs depends on the homing efficacy to the injured sites. HGF is the most effective mitogen in hepatocyte regeneration during tissue injury, and its biological effects rely on tyrosine kinase receptors and on c-Met. The HGF-c-Met axis played a crucial role in the homing of MSCs during liver injury .Our primary experiment demonstrated that the highest concentration of HGF was observed in the liver at 24 h post-DGalN/LPS coinjection. Meanwhile, overexpressed c-Met in BM-MSCs improved the homing efficacy to the injured liver .In addition, during expansion, primary MSCs lose ligands or receptors that respond to migratory signals , 16. OurMigration within the injured tissues is influenced by multiple factors. Administration of the MSCs via the portal vein or hepatic artery shows homing efficacy less than 5% and 20–30%, respectively , 37. Morin vitro, such as chemokine receptors or adhesion molecules, which has also been shown to affect the homing of HSCs [in vivo is dependent on the level of c-Met.Recent studies have detailed the potential benefit of hUC-MSC infusion for the treatment of ALF. The administration shows that systemic hUC-MSC therapy has profound inhibitory effects on hepatocellular apoptosis and stimulates liver regeneration for compensated liver function and also improves survival rates in rats with D-GalN/LPS-induced ALF. Furthermore, our results suggested that P5 hUC-MSCs migrate more efficiently to the injured liver, compared with P10 hUC-MSCs. The primary mechanism seems to be the regulation of homing molecules on MSCs during incubation  of HSCs , 42. HowThus, hUC-MSCs may be a potential alternative source for cell therapy of ALF and may additionally mitigate the shortage of hepatocytes.


No adverse effects were noted among students who used Empowered Brain. New technologies may herald novel ways of identifying and characterizing symptoms of ADHD in student populations. This study provides evidence that Empowered Brain in-game performance correlates with ADHD symptom severity in students with ASD. Larger samples are required to validate these findings, with more diverse participants that can also widen the generalizability of these findings to a broader range of brain conditions that manifest with inattention, impulsivity, and hyperactivity. Through further research, we may find that such technologies can help us to identify and longitudinally monitor such symptoms, and potentially aid in severity stratification and digital phenotyping.As many as half of school children with autism spectrum disorder (ASD) exhibit symptoms of attention-deficit/hyperactivity disorder (ADHD), resulting in marked negative academic, social, and behavioral outcomes. The focus of the US Food and Drug Administration (FDA) on real-world data from novel digital sources, and the emergence of Current Procedural Terminology (CPT) codes to reimburse for digital monitoring and neurobehavioral testing suggest an increasing acceptance of the role of technology in augmenting clinical care and research. Empowered Brain is an augmented reality and artificial intelligence-based social-emotional communication aid for students with ASD. In this study, student performance on Empowered Brain is correlated to validated clinical measures of ADHD. Seven high school students with a diagnosis of ASD were recruited from a public high school. All students were assessed for severity of ADHD-related symptoms via three clinical gold-standard assessments, namely the Aberrant Behavioral Checklist (ABC), Social Responsiveness Scale 2 (SRS-2), and Teacher Report Form (TRF). Students used Empowered Brain over a one-week period. We measured the correlation of student in-game performance (as measured by point- and star-based rewards) relative to the hyperactivity subscale of the ABC (ABC-H), and the ADHD-subscale of the TRF. All seven students completed the study and managed to successfully use Empowered Brain. Students received a culminative total of 32 sessions, an average of 4.6 sessions per student (range 2–8). Student in-game performance demonstrated highly significant correlation relative to ABC-H (points:  Autism spectrum disorder (ASD) is a life-long, neurodevelopmental condition predominantly characterized by challenges in social communication . People Up to half of individuals with ASD demonstrate symptoms associated with attention-deficit/hyperactivity disorder (ADHD) ,8, manifAt present, there are a variety of ways that ADHD can be diagnosed. Most typically, ADHD is a clinical diagnosis that is given by a behavioral specialist following the gathering of a clinical/educational history, observations of the individual, and collateral history from family members, educators, and other professionals. For almost 50 years, ADHD rating scales have supplemented this process, with current use favoring scales such as the Swanson, Nolan and Pelham Questionnaire, Fourth Edition (SNAP IV), Conners 3rd edition, and the Vanderbilt ADHD diagnostic rating scale (VADRS) . TheWhile a range of effective pharmaceutical treatments has been developed for ADHD, there is a lack of robust, ecologically valid measures to quantitatively assess and monitor the response to medical treatment. The importance of ecological validity should not be underestimated when dealing with individuals who have conditions that are diagnosed based on behavioral criteria. Obtaining patient-generated data from outside of clinical settings using new digital devices has been emphasized by FDA interest in the use of real world data (RWD) and real world evidence (RWE), to understand the potential benefits and adverse effects related to a medical intervention . DigitalAttempts to develop quantitative assessment tools for ADHD has led to the development of several continuous performance tests (CPTs). These tests aim to objectively measure ADHD symptoms, especially in research settings. Examples of CPTs include Test of Variables of Attention (TOVA) and Connors CPT . TypicalTherefore, there is a need to