Lower birth weight (BW) is associated with increased chronic disease risk later in life. Previous studies suggest that this may be mediated principally via physical activity (PA). However, the association between BW and PA in children has not been clarified. The purpose of this study was to examine the association between BW and PA in school-aged children in Japan.Participants were children from a prospective birth cohort study (Project Koshu) who were born from 1996 through 2002 in rural Japan. BWs were obtained from the Maternal and Child Health Handbook. Data on PA during childhood were collected using a self-reported questionnaire when participants were 9–15 years of age in July 2011. Analysis of covariance was used to evaluate exercise duration; Poisson regression analysis was used to evaluate if the recommended PA amount was met.P = 0.010), and were more likely to not meet the recommended PA level .Data from 657 children  were analyzed. Compared with the normal BW group, only girls in the low-BW group had significantly lower PA level (normal BW, 11.4  hours/week; low BW, 5.8  hours/week, Low BW was associated with a lower PA level in school-aged girls but not boys. Earlier consideration of BW may be an important public health strategy to prevent physical inactivity in school-aged girls. To date, a broad range of factors has been investigated, including interpersonal, demographic, biological, psychological, social, cultural, and environmental factors.The aim of this study was to examine the association between BW and PA in school-aged children in Japan.25 The data of the present study were based on a follow-up study carried out during 2011.The study participants comprised children born in the Enzan area of Koshu City, Yamanashi Prefecture, Japan between April 2, 1996 and April 1, 2002. The participants were from Project Koshu, a community-based prospective birth cohort study. Project Koshu is an ongoing study started in 1988, in which all expectant mothers who responded to a survey during the obligatory visit at the city office for pregnancy registration were recruited into the cohort. The children were followed from birth onwards. Further details of the project have been reported elsewhere.This study was approved by the Ethics Review Board of the University of Yamanashi School of Medicine and conducted in accordance with the Guidelines Concerning Epidemiological Research, with cooperation of Health Promotion Division and Board of Education of the Koshu City administration office. Informed consent was obtained from the participants.23 BW was categorized into the following three groups: low , normal , or high .Data regarding the sex of the infants, BW and birth length, and gestational age at delivery were obtained from the data recorded in the Maternal and Child Health Handbook by the obstetrician or midwife in charge of delivery. This handbook is an official publication containing guidelines for obstetric professionals and pregnant women. These data were based on birth registration. Low BW was defined as BW <2,500 g. As a previous study provides evidence that low  and high  BWs are associated with a lower probability of undertaking leisure-time PA,26 To investigate whether there is a difference between BW and PA in children who did and did not meet the guideline for PA for Japanese children,11 participants were classified into two groups according to whether they met the recommended guidelines .Data concerning PA was obtained from children using a self-reporting questionnaire conducted in July 2011. The following question was used to obtain PA levels: “How many hours per week do you usually spend on PA except for physical education class ?” This simple question has been used for other studies in children and has shown acceptable validity.18,27–29 Age and BMI of children were collected via physical measurements taken during medical checkups conducted at elementary and junior high schools, which are measured annually in April for each grade, in accordance with Japanese School Health and Safety Law. BMI (kg/m2) was calculated from height and weight. Participants were classified as overweight  or non-overweight based on age- and sex-specific international cut-off points for BMI.30 The highest parental educational levels were collected from mothers using a self-reported questionnaire at pregnancy registration. The responses were collapsed into two categories by number of education years: ≤12 years (up to high school) and ≥13 years (college or higher). A variable was then created combining the highest education level by each parent as follows: ≤12 years (both parents), ≥13 years (only father), ≥13 years (only mother), and ≥13 years (both parents).Gestational age, age in months, body mass index (BMI) during childhood, and parental educational levels were identified as potential confounders based on previous studies.31 Analysis of covariance was used to compare the mean PA time among BW groups. When prevalence of an outcome is common in the study population (>10%), the odds ratio derived from logistic regression tends to overestimate the strength of an association.32,33 The prevalence of children not meeting the recommended guideline for PA was high. Therefore, Poisson regression analyses with robust variance estimators were conducted to examine the associations between BW and the proportion not meeting recommended PA, and prevalence ratio (PR) was used instead of odds ratio. Then, the analyses were adjusted for gestational age, age in months, age- and sex-specific BMI categories (overweight or non-overweight), and parental education levels.Data were analyzed separately for boys and girls based on the results of a previous study that revealed sex difference in PA levels.P-value <0.05 (two-sided) was considered statistically significant.All statistical analyses were performed using SPSS statistical software version 19.0 . A During the study period, maternal information during pregnancy and BW were collected from 847 children. Of these, the complete follow-up data in 2011 were collected from 657 children (boys: 54.8%). Therefore, the follow-up rate at 9–15 years of age was 77.6%. Table There was no significant difference in birth data between boys and girls, except for gestational age. Height and PA time of boys were significantly higher than those of girls; thus, girls were more likely not to meet the recommended PA Table .No significant differences were found in PA time among BW categories in boys Figure A. There In girls, when compared with the normal-BW group, those in the low-BW group were more likely not to meet the recommended PA Table . This asThis study examined whether BW was associated with PA in children aged 9–15 years in Japan. The results demonstrated that girls with low BW have a significantly lower activity level compared to girls with normal BW, with a medium-to-large effect size. In addition, when the hours per week were converted to minutes per day (min/day), the mean time spent in physical activity was 97.7 min/day for the normal-BW group and 49.9 min/day for the low-BW group. These results indicate that the normal-BW group met the recommended PA level, but the low-BW group did not. Meanwhile, this significant difference was not observed in boys.24,34 Gopinath et al18 showed that children aged 12 years with low BW participate in less outdoor PA. Although the exact mechanisms for the difference in time spent in PA between low- and normal-BW individuals are unknown, previous studies have shown that low BW could be related to reduced physical capacity, including reduced muscle strength35 and insufficient anaerobic capacity.36 These negative physiological factors could reduce the willingness to participate in competitive PA because of early fatigue and a reduced ability to perform PA.18,23 However, our study found this association only in girls. It is unclear why this sex difference was observed; we speculate that it may be explained by the difference in time spent in sports activities and PA between boys and girls. In Japan, available opportunities for girls to participate in sports or PA are limited compared to boys. Parents spend less money on sports activities and PA for girls than boys, whereas they spend three times more on artistic activities for girls.37 Therefore, girls with low BW who are thought to have poor exercise capacity may have been participating in non-exercise activities, such as music and the arts . In addition, animal studies have indicated that intrauterine growth restriction leads to low BW and causes decreased PA, especially in female mouse offspring.38 Although it is unclear why this occurred, the mechanism of sex-specific alterations in epigenetic regulation in the hypothalamus and other regions of the central nervous system has received attention39; it has been suggested that androgen-mediated masculinization of the male mouse brain  protects the central nervous system against the deleterious effects of fetal growth restriction.40 It is uncertain whether similar processes occur in humans; thus, extensive future studies are required to elucidate the molecular mechanism by which fetal growth restriction may lead to a lack of PA participation.Several studies have investigated the association between BW and PA in children and adolescents.24,34 It is possible that objective measures of PA and self-reported PA are capturing different aspects of PA. A previous study suggested that self-reported PA may capture only specific types of exercise and leisure-time PA, whereas accelerometers measure all body movement throughout a measurement period.41 Although sex was adjusted for in all of these studies, PA levels between boys and girls is markedly different.31,42 Additionally, PA frequency and intensity among school-aged children across domains  is markedly different.43,44 Thus, future studies require stratification by sex and PA domain.Meanwhile, other studies that objectively measured PA with an accelerometer did not confirm the association between BW and PA in children and adolescents.23 However, our study did not observe an association between high BW and PA time. This may be because of the difference in range of BW. Although BW of the previous study exceeded 4,500 g or 5,000 g, in our study, the highest was 4,300 g. In addition, the biological mechanism explaining the relationship between high BW and physical inactivity could be related to insufficient aerobic capacity or reduced motivation to engage in PA.44 Therefore, children of high BW would be more likely to be obese in adulthood through increased physical inactivity. Moreover, the associations between BW and chronic disease that are based on obesity tend to be more apparent later in life.21,22 Similarly, the association between high BW and PA may also tend to be more pronounced in adulthood.In a meta-analysis including Scandinavian adolescents and adults, both low and high BW were inversely associated with self-reported leisure PA.45 Further studies using a combined assessment of subjective and objective methods are needed to evaluate PA more accurately. Finally, although we adjusted for several important confounders, we could not exclude unmeasured confounding variables, such as genetic factors and dietary information.The strengths of this study include its prospective cohort design and relatively high follow-up rate. In addition, the birth parameters ensured validity because they were obtained from the Maternal and Child Health Handbook. However, our study had the following limitations. First, children with low BW were relatively small in number because only one rural area in Japan was used for the study, resulting in a small sample. Future studies with different populations and more participants are required. Second, PA levels were self-reported. However, the simple question has reasonable agreement with the accelerometer, and a single-item measure was found to be equally valid and reliable as an in-depth questionnaire.In conclusion, this study found that Japanese school-aged girls, but not boys, with low BW were less likely to spend time in PA at aged 9–15 years old. Although further prospective studies are needed, our study suggests that low BW may be an early predictor of physical inactivity in childhood. Therefore, parents of low-BW children should encourage them to be active and to participate in noncompetitive PAs. Additionally, to prevent physical inactivity in childhood, especially for girls, an important public health strategy should be implemented that is aimed at encouraging participation in PA for low-BW children. These may lead to prevention of chronic disease in adulthood.


