Aims: The aims of the current study are to examine whether parents’ work-family conflict, emotional distress (anxiety/depressive symptoms and parenting stress) and mindful parenting vary according to the type of employment , the type of work schedule , and the number of working hours per week and to explore whether parental emotional distress mediates the association between work-family conflict and mindful parenting dimensions.Methods: A sample of 335 employed parents (86.3% mothers) of children and adolescents between the ages of 1 and 19 years old completed a sociodemographic form and measures of work-family conflict, anxiety/depression symptoms, parenting stress, and mindful parenting. The differences in study variables among types of employment, work schedules and number of weekly working hours were analyzed. A path model was tested through structural equation modeling in AMOS to explore the indirect effect of work-family conflict on mindful parenting dimensions through anxiety, depression and parenting stress. The invariance of the path model across children’s age groups  and parents’ gender was also examined.Results: Parents with a shift work schedule, working full-time and 40 h or more per week, presented significantly higher levels of work-family conflict than those with a fixed or flexible schedule, working part-time and less than 40 h per week, respectively. Parents with a flexible work schedule presented significantly higher levels of self-regulation in parenting and of non-judgmental acceptance of parental functioning than parents with a shift work schedule. Higher levels of work-family conflict were associated with lower levels of mindful parenting dimensions through higher levels of anxiety/depression symptoms and parenting stress. The model was invariant across children’s age groups and parents’ gender.Discussion: Work-family conflict is associated with poorer parental mental health and with less mindful parenting. Workplaces should implement family-friendly policies  that help parents successfully balance the competing responsibilities and demands of their work and family roles. These policies could have a critical impact on the mental health of parents and, consequently, on their parental practices. Balancing the dual demands of work and parenting pose a great challenge to contemporary parents. Labor markets are becoming increasingly competitive and insecure, requiring parents to make a great commitment to work and dedicate much of their family and personal time to their jobs. In Portugal, the employment rate for all Portuguese mothers (aged 15–64) with at least one child aged 0–14 is 75.7% (68.4% working full-time), which is higher than the OECD average (66.2%) and one of the highest rates among OECD countries. The proportion of children (aged 0–14) that live in households where both parents work full-time is 61.9%, which is also higher than the OECD average of 56%. In addition, family-friendly workplace policies, which are key determinants of a family ability to reconcile work and family life, are not employed by the majority of companies in Portugal. For instance, only 34.5% of companies report providing flexible working time arrangements, such as the possibility to accumulate hours for days off  and to vary the start and end of daily work, to at least some employees (the OECD average is 53.4%) .Some studies show that the pressure parents feel on their jobs  along with certain working conditions  may create a work-family conflict and have a strong impact on parents’ well-being and on their parental behaviors e.g., . When exmindful parenting, this parental approach “means seeing if we can remember to bring this kind of attention and openness and wisdom to all moments with our children” (p. 25); it “is a continual process of deepening and refining our awareness and our ability to be present and to act wisely” (p. 28).Over the last decade, several researchers, particularly those interested in family and parent–child relationships, have been showing an increasing interest in the study of the applications of mindfulness to the parenting context e.g., . Mindfulbe in the present moment when interacting with their children, to be sensible and responsive to their child’s needs, and to exert self-regulation in difficult moments with the child and thereby choose parenting behaviors  that are in accordance with their parental values and goals , child , and social  variables . For insOther potential determinants of mindful parenting are the parents’ mental health and their levels of parenting stress , type of employment , and number of weekly working hours . Based on previous investigations, we expected to find lower levels of work-family conflict, anxiety/depression symptoms and parenting stress, and higher levels of mindful parenting among women compared to men, and among parents with a flexible work schedule, parents with a part-time job and parents who work fewer hours per week.The second goal of this study was to investigate whether work-family conflict could play a role in parents’ ability to be mindful in the relationship with their children and whether this relationship could be mediated by parenting stress and by anxiety and depressive symptoms. To understand whether this model could be applicable to mothers and fathers and to various developmental stages of the child, we included mothers and fathers of toddlers (1–3 years), preschool and grade school children (4–11 years) and adolescents (12–19 years) in our sample, and we tested the invariance of the model with respect to the parents’ gender and the children’s age group. Based on previous studies showing that work-family conflict is associated with negative parenting experiences e.g., , we expeAs presented in n = 266, 79.4%) and in one public basic education school in the central region of Portugal  between December 2017 and April 2018. The only inclusion criterion was to be the parent of a child or adolescent between the ages of 1 and 19 years old. Participants who were recruited online completed the questionnaires in a data collection website (LimeSurvey®). The survey link was shared on social networks and through email. In the first page of the online survey, a brief description of the study goals, the inclusion criterion, and the ethical issues that guided the study were presented. In particular, in this first page, it was clearly stated that participation in the study was anonymous and that no identifying information could be collected. Since the data was collected online, participants did not provide written informed consent. Instead, participants provided informed consent by clicking on the option “I understood and accept the conditions of the study,” which was on the second page of the survey. Only those who selected this option were granted access to the assessment protocol. Parents who were recruited in the school received, through their children, a letter explaining the study, an informed consent form, and the questionnaires that should be completed at home and returned a week later. Research assistants collected the written informed consents and the questionnaires at the school on a date agreed upon with the class director. Authorization for the sample collection was obtained from the Ethics Committee of the Faculty of Psychology and Education Sciences of the University of Coimbra and from the board of directors of the school.The sample was collected online , number of working hours per week, and work schedule. The variable work schedule comprised three categories: a fixed work schedule , a flexible work schedule , and a shift work schedule .very strongly disagree) to 7 (very strongly agree). The total score of this subscale is the sum of all items and higher scores indicate higher levels of conflict. Although the Work-Family Conflict Scale has also a Family-Work Conflict subscale, we have only included in the study the WFC subscale since we were only interested in assessing the interference of work with the family. The original version presented adequate internal consistency and convergent, concurrent and predictive validity. Preliminary data of the Portuguese version has also exhibited adequate internal consistency and construct validity. In the current study, the Cronbach’s alpha was 0.89.The Portuguese version of the Work-Family Conflict (WFC) subscale of the Work-Family Conflict Scale  was usednot at all/only occasionally) to 3 . The items are organized into two subscales: Anxiety and Depression. The total score of each subscale is the sum of all items, with higher scores indicating higher levels of symptomatology. The HADS is frequently used for screening anxious and depressive symptomatology in clinical settings and in the general community and it has shown robust psychometric properties in a wide range of populations and cultures. The Portuguese version has also robust psychometric properties, including adequate reliability and construct validity  to 5 (strongly agree). The total score results from the sum of the items and higher scores indicate higher levels of parenting stress. The scale presented adequate psychometric properties, in the original and Portuguese versions, including adequate reliability  and construct validity in samples of parents mostly from the general community. In the current study, the Cronbach’s alpha was 0.70.To assess the distress associated with the parental role, the Portuguese version of the Parental Stress Scale PSS;  was emplnever true) to 5 . The subscale scores result from the sum of the items, and higher scores suggest higher levels of each mindful parenting dimension. Parents were requested to think on only one of their children when answering the questionnaire, if they had more than one child. In the online data collection, parents were instructed to choose, preferably, their youngest child; in the data collection in schools, parents were instructed to think about the child who received the questionnaire in the school. IM-P items were distributed across the following subscales: (1) Listening with Full Attention , (2) Compassion for the Child , (3) Non-Judgmental Acceptance of Parental Functioning , (4) Self-Regulation in Parenting , and (5) Emotional Awareness of the Child . Although the psychometric properties of the original version of IM-P scale are unknown, the scale has shown reliability and construct validity in Dutch samples  were used for data analyses. Descriptive statistics were computed for all sociodemographic and study variables. Since parents were collected through two different procedures, differences in sociodemographic and study variables between parents who participated online and parents who were collected at the school were analyzed through ANOVAs and chi-square tests. Next, controlling for the sociodemographic variables that differed significantly between parents collected online and at the school, differences in study variables were analyzed through one-way ANCOVAs (work-family conflict and parenting stress) and MANCOVAs (anxiety/depressive symptoms and mindful parenting dimensions). To examine the bivariate associations between study variables, Pearson correlations were computed. In addition, correlations between the sociodemographic/working variables and the mindful parenting dimensions were computed with the aim of identifying potential covariates that should be controlled in the path model. Correlations close to 0.10 were considered small, close to 0.30 were considered medium, and at 0.50 or higher were considered large  and the AMOS 20 , type of employment , and number of working hours per week (less than 40 h versus 40 h or more) through ANOVAs and MANOVAs. The part-time and occasional categories were merged into one group because only five individuals (1.5%) reported having occasional work. Because the work schedule had three categories, 2 was non-significant (p > 0.05), the CFI was ≥0.95, the RMSEA was ≤0.06, and the SRMR was ≤0.08 (2) between the two models indicated that the path model was invariant