The lack of high-quality data to support evidence-based policies continues to be a concern in African cities, which present marked social, economic and cultural disparities that may differently impact the health of the groups living in different urban contexts. This study explores three urban units—formal, transition and informal—of the capital of Cape Verde, in terms of overweight/obesity, cardiometabolic risk, physical activity and other aspects related to the urban environment.n = 1912 adults), based on geographical coordinates of private households, was selected to apply the UPHI-STAT questionnaire. In a second stage (n = 599), local nutritionists collected anthropometric measurements  and body composition by bioelectric impedance . In a third stage, pedometers were used to count study participants’ steps on working and non-working days for one week (n = 118). After a preliminary statistical analysis, a qualitative study was developed to complement the quantitative approach. Generalized linear models, among others, were used in the multivariate analysis.Quantitative and qualitative research methods were used in this intra-urban study. A proportional stratified random sample (p < 0.001) among units. About three-quarters (76.6%) of the participants of the informal unit emphasised the need for more security. The formal unit presents an older age structure (61.3% above 40 years old) and the transition unit a younger age structure (only 30.5% above 40 years old). Some health-related variables were analysed in each unit, revealing an excess of chronic conditions reported by inhabitants of informal unit, compared with the formal unit despite the informal unit’s younger age profile. The self-reported hypertension varied significantly among urban units (p < 0.001), with 19.3% in the formal unit, 11.4% in the transition unit and 22.5% in the informal unit. Women of the urban units present significant differences (5% level) for body mass index calculated from self-reported measures (p < 0.001), fat mass (p = 0.005), waist circumference (p = 0.046) and waist-to-height ratio (p = 0.017). For women, overall physical activity was 67.4% , with differences among urban units (p = 0.025). For men it was of 85.2% , without significant differences among urban units (p = 0.266). The percentage of women and men who reported physical activity in leisure time was discrepant, with 95%CI  and , respectively. The results of pedometers also indicated that men walk significantly more than women (p < 0.001), with a difference of approximately 2000 steps/day.Insecurity was the main concern among survey respondents in the three units, notwithstanding with significant differences  suggests these as the priority target groups for health promotion campaigns. The link between health planning, urban planning and security of the city needs to be reinforced to minimize health, social and gender inequalities. Social and physical environments have been recognized as important determinants of health , 2. In AWorldwide, it is estimated that about one billion people live in informal settlements and slums , 6. AccuAccording to Ziraba et al , overweiUrban Planning and Health Inequities—moving from macro to micro statistics (UPHI-STAT project), which aims to study three urban units/areas—formal, informal and transition—in the city of Praia, using a mixed of quantitative and qualitative research methods to provide critical information for understanding how socio-economic-cultural inequalities and the urban morphology affect the health of their residents. According to its national census , obtained by Wilson method. In the same way, after excluding four pregnant women, the magnitude of the same event was 338/595 (56.7%) 95%CI , using the real BMI. Taking into account the issues associated with both confidence intervals, we use concepts of an imperfect diagnostic test (self-reported) to correct the first estimate. In fact, it is possible to use the sub-sample with both BMI (n = 395) to estimate the sensitivity (80.6%) and the specificity (90.2%) of the indirect binary self-classification as overweight/obesity , considering the measures performed by nutritionists as a gold standard. After that, confidence limits for prevalence of overweight/obesity adjusted for sensitivity and specificity are calculated—95%CI —using Blaker’s, Sterne, Clopper-Pearson and Wilson methods as described by  for women and  for men.p < 0.050 and p < 0.010, respectively). By gender, men walked significantly more than women (p < 0.001), with a difference in the medians of approximately 2000 steps/day.As global physical activity also includes walking, it is important to refer the complementary information of the third stage, based on the report sheets of steps obtained with the pedometer, available only for transition and informal unit . We analp = 0.040) with perception of need for more security . Overall and among men in the transition unit, there was a positive association between physical activity in leisure time and the need for more sport facilities , respectively). There was a positive association between physical activity in leisure time and the need for more gardens and green spaces for men and overall  in transition unit and also for men of the formal unit ). Men who engage in physical activity during leisure time seem to require more infrastructures in their neighbourhood.Possible relationships between physical activity in leisure time and (i) the need for increased security, and (ii) lack of some infrastructures were explored using some binary variables already described in Do you walk or use a bicycle  for at least 10 minutes continuously to get to and from places?) shows a similar trend. Stratifying by gender, a negative association between “walking and cycling” and the need for more security appears for women . Stratifying by gender and urban unit, the significance of this association was verified for women of the transition and informal units . The relationship between “walking and cycling” and “gardens and green spaces” presented significant positive associations (results omitted) for both men and women of the transition and informal units. Again, participants who walk and bike tend to report a need for more gardens and green spaces.Exploring this type of association with another binary variable “walking and cycling” “I’ve been the victim of robbery. I was walking.” “It is late for me and there is no security on the street …” “There’s a lot of insecurity in the neighbourhood, I’d rather not go to practice physical exercise … Yes this is my problem and here where I live there are many delinquents.” “No one can leave the house very early, you never know who you’ll meet on the walk, where you can be assaulted, be beaten.” “Observation during fieldwork revealed unequal distribution of infrastructures for physical activity within the city. Focus groups allowed us to understand some determinants of physical activity, according to the perceptions of the populations of the three areas under study. Discussions of the focus groups seem to reinforce that insecurity of the city is a potential explanatory factor for not practicing physical activity, particularly in the informal unit, as suggested by some participant opinions:In addition to the differences in terms of urbanization of the three units, n = 2200), but is very dissimilar to the percentage—34.9%—found when hypertension was measured using conventional procedures [Overall, self-reported hypertension percentage was 15.7%, varying significantly among urban units, with 19.3% in the formal unit, 11.4% in the transition unit and 22.5% in the informal unit. This overall percentage was similar to the percentage of 14.5% found in Cape Verde, in 2007, for adults between 25–64 . Doulougou et al [vs 17.2%).Doulougou et al  studied ou et al  found loOur study concerns a very small scale, where the three urban units are geographically near each other. Despite this proximity, some related aspects of the nutritional status of participants varied significantly between urban units. Gender disparities in overweight and obesity are also marked in Cape Verde. This fact is described for some developing countries, particularly in the North Africa and Middle East, where the cultural environment favors a larger body size because is linked to fertility, prosperity and healthfulness in women . In factWomen of the three urban units present significant differences in terms of BMI calculated from self-reported measures, fat mass, waist circumference and waist-to-height ratio . The perIn a national study , 45, basNo significant differences were found among urban units, in terms of cardiometabolic risk of women, according to WHO or WHtR definitions, with 74.6% and 72.5%, respectively. For men, it should be noted that these percentages were lower 22% and 35.9% (data not shown). In Tunisia, Ati et al  reportedp = 0.025). For men, it was 85.2% , without significant differences among urban units. The difference between the percentages of women and men who reported physical activity in leisure time was particularly discrepant . Pedometers also indicated men walked significantly more than women (p < 0.001), with a difference of approximately 2000 steps/day. In this context, recent studies show the link between pedometers and health and promotion health messages, but there is a lack of this type of data from developing countries, specifically African countries [Within the multifactorial nature and the complexity of health problems, neighbourhood environment factors such as safety from crime and traffic were associated with overweight among Nigerian adults . Among oountries . The fewWalking has been suggested as a good from of physical activity in particular in developing countries, because is inexpensive and accessible for a vast population  was found in informal unit . The parn = 1912 was obtained using proportional allocation. In each household, one adult was selected at random, from the list enumerated of all adults (at least 18 years old and having lived for at least six months in the respective urban unit). Each participant was interviewed in a first contact or using two more additional contacts, in case of failure of the first or second contacts. After the UPHI-STAT questionnaire was administered, the selected adult was invited to be observed by a nutritionist in a nearby location, to collect data about dietary consumption, anthropometric measurements and body composition by bioelectric impedance. In the third stage, walking was measured via pedometers. In Cape Verde, to our knowledge, there were no previous studies using pedometers. The use of appropriate equipment is particulary relevant in the African context.In the UPHI-STAT research project we developed a sampling frame based on the geographical coordinates of private households in each area, combining GIS and statistical software. This strategy may be applicable to similar settings, where the identification of geographical coordinates of households is possible. A stratified random sample of size Many studies are focused on self-reported and measured BMI and do not explore other important body composition measures. It is well-known that BMI does not differentiate between fat mass and fat-free mass, being a poor predictor of body fat . Among sIn terms of the second stage, the results presented in n = 1912), a discrepancy between the percentage of female (64.4%) and male (35.6%) was observed. Perhaps, in the sampling process to locate a man more contacts are needed or men of these urban units do not participate as much as women in health studies. Another study on Santiago Island [n = 599), the participation was 75.1% for women and 24.9% for men. As the second stage required participant time, and our teams worked mostly during the day, this difference may also be due to a lower employment rate for women. However, the literature indicates that women are more likely to participate in health studies . Neverts [Given the bias of the second stage, in which BMI based on self-reported measures influenced participation, it is expected that overall adiposity and abdominal adiposity would be overestimated. On the other hand, BMI calculated from self-reported measures leads to underestimation of overweight and obesity because women  observed in our study, despite reporting their weight correctly, tend to overestimate their height. This is a common issue reported in literature, varying across different groups , 67. In ividuals), Africanividuals), 69.In spite of the aforementioned limitations, through a mix of quantitative and qualitative research methods, this study adds important findings regarding an understudied African country and provides new insights for development of future research.Our findings indicated that residents of the informal unit and women are the most disadvantaged groups in terms of health outcomes and socioeconomic variables. Focus group discussions and the intensive fieldwork reinforced the higher participation of residents of the informal unit and women in all stages, suggesting the practicability of health promotion campaigns, taking into account the potential of social capital of the informal settlements and the role of the woman in family and society in Cape Verde. The qualitative study also helped us to understand how this particular context can be used to involve women in health promotion in their neighbourhoods, taking into account their decision-making power, their multi-dimensional role in purchasing, processing and preparing food as the pillar of familial food security and also their contributing via non-formal economic activities for their families. On the other hand, the built environment and insecurity of the neighbourhood/urban unit are also modifiable factors in order to promote healthy lifestyles .The role of urban planners and developers, in planning and/or modifying the built environment, to improve populations’ health and reduce harmful exposures is still not well established in Africa. The complexity and specificity of the dynamic of each city highlight the importance of local studies to bring informal settlements into health statistics and to promote better health in these poorest communities. The link between health planning, urban planning and security of the city needs to be reinforced to minimize health, social and gender inequalities.


