The shortage in Hong Kong of construction workers is expected to worsen in future due to the aging population and increasing construction activity. Construction work is dangerous and to help reduce the premature loss of construction workers due to work-related disabilities, this study measured the work ability of 420 Hong Kong construction workers with a Work Ability Index (WAI) which can be used to predict present and future work performance. Given the importance of WAI, in this study the effects of individual and work-related factors on WAI were examined to develop and validate a WAI model to predict how individual and work-related factors affect work ability. The findings will be useful for formulating a pragmatic intervention program to improve the work ability of construction workers and keep them in the work force. Because construction workers are required to perform physically demanding and repetitive work, they are exposed to higher risk of work-related disabilities than workers in other industries ,2. With The term “work ability” was first introduced in Finland in the 1980s and was defined as: “how good is the worker at present and in the near future, and how able is he/she to do his/her job with respect to work demands, health, and mental resources?” . In contIn order to quantify work ability and provide a work capacity indicator for existing workers, the Work Ability Index (WAI) was developed by Finnish researchers ,13. SincPast studies have reported that work ability can be affected by individual and work-related factors ,17. RegaAs for the effect of lifestyle on work ability, having a smoking habit was associated with a lower WAI among municipal employees in Finland and Poland . HoweverFor the health-related factors, self-perceived poor health was found to be the strongest factor associated with poor work ability, and was significant even after controlling for age. This association with lower work ability has been shown to extend to workers with musculoskeletal and psychosomatic symptoms ,31. AlsoIndividual  competence is one of the dimensions featured in the work ability house model of Ilmarinen ; howeverApart from individual factors, work-related factors have been reported to significantly affect WAI. A recent review conducted by van den Berg et al.  revealedAccording to the Job Demand-Control (-Support) model , three iGiven that Hong Kong is very likely to suffer from an unprecedented manpower shortage in the coming decades, and the number of older workers having to consider extending their working years will increase for various reasons, the major one being financial problems that they would normally extend their working life to earn more saving to support their living after retirement. Therefore, the primary aims of this study were to examine the work ability of Hong Kong construction workers and to develop and validate a WAI conceptual model for predicting how individual and work-related factors affect the work ability of construction workers. Path analysis was used to test the WAI model and to provide explanations for the casual relations (direct and/or indirect) among the variables in the model and their relative importance. Goodness-of-fit statistic was calculated to examine the fit of the model, and the model was used to predict regression weight. The more information available, the more confident we can be that proposed work ability interventions will be successful, and that promotion programs among construction workers in Hong Kong will sustain this valuable workforce and prevent premature dropouts.Hypothesis 1 (H1).Lifestyle factors are associated with the WAI.H1.1. Alcohol consumption is negatively associated with the WAI.H1.2. Smoking habit is negatively associated with the WAI.H1.3. Leisure-time physical activity is positively associated with the WAI.H1.4. Sleep quality is positively associated with the WAI.Hypothesis 2 (H2).The associations between the lifestyle factors and the WAI are mediated by health-related factors.H2.1. Self-reported general health status is positively associated with the WAI.H2.2. Self-reported MSD symptoms are negatively associated with the WAI.H2.3. Self-reported psychological distress is negatively associated with the WAI.Hypothesis 3 (H3).Individual competence is positively associated with the WAI.Hypothesis 4 (H4).Work demand factors are associated with the WAI.H4.1. Physical demands are negatively associated with the WAI.H4.2. Psychological demands are negatively associated with the WAI.H4.3. Job control is positively associated with the WAI.H4.4. Social support is positively associated with the WAI.Hypothesis 5 (H5).The associations between the work-related factors and the WAI are mediated by individual health-related factors.In fact, work demands, social support and job control examined in this study are linked with psychosocial hazards at the workplace. Psychosocial hazards can be regarded as the aspects of the work design and management as well as the social and organizational context of the work that potentially leading to psychological or physical harm to workers . TherefoA total of 420 Hong Kong construction workers were interviewed. Among them, 385 (91.67%) were male and 35 (8.33%) were female, with ages ranging from 31 to 50 years old. Among the female participants, most of them were laborer or cleaner (13) followed by building service technician (9). The pattern of working hours of the construction industry is quite stable, such that workers usually work from 8 a.m. to 5 p.m. for 5 to 6 days per week. The construction workers were reached with the assistance of 20 trade unions and 60 construction companies and had diverse demographic backgrounds, which made the sample representative to the construction workforce in Hong Kong.All participants gave informed consent before the start of the interview. They were informed about the purpose of the study and the use of the data, and they could withdraw from the interview at any time without providing any reason. Interviews were conducted by three different interviewers individually when the construction workers were paying visits to the amenity or resting facilities of the supporting organizations. The whole data collection process was not influenced or interfered by the supporting organizations. All the respondents voluntarily participated in the survey with no presence of staff of the supporting organizations, or people other than the research staff. They were assured that the whole study was conducted by university staff with a high level of data anonymity, security and confidentiality. The interviewer adopted a face-to-face approach to read aloud the questions one by one according to the sequence listed in the questionnaire. The participants’ responses were then marked on the questionnaire by the interviewer. The interviews were conducted in Cantonese and lasted for approximately 15 min for each participant.The interview survey measurement consisted of three major sections: (1) WAI measurement; (2) individual factors; and (3) work-related factors. The questionnaires were translated from English into Chinese by a back-translation method. With this method, the English questionnaire was first translated into Chinese by a translator and then translated back into English by another translator who was blinded to the original questionnaire. The original and the translated questionnaires were then compared. For any discrepancy, a safety and health professional was asked to determine which wording was better to reflect the content, given the fact that the work ability model itself is relying on occupational health and safety. In addition, a pilot study was also conducted with a few construction workers to ensure that they understood the meaning of the questions.Work ability was measured by the Work Ability Index (WAI) questionnaire developed by Ilmarinen and his colleagues ,15.The individual factors examined in this study were: lifestyle factors, health-related factors, individual competence and the demographic factors for the workers.There were four questions concerning the lifestyle of the workers. The questions covered smoking habit and alcohol consumption, sufficiency of sleep and frequency of leisure-time physical activity. The questions regarding alcohol consumption were: What is the average amount of alcoholic drinks you consume per week? How many years have you been drinking alcohol? The questions regarding smoking were: How many cigarettes do you smoke per day? How many years have you been smoking? The question “Did you have enough sleep in the past month?” was used to measure the sleep quality. For leisure-time physical activity, two questions “How much did you move about physically in your spare time?” and “How hard did you exert yourself physically in your spare time?” were asked and participants responded to these two questions using a 5-point Likert scale. The scale for Frequency of physical activity was 1: seldom, 5: always, and the scale for strength of physical activity was 1: extremely low, 5: extremely high. For the health-related factors, measuring physical capacity  and psychological capacity  of construction workers through the various tests and measurements required was impractical. Therefore, self-reports on their general health status, musculoskeletal disorders (MSDs), and psychological distress were used for individual physical and psychological capacity evaluation. The general health status of the workers was assessed by requiring them to answer two questions, one was on how they perceive their own health conditions and, the other was about their health conditions compared with those of others in the same age group. Both questions were measured using a five-point Likert-type scale . MSD symptoms were measured using a modified Nordic questionnaire that contained three questions regarding nine anatomic positions  of the workers ,54. For For the measurement of individual competence, the Career Competencies Questionnaire (CCQ) developed and validated by Akkermans et al.  was adop2), overweight (≥25 kg/m2), or obese (≥30 kg/m2) [The demographic factors of age, gender, height, weight, marital status, education level, job category, family scenario, and anticipated age of retirement were included in the questionnaire. BMI was calculated to determine whether the participants were normal (<25 kg/m0 kg/m2) .In this study, the Job Content Questionnaire (JCQ), which is a job demand measure that has been extensively used for many occupations, was used to assess the physical and psychological workloads of the construction workers. Ten items concerning perceived physical (5 items) and psychological (5 items) demands at work from the JCQ were used ,59. For Cronbach’s alpha values for the measurements of WAI, psychological distress, career competence, physical demands, psychological demands, decision latitude, supervisor/company support, and co-worker support were 0.62, 0.83, 0.94, 0.60, 0.66, 0.76, 0.89 and 0.90, respectively. Because all Cronbach’s alpha values were equal to or larger than 0.60, the internal consistency reliability for the different measurements was considered acceptable ,62.Work ability index (WAI) scores for the 420 participants were obtained. The causal relations between WAI score and the individual and work-related factors were examined by the WAI conceptual model using Path Analysis. Cronbach’s alpha test was conducted to check the internal consistency of the items in each factor to ensure that they were measuring the same underlying construct.t-test (p > 0.05), implying that male and female construction workers had no significant difference in their self-reported work ability.The average score for each subscale and the overall WAI score are shown in N = 93) on average was 1707.04 mL per week and they had been drinking for an average of 12.56 years. Pearson’s correlations were calculated to evaluate the correlations between WAI and alcohol consumption. The results showed significant negative correlations between the WAI and the amount of alcohol consumption , as well as between the WAI and the years of alcohol drinking   , indicatN = 127) smoked an average of 12.46 cigarettes per day, and had been smoking for an average of 13.60 years. Correlation analysis showed significant negative correlations between the WAI and smoking habit. The more cigarettes that the participant smoked, the lower their WAI , and the longer the years the participants smoked, the lower their WAI   .n = 420, p < 0.001) and the strength of physical activity  , and the strength of the physical activity was 3.15  . Correla< 0.001) .n = 420, p < 0.001)  , indicatn = 420, p < 0.001), moderate  and severe  levels of MSD symptoms , moderate (prevented from doing day’s work), and severe (consulted a physician). The average number of mild, moderate and severe MSD symptoms was 1.08, 0.52 and 0.44, respectively. Overall, the participants suffered from 2.04 MSD symptoms . Correlasymptoms . These rn = 420, p < 0.001)  , implyinn = 420, p < 0.001)  , indicatn = 420, p < 0.01)  , implyinn = 420, p < 0.001)  , indicatn = 420, p < 0.001)  . The resn = 420, p < 0.001)  , indicatn = 420, p < 0.001)  , indicat2 = 50%)  (0.94) was larger than 0.90 and both Standardized Root Mean Square Residual (SRMR) (0.036) and Root Mean Square Error of Approximation (RMSEA) (0.066) were smaller than 0.10. Chi-square statistic was non-significant and the model explains 50% of the variance in WAI score (R2 = 50%) .As shown in previous sections, sleep quality, smoking habit, leisure-time physical activity, job control, supervisor/company support, co-worker support, and psychological demands all directly influenced the WAI. However, in this study, these effects were mediated by general health status, MSD symptoms, and psychological distress, and Path analysis also revealed significant mediation effects on job control, supervisor/company support, and co-worker support on the WAI through general health status. The results of the hypothesis testing are summarized in The average WAI score in this study was relatively higher than those found in previous studies on construction workers in Western countries ,48. The Several studies have shown that age is a significant factor leading to a decline in work ability ,19,20. HAs outlined in the proposed conceptual work ability model, self-reported general health status, self-reported MSD symptoms, and self-reported psychological distress are regarded as the health-related factors having mediating effects between lifestyle factors and work ability, as well as between work-related factors and work ability. The findings of this study indicated that, for lifestyle factors, the effects of sleep quality, smoking habit, and leisure-time physical activity on WAI scores were fully mediated by self-reported general health status. Self-rated health status has been shown to be a valid health measure in previous studies ,66, and The findings of this study show that the positive impact of sleep quality on work ability was fully mediated by self-reported general health status. Sleepiness and sleep quality have been reported to be crucial factors affecting general health status . TherefoFor smoking habit, the findings of this study indicated that the effect of smoking on work ability was fully mediated by general health status. Simply put, participants with longer years of smoking will have worse general health status and therefore a decline in work ability. The association between smoking and reported general health was also found by Laaksonen et al. ; currentThe effect of the frequency of physical activity on work ability was fully mediated by general health status and psychological distress. Epidemiologic and experimental studies have revealed that physical activity can improve cardiorespiratory fitness  and reduIndividual/career competence is an important yet rarely studied factor for work ability measurement. The results of this study showed that participants with a higher level of career competence had higher WAI scores. The measurement of individual competence reflected the participants’ professional competences in exercising their duties at work. Thus, participants who were more capable of mastering their work and had clearer career plans and goals had better work ability.For work-related factors, physical demands directly influenced work ability, while the effect of psychological demands on work ability was partially mediated by all of the health-related factors, viz., general health status, MSD symptoms, and psychological distress. Physically demanding jobs have been consistently reported to be positively associated with a lower WAI ,19,25,78The effect of psychological demands on work ability was partially mediated by all the health-related factors. The negative relationship between psychological demands and self-reported general health status was consistent with the findings of Shen et al.  that lowThe effects of job control and social support on work ability were found to be mediated by general health status. This finding is similar to results reported by Smith et al.  on the rDespite the promising contributions made by this study, there are some limitations of this study. It is known that with a large sample size of 420, correlations as low as <0.2 are still statistically significant. However, such low values, though statistically proven to be significant, may be regarded as practically insignificant to certain extent by practitioners. Also, this study is somewhat ambitious to include a large number of factors in the model, which might have obscured some points of the study. In addition, the relationship between sleep quality and work conditions was not considered here.In order to formulate pragmatic strategies for sustaining the construction workforce in Hong Kong, the findings of this study can be used as the basis for formulating an effective intervention program for the construction industry, with the aim of promoting healthy behavior to construction workers, lowering their work demands, and increasing their influence and support in the workplace. The approach of intervention mapping (IM) has been increasingly used as an effective method for complex health promotion interventions, given its systematic approach to program planning along with the inclusion of robust theories, empirical evidence, and practical information ,97. The The findings of this study suggested that the work ability of the construction workers was significantly affected by different lifestyle and work-related factors, including the physical and psychological demands of their work, job control, and social support. Except for physical demands and individual competence, all the effects of individual and work-related factors on work ability were fully or partially mediated by health-related factors, indicating that the health of the workers was a determining factor for their work ability and for possible retention of workers in the industry. Work ability was found to decline along with deteriorating health of participants due to poor sleep quality, having a smoking habit, lack of physical exercise, high psychological demands of the work, as well as low levels of job control and social support from work. In addition, poor work ability was directly associated with high physical demands of work and low competence of participants. The results obtained in this study provide solid evidence of the impact of various individual and work-related factors on the work ability of Hong Kong construction workers. The influence of these significant factors should be taken into consideration when formulating comprehensive intervention programs to better retain the valuable construction workforce in Hong Kong.


The long-term mortality of acetaminophen (APAP) poisoning has not yet been well studied; hence, we conducted this study to gain understanding of this issue.We conducted a nationwide population-based cohort study by identifying 3235 participants with APAP poisoning and 9705 participants without APAP poisoning in Taiwan between 2003 and 2012 in the Nationwide Poisoning Database and Longitudinal Health Insurance Database 2000. Participants with APAP poisoning and control subjects were compared for the risk of all-cause mortality by follow-up until 2013.Two hundred forty-one participants with APAP poisoning (7.5%) and ninety-four control subjects (1.0%) died during the follow-up. Participants with APAP poisoning had a higher risk of all-cause mortality than the control subjects , especially in the subgroup aged 20 years and younger  and in the first 12 months after poisoning . The increased risk of all-cause mortality was found even up to 2 years after the index poisoning.APAP poisoning was associated with increased long-term mortality. Early referral for intensive aftercare and associated interventions are suggested; however, further studies of the method are needed for clarification. N-acetylcysteine, the morbidity and mortality of APAP poisoning are still high. According to a recent study in the United States, APAP poisoning is one of the leading causes of acute liver failure and results in over 30,000 hospitalizations annually [Acetaminophen (APAP) is one of the most commonly used antipyretics and analgesics. It can be bought in either pharmacy or nonpharmacy outlets or prescribed by physicians. Like all drugs, APAP is effective and safe when used at recommended doses, less than a daily maximum of dose 4 g/day in an adult; however, its overdose can result in toxicity . Some ofThere is not much data on long-term mortality of APAP poisoning, because previous studies were focused mainly on short-term mortality, risk factors of complications, and management of APAP poisoning –7. In a The Nationwide Poisoning Database (NPD) and Longitudinal Health Insurance Database 2000 (LHID2000) were used for this study. These are the two data subsets of the National Health Insurance Research Database (NHIRD). The Taiwan National Health Insurance program covers 99% of whole population (23.3 million) in Taiwan, and its dataset, NHIRD, is one of the most complete, biggest, and most comprehensive databases in the world . The NHIAll the participants who had been diagnosed with APAP poisoning (ICD-9 code 965.4 or E850.4) in the NPD between January 1, 2003, and December 31, 2012, were identified as the study participants in the APAP group. In addition to APAP poisoning, participants in the APAP group may have had other diagnoses at the same time. The diagnosis of APAP poisoning depends on the history of taking APAP, blood APAP level, and the treating physician’s high index of suspicion , 14. In This study was approved by the institutional review board at Chi-Mei Medical Center and conducted according to the principles of the Declaration of Helsinki. Because the two datasets used in this study contain unidentified information of the participants, the need for informed consent was waived.t test and the chi-square test were used for the comparison of continuous variables and categorical variables between participants with APAP poisoning and control subjects, respectively. We used Poisson regression to calculate the incidence rate ratio (IRR) of the risk of all-cause mortality between the two groups. Kaplan–Meier analysis and the log-rank test were used for comparison of cumulative survival rates between the two groups. We also investigated the independent mortality predictors by Cox proportional hazards regression. SAS 9.4 for Windows software  was used for all the analyses. The significance level was set at p < 0.05 (two-tailed).A two-sample A total of 3235 participants with APAP poisoning and 9705 control subjects were identified for inclusion in the study Table . The meaDuring the follow-up period, the all-cause mortality of the participants with APAP poisoning and control subjects was 7.5% 241 of 3235) and 1.0% (94 of 9705), respectively , the reactive metabolite of APAP, as the main source of toxicity [A possible explanation for the increased long-term all-cause mortality in participants with APAP poisoning is that the related oxidative stress causes damage to the pancreas, liver, kidney, vascular walls, and other organs . The APAtoxicity . Intake toxicity , 18.This study shows that the risk of all-cause mortality after APAP poisoning was higher in the younger population than in the older population. A possible explanation is that the younger population has fewer comorbidities than the older population, and therefore APAP poisoning may become the major contributor to death. This finding is consistent with results of previous studies on poisoning , 20. TheOlder age and male sex were independent mortality predictors, which is consistent with previous studies –23. In aThe present study shows that participants with APAP poisoning had a lower monthly income and a higher prevalence of mental disorders than those without APAP poisoning, which is compatible with findings of a previous study . In a stIn this study, a direct comparison of all-cause mortality between participants with and without APAP poisoning was performed, which was different from two previous studies in which researchers compared mortality among subgroups of APAP poisoning , 10. A sN-acetylcysteine and mortality in this