As in adults, obesity also plays a central role in the development of metabolic syndrome (MS) in children. Non-alcoholic fatty liver disease (NAFLD) is considered a manifestation of MS. Not only MS but also NAFLD seem to be inversely associated with serum bilirubin concentrations, an important endogenous tissue protector when only mild elevated. The aim of the study was to evaluate the association between serum bilirubin levels and the prevalence of MS and NAFLD in Italian obese children and adolescents. A retrospective cross-sectional study was performed in 1672 patients aged from 5 to 18 years. Clinical and laboratory parameters were assessed. NAFLD was measured by liver ultrasonography. The study was approved by the Ethical Committee of the Istituto Auxologico Italiano . MS was present in 24% and fatty liver (FL) in 38% of this population. Bilirubin was not associated with FL and MS as a whole, but it was inversely associated only with selected components of MS, i.e., large WC, high blood pressure and high triglycerides. Our data suggest that bilirubin is not protective against MS and NAFLD in the presence of severe obesity. The prevalence of overweight and obesity in children and adolescents has substantially increased in recent years . As in aBilirubin belongs to the tetrapyrrolic compounds superfamily and it is the end product of heme catabolism. Senescent erythrocytes are the principal sources of the heme group, together with the turnover of myoglobin, cytochromes, and other hemoproteins such as microsomal cytochrome CYP-450 . BilirubFor a long time, bilirubin has been considered a useless waste product of heme metabolism at best, or a toxic compound, especially for the central nervous system, at worst. Although its excessive accumulation is neurotoxic in neonates, more recent data indicate that bilirubin, when only mildly elevated, serves as an important endogenous tissue protector and a physiological modulator of oxidative stress and chronic inflammation in MS ,24,25. TNot only MS but also non-alcoholic fatty liver disease (NAFLD)  and non-The objective of the present study was to evaluate the association between serum bilirubin levels and the prevalence of MS and NAFLD in a large sample of obese Italian children and adolescents followed at a tertiary care center for pediatric obesity.A retrospective cross-sectional study was performed using an already available dataset of obese children followed at our tertiary care center for the treatment of pediatric obesity. The children were admitted to the clinic to undergo a short-term structured multidisciplinary weight-loss program. The inclusion criteria were: (1) Caucasian ethnic group; (2) age ≤ 18 years; (3) BMI ≥ 95th percentile for age and sex according to Italian growth charts ; (4) ava2. Standard deviation scores (SDS) of weight, stature, and BMI were calculated using Italian growth charts [Pubertal status was classified in 5 stages according to Tanner . Weight h charts . Waist ch charts . AlcoholHBV surface antigen and antibodies against HCV were measured to exclude hepatitis B and C . AlanineLUS was performed using standardized criteria ,52. NormeCRP) with bilirubin. Logistic regression models were used to quantify the association of binary outcomes  with bilirubin [Most continuous variables were not Gaussian-distributed and all were reported as median (50th percentile) and interquartile range . Discrete variables were reported as number and proportion. Linear regression models were used to quantify the association of continuous outcomes  explained by bilirubin was very small and of no biological relevance.Bilirubin was not associated with BMI and insulin, while it was inversely associated with weight:height ratio and CRP. However, the proportion of variance of weight:height ratio (0.2%) and logBilirubin was not associated with FL, MS, high glucose and low HDL, while it was inversely associated with large waist circumference, high blood pressure, and high triglycerides. However, as can be clearly seen from the probability plots given in In the present study, performed on 1672 obese subjects aged 5 to 18 years, we tested whether bilirubin is associated with FL and MS and its components. Bilirubin was not associated with fatty liver categorized both as binary (yes vs. no) and ordinal (none vs. light vs. moderate vs. severe) . BilirubBilirubin levels increased with increasing age and pubertal status and were higher in boys than in girls. These findings are in line with those obtained in the white subjects aged 5 to 30 years studied by the Bogalusa Heart Study . Serum bp < 0.05), HOMA-IR (p < 0.05), and CRP (p < 0.001) (Bilirubin levels were inversely associated with waist:height ratio (< 0.001) . Howeverp = 0.001). The negative association that we detected between bilirubin and CRP, even with the normal range of the latter, is in line with these findings and the anti-inflammatory activity of bilirubin [Chronic systemic inflammation plays a major role in the pathogenesis of MS-associated disease . The serilirubin ,61,62,63p < 0.001) (A mechanism linking bilirubin and plasma lipids has been proposed . Reduced< 0.001) .Little is known about the association between bilirubin and MS in children and adolescents. In a representative sample of the non-institutionalized civilian US population (NHANES), Lin et al. examined 4723 children and adolescents aged 12 to 17 years and identified 190 (4%) with MS. Serum total bilirubin was significantly higher in subjects without MS than in those with it. The authors speculated that in young subjects, when the metabolic dysregulation is in its early stages, bilirubin may exert its anti-oxidative effect within the tissues. Serum bilirubin levels, even within the normal range, might have graded associations with the prevalence of MS in children . SimilarIn our study, total serum bilirubin was not associated with MS as a whole, but only with some of its components. The only available study of young obese children was performed in Portugal and showed an association between total bilirubin and percentage of body fat . It is wIn the present study, 38% of a large sample of obese children had NAFLD. Even if a prevalence of 38% is within the expected range , it is sThe present study has some limitations. First, its results cannot be extended to the general pediatric population comprising of non-obese children. Second, as we have discussed in detail elsewhere ,75, althIn conclusion, in a population of severely obese children and adolescents, we did not detect any association between serum total bilirubin, FL and MS as a whole. Bilirubin was nonetheless inversely associated with HOMA-IR, CRP, and with three components of MS, i.e., large WC, high blood pressure, and high triglycerides. Although these associations were statistically significant, they cannot be considered biologically relevant on the basis of the underlying effect size. Our data seem to be in contrast with the available literature showing an inverse association between bilirubin and MS. Conversely, our data adds something new, focusing on the grade of obesity and suggesting that bilirubin is not protective against MS and NAFLD in the presence of severe obesity.


Temperament and character of pregnant women, especially harm avoidance (HA) and self-directedness (SD) have been identified as risk factors for postpartum depression, in addition to poor social support. However, the relationship between these personality traits and social support for depressive symptoms after delivery has not been examined.Data were extracted from a prospective cohort survey on pregnant women conducted in Nagoya, Japan that included the Temperament and Character Inventory (TCI), the Social Support Questionnaire (J-SSQ), and the Edinburgh Postnatal Depression Scale (EPDS) at approximately week 25 and 1 month postpartum. A mediation analysis using structural equation modeling (SEM) was used to test if social support in pregnancy is a mediator between personality traits and postpartum depressive symptoms.P < 0.001 for harm avoidance; total effect: β [SE], −0.265 [0.067], P < 0.001 for SD). Mediation analysis showed that the effect of harm avoidance on depressive symptoms was partially mediated by low social support . Self-directedness on depressive symptoms was not found to be mediated by low social support.Thousand five hundred and fifty-nine women were included in the analysis. Both harm avoidance and SD were significantly associated with depressive symptoms (total effect: β [SE], 0.298 [0.041], Results indicate that poor social support worsens depressive symptoms in women with high HA during pregnancy. Limitations include a possible selection bias due to the limited target facilities; most variables being evaluated based on self-report questionnaires, and different number of samples available for analysis between harm avoidance and SD. Postpartum depression, which has an approximate prevalence of 10–15% in mothers , can leaTemperament and Character Inventory is based on a seven-dimensional model consisting of temperament (four dimensions) and personality (three dimensions). The four dimensions of temperament are Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and persistence (P), and the three dimensions of personality are, self-directedness (SD), Cooperativeness (C), and Self-Transcendence (ST) . Of the Previously we found that scores of HA increase with the severity of depressive symptoms , and thaIn addition to the above, social support during pregnancy has been shown to be protective against postpartum depression . HoweverIn the present study, therefore, we used SEM to clarify the relationship between personality traits, social support, and postpartum depression using data from our prospective perinatal cohort and identify protective factors in subjects with high-risk personality traits for the development of postpartum depression.Data from this study were extracted from a prospective cohort study carried out in Nagoya, Japan, from August 2004 to March 2020. Three questionnaires, the Edinburgh Postnatal Depression Scale (EPDS), TCI, and Japanese version of Social Support Questionnaire (J-SSQ) were used to measure depressive symptoms and related factors. The socio-demographic variables included age, partner's age, and number of children. Participants answered the questionnaire during early pregnancy (T1: around 25 weeks of gestation) which included the EPDS, TCI, and J-SSQ. One month after delivery (Q2), the EPDS, were filled out and the questionnaire was mailed back. This study followed the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) reporting guideline.Participants were recruited from a general hospital, two obstetric and gynecological hospitals and a university hospital. Pregnant women participating in prenatal classes before the 25th week of pregnancy were invited to participate if they were aged 20 years or older and able to read and write Japanese. Since the age of adulthood in Japan is 20 years, we excluded pregnant women under the aged 20 years in this study.A written informed consent was obtained from all those who agreed to participate in the study. The study protocol was approved by the Ethics Committee of the Nagoya University Graduate School