The objective of the study is to evaluate a range of potential risk factors in the etiology of varicose veins with superficial venous reflux. Forty-nine patients attending a cardiovascular surgery clinic for the management of varicose disease between 2009 and 2010 were enrolled for the study. The age range of the patient group was 44,04 ± 15,05 years and female/male (F/M) ratio was 30/19. Twenty-six normal, healthy volunteers with the age of 40,94 ± 13,60 years and with the female/male ratio of 15/11 acted as control subjects. We investigated several parameters including body mass index, age, birth number > 1, standing for a long time (standing for 8 or more hours without taking a break), systemic diseases, family history, venous Doppler fındings, the levels of homocysteine, ferritin, vitamin B12, and hemoglobin, sedimentation rate, mean corpuscular volume, low density lipoprotein, and rheumatoid factor of the patient group and the control group. We also determined the contribution of the methylene tetrahydrofolate reductase 677 C>T and 1298 A>C gene polymorphisms and FV Leiden in both groups. In this small study, there appears to be no association between varicose veins and body mass index, smoking, type 2 DM, hypertension, family history, and birth number. A history of increased standing duration period (>8 hours) and rheumatoid factor positivity have association with varicose veins with superficial venous reflux. Varicose veins occur commonly in the general population but despite much research the etiology of venous disease is still poorly understood. Obesity, age, parity, standing for long times, and family history are risk factors. Incidence of varicose veins in adult population has been shown to vary among populations (between 10% and 60%) and to increase by age in various studies , 7, 8.A number of epidemiological studies have shown that, in addition to environmental factors, genetic mechanisms may play a role in determining susceptibility to vascular disease. In particular, abnormalities in the enzymes that control homocysteine metabolism have been shown to cause atherosclerotic vascular disease .Since genetic mechanisms may play a role in determining susceptibility to vascular disease, we studied several mutations in patients with varicose veins to look for any association between varicose veins and homocysteine level, protein C, protein S, FV, FVIII, D-dimer, vitamin B12 level, folic acid level, MTHFR, FVR2, B fibrinogen, FV Leiden, and prothrombin mutations besides other possible factors.MTHFR-677 and MTHFR-1298) and FV Leiden mutations in patients with primary varicose veins.The present study is planned to determine various risk factors and to analyze the methylenetetrahydrofolate reductase polymorphisms , standing for a long time before, and additional diseases. Informed written consent was obtained from all patients and control volunteers fulfilling the entry criteria. This study protocol was approved by the Ethics Committee of Ankara Education and Research Hospital.The diagnosis of primary varicose vein was performed by the combination of clinical and duplex scanning examination. All patients in the study had normal arterial examination. Every patient in the control and patient group had duplex examination. The exclusion criteria for the study were deep vein thrombosis, postthrombophlebitic syndrome, and recent infection.There were 45 patients with superficial venous reflux, 2 patients with superficial and perforator venous reflux, and 2 patients with superficial venous reflux and healed venous ulcer. The reflux level was between grades 2 and 4 in the patient group. There were no patients with deep venous insufficiency in the study group. The effects of the grade and type of the reflux on the results were not studied in the paper. We could not evaluate the location of valvular reflux at the various levels, SFJ, upper thigh, midthigh, lower thigh, or below the knee, because of outpatient density in the Radiology Department. Since there were not enough patients in the study group, the differences in the gene polymorphism or the procoagulant parameters between C2 and C3 patients versus the control group were not analysed.Twenty-six normal, healthy volunteers acted as control subjects. They had no symptoms or signs of arterial or venous disease in either limb. Venous Doppler findings of control subjects were normal. They did not have any superficial or deep venous reflux. The control subjects did not have any disease established by careful history, examination, and routine laboratory test including the levels of homocysteine, ferritin, vitamin B12, hemoglobin, sedimentation rate, mean corpuscular volume, low density lipoprotein, and rheumatoid factor. The patients in the observation group and the control group were similar regarding gender, body mass index, smoking habits, medical history, family medical history, and age. We obtained information about standing duration while obtaining history. We asked patients one by one about how long they stand up all through the day and recorded the duration of time in hours for each patient separately.In the physical examination, subjects stood on a raised platform with their feet in three standard positions during inspection of the legs: facing towards the examiner with heels together and forefeet spread wide apart, facing away from the examiner in a similar position, and facing away from the examiner with feet parallel. They were asked to remain in a standing position for a minimum of two minutes before examination of their veins, to allow the blood to pool in the legs. Any scars or notable findings on the legs were recorded.Real-time images of the common femoral, deep femoral, femoral, and popliteal veins were obtained before and after compression. Color and pulsed-wave Doppler sonography also was performed. All patients were evaluated with color duplex scanning in a warm, comfortable examination room by a radiology physician. The examination was performed using a GE Logic venous ultrasonography device. A 5–12 MHz linear transducer was used to measure the diameters of the great saphenous vein (GSV) and the small saphenous vein (SSV) and to rule out acute or chronic deep venous thrombosis (DVT) in supine position. Using color flow imaging in the longitudinal view, the valvular function of the GSV was evaluated at the SFJ, upper thigh, midthigh, lower thigh, and below the knee. The valvular function of the SSV was evaluated at the level of the popliteal fossa. Flow direction was noted with distal compression and release. The reflux was quantified based on valve closure time, with the Doppler spectral tracings obtained in a longitudinal plane. Reflux was defined as being present if the valve closure time was greater than 0.5 seconds. Examination for reflux was made with the patients standing, with upper body elevation of more than 45°, or in reverse Trendelenburg position.The study was conducted in room temperature. Blood samples were taken from the antecubital vein by atraumatic puncture. Blood samples were collected into citrate tubes  and centrifuged at 4000 rpm (revolutions per minute) for 4 min to obtain plasma and serum fractions. Samples were then stored at 22°C until being assayed. Before assay, the samples were thawed at room temperature.The assays were performed by international laboratory supported by Beckman Coulter. Quantitative determination of functional protein C depended on the prolongation of activated partial thromboplastin time. Protein S was determined in accordance with the inhibition of activated factor V. The normal ranges of protein C and S antigens in plasma were 70–130% and 65–140%, respectively.Serum total homocysteine levels were determined by chemiluminescence immunoassay.FXIII testing was performed using commercially available kits according to the manufacturer's instructions. The assay kit is designed to quantitate the true functional FXIII and FXIIIa activity in plasma by measuring transglutaminase activity. In this assay, the thrombin-activated FXIIIa from the patient plasma binds to a substrate coated plate. Next, a horse radish peroxidase- (HRP-) conjugated FXIII is cross-linked to the captured FXIIIa. The cross-linked HRP is then detected with a HRP chromogenic substrate at 450 nm. The data was analyzed to evaluate the correlation between FXIII activity and other DIC markers which included platelet count, fibrinogen activities, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrin degradation product (D-dimer). PT, APTT, fibrinogen, and D-dimer results were generated with an automated clotting analyzer (STA-R).For the genetic testing, a sample of 10 mL 0.05 M EDTA-anticoagulated blood was taken. DNA was extracted according to a standard salting-out procedure. For DNA analysis, commercially available kits were used and the procedure was performed in accordance with the manufacturer's instructions. Mutation status  was determined for all mutations. The analysis of factor V Leiden and prothrombin G20210A mutations was done. For determination of the mutation status of the MTHFR C677T and A1298C mutations, we used PCR amplification and restriction fragment length polymorphism analysis that was performed according to Kim et al., Frosst et al. , respect U at 95% confidence interval . All analyses were performed using SPSS 17.0 for Windows (SPSS Inc. Illinois).Since the control group has less than 30 patients, all parameters in the study were assumed nonparametric and the statistical analyses were chosen for nonparametric tests. Nominal parameters were described using frequency analysis, whereas