Experiencing maltreatment during childhood exerts substantial stress on the child and increases the risk for overweight and obesity later in life. The current study tests whether hair cortisol—a measure of chronic stress—and its metabolite cortisone mediate the relation between abuse and neglect on the one hand, and body mass index (BMI) on the other.The sample consisted of 249 participants aged 8 to 87 years . We collected data on child abuse and neglect using questionnaires, measured cortisol and cortisone concentrations in hair, and BMI. In a structural model, the effects of abuse and neglect on hair cortisol, hair cortisone, and BMI were tested, as well as the covariance between hair cortisol and BMI, and hair cortisone and BMI.p < .001) and higher BMI . Neglect was not related to hair cortisol, hair cortisone, or BMI. Hair cortisol and cortisone did not mediate the association between maltreatment, and BMI. Sensitivity analyses demonstrate the same pattern of results in a subsample of adult participants currently not living with their parents. However, in younger participants who were still living with their parents, the associations between abuse and cortisone  and abuse and BMI  were no longer significant.Within the sample, 23% were overweight but not obese and 14% were obese. Higher levels of experienced abuse were related to higher cortisone concentrations in hair (β = 0.24, These findings confirm that experiencing abuse is related to higher BMI but suggest that hair cortisol and cortisone are not the mechanism underlying the association between child maltreatment and BMI. This is the first study to show abuse may be associated to elevated concentrations of hair cortisone—evidence of long-term alterations in chronic stress levels. Future research may benefit from exploring the effects of maltreatment on weight gain in longitudinal designs, including measures of other potential mediators such as eating as a coping mechanism, and more direct indicators of metabolic health. Abuse and neglect are adverse childhood experiences that exert substantial stress on the child, and violate expectations of a safe and stable environment , 2. ExpeOverweight and obesity present a global health challenge with rising prevalence  and withIf abuse and neglect are encountered during developmentally sensitive periods, they have the potential to not only elicit an acute stress response but also to reprogram one of the central human stress response systems: the hypothalamic–pituitary–adrenal axis . When cThe majority of the above described research has investigated HPA-axis functioning by measuring circulating cortisol in saliva, which offers insight into acute cortisol levels across the day and in response to specific stressors. In recent years, measures have been complemented by assessing cortisol concentrations in hair samples, which represent a more chronic measure of cortisol , 35. CorSeveral studies have found associations between experienced maltreatment and hair cortisol levels later in life e.g., , 37. A mIn addition to cortisol levels, cortisone levels may be relevant in the context of maltreatment and BMI. Cortisol can be metabolized into the inactive cortisone by 11β-hydroxysteroid dehydrogenase (11B-HSD) type 2 . EssentiStress and cortisol also play a central role in obesity. Early evidence of the causal role cortisol plays in obesity comes from studies observing weight gain in patients who are administered glucocorticoids –42. AddiThe current study adds to the existing research by testing the mediating role of hair cortisol—as an objective measure of chronic stress and HPA-axis functioning—in the relation between retrospectively measured maltreatment and the BMI of children and adults. To our knowledge, only one study has investigated cortisol dysregulation as a mediator between maltreatment and BMI . This stWe expected that abuse and neglect experienced in childhood would be associated with higher BMI at the time of the study. Further, we expected that abuse and neglect would be related to hair cortisol and cortisone concentrations and that these would in turn be related to BMI. We hypothesize that the effect of maltreatment on BMI would be mediated by elevated hair cortisol and cortisone concentrations. Given mixed results in previous research, we explored whether abuse and neglect had differential effects.It has been argued that the initial response to experiencing maltreatment is an increased stress reaction, but that over time chronic stress results in down-regulation , 32, 58.The sample of the current study was drawn from the Dutch 3G Parenting Study that investigates intergenerational transmission of parenting styles, stress and emotion regulation using a multi-generational design , aged 8 to 87 years .Participants attended one or two 7-hour lab visits at the Leiden University Medical Center with their nuclear families. During these lab visits, participants completed questionnaires, computer tasks, interviews, and family interaction tasks. In addition, samples of hair, saliva, and buccal cells were collected. All participants signed informed consent. Parents cosigned informed consent if the participant was under the age of 18 years. Also, maltreatment questionnaires of underage participants were inspected after each lab visit. Ethical approval was obtained from the Ethics Committee of the Leiden University Medical Centre (reference number: P11.134).We measured child maltreatment experiences with a combination of two self-report questionnaires: the Parent-Child Conflict Tactics Scales CTSPC,  and the r(247) =.64, p < .001) and the average for physical and the average for emotional neglect (r(247) =.38, p < .001), respectively. Cronbach's αs show acceptable internal consistency for child-report  and parent-report .To measure maltreatment, we used a multi-informant approach in which we combined child- and parent-reports. All participants reported on whether they had experienced maltreatment . For the child-report score, participants reported on maternal and paternal behavior separately. Per subtype, we first calculated averages for maltreatment perpetrated by mother and maltreatment perpetrated by father. Then, per subtype, the higher score of mother or father was included in the child-report score. In addition, if a participant participated with a parent, that parent also reported on whether they had perpetrated maltreatment towards that particular participant . The same approach was used to calculate the parent-report score. At least one parent score was available for 61% of the participants. Child-report and parent-report were averaged. Lastly, abuse and neglect scores were calculated by averaging the average for physical and the average for emotional abuse  for 18 h at 25°C while gently shaking to extract cortisol and cortisone. In line with previous research e.g., , 57, we At a growth-rate of approximately one centimeter per month, one centimeter of hair represents the cumulative cortisol secretion of the past month . It is p2). BMI and age were correlated . When assessing BMI in children and adolescents, it has been recommended to use age and gender specific scores based on external reference values , RMSEA = 0.90, and CFI = 0.78). Of all the confounding variables, only season (summer vs. other season) was significantly related to cortisol  and medication use was related to cortisone . This is in line with the preliminary analyses . To assess SES we asked participant of 18 years and older about their household income and highest completed education. Yearly household income was measured on a 7-point scale ranging from (z > ± 3.29) were winsorized  indicating that data was MCAR. Therefore, we imputed missing values using full information maximum likelihood (FIML).The missing information were as follows: 2.4% hair cortisol, 1.2% hair cortisone, 5.6% BMI, 1.2% hair dyed, 1.2% hair bleached, 0.8% hair permed, 0.4% hair washing frequency, 0.4% on last hair wash, and 0.8% on hair product use. Little's missing completely at random (MCAR) test was not significant  because some of the variables had a non-normal distribution. To assess fit, we inspected comparative fit index (CFI) and the root mean square error of approximation (RMSEA). A CFI above .90 and an RMSEA below .06 was considered to describe a good fit between the model and the observed data .ps < .01). SES was negatively related to neglect and BMI-z (ps < .05). Abuse and neglect were correlated (p < .01) as were cortisol and cortisone (p < .01). Lastly, abuse was correlated to cortisol, cortisone, and BMI-z (p < .05) whereas neglect was only related to cortisone (p < .05). For participants who were younger than 21 years, a BMI SDS of 1 or higher was considered overweight and of 2 or higher was considered obese (z) in the analyses for optimal power , RMSEA = 0.00, and CFI = 1.00. The complete model with standardized path coefficients is presented in The hypothesized model fit the observed data well with z scores . Age and sex were not included as covariates as BMI-z was already corrected for age and sex. There was a significant positive association between abuse and BMI-z  with higher levels of experienced abuse predicting higher BMI-z. The effect of experienced neglect on BMI-z was not significant . Hair cortisol and hair cortisone were not associated with BMI-z .Lower SES was associated with higher BMI-p < .001) and participants with a higher SES  but were not signif ica ntly associated with sex . Taking into account these demographic variables, there were no significant relations with abuse  or neglect .Hair cortisol concentrations were higher in older participants  and men compared to women . There was no association with SES . Controlling for age, sex, and SES, experiencing abuse was significantly related to hair cortisone. Higher levels of experienced abuse were related to greater cortisone concentrations . Conversely, the effect of experienced neglect was not significant .We observed higher hair cortisone levels for older participants .An indirect effect can be significant even if not all of the direct paths are significant. For completeness, we tested whether any of the indirect effects were significant, however, this was not the case , RMSEA = 0.00, and CFI = 1.00]. We found the same pattern of significant results and similar strength and direction of path coefficients. There were 76 participants who were living with their parents at the time of the data collection. The model fit for this subsample was acceptable . However, running the