of Medicine and all study procedures met the Committee's guidelines and regulations. All study protocols were in accordance with the 1964 Helsinki Declaration and its later amendments.Personality traits including HA and SD were measured using the TCI. The TCI is a self-report questionnaire consisted of 125 items that look at four dimensions of temperament  and three dimensions of character . We used the Japanese version of the TCI-125, which includes 125 questions covering 20 items pertaining to HA . The relWe used the J-SSQ  to measuThe EPDS is a self-administered questionnaire developed by Cox et al. for the screening of postpartum depression. EPDS comprises 10 items and was scored on a four-point scales with total scores ranging from 0 to 30 . The Japmedsem command in Stata was used to estimate indirect effects in the mediation model . The analysis of the outcome  included all observed and latent variables in a single step. The on model . We usedon model . Comparan = 1,542). There were 1,138 (72.9%) primiparas, 381 (24.4%) multiparas, and 40 unanswered about parity.In total, 1,559 pregnant women were included in the analysis who submitted valid questionnaires at around the 25th week of pregnancy. The average age of the participants was 32.4 ± 4.6 years  and negatively correlated with SD , J-SSQ Number , and Satisfaction . The recruitment process was described in P < 0.001). Mediation analysis showed that the effect of HA on depressive symptoms was partially mediated by low social support , indicating that 29.8% of the total effect of HA on EPDS scores was mediated through low social support.P < 0.001). Mediation analysis showed that the effect of SD on depressive symptoms was not mediated by low social support .In the present study, we confirmed that personality traits during pregnancy predict the depressive symptomatology at 1 month postpartum. Additionally, we identified social support during pregnancy as a mediator for the severity of depressive symptoms in women at high risk for postpartum depression, which could be a potential target for intervention to protect the development of the illness.Our results showed that high HA and low SD around 25 weeks' gestation are associated with higher EPDS scores in the first month of postpartum, which successfully replicates previous studies of postpartum depression using relatively small sample sizes –29. In oWe have also confirmed that social support during pregnancy is a protective factor for postpartum depression. This result was consistent with our previous papers , 43–45. Some limitations should be considered in this study. First, there is a possible selection bias due to the limited target facilities. In addition, we included only pregnant women who participated in the perinatal class. Second, the variables used in this study were mostly evaluated based on self-report questionnaires, not on a diagnosis by a psychiatrist nor a structured clinical interview. Third, we started evaluating HA, J-SSQ, and EPDS in 2004, while evaluating SD started in 2011. Therefore, the number of samples available for analysis differs between HA and SD, which may have affected the results. Finally, there is a possibility that HA and SD itself has been affected by maternal symptoms.In conclusion, in this study we have shown that social support may work differently with specific personality traits on depressive symptoms after delivery. It is important to provide appropriate support according to mothers' temperament and characteristics to prevent the development of postpartum depression.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the Nagoya University Graduate School of Medicine. The patients/participants provided their written informed consent to participate in this study.YN, NT, AY, and NO conceptualized, designed the study, and interpreted the data. YN, NT, AY, TO, MM, and NO acquired and analyzed the data. YN, NT, and NO drafted the manuscript, tables, and figures. All authors approved the final version to be published.This work was supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Ministry of Health, Labor and Welfare of Japan; the Academic Frontier Project for Private Universities, Comparative Cognitive Science Institutes, Meijo University; the Core Research for Evolutional Science and Technology; Intramural Research Grant (21B-2) for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry and the New Technology Development Foundation ; Research and Development Grants for Comprehensive Research for Persons with Disabilities from the Japan Agency for Medical Research and Development ; JSPS KAKENHI (JP20K07943 to YN and 21K07479 to NT).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Stress management in the workplace is essential for a healthy mental and physical state. Due to technological advancements, individually tailored therapy and online cognitive behavioral therapy (CBT) are on the rise.This study analyzed the efficacy of a smartphone app based on third-wave CBT tailored to an individual.A randomized controlled trial was conducted with 126 participants who were divided into 2 groups. The intervention group used the smartphone app BetterLife for 10 weeks, while the control group was placed on a waiting list for the same duration. The Perceived Stress Scale–10 (PSS), Korean Utrecht Work Engagement Scale–9 (UWES), World Health Organization Quality of Life Assessment (WHOQOL), Beck Depression Inventory–II (BDI), and Beck Anxiety Inventory (BAI) were administered at baseline and after 10 weeks to both groups.F=24.33, P<.001, η2=0.17) and UWESK scores  in the intervention group than in the control group. WHOQOL scores exhibited statistically significant improvement in the intervention group in the overall quality of life , physical health , psychological health , social relationships , and environmental domains  but not overall health . BDI  and BAI  showed a statistically significant improvement in the intervention group, but this significance did not survive the Bonferroni correction (P<.005).Of the 126 participants, 11 dropped out during the trial. A 2-way repeated measure analysis of covariance was conducted, controlling for baseline BDI. There were greater improvements in PSS (These results provide evidence that smartphone-based CBT is a viable option for reducing stress in the workplace.Clinical Research Information Service KCT0003231; https://cris.nih.go.kr/cris/search/detailSearch.do/15137 Stress management is undoubtedly crucial to the mental health as well as physical health of individuals. Chronic and high stress have been linked to depression , anxietyOf the known methods for stress management, cognitive behavioral therapy (CBT) has been identified as effective ,9. TradiAlthough online CBT has advantages over traditional CBT in terms of anonymity and accessibility , in tradWe hypothesized that using an online CBT-based app designed to help manage work stress for 10 weeks would result in a statistically significant improvement in stress-related scales compared to a waiting group.f=0.20). Based on these calculations, 51 participants were needed in each group, and after calculating a 20% dropout rate, the required total sample size was set at 128 participants.The sample size was calculated using G*Power (Heinrich-Heine-Universität Düsseldorf), based on a statistical test on repeated measure analysis of variance (ANOVA), since the covariance number was not determined. A type I error of .05 and statistical power of 0.8 were used. The correlation among repeated measures was set conservatively at 0, and based on previous similar studies [Participants were recruited through billboard advertisements between November 2019 and January 2020. The inclusion criteria for the trial were as follows: (1) elevated perceived stress defined by a score of 14 or higher on the Perceived Stress Scale–10 (PSS); (2) indication that the reason for stress was mainly work-related (the reason for stress was considered to be work-related if the participant could identify one or more stress-related factors that they experienced in the work environment and stress in other areas such as family were minor in comparison to work-related stress); (3) employment of at least 20 hours per week and not self-employed; (4) aged 18 to 60 years; and (5) ability to provide informed consent to participate after being given information about the trial and other information that the participant must know to participate. The exclusion criteria were as follows: (1) inability to provide informed consent; (2) education level below the 9th grade; (3) history of congenital brain disorder, cerebral palsy, or other acquired brain injuries; (4) history of neurological disorders; (5) severe anxiety, depression, or psychotic disorder as assessed by the Korean Symptom Checklist–95; or (6) history of drug or alcohol abuse.In total, 131 individuals who had work-related stress expressed interest in the trial. Of these, 3 withdrew participation after being informed of the detailed trial protocol; written consent was received from the remaining 128 participants. Two patients were excluded because of clinically relevant scores in the Korean Symptom Checklist–95. A total of 126 participants were included in the trial and randomized into 2 parallel groups with equal allocation ratios . RandomiThe intervention group was given a random individual application ID to access the app, a link for downloading the app, and a manual of the program. Further, they were instructed to use the BetterLife program for 50 minutes per week for 10 weeks. They had the option to contact a designated person to ask for help in operating the app. Participants were sent a text message as a prompt to notify them of their app use every week during the trial. Members of the control group were placed on a waiting list for 10 weeks after which they were given access to the BetterLife program for the next 10 weeks. This was primarily done for ethical reasons, and data collected from the control group after using the BetterLife program were not used in this analysis. These data are being considered for use in secondary analyses, which can strengthen our research. This trial was approved by the institutional review board of Chung-Ang University Hospital (1712-008-304) and registered in the Clinical Research Information Service of Republic of Korea (KCT0003231), a member of the WHO International Clinical Trials Registry Platform. All participants enrolled in the trial provided written informed consent.Of the 126 participants, 11 dropped out of the trial: 9 from the intervention group (14.3%) and 2 from the control group (3.2%). Of the 9 participants who were excluded from the intervention group, 2 left the trial due to personal reasons and 7 wished to leave due to lack of interest. Of the 2 participants who were excluded from the control group, 1 wished to leave the trial due to lack of interest and 1 was excluded because they were starting psychiatric treatment. Finally, 115 participants—54 in the intervention group and 61 in the control group—completed the 10-week trial and post-10-week data were collected. The 11 excluded participants’ post-10-week data were produced by the baseline observation carried forward method, and data were