The individual's experiences of stress as well as constitutional factors, including high neuroticism and female gender, are known determinants for migraine. The present aim was to further elucidate factors of personality and stress, including life events, in relation to gender in migraine.A cross-sectional study was performed on 150 persons, 106 women and 44 men, suffering from at least two migraine attacks a month. All obtained a doctor-defined migraine diagnosis based on a structured face-to-face interview concerning their health situation and current and prior stress. All of them also answered validated questionnaires regarding personality traits (SSP), life events, and perceived ongoing stress.The personality trait inventory showed high mean scores for stress susceptibility and low mean scores for aggressiveness and adventure seeking, both for women and for men, as well as high mean scores for psychic and somatic anxiety in women. Stress susceptibility, the overall most deviant trait, correlated strikingly with current level of stress in both sexes. In women, stress susceptibility also correlated strongly with experiences of negative life events. Tension-type headache, anxiety, and depression were approximately twice as prevalent in women compared to men.The present study confirms previous research, showing that stress is an important factor in migraine. Stress susceptibility, life events, and concomitant psychosomatic illnesses should be considered important when evaluating individuals with migraine, and gender aspects need to be taken into account. Migraine is one of the most common neurological disorders ,2. Both The importance of personality traits in migraine has been widely debated. Claims have been made that migraineurs display increased neuroticism and anxiety and are anti-aggressive, but complex interactions regarding personality traits need to be considered . It may Women and men display differences in the prevalence of many disorders that could be considered to be stress-related , includiIn view of the complexity of the roles of personality, stress, life events, and gender in individuals with migraine, the aim of the present study was to examine and describe these aspects in a cross-sectional study of 150 migraineurs.The study population comprised 150 consecutively enrolled adults (18 years of age and above), 106 women and 44 men, with moderate to severe migraine, defined as two or more migraine attacks a month. The subjects were recruited through advertisements in the local daily newspaper. All participants were interviewed by K.H. and C.M. A medical history was recorded regarding headache characteristics, stress as a trigger for migraine, concomitant illnesses, and general well-being, followed by a neurological examination performed by one of the researchers, C.M., a specialist in neurology, thus ensuring a uniform mode of data collection. The migraine diagnosis was confirmed on the basis of the International Classification of Headache Disorders . The stuIn connection with the interview, all participants answered questionnaires, which are described below, on a computer. Complete responses were obtained from all participants. The time required to answer these questionnaires was approximately one hour. All answers were directly transferred into the Statistical Package for the Social Sciences 18.0 (SPSS) program for further analysis.Somatic trait anxiety ; 2) Psychic trait anxiety , 3) Stress susceptibility ; 4) Lack of assertiveness ; 5) Impulsiveness ; 6) Adventure seeking ; 7) Detachment ; 8) Social desirability ; 9) Embitterment ; 10) Trait irritability ; 11) Mistrust ; 12) Verbal trait aggression ; and 13) Physical trait aggression . Each item is a statement, to which the participant responds by choosing an alternative on a four-point scale: ‘does not apply at all’, ‘applies to a certain extent’, ‘applies fairly well’, and ‘applies completely’. The SSP inventory results were standardized to normative data. The normative data were drawn from a random sample of the Swedish population, with the normative average for each trait defined as 50 and with a standard deviation of 10. Factor analysis for the instrument , Uppsala University, Sweden, was used . Forty-tFeeling of meaningfulness regarding your home situation and your social situation; Factor 2: Mental symptoms; Factor 3: Subjective level of stress; Factor 4: Quality of sleep; Factor 5: General health; Factor 6: Difficulties with concentration and memory; Factor 7: Ability to prioritize recovery from stress; Factor 8: Ability to cope with stress. The reliability of these eight components was tested using the Cronbach method, which yielded alpha values between 0.730 and 0.897 (Appendix).To identify groups of the 43 stress-related items, a factor analysis with Varimax rotation was conducted on the current responses to the 43 items answered on a VAS scale. The eight factors with the highest eigenvalues were chosen to represent a measurement of current stress, all of which had eigenvalues above 1.0. These factors covered 29 of the 43 stress-related items (Appendix). Our designations of these factors were as follows and are listed in order of magnitude of their eigenvalues: Factor 1: As a measure of stress in the long-term, life events were evaluated. These were separated into events that had occurred during childhood/adolescence and during adulthood. The respective periods were defined by an age limit of 18 years. The instrument used ,40 consit-test or the Mann–Whitney test, depending on the distribution and sample size of the variables. Covariation was analyzed using correlation analyses, and the result was expressed as the Spearman's rho coefficient. Factor analysis was performed by means of principal components analysis with Varimax rotation. The number of latent variables was determined by using eigenvalues above 1.0 and scree plot analysis. Cronbach's alpha was used as a measure of the reliability of each component. All analyses were performed with SPSS 18.0 software. The significance level was uniformly set at 0.05, two-tailed test.Differences in proportions were analyzed using the chi-square test. Mean differences were examined using either the The distribution of participant age at inclusion is shown in 5-year intervals in Migraine frequency, time since onset and age at onset of migraine, presence of aura and associated symptoms, pain degree, chronicity of symptoms, and menstrual correlation are presented in P < 0.001 (Z = 3.7), Mann–Whitney test.Most notable gender differences, with up to double the frequency in women compared to men, were: associated nausea and osmophobia, tension-type headache, anxiety, and depression. Gender differences were seen also in age at migraine onset . The perPersonality traits were analyzed by gender and are shown in A factor analysis of our data on personality traits yielded a neuroticism factor very similar to that of the normative data of the SSP instrument , with soDetails of event categories rated as having had a ‘strongly negative’ impact are presented by gender in n = 57) and men (n = 24) from our study population, it appears that our migraineurs had experienced significantly more events—about twice as many. The respective ratios  and men: 1.9 (P = 0.015); ‘strongly negative’ childhood/adolescence events, women: 2.4 (P = 0.017) and men: 1.5 (P = 0.598); ‘any’ adulthood event, women: 2.0 (P < 0.001) and men: 2.6 (P < 0.001); ‘strongly negative’ adulthood events, women: 3.4 (P < 0.001) and men: 2.2 (P = 0.139).The life events reported in the present study were also compared to those of a healthy control group (45 women and 30 men) presented in another study from the same time period and geographical region . When anr et al. ) for womA gender-based correlation analysis was performed to discern interdependence between personality and stress as measured by life events or as current stress according to our CEOS instrument. For this purpose we selected the overall most deviant personality trait—stress susceptibility—which was compared to scores for negative life events and to factors of current stress in the present study, respectively: correlation analysis (Spearman) between stress susceptibility scores and number of life events revealed that these parameters were correlated in women, independent of the severity of the life events or the period in life in which they occurred . In men,The aim of the present study was to elucidate factors of personality and of past and on-going stress in migraineurs and the gender dependence of these factors. With regard to personality, we found that stress susceptibility was the overall most deviant trait. Women displayed significantly elevated scores also for the anxiety traits of the neuroticism cluster, and both sexes scored significantly lower for traits of aggression and adventure seeking than normative data. These profiles are in concordance with previous findings on personality traits in migraineurs ,24. RegaApart from traits of neuroticism, we found low average scores for traits of aggression and for adventure seeking in both sexes in the present study, which is in agreement with early data by Wolff, who suggested that migraineurs repress strong emotions, in particular aggression . It is pPrevious research speaks strongly in favor of the negative influence of stress on migraine ,5,7,8,10Interestingly, we found that our measurements of current stress were highly correlated with scores for the most deviant personality trait found, stress susceptibility. Intuitively, this appears logical, but we have not found any reference to this correlation in previous personality studies regarding migraine. It has been reported that migraineurs are not exposed to external stress to a greater degree than comparable controls , which wRegarding life events, obvious gender differences were seen in the present study. Overall, women reported approximately three times more experiences of strongly negative events. When separated by individual event category, higher female rates for such experiences were reported in all 32 categories, reaching statistical significance in 12 of them. These clear gender differences may reflect both differences in life situations for women and men and gender-dependent differences in how the events were perceived. For example, it is possible that life events related to the support of close relatives or friends are more negative for women because they face greater expectations to provide care. On the other hand, it seems reasonable that gender differences in perception of stress could explain why the women more often rated life events concerning their own disease, or the death of a close relative or friend, as having a strong negative influence. It is therefore possible that women are more sensitive to all kinds of stress. This is indicated by several studies showing that women experience more anxiety and depressive disorders, particularly in relation to different kinds of long-lasting perceived stress e.g. in fibromyalgia—another pain disorder that also is found to be related to stress and negative life events ,47,48. CIt is well documented that migraine is concomitant with psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder ,19,49. IThe number of male participants in our study was more limited compared to the number of females, despite special efforts to recruit men. Hence, low statistical power may have led to lack of detection of correlations in the male group as well as to detection of gender differences. Due to our mode of recruitment via advertisements in the local press, selection factors may also have influenced our results. Given its cross-sectional design, the study is descriptive in nature, and thus drawing conclusions about causality is precluded. Another weakness is the lack of a control group. Regarding life events, a healthy, age-matched control group from another study provided a possibility to compare our data, as described. With respect to personality we used normative data provided in the SSP instrument. Our own factor analysis of the SSP results yielded a profile similar to that described in the instrument, strengthening the validity of the instrument in our setting.The present study confirms previous research showing that stress is an important factor in migraine. It indicates that high stress susceptibility is characteristic for migraine sufferers, and that stress susceptibility correlates with the individual's level of stress. Clear gender differences were found in personality traits and in the number of stressful life events, in particular those rated as strongly negative. Furthermore, anxiety, depression, and tension-type headache were twice as frequent in women. We conclude that stress susceptibility, life events, and concomitant disorders, especially of psychiatric nature, ought to be considered when investigating and treating individuals with migraine.