across groups.To examine whether work-family conflict was associated with mindful parenting dimensions through parents’ anxiety and depressive symptoms and parenting stress, a path model was tested in AMOS (maximum likelihood estimation method). The model fit was considered good when χas ≤0.08 . A boots2(1) = 6.56, p = 0.010], education , and income . Controlling for these sociodemographic variables, differences between groups were analyzed for all the study variables. No significant differences were found for any study variable: work-family conflict , parenting stress , anxiety and depressive symptoms , and mindful parenting dimensions . Therefore, the two groups were combined and analyzed together.Differences in the sociodemographic and working variables between parents recruited online and parents recruited in the school were analyzed. Significant differences were only found for parents’ gender, . The examination of the univariate effects revealed that differences were only significant for the self-regulation in parenting and non-judgmental acceptance of parental functioning dimensions, with parents with a flexible schedule reporting significantly higher levels of self-regulation and of non-judgmental acceptance than parents with a shift work schedule (no significant differences were found between fixed and flexible or shift work schedules).Differences in study variables as a function of work schedule (fixed versus flexible versus shift work), type of employment , and number of working hours per week (less than 40 versus 40 or more) are presented in Differences in study variables as a function of parents’ gender are presented in 2(60) = 641.59, p < 0.001; CFI = 0.500; SRMR = 0.156; RMSEA = 0.170, p < 0.001, 90% CI = . Therefore, we examined the modification indices, which suggested that some residuals might be correlated. We initially allowed the correlation between the residuals belonging to depression, anxiety and parenting stress and between income and education, which presented the largest modification indices. Although the model fit improved significantly , it did not achieve a good fit (χ2(56) = 292.46, p < 0.001; CFI = 0.797; SRMR = 0.089; RMSEA = 0.112, p < 0.001, 90% CI = ). Therefore, some residuals from mindful parenting dimensions were also allowed to correlate . The respecified path model presented a very good fit to the data, χ2(49) = 83.46, p = 0.002; CFI = 0.970; SRMR = 0.060; RMSEA = 0.046, p = 0.638, 90% CI =   = 69.98, p = 0.016; CFI = 0.971; SRMR = 0.068; RMSEA = 0.046, p = 0.581; 90% CI = . Among parents of toddlers and adolescents, the model presented a poorer fit to the data (toddlers: χ2(49) = 64.06, p = 0.073; CFI = 0.948; SRMR = 0.100; RMSEA = 0.065, p = 0.279; 90% CI = ; adolescents: χ2(49) = 73.28, p = 0.014; CFI = 0.865; SRMR = 0.112; RMSEA = 0.092, p = 0.074; 90% CI = ). Then, we compared the unconstrained and constrained models (unconstrained: χ2(147) = 207.92, p < 0.001; CFI = 0.949; SRMR = 0.101; RMSEA = 0.035, p = 0.990; 90% CI = ; constrained: χ2(209) = 269.11, p = 0.003; CFI = 0.950; SRMR = 0.107; RMSEA = 0.029, p = 1.00; 90% CI = ) and found that the difference between both models was not significant, Δχ2(62) = 61.19, p = 0.505, which indicates that the relationships between the variables in the model were invariant across groups.Multigroup analyses were performed to test the structural invariance of the path model across children’s age groups (toddlers versus preschool and grade school children versus adolescents) and parents’ gender. Concerning the invariance analyses for children’s age groups, the baseline model demonstrated a good fit to the data in the group of parents of preschool and grade school children, χ2(37) = 51.47, p = 0.057; CFI = 0.986; SRMR = 0.058; RMSEA = 0.037, p = 0.815; 90% CI = ); however, the model did not present a good fit in the group of fathers (χ2(37) = 67.59, p = 0.002; CFI = 0.815; SRMR = 0.131; RMSEA = 0.136, p = 0.008; 90% CI = ). The comparison between the unconstrained and the constrained models (unconstrained: χ2(74) = 120.02, p < 0.001; CFI = 0.961; SRMR = 0.131; RMSEA = 0.043, p = 0.779, 90% CI = ; constrained: χ2(104) = 146.86, p = 0.004; CFI = 0.964; SRMR = 0.143; RMSEA = 0.035, p = 0.975, 90% CI = ) revealed a non-significant difference, Δχ2(30) = 26.84, p = 0.632, which indicates that the relationships between variables in the model were invariant across groups.To explore if the path model was invariant across mothers and fathers, another multigroup analysis was performed. In this analysis, parents’ gender was not introduced as a covariate. The baseline model for mothers demonstrated a good fit to the data  and parenting practices . We found that parents with a shift work schedule, parents with a full-time job, and parents who work 40 h or more per week had higher levels of work-family conflict than parents with a flexible or fixed work schedule, parents with a part-time job and parents who work less than 40 h per week, respectively. We also found that parents with a flexible work schedule had higher levels of self-regulation in parenting and higher levels of non-judgmental acceptance of parental functioning than parents with a fixed or shift work schedule. Another major goal of this study was to investigate whether work-family conflict was linked to mindful parenting dimensions through parental psychopathology and parenting stress. Overall, we found that higher levels of work-family conflict were indirectly associated with lower levels of mindful parenting dimensions through anxiety and depression symptoms and parenting stress. This model was shown to be invariant between mothers and fathers and between parents of children from different age groups. These results will be discussed in further detail below.Corroborating the results of previous studies e.g., , we founThe results of our study also suggest that flexible work schedules can be protective of parenting. These findings are in line with those of previous investigations that found that working time flexibility can facilitate the work-life balance of employees and, particularly, of parents . InteresWe also analyzed gender differences in study variables. No differences were found in any variable, with the exception of the mindful parenting dimension listening with full attention. While it is important to keep in mind that our study comprised a very small number of fathers  and that our group of fathers was a self-selected sample , our results suggest that the mothers and fathers in our sample experience similar levels of work-family conflict, anxiety/depression symptomatology, and parenting stress. In the majority of contemporary families, both parents work outside the home and both take an active role in caring for their children. In fact, according to the OECD data on gender equality, although Portuguese women are less likely to be employed than men, the gender gap is smaller than the OECD mean (10.8% points). Specifically, in 2017, in Portugal, the female employment rate (64.8%) was only 6.3% points lower than the average employment rate for men (71.1%) . HoweverWith regard to gender differences in mindful parenting, it is interesting to note that in our sample, fathers reported higher levels of listening with full attention than mothers, a dimension that refers to the parents’ ability to direct their attention and awareness to the child and be fully present during parent–child interactions. A possible explanation is that mothers, because they still assume the most salient roles in the childcare and at home and spend more time than fathers with their children , may feeWith regard to the path model, we found that, although work-family conflict was indirectly associated with all mindful parenting dimensions through anxiety, depression, and/or parenting stress, it only had a direct effect on the listening with full attention dimension. This direct effect suggests that perceiving a greater level of interference of work with family life  can translate into a diminished ability to listen to the child and engage in activities together in a calm and attentive way. Objectively, those who have fewer opportunities to be with their family because of work also have fewer opportunities to bring their mindful awareness to interactions with their children. In addition, we may hypothesize that parents with higher levels of work-family conflict may be absorbed by work-related concerns or by ruminations related to the frustration they feel at having so little time for the family, which may consume their attention resources and leave them with a diminished ability to concentrate on the present when they are with their children. For example, if parents are worried about a deadline, an outstanding task, or any other work-related issue, or if parents are focused on the fact that they usually have little time to be with their children (“I should have more time for my family”), they may be so consumed by those thoughts and concerns that they may not be able to be fully present and focus entirely on what is going on when they are interacting with their children .As mentioned, we found several indirect effects between work-family conflict and mindful parenting through anxiety, depression, and/or parenting stress. These indirect effects occurred through positive associations between work-family conflict and the three mediators and negative associations between the mediators and the mindful parenting dimensions. With regard to the positive associations between work-family conflict and anxiety, depression, and parenting stress, these results are in accordance with previous investigations that have shown that work-family conflict is an important risk factor for parental psychopathology and parenting stress e.g., . ManaginWith regard to the links between the mediators  and the mindful parenting dimensions, we found that while parenting stress was negatively associated with all mindful parenting dimensions , anxiety and depression were predominantly associated with parent-centered dimensions. Specifically, anxiety was negatively associated with self-regulation, non-judgmental acceptance of the parenting functioning and listening with full attention, and depression was only negatively associated with self-regulation. These findings suggest that individual factors, such as psychopathology, seem to play a more relevant role on mindful parental behaviors that are more focused on the parent themselves , whereas parenting stress seem to have a broader effect and to also play a role in dimensions more focused on the child, such as the emotional awareness of child and the compassion for the child.With regard to parenting stress, several previous studies have already shown a consistent association between this type of stress and mindful parenting e.g., . While pOur model also suggests that parents’ anxiety and depression symptoms also play a role, albeit a less prominent role than parenting stress, in explaining why work-family conflict is associated with lower levels of mindful parenting. Several specific indirect effects were found, which corroborate the large body of research indicating that parental psychopathology suffers the influence of work-related variables  and is oIn addition, we found that higher levels of anxiety were a mediator of the relationship between work-family conflict and listening with full attention. This result corroborate previous studies showing, for instance, that anxious parents tend to be less engaged and more withdrawn during interactions with their children , to haveAnxiety symptoms also mediated the link between work-family conflict and non-judgmental acceptance of parental functioning. These associations are consistent with previous research that has shown that distressed mothers are usually more self-critical and, consequently, are more likely to endorse a negative view of themselves as mothers . Self-crThe invariance analyses revealed that the relationships in the model were independent of the parents’ gender and