Background: The objective of this study was to compare the postoperative neck pain and discomfort, swallowing difficulty, and voice change after conventional open thyroidectomy (COT), endoscopic thyroidectomy (ET), or robotic thyroidectomy (RT) performed by a single surgeon.Methods: From January 2013 to December 2017, 254 patients underwent COT, ET, or RT performed by a single surgeon and completed a postoperative symptom survey conducted in the outpatient clinic by three nurses. The survey collected information on postoperative neck pain and discomfort, swallowing difficulty, and voice change.Results: Of the 254 patients, 169 underwent COT, 32 underwent ET, and 53 underwent RT. The mean age in the COT, ET, and RT groups was 50.1, 44.5, and 41.6 years, respectively. The mean interval between thyroidectomy and survey in the COT, ET, and RT groups was 42.7, 50.2, and 9.2 months, respectively. Postoperative neck pain was significantly higher in the ET and RT groups than in the COT group (p = 0.026). The average neck impairment index score in the RT group was significantly higher than that in the COT group (p < 0.001). There were no significant differences in pain scale scores, swallowing difficulty, swallowing impairment index, voice change, and voice hand index among the three groups.Conclusions: There were no significant differences in postoperative voice change or swallowing difficulty among the COT, ET, and RT groups, whereas neck pain and discomfort were more common after ET and RT than COT. Until recently, the gold standard of surgical treatment for thyroid diseases with low morbidity and negligible mortality was conventional open thyroidectomy (COT) through a Kocher collar incision , 2. The The excellent aesthetic outcomes and the surgical usefulness of ET and RT in comparison to COT have been previously reported –9. RecenFrom January 2013 to December 2017, 725 patients  underwent COT, ET, or RT for thyroid diseases at Busan Pak Hospital performed by a single surgeon (TKH). This surgeon has 8 years' experience in COT (50–80 cases/year), 6 years' experience in ET (20–30 cases/year), and 2 years' experience in RT (40–50 cases/year). Of the 725 patients, 153 were not followed-up postoperatively and 418 did not take this survey. Ultimately, 254 patients  were included in this study. The institutional review board approved this study, and the need for informed consent was waived.In the case of benign neoplasms where potential malignancy could not be excluded, unilateral lobectomy was performed. ET or RT was performed in patients with a malignant neoplasm smaller than 2 cm in size and limited to the thyroid gland regardless of patient age. None of these patients showed either lateral lymph node metastasis or extrathyroidal extension on preoperative imaging studies, distant metastasis, or a history of neck surgery or radiation treatment.The patient was placed in a supine position with the neck extended. A 5 to 6 cm circular incision was performed along the natural crease two finger breadths above the sternal notch, up to both lateral surfaces of the sternocleidomastoid muscle. A subplatysmal flap was created until the deep cervical fascia was exposed. After dividing the strap muscle in the center and inducing its lateral traction, the thyroid was exposed and thyroidectomy was performed.After a 4 to 6 cm vertical incision was made in the axilla, a subplatysmal skin flap was created from the axilla to the anterior neck through the upper pectoralis major muscle using electrocautery under gross observation. The strap muscle was lifted by approaching the space between the clavicular head and the sternal head of the sternocleidomastoid muscle and the thyroid was subsequently exposed. After creating a sufficient space up to the upper and lower poles of the thyroid gland and the opposite lobe was revealed, Jung's retractor was inserted and the flap was lifted. Through the axillary incision, the operative field was lit by a 30-degree endoscopic camera pointed toward the head. Thyroidectomy was performed using an endoscopic dissector and a grasper that could hold and retract the thyroid gland, as well as a Harmonic Scalpel  capable of simultaneous coagulation and cutting.RT  using a gasless transaxillary approach was performed in identical fashion to ET, except for the robot docking procedure, until an operative space was created and an external retractor inserted. Moreover, its key maneuvers were the same as those of COT, except for docking by creating a flap. The patient under general anesthesia was placed in a supine position with the neck extended. The patient's upper arm on the affected side was then lifted and fixed. After the retractor was inserted and the operative field was formed, robot docking was performed. Four robot arms were used. A dual-channel 30-degree endoscope  was placed in the central camera arm using a 12-mm trocar. Harmonic cured shears  were placed on the right side of the scope using an 8-mm trocar, and a Maryland dissector & ProGrasp forceps  were placed at the top and bottom on the left side of the scope. Using these tools, thyroid gland traction and dissection were performed. Thyroidectomy was performed in a manner similar to COT.From July 2017 to December 2017, the survey for postoperative symptoms was conducted by three nurses in the outpatient clinic. In each patient, all postoperative symptoms were investigated on the basis of comparison with their preoperative condition. All the patients answered questionnaires regarding the pain score of the surgical area, voice handicap index (VHI), swallowing impairment score (SIS), and neck impairment index (NII) –13. The 2 test or, for small cell values, Fisher's exact test. All statistical analyses were performed with statistical software  and p < 0.05 was considered statistically significant.The data were tested for normal distribution using a Kolmogorov-Smirnov test. Normally distributed variables were compared using the one-way analysis of variance and expressed as the mean ± standard deviation. Tukey's honestly significant difference test was used for the post hoc multiple comparisons. Group comparisons of categorical variables were performed using the χp < 0.0001). The mean age in the COT group was significantly higher than in the ET or RT groups. However, there was no statistical difference in patient age between the ET and RT groups. Female predominance was observed in the COT group, while all patients in both the ET and RT groups were female . As for the type of thyroid surgery, only 41.4% (70/169) of patients in the COT group underwent hemithyroidectomy, whereas the majority in the ET and RT groups underwent hemithyroidectomy. Of those who received surgery for thyroid disease, thyroid cancer comprised the overwhelmingly largest proportion with 243 cases (95.7%), followed by 8 cases of nodular hyperplasia, 3 cases of follicular adenomas, and 1 case of Hurthle cell adenoma. The average interval between the surgery and survey was 36.6 ± 29.1 months . The interval between thyroid surgery and survey in the RT group was shorter than that in the COT and ET groups (p < 0.0001).Of the 254 patients , 169 underwent COT, 32 underwent ET, and 53 underwent RT. Patient demographics and characteristics are summarized in Table p = 0.026), whereas no significant difference was found in pain scale scores among the three groups (p = 0.2). Neck discomfort exhibited a correspondence with NII in the COT, ET, and RT groups. The RT group exhibited the highest frequency of neck discomfort and the highest mean NII, whereas the COT group had the lowest frequency of neck discomfort and lowest mean NII. In all patients with voice change, no direct recurrent laryngeal nerve injury was confirmed through laryngoscopy and complete recovery of the voice was observed.In all patients, the survey for postoperative symptoms was performed in a single session after thyroidectomy. The postoperative symptoms after COT, ET, and RT are compared in Table As surgeons have accumulated knowledge of endoscopic head and neck anatomy, various methods of thyroidectomy have been developed for thyroid tumors , 4–9. ETSwallowing difficulty is one of the important complications after thyroidectomy. The cause is still unclear, but it is usually transient and occurs early after the surgical procedure . The cauThe main cause of voice change after thyroidectomy is injury to the recurrent laryngeal nerve . HoweverOur study has several limitations. First, the sizes of the three thyroidectomy approach groups were not equal. In particular, the sample size in the ET group was small. Second, there was a lack of systematic evaluation of postoperative symptoms due to the variable frequency and interval of patient follow-up in the outpatient clinic. In particular, 40 patients (15.7%) had an interval of 6 months or less between their thyroid surgery and survey. Furthermore, the number of survey sessions for postoperative symptoms was only one. In addition, three different nurses conducted the survey. Finally, a large number of total thyroidectomies were included in the COT group, whereas only few were included in the ET and RT groups. Namely, we did not compare postoperative symptoms among the three groups according to hemithyroidectomy or total thyroidectomy and with or without nodal dissection. For clarity, further comparative studies with closely matched patients and procedures are needed.In conclusion, this is the first study to compare postoperative symptoms after COT, ET, and RT, which were performed by a single surgeon. Our study demonstrated that there were no significant differences in postoperative voice change or swallowing difficulty among the COT, ET, and RT groups, whereas neck pain and discomfort were more common in the ET and RT groups than in the COT group.This study follows the principles expressed in the Declaration of Helsinki. All study participants waived informed consents owing to the retrospective analysis, and the study design was approved by the appropriate ethics review boards.DWK: concept and design, review of final manuscript; All authors: acquisition of data, literature review, and refinement of manuscript; HB and DWK: analysis and interpretation of data; TH: manuscript writing.