path model for this subgroup led to a different pattern of results with the previously significant effects of abuse on hair cortisone concentration  and BMI-z  disappearing. This might suggest an age effect but could also be the result of a lack of power in the last analysis as this group was smaller than the group of participants who were not living with their parents.A number of additional analyses were conducted to exclude alternative explanations for the findings. For one, trauma may affect individuals in a different way depending on whether it is ongoing or not. Therefore, we ran the analyses separately for participants who were still sharing a household with their parents and those who were not. Of the total sample, 173 participants were not living with their parents at the time of the data collection. Running the model in this subsample, we found good model fit  and the same pattern of significant results emerged, with similar path coefficients, suggesting that there was no suppression effect. It has also been suggested that the cortisol:cortisone ratio and the sum of cortisol and cortisone may be meaningful indicators of HPA-axis activity , RMSEA = 0.00, and CFI = 1.00; sum: X2 = 7.64 , RMSEA = 0.00, and CFI = 1.00]. Ratio was predicted by age  and SES  but not abuse or neglect. Ratio and BMI-z were also not related . The sum of cortisol and cortisone was related to age  and abuse  but not BMI-z .We initially tested the unique effects of cortisol and cortisone. Cortisol and cortisone were highly correlated. In two sensitivity analyses we tested whether cortisone suppressed the effects of cortisol and vice versa by running the analyses for cortisol and cortisone separately. In both cases the estimates of model fit were satisfactory . Physical abuse showed similar associations with the variables in the model as overall abuse did. There was a significant association with BMI-z , cortisol  and cortisone . Results were also similar for emotional abuse . Emotional abuse was associated with BMI-z , cortisol , and cortisone . The pattern of results for emotional neglect was also similar to overall neglect. Model fit was adequate . Emotional neglect was not associated with any variables of interest .Physical and emotional maltreatment might have differential effects. Therefore, we explored physical and emotional abuse, and emotional neglect in separate models. We omitted physical neglect from these analyses because on its own, physical neglect did not have sufficient variance  or internal reliability (α =.24–.64). For physical abuse, model fit was good  and did not affect the path coefficients substantially.We also ran the model again with season and medication use as control variables for hair cortisol and cortisone, respectively. This resulted in a model that fit the data adequately [z. Moreover, we observed higher concentrations of hair cortisone in individuals who had experienced abuse. However, contrary to our expectations, neither hair cortisol nor hair cortisone mediated the association between abuse and BMI-z. Neither hair cortisol nor hair cortisone had a direct effect on BMI. Moreover, neglect did not affect hair cortisol, hair cortisone, or BMI-z.This study investigated the effect of experiencing child maltreatment on BMI and the mediating role of chronic stress, indexed by hair cortisol and cortisone. Confirming previous research , 13, we In line with most previous research , 13, abuAs expected, abuse was related to increases in hair cortisone (and trend-level increases in cortisol) suggesting chronic levels of stress in individuals with abuse experiences – in some cases decades after the abuse occurred. This is also in line with the majority of research on maltreatment and hair cortisol which suggest elevated cortisol secretion . It is iEvidence of hypocortisolism has generally been interpreted in the context of the allostatic load model: over time the stress response is downregulated to maintain homeostasis. The current study found evidence of elevated cortisone levels in abused individuals—in particular in adults. However, this is not necessarily in contradiction to the allostatic load model since intra-individual cortisone levels may have been downregulated over time, but the cross-sectional nature of the study does not allow us to test this hypothesis. Collectively, these findings show that experiences of abuse get embedded in the body's physiology by reprogramming HPA-axis and higher BMI but that these might be separate processes.From a methodologic perspective, this finding also supports the measurement of hair cortisone in addition to hair cortisol. At the moment, the majority of studies focus on hair cortisol and do not include a hair cortisone measures. Cortisone levels are generally higher than cortisol levels. It has been suggested that this might make cortisone more readily detectable and a more powerful indicator of chronic stress . Effectsz. Previous research has suggested a relation between HPA-axis dysregulation and obesity but results were inconsistent  and grants of Leiden University to initiate and support the Research Profile Area Health, Prevention and the Human Life Cycle awarded to MI, P. Assendelft, and B. van Hemert.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.


Baduanjin is an ancient technique of physical and breathing exercises (Dao Yin). This technique is divided into eight sections and each section is a motion, so it is called “Baduanjin”. It is practice without equipment, simple and easy to learn, whose effect is significant leading to good fitness effect. Diabetes mellitus is a chronic metabolic disease. Clinical studies have reported that Baduanjin can affect the metabolism of blood glucose and blood lipid in diabetic patients, but the reported efficacy is different among different studies. Therefore, the study is aimed to systematically evaluate the size and differences of the impact of Baduanjin on the metabolism of glucose and lipid in diabetic patients.Retrieved randomized controlled trials(RCTs) on effects of Baduanjin on glucose and lipid metabolism in diabetic patients from PubMed, Web of Science, the Cochrane Library, Embase, CNKI with computer while mutually retrieved the same things from Chinese Clinical Trial Registry(ChiCTR), Google Academic and Baidu Academic. The retrieval time was from their establishment to October 2020. Then 2 researchers independently extracted relevant data and evaluated the quality of the included literatures, and meta-analysis was conducted on the included literatures using RevMan5.3.This research used outcome indicators like fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, total cholesterol content and triglyceride content to explore the effect of Baduanjin on glucose and lipid metabolism in diabetic patients specifically.The research will provide reliable evidence-based proof for Baduanjin improving glucose and lipid metabolism of diabetic patients.Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.DOI 10.17605/ OSF.IO/AGJHQ. According to the functional status of insulin, diabetes mellitus is divided into type 1 diabetes and type 2 diabetes, of which about 90% is type 2 diabetes. Type 2 diabetes is a metabolic disease caused by multiple causes and characterized by hyperglycemia. It is commonly seen in middle-aged and elderly people, with insidious onset and no obvious symptoms in the early stage.,4 With the acceleration of population aging and the change of people's lifestyle in recent years, the incidence of diabetes mellitus is on the rise. The prevalence of diabetes mellitus throughout the world has caused a huge economic burden on the health care system and has a negative impact on the life quality of individuals.Diabetes mellitus is a common chronic metabolic disease that seriously endangers human health, mainly manifested by hyperglycemia and often accompanied by disorders of blood-lipid metabolism. Modern clinical practice has proved that Baduanjin plays a therapeutic and rehabilitative role in hypertension, chronic obstructive pulmonary disease (COPD), chronic heart failure, myocardial infarction and etc.–11 Baduanjin does not require the use of equipment, and will not be restricted because of the site. It is a long-term, low-intensity aerobic exercise. More and more studies have shown that Baduanjin has certain efficacy in controlling blood glucose and blood lipid levels in diabetic patients improving patients quality of life.–15 Studies have shown that Baduanjin prevents and improves hyperlipidemia mainly by promoting glucose decomposition and consumption, improving psychological state, relieving anxiety and depression, spreading knowledge of keeping health and changing patients diet custom. However, as for how Baduanjin affects glucose and lipid metabolism of diabetic patients, as well as the size and difference of its influence, there are differences among different research results. In this study, through a systematic review of published RCTS, the evidence-based basis of Baduanjin's influence on glucose and lipid metabolism of diabetic patients was obtained.Physical exercise is an important strategy for the prevention and treatment of non-communicable diseases. Therefore, as a non-drug, economical and effective means for the prevention and treatment of diabetes mellitus, it has gradually attracted peoples attention. Baduanjin is a kind of guiding art in ancient China, which has the effect of regulating the body, qi movement and functions of zang-fu viscera, dispelling diseases and keeping fit. It is the wealth created by health-keeping experts and martial arts practitioners in past dynasties.22.1This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analysis protocols (PRISMA-P). Moreover, it has been registered on the open science framework (OSF) on October 24, 2020. (registration number: DOI 10.17605/OSF.IO / AGJHQ).2.2Since the protocol does not involve the patient's personal information, it is not involved in ethical issues and approval from the ethics committee is not required.2.32.3.1We will collect all available RCTs on the effects of Baduanjin on glucose and lipid metabolism in patients with diabetes mellitus, regardless of blinding, publication status, or region, but the language is limited to Chinese and English.2.3.2Patients who is definitely diagnosed as diabetes mellitus, regardless of nationality, race, age, sex, region, course of disease, or blood glucose level.2.3.3The treatment group was treated with Baduanjin plus western medicine, including the treatment with Baduanjin