Internet addiction (IA) is considered as one of behavioral addictions. Although common neurobiological mechanisms have been suggested to underlie behavioral addiction and substance dependence, few studies have directly compared IA with substance dependence, such as alcohol dependence (AD).We compared patients with IA, AD, and healthy controls (HC) in terms of the Five Factor Model of personality and with regard to impulsiveness, anger expression, and mood to explore psychological factors that are linked to aggression. All patients were treatment-seeking and had moderate-to-severe symptoms.The IA and AD groups showed a lower level of agreeableness and higher levels of neuroticism, impulsivity, and anger expression compared with the HC group, which are characteristics related to aggression. The addiction groups showed lower levels of extraversion, openness to experience, and conscientiousness and were more depressive and anxious than the HCs, and the severity of IA and AD symptoms was positively correlated with these types of psychopathology.IA and AD are similar in terms of personality, temperament, and emotion, and they share common characteristics that may lead to aggression. Our findings suggest that strategies to reduce aggression in patients with IA are necessary and that IA and AD are closely related and should be dealt with as having a close nosological relationship. Internet addiction (IA) is considered a behavioral addiction , and behThe relationship between AD and aggression is well known. Acute alcohol use is related to about a half of all violent crimes and sexual assaults, and it increases the risk of domestic partner violence . SimilarAlthough it is evident that IA and AD are associated with aggression, aggression itself is moderated by a complex psychological process. Anger is one of the emotional components of aggressive behavior when it is expressed in a destructive way . ImpulsiTherefore, we compared patients with IA with those with AD in terms of psychological factors that could lead to aggressive behaviors, such as anger, impulsivity, and personality characteristics from the Five Factor Model. We hypothesized that if IA and AD shared common characteristics linked to aggression, patients in both groups would show high levels of anger expression, impulsivity, and neuroticism and a low level of agreeableness compared with healthy control subjects. Linking IA with AD by showing shared characteristics may help to clarify the nosology of IA which has been controversial since its development.We enrolled 30 patients diagnosed with IA , 30 patients diagnosed with AD , and 30 healthy controls . All patients were treatment-seeking, visiting our clinic complaining of compulsive Internet use, or having alcohol-related problems. We restricted enrollment to male patients and healthy controls because males have a higher prevalence of problematic Internet use than females do ,16. PatiPatients with IA were assessed using the standardized Korean version of Young's Internet Addition Test (IAT) ,18. We rAD was diagnosed using the Structured Clinical Interview for DSM-IV (SCID) . The AlcThe SCID was used to identify past and current psychiatric illnesses. Of the 30 patients diagnosed with IA, 5 fulfilled the DSM-IV criteria for depressive disorders and 2 fulfilled them for anxiety disorders. All patients with IA used the Internet primarily for online gaming. HCs were recruited from the local community and had no history of psychiatric disorders. Subjects were enrolled in the AD and HC groups if they used the Internet less than 2 h per day. All patients were drug-naïve. The Beck Depression Inventory (BDI)  and BeckPersonality was assessed using the short form of the Korean version of the NEO Personality Inventory-Revised (NEO-PI-R) ,26. The Impulsivity was measured using the Korean version of the Barratt Impulsiveness Scale-Version 11 (BIS-11) ,30. The Anger was assessed using the Korean version of the State–Trait Anger Expression Inventory (STAXI-K) ,35. Thispost hoc analysis was performed using a nonparametric Mann–Whitney U test and a Bonferroni correction for multiple comparisons involving the three groups. Pearson's correlation analysis was used to identify correlations between symptom severity and various factors in the IA and AD groups. All statistical analyses were performed using the Statistical Package for the Social Sciences version 20.0 . A p value of 0.05 was deemed statistically significant. The Institutional Review Boards of the SMG-SNU Boramae Medical Center approved the study protocol, and all subjects provided written informed consent prior to participation.Although the data on all variables, with the exception of those on education and state anger expression collected from HCs, conformed to a Gaussian distribution, we performed a nonparametric Kruskal–Wallis test to compare the distributions of continuous variables across the three groups because the within-group variances were not equal for most variables. The The mean duration of illness was 11.17 ± 5.64 years in the IA group and 12.67 ± 6.10 years in the AD group. The mean IAT score for the IA group was 76.33 ± 5.79, and the mean AUDIT-K score for the AD group was 25.07 ± 6.70. The mean number of hours of Internet use per day and per week in the IA group was 6.75 ± 2.86 and 47.61 ± 15.83, respectively. The mean amount of alcohol consumed per day by the AD group was 12.60 ± 4.65 drinks. These characteristics indicate that patients in both groups had moderate-to-severe problems.p = 0.131), age did significantly differ across groups (p < 0.001). The post hoc test revealed that patients with AD were the oldest and patients with IA were the youngest.Although education years did not differ across groups (p < 0.001 for the BDI and BAI). Thus, the IA and AD groups were similar in this regard . Moreover, the NEO-PI-R results did not significantly differ between the IA and AD groups in the post hoc analyses.The three-group comparison and p < 0.001). Cognitive impulsiveness was significantly higher in the AD than in the IA and HC groups, (p = 0.006), although motor and nonplanning impulsiveness were significantly higher in the IA and AD groups than in the HC group (p < 0.001 for both).The total BIS-11 score, a measure of overall impulsivity, was higher in the IA and AD groups than in the HC group (p < 0.001 for both).Expression of both state and trait anger was significantly higher in the IA and AD groups than in the HC group , agreeableness , BIS-11 total , state anger , and trait anger  scores. AD severity, as measured by AUDIT-K total scores, was significantly correlated with BDI , BAI , neuroticism , BIS-11 total , and state anger  scores.The Pearson's correlation analysis revealed that the severity of IA, as measured by IAT total scores, was significantly correlated with BDI  were not met to adjust for the potentially confounding effect of age. In the Five Factor Model, younger age in early adulthood is associated with lower levels of agreeableness and conscientiousness and higher levels of extraversion and openness . In thisOverall, our findings indicate that IA and AD are similar in terms of personality and temperament with regard to traits that are linked to aggression and those that are not. IA has not been included as an official diagnostic classification in the DSM-IV or the tenth revision of the International Classification of Diseases (ICD-10). The DSM 5 only recently recognized IA as Internet Gaming Disorder, which is a significant component of a much broader IA category; however, the condition was not included in the formal diagnostic criteria but as a ‘condition for further study’ . AlthougThe present study has several limitations. Because all participants were male, our findings may not be generalizable to females. However, this homogeneity eliminated sex as a potential confounder. We excluded subjects having IA and AD to eliminate potential ambiguity in the interpretation of our findings although coexistence of excessive Internet use and alcohol abuse is not uncommon . The chaThe present study has several strengths. Unlike most previous investigations, we studied patients who sought treatment for IA or AD. As reflected by IAT and AUDIT-K scores, both groups exhibited moderate-to-severe addictive behavior. Thus, our study has the advantage of identifying the characteristics of treatment-seeking patients with much severe psychopathology, making our findings relevant in clinical settings. The patients in previous investigations of AD were significantly older than were those in our study and, given the age difference, it is difficult to make a meaningful comparison between AD and IA. In contrast, we enrolled only young patients with AD, who were comparable to our patients with IA in terms of age, enabling a direct comparison.IA and AD are similar in terms of emotional, temperamental, and personality traits, and they share characteristics that may lead to aggression. Our findings suggest that IA and AD should be dealt with as having a close nosological relationship and that they might share common neurobiological mechanisms which may underlie their similar psychological characteristics. Further research to elucidate the nature of the relationship between IA and AD and clarify their neurobiological substrates is warranted.The authors declare that they have no competing interests.JYH contributed to the design of the study, analysis of data, and writing of the paper. ARG and DJ were involved in recruiting participants and collected data. SWC, JL, JYL, HYJ, and DJK contributed to theoretical interpretation and provided significant input on the manuscript. JSC contributed to the design of the project, supervision of data collection, and provision of significant input on the manuscript. All authors read and approved the final manuscript.