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The CONUT score and PNI had the highest correlation between the SLE disease activity index-2000  and was significantly associated with SLE activity-related measures. In the Cox-proportional hazard analysis, PNI  was independently associated with ESRF along with creatinine and chronicity index, and the renal survival rate was significantly lower in patients with PNI ≤35.41 than in those with PNI >35.41 (p = 0.003). Among nutritional indices, the CONUT score and PNI better correlated with disease activity and PNI was associated with ESRF.Systemic lupus erythematosus (SLE) is characterized with aberrant responses in the immune systems and lupus nephritis (LN) is one of the most serious complications of SLE. This study evaluated the clinical significance of different nutritional indices in 207 renal biopsy-proven LN patients. The clinical and laboratory data were reviewed, and five different nutritional indices were calculated: (i) Controlling nutritional status (CONUT) score; (ii) prognostic nutritional index (PNI); (iii) nutritional risk index; (iv) neutrophil-to-lymphocyte ratio; and (v) body mass index. The factors associated with end-stage renal failure (ESRF) were assessed using a Cox-proportional hazard analysis. The patients with ESRF had significantly lower median PNI (31.1 vs. 34.7,  Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, with a characteristic feature of aberrant responses in the innate and adaptive immune system . These aIn general, malnutrition is considered to be a condition associated with increased morbidity and mortality . MeanwhiTraditionally, anthropometric measures, such as the height or body mass index (BMI) or laboratory tests, i.e., albumin, prealbumin, and total cholesterol level in the blood, have been used to assess the individual’s nutritional status ,11. NoneThe medical records of 260 patients who had undergone renal biopsy between August 2005 and August 2018 and were diagnosed with LN were reviewed. From the 260 patients included, this study excluded 53 for the following reasons: (i) Patients who did not fulfil the 1997 revised American College of Rheumatology (ACR) classification criteria for SLE ,16; (ii)The authors obtained the clinical and laboratory data of the date when the pathologic diagnosis of LN was made. The demographic data collected included age and sex. For SLE activity-related measures, the following were evaluated: The SLE disease activity index-2000 (SLEDAI-2K); white blood cell (WBC) and platelet counts; the levels of complement (C)3, C4, and anti-dsDNA; and the urinary protein/creatinine ratio (P/Cr), which is a laboratory component of SLEDAI-2K . The cli3) ;  ; (iii) N3) ; (iv) NL3) [3) ; (v) BMIfication .p < 0.05 was considered to be significant.All statistical analyses were performed using MedCalc statistical software version 18.11 . The continuous variables were presented as median and interquartile ranges, and categorical variables were presented as frequencies and percentages. For the comparison of continuous and categorical variables, the Mann-Whitney U test and Kruskal-Wallis test, and the chi-square or Fisher’s exact test were used as appropriate. The correlation between nutritional indices and variables were assessed using the Pearson’s correlation analysis. Low and high PNI was defined using receiver operating characteristics (ROC) curve and patients with PNI ≤35.41 were classified as having low PNI, while patients with PNI >35.41 were classified as having high PNI. Kaplan-Meier analysis was used to compare the renal survival rate of patients with low and high PNI. Univariable and multivariable Cox-proportional hazard analysis was used to evaluate factors associated with ESRF. In all statistical analysis, a two-tailed p = 0.012). No significant differences were noted regarding the medications that were administered in both groups during the follow up . Although SLEDAI-2K and C3 were correlated with NRI, the association was weak. Moreover, significant correlations between the WBC count and the NLR were found, and urinary P/Cr ratio was associated with BMI among SLE activity-related measures . In addition, the PNI was significantly correlated with NRI and NLR  and the NRI with BMI   .p = 0.002), and the optimal cut-off of PNI in predicting ESRF was determined to be PNI ≤35.41 , chronicity index , and PNI  were independent factors for ESRF (p = 0.003)  1.623, 95% CI 1.322–1.993, for ESRF . The Kap= 0.003) .To the best of the authors knowledge, the present study is the first to evaluate the clinical significance of 5 different nutritional indices in patients with LN. Among the included indices, the CONUT score and PNI were better correlated with SLE disease activity-related measures to assess disease activity in LN. However, only the PNI was significantly lower in patients with ESRF at LN diagnosis. On the Cox-proportional hazard analysis, the PNI was an independent predictor of ESRF along with creatinine and chronicity index. Our observations imply that among the nutritional indices, the CONUT score and PNI could be useful to assess disease activity. However, only PNI was seen to have prognostic implications in identifying patients with LN at a high risk of developing ESRF.The findings of our study indicate that the CONUT score and PNI could be useful markers to assess both global and localized disease activity in patients with LN. Notably, the correlation analysis between nutritional indices and SLE activity-related measures revealed that the CONUT score and PNI were better correlated with the SLEDAI-2K, which is the most widely used index to assess global SLE disease activity, along with WBC and platelet counts, C3, C4, and anti-dsDNA levels, urinary P/Cr ratio (which is a laboratory component of the SLEDAI-2K), and the activity index as determined through renal biopsy. Moreover, in patients with pure class IV LN, which is the most devastating form of LN, the CONUT score and PNI were found to be significantly different compared to those of other subclasses.The CONUT score and PNI were first developed to estimate undernutrition and the risk of postoperative complications in patients with gastrointestinal cancers, respectively. However, accumulating evidences have identified that they are also associated with the prognosis of patients with other malignancies and disorders related to malnourishment ,26,27,28Owing to the poor prognosis of LN, numerous attempts have been made to evaluate the prognostic factors associated with LN. Regarding histopathological factors, the presence of proliferative LN and higher activity and chronicity indices at diagnosis have been proposed to be associated with a poor prognosis . ContrerAmong nutritional indices included, our study indicated that only PNI was capable of assessing renal outcome in patients with LN. Surprisingly, because the CONUT score had the highest correlation with SLEDAI-2K and laboratory variables included in SLEDAI-2K at baseline, the association between PNI and ESRF, instead of the CONUT score, was rather unexpected. However, the discordant results between disease activity and the development of ESRF could be attributed to the fact that baseline disease activity is not a predictive factor for patient prognosis in SLE . In contIn the treatment of proliferative LN, current guidelines recommend treating patients with induction therapy using either cyclophosphamide or mycophenolate mofetil, followed by sustained maintenance therapy with mycophenolate mofetil or azathioprine . When thBMI is the most widely used measure to assess obesity in the general population. A previous study has indicated that the prevalence of obesity in patients with SLE was reported to range from 28–50% . SimilarThe strength of this study is that, to the best of the authors’ knowledge, this is the first study that evaluated the clinical significance of different nutritional indices in patients with LN. However, several limitations were also present in our study. First, the assessment of clinical and laboratory data was performed by reviewing patients’ medical records. Second, the number of patients with ESRF included was relatively small. Third, serial changes in the nutritional indices were not assessable and the adjustment for treatment was not possible owing to the retrospective study design. Fourth, it remains uncertain if albumin replacement therapy could be beneficial in improving the prognosis in patients with LN. Additional studies are required to validate our findings and reveal the association between nutritional status and patient prognosis in LN.In conclusion, the authors have demonstrated that among the nutritional indices examined in this study, the CONUT score and PNI were better correlated with disease activity and the PNI was associated with ESRF in patients with LN. Both the CONUT score and PNI could be useful measures to assess disease activity; in particular, PNI may provide useful information in stratifying patients at high risk of ESRF in LN.