alone. There was no restriction on the types and schools of Baduanjin. The control group only used western medicine treatment and the type, dose and the course of treatment were not limited.2.3.41.Glucose metabolism level: ①fasting blood glucose (FPG); ②2 hour postprandial blood glucose (P2hPG); ③glycosylated haemoglobin (HbA1c);2.Lipid metabolism level: ①total cholesterol (TC); ②triglyceride (TG); ③low density lipoprotein (LDL); ④high density lipoprotein (HDL).2.41.Studies that can not obtain the full text.2.Studies published as abstracts, with uncomplete data and unable to obtain data after contacting the author;3.Studies published repeatedly except the one who has the intact data and best quality.4.Studies with no relevant outcome indicators.5.Treatment or control group use other exercises or Chinese medical therapy like Tai Chi, yoga, acupuncture, etc.2.5“Ba Duan Jin (Baduanjin)”, “Tang Niao Bing (Diabetes mellitus)”, “Tang Zhi Dai Xie (Glucose and lipid metabolism)”, and other Chinese terms were searched on Chinese database like CNKI, VIP, Wanfang Data Knowledge service platform, and China Biomedical Database. “Eight trigrams boxing”, “Baduanjin” and “Diabetes Mellitus” were searched as English searching terms in PubMed, Web of Science, the Cochrane Library and Embase, at the same time, we searched mutually in Google Academic, Baidu Academic and Chinese Clinical Trial Registry (ChiCTR). The searching time was from their establishment to October 2020. All above is for collecting domestic and foreign literatures on the effect of Baduanjin on glucose and lipid metabolism in diabetic patients. Taking PubMed as an example, its retrieval strategy was shown in the Table 2.6Referring to Cochrane Handbook for Systematic Reviews of Interventions, 2 researchers used EndNote X7 to independently screen according to inclusion and exclusion criteria. Firstly, the literature of each data was imported into EndNote X7 so, and then repeated literatures were removed. Then, the title and abstract were read for preliminary screening. After the preliminary screening, the full text was further read for screening, and finally qualified studies were included for systematic evaluation and meta-analysis. Marked down reasons for exclusion for each article during the filtering process. The 2 researchers checked the screening results and discussed the results with the third researcher for those studies that were difficult to be included due to differences. At the same time, Excel 2013 was used to extract relevant information, including: ①First author of the literature, year of publication; ②Basic information of the subjects: age, sex, height, weight, course of disease and complications; ③Intervention methods of the treatment group and the control group: The treatment group was treated with Baduanjin exercise or Baduanjin combined with western medicine, while the control group was treated with western medicine only. Their frequency, dosages and courses; ④ Outcome indicators: FPG, P2hPG, HbA1c, TC, TG, HDL, etc. ⑤The quality evaluation factors of the literatures; ⑥Adverse events and follow-up. The process of literature filtering was shown in Figure 2.7Use the Cochrane collaborations tool for assessing risk of bias to performed risk bias assessment of the included studies. According to the performance of the included literatures in the evaluation items below which are random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other bias, the 2 researchers will give low risk, unclear and high risk judgments one by one and cross-check after completion respectively. In case of any disagreement, discussion will be carried out. If no agreement can be reached, discussion will be made with the researchers of the third party.2.82 and I2.If P ≥ .1and I2 ≤ 50%, which meant low heterogeneity, we used fixed-effect model to do meta-analysis; If P < .1 and I2 > 50%, which indicated inter-study heterogeneity, the source of heterogeneity would be explored, and then the clinical heterogeneity was dealt with through subgroup analysis. If no significant clinical or methodological heterogeneity were found, statistical heterogeneity was considered and the random-effect model was used for analysis. If the clinical heterogeneity was too obvious and the subgroup analysis could not be performed, descriptive analysis was performed instead of making meta-analysis.The RevMan 5.3 software was used for meta-analysis. Relative risk (RR) was selected as the statistic for the dichotomous variable. For continuous variables, weighted mean difference (WMD) was selected when the tools and units of measurement indicators were the same, standardized mean difference (SMD) was selected as effect value if tools or units of measurement were different. And all above were represented by 95% confidence interval (CI). Heterogeneity was determined by χ2.8.1If there is missing data in the article, contact the first author or corresponding author via email or phone to obtain accurate data. If the author cannot be contacted, or the author has lost relevant data, descriptive analysis will be conducted instead of meta-analysis.2.8.2Subgroup analysis was performed according to that if use Baduanjin alone or Baduanjin combined with western medicine in the treatment group. Subgroup analysis was performed according to the age of the patients. Subgroup analysis was performed according to the type of diabetes mellitus. Subgroup analysis was performed according to the courses of treatment.2.8.3In order to determine the stability of outcome indicators, sensitivity analysis was used to analyze each outcome indicator.2.8.4Funnel plots were used to assess publication bias if no fewer than 10 studies were included in an outcome measure. Otherwise, Egger and Begg test were used for the evaluation of potential publication bias.3 Diabetes mellitus has a long course of disease and many complications, which cause a great burden on families. In developed countries, two-thirds of patients has poor disease management. Common complications of diabetes mellitus include cardiovascular and cerebrovascular diseases, diabetic foot, diabetic gastroparesis, etc., all of which are common causes of death and disability in diabetic patients. Diabetes mellitus is divided into type 1 and type 2. Insulin resistance is considered to be the main cause of type 2 diabetes, and abnormal glucose and lipid metabolism is a symptom of insulin resistance. The symptoms of diabetic patients are mainly polydipsia, polyphagia, and polyuria, etc. With the aggravation of the disease, the weight of the patients will gradually decrease and people will become relatively thin, which is more obvious in type 1 diabetes. In type 2 diabetes, the symptoms are mostly systemic fatigue and weight gain before onset. If not treated promptly, weight loss will gradually occur. At present, most of the drugs in western medicine for the treatment of diabetes mellitus are symptomatic treatment with large adverse reactions.Diabetes mellitus is one of the chronic diseases in developed and developing countries around the world. According to the International Diabetes Federation, the number of diabetics worldwide will reach 693 million by 2045. Studies have shown that exercise can improve the condition of blood lipid and blood pressure of diabetic patients and improve their quality of life. As a non-drug and economical means, Baduanjin has a long history and culture as well as health value. It is simple and easy to learn and suitable for people of all ages. While improving the health of the masses, it also reduces the burden of medical care for the country and the people. Baduanjin exercise can significantly improve endothelium-dependent vasodilation function in type 2 diabetes patients, which is very beneficial to restore the health of patients with diabetes mellitus. The specific reasons are related to the fact that Baduanjin can improve the skin temperature of the Governor Vessel points, increase the Yang Qi of human body, excite the vital gate fire of human body and regulate the running of qi and blood in meridians.Studies have shown that Baduanjin can play an anti-diabetes role by regulating the expression of mRNA, IncRNA, and circRNA. Non-medical intervention of physical rehabilitation has a great positive effect on the rehabilitation of diabetic patients, mainly treating the interior to cure the root of diabetes. And where traditional Chinese medical physiotherapy is superior to western medicine treatment is that it has no toxic and side effects at all. However, the clinical efficacy of Baduanjin in the treatment of diabetes mellitus has not been recognized by international authoritative medical organizations. Therefore, we analyzed the RCTs of the specific impact of Baduanjin on glucose and lipid metabolism of diabetic patients, obtained the theoretical basis of improving glucose and lipid metabolism of diabetic patients with Baduanjin and objectively evaluated the impact of Baduanjin on diabetic patients. However, this study also has some limitations. Due to the special operation of Baduanjin, it is difficult for us to use blind method. Moreover, due to language restrictions, we only searched Chinese and English literatures, which may have some publication bias.In traditional Chinese medicine, diabetes mellitus belongs to the categories of “consumptive thirst (Xiao Ke)”, “consumptive disease (Xu Lao)” and etc. In general treatise on causes and manifestations of all diseases (Zhu Bing Yuan Hou Lun), it is indicated that if consumptive thirst (Xiao Ke) is improperly treated, or if the course of the disease persists indefinitely, it may develop into carbuncle and abscess (Yong Ju) or edema, which are diabetic foot and diabetic nephropathy in modern medicine. Traditional Chinese medicine advocates prevention before disease, which is of great significance for the prevention and treatment of diabetes. The main treatment measures for diabetes mellitus are “5 carriages”, namely, diabetic education, diet control, exercise, drugs and blood glucose monitoring, among which exercise is a necessary means for diabetes mellitus treatment.Conceptualization: Hanzhang Li.Data collection: Qiaojun Ma and Hanzhang Li.Data curation: Qiaojun Ma, Hanzhang Li.Funding acquisition: Hanzhang Li.Funding support: Hanzhang Li.Investigation: Qiaojun Ma, Hanzhang Li.Literature retrieval: Qiaojun Ma and Hanzhang Li.Software: Yinping Gao.Software operating: Yinping Gao.Supervision: Yalan Zou.Writing – original draft: Qiaojun Ma, Hanzhang Li.Writing – review & editing: Yinping Gao.