analyzed using an intention-to-treat method. The average use time of the program was 56.40 (SD 8.42) minutes per week; this was calculated by using the program time of the 54 participants who finished the 10-week program only. No substantial harm or unintended effects were observed.Participant demographic data were collected including age, sex, education level, marital status, alcohol consumption, and smoking habits. Information on employment was also collected, including company size, work field, type of employment, job grade, whether they handle direct customer complaints, income, workdays per week, work hours per day, work experience in the current work field, and job. Information regarding the number of late days, early leave days, and absent days of the past month was also collected. The participants were asked to complete the PSS, Korean Utrecht Work Engagement Scale–9 (UWES), abbreviated version of the World Health Organization Quality of Life Assessment (WHOQOL), Beck Depression Inventory–II (BDI), and Beck Anxiety Inventory (BAI) to assess psychological and work stress-related status at baseline and after the 10-week intervention. PSS and the overall quality of life score of the WHOQOL at 10 weeks were set as the primary outcomes. Data were collected in a face-to-face setting by the researchers of Chung-Ang University Hospital at a separate location preferred by the participant. Participants received 100,000 Won (US $83) as compensation for their travel fees.The PSS was developed by Cohen et al  and valiUWES is one of the most frequently used scales related to work engagement. It calculates work engagement by measuring vigor, dedication, and work absorption through a 7-point frequency rating scale ranging from 0 (never) to 6 . It was developed by Schaufeli et al  and has WHOQOL was developed by the WHO as a measure to assess the quality of life (QoL) in individuals across different cultures . It has Diagnostic and Statistical Manual of Mental Disorders, fourth edition diagnosis for depressive disorders [The BDI was initially developed by Beck in 1961 and revised in 1979 to BDI-IA and finally to BDI-II in 1996 to accommodate the changes in the isorders . It is aisorders . The BDIThe BAI was developed by Beck in 1988 . It is aBetterLife is a smartphone-based program for the treatment of stress, depression, anxiety, and sleep disorders used for guided self-help therapy; it can be used for both prevention and treatment. It is designed for anonymous treatment, targeting individuals with mild or moderate symptoms. BetterLife uses recognized manuals for CBT and problem-solving therapy and consists of approximately 600 modules of 7 types: test modules, psychoeducational modules, cognitive exercises, practical exercises, diary modules, notification modules, and comment modules. The test modules included the World Health Organization Well-Being Index (WHO-5) , the MajAll treatment components in the program are based on evidence-based methods documented in scientific studies ,34. BettThe chance to use the WHO-5 questionnaire was provided every week to tailor to each user. Thus, the user could follow the improvement over time, even in a graph. If the test value is low (meaning low well-being), the user is referred to the depression (MDI) and anxiety (GAD-7) modules. When acceptable values of these tests are obtained (showing a low degree of depression and anxiety symptoms), the user automatically returns to the other parts of the program. Another feature to personalize the program to the user is the user’s own estimation of stressors in work and daily life. The user is guided to modules specifically concerning the problems pinpointed by the user. An overview of the program can be found in the supplements  and 2.t test. Intervention outcomes were measured using work-related scales and psychological scores. Changes in late days, early leave days, and absent days in the past month were also collected to determine whether the app could have a tangible effect on work life.All data were analyzed using SPSS . The data presented here concern the intervention group compared to the waiting list group (controls) at baseline and follow-up. Data on the controls after using the BetterLife program and those on the program’s long-term effects are not presented. Baseline information, including demographic and psychological scales, was compared using the chi-square test, Fisher exact test, and independent For all participant data, univariate logistic regression analyses were conducted to determine whether variables of independent factors—such as age, gender ratio, education level, marital status, alcohol consumption, smoking, BDI scores, BAI scores, type of work field, workdays, work hours, and work experience—could explain a significant amount of variance in the dependent variable (high perceived stress) after considering all other variables. Statistically significant independent factors were evaluated using a multivariate logistic regression analysis using a stepwise forward conditional method. High perceived stress was defined as a PSS score of 27 or higher.P<.005 was considered statistically significant. The number of late days, early leave days, and absent days were analyzed separately by 2-way repeated measure ANOVA with time as a within-factor and group as a between-factor since they were not collected as part of the initial intervention outcome.Using 2-way repeated-measures analysis of covariance  with time as a within-factor and group as a between-factor, controlling covariates determined from the logistic regression and the changes in PSS, UWES, WHOQOL, BDI, and BAI scores were calculated. Bonferroni correction was used to compensate for multiple comparisons, and α=.05/10=.005. There were no significant differences in age, gender ratio, education level, marital status, alcohol consumption, smoking, company size, work field, type of employment, job grade, direct customer complaint handling, workdays, work hours, work experience, and late days, early leave days, and absent days in the past month between the intervention and control groups . At baseP<.001; t test of the repeated measures of the control group showed no significant differences after the Bonferroni correction =1.22, rrection .P>.05) and covariances (P>.001), as assessed by the Levene test of homogeneity of variances and Box M test, respectively, in all categories except for the number of late days, early leave days, and absent days in the past month. The Mauchly test of sphericity was ignored because there were only two groups for each factor. Controlling baseline BDI scores, the intervention group showed greater improvement in the changes in PSS  and UWESK scores  compared to the control group  and physical health , psychological , social relationships , and environmental domains  but not overall health  and BAI  showed traditionally low P values, they did not survive the Bonferroni correction. Unadjusted ANOVA yielded similar results except for BDI , which showed a significant interaction between treatment groups and pretests/posttests  and covariances (P>.001) were assessed by the Levene test of homogeneity of variances and Box M test, and the Mauchly test of sphericity was ignored. There were no significant interactions in the number of late days, early leave days, and absent days in the past month between the treatment groups and pretests/posttests  ct sizes . Little ct sizes .t=3.63, P<.001; t=3.63, P<.001) and social relationship scores in the WHOQOL .Dropout analysis was also performed, comparing the baseline values of the 11 participants who dropped out and the 115 participants who completed the trial. In the demographic data, work hours per day were significantly lower in the dropout group  on stress reduction [F=24.83, P<.001, η2=0.17). We estimate this large effect size to be because of meditation, emotional acceptance, and other third-wave CBT qualities incorporated in the program. Asplund et al [The effects of CBT on stress management in online settings have been well documented in previous studies ,35. A meeduction . Howevereduction  identifieduction  also obseduction . Our stund et al  and Ebernd et al  also usend et al . It has nd et al .The intervention group also showed improved work engagement, represented by improvements in the UWES. Work engagement, often considered the opposite of burnout, is a positive work-associated mindset with characteristics such as vigor, dedication, and absorption . ExtensiImprovement of QoL in all domains, including overall QoL, was seen in the intervention group. However, the perception of overall health did not differ between the control and intervention groups. QoL improvement by CBT has been observed in literature: Hofmann et al  used a m2=0.14), in addition to our primary result, perceived stress. We attribute this improvement to the helper system that asked participants to find a helper, someone who can talk to and confide in about work. Participants also provided feedback that using this app with a helper allowed them to be more engaged in using the program and made the work environment more enjoyable. Improved social relationships within the workplace are estimated to increase employee well-being and company efficiency [The social relationship domain of QoL had the most significant effect size . The program incorporated modules that directly help deal with depression and anxiety, as controlling psychological symptoms is essential in reducing perceived stress. The efficacy of web-based CBTs has been proven in patients with major depressive disorder and anxiety disorder with mild and moderate symptoms [Although our initial analysis showed that the BetterLife program significantly improved BDI and BAI levels, this significance did not survive the Bonferroni correction. We assume that this is because of the baseline observation carried forward method used to create the missing data of the participants who dropped out, which is one of the most conservative ways to estimate missing data. Notably, the per-protocol analysis showed that BDI and BAI scores were significantly improved using the BetterLife program with moderate effect size (symptoms . AlthougThe dropout rate of the intervention was 14.3%, slightly lower than the average dropout rate of internet-based CBTs according to a recent meta-analysis . This, aAlthough our study design did not include a direct comparison with face-to-face CBT, recent research comparing internet-based and face-to-face CBT showed similar results. Peter et al  showed sOur study has several limitations. First, only psychological scales were used in the trial. Although using objective measurements such as heart rate variance or blood cortisol levels would have complemented the results, we avoided this so that the participants would not have to visit a psychiatric clinic. Stigma regarding psychiatric interventions remains widespread in Korea, and having participants with work stress visit a psychiatric ward could negatively impact the trial . Second,BetterLife, a smartphone-based individually tailored CBT, effectively reduced stress and increased work engagement and QoL in people with work-related stress. This is a viable option for reducing workplace stress.