scale parameters were described using mean and standard deviations. Comparison between groups was tested by Mann-WhitneyGender distribution, age, BMI, smoking, diabetes mellitus, rheumatoid factor positivity, hypertension, family history, long standing duration, and birth of more than one child for patient and control groups are gathered as baseline characteristics of the respondents. The ages of the forty-nine subjects with varicose veins included in the study group ranged between 15 and 85 years  and the ages of the sixteen subjects in the control group ranged between 22 and 68 years . There was no statistically significant difference between the ages of the two groups. The women/men ratio was 30/19 in the study group and 15/11 in the control group.P > 0,05) except for standing for long durations  and rheumatoid factor positivity that were found to be statistically significant . CEAP classification of patients was shown in BMI value of the study group was higher than of the control group. The difference was insignificant. The study group included more smokers which is not statistically significant. Diabetes mellitus, hypertension, family history of varicosis, and birth of more than one child of the study group were higher than of the control group. Differences between the two groups were found statistically insignificant  and to increase by age in various studies , 7, 8.On the basis of experimental and clinical evidence collected for the past decade, it is possible to suggest that the cause of dilatation of the varicose vein is in the vascular wall , 13. TheJavien's study showed that varicose veins were more common in women, but female sex was not found to be a strong risk factor. Among the risk factors most closely associated with chronic venous insufficiency (CVI) were age, family history of varicose veins , and conA number of epidemiological studies have shown that, in addition to environmental factors, genetic mechanisms may play a role in determining susceptibility to vascular disease. In particular, abnormalities in the enzymes that control homocysteine metabolism have been shown to cause vascular disease . MTHFR gene, homocysteine levels may not be regulated properly. Genetic mutations in MTHFR are the most commonly known inherited risk factor for elevated homocysteine levels. The most common MTHFR mutation is called the MTHFR C677T mutation, or the “thermolabile” MTHFR mutation. Another common mutation is called MTHFR A1298C. Even when 2 MTHFR mutations are present , not all people will develop high homocysteine levels. Although these mutations do impair the regulation of homocysteine, adequate folate levels essentially “cancel out” this defect. The MTHFR polymorphism, which is associated with a predisposition for elevated plasma concentrations of homocysteine, has been reported to represent a genetic risk factor for occlusive vascular diseases, carotid atherosclerosis, silent brain infarction, and small artery occlusion with ischemic stroke, although these associations remain controversial [Methylenetetrahydrofolate reductase (MTHFR) plays an important role in the folate cycle and contributes to the metabolism of the aminoacid homocysteine. It catalyses the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, thus generating the active form of folate required for remethylation of homocysteine to methionine. Some of the mutations in the MTHFR gene cause a decrease in MTHFR activity. If there is a genetic mutation in theoversial . WhetherIn our study, we did not observe high levels of homocysteine in our varicose disease patients compared to control group. The results of our study showed that there was no statistically significant difference between patients and control groups based on their baseline characteristics except for standing durations of the patients and rheumatoid factor positivity. Age, BMI, gender distribution, HT, family history, and birth of more than one child were not different between groups. Although some researches reported that family history of the patients has an effect on varicose veins , we founP < 0,005) [Genetic abnormalities specific to factor V, prothrombin, and homocysteine metabolism were shown to increase the risk for myocardial infarction and ischemic stroke, particularly among younger patients and women in a study . Unlike < 0,005) . This wa< 0,005) . We did There are some other limitations in our study also. Since the number of cases in the patient and control group is small, we did not take the effect of the type  and the degree of reflux into consideration in the study. Economical factors and the type of rheumatic diseases were not evaluated in the study also. We only studied rheumatic factor positivity which was found to be statistically significant compared to the control group.While there was a trend towards an increase in certain biochemical parameters in our study, ultimately there was no statistically significant difference in hematological or biochemical markers between the subject group and the control group. In this small study, there appear to be no significant genetic differences related to folate metabolism or procoagulant predisposition or medical risk factors including BMI value, smoking, diabetes mellitus, hypertension, family history of varicosis, and birth of more than one child. A history of increased standing and rheumatoid factor positivity were found to be associated with varicose veins. Further studies, perhaps with a larger cohort, could show significance of parameters that were found to be insignificant in our study. Further studies should also be conducted to find any association between rheumatic diseases and varicose vein development.


Objective: This study compared the effectiveness of two group treatments, behavioral activation (BA) and cognitive therapy (CT), in reducing subsyndromal anxiety and depressive symptoms in a sample of Iranian university students.Method: Twenty-seven Iranian university students who scored 18 or higher on the depression subscale and 16 or higher on the anxiety subscale of the Depression, Anxiety, and Stress Scale (DASS-42) were randomly assigned into treatment groups. One group received 8 sessions of BA (n = 14), and the other received 8 sessions of group CT (n = 13).Result: Analysis of covariance revealed that the BA group had a significantly greater reduction in depressive symptoms than the CT group. However, there were no significant differences between the two groups in the levels of anxiety, stress symptoms or functional impairment after treatment.Conclusion: This study found evidence for the effectiveness of BA in reducing anxiety, depressive and stress symptoms and functional impairment compared to CT. BA was more effective than CT in improving depressive symptoms and was as effective as CT in decreasing anxiety, stress and functional impairment. BA is also a cost-effective intervention, particularly in group formats. According to the World Health Organization (WHO), anxiety and depressive disorders are the most common and prevalent mental disorders, with anxiety disorders as the most prevalent mental disorder , 2. The Subsyndromal anxiety and depression, though clinically failing to meet formal diagnostic criteria, has a significant potential to impair day-to-day functioning . DespiteEpidemiological studies have found an elevated rate of anxiety and depressive symptoms in university students in Iran –13, withCognitive therapy (CT) and behavior therapy have demonstrated effectiveness in treating anxiety and depressive disorders –17. TherOutcome studies have indicated the efficacy of CT for a variety of mental disorders, including major depressive disorder, generalized anxiety disorder, panic disorder and social anxiety disorder , 24. CT Behavioral activation (BA) is a behaviorally-oriented psychotherapy that helps clients identify and modify inactivity and avoidance patterns . It was Avoidant behavior plays a key role in fostering and maintaining anxiety disorders and depression. For example, depressed patients are frequently involved in avoidant behaviors like complaining, which means they often lose any chance of gaining positive reinforcement . These iBecause BA targets avoidant behaviors, the treatment is appropriate for managing comorbid anxiety and depression , 38. TheGroup and short-term modalities yield several benefits, including cost-effectiveness and an ability to cover more patients than is possible with individual therapies or long-term treatments . Group aIt is important to note that there have been a number of recent empirical studies that support the use of BA and CT in a variety of settings and populations  recruited through advertisements in several universities in Tehran. This sample size was determined on the basis of Cohen’s table  for a poCriteria for participant inclusion in the study were the existence of subsyndromal anxiety and depressive symptoms as measured by a score of 18 or higher on the depression subscale and 16 or higher on the anxiety subscale of the Depression, Anxiety and Stress Scale (DASS-42). This cutoff was selected to reflect the criteria used by Sahebi and colleagues  in theirThe dropout criterion was three absences in eight sessions, consistent with the recommendation of Gollan and colleagues . Two parMaterials and ProcedureThis study compared two groups of BA as the experimental condition and CT as the comparison condition. Participants were randomly assigned into one of the groups. CT was considered the comparison condition because of its demonstrated efficacy in treating depressive and anxiety disorders , 17 and