In Parkinson’s disease (PD) population, performing secondary tasks while walking further deteriorates gait and restrict mobility in functional contexts of daily life. This study (1) analyzed the interference of functional cognitive and motor secondary task on untrained people with PD and (2) compared their walking with healthy subjects.Forty people with PD  composed the PD group (PDG) and 43 participants (aged 66.60 [8.75] years) formed the group of healthy counterparts (HG). Gait was evaluated through spatiotemporal, kinematic and kinetic outcomes in five conditions: single task (ST) and visual, verbal, auditory and motor dual-task (DT).p < .05), and inferior in double support time and midstance force (p < .05). The same pattern was observed when compared the ST and visual DT condition, where participants showed a significantly higher stride length, double support time and braking force in the ST (p < .05). In addition, the PDG exhibited a significant shorter double support time and midstance force, and showed a higher braking force in the visual DT than in the verbal DT (p < .05). Similarly, the PDG showed a wider stride in the visual DT than in the motor DT condition (p < .05). PDG participants had a significantly lower performance than the HG in all the variables analyzed except for the maximum hip extension in the stance phase (p > .05). Conclusions: In untrained participants with PD, verbal and motor secondary tasks affect gait significantly, while auditory and visual tasks interfere to a lesser extent. Untrained people with PD have a poorer gait performance than their healthy counterparts, but in different grades according to the analyzed variables.The velocity, stride length, and braking force performance of both groups was statistically higher in the ST condition than in verbal, auditory and motor DT (clinicaltrial.govNCT04038866.The data in this paper are part of a single-blind, randomized, controlled trial and correspond to the evaluations performed before a physical rehabilitation program, retrospectively registered with the number at  Parkinson’s disease (PD) is a chronic, progressive and neurodegenerative pathology, with motor and non-motor disorders , which aHowever, walking in everyday situations is carried out simultaneously with other activities. This is known as dual-tasking (DT) and involves the development of two tasks with different objectives at the same time , where aDespite the amount of published information regarding how DT affects gait in PD, so far as we know, these studies do not include kinematic and kinetic variables  simultanGait assessment with secondary functional tasks, such as talking with another person or carrying something with the hands, would allow observing the performance of people with PD in everyday contexts and guiding physical therapy with the aim of preparing patients for these probable challenges. This is of special interest in PD because the basal ganglia are involved in the control of different aspects besides motor control , 9 and tBased on the foregoing, the general objective of the present study was to analyze the degree of interference of functional cognitive and motor secondary tasks on the walking biomechanics in untrained people with Parkinson’s disease. Likewise, a secondary aim of the study was to compare a parkinsonian walking pattern with gait in healthy older people during the execution of single and dual-tasks.http://www.strobe-statement.org/). Eighty-three participants integrated the sample, of which 40 people with Parkinson’s disease composed the PD group (PDG) and 43 participants formed the group of healthy counterparts (HG) matched by age, gender, and height. PDG participants were recruited from two centers: a Parkinson’s disease Association and the Neurology Service of a local public hospital. HG individuals were from a Municipal Senior Social Activity Center. Inclusion criteria for PDG were: diagnosis of idiopathic PD and to present Hoehn & Yahr stadium I, II or III. In addition, both groups should be able to walk by themselves, have a normal cognitive state (i.e. score > 25) according to the Minimental test adapted for PD [The study design was cross-sectional with a convenience sample  and adhered to the STROBE guidelines : walking without secondary tasks with the attention focused only on walking performance, ii. visual DT: walking while checking the time on an analog clock projected at the end of the walkway, iii. Verbal DT: walking while telling the evaluator the activities they had performed the previous day in chronological order, iv. auditory DT: walking while listening and recognizing different daily noises and, v. motor DT: walking while carrying one glass in each hand and repeatedly transferring their contents from one to the other (beans). These tasks were intended to simulate the action of looking at the time, talking with another person, listening to the sounds of the environment and manipulating objects with hands while walking. All these tasks are representatives of daily life activities, which provide external validity to the study and concur with skills previously studied [The assessments were carried out at the Medicine Department of the University of Valencia. PDG participants were evaluated in the on-medication state . The ass studied , 12. Durconditions, 10 repetitions were performed, five with each foot, to later use the average of these. Participants were allowed to rest between repetitions, sitting on a stool for less than three minutes, when fatigue was reported.Gait assessment was carried out in a corridor 10 m long and data were registered using 3D photogrammetry with 12 smart cams  and two force platforms . A valid repetition is one in which the patient performs at least five complete strides along the corridor and where one complete and isolated footprint (rigth or left) from the third stride coincide with the dynamometric platform located in the center of the corridor. The previous and subsequent strides were discarded to avoid acceleration and deceleration phases, at the beginning and at the end of the gait, respectively. For each of the five evaluated walking The biomechanical model was composed of 35 landmarks located in specific anatomical points on both sides of the body: i. the spinous process of the seventh cervical vertebra, ii. the acromioclavicular joint, iii. The posterosuperior iliac spine, iv. the anterior-superior iliac spine, v. the greater trochanter of the femur, vi. the anterior vertex triangle forming the thigh segment, vi. the medial condyle of the knee, vii. The lateral condyle of the knee, viii. The posterior vertex triangle of the leg segment, ix. the medial malleolus of the ankle, x. lateral malleolus of the ankle, xi. the posterior surface of calcaneus, xii. The tuberosity of fifth metatarsal and xiii. Cuboids. For suitable biomechanical modeling, the patient’s clothing included shorts, sleeveless shirt and slip-on paddings (with the top of the foot uncovered). Before recording gait, participants were allowed to walk in the corridor (ST condition) to familiarize themselves with the test.For calculation of biomechanical variables based on the data exported from the photogrammetry system and the dynamometric platform, the software was programmed with Matlab . The average of these dependent variables was calculated from the 10 repetitions for each condition: i. Velocity: distance travelled by the body per unit of time (m/s), ii. Stride length: distance measured between two consecutive heel strikes of the same foot (i.e. two steps) (m), iii. Cadence: number of steps taken in a minute (steps/min), iv. Double support time: the sum of the amount of time in which there is double-limb support in a gait cycle (%), v. Ankle range: range of motion (ROM) that corresponds to the sum of the maximum angle of plantar flexion and maximum angle of dorsiflexion of the foot (°), vi. Hip flexion: maximum flexion angle reached by the hip joint during the swing phase of the gait cycle (°), vii. Hip extension: maximum extension angle reached by the hip joint during the stance phase of the gait cycle (°), viii. Weight-acceptance force: first peak of the vertical component curve of reaction forces corresponding to the maximal weight-acceptance (N), ix. Midstance force: minimum value between the two force peaks of the vertical component curve of reaction forces corresponding to the midstance of the gait cycle (N), x. Braking force: first negative peak of anteroposterior component curve of reaction force that corresponds to the braking (N).conditions (Eq. 1) [In addition, to inform about the degree of interference of dual tasks during gait, the Dual-task cost was calculated as the percentage measure of performance decline observed under DT  (Eq. 1) , 13. Negconditions with five categories  and between-subject factor group with two categories (i.e. PDG and HG) on the dependent biomechanics variables. Some of these variables were standardized according to anthropometric data, concretely, ‘stride length’, which was standardized by the lower limb length, and ground reaction force variables were standardized according to the weight of the participants.Statistical analyses were performed using IBM SPSS v.24 . Standard statistical methods were used to obtain the mean and standard deviation (SD). Also, as descriptive results, the confidence interval, PPgait percentage, and DT cost were calculated. A two-factor mixed Multivariate analysis of variance was conducted to analyze the effect of within-subject factor p < 0.05 and the 95% confidence interval (CI) of the pairwise mean differences was reported.When significant factor effects were found, the Bonferroni correction, provided by the statistics package, was used for pairwise comparisons. Differences were declared statistically significant if group was conducted. Further, to demonstrate differences in gender between groups, a chi-square test was used.To check for differences between the demographic outcomes between groups, multivariate analysis with one-way between-subject factor p > .05). Throughout the evaluation, the PD participants did not present disorientation in any of the dual-task cognitive conditions or apparent loss of memory during the verbal dual-task condition.Eighty-three participants completed this study. Their characteristics are shown in Table group are reported with 95% CI and the difference between Gender from chi-square test are indicated by the p value . * Indicates statistically significant effects.Main demographic data for Parkinson’s disease group (PDG) and healthy control (HG). Range, mean, standard deviation (SD) and frequency are shown. NA: not applicable. BMI: body mass index. Differences between groups from multivariate analysis with one-way between-subject factor condition and group factor was statistically significant (p < .05) on double support time, ankle range and midstance force outcomes (Table p > .05).The interaction effect between es Table . This ines Table . On the F), the number of degrees of freedom of factor and error, the p-value and the eta square are shown. * Indicates statistically significant effects (p < .05).For each effect, the value of the F ratio (p < .05). In velocity, cadence and both vertical forces measured, the performance of participants was similar in both, visual DT and ST condition (p > .05).Post-hoc analyses showed that the performance of both groups for the ST condition was higher than visual DT (p < .05) only in stride length, double support time and braking force Fig. , which rp < .05), shown in Fig. p < .05), in the