of the child’s developmental stage. With regard to parents’ gender, and although men and women struggle with different gender-role stereotypes, work-family conflict seems to play an identical role in mothers’ and fathers’ emotional distress and in their parenting practices. Given the large number of dual-earner families in today’s society, it is possible that, in some cases, both parents may have high levels of work-family conflict, which may have a cumulative effect on the risk of less mindful parenting practices. Furthermore, although the developmental challenges are different in young children, school-aged children and adolescents e.g., , the effThis study presents several limitations that should be noted. First, this study has a cross-sectional design, which does not allow for determining with confidence the direction of the associations between the variables. For instance, it is also possible that experiencing higher levels of psychopathology symptoms and parenting stress leads to a greater strain between work and family demands. On the other hand, mindful parenting can also predict parenting stress and even work-family conflict. For instance, more mindful parents may be more able to positively manage the challenges and demands of parenting, consequently feeling less parenting stress. Mindful parents might also manage in a more balanced way the demands of work and family, feeling less conflict between these two roles. Future longitudinal studies should be conducted to understand the direction of the associations between these variables. In addition, and although we have considered psychopathology symptoms and parenting stress as parallel mediators, future longitudinal studies, in which all variables are assessed through several time points, may contribute to clarify the directionally between these variables. Second, 86.3% of the participants were mothers, which limits the generalizability of the results to fathers. Future studies should include a larger number of fathers to explore in further detail gender effects on the associations studied. Third, most parents were married or living with a partner, had completed higher education, had a child between the ages of 3 and 10 years old, and had a full-time job and a fixed work schedule, which may limit the generalization of results to parents with other sociodemographic characteristics, with younger or older children  and with other work conditions. Fourth, the sample was recruited online and at schools. Although no differences were found in study variables as a function of the local of recruitment, the two groups differed in some sociodemographic variables. In addition, online recruitment is often associated with a self-selection bias , which may compromise the representativeness of the sample. Fifth, the Cronbach’s alpha of the Emotional Awareness of the Child subscale was below the recommended threshold of 0.70. Although some authors argue that Cronbach’s alphas of 0.60 are acceptable in research in the social sciences , some caThe results of the present study provide further evidence that certain working conditions  and work-family conflict may have an adverse impact on the lives of employed parents, particularly on their mental health and parental behaviors. It is critically important that policy makers and employers recognize this impact and devise strategies that can help parents better balance their work and family responsibilities. With the growing rates of dual-earner families, it is increasingly important that workplaces adopt and implement family-friendly policies that can minimize the impact of work on family, such as more extended maternity and paternity leaves , sickness leaves, career breaks and extended leave, part-time work, and flexible work arrangements  . The resIn addition, our study suggests that work-family conflict plays a detrimental role on parents’ mental health and parenting practices at different stages of child development, particularly during preschool and grade school years. Although most family support policies in Portugal are designed for parents in the postpartum period , our study draws attention to the importance of supporting parents in the later stages of child development. Therefore, family-friendly work arrangements should include parents of children and adolescents of all ages and should not be exclusive of parents during the postpartum period.When it is not possible to change work conditions  and/or when workplaces are not willing to implement family-friendly policies, targeted interventions for parents who are experiencing high levels of stress and difficulty in reconciling work and family demands, aimed at helping them develop strategies to better cope with the work-family conflict, can be very useful. In addition, preventive parenting interventions designed to promote more positive and mindful parenting practices, regardless of parents’ work conditions, should consider the impact that work can have on parents’ mental health and parenting and, therefore, help them to develop skills that allow them to more adaptively balance work and family responsibilities  in order to prevent them from experiencing high levels of conflict between their work and family roles.Another result of our study with important implications is that anxiety, rather than depression, seems to play an important role in how parents see themselves as parents and in their ability to be fully present when interacting with their children. These findings underline the importance of assessing, in clinical context, the relationship that anxious parents establish with their children, in order to provide them strategies that not only reduce their anxiety but also promote a greater acceptance of perceived mistakes and limitations as parents, a greater self-regulation in parenting, and a greater ability to defuse from their problems and to be present when interacting with their children. Although the literature has predominantly emphasized the negative role that parental depression plays in parenting behaviors and in child development , our stube mindful in the relationship with their children, is extraordinarily important not only for parents but also for children. Mindful parenting can be a privileged vehicle to foster a positive and secure relationship between the parents and the children (Promoting mindful parenting, namely, by creating better working conditions so that parents can effectively children , and in children . TherefoThe datasets generated for this study are available on request to the corresponding author.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Ethics Committee of the Faculty of Psychology and Education Sciences of the University of Coimbra approved the study. Informed consent was obtained from all participants included in the study. Participants recruited through a data collection website provided informed consent by clicking on the option “I understood and accept the conditions of the study.” Participants recruited at the school provided written informed consent.HM designed the study, performed the data analyses, and wrote the manuscript. AF designed the study and revised the final draft of the manuscript. BC contributed to the interpretation of data. MC collaborated in the editing of the final manuscript.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.


Stroke is a leading cause of disability worldwide. Motor impairments occur in most of the patients with stroke in the acute phase and contribute substantially to disability. Diffusion tensor imaging (DTI) biomarkers such as fractional anisotropy (FA) measured at an early phase after stroke have emerged as potential predictors of motor recovery. In this narrative review, we: (1) review key concepts of diffusion MRI (dMRI); (2) present an overview of state-of-art methodological aspects of data collection, analysis and reporting; and (3) critically review challenges of DTI in stroke as well as results of studies that investigated the correlation between DTI metrics within the corticospinal tract and motor outcomes at different stages after stroke. We reviewed studies published between January, 2008 and December, 2018, that reported correlations between DTI metrics collected within the first 24 h (hyperacute), 2–7 days (acute), and >7–90 days (early subacute) after stroke. Nineteen studies were included. Our review shows that there is no consensus about gold standards for DTI data collection or processing. We found great methodological differences across studies that evaluated DTI metrics within the corticospinal tract. Despite heterogeneity in stroke lesions and analysis approaches, the majority of studies reported significant correlations between DTI biomarkers and motor impairments. It remains to be determined whether DTI results could enhance the predictive value of motor disability models based on clinical and neurophysiological variables. Stroke is the second cause of death and the third leading cause of loss of DALYs (Disability-Adjusted Life Years) worldwide. Despite substantial advances in prevention and treatment, the global burden of this condition remains massive . In ischDiffusion MRI (dMRI) is a powerful diagnostic tool in acute IS  and is wStroke can directly injure WM tracts and also lead to Wallerian degeneration, the anterograde distal degeneration of injured axons accompanied by demyelination . DTI metTwo meta-analyses included from six to eight studies and reported strong correlations between DTI metrics and upper-limb motor recovery in IS and HS , 18. In In this narrative review, first we review the key concepts of dMRI. Second, we present an overview of state-of-art methodological practices in DTI processing. Third, we critically review challenges of DTI in stroke and results of studies that investigated the correlation between DTI metrics in the CST and motor outcomes at different stages after stroke, according to recommendations of the Stroke Recovery and Rehabilitation Roundtable taskforce .Different MRI paradigms address WM qualitatively and quantitatively , but only dMRI allows indirect inferences about WM microstructure by providing information about the underlying organization of the tissue. In regions of little restriction of water displacement (such as the ventricles), water molecules tend to move almost freely (randomly). On the other hand, within tracts, the environment tends to be organized within sets of axons aligned in parallel orientation. Water movement usually follows a specific orientation near axons compactly organized and constrained by the myelin packing .1 ≈ λ2 ≈ λ3), which can be depicted by a sphere. By contrast, if there is a preferential orientation of the diffusion, then the first eigenvalue is bigger than the other two, which can be visualized typically by an ellipsoid   and eigenvectors (ε), required to characterize the signal of water displacement within a voxel. Each eigenvector represents an axis of dominant diffusion with the magnitude of diffusion determined by the corresponding eigenvalues. If the diffusion is isotropic , then the eigenvalues have approximately the same magnitude  .Hence, the tensor calculation is typically based on a 3 × 3 symmetric matrix, in which the eigenvalues derived from each combination of directions provide different metrics. At least one b0 (non-diffusion-weighted) and 6 non-collinear directions of diffusion-weighted acquisitions are required to minimally describe water displacement with DTI . GeneralThe most widely used DTI metrics are: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). FA describes the degree of anisotropy (represented as an ellipsoid), a value between 0 (isotropic) and 1 (the most anisotropic). Anisotropy tends to increase in the presence of highly oriented fibers . The bigMD describes the magnitude of diffusion and the biggest value is supposed to be found in the ventricles. RD represents the average diffusivity perpendicular to the first eigenvector and AD is the first eigenvalue (λ1) representing the