However, the mechanisms by which pancreatic cancer cells utilize their extracellular molecules to counteract the proapoptotic signaling mediated by the TNF family are largely unknown. In this study, we demonstrate for the first time that DcR3, a secreted decoy receptor that malignant pancreatic cancer cells express at a high level, acts as an extracellular antiapoptotic molecule by binding to TRAIL and counteracting its death-promoting function. The reduction of DcR3 with siRNA unmasked TRAIL and greatly enhanced TRAIL-induced apoptosis. Gemcitabine, a first-line drug for pancreatic cancer, also reduced the level of DcR3. The addition of DcR3 siRNA further enhanced gemcitabine-induced apoptosis. Notably, our  The balance between proapoptotic and antiapoptotic factors is a major determinant in the fate of tumor cells. These cells manage to tip the balance towards survival by overexpressing antiapoptotic molecules in intracellular and intercellular sites. A body of studies has demonstrated that intracellular B-cell lymphoma 2 (Bcl-2) promotes malignancy in several types of tumors, whereas blocking its function enhances the effect of anticancer treatments However, the majority of apoptotic signaling is activated extracellularly via the binding of proapoptotic ligands from one cell to death receptors on the surface of another cell in vitro and slows tumor growth in vivo, suggesting that the downregulation of extracellular antiapoptotic DcR3 may enhance anticancer therapy. This is especially true for aggressive pancreatic cancer, which utilizes DcR3 as the means for its progression.Tumor cells utilize 2 layers of protection: (1) an active defense system in which decoy receptors block the death ligand before they reach the receptors of the TNF family on the cell surface and prevent the initiation of death signaling; and (2) a passive defense system in which antiapoptotic machinery plays a role once the death signal is triggered inside the cells. Since portions of the molecules of type I cell-death receptors  and death ligands  share functionally similar domains, especially among the 6 members of the TNFR family 2 atmosphere. DcR3-related reagents were provided by BioPowerTech . Gemcitabine was purchased from the pharmacy at the University of Rochester Medical Center . The siRNA for DcR3 was synthesized at Integrated DNA Technologies, Inc. . Recombinant FasL and TRAIL and their antibodies were purchased from R&D Systems  and BioLegend, Inc. . Protein A Sepharose beads were purchased from Pharmacia . Anti-cleaved poly (ADP-ribose) polymerase (PARP) polyclonal antibodies were purchased from Cell Signaling Technology, Inc.  and anti-glyceraldehyde 3-phosphate dehydrogenase (GAPDH) polyclonal antibody was purchased from Santa Cruz, Inc. .Two human pancreatic cancer cell lines, AsPC-1 and MiaPaCa-2, and a colon carcinoma cell line, SW480, were obtained from the American Type Culture Collection . Cells were maintained as mono-layer cultures in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum, 100 μg/ml of streptomycin, and 100 U/ml of penicillin at 37°C in a humidified 5% COThe binding of recombinant human TRAIL to human DcR3 was analyzed on a Biacore 3000 instrument . DcR3 was covalently conjugated to Biacore sensor flow cells (CM5 chip) via amine groups using N-ethyl-N'-(dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide. Various dilutions of TRAIL (1 to 2048 nM) were passed through the conjugated flow cell and blank surface at 20 µl/minute for a total volume of 70 µl. The amount of bound protein was determined during washing of the flow cell with HBS-EP buffer . To regenerate the flow-cell surface, the bound proteins were washed with 20 mM of NaOH. Recombinant human LIGHT diluted in HBS-EP buffer (1 to 512 nM) was used as a positive control. The association, dissociation, and equilibrium constants were determined with a kinetic evaluation program in the Bia Evaluation software  using a 1∶1 binding model and the global analysis method.AsPC-1 and MiaPaCa-2 cells were incubated with or without recombinant DcR3 (5 μg/ml), TRAIL (5 μg/ml), or murine anti-TRAIL monoclonal antibody (1 μg/ml) in the same or different tubes for 1 hour at 4°C, followed by biotinylated DcR3 monoclonal antibody (0.5 μg/ml), and then fluorescein isothiocyanate (FITC)-conjugated streptavidin secondary antibody for 1 hour at 4°C. After washing, the bound DcR3 on the cell surface was detected with FACStarPlus . Data were expressed as the percentage of positively stained cells.The physical association of DcR3 with TRAIL was examined with immunoprecipitation (IP) and Western blotting in 3 different settings. To examine the interaction between 2 pure recombination proteins, 100–μl mixture of DcR3 with TRAIL (1 μg/ml) was precipitated with either anti-DcR3 or anti-TRAIL (3–5 μg) with 20 μl of protein A beads slurry. After washing, the bound DcR3-TRAIL complex on the beads was eluted with 30 μl of 1X non-denatured Laemmli sample buffer, electrophoresed on 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), transferred to a nitrocellulose membrane, detected with biotinylated anti-TRAIL or anti-DcR3 (1–2 μg/ml) followed by streptavidin (SA)-HRP, and visualized with a sensitive chemiluminescent substrate . To detect soluble DcR3-TRAIL complex in cell culture media and the membrane-bound complex in cell lysate, samples with protease inhibitor cocktail  were cleaned with protein A beads and then incubated with either anti-DcR3 or anti-TRAIL at 4°C overnight while being gently shaken. The bound DcR3-TRAIL complex on the beads was