Background and Objectives: Irisin plays an important role in the metabolism and homeostasis of energy balance, which is involved in cognitive impairment. This study aimed to investigate the role of irisin in mild cognitive impairment (MCI) among Chinese patients with type 2 diabetes mellitus (T2DM).Methods: We recruited 133 Chinese patients with T2DM, and divided them according to the Montreal Cognitive Assessment score. Demographic data were collected and the level of irisin in the plasma was determined. In addition, the results of neuropsychological testing were examined. The concentration of irisin in the plasma was measured using an enzyme immunoassay.Results: A total of 59 patients were diagnosed with MCI and 74 patients were included as healthy-cognition controls. The level of irisin in the plasma (p = 0.043) and homeostasis model of assessment for insulin resistance (p = 0.032) in diabetic patients with MCI were higher than those observed in the healthy controls. A higher level of irisin in the plasma was associated with impaired overall cognition, specifically executive function. Linear regression analysis suggested that irisin (p = 0.017) and glycosylated hemoglobin (p = 0.036) were independent factors of diabetic MCI.Conclusions: The level of irisin in the plasma correlated with cognitive impairment in T2DM patients, particularly with executive function. These results further suggest that, in addition to poor glycemic control, a high level of irisin in the plasma portends early cognitive deficits clinically in Chinese patients with T2DM. Individuals with type 2 diabetes mellitus (T2DM) exhibit a higher prevalence of mild cognitive impairment (MCI) in comparison with the general population . The risIrisin, a novel glycosylated polypeptide hormone, plays an important role in the homeostasis and metabolism of energy balance . It had Therefore, the aim of this study was to investigate the association between the level of irisin in the plasma and cognition performance in patients with T2DM.We recruited 133 patients (aged 45–75 years) who were admitted to the Department of Endocrinology of the Affiliated Zhongda Hospital of Southeast University  between February 2015 and June 2017. The patients were diagnosed with T2DM for ≥3 years according to the 1999 World Health Organization criteria . The exc2).We collected the demographic and clinical characteristics of the patients, including gender, age, educational level, contact details, duration of T2DM, medical history , fasting blood glucose, fasting C-peptide (FCP), glycosylated hemoglobin (HbA1c), triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein. We obtained physical measurements  using a standard balance beam scale. The body mass index (BMI) is defined as the body weight (kg) divided by the square of the body height  kit  according to the instructions provided by the manufacturer. The accuracy of this kit is comparable to that of EK-067-29 produced by Phoenix Pharmaceuticals, USA .Neuropsychological testing, including the Montreal Cognitive Assessment (MoCA), Mini Mental State Exam (MMSE), digit span test (DST), verbal fluency test (VFT), clock drawing test, logical memory test (LMT), auditory verbal learning test, and trail making tests A and B (TMT-A and TMT-B) were performed to assess the cognitive functions . Based on the MoCA scoring system, 59 patients with MoCA scores <26 and the remaining 74 patients with MoCA scores ≥26 were classified in the MCI group and normal cognition group (control group), respectively. One point was added to the MoCA score for patients with a number of education years <12 .t-test were used to compare differences between groups at baseline. The chi-squared (χ2) test was employed for categorical variables. Spearman's correlation was used to examine the correlation between neuropsychological test scores and the level of irisin in the plasma. The relationship of cognitive performance with the level of irisin in the plasma, as well as demographic and clinical characteristics, was investigated using multiple linear regression analysis. A p < 0.05 denoted statistical significance.Statistical analyses were performed using the SPSS Version 21.0 software . For continuous variables, analysis of variance and Student's p > 0.05). The MCI group demonstrated a significantly higher level of irisin in the plasma and homeostasis model of assessment for insulin resistance (HOMA-IR) than the control group (p < 0.05). Moreover, significant differences between the two groups were also observed in the neuropsychological test scores (p < 0.01). The memory, attention, executive function, psychomotor speed, and visuospatial skills in the MCI group were significantly lower compared with those reported in the control group.We subsequently explored the correlation of the level of irisin in the plasma with clinical and the different neuropsychological test scores in all patients using Spearman rank correlation analysis. The level of plasma irisin was positively correlated with the BMI, FCP, HOMA-IR, and TMT-A and TMT-B scores. Of note, it was negatively correlated with the MoCA, MMSE, VFT, LMT, and DST score in total . The levp < 0.05)  . These tThe results of the present study demonstrated that the level of irisin in the plasma of T2DM patients with MCI increased. This level was negatively associated with the MoCA, MMSE, VFT, LMT, and DST scores, whereas it was positively correlated with the TMT-A and TMT-B scores. These findings indicated worse overall cognitive, executive, and attention functions. The multivariable regression analysis indicated that a high level of plasma irisin and HbA1c may play important roles in the development of MCI in T2DM patients.This was the first study to investigate the correlation between the level of irisin in the plasma and cognitive function in T2DM patients. Correlations were found between irisin and the MoCA, MMSE, VFT, LMT, DST, TMT-A, and TMT-B scores. Higher levels of irisin indicated poorer cognitive function in the patients. Additionally, we found that the BMI, FCP, and HOMA-IR were positively correlated with irisin, suggesting that the increased level of irisin in T2DM patients may be correlated with higher BMI, FCP, and HOMA-IR values. Previous studies suggested that the level of plasma irisin was increased in obese subjects –35. FurtBased on these findings, the relationship between irisin and cognitive function is contrary to that reported by Lourenco et al. , which sIn addition, in this study, the MoCA score was negatively correlated with HbA1c and positively correlated with the educational level. These findings were congruous with those reported by previous studies. Chronic exposure to hyperglycemia may damage cognitive function , 48. HigSeveral limitations of this study should be considered. Firstly, it was a cross-sectional study with a small sample size, which may limit the robustness of the results. Secondly, there were concerns regarding the accuracy of the irisin antibody kits . FurtherIn summary, this study showed that the MCI group had a higher level of irisin vs. the control group. Additionally, a higher level of irisin was associated with overall cognitive impairment, especially poorer executive function. Furthermore, irisin, HbA1c, and the educational level were identified as independent variables of MCI in all individuals, suggesting that low levels of irisin and HbA1c may be good predictors of MCI in T2DM patients. Further evidence, especially from longitudinal studies, is required to investigate the value of irisin as a predictive biomarker of MCI in T2DM patients.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by the Research Ethics Committee of the Affiliated Zhongda Hospital of Southeast University. The patients/participants provided their written informed consent to participate in this study.SW, HL, and YY contributed to the conception and design of the study. HL conducted the study and statistical analysis, and wrote the manuscript. ST participated in the data analysis and interpretation. JH, RH, DG, JW, and KA performed the data collection. All authors read and approved the submitted version of this 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.


This study investigated psychological mechanisms underlying the relationship between stressful life events and school adjustment in Chinese adolescents. The Adolescent Self-rating Life Events Checklist, the Adolescent Executive Function Scale, the Chinese version of the Resilience Scale, and the School-adjustment Scale were administered to 1101 Chinese adolescents , aged 11–19 years, from three secondary schools. Results from serial mediation analysis revealed that perceived stressful life events could affect school adjustment through the mediation of executive function and resilience. The mediation effect contained three paths, the separate mediation effect of executive function, the separate mediation effect of resilience, and the serial mediation effect of executive function and resilience. These findings provide valuable insights into the effect of perceived stressful life events on school adjustment of Chinese adolescents, and suggest that, the researchers and educators could enhance school adjustment in vulnerable groups by improving their executive function and resilience. We will encounter various stressful events in our daily life. Indeed, stressors begin to affect individuals from birth , and occExecutive function refers to a family of top-down mental processes that are essential for tasks requiring concentration and attention, performed in such instances when relying on instinct or intuition would be ill advised or insufficient. Core executive functions include inhibition control, working memory, and cognitive flexibility . Prior sResilience can be broadly defined as the potential or manifested capacity of a dynamic system to adjust successfully to disturbances that threaten the function, survival, or development of the system . As MastIn addition, a large scale of studies showed that, resilience was positively relate to people’s mental health  and qualAlthough perceived stress has a detrimental effect on resilience, In sum, the purpose of this study is to examine the influence of stressful life events on the school adjustment of adolescents and the potential mediators  behind this association. Adolescence is a fragile developmental stage characterized by exposure to stressful life events and the adolescents’ school adjustment is an important problem that the whole society need pay special attention to , exploriH1:Executive function would mediate the impact of stressful life events on school adjustment.H2:Resilience would mediate the impact of stressful life events on school adjustment.H3:Executive function and resilience would serially mediate the impact of stressful life events and school adjustment. This mediation model contains three paths.M = 14.77). All of adolescents and their parents had provided written informed consent before data collection, and then all of adolescents filled out all the paper questionnaires in pen. This study was carried out in accordance with the recommendations of the Human Ethics Committee of the Southwest University. All the adolescents gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Human Ethics Committee of the Southwest University.Participants were 1175 adolescents randomly recruited from three secondary schools in the southwest of China. Because the invalid questionnaires of some participants, a total of 74 adolescents were excluded from analyses. Thus, data from 1101 adolescents were used after data screening procedures . This measure incorporates 26 items, including five dimensions: being punished, loss, relationship pressure, learning pressure, and adaptation problems . Higher scores on this metric typically indicate worse executive function performance. However, in the current study, all items were reverse-scored so that high scores indicated better executive function performance. The Cronbach’s alpha in the current study was 0.852, the composite reliability was 0.793, the average variance extracted was 0.561, and the MacDonald’s omega was 0.850, 95% CI = 0.832 to 0.864.The Adolescent Executive Function Scale  was origdisagree to 7 = agree). In this study, the Cronbach’s alpha reliability coefficient was 0.880, the composite reliability was 0.908, the average variance extracted was 0.831, and the MacDonald’s omega was 0.855, 95% CI = 0.841 to 0.869.Resilience was originally assessed with