This study examines the association between future work self and employee workplace wellbeing by proposing a moderated mediation model. On the basis of the self-determination theory, self-management is identified as the mediator, and person–organization fit is recognized as the moderator in this study. We collected two waves of data from 239 Chinese employees. The results of the analysis revealed that the future work self is related to greater employee workplace wellbeing, and self-management mediates the links between them. We also found that the person–organization fit strengthens the positive relationship between future work self and self-management, and the indirect effect of future work self on employee workplace wellbeing through self-management. The results of this study extend the antecedents of employee workplace wellbeing and highlight the importance of future work self in current work-related output. Humans tend to desire and pursue a better experience, such as wellbeing , a questionnaire on employee workplace wellbeing was distributed to those who responded with valid answers during the first stage. We matched and combined the two questionnaires collected from each participant to form a complete questionnaire. We approached 380 full-time employees in phase 1. After phase 2, 250 questionnaires were matched. We excluded invalid questionnaires that were not filled in carefully , thus obtaining 239 valid questionnaires. The effective questionnaire recovery rate was 62.89%. The sample included 51.90% males and 48.10% females. The average age and average job tenure were 30.25 and 6.92 years, respectively.To ensure the reliability of the measurement tools, all the measurement tools used in this study are the scales used in the existing literature published in authoritative journals. A 5-point Likert response scale was used, ranging from 1  to 5 .Future work self was assessed by using the four-item scale suggested by Guan et al. , which wWe measured self-management using the three-item scale suggested by Renn et al. , which wWe measured person–organization fit using the three-item scale suggested by Cable and Derue . A samplWe measured employee workplace wellbeing using the six-item scale suggested by Zheng et al. . A samplAccording to the earlier study, we selected age, gender , education, and tenure as control variables because they potentially affect the cognitions and attitudes of the Chinese employees at work  was performed to examine construct validity. SPSS 26.0 was used to perform descriptive statistics. Concerning the analyses of mediation and moderated mediation, we used Models 4 and 7 of the Process macro of SPSS 26.0 to test the mediation effect and the moderated mediation effect, respectively . The fit of the three-factor model combing self-management and person–organization fit into one factor was as follows: χ2 = 120.91, df = 24, CFI = 0.90, TLI = 0.84, RMSEA = 0.13, SRMR = 0.08. The fit of the two-factor model combing self-management, person–organization fit, and future work self into one factor was as follows: χ2 = 265.66, df = 26, CFI = 0.74, TLI = 0.64, RMSEA = 0.20, SRMR = 0.11. The fit of the one-factor model combing self-management, person–organization fit, future work self, and employee workplace wellbeing into one factor was as follows: χ2 = 297.18, df = 27, CFI = 0.71, TLI = 0.61, RMSEA = 0.21, SRMR = 0.12.The convergent validity and discriminant validities were tested using the measures of composite reliability (CR) and average variance extracted (AVE). According to Bagozzi and Yi , the valr = 0.47, p < 0.01) and employee workplace wellbeing . Self-management was positively related to employee workplace wellbeing .p < 0.01). Thus, Hypothesis 1 was supported. In addition, we used the bootstrapping method for assessing mediation ]. When the person–organization fit was lower (at −1 SD of mean), the indirect effect of future work self on employee workplace wellbeing through self-management was significant . The index of moderated mediation was significant . Hence, Hypothesis 3 was supported.For Hypothesis 3, this study tested whether the person–organization fit moderate the relationship between future work self and employee workplace wellbeing through self-management. We calculated the conditional mediating effect of self-management at different levels of person–organization fit. In this study, we used Model 7 of the Process macro of SPSS 26.0. As shown in The prevalence of future work self among employees creates challenges in managing organizations efficiently. We explored the positive effect of future work self on employee workplace wellbeing, the mediating effect of self-management, and the moderating effect of person–organization fit in this relationship. Based on the self-determination theory, using a time-lagged analysis on 239 employees from Chinese enterprises, this study clarifies how, why, and when future work self may lead to employee workplace wellbeing in the workplace.Our findings have several notable theoretical implications. First, we extended the literature of employee workplace wellbeing by identifying future work self as a potential antecedent of employee workplace wellbeing. Prior study has explored many individual motivational resources in predicting employee workplace wellbeing (Nielsen et al., Second, the mediating effect of self-management between future work self and employee workplace wellbeing was further clarified and confirmed. The linkage from future work self to employee workplace wellbeing and the underlying mediating effect of self-management have not been established. The self-determination perspective widens the scope of explanation for the effects of future work self by realizing the gap between the present and the future, focusing on the positive outcomes of employee workplace wellbeing. For employees with a high level of future work self, their long-term work goals are more closely aligned with their immediate work goals, and this may enhance their dedication (Lin et al., Third, by applying a moderated mediation framework, we revealed the moderating role of the person–organization fit, supporting the applicability of a self-determination perspective in explaining the link between future work self and employee workplace wellbeing through self-management. This conclusion is consistent with the finding in the literature that the person–organization fit has a positive interaction effect on satisfaction (Liu et al., Simultaneously, this study offers specific practical contributions. First, our empirical results demonstrated that future work self is associated with employee workplace wellbeing. Therefore, enterprises should promote and train salient future work self among employees, which might foster employee workplace wellbeing. For example, enterprises need to pay attention to the characteristics and professional values of employees. When mentoring employees, enterprise managers can help employees to clarify their future work self by specifying their future work expectations and visions, which in turn may motivate individuals to actively engage in career-discovery behaviors and work and thus increase their employee workplace wellbeing.Second, given the findings of this study, self-management can serve as a mediator in the relationship between future work self and employee workplace wellbeing. We suggest that employees should aim to improve their self-clarity by paying attention to their possible selves in their future careers to enhance self-management. Enterprises should also give careful consideration to creating environments that foster the improvement of self-management. For example, they can implement training or coaching interventions focusing on promoting self-management of individuals.Third, considering the moderating effect of person–organization fit, we suggest that organizational values need to be integrated into the values of employee training. That is, when fostering the values of employees, managers should attach importance to the input of corporate culture, realize appropriate value-matching between people and the organization, and help employees adapt more effectively to the organization.There are some limitations in this study. First, although the data were collected from multiple sources and a time-lagged design was used, the current data may have reverse causality. Employees with higher levels of employee workplace wellbeing may be more likely to have a conception of their future work self. To improve the causal direction of the model in this research, a longitudinal way is needed in future research. Second, the data sources of this study are not diverse. This research collected data only from the Chinese enterprises, and hence, all participants had the same cultural background. Future research might consider replicating the findings of this study in different cultural contexts. Third, this study utilizeed a limited number of variables. Future studies ought to contemplate including more contextual factors to explore their influence on the behavioral outcomes of future work self. In particular, a study that extends the fundamental theory of self-determination argues that contextual conditions that promote autonomous motivation can facilitate people to motivate themselves autonomously and, in turn, work well and feel good (Deci et al., Employee workplace wellbeing is the overall quality of experience of an employee that can improve organizational effectiveness. To maintain competitive advantage of the enterprises, organizations increasingly adopt multiple methods to enhance employee wellbeing, such as an opportunity for skill use, a variety at work, environmental clarity, availability of money, and physical security Guest, . This stThe data that support the findings of this study are available from the corresponding author upon reasonable request.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements.Z-QL and YY conceived the idea of the study. Z-QL and XZ collected the data and wrote the manuscript. All authors discussed the results and revised the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Additionally, there was a significant G group X hypertension interaction (p < 0.003) for inhibitory control, indicating that those with both a G diagnosis and hypertension performed more poorly than the NG group with hypertension. These findings suggest that the separation of G vs. NG CKD produced minimal, but specific group differences were observed. Ongoing examination of the heterogeneity of pediatric CKD on neurocognition, perhaps at a different time point in disease progression or using a different model, appears warranted.Pediatric chronic kidney disease (CKD) appears to be a heterogeneous group of conditions, but this heterogeneity has not been explored with respect to its impact on neurocognitive functioning. This study investigated the neurocognitive functioning of those with glomerular (G) vs. non-glomerular (NG) diagnoses. Data from the North American CKiD Study were employed and the current study included 1,003 children and adolescents with mild to moderate CKD. The G Group included 260 participants (median age = 14.7 years) and the NG Group included 743 individuals (median age = 9.0 years). Neurocognitive measures assessed IQ, inhibitory control, attention regulation, problem solving, working memory, and overall executive functioning. Data from all visits were included in the linear mixed model analyses. After adjusting for sociodemographic and CKD-related covariates, results indicated no differences between the diagnostic groups on measures of IQ, problem solving, working memory, and attention regulation. There was a trend for the G group to receive better parent ratings on their overall executive functions ( It is now known in both adult and pediatric literature that one potential health-related problem pertaining to chronic kidney disease (CKD) is the disruption