subjected to Western blotting in a manner similar to that described above.450.The binding of DcR3 with TRAIL was examined with a modified ELISA. Wells were coated with recombinant FasL or TRAIL (100 μl of 1 μg /ml). After the plates were washed with washing buffer (0.01% Tween 20 in PBS) and blocked with 5% PBS-T (5% Tween 20 in PBS), 100 μl of recombinant DcR3 (1 μg/ml) with or without recombinant TRAIL or FasL  was added to each well and incubated at 4°C overnight. After washing, biotinylated-DcR3 antibody (0.2 ng/ml) was added to each well and incubated at 37°C for 1 hour; thereafter, 100 μl of 1∶4000 streptavidin-horseradish peroxidase (SA-HRP) was added and incubated in wells for 45 minutes at 37°C, washed, visualized with 3, 3′, 5, 5′ tetramethyl benzidine (TMB), and read at a wavelength of 450 nm. In reverse, the plates were coated with DcR3 (100 μl of 2 μg/ml) and then incubated with recombinant FasL or TRAIL (100 μl of 1 μg/ml) with or without DcR3 , followed by biotinylated anti-FasL or anti-TRAIL (0.5 μg/ml), SA-HRP, TMB and read at ADcR3 was quantitatively measured, as described previously 17]. Since DcR3 is a secreted protein, 100 μl of culture media was used. Briefly, it was incubated overnight with an ELISA plate coated with anti-DcR3 McAb (2 μg/ml) at 4°C. After miscellaneous proteins were washed off, the bound DcR3 was detected with biotinylated anti-DcR3 McAb and SA-HRP and visualized with TMB substrate. The unknown sample concentration was determined from the standard curve, which was calculated simultaneously.in vivo study.Small interfering RNA sequences for human DcR3 were designed using the BLOCK-iT RNAi Designer . The siRNA sequence was 5′- CGCUGCAGCCUCUUGAUGGAGAUGUCC-3′, and the control siRNA sequence was 5′-AGGUAGUUCCAGAACUGCGUGUAGUGG-3′. They were chemically synthesized for transient knockdown of DcR3 in cell culture. In addition, similar sequences were inserted into the pSilencer expression vector for a stable low-DcR3 expresser. Transfection was carried out with Lipofectamine LTX reagent (Invitrogen Life Technologies) and Opti-MEM media, according to the manufacturer's instructions. The cells with transient knockdown of DcR3 were used within 3 days. The stable transfectants were selected in 50 μg/ml of hygromycin B. The surviving cells were pooled to avoid colony variation and use for Apoptotic cells were detected with 3 assays. Cells were harvested at 24–48 hours and stained with Annexin V/propidium iodide (PI) for apoptotic cells or fixed in 75% alcohol followed by PI staining for the sub-G1 fraction, according to standard protocol from the manufacturers. The results were analyzed by flow cytometry. Western blotting was performed for cleaved PARP. The harvested cells were lysed with 1% NP-40-Tris lysis buffer containing a cocktail of protease inhibitors, and the protein concentration of lysate was determined with the BCA method . Protein (30 μg) was loaded onto 10% SDS-PAGE, electrophoresed, transferred to a nitrocellulose membrane, incubated with 0.5 μg/ml of rabbit anti-cleaved PARP or anti-GAPDH (as loading control) followed by anti-rabbit-HRP, and visualized with ECL chemiluminescent substrate.Manual on the Responsible Care and Use of Laboratory Animals. All efforts were made to minimize suffering and limit animal numbers. Any animals that showed signs of weakness and dehydration due to treatment received a wet food diet. Animals that continued to exhibit signs of weakness were humanely euthanized through cervical dislocation.This study was performed in strict accordance with and approved by the University of Rochester  Institutional Animal Care and Use Committee (IACUC), the University Committee on Animal Resources (UCAR), as outlined in the 6 in 0.2 ml saline) were injected subcutaneously into the hind legs of athymic nude mice (5–6 weeks old) with a 27.5-gauge needle. Tumors were allowed to grow for 7 days (approximately 0.1 cm3) before treatment. Mice bearing tumors formed by either control transfectants or transfectants with low DcR3 expression were randomly divided into 2 groups (8 mice/group), treated with saline as a control or gemcitabine (IV 100 mg/kg) twice a week for 4 weeks. For the tumor growth curve, tumor size was measured twice weekly with vernier calipers. The tumor volumes were calculated according to the formula (L x W2)/2 by measuring tumor length (L) and width (W). At the end of experiment, the tumors were removed and weighed. An ELISA was used to assess the DcR3 level in tumor homogenate (30 μg). Western blotting was performed for DcR3, TRAIL, and cleaved PARP.Control transfectants or transfectants with low DcR3 expression . P<0.05 indicated statistical significance.All data were expressed as the mean ± standard deviation (SD) of at least 3 determinations, unless otherwise stated. The differences among or between the control and treatment groups were determined by Student's TRAIL is a membrane-bound death ligand with low levels under normal culture conditions, and DcR3 is a secreted decoy receptor. Although FasL, TL1A, and LIGHT have been identified as ligands of DcR3 eqK) of recombinant human LIGHT to DcR3 was 13.2 nM, the association rate constant (aK) and disassociation rate constant (dK) for recombinant human TRAIL to DcR3 were 1.97×104 1/Ms and 1.04×10−3 1/s, respectively, and the eqK was 52.8 nM, indicating binding between TRAIL and DcR3; however, the affinity was lower than that of LIGHT to DcR3.To determine whether DcR3 binds to TRAIL, we conducted state of the art Biacore binding analysis. The recombinant pure DcR3 was covalently