PDG only this decrease was observed during the verbal DT condition (p < .05).Regarding the verbal, auditory and motor dual-tasks, a significant worsening of gait velocity, stride length, double support time, midstance and braking forces were observed in both groups (= −.28 to −.02). Also, we observed that the performance of the PDG during verbal DT was significantly worse than the auditory DT condition (p < .05) in double support time , ankle range  and braking force  outcomes. In a different way, HG showed differences between dual conditions chiefly in the midstance force, where they had worse performance with verbal , auditory  and motor  tasks compared to the visual task.In addition, significant differences between dual conditions were observed, mainly between the visual DT and another dual-task. Specifically, PDG performance was significantly better during the visual DT condition than the motor DT on stride length  and the verbal DT condition on double support time , midstance  and braking forces .The differences between post-hoc analysis pairs of measures are shown in Table These differences between PDG and HG are reflected in the PPgait%, whose value changes according to the analyzed variables. PDG participants walk slower and perform a lower braking force, by more than 20% in relation to the performance of HG participants. This deficit drops between 15 and 10% approximately in the stride length, double support time, ankle range and midstance force outcomes.This study analyzed how functional dual tasks affect parkinsonian gait and compared walking performance of people with Parkinson’s disease with healthy older adults under single and dual-task. To our knowledge, this is the first study that uses functional dual-task in parkinsonian gait assessment and analyzes kinematic and kinetic parameters, in addition to spatiotemporal variables, which are the most used in previous studies , 14.Regarding dual-task interference, the gait of participants with PD and healthy controls significantly deteriorated when performing a dual-task but, this impairment depended on the type of secondary task and outcomes analyzed. First of all, we observed that the visual secondary task showed the least interference on gait in both groups, since this was the only condition in which all study participants showed a similar gait pattern to ST condition, specifically in gait velocity, cadence and both vertical forces. Indeed, both groups showed a better walking with a visual task than with other secondary tasks, although the differences between dual tasks were more evident in the PDG. To explain why visual tasks may interfere less during gait compared to other secondary tasks is complex due to sight is a common resource for performing an appropriate walking pattern , consequBy contrast, the secondary task that most interfered with gait was not the same for both groups. For HG, the interference caused by verbal, auditory and motor secondary tasks was similar between the measured outcomes, that is, no significant differences were observed between the dual conditions beyond the differences observed with visual tasks and the percentages of DT cost are similar between them.Nevertheless, participants with PD showed the most interference on gait with the verbal and motor secondary tasks, specifically in the outcomes where the interaction of the factors analyzed in this study was statistically significant , besides of braking force. That is to say, the PD participants achieved a better gait with a visual or auditory task than with verbal or motor secondary tasks.The verbal tasks could be more complex to perform than other secondary tasks due to the subcomponents involved: lexicon, message planning, message extension and oral motor movement. From there, the motor part of speech produces the largest interference in the context of the dual-task paradigm , so it cConcerning the second objective of this study, the results showed that the performance of PDG is significantly lower than the performance by HG, in all the outcomes except for hip extension during the stance phase of the gait cycle. However, the lower performance of the PDG was not always the same for all the variables, which was evidenced by the PPgait percentage. While in velocity and braking force the PPgait percentage was greater than 20%, in the stride length, double support time, ankle range, hip flexion and midstance force outcomes, the PPgait percentage varied between approximately 10 and 15%. On the other hand, a performance below or around 5% was observed in cadence and weight-acceptance force.In general, it seems interesting to note that PPgait is especially high during the motor condition when observing most of the variables analyzed, reaching a 34% deficit in the braking force while developing the motor DT. This could indicate that there are aspects of Parkinsonian gait that are more affected than others and that the context of the gait could influence it as well. An example of this is that people with PD have difficulty to take large steps while the ability to control cadence is maintained or deteriorates more progressively , 22.Further, the results of the kinematic variables are in consonance with these results. We have observed that participants with PD only differed from control participants in the ankle range and hip flexion, achieving a similar maximum hip extension. Other authors have previously observed a decreased plantar flexion in the first stages of PD (Hoehn & Yahr II) , while ipost-hoc comparisons could lead to an increase of the type II error [The results of this study, however, are obtained from participants with normal cognitive status, so future studies are needed to establish how functional tasks, secondary to gait, could interfere in people with PD in advanced stages and cognitive impairment. Another limitation of the study is that we used only day-to-day tasks in the evaluation, consequently, it is possible that the interference on the gait is influenced by the amount of daily practice of the selected tasks. Further, regarding the statistics, we should take into consideration that the Bonferroni adjustments conducted in the II error . MoreoveOn the contrary, we conducted several DT conditions trying to cover the assessment of gait interference by secondary tasks, as it happens in habitual environments with multiples cognitive and motor demands. To assure face validity, the tests included were agreed by all the researchers and aligned with previous studies in which gait assessment was conducted , 12. HowIn untrained participants with PD, verbal and motor secondary tasks affect gait adversely and significantly, while auditory and visual tasks interfere to a lesser extent. Untrained people with PD have a poorer gait performance than their healthy counterparts both for the spatiotemporal, kinematic and kinetic variables analyzed, with the exception of the maximum hip extension during the stance phase of the gait cycle.Additional file 1.


In male students , depressive symptoms were the only significant predictor for disordered eating. In females, the strongest predictor was depressive symptoms , followed by body size satisfaction  and body appreciation . These findings suggest that there are gender differences in the factors associated with disordered eating among Malaysian university students. Intervention programmes that address disordered eating should take into account these sex differences and its contributing factors.Disordered eating is prevalent among university students, especially females. Whilst literature suggests that factors associated with disordered eating may differ according to gender, such an association has not been studied in Malaysia. This cross-sectional study aims to compare factors associated with disordered eating between male and female university students. A total of 716 university students  were recruited in Kuala Lumpur and Selangor, Malaysia. All participants completed a set of self-administered questionnaires and their body weight and height were recorded. About one in five of the university students (20.3%) were found to have disordered eating. There were more female students (22.9%) disordered eating compared to males (13.3%, χ University students, specifically undergraduate students, are typically aged between 18 and 25 years and are therefore in a period of emerging adulthood . During Body image is a multidimensional construct that includes how one perceives, thinks, feels, and acts towards one’s body , all of Disordered eating (DE) is defined as a constellation of unhealthy eating and weight-related behaviours and attitudes that do not meet the criteria for eating disorders, but that may have medical and/or psychological consequences . The preStudies have found DE to be confined to certain sections of SES, either high or low SES ,24. FurtThis is a cross-sectional study carried out in three public universities and four private universities in Kuala Lumpur and Selangor, Malaysia. A total of 716 students studying in one of the seven universities consented to take part in this study. Students enrolled in postgraduate studies, part-time students, and those who were pregnant were excluded from the present study. The height and weight of all participants were measured and they were asked to complete a paper questionnaire that contained questions on socio-demographic characteristics, eating attitudes, body image, and depressive symptoms.Socio-demographic characteristics that were assessed in this study included sex, age, ethnicity, and year of study. The university students who participated in the current study were from the three major ethnic groups in Malaysia, namely Malays, Chinese, and Indians. Other ethnic groups such as Indigenous people, Sabah Aborigines and Sarawak Aborigines are the minorities in Malaysia. The other ethnic group was chosen as the reference group in the current study which allows for comparison with other studies in Malaysia.The Eating Attitudes Test-26 (EAT-26)  is a 26-The Body Appreciation Scale (BAS)  is a 13-The Contour Drawing Rating Scale (CDRS)  was usedBody parts satisfaction was measured with a 16-item version of the Body Satisfaction Scale (BSS) . The resThe 20-item Centre for Epidemiological Studies-Depressed Mood Scale (CES-D)  was used2 and categorised into four categories based on the WHO reference, namely underweight, normal weight, overweight, and obesity [Body weight was measured to the nearest 0.1 kg with a digital weighing scale . Height was measured using a portable stadiometer  to the nearest 0.1 cm. Body mass index (BMI) was calculated as kg/m obesity .t-test was used to determine the mean differences of continuous variables, whilst the Chi-square test was used to determine the association of categorical variables between male and female university students. Pearson and Spearman correlation analyses between gender and DE were also performed. Hierarchical multiple regression analyses were also conducted to examine whether psychological factors contributed significantly to the prediction of individual DE problem, after accounting for the predictive contribution of previously identified BMI and socio-demographic variables for males and females, respectively. Each regression consisted of three separate blocks of variables, with the independent variables in each block entered sequentially. This approach reduced the effects of multicollinearity as it measures the degree to which each set of independent variables account for variances of the dependent variable, without the influence of subsequent