of neurocognitive functioning. Hooper et al. –3 found Additionally, there has been emergent scientific inquiry into the mechanisms that contribute to neurocognitive difficulties in pediatric CKD that include ischemic stroke , lead exThere is significant diagnostic complexity regarding the various causes for CKD in the pediatric population and a variety of strategies to attack this problem , but a straightforward translational approach is to begin with a clinical sorting of the various CKD diagnoses. One strategy for addressing this heterogeneity from a clinical perspective is to organize the various CKD diagnoses into glomerular vs. non-glomerular diagnoses.Glomerular (G) diagnoses include such conditions as focal segmental glomerulosclerosis, hemolytic uremic syndrome, and systemic immunological disease such as systemic lupus erythematosus. Non-glomerular (NG) CKD diagnoses include conditions such as aplastic/hypoplastic/dysplastic kidneys, reflux nephropathy, obstructive uropathy, and congenital urologic disease. In general, children and adolescents in the NG diagnostic groups tend to be younger in terms of their age of CKD onset than the G diagnostic groups, have CKD for a greater percentage of their life given the younger age of onset, and show slower rate of CKD progression when compared to their G diagnoses counterparts. Additionally, children and adolescents with NG-CKD are more likely to be born prematurely and have a low birth weight than their peers with glomerular diagnoses. They also tend to be smaller in terms of their height and weight . Warady While it may be tempting to predict that children and adolescent with G diagnoses may perform more poorly than children and adolescents with NG diagnoses on the neurocognitive measures, due in large part to their faster rate of disease progression, to date, few, if any, studies have examined the difference between these clinical groups on neurocognitive functioning. Several studies have examined these outcomes in targeted G and NG groups. For example, despite the overall findings provided by Hooper and colleagues  and ChenThe primary aim of this study was to examine the neurocognitive similarities and differences in IQ, attention regulation and related executive functions between children and adolescents with G vs. NG diagnoses. In conjunction with the significant, but subtle neurocognitive findings for the overall sample, and the relatively positive findings on the neurocognitive findings for a G condition [Lupus Nephritis ] and a NThe sample included all of the available visits from participants enrolled in the NIDDK-funded CKiD Study. The CKiD Study comprises 54 clinical sites in the United States and Canada. Children and adolescents with mild to moderate CKD, ages 6 months to 16 years of age, are enrolled across sites to participate in the CKiD protocol examining issues of progression, growth, cardiovascular health, and neurocognition . The samNeurocognitive measures were conceptualized to assess overall intellectual abilities as well as targeted executive functions. Specific measures assessed IQ , inhibitory control [Conners' Continuous Performance Test-II (CPT-II) Errors of Commission], attention regulation (CPT-II Variability), problem solving [Delis-Kaplan Executive Function System (D-KEFS) Tower Task Total Achievement Score], working memory , and parent ratings of overall executive functioning .In addition to subdividing the sample into G and NG diagnostic groups, additional sample description variables and targeted covariates were collected on nearly all participants at study enrollment (~96%). Sociodemographic variables included sex, race/ethnicity (for sample description only), maternal education , and chronological age at study entry. CKD-related variables included the presence of an abnormal birth history—a combined variable comprising low birth weight, prematurity, and small for gestational age, U25eGFR at study entry,  nephrotiNeurocognitive data from all available visits on participants enrolled in the CKiD Study were employed in the data analyses such that the available data on each of the measures ranged from 1,197 on the D-KEFS Total Achievement Test to 2,058 for the parent-rated BRIEF Global Executive Composite. To address the primary and secondary research questions, a series of linear mixed model regressions were conducted for all of the neurocognitive outcomes. Each linear mixed model included the G/NG diagnostic group, the targeted sociodemographic and CKD-related covariates, and interactions terms for G/NG X nephrotic proteinuria and G/NG X hypertension. For models where the interactions were not significant, the interaction terms were removed, and the simple linear mixed models were examined for the presence of differences between the CKD groups on the neurocognitive outcomes.n = 260) when compared to the non-glomerular group (n = 743). When compared to the NG group, the G group was older (p < 0.0001), had significant fewer males (p < 0.0001), more African-Americans (p < 0.0001), and a similar number of participants who identified with Hispanic ethnicity (p = 0.55). The G group also had mothers with less education (p < 0.03). While the two groups were similar on the presence of an abnormal birth history (p = 0.28) and hypertension (p = 0.11), the G group demonstrated higher U25eGFR (p < 0.0001), a greater percentage of individuals with nephrotic proteinuria (p < 0.0001), shorter CKD duration (p < 0.0001), a generally older age of CKD onset (p < 0.0001), higher rates of anemia (p < 0.0001), and a history that included seizures (p < 0.0005) than the NG group.The sample included a total of 1,003 children and adolescents with mild to moderate CKD that were subdivided into those with glomerular diagnoses and non-glomerular diagnoses. As can be seen in As can be seen in n = 2,009, p = 0.85), attention variability , problem solving , or working memory . None of the interactions involving diagnostic grouping and hypertension and diagnostic grouping and nephrotic proteinuria were significant.When adjusted for the targeted covariates, the linear mixed model regressions revealed that the diagnostic groupings of glomerular vs. non-glomerular disease did not seem to affect measures of IQ . Specifically, for the BRIEF Global Executive Composite, a parent rating of overall executive capabilities, the glomerular group performed better than the non-glomerular group, with scores being ~2.35 points higher  and reflecting a small effect size (Cohen's d = 0.23–0.24). The interactions between diagnostic grouping, hypertension, and nephrotic proteinuria were not significant.In contrast, as can be seen in n = 1,640, p < 0.06); however, as can be seen in p < 0.003). This interaction negates the main effect and indicates that those with a glomerular diagnosis and hypertension will score 4.43 points worse on this measure. To determine the effect size, the effect of having a non-glomerular disease and being hypertensive (0.94) is removed from the parameter estimate of 4.43 (4.43–0.94 = 3.49), resulting in a small effect size being present (Cohen's d = 0.34). The interaction between diagnostic grouping and nephrotic proteinuria was not significant.There also was a strong trend for the glomerular group to perform better than the non-glomerular group on the measure of inhibitory control, the CPT-II Errors of Commission  between a subject's age at CKD onset and their observed CKD progression ; thus, not a factor that should influence our current findings. Finally, our findings did show an independent contribution of both sex and maternal education wherein the groups differed. While these variables were automatically adjusted in the model to address the G vs. NG comparisons on the neurocognitive outcomes, the findings do raise some questions about not only how sex and lower education may impact neurocognitive outcomes. In our sample, sex produced mixed findings wherein males performed worse than females on the GEC, but better than females on the CPT-II Errors of Commission. In each instance, the effect sizes were small. In contrast, higher maternal education was related to better performance across groups on both the parent-rated GEC and the CPT-II Errors of Commission, suggesting possible protective factors of higher maternal education with respect to cognitive outcomes in pediatric CKD. Taken together, these factors provide the basis for future studies examining these key variables in the neurocognitive functioning of children and adolescents with CKD.In addition, a number of other interesting possibilities could be contributing to these relationships or lack thereof. First, we wondered how repeated hospitalizations may have impacted the findings. While this is a worthwhile consideration, given the mild to moderate level of severity in our sample there actually were few repeated hospitalizations with nearly all of the sample having their health care in outpatient settings and none of them yet receiving any type of renal replacement therapy . Furthermore, we would note that this is one of the reasons for including percent of life with CKD as a predictor in our model. A second area for ongoing exploration involves the potential relationship between age of onset and eGFR. This interaction was not included in our model due to the small correlation between variables (Rho = 0.19), so there was little need to include this in our modeling; however, it does not negate it possible influence with ongoing disease progression. A third, related possibility pertains to the relationship between age of onset and change in eGFR. This is an intriguing question as it goes to the core of whether cognitive abilities change in relationship to disease severity. For our sample, there was no correlation  with clinical coordinating centers  at Children's Mercy Hospital and the University of Missouri – Kansas City (BW) and Children's Hospital of Philadelphia (SF), central laboratory  at the Department of Pediatrics, University of Rochester Medical Center (George Schwartz), and data coordinating center  at the Johns Hopkins Bloomberg School of Public Health (Alvaro Muñoz). The CKiD is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute . The CKiD website is located at The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Menopause is the natural termination of menstruation which affects the quality and important aspects of women's life. To evaluate the effect of regular resistance training (Ex) with vitamin D (Vit. D) and calcium (Ca) supplements in the postmenopausal period on muscle tissue in rats. In this experimental study, 72 female Wistar rats (8-10-wk old) were randomly divided into control, placebo, Vit. D, Ca, Ex, Ca + Vit. D, Ex + Ca, Ex + Vit. D, and Ex + Ca + Vit. D groups. Control and placebo groups were fed with a standard diet and sesame oil, respectively. Two month after the ovariectomy, Ex, Ca (35 mg/kg), and Vit. D (10000 IU) were administred in all groups except the control. The number of muscle and inflammatory cells, fiber diameter, endomysium thickness, and degenerative collagen fiber area were assessed through hematoxylin-eosin staining.Muscle cell number was increased in the Ex + Vit. D + Ca, Vit. D + Ex, and Vit. D groups compared to the control group; also, inflammatory cell number showed significant increase in the Ex + Vit. D + Ca (12  Regular resistance exercise, Vit. D, and Ca supplements can improve muscle morphological features in the postmenopausal period. Women naturally spend a third of their lives in a stage called menopause (1). The average age of menopause in developed countries is 51 years, and approximately 4% of women experience menopause before the age of 40 (early menopause) (2). Physiologically, menopause is associated with a decrease in estrogen hormone secretion due to lack of follicular function and is characterized by symptoms such as exhaustion, depression, and muscle pain