develop novel technologies to assess ADHD-symptomatology. These technologies should objectively assess symptoms across all ADHD-symptom clusters (attention/impulsivity/hyperactivity) and should also demonstrate high ecological validity/ability to gather real-world data.In this paper we report on the use of Empowered Brain during typical public high school classroom settings. Empowered Brain is a novel technology that combines computerized smartglasses, like Google Glass, and a series of game-like software modules. It is designed to be used by students as a wearable socio-affective aid as part of a daily school or home intervention program. Empowered Brain uses artificial intelligence to analyze video, audio, affective, and behavioral data and provides users with in-game rewards, such as points and stars, based on their performance. In this study of students with ASD, we report on the correlation between student ADHD symptoms and their in-game performance measurements. Student ADHD symptoms were determined through the use of validated scales, namely the hyperactivity subscales of the aberrant behavioral checklist (ABC) and the ADHD component of the Teacher Report Form (TRF) ,23,24. BEmerging research has demonstrated that Google Glass can be used as an assistive communicative and therapeutic technology for people with ASD, although both encouraging results and controversy have arisen. The Kushki lab at the University of Toronto has demonstrated the feasibility and usability of their unique system using Google Glass as a communication aid in ASD . The WalEmpowered Brain is a wearable technology based on computerized glasses loaded with assistive software . EmpowerEmpowered Brain is worn on the face in a similar manner to glasses. Users of the device see visual guidance through a translucent display over their right eye and hear sounds through a right-sided bone conduction device. Empowered Brain consists of a variety of sensors, including a camera, microphone, accelerometer, gyroscope, and an inward-facing infrared sensor. Data from the sensors are gathered and are processed through AI-powered software. In-game rewards of points and stars are awarded based on performance and displayed in real-time to the user. These in-game rewards are awarded based on the same sensor data, and a number of points will result in a star reward that unlocks an “achievement” in the game and results in a temporary cartoon mask or embellishment of the partner’s face visible through the screen.Empowered Brain has previously been found to be feasible to use across multiple studies ,32. The A convenience sample of high school students were selected by educators to take part in the study. Criterion for inclusion was a current diagnosis of ASD according to school Individualized Education Program (IEP) records. An IEP is a collaboratively created document for students with special educational needs. An IEP outlines their educational needs and goals, while also setting out the interventions and resources that will be provided to the student. Educators were asked to assess students via an aberrant behavioral checklist (ABC) and the Social Responsiveness Scale (SRS-2). The ABC and SRS-2 are validated behavioral and social communication measures commonly used in ASD research, respectively . AdditioOver a one-week period of time, students were able to use Empowered Brain dependent on the availability of an educator to provide the intervention . The tecThe intervention involved a dyadic interaction between the student and the educator. The student wore Empowered Brain in a similar manner to glasses, and the educator sat in front of the student. At the start of the intervention, the educator powered on the system and loaded the Empowered Brain module. The educator then provided the system to the student and initiated an unstructured academic discussion with him/her regarding a variety of recommended topics, such as homework assignments, classroom projects, or behaviors in relation to home and/or peers. During this time, Empowered Brain monitored the student-educator interaction and provided the student with appropriate visual and auditory guidance to help direct his/her attention to emotional and social communication cues.As the participant followed the provided digital guidance, for instance by increasing and sustaining attention to the central facial area of the educator, he/she received in-game rewards.During the interaction, improvement in student social communication skills is met with increased game difficulty, whereas lapses in attention or reduced markers of social engagement are met with increased guidance/decreased game difficulty.The main assessed measures used in this study were those from the hyperactivity subscale of the Aberrant Behavior Checklist (ABC–H)  and the There were seven participants in this research study (M = 6: F = 1) . Mean agResearch of Empowered Brain running on multiple head-worn computing devices and its use with children and adults with ASD was approved by Asentral, Inc., IRB, an affiliate of the Commonwealth of Massachusetts Department of Public Health . The study was performed in accordance with relevant guidelines and regulations, and in accordance with the Helsinki Declaration. Written informed consent was obtained from all parents/legal guardians of all minors involved in this study and consent was provided by all capable participants. Consent to conduct this research was also obtained from all educators involved in the study. Written informed consent was obtained for the publication of photographs and other identifiable information of participants.p = 0.01).Participants (n = 7) had a mean SRS-2 T-score of 78.3 (range 73 to >90), and a mean ABC-H of 7.9 (range 0–20). Participants’ mean TRF ADHD raw score was 7.7 (range 0–15) with a mean TRF ADHD T-score of 56.7 (50–65). Participant ABC-H score and TRF ADHD raw scores were significantly correlated . All participants were able to demonstrate an ability to obtain