study. Fourth, although this was a nationwide study, it may not be generalizable to other nations, owing to differences in race, medical resources, and culture. All the limitations mentioned above warrant further studies to provide more insight into this area.This nationwide cohort study has two major strengths: (1) a large sample size and (2) insights into an area with limited data. However, there are some limitations as well. First, some information, including body mass index, lifestyle factors, smoking, substance abuse, physical activity, family history, suicide attempts, causes of poisoning , concomitant poisoning, and causes of mortality, was not included in this study, which might affect the causal relationship between APAP poisoning and mortality. For example, concomitant poisoning may be more dangerous than APAP poisoning, and the increased mortality in the young patients may be due to accidents or suicide. We adjusted for many major comorbidities that can be surrogates for some unavailable variables above. For example, DM and HTN were adjusted for body mass index and lifestyle factors, and liver disease was adjusted for substance abuse. Therefore, we believe the influence of missing comorbidities to be minimal. Second, this study provides only diagnosis codes of APAP poisoning, regardless of severity, including development into liver injury and hepatotoxicity or not. Third, we did not evaluate the association between N-acetylcysteine, causes of mortality, and methods of aftercare are warranted.APAP poisoning was associated with increased long-term all-cause mortality. The increased all-cause mortality was more prominent in the younger population and in the first 12 months after poisoning. Independent mortality predictors included older age, male sex, DM, liver disease, cancer, lower monthly income, and living in the eastern region of Taiwan. Early recognition of APAP poisoning and timely management of the above-mentioned risk factors are suggested to prevent subsequent death. Further studies investigating the severity of APAP poisoning, causes of poisoning, use of


To compare the muscle thickness, fascicle length, and pennation angle of the gastrocnemius, soleus, and tibialis anterior between Asian children with spastic cerebral palsy (CP) and typically developing (TD) peers.This cross-sectional study involved a total of 72 children with hemiplegic CP (n = 24), and diplegic CP (n = 24) and their TD peers (n = 24). Muscle architecture was measured at rest using ultrasound. Clinical measures included gross motor function and a modified Ashworth scale.p<0.05) than in those of their TD peers. Additionally, the lengths of the lateral gastrocnemius and soleus fascicle were shorter (p<0.05) in children with diplegic CP than in their TD peers. The fascicle length was shorter in the affected calf of children with CP (p<0.05) than in the calves of their TD peers or the unaffected calf of children with hemiplegic CP. However, the length of the lateral gastrocnemius fascicle was similar between the two legs of children with hemiplegic CP. The pennation angles of the medial gastrocnemius and soleus muscles were larger (p<0.05) in the affected calf in children with hemiplegic CP than in the calves of their TD peers. The fascicle length of the lateral gastrocnemius and the thickness of the soleus muscle were positively correlated with gross motor function scores in children with CP (p<0.05).The thicknesses of the tibialis anterior and medial gastrocnemius muscles were smaller in the affected calf of children with CP (Muscle thickness and fascicle length were lower in the affected tibialis anterior, gastrocnemius, and soleus in children with spastic CP. These changes may limit the ability to stand and walk, and indicate a need to strengthen the affected muscle. The key feature of spastic cerebral palsy (CP) is spasticity, which causes significant alterations to muscle morphology and architecture over time despite the non-progressive nature of its brain lesions.,2 The spA muscle’s function is indicated by its architecture, including its muscle thickness, fascicle length, and pennation angle–12. StudUltrasound has recently become more widely used in musculoskeletal research because it is a relatively useful, quick, cheap and child-friendly assessment tool–26, evenTherefore, the objectives of this study were to use ultrasound to investigate the muscle thickness, fascicle length, and pennation angle of the calf agonist  and antagonist  muscles between Asian children with spastic CP and their TD peers. Furthermore, we analyzed the correlations between muscle architecture and walking ability.Children with hemiplegic and diplegic CP  who were treated in the Rehabilitation Department of Guangzhou Women and Children’s Medical Center from December 2014 to December 2015 were selected. Children with CP were excluded if they had been treated with serial casting, botulinum toxin injections or surgery to the legs during the previous 6 months. Twenty-four children with hemiplegic CP and 24 age-matched children with diplegic CP were recruited into the study among 97 eligible candidates. The participants with hemiplegic and diplegic CP were classified as level I (n = 29), II (n = 7) or Ⅲ (n = 12) according to the gross motor function classification system (GMFCS) for dynaThis was a cross-sectional study . The proDemographic characteristics were recorded for each participant and included age, gender, height, weight, body mass index, and calf length and circumference. Calf length was defined as the distance between the popliteal fossa and calcaneus. All children with hemiplegic and diplegic CP were assessed by two experienced physical therapists to determine the GMFCS, the D and E dimensions of the gross motor function measure (GMFM), and thea) was used during the measurement phases. Measurements were obtained from the calf muscle in the sagittal plane and horizontal planes. To avoid the effects of different system conditions, which could potentially alter the images, the performer standardized the setting of scanner and kept it constant during the examinations.A computer-based ultrasound system equipped with an 11.0-MHz linear transducer with a 50-mm field of view /2), fascicle length , and pennation angle. Measurements were obtained according to the recommendations of previous studies,23,33,34b was used to perform the analysis. If the values were normally distributed, the Independent-Samples t test, one-way ANOVA and a post hoc analysis  were used. Otherwise, the Mann-Whitney U test, Kruskal-Wallis test and Chi-square test were used. The affected and unaffected limbs of the HCP group, the mean of both limbs in the DCP group, and the right limbs of the TD group were used in the analysis of muscle architecture data, calf length and circumference, and muscle spasticity. The Chi-square test was used to determine whether there were differences in gender and GMFCS levels. Correlations between muscle architecture and clinical functions were analyzed with Pearson’s  or Spearman’s  correlation analysis. Significance was set at 0.05.SPSS version 20.0 p>0.05) were found in age, gender, and body mass index among the three groups or in MAS scores for the ankle between the HCP and DCP groups. Height, weight, and calf circumference and length were significantly lower in the DCP group than in the TD group (p<0.01). The lengths of both calves and the circumference of the affected calf were significantly smaller in the HCP group than in the TD group, and calf circumference was smaller in the DCP group than in the HCP group (p<0.05). GMFCS levels and GMFM scores were significantly better in the HCP group than in the DCP group (p<0.05).Demographic, anthropometric and clinical function data for the three groups are shown in p>0.05, p<0.05, There were no significant differences p>0.05, , Fig 3 ip>0.05, p<0.05, No significant differences were found in any of the muscle architecture parameters between the targeted muscles in the TD group and the targeted muscles on the unaffected side of the HCP group. There was also no difference in the thickness of the lateral gastrocnemius and soleus muscles or in the pennation angle of the tibialis anterior and lateral gastrocnemius muscles between the TD group and the affected side of the HCP group p>0.05, , Fig 3. p<0.05, The thickness of the tibialis anterior and lateral gastrocnemius muscles and the fascicle length of all of the targeted muscles were significantly smaller in the DCP group than on the unaffected side of the HCP group p<0.05, , Fig 3.p>0.05, p<0.05, No significant differences were found in the pennation angle of the calf muscles between the DCP and TD groups p>0.05, , Fig 3. p>0.05). However, lateral gastrocnemius fascicle length and soleus muscle thickness were correlated with GMFM scores in all children with CP .MAS scores were not well correlated with any of the muscle architecture parameters in children with CP  and antagonist  muscles between Asian children with CP and their typical peers. In this study, we demonstrated that muscle thickness and fascicle length were significantly lower in the affected than in the TD muscles and in the affected than in the unaffected muscles for the tibialis anterior, gastrocnemius, and soleus muscles. However, the pennation angles of the medial gastrocnemius and soleus muscles were significantly higher on the affected side of children with hemiplegic CP than in their TD peers. In addition, our results also indicate that the ability to stand and walk is associated with lateral gastrocnemius fascicle length and soleus muscle thickness.Skeletal muscles are subject to reshaping in the body and can be adapted by a variety of positive and negative stimulations, such as strength training, disuse, spasticity, and immobilization–17. DataMuscle thickness is positively correlated with force capacity,35–37. PBased on the clinical experience, motor dysfunctions may be influenced more by limitations related to mechanical factors in soft tissues than to neurological factors in central command disorders as children with CP have grown up to be youths and adults. Fascicle length is especially important when analyzing muscle architecture because it is highly related to secondary musculoskeletal contracture development, which can severely limit the initial length of muscle contraction and excursion,40,46,47Muscle fibers often do not run the entire muscle length from origin to insertion parallel to the action of the muscle, but are instead at the pennation angle. Although Malaiya et al and ShorMuscle thickness and fascicle length were decreased in the affected tibialis anterior, gastrocnemius, and soleus muscles. Furthermore, GMFCS levels and GMFM scores were poorer in the DCP group, indicating that a smaller muscle thickness and a shorter fascicle length decrease muscle strength, resulting in the loss of good functions in the legs.With regard for the effects of CP, the calf muscles have been the most well-studied muscle group because they are easily induced to contract in children with CP. Most studies have used ultrasound to measure muscle architecture parameters. While ultrasound imaging is a specialized and complicated process, MRI is used less often because it is expensive and problematic to perform in that it requires prolonged relaxation, which is difficult to achieve in a primarily pediatric population. A previous systematic review suggested that ultrasound imaging is accurate when measuring the architectural features of human skeletal muscles in vivo if certain conditions are met, including the relaxation of and maintenance of a static position in joints In the pFirst, we investigated the muscle architectures of the calf only while the ankle was in a resting position with the knee extended. Defining the muscle architecture associated with different ankle joint angles during voluntary contraction will require further investigation. Second, we did not measure tendon length. Some previous studies,51 have Muscle thickness and fascicle length are decreased in the affected tibialis anterior, gastrocnemius, and soleus muscles of children with CP. These changes may limit the ability of these individuals to stand and walk. Additionally, these alterations indicate that there is a need to strengthen the affected muscles in children with spastic CP. Further studies are needed to determine whether muscle growth and architecture can be improved in children with spastic CP by interventions such as treatment with botulinum toxin and strength training.S1 Raw data(XLS)Click here for additional data file.S1 Protocol(DOC)Click here for additional data file.