the Chinese version of the Resilience Scale RS; , which hstrongly disagree to 6 strongly agree) was used to indicate the agreement level of each statement with regard to school adjustment. The higher the score, the higher the school adjustment level of the respondents. In the current study, the Cronbach’s alpha value is 0.852, the composite reliability was 0.837, the average variance extracted was 0.631, and the MacDonald’s omega was 0.855, 95% CI = 0.838–0.869.School adjustment was originally assessed with the School-adjustment Scale  and contOur analytic approach involved two steps. Prior to the examination of the hypothesized mediational model regarding the mediating effects of execution function and resilience on the relation between perceived stressful life events and school adjustment, descriptive statistics and correlations were conducted with for all variables in the total sample by SPSS 21.0. Then, a two-step procedure was applied to analyze the mediation effect . FirstlyWe used the following indices to evaluate the model’s data fit: the confirmatory fit index (CFI), the Tucker-Lewis index (TLI), the root mean square error of approximation (RMSEA), and the self-reunion multiple regression (SRMR). According to previous study, values >0.90 for the CFI and TLI, and <0.6 and <0.8 for the RMSEA and SRMR, respectively, were considered to indicate good model fit .p < 0.01), their correlation coefficients were less than 0.30, which cannot be considered as a significative correlation.2= 420.324, df = 59, χ2/df = 7.124, CFI = 0.925, TLI = 0.901, SRMR = 0.051, and RMSEA = 0.075.Confirmatory factor analysis (CFA) was conducted to test the measurement model comprising the four interrelated latent variables: stressful life events, executive function, resilience, and school adjustment. The latent stressful life events variables were described as a being punished factor, loss factor, relationship pressure factor, learning pressure factor, and adaptation problem factor. The latent executive function variables were described by inhibitory control, working memory, and cognitive flexibility. The resilience latent variable was described by personal competence, and acceptance of self and life. The school adjustment variable was described by teacher-student relationships, peer relationships, and self-adjustment. The measurement model fit the observed data well: χ2= 420.324, df = 59, χ2/df = 7.124, CFI = 0.925, TLI = 0.901, SRMR = 0.051, and RMSEA = 0.075. Specifically, the results provided support for H1 , H2 , and H3  ] see . We subs91)] see . ExecutiThe purpose of present study was to explore the role of executive function and resilience in the relationship between perceived stressful life events and school adjustment among adolescents. Consistent with our hypotheses, perceived stressful life events affected school adjustment through the mediation of executive function and resilience. The mediation effect contained three paths: the separate mediation effect of executive function, the separate mediation effect of resilience, and the serial mediation effect of executive function and resilience. The serial mediation model indicated that, the experience of multiple stressful life events impeded the development of executive function, adversely affected the formation of resilience, and led to poor school adjustment among adolescents, which is consistent with results reported in prior studies .The findings from the current study revealed the mediating effect of executive function on the association between perceived stressful life events and school adjustment among adolescents. The result is consistent with previous studies regarding the negative link between stressful life events and executive function , the posThe findings from the current study also indicate the mediating effect of resilience on the association between perceived stressful life events and school adjustment among adolescents. Some previous studies found that, the more stressful life events could lead to poorer resilience . ContrarMore interestingly, the current study suggests that, the perceived stressful life events may affect school adjustment of adolescents via the serial mediation effect of executive function and resilience, which emphasizes the serial effect of executive function and resilience on the association between stressful life events and school adjustment. The finding that executive function predicts resilience is consistent with previous research , and furThe current study is not without limitations, which also implies suggestions for future research. First, since the study was cross-sectional, it precluded deriving any causal relationship between the variables. To address this issue and facilitate a better understanding of causal mechanisms, future research should conduct longitudinal, experimental or intervention studies. Second, the present study is one of the few studies to utilize a self-reported executive function scale among adolescents. In order to achieve a better understanding of the role of executive function in the relationship between perceived stressful life events and school adjustment among adolescents, future research should compare the differences between experimental and self-report methods in adolescent population. Third, in the present study, participants completed the questionnaires with pen and paper, questionnaire survey was conducted in a physical way may have some limitations, that is, lack of control of the time dedicated to each response and some data encoding errors, etc.,. Some online questionnaire survey App  could overcome these limitations. In order to obtain more scientific and rigorous research data, online questionnaire survey App should be used more often in the future. Forth, the present study was conducted in the background of Chinese population, the findings cannot provide differences between Chinese population and the population of the West in the psychological mechanisms underlying the relationship between stressful life events and school adjustment. Therefore, cross-cultural studies should be conducted to compare the differences between eastern and western population in the future.In conclusion, to the best of our knowledge, the current study represents a new attempt to explore executive function and resilience as the underlying mechanisms in the relationship between perceived stressful life events and school adjustment among adolescents. Furthermore, as the significant indirect effects of perceived stressful life events on school adjustment separately via executive function or resilience, and a serial mediation effect of executive function and resilience were found, the current study also sheds light on how adolescents who perceived more stressful life events achieve worse school adjustment. The findings from the current study are significantly meaningful for conducting effective measures to break the cyclical relationship between stressful life events and school adjustment, thus having some practical implications.YZ and CG collected the data together. YZ, XZ, and CG analyzed the results and wrote the manuscript. LZ participated in the revision of 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.


Case 1: 14-year-old patient, admitted to the pediatric ICU for altered state of consciousness. This child, an outpatient since 2009 for chronic arthralgia, was hospitalized five days previously in the pediatric ward for suspicion of severe SLE, before presenting abdominal pain and vomiting. Hyperlipasemia was found, and an abdominal CT scan confirmed the diagnosis of acute pancreatitis. The patient was put under immunosuppressive therapy composed of high-dosage of corticosteroid and cyclophosphamide cures. She died 20 days after her hospitalization by severe lupus flare with multiorgan failure. Case 2: 14-year-old child, admitted to the Pediatric ward for prolonged fever associated with polyarthralgia  that had been progressing since 6 months with altered general state; his symptoms got worst 15 days before his hospitalization by having behavioral disorders and epigastralgia with vomiting. Pancreatitis was strongly suspected in the absence of improvement on symptomatic treatment and confirmed by hyperlipasemia 6 times the normal value and a swollen pancreas on the abdominal CT scan. The child was treated with Solumedrol and cyclophosphamide without improvement and then died after one month of hospitalization by a septic shock.Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease of unknown cause, characterized by multisystemic involvement. Its occurrence in children is rare, and acute pancreatitis is exceptional in this matter. Its diagnosis is clinical, biological, and radiological. Its treatment is based on corticosteroid therapy, and its progress is generally lethal. We report two cases of acute pancreatitis in the course of SLE, highlighting its life-threatening severity despite well-conducted treatment.  Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease, characterized by the existence of an array of autoantibodies, as well as the creation of immune complexes. It can be as early as childhood in 15 to 20% of cases, or even from the age of three years. Although gastrointestinal symptoms are frequent, acute pancreatitis remains exceptional, since less than 100 cases have been reported in the literature [A 14-year-old girl was hospitalized in pediatric ICU for abdominal pain, respiratory distress, and progressive alteration of her consciousness. This patient with no medical history or family history of autoimmune disease has been suffering from chronic arthralgia for five years. She was first admitted to the pediatric ward before being transferred five days later to pediatric ICU for clinical exacerbation.Upon admission, she opened her eyes spontaneously, executed orders but had illogical speech. She was normotensive, tachycardiac at 105 bpm, and tachypneic at 35 cpm, and her peripheral oxygen saturation was 92% at room air. Cardiothoracic auscultation had revealed muted heart sounds and bilateral pleural effusion syndrome. The abdominal examination had found epigastric tenderness and ascites of moderate quantity. In addition, generalized edematous syndromes associated with cutaneous signs were noted .3, and thrombocytopenia at 62000/mm3, as well as an impairment of renal function, with urea at 1, 06 g/l and creatinine at 61 mg/l. Her natremia was collapsed (106 mmol/l), and her calcemia and albumin too.The biological assessment showed a normochromic normocytic anemia at 9.9 g/dl, leukocytosis at 16900 elements/mmThe diagnosis of pancreatitis was based on the measurement of lipasemia at 810 IU/L, with an edematous pancreas on abdominal ultrasonography and intrapancreatic necrosis on abdominal CT  . RadioloIn front of the multisystemic symptoms and following the criteria of the American College of Rheumatology (ACR), an immunological assessment was carried out and the diagnosis of SLE was retained with the existence of nonerosive arthritis, pleurisy and pericarditis, neurological involvement (seizures) renal involvement, hematologic abnormalities as well as immunological disorders confirmed by the decreased complement factors C3 and C4, and the positivity of anti-RNP antibodies, anti-Sm antibodies, anti-SSA as well as anti-SSB; however, antiphospholipid antibodies were negative.The plan of management started by the correction of metabolic disorders and renal function, and the initiation of an immunosuppressive therapy was based on steroids and cyclophosphamides as a bolus. She died 20 days after her hospitalization by a severe lupus flare with multiorgan failure.A 14-year-old girl, with no particular history, admitted to the Pediatric ward for prolonged fever associated with polyarthralgia  that had been progressing since 6 months with altered general state. His symptoms got worst 15 days before his hospitalization by having headache, behavioral disorders like agitation, and severe epigastralgia with vomiting.