The binary regression analysis showed that upright posture, DLOC, daily frequency of attacks, and BMI were independent variables to distinguish between PPS and VVS. Based on the OR values of each independent variable, a score of 5 as the cut-off point for differentiating PPS from VVS yielded the sensitivity and specificity of 92.0% and 90.7%, respectively, and the AUC value was 0.965 . The sensitivity, specificity, and accuracy of this scoring model in the external validation set to distinguish PPS from VVS were 73.7%, 93.0%, and 87.7%, respectively. Therefore, the clinical manifestation-based scoring model is a simple and efficient measure to distinguish between PPS and VVS.The study was designed to explore a clinical manifestation-based quantitative scoring model to assist the differentiation between psychogenic pseudosyncope (PPS) and vasovagal syncope (VVS) in children. In this retrospective case-control study, the training set included 233 pediatric patients aged 5–17 years (183 children with VVS and 50 with PPS) and the validation set consisted of another 138 patients aged 5–15 years (100 children with VVS and 38 with PPS). In the training set study, the demographic characteristics and clinical presentation of patients were compared between PPS and VVS. The independent variables were analyzed by binary logistic regression, and the score for each variable was given according to the approximate values of odds ratio (OR) to develop a scoring model for distinguishing PPS and VVS. The cut-off scores and area under the curve (AUC) for differentiating PPS and VVS cases were calculated using receiver operating characteristic (ROC) curve. Then, the ability of the scoring model to differentiate PPS from VVS was validated by the true clinical diagnosis of PPS and VVS in the validation set. In the training set, there were 7 variables with significant differences between the PPS and VVS groups, including duration of loss of consciousness (DLOC) ( Syncope is the inability to maintain an autonomous body position due to recoverable whole-brain hypoperfusion and manifests as a transient loss of consciousness (TLOC) . It is tAt present, there has not been any acknowledged clinical manifestation-based systematic procedure to differentiate PPS and VVS in children. Head-up tilt test (HUTT) has been performed to clarify the cause of syncope and is one of the auxiliary examinations to distinguish between VVS and PPS , 17. HowPrevious studies have shown that the episodes of unconsciousness in children with PPS usually last for a longer time (from 5 to 20 min or longer) and occur more frequently than those in children with VVS . Other cTherefore, the present study was undertaken to develop a new scoring model to differentiate between PPS and VVS using recognized clinical features to help pediatricians, especially those working in grassroots hospitals, to differentiate pediatric PPS from VVS in a simple and rapid way.Totally, 233 children hospitalized in the Department of Pediatrics, Peking University First Hospital, China, from January 2012 to June 2021 were included in the training set. Of whom, 183 children  had VVS with a median age of 11.0  years, and 50 children  had PPS with a median age of 12.0  years. An additional 138 children treated at the Cardiovascular Center, Children's Hospital, Fudan University, China, from January 2009 to June 2021 were included in the external validation set, of whom 100 children  had VVS with a median age of 10.0  years and 38 children  had PPS with a median age of 11.0  years.The diagnostic criteria of VVS are: (1) occurring primarily in older children and adolescents; (2) often accompanied by precipitating factors such as long periods of uprightness, mental tension, and sultry environment; (3) a clear history or aura of syncope; (4) a positive HUTT test; and (5) exclusion of other diseases such as cardiogenic, cerebrovascular or metabolic diseases , 20. TheThe inclusion criteria of the study subjects: (1) those diagnosed as VVS or PPS; (2) patients under the age of 18 years old; (3) patients with normal routine biochemistry and 24-h Holter recordings results; (4) the data of the first confirmed hospitalization were included in the study for those with multiple hospitalizations; and (5) the children did not receive medication within 2 weeks.Exclusion criteria of research subjects: (1) syncope caused by cardiogenic, cerebrovascular, and other diseases; (2) patients with non-sinus rhythm in electrocardiogram (ECG); (3) patients with incomplete medical records, and loss of data; (4) the children without HUTT examination; (5) patients diagnosed as PPS with VVS.This study was approved by the Ethics Committee of Peking University First Hospital (2021–424) and Children's Hospital of Fudan University (2021–476), and the informed consent was permitted to be waived.We collected the demographic data of all the participants based on the medical records during their hospitalizations, including sex, age, and body mass index (BMI). The clinical manifestations as triggers or predisposing factors , precursors, duration of loss of consciousness (DLOC), the daily frequency of attacks  in the present history and the family history of syncope were collected. The upright posture means that the attacks happen when the patient is at an orthostatic posture, including standing for a long time and/or just standing up suddenly. Other kinds of situations were non-upright posture, for example, postures except orthostatism or walking, and/or exercising in the upright position. DLOC referred to the maximum recorded duration of the real or apparent LOC reported by the witness according to the medical records. We defined a child with a history of syncope in the family within two generations as having a positive family history. Besides, the baseline data of resting HR, resting systolic blood pressure (SBP), and resting diastolic blood pressure (DBP) as well as the 24-h average HR in Holter monitoring records of the patients were also recorded. The above data were obtained from the Medical Recording Management Digital System . The medical history and laboratory findings of all the patients were reviewed in detail and recorded by a specialized investigator. The records were carefully proofread by another investigator independently.Children fasted for at least 4 h before the testing, stopped any vasoactive medication for at least five half-lives, and avoided the drink that could affect autonomic nervous system function . The test was performed in the morning, and the environment was kept quiet and dimly-lit at a suitable room temperature. Children first laid on the tilt table  for 10–30 min. During HUTT, HR, BP and ECG were recorded continuously with an ECG monitor  and Finapres Medical System . After the stabilization of HR and BP, the table was tilted upward at 60° and HR, BP, and ECG were continuously monitored till the positive response appeared, or otherwise till the whole test duration (45 min) if no positive response was observed. Positive response criteria of HUTT are listed below: (1) significant blood pressure drop ; (2) bradycardia ; (3) the presence of sinus arrest, premature junctional contractions; or (4) transient second-degree or higher atrioventricular block or cardiac arrest ≥3 s , 26, 27.A 24-h ECG was recorded with an ECG recorder  and coffee, tea, or other drugs and strenuous exercise were avoided during the 24-h ECG. The 24-h ECG results were automatically analyzed by Mortara software  to obtain the 24-h average HR after automatic analysis.x ± s) and the t-test was used to compare between the two groups. Non-normally distributed data were described as median  and the differences between groups were compared using the Mann-Whitney U test. The categorical variables were described by frequency and constituent ratio, and comparisons between groups were made using chi-square tests.All statistical analyses were performed using SPSS version 25.0 . The normality test of continuous variables was performed using the Shapiro–Wilk test. For data where both groups obeyed a normal distribution, the measured data were expressed as  curves. Each variable derived from the regression was given a score according to the approximate odds ratio (OR) values, and the total score of a patient was calculated by adding up the scores of all identified variables, forming a scoring model. The Hosmer-Lemeshow test was used to assess the goodness of fit of the discriminant model. The ROC curve was performed to assess the power of the above scoring model in the differential diagnosis and determine the optimal cut-off score based on the maximum Youden index. Finally, the sensitivity, specificity, and accuracy of the scoring model were evaluated in the differentiation between PPS and VVS in an external verification study. A p-value <0.05 was considered significant.To establish a scoring system for differential diagnosis, variables with a statistical difference of p > 0.05). Children in the PPS group had a much higher BMI (21.0 kg/m2 vs. 17.7 kg/m2) and 24-h average HR (84.0 bpm vs. 81.0 bpm) than those in VVS group, and the differences were statistically significant  and stuffy environment (p = 0.096) before syncopal episode between the two groups; while, the significant differences were found in other manifestations, including DLOC (p < 0.01), daily frequency of attacks (p < 0.01), upright posture (p < 0.01), precursors (p < 0.01), and family history of syncope  in comparison between PPS and VVS groups, including upright posture, DLOC, daily frequency of attacks, BMI, precursors, family history of syncope and 24-h average HR, there were 4 continuous variables  which were converted into dichotomous variables, respectively, for the ease of clinical application. The cut-off value, p-value, sensitivity and specificity of these continuous variables were shown in Among the 7 variables showing statistical differences (2/ <20.5 kg/m2), precursors (Yes/No), family history of syncope (Yes/No) and 24-h average HR (≥93.0 bpm/ <93.0 bpm). Finally, four variables  were determined as the independent variables to distinguish PPS from VVS. The statistical data of Hosmer-Lemeshow in each step did not show any significance (p > 0.05), suggesting that the goodness of fit was satisfactory.Totally seven dichotomous variables were selected as independent variables for further logistic regression analysis using the backward conditional method, including upright posture (Yes/No), DLOC (≥9 min/ <9 min), daily frequency of attacks (≥twice/ < twice), BMI  Uprp < 0.01). When the total score ≥5 points was used as the cut-off value for initial differentiation between pediatric PPS and VVS, its sensitivity was 92.0% and specificity was 90.7% for the diagnosis of PPS  was established through binary logistic regression. By assigning scores for the four variables according to the OR values, we determined the final model with a maximum total score of 17 points. When the total score of the child was ≥5 points, the sensitivity and specificity for the possible differentiation of PPS from VVS were 92.0% and 90.7%, respectively.p < 0.01). VVS is an important form of acute orthostatic intolerance. When standing, the peripheral blood volume in the abdomen and lower limbs increases due to the gravity; therefore, when paradoxical vagal activation occurs in children with VVS during the adaptation to upright posture, a decrease in blood return volume causes a sharp drop in cardiac output, leading to syncope  in indicating the diagnosis of PPS, followed by DLOC ≥9 min (four points) and onset without predisposing upright posture (four points). In other words, children with PPS were more likely to experience more than one event within 1 day and have a longer duration of each episode. The median of DLOC in the PPS group reached 20 min in this study. The difference in frequency and DLOC between PPS and VVS are closely related to their distinct pathogenesis. A PPS-like event can occur anytime and anywhere with or without psychological triggers, which may vary from person to person and the duration may also differ in length without the challenge of cerebral ischemia. As for VVS, the syncopal events often occur under specific inducement and the events are usually not that frequent . Althoug syncope . In contcontrols . This macontrols . HoweverIn the external validation, the sensitivity of the scoring model is not as high as that of the training set in our study. The reason may be the fact that BMI and clinical characteristics of children