linked on the flow chip surface, and the pure recombinant TRAIL and LIGHT (as a positive control) were flushed through the surface at various concentrations. To determine whether DcR3 binds to TRAIL, we preincubated AsPC-1 human pancreatic cancer cells with or without recombinant DcR3, TRAIL, or anti-TRAIL McAb, and then stained them with biotinylated anti-DcR3 followed by streptavidin-FITC. Flow cytometry Fig 1B dTo better observe the interaction between TRAIL and DcR3, we used gemcitabine, a first-line antipancreatic cancer drug and known TRAIL inducer, to upregulate TRAIL. Due to drug sensitivity differences, AsPC-1 cells Fig 1C rTo further determine the binding of DcR3 to TRAIL, we used gemcitabine to trigger the overexpression of TRAIL To confirm the physical association of DcR3 with TRAIL, we performed immunoprecipitation and Western blotting. FasL, a known ligand for DcR3, was used as a positive control. The results showed that the anti-DcR3-captured DcR3-TRAIL complex (approximately 70 kDa MW under mildly denaturing conditions) could be detected by anti-TRAIL in a mixture of pure recombinant DcR3 and TRAIL Fig 1G, To further confirm the association of DcR3 with TRAIL, we performed an ELISA-like assay. When TRAIL or FasL was coated onto ELISA plates, the binding of DcR3 to these ligands could be detected with anti-DcR3 and reduced by the addition of free recombinant TRAIL or FasL, which competed with DcR3 for the immobilized TRAIL or FasL Fig 1M. . 1L and 1M), strongly supporting that TRAIL is indeed a new ligand of DcR3.In all tests, the FasL-DcR3 complex served as a side-by-side positive control and showed a pattern similar to that of the DcR3-TRAIL complex ( A), which is consistent with other reports To study the biological function of DcR3 in pancreatic cancer, we measured the level of DcR3 by a quantitative ELISA for DcR3 To determine the interactive effect of DcR3 and TRAIL on cancer cells, gemcitabine and siRNA for DcR3 were used to regulate the level of DcR3. The AsPC-1 and MiaPaCa-2 cells were treated with different doses of gemcitabine for 48 hours, and the level of DcR3 in the media was measured with an ELISA. The results showed that gemcitabine reduced DcR3 in a dose-dependent manner in both cell lines Fig 2D.. Similarly, the gemcitabine-induced increase of caspase 3 activity was reversed by DcR3  in a dose–dependent manner . SimilarTo test if the unmasking of TRAIL could increase its accessibility to its receptor and enhance this death pathway, we examined the effect of DcR3 on TRAIL-mediated apoptosis. The DNA fragmentation (sub-G1) assay showed that when AsPC-1 cells were treated with FasL or LIGHT plus control siRNA or DcR3 siRNA, apoptosis did not increase significantly. However, when treated with TRAIL and DcR3 siRNA, AsPC-1 cells exhibited a dramatic increase in apoptosis, as compared to cells treated with TRAIL plus control siRNA Fig 4A.  and DcR3 siRNA and gemcitabine reduced the expression level of DcR3  and 4. We wThese results are consistent with those in in vitro results, we wanted to determine if the reduction of DcR3 could enhance the effectiveness of chemotherapy in vivo. AsPC-1 cells were transfected with a mammalian expression vector that contained siRNA to knockdown the expression of DcR3 and a cassette for G418 selection. The pooled vector mock-transfection cells (as control), or DcR3 siRNA transfected cells with low DcR3 expression (confirmed by ELISA) were injected into nude mice, and the established tumors (60 mm3) were then treated with gemcitabine. The results showed that DcR3 siRNA alone did not slow tumor growth .Encouraged by promising r growth Fig 6A oin vitro cell culture lysate  is a prerequisite for the action of DcR3. The dual action of gemcitabine, the induction of TRAIL, and the downregulation of its antagonist DcR3 reveal a new mechanism by which gemcitabine exerts its powerful antipancreatic cancer effect.in vitro and in vivo.Pancreatic cancer is a devastating and particularly malignant cancer with a very low 14% 5-year survival rate for stage 1A and an abysmal 1% for stage IV Based on the finding that transformed cells and normal cells possess the DR4/DR5 receptors for TRAIL, several studies have determined that TRAIL is a promising molecule for controlling cancer progression in vitro and in vivo . The combination of gemcitabine with siRNA strongly enhanced apoptosis; this was observed not only in vitro ( and in vivo, as evidenced by the slow growth and lower weight of primary tumors (Although the primary action of gemcitabine is to interrupt cellular DNA synthesis, it also indirectly promotes apoptosis. This study indicates that the underlying mechanism by which gemcitabine induces apoptosis is related to its ability to reduce DcR3 and to increase TRAIL expression 6D, whicet alNotably, our binding data are inconsistent with the finds of Piiti et al reported that the expression of DcR3 in AsPC-1 cells is related to phosphatidylinositol 3-kinase-, Akt-, and NF-kappaB-dependent pathways The function of DcR3 varies with the cell lines. For example, DcR3 induces apoptosis of dendritic cells, but it protects cancer cells and inversely correlates with the overall survival time of pancreatic cancer patients Taken together, our data strongly support the notion that tumor cells utilize binding of DcR3 to TRAIL to escape TRAIL-mediated apoptosis, an extracellular protection system for malignancy. As the reduction of DcR3 is likely to tip the balance from antiapoptosis to proapoptosis, it represents a new potential approach to treat pancreatic cancer.