Concentrations were in the range 0.011–2.26 ng g−1 for the six “indicator” non-dioxin-like PCBs (NDL-PCBs), and 0.0009–0.096 pg WHO toxic equivalent (TEQ) g−1 for the sum of dioxin-like PCBs (DL-PCBs) and PCDD/Fs. Lacking maximum limits for these contaminants in fruit and vegetables, the concentration values found were compared with the action levels set out in the EU Recommendations. These levels were never exceeded in the examined samples. In the present study, the highest mean value for PCDD/Fs + DL-PCB corresponded to apricots, olives, and nuts, while the lowest values were observed in endive and green beans. The results showed also that NDL-PCB levels in apricots were much higher than in any other food, suggesting that they can accumulate PCBs: this fruit might be proposed as a “sentinel” of the presence of these contaminants in the environment.The concentrations of polychlorinated dibenzo- It was recently estimated that the average dietary exposure to dioxins and dioxin-like compounds in the Italian general population is close to the tolerable daily intake (TDI) of 2 pg WHO toxic equivalent (TEQ) kgy weight , establiy weight , and in y weight . Human exposure to dioxins predominantly occurs via food intake . The maiKnowledge of diet intake of certain persistent pollutants such as dioxins and PCBs therefore represents an important factor in ensuring the population’s health . At the In the present study, a first detailed investigation relating to the concentrations of dioxins and PCB in fruits and vegetables from the Campania Region of Italy was performed. In the past decade, the interest in these substances has increased in the Campania Region after its lands were involved in illegal waste dumping phenomena and uncontrolled burning of wheels, plastics, textiles, and other industrial residuals along the roads bordering cultivated fields. The attention was paid in particular to that area between Napoli and Caserta sadly known as “Land of Fires,” which has been used for the illegal dumping, burning, and disposal of toxic waste and that houses a municipal waste incinerator.This area is of interest due to past environmental pollution events that were discovered by finding high levels of dioxin in foods that were above permitted values ,14,15. p-dioxins and dibenzofurans (PCDD/Fs), 12 congeners of dioxin-like polychlorobiphenyls (DL-PCBs), and 6 non-dioxin-like polychlorobiphenyls (NDL-PCBs).To this aim, different fruits and vegetables were collected from the cultivated lands within the “Land of Fires” area between 2014 and 2016 in the proper seasonal period and analyzed for 17 polychlorinated dibenzo-While there is sufficient data available on the levels of PCDDs, PCDFs, and PCBs in foods of animal origin, there is much less on their levels in fruit and vegetables ,16, and Mainly due to low levels of dioxins in vegetables, the determination of the average content in samples resulted in an estimate with substantial uncertainty. Therefore, the present study was conducted based on composite samples for all relevant types of fruit and vegetables.Based on the typical plantation of the Campania region lands, 16 fruits and 26 vegetables were selected : below-gSamples were collected in their specific growing period between 2014 and 2016 from orchards or vegetable plantations located in different parts of the “Land of Fires,” in the Campania Region, mainly where there are some potential sources of contamination, such as an incinerator or waste burning. In particular, this area is located between the Domizio-Phlegrean Coast, the Agro Aversano-Atellano lands, the districts of Acerra and Nola, the lands around Vesuvius, and the city of Naples, affecting a total of 95 municipalities in the provinces of Benevento, Caserta, and Naples .As established by the sampling procedures , a hypotSamples were collected by qualified staff wearing vinyl gloves, put into zip bags, and immediately sent to the laboratory. Before analysis, adherent matter such as soil, foul parts, and non-edible leaves and stems were removed manually and samples were washed. From each kind of fruit or vegetable, individual samples were combined to make a pooled sample. Other samples and the remainder of the individual samples were stored at −20 °C and available for further investigations.13C12-labeled internal standard (IS) of DL-PCBs , six indicator NDL-PCBs , and PCDD/Fs  .All solvents  were of ultra-trace analysis grade and were purchased from Sigma-Aldrich . Pre-packed multi-layer silica, alumina, and carbon columns were obtained from a Fluid Management System . All standard solutions were supplied by Wellington Laboratories . Before analysis, all samples were spiked with a mixture of 13C12-labeled congeners).The sample extraction and clean-up were carried out as previously reported . The fraThe HRGC/HRMS measurements were carried out using a GC Trace Series 2000 coupled with an MAT 95 XP . The congeners of PCDD/Fs were separated by high resolution gas chromatography (HRGC) on a DB-5 MS capillary column  and determined by high resolution mass spectrometry (HRMS). The congeners of DL-PCBs and NDL-PCBs were separated by HRGC on an HT-8 capillary column  and determined by HRMS. Samples were tested by a validated method routinely used for PCDD/Fs and PCBs analysis in food and feed and successfully tested in a number of inter-laboratory studies. The method used was an in-house adaptation of the US EPA Methods .PCDD/Fs and DL-PCBs TEQ values were calculated using the World Health Organization Toxic Equivalency Factors (WHO-TEFs2005). The upperbound (UB) concentrations were calculated assuming that all values of the different congeners less than the limit of quantification were equal to the limit of quantification and were expressed in pg-TEQ/g fresh weight. The sum of six indicator congeners was calculated for NDL-PCBs as UB concentration, and expressed as ng/g.A laboratory blank and a control sample were analyzed for each batch of 10 and 20 samples, respectively. Recovery rates of labeled congeners ranged from 60% to 90%, and the analytical uncertainty was in the order of ±20% for WHO-TEQs and the sum of six NDL-PCBs.Results were also analyzed through a determination of Pearson correlation coefficients and principal component analysis (PCA) using the Minitab Statistical Software by Minitab Company.A total number of 228 samples were collected from cultivated fields located in the so-called “Land of Fires” area in the Campania Region. The concentrations  of WHO-PCDD/F-TEQs, WHO-PCB-TEQs, and Σ6PCB found in the respective fruit and vegetable items were summarized in terms of minimum, mean, median, and maximum in In the analyses of vegetables, extremely low detection limits were obtained (<1 pg/g fresh weight for each congener). As regards the NDL-PCB, the mean content value obtained for all samples was 0.17 ng/g fresh weight with a range from 0.01 to 2.6 ng/g. Between fruits, apricots showed a mean concentration higher than any other vegetables analyzed: mean concentration was 0.91 ng/g with values ranging from 0.003 to 1.56 ng/g. However, the highest value of concentration was detected in one sample of hazelnut (2.6 ng/g), and in general nuts  showed similar levels of NDL-PCBs (mean 0.44 ng/g).Brassicaceae, Solanaceae, etc.), kohlrabi (roots) revealed a high value for the sum of NDL-PCBs (mean 1.26 ng/g). This has been predicted and observed before since it has a large surface/content ratio that perfectly absorbs hydrophobic contaminants from soil, and for its extremely long presence on the field (9 months) [Between vegetable species ( months) .High values with respect to other vegetables were found in olives (mean content 0.52 ng/g): this result can be explained by their high fat content and hence the accumulation availability of these lipophilic contaminants.The lack of maximum limits as well as action levels for NDL-PCB makes it difficult to assess the risk associated with their levels in vegetables grown in the Campania Region; however, they can be compared with the literature data, even if such data are scarce.The overall median and mean Σ6PCB level amounted to 0.055 and 0.174 ng/g, respectively, and is relatively higher than that obtained in a similar background contamination study in Germany  . On the With regard to the PCDD/F content, the results of analyses revealed that most of the congeners were measured below the limit of quantification (LOQ).Therefore, the sum values are very low compared to action levels fixed for DL-PCBs and PCDD/Fs by Commission Recommendation 2014/663/EU and to those reported in the literature for vegetables collected in highly polluted areas ,22,23,24Since soil–plant transfer of PCDD/Fs was found to be highest in the cucumber family (Cucurbitaceae) , the relAs regards DL-PCBs, in general, LOQ amounts higher than those of Congeners 81 and 169 were obtained only in 1.3% and 6.0% of cases, while Congeners 118, 105, and 77 were more abundant and recurring in the vegetable samples. In particular, Congeners 118 and 105, characterized by low chlorination, were found in all vegetable samples, and the presence of these more volatile congeners led to the hypothesis of a mechanism of accumulation based on the re-suspension of PCBs in air from the soil with subsequent deposition on the vegetables [Taking the DL-PCB content in the different vegetable species into consideration, in confirmation of that already observed for the six indicator PCBs, only wheat, melon, apricots, kohlrabi, and walnuts showed significant concentration values. In particular, melon exhibited the highest mean lowerbound value for ∑DL-PCBs on fresh weight (0.056 pg TEQ/g), followed by kohlrabi (0.049 pg TEQ/g), wheat (0.045 pg TEQ/g), apricots (0.043 pg TEQ/g), and walnuts (0.028 pg TEQ/g). For the latter product, the higher fat content might explain a higher accumulation. Besides nuts, compared to other plant species, a high content of microelements has also been observed in the same area . Figure A multivariate statistical analysis of the data was assessed through the PCA, as shown in PCA estimates the correlation structure of the variables by finding hypothetical new variables ) that account for as much of the variance (or correlation) as possible in a multidimensional data set. These new variables are linear combinations of the original variables . The sigIn this plot, olive, apricot, kohlrabi, hazelnut, and walnut samples were mainly located in the positive direction of the first principal component, whereas the majority of the other samples were restricted in the axis center, in the negative direction of the two principal component, revealing their reduced influence on the reference sample group. Thus, results of the PCA indicated that the PCB congener profile of apricots and kohlrabi were richer in NDL-PCBs than the other samples. In the interpretation of PCA patterns, factor loadings greater than 0.71 are defined as excellent, while those less than 0.32 are regarded as poor . Communa−1 bw/day) and the Agency of Toxic Substances and Disease Registry [−1 bw/day). Exposure to the contaminants under investigation through vegetable and fruit intake was assessed by combining typical Italian consumption data for children and adults  with theRegistry  for the i: iw is the individual body weight of the individual I; ijC is the consumption of food j by the individual I; jT is the average PCDD/F or DL-PCB contamination of food j.The standard deterministic method to estimate exposure can be described according to Equation (1) for an individual −1 bw/day in adults for the consumption of fruit. NDL-PCB intake ranged from 0.00687 in adults for the consumption of vegetables to 0.0564 ng kg−1 bw/day in children (3–10 years) for the consumption of fruit. The average intake of contaminants was estimated by multiplication and summation of the average consumption of the various vegetables per capita with the concentrations in these vegetables. It appears that the total intake related to PCDD/Fs and DL-PCBs varies from 0.00021 in children (3–10 years) for the consumption of vegetables to 0.00103 pg TEQ kg−1 bw/day in children to 0.00021 pg TEQ kg−1 bw/day in adults; NDL-PCB concentrations ranged from 0.0147 ng kg−1 bw/day to 0.00636 ng kg−1 bw/day. Therefore, we can affirm that the low concentrations of these substances ensure a low exposure of these substances to consumers of the vegetables and fruits produced in the studied area. The contributions to the total intake from potatoes were calculated separately because of their high consumption. Dioxin concentrations ranged from 0.00063 pg TEQ kgDioxins and PCBs in soil and in atmosphere may be the source of these pollutants in the vegetables growing in this environment. In this study, carried out in the cultivated field located in the so-called “Land of Fires” in the Campania Region of Southern Italy, the results showed a very low contamination level in vegetables.The low levels of dioxins and PCBs found in plants demonstrate that these matrices poorly accumulate these types of pollutants and thus that the degree of environmental pollution by dioxins and PCBs in the Land of Fires is low, as demonstrated by recent results obtained in animal matrices ,33. The