in different regions may not be that identical. In addition, the DLOC is difficult to be reported exactly because the duration is often estimated by the witness. Therefore, the large sample sizes and multicenter studies are still necessary to improve the efficiency of the discriminant model.In the previous clinical differential diagnosis between PPS and VVS, no clinical manifestations are specific and the weight of each feature is not clear. Therefore, pediatricians can only analyze the clinical data and make judgment according to their own experiences. HUTT is an important examination to identify the causes of syncope, but as mentioned above, its value in distinguishing between PPS and VVS is limited .In this present study, several features with the most distinguishing significance were analyzed, and these variables were quantified according to the weight assignment. By this scoring model, a rapid preliminary judgment between PPS and VVS can be made just through a simple inquiry of medical history and basic measurement of height and weight, which is highly practical and easy to be popularized. Of course, in the diagnostic procedure of TLOC, it is also necessary to identify other causes except for PPS and VVS. Nevertheless, the significance of this study is that, contrary to the relatively complex diagnostic procedure at present, doctors at different levels can obtain a preliminary judgment and make a more targeted investigation plan for children suffering from TLOC with the help of our scoring model. If the total score indicates PPS, the patient should be recommended to see the psychiatric specialists for further evaluation while screening for other physical diseases, to manage the patient in a more efficient and comprehensive way. While, if the total score suggests VVS, the patient should be recommended to have HUTT, etc. Therefore, the results of this study will be helpful to suggest reasonable referrals and optimize the differential diagnostic process in clinical practice. Furthermore, compared with the previous study , this scOur study also had some limitations. Children with VVS were unable to accurately describe the frequency and duration of syncope, and the information of syncopal attack was sometimes described by their family members or bystanders. In the training set, we included children aged 5–17 years, and in the validation set, we recruited the subjects aged 5–15 years, although the diagnostic criteria were kept the same. The study was a retrospective study, in which only hospitalized children were included. Therefore, prospective, multicenter and large sample-sized studies are still necessary to optimize this model. Nevertheless, in the present study, we developed a useful, easy-to-operate, and very inexpensive clinical characteristics-based scoring model for pediatricians to make a quick and initial differentiation between PPS and VVS in children.This study developed a clinical manifestation-based scoring model to differentiate PPS from VVS, assisting in making a quick initial differential diagnosis. Further multicenter studies are still needed to improve the ability to differentially diagnose pediatric TLOC cases.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Peking University First Hospital and Children's Hospital of Fudan University. Written informed consent for participation was not provided by the participants' legal guardians/next of kin because the required informed consent was permitted to be waived by the Ethics Committee of Peking University First Hospital and Children's Hospital of Fudan University.YZ, HJ, JD, and HT presented thesis ideas and contributed to discussion. CL, YL, JD, HJ, and QZ assisted in collecting and analyzing data. HT, LH, and SL provided external validation data and performed analysis. JF and DZ contributed to discussion. CL, YL, and LH wrote the original manuscript. JD, YZ, HJ, and HT critically reviewed and proofread the manuscript. All authors have read and agreed to submit the manuscript.This study was supported by Peking University Clinical Scientist Program (BJMU2019LCKXJ001) and the Fundamental Research Funds for the Central Universities.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Despite freely distributed insecticide-treated nets (ITNs) and health information campaigns to increase their use among populations at risk, malaria transmission persists in forested areas in Vietnam, especially among ethnic minority communities. A mixed-methods study was conducted in four villages of Ca Dong and M’nong ethnicity in Central Vietnam between 2009 and 2011 to assess factors limiting the uptake of ITNs.The mixed-methods research design consisted of a qualitative study to explore the context and barriers to ITN use, and a cross-sectional household survey (n = 141) to quantify factors for limited and appropriate net use.The Ca Dong and M’nong’s livelihood was dependent on swidden farming in the forest. Poverty-related factors, including the lack of beds, blankets, the practice of sleeping around the kitchen fire and deteriorated ITNs due to open housing structures, were reasons for alternative and non-use of ITNs. When household members stayed overnight in plot huts at fields, ITNs were even more unavailable and easily deteriorated. 72.5% of households reported having received one net for every two persons, and 82.2% of participants reported to have used ITNs the night before the survey. However, only 18.4% of participants were estimated to be effectively protected by ITNs after accounting for the availability of torn ITNs and the way ITNs were used, for example as blankets, at both village and fields. Multi-variable logistic regression showed the effect of four significant factors for appropriate ITN use: i) being female ; ii) aware of mosquito bites as the sole cause of malaria ; iii) not sleeping around the kitchen fire ; and iv) having sufficient number of ITNs in the household .This study showed how social factors rooted in poverty and swidden agriculture limited the effective use of ITNs, despite high coverage, among ethnic minority populations in Central Vietnam. An in-depth understanding of the local context is essential to develop specific indicators for measuring ITN use. BetweUniversal coverage of ITNs and long-lasting insecticidal nets (LLINs) for populations at risk of malaria has been repeatedly proven as a highly cost-effective public health intervention to avert malaria infections and deaths –12. FromPlasmodium vivax [High bed net coverage, however, does not necessarily equate with effective use, and the sub-optimal use of freely distributed bed nets has been reported in different settings, particularly among ethnic minority populations , 16. In um vivax , 24.The study was conducted in four villages of Tra Leng and Tra Don communes in Nam Tra My district of Quang Nam province. In the 2009 census, the total population consisted of 1810 individuals (352 households) with a majority being of M’nong and Ca Dong ethnicities and a minority of Kinh, the dominant ethnic group in Vietnam . DespitePlasmodium falciparum infections (81.4%) being confirmed by light microscopy. However, by molecular techniques (PCR), the prevalence was three times higher (22.6%) with P. vivax accounting for a higher proportion of cases (43.2%) [Anopheles dirus, which is highly anthropophilic and displays behavioural complexity, including outdoor biting and early feeding [Malaria transmission was perennial in the study area with two peaks in May–June and October–November. In April 2009, malaria prevalence was determined at 7.8% with a majority of  (43.2%) . The mai feeding . Exposur feeding .The study used a two-stage exploratory mixed-methods design, starting with a qualitative strand followed by a quantitative strand . In the Qualitative data were collected in the four study villages during three periods of fieldwork between April 2009 and January 2011. The researchers stayed in the villages to get familiarized with local people. Data were collected in both rainy and dry seasons through participant observation (PO), informal conversations (ICs), in-depth interviews (IDIs) and informal group discussions (IGDs). For PO, the researchers immersed themselves in the study context by participating in everyday activities in the communities, observing events, and acquiring an in-depth understanding of the local social and cultural aspects that were unspoken or taken for granted. During PO, the researchers engaged with local people in informal conversations to build up rapport and trust. ICs were often spontaneous and occurred as part of the social interaction between the researchers and local people. As part of the fieldwork, the researchers took notes during the POs and ICs, and completed their notes immediately after each PO or IC. Once trust was built with the participants and response bias due to social desirability was minimized, the researchers proceeded to IDIs and IGDs to discuss aspects of bed net use with participants. IDIs and IGDs were conducted in Vietnamese and local languages with the help of translators when needed. Informal rather than formal interviews and discussions were preferred as formality exacerbated social hierarchies among Kinh, M’nong, and Ca Dong participants, and was expected to increase socially desirable responses. IDIs and IGDs were audio-recorded, transcribed in Vietnamese, and translated into English.The sampling strategy was theoretical . During i.e. data saturation) [The researchers followed a continuous, flexible and iterative process for data analysis. During fieldwork, emergent codes and themes were discussed among the research team until consensus was obtained. Preliminary data were intermittently analysed to adapt interview guides. Emerging themes were continuously identified and new research hypotheses were further tested until no new findings emerged (uration) . The resuration) . Once daQuantitative data were collected from October to December 2010. Preliminary results from the qualitative strand on kinship, resettlement patterns, mobility, sleeping places, forest activities, bed net use, and health-seeking behaviour were used to inform the design of the quantitative survey. A paper-based questionnaire (in English and Vietnamese), consisting of structured questions for the household-level and the individual-level, was developed and field-tested before finalization in Vietnamese. The household-level questions were asked to household leaders (HHLs) to quantify net ownership, mobility patterns, and sleeping places. The individual-level questions were asked to individual household members (HHMs) to quantify their knowledge of malaria causation as promoted by ITN distribution campaigns, exposure to the vector and bed net use. Parents or guardians answered on behalf of minors. The survey questionnaire was administered by experienced field workers who had gained the confidence of the study populations owing to their previous research in the study setting. Prior to the survey, field workers were trained to administer the questionnaire to the study population. During the survey, field workers validated self-reporting bed net ownership and status through direct observation. No systematic measurement or counting of holes and tears was used to assess bed net status. Nets were considered torn when respondents stated they were broken and that mosquitoes entered the nets.Village 1, where the highest number of vivax malaria cases was reported in the main cohort study in 2009, was selected for the survey . The sami.e., “svyset idhouse”; no other parameter used). A multi-variable analysis using survey logistic regression was conducted to determine the effect of independent risk factors  on the appropriate net use. The latter was defined as reported sleeping under a hung-up net the night before the survey. The final model was built by selecting all variables that were significantly associated with the outcome (i.e. appropriate use of net) in the univariate analysis  and using a backward stepwise selection method at a 10% significance (p < 0.1).Data were entered using Epi-Info 6.04 and analysed using Stata 12.0 . Summary statistics were done using Chi-square- or Fisher’s exact tests accordingly for differences between categorical variables, while Student’s t-test or Wilcoxon rank-sum tests were used to compare continuous variables as required (significant p < 0.05). The survey design was taken into account using the “svy” command in Stata with household as the primary sampling unit (i.e. village