that have negative effects on quality of life (3).Aging is associated with loss of muscle mass and muscle strength and function of the musculoskeletal system that is clinically known as sarcopenia (4). Although sarcopenia is characterized by loss and atrophy of muscle fibers, there is no identified scientific evidence for the cause of sarcopenia (5). Experiments have shown that postmenopausal women lose their muscle tissue rapidly within 10 years . Studies have also shown that exercise (Ex) in old age can improve physiological conditions, increase protein biosynthesis, increase muscle strength and function, glycolytic fiber hypertrophy, and reduce or prevent the prevalence of sarcopenia . Although physical activity has many benefits for postmenopausal women, studies available in this field are limited and have reported conflicting results. Aubertin-Leheudre and others, and Liberman and coworkers in two separate studies evaluated the effect of Ex on muscle size in the elderly (10). Although they did not show the effect of Ex on the muscle size in the postmenopausal period, they confirmed that there were evidences that Ex could improve muscle function.Vitamin D (Vit. D), calcium (Ca), and parathormone metabolism are altered during menopause (11). Menopause is associated with changes in Ca metabolism. In recent years, bone mineral density test, has been able to show the sufficiency of Ca and serum Vit. D levels in human body (12). Gimigliano and colleagues found a positive relationship between Vit. D levels and muscle mass in the elderly. Also, they concluded that people with low Vit. D levels are at a higher risk of musculoskeletal disorders (6). Changes in skeletal muscles mass have significant negative effects on the quality of life. In addition, the burden of diseases increases with age, especially musculoskeletal disorders, so it is necessary to find a suitable method to preserve the strength of muscles in old age. Because women are more susceptible than men to age-related musculoskeletal disorders, it is important to investigate the factors of age-related musculoskeletal disorders in women. Since ex and good nutrition are two identified factors for the health of the musculoskeletal system, reports show that 81.3% of Iran's urban population has Vit. D deficiency and that this is higher in women than men . Also, the prevalence of inactivity in women is higher in developing countries and this is associated with a high prevalence of musculoskeletal disorders (15).Therefore, the present study aimed to investigate the effect of resistance Ex with Vit. D and Ca supplementations on the gastrocnemius muscle in rats in post-menopausal period.In this experimental study, 72 female Wistar rats . Following the two months of housing, animals in the control group were fed with a standard diet until the end of the experiment, while those in the placebo group were only administrated sesame oil for 2 months. In the Ca group, Ca supplement , and in the Vit. D group, intramuscular injection of 10000 IU/wk Vit D supplement were administered for 2 months in the Ca + Vit D group, both 35 mg/kg and 10000 IU Vit. D supplements were administrated for 2 months. In the Ex group, resistant Ex was performed for 2 months, additionally, in the Ex + Ca, Ex + Vit. D, and Ex + Ca + Vit. D groups, resistant Ex, Ca, and Vit. D were performed, respectively, during the two months. Resistance-trained rats were familiarized with climbing a ladder  before starting the resistance training. The initial weight was 30% of their body weight and was attached to their tails. Weights were increased to 100% of their body weight gradually throughout the 8 wk. The resistance training consisted of three sets of five repetitions with a 30-sec rest interval between the reps and 3 min between the sets (17). After the last resistance Ex sessions or the supplement administration, all animals were sacrificed by decapitation 24 wk after the beginning of the experiment (at 28 wk of age).Fresh gastrocnemius muscle was rinsed with PBS buffer, and then tissues fixed in a 10% formalin solution 5-10 times the volume of tissue for 24 hr at room temperature. After the fixation, the tissue samples were embedded in paraffin wax blocks as follows: one change 70% ethanol (30 min), 80% ethanol (2 hr), 95% ethanol (2 hr), three changes 100% ethanol (1.5 hr), two changes xylene (30 min). For embedding tissues into paraffin blocks, the melted hard wax was put into the embedding metal box, and then the tissue was placed quickly in the box. Paraffin blocks were trimmed as necessary and 5-µm slice thickness was commonly used. For rehydration, paraffin sections were placed in xylene for 10 min and in 100%, 95%, 80%, and 75% ethanol solution, each time for 3 min, and then rinsed with distilled water for 5 min. Slides were stained with hematoxylin and eosin (H&E) dyes for about 10 and 2 min, respectively. Eventually, the samples were put into 75%, 80%, 95%, l00% ethanol and xylene solutions for 5 min each (18). The microscopic check showed muscle tissue with the blue nucleus and red cytoplasm and fiber.The morphological features of the muscle tissue such as the number of muscle nucleus, inflammatory and adipocyte area, fiber diameter, endomysium thickness, degenerative collagen fiber, fibrosis, the pattern of muscle fiber and interstitial edema were identified using a bright-light microscope . The study was approved by the Animal Ethic Committee of Yazd Reproduction Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran (IR.SSU.RSI.REC.1398.020).The results of the experiments were expressed as mean and standard deviations of the different variables. The statistical analysis was done initially by SPSS, version 20 and one-way test. P Table I shows the muscle cell number, inflammatory cell number, and adipocyte cell area in the cross-section of gastrocnemius muscle. Clearly, the muscle cell number showed a significant increase in the Ex + Vit. D + Ca, Vit. D + Ex, Ex, and Vit. D groups . Also, decreased estrogen may have a direct effect on muscle tissue (21) so in this study we assessed the effect of regular resistance training in combination of Vit. D and Ca supplements on the muscle tissue in rats in their postmenopausal period.The results of the present study in muscle cell number counting showed a significant increase in the Ex + Vit. D + Ca, Vit D + Ex, Ex, Vit. D, Ca + Ex, and Ca + Vit. D groups in comparison with the control and placebo groups. Maltais and co-workers reported a decline in muscle mass and strength after menopause and showed loss of muscle strength is associated with menopause (22). Muscles in the human body play an important role in physical function and quality of life. The Ex, good nutrition, hormone therapy, and Vit. D intake are essential factors to preserve muscle mass, strength, and quality of life. Fu and colleagues, similar to our result, reported that the muscle cells in women who practiced regular Ex and took Vit. D supplements for 12 wk repaired and the obesity decreased (23). Low physical activity, low protein intake, and high oxidative stress are the most common causes of sarcopenia in postmenopausal women (4). Evidence have shown the presence of estrogen receptors in human muscles (24). Dehaini and others reported that estrogen receptors are present in muscle cells, especially in type II muscle (25). These receptors may help to increase muscle cells after regular resistance Ex in premenopausal women. Perhaps, the increase in muscle cell number in Ex and supplement-intake groups in our study is due to the increase in estrogen receptors in muscle tissue.It has also been suggested that Vit. D and regular Ex may also have positive effects on myogenic factors and subsequent proliferation of muscle cells and muscle growth due to decreased myostatin expression (a negative regulator of muscle growth) . Based on this hypothesis, it seems that one of the most important causes of atrophy and a decrease in the number of muscle cells during the aging process is due to increased myostatin expression. Myostatin is a type of beta-modified growth factor, which is known to negatively regulate the process of myogenesis in skeletal muscle (28). Latres and colleagues in their animal experiments have shown that in myostatin gene expression-knocked animals, the muscle cells and muscle mass increased significantly. On the other hand, hypertrophy and severe hyperplasia formed in the muscle cell and fibers (29). Kim and co-workers showed after a resistance activity session, myostatin mRNA levels were significantly reduced in people aged between 50 and 75 yr (44%) . Many reports suggested that Vit. D plays an important role in all body tissues, including the skeletal muscle, so that there are high levels of Vit. D receptors on the surface of skeletal muscle cells, and the number of these receptors decreased with aging . Maybe, a decrease in myostatin level in our study groups (Ex and Vit. D) is responsible for increased muscle cells.Our results in the inflammatory cell number showed a significant increase in the Ex + Vit. D + Ca . Ortmeyer and colleagues reported six-month Ex and healthy diets can decrease adipocyte cells in muscles (36). In our study, the Ex and Vit. D and Ca supplementations decreased the adipocyte cells in gastrocnemius muscle. Our findings were similar to Ortmeyer's results.Joseph and co-workers reported that 12 wk of Ex cannot change the lipid profile and adipocyte cells in the menopause women (37). This was in contrast to our results. Maybe the difference between our result and Joseph's was the duration of training and supplementation with Vit. D and Ca in our groups.The results of our study showed a fiber diameter increase in the Ex + Vit. D + Ca and Vit. D + Ex groups. This increase was significant in the Ex and Vit. D group compared with the control and placebo groups.Studies have shown that in the young athletes, the muscle fibers' diameter was greater than the control group; however, limited data are available to assess the effect of Ex on the myofibrillar size in the elderly . Skeletal muscle fibers have the ability to change the phenotype in response to environmental stimulation. This capacity is for adaptive change or cellular plasticity and hypertrophy after Ex. There is a general agreement that resistance Ex can cause hypertrophy in all types of muscle fibers. On the other hand, it is suggested that resistance Ex is an effective way to improve age-related atrophy and increase the size and strength of skeletal muscles in the elderly . Consitt and colleagues in their study assessed the effect of resistance Ex on muscle cells. They reported after a period of resistance Ex in post-menopausal women, the level of androgens elevated and this elevation is responsible for an increase in muscle fiber diameters (42). Also, Maltais and others reported that resistance training and adequate protein intake can reduce the risk of sarcopenia and muscle loss. They suggested regular Ex and supplementation are beneficial to prevent menopausal complications. They have also reported that isoflavone supplementation could potentially be effective in increasing the secretion of sex hormones and has a constructive role in muscle mass in postmenopausal women (22). According to the results of the present study and other studies mentioned, Ex and Vit. D may be the two main factors for the production of androgens and thus increasing muscle fibers.Our findings demonstrated that resistance Ex in combination with Vit. D represents preventive and therapeutic effect on the onset of muscle atrophy. Regular resistance Ex, Vit. D, and Ca supplements can improve muscle morphological features in the postmenopausal period. However, additional investigations are required for the evaluation of all effective parameters on muscle health, particularly from the molecular mechanism.The authors declare that there is no conflict of interest.