blocks of variables. In each regression model, age, ethnicity, and type of university representing the socio-demographic variables were entered in the first block. BMI was entered in the second block. Next, the predictive contribution of psychological factors, such as body appreciation, body size satisfaction, body parts satisfaction, and depression, were entered as these factors had previously been associated with a DE problem. The R-square changed for each block is tested with an F-test. The significance level was set at <0.05 for all analyses.Data were analysed using the IBM SPSS Statistics version 21 software . Data were presented as mean and standard deviation (SD) for continuous variables and as frequencies and percentages for categorical variables. Independent student The study was approved by the Universiti Teknologi MARA (UiTM) Research Ethics Committee (Ref: 600-RMI (5/1/6)). The researchers explained about the study protocol to potential respondents and written informed consent was obtained from all respondents prior to participating in the study.p < 0.05). The results show that there were more male students (21.9%) who were overweight and obese when compared to female students (13.3%) . In addition, there were more female students (16.7%) who were underweight when compared to male students (8.2%) (p < 0.05) and there was a significantly  higher percentage of female students (22.9%) who were engaged in DE when compared to males (13.3%) (p < 0.05). There were no significant differences in terms of mean scores of body appreciation and body parts satisfaction between males and females. There was also no significant sex difference in depressive symptom scores (As shown in s (8.2%) . The fem (13.3%) . The resm scores .s = −0.104, p < 0.05), BMI , body parts satisfaction , depressive symptoms , body appreciation , and body size satisfaction . When stratified by gender, DE was positively correlated with depressive symptoms, but inversely correlated with body appreciation, for both male and female participants. Among female participants, DE was also negatively correlated with ethnicity  and body size satisfaction , but positively correlated with BMI .As shown in p < 0.01). The inclusion of BMI in Block 2 did not contribute significantly to the prediction of DE. When psychological factors, including body parts satisfaction, depressive symptoms, body appreciation, and body size satisfaction, were entered in Block 3, these appear to contribute significantly to the individual prediction of DE, accounting for a further 9.4% increase in the prediction of DE . In the final model, it was shown that depressive symptoms contributed to the largest number of variances explained . Taken together, these variables explained 16.4% of the variances in DE model of male university students.p < 0.05) and Block 2  and appear to give significant contributions to the variation in DE of female university students . In the final model, depressive symptoms contributed the largest amount of explained variance , followed by body size satisfaction  and body appreciation . Taken together, these variables explained 10.2% of the variances in DE among female university students.students . In Blocp < 0.05; Block 2: β = 0.146, p < 0.05) and the results from public university were compared to private university  as these appeared to be significant predictors of DE in the first two blocks . In the final model, depressive symptoms contributed the largest amount of explained variances , followed by lower body size satisfaction , poorer body appreciation , and Malay university students as compared to other ethnic groups . Taken together, these variables accounted for 15.8% of explained variances in DE among overall university students.Overall, the results from Indian university students were compared to results from other ethnic groups  were found to have DE when compared to male students (13.3%). The findings were similar to the results of the Wave III of the National Longitudinal Study of Adolescent to Adult Health , which also found a higher proportion of female young adults to be engaged in unhealthy weight control behaviours, binge eating behaviour, and being diagnosed with eating disorders when compared to their male counterparts . The DE p < 0.001) [Malaysia is a multi-ethnic country with Malay, Chinese and Indian as the major ethnic groups. However, the current study found that ethnicity was not a significant predictor of DE among male or female students from different universities after adjustment for confounders. In other words, all ethnic groups were at risk of DE in university students. Contrary to the several local studies, ethnicity was significantly associated with disordered eating in Malaysian children and adolescents ,17,27. I< 0.001) . In a sa< 0.001) .In a review by McBride and Cole , longituA key strength of the current study is to highlight both male and female Malaysian university students were facing DE problems, and different factors were associated with DE between males and females. The present study has several limitations to be taken into consideration. Firstly, this study is a cross-sectional survey and no causal relationship could be made. Secondly, this study involved university students in urban areas of Kuala Lumpur and Selangor. Therefore, the outcomes of the present study cannot be used to generalise all university students in Malaysia. Furthermore, self-reported questionnaires were used to obtain information from the participants, which could have led to biases and elicit more socially desirable responses from participants. Nonetheless, the questionnaires used are valid and reliable instruments and widely used by researchers, such as EAT-26, which is one of the most common measures for disordered eating or eating disorders risk.In conclusion, the present study found that depressive symptoms were the only significant predictor for disordered eating among male students. Depressive symptoms were also the most significant predictor for disordered eating in female students, followed by body image perception and body appreciation. The present study adds to the body of knowledge in that there are gender differences in the factors associated with DE among Malaysian university students. The outcome of this study could be used as a basis to develop an intervention in preventing DE among university students. Promoting psychological well-being should be included as one of the key components in the prevention programme of DE among university students. For future research, it is suggested to determine the contributing factors of the different forms of DE, such as binge eating/binge eating disorder, loss of control eating, emotional eating, compulsive exercise, and androgenic anabolic steroid use. This is because the contributing factors might be different for different forms of DE and at the same time, they might also share similar factors.


Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline in elderly people and development of Alzheimer’s disease (AD). Blood–brain barrier (BBB) leakage is a key pathophysiological mechanism of amyloidal CSVD. Sleep plays a crucial role in keeping health of the central nervous system and in resistance to CSVD. The deficit of sleep contributes to accumulation of metabolites and toxins such as beta-amyloid in the brain and can lead to BBB disruption. Currently, sleep is considered as an important informative platform for diagnosis and therapy of AD. However, there are no effective methods for extracting of diagnostic information from sleep characteristics. In this review, we show strong evidence that slow wave activity (SWA) (0–0.5 Hz) during deep sleep reflects glymphatic pathology, the BBB leakage and memory deficit in AD. We also discuss that diagnostic and therapeutic targeting of SWA in AD might lead to be a novel era in effective therapy of AD. Moreover, we demonstrate that SWA can be pioneering non-invasive and bed–side technology for express diagnosis of the BBB permeability. Finally, we review the novel data about the methods of detection and enhancement of SWA that can be biomarker and a promising therapy of amyloidal CSVD and CSVD associated with the BBB disorders. Why do we need to sleep and how long should we sleep? Such very highly active people as Margaret Thatcher resent the idea of spending one third of their lives asleep and train themselves to get by with significantly less sleep than others. The surrealist painter Salvador Dali claimed to sleep for only three or four hours every night and to compensate for this by taking short naps during the day. On the other hand, Einstein liked to sleep about 14 h a day. However, regardless of the regime of sleep, without it, we become tired, our brain functions less well and prolonged sleep deprivation can be fatal. Indeed, the brain eats itself after short and chronic sleep loss via microglial activation and astrocytic phagocytosis of synaptic elements ,3,4 and ep sleep .Measuring how people sleep can be a promising approach to screen for Alzheimer’s disease (AD) ,12,13. Pulk flow . Furthermulation . Thus, techanism . HoweverSleep consists of rapid eye movement (REM) associated with dreams and non-rapid eye movement (NREM) or deep sleep. REM sleep is characterized by desynchronization of EEG dynamics with faster oscillations and low voltage waveforms . Human NIn humans, atrophy and Ar adults ,40. Lucer adults . The char adults . The impe brain. . Taking e brain. ,42.Why SWA reflects AD pathology remains unknown but there is strong evidence that it can be related to recently discovered correlation between SAW and activation of glymphatic clearance during deep sleep . Neitherhe brain ,43. The he brain ,45 due tE (apoE) . The decE (apoE) ,47,48,49E (apoE)  and vasoE (apoE) . Thus, tThere is intrigue idea that the body posture during sleep can be used as an additional sign in diagnosis of impairment of glymphatic functions . There in humans .Ae of SWA ,54,55,56f SWA [β  and blocf SWA [β ,54. The f SWA [β ,54. Opto density ,36,57. O density . Taken tThe aberrant astrocytic activity can also contribute to the SWA disruption in AD. Astrocytes maintain glutamate and GABA recycling and form the tripartite synapses to regulate synaptic transmission via calcium signaling ,60. Aβ decycling ,62,63. Tecycling . The astecycling ,66. Thusis of AD .Sleep and the blood–brain barrier (BBB) are two important gamers in scenarios of the homeostasis of the central nervous system (CNS). Sleep is essential for maintenance of the health of the CNS via clearance of metabolites and neurotoxic wastes from the brain ,10.It is generally accepted that the BBB acts as the blood–brain interface protecting the CNS from the penetration of microorganisms and toxins from the blood. Therefore, the methods for opening the BBB are usually used for brain drug delivery and therapy of CNS diseases . Howeverloidosis ,71,72,73loidosis ,68,69. Tloidosis ,71,72,73he brain , that behe brain . The SWAhe brain ,75,76 anThe mechanisms of BBB-mediated changes of neural activity are not fully understood. The BBB opening can affect EEG activity by direct and indirect ways. Direct influence of an increased BBB permeability on the EED dynamics is generation signals of the BBB via electrophysiological properties of brain endothelial cells forming the BBB. The signals generated by the BBB originate from a trans-endothelial voltage between blood and brain tissue This voltage is a consequence of unequal endothelial cell apical and basolateral membrane potentials . The ionIn the 1970s, it was discovered