house and plot hut), net ownership at the plot huts, and whether the net was hung up at both village house and plot hut. A composite variable for bed net use was generated as follows: (i) “effectively protected by ITNs” for participants who reported they “always” slept under a hung-up net at both their village house and plot hut; or, reported doing so at the village and did not have a plot hut; (ii) “unprotected by ITNs” for participants who reported that they inconsistently slept under a net at their village house, and/or at fields.The socio-economic status (SES) of households was categorized as lowest, low, and higher SES according to their livestock ownership as defined by the larger study . Bed nete.g. people’s sleeping places and their feedback on the nets given by the government. The researchers treated qualitative data with the highest confidentiality and stored data in password-protected devices. Participants in the survey were asked to consent before answering the questionnaire. When participants were under 16 years old, their parents or guardians were asked to consent and respond on behalf of the minors. All participants were informed of the intended use of the study results for scientific publication, and their responses were anonymized as to protect their access to and use of public health services.This study was approved by the Ethical Committee of the National Institute of Malariology, Parasitology and Entomology (NIMPE) in Hanoi, Vietnam , and the Institutional Review Board of the Institute of Tropical Medicine in Antwerp, Belgium (IRB/AB/dvm/183). All fieldwork in the qualitative strand followed the Code of Ethics of the American Anthropological Association (AAA) . VillageThe qualitative strand included 20 IDIs, 23 ICs, three group discussions and POs conducted by the researchers during 3 months. Participants were men and women in different age groups and had different professions such as farmers, plantation workers, students, teachers, health workers, local authorities and leaders. 141 individuals participated in the quantitative strand, including 80 HHLs and 61 HHMs. Of 61 HHMs, there were 15 adults and 46 children. The number of participating households accounted for 98.8% (80/81) of all households living in village 1. Demographic characteristics of survey participants are presented in Table Prior to the study, the local population had received ITNs from the NMCP in 1998 and 2004. Participants said that between 2009 and 2010, they received LLINs for double beds from the government. At the time of the survey, households had both ITNs and LLINs (hereafter referred to as “ITNs”) at home. Participants perceived ITNs as part of the state’s subsidies to poor ethnic minority populations. They were hesitant to share their critical feedback on ITNs due to fears of being excluded from future free-of-charge public services, including health services if their information was disclosed to outsiders and local authorities. Concerning the distribution of ITNs, some participants said they received fewer ITNs than the recommended quantity, one net for every two adults, as advised by the NMCP. They said that while people did not object to using ITNs, they felt that these nets did not offer their preferred features. Commercial nets had characteristics that people preferred such as different colours, decorative contours, and an opening to enter the net (which ITNs did not have). However, the lack of financial means was the main reason for many not to buy nets in addition to the freely distributed LLINs. Field workers observed, at the time of the survey, that 72.5% (59/80) of households had at least one ITN for a maximum of two people. In 24.3% (19/78) of households, ITNs were observed to be still intact while in another 33.3% (26/78) of households they were broken  said they actually slept under a hung-up ITN and the majority  reported to have used their net as a blanket (Table e.g. for cassava and hybrid rice) and settled Ca Dong and M’nong villages there. Swidden agriculture and subsistence activities were discouraged by the government, and hunting and logging were made illegal.M’nong households traditionally used swidden agriculture which involved clearing plots of forest land and rotating every five to six years. In 1991, the government legitimized its role in forest management through reinforcing a national law on forest protection; and in 2004 swidden agricultural practices and hunting among other forest exploitation activities were prohibited by local laws , 36. UndThe survey showed that the majority of households  owned a field and that the average time to commute on foot between the village and the field was over one hour Table . 71.2% o“We are used to sleeping in the kitchen. We believe the kitchen is a sacred place where the spirits stay, so we sleep there to be close to them. In my family, my parents worshipped the spirits and dedicated the kitchen to them. I do the same, I follow what my parents did. In the kitchen, I placed three stones to make a cooking fire. A lady shaman helped me invite the spirits to live in the stones. Twice a year, I make a sacrifice to the spirits.” .Sleeping around the kitchen fire was common practice in the area. Part of this practice was due to the cold and humid climate, and the house structure (see housing conditions). Participants also explained that sleeping around the kitchen fire was linked to their traditional sleeping arrangements and animistic beliefs.ITNs were rarely hung up in the kitchen/cooking space due to fire hazards and the lack of space to properly hang up a net. Indeed, partially burnt ITNs were sometimes observed. Up to 60.0% (48/80) of HHLs answered that their household members, predominantly elders, often slept around the kitchen fire Table . The majIn villages, the government provided households wooden planks to build houses directly on the ground instead of on stilts, as was the case for the Ca Dong and M’nong traditional long houses. Furniture, including beds, was  required to sleep inside the government-supported houses, but the cost was not affordable to everyone. At fields, plot huts were on stilts, made of wood, bamboo, and forest leaves, and often small. Extracted data from the cohort study showed that village houses were made of temporary materials including wooden walls  and tin roofs . The house structures were open with gaps between wooden planks constituting the floor, and between the walls and the roofs, allowing mosquitoes to easily enter and exit. Due to the open structure, houses were quite cold and humid at night, particularly in the rainy/malaria season. Participants explained that the lack of financial means limited their ability to buy sufficient blankets to keep warm at night. In the survey, 75.6% (59/78) of HHLs reported using their broken ITNs either as pillows  or blankets  , these factors contributed to more frequent net washing. 35.9% 28/78) of HHLs responded that they washed their nets every week Table . Frequen8/78 of HThe local malaria control programme provided the population with health messages through printed materials and public campaigns focusing on the mosquito-malaria link and the benefits of sleeping under a net for malaria prevention. These messages in Kinh (Vietnamese) language were often not comprehended by local people. People linked fevers, including malaria fever, to an offense to the spirits or difficult living conditions at fields, such as intensive labour, poverty, poor housing and the lack of safe drinking water and a nutritious diet. The survey found that 43.3% 61/141) of participants identified that malaria was caused by mosquito bites. However, they answered that malaria could additionally be caused by the hot sun , hard work , and drinking bad water  , sleeping practices (e.g. sleeping near the kitchen fire) and places (at village houses or fields), less than onefifth of the study population was estimated to be effectively protected by ITNs.This mixed-methods study shows the structural factors embedded in the local context and swidden agricultural setting that limited ITN use among the M’nong and Ca Dong communities. Despite relatively high ITN coverage and a high proportion of reported ITN use the night before the survey, after accounting for a combination of individual and household factors, i.e. privacy, ease of use, type of material considering climatic conditions, and net size in relation to housing size and structures [The study findings highlight the influence of social factors on ITN use, which has been reported by studies in a variety of contexts. A set of factors relates to the acceptability or appropriateness of specific bed net characteristics. For certain populations, the uptake of ITNs relates to product features such as smell, colour, texture, size, or how the design of nets meets user preference and expectations, ructures , 37–44. ructures , 45. In ructures . In Vietructures , the desructures , 48. TheHowever, beyond ITN characteristics, structural social factors directly affect net use. As shown in this study, poverty, mobility patterns, and multiple residences linked to swidden farming constrained effective ITN use and the product’s lifespan. In Southeast Asia, a unique factor among ethnic minority farmers is the multiple residency system whereby people live in more than one place, such as in the formal villages and combining  with homes at fields and/or rice paddies , 49. In In sub-Saharan Africa, several structural factors limit ITN use, such as specific occupational nighttime activities like fishing, hunting, and brick-making , 54, slei.e. responses to the question “did you sleep under a bed net last night”, across variable social contexts, however, leads to ignoring relevant heterogeneity and related contextual factors, the collection of “pseudo” data, and the construction of incomplete knowledge about the complexities of malaria elimination [In this study, the significant difference between the reported ITN use and the estimated effective protection of ITNs shows the importance of applying adequate research methods and measurements for social variability to inform public health measures. Standard indicators for ITN use offer the convenience of implementation and comparability across settings. The use of these indicators, mination . As illumination , 60. In mination , 61. Othmination , 62–64. mination , 66. In mination .e.g. the cold and humidity). This practice was in line with M’nong social organization  and an adaptation to local ecological conditions . The second most important risk factor was insufficient ITN coverage. Similar to this study, studies in Cambodia and Vietnam also reported the issue of low coverage of ITNs among ethnic minority populations whose mobility patterns and multiple residence systems were unaccounted for by the national ITN distribution plan [The study found the most important risk factor for inappropriate ITN use was the practice of sleeping around the kitchen fire for both spiritual and practical reasons . Despite this, the study findings are still relevant for Vietnam. The NMCP has continued to include ITN distribution as an important element of vector control in the elimination strategies to 2030, and recent studies in ethnic minority settings have continued to report on limited uptake of bed nets , 47.e.g. Ra-glai) living in forested areas in Vietnam [In terms of the survey response, outcomes of bed net use the previous night might have been inflated due to self-reporting. However, this inflation was likely to be homogenously distributed in the study population and therefore unlikely to have biased the estimates of the multivariate analysis. Factors limiting ITN use presented in this paper were specific to the minority populations of Tra Leng and Tra Cang communes, however, the operationalization of the concept of ITN use can be theoretically transferrable to similar ethnic minority settings in Central Vietnam. Indeed, the study population represents the challenges faced by several minority groups ( Vietnam , 47, 61  Vietnam , 76, 77,While knowledge of malaria and bed net coverage are important aspects of malaria prevention, it was mainly the hardship and poverty people endured that reduced ITN use, thus, exposing them to malaria. This study also illustrates how bed net use as a complex concept was operationalized and assessed in a minority setting. The study calls for the inclusion of an in-depth understanding of the local context to further improve the indicators for measuring ITN use.