Possible association between diabetes mellitus (DM) and Alzheimer’s disease (AD) has been controversial. This study used a nationwide population-based dataset to investigate the relationship between DM and subsequent AD incidence.Data were collected from Taiwan’s National Health Insurance Research Database, which released a cohort dataset of 1,000,000 randomly sampled people and confirmed it to be representative of the Taiwanese population. We identified 71,433 patients newly diagnosed with diabetes (age 58.74±14.02 years) since January 1997. Using propensity score, we matched them with 71,311 non-diabetic subjects by time of enrollment, age, gender, hypertension, hyperlipidemia, and previous stroke history. All the patients were followed up to December 31, 2007. The endpoint of the study was occurrence of AD.p<0.001). After Cox proportional hazard regression model analysis, DM , age , female gender , hypertension , previous stroke history , and urbanization status  were independently associated with the increased risk of AD. Neither monotherapy nor combination therapy with oral antidiabetic medications were associated with the risk of AD after adjusting for underlying risk factors and the duration of DM since diagnosis. However, combination therapy with insulin was found to be associated with greater risk of AD .Over a maximum 11 years of follow-up, diabetic patients experienced a higher incidence of AD than non-diabetic subjects (0.48% vs. 0.37%, Newly diagnosed DM was associated with increased risk of AD. Use of hypoglycemic agents did not ameliorate the risk. Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. With the increasing prevalence of AD, more and more people are becoming interested in identifying their risk of developing it Although some epidemiologic studies have shown that vascular risk factors are related to increased risk of AD, the cause and progression of AD are not well understood The National Health Insurance program in Taiwan has operated since 1995 and enrolls nearly all the inhabitants of Taiwan  This study was conducted with the NHIRD, in which the diagnosis was supposed to be confirmed clinically by the individual physicians in charge for insurance claim purposes. Subjects with previously diagnosed DM and AD before 1997 were excluded from this study. Newly diagnosed diabetic patients were identified from the cohort database : A181) since January 1, 1997. The identification of DM had been proved valid and used in previous studies We used propensity scoring to match non-diabetic subjects to diabetic patients, a widely used method for avoiding selection bias in databases with large sample sizes To investigate whether use of DM medication would affect the course of AD, we evaluated patients’ use of DM medications at baseline . These medications were identified and classified by the National Drug Code and the Anatomic Therapeutic Chemical Code, a well-accepted international drug classification system coordinated by the WHO Collaborating Center for Drug Statistics Methodology The endpoint of the study was occurrence of administrative claims with AD (ICD-9-CM code: 331.0) as the main diagnosis, either during hospitalization or subsequent outpatient department visits. All the patients were followed up to December 31, 2007. The diagnoses of AD were based on history, physical examination, laboratory and imaging studies, and the Mini-Mental State Examination t-test. The categorical data between the two groups were compared with Chi-square test and Yates’ correction or Fisher’s exact test as appropriate. Survival analysis was assessed using Kaplan-Meier analysis, with the significance based on the log-rank test. The survival time was calculated from the date of DM diagnosis to the date of AD diagnosis. To assess the independent effects of DM, we conducted Cox proportional hazard regression models in all the patients with age, sex, comorbidities , geographic area, urbanization status, and medications for DM treatment  adjusted simultaneously in the model. To assess the independent effects of medications for DM treatment, we conducted Cox proportional hazard regression models in diabetic patients with age, sex, comorbidities , geographic area, and urbanization status adjusted simultaneously in the model. Statistical significance was inferred at a two-sided p value of <0.05.Microsoft SQL Server 2005 was used for data management and computing. Statistical analysis was performed utilizing SPSS software . All data were expressed as the frequency (percentage) or mean ± standard deviation. The parametric continuous data between the diabetic patients and the non-diabetic subjects were compared by unpaired Student’s p<0.001), arrhythmia , heart failure , and depression  than non-diabetic subjects. The medications used for diabetes treatment for patients with DM included metformin (16.5%), sulfonylureas (74.9%), thiazolidinediones (9.9%), α-glucosidase blockers (9.5%), non-sulfonylurea insulin secretagouge (6.5%), and insulin (18.2%).A total of 71,433 newly diagnosed diabetic patients  were identified from the 1,000,000 sampling cohort dataset between January 1997 and December 2007. Another 71,311 non-diabetic subjects who were matched using propensity score were enrolled as non-exposure controls. The demographics parameters of study subjects are shown in . To investigate the independent factors associated with the risk of developing AD, Cox regression analysis was performed, with the finding of DM , p<0.001), age , female gender , hypertension , previous stroke history , and urbanization status  were independently associated with the increased risk of AD .During a maximum 11 years’ follow-up (mean 5.5±3.1 years), 346 (0.48%) of the diabetic patients were diagnosed with AD, and 266 non-diabetic subjects (0.37%) were diagnosed with AD. . To invep = 0.004) and type 2 DM  increased the risk of AD.Among the 71,433 diabetic patients, there were 2,791 patients with type 1 DM and 68,462 patients with type 2 DM. Both type 1 DM .Medications for DM treatment were analyzed to investigate the relationship between hypoglycemic agents and risk of developing AD in diabetic patients. In initial crude analysis, monotherapy with sulfonylureas  was associated with reduced risk of AD. Combination therapy with non-sulfonylurea insulin secretagouge , and either monotherapy  or combination therapy with insulin  were found to be associated with the risk of AD Our current study revealed that newly diagnosed DM was associated with increased risk of future AD development in this cohort after a maximum of 11 years’ follow-up. Additionally, increasing risk of AD was found to be associated with DM duration, indicating DM maybe an important contribution in the pathogenesis of AD. Furthermore, neither monotherapy nor combination therapy with oral antidiabetic medications were found to be associated with the risk of AD occurrence. However, combination therapy with insulin was found to be associated with the risk of AD occurrence.The association between DM and AD has been noted in these years. In the Rotterdam Study There are some possible mechanisms for the association between DM and AD. First, hyperglycemia may cause increased oxidative stress and accumulation of advanced glycation end-products Since DM has been reported to be associated with AD, therapeutic strategies aim at treating DM is a topic of interest for avoiding AD development Another important issue is whether antidiabetic medications prolong the life of the patients with AD. In our current study, we failed to find the beneficial effects of insulin or oral antidiabetic medications in prolonging the life of the patients who developed AD (data not shown). However, it was not the goal of our study and the data is limited to the small sample size of the patients with AD. Further studies are still needed to answer this question.In addition to DM, the incidence of AD was independently associated with age, female gender, hypertension, and previous history of stroke in our study. Our findings were compatible with previous studies that age and female gender were risk factors for AD occurrence The main strength of our study is the use of a population-based dataset, which enrolls large sample-size subjects and enables us to trace prospectively the differences between the two groups. However, there are still some limitations in our study. First, the diagnosis of DM was identified using the ICD-9 code from the database. This study was conducted with the NHIRD, in which the diagnosis was supposed to be confirmed clinically by the individual physicians in charge. The identification of DM had been proved valid and used in previous studies The present study demonstrates an association between DM and future development of AD, suggesting that DM could play an important role in determining future risk of AD occurrence. However, we found that use of hypoglycemic agents had no beneficial effects for preventing development of AD. Further therapeutic strategies should be investigated for the prevention of AD, such as preventing DM or improving DM treatment.


Objectives. To examine the impact of the availability, use, and cultivation of a support network on the well-being of community-dwelling, middle-aged, and older Chinese. Methods. A total of 2,970 Hong Kong Chinese aged 40–74 years were interviewed using a structured questionnaire in 2004. Out of the original group of interviewees, 2,120 (71.4%) were interviewed again in 2005. Results. Structural equation modeling revealed a good fit of the model employing Wave 1 support network data and demographic characteristics to predict Wave 2 well-being. As hypothesized, the availability of important social ties and the cultivation of one's support networks were found to predict well-being one year later, but not the use of support networks to meet emotional, financial, or companion needs after controlling for demographic variables and baseline well-being. Discussion. Cultivating support networks can be interpreted as positive and active coping. Such cultivation is in line with what socioemotional selectivity theory predicts; specifically, when people age, they become more selective and concentrate on strengthening their relationship with those they are emotionally close to. We argue that network cultivation deserves more attention in theory, practice, and research to strengthen the resilience and adaptability of individuals approaching and experiencing old age. Social support is associated with well-being in old age, including better mental and physical health –3 and sause when the need arises. Another important but overlooked issue is whether or not individuals exert effort to cultivate their significant others or their support networks, to maintain or replenish old networks, and to expand new networks that may strengthen their resilience and adaptability in old age.Existing studies usually focus on the size of support networks , 14, 15.To answer these questions, a panel study of 2,970 community-dwelling Hong Kong Chinese aged 40–74 years was carried out in 2004 and 2005. The objective was to test the interplay between the availability, use, and cultivation of social support networks, and to discover the effects of network cultivation on well-being as measured by positive aging components. In addition, this study addresses the relative neglect of midlife in aging research. It examines aging during and from midlife to provide a wider life-span perspective in identifying age-related changes and social network strategies that strengthen an individual's resilience and adaptability to aging. Midlife is a time when there are opportunities for meaningful intervention and preparation for successful aging . MoreoveThe term “social support” and “support networks” are often used interchangeably and can be defined as “an interrelated group of people, resources, and organizations that provide individuals with emotional, informational, materials, and affectional sustenance” , or as iCaring engagement with others by showing care and love constitutes a major form of social engagement in Chinese culture [productive engagement. This aspect is grounded on the Chinese folk belief that “elders have roles to play” which exhorts elders to continue contributing to society, and is firmly entrenched in the Confucian ethics of diligence and social contribution [Well-being, the second key aspect of the present paper, has been the subject of numerous studies. According to the literature on successful aging, well-being in late life has been thought of in terms of physical health, functional independence, and active social engagement . However culture , and is ribution .Taken together, aging well goes beyond the avoidance of illness and continuous proper functioning, but also to social well-being as a caring and productive member of one's family, community, and society. Ng and his colleagues  have recBased on prior studies on support networks and well-being in late life, three hypotheses form the guidepost of the present study.Network availability in Wave 1 will positively predict well-being components in Wave 2.Network availability refers to the size of active networks, namely, the number of people whom the respondents feel close to or are important to them. Network size has often been found to be associated with well-being in old age , 26. HowThe use of personal support networks negatively predicts well-being components one year later.While some studies have found that giving and receiving support from others have positive and negative consequences , other sStudies , 31 haveNetwork cultivation in Wave 1 