Recruitment advertisements were placed at several Iranian universities. Volunteers were individually evaluated onsite to confirm their eligibility for the study and obtain informed consent. For determining eligibility, a clinical interview using ADIS-IV and DASS-42 was conducted for each participant. To measure functional impairment, the participants were asked to complete the Work and Social Adjustment Scale (WSAS) . ParticiTreatment and TherapistsBA treatment followed the guidelines of Gollan and Martell and colleagues , 60, 61 CT followed the published guidelines . As in tParticipants in the CT condition were asked to identify relations between their thoughts and emotions, automatic thoughts and cognitive distortions. They were then encouraged to challenge them with cognitive techniques.The two CT therapists were both PhD students in a clinical psychology program with at least 2 years of experience in the psychotherapy of anxiety and depressive disorders obtained in university counseling centers. They were also trained in cognitive behavioral therapy for the treatment of anxiety and depressive disorders. Prior to the study, they reviewed treatment manuals, and during the study, they received copies of session agendas.MeasuresAnxiety, Depressive and Stress Symptoms: The Depression, Anxiety and Stress Scale (DASS) (e (DASS)  was usede (DASS)  for the e (DASS)  for the e (DASS) .Diagnostic Interview: The Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV) (ADIS-IV)  was usedADIS-IV)  reportedFunctional Impairment: In order to assess functional impairment, the five-item Work and Social Adjustment Scale (WSAS) was used, which has been shown to be a valid and reliable tool to assess anxiety and depressive disorders  was used to determine the equivalence of the treatment conditions on outcome measures at the pretest point. The results did not indicate a significant difference between BA and CT conditions on outcome measures at the pretest point for depressive symptoms, F = 1.13, p > .05; for anxiety symptoms, F = 0.02, p > .05; for stress symptoms, F = 1.44, p > .05; for functional impairment, F = 0.18, p > .05. These results demonstrated the success of random assignment in producing equivalent groups on these variables at the pretest point.To analyze the effect of each treatment condition on outcome measures, the paired t test was used. Results are presented in To compare the BA and CT conditions on the outcome measures, Analysis of Covariance (ANCOVA) was used with pretest scores as the covariate. The ANCOVA results and the means and standard deviations of the outcome measures at the pretest and posttest points are presented in 2 = .24 (a large effect), but there was no difference between the two treatment conditions in improving anxiety and stress symptoms or functional impairment (p > .05) for anxiety symptoms, partial η2= .01; for stress symptoms, partial η2= .02; for functional impairment, partial η2= .00. The effect size (Cohen’s d) for BA relative to CT was also calculated from the ANCOVA F value  = 7.80, p < .05, partial η F value : For depAccording to the definition of a clinically significant change , two treFor depressive symptoms, 71% of the participants of BA condition (n = 10) were assessed to be in the functional range, compared with 31% of CT participants (n = 4). For anxiety symptoms, 50% of BA participants (n = 7) showed a clinically significant improvement in symptoms, compared to 61% of the CT participants (n = 8). Finally, all participants in both conditions reached the functional range in stress symptoms.This study compared the effectiveness of BA and CT administered in group settings in university students with subsyndromal anxiety and depressive symptoms. The results revealed that both treatments could decrease the severity of symptoms and functional impairments in participants. However, BA was more effective than CT in reducing depressive symptoms as assessed through both statistical and clinical significance. This finding was consistent with a previous, large sample investigation  that fouBA and CT were similarly effective in reducing anxiety, stress symptoms and functional impairment. The finding of this study revealed that BA effectively reduced anxiety symptoms, which is consistent with previous studies –43, and Limitations and Future DirectionsThis was a pilot study; and as a result, there were several limitations. First, the sample size was not large, possibly limiting the generalizability of the results. Therefore, future studies should consider increasing the sample size to improve generalizability. Second, the CT condition in the present study was a subset rather than the full protocol, and this may limit its effectiveness, which can be increased when implemented with other techniques in the complete CT protocol. Finally, the sample was taken from a specific, highly educated population, and the findings might be limited to this population. Future studies should compare the BA and CT interventions on other populations, including clinical samples. Furthermore, it may be useful to investigate the preventive effect of BA and explore the mechanisms of change in the intervention.Participants in the present study had subsyndromal symptoms of anxiety and depression. As noted previously, these symptoms can lead to the significant functional impairments , 14. As The effects of both treatments on anxiety and depressive symptoms indirectly support the notion that a common etiology underlies depressive and anxiety disorders, and it is consistent with the transdiagnostic approach , 20 to gIn summary, this study found positive evidence for the effectiveness of BA in reducing anxiety, depressive and stress symptoms and functional impairment relative to CT. BA was more effective than CT in improving depressive symptoms and was as effective as CT in decreasing anxiety, stress and functional impairment. BA is also a cost-effective intervention, particularly in group formats for clients and managed care.


Papaver nudicaule cultivars. The color of the petals is essential to attract pollinators. We investigated the occurrence of flavonoids in basal and apical petal areas, stamens, and capsules of four differently colored P. nudicaule cultivars by means of chromatographic and spectroscopic methods. The results reveal the specific occurrence of gossypetin glycosides in the basal spot of all cultivars and demonstrate that kaempferol glycosides are the major secondary metabolites in the capsules. Unlike previous reports, the yellow-colored stamens of all four P. nudicaule cultivars are shown to contain not nudicaulins but carotenoids. In addition, the presence of nudicaulins, pelargonidin, and kaempferol glycosides in the apical petal area was confirmed. The flavonoids and related compounds in the investigated flower parts and cultivars of P. nudicaule are profiled, and their potential ecological role is discussed.Flavonoids play an important role in the pigmentation of flowers; in addition, they protect petals and other flower parts from UV irradiation and oxidative stress. Nudicaulins, flavonoid-derived indole alkaloids, along with pelargonidin, kaempferol, and gossypetin glycosides, are responsible for the color of white, red, orange, and yellow petals of different  Ubiquitous in angiosperms, flavonoids are extremely diverse in their chemical structure, color, and biological function. Flavonols, flavones, flavanones, flavanols, and anthocyanidins are just a few examples of the wide range of subclasses . AnthocyPapaver nudicaule, a poppy species originating from Siberia [In 1931, the first flower pigments of  Siberia  but comm Siberia ,6. The s Siberia ,8.P. nudicaule contain the yellow nudicaulins, an unusual group of indole alkaloids with three glucose substituents (O-glucoside (gossypitrin) and seven kaempferol glycosides whose substitution patterns correspond to those of the indole alkaloids [Yellow and orange flowers of tituents , that arlkaloids . In the lkaloids . Additiolkaloids .P. nudicaule; pelargonidin glycosides were limited to the petals of garden varieties [Papaver species, but there was no accompanying detailed chemical analysis [In 1962, it was shown that yellow compounds are present in both the petals and stamens of wild-type and cultivars of arieties . Furtheranalysis .P. nudicaule cultivars. The potential biological and ecological function of the constituents of P. nudicaule is discussed in the context of current knowledge and hypothetical considerations.In the present study, we report on the occurrence of flavonoids and the biosynthetically related nudicaulins in two petal areas, capsules, and stamens  of whiteP.nudicaule cultivars. Two of these glycosides are present in all flower samples (indicated by blue boxes in High-performance liquid chromatography–photodiode array detection (HPLC-PDA) analysis of fresh extracts obtained from the apical petal areas of the white, yellow, orange, and red cultivars confirmed the presence of nudicaulins, kaempferol, and pelargonidin glycosides. In previous studies, the aglycone structures and the substitution patterns of the apical pigments were already elucidated by LC-MS  and NMR R) of 16 min, indicating a lower polarity and a reduced degree of glycosylation compared with kaempferol glycosides occurring in petals of other cultivars.White flowers possess the most kaempferol glycosides but lack pelargonidin glycosides and nudicaulins. The two major kaempferols elute after a retention time , one anthocyanidin , and flavonoid-derived indole alkaloids (nudicaulins), as well as carotenoids were detected. Their