diffusivity along the dominant diffusion direction.Many studies have focused exclusively on FA. The proper interpretation of FA often demands knowledge about results of the other three DTI metrics . ChangesDWI is a noise-sensitive and artifact-prone sequence, emphasizing the need for robust acquisitions and processing handling to avoid bias . SeveraldMRI acquisitions and analytical strategies are based on the goal of the study, balancing the pros  and cons . In addition to constraints related to the number of subjects with stroke in the studies, criteria to perform a reliable protocol should be weighted prior to data collection .b-value is a scalar that reflects the degree of diffusion, influenced by the duration, amplitude, and interval between the gradients. B-values are comparable to an inverse zoom factor: the higher they are , the smaller the sampled space  acquisitions. Two high-amplitude magnetic gradients are applied. The ed space .b-value (b0 for example), for every 5–6 volumes with high b-value and leave it interspersed with those with high values; optimal sampling schemes of the directions in the sphere of distribution and gradient ordering (http://www.mrtrix.org/) or ExploreDTI (http://www.exploredti.com).EPI acquisitions are prone to many unexpected distortions , therefoordering , 31. Opta posteriori corrections are performed in the pre-processing step.Off-resonance artifacts such as eddy currents and magnetic field inhomogeneities are intrinsic to EPI acquisitions and interfere in the expected signal, causing susceptibility-induced distortions . AcquisiIn stroke studies, the duration of scans should be planned by pondering the risk of fatigue and increased head motion in patients with neurologic impairments. These impairments are often not restricted to motor deficits and may involve executive dysfunction or anxiety that contribute to increase head motion and hence, artifacts. Again, trade-offs between “optimal” acquisition parameters, feasibility and noise must be weighted during study design.b-values; number of b-values; number of averages, repetitions to improve signal in relation to noise and tensor estimation   , 35.www.nitrc.org). There is no consensus but some agreement about diffusion imaging processing. One can decide to use a mix of softwares to process the data, as long as key steps are completed and a detailed methodological report is made. Documentation is invariably available on-line and discussion forums can provide additional support. It is desirable, to allow reproducibility and comparisons across studies, to transparently report analytical procedures when in-house pipelines are employed  with a b value around 1,000 s/mm2, with subsequent tensor modeling.Here, we will briefly cite some suggestions for processing practices, considering an ordinary single-shell acquisition , eddy currents-induced distortions and subject motion , 37, so A gold-standard pre-processing pipeline does not exist. Pre-processing is intrinsically dependent on the chosen software. Users can employ different softwares to perform a miscellaneous of corrections, but it is mandatory to follow the basic steps recommended by each developer. Steps of a typical preprocessing pipeline might be:A procedure frequently required, DICOM or PAR/REC conversion to NIfTI format (most diffusion processing softwares use this format).Inspection of DWI images for motion, artifacts  , 39 and B-matrix rotation: this notion was first introduced by Leemans and Jones . The rotBrain extraction: an automated segmentation method to delete non-brain tissue from the whole-head. This optional but frequently performed procedure improves registration and normalization.https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FSL. It must be emphasized that an adequate acquisition is required in order to be able to perform such corrections (Eddy currents and EPI distortions correction: off-resonance artifacts (as detailed previously) must be corrected. Tools are available, for example, in the ExploreDTI software and in the FSL platform (Topup and Eddy). Further details on how to acquire data and how to perform corrections can be also found at rections .Tensor estimation in each voxel and generation of maps of FA, MD, RD, and AD . This esDTI maps generated in the native space for each subject can be co-registered so that group-wise comparisons can be performed. Co-registration refers to intra or inter-subject spatial alignment of images within or between MRI sequences. Decisions about co-registration tools must consider the paradigm of study, assumptions and specific steps of image processing –47. TypiWe will review the types of analyses more frequently applied in DTI studies in stroke: ROI-based analysis, tractography, and whole-brain analysis.ROIs can be drawn on T1, T2, FA, or ADC images. They can be placed on the abnormal/lesion regions or on predetermined anatomic regions. In the WM, the homogenous signal and EPI distortions might impair robust anatomical delimitation of ROI and reproducibility.Basic steps of ROI processing are:Registration to improve delineation and to align corresponding voxels in different datasets.Normalization to allow standardized localization and comparisons between subjects within a study. For instance, data from each subject can be transferred to standard space, using a validated template or atlas  . The choDefinition of the ROI, manually or semi-automatically. Manual delineation can be achieved by free-hand drawing, by placement of basic shapes such as circles/squares or by drawing of the region. In the former, ROI size differs between subjects while in the latter, it remains constant. Small ROIs may be more specific, but also more prone to errors while large ROIs may be less specific for definition of particular structures and more prone to partial volume effects (inclusion of structures other than the target area) .Manual segmentation has high precision but has disadvantages such as the risk of low reproducibility due to dependence on prior knowledge of the researcher and the lack of feasibility of use in large datasets . Semi-auQuality control involves: assessment of accuracy of segmentation and registration; report of intra- and inter-rater reliabilities of ROI delineation; clarity of criteria for the location of the ROI  - for details, refer to Froeling et al. .Extraction of DTI metrics from the ROI, as absolute values from the ipsilesional/contralesional site or ratios between both .When more than one ROI is chosen, the correction for multiple comparisons is recommended to reduce false positives—for details, refer to Froeling et al. .Tractography corresponds to the mathematical reconstruction of tracts , 58. By Deterministic, following the best-fit pathway (the main eigenvector λ1), the principal axis of the tensor aligning with the principal direction of the fibers. It estimates the most likely fiber orientation in each voxel. This method tends to show the best valid/invalid connection trade-offs, but presents low spatial bundle coverage in comparison to the probabilistic method .Probabilistic, based on the estimation of uncertainty in fiber orientation , 62. It Noise and artifacts affect reconstructions. There is no “ground-truth” solution to validate tracking results . Several.Path reconstruction can be constrained by three main steps: seeding, propagation and termination . UsuallyTermination of streamlines is usually guided by a set of parameters: FA threshold (between 0.1 and 0.3 for adult brain), turning angle threshold  to avoid streamlines propagating voxels of high uncertainty, such as the cerebrospinal fluid (CSF) and gray matter . Fully aSeveral methods of CST reconstruction are available with no consensus. For instance, DTI metrics can be extracted from the entire tract or from ROIs within these tracts, as absolute values from the ipsilesional/contralesional site or as a ratio between both . Recentlb-values - b ~1,000 mm/s2) would solve this problem   Figure . It was  problem , 67. How problem , 66.b-values, to measure the diffusion signal (High angular resolution diffusion imaging (HARDI) uses a larger number of diffusion gradient directions, often in combination with multiple n signal . By doinn signal . To reacn signal , 69. HARn signal , 71. Howb values in the range of 1,000 s/mm2  , typical00 s/mm2 , 73. CSD00 s/mm2 . It has 00 s/mm2 . Excelle00 s/mm2 .Whole-brain analysis is an exploratory approach that can be applied to investigate global WM changes or whether such changes are heterogeneous across patients within a study. Analyses can be performed and measures can be extracted using different approaches, such as:Histogram analysis of all voxels in the brain. Histograms that express the frequencies of voxels with a specific value for a DTI metric such as FA can be built. Median, mean, peak height, and peak location of DTI metrics can thus be estimated , 77.Brain or WM voxels defined by a mask created from either segmentation of an anatomical MRI or by whole brain tractography. If the former strategy is chosen, DTI values in the voxels can be extracted after registration of anatomical MRI to the non-diffusion weighted image by means of an affine transformation. If whole-brain tractography is performed, then DTI measures can be extracted from voxels that are part of the streamlines.The most popular approach is voxel-based analysis (VBA) and compares DTI metrics in every voxel of the brain . This stThe main challenge of DTI in stroke is heterogeneity of lesions—for a review, see de Haan and Karnath . Lesion The mismatch between images from patients and templates in atlases based on brains from healthy subjects affects normalization . Two posLesion masks can be created by changing the intensity of pixels inside or outside the segmented lesion and hence, obtaining binary images (zero-one intensity). Lesion masks can be manually drawn , but seMasking out lesions may require large deformations, particularly in WM regions adjacent to gray matter and cerebrospinal fluid. An interesting approach to deal with this problem is DR-TAMAS   that optThe low resolution of DTI images can hinder delineation of the ROI. Registration of the DTI dataset to anatomical T1/T2 images can improve spatial resolution and facilitate ROI drawing. However, misregistration/misalignment can occur, mainly driven by the different distortions in the two types of images and the lower resolution of DTI images resulting in partial volume effects , 78. SliFurthermore, the best choice for ROI placement within the CST remains an open question. According to Koyama et al. , outcomeIn stroke, tractography may be used to reconstruct a tract of interest based on a prior hypothesis, to obtain qualitative anatomical information , extract quantitative measures (volumetric and diffusion metrics) or make inferences about connectivity .To track the CST, a standard template based on healthy subjects can be reliably used to extract metrics from the whole-tract or from a section of it, such as within the PLIC . In stroTypical steps of whole-brain processing pipeline involve co-registration and normalization so that group-wise statistical comparisons can be made. Stroke lesions can be obstacles for automatic whole-brain voxel-wise analysis such as TBSS. The cost function masking and enantiomorphic normalization can be used as alternatives to overcome lesion deformations.http://qibawiki.rsna.org/index.php/Main_Page. Also, it is crucial to use the same package and software version within the same study and while processing longitudinal datasets. Whenever possible, the most updated version should be chosen  and Web of Science, using the following keywords: motor (stroke or infarct or infarction or hemorrhage) and corticospinal tract and diffusion (imaging or tensor imaging). A complementary search was made using the first two keywords combination and tractography or FA. Studies were selected according to the following criteria.http://www.who.int/classification/icf/en/  , acute , or earl/icf/en/ ; evaluatb value (s/mm2); methods of analysis (technique/software/metrics); whether lesion masks were mentioned; whether ipsilesional and contralesional CST were assessed; when motor evaluation was performed (time from stroke); motor outcome; whether DTI correlated with outcome and correlation coefficients.The following information was retrieved from the manuscripts –3: type n = 60) (n = 10 (n = 27 (n = 101) in hyperacute, six (n = 172) in the acute and nine (n = 297), in the early subacute phase after stroke. A total of 667 scans were performed. Ages ranged from 19 to 99 years and 56.5% of the patients were men. 62.8% of the patients had IS and 37.2%, HS. 36.8% of the studies reported that patients received rehabilitation during the time between the MRI scan and the evaluation of motor outcomes. All of the studies reported at least one metric of body structure and function and 47.4%, at least one metric of activity according to the ICF. The Motricity Index, an ordinal measure of limb strength (1–100)   performe  , was the2.MRI scans were performed on 3T scanners in 57.9% of the studies. The number of directions during diffusion acquisitions ranged from 6 to 64 and the number of b0, from 1 to 10. 