positively predicts positive well-being components in Wave 2.Very little studies have been conducted on network cultivation. Cultivating one's relationships with kin and nonkin implies taking the initiative and exerting effort to strengthen relationships with people they already know. All these call for positive motivation and an active approach in network behavior, and can count as a form of coping strategy to enable individuals to build their social resources in preparation for the different challenges and stresses in life . It is tThe current panel study was conducted in 2004 (Wave 1) and 2005 (Wave 2) through face-to-face interviews by trained interviewers who were undergraduates in the social sciences. The interviews were carried out at either the interviewees' home or in venues nominated by the interviewees themselves. A few interviews (.6%) also took place over the phone at the interviewees' request. The interval between each pair of interviews was 12 months. Random checking of 10% of each interviewer's interviews by the research team was undertaken for quality assurance. More details on the study method, which includes sampling, can be found in another article written by the authors .another undergraduate for interviewing. The goal of the process was to interview 800 adults each for the three younger age groups: 40s, 50s, and 60s. For participants aged 70–74 years, the target number was increased from 400  to 500. The increase would serve as a buffer in case there was difficulty contacting the original group of participants for the follow-up survey. The overall nonresponse rate was less than 8%. Twelve months later, the follow-up survey was conducted with 2,120 of the previous year's participants, a successful retention rate of 71.4% [The sampling criteria were Hong Kong Chinese 40–74 years of age, living in the community, and able to communicate verbally with the interviewers. A crucial sampling criterion was the participants' willingness to respond to the survey again one year later. Therefore, a special sampling method was designed to achieve this. In Wave 1, a total of 2,970 participants were recruited by 68 paid undergraduate interviewers who each nominated 40 adults who met the sampling criteria. The nominees' names were assigned to of 71.4% . After eThe personal support network was measured by a specially constructed 23-item Support Network Scale . The SN Scale is composed of three theoretical social network components, namely, network availability, use, and cultivation, which were developed along the findings of a qualitative study on 15 focus groups of middle-aged and older Hong Kong Chinese . The SN-The SN-Use Subscale (14 items) measured the extent to which the respondents utilized their various support networks of family, relatives, friends, neighbors, and others  when experiencing different emotional, financial, and relational needs. Five items were concerned with seeking emotional support, such as the participants being asked if they would seek help from their family during emotional problems. Another five items were about seeking financial support during economic hardship while four items explored the extent to which participants sought company for social leisure activities. The SN-Cultivation Subscale (4 items) examined the amount of time and effort the respondents devoted to cultivate their relationship with family, relatives, friends, and neighbors. All items on the SN Scale adopted a five-point rating scale, with 1 being the lowest value and 5 as the highest value. The overall score of each subscale was the mean of all items in the relevant subscale.The Cronbach's alpha coefficients were  .82, .63, .75, and  .60 for the overall SN Scale, SN-Availability Subscale, SN-Use Subscale, and SN-Cultivation Subscale, respectively, in Wave 1. The coefficients slightly improved in Wave 2 at  .83,  .65,  .78, and  .64, respectively, indicating good reliability in the overall scale and moderate reliability in the three subscales.Well-being components were measured by the Positive Aging Index (PAI), which was created by the research team. The index has good psychometric properties based on a validation study of 233 Chinese adults (40–90 years) and a longitudinal study of 2,970 Hong Kong Chinese . The PAIplus [Structural equation modeling via Mplus  estimateThe 2,970 respondents interviewed in Wave 1 were stratified into the following four age groups: 40–49, 50–59, 60–69, and 70–74. Their percentages were 39% (873), 27% (811), 26% (771), and 17% (515), respectively. Majority of the participants were women (62.3%), married (78%), living with spouses only or living with spouse together with others (74.4%), with 1–3 children (67.8%), engaged in gainful employment (40.6%), and had received primary education or below (65%). In the Wave 2 survey, the respective numbers were 609 (40 s), 584 (50 s), 553 (60 s), and 374 (70–74 years) for a total of 2,120 respondents. The demographic profile of the participants in Wave 2 was very similar to that of Wave 1. When compared with the census data , the samt-test. The participants' overall support network fell slightly below the scalar midpoint of 3 . From the three support network components, participants had the highest score in SN-Availability , followed by SN-Cultivation , and network use  which had the lowest score. Paired samples t-tests found no significant difference in scores of the overall support network and the various network components between Waves 1 and 2. The only exception was the use of network, which was slightly higher in Wave 2 (P < .01). The general similarity in the scores of network components between Wave 1 and Wave 2 suggests that support networks are relatively stable among the participants. The frequency distributions of SN subscales at Wave 1 are reported in the following paragraphs.M = 3.96, SD = .72), followed closely by health  and CE . They had a relatively low score in PE . Paired samples t-test found significant differences in both waves for overall well-being and its components of health and functioning.L2(9) = 44.1, SRMR = .010, RMSEA = .036, CFI = .996). Among the Wave 1 variables, support network availability (β = .031) and support network cultivation (β = .055) had significant positive effects on the four well-being components (The model using Wave 1 variables to predict Wave 2 well-being components attained a very good fit (mponents . Note thR2 = .221–.272).The other significant predictors of Wave 2 well-being were Wave 1 well-being, gender, age, education, marital status, and family income . The finThe objective of this study was to examine the predicting effect of support network components  on well-being among community-dwelling middle-aged and older people one year later. A panel study was conducted through face-to-face interviews with 2,920 Hong Kong Chinese aged 40–70 in 2004 (Wave 1); 71% of whom were interviewed again one year later (Wave 2). Results show that, in general, the participants had a high level of well-being in terms of health  and functioning . They were found to be below scalar midpoint in terms of PE in the community and the society as a whole. Therefore, greater effort is required to enhance the PE of older people (such as volunteering) and to promote proper recognition of their contributions  which are commonly delegated to older people. The availability of active networks was found to predict overall well-being one year later, even after controlling for personal variables and Wave 1 well-being. Thus, the first hypothesis that network availability in Wave 1 will positively predict well-being and its components in Wave 2 was supported. M = 3.23, SD = .82) implies that, on average, the participants felt close to 3 to 4 persons among family members, friends, relatives, or neighbors. The finding supports the Roberts and associates' [Network availability carried a positive prediction on well-being. This finding implies that the larger the network size, the higher the well-being. Nevertheless, the mean score of SN-Availability (ociates'  argumentThe second hypothesis was that the use of personal support networks would negatively predict well-being one year later. The present study found that the use of personal networks for emotional, financial, and social support did not predict the participants' well-being one year later. Support networks serve different functions; some are associated with pleasant experiences such as seeking companionship in social-recreational activities. In contrast, support networks within the context of seeking help for financial and emotional problems are negative by nature. Even if some significant others help, there is concern over reciprocity and incurring a sense of indebtedness which do not contribute to a sense of well-being. This lack of association between seeking support and well-being is partly explained by cultural concern on the negative relational consequences of help seeking in a collectivistic culture . Social Cultivation of support networks predicted well-being one year later, supporting the third hypothesis. The greater the efforts exerted by middle-aged and older participants in cultivating their social relationships, the greater their possibility of achieving better well-being. Most likely this is due to a higher likelihood of establishing a social network that is enduring and ready to provide various kinds of support when needed. Nevertheless, it was found that network use cannot predict well-being one year later. Taken together, these results suggest that the positive effect of network cultivation might come more from positive coping rather than the reassurance of supportive networks or the actual use of the networks. For older people, coping strategies are frequently applied when they are confronted with aging-related problems and obstacles . CultivaThe finding provides some support to the socioemotional selectivity theory , 37, whiSimilar to other studies that established social relations as an important determinant of well-being , 39, theThis study has several limitations. First, the sampling approach was not random, thus limiting the generalizability of the findings. Nevertheless, the sample was large enough to reflect the major views of middle-aged and older Chinese people in Hong Kong. Moreover, a year's worth of panel data was too short to identify significant changes in social networks and well-being over time. The measure of social support relied on self-reports that reflect intention or attitudes rather than actual behavior. Participants may behave differently in real-life situations. This panel study, conducted over a one-year period, found that among the three social network components, cultivating relationship with significant others had the strongest predicting effect on well-being. This was followed by the size of available support networks. The use of support networks to meet various financial, social, and emotional needs did not predict well-being. This illustrates that middle-aged and older people age well if they had a relatively large number of kin and nonkin members with whom they felt close, and if they had taken efforts to cultivate their relationships with their significant others. Whether they used their support networks for help or support was not related to their sense of well-being. This is possibly due to the cultural reservations associated with help seeking such as losing face, unduly being a burden on others, and the cultural emphasis on self-sufficiency. Cultivating support networks also reflected a positive and approach-oriented coping strategy. These findings carry important theoretical and practice implications. The findings lend support to the socioemotional selectivity theory, which argues that when people age, they become more selective and concentrate on strengthening their relationship with those they feel close to. The findings also support the argument to include caring and productive engagement in addition to health and functional abilities in the successful aging framework. In practice, human service professionals like social workers should enhance older people's people skills, such as skills to communicate with and engage their significant others, as well as skills in the use of modern communication technologies such as email and Facebook to communicate with the younger members of the family. In traditional Chinese society, older people enjoy high status and seldom take the initiative to build relationships with their family members. It is the younger generation who actively pays respect to the senior members of the family. Therefore, human service professionals should encourage senior citizens to take active roles in building and sustaining their relationships with their significant others. As far as we know, the present study is one of the very few attempts to examine an individual's active efforts in network cultivation. We argue that network cultivation deserves more attention in theory building, further studies, and human service practice to strengthen the resilience and adaptability of individuals approaching and experiencing old age. While this study was conducted in the Chinese community of Hong Kong, the findings may provide some useful reference to other Chinese societies in Shanghai, Singapore, Taiwan, and Chinese immigrant communities in the West. Many of the older people in these societies were born in their homelands and migrated to different societies in their youth due to wars, famine, and economic hardship. They may share similar childhood experiences, developmental experiences, and value systems with those of Hong Kong Chinese.