Evidence-based health promotion programs that are disseminated in community settings can improve population health. However, little is known about how effective such programs are when they are implemented in communities. We examined community implementation of an evidence-based program, Body and Soul, to promote consumption of fruits and vegetables.We randomly assigned 19 churches to 1 of 2 arms, a colon cancer screening intervention or Body and Soul. We conducted our study from 2008 through 2010. We used the RE-AIM  framework to evaluate the program and collected data via participant surveys, on-site observations, and interviews with church coordinators and pastors.P = .04). The program reached 41.4% of the eligible congregation. Six of the 8 churches partially or fully completed at least 3 of the 4 program components. Six churches expressed intention to maintain the program. Church coordinators reported limited time and help to plan and implement activities, competing church events, and lack of motivation among congregation members as barriers to implementation.Members of 8 churches in Michigan and North Carolina participated in the Body and Soul program. Mean fruit and vegetable consumption increased from baseline (3.9 servings/d) to follow-up (+0.35, The RE-AIM framework provided an effective approach to evaluating the dissemination of an evidence-based program to promote health. Stronger emphasis should be placed on providing technical assistance as a way to improve other community-based translational efforts. Adequate consumption of fruits and vegetables, 5 or more servings per day, may reduce the risk of several chronic diseases ,2 and prIn general, behavioral interventions that perform well in research settings rarely reach the general public . Once anhttp://rtips.cancer.gov/rtips/index.do). However, we know little about its implementation fidelity. The RE-AIM  framework  of Wellness program was a randomized, controlled trial conducted in black churches in North Carolina and Michigan from 2008 through 2010 to increase colorectal cancer screening and physical activity. Participants at 10 intervention churches received 2 newsletters about physical activity and colorectal cancer screening tailored to their individual behavioral characteristics and up to 3 motivational interviewing counseling calls with peer counselors. Churches in the control arm (n = 8) implemented Body and Soul. Technical assistance from research staff to each church was limited to a 2-hour meeting discussing program components, resources needed, and logistics. Thus, this project provided an opportunity to evaluate the implementation of Body and Soul under real-world conditions. The institutional review board of the University of North Carolina at Chapel Hill approved this study.A detailed description of Body and Soul was published previously ,17. EarlThe Body and Soul program has 4 “pillars”: pastoral involvement , educational activities , church environmental changes , and peer counseling , a community partner working in black communities.To be eligible to participate, churches were required to have a predominantly black congregation, 250 or more active adult members, and 100 or more members aged 50 years or older. They also had to agree to randomization. We contacted 40 churches in Michigan and North Carolina . Of thesChurch coordinators arranged meetings with potential participants, usually after Sunday services. Study staff then presented information about the study, and members willing to participate provided consent and completed the baseline survey. Church members were eligible if they spoke English and were aged 50 years or older . We offered incentives for participants at baseline, including meals provided at survey collection, pedometers for intervention participants, and kitchen aprons for control participants. At follow-up, intervention participants received aprons and control participants received pedometers. Although we tried to collect all follow-up surveys 6 months after baseline, some data collection occurred as late as 12 months post-baseline because of scheduling conflicts at the churches.Reach is the estimated proportion of participating eligible church members. Data were available from 6 of the 8 churches about the number of eligible congregants on which to base this calculation (some membership data were missing because the churches’ bookkeeping was out of date). We determined effectiveness, the positive effect of the program on fruit and vegetable consumption, by using 2 measures included on baseline and follow-up surveys: a 9-item questionnaire about fruit and vegetable consumption adapted from a 35-item measure for US Southern blacks (Adoption is the proportion and representativeness of settings and of the people who implement the program (a report of adoption is not included because assignment to Body and Soul was random). Implementation is the extent to which the intervention was delivered as intended . Maintenance is the long-term adoption and implementation of the intervention .Using both quantitative and qualitative data sources, we examined the 5 core components of RE-AIM to understand implementation. n blacks  that mean blacks  that assP value of ≤.05 was considered significant.We used SAS 9.2  to analyze data. We generated descriptive statistics for all variables and summarized continuous variables by mean and standard deviation and categorical variables by frequency and percentage. Because the randomization was based on churches, we used linear mixed-effect models with random intercept to control for the clustering effect of church. A 2-sided Trained research staff conducted interviews, which lasted approximately 30 minutes. Staff audio recorded and transcribed telephone interviews with coordinators (n = 6) and pastors (n = 5). Pastor interviews asked about awareness of Body and Soul activities and pastors’ involvement in implementation. Coordinators were asked about perceived facilitators and barriers to implementation, activities conducted, and changes to organizational policies and procedures as a result of implementing Bodyand Soul. Two team members conducted thematic analyses to identify recurring themes. They compared codes, resolved differences through discussion with project team members, and summarized key findings in relation to program implementation and maintenance.Of the 8 Body and Soul churches, 4 were in North Carolina and 4 in Michigan. Data for the number of active congregants aged 50 years or older were available for 6 churches and totaled 730 , and 302 congregants from these 6 churches  completed the baseline and follow-up surveys. Overall reach (proportion of eligible congregants who participated in the full study) is therefore estimated at 32% (231/730), 23% of the women and 9% of the men congregants. Study participants were mainly women (71%), married or partnered (51.5%), had some college education or a college degree (71%), and had annual household incomes of less than $50,000.P = .63), but this increase was not significant. However, with the 2-item measure, the increase was small but significant .Baseline mean fruit and vegetable consumption for Body and Soul participants (n = 302) was 4.07 servings per day using the 9-item scale and 3.89 servings per day using the 2-item scale. Servings per day at follow-up was higher when the 9-item measure was used . The research team observed peer counselor training at 7 churches; only 2 churches initiated the peer counseling program. Two churches implemented 2 of the 4 