83.3% of the studies used b values of 1,000 s/mmOnly 15.8% of the studies explicitly mentioned lesion masks during pre-processing and 18 different softwares were used for data analysis. 52.6% measured DTI metrics according to ROI-based methods, 36.8%, according to ROI in tractographies, and 10.5% within the entire CST according to tractography; 10.5% extracted the entire CST as a ROI based in whole-brain processing in TBSS . The mosDespite great heterogeneity in methods of collecting and analyzing the data, the majority of studies reported statistically significant correlations between DTI biomarkers and motor outcomes: 66.7% in the hyperacute, 83.3% in the acute, and 92.3% in the early subacute phases after stroke. Motor impairments were evaluated from 4 weeks to up to 6 months later in the hyperacute/acute studies, and up to 2 years in the subacute studies. DTI results closer to normal, from the 1 day up to 3 months after stroke, were correlated with less severe impairments.FA, rFA, or aFA were measured in 100% of the studies. At least one of these metrics was significantly correlated with motor outcomes in 66.7% of hyperacute or acute, and in 92.3% of early subacute studies. FA values vary across subjects and are influenced not only by the stroke, but also by subclinical white matter lesions that are frequent in patients with vascular disease in the ipsilesional as well as in the contralesional hemisphere , 99. HowPuig et al., Groisser et al., and Jang et al. did not find significant correlations between FA metrics and motor outcomes at some of the stages , 94, 100Puig et al.  assessedGroisser et al. measured not only FA, but also AD, MD, and RD in 10 patients at 3–7 days and 1–2 months post-stroke. Only asymmetries in AD at 3–7 days correlated with hand grip and the Motricity Index at 1–2 months, but not with performance in the nine-hole peg test. In contrast with other studies, the authors performed tractography and evaluated DTI measurements in the 10 voxels with the highest CST density ipsilesionally. This methodological difference may have contributed to the discrepant result, particularly in subjects with large lesions: 70% of the patients had large infarcts  . DTI anaOn the other hand, Groisser et al. found that changes in FA measured at a later stage (1–2 months) correlated with hand grip, Motricity Index and nine-hole peg test measured at 6 months, in line with other studies that assessed DTI at the early subacute phase post-stroke .Jang et al. were the only authors who did not report correlations between FA or rFA at the early subacute phase, and motor impairments. Only subjects with pontine infarcts were included, and measures were made at the pons, from 7 to 28 days post-stroke, according to tractography. The authors hypothesized that lack of a significant difference in the directionality of the residual CST at this level may have contributed to this finding .Few of the selected studies measured AD, MD, and RD , 112. FAA key question is whether DTI results enhance the predictive value of models of motor disability based on clinical information such as age and motor impairments, and neurophysiological testing. For instance, Stinear et al. reviewed data from 207 patients clinically assessed for upper limb impairments (SAFE score: shoulder abduction and wrist extension) and overall neurological impairments  within 3 days post-stroke. The patients underwent transcranial magnetic stimulation to determine the presence of upper limb motor evoked potentials contralateral to the lesion, and MRI at 10–14 days to assess: FA asymmetry , lesion load evaluated with tractography in the CST and in sensorimotor tracts. The primary upper limb motor outcome was the Action Research Arm Test, a measure of upper limb activity according to the ICF. Different prediction models were tested and the authors concluded that the PREP2 score, that includes age, SAFE and NIHSS scores as well as transcranial magnetic stimulation results, without any MRI biomarker, made correct predictions for 75% of the patients . DTI reshttp://enigma.ini.usc.edu/ongoing/enigma-stroke-recovery/) is expected to help in closing the gap in knowledge about the relevance of DTI biomarkers in research and clinical practice, to define motor prognosis. At the moment, DTI is not routinely performed in clinical practice for motor prognostication in stroke.The analysis of large sets of data, such as the ongoing ENIGMA project , reducing the risk of systematic errors due to subject motion , depending on the other physical parameters  acquire at least 30 non-collinear directions, as more accurate sampling reduces orientational dependence and enhances accuracy and precision of DTI metrics ; (2) uset motion ; (3) userameters , 31, 33;rameters , 116; (5The decrease in methodological heterogeneity and enhancement of reproducibility will advance the field by setting the stage for large studies with good-quality data in order to define the clinical relevance of DTI in prediction of motor disability from stroke.Finally, in the revised studies, the goal was not to test comprehensive predictive models that included DTI results. In order to determine whether DTI will have a role on prediction of motor recovery after stroke, it is necessary to test different models in large sets of data. DTI may reach a place in clinical practice if accuracy of a model is enhanced by this imaging tool, compared to models that only include variables that can be quickly and easily obtained such as bedside clinical evaluation.AC and LM contributed to the conception and design of the study. LM wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.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.


Supplemental Digital Content is available in the text Insomnia has become a universal subhealth disease, affecting more and more modern people's health and quality of life. At present, western medicine is only symptomatic treatment for insomnia. Bailemian Capsule (BLMC) is a proprietary Chinese medicine for treating insomnia. It has been widely used in China, but lacks evidence for evidence-based medicine. At the same time, the clinical efficacy and safety of BLMC are controversial. Therefore, the effectiveness and safety of BLMC in the treatment of insomnia are studied and systematically evaluated in this study. It provides reliable theoretical support for the treatment of insomnia with Traditional Chinese Medicine and the combination of traditional Chinese and Western medicine.The information was retrieved from electronic databases, Cochrane, PubMed, EMBASE, SinoMed, China National Knowledge Infrastructure, VIP Data, and WangFang Data. Randomized controlled trials on the BLMC in the treatment of insomnia were conducted. There was no limitation on the literature language. RevMan 5.3 software and STATA 12.0 software were used to perform the meta-analysis.This review will be to assess the efficacy and safety of BLMC for insomnia.Our systematic evaluation will provide evidence for the clinical efficacy and safety of BLMC in the treatment of insomnia, and will be published in the form of academic papers in the future to provide new ideas for clinicians in the treatment of insomnia. If people are so anxious about the initial insomnia symptoms that they cannot remove the interference factors, as these symptoms develop with time, then the initial symptoms tend to be fixed and eventually develop into insomnia. Reports have shown that among all complaints about sleep, insomnia is the most common. A 1979 Gallup poll shows that 95% of American adults suffer from insomnia. Based on this Gallup poll, half of the adults in the United States suffer from sleep disorders; 35% are reported to have insomnia, and 12% are reported to have serious insomnia. In the United States, 300 hundred million to 1080 hundred million dollars are used for the treatment of sleep disorders each year, leading to a great consumption of medical resources, a decline in individual social function and productivity, an increase in the number of sick leave days, and thus a great influence on the overall economic power of the whole country. In the current society, the incidence of insomnia among Chinese adults can reach 5% to 45%, and insomnia is more common among elderly individuals. Among several types of sleep disorders, the incidence of insomnia is the highest, accounting for approximately 97.5%.Insomnia refers to a lack of normal sleep time due to various reasons. Physiologically, insomnia reflects the weakening of the suppression function. Clinically, insomnia is characterized by difficulty in falling asleep and a sleeping time of no more than 30 minutes; the quality of sleep is decreased, sleep is maintained, and the number of awakenings is ≥2, with early waking and declined sleep quality; total sleep time (TST) is reduced and is usually <6 hours with nightmares and dreams.1.2 From ancient times, Traditional Chinese Medicine (TCM) has recorded insomnia as “bumei” (sleepless in Chinese). Based on the theory of TCM, insomnia is caused by many factors, including the enfeeblement of viscera and the imbalance of Yin and Yang, which lead to interference of the mind. In contrast to western medicine, which treats insomnia at the surface, TCM focuses on developing the general symptoms to treat both the manifestation and root cause of insomnia. As a Chinese patent medicine against insomnia, the Bailemian capsule (BLMC) in this article is made of 15 Chinese medicines: Mother-of-pearl; Lilium brownii F.E. Brown ex Miellez var. viridulum Baker; Gypsum; Spina Date Seed; Albizia julibrissin Durazz; Tuber Fleeceflower Stem; Codonopsis pilosula (Franch.) Nannf; Rehmannia glutinosa (Gaertn.) Li-bosch; Polygala tenuifolia Willd; Schisandra chinensis (Turcz.) Baill; Juncus effusus Linn; Acanthopanax senticosus (Rupr. et Maxim.) Harms; Ophiopogon japonicus (Linn. f.) Ker-Gawl; Salvia miltiorrhiza Bunge; and Smilax glabra Roxb, which has been widely used in China. Some studies have shown that the BLMC has a good curative effect in treating insomnia. Therefore, based on the theory of TCM and evidence-based medicine, this article collected and systematically evaluated randomized controlled trials (RCTs) of the BLMC in the treatment of insomnia that were completed or published before May 1, 2018. To this end, the aims of this study were to systematically study and evaluate the effectiveness and safety of the BLMC in the treatment of insomnia based on the available literature and to provide reliable theoretic support for the treatment of insomnia by TCM and by the combination of western medicine and TCM. This study has been supported by the Fund. For relevant information, see Supplemental.Currently, western medicine treats insomnia by drug therapy, including first-generation barbiturates, second-generation