Bythotrephes longimanus in its Central European native range. Communities were mainly dominated by widespread species typical of lowland habitats, and only a few true specialists of oligotrophic alpine lakes were present. The most frequent taxa were the Daphnia longispina complex and Eudiaptomus gracilis, with 48 and 45 occurrences, respectively. Species richness decreased with altitude and increased with lake area. The main structuring factors of community composition were chlorophyll a concentration and depth, which drove an apparent separation of mesotrophic and oligotrophic communities. Bythotrephes had 13 occurrences, showing a preference for deep oligotrophic lakes. Its presence was not coupled with lower crustacean species richness, as was repeatedly observed in North America. Additionally, it frequently co-occurred with the other large predatory cladoceran, Leptodora kindtii. B. longimanus might be considered a truly montane species in Central Europe, given its absence in lowland and alpine lakes.Lakes in the Alps represent a considerable fraction of nutrient-poor lakes in Central Europe, with unique biodiversity and ecosystem properties. Although some individual lakes are well studied, less knowledge is available on large-scale patterns essential to general understanding of their functioning. Here, we aimed to describe crustacean zooplankton communities  and identify their environmental drivers in the pelagic zone of 54 oligotrophic lakes in the montane region of the Alps (400–1200 m) in Austria, Germany, and Switzerland, covering a spatial scale of 650 km. Moreover, we aimed to provide data on the distribution and ecological requirements of the North American invader  In oligotrophic lakes, nutrients are the primary limiting factor for biomass production. Such nutrient-poor lakes can be numerous in the boreal and mountainous regions. In these lakes, plankton communities are relatively simple and species-poor, yet zooplankton–phytoplankton interactions are stronger than in eutrophic lakes  and in the Alps in Central Europe , Germany, and Austria , with most of the lakes situated in the montane region of the Alps  and at a location with a depth of >15 m in large, deep lakes.a (Chl-a), total phosphorus (TP), soluble reactive phosphorus (PO4), and total nitrogen (TN). For Chl-a, we used fluorometry with aceton extraction .During sampling of German and Austrian lakes, a depth-integrated water sample was taken with a 1 m tube sampler covering the whole epilimnion . The mixed sample was used to measure concentrations of chlorophyll i et al. , and afti et al. . In the Zooplankton was sampled in the German and Austrian lakes with a 100 μm mesh size (diameter: 40 cm) plankton net, for most lakes by taking a vertical net haul of the upper 15 m water layer. In shallow lakes, the net was towed from a few meters above the sediment, and in deep lakes (epilimnion thickness >15 m), the net was hauled from 25 m depth. In cases of low zooplankton abundance, an additional net haul was performed. All samples were fixed with ethanol (70%). In the Swiss lakes, zooplankton were analysed from samples collected for molecular analyses (not part of the present study) with a 100 μm mesh sized net (diameter: 50 cm) hauled through the entire water column (maximum 140 m in Lake Zurich); zooplankton were then concentrated and stored frozen until analysis, when they were transferred to 70% ethanol.Daphnia longispina complex, which was treated as one species, D. longispina) based on the keys of Flössner  were identified to species , lake volume (lake_vol), and concentrations of Chl-a, TP, and TN were ln transformed, whereas maximum depth (Zmax) was square root transformed to minimise residuals. We focused on lakes situated in the calcareous northern fringe of the Alps. There were 2 non-alkaline lakes with low Cond , 1 lake with high TP , and 1 lake situated at high altitude ; these 4 lakes were excluded from all analyses involving environmental predictors.For the statistical analyses, altitude (Alt), conductivity (Cond), Secchi disk transparency , TP and TN data were not available from the Swiss lakes; therefore, for the analysis of the predictors of species number , we included only PO4 and Chl-a concentrations, which were not correlated . We also excluded ZS from the analyses because of its high correlation with Chl-a . We also reduced the correlated lake size parameters  to 2 uncorrelated predictors, lake area and Zmax, a priori  to avoid possible overfitting.Among trophic predictors . We built 3 separate models for total zooplankton, cladoceran, and copepod species numbers. We performed stepwise model selection by Akaike information criterion (AIC) with 1000 permutation steps, using “both” as the mode of stepwise search.We used multiple linear regression models to test which environmental parameters affect species richness (n = 31) because more environmental predictors together with density data were measured in this dataset than in the Swiss dataset . Because of the large variation in zooplankton densities, data were square root transformed prior to analysis. In the null model, we included Alt, lake area, Zmax, TP, TN, ZS, Chl-a, and Cond as environmental predictors. Significant predictors were selected with the ordistep function  of the R package vegan . Here we analysed Austrian and German lakes only  using the presence–absence matrix of 54 lakes. The algorithm calculates the observed and expected frequencies of co-occurrence between each pair of species and classifies all possible species pairs as positively, negatively, or randomly associated.Bythotrephes in Austrian and German lakes (n = 31) based on stepwise model selection by AIC of multiple linear regressions . Apart from the environmental predictors previously used for the CCA, we also included here the total density of other zooplankters (square root transformed) to represent the potential prey abundance. We made a model prediction based on the 2 most important environmental predictors. We compared models with all possible combinations of linear and generalised additive model (GAM) fitting of these 2 significant predictors based on AIC and found linear fitting to be best for both predictors. Hence, we used this model in a graphical representation of the abundance distribution of the species along the 2 most important environmental gradients, based on a surface fitting. Here the surface is represented by a contour map, whereas the empirical abundance data can be illustrated with coloured symbols.We studied the effect of local environment on the abundance of Bythotrephes for the entire dataset (n = 50) to confirm the results on the entire spatial scale of our study. We used a general linear model (GLM) with a logistic function and a stepwise model selection by AIC . Zmax, Alt, lake area, ZS, Chl-a, and Cond were included in the null model.The test was repeated on the presence–absence data of Bythotrephes predation on zooplankton communities. We first carried out a redundancy analysis (RDA) on the Austrian and German lakes , in which significant predictors were selected with the ordistep function . We chose RDA over CCA because the subsequent variation partitioning is based on RDA. We carried out a variation partitioning analysis on the zooplankton community, with the significant local predictors grouped together and Bythotrephes density as the other explanatory table.We ran a variation partitioning model to compare the role of local environmental factors and the possible effect of Bythotrephes affected species richness in the lakes. We included all lakes except the 4 excluded lakes discussed earlier (n = 50) and ran a Welch’s 2-sample t-test , with the number of zooplankton species (excluding Bythotrephes) as the explained variable and the presence or absence of Bythotrephes as the grouping factor.Additionally, we tested whether the presence of Bythotrephes in the Alps, including data reported in the last 30 years. All analyses were carried out with packages MASS  and Eudiaptomus gracilis (45 lakes) were the most frequent species. Seven other species occurred in >10 lakes , whereas the other 25 species were less frequent . Bythotrephes was present in all 3 countries in 13 lakes  and 17 belonged to cladocerans. a also proved to have a significant negative effect . According to the multiple linear regression models, larger lakes at lower altitudes held more species. Altitude was a significant (negative) predictor of total zooplankton, copepod, and cladoceran richness. Additionally, lake area had a positive effect on both total zooplankton and cladoceran richness. For cladoceran richness, Chl-L. kindtii and B. longimanus, showed a positive co-occurrence  clearly separated in the lakes, with B. longirostris negatively and B. longispina positively associated with D. longispina. The 2 mesotrophic cyclopoids, Thermocyclops crassus and M. leuckarti, also showed a positive co-occurrence.The 2 large predatory cladocerans, −1, with most (90%) of the data <20 ind L−1. Chl-a and Zmax were identified as significant environmental predictors of the zooplankton communities , the repeated test with logistic GLM confirmed the positive effect of Zmax because it was the only significant predictor for the presence of Bythotrephes (p = 0.005).In our separate analysis carried out for es Table , Fig. 4.Bythotrephes, the same environmental predictors proved significant, as in the CCA model built for the whole communities . According to the results of the variation partitioning, Bythotrephes had no individual effect on the communities , and only the local environmental predictors had a significant individual effect , with a shared effect of 3%. Similarly, Bythotrephes had no significant effect on zooplankton species richness .In the RDA carried out for the communities without Bythotrephes has been reported in the Alps within the last 30 years  nor in the subset of Austrian and German lakes .The lakes varied widely in TP and environmental conditions. Trophic state, in general, had a strong effect on the zooplankton communities and was a primary structuring factor for the communities and a significant predictor of cladoceran species richness. Lake trophic state is overall an important shaping factor for zooplankton , expanding also to lower-montane regions , and has a broad geographic distribution  in our dataset.s Einsle , where is Einsle . This prB. longspina and D. longispina were typical. Among the 3 congeneric Bosmina species we found, B. coregoni was the rarest (n = 3), followed by B. longirostris (n = 8), and B. longispina was the most frequent (n = 33). The latter 2 species are frequently used in paleolimnology to track changes in trophic conditions because B. longispina is a typical species of oligotrophic waters and B. longirostris is a eutrophic species , together with a few alpine species  or specialists of oligotrophic lakes . Therefore, regarding zooplankton communities, the montane region of the Alps represents a transitional zone between lowland lakes and the alpine lakes at higher elevations. B. longimanus seems to represent the only exception and might be considered a truly montane species; it is rarely found in lakes >1200 m and is not present in lowland lakes around the Alps.Regional plankton biodiversity in the Alps is, in general, much less studied compared to northern European boreal lakes. Within the Alps, most of the available regional-scale knowledge on the diversity and its environmental constraints is from high-altitude alpine lakes above the treeline  can be avoiding fish predation. Although the spiny Bythotrephes is protected against predation by juvenile fish  in which we did not find Bythotrephes has been shown to have strong multiple effects on the zooplankton communities in invaded North American lakes. Previous works found that the appearance of Bythotrephes decreased species richness (Yan et al. Leptodora (Lehman and Cáceres Daphnia (Lehman and Cáceres Bythotrephes on the zooplankton communities in our survey. In northern Europe, Walseng et al. (Bythotrephes on crustacean zooplankton; however, their study represents a special case because it is embedded in a spatial diversity gradient of phytoplankton and zooplankton (Hessen et al. Bythotrephes was much stronger in invaded Canadian lakes than in Norwegian lakes. This information collectively suggests a possibly general difference among communities co-evolved with Bythotrephes and communities of lakes only recently invaded by the species, which should receive more focus in future research.g et al.  reportedThis work was supported by Austrian Research Foundation ; Office of the Regional Government of Lower Austria; SNF [31003A-125006].https://doi.org/10.1080/20442041.2017.1294317Supplemental data for this article can be accessed here. Click here for additional data file.