distribution in different flower parts of the examined white, yellow, orange, and red cultivars is summarized in This study investigated the occurrence of UV/Vis absorbing pigments in the apical and basal petal areas, capsules, and stamens of P. nudicaule flowers. This is in agreement with results from previous studies [Pelargonidin glycosides and nudicaulins are present in the apical parts of red, orange, and yellow  studies ,8,10.Since pelargonidin glycosides represent biosynthetic precursors of the nudicaulins , the facThe identified kaempferol glycosides are the main flavonoids in the apical area of white petals and may function as UV pigments, as reported for other plants . AdditioPapaver plants are open during both day and night, a broad pollinator audience with varying color preferences may be attracted. Consequently, the various flower constituents in P. nudicaule cultivars may affect different processes, each of which contributes to the survival of the species.Pigments coloring the apical area serve an important ecological function by attracting pollinators such as bees and bumblebees. Differently appearing petals might attract different pollinators and therefore improve reproductive success . FurtherO-glucoside, had been reported in yellow petals [Chrysanthemum segetum flowers and, along with herbacitrin (missing OH group in position 3′), of P. radicatum [P. nudicaule, because the basal flower part is visually covered by stamens and the capsule. Similarly, the functions as a UV protector  or as a visual nectar guide for insects, as described for example in Rudbeckia hirta [The present study describes for the first time the occurrence of several gossypetin glycosides exclusively in the basal area of the petals of all four cultivars. Until now, only gossypitrin, the gossypetin 7-w petals . The facw petals . Gossypiadicatum ,21. It iia hirta , are notP. nudicaule cultivars. It may be that in P. nudicaule the found flavonols play a role in pollen germination or pollen tube development, as it was previously reported in maize and petunia [However, it is noticeable that gossypetin glycosides also occur, together with kaempferol glycosides, in the stamens of all four  petunia .Eschscholzia californica Cham. [Papaver species—tentatively reported by Tétényi to be nudicaulins—may have been confused with these indole alkaloids because of their similar color. As of now, nudicaulins are known only from petals of P. nudicaule, Papaver alpinum, and Meconopsis cambrica [Furthermore, contrary to preceding reports , we showca Cham. . The yelcambrica .P. nudicaule cultivars, while strongly colored pelargonidin glycosides are restricted to apical petal areas of the orange and red cultivars and nudicaulins to apical petal areas of the yellow and orange flowers. This distribution pattern suggests that each group of compounds serves a different function. While the role in pigmentation is obvious, it may also be that some of the flavonoids have specific functions in growth and reproduction processes. Certain compounds may represent important metabolites that are present during petal development rather than biosynthesis products assigned to functions in the flowering stage. For example, it was already shown in yellow P. nudicaule flowers that pelargonidin glycosides decrease in favor of nudicaulin accumulation during petal development [Our results show a defined distribution of weakly colored kaempferol and gossypetin glycosides in all four elopment . Future Papaver nudicaule cultivars were purchased from Jelitto Staudensamen GmbH  and Syringia (“Wonderland White” and “Matador Red”). The plants were reared in soil in the greenhouse facility of the Max Planck Institute for Chemical Ecology at temperatures between 21 °C and 23 °C during the day and between 19 °C and 21 °C during the night, with an average humidity of 55%. Phillips Sun-T Agro 400 Na lights were used to ensure a daily light period of 14 h. Plants were watered daily for 10 min. After sowing, a period of six to eight weeks passed before multiple buds developed on individual plants.Seeds of v:v) ratio of water to methanol was added to achieve a uniform concentration of 1 mg of material per 10 µL of solvent . After 30 min of extraction in the ultrasonic bath, samples were centrifuged , and the supernatant was used for HPLC-PDA analysis. The entire procedure was carried out with three biological replicates.After freshly opened flowers were harvested, petals were separated, washed with deionized water and wiped dry, and the apical and basal areas were dissected. Every flower compartment was weighed and coarsely ground under liquid nitrogen. For extraction (Method 1), an amount of solvent in a 1:1  equipped with an EC250/4 Nucleodur C18 HTec column from Macherey-Nagel . The method included a 21-min gradient from 20% to 67% of methanol in acidified water (0.1% trifluoroacetic acid) with a subsequent washing step (100% methanol) and equilibration to starting conditions. The flow rate was 1 mL·minFor recording UV/Vis absorption spectra of carotenoids, the stamen and the upper capsule were separated, hexane was added, and the samples were homogenized using Bertin Minilys  (Method 2). After extraction in the ultrasonic bath for 3 min and centrifugation , spectra of the supernatant were measured against a hexane reference. Samples were applied inside a quartz cuvette with an internal width of 1 cm to a Jasco V-550 UV/Vis spectrophotometer.


Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery) have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy. Historically, whole brain radiation therapy (WBRT) was the main treatment modality used for patients with BM, and the median survival of untreated patients was one month . HoweverIn addition to these prognostic factors, due to different natural histories and responses to treatment according to the histological type and molecular characteristics of the primary tumor, the primary site has become a determining factor in the therapeutic decision. Indeed, diagnosis-specific classifications have highlighted the importance of the primary site in determining differences in prognostic factors for survival, as well as in median survival  4 breast cancer (BC) and other primaries, respectively) .–22.19–22et al., the significant impact of efaproxiral was observed on the median survival (which was doubled) of pre-stratified patients with BC, and there was an increase of 13% in terms of tumor response for the population with lung/breast (p = 0.01) .,26.25,26These trials showed that at the best, there was an improvement in local control and an increased time to cerebral progression. However, this was at the cost of increased toxicity, and there was no improvement in survival.et al. reported the results of a randomized phase II trial assessing WBRT with or without temozolomide as a radiosensitizer for patients with BM from BC [At the San Antonio Breast Cancer Symposium, 2011, Kirova  from BC ; no advaFurther trials assessing chemotherapy combined with targeted therapies and WBRT are currently under investigation.2.5.Therapies targeting the human epidermal growth factor receptor 2 (HER2) have been evaluated or are currently under investigation in combination with WBRT for BMBC.Only one retrospective study on 31 patients showed the feasibility of the trastuzumab-WBRT combination with good tolerance and an encouraging objective response . A recenThe use of lapatinib concurrently with WBRT has been assessed in a feasibility phase I study for patients with BM from HER2-positive BC, but this study did not meet the predefined criteria for feasibility  . HoweverFinally, an ongoing feasibility phase I study is currently examining different sequences of combined trastuzumab emtansine (TDM-1) and WBRT in patients with BM from HER2-positive BC .2.6.The benefit of an SRS-boost as part of WBRT has been shown in patients with oligometastatic BM –32. Howeet al. conducted an RCT with a similar design, for patients with 2–4 BM [vs. 6 months, p = 0.0005) and a dramatic increase in the rate of one-year local control . In a meta-analysis, involving 358 patients with 1–4 BM from unselected primary tumors, no significant difference was observed in the survival between the patients with or without a boost  [vs. 4.9 months, p = 0.04) and less local recurrence  than the patients receiving only WBRT. In addition, a statistically significant improvement in Karnofsky performance status (KPS) and a decreased use of corticosteroids was observed. To our knowledge, there is no specific study for BM from BC in this context, but these data promote an additional SRS-boost for patients with 1–3 BM. However, if extra-cerebral disease is uncontrolled, giving a short life expectancy, the value of maximalist intra-cerebral control, and thus of a boost, remains questionable.The Radiation Therapy Oncology Group (RTOG)-9508 trial (comprising only 10% of patients with BM from BC) showed that WBRT plus SRS was better than WBRT alone in terms of survival rates for patients with single BM and that there was a trend towards a survival benefit for patients with 2–3 BM . Kondzioh 2–4 BM . The sam5; 1.02) . HoweverFour ongoing prospective trials are currently assessing the interest in, or feasibility of, an integrated boost during WBRT  for patients with multiple BMs from mixed primaries .2.7.et al. [vs. 72.5%, p = 0.002), better remote control in the brain (58.5% vs. 36.3% p = 0.003) and one-year actuarial survival not being significantly improved , but the median survival was similar. There was no difference in the neurological death rate and or incidence of toxicity  between the two arms. The authors concluded that omission of WBRT was appropriate. This study was the basis of a second analysis focusing on mini mental state examination (MMSE) change as a function of the treatment arm [vs. 7.6 months, p = 0.05), suggesting that the recurrence itself may be responsible for neurocognitive deterioration.The value of WBRT in addition to an SRS procedure was the subject of two randomized phase III trials ,34. Howeet al.  randomizment arm . The MMSvs. 