benzodiazepines, and third-generation nonbenzodiazepines. First-generation barbiturates are rarely used in the clinic. Second-generation benzodiazepines are the most widely used medicine in the treatment of insomnia, and they can shorten the time for falling asleep, reduce the awakening time and frequency, and increase total hours of sleep. However, this kind of medicine also has disadvantages because it is easy to form drug dependence and experience discontinuation of recoil and memory deterioration.22.1https://www.crd.york.ac.uk/PROSPERO).A protocol had been registered for this systematic review and meta-analysis in PROSPERO (CRD42018114512)  was adopted in the selected study. This study is based on the preferred reporting items for systematic reviews and meta-analysis (PRISMA statement).2.3.2The selected patients should be diagnosed with primary or secondary insomnia. There should be clear diagnostic criteria (Chinese medicine diagnostic criteria or Western diagnostic criteria are not limited), no other drugs had been taken before the study. Patient's age, gender, time of illness, and whether other diseases are not restricted.2.3.3This study is a systematic review. All patient data are obtained from published papers.2.3.4The experimental group received single therapy with the BLMC alone or in combination with western medicine or TCM . The control group received single therapy consisting of western medicine or TCM .2.3.52.3.5.1 Clinical recovery: sleep time returned to normal or increased to >6 hours per night, deep sleep, wake up energetic. Markedly effective: sleep time increased by >3 hours, and sleep depth increased. Effective: sleep time increased by <3 hours, and symptoms relieved. Invalid: no improvement or aggravation of insomnia; TCM syndrome curative effects standard: it is divided into 4 grades: those whose symptoms disappear after treatment are cured; those whose integral value decreases 2/3 after treatment are effective; those whose integral value decreases 2/3 to 1/3 after treatment are effective; those whose integral value decreases <1/3 after treatment are ineffective. The total effective rate = /Total number of cases × 100%.The total effective rate was calculated based on the criteria for the therapeutic effects of western medicine and TCM. Refer to the criteria for the efficacy of insomnia in Guiding Principles for Clinical Research of New Chinese Medicine.2.3.5.2: it is widely used in clinical evaluation of insomnia. It is characterized by the organic combination of the quality and quantity of sleep to assess, indicators include patients’ sleep quality, sleep time, sleep efficiency, sleep disorders, hypnotics, and daytime functions. A total of 4 surveys were conducted for each patient .Pittsburgh Sleep Quality Index scoreRecurrence rate.Adverse reaction ratio.2.42.4.1The network electronic databases were searched using a computer. The retrieved foreign databases included the Cochrane Library, PubMed, and EMBASE, while the retrieved Chinese databases included SinoMed, China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (VIP) Data, and WangFang Data. A combination of keywords and free words was used as the retrieval strategy.2.4.2Manual search of supplements to the following magazines (no electronic version of the file), including “China Journal of Chinese Materia Medica,” “Chinese Journal of Experimental Traditional Medical Formulae,” “China Journal of Chinese Traditional Medicine and Pharmacy,” “Shizhen Journal of Traditional Chinese Medicine,” and “Journal of Traditional Chinese Medicine,” related conference papers and papers collected after 2010 were retrieved by hand.2.4.3The network electronic databases were searched using a computer. The retrieved foreign databases included the Cochrane Library, PubMed, and EMBASE, while the retrieved Chinese databases included SinoMed, CNKI, VIP Data, and WangFang Data. A combination of keywords and free words was used as the retrieval strategy. Chinese retrieval words included “Bailemian,” “Shimian,” “Bumei,” and “Shuimianzhangai,” while English retrieval words included “Bailemian capsule,” “Bailemian Capsule,” “insomnia,” “agrypnia,” “hyposomnia,” “sleeplessness,” “dyssomnia,” “sleep disorders,” and “sleep disorder.” There was no limitation on the language. The literature search strategies used are shown in Table 2.52.5.1Two researchers (Jianxin Wang and Lian Hua) separately read the titles and abstracts of the retrieved literature and excluded those that did not meet the standards. For the remaining literature that met the absorption standards, the researchers obtained the full texts for further exclusion, and a screening table was created to indicate the reasons for exclusion. Finally, the researchers conducted data extraction of the absorbed literature, including author name, publication time, gender ratio, average age, average course of the disease, number of positive cases in the experimental and control groups, course of treatment, diagnosis standard, curative effect standard, and final index. Two researchers crosschecked the average results and determined whether to receive the controversial literature by discussion or invite a third reviewer who had rich experience in meta-analysis to arbitrate. The screening process of the paper is shown in Fig. 2.5.2For papers with incomplete data coverage, the author of the paper is first requested by e-mail or telephone. If the author of the paper does not agree to provide data or cannot contact the author of the paper, we will discuss the trade-offs of the paper.2.5.3: random allocation; allocation concealment; the use of an objective blind method, treatment options, and results measurement personnel; data integrity; selective results reporting; and other sources of bias . Two evaluators performed quality evaluations by reading the full text separately. Then, the quality evaluation results were crosschecked. Controversial results were managed by discussion or evaluation by a third party.Based on risk of bias assessment tool, the quality evaluation included the following 6 aspects2.5.42 quantification. If there was statistical homogeneity  among the research results, then the fixed-effect model was used for the meta-analysis. If there was statistical heterogeneity  among the research results, a random-effect model was used for the meta-analysis after excluding the influence of obvious clinical heterogeneity. Obvious clinical heterogeneity was managed by subgroup analysis, sensitivity analysis, or descriptive analysis.Meta-analysis was conducted by RevMan 5.3 software. In this article, the risk ratios and 95% confidence interval (CI) were used for the effect analysis of statistics to evaluate the ending calculation data. For the same unit, the weighted mean differences and the 95% CI analysis were used for the continuous data, and for different units, the standardized mean difference and 95% CI were used. The heterogeneity of the research results was analyzed by a chi-squared test , and the size of the heterogeneity was determined by combining with the I2.5.5To test the certainty of the results, we carried out a sensitivity analysis, removing studies that would have a greater impact on the results if the results remained unchanged and would ascertain their certainty. On the other hand, if the results changed, then we would have to analyze and examine the removed studies more carefully to find the source of heterogeneity and draw a cautious conclusion or carry out a descriptive analysis of the results.2.5.6For outcome indicators with more heterogeneous results, we carried out subgroup analysis on the more heterogeneous results, based on information found in the literature, to determine the reason for the increased heterogeneity. Simultaneously, with appropriate subgroup analysis, we can reduce the degree of heterogeneity and increase the certainty of the results. In this study, subgroup analysis was conducted according to the intervention measures, which had a great influence on outcome indicators, and was divided into BLMC versus western medicine and BLMC versus other Chinese medicine.2.5.7P < .05 concluded that there was publication bias in outcome indicators.For the heterogeneous results, publication bias was tested using Egger test in STATA 12.0 software, and 3 The combination of western medicine and TCM can overcome this slow effect and improve symptoms in a short time. In this way, patients will show higher dependence and continue the therapy.Insomnia is a common disease with symptoms including difficulty falling asleep and early awakening. This condition features a reduction in the time and depth of sleeping. Currently, with the increasingly faster pace of life, the incidence of insomnia is also increasing. This increase may lead to great harm, such as lower productivity and psychological barriers. Serious insomnia may cause certain physiological and psychological diseases, including mood disorders, a rise in blood pressure or blood sugar, anorexia, and even suicide due to depression.L brownii F.E. Brown ex Miellez var. viridulum Baker contains lily saponins, which can significantly reduce the independent activity and prolong the sleep time of mice caused by pentobarbital sodium, and the sedative and hypnotic effects of these saponins increase with increasing dose; S chinensis (Turcz.) Baill and A senticosus (Rupr. et Maxim.) Harms have inhibitory effects on the central nervous system. Li et al studied the effect of A senticosus saponin extract on sleep in mice through animal experiments. The sleep latency, incidence, and prolonged time in the A senticosus saponin group and control group were observed within 30 minutes after pentobarbital injection. The results showed that A senticosus saponin extract can shorten sleep latency, increase the incidence of sleep, and prolong the sleep time in mice. In addition, A senticosus saponins have no direct effect on the sleep of the mice, suggesting that A senticosus can promote sleep in mice.Schisandra chinensis (Turcz.) Baill is a raw material that can be used in health food. Yang observed the effect of S chinensis (Turcz.) Baill decoction on the sleep phase of free-moving rats by animal experiments, and the results showed that S chinensis (Turcz.) Baill decoction could prolong the TST of normal rats. In the sleep time phase, slow wave sleep phase II was significantly prolonged during sleep, but slow wave sleep phase I and fast wave sleep were not affected. These results showed that the decoction of S chinensis (Turcz.) Baill has the effect of improving sleep; A senticosus (Rupr. et Maxim.) Harms is good for clearing heat and relieving restlessness. Smilax glabra Roxb is good for relieving the uneasiness of the mind and nourishing the blood. The combination of the above medicines functions to significantly relieve the uneasiness of the mind, nourish the blood, relieve restlessness, and ease heart palpitations.Moreover, the dosage of western medicine will be reduced, which can also prevent the side effects caused by single western medicine therapy. Current studies have shown that BLMC is a safe and effective drug for treating insomnia. First, Through the systematic evaluation of the effect of the BLMC on the treatment of insomnia, this article aimed to increase the sample size, improve the reliability, and provide reliable theoretical support for clinical treatment based on meta-analysis.This work was done by the authors named in this article. Jingzhi Guan and Tian Tian designed the study and wrote the article. Jingzhi Guan, Tian Tian, Lian Hua, and Jianxin Wang collected and analyzed the data. Jingzhi Guan reviewed the full text and proofread the manuscript.Conceptualization: Tian Tian, Jingzhi Guan.Data curation: Tian Tian, Lian Hua, Jianxin Wang, Jingzhi Guan.Investigation: Jingzhi Guan.Resources: Lian Hua, Jianxin Wang.Software: Tian Tian.Writing – original draft: Tian Tian, Lian Hua, Jianxin Wang.Writing – review & editing: Jingzhi Guan.Jingzhi Guan orcid: 0000-0002-3086-477X.