that large-amplitude brain-potential shifts originate from a potential difference, which can occur during the BBB opening induced by respiratory acidosis in different animals species, including cats, money, and rats ,81,82. OIndirect influences of the BBB on the EEG behavior are astrocytes which are essential for the formation and maintenance of the BBB. Reduction in astrocyte number in the mPFC was associated with impaired cognitive flexibility and reduced power across delta (1–4 Hz), alpha (12–20 Hz), and gamma (30–80 Hz) frequency ranges ,86. The We consider that the clearance of different compounds from the brain can be possible bridge between the similar changes in EEG dynamics co-occur during sleep and the BBB opening . It is bThe SWA would be the cleaning power of sleep . Indeed,https://www.alzforum.org/news/research-news/biogeneisai-haltphase-3-aducanumab-trial).Current, there are no therapy of AD ,100,101.Obviously, in the next couple of decades, the main strategies for a treatment of AD will be non-invasive methods of stimulation of clearance of the toxic Alidation .Auditory stimulation of SWA appeared to be more effective in increasing SWA and improvement of memory consolidation as well as cognitive functions ,106,107.Auditory stimulation is used in overnight and nap studies ,110,111.Therefore, the optimization of acoustic stimulation of SWA such as intensity, frequency, and timing is in the trend of development of breakthrough technologies in the enhancement of SWA ,106,107.Transcranial electrical (tDCS) and magnetic stimulation have been successfully applied to enhance SWA with the aim to improve quality of sleep and behavior/cognitive functions ,121,122.Pharmacological methods can also lead increase the time of SWA and might be alternative strategies relying on electric, magnetic, or auditory stimulation of SWA for improving of quality of sleep and brain functions. The administration of tiagabine ,124, gabOptogenetic modulation of SWA is a leading-edge research method that can be used for restoring brain oscillatory brain activity, including SWA. This method is based on light cell-targeting manipulation of proteins expression in cells leading to modulation of the neural activity within neural circuits interest. Optogenetic-mediated activation of neural nitric oxide synthase (nNOS) or somatostatine neurons is useful for restoring SWA . The optCerebral small vessel disease (CSVD) is an important course of cognitive decline and AD. An key pathophysiological mechanism of CSVD is BBB leakage leading to progression of CSVD. Currently, there are no specific preventive or therapeutic measures to improve CSVD. Sleep can be a novel biomarker and a promising therapeutic target for amyloid CSVD and for CSVD associated with BBB disruption. Amyloid CSVD such as AD is correlated with SWA deficit at early stages of disease and was found in asymptomatic cognitively normal adults. Since SWA disruption is an early event, it can be an early biomarker for AD. The level of A


Many elite female athletes struggle to maintain performance while transitioning from high school to university-level (senior) sports. This study explores factors of body composition that influenced performance in elite junior female track and field athletes transitioning to the senior division. Forty-two elite female track and field athletes, ranked among the top 100 in Japan, were enrolled in this study. Whole-body mode dual-energy X-ray absorptiometry scans were performed during the post-season of 2016 and 2017. Athletes’ performances were assessed using the International Association of Athletics Federation scoring system. Relationships between changes in performance and those in body composition were investigated. There were significant negative correlations between changes in performance and fat mass (FM), and percentage FM (FM%). This was seen in total body and lower extremities, and not in the trunk and upper extremities. In addition, there was a positive correlation between changes in performance and percentage lean mass (LM%). However, there were no correlations between changes in performance and LM and total mass. Elite female track and field athletes transitioning to senior division should decrease their FM and FM% and increase LM%, to sustain or improve performance. It is also more important to monitor changes in body composition than body mass. Maintaining performance is a crucial issue for elite athletes aiming to continue their sports activities. Elite junior track and field athletes are competing at a higher level year by year in both national and international events, and in fact, in 2019, four outdoor events in women have set a world U20 record , and theFactors of body composition and its correlation to performances have been investigated in various types of sports ,9,10,11.Because fat accumulation occurs during early adulthood, and fat mass has been reported to have a negative influence on performance, we sought the relationship of performances with body fat and other body composition factors. Since sprinters and jumpers mainly rely on lower extremities, we hypothesized that the body composition of the lower extremities has a stronger relationship to their performances than that of other regions.The study participants were female track and field athletes who ranked among the top 100 in Japan, including those who participated in the International Association of Athletics Federation (IAAF) world junior or youth championships. All participants were aged 17 or 18 years at the school year of 2016. The athletes were mostly recruited from the Kanto, Kansai and Tokai regions and were examined at a designated hospital. Athletes who specialized in one of the following four categories were enrolled: Sprinters , middle distance runners (800 m and 1500 m), jumpers (long jump and triple jump), and heptathlon athletes. We decided to exclude long-distance runners from this study, since, in Japan, the “ekiden (long-distance relay running race mostly on roads)” season begins after track season and does not have an off-season. Throwers, high jumpers, and pole vault athletes were also excluded, since these events are more of technique sports, and throwers tend to have a substantially different body composition to other track and field athletes . We alsoLongitudinal data were obtained at post-season in 2016 (T-1) and 2017 (T-2) during a one-year period. We defined post-season as October–December, since track and field season is roughly from April through October in Japan. We used the records from September–October as their performance each year.On a questionnaire, athletes wrote their best season performance, and we scored the records using IAAF scoring tables of athletics 2017 [Height was measured without shoes to the nearest 0.1 cm using a stadiometer with the athlete standing erect. Body weight was measured before training, and at least 2 h after from their last meal. Body composition was assessed by whole-body mode dual-energy X-ray absorptiometry (DXA) using a device from Hologic Delphi A . After calibration, the subjects, wearing a t-shirt without objects that interfere with the test, lay on the table with their shoulders slightly abducted and elbows slightly flexed, so that their forearms were parallel to the body axis. Their fingers were kept extended without spreading with their palms on the table. A polystyrene block, in the shape of an isosceles triangle with the vertex angle of 30 degrees, was placed between the feet, which were bound to the block, so that the fibulae were not be hidden by the tibiae. Total mass (TM), lean mass (LM), fat mass (FM), bone mineral content (BMC), percentage lean mass (LM%), percentage fat mass (FM%), and percentage bone mass (BM%) were measured in the upper extremities (UE), trunk, lower extremities (LE), and total body. We used TM of the whole body for body weight, since there was little, if any, difference between the two. The same technician performed the scans at each site.On a questionnaire, athletes answered their training hours per day on both weekdays and weekends.p-values less than 0.05 were considered significant.The data were analyzed with the Statistical Package for Social Sciences Statistics 22 . The results are listed as means ± standard deviation (SD). The Shapiro-Wilk test was applied to assess distribution. Pearson correlation analyses were conducted to explore the association between performance and body composition. Continuous data were compared using the independent t-test. Total of 42 athletes proceeded to analysis. Characteristics of the subjects, including season performance and training hours per day are listed in Total bodyp < 0.05) and LM%  in T-1, and FM%  and LM%  in T-2 (p < 0.05) and FM% . Furthermore, there were positive correlation between changes in performance and LM% . However, there were no correlations between changes in performance and LM and TM  in T-2 . There wM and TM .Upper extremitiesFM% increased, while LM and LM% decreased significantly, after a year . There wTrunkTM, FM, BMC and FM% increased, while LM% decreased significantly, after a year . There wLower extremitiesp < 0.05) and FM% . Furthermore, there were positive correlation between changes in performance and LM% (r = 0.34, p < 0.05; FM, BMC and FM% increased, while LM and LM% decreased significantly, after a year . SignifiWe investigated the relationships between changes in performance and body composition over a period of one year among elite female track and field athletes; such a longitudinal study has not been done to the best of our knowledge. In both T-1 and T-2, performance was associated with FM% and LM%, and as a whole, although TM increased significantly after a year, FM and FM% increased more significantly . In addiAlthough coaches reported using body weight as an important index for athletes’ physiques , since tSeveral limitations of this study should be noted. First, we were only able to obtain data for two school years, and the numbers of subjects were not sufficient to perform multiple regression analysis, which could have been more suitable in our study, although 42 is quite a large number when dealing with elite-level athletes. In addition, even though the actual number of subjects participated in this study was much larger than 42, the majority of subjects did not participate in events in some seasons—some did not perform that season, and therefore, were not analyzed. Investigating the cause of the fact that many subjects could not participate in some seasons would be warranted. Accordingly, we plan to continue this longitudinal study for a longer duration and with a larger cohort. Second, previous studies have indicated a positive correlation between dietary fat intake and an increase in body fat over one year in adolescent females , which mTrack and field is a sport that allows easy evaluation of athlete performance. Even though the use of DXA scanning to assess body composition is increasing , many coThis one-year study examined the influence of body composition on performance in elite female track and field athletes transitioning to senior. The following findings were obtained: FM and FM% increased significantly, especially in the total body and lower extremities after a year, and changes in these were associated with performance. Thus, it is important for elite female track and field athletes not to increase FM and FM%, and increase LM%, in order to maintain or improve their performance. It is recommended to assess body composition from time to time in addition to measuring their body weight.