People with physical disability (PWPD) is the largest subgroup of people with disability (PWD) in China, but few studies have been conducted among this vulnerable population. The objective of this study was to investigate the level of quality of life (QoL), self-perceived quality of care and support (QOCS), severity of disability and personal attitude towards disability among people with physical disability in China, as well as to identify how QoL can be affected by severity of disability through QOCS and personal attitude towards disability among PWPD.A cross-sectional study was conducted among 1,853 PWPD in Guangzhou, China. Data were collected on participants’ QoL, QOCS, personal attitude towards disability and severity of disability. Structural equation modeling was used to examine the effects of the other variables on QoL.Even with a mild disability (mean score:1.72), relatively low levels of QoL (mean score: 2.65- 3.22) and QOCS (mean score: 2.95 to 3.28), as well as unfavorable personal attitude towards disability (mean score: 2.75 to 3.36) were identified among PWPD. According to SEM, we found that the influence of severity of physical disability on QoL is not only exerted directly, but is also indirectly through QOCS and their personal attitudes towards disability, with QOCS playing a more important mediating role than PWPD’s attitudes towards their own disability.Unfavorable health status was identified among PWPD in China. Focusing on improvement of assistance and care services has the potential to substantially improve PWPD’s QoL. Further research should focus on understanding the needs and their current state of health care of PWPD in China thus being able to develop better interventions for them. Disabilities have caused a substantial global disease burden . By the It is well known that PWPD experience more restrictions on participation in social activities than people without physical disability, which is associated with lower level of well-being, including their relative poorer quality of life (QoL) -9. WhileBesides attitude towards disability, quality of care and support (QOCS) is another important factor within the association between severity of disability and QoL among PWPD ,22. AccoThe aim of this study was to investigate the level of QoL, self-perceived QOCS, severity of disability, and personal attitude towards disability among PWPD in China, as well as to identify how QoL can be affected by severity of disability through QOCS and personal attitude towards disability among PWPD. Based on the above-reviewed literature, we hypothesized that severity of disability would have a direct relationship with attitude towards disability, QOCS and QoL. We also hypothesized that attitude towards disability and QOCS would be related to QoL, and QOCS would be related to attitude towards disability. Finally, we hypothesized that the relationship between severity of disability and QoL would be mediated by both QOCS and attitude towards disability Figure .From March to August in 2008, this cross-sectional study was conducted in Guangzhou, the capital of Guangdong Province in southern China. This city has a population size of about 13 million  with appA DPF staff member and a doctor confirmed eligibility and obtained informed consent from participants. Then each participant was assigned a unique identification code for the questionnaire. The questionnaire was administered in person by an experienced research interviewer in a private room in each community. The interview was conducted in Chinese and took around 30 minutes. Each questionnaire was signed and dated by the interviewer, and all the questionnaires was reviewed for completeness and consistency by a research assistant who supervised the data collection. All the participants who completed the interview were given an assistive device (a wheelchair or a pair of crutches). The study protocol was approved by the Institutional Review Boards of Sun Yat-sen University and Guangzhou Disabled Persons’ Federation.The 12-item World Health Organization Disability Assessment ScheduleII(WHODAS II) was used to assess the severity of disability . The magInclusion , Discrimination , Gains , and Prospects . Higher mean scores for each domain were indicative of better inclusion, less discrimination, more gains and better prospects. The Cronbach’s alphas of the domains in this study were 0.76, 0.76, 0.78, and 0.73, respectively.The Attitude to Disability Scale (ADS) was used to assess personal attitude of individuals towards their own disability . The 16-Staff quality , Accessibility of care , Meeting needs , and Information . Higher mean scores for each domain were indicative of higher self-perceived levels of staff quality, accessibility of care, meeting needs or information. Cronbach’s alphas were 0.78, 0.74, 0.75, and 0.83, respectively.The QOCS was measured using the Quality of Care and Support Scale , a 17-itPhysical health , Psychological , Social relationships  and Environmental . The WHOQOL-DIS, also named Disability and usually used as the fifth QoL-domain for PWD, has been applied in other studies [The QoL of PWPD was measured using the short version of the WHO Quality of Life (WHOQOL-BREF)  and the  studies ,37, and ADS, QOCS and WHOQOL-DIS were developed by the DISQOL project: “Quality of Care and Quality of Life for People with Intellectual and Physical Disabilities: Integrated Living, Social Inclusion, and Service User Participation” ,35,37, aInclusion, Discrimination, Gains, and Prospects. The latent variable QOCS was explained with four indicators: Staff quality, Accessibility of care, Meeting needs and Information. The latent variable QoL was indexed with five indicator variables: Physical Health, Psychological Health, Social relationships, Environment and Disability. Duration of disability and comorbidity, which were variables significantly associated with QOCS, attitude and QoL, were controlled as the covariates for these three latent variables in the model. The overall fit of the model was assessed with the Comparative Fit Index , Tucker-Lewis Index , the root mean square error of approximation  [Data were double-entered, and the two sets of data were compared using the EpiData software . We first performed Pearson’s correlations with SPSS 20.0  to explore the relationship between all variables . Structural equation modeling (SEM) with maximum likelihood method with robust standard errors (MLR)  was then ≤ 0.08) , and the ≤ 0.08) .Finally, direct, indirect and total effects were examined from the severity of disability to QoL. The effect of an independent variable on a dependent variable represented a direct effect, and the effect of an independent variable on a dependent variable through a mediating variable represented an indirect effect . In thisThe results reporting followed the SEM and confirmatory factor analysis (CFA) reporting guidelines which was suggested by Schreiber .p = 0.13). However, urban PWPDs reported a younger age of disability onset than suburban PWPD . Meanwhile, urban PWPD had a higher education level  and a higher employment rate  than suburban ones. Of the 1,853 participants, 38.8% were comorbid with other health problems: musculoskeletal problems , cardiovascular diseases , respiratory problems , neuropsychological problems , digestive problems , diabetes (4.0%), sensory organ damage , cancer (0.6%) and others .Table Social relations (3.22), the means of the scores on other four domains of QoL were between poor to neither poor/nor good levels (ranging from 2.65 to 2.98), indicating participants’ relatively low level of QoL.Table r = -0.28 to -0.09, p < 0.01), between severity of disability and QOCS , and between severity of disability and QoL . Significant positive correlations were found between attitude towards disability and QoL , and between QOCS and QoL . As to the correlation between QOCS and attitude towards disability, except for the relationship of Inclusion with Staff quality, Gains with Accessibility, Information, and Discrimination, all other correlation coefficients were significantly positive .As can be seen in Table Additionally, duration of disability and comorbidity were significantly associated with QOCS, attitude and QoL. Thus, both variables were included in the following SEM as covariates.β = -0.59, p <0.001); both QOCS  and attitude towards disability  had a positive influence on QoL among PWPD.The model is presented in Figure p < 0.001). Out of the total effect, the direct effect from severity of disability to QoL was significant , which accounted for 59% of the covariance between severity of disability and QoL. Out of such total effect, the total indirect effect from severity of disability to QoL was also significant , and the remaining 41% of the covariance was mediated through a combination of QOCS, attitude, as well as QOCS and attitude. There were three different indirect paths that severity of disability could take to influence QoL. The first is mediated through QOCS , the second through attitude towards disability , and the third through a compound mediation of QOCS and attitude towards disability . The proportion of the specific indirect effect through QOCS compared to the total effect (27.4%) was much higher than through attitude towards disability (4.1%) and through the compound mediation of QOCS and attitude towards disability (9.5%) (data not shown). Similarly, the indirect effect through QOCS  account for 70% of the total effect  from severity of disability to attitude towards disability.Table R2 = 0.19) of variance of QOCS; severity of disability and QOCS together account for 33% (R2 = 0.33) of variance of attitude towards disability; severity of disability, QOCS and attitude together account for 64% (R2 = 0.64) of variance of QoL.Overall, severity of disability accounts for 19% . QZ also contributed to the data collection and data analysis. Furthermore, QZ and QT contributed to the results interpretation and writing of the manuscript. JG and R L-C also contributed to the writing and revising of the manuscript. CH contributed to the writing, reviewing, and final editing of the manuscript. YH not only contributed to the study design and manuscript revision, but also supervised the project progress. CH and YH takes full responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript.