Introduction: This paper explores frequency of experiences of sexual harassment (SH) among fitness instructors, outlines the typical perpetrator, and explores associated mental health symptoms.Design: Cross-sectional survey.Materials and Methods: A total of 270 Norwegian fitness instructors, recruited in social media, responded to an electronic questionnaire in 2019/2020 on experiences of body appearance pressure, SH, and mental health symptoms. Outcomes included in this publication are experiences of SH, and symptoms of mental health issues based on the Hopkins symptom checklist, SCL-10; Beck Depression Inventory, BDI-1a; and Eating Disorder Examination Questionnaire, EDE-q.Results: The frequencies of SH experiences were 30% among 211 women and 22% among 59 men, respectively, with customers being the most frequent source of such approaches and personal trainers (PTs) more often reporting such experiences compared to group instructors (GIs) and to those operating as both PT and GI. Women having experienced SH had significantly higher scores in symptoms of depression, anxiety, and eating disorders compared to women with no such experience.Conclusion: The high frequency of SH experiences among fitness instructors, with customers emerging as perpetrators and typically in the context of personal training, necessitates increased awareness of SH in the fitness industry. To reduce the occurrence of SH, the fitness centers need to communicate countermeasures with high level of compliance. Sexual harassment (SH) concerns a subjective perception of unwanted sexual attention . It is aA common understanding has been that SH occurs in relationships where the perpetrator has a higher position on the hierarchical ladder . The impSimilar explanations may apply to between-colleague harassment, where SH may be motivated by body objectivization within a milieu  and wherFor decades, the marketing and promotion of fitness centers, and the services within the centers in particular, has been centered on objectivization of the body , 14. SpeNegative consequences of experienced SH at work may vary depending on the type of harassment, who the perpetrator(s) was, the personal traits of the individual who experienced SH, where it happened, and how frequently it happened. It may be personal consequences causing serious mental strain, and financial difficulties or work-related consequences like job loss , 3, 10. Little is known on the prevalence of, and associations to, mental health from experiences of SH among fitness employees. The aim of this paper is to explore the frequency of experiences of SH at the work arena among female and male fitness instructors, and to study any differences between sex, and between personal trainers (PTs) and group instructors (GIs), and to study the origin of the perpetrator of SH in the fitness center arena. Additionally, this paper aims to explore any association between experiences of SH with mental health symptoms including symptoms of eating disorders. Considering the previous findings of high frequency of SH in health service professions, women more typically being offended compared to men, clients compromising a frequent perpetrator in health services, and resting on the four-factor theory , we hypoWe recruited for a cross-sectional study of PTs and group fitness instructors in Norway between November 2019 and March 2020. The study aimed to explore body figure idealization, experiences of body appearance pressure, and SH in fitness instructors of different sex and professions. For the purpose of this paper, only results related to SH are presented. All participants responded to an electronic questionnaire, estimated to take 40 min to complete with opportunities to pause, and having the topics within the questionnaire clearly described in an informed consent. There was no compensation offered for participation.CEOs or the heads of instructors in fitness centers in Norway were asked to distribute recruitment information by email and poster to the fitness instructors, and concurrently we also recruited participants through interest groups for instructors in social media (Facebook).We invited fitness instructors to participate in a survey on motives and attitudes toward physical activity, diet, and body appearance pressure, and experiences of SH. To qualify for participation, respondents had to operate as a PT or GI, or a combination of both (combo) in any fitness center facility at the time of recruitment, and to understand Norwegian written language. The numbers recruited and included are presented in The first part of the survey asked for demographic information of which the following is presented in the current paper: age, education, profession, and BMI. To keep the comprehensive questionnaire short, we chose to use shortened, validated versions of questionnaires on mental health when available.Experiences of SH were explored by asking for any experience of such in current work position by using three categories , all with response rates of “no” or “yes,” with the latter differenced into “from customers,” “from colleagues,” and “from leaders.” In lack of a consensus or common definition of the concept “sexual harassment,” we applied previously suggested definition of SH and the categorization of such . First, The BDI-1a (Cronbach's α in the current study 0.88) measures current (past week) self-reported symptoms of depression . It consThe SCL-10 (Cronbach's α in the current study 0.90) is the short version of the SCL-25 , which validly and reliably measures symptoms of depression (six items) and anxiety (four items) . It consThe EDE-q (Cronbach's α in the current study 0.95) is a self-report questionnaire measuring the symptoms of eating disorders . It consThis study was approved by the Norwegian Regional Committees for medical and health research ethics (No. 28855) and the Norwegian Centre for Research data (No. 868768) and was registered in the Clinical Trial registry (No. NCT04135729). The participants consented to participation by responding to an email containing study information, clearly describing the topics within the questionnaire, followed by signing a letter of informed consent. The consent and questionnaire were made in the web-based system SurveyXact 8.2 offered by Ramböll, Aarhus, Denmark. Considerations were made with regard to the risk–benefit for harms or regrets from participating in a questionnaire-based survey including sensitive information. This questionnaire-based survey was continued inasmuch as the rationale was explicitly prospectively explained to participants by written invitation, participation was anonymous and voluntary, and by having previous positive evaluations on risk–benefit ratios regarding sensitive data contribution in surveys .hypothesis 2) in addition to comparisons between exercise profession  (hypothesis 3). We further compared whether customers, clients, or leaders were more frequently reported as perpetrators (hypothesis 4) and finally explored if there were any differences in symptoms of mental health issues between those who had experienced SH and those with no such experience (separately by sexes) (hypothesis 5). Categorical data were compared by Pearson's chi-squared test, while continuous data were compared by Mann–Whitney U. Considering the explorative approach of this study, a Bonferroni correction was considered too conservative; hence, p ≤ 0.01 were evaluated as statistically significant for all main analyses.All data were analyzed with SPSS version 26 . Data were visually inspected for normality and presented as median  as none were normally distributed, except for demographic data, which are presented as mean (Sd) and range and with a significance level of 0.05. We compared the frequency of experience of SH between women and men  (p < 0.001). Among those experiencing any SH, verbal harassment was most common (reported by 83%).The majority of participants had never experienced any SH at the fitness centers where they were working. Still a total of 63 (30%) women and 13 (22%) men reported some sort of SH, with no between-sex differences either in this overall finding or within each SH category ( > 0.21) . In the p = 0.06). Customers were found to be the most frequent source for any sexual harassing behavior reported by 63 participants  compared to colleagues with 27 reports  and to leaders with 6 reports  (p < 0.001) and from colleagues compared to leaders (p < 0.001), but no statistical difference between SH from clients compared to leaders (p = 0.5).Evaluating the participants by profession, 16 (44%) of PTs, 45 (25%) of GIs, and 15 (28%) of combo had experienced some sort of SH, with no statistical difference between professions ( sample) . There wZ = −2.4, p = 0.018; Z = −3.7, p < 0.001; and Z = −3.3, p = 0.001, respectively). Additionally, significantly more female GIs having experienced verbal SH scored higher in SCL-10 and EDE-q global compared to female GIs with no such experiences . No other statistically significant differences according to sex or profession were found in symptoms of anxiety, depression, or eating disorders.The aim of this study was to explore the frequency of work-related experiences of SH among female and male fitness instructors, to study any differences between sexes and between professions, to study the origin of SH, and to identify any differences in mental health symptoms between those with or without reported experience of SH. Corresponding to our first hypothesis, and with reference to previous findings of SH in health service professionals  , we idenOur findings render support to a previous suggestion that SH more typically occurs in relationships where the perpetrator has a higher position on the hierarchical ladder, hence implicating that workplaces provide a risk arena . Rather Working within the fitness industry, that for decades has profited and marketed on body figure and appearance matter , may briOverall, our result aligns with previous observations, in which women, regardless of age, predominantly working in service and health professions, are most frequently exposed to SH and most typically report clients/customers as the perpetrator , 5, 6. Onot taking part in the objectivization of the body. Importantly, we identified a higher intensity of symptoms for depression, anxiety, and eating disorders among women with experiences of SH compared to women with no such experiences. Previous findings from women with experiences of SH at work identified a two times higher chance of reporting psychological distress 2 years later, compared to those with no such experiences  definition of SH with examples of harassing behaviors presented, including both men and women. Limiting the generalizability is the cross-sectional design, depriving us from the opportunity to suggest causes and