This study aimed to evaluate the psychological effects of the partial lockdown on the people in Vietnam during the COVID-19 pandemic. An online questionnaire regarding attitudes toward COVID-19 along with psychological parameters, including the Impact of Event Scale-Revised (IES-R) Depression, Anxiety, Stress Scale-21 (DASS-21) was conducted. From a total of 1,382 questionnaires, the respondents reported low prevalence of depression (4.9%), anxiety (7.0%), and stress (3.4%). The mean DASS-21 scores recorded were also markedly lower compared to similar studies conducted in China, Italy, and Iran. Respondents who reported severe PTSD had significantly higher depression, anxiety, and stress levels. Factors that were associated with an increased level of depression, stress, and anxiety were being single, separated, or widowed, a higher education level, a larger family size, loss of jobs and being in contact with potential COVID-19 patients. Contrary to expectations, the level of depression, stress, and anxiety observed has been low. Our findings can aid in future research on the impact of a partial lockdown and guide mental health professionals in Vietnam and other countries in the preparation of better care for populations under such circumstances. The 2019 outbreak of Coronavirus Disease (COVID-19) was first documented in Wuhan, China in early December 2019 and resulted in over 16 million infected and over 600,000 deaths worldwide to date. The World Health Organisation (WHO) has since declared it a pandemic. Following the outbreak, the Vietnam government tightened border control and implemented social distancing measures. With the increasing numbers of cases locally and worldwide, Vietnam implemented a partial lockdown on April 1, 2020 where residents must stay at home and can only go outside for “essential needs.” “Essential needs” referred to buying food, medicine, emergency circumstances, going to work at factories and businesses that do not close or suspend their operations. The nationwide lockdown lasted 2 weeks, with an extension for 12 of the major cities. Jobs were affected, with many workers left without a job or were furloughed as the economy ground to a halt. With prolonged quarantines, restrictions on public life and worries of job security, there might be rising levels of psychiatric issues such as anxiety, stress, and depression amongst the population  Giving online informed consent for the survey, (2) Having the ability to access the questionnaire online, and (3) Having the ability to understand and respond to the questionnaire.The snowball sampling technique was used to recruit the respondents. Firstly, staff, and medical students at Hanoi Medical University and Hanoi Medical University Hospital were invited to enroll in the study through social media. In addition to their participation, the respondents were encouraged to invite their contacts to participate in the survey.A total of 1,382 respondents  throughout all 63 provinces of Vietnam were sampled within 1 week.The survey included questions on (1) social-economics characteristics, (2) respondents' comorbidities, (3) whether they underwent COVID-19 testing and quarantine, (4) Depression, Anxiety and Stress Scale (DASS-21), and (5) Impact of Event Scale—Revised (IES-R).Social demographic characteristics including gender, region, age, marital status, occupation, number of children, and educational level.The DASS-21 is a subjective measure in which respondents rate the frequency and severity of experiencing negative emotions over the last week based on 42 questions. The ratings of the DASS scale is as follows from 1—Did not apply to me at all to 4—applied to me most of the time. There are three subscale domains divided from the scale: depression, anxiety, and stress. The calculated scores can then be used to stratify patients into varying severities of depression, anxiety and stress in which the higher the score, the greater the severity of symptoms.The Impact of Event Scale—Revised (IES-R) was used to assess subjective distress caused by traumatic events. This scale has 22-item self-report with a 5-point scale ranging from 0 “not at all” to 4 “extremely” for each item. The IES-R yields a total score ranging from 0 to 88 and is divided into four domains: “Normal,” “Clinical concern,” “Post-traumatic stress disorder diagnosis,” and “Severe post-traumatic stress disorder.”Respondents were asked about the Impact of COVID 19 on their income and occupation status.Additionally, we collected data on respondents' comorbidities, whether they underwent COVID testing and if they were subjected to a 14-day quarantine.T-test or Mann Whitney test for quantitative variables. A general multivariable regression model was used to identify factors associated with depression, anxiety, stress. To achieve reduced models, stepwise forward selection strategies were utilized with a log-likelihood ratio test at a p-value of 0.2. Statistical significance was defined at a p-value of < 0.05.STATA 15.0 software was used to analyze the data. Descriptive statistics were used to examine characteristic data, including frequency, percent, mean, and standard deviation. Inferential statistics were applied to perform the comparison among two subject groups by the Fisher-exact test or Chi-squared test for qualitative variables and by The Review Committee at the Institute for Preventive Medicine and Public Health, Hanoi Medical University approved the research on March 28, 2020. The purpose of research and informed consent were available on the online web-based survey for participants to examine prior to deciding on participating. Participation was voluntary and anonymity was assured. Respondents could decline to participate or withdraw from the online survey at any time.n = 857). A total of 76.7% were married, and 23.3% were single, divorced, or widowed. Most respondents lived in a household of 3–5 family members (73.2%), and the mean number of children in the family was 1.3 (SD = 0.9). Majority of the respondents were from Northern Vietnam (47.1%) and belonged to the 25–34 age group (40.2%). Forty-seven percent of respondents reported that their income decreased due to COVID 19. In terms of education levels, most of the respondents had the highest attained education level of undergraduate (79.9%). In terms of occupation, the respondents are mainly healthcare workers (69.7%) and workers permanently employed by their companies (64.7%).p < 0.05). A larger family size of more than 5 people was also linked to higher levels of depression, anxiety, and stress (p < 0.1) than those with family size of 1–2 people. Respondents who were fired were more likely to be depressed (p < 0.05). Compared to respondents reporting normal levels on the IES-R scale, those who reported severe PTSD had significantly higher depression, anxiety, and stress levels with p-value were < 0.01. Respondents who had IES-R score in the partial PTSD (p < 0.01) and diagnosis of PTSD range (p < 0.01) also reported significantly higher levels of depression, anxiety and stress levels than those with normal scores. Coming into contact with suspected COVID-19 patients made participants more stressed than those who had no contact. There was also a possible association between people coming into contact with fomites possibly containing the COVID-19 virus and higher anxiety levels (p < 0.05).As this study was conducted within the first week of the partial lockdown in Vietnam, it was able to capture the burden of COVID-19 on the Vietnamese population at the pinnacle of the pandemic.There is generally a low prevalence of reported depression, anxiety, and stress symptoms based on the surveys. The mean DASS-21 depression, anxiety, and stress scores were lower than those previously reported in other countries, such as China, Iran, and Italy –11 Confip < 0.05). One postulation that could explain this phenomenon could be that those with a higher education attainment have invested significantly more resources and as such may possibly have a higher expectation for their future employment. Additionally, higher education often comes with greater financial stress upon students because of steeper tuition fees. This effect of higher education and financial stress was explored in the UK, which showed that students with greater financial stress were associated with worse mental health outcomes (Our reports suggested that respondents who had an education level of postgraduate have significantly higher stress levels than those with an education level of high school and below (outcomes . With COoutcomes .Our results suggest that respondents who were fired due to COVID-19 reported higher levels of stress, anxiety, and depression. When faced with job losses, individuals experience stress related conditions and even physical symptoms . MoreoveOur results also suggest the respondents were more likely to experience stress after contact with a suspected case of COVID-19. Besides the fear of severe complications of COVID-19, it is likely that respondents are worried that they might have to be isolated after contracting the disease. Isolation could lead to loneliness and even lead to suicidal ideations , 18. AnoWhile this study showed a correlation between the IES-R score and the prevalence of depression, anxiety, and stress, the likelihood of moderate to severe mental health burden measured by IES-R was greater than that of DASS-21. The main distinction between IES-R and DASS-21 is that IES-R measures the mental health burden after an event, which is COVID-19 in this case .A larger family size is associated with higher levels of depression, anxiety, and stress . This asThis study has several strengths. One of the strengths is that our study is the first to evaluate the effect of the partial lockdown on the mental health of the Vietnamese population at the peak of the COVID-19 pandemic. As previous studies mainly focus on populations in China, very little is known about the effects of COVID-19 on countries that are further away from the origin and the possible effects it could have on their populations. Another strength of our paper is that it can serve as a guide for the Vietnamese policymakers and healthcare organizations to place further emphasis on the mental well-being of the population as one of the key indicators of the effectiveness of the partial lockdown.This study has several limitations. Due to the COVID-19 outbreak and social distancing measures, the snowball sampling strategy was used to recruit respondents. This method may not be representative of the population. Sampling bias may also be presented as respondents tend to share the survey with their close friends who may share similar traits. Our study established that there are many factors associated with increased levels of stress, anxiety, and depression amongst respondents during the partial lockdown. While we assessed for associations between more common causative factors such as job losses, health and isolation, future studies can explore the reasons behind these associations which can help provide greater clarity and allow for more targeted interventions.Our paper provides information on factors affecting depression, anxiety, and stress during a nationwide lockdown. This study contributes to the existing literature to explore the acute effects of a lockdown on the mental health of the population. While long term psychological effects of the lockdown may yet to manifest, these early signs of anxiety, stress, and depression amongst the population can serve as a marker to predict the long term psychological impact. Furthermore, it raises the awareness on the topic of mental health during the COVID 19 pandemic, which will hopefully be addressed by organizations and governmental policies in the future to guide a greater holistic pandemic response. These results can guide policy making in future pandemics to take into account mental health issues faced by the public. This can improve psychological well-being of the population and create a more resilient country to get through such taxing times.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 Review Committee at the Institute for Preventive Medicine and Public Health, Hanoi Medical University. The patients/participants provided their written informed consent to participate in this study.BT: conceptualization, methodology, supervision, writing—original draft, writing—review and editing. AL and JS: writing—original draft, writing—review and editing. HP: conceptualization, data curation, formal analysis, writing—review and editing. LV: data curation, formal analysis, writing—review and editing. MH: conceptualization, project administration, writing—review and editing. THN: writing—review and editing. HL: conceptualization, supervision, writing—review and editing. CL, CH, and RH: supervision, writing—review and editing. XL: conceptualization, methodology, supervision, writing—review and editing. TTN: data curation, project administration, writing—review and editing. QP, NT, and QN: project administration, writing—review and editing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.