31%, p = 0.04; remote site: 33% vs. 48%, p = 0.023) and in neurological deaths, without any difference in functional independence time or survival. This study generated a second analysis reporting the quality of life and a self-reporting assessment of cognitive function [vs. mean, 69.7; SE, 4.0 for WBRT; p = 0.0486).Similar results were observed in the European Organization for Research and Treatment of Cancer (EORTC) trial, which included 199 patients with 1–3 BM who were randomized to SRS alone or SRS plus WBRT . Upfrontfunction . A statiFinally, a retrospective trial suggested a survival advantage for patients with single BM and controlled extra-cranial disease who underwent SRS followed by WBRT, compared with those receiving only SRS .et al. [The above is a summary of the literature related to the current debate regarding the best choice for patients with oligometastatic brain disease. On the one hand, since WBRT appears to significantly reduce the number of recurrent BMs, it could reasonably be concluded that the trial from Aoyama et al.  supportset al.  argue thet al. [vs. 24%). These interesting results required further investigations, as several biases were highlighted .An ongoing multicenter randomized phase III trial with the primary end-point of overall survival is assessing the neurocognitive effect of WBRT added to SRS for patients with 1–3 BM from unselected solid tumors as a secondary end-point (NCT00377156), in order to verify the results of the RCT from Chang et al. , which f2.8.Surgery for BM has usually been considered only in cases of vital threat, major neurological risk or the need for histological diagnosis. For patients with a single BM, the treatment strategy has now been modified, based on the results of three RCTs –41. In tvs. 8 weeks) [et al. [These trials included a limited number of patients with BM from BC, but are the only trials to provide information related to this type of therapeutic strategy. Two of the trials showed an improvement in the median survival for patients with controlled extra-cranial metastases who underwent surgery, as well as a significant improvement in functionality (KPS ≥ 70: 38 8 weeks) ,40,42. T8 weeks) . However [et al.  did not 2.9.vs. 46%–59%; remote sites 14%–23% vs. 37%–42%) and neurological death (14%–28% vs. 44% without surgery), without any difference in overall survival. It could be expected that for patients with controlled extra-cranial disease, a survival advantage would emerge from the combined strategy. Less than half of the participating patients in both trials had controlled extra-cranial disease, and no subgroup analysis for survival was performed. Moreover, since the neurological death rate was significantly higher for patients with delayed WBRT in both studies, it appears that salvage therapy is less effective on brain control than upfront WBRT.Surgery without upfront WBRT has also been evaluated in two RCTs, wherein 10% of the patients had BM from BC ,43. In tFurthermore, two retrospective studies that included patients with single BM and no extra-cerebral disease showed a survival advantage for the group of patients receiving WBRT after BM surgical resection ,45.Other therapeutic strategies are currently under investigation, but have not yet been published in RCT, e.g., “on demand” SRS, surgery followed by tumor bed irradiation.3.To summarize, scarce data exists in relation to the management of BM, specifically from BC, the purpose of which ranges from maximal brain disease control to symptom palliation. It is considered that, despite a relatively good response rate and good symptom palliation, WBRT alone remains insufficient in the treatment of oligometastatic brain disease and should be considered only for multiple (>4) BMs.The main dilemma relies on the use of WBRT after local treatment for oligometastatic brain disease (1–4 BM). Despite the benefits that would be delivered in terms of increased brain control, postponing WBRT after local treatment is considered to be a reasonable option, due to the lack of survival benefit from upfront WBRT, as has been discussed in the EORTC trial .However, it is of note that, firstly, some data support the hypothesis that survival after a diagnosis of BM in patients with BC improves with the addition of modern multimodalities treatment ; and secvs. 48% in the adjuvant WBRT arm (p = 0.002) [Participants in the EORTC trial consisted of 53% with BM from lung cancer, 12% with BM from BC and 35% with BM from other causes. Despite a statistically significant decrease in neurological deaths in patients who received upfront WBRT, the median survival was not altered. Death was considered as being from neurological causes if intracranial failure was a component of the cause of death. In other words, the death rate was the same in both arms, whatever the neurological status, meaning that the cause of death was not related to the brain disease, but rather to systemic disease. That is considered to be the reason why an improvement in brain control does not lead to prolonged survival. For patients whose lives are not jeopardized by uncontrolled systemic or primary disease, an improvement in brain control may lead to an increase in median survival, as suggested by some authors ,44,45. I= 0.002) . Hence, p = 0.004) [Moreover, leptomeningeal disease (LMD), which is a well-known pattern of central nervous system (CNS) failure in patients with metastatic breast cancer, is usually associated with a very poor outcome. This failure pattern has been significantly associated with BC as the primary site in patients treated with SRS alone, and WBRT has been found to significantly lower this risk ,50. The Some BC subtypes, such as HER2 and triple negative , are at high risk of brain recurrence even after initial treatment ,52, withBased on these findings, there are at least two arguments favoring upfront WBRT for oligometastatic brain disease from BC: firstly, the fact that patients with BC are more likely to have controlled systemic disease and are thus more exposed to suffering from neurological death; and secondly, the fact that leptomeningeal disease  is associated with a very poor prognosis and quality of life, but its incidence is lowered by WBRT.Opponents to upfront WBRT propose an “on demand” SRS strategy, in order to avoid potential neurotoxicity, with an MRI survey every three months. However, it is also known that brain recurrence negatively impacts neurocognitive function ,53. FurtN-methyl-d-aspartate receptor antagonist) in preventing cognitive dysfunction following WBRT [The problem with upfront WBRT concerns long-term neurotoxicities as assessed through RCTs . The ideing WBRT ; hippoca4.Relevant studies were identified by searching the electronic database, Medlin/PubMed , between January 2000 and September 2013, using the following keywords: WBRT, BM, BC. Reference lists from these sources were then manually searched to identify additional relevant publications. To be eligible for inclusion, studies had to meet the following criteria: published data on WBRT alone or combined with other treatments, in the management of newly diagnosed BM, either in the particular setting of BM from BC or in a general setting from which data for patients with primary BC (more than 20) were extracted and included in the study. As this review focuses on the efficiency of WBRT, studies on radiation therapy schedules and treatments combined with WBRT, such as local , radiosensitizers, chemotherapy and targeted therapies, were also included. Articles were excluded from our review if they were non-English language papers, individual case reports, review articles, phase I and II trials for which phase III trials were already available, trials not assessing WBRT itself and studies not including patients with BM from BC. Data extracted from the studies were: the number of patients accrued and/or evaluated, the impact of therapeutic combinations and radiation therapy schedules on the response rate to treatments, overall survival and toxicity.The aim was to evaluate whether WBRT for patients with BM from BC is still considered to be an appropriate treatment.5.When the benefit of controlling brain disease is not offset by active extra-cranial disease, there is an actual need for the use of aggressive treatments in patients with BM with controlled systemic disease. Due to the improvement of systemic disease treatment in BC, the overall survival of these patients has been significantly lengthened. Some particular molecular profiles of BC, such as HER2-positive and triple negative, are responsible for an increased incidence of BM. In these patients the survival rate is actually associated with neurological death, making BM treatment in this population an actual challenge. Indeed, brain disease control in this specific population is crucial and potentially could impact overall survival. For these reasons, the findings of the EORTC phase III study should not be generalized to a particular population, and the upfront WBRT should be reappraised focusing on the impact of brain tumor control on overall survival.