effects of the measures. We did unfortunately not explore the knowledge by the employees on intra-organizational policy and measures toward SH. However, from observational and professional experience within the scientific group, and based on knowledge from other comparable findings, such policy and measures are in general under-communicated in the fitness industry, and few leaders in Norwegian organizations are aware of their organizational definition of SH and of established measures . ImportaWe identified an alarmingly high frequency of experiences with SH among female and male fitness instructors. Customers were identified as the most common cause to such experiences, which may complicate the process of addressing the issue. To make the professional individual confident in how to handle and act toward such unwanted experiences, the fitness industry needs to implement a common and publicly well-known policy against SH with jointly measures .The raw data supporting the conclusions of this article will be made available at request by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Norwegian Regional Committees for Medical and Health Research Ethics (No. 28855). The patients/participants provided their written informed consent to participate in this study.TM initiated the research, attained ethical approvals, and administered the recruitment and communication. NS, CS-B, and JS-B contributed during the planning of the study. All authors contributed with writing the manuscript and approving final 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Diabetic polyneuropathy (DPN) was not associated with CTR, and we did not find any factors correlating with CTR in DPN patients. We found that CTS patients with more comorbidities or combined with a longer duration of DM were undertreated in real-word practice. Actual outcomes of CTR in CTS patents with various comorbidities should be investigated in future studies for optimal management of CTS.The objective of this study was to evaluate the effects of diabetes mellitus (DM) on the rate of carpal tunnel release (CTR) using a large nationwide cohort in Korea and to identify risk factors, including comorbidities and socioeconomic status (SES), associated with CTR. Patients with a primary or secondary diagnosis of carpal tunnel syndrome  were selected and divided into two groups according to the presence of DM. A Cox proportional hazard model was used to assess the rate of CTR between the two groups. To evaluate the influence of demographic factors, comorbidities, and SES on CTR, multivariate Cox proportional hazard regression models were used to adjust for confounding variables. In total, 12,419 patients with CTS were included in the study: 2487 in DM cohort and 9932 in non-DM cohort. DM duration was negatively related with the rate of CTR  in CTS patients with DM. The rate of CTR was decreased in patients with DM compared to those without DM in the unadjusted model; however, after adjusting for comorbidities, DM had no significant effect on the rate of CTR. Female sex  correlated with the rate of CTR, and an inverse relationship between the number of comorbidities and CTR was found ( Recently, a meta-analysis of 25 studies suggested that both type 1 and type 2 diabetes are risk factors for CTS3. The prevalence of CTS is estimated to be approximately 3%4 in the general population and 14%5 in individuals with DM, increasing to 30%5 in the presence of diabetic polyneuropathy (DPN).Various factors, such as repetitive wrist movement, hypothyroidism, obesity, diabetes mellitus (DM), and rheumatoid arthritis, have been suggested to be risk factors for Carpal tunnel syndrome (CTS)6. Several attempts, including rehabilitation and glycemic control, have been made to modify the natural history of CTS in diabetic patients, suggesting a potential role for improved glycemic control in the restoration of nerve function8. The effects of CTR in patients with both CTS and DM or DPN have been controversial. DM has been suggested to be associated with poorer outcomes after CTR in both short-term and long-term follow up10. However, several other studies have shown improvements in diabetic patients with CTS after CTR11, and some studies have found that CTR had similar effects in CTS patients irrespective of DM13. A recent meta-analysis showed the efficacy of CTR in relieving neurologic symptoms and restoring sensory deficits in patients with DPN14.Treatment options for CTS include medication, splinting, injections, and carpal tunnel release (CTR)15. Differences in ethnic factors and healthcare management systems across countries might affect the rate of CTR. Comorbidities and socioeconomic status (SES) could also influence the rate of CTR in diabetic patients with CTS in real-world practice. Therefore, our aim in this study was to evaluate the effects of DM on CTR in patients with CTS using a large, nationwide, population-based cohort in Korea and to identify risk factors, including comorbidities and SES, associated with CTR. Additionally we assessed the effects of DPN on CTR and its risk factors for diabetic patients with CTS.Previous studies about CTR in diabetic patients with CTS included a relatively small number of patients, and most previous work was conducted in western countriesp < 0.0001). Patients older than 60 years made up more than 50% of the DM group but only about 25% of the non-DM group (p < 0.0001). More patients in the DM group received medical aid insurance compared with the non-DM group (p < 0.0001). Patients with DM also had higher CCI scores and more comorbidities, including hypertension, hypothyroidism, and rheumatoid arthritis, than the non-DM group. Patients with DM had a lower rate of CTR than the non-DM group (p < 0.0001).In total, 12,419 patients with CTS were included in this study: 2487 in the DM cohort and 9932 in the non-DM cohort . CTR correlated significantly with increasing age in the non-DM group; however, age and CTR did not correlate significantly in the DM group. Regarding residential area, patients living in rural areas showed an increased rate of CTR compared with patients living in the capital  only in the non-DM group. Income level and insurance type showed no significant influence on CTR in either group.Table The incidence rate of CTR in the DM group was 47 per 1000 person-years, whereas that in the non-DM group was 66 per 1000 person-years. Table p = 0.907). Table p < 0.0001)  patients were diagnosed with DPN. 78 (21.1%) DPN patients received CTR and 292 DPN patients (78.9%) did not received CTR (1) Table . We founIn this study, we analyzed 12,419 patients with CTS using information extracted from a nationwide cohort database (DB) of 1 million people. DM duration was negatively related with the rate of CTR in CTS patients combined with DM. On the other hand, there was no significant difference of the rate of CTR between CTS patients with and without DM after adjusting for comorbidities. An increased number of comorbidities significantly decreased the rate of CTR in both the DM and non-DM groups of CTS patients. Overall, female patients received more CTR than male patients. The rate of CTR increased gradually with patient age but only in the non-DM group; age did not influence CTR in the DM group. In the analysis of the DPN group, we found no factors correlated with CTR; not even female sex and comorbidities were related to CTR in the DPN group.16. However, the AAOS CTS guidelines are based on studies that did not take patients’ medical comorbidities into account. Therefore, the AAOS treatment recommendations are considered inconclusive for patients with CTS and comorbidities such as DM. The influence of DM on the outcome of CTR has been controversial11, though some studies have suggested that CTR has similar effects in all CTS patients, irrespective of DM13. A previous meta-analysis found that patients with both CTS and DPN experienced beneficial effects from CTR in the form of relief from neurologic symptoms and restored sensory deficits14. These differences in the effects of CTR in diabetic patients with CTS might be caused by differences in study design, diagnostic criteria, or outcome variables. A diagnosis of CTS is usually based on clinical or electrophysiological findings, and the various labs in which tests were performed might have used different electrodiagnostic standards. Some studies focused on improvement in symptoms such as pain, numbness, or weakness12, whereas others evaluated improvement using electrophysiologic findings15.According to guidelines from the American Academy of Orthopedic Surgeons (AAOS), CTR is recommended as a grade A, level I treatment for CTSIn our results, DM duration showed negative relationship with the rate of CTR in CTS patients with combined DM. However, comparison for CTR between CTS patients with and without DM reveled somewhat different results. Patients with CTS and DM received less CTR in the unadjusted model; however, DM had no significant effect on CTR after adjusting for comorbidities. As the number of comorbidities increased, the rate of CTR decreased in all CTS patients, both with and without DM. In our results, patients with DM had more comorbidities than those without DM. We found that although patients with DM seemed to receive less surgery than those without DM, it was not the DM itself but the underlying comorbidities that truly affected the rate of CTR in CTS patients with DM.6. In a previous study using a neural network to develop a prognostic model for CTR outcomes, hypertension was suggested to be related to poor outcomes17. However, no previous study has evaluated the relationship between the cumulative effects of comorbidities and CTR. Our results indicate that clinicians generally perform fewer CTR operations in patients with more comorbidities and in patients with a longer duration of DM. The actual effects of comorbidities, including DM, on the outcomes after CTR still remains uncertain. However, CTS patients with many comorbidities or combined with a longer duration of DM were undertreated in the real-word practice based on our results.Few reports have considered the effects of comorbidities on the outcomes of CTR. One previous study of the effect of comorbidities on CTR suggested that symptom severity and hand function improved significantly after CTR regardless of comorbidities20. In one retrospective cohort study in USA, among 1,795 patients with CTS, 254 patients (15%) were diagnosed with DM21. The CTS patients combined with DM have been reported as up be to 21% of all CTS patients in a prospective ultrasonographic and electrophysiologic study2, which is consistent with our finding. One possible reason for the relative high prevalence of DM in CTS patients in our study was that we included a DM diagnosis not only baseline but also during follow-up