Purpose: Despite numerous studies on the effects of complementary medicine, to our knowledge, there is no study on the effects of Capparis spinosa on disease regression in non-alcoholic fatty liver disease (NAFLD) patients. We compared the effects of caper fruit pickle consumption, as an Iranian traditional medicine product, on the anthropometric measures and biochemical parameters in different NAFLD patients.Methods: A 12-weeks randomized, controlled, double-blind trial was designed in 44 NAFLD patients randomly categorized for the control (n=22) or caper (n=22). The caper group received 40-50 gr of caper fruit pickles with meals daily. Before and after treatment, we assessed anthropometric measures, grade of fatty liver, serum lipoproteins and liver enzymes.Results: Weight and BMI were significantly decreased in the caper (p<0.001 and p<0.001) and control group (p=0.001 and p=0.001), respectively. Serum TG, TC and LDL.C just were significantly decreased in the control group . Adjusted to the baseline measures, serum ALT and AST reduction were significantly higher in the caper than control group from baseline up to the end of the study . After weeks 12, disease severity was significantly decreased in the caper group (p <0.001).Conclusion: Our results suggest that daily caper fruit pickle consumption for 12 weeks may be potentially effective on improving the biochemical parameters in NAFLD patients. Further, additional larger controlled trials are needed for the verification of these results. Currently, plants and/or functional foods have been noticed for the disease control or treatment due to the ease of access and in some cases, due to fewer side effects.10 Several traditional medicinal plants are used in different areas of the world to treat metabolic disorders.12Capparis spinosa (caper) belongs to the family of Capparidaceae and is widely found in the southern area of Iran and the western or central regions of Asia.14 Caper’s root includes flavonoids, pectin, saponins, essential oils, tannins and particularly glycosinolate and glycosides as valuable biochemical compounds.16 Aqueous extract of C. spinosa showed blood glucose and lipid profile lowering effects in diabetic patients.18 Different parts of the plant, including fruits, leaves, seeds, etc., may have different effects due to various active ingredients. To our knowledge, human and animal studies have verified the positive effects of caper fruit on blood glucose in type 2 diabetic patients, and it has been used traditionally as an anti-hyperglycemic food by Iranian diabetic patients.19 Despite numerous studies about the beneficial effects of caper aqueous extract consumption on disease control in type 2 diabetic patients, no study, to our knowledge, has evaluated whether daily caper fruit consumption as a food additive can be effective in disease regression or not. Moreover, there is no human trial in this field.Non-alcoholic fatty liver disease (NAFLD) is one of the increasing metabolic disorders which has a direct link with obesity, glucose intolerance, inflammatory pathways and dyslipidemia.The purpose of this study was to assess the effects of caper fruit consumption, as an Iranian Traditional Medicine product, change in biochemical parameters include serum lipids, liver enzymes and disease severity as primary outcome, and change in anthropometric or nutritional parameters as secondary outcome in NAFLD patients after 12 weeks. We hypothesized that daily caper fruit pickle consumption leads to the improvement in anthropometric measures, liver function tests, lipid profile and grade of fatty liver in patients with NAFLD.2) of 25- 35, and willingness to consume caper fruit pickle as food additive. The exclusion criteria were any known allergies to caper, cigarette smoking, pregnancy or pregnancy planning in the next 6 months, breastfeeding, history of stroke, cirrhosis, viral hepatitis, liver obstructive diseases, heart disease or thyroid disorders, diabetes, dyslipidemia, intake of anti-diabetic or lipid lowering drugs, as well as anticoagulants, intake of medications that could affect body weight and/or energy expenditure, following vegetarian or weight-loss diets up to 2 months before the beginning of the study. Caper has interaction with coagulopathies due to involvement in the coagulation pathways. Then, we excluded all the patients with coagulopathy diseases.20In total, 44 NAFLD patients were selected between March 2016 and April 2017 from among patients with NAFLD diagnosis who were attending the Metabolic Disease Research Center and Valie-Asr Hospital, Zanjan University of Medical Sciences, Zanjan, Iran. The inclusion criteria were as follows: patients aged 12-80 y, BMI  or control group (n=22) . Caper fIn the beginning, 24-hour dietary recall forms were completed and analyzed by the N4 software . Anthropometric measures were recorded at the beginning and end of the intervention in both groups.Blood samples of all patients were taken from the antecubital vein after 10-12 h fasting, at baseline and at 12 weeks for biochemical measurements. After centrifugation for 15 min (2500 g), the serum samples were frozen simultaneously and stored at -80 °C until analyzed. Lipid profile and liver enzyme tests were measured by an enzymatic method  using Liasys autoanalyzer.21Liver ultra-sonography (US) was performed by Siemens brand Sonoline G50 series - 3.5e5 MHz probe made in Germany. Liver steatosis was classified through sonographic echogenicity of liver as: 1) normal: echogenicity, the same as renal cortex; 2) grade I: mild steatosis that increased liver echogenicity with visible diaphragmatic and periportal echogenicity; 3) grade II: moderate steatosis, increased liver echogenicity with imperceptible periportal echogenicity, without obscuration of diaphragm; 4) grade III: severe, steatosis; increased liver echogenicity with imperceptible periportal echogenicity and obscuration of diaphragm.22 the number of participants needed to detect this difference was 22 in each group. By considering the dropout rate of 10 percent, we set the enrollment target of 25 subjects.In the present study, power of 80% with a two-sided test with α=0.05 (type I error) and mean difference of 25 IU/L for changes in ALT levels were considered to determine the sample size. On the basis of means, as stated in the previous studies,Numeric variables were expressed by means ± SD. The level of significance was set at P < 0.05. Statistical analyses were accomplished with IBM SPSS Statistics software . We used Kolmogorov-Smirnov Test to assess the normal distribution of the data. Independent sample t-test was used to assess the differences in mean values of the variables between the two groups. The comparison of mean values of variables before and after the intervention in each group was examined by paired t-tests. For non-normally distributed data, appropriate non-parametric test was used. The comparison of mean change in each parameter during the trial was assessed by ANCOVA test, adjusted for baseline measures as covariates.Dietary intake and physical activity had no significant difference between the two studied groups (p>0.05). Baseline levels of AST, HDL.C and LDL.C were significantly different between the two groups (p<0.001). 72.7% of the participants in the caper and 59.1% of them in the control group were female. Gender distribution between the two groups were not significantly different (p=0.4). Mean age of the participants was 40.32±10.04 y in the caper and 45±10.03 y in the control group, with no significant difference between the two groups. Weight and BMI were significantly decreased in the caper (p<0.001 and p<0.001) and control groups (p=0.001 and p=0.001), respectively.Serum ALT levels were significantly decreased at the end of the study in the caper and control groups . Also, serum AST levels decreased in both of the studied groups . Serum TG, TC and LDL.C were significantly decreased only in the control group  .Adjusted to the baseline measures, the mean change in serum ALT and AST concentrations was significantly higher in the caper than the control group . The mean change in serum of LDL.C levels was significantly higher in the control than the caper group, adjusted for the baseline measures (p=0.03) .At the end of the study, grade of fatty liver was significantly different between the two studied groups (p <0.001). Improve on the stage of NAFLD was significantly higher in the caper group than the control group, adjusted for the baseline measures .10 To our knowledge, there is no concise therapy for NAFLD treatment. Thus more studies on dietary supplements and/or functional foods are needed for prevention or regression of NAFLD. Dietary supplements or functional foods which have beneficial effects on insulin resistance and blood glucose control, as well as antioxidant and anti-inflammatory activity, may be effective in the NAFLD treatment. On the other hand, many patients tend to use traditional medicine and its products for disease treatment. The present study has shown that weight loss, as the routine method for NAFLD treatment, was more pronounced in the caper than in the control L. Furthermore, a mean difference of change in serum ALT and AST concentrations was higher pronounced in the caper than the control group. Also, disease severity was significantly decreased in the caper group, adjusting for the baseline measures. Results showed that caper fruit pickle consumption in the diet can show fatty liver progression. Our results are in agreement with the previous study showing the weight-reducing effect of caper.23Although the standard method for NAFLD treatment is weight loss, drug and supplement trials have shown inconclusive results.24 The anti-hyperglycemic property of caper is due to the reduced absorption of carbohydrates from the small intestine, increased glucose uptake in the tissue, glucose-depletion in the liver, and the regeneration or protection of the beta cells of the pancreas.21 Caper is known as an herb with antioxidant properties.16 In addition to the effect of alcoholic and aqueous extract of caper on lipid profile, it is shown that it has hepato- and nephroprotctive effects against toxins.25 The most useful effects of caper fruit pickle on health are due to high bioactive compounds, especially polyphenols.26 According to the ITM opinion, caper has an important role in spleen performance, excretion of toxins, as well as excess “Soda” and “Balgham”, from the liver.27 One study reported that “Balgham”, as a component of quadruple humors, has a relationship with lipid profile.28Caper fruit, as an ITM herb, has a bitter taste which is not favored by consumers. Therefore, we prepared its pickle for patients’ convenience. Numerous studies are available assessing the effect of caper components, including fruit, seed, stem, leaf and the whole of the plant in the treatment of several other diseases such as metabolic syndrome and type II diabetes.29 One study has shown that Capparis spinosa as an antidiabetic plant is capable to reduce blood glucose in streptozotocin-induced diabetic mice.30 In another study with the aim of evaluaaing the hepatoprotective effect of C.spinosa, ethanolic root bark extract of this medicinal plant was evaluated in a mouse model of CCl4-induced hepatotoxicity. Serum liver enzymes were reduced in the C-spinosa supplemented group with ethanolic extract of C.spinosa.31 In contrast, another study showed no significant effect of aqueous extract of caper fruit on liver enzyme tests in patients with type II diabetes.19 Serum liver enzymes were in normal range in the mentioned study, which may be one of probable reasons for this result. On the other hand, the effect of caper on reducing serum glucose and lipid profile is dose-dependent manner. Therefore, inconclusive results of the previous studies may be due to the effective dose. Also, caper fruit may have various components and/or amounts of polyphenols in different regions depending on the cultivation soil. Serum levels of lipid profile and/or liver enzymes shown inconsistency in various studies. These differences lead to various results.After 12 weeks of daily caper fruit consumption, ALT and AST reduction were higher compared with the control group. One study showed the same results. Streptozotocin induced diabetic rats were treated with the caper root extract for four weeks. Serum glucose level was decreased without any change in serum insulin level. Also, liver enzyme tests were significantly decreased in the caper extract-fed group.32 Cellular necrosis occurred in the liver, pancreas and kidneys of diabetic rats, but changes in the diabetic treated group with caper fruit extract were lower than the control group. Similarly, the serum levels of creatinine, liver enzymes, and other factors decreased. Another study assessed the anti-inflammatory properties of caper in the cell line. They showed that caper fruit inhibits