program pillars, 3 implemented 3 pillars, and 3 implemented all pillars. The overall intervention period varied from 9 to 17 months depending on church personnel changes, the coordinator’s availability, and other events in the church taking priority over study activities.Implementation of pillar 1 . All 8 churches had pastoral support via pastoral consent for the program and pastor’s attendance at events; some pastors delivered health-centered messages during sermons. One pastor stated, “The body and soul are intertwined, and it would be pathetic of me to just talk about someone's soul and not touch on their body.” Pastoral counseling to individual members about health (n = 8) and encouraging church members from the pulpit about weight loss (n = 3) were other indicators of pastoral support.Implementation of pillar 2 . Six of the 8 churches reported conducting church-wide educational activities including food tastings, free food fairs that showcased healthful food options and preparation, substituting more healthful foods at church events , and placing inserts about healthful eating in church bulletins. Church coordinators also provided sample menus, recipes, and videos to congregants. In addition to these nutrition activities, 3 churches began fitness programs emphasizing weight loss . At follow-up, 60% of participants reported attending or being exposed to health education activities. Of those, 76% indicated that the events focused on fruits and vegetables. After controlling for baseline demographics, fruit and vegetable consumption was higher at follow-up (P = .001) among participants who recalled Body and Soul events   .Implementation of pillar 3 . Four churches reported making environmental changes, such as serving more healthful foods, substituting fruit for doughnuts at church breakfasts, serving water instead of sugary drinks, and using fruit in gift baskets.Implementation of pillar 4 (peer counseling). Seven of the 8 churches trained volunteers to serve as peer counselors, but only 2 churches had begun to roll out the program to congregation members. We trained 26 volunteer peer counselors ; 22 were women. Average number of peer counselors per church was 4 . Research staff observed 5 trainings that church coordinators conducted. Observers found that the trainings lasted approximately 2 hours (range 2–2.5 hours) and trainers used 2 of the 4 DVD modules we provided. Coordinators were able to use the DVDs and manuals with ease. In debriefing sessions, peer counselor trainees rated the DVD and training materials favorably. Only 32% of participants across all the churches reported being aware of peer counseling, and of these, 13% talked with a peer counselor. We found no relationship between fruit and vegetable consumption and report of talking to a peer counselor, for either fruit or vegetable measure.At follow-up, 6 coordinators reported intentions to continue the program, but 1 stipulated that extra staff would be needed to do so. The 2 churches that had no plans for continuing cited low interest of congregants, competing church programs, and lack of personnel. Five of the 8 pastors were pleased with the program and wanted to see it continue. Maintaining healthful food alternatives during church events and continuing to provide information about healthy living were actions coordinators believed they could sustain without additional cost or effort.Challenges reported by pastors and coordinators included lack of time to plan and implement activities, difficulty scheduling events at convenient times, competing church programs, inability to reach congregants consistently, and congregant lack of motivation. Four churches made no environmental or policy changes because coordinators in these churches were focused on implementing other aspects of the study . Another challenge coordinators noted was that some participants did not want to disclose personal information to peer counselors. Some coordinators said they lacked confidence to implement and promote the program, leading to delays in start-up and failure to delegate tasks. Implementing the program without ongoing technical assistance was cited as a barrier .This study focused on understanding the implementation of an evidence-based program in response to the knowledge gap about the uptake of programs disseminated to communities. We used RE-AIM to provide a comprehensive assessment of implementation of Body and Soul. Program reach was low and may have been hindered by the parent study’s parameters, which required that participants be 50 years or older given the focus on colorectal cancer screening. Although data for younger participants were not collected, 3 of the 4 Body and Soul components were adopted on a church-wide basis (peer counseling excluded) and not limited to those 50 years or older. It is possible that other members benefited and participated in these study components, but data on their participation were not captured. The program showed overall improvements in fruit and vegetable consumption (2-item measure) among congregation members. Regarding implementation, all churches had pastoral involvement, all conducted at least 1 church-wide nutrition event, and half achieved an environmental change. Only 2 churches began peer counseling. Given the low intensity of the intervention as it was delivered, the small increase in fruit and vegetable consumption is substantial. Regarding maintenance, all but 2 churches indicated their intention to continue some aspect of the program.Our findings of low reach and suboptimal implementation replicate those of a previous evaluation assessing independent church implementation of health promotion programs . It is eDespite these barriers, we were interested to see that 3 churches expanded the program by adding a physical activity component. Promoting fruit and vegetable consumption may have had the unintentional effect of encouraging physical activity programs. Fitness activities may have taken time and resources from the Body and Soul nutrition program but may also have encouraged participation given congregants’ interest in weight management.This study had several limitations. The geographic dispersion of churches limited our ability to conduct direct observation of some program activities. A second limitation may have been in the measures used to evaluate fruit and vegetable consumption. The 9-item measure included specific foods that were culturally appropriate and was validated in a black church-based population . The 2-iStrong evidence from studies continues to accumulate for the efficacy of promoting health behavior changes through black churches ,24,26,30The RE-AIM model was useful in understanding impact and implementation and for gaining insight about maintenance — factors relevant to external validity. This program was designed for black congregations, but it is adaptable to other racial, ethnic, or religious populations. With any faith-based community, understanding the context in which a program operates is a factor for success of health promotion efforts. We included a diverse sample of denominations and selected churches in 2 geographic regions to improve generalizability of findings. Future studies should allow longer intervention periods; find innovative ways to build interest across the population, such as including other behaviors of interest; and provide technical assistance on implementing all program components . Research that addresses these factors could provide a true evaluation of effectiveness of the disseminated program.