μl and lymphopenia at 1200/μl, SV at 50 mm at the first hour, and CRP at 69 mg/l, and proteinuria 24 to 16 mg/kg/24 h and normal renal function.On admission: clinical examination found a confused patient, feverish at 38.5°C, normotensive, tachycardic at 125 bpm, and tachypneic at 36 cpm. Also noted the existence of skin rash on the face, mouth ulcers bleeding on contact, pain in both passive and active mobility in large joints, no inflammatory signs, and general abdominal tenderness. The rest of the somatic examination including the neurological examination was ordinary. Biologically, normochromic normocytic anemia was observed at 7.2 g/dl without signs of haemolysis, thrombocytopenia at 86 000/The diagnosis of pancreatitis was strongly suspected and confirmed by hyperlipasemia at 610 IU/L and a swollen form of the pancreas on abdominal CT scan. Cerebral MRI was also mandatory in front of persistent headache and found signal abnormality of subtentorial white matter of the left frontoparietal and right occipital that could be part of neurolupus.The diagnosis of SLE was retained in front of the multisystemic symptoms and meeting the criteria of the American College of Rheumatology (ACR). The antinuclear antibodies, anti-Sm, and native anti-DNAs were positive associated with C3 hypocomplementemia.The child was treated with bolus of Solumedrol and cyclophosphamide beside his symptomatic treatment without improvement and then died after one month of hospitalization by a septic shock.These two cases illuminate a rare manifestation of SLE which is acute pancreatitis (AP). The aim of our work is on one hand to show that SLE can be extremely rarely exposed by acute AP, on the other hand, is how this clinical presentation revealed in the child.AP is an extremely rare and potentially lethal manifestation of SLE. The incidence of AP associated with SLE varies from 0.7 to 4% –5. The lThe pathogenic mechanism of AP in SLE is complex and multifactorial; it includes vasculitis, interstitial edema, and immune complex deposition associated with arterial or arteriolar occlusions. Other physiopathological hypotheses have been put forward, mainly the production of autoantibodies, an abnormal immune response of pancreatic cells, and drug toxicity , 6.The diagnosis of pancreatitis on SLE can only be made after elimination of other causes of acute pancreatitis. Viral causes of HIV are included in immunocompromised patients , 4.Both of our patients had multiple-organ involvement in their lupus, such as hematologic, renal, neurological, gastrointestinal, and dermatological, but the most distinctive feature of their clinical pictures was the pancreatitis.The direct diagnosis of pancreatitis is usually based on clinical signs of abdominal pain, nausea, and vomiting, supported by lab results of abnormal pancreatic enzymes and tomographic signs in favor. These symptoms can also be described for other gastrointestinal disease or side effects of multiple therapies, which can lead to misguidance. It has been reported that these clinical signs were wrongly accredited to etiologies other than AP in 88.6% , 7. ThisClinically, AP symptoms can range from simple benign form with self-limitation of the disease to severe form with fulminant progression. In the SLE, in addition to the obvious cases of AP, there were also cases of subclinical pancreatitis with elevation of pancreatic enzymes without clinical symptoms. The incidence of subclinical pancreatitis may be significantly higher than that of clinical pancreatitis. One study found hyperamylasemia in 30.5% of SLE in asymptomatic patients. The diagnosis is made by CT in 70% to 90% of cases [Both patients had abdominal pain, nausea, vomiting, and remarkably high levels of pancreatic enzymes, and abdominal CT findings concurred with the diagnosis of AP.Gormezano et al. reported high mortality in children with SLE and AP. Indeed, in their large cohort, among 13 patients with SLE and AP, with an average age of 13.5 years, 4 (31%) died, whereas none of the adult patients with SLE and AP had had a lethal problem . Yang etArticular and neurological involvement is significantly more frequent in patients with AP during SLE, and this could be explained by lupus disease with relatively severe flare . The absAP is a rare manifestation of SLE; however, it remains linked to high mortality. This mortality is even more important in case of multiple-organ involvement. The activities of lupus disease and hematological and renal damage worsen the already critical prognosis of lupus-related acute pancreatitis. The early diagnosis of SLE-related AP, suspected in front of any abdominal pain, and appropriate treatment with glucocorticoids are necessary for proper management and prognosis improvement in these patients.


Pain is frequent in Parkinson's disease (PD) and Parkinson-plus syndrome. This study aimed to assess the prevalence, characteristics, therapy , and associated symptoms of pain in Parkinson's disease and multiple system atrophy (MSA) patients.  Seventy-one PD patients, sixty-five MSA patients, and forty age-matched healthy controls were enrolled and evaluated by using the German pain questionnaire and visual analogue scale (VAS). In addition, the influence of pain in PD patients on anxiety, depression, and the quality of life was assessed with the Hospital Anxiety and Depression Scale (HADS) and Parkinson's Disease Questionnaire (PDQ-39). P < 0.01, P < 0.01). PD patients had a higher presence of pain than MSA patients (P=0.007). No difference in VAS scores was observed between the PD and MSA patients (P=0.148). A total of 21 PD patients (42.85%) with pain and 13 MSA patients (43.33%) with pain received treatment. A total of 13 PD patients with pain and 6 MSA patients with pain had an improved pain intensity after using dopaminergic medication. The differences in the disease duration, Hoehn and Yahr stages, and scores on the Unified Parkinson's Disease Rating Scale motor score, HAD-D, HAD-A, and PDQ-39 were significant between the PD patients with and without pain.  Compared to that of the healthy controls, the PD and MSA patients had a significantly higher presence of pain ( PD and MSA patients are prone to pain with insufficient treatment. Pain interventions should be provided as soon as possible to improve the patient's life. Parkinson's disease (PD) is a common neurodegenerative disorder with a prevalence of approximately 1.7% in the population over 65 years of age in China. Pain is an important and common nonmotor symptom in PD, which has been frequently studied . StudiesA previous study showed that both PD and MSA patients were more likely to complain about pain than other Parkinson-plus disease patients. However, the differences in clinical characteristics and treatment of pain between PD and MSA patients have not been studied.Quantitative measurement of pain is difficult because pain is a subjective symptom. In addition, the disparity of pain questionnaires contributes to the differences in the prevalence rate of pain in PD patients. Survey-based prevalence studies of PD have used short and simple questionnaires, such as the Brief Pain Inventory . TherefoTherefore, this study aimed to assess the prevalence, basic characteristics, and therapy  of pain in PD and MSA patients with the DSF and visual analogue scale (VAS). We also aimed to study the influence of pain on anxiety, depression, and quality of life with the Hospital Anxiety and Depression Scale (HADS) and Parkinson's Disease Questionnaire (PDQ-39) in PD patients with pain.A total of 71 PD patients, 65 MSA patients, and 40 age-matched healthy controls (HC) were enrolled from the Anhui Provincial Hospital between January 2016 and September 2018. The PD diagnosis was based on the United Kingdom Brain Bank criteria [The pain intensity was evaluated using the VAS. The VAS is designed to present to the respondents a rating scale with minimum constraints. Respondents mark the location on the 10-centimetre line corresponding to the amount of pain they have experienced.The DSF is designed based on the principle of “Medical-Psychology-Society.” Compared with other more popular pain questionnaires, the DSF can be used to record the pain history more entirely and in a more orderly manner . In thisBasic clinical characteristics were recorded, including age, gender, and disease duration. For the PD patients, disease severity was assessed according to Hoehn and Yahr (H&Y), and the motor disability and motor type were assessed using the Unified Parkinson's Disease Rating Scale motor score (UPDRS-III). We used the HADS to record depression and anxiety and the PDQ-39 to assess the quality of life in the PD patients. We divided the MSA patients into MSA-P and MSA-C groups.t-test, and categorical data were compared using the chi-square test.For descriptive analysis, quantitative parameters were expressed as mean ± standard deviation and qualitative parameters as frequency and percentage. Means were compared using t-test.At first, pain presence and gender among the groups of PD patients, MSA patients, and healthy controls were analyzed using the chi-square test. Age and disease duration among the three groups were assessed by the independent-samples t-test. Gender differences between the two groups were compared by the chi-square test. We divided PD patients with pain into three types: tremor-dominant group, akinetic-rigid group, and equivalent group and divided MSA patients with pain into two types (MSA-P and MSA-C). The differences of pain presence of PD types and MSA types were analyzed with the chi-square test, respectively. And we analyzed the pain localization proportions and treatment in PD and MSA patients with pain by the means of bar chart.Secondly, clinical and demographic characteristics between PD and MSA patients with pain were further compared. The statistical differences of VAS scores, age, and disease duration between the two groups were estimated using the independent-samples t-test.At last, according to accompanied with or without pain, we divided PD patients into two groups and compared clinical and demographic characteristics. Age, disease duration, HY stage, the UPDRS-III, and scores of HAD-D, HAD-A, and PDQ-39 between the PD patients with and without pain were compared using independent-samples P value < 0.05 was considered significant.SPSS version 22.0 was used to analyze the data. A two-tailed P < 0.01, P < 0.01). And PD patients had a higher presence of pain than MSA patients (P=0.007). According to clinical features, we divided 49 PD patients with pain into three types  and 30 MSA patients with pain into two types (21 MSA-P and 9 MSA-C). No difference was observed in the presence of pain among the PD types. And no difference was observed in the presence of pain between the MSA-P and MSA-C groups . The demographic data and pain presence of the PD patients, MSA patients, and HC are presented in P=0.148). Compared to that of the MSA patients with pain, the PD patients with pain had longer disease durations (P=0.008). The means of VAS scores of PD and MSA patients with pain were 5.08 ± 1.98 and 4.47 ± 1.60, respectively. There was no difference of VAS scores between the two groups (The most common pain location in the PD patients was back pain (38.8%), followed by neck or shoulder, multiple sites, legs, and arms pain. The top two most common pain locations in the MSA patients were back pain (36.7%) and neck or shoulder pain (23.3%). P=0.018). And there were differences of HY stages and UPDRS-III scores between the two types . In addition, differences of scores on the HAD-A, HAD-D, and PDQ-39 were significantly different between the PD patients with and without pain   .Our study found that pain was prevalent in PD and MSA patients. However, only approximately half of the PD or MSA patients with pain received treatment, suggesting that the current treatment of pain associated with Parkinson's syndrome was not valued and that no effective and specific treatment was available. PD patients with pain are more likely to be anxious and depressed and have a reduced quality of life than PD patients without pain.We found that 69.1% of the PD patients suffered from pain. At present, the pathological mechanism of pain is still unclear. The basal ganglia integrate incoming nociceptive information and contribute to coordinated motor responses in pain avoidance and nocifensive behaviors. Nigral and extranigral pathology involving the cortical areas, brainstem nuclei, and spinal cord may contribute to abnormal central nociceptive processing in PD patients with or without pain . A meta-We found that 30 MSA patients (46.15%) suffered from pain. There was a trend towards a higher prevalence in MSA-P compared to MSA-C patients although the difference was not significant, which might be due to the small sample size. Few studies have investigated the pain mechanism in MSA patients. Several brain regions are neurodegenerative in MSA, such as the thalamus and the locus coeruleus, resulting in striatal