period. As the population ages, patients combined with CTS and various comorbidities including DM might become more prevalent, and the outcomes of CTR in these populations need further investigation for optimal management of CTS.In this study, the number of CTS patients combined with DM is 2487, approximately 20% of total CTS patients. In pervious large cohort studies, the prevalence of DM in patients with CTS ranged from 3 to 5%22. Some putative reasons for the higher rate of CTR in female patients are that females have more intense subjective symptoms and are more prepared than males to undergo surgical treatment22.Overall, female sex was associated with the rate of CTR in both groups. Our findings support earlier studies that reported that female patients received CTR 3.0–5.5 times more than male patients23. In a previous epidemiologic study, the rate of CTR peaked at 50–59 years in women and 60–69 years in men, suggesting a tendency for the elderly to avoid surgery22. However, in our analysis of recent data, the peak surgical rate was observed at or above 70 years. This implies that CTS patients with more severe symptoms get surgery irrespective of age, which is in line with other recent studies25. With regard to residential area, patients in rural areas received more CTR than those in the capital region, which might be related to their occupations, such as agriculture which is strenuous on wrist. However, among patients with both CTS and DM, age and residential area did not influence the rate of CTR, so it seems that overuse and a hand-intensive workload are not related to the rate of CTR in patients with DM. In terms of SES, we found no effects on the rate of CTR.According to the presence of DM, age and residential area showed different results: they were related to CTR in the non-DM group but showed no relationship with CTR in the DM group. Median nerve impairment has been suggested to become more severe with increasing age5 The severity of median nerve impairment and the symptoms of neuropathy might affect the rate of CTR irrespective of sex or comorbidities. Studies are warranted to determine the factors that predict the effects of CTR in DPN patients.In patients with both CTS and DPN, we found no factors associated with CTR; not even female sex and comorbidities affected the rate of CTR in this subpopulation. It was previously suggested that DPN, a length-dependent axonopathy, makes the median nerve more susceptible to CTSThis study has several limitations. First, the diagnoses of DM, DPN, and CTS are based entirely on ICD codes instead of a standardized electrodiagnostic process. This was a retrospective study using NHIS cohort data, so we could not get the electrophysiologic findings. However, the disease diagnoses are valid and relatively reliable because the NHIS program conducts regular cross-checking by reviewing chart records and laboratory results to prevent miscoding or inaccurate medical claims data. Second, some information including the side of CTR, lifestyle factors, medication, or certain laboratory result such as HbA1c were not considered in the analyses, which could affect the results. Instead, we tried to adjust other various factors including SES and comorbidities available in our DB. Third, in this epidemiologic study, we sought factors related to CTR, including DM, DPN, comorbidities, and SES, but we could not elucidate the effects of the various factors on the outcomes after CTR. Future studies are needed that will investigate predictive factors for CTR based on the variables in this study.In conclusion, we evaluated the effects of DM on CTR in patients with CTS using a large, nationwide, population-based cohort in Korea and found that although patients with DM seemed to receive less surgery than those without DM, it was not the DM itself but the underlying comorbidities that truly affected the rate of CTR in CTS patients with DM. On the other hand, in CTS patients with DM, as the DM duration increased the rate of CTR decreased. As for DPN group, we found no factors correlated with CTR; not even female sex and comorbidities were related to CTR in the DPN group. In this study, we found that CTS patients with more comorbidities or combined with a longer duration of DM were undertreated in real- word practice. Based on our results, outcomes of CTR in CTS patents with various comorbidities should be investigated in future studies for optimal management of CTS.28. Also, it has been shown that this database provides reliable estimates of the real prevalence of various diseases in Korea31. This study was approved by the Institutional Review Board of Bundang Jesaeng General Hospital, which waived the need for informed consent. All methods were carried out in accordance with relevant guidelines and regulations.The Korean National Health Insurance Service (NHIS), a single-payer system, is mandatory for all residents of Korea, and nearly all of the data in the health system are centralized in large DB. This nationwide, population-based cohort study was conducted using Korean National Health Insurance Service (NHIS) – National Sample Cohort (NSC) data. NHIS NSC DB is an approximately 2% random sample  of all citizens stratified according to age, sex, income level and regional area in 2006. Data were produced by the NHIS using a systematic sampling method for the purpose of research. Random sampling was used based on 2142 strata . The data include a unique anonymous number for each patient and summarize age, sex, type of insurance, a list of diagnoses according to the International Classification of Diseases (ICD-10), and medical costs claimed. The NHIS DB represents the entire Korean population; therefore, it can be used for nationwide population-based studies of various diseases35. We excluded individuals who were diagnosed with CTS in 2002 and 2003 to ensure that the CTS group included only subjects with new episodes. Among the patients diagnosed with CTS, we selected patients who also had a primary of secondary diagnosis of DM  to divide our cohort into two groups according to the presence of DM. For patients who received CTR, DM at baseline and during the follow-up period to the date of CTR was selected, and for patients who did not receive CTR, DM at baseline and until end of follow-up period was selected. CTS patients who received surgical procedures coded as N0931 (simple reconstruction of tendon and ligament) or N0932 (complex reconstruction of tendon and ligament) were considered to have received CTR.From the DB, we first selected patients with a primary or secondary diagnosis of CTS (ICD-10 code: G560) between 2002 and 2015. To ensure diagnostic validity, we included only individuals who visited clinics and received a diagnosis of CTS more than three timesAge was categorized into 5 groups: ≤ 40 years, 40–49 years, 50–59 years, 60–69 years, and ≥ 70 years. We divided residential areas into capital, metropolitan, and rural areas. Korea contains six metropolitan cities with populations exceeding 1 million people: Busan, Incheon, Daejeon, Daegu, Gwangju, and Ulsan. Patients living in those cities were categorized as living in a ‘metropolitan’ area. Patients living in areas other than Seoul, the capital of Korea, or other metropolitan cities were classified as living in ‘rural’ areas. The NHIS premium was used as a proxy measure of precise income because it is proportional to monthly income, including earnings and capital gains. The income deciles of enrolled subjects were categorized into four categories .37. Its validity has been confirmed by comparing with other morbidity indices, and it is applicable to the longitudinal study design38. Diseases in the CCI are congestive heart failure, myocardial infarction, cerebrovascular disease, peripheral vascular disease, connective tissue disease, chronic lung disease, ulcer, chronic liver disease, severe liver disease, dementia, diabetes, hemiplegia, moderate or severe kidney disease, tumor, leukemia, lymphoma, moderate or metastatic solid tumor, and acquired immunodeficiency syndrome. In this study, due to data missing from the NHIS-NSC DB, we could not include diagnoses related to dementia, tumor, or acquired immunodeficiency syndrome. Because DM was the main independent variable in this study, we also excluded DM from the CCI scoring. For the calculation of CCI score, each disease was scored from 0 to 3 points, and the greater score presents more comorbid condition. Then we categorized CCI scores into four ranges: 0, 1, 2, and 3 or more. In addition to the CCI, we extracted several diseases that could be related to DM or CTS using the ICD-10 codes for hypertension, hypothyroidism, and rheumatoid arthritis.DPN was defined as ICD-10 codes E1041, E1141, E1341, E1441, G628, G629, G632, G633, and G638. Comorbidity was defined using the Charlson Comorbidity Index (CCI). The CCI is the most widely used morbidity index, which has been used to represent various comorbidities in previous epidemiologic studiesP < 0.05 was considered statistically significant.The baseline categorical variables of both groups are expressed as numbers and percentages. The chi-squared test was used to compare the distributions of baseline demographic characteristics and selected comorbidities between patients with and without DM. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify hazards associated with CTR depending on the presence of DM or DPN in terms of hazards ratios (HRs) and 95% confidence intervals (CIs). To evaluate the influence of demographic factors, comorbidities, and SES in both groups (with/without DM), multivariate Cox proportional hazard regression models were used after adjusting for confounding variables. We used SAS software version 9.4  to perform all statistical analyses. SAS System for Windows statistical software, version 9.4  was used to perform all statistical analyses.