Burnout syndrome is a work-related chronic stress that is described as emotional exhaustion, a decreased sense of personal accomplishment, and depersonalization. it has been considered an important problem especially among workers in the health sector.The aim of this research was to study the prevalence of burnout among Syrian residents during the Syrian crisis, which started 9 years ago, and to assess the factors related to burnout syndrome.A cross-sectional study was conducted to assess the levels of burnout syndrome; data were collected from residents doing their residency in 12 different hospitals spread over 8 governorates in Syria. A web-based Arabic version of Maslach Burnout Inventory questionnaire was used. The final sample size was 3350 residents from different specialties. SPSS V.22 was used to analyses the data using descriptive and inferential statistics.(93.75%) had a high level in at least one of the three domains of the burnout index, and (19.3%) of the residents had a high level of burnout in all three domains. Significant relation was found between gender, age group and affiliated authority variables and the levels of burnout. However no significant relation was found between burnout and the specialties or geographic variables. Males, residents in Ministry of Defense, and emergency medicine residents had the highest levels of burnout.High levels of burnout was found among residents during the Syrian crisis in comparison with other studies, which highlights the role of the current situation in raising workload on the Syrian residents. Burnout syndrome was first described in 1974 among healthcare volunteers , 3. QuanWork-related stress among healthcare professionals has become a serious health problem.For workers and the world economy , and burBurnout was found to be a significant predictor of the following physical conditions: hypercholesterolemia, type 2 diabetes, coronary heart disease, hospitalization due to cardiovascular disorder, musculoskeletal pain, changes in pain experiences, prolonged fatigue, headaches, gastrointestinal issues, respiratory problems, severe injuries and early mortality age, while psychological effects include: insomnia, depressive symptoms, use of psychotropic and antidepressant medications, hospitalization for mental disorders and psychological ill-health symptoms, in addition to a correlation between burnout and suicidal thinking . TherefoOn the other hand, The Syrian crisis began in 2011 and has had serious consequences on all of the Syrians. There are roughly 13 million people currently in need of medical services, and the requirements necessary to help these people have exceeded the available resources. WHO -World Health Organization- has only received 1/3 of the funding needed to implement the Humanitarian Activities Plan for 2016 . The negThe purposes of our study were to investigate the prevalence of burnout syndrome among resident physicians of all specialties in Syria, and to identify the main demographic factors associated with Burnout Syndrome.A cross-sectional study was conducted on a large sample of resident physicians training in Syrian hospitals affiliated to 3 residency programs in Syria: Ministry of Higher Education (MHE), Ministry of Health (MH), and Ministry of Defense (MD). We had also collected data from residents working in private hospitals in Syria. Data were collected from 12 hospitals located in 8 governorates , other governorates were not reachable during the time of data collection. All of the included doctors were current medical residents who spent at least one year in a residency program approved by the Syrian Commission of the Medical Specialties. We excluded residents who did not complete the research questionnaire, or had spent less than one complete year in residency, doctors who had finished their residency were also excluded.Residents were contacted by Email, the purpose of the study was thoroughly explained and participation was voluntary, the data was collected during the month of July 2018.We designed a special survey to collect the data, all residents of all specialties and hospitals were invited to participate. The survey consisted two parts: the first part was demographic data sheet that was designed especially for the purpose of this study, containing questions about age, gender, governorate, hospital of residency, residency program, the resident’s specialty, and the residency year. The second part was the Maslach Burnout Inventory - Human Services Survey (MBI-HSS), we used an Arabic validated version , MBI-HSSWe contacted (3837) resident physicians across Syria, (3350) residents completed the questionnaire and therefore, the response rate was (87.3%).p < 0.05.Data were analyzed using SPSS v.22 for descriptive data , and inferential statistics. The following tests were used to compare proportions of high levels of burnout: T-test, ANOVA test, Pearson’s correlations, and the significance level was defined as The final sample size was (3350), Table Levels of emotional exhaustion, depersonalization, and personal accomplishment are displayed in Table p = 0.004).Table p = .007).Residents working in the ministry of defense’s hospitals (MD), had the highest rates of high EE (89.4%) and DP (63.1%). while residents working in private hospitals had the highest rates of low PA Fig. . ANOVA tp = .067). Moreover, Fig. Physicians in their fifth year of residency had the highest percentage of high EE and DP and low PA, however no significant relation was found between those two variables .p = .037). Figure Third age group (31–35 years) had the highest rates of burnout on all of the three domains: EE, DP and PA (86.3%), (59%) and (27.2%) respectively. ANOVA test showed significant relation between age group and level of Emotional Exhaustion (p = .528).For the geographical distribution, Hamah had the highest level of EE (88.2%), Rif Dimashq had the highest level of DP (87.5%), and latakia had the highest level of PA (17.5%), No significant relation was found between the geographical governorate and the burnout variables  subcategories of the burnout is higher than the EGPRN -European General Practice Research Network- report which revealed 12% for EE, 35% for DP, and 32% for PA , only PAA recent systematic review indicated that the overall prevalence of burnout for all specialties is almost 35%. As for the burnout dimensions, the prevalence estimate of high DP, EE, and low PA for all specialties was 43.6%, 38,9%, and 34,4% respectively . In UnitFifth year residents had the highest rates of EE, DP, and PA. Aside from first year residents, burnout levels seemed to increase as physicians spent more years in residency, Although no statistically significant relation was found here in our study, many others stated the same notice , 26. FirOne of the unusual findings in our study was the relationship between gender and burnout. Male physicians registered higher levels of EE and DP and lower levels of PA than female physicians, with the knowledge that this difference was statistically significant only for emotional exhaustion dimension, although the opposite is usually reported by other studies , 27, 28.In our research, we found significant relation between EE and DP and residency in military hospitals, that is because physicians working for those hospitals are subjected to military regulations that adds on to the list of stressors related to the years of residency. Not many published literatures discussed this matter, although one study reported no significant difference in high EE or low PA rates between military orthopedic residents and their civilian peers. However, military residents had a significantly lower rate of high DP than civilian residents . AnotherHigh levels of burnout syndrome have been found among Syrian residents during the period of the Syrian crisis. Male physicians had higher emotional exhaustion, and residents working for Ministry of Defense had the highest rates of burnout syndrome. There was a significant relation between Burnout and gender, affiliated authority, and no other significant results between the other variables were found.more studies are needed to understand the coping mechanisms in order to prevent and reduce the effects of chronic stress on Syrian physicians.