cytokine gene expression, including IFNγ, IL-17 and IL-4. They concluded that the beneficial effects of caper fruit are due to saponins, flavonoids and alkaloids.33One study assessed the effects of the caper fruit extract on the serum levels of ALT, AST, ALP, bilirubin, creatinine, urea and uric acid, as well as histo-pathologic properties of the liver, kidneys, pancreas and stomach in a rat model of type 1 diabetes.To our knowledge, this is the preliminary RCT aimed to assess the effect of caper fruit pickle consumption on the hepatic lipid accumulation, serum lipid profile and liver enzyme tests in the patients with NAFLD. Caper has more benefits on lipid accumulation in the liver and grade of fatty liver. However, a study with more sample size and longer duration is needed before reaching conclusive results. There are some limitations to our results; firstly that NAFLD was diagnosed by biochemical and ultra-sonographic findings in our patients, which is not able to distinguish between simple fatty liver and NASH. Fibroscan, as a precise method for detection and staging of the liver diseases, is more expensive. Liver biopsy is the gold standard for NAFLD diagnosis, but it is an invasive and expensive method. Secondly, we did not match the patients according to their NAFLD at enrollementwe. We suggest that patients could be matched according to the grade of the fatty liver disease in the oncoming studies. In future studies, precise control of dietary intake and physical activity level is suggested. Also, caper components should be analyzed in future. Another study with the higher levels of these enzymes is needed to assess the effects of caper fruit on NAFLD progression. Insulin resistance, inflammatory and oxidative pathways should be assessed to determine the involved signaling pathways.The present study showed that caper fruit as an herbal drug may be effective in reducing the NAFLD progression because of natural compounds such as comarin and flavonoids. Thus, this fruit has medicinal properties. However, more studies are needed to obtain concise results.Authors are very thankful to all participated patients. Fund of the present study was provided by Vice chancellor for research, Tabriz University of Medical Sciences, Tabriz, Iran.The present study was approved by the Ethical Committee of Tabriz University of Medical Sciences, Tabriz, Iran (TBZMED.REC.1394.650).The authors declare that there is no conflict of interest.


Therefore, aggressive weight support and gait training at an early stage using a robotic device are helpful, and robotic intervention should be applied according to the patient's functional level and onset time of stroke.The purpose of this study was to critically evaluate the effects of robot-assisted gait training (RAGT) on gait-related function in patients with acute/subacute stroke. We conducted a systematic review of randomized controlled trials published between May 2012 and April 2016. This search included 334 articles . Based on the inclusion and exclusion criteria, 7 studies were selected for this review. We performed a quality evaluation using the PEDro scale. In this review, 3 studies used an exoskeletal robot, and 4 studies used an end-effector robot as interventions. As a result, RAGT was found to be effective in improving walking ability in subacute stroke patients. Significant improvements in gait speed, functional ambulatory category, and Rivermead mobility index were found with RAGT compared with conventional physical therapy ( Stroke is a common disease . In mostGait impairment is one of the most important problems after stroke and is associated with activities of daily living and mobility issues . TherefoRobot-assisted gait training (RAGT) for patients in the acute/subacute stage who are nonambulatory is effective at reeducating motor control function through repetitive training of a specific task ; RAGT prTherefore, the aim of this systematic review was to investigate the effects of RAGT on acute/subacute stroke. The specific goals included identifying the effects of RAGT using assessment tools associated with gait and gait-related function in patients with acute/subacute stroke.This study collected data from Cochrane, Embase, and PubMed databases from May 2012 to April 2016 to analyze the data of the last 5 years and to obtain the latest information on RAGT. We searched the data for a specific time frame to provide a recent basis for the effectiveness of RAGT for stroke patients with a specific onset of illness (subacute phase). The authors selected keywords based on the population, intervention, comparison, and outcomes (PICO) model and MeSH terms, and the search algorithm was stroke AND (robot OR robotics) AND  AND rehabilitation. As a result, 51 articles from Cochrane, 175 articles from Embase, and 108 articles from PubMed were found. Four professional physical therapists analyzed the title and abstract of the articles 4 times, based on the inclusion and exclusion criteria, and 7 articles were finally selected after analyzing the full text . AnotherStudies conducted on adult stroke patients aged ≥ 18 yearsStudies conducted on patients with acute/subacute stroke (within 3 months after onset)Studies that included RAGT in combination with physiotherapy  versus physiotherapy  as the intervention method for regaining and improving walking ability after strokeStudies that used measurement tools associated with gait and gait-related functionRandomized clinical trialControl group which received conventional rehabilitation therapyStudy using an upper-limb robot as an intervention methodStudies that compared different types of robotsStudies on other interventions combined with RAGT except for usual care for regaining and improving walking ability after strokeStudies written in languages other than EnglishStudies for which the full text was not foundThe selected papers were analyzed with regard to methodological quality using the PEDro scale. The PEDro scale contains the following 11 items: eligibility, random allocation, concealed allocation, baseline comparability, blinded subjects, blinded therapists, blinded raters, key outcomes, intention-to-treat analysis, between-group comparison, and precision and variability. The official score of the papers described in the electronic database was used. Five professional physical therapists and researchers with at least 5 years of clinical experience evaluated each item for quality. After scoring according to each item, the authors were cross-checked and measured the score in the controversial items after discussion.The authors systematically reviewed general characteristics, such as the number of subjects, sex, age, diagnosis, side of hemiplegia, time after stroke, intervention method, measurement tools for gait and gait-related function, and characteristics of the studies associated with the results. d was applied for effect size calculation by using the difference between 2 means divided by the pooled standard deviations. First, pretest, posttest, and follow-up between-group comparisons were analyzed. Second, intragroup comparisons were analyzed for pretest versus posttest, posttest versus follow-up, and pretest versus follow-up results. Effect sizes ranging from 0.2 to 0.5, from 0.5 to 0.8, and from 0.8 to infinity were defined as small, medium, and large, respectively [Cohen'sectively .Quality evaluation was performed based on the PEDro score suggested for evidence-based review of stroke rehabilitation. The final score was settled when 3 of the 4 authors reached agreement after repeated review and analysis. All 7 studies conducted randomized trials, and the PEDro score ranged from 7 to a maximum of 10, with a mean of 8.28 .The authors analyzed the therapeutic effects of RAGT by reviewing the 7 articles. Among 220 subjects, 112 received RAGT and 108 were included in the control group. The male participants comprised 61.05% , and the patients with left and right paralysis comprised 53.85% and 46.15%, respectively, of the study subjects. The mean progression time after the onset of stroke was between 16.1 and 116.2 days, all of which were included in the acute/subacute stage, and the age range of the subjects was 40.4 to 80 years .The most commonly used assessment tools for gait and gait-related function included the TWT, which is used to assess walking speed or gait velocity; FAC, which was used in 5 studies; RMI, which was used in 3 studies; and FIM and BI, which were used as assessment tools in 2 of the 7 studies. The BBS, 6 MWT, and TUG test were used as assessment tools in 1 of the studies associated with gait .The period of RAGT ranged from 2 to 5 weeks, with varied intervention durations ranging from 400 to 960 minutes. Five studies –17, 19  of the studies used Lokomat as an intervention method , 17, 19,2.85% of p < 0.01, medium effect size) and the control group  showed significant improvements in gait speed after 10 weeks of intervention and at 24 and 36 weeks during the follow-up period as compared with baseline values but found no significant difference between the groups . In addition, both groups showed significant improvements in FAC , BBS score , RMI , and TUG time, but no significant difference was found between the groups . Taveggia et al. [p < 0.05, large effect size) and FIM  after 5 weeks of intervention and at follow-up after 17 weeks, but no significant difference was found between the groups (posttest: median effect size). In other studies that used other robots as intervention methods, Morone et al. [p = 0.001, large effect size), BI , and RMI  between the RAGT group with poor motor function and the control group alone. This difference remained significant after the follow-up period. During the follow-up period, significant differences were found in FAC , BI , and RMI  between the RAGT group with poor motor function and the control group. Hesse et al. [p < 0.001). In addition, the RAGT group showed substantial improvements in FAC, gait speed, and RMI after the intervention in the between-group comparison; the improvement in FAC continued after follow-up. Dragin et al. [p < 0.05, small effect size) and that the gait speed in the RAGT group remained significant after the intervention and follow-up . In the between-group comparison, gait speed (large effect size) and BBS score  remained significant after 4 weeks and only gait speed remained significant after 6 months of follow-up (large effect size). In a study by Ochi et al. [p < 0.01) and FIM (p < 0.01) mobility score, and the RAGT group showed significant improvement in FAC in the between-group comparison (p = 0.02).In a study that used Lokomat as an intervention method, Chang et al.  reporteda et al. , in anote et al.  assessede et al.  conductei et al. , in whicThe purpose of this study was to investigate the effects of RAGT on gait and gait-related function and to investigate up-to-date evidence for an effective robotic intervention method for patients with acute/subacute stroke.Recent evidence suggests that intensive stroke rehabilitation is effective when performed in the early stage and should be task-specific, with multisensory stimulation , 22. ThiA common advantage of RAGT is that it partially or totally supports body weight bearing and allows high-intensity, complex gait cycle training for nonambulatory patients, which is difficult for the therapist to achieve alone. Body weight support through a robotic device facilitates gait recovery in nonambulatory patients . In addiRobotic use for walking rehabilitation can be classified according to the method applied to the body. For instance, “exoskeletal robots” move hip, knee, and ankle joints and apply control during the gait cycle, whereas “end-effector robots” move only the feet and are often placed on a support (footplate) that simulates the stance and swing phases . Of the Lokomat, which is generally used in gait rehabilitation, is a robot-assisted gait device combined with a harness-supported body weight system, used in combination with a treadmill. The legs of the robot are controlled by a computer, whereas the hip and knee joints are fixed on an exoskeletal device for training , 33. TheA Cochrane review in 2013 analyzed 23 randomized trials that were conducted among 999 stroke patients and reported that patients who receive electromechanical-assisted gait training in combination with physiotherapy after stroke were more likely to achieve independent walking than those who received gait training without these devices . In addiThis review has several limitations. It included a small number of studies (and subjects). Future review studies should include a qualitative analysis of the frequency and intensity of interventions, including more studies on subacute stroke patients. Further studies are needed to demonstrate the effectiveness of RAGT according to the functional level of stroke patients in not only the subacute phase but also the chronic phase.