Telehealth has become an increasingly applied solution to delivering health care to rural and underserved areas by remote health care professionals. This study integrated social capital theory, social cognitive theory, and the technology acceptance model (TAM) to develop a comprehensive behavioral model for analyzing the relationships among social capital factors , technological factors (TAM), and system self-efficacy  in telehealth. The proposed framework was validated with 365 respondents from Nantou County, located in Central Taiwan. Structural equation modeling (SEM) was used to assess the causal relationships that were hypothesized in the proposed model. The finding indicates that elderly residents generally reported positive perceptions toward the telehealth system. Generally, the findings show that social capital factors  significantly positively affect the technological factors (perceived ease of use and perceived usefulness respectively), which influenced usage intention. This study also confirmed that system self-efficacy was the salient antecedent of perceived ease of use. In addition, regarding the samples, the proposed model fitted considerably well. The proposed integrative psychosocial-technological model may serve as a theoretical basis for future research and can also offer empirical foresight to practitioners and researchers in the health departments of governments, hospitals, and rural communities. Demographic structures change as society changes. Developed countries worldwide are experiencing aging problems. Statistics by the Ministry of Interior, Executive Yuan of the R.O.C.  revealed that the senior citizen population was 7% of the total population in Taiwan in 1993. Taiwan has become an aging society, as defined by the World Health Organization. This percentage reached 10.9% at the end of 2011, and the aging index increased from 42.3% to 72.2%. The population aged 65 or older is estimated to exceed 20% by 2026. Taiwan would then become a super-aged society. In addition, the senior citizen population is estimated to be 36.97% of the total population by 2051; in other words, one senior citizen aged 65 or older for every three citizens.With the phenomenon of the aging of the population, some crucial issues with seeking medical services have been emerged, including emergency medical care, life care when physical and mental functions are lost, chronic diseases, and so on. These care issues have revealed the increasing demands of long-term care and senior health management. Telhealth is considered one possible solution to answer these demands by providing cost-effective care through the use of information technology and biomedical technology.Under the promotion of the National Information Infrastructure (NII), Executive Yuan, R.O.C. (Taiwan), Taiwan’s government has accumulated experience in implementing Telemedicine/Telecare/Telehealth Policy for more than 10 years with focus in supporting people living in offshore islands and mountain areas. Since 1995 the Department of Health, Executive Yuan, R.O.C. (Taiwan) has been promoting Telemedicine Pilot Program to remedy the problem of inadequate medical resources in rural area. The applications of Telemedicine can be categorized into three areas—Teleconsultation, Telediagnosis and Teleeducation. Since 2007 the Department of Health has commissioned Information and Communications Laboratories, Industrial Technology Research Institute to develop Telecare Pilot Program. It is aimed at developing Community-based, Home-based, Institution-based Telecare service models and their application systems with user-friendly human/machine interface through introduction and application of the information and communication technology, thus further establishing Telecare Information Integration Platform. In 2008 Telecare Quality and Service Improvement Program was launched. An integrated and continual network of Telemedicine was developed based upon two original telemedicine models consisting of Home/Community-based and Institution-based models. Meanwhile Ministry of Economic Affairs began to launch two famous telehealth projects. The M-care project, which was one of Mobile Taiwan Applications promotion projects (M-Taiwan), was one of the initial telehealth projects in 2006. The purpose of this project was to deliver health care into remote country to improve residents’ health. In 2007 the U-Care project was launched. The scope of this project was to integrate various industries to create a valuable and innovative business model of telehealth care service. Owing to the advantages of telecommunication technology and medical care, the Taiwanese government in 2008 included telecare and telehealth as a development project in the emerging service industry [The R.O.C. government is promoting relevant health care plans to resolve the weakening care-giving capability of families from the increase of nuclear family, which is made up of the parents and their children, and to manage increasing demands for long-term health care services in an aging society. Information technology (IT) has gradually been integrated into health care services. For residents in rural areas, resources in the community may be effectively combined with medical care and localized through community-based telecare services, helping people self-monitor their physiological conditions and develop healthy behaviors.Telemedicine has been defined as the electronically transmitted rapid exchange of medical information between sites of clinical practice for the purposes of relief and/or education. Telemedicine includes diagnosis, treatment, monitoring, and education of patients by using systems that allow ready access to expert advice and patient information no matter where the patient or relevant information is located . That isThe Technology Acceptance Model (TAM) has been found more favorable in many studies . Many stet al. [Social capital refers to the features of social structure, such as networks, norms, and social trust, which facilitate coordination and cooperation for mutual benefits . Social et al.  also sugAccordingly, the objective of this study is to integrate the theoretical perspectives of the TAM, social capital theory, and social cognitive theory to theoretically develop and empirically examine the behavioral model of residents in a rural community in using telehealth and to understand the relationships among those crucial factors that affect their behavioral intention of telehealth. Furthermore, the structural equation modeling (SEM) was used to examine the psychometric properties of questionnaires and validate the proposed model and hypotheses. The insights of these findings can be used for the further implementation of telehealth systems and may contribute to the future academic studies in this field.Telecare is defined as “the continuous, automatic and remote monitoring of real time emergencies and lifestyle changes over time in order to manage the risks associated with independent living” . TelecarIn 2007, the Department of Health of Executive Yuan in Taiwan commissioned telecare projects that established three telecare models: community-, home-, and institution-based telecare . This prProponents of telecare suggest that it can enable older people to live safely and independently. Three generations of telecare systems can be identified. The first generation of telecare systems was technically simple because the systems comprised no embedded intelligence and relied entirely on the user to activate calls. The second generation systems have all of the features of the first generation but also provide some level of intelligence and automatic detection under limited alert conditions. The third-generation systems provide additional support capabilities, such as lifestyle monitoring or reassurance and the introduction of virtual neighborhoods .Telehealth refers to the remote exchange of data between a patient  and healthcare professionals (at a monitoring center) to assist in the management of an existing long-term condition . The serThe Technology Acceptance Model (TAM) is a frequently used behavioral model for predicting and explaining IT usage . The TAMversus voluntary, informed versus uninformed, effective versus ineffective, and so on), DeLone and McLean [In this study user adoption was examined by intention to use telehealth systems rather than actual adoption. There are a couple of reasons as follows. Firstly, owing to the difficulties in interpreting the multidimensional aspects of “use”  has been associated with the clinical or technical competence of the providers, interpersonal quality of care, and concern for the person rather that the disease only. In addition, patient trust in the health care system  also encourages the use of services, submission to treatment, and patient compliance [Social capital has mostly been measured as patient trust or social participation/social networks ,37. Patimpliance . Social participation is an observable feature of social capital that can be measured according to the density of an organization in a geographical area or by the level of participation by respondents in formal or informal social activities within a society ,38,40. SSeveral previous empirical studies have supported integrating social capital with the TAM. Reid  integratThe utility of telehealth is that it could improve older people’s ability to remain within their homes as long as possible, with easier access to care and more support services that enable them to do this safely. Trust enable residents to believe that the healthcare providers or the health institution  have enough ability, benevolence, and integrity to provide expected positive outcome to them. Similarly, trust enable residents to believe that the healthcare providers or the health institution  will provide required assistances and supports  to improve perceived ease of use of telehealth. Also, if the community residents show higher levels of social participation, then they will become more actively involved in associational activities. These associations often offer opportunities for residents to acquire, maintain, or improve the skills of using telehealth, which in turn, may improve perceived ease of use of telehealth. Besides, higher levels of social participation enable residents to share more feeling, health knowledge and resources about telehealth, which in turn, may also promote perceived usefulness of telehealth.Social cognitive theory (SCT) is a theoretical framework for analyzing human motivation, thought, and action that embraces an interact model of causation in which behavior, cognition and other personal factors, and environmental influences all operate as interacting determinants that influence each other bidirectionally ,46. Selfet al. [et al. suggested that system self-efficacy is likely to be crucial and should be incorporated into the TAM to develop an extended model for the acceptance of telehealth by patients. Adapted from the general concept of self-efficacy, Compeau and Higgins  defined et al.  conceptui.e., system self-efficacy), and will require direct interaction with a system in order to be able to form perceptions about more tangible aspects of the system. These two studies have showed that system self-efficacy is a strong determinant of perceived ease of use before hands-on experience. Many previous empirical studies have also found system self-efficacy had a positive effect on perceived ease of use [Venkatesh and Davis  and Venke of use ,50. i.e., perceived usefulness) [In addition, some studies have indicated that significantly positive relationships exist between system self-efficacy and outcome expectation , which rfulness) . Some stfulness) ,49,50.H1: Social trust positively affects perceived ease of use in a telehealth context.H2: Social trust positively affects perceived usefulness in a telehealth context.H3: Institutional trust positively affects perceived ease of use in a telehealth context.H4: Institutional trust positively affects perceived usefulness in a telehealth context.H5: Social participation positively affects perceived ease of use in a telehealth context.H6: Social participation positively affects perceived usefulness in a telehealth context.H7: System self-efficacy positively affects perceived ease of use in a telehealth context.H8: System self-efficacy positively affects perceived usefulness in a telehealth context.H9: Perceived ease of use positively affects perceived usefulness in a telehealth context.H10: Perceived ease of use positively affects usage intention in a telehealth context.H11: Perceived usefulness positively affects usage intention in a telehealth context.Accordingly, this study proposes the following hypotheses:The previous arguments support the proposed research model illustrated in We used a self-report questionnaire to