Postoperative atrial fibrillation (POAF) remains the most common complication after cardiac surgery. Current guidelines recommend β-blockers to prevent POAF. Carvedilol is a non-selective β-adrenergic blocker with anti-inflammatory, antioxidant, and multiple cationic channel blocking properties. These unique properties of carvedilol have generated interest in its use as a prophylaxis for POAF.To investigate the efficacy of carvedilol in preventing POAF.PubMed from the inception to September 2013 was searched for studies assessing the effect of carvedilol on POAF occurrence. Pooled relative risk (RR) with 95% confidence interval (CI) was calculated using random- or fixed-effect models when appropriate. Six comparative trials  including 765 participants met the inclusion criteria.Carvedilol was associated with a significant reduction in POAF . Subgroup analyses yielded similar results. In a subgroup analysis, carvedilol appeared to be superior to metoprolol for the prevention of POAF . No evidence of heterogeneity was observed.In conclusion, carvedilol may effectively reduce the incidence of POAF in patients undergoing cardiac surgery. It appeared to be superior to metoprolol. A large-scale, well-designed randomized controlled trial is needed to conclusively answer the question regarding the utility of carvedilol in the prevention of POAF. Despite significant advances in anesthetic and surgical techniques, postoperative atrial fibrillation (POAF) remains the most common complication after cardiac surgery Despite the extensive studies, the exact pathophysiology of POAF is for the moment far from being fully elucidated Two investigators searched PubMed database for relevant articles published up to September 2013. The initial search terms were carvedilol and atrial fibrillation. No language restriction was imposed. In addition, the reference lists of identified studies were manually checked to include other potentially eligible trials. This process was performed iteratively until no additional articles could be identified.The following inclusive selection criteria were applied: (i) study design: comparative trial; (ii) study population: adult patients undergoing cardiac surgery; (iii) intervention: carvedilol (no matter what regimen applied); (iv) comparison intervention: control (placebo or other beta-blockers) and (v) outcome measure: the incidence of POAF.Two investigators independently extracted the following data from each trial: first author, publication year, number of patients (carvedilol/control), patient characteristic, regimen of intervention (carvedilol/control), definition and monitoring of POAF, study design, the incidence of POAF, and length of hospital stay (LOS). Extracted data were entered into a standardized Excel file. The primary outcome was the incidence of POAF. Secondary outcome included LOS.2 statistic, which was a quantitative measure of inconsistency across studies. Studies with an I2 statistic of 25% to 50% were considered to have low heterogeneity, those with an I2 statistic of 50% to 75% were considered to have moderate heterogeneity, and those with an I2 statistic of >75% were considered to have a high degree of heterogeneity 2 value greater than 50% indicates significant heterogeneity 2≤50%), and a random-effects model was used in the case of significant heterogeneity (I2>50%). We further conducted subgroup analyses according to type of control, surgery type, and study design. We also investigated the influence of a single study on the overall risk estimate by omitting one study in each turn. We did not assess publication bias Differences were expressed as relative risks (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes, and weighted mean differences (WMDs) with 95% CIs for continuous outcomes. Heterogeneity across studies was tested by using the IThe initial search yielded 87 relevant publications of which 79 were excluded for various reasons  based on the titles and abstracts. The remaining eight were then retrieved for full text review, two of them were also excluded because one was focused in patients undergoing coronary bypass graft with heart failure and one was currently ongoing The basic characteristics of studies included in the meta-analysis are shown in 2 = 0%, heterogeneity p = 0.645; The definition and monitoring of POAF in each trial are summarized in Then we further conducted subgroup analyses based on type of control (metoprolol vs. placebo), surgery type , and study design . 2 = 82.9%, heterogeneity p = 0.016).Two trials reported the effect of carvedilol on LOS and provided available data (expressed as mean ± standard deviation) with a total of 275 patients. The combined analysis using a random-effects model showed that carvedilol did not significantly reduce LOS , with a high degree of heterogeneity between the trials (IPublication bias was not assessed because of the limited number (below 10) of studies included in the analysis.Meta-analysis of all six included studies using a fixed-effects model illustrates that carvedilol may effectively reduce the incidence of POAF in adult patients undergoing cardiac surgery.The mechanisms that carvedilol reduces the incidence of POAF are not entirely known. However, there is now an increasing body of evidences that oxidative stress +, K+, and Ca2+) Recently, Khan et al carried out a meta-analysis of randomized controlled trials and confirmed the efficacy of prophylactic beta-blockers against POAF In this meta-analysis carvedilol did not significantly reduce the LOS. The total incidence of POAF is 26.1% (200 of 765), less than one-third of patients develop POAF and still fewer develop prolonged atrial fibrillation, so the effect of carvedilol on LOS in patients prone to atrial fibrillation would have to be very large to be able to detect an effect of LOS in the total population. In addition, a relatively small number of samples (only two studies) provided available data on LOS, additional studies or data are warranted.One problem with the use of carvedilol to prevent