The treatment of noncommunicable diseases (NCD), like coronary heart disease or type 2 diabetes mellitus, causes rising costs for the health system. Physical activity is supposed to reduce the risk for these diseases. Results of cross-sectional studies showed that physical activity is associated with better health, and that physical activity could prevent the development of these diseases. The purpose of this review is to summarize existing evidence for the long-term (>5 years) relationship between physical activity and weight gain, obesity, coronary heart disease, type 2 diabetes mellitus, Alzheimer’s disease and dementia.Fifteen longitudinal studies with at least 5-year follow up times and a total of 288,724 subjects (>500 participants in each study), aged between 18 and 85 years, were identified using digital databases. Only studies published in English, about healthy adults at baseline, intentional physical activity and the listed NCDs were included.The results of these studies show that physical activity appears to have a positive long-term influence on all selected diseases.This review revealed a paucity of long-term studies on the relationship between physical activity and the incidence of NCD. Most rn world. Noncommrn world.Most NCDs primarily result from unhealthy lifestyles including the consumption of too much or unhealthy food,6,8,9, tAlthough these diseases are very prominent in many western countries, only few longitudinal studies exist that focus on their development during a person’s lifetime and their association with other habitual factors such as physical activity.Many cross sectional studies have researched the relationship between physical activity and health outcomes - these results are summarized in quite a number of reviews. As opposed to this, only few long-term studies about the effect of physical activity on diseases exist, and to date there are no reviews that concentrate on long-term results in an epidemiologic view.Therefore, the purpose of this article was to review long-term effects of physical activity on the development of weight gain and obesity, CHD and type 2 diabetes mellitus in healthy adults.Furthermore, dementia and Alzheimer’s disease, two diseases which are of rising importance in modern societies and which develop over a long period of time, are regarded in the context of the long-term influences of physical activity. There is some evidence which indicates that physical activity has a positive effect against the development and progress of these two diseases.weight gain and obesity, CHD, type 2 diabetes mellitus and dementia and Alzheimer’s disease were included in this review. We searched the electronic databases Pubmed, BASE and OVID for articles published between January 1980 and May 2012 using the following search terms : “longitudinal / long-term, physical activity, adult” (3708 articles); “longitudinal / long-term, physical activity, adult, weight gain” (180 articles); “longitudinal / long-term, physical activity, adult, obesity” (483 articles); “longitudinal / long-term, physical activity, adult, CHD / coronary heart disease” (224 articles); “longitudinal / long-term, physical activity, adult, t2dm / type 2 diabetes mellitus” (87 articles); “longitudinal / long-term, physical activity, adult, dementia” (103 articles); and “longitudinal / long-term, physical activity, adult, Alzheimer’s disease” (60 articles)  conducted by the Cooper Clinic, Texas. Betweenth percentile of baseline weight showed no significant relation between walking duration and weight gain. In contrast, data for people in the 50th percentile of baseline weight revealed that for every 30 minutes of daily walking the weight gain was 0.15 kg per year less for men and 0.29 kg per year less for women. Finally, data for people in the 75th percentile of baseline weight showed the smallest weight gain: for every 30 minutes of walking per day, men reduced their weight gain by about 0.25 kg per year and women by about 0.53 kg per year without making any other changes to their habitual lifestyle. Hence, the results of this study indicate that participants with a higher baseline weight benefit more from being physically active .Gordon-Larsen et al. investigHankinson et al. used thest at baseline, 2nd after five years, 3rd after 10 years) also showed a negative relationship between physical activity and weight. The preventing effects of medium leisure time physical activity (LTPA) on obesity were lower than those of high LTPA for both genders. The longitudinal analysis revealed a significant direct correlation between the level of LTPA and the risk of becoming obese for men but not for women. In contrast to the results of the cross-sectional analysis, the more active participants had a higher risk of becoming obese. Moreover, the results of that study indicate that obesity may lead to physical inactivity.The Copenhagen City Heart Study by Petersen, Schnohr and Sorensen linked cTherefore, the results of the first three studies-18 suggeOf all modern diseases, coronary heart disease (CHD) has received the most scientific scrutiny. Overall, most studies reported a negative relationship between physical activity and the occurrence of CHD for physical activity levels above the minimum energy expenditure. Additional fileIn 1948, the National Heart, Lung and Blood Institute founded by Kannel et al. established the Framingham Heart Study. This research group investigated the general causes and the development of coronary heart disease in 5,209 men and women, aged 30 to 62 years at baseline. The resThe relationship between energy expenditure and the incidence of stroke showed a u-shape pattern. SpecifiComparable results were also reported by the Honolulu Heart Program,23 incluThe studies cited in the next section had similar results but also featured the following additional findings.The Alameda County Health Study by Kaplan et al. reportedGillum et al. investigTo investigate the link between obesity and associated diseases, Li et al. quantifiOverall, all studies included in this review section showed a predicted negative relation between physical activity and the risk of CHD over time. Two studies,21 showeWhile the incidence of type 2 diabetes mellitus in older people has increased rapidly, all stuIn their Nurses’ Health Study involving 70,120 nurses aged 40 to 64, which has been on-going since 1976, Hu et al. investigBerenzen et al. and Dema2 and a waist circumference below 88 cm for women or below 92 cm for men. With every healthy lifestyle factor the incidence for type 2 diabetes mellitus decreased by 35%. For people scoring lowest  in every lifestyle factor, an 82% lower risk for type 2 diabetes mellitus was predicted compared to all other patients. In addition, it was predicted that if these associations were causal, 8 of 10 cases of type 2 diabetes mellitus could be prevented.A high body weight or obesity, often described by the relation between body weight and body height (body mass index—BMI), and socioeconomic status are strong covariates for the relationship between physical activity and the incidence of type 2 diabetes mellitus. For instance, Katzmarzyk et al. analysedAll studies-31 reporThe relationship between physical activity and dementia, particularly Alzheimer’s disease, is important for the general public because the incidence of dementia increases with increasing age. AdditioThe few existing studies-37 foundThe results of the reviewed studies indicate that physical activity seems to be an important factor that can have beneficial effects for the reviewed noncommunicable diseases weight gain and obesity, CHD and type 2 diabetes mellitus, the risk factors weight gain and obesity and the age-related diseases dementia and Alzheimer’s disease.Two of the three longitudinal studies with at least 5-year follow-up focusing on the development of obesity over time showed a negative relationship between physical activity and obesity,17. SurpSeveral studies-26,38 inThe results of studies-31 examiFinally, six studies-37 focusHowever, several problems in the reviewed studies have become apparent.First: There are only few long-term studies on the relationship between physical activity and the incidence of NCD, which stresses the general paucity of longitudinal research in this area. More long-term studies, following the development of diseases and the impact of lifestyle, especially physical activity, are needed. Further longitudinal studies are needed that differentiate between ethnic groups, genders and groups with different social backgrounds. The results presented in this review only encompass the relationship between physical activity and the incidence of NCD in western countries and mainly for Caucasian participants. In addition, only adults were included in these studies, and hence the results cannot be generalized to other groups. Many age related diseases, such as type 2 diabetes mellitus, CHD or certain types of cancer, develop over a long time before they are diagnosed by a physician. To identify this development in detail, longitudinal studies involving healthy participants at baseline should be conducted and these participants should be followed into older age when the disease occurs. To understand this lifelong development of NCD, studies following children throughout their lifespan are desirable. To the best of our knowledge, there are only very few studies that follow children through their adolescence into their adulthood,42. The Second: However, more research is necessary on the clinical picture and the development of NCD. Clearly, a thorough insight into these aspects is a prerequisite for the design and development of effective prevention programs. In addition, the relationship between physical activity and the development of NCD must be better understood including the role of other parameters, such as, for instance, nutrition, body composition, alcohol consumption and smoking behaviour. Indeed, results of some of the included studies,24,26,27Third: Most studies,29,31-38The reviewed studies have shown that physical activity could help in the prevention of non-communicable and age-related diseases. The studies have shown that it is necessary to include physical activity into prevention programs for NCD and to inform the patients and the population in general about its virtues. To achieve this, a closer cooperation between physicians, research and sport facilities is needed. Research and physical activity service providers, e.g. gyms or sports clubs, health insurances or public providers (e.g. adult education centers) have to cooperate together to improve the general health. In addition, the knowledge about the causes and the development of modern diseases in the population should be improved. Instead of treating with medicine alone, physicians should advise patients to be more physically active within their limits. Children and adolescents should generally be encouraged to maintain a healthy lifestyle throughout their lives. In addition, public health projects that are targeted at improving the general health during adulthood and older age should focus on effective disease prevention starting during childhood.It is important to highlight the limitations of this review in order to provide a context for the results. First, the assessment is limited to published work and may be subject to publication bias. Second, the influence of several confounders, as age, the lag between baseline and follow-up, or attrition rate, could affect conclusions of this review. Third, the work contained in this review is limited to English-written journals and thus the results cannot generalize to studies conducted and published in other languages. Fourth, we included only studies with more than 500 participants. Fifth, the literature reviewed consisted of self-reported physical activity. Finally, the review is limited to the search terms and data-bases contained in our “Methods” section. Studies that have not been abstracted with these key words will be missing from our review.This review indicates the relative lack of epidemiologic longitudinal studies on the effects of physical activity in addition to non-communicable diseases. The presented studies exclusively illustrate positive results. To the best of our knowledge no other studies reporting no or negative results over time exist.To show the longitudinal improvements of physical activity in addition to the presented non-communicable diseases of a large number of adults within normal communities, no studies with subsamples or unhealthy participants alone were considered. This review just focuses on studies with more than 500 healthy participants. Other studies [e.g. followinOverall, the results of the reviewed articles provide a general view about the longitudinal relationship between physical activity and the incidence of NCD and health problems. Physical activity seems to be a relevant factor for preventing age-related diseases; however more long-term research is necessary.The authors declare that they have no competing interests.MR searched for relevant literature and wrote the manuscript. CN and DJ helped writing and drafting the manuscript. AW has given final approval of the version to be published. All authors read and appropriated the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/813/prepubDescription of studies on the association between physical activity and weight gain / obesity. Description of dataset: Table S1 describes the included studies on the association between physical activity and weight gain or obesity .Click here for fileDescription of studies of the association between physical activity and coronary heart diseases. Description of dataset: Table S2 describes the included studies on the association between physical activity and coronary heart diseases .Click here for fileDescription of studies on the association between physical activity and type 2 diabetes mellitus. Description of dataset: Table S3 describes the included studies on the association between physical activity and type 2 diabetes mellitus .Click here for fileDescription of studies on the association between physical activity and Alzheimer’s disease and dementia. Description of dataset: Table S4 describes the included studies on the association between physical activity and Alzheimer’s disease and dementia .Click here for file


HIV and tuberculosis (TB) are so closely connected that their relationship is often described as a co-epidemic. Dual infection with HIV and TB leads to reciprocal interactions that have significant clinical impact. The approach to the treatment of tuberculosis in the HIV-infected patient is complex and must address the patient's requirement for antiretroviral therapy, potential drug reactions, and complications related to the immune reconstitution inflammatory syndrome (IRIS). Poverty and poor access to services are challenges for the successful treatment of those affected by TB and HIV.A case control study was set up to determine the proportion of patients with HIV/AIDS and TB co-infection among the patients attending for medical assistance, to correlate its prevalence with the Deprivation Index. Data were collected from medical records and from interviewing patients about their social and economic status.Prevalence of tuberculosis infection is increased eight times in HIV/AIDS patients compared to the general population. TB co-infection risk is proportionally increased with deprivation and disadvantage higher scores. People with no income or low income, and/or with low level of education, and/or homeless, and/or with difficult access to health services, are statistically significantly correlated (p<0.0001) with the presence of TB co-infection. Relative risks of TB co-infection increase for people with higher disadvantage scores, and/or low income, and/or unemployed status and/or homeless (p<0.0022). Association of TB infection is correlated with B3, C2, C3 stage of HIV infection (p=0.000) compared with other cases. Of 150 patients, 14.66% presented also TB infection. The relative risk for HIV/AIDS detection in C3 stage in a TB patient is 7.2 times higher than in the absence of co-infection (p<0.0001).Lack of awareness of TB or HIV status can prevent adequate treatment. TB disease is, in fact, an AIDS-defining condition. Those living in poverty suffer from a lower quality of life and present an increased risk for the disease, including infectious diseases.