This study aimed to evaluate the therapeutic value of adalimumab (ADA) for fistula in Crohn's disease (CD).  A computerized search of electronic databases, including PubMed, Web of Science, Embase, Google scholar, and the Cochrane Library from 2000 to October 2016, was performed. Randomized controlled trials (rcts) or nonrandomized controlled trials (n-rcts) were included in this article to evaluate the role of ADA in the management of fistula in CD. The methodological index for nonrandomized studies  was used to assess the quality of every study.  Overall, seven studies and 379 patients comforted to the inclusion criteria of this meta-analysis. The result showed that 36% (95% CI: 0.31–0.41) of patients with complete fistula closure and 31% (95% CI: 0.031–0.61) of patients with partial response were received in CD with ADA treatment.  We concluded that ADA is effective and safe for the treatment of fistula in CD according to current evidence. Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract resulting in inflammation, stricturing, and fistula secondary to transmural inflammation . The conDifferent drugs have been used to treat the perianal fistulizing disease. One randomized trial reported that antibiotics (metronidazole and ciprofloxacin) have importantly improved the symptoms but rarely induce fistula healing completely . ImmunosClinical trials were researched through PubMed, Web of Science, Embase, Google scholar, and the Cochrane Library and used the following keywords: tumor necrosis factor, anti-TNF, TNF, adalimumab, Crohn's disease, fistula, randomized, randomly, and clinical trials between 2000 and October 2016; finally, seven studies were selected, and all these studies in this meta-analysis were written in English. When multiple reports describing the same population were published, the most recent or complete report was used.The inclusion criteria are the following: (1) study types—rcts, n-rcts, case-control study, and cohort study. (2) Study object: definite diagnostic criteria  in patients with CD who have fistula. (3) Intervention measures—a test group to give any ANA treatment of the dosage, whether to set the control group is not limited, if the control group is set, the intervention measures are antibiotics such as metronidazole and ciprofloxacin; immunosuppressive agents such as azathioprine (AZA), 6-mercaptopurine (6MP), and methotrexate (MTX); and immunomodulators such as antagonists of tumor necrosis factor (TNF)-alpha (infliximab (IFX)), but not surgery or stem cells. (4) Outcome—assessment of efficacy of fistula closure and safety treated with ADA.The exclusion criteria are the following: (1) studies not accessible to full research data, review, case report, letter, and editorial; articles about children or pregnant woman were also excluded, (2) CD patients without fistula or not receiving ADA treatment, and (3) the same center repeated in the same study.Data from the included studies were extracted and summarized independently by two of the authors (Ming Chen and Yin-mei Fu). Two authors were both blinded to the writers, the institutions, and the journals of each article. Each disagreement had been solved by the senior author (Ai-jun Liao).Seven studies were included in the meta-analysis, most of which were nonrandomized. Few validated instruments are available to determine the methodological quality of observational or non-randomized studies, either from the reader's perspective or for the purpose of the meta-analysis. The methodological index for nonrandomized studies   was usedQ test to assess the heterogeneity of the results of the study and I2 for the quality analysis of the heterogeneity. Q and I2 statistics were used to perform the heterogeneity across trials. I2 values ranged from 0 to 100% . P value less than 0.1 was considered significant heterogeneity. If heterogeneity existed, a random effect model was used to assess the overall estimate; otherwise, a fixed effect model was chosen.All analyses were performed using Stata software . We used a Sensitivity analyses, which were assessed by using high-quality articles, were performed to explore the potential sources of heterogeneity and to eliminate the effect of low-quality articles. Funnel plots were used to screen for potential publication bias.There were 292 relevant articles through PubMed, Embase, Web of Science, the Cochrane Library, and Google scholar. EndNote software was used to eliminate duplicate documents, and the authors considered ten studies after full-text review and eventually included seven studies in the meta-analysis , 19, 20 It is important to assess complete fistula closure by adalimumab treatment in Crohn's disease . The triThe first study by Hinojosa et al.  was a prThis study by Colombel et al.  was a phThe CHOICE trial was written by Lichtiger et al.  to evaluThe other trial by Dewint et al.  was a raThe fifth study by Castaño-Milla et al.  was a reThe sixth study by Panaccione et al.  was a phThe seventh study by Rizzello et al.  was to eI2 = 26.5%, P = 0.000.1)  .In clinical practice, not every patient can achieve complete closure fistula, so goals for partial response are also important. Three studies , 15, 16 There was a multicenter, prospective, open-label, observational, 52-week study by Hinojosa et al.  PatientsThe other trial by Dewint et al.  was a raThe third study by Castaño-Milla et al.  was a reI2 = 92.7%; P = 0.000, <0.1). For high significant heterogeneity, the authors made sensitivity analysis that the trial by Hinojosa et al. [I2 = 94.7%; P = 0.001, <0.1). So authors guessed that fewer trials brought about heterogeneity.There was clearly high significant heterogeneity in the partial response rate of fistula in CD with ADA treatment using a fixed-effect model; authors observed statistical significance  . At the same time, ADA did not also increase the risk of common adverse events by this article [We analyzed the incidence of adverse events (AEs). Five trials had reported the safety of ADA, and the AEs included infections, injection site reactions, abdominal tenderness, nausea, flatulence, nasopharyngitis, pharyngitis, and headache. The appearance of AEs during these two trials , 15 is i article .The seven studies were drawn by software Stata12 as a funnel plot which showed dissymmetry . The EggCD is a group of idiopathic chronic inflammatory intestinal disease that can damage any part of the gastrointestinal tract, mostly the ileum and colon. The prevalence of CD appears to be higher with time . FistulaAccording to our knowledge, this is a meta-analysis of the available published rcts or n-rcts to examine therapeutic value adalimumb on fistula closure in Crohn's disease. For the complete closure rate of ADA treatment on CD and fistula, we found that the heterogeneity across studies was not been found. In an overall analysis, the efficacy of complete fistula closure in CD by ADA treatment was 36%. It was not clear to examine the efficacy of the partial response of adalimumab on fistula healing in Crohn's disease. The few patients included may be the key to high heterogeneity about meta-analysis of efficacy of partial response of fistula healing in CD with ADA. The reasons, from a professional point of view, maybe were treatment time and fewer patients included which could not be proved. So more studies should be required to confirm those conclusions.In addition to side effects, the rates of adverse reactions were similar in the two groups. However, these data should be noticed because of several limitations. Patients in trials might not represent patients seen in clinical practice, and follow-up might not be sufficiently long for some serious events such as malignancy to occur .In the analysis, statistical heterogeneity was found in AEs; we considered that this heterogeneity may emerge for three reasons which are the number of the patients enrolled, the induction/maintenance doses for ADA among the trials, and treatment time.There are also several limitations; we only searched the English language literature in this meta-analysis. Therefore, it is possible that they may have missed potentially relevant trials in the non-English language literature. We did not assess the factors that resulted in heterogeneity, and all studies were not rcts and a number of studies are few. However, all studies included were of high quality.In summary, our findings update the previously published studies and evaluate the clinical efficacy and safety of ADA in CD patients who develop loss of response to IFX or are naive to biological treatment with perianal disease. Treatment benefit should be weighed against side effects. Although ADA for CD with fistula was largely safe, it was necessary to notice AEs. Due to the limitations of this meta-analysis, more prospective randomized trials are needed to confirm the results, especially for partial response of ADA treatment on CD with fistula. Long-term therapeutic efficacy and adverse reactions by ADA should also be concerned.