POAF is that the majority of patients does not develop POAF after cardiac surgery but would still be exposed to possible side effects. In this meta-analysis, two trials reported carvedilol was well tolerated and side effects attributable to carvedilol were detected. And one trial reported complication rates were similar between carvedilol and control groups, including postoperative myocardial infarction and renal dysfunction.Several potential limitations of this meta-analysis merit consideration. First, our study included only six studies and some of them have a modest sample size. Overestimation of the treatment effect is more likely in smaller studies compared with larger samples. Second, our analysis is based on six clinical studies, and half of them were non-randomized controlled trials. The targeted population, adopted carvedilol protocols, type of control, and study design differed among the included studies. These factors may result in the heterogeneity and have potential impact on our results. Furthermore, these studies lack homogeneity in both the method of postoperative monitoring and in their definition of POAF. This may lead to potential underestimation and/or overestimation of the true incidence of POAF. Finally, it was possible that some missing and unpublished data may lead to bias in effect size.In conclusion, despite its various limitations, our study is clinically valuable because it revealed that carvedilol leads to lower incidence of POAF than control and appears to be superior to metoprolol as the current study clearly delineated. Carvedilol may effectively reduce the incidence of POAF in patients undergoing cardiac surgery. On the basis of this encouraging finding, we believe that research on the field is promising and should be continued. At least the ongoing COMPACT Checklist S1PRISMA Checklist.(DOC)Click here for additional data file.


To evaluate changes in nucleus pulposus volume as a potential parameter for the effects of disc decompression.http://www.osirix-viewer.com). After randomization, one group was treated with nucleoplasty, while the placebo group was treated with an identical procedure but without coblation current. The readers analyzing the MR images were blinded to the kind of procedure performed. Baseline and postinterventional volumes were compared between the nucleoplasty and placebo group.Fifty-two discs (T8 to L1) were extracted from 26 pigs and separated into thoracic (T8 to T11) and thoracolumbar discs (T12 to L1). The discs were imaged using 7.1 Tesla ultrahigh-field magnetic resonance imaging (MRI) with acquisition of axial T2-weighted turbo spin-echo sequences for determination of baseline and postinterventional nucleus pulposus volumes. Volumes were calculated using OsiriX®  ml. Postinterventional volume reduction in the nucleoplasty group was significant at 0.052 (SD: 0.035) ml or 6.30% (p<0.0001) (thoracic discs) and 0.082 (SD: 0.042) ml or 7.25% (p = 0.0078) (thoracolumbar discs). Nucleoplasty achieved volume reductions of 0.114 (SD: 0.054) ml or 14.72% (thoracic) and 0.093 (SD: 0.081) ml or 11.61% (thoracolumbar) compared with the placebo group.Nucleoplasty significantly reduces thoracic and thoracolumbar nucleus pulposus volumes in porcine discs. Magnetic resonance imaging (MRI) has gained an important role as a noninvasive tool in biomedical research. No harmful side effects are known, and its excellent soft tissue contrast makes it the imaging procedure of choice for examinations of the spine In the past a variety of different intradiscal procedures were used for treating symptomatic disc prolapse More than 10 years ago, in July 2000, nucleoplasty was approved in the USA by the Food and Drug Administration (FDA) as a treatment for symptomatic disc prolapse This study investigated the question of whether nucleoplasty has volume-reducing effects on biomechanically different spinal segments in pigs - the thoracic and thoracolumbar spine Our study included 53 ex vivo discs (T8- L1) from 26 freshly slaughtered “German native breed” pigs . We differentiated between thoracic (T8 to T11) and thoracolumbar junction discs (T12 to L1).Discs were assigned randomly to either the nucleoplasty group or the placebo group, and the experiment was performed within 24 hours of slaughter. Discs showing damage  on gross inspection or MRI were excluded from analysis (n = 1).Imaging was performed on a 7.1 Tesla MR imager . Discs were placed on 1-channel surface coils with the ventral side down and examined. Before treatment, a mark was placed on each disc to match preoperative and postoperative disc positions relative to the coil. The entire nucleus pulposus was imaged  using axhttp://www.osirix-viewer.com) MR images were viewed and processed using the OsiriX® software  with control unit, foot switch, and Convenience Pack (DLR SpineWand and sterile 17-gauge Crawford needle (6“) with mandrin). Appropriate to the manufacturer’s instructions, the ex vivo coblation current, in the nucleoplasty group , was appA total of 52 discs were included. Unpaired samples – randomly selected, independent value pairs – were assigned to one of two groups: thoracic discs and thoracolumbar junction discs, which have different biomechanical characteristics. Independent value pairs were selected randomly to minimize the potential for systematic bias . Thus, only one functional lumbar spinal unit (vertebra-disc-vertebra) (T8/T9 and T9/T10) was considered per spine. The two groups (therapy versus placebo group) were formed using the SAS randomization program. For the thoracic spine, 18 discs were assigned to the therapy group and 18 to the placebo group. For the thoracolumbar spine, each group was assigned 8 discs.The data were assessed with the Wilcoxon test for independent (nonparametric) samples using SAS 9.1 TS . Data are given as absolute values and standard deviations. Calculated differences were considered statistically significant at p<0.05.There were no complications during the interventions. All porcine discs were found to be normal, showing