Sarcopenia and bone disorders, such as osteopenia and osteoporosis, are common musculoskeletal disorders in older adults. Therefore, this study aimed to establish the association between sarcopenia and bone disorders such as osteoporosis and osteopenia according to sex. We analyzed 3077 participants from the 2008–2011 Korean National Health and Nutrition Examination Survey aged 65 years or older. After adjusting for all covariates, such as physical examinations, exercise, and nutrient intake (model 4), the odds ratios for the association between sarcopenia and bone disorders were 2.051  in osteopenia and 2.258 (95% CI: 1.584–3.218) in osteoporosis. However, when sex was analyzed separately, the odds ratio was significantly different in men , but not in women. Therefore, the results of this study show an association between sarcopenia and bone disorders in older Korean adults. Sarcopenia is significantly related to osteopenia and osteoporosis, especially in men, when stratified by sex. Age-related sarcopenia and osteoporosis are the most common musculoskeletal disorders . DecreasAlthough its mechanisms have not yet been identified, sarcopenia is defined as a decrease in muscle mass and muscle strength due to changes in numerous body components triggered by aging, lack of exercise, and hormonal imbalance ,9,10,11.Osteopenia and osteoporosis are diseases in which the bone strength decreases due to reduced bone density, which increases the risk of fracture . These tBoth sarcopenia and osteoporosis are caused by several factors, and some of the factors that cause osteoporosis also trigger sarcopenia . In partSarcopenia and osteoporosis can lead to secondary diseases such as falls, fractures, and functional damage . Recent As such, sarcopenia and bone disorders are common diseases caused by aging, but it remains unclear whether they should be considered as one disease or two different diseases . Bone diPreliminary studies on the association between sarcopenia and osteoporosis were either only conducted in women ,36, or tThis study used the data from KNHANES (2008–2011) conducted by the Korean Centers for Disease Control and Prevention. Prior to the survey, its content was explained to all subjects, and informed consent was obtained. The survey was conducted by trained interviewers. The researchers who created the questionnaire trained the interviewers to obtain appropriate information and to become familiarized with the matters that required attention for the interview by explaining the questionnaires and role-playing for four days.Those who responded to both the examination survey and the health survey among adults aged 65 years or older who underwent whole-body dual-energy X-ray absorptiometry (DXA) were included in this study. Among the 37,753 individuals who participated in the KNHANES, 31,383 individuals who were <65 years old, 2682 individuals whose sarcopenia status and BMD were not measured, and 611 non-participants in the health survey because factors such as smoking, drinking status, and exercise frequency were excluded. Finally, 3077 individuals were selected .2)]. Smoking status was categorized as never smokers, ex-smokers, and current smokers, while drinking status was categorized as current users and non-users.The physical examinations performed in this study included height, weight, diastolic and systolic blood pressure , waist circumference (WC), triglyceride level, fasting blood glucose level, and vitamin D measurements. BP was measured using a mercury sphygmomanometer in a seated position after a 10-min rest period. Two measurements were performed in all participants at 5-min intervals. An average of two measurements was used for the data analyses. Measurements of the vitamin D concentration, 25(OH)D3 (ng/mL), was performed using a 25-hydroxyvitamin D 125 I RIA Kit . WC was measured at the midpoint between the bottom of the rib cage and the top of the lateral border of the iliac crest with full expiration. Blood samples were collected from participants in the morning after overnight fasting and were analyzed at a national central laboratory. Body mass index (BMI) was calculated by dividing the weight (kg) by height in meters squared  a week?” The short version of the International Physical Activity Questionnaire in Korea , which mTo assess the nutrient intake, all participants were instructed to maintain their usual dietary habits before the assessment of dietary intake. Daily food intake was measured using the 24-h recall method, while the daily nutrient intake was calculated using the Can-Pro 2.0, a nutrient intake assessment software developed by the Korean Nutrition Society . The daily intake of proteins and calcium was also assessed.Bone mineral content and body composition were measured by licensed technicians using DXA . The participants fasted prior to the assessment and were placed in the supine position during the assessment. All non-fat and non-bone tissues were assumed to be skeletal muscles.2). Sarcopenia was defined as SMI values of <7.0 kg/m2 for men and <5.4 kg/m2 for women, as recommended by the Asian Working Group for Sarcopenia (AWGS) [Appendicular skeletal muscle mass (ASM) was calculated as the sum of skeletal muscle mass in both arms and legs and was measured by DXA. The participants’ skeletal muscle mass index (SMI) was calculated as ASM (kg) divided by height in meters squared (ma (AWGS) .BMD was measured at the lumbar spine, whole femur, and femoral neck using DXA. According to the World Health Organization criteria, the diagnosis of osteoporosis, osteopenia, and normal bone mass was determined based on the following T-scores: ≤−2.5, −2.5 to 1.0, and >−1.0, respectively, in the femur, femoral neck, or lumbar area .2 test or Student’s t-test or ANOVA was used to evaluate the differences in demographic and clinical characteristics by sex according to sarcopenia and osteoporosis. Complex sampling design multivariate logistic regression analysis adjusted for covariates was conducted to calculate ORs and 95% CIs and assess the association between sarcopenia, osteopenia, and osteoporosis. A p-value of <0.05 was considered significant.The data were analyzed using SPSS 27.0 Windows version . This study was conducted as a cross-sectional study. As KNHANES is a sample survey rather than a census, all data analyses were performed using a weighted complex sample design. Therefore, the responses were weighted by multistage, complex, probability sampling. Continuous variables are presented as mean and standard deviation, and categorical variables as frequency and percentage (%). The Rao-Scott χThe percentage of participants who did not exercise at all was significantly higher in the osteoporosis group than in the normal group , and the difference in aerobic exercise was only found in women (82.61 vs. 59.89 in TWT). Protein intake was significantly lower in men and women than in women with osteoporosis, while calcium intake was lower only in men. Triglyceride and fasting blood glucose levels were also significantly lower in men with osteoporosis. The prevalence of sarcopenia was higher in osteopenia and osteoporosis than in normal individuals (22.0% vs. 47.5% vs. 71.4% in men and 15.3% vs. 32.0% vs. 43.6% in women).The main findings of this study were that sarcopenia is independently related to osteopenia and osteoporosis in older Korean adults, after adjusting for various confounding covariates. This association was particularly strong among men.The prevalence rates of sarcopenia in Korea were 8.7% in men and 11.2% in women in those >20 years old , and 18.The number of days of resistance exercise in older men with sarcopenia was significantly lower than normal, while aerobic exercise was more prevalent in those with sarcopenia . These fNo difference was observed in the prevalence of sarcopenia according to the type of exercise in women, whereas a difference was found in the rate of current smoking between men and women . In a prProtein and calcium intakes were significantly lower in participants with sarcopenia, regardless of sex . ProteinIn this study, the prevalence rates of osteopenia were 53.1% in men and 37.0% in women, while the prevalence rates of osteoporosis were 12.6% in men and 59.9% in women . In prevThe mechanisms underlying the association between sarcopenia and bone disorders, such as osteopenia and osteoporosis, can be explained in several ways. First, it can be explained based on the “mechanostat theory,” in which mechanical stimulation of the muscles affects the formation and recovery of the bones . In otheAfter adjusting for many confounding variables affecting the prevalence of sarcopenia and bone disorder, the association between sarcopenia and bone disorders was only observed in older men. Aging causes bone and muscle mass loss , which aRecent randomized controlled trials show that resistance exercise and sufficient intake of nutrients such as protein and vitamin D improve the muscle strength and physical performance of the older frail . In addiTaken together, the results of this study revealed that sarcopenia is significantly related to osteopenia and osteoporosis in the elderly. In addition, therapeutic management is required through the proper provision of physical activity, especially resistance exercise, and nutrients such as hyper protein, vitamin D, and calcium is to improve falls, fractures, and weaknesses in these patients.These KNHANES data have the following strengths: the response rates and accuracy as measured by professional medical staff were high. Despite some meaningful findings in this study, there are some limitations that must be taken into consideration while evaluating the results of this study. First, the individuals who participated in the KNHANES had a relatively mild level of disease; therefore, the non-participation of a small number of severe sarcopenia or osteoporosis patients may affect the analysis of the results. However, since these data were obtained from the national population, potential disturbing factors will not have a significant impact on the results. Second, a new guideline for the 2019 AWGS suggested measuring muscle strength or physical performance as well as muscle mass when diagnosing sarcopenia. However, this was not measured in the KNHANES. Third, although this study found the association between sarcopenia and bone disorder by adjusting various covariates, it was a cross-sectional study that simultaneously measured sarcopenia and bone disorder factors. Therefore, the temporal concern could not be determined, which made it impossible to accurately identify the order of fundamental causes between the two diseases. Therefore, it will be valuable to uncover the mechanism that can clarify the causal relationship between the two through future longitudinal studies.This study was conducted to determine the association between sarcopenia and bone disorders in older Korean adults. Sarcopenia is significantly related to osteopenia and osteoporosis, especially in men, when stratified by sex. To improve falls, fractures, weaknesses, and the incidence of these patients, therapeutic management is necessary through the proper provision of physical activity, particularly resistance training, and nutrients such as high protein, vitamin D, and calcium.