examine the proposed research model empirically. A self-report method refers to an approach in which observation data are provided by participants instead of raters or coders. The method is commonly used in behavioral and management science research. The items of measurement used in the questionnaire were developed based on previous studies. Responses to the various variables related to the perceptions of the individual subjects were measured with 5-point Likert-type scales, ranging from 1 (strongly disagree) to 5 (strongly agree).Following the public explanation session, the residents were arranged to visit the community center and participated in the survey. Before the interview, the researcher, research assistants, and well-trained interviewers introduced the investigation and invited them to participate in the study. The survey subjects of the questionnaire were those residents who were the end users of a telehealth system from Nantou County, Taiwan. All of these end users had used the telehealth system for at least one month. The participants were interviewed in person. The survey questions were read to participants by interviewers in Chinese and they verbalized their answers or wrote down directly on the survey response scale. The interviews lasted for 20 to 30 min.The telehealth system was developed and installed by a community hospital in Jhushang township, namely Chu Shang Show Chwan Hospital. The overall telehealth system is shown in The hardware includes weight scale, blood pressure cuff, blood glucose meter, and pulse oximeter. The equipment measures vital signs tailored to residents’ clinical needs, such as weight, blood pressure, blood glucose, heart rate, and oxygen saturation.Before the study, we conducted a pretest to refine and finalize the survey instruments. A pretest was conducted on 20 selected residents of Nantou County, Taiwan. The respondents were provided with verbal and written feedback on individual items after completing the questionnaire. The scale items were modified according to the feedback of these respondents.The measurement items of the questionnaire in the study were generated from in-depth interviews with senior physicians, nurses, residents who have ever used the telehealth system, and adjusted from the original constructs’ instruments developed by previous studies. The demographic variables include five questions: gender, age, marital status, educational level, and elderly main carer.Perceived ease of use describes the extent to which a person believes that using the telehealth system will be free of effort. Perceived ease of use was measured with two items which adapted from Davis , Davis, Perceived usefulness is defined as the extent to which a person believes that using the telehealth system will enhance her/his health. Perceived usefulness was measured with three items which adapted from Davis , Davis, Usage intention is the strength of one’s intention to use the telehealth systems. Usage intention was measured with two items which adapted from Davis , Davis, et al. [System self-efficacy refers to a belief of one’s capability to use the telehealth systems. System self-efficacy was measured with three items which adapted from Compeau and Higgins , Venkateet al. . A totalSocial trust refers to the expectation that health-care providers will act competently, fairly, openly, and considerately. Social trust was measured with three items which adapted from Mohseni and Lindstrom . A totalInstitutional trust refers to an individual’s trust in the hospital. Institutional trust was measured with three items which adapted from Mohseni and Lindstrom . A totalet al. [Social participation describes how actively a person has taken part in social free-time activities. Social participation was measured with three items which adapted from Nummela et al. . A totalFor examining the proposed model empirically, structural equation modeling (SEM) was used to validate the model and hypotheses. SEM is a statistical methodology that involves a confirmatory approach to analyzing a structural theory bearing on a particular phenomenon. Typically, this theory represents “causal” processes that generate observations of multiple variables . The datAmong the 370 subjects recruited, 365 subjects participated in this study. Among the respondents, 217 respondents were women (59.5%) and 148 were men (40.5%). Most of the respondents were aged 71–80 years (41.9%) and held elementary school diplomas (46.8%). Most of the caregivers were married (48.8%). The respondents suffered from at least one chronic disease (71.2%). To validate the measurement model, three types of validity were assessed: content validity, convergent validity, and discriminant validity. Content validity was done by interviewing senior system users and pilot-testing the instrument. And the convergent validity was validated by examining Cronbach’s α, composite reliability and average variance extracted from the measures . As show2γ is equal to the variance shared between these two constructs in the model. The average variance extracted (AVE) of these two constructs, namely ρ(η) and ρ(ε) can be used to evaluate discriminant validity. To fully satisfy the requirements for discriminant validity, ρ(η) > 2γ and ρ(ε) > 2γ. That is, the AVE of the construct should be greater than the variance shared between the construct and other constructs in the model. 2γ) and AVE (ρ) matrix, with the squared correlations among constructs and the AVE on the diagonal. In addition, according to Fornell and Larcker , if all In all cases, the AVE for each construct is larger than the squared correlation of that construct with all other constructs in the model. Therefore, the results confirm that the discriminant validity of constructs in the study is satisfactory.χ2 /d.f.), goodness-of-fit index (GFI), adjusted goodness-of-fit index (AGFI), root mean square error of approximation (RMSEA), root mean square residual (RMR), normed fit index (NFI), relative fit index (RFI), incremental index of fit (IFI), Tucker-Lewis index (TLI), and comparative fit index (CFI). The following indices recommended by Hair  et al. [χ2 /d.f. should be less than 3, (2) GFI should be more than 0.9, (3) AGFI should be more than 0.9, (4) RMSEA should be less than 0.05, (5) RMR should be less than 0.05, (6) NFI should be more than 0.9, (7) RFI should be more than 0.9, (8) IFI should be more than 0.9, (9) TLI should be more than 0.9, (10) CFI should be more than 0.9. In general, the closer the observed data is to the theoretical model, the better the fit of the model, and the easier it will be to satisfy the thresholds of the above indices. If the threshold of an index cannot be met, it means the model must be modified [Subsequently, the structural model (which includes hypotheses in addition to the paths between the item and its latent construct) was examined on the measurement model. To validate the structural model, we used AMOS 18.0 to assess the analysis. Several goodness-of-fit statistics were used to access the overall goodness-of-fit of proposed model: the ratio of chi-square to the degree of freedom , GFI = 0.952, AGFI = 0.933, RMSEA = 0.028, RMR = 0.024, NFI = 0.986, RFI = 0.982, IFI = 0.997, TLI = 0.996, and CFI = 0.997. As shown in the χ2 /d.f. value was less than the recommended threshold value 5, RMSEA value was less than the recommended threshold value 0.05, and RMR value was less than the recommended threshold value 0.05. Accordingly, the summary of the overall goodness-of-fit indices indicated excellent fit of the model and data. That is, the proposed research model has good fitness.These fit statistics of GFI, AGFI, NFI, RFI, IFI, TLI, and CFI were all far greater than the recommended threshold value 0.9. Furthermore, 2) value represents the proportion of variance that is explained based on the predictors of the variables in a model. As predicted, almost all of the proposed hypotheses are supported. As expected, social trust , institutional trust , social participation , and system self-efficacy  significantly affected perceived ease of use, accounting for 23.7% of the variance among the constructs. This means that H1, H3, H5, and H7 are supported. Institutional trust , social participation , and perceived ease of use  significantly affected perceived usefulness, accounting for 35.3% of the variance among the constructs. Thus, H4, H6, and H9 are supported. However, social trust and system self-efficacy affected perceived usefulness nonsignificantly, implying that H2 and H8 were not supported. In addition, perceived ease of use , and perceived usefulness  both significantly affected usage intention, accounting for 35.9% of the variance among the constructs. Thus, H10 and H11 are supported. The results for the structural model with the estimated standardized path coefficients and path significance among the constructs are presented in This study investigated the determinants of behavioral intention toward the telehealth acceptance of elderly rural residents in Taiwan by integrating social capital, system self-efficacy, and the TAM. The results strongly support the proposed behavioral model and provide comprehensive understanding of the relationships among social capital , system self-efficacy, technological factors (perceived ease of use and perceived usefulness), and behavioral intention to use this system. Based on the results of SEM, the hypotheses validate the fit of empirical data and the proposed model. The results show that nearly all of the relationships proposed in the model are supported. In addition, the model demonstrated excellent fit and is thus valuable for evaluating and predicting the behavioral intention toward adopting telehealth. β = −0.028). One possible explanation is that people exhibiting high system self-efficacy beliefs may be able to identify the limitations of telehealth systems that may not be immediately obvious to those exhibiting low efficacy beliefs [However, social trust affected perceived usefulness nonsignificantly. This unexpected finding can be attributed to the interpersonal trusting climate that may not directly affect the perception of usefulness of people. The effect of social trust on perceived usefulness may be mediated by social participation. Nahapiet and Ghoshal  argued t beliefs .The results of this study indicate that the elderly rural residents generally reported positive perceptions toward ease of use, usefulness, and intention to use the telehealth system. Moreover, perceived usefulness was the most significantly direct antecedent of behavioral intention. This result is consistent with that presented in Liu, Tsai, and Jang , who foci.e., community identity). Kwak, Shah, and Holbert [The findings of this study also imply that social capital factors play a key role in perceived ease of use and perceived usefulness. Accordingly, some practices can increase social trust by encouraging interpersonal interactions of residents through, for example, religious communities, sports or dancing clubs, formal or informal meetings, and activities that facilitate the flow of affection within a community. In addition, to improve institutional trust, cultivating equality and a partnership in the doctor-patient relationship is crucial. Health service providers expressing their willingness to refer to and respect patients’ feelings, opinions, and self-knowledge is critical. Social participation encourages the attachment of people in public  to provide a comprehensive behavioral model for understanding elderly rural residents’ intention toward using telehealth systems. The framework was extended from the original TAM by considering the relationships among social capital factors , technological factors (perceived ease of use and perceived usefulness), social cognitive factors (system self-efficacy), and behavioral intention to use the system. The proposed model has been proven to be valuable for evaluating and predicting the behavioral intention of telehealth system because it provides an integrative perspective that prompts researchers and practitioners to pay attention to the interdependence of these aspects. The integrative psychosocial-technological viewpoint implies that hospital managers should consider these key factors simultaneously.This study integrated two sociopsychological theories, social capital theory and social cognitive theory, with a widely used IS technology acceptance model  have limited the generalizability of most previous telemedicine/telecare/telehealth studies, causing barriers to knowledge development in the telemedicine/telecare/telehealth area . The larThe delivery of health care is being transformed by advances in e-health and by an empowered, computer-literate public. However, interactive IS developed for both patients and physicians remain at the early stages of development . This st