The aim of this study was to explore the clinical efficacy of conventional heparin anticoagulation in combination with apixaban in the treatment of patients with cerebral venous thrombosis (CVT) and its influence on serum D-dimer  One hundred and fifty-seven consecutive CVT patients admitted to our hospital from January 1, 2006, to December 31, 2013, were allocated into two groups according to the different treatment methods, of which 95 cases received standard anticoagulation therapy (standard group (SG)) and the remaining 62 cases were given apixaban therapy (research group (RG)). The curative effects and the changes of coagulation function during the treatment, as well as the incidence of adverse reactions, were analyzed in the two groups. The changes of D-D and FIB levels before treatment and at days 1, 4, and 7 posttreatment were detected.  In treatment efficacy, RG was superior to SG. No evident difference was observed in the incidence of adverse events or coagulation function between the two groups. At day 1 posttreatment, D-D level was increased largely in both SG and RG, but the increase was much more significant in RG. However, D-D level was decreased gradually with time in both groups, and the reduction was more notable in RG. The FIB level in SG declined gradually with time after treatment and was higher than that in RG at the same time point. In RG, FIB was decreased gradually at day 1 and day 4 posttreatment, and its level at day 7 posttreatment showed no difference compared with that at day 4 posttreatment. Spearman's analysis identified that the higher the D-D level or the lower the FIB level at day 1 posttreatment was, the better the treatment efficacy was. After seven-day treatment, the lower the level of D-D and FIB was, the better the therapeutic effect was. Logistic analysis indicated that age, time of diagnosis, deep vein thrombosis (DVT), Glasgow Coma Scale (GCS) score, infection, Apixaban, D-D, and FIB all independently affect the treatment effect of patients.  The combined use of Apixaban with heparin is high-performing and safe in the treatment of CVT. The changes of D-D and FIB levels during the treatment are strongly linked to the therapeutic effect, which can be used as plausible evaluation indexes for the efficacy of CVT. Cerebral venous thrombosis (CVT), also known as cerebral venous sinus thrombosis (CVST), has an annual incidence of approximately 1.32-1.57/100,000 people .Although the mortality rate of CVT has been profoundly reduced with the improvement of treatment and diagnostic techniques, the mortality rate of severe CVT is still as high as 34.2% .If CVT can be identified correctly at an early stage, patients could receive appropriate treatment in time, such as anticoagulation, intracranial pressure reduction, or neurosurgery. Thus, most patients diagnosed and treated at an early stage could have a favorable prognosis , 7. AfteApixaban belonged to an oral FXa inhibitor, which exerted an inhibitory effect on both free and clot-bound factor Xa, and also, it got approval in the clinical use of several thromboembolic disorders including reduction of stroke risk in nonvalvular atrial fibrillation, thromboprophylaxis following hip or knee replacement surgery, the treatment of deep vein thrombosis (DVT) or pulmonary embolism, and prevention of recurrent DVT and pulmonary embolism –6. ApixaIn this context, the therapeutic effect of apixaban in 62 CVT patients was analyzed, and the changes of D-dimer (D-D) and fibrinogen (FIB) levels in patients' peripheral blood were detected, so as to evaluate the therapeutic effect of Apixaban in this disease.This study is a prospective cohort analysis, with 157 CVT patients admitted to our hospital between January 1, 2006, and December 31, 2013, and enrolled. The following are the inclusion criteria: all patients were diagnosed as CVT by X-ray and CT angiography and received oral anticoagulation therapy for at least 3 to 6 months. The following are the exclusion criteria: patients excluded were those (1) aged <18 years; (2) with severe liver and kidney dysfunction, mental abnormality, consciousness disorder, or inability to swallow oral drugs; (3) with CVT and central nervous system infection or severe head trauma; (4) with planned CVT surgical procedures; (5) with tumors; or (6) incomplete clinical data. This study conforms to the Declaration of Helsinki and has been ratified by the hospital's Medical Ethics Committee. All patients have signed the informed consent form.Patients were divided into two groups based on different treatment methods. Of them, 95 patients were given standard anticoagulation therapy (standard group (SG)), and the other 62 patients were treated with apixaban therapy (research group (RG)). Standard treatment began with subcutaneous injection of low-molecular-weight enoxaparin (1 mg/kg) twice daily for 5-15 days. Warfarin was not used until the acute phase. In principle, warfarin and heparin were used repeatedly for 3-5 days, and heparin was withdrawn when the International Normalized Ratio (INR) of warfarin reached 2.0-3.0. The INR was detected regularly to adjust the dosage of warfarin, and the treatment duration was ≤24 weeks. After discontinuation of intravenous heparin therapy, apixaban was administered orally twice a day at a dose of 5 mg and measured 5 weeks later.After discharge, the patients were followed up by interview, which lasted for 6 months and was conducted once a month.Clinical efficacy: the efficacy was evaluated referring to the score standards of Clinical neurological impairment in Stroke Patients (1995).Basically cured: the patients' functional impairment score reduced by 91-100%, and the degree of disability was grade 0.Significantly improved: the patient's functional impairment score decreased by 46%-90%, and the degree of disability was 1-3.Improved: the patient's functional impairment score decreased by 18%-45%.No change: the patient's functional impairment score decreased by about 17%.Deteriorated: the patient's functional impairment score decreased or increased by more than 18%.Death: total effective rate = number of cases with /total number of cases∗100%.Statistics on adverse events: severe bleeding is defined as significant bleeding with a hemoglobin drop of more than 2 g/dL and/or requiring blood product infusion of more than 2 U, when the patient should stop the study medication.Coagulation function analysis: the coagulation function, including activated partial thromboplastin time (APTT), partial prothrombin time (PT), and platelet (PLT), was compared between the two series before and after the last treatment.Determination of D-D and FIB levels: fasting venous blood was collected before treatment and 1, 4, and 7 days after treatment for the determination of D-D and FIB via the SysmexCA7000 automatic blood coagulation analyzer , specifically by immunoturbidimetry.The following are the outcome measures:n (%), and the differences between groups were compared by a χ2 test. The measurement data were recorded as the mean ± SD. One-way ANOVA was used for comparison among groups, LSD test for back testing, repeated measures ANOVA for comparison at different time points, and LSD test for post hoc testing. Correlation analysis was done by Spearman's analysis, and the risk factors affecting efficacy were determined by logistic analysis. P < 0.05 was considered statistically significant.SPSS19.0 was used for statistical analysis of the data. The counting data were represented by A total of 157 CVT patients were included in this study, including 95 cases in SG and 62 cases in RG. Basic data analysis revealed no statistical difference between RG and SG in terms of sex ratio, age, CVT diagnosis method, time of admission, time of diagnosis, hospitalization time, symptoms, DVT, GCS score, and infection .The total effective rate of patients in RG was higher than that in SG. RG had higher proportion of patients who were basically cured and lower proportion of patients who showed no change after treatment than SG .Statistical analysis showed no difference in the incidence of single adverse event or total adverse event between the two series .P > 0.05)  .The pretreatment D-D and FIB levels showed no marked differences between the two series. On posttreatment day 1, D-D increased observably in both SG and RG, but the increase was more significant in RG. However, D-D decreased gradually with time in both series, and the reduction was more notable in RG. The FIB level in SG declined gradually with time after treatment and was higher than that in RG at the same time point. In RG, FIB decreased gradually on posttreatment day 1 and day 4, and its level at 7 days after treatment showed no difference compared with that at 4 days after treatment .We analyzed the correlation of D-D and FIB with therapeutic effect one day and seven days after treatment. It was identified that the higher the D-D level or the lower the FIB level one day after treatment, the better the treatment effect. Seven days after treatment, the lower the levels of D-D and FIB, the better the therapeutic effect .In order to analyze the factors influencing the curative effect of patients, we established a logistic model. The results identified that age, time of diagnosis, DVT, GCS score, infection, apixaban, D-D, and FIB can independently influence the curative effect of patients .CVT is a rare cause of stroke, and the prognosis of patients is good. However, due to persistent neuropsychiatric symptoms and cognitive problems, approximately 1/4 of patients still cannot resume normal life and work , 14. Thein vivo and in vitro. This paper analyzed the efficacy of apixaban in CVT patients on the basis of LMWH. The results exhibited that the patients supplemented with apixaban had better therapeutic effect. According to the score standards of clinical neurological impairment in stroke patients (1995), the basic recovery rate of patients treated with apixaban is 41.94%, which is notably higher than that of patients treated with LMWH (9.47%). Meanwhile, apixaban supplementation does not increase additional adverse reactions and has no significant effect on the coagulation function of the patients, suggesting that apixaban enjoys promising efficacy and safety in CVT treatment.As an Xa inhibitor, apixaban has been approved in many countries for several indications –6. The rIt is often applied to prevent thrombosis in cancer patients due to its merits in administration route, convenient use, and cost , 19. ApiThe coagulation and fibrinolysis state were altered in CVT patients, and the changes play an important role in thrombolytic therapy , 25. We in vivo.During CVT treatment, warfarin needs routine monitoring and dose adjustment, heparin requires intravenous administration, and there is a risk of heparin-induced thrombocytopenia. Apixaban has a high binding rate to plasma protein, and its metabolism depends on the liver and kidney, so it cannot be cleared through hemodialysis. Once uncontrollable bleeding occurs, it will be very dangerous. Hence, it is necessary to constantly detect the changes of physiological state of patients during medication. Though a randomized trial is undertaken, one thing is for sure: given the rarity of CVT, it will only succeed through collaboration of a large number of hospitals. Follow-up should be extended to observe the efficacy of them in CVT patients. More researches should be done to explore the underlying mechanism of apixaban/heparin or their combined use To sum up, apixaban combined with heparin is effective and safe in treating CVT, and the changes of D-D and FIB levels during treatment are closely related to the therapeutic effect, all indicating that their combined use can be valid evaluation indexes for the efficacy of CVT.