The triglyceride lipase gene subfamily plays a central role in lipid and lipoprotein metabolism. There are three members of this subfamily: lipoprotein lipase, hepatic lipase, and endothelial lipase. Although these lipases are implicated in the pathophysiology of hyperlipidemia and atherosclerosis, their structures have not been fully solved. In the current study, we established homology models of these three lipases, and carried out analysis of their activity sites. In addition, we investigated the kinetic characteristics for the catalytic residues using a molecular dynamics simulation strategy. To elucidate the molecular interactions and determine potential key residues involved in the binding to lipase inhibitors, we analyzed the binding pockets and binding poses of known inhibitors of the three lipases. We identified the spatial consensus catalytic triad “Ser-Asp-His”, a characteristic motif in all three lipases. Furthermore, we found that the spatial characteristics of the binding pockets of the lipase molecules play a key role in ligand recognition, binding poses, and affinities. To the best of our knowledge, this is the first report that systematically builds homology models of all the triglyceride lipase gene subfamily members. Our data provide novel insights into the molecular structures of lipases and their structure-function relationship, and thus provides groundwork for functional probe design towards lipase-based therapeutic inhibitors for the treatment of hyperlipidemia and atherosclerosis. The triglyceride lipase gene subfamily (TLGS) is comprised of three evolutionarily related lipases: lipoprotein lipase (LPL), hepatic lipase (HL), and endothelial lipase (EL), and plays a central role in plasma lipoprotein metabolism and homeostasis Because of their diverse range of important functions in maintaining lipoprotein homeostasis and their involvement in the pathophysiology of hyperlipidemia and atherosclerosis, the TLGS members are attractive biomarkers and potential therapeutic targets for the treatment of metabolic diseases Previous studies have revealed that these lipases share common motifs, including a heparin-binding domain, and key active site residues  In this study, we used a computational strategy including homology modeling, molecular dynamics simulation (MDS), binding site detection and docking validation. The aims of this strategy were: (1) Homology modeling and comparison of the structures of LPL, HL and EL. This is the first attempt to generate the 3-dimensional (3D) homology modelled structures of all the TLGS members simultaneously. Since they belong to the same subfamily, the comparison might be expected to explain the differences of their functions stemming from structural differences; (2) The motion of the catalytic triad and key residues within the binding pockets, which will provide important information on the substrate catalytic process; (3) The binding poses of known inhibitors, especially specific and non-specific inhibitors, to compare the binding characteristics; and (4) Modeling of comprehensive 3D models for these lipases, which can be used for further drug design applications such as virtual screening and detailed protein-ligand reciprocity.http://www.ncbi.nlm.nih.gov/entrez). Discovery Studio 2.5  was used for all the sequence studies. Sequence similarity searching was then carried out using BLAST searches against the protein data bank The human sequences of LPL, HL, and EL were acquired from the PubMed database  value was calculated for further computational study.https://prosa.services.came.sbg.ac.at/prosa.php)  see . The pro−). To reduce the effect of unfavorable interactions produced by solvents and ion generation, each system was subjected to 5000 steps of energy minimization using conjugate gradient methods MDS was carried out to examine the quality of the homology models by assessing their stability. Three models were placed in respective 1.0 nm cubic boxes, and refined with the GROMACS package using the GROMOS96 force field The binding pockets of the lipase models were derived from MDS results, and further studied by Cavity in LigBuilder V2.0 Program AutoDock Vina was used to carry out docking analysis The molecular docking study included two tasks. Firstly, known inhibitors of TLGS members, extracted from the ChEMBL database 50 values for each lipase were selected , bit scores (192.2 in 1 GPL vs 191.8 in 1 LPA), and expectation values , we selected 1 GPL as the template for HL modeling definitively. The E-values for LPL, HL, and EL were 9.8e−55, 7.9e−55, and 1.7e−55, respectively. Because an E-value represents a number of different alignments with scores equivalent to, or better than, the scores that are expected to occur in a random database search, the low E-values of LPL, HL, and EL indicate that the alignments were real and did not occur by chance.By aligning the sequences of three lipases against the sequences with known crystal structures, we found that Homo sapiens pancreatic triacylglycerol lipase (PDB entry: 1LPA with 3.04 Å resolution) Additional multiple alignments were then performed between TLGS members and PL. The crystal structure of PL, a member of the human triacylglycerol lipase family with a closely genetic relationship to the subfamily containing LPL, HL, and EL, has been resolved Three-dimensional molecular models of the three lipases were generated using the B-chain of 1 LPA as the template for both LPL and EL, and using the A-chain of 1 GPL as the template for HL. The models constructed were stereo-chemically validated using additional parameters such as PROCHECK It is well known that cofactors are required for enzymatic activation. ApoC-II is a key cofactor for LPL activation, while cofactors for HL and EL are yet to be defined Initial models of TLGS were further refined using MDS to improve their stability. This strategy was also implemented to find energetically favorable structures for further docking analysis. The system of LPL contains one positive charge, and therefore one chloride ion was added to the model. For HL and EL, ten and four chloride ions were added to the models for MDS, respectively. The results, based on the trajectory, revealed that the potential energy of the LPL model decreased from −0.994 e+06 KJ/mol to −1.001 e+06 KJ/mol. However in the HL model, the decrease in potential energy varied from −1.034 e+06 KJ/mol to −1.039 e+06 KJ/mol. For the EL model, the decrease in potential energy varied from −1.028 e+06 KJ/mol to −1.035 e+06 KJ/mol. Most of the structures are in the region of 0.998 e+06 KJ/mol, 1.037 e+06 KJ/mol, and 1.032 e+06 KJ/mol for LPL, HL and EL, respectively. These results determine the energetic stability for LPL, HL and EL .These models were further analyzed according to their structural stability using RMSD. One thousand ps were carried out for equilibrating. For LPL, a gradual rise was observed until 0.39 nm, and a plateau was observed thereafter. In the case of HL, a gradual rise was observed until 0.40 nm, before a plateau occurred for the rest of the study. Finally, there was a gradual rise until 0.49 nm, followed by a plateau, in the model for EL. The potential energy plots for LPL, HL, and EL are depicted in Kd) were predicted to be 10.47, 9.20, and 8.39. In the case of HL, four binding pockets were detected, and the potential best pKd values were 9.28, 8.25, 7.92, and 7.41. For EL, a total of five binding pockets were suggested, and the potential pKd values with ligands were 8.89, 8.76, 7.88, 7.87, and 6.76 for pockets 1–5, respectively. These possible binding pockets were then further filtered using the following two criteria: high predicted pKd values , and the location of the catalytic triad. The final proposed binding pocket is therefore pocket 1 of each TLGS member for the following structure-based investigations.More than one possible ligand-binding pocket was proposed for each lipase by Cavity. In In order to characterize the similarities and differences of the binding pockets of LPL, HL, and EL, the residues of three pockets proposed above (0.6 nm in diameter) were investigated.The residues of each lipase that may bind with ligands are shown in When considering the characteristics of the binding pocket, there were several issues that were always considered. One important consideration was whether spatial conservativeness could be determined for the conserved sequences and residues, which was important and meaningful for the realization of structure-based biological functions. The orientation and spatial coordinates of the side chains included in binding pockets were further analyzed, which is important for structure-based interactions and molecular recognition. Generally, there are two main factors that can alter the orientation of a residues side chain. The first is distortion of protein backbone, and the second is the flexibility of the residue itself, both of which should be considered during the binding process. In 50 values of their respective inhibitors . In Feature differences, especially in the shape of three lipase pockets, may be responsible for the differing ICTo further verify the feasibility of the homology models constructed above, and to investigate the spatial characteristics of the ligand binding properties, several inhibitors were selected for docking analysis. The protein-inhibitor interactions of each lipase with their two best inhibitors When LPL accommodated its inhibitors, its binding pocket appeared open, shallow, and basket-like in shape see . Hydroph50 values of LPL inhibitors were not good enough to reach nM degree. Compared with CHEMBL339297, CHEMBL485946 did not fit as well in to the pocket, and was localized to the corner of the binding site. The binding energies of CHEMBL339297 