Logistic regressions adjusted for age were used to determine the impact of socioeconomic status (SES) on sports participation and to measure the changes in sport participation rates. Participation declined among all subgroups of adolescents: from 79.0% to 65.8%. The greatest decrease was observed for boys with a high SES, whilst the lowest was for the high-SES girls. We observed that SES inequalities in access to sport increased among the girls, whilst they reduced among the boys. National government plans seem to have had limited success in this territory. Next to national studies, there is a need to develop territory specific studies which could show important disparities across the national territory.Improving adolescents’ levels of sport and physical activity (PA) is an official public health issue. French national government plans were launched in 2001, 2006, and 2011 to improve the participation levels of citizens. These plans should be monitored. To date, information on temporal trends in sports has come from the national population. However, no data are available to measure temporal trends in different territories across the country. Our study aimed to measure these trends among a representative sample of adolescent students of the third biggest French region (Bouches-du-Rhône), but also one of the poorest, between 2001 and 2015. Three surveys were conducted in 2001, 2008, and 2015 in high schools ( Many studies show the positive effect of physical activity (PA) on adolescents’ health ,2 and weThis importance has been highlighted in multiple plans developed by the French Government during the last decades to improve physical and sports activities at all ages of life . In 2001Along with these national findings, it is also important to estimate levels of participation in different territories across the country. It has been shown that factors influencing sport participation differed according to the area of residence. For example, the effects of socioeconomic status (SES) and sex were different between countries and areas within countries . Toftegahttps://www.reseau-canope.fr/education-prioritaire/comprendre/donnees-cles.html]. It is recognized that these territories were also those with the fewest sports facilities per inhabitant [The main purpose of this study was to measure the temporal trends in adolescents’ sports participation in a specific French territory between 2001 and 2015. The third biggest department of France (Bouches-du-Rhône)  represenhabitant . Given tThree sets of data collection on French adolescent students’ health were carried out between 23 March and 13 April 2001; 1 February and 1 April 2008; and 2 February and 10 April 2015, in 11 junior and 19 senior high schools in Bouches-du-Rhône, Provence, France. Each survey  was approved by the Rector of the school academy—also named Chancellor of the Universities—where our surveys were conducted. He is the territorial represent of the Minister of National Education and Research. In that respect, he has the authority concerning initiatives or research launched among schools (from primary to university levels).http://www.education.gouv.fr/cid76427/refonder-education-prioritaire.html). To keep our sample representative of the students in the department of Bouches-du-Rhône, we selected high schools so as to maintain the proportion of “classic” establishments and those classified under REP, DERS, EQEB, or ZEP. Each year, we randomly selected among junior high schools 3 REP and 16 “classic” establishments. Among the senior high schools, we randomly selected 4 DERS, EQEB, or ZEP, and 7 “classic” establishments. The adolescents invited to fill out the surveys were in their third year of junior high school or their last year of senior high school (9th and 12th grade). Only adolescents who agreed to participate and who returned signed parental informed consent forms were included in the study . Every student participated in the survey under the supervision of a physical education teacher and a researcher.In this area, there were 136 public junior high schools of which 23 were classified as priority education networks (REP) . Among 8In 2001, the sample comprised 878 adolescents , representing 2.8% of the students in these grades in Bouches-du-Rhône. In 2008, the sample comprised 1321 adolescents , representing 3.4% of the students in these grades in Bouches-du-Rhône. In 2015, the sample comprised 1019 adolescents , representing 3.0% of the students in these grades in Bouches-du-Rhône.The variables covered in the questionnaire concerned demographics and sports participation.n is sample size needed, z is the statistic for the level of confidence , P the prevalence expected , and d the allowable error (0.05 chosen). Given that our sample size was between 878 and 1321, it was more reliable to divide SES into two groups rather than three or more . It helped obtain the most precise estimation of sport participation rates in the parent population.Students were asked to report their age, sex, and the head of their family’s employment status. Similarly to other French studies, the head of their family’s employment status was used to estimate the SES. Adolescents had to answer the question: ‘What is the occupation of the head of your family?’ by checking the applicable box ; intermediate professions ; salaried employee; manual worker; retiree; unemployed; other). In view of previous studies on the link between SES and sport participation, with some focusing on high and low SES for the analyses ,22, we an = 1445). Occupations which had an AAI over 21,955 € were considered as having high socio-economic status. These were persons in intellectual occupations  or intermediate occupations  (n = 1503). Young people whose parents’ occupations were unknown were excluded from the SES analyses . Official statistics did not provide information about the AAI of farmers. Thus, they were classified as unknown . In 2001, 44.2% of adolescents were from low-SES families, 40.5% from high SES, and 15.3% have an unknown SES. In 2008, 46.4% of adolescents were from low-SES families, 48.8% of high SES, and 4.8% of unknown SES. In 2015, 43.6% of adolescents were from low-SES families, 49.3% of high SES, and 7.2% of unknown SES.For the cutting point, our criterion was average annual income (AAI). In 2013, in the department of Bouches-du-Rhône, AAI was 21,955 € per inhabitant ,33. Occun = 6) was formed to decide whether or not these activities could be considered sports with regard to the definition of the Council of Europe [n = 5). The lists of preferred sport activities considered as being sports and as non-sports by the committee are presented in The outcome variable was sport player, coded as ‘yes’ or ‘no’. Sport was defined according to the definition of the Council of Europe : “Sportsf Europe . Studenthttp://www.injep.fr/article/tableaux-statistiques-relatifs-au-recensement-des-licences-sportives-de-2016-11533.html). This rate was around 21% for organized sport at school, according to official statistics of the National Union of School Sport (see https://unss.org/wp-content/uploads/2018/02/UNSS-PDNSS-2016-2020.pdf).For the reader’s interest, typically, in France, organized sport is played in community clubs. At the national level, there was around 38% of 15–24 year olds holding a federation license in 2016 . Firstly, sport participation rates were calculated by sex, SES (low/high), and year. The chi-square statistical test was used to give general effects of sex and SES on sport participation. Secondly, a binary logistic regression adjusted for age was performed to determine the effect of SES by year and by sex. Thirdly, multiple binary logistic regressions adjusted for age were performed to determine the changes in sport participation between 2001 and 2008, between 2008 and 2015, and between 2001 and 2015 by sex and SES. No specific analyses were performed to measure the temporal trends in preferred sports activities chosen by adolescents between 2001 and 2015. This analysis will be done in subsequent papers treating that topic specifically.Sports players were 79.0% in 2001, 71.8% in 2008, and 65.8% in 2015. A greater proportion preferred the organized context of participation . 2 = 45.20; diff = 22.3%, Chi2 = 77.38, respectively; diff = 21.3%, Chi2 = 68.18, overall: p < 0.001).In 2001, 2008, and 2015, sport participation was higher in adolescent boys compared to adolescent girls In 2008 and 2015, sport participation was higher in adolescents of a high SES compared to low SES .In 2001, 2008, and 2015, sport participation was lower in adolescent girls with a low SES compared to adolescent boys with a low SES .In 2001, 2008, and 2015, sport participation was lower in adolescent girls with a high SES compared to adolescent boys with a high SES  and OR: 0.61 (95% CI: 0.42–0.87), respectively.In 2008, girls with low SES were less likely to play sport compared to 2001.In 2015, girls and boys with a high SES were less likely to play sport than in 2008.In 2015, compared with 2001, all the adolescent populations were less likely to play sport.Our study treated both the effects of SES by sex and year and the evolution in sports participation by sex and SES from 2001 to 2015.As regards the SES effects, consistent with previous findings, we observed that, regardless of SES, girls practice sports less than boys ,8,21,22 Regarding the temporal trends in sports, we observed a decline in adolescent sport participation, regardless sex or SES. This variation in sport participation was different from that seen in the Eurobarometers ,20, whicAlong with the French national trends observed in the Eurobarometers, these results highlighted the need to develop territory specific studies within the country. As we mentioned in the introduction, the former reflected the global situation without being able to provide estimation of participation in specific territories. The sample sizes were too low. Our study revealed the importance of this problem. In spite of the stability in national adolescent sport participation, the department of Bouches-du-Rhône presented an important decline. In addition, this revealed, for the first time, important disparities in participation across the year. This is an important issue to help understand why inequalities increased among the girls, whilst they reduced among the boys. Future researches should be done. In terms of public policy, it is important to consider local specificities and their influence on sport participation, to develop the most adequate sport and physical activities promotions programs. To improve local knowledge, firstly, it would be interesting to conduct similar studies in both (i) the poorest, (ii) the richest areas of France. It is likely that temporal trends in sports will be quite different as a function of the overall SES levels and sports infrastructures of each territory. Such findings could provide important information to help the development of future sport and PA promotions programs based on scientific evidence.One of the major features of our study was the three-assessment points during a 15-year period within the same methodology in a specific French territory. This is the first time that a territory-specific study has been conducted since the launch of the physical and sports activities promotions programs by the French Government. In addition, it was considered that having invited students’ populations in junior and senior high schools to participate was of great importance. With this methodology, we were able to select high schools in order to keep the sample representative in terms of level of pupil achievement, parents’ occupations, and place of residence. In our opinion, the relative important representativeness of the sample ensures reliable results. They should represent valuable information for public health officials.This study also entailed several limitations.Firstly, and regrettably, our study could not help to determine distinctly the sport participation rates in organized and unorganized context. Adolescents were asked to report how many hours per week they played sport, regardless of the context of participation. However, information related to the times spent in each context was not provided. Adolescents were asked to report their preferred context of participation. Although we observed stability in the preferred context of participation (organized), we cannot assume that their preferred context of participation is equal with their usual and more frequent context of sport participation. It is thus impossible to address whether the decrease in sport participation observed was more pronounced in the unorganized or the organized context. Future studies could consider all these methodological questions in order to obtain the most wide and precise information regarding the temporal trends in adolescent sport participation.Secondly, public health policies aim to improve PA, and sports are viewed as a means to attain recommended levels of PA. In this study, we measured only sport participation rates. Although we observed a decrease in sport participation, results did not provide information about the temporal trends in overall levels of PA, for example, active transportation. Future studies should combine measures of sport participation and levels of PA as proposed in the Global Physical Activity Questionnaire , which sThirdly, the seven-year interval between surveys is too large to accurately situate the variations in sports practice rates. It is thus impossible to connect them to precisely situated environmental factors and actions.Finally, future studies on trends in youth sports practice should include more factors  that areSports participation rates (organized and unorganized) of adolescent students living in this area were lower in 2015 compared to 2001, regardless of sex and SES. The results are in contrast with those observed by national reports. These findings suggest a limited effect of the French national plans to improve the sport activities levels of adolescents living in the department of Bouches-du-Rhône. The specificity of this area could explain these differences. Notably, the results highlighted that social inequalities in sport participation changed differently across the adolescents’ sex. The differences in sport participation rates between boys with a low SES and those with a high SES diminished over the time. On the contrary, there were increasing inequalities linked to SES in access to sport among the girls. Future researches should be done to understand this phenomenon. Alongside national studies, there is a need to develop territory-specific studies which could show important local phenomenon and disparities across the national territory.