neurodegeneration and changes in dopaminergic system function. Thus, pain in MSA results from striatal neurodegeneration. MSA patients presented alteration of pain perception with both lower subjective and objective pain thresholds than those of healthy controls . In addiP=0.007). The result was inconsistent to that of a recent study with 65 PD patients and 21 MSA patients [β-CIT SPECT images, with greater atrophy of the middle cerebellar peduncle, the cerebellum or the pons (including the locus coeruleus), and hypometabolism in the brainstem [In our study, there was difference in the pain presence between the PD and MSA patients with pain. PD patients had a higher presence of pain than MSA patients  with pain and 13 MSA patients (43.33%) with pain received treatment. A total of 13 PD patients with pain were diagnosed with PD relevant pain, whereas the others improved their pain using massage or pain killers. The low rate of clinical treatment for pain may be related to the lack of effective treatment for pain. For PD patients with pain, there are two pain treatment methods (drug and nondrug treatment). For pharmacological therapy, pain can be significantly alleviated or abolished by adjustment of dopaminergic medication . In our For MSA patients, few studies have found useful treatment. In our study, we found that 6 MSA patients with pain improved their pain intensity through the use of dopaminergic medication, including levodopa and pramipexole. Therefore, although dopaminergic medication is not useful for motor symptoms, it can be experimentally used for the treatment of pain for MSA patients with pain. Four MSA patients with pain in our study improved their pain intensity with regular rehabilitation exercise, which showed that regular exercise might be another pain treatment method.In this study, the predominant sites of pain in the PD and MSA patients were the back and the neck and shoulder, which were considered to be skeletal muscle pain by Ford . SkeletaPain is a nonmotor symptom that is somewhat neglected. In this study, we found that anxiety and depression were more likely to occur when PD patients suffered from pain and that the quality of life declined. Therefore, formulating an effective treatment for pain in PD and MSA can largely improve a patient's emotional state and quality of life.Although the DSF scale is not a widely accepted questionnaire for PD patients with pain globally, our study selected the DSF scale as a tool to evaluate features of pain. The DSF is an effective and reliable tool that records the multidimensional experiences of patients with pain. The pain of more than 85% of patients can be fully assessed using this questionnaire. A high degree of agreement was found between clinical and psychosocial diagnoses of pain and the patients' pain data collected by the DSF. Therefore, doctors can adjust the treatment of pain according to the patient's pain clinical characteristics, basic psychological state, and influence on social work collected by the DSF [This study has some limitations. First, this study is a cross-sectional observational and retrospective study. Second, the selected population and the number of patients have limitations. In addition, the pain score of the study was evaluated using questionnaires, which can easily be affected by subjective factors. Our follow-up plan is to select quantitatively detectable pain thresholds and obtain more objective results.This study found that PD and MSA patients often experienced pain. However, treatment of pain associated with Parkinson's syndrome has not been taken seriously. Clinicians should treat pain as seriously as the motor symptoms of Parkinson's syndrome and take corresponding measures for the treatment of pain to improve the patients' quality of life.


Young women in their late teens and early 20s are at the highest risk for depression onset. The present study aimed to assess depressive symptoms among female college students in Fukushima. More specifically, it aimed to clarify factors predicting possible symptom profiles, with an emphasis on determining how nuclear radiation risks affect the reporting of depression symptoms. A cross-sectional survey was conducted of 310 female students at a college in the Fukushima prefecture, Japan, in December 2015, and 288 participants submitted valid questionnaires. In total, 222 (77.1%) participants lived in Fukushima at the time of the Great East Japan Earthquake. The measures included the World Health Organization-Five Well-Being Index, the Fukushima Future Parents Attitude Measure, and risk perception of radiation health effects. A total of 46.5% of participants reported depressive symptoms. Path analysis revealed that higher radiation risk perceptions and reduced efficacy with reproduction related to a decline in self-esteem and self-efficacy, which was subsequently associated with increased depressive symptoms. These findings highlight the importance of radiation education among children and young adults, both after a nuclear accident and during disaster preparation, particularly in the context of reproductive and mental health. The Great East Japan Earthquake occurred on 11 March 2011. A subsequent tsunami hit the Tokyo Electric Power Company’s Fukushima Daiichi Nuclear Power Plant, causing leakage of radioactive material from the plant. Exposure to both natural and man-made disasters is associated with long-lasting psychological problems ,4,5. UsiIn the offspring of people exposed to radiation, increased cancer incidence related to hereditary effects has not been reliably demonstrated for any level of exposure ,7. HowevThe 12-month prevalence rate for major depressive disorder according to diagnostic criteria based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was roughly 7% . This prWe hypothesized that the proportion of female students in Fukushima reporting depressive symptoms would be higher relative to those of female students in other areas. Further, we hypothesized that, after radiation exposure, radiation risk perception and anxiety related to pregnancy and childbirth would be related to the reporting of depressive symptoms. The aim of the present study was to determine the frequency with which female college students reported depressive symptoms in Fukushima. In addition, we sought to clarify the factors underlying symptom profiles, with a focus on radiation risk perception.A cross-sectional survey was distributed to 310 female students at a college in the Fukushima prefecture, Japan, in December 2015. As random sampling of participants and colleges was difficult, a college with a high proportion of female students from Fukushima was selected by the authors. Prior to the study period, we obtained university approval and held preparatory meetings with teachers. The teacher of each class distributed the questionnaires and collected them from participants once complete. The participants were all female students at all levels and specialized in nutrition. Potential participants were excluded on the following grounds: currently married (n = 3); provided the same response to all questions (n = 1); missing data in the World Health Organization-Five Well-Being Index  ; a scoreConcerning demographics, we evaluated age, living arrangements, and residence prefecture at the time of the Great East Japan Earthquake. The WHO-5 , which iAdditional measures included the Fukushima Future Parents Attitude Measure (FPAM) , the RSETo assess potential group differences in sociodemographic characteristics between participants with (“Positive” group) and without (“Negative”) depressive symptoms, we conducted chi-squared tests, Student’s t tests, and Mann-Whitney U tests. Conformity to linearity was checked graphically. To assess predictors of depressive symptoms, we conducted a multivariate logistic regression analysis via the forced entry method. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). In the logistic regression analysis (Model 1), the dependent variable was the presence or absence of depressive symptoms, and the independent variables were living arrangements, age, prefecture (residence prefecture at the time of the Great East Japan Earthquake: Fukushima or other prefecture), and perception of radiation risk. Model 2 was created as multiple logistic regressions with adjustment for RSES and GSES scores. The independent variables in Model 2 were living arrangements, age, prefecture, and perception of radiation risk. In addition, we performed path analysis. In the first model , Model AThe Fukushima Medical University ethics committee approved this study (No. 2462). The survey was anonymized using a bubble answer sheet and the separate distribution of the questionnaire and answer sheet. The survey aims were explained to all participants in a cover letter that was distributed with the questionnaire. The cover letter stated that students should return a blank questionnaire if they did not wish to participate. We also informed participants that the survey was anonymous and they would not suffer adverse consequences based on their responses or withdrawal of participation. Participants were considered to have provided consent by returning the survey.p < 0.01), “Giving birth to a baby” (p < 0.05), self-esteem (p < 0.01), and self-efficacy (p < 0.05) scores were significantly associated with depressive symptoms.We received responses from all 310 participants, and 288 participants submitted valid responses (response rate = 92.9%). The data for participants with missing values in each measurement were excluded from the analysis. Participants’ characteristics, based on the presence and absence of depressive symptoms, are shown in The correlations between the variables are presented in We performed path analysis to identify a causal model for depressive symptoms. We constructed a model in which “perception of radiation risk” influenced FPAM scores, FPAM scores influenced self-esteem and self-efficacy, and self-esteem and self-efficacy influenced depressive symptoms , Model AIn total, 46.5% female college students from Fukushima reported depressive symptoms. Symptom reports were significantly associated with “Caring for a baby”, “Giving birth to a baby”, self-esteem, and self-efficacy. In contrast, living arrangements, place of residence, and perception of radiation risk were not significantly related to depressive symptoms. Based on the path analysis, perception of higher radiation risk was predictive of reduced reproductive confidence, which was associated with decline in self-esteem and self-efficacy, and ultimately associated with increased depressive symptoms. Although no clear epidemiological hereditary effects of radiation exposure in human beings have been reported ,3, the pThe proportion of female students reporting depressive symptoms in Fukushima was quite high. This was inconsistent with the findings of prior studies assessing mothers with infants in Fukushima, in which rates of depression ranged from 23.4% to 27.1% based on results obtained via a 2-item screening instrument ,35 and dAccording to the path analysis, perception of radiation risk did not directly influence depressive symptoms. Instead, the results showed an indirect relationship between these two variables, which is inconsistent with the findings of previous studies ,36. AmonThree notable methodological limitations were present in the current study. First, the study design was cross-sectional, and further studies are needed to clarify potential causal relationships between the variables assessed. Second, the research was conducted with a sample of women from a single college. In the Fukushima prefecture alone, there are 14,053 students  across eight colleges, including an additional 1711 students  across five two-year colleges as of 2016. Thus, the small sample, relative to the broader population affected by the 2011 accident, might limit the generalizability of the present findings. In particular, it is unclear whether the prevalence rate for depression differs from those reported by previous studies, as poorer response rates tend to be associated with higher prevalence rates . Thus, fGiven the relatively high rate of depressive symptoms observed in the present sample, improving mental health support over the long term is imperative for women in Fukushima. Specifically, the provision of support should target not only the paucity of knowledge regarding radiation exposure risk but also anxiety related to both reproductive and mental health.