and CHEMBL485946 in the LPL pocket were −7.4 kcal/mol, and −6.1 kcal/mol, respectively, which explained why the experimentally calculated IC50 value of CHEMBL339297 (0.2 µM) was lower than that of CHEMBL485946 (1.4 µM).The two inhibitors were half-embedded into the binding site of LPL but did not completely fit within the pocket. This may help to explain why the IC50 of CHEMBL485946 was higher than that of CHEMBL339297.The binding pose and pattern  showed tBased on the binding poses and patterns, more work can be done to improve the biological activity of LPL inhibitors by increasing their molecular volume, the number of typical hydrogen bonds, and electrostatic interactions. In this way, it is possible to increase the binding capability of LPL inhibitors, and thus improve their effectiveness.CHEMBL339297 and CHEMBL133897 were selected to investigate HL-inhibitor interactions 50 value of CHEMBL339297 (1.8 µM) is better than that of CHEMBL133897 (15 µM).The inhibitors were embedded in a narrow elongated pocket of HL see . Both enIn addition, it is clear in Based on the binding pattern of HL inhibitors in the pocket of HL, we can conclude that in order to increase the binding affinity of HL inhibitors, the first step is to consider how to introduce more electropositive groups at both ends to enhance the formation of additional hydrogen bonds and electrostatic interactions between the inhibitors and HL. The shape of the HL binding pocket should also be considered. Since the pocket is a dumbbell-like shape with a narrow linker space, and the narrowest part (0.36 nm) cannot be flattened down a heterocyclic ring, it may be beneficial to consider designing an inhibitor that is geometrically complementary with the linker space, to design suitable inhibitors that fit well within the HL binding site. Unfortunately, this will complicate the design process, and at the present time there are only five compounds identified as inhibitors of HL.Two types of structurally diverse small molecule inhibitors of EL have been reported in the literature 50 value was as good as 0.06 µM. The inhibitors could be further improved by altering the sulfanilamide and the benzene group in the shallow groove, and the linker arm between them. The compound CHEMBL485946 is a dual inhibitor that binds to both LPL and EL. The cyclohexane region of CHEMBL467023, a specific inhibitor of EL, was deeply inserted in the EL pocket, and the rest of the inhibitor was located in the shallow groove. The structure of CHEMBL467023 is well matched with the EL binding pocket, and explains why its IC50 values, this correlation can be inconsistent because, in addition to binding affinity, the IC50 value can also be affected by other factors including the measurement methods, and the membrane permeability of the compounds.Additional binding analyses are shown in As stated above, both LPL inhibitors chosen were non-specific. In fact, when searching the CHEMBL database, we found that most LPL inhibitors could also inhibit EL, and consequently there are more inhibitors for EL than for LPL or HL. In the current study, the dual inhibitors CHEMBL339297 and CHEMBL485946, which are inhibitory for both LPL and EL, were further investigated.The binding pockets of LPL and HL are quite different, as mentioned above see . AnotherAlthough CHEMBL485946 is not considered drug-like by many medicinal chemists, its long flexible fatty acid chain means that it can bind to a large number of proteins. When binding to LPL and EL, the oxygen atom of its hydroxyl group forms a hydrogen bond with the lipases. When binding to LPL, a hydrogen bond is formed with Arg192, which is not predicted to be a typical pharmacophore feature above. In the case of EL, the boric acid group acts as an anchor, and allows CHEMBL485946 to bind deeply into the hole. The residue involved in hydrogen bond formation corresponded to His256, a typical pharmacophore as predicted. These results may explain why the inhibitory activity against EL is 10-fold stronger than against LPL.50<2 µM), moderate (2 µM ≤ IC50<50 µM) and poor (IC50≥50 µM)], and performed docking analysis with the constructed models of each lipase. Our results showed that there was consistency between the results of biological experiments and the predicted ΔG values , which was consistent with our docking scores. Taken together, these results consistently demonstrate that the constructed models of LPL, HL, and EL were reliable and accurate for the evaluation of inhibitor activity.The docking studies described above using known inhibitors clarified the relationship between inhibitory activity and binding affinity, suggesting that the models of LPL, HL and EL constructed in the current study were reliable and useful. Importantly, a reliable protein model could be used not only to identify effective inhibitors, but also to distinguish the good from poor inhibitors. In order to evaluate the quality of these models, we selected inhibitors with different inhibitory activities [defined as follows: good (ICG values , indicatIn conclusion, we have systematically built homology models for all the TLGS members. In addition, we have identified the lipase binding pockets and residues of the lipases involved in binding, and also investigated the binding poses of specific and non-specific inhibitors towards TLGS members. Although LPL, HL, and EL belong to the same subfamily, their binding pockets are quite different. MDS indicated that the conformation of the EL active site changes more than LPL and HL during the catalytic process. This demonstrates that the EL pocket is more flexible when compared with the pockets of LPL and HL.The lipase inhibitory activity is a result of blocking the catalytic site, rather than forming a strong interaction with the catalytic residues. Compound studies were therefore essential for designing effective lipase tools and inhibitors.The proposed homology models could distinguish between good, moderate, and poor inhibitors. Consistent docking studies showed that the constructed models could be used to distinguish inhibitors that had potent inhibitory activity, suggesting that these models will be useful for designing efficient inhibitors and virtual screening in the future.Our results provide important information on the molecular structures of lipases, indicating that the proposed models will be reliable for designing effective potential therapies for the treatment of hyperlipidemia and atherosclerosis.


Eighty-five years ago Dr. Guido Fanconi described a family with three brothers with microcephaly, hyperpigmentation of the skin, hypoplasia of the testes, and who developed a lethal anemia between the ages of 5 and 7 , 2. SincIn addition to anemia, FA patients are highly predisposed to leukemia, head and neck squamous cell carcinoma, and gynecological cancers . FA is cFANCC c.67delG mutation in the Dutch and Canadian Manitoba Mennonite populations originate from a common founder.This special issue provides a wide range of scientific papers and reviews that examine in detail techniques for diagnosis of FA, molecular and genetic mechanisms of FA protein function, comprehensive details of the varied clinical manifestations, new model systems for study of this disease, and potential new therapeutics. Three papers describe FA relevant aspects in FA diagnoses using chromosomal breakage analysis and mutation detection by multiplex ligation-dependent probe amplification (MLPA) and PCR-based Sanger sequencing, or next generation sequencing. The strategy to detect mutations and the genetic counseling of involved families should be adapted when there is evidence for a founder effect, which results in a high prevalence of a common mutation in a specific population. In this special issue, Y. de Vries et al. provide evidence that FA-C patients with the ERCC1 mutations have been detected in FA patients, ERCC1 interacts with FANCP/SLX4 and functions in interstrand crosslink repair [One impediment to FA research has been the relative lack of a murine model that truly recapitulates the severity of FA hematopoietic defects. In the data reported by J. H. E. Verhagen-Oldenampsen et al., Ercc1-deficient mice were used as model for FA-like bone marrow failure. Although no k repair , the crik repair   has been responsible for sponsoring a significant amount of research for over 20 years. Also in existence over a similar period, the German group Deutsche Fanconi-Anämie-Hilfe e.V. (Fanconi Anemia Aid Association: http://www.fanconi.de/), has been actively involved on an international scale in long-term research programs. The more recently formed UK-based organization, Fanconi Hope (http://www.fanconi.org.uk/) has been supporting research through the auspices of the FARF Scientific Advisory Board, for UK research projects selected by FARF. FA patients, although relatively few in number in each country, are fortunate in having a number of strong family support groups that coordinate their activities on an international basis to ensure a coherent approach to supporting research. The longest established group, the United States-based Fanconi Anemia Research Fund (FARF: Fanconi Hope and FARF also sponsor an International FA Gene Therapy Working Group, now in its third year, which aims to accelerate the transition from research to gene therapy trials for FA patients by coordinating activities on an international scale. FA patients, their families and friends are in large part responsible for raising the funds for this research. This is of great benefit to those affected as this allows them to believe they can make a difference, if not to the current generation of FA patients then at least as a legacy to the benefit of the next generation.Laura E. HaysStefan MeyerHenri J. van de Vrugt