rewards.p-value was determined from this score. Participant in-game performance demonstrated highly significant correlation to baseline ABC-H for both game points (p = 0.0013) and game stars (p = 0.0013) (p = 0.012) and stars (p = 0.012)  . TRF ADH= 0.012) . Mean paNew technologies may herald novel ways of identifying and characterizing symptoms of ADHD in student populations. Over 6.4 million children and adolescents in the US have been diagnosed with ADHD , and theThis study provides supportive evidence that Empowered Brain is a technology that can be used by students and teachers within a regular classroom setting. The usability of this system was demonstrated despite methodologically-imposed limitations designed to ensure high ecologically validity. These limitations include student use of the technology, as facilitated by their own regular teachers, during their regular lessons/school day, and within their own classrooms. No additional time, staff, or fiscal resources were provided except for initial teacher training. The study demonstrated that the in-game performance of the students was significantly correlated to two clinically validated measures of ADHD symptom severity. The findings were highly significant in the case of the ABC-H measure.While this study has a sample size of only seven participants, to the authors knowledge, this is the first report of the use of assessment of ADHD symptom severity through the use of socio-emotional game performance on smartglasses. The data were collected over a one-week period and involved a total of 32 game sessions, each lasting 10 min in duration, providing for 320 min of use. Given these findings, it would be important to conduct further studies that address questions raised by this study. Firstly, further research should attempt to reproduce the results with a larger student sample size. Secondly, use of a broader age range of students across different school types could aid the generalizability of the findings across a broader range of students. Thirdly, a more detailed assessment of the presence of confounding disorders such as anxiety and depression should be undertaken, especially as they influence social interaction.Future work will focus on gathering data on the use of Empowered Brain in non-ASD populations who may experience challenges in inattention, hyperactivity, and impulsivity. As symptoms of inattention and impulsivity occur across a broad transdiagnostic range of conditions, the possibility of using this technology across a much broader student and clinical population can also be considered.Despite these limitations, Empowered Brain has already been shown to improve social communication and behavior in people with ASD when used as a daily socio-affective coaching tool. While providing this intervention through game-like experiences, Empowered Brain collects and analyzes important information about the user through data-gathering sensors and artificial intelligence-based analysis. While further research is warranted, the potential for Empowered Brain to be able assess ADHD symptom load would be an interesting possibility. A digital tool that is practical to use while providing quantitative stratification of ADHD symptom severity could help identify the needs of students while not unduly impacting school resources. This technological approach may have utility to further aid digital phenotyping efforts seen in mental health conditions ,49.Additional research is warranted to determine whether the system could function in a longitudinal monitoring role. Empowered Brain has already demonstrated its ability to generate real-world data and real-world evidence in a series of research studies. Gathering more robust evidence to validate the ability of Empowered Brain to objectively and accurately measure ADHD symptoms is important. This validation could allow for the use of such technology as an outcome measure tool in ADHD clinical research. The ability to do this in a quantitative and standardized manner is highly desirable. We should also consider that there is evidence Empowered Brain can improve ADHD symptoms. Therefore, there is a possibility that participant ADHD symptom load may have changed during their use of Empowered Brain in this study (mean number of sessions: 4.6). We should also note that prior attempts to use CPT as an objective measure of ADHD symptoms have often focused on the measurement of attention and impulsivity, with limited assessment of hyperactivity/motor behavior. This is important given inattention and impulsivity are commonly encountered transdiagnostic symptoms across many behavioral conditions, whereas hyperactivity may be much more specific to ADHD . The EmpThe research and development of technologies that can quantify behavior represents a broader trend to use technology to obtain patient-generated data from non-clinical settings. This data can help to understand the risks and benefits associated with new health interventions [RWE). Additionally, digital patient monitoring and neuropsychological testing have been introduced as new codes for the Current Procedural Terminology code set for 2019, allowing them to be billable services for health insurers and Medicare.This study demonstrates that Empowered Brain in-game performance correlates with, and may be predictive of, ADHD-related symptoms in students with ASD. These preliminary findings were obtained in real world educational settings, without the provision of any additional school resources. Further research with larger participant numbers is required to replicate these findings. There is potential for this type of technology not only to aid identification and longitudinal monitoring of such symptoms, but also to provide for an assessment of severity level and subtype. Larger and more diverse samples will be required to improve the generalizability of the present findings to a broader range of brain conditions that manifest with inattention, impulsivity, and hyperactivity.