Endometriosis is a common benign gynecological disease that has the potential to debilitate due to pain and reduced quality of life. Treatment modalities such as hormones and surgery have limitations and do not treat all dimensions of the problems caused by endometriosis, and physical activity (PA) and exercise have been suggested as alternative treatments. Aim of this study was to perform a systematic review and meta-analysis to assess the effect of PA and exercise on endometriosis-associated symptoms.Eleven databases were searched systematically. Study selection, quality assessment, and data extraction were carried out by two independent researchers in accordance with PRISMA guidelines. Eligibility criteria were women with diagnosed endometriosis receiving an intervention (PA and/or exercise). The primary outcome was pain intensity, but all outcomes were accepted.This study screened 1045 citations for eligibility. Four interventional studies were identified, of which one showed fatal design flaws and so was excluded. Three studies, two randomized controlled trials (RCT) and one pre-post study with no control group, involving 109 patients were included in a descriptive synthesis. The interventions included flexibility and strength training, cardiovascular fitness, and yoga, and were performed from one to four times per week for a total duration of 8–24 weeks, with or without supervision. Only one study found improvements in pain intensity. One study showed decreases in stress levels. Due to the heterogeneity of the study outcomes and measures, as well as confounding factors, a quantitative meta-analysis could not be performed.The effect of PA and exercise as treatments for endometrioses-associated symptoms could not be determined due to significant limitations of the included studies. Future research should be based on RCTs of high methodological quality, measuring and reporting relevant core outcomes such as pain, improvements in symptoms and quality of life, and acceptability and satisfaction from the perspectives of patients. Furthermore, these outcomes need to be measured using reliable and validated tools.CRD42021233138.The online version contains supplementary material available at 10.1186/s12905-021-01500-4. Endometriosis is a benign gynecological condition in which ectopic, endometrium-like cells are located outside of the uterine cavity . The conThere is no definite cure for endometriosis, and so the main focus of management is to control the associated pain, which is achieved by hormonal suppression of the disease or surgical excision . UnfortuPA and exercise were introduced for treating endometriosis-associated symptoms more than 3 decades ago . HoweverTwo previous systematic reviews have addressed the effect of PA and exercise on endometriosis-associated symptoms , 18. HowThe present systematic review attempted to identify interventional studies of high quality to assess the effect of PA and exercise specifically in treating women with endometriosis-associated symptoms.What is the effect of PA and exercise on endometriosis-associated symptoms?This systematic review was registered in the International Prospective Register of Systematic Reviews CRD42021233138), and was performed in accordance with the PRISMA  guidelines [21233138,Studies of interventions involving any type of PA and exercise were eligible for inclusion. PA was defined as “any bodily movement produced by skeletal muscles that requires energy expenditure”  and exerThe study population consisted of women with any degree of endometriosis as diagnosed with an imaging or surgical modality, who presented with pain in the pelvic region . The primary outcome measure was the pain intensity, but all outcomes were accepted.Exclusion criteria were data presented in short communications, reviews, letters to the editor, and congress abstracts, and the application of passive interventions such as manual therapy to patients. The literature search was completed with support from a trained medical librarian. The search included the Cochrane Central Register of Controlled Trials, Embase, PubMed, MEDLINE, PsycInfo, CINAHL, AMED, Scopus, Web of Science, PEDro, and SveMed + , without time limitation up to December 2020. Publications could be in English, Swedish, Norwegian, Danish, or German. Search terms were identified through a pilot search for relevant literature. The electronic search strategy for this systematic review is presented in Additional file In the first step, all obtained references were independently screened on the basis of the title and Abstract by M.K.T. and T.T. using the Rayyan web application  that allThe full text of eligible articles was read by two reviewers (M.K.T. and T.T.), who independently extracted the following data: author(s), year of publication, study period, country of origin, study design, sample size, inclusion and exclusion criteria, intervention type, description of intervention, follow-up period, primary and secondary outcomes, and dropout rate.p < 0.001. Confidence intervals were provided if available.A meta-analysis was planned, but it could not be performed due to the substantial heterogeneity found in study designs and outcomes. Results from the studies are reported as between- and within-group differences using mean ± standard-deviation values or numbers with percentages, according to availability. Probability values were rounded to two decimal places, with the exception of This study identified 1879 citations Fig. .Fig. 1POne study was rated as being of fair quality , while tThe RCT of Goncalves et al.  was judgThe study of Friggi Sebe Petrelluzzi et al.  was judgThe study of Awad et al.  was judgThe individual scores for the articles based on the CERT checklist . Furthermore, the scores in pain-related domains on Endometriosis Health Profile-30 (EHP-30) were significantly lower in the yoga group than the control group at postintervention . Notably, the control group also received physiotherapy following the intervention at their institution.Goncalves et al.  reportedp > 0.05). Carpenter et al. [Friggi Sebe Petrelluzzi et al.  did not r et al.  found thp < 0.05). Significant improvements in the vitality and physical functioning domains of the SF-36 were also found (p < 0.05), but these effects were no longer significant after performing a multivariate analysis that included each variable in the SF-36. There was an overall decrease in salivary cortisol levels from pretreatment to posttreatment (p = 0.04), but this was not correlated with perceived stress as measured with PSQ. Goncalves et al. [p < 0.001).The study of Friggi Sebe Petrelluzzi et al.  measureds et al.  found siThe study of Carpenter et al.  assessedThis systematic review has summarized the available evidence for the effect of PA and exercise on endometriosis-associated symptoms. We identified 4 interventional studies involving 129 women. However, 1 of these studies was excluded after the quality assessment revealed fatal flaws in its design, leaving 109 women being finally included. Each included study found some improvement in pain intensity, stress levels, well-being, or self-image. However, due to confounding factors, the effect of PA and exercise alone could not be determined. Furthermore, the heterogeneity of the outcome measures and incomplete outcome reporting made it impossible to conduct a quantitative meta-analysis.The relationship of PA and exercise with endometriosis has been widely studied in the past, and several reviews have been published on this topic , 18, 19.A multimodal approach that includes physiotherapy has been suggested to alleviate endometriosis symptoms , 30, 31.The present review specifically focused on PA and exercise, but it was not possible to summarize the effect due to significant limitations of the included studies. However, some trends could be identified. One study showed improvements in daily pain scores , but no There seems to be a dose–response relationship between regular, high-intensity exercise and the effect on the inflammatory profile in general . Since nPrevious research has found that the pelvic floor muscle tension in higher in women suffering from endometriosis pain  than in In a recent initiative, healthcare professionals and women suffering from endometriosis were able to recommend a minimum set of outcomes to be measured and reported in all interventional clinical trials of endometriosis . Those sThe strengths of this systematic review include its originality, rigorous search strategy, and methodological robustness. Its main limitation is the low grade of evidence that could be obtained from the previous studies. The small samples, confounding factors, heterogeneity of interventions, and poor reporting of details about the exercise intervention and outcome measures restricts our ability to draw overall conclusions about the effect of PA and exercise in treating endometriosis-associated symptoms.PA and exercise might exert a range of beneficial effects on endometriosis-associated symptoms, but unfortunately these effects cannot be robustly determined based on the existing literature. Nevertheless, the potentially beneficial role of PA and exercise should be communicated to women with endometriosis-associated symptoms. Future research should be based on RCTs of high methodological quality, measuring and reporting relevant core outcomes such as pain, improvements in symptoms and quality of life, and acceptability and satisfaction from the perspectives of patients. Furthermore, these outcomes need to be measured using reliable and validated tools. A focus on the type and dose of PA and exercise as well as patient selection is warranted, and using appropriate checklists such as the CERT is recommended. Since endometriosis patients can show complex symptomatology, the cooperation of multiple disciplines such as physiotherapists and gynecologists could improve the quality of clinical research in this field.Additional file 1. PRISMA .Additional file 2. Electronic search strategy with search terms.Additional file 3. CERT (Consensus on Exercise Reporting Template).