This study used mediation analyses to examine the assumption that the presence of borderline personality features mediates the relationship between rejection sensitivity (RS), self-compassion, and aggressive behavior. Sixty adults consisting of 31 participants diagnosed with borderline personality disorder and 29 participants with no diagnosis of borderline personality disorder were assessed for RS, self-compassion, aggressive behavior, and borderline personality features. Mediation was found for the total aggression score, anger score, and hostility score regarding both self-compassion and RS. Mediation was also found regarding RS and verbal and physical aggression, and regarding self-compassion and verbal and physical aggression. These findings provide evidence that the presence of borderline personality features is an important factor in explaining the associations linking RS and self-compassion to aggressive behavior. High RS and low self-compassion are associated with greater borderline personality features, which in turn relate to increased aggressive behavior. Interpersonal aggression is closely dependent on the ways people perceive and interpret themselves and others in interpersonal situations. Rejection sensitivity (RS) and self-compassion are two constructs that capture the way that individuals feel in relation to themselves and to others and are presumed to be related to aggressive behavior e.g., . Borderlfeel rejected in various situations and thus in the ways they respond to these experiences. RS is defined as a cognitive–affective processing disposition  self-compassion, rejection-sensitivity, and borderline personality features are associated with aggressive behavior; (b) self-compassion and RS are associated with aggressive behavior; and (c) the direct relationship between self-compassion and aggressive behavior and the direct relationship between RS and aggressive behavior are reduced in the presence of borderline personality features. The model was tested separately for the total score of aggressive behavior, as well as for the different components of aggressive behavior: i.e., verbal aggression, physical aggression, anger, and hostility.The study included 60 adults  . The first group included 31 participants, who were members in a support group for people suffering from borderline personality disorder, after being formally diagnosed with this condition by a psychiatrist. The second group included 29 participants with no psychiatric history, who were sampled from the community. Most of the participants were single (80%), while the others were married (13.3%) or divorced (6.7%). Only seven participants (11.7%) had children. Almost all participants (95%) reported being secular. About half of them (51.7%) had a high school education, with the others (48.3%) reporting higher academic education.M = 26.8, SD = 5.9) and the control group , were found to be non-significant for age, t(58) = 0.60, p > 0.05, and for gender, χ2 = 1.60, df = 1, p > 0.05.The study was approved by the institutional review board. The data were gathered by means of a contact person who served as a mediator between the researchers and a support group of people diagnosed as suffering from a borderline disorder. The contact person approached people in the support group personally and asked whether they would be willing to participate in the study. Potential participants were screened by being asked to report all their known psychiatric diagnoses, as formally diagnosed by a psychiatrist, as well as the circumstances of receiving the psychiatric diagnoses. The inclusion criterion was reporting of having been diagnosed with borderline personality disorder. It should be noted that in our country the diagnosis of borderline personality disorder is conducted on the basis of the DSM criteria. Exclusion criterion was reporting of having been diagnosed with a psychotic spectrum disorder. After signing an informed consent form, the questionnaire was sent to them by e-mail. All participants received an explanation of the study and the questionnaire was sent by e-mail to the 36 people who gave their consent. Thirty-one fully completed questionnaires were returned. After gathering the data of the trial group, and in order to reach as similar a sample as possible with regard to demographic features , a notice was posted at the university seeking suitable respondents. Potential participants were screened and included only if they reported not suffering from any personality disorder or other psychiatric problem and never experiencing recourse to psychiatric services., Both groups were matched by age and gender. The differences between the borderline group  (gs (QTF)  is a selgs (QTF)  as well gs (QTF) . Each itgs (QTF) . In the Aggression Questionnaire  = 3.68, p < 0.001]. Therefore, analyses were controlled for work status. Variables were standardized.We used SPSS version 21  for condF = 3.77, p < 0.001, partial eta squared = 0.52. The univariate analyses are presented in The multivariate analysis revealed that the differences between participants with borderline personality disorder and controls were overall significant, The results of the mediation analyses are presented in As can be seen, all indirect effects are significant. Self-compassion was negatively related with borderline cognitions, which were then positively related with aggression. RS was positively related with borderline cognitions, which were then positively related with aggression. Mediation was found for the total aggression score, anger score, and hostility score regarding both self-compassion and RS. Mediation was also found regarding RS and verbal and physical aggression, as well as regarding self-compassion and verbal and physical aggression.Z = 1.078, p = 0.281, 95% CI = −0.336, 0.086; for RS: indirect effect = 0.098, SE = 0.099, Z = 0.979, p = 0.328, 95% CI = −0.309, 0.092).In the context of a competing model strategy , in whicIn the present study, we found that individuals who are highly sensitive to interpersonal rejection and who are less compassionate toward themselves tend to be more aggressive in their social relations. These findings are compatible with former studies that found a rejection–aggression link in children e.g.,  and adulIn addition to the direct associations, our findings show that the relationships between RS and self-compassion and aggressive behaviors are mediated by borderline personality features. These findings add knowledge regarding the role of borderline personality features as a mediator in the relationship between RS, self-compassion, and aggressive behavior. They are consistent with other studies in which borderline personality was found to mediate the association between attachment insecurities and partner violence .Regarding RS, borderline personality features mediated its association with the total aggression score, anger score, hostility, and verbal and physical aggression. Regarding self-compassion, borderline personality features mediated its association with the total aggression score, anger score, hostility, and verbal and physical aggression. These findings imply that these specific personality traits  may constitute specific aspects of the broader concept of borderline personality, which encompasses negative cognitions and emotions regarding self and others . In otheThese findings imply that self-compassion and RS explain variance in borderline personality features, and support a dimensional conceptualization of BPD. It may also support the notion of a developmental pathway , by whicAccording to our findings, self-compassion and RS are negatively associated. We found that the more individuals are kind to themselves, the less they are prone to anxiously expect, readily perceive, and intensely react to rejection. As this finding is correlative, it is impossible to determine its causal direction. However, there are findings indicating that self-compassion is associated with lower levels of negative emotions in distressful interpersonal situations . SpecifiThe present study has several limitations. First, the sample size was limited. Therefore, the conclusions of the present study should be taken cautiously. Due to the small sample size, we conducted the mediation analysis on both groups pooled together. However, this might introduce deviations in the obtained results., Future studies should examine the replication of our findings in a larger sample. A larger sample will also allow to examine the role of gender as a moderating variable of the mediation. In addition, the borderline group was based on self-reported diagnosis, as other researchers have done in similar studies e.g., . ParticiIn sum, the present study shows that RS and self-compassion are associated with borderline personality features, supporting the notion that borderline personality features are important in understanding the relationship between self-compassion and aggressive behavior, as well as between RS and aggressive behavior. The findings of the current study contribute to raising awareness of the relationships found in the study. They can help therapists find appropriate ways to deal with aggression, even with regard to personality traits, beyond observed behavior. Interventions with borderline patients should set as goals the reduction of RS and strengthening of self-compassion. These interventions may lessen borderline cognitions and emotions, and, therefore, decrease patient proneness to hostile and aggressive responses.All datasets generated for this study are included in the article/supplementary material.This study was carried out in accordance with the recommendations of Ariel University Institutional Review Board (IRB). Written informed consent was obtained from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Ariel University IRB.Both authors were involved in planning, data analyses, and the preparation of 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.