The present study aimed to validate the Italian version of the Hyperphagia Questionnaire (HQ), a 11-items questionnaire developed to assess hyperphagia in individuals with Prader-Willi syndrome (PWS). This is a complex neurodevelopmental disorder characterized by endocrine dysfunction, hypotonia, intellectual disability, psychiatric disorders and obesity.age = 17.90; 108 Males), recruited in 12 hospitals in Italy responded to HQ during routine visits. In function of the level of analyses the sample was divided into two subgroups (<18> years) or into four age-subgroups  corresponding to different clinical stages.Parents of 219 individuals with PWS  confirmed the three hyperphagic subdimensions of the original structure , but one item was dropped out, reducing the final version to 10 items. Using multi-group CFA, HQ showed satisfactory indexes of measurement invariance by age. Good indexes of internal consistency  were found for each subdimension. The three hyperphagia subdimensions positively converged with other food-related measures: emotional overeating, food enjoyment, food responsiveness, and satiety responsiveness. A significant increase of all hyperphagic subdimensions was found across age groups. Higher hyperphagic levels were found in participants with higher body mass index. Hyperphagic drive differently increased in function of the interaction between age and underlying genetic mechanisms.The Italian version of the HQ is a psychometrically valid and reliable instrument for assessing hyperphagia in individuals with PWS. This tool may prove useful to evaluate the efficacy of pharmacologic and rehabilitative treatments. This loss of activity may be determined by three major genetic mechanisms: (i) microdeletion (DEL) of the paternally inherited chromosome (60–70% of cases); (ii) maternal uniparental disomy (mUPD) subsequent to trisomic rescue (30–40% of cases); (iii) imprinting center defect (IC) or translocation (3–5% of cases) (Prader–Willi syndrome (PWS) is a rare genetic disorder with a birth incidence ranging from 1/10,000 to 1/30,000 . PWS is PWS is a multifaceted neurodevelopmental disorder characterized by endocrine dysfunction, hypotonia, intellectual disability, psychiatric disorders and obesity , 4. PsycA hallmark of PWS is represented by hyperphagia, commonly defined by an excessive hunger and abnormal intake of food. Forms and severity of hyperphagia in individuals with PWS vary across the life-span. According to Miller et al.  seven deTo investigate hyperphagia in individuals with PWS posits challenging issues for many reasons. A first critical question concerns the operationalization of the construct of hyperphagia. As Yanovsky  pointed The most used tool for assessing hyperphagia in PWS is the Hyperphagia Questionnaire (HQ) specifically designed by Dykens et al.  to measuWhether sex and genetic subtypes differentially affected the seriousness and the onset of hyperphagia remain challenging questions . The litAlso the association between obesity and PWS requires further investigation. It is undeniable that obesity is a common characteristic of PWS caused by the combined excessive eating and reduced physical activity even though, in her seminal study, Dykens  found anTherefore, the aims of the current research were:(i) To validate the hyperphagia questionnaire  in indiv(ii) To compare the hyperphagic scores in individuals with PWS by gender, age, obesity and genetic subtypes. We expected differences in hyperphagic scores by age groups with a peak, according to the theory, between 8 and 18 years. We did not advance specific hypotheses regarding differences by sex, weight status and genetic subtypes given to the limited literature at this regard.Parents or primary guardians of persons with confirmed genetic diagnosis of PWS (age range 3–54 years) were consecutively invited to participate to this multicentric and cross-sectional study. They were recruited in 12 hospitals distributed across northern , central (Rome and Modena), and Southern Italy .All participants were invited to take part to the study during routine visits between January and December 2019. The study was approved by the Ethical Committee of the Santobono-Pausilipon Hospital (leader center of the study) and by the Review Board of the Genetic Obesity Study Group of the Italian Society of Pediatric Endocrinology and Diabetology. Written informed consent was obtained from all participants in accordance with the revised version of the Helsinki Declaration regarding research involving human subjects.Fifteen parents refused to participate to the study. Finally, the collected data regarded 219 individuals with PWS . In function of the level of analyses, the sample was considered as a whole, or it was divided into subgroups. Two age subgroups (children <18 years vs. adults >18 years) were used to validate HQ. Four age subgroups  were created to investigate how food behavioral problems in individuals with PWS differ across the four main developmental nutritional periods , 29.2). Absolute values of BMI were employed in adults (>18 years) to define normal-weight (NW: BMI 18–24.9), Overweight (OW: BMI 25–29.9), Obese (OB: 30–34.9), Severe Obese (SOB: >35)  , 32. NW All individuals received genetic diagnosis of PWS even though 8 individuals had a positive methylation test, but the underlying genetic defect was not identified. Sample's characteristics related to age, sex, genetic and weight status are reported in the how persistent in asking for food); Hyperphagic Behaviors , and Hyperphagic Severity .We used the 11-item version of the Hyperphagia Questionnaire . Items rMy child eats more when anxious), food responsiveness , satiety responsiveness , food enjoyment . Items were rated by care providers on a 5-point scale (1 = never to 5 = often).In order to establish convergent validity of the questionnaire we invited care providers to respond to a set of 10 items drawn from Children's Eating Behavior Questionnaire . Despite2/df ≤ 3), the comparative fit index (CFI), the root mean square error of approximation with associated 90% confidence intervals (RMSEA), and the standardized root mean square residual (SRMR) were used to evaluate the adequacy of models to data  using a multiple-group structural equation model. A series of chi-square difference tests comparing fit statistics of hierarchical models were performed in order to investigate: configural invariance, with factor loadings, intercepts, and error variances free to vary across subsamples; metric invariance, with invariant factor loadings across the two subsamples, and intercepts and error variances allowed to vary; scalar invariance, with invariant factor loading and intercepts across subsamples, and error variances free to vary.As a second step, we investigated the invariance of the factor structure across age groups  were performed. First, we compared HQ scores by age-group. Then, a series of two-way ANOVAs with age group as one of the two fixed factors were performed to compare the HQ scores by gender, genetic status, and weight status. Interactions with age group were also investigated. Sidak's multiple comparisons r ≥ 0.80, supporting the absence of content redundancy. However, one item in the Hyperphagic Behavior scale showed two marginally acceptable inter-items correlations . Thus, it was removed from further analyses.Overall, the examination of inter-item correlations highlighted significant high associations among items in the same hypothesized subscale . No inte2 difference between the two hypothesized competitive model fits indicated that the three-factor model provides an adequate fit to the data compared to the one-factor model, p < 0.001. Although the χ2 was significant, p < 0.001, all the goodness-of-fit indices for the three-factor model reached acceptable values, χ2/df = 2.49; CFI = 0.96; SRMR = 0.04; RMSEA = 0.08 . On the contrary, fit statistics for the one-factor model were definitely worse, p < 0.001; χ2/df = 3.91, CFI = 0.91; SRMR = 0.06; RMSEA = 0.12 .The χp < 0.004; χ2/df = 1.81, CFI = 0.98; SRMR = 0.04; RMSEA = 0.06 , as demonstrated by the significant χ2 difference, p < 0.001.Based on the inspection of modification indices, the three-factor model could further improve by freeing the error covariances between item 7 and item 5, and between item 9 and item 11. Allowing the estimation of these parameters significantly improved the three-factor model, The standardized factor loadings and latent correlations for each of the three HQ factors are reported in In order to investigate the hypothesis that the same three-factor structure is invariant across age groups (children vs. adults), we performed a series of multigroup structural equation modeling with hierarchical invariance tests. As can be observed from the comparison of fit statistics for invariance tests shown in HQ factors were positively associated, in both groups <18 ys>, to the hypothesized convergent measures represented by emotional overeating, food enjoyment, food responsiveness, and satiety responsiveness. Pearson's coefficients ranged from 0.37 to 0.73 .F =10.96, p < 0.001; η2 = 0.13], Hyperphagic Behavior , and Hyperphagic Severity . Post-hoc comparison revealed that Group A (2.1–4.5 years) showed lower scores in all three HQ scores than group C (8–18) and group D (>18); group B had lower scores in all three HQ scores than group D; group C had lower scores in Hyperphagic Behavior than group D. Differences by age groups are plotted in There was a significant main effect of age on Hyperphagic Drive , Hyperphagic Behavior , and Hyperphagic Severity . Post-hoc comparison revealed that in Hyperphagic Behavior and in Hyperphagic Drive, NW showed lower scores than OB and SOB group, OV were lower than SO, and OB were lower than SOB; in Hyperphagic Severity, NW and OV were lower than SOB. Non-interaction effect with age groups emerged. Differences by weight status are plotted in There was a significant main effect of weight status on Hyperphagic Drive . Means reported in No differences emerged by genetic status whereas there was an interaction effect with age group for Hyperphagic Drive [A detailed report of ANOVAs results is shown in Hyperphagia is a hallmark of PWS. The HQ by Dykens et al.  is consiOur findings confirmed a three-factor solution corresponding to the three original subdimensions even if we dropped-out one item  because of weak correlation with the other items. The questionnaire evidenced a satisfactory invariance by age (<18>) and a convergent validity with measures concerned proximal food-related behaviors and attitudes.Having a valid and reliable measure for assessing hyperphagia is of crucial importance in individuals with PWS both in the diagnostic process and in the treatment. Despite clinical correlates of PWS seem stably recurrent, hyperphagic symptoms highly varies among individuals and changes in hyperphagia are significant markers of the efficacy of the treatment.Regarding to the second aim of the research, the comparison of the hyperphagic scores by age, gender, weight status and genetic subtypes partially confirmed our hypotheses. As we expected, all the three subdimension of the hyperphagia tend to linearly increase during the developing years. Lower levels characterize the first group of age from 2.5 to 4.5 years when hyperphagia is not fully manifest even though metabolic disorders begin to manifest. An increase of hyperphagia occurs in the second period from 4.5 to 8 years to reach a further increasing in the third period from 8 to 18 years. Nevertheless, we did not find a mitigation of hyperphagia in the adult group, since a further increase of the levels of hyperphagia occurred, especially of the Hyperphagic Behavior. Despite the great audience received in the literature about the assumption that hyperphagia decreases and becomes more treatable in the adult age , other rOur findings evidenced that hyperphagia is more pronounced in individuals with PWS with higher weight status even accounting for the age-group. This result may seem obvious, since weight status is a direct effect of hyperphagia, but it should be noted that within each age-group obesity is variably distributed, suggesting again that individual responses to the syndrome can be highly variable .We did not find a main effect of the genetic status on hyperphagia., in agreement with a previous study . HoweverThis is the first systematic study carried out on hyperphagia in Italian individuals with PWS. The sample is highly representative (by gender and age) since the recruitment involved the main Clinical Units of PWS in the Italian country. The affiliation of the researchers to the same scientific society has guaranteed a high uniformity in terms of procedures. The study also presents a series of limitations, such as the lack of test-retest investigation to consider the stability of the responses across time. In addition, information related to the parenting practices in exerting a control on dysfunctional behavior of their children was missing. Lastly, the use of a cross-sectional research design does not allow to conclude whether differences among individuals in function of the age-groups are due to maturational processes, pharmacological treatments or psycho-educational approaches. A further critical issue of the HQ concerns the presence of different timeframes for caregiver recall of the hyperphagic symptoms across the HQ questions. To overcome this limitation, the 9-item version (HQ-CT)  sets theThe availability of a valid measure to assess hyperphagia represents an additional tool for RCT aimed to evaluate the effectiveness of intervention protocols. Reducing hyperphagia should be a goal in the treatment of individuals with PWS whose physical health is seriously compromised by an excessive weight gain. Moreover, their quality of life could significantly improve limiting the persistent and compulsory search of food . To dateThe original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethical Committee of the Santobono-Pausilipon Hospital (leader center of the study) and by the Review Board of the Genetic Obesity Study Group of the Italian Society of Pediatric Endocrinology and Diabetology. The patients/participants provided their written informed consent to participate in this study.DB, ML, and GV designed the study. ML, AC, DF, GG, SO, LR, MS, LI, LD, AF, MW, MF, and MD conducted the study. DB and CE analyzed the data. DB and ML interpreted the data and drafted the manuscript. GV contributed to literature review, conceptualization of the findings, and provided critical revisions to the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by SIEDP.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.