no abnormalities or degenerative changes. In both postoperative groups we were able to track the placebo/nucleoplasty channel created in the center of the disc . The aveThe results for thoracic discs were as follows. The average baseline volume was 0.754 (SD: 0.203) ml in the nucleoplasty group (n = 18) and 0.786 (SD: 0.219) ml in the placebo group (n = 18), showing no statistically significant difference (p = 0.130) . ThoraciIn the thoracic group, nucleoplasty decreased nucleus volume by 0.114 (SD: 0.054) ml or 14.72% compared with the placebo group , Fig. 4.The average baseline volume of the larger thoracolumbar junction nuclei was 0.850 (SD: 0.200) ml for the nucleoplasty group (n = 8) and 0.881 (SD: 0.214) ml for the placebo group (n = 8), showing no significant difference (p = 0.461) . For theIn the thoracolumbar junction group, nucleoplasty decreased nucleus volume by 0.093 (SD: 0.081) ml or 11.61% compared with the placebo group , Fig. 4.Different studies have demonstrated the effectiveness of minimally invasive intradiscal procedures in treating symptomatic disc prolapse Coblation employs an electrolyte-rich medium to generate a plasma field of highly ionized particles with enough energy to break the molecular bonds in soft tissue, so that tissue is vaporized and escapes through the introducer needle The risk of indirect injury to nerve structures close to the discs has been discussed repeatedly. Temperatures of 60 to 65°C or even higher can be reached at a distance of 3–4 mm from the probe Some intradiscal procedures have proven to be more effective when they are restricted to discs that have not lost too much height or volume due to degeneration Chen et al. demonstrated experimentally that nucleoplasty involves a reduction in pressure within the disc The mechanism of action of PLDD can be described as volume reduction – which also results in intradiscal pressure reduction Tissue vaporization with reduction of the nucleus pulposus volume appears to be the mechanism of action by which nucleoplasty reduces pressure in intact discs as used in our study. Chen et al. demonstrated this volume-reducing effect qualitatively by performing postoperative histological examinations Our experimental data show that, in a placebo-controlled setting, nucleoplasty can be used to reduce the initial volume of nucleus pulposus by a statistically highly significant degree. We attribute the volume increase in the placebo group to the fact that the nucleus was pushed aside and compressed by insertion of the Spine Wand. Conversely, in the nucleoplasty group, the compressed volume was reduced with the coblation current.Our study examined regions of the porcine spine that bear the closest anatomical resemblance to the human spine While the thoracic discs of the thoracic spine were smaller than the discs of the thoracolumbar junction, the volume reduction achieved by nucleoplasty was similar in the two groups. It can be assumed that decompression involves the entire anulus fibrosus and not the herniated disc portion alone Our study demonstrates that nucleoplasty has a volume-reducing effect on the nucleus pulposus of the thoracic and thoracolumbar spine. While this effect was demonstrated in an experimental setting and remains to be verified in patients, our results suggest that the potential benefit likely to be achieved in the clinical setting is of interest and deserves to be pursued further.


In China, illicit drug use and addiction have been rapidly increasing over the last two decades. Traditional compulsory rehabilitation models in China are widely considered ineffective. Recently, a new model of drug user rehabilitation called the 'Yulu Shequ Program' has gained a national reputation for successful rehabilitation in the city of Kaiyuan in southwest China. The aim of this study was to describe this program to the international public and to assess the program's effectiveness in terms of relapse rates and costs to participants and public payers.The Yulu Shequ program provides up to one hundred participants at any point in time with the opportunity to live and work in a purpose-built, drug-free community after completing compulsory rehabilitation. The length of stay is not limited. Community members receive medical and psychological treatment and have the option to participate in social activities and highly valued job skills training. The program has very strict policies to prevent illicit drugs entering the community.The evaluation was carried out through 1) a review of literature, official documents and websites in Chinese language describing the program and 2) an on-site visit and conduct of semi-structured interviews with key staff members of the Yulu Shequ program. The relapse rate in 2007 was 60% compared to 96% in the compulsory program. Annual costs to public payers of CNY4800 (US$700) were largely offset by income earned through on-site labour by participants totalling CNY4600 (US$670).The Yulu Shequ program is an interesting model for drug rehabilitation that could lead the way for a new Chinese national policy away from compulsory rehabilitation towards a more collaborative and effective approach. Caution is needed when interpreting relapse rates as Yulu Shequ participants need to have completed compulsory rehabilitation before entering the program. A more comprehensive evaluation of this program would be desirable before implementation in other parts of China or in other countries facing similar problems. The number of drug users in China has rapidly increased as the availability of illicit drugs has become more widespread over the last twenty years. By the end of 2005, over one million people were registered drug users  represenThe city of Kaiyuan is located in the southwest region of China. It is near the 'Golden Triangle', including Myanmar, Laos, Vietnam and Thailand, where illicit drugs are produced in large quantities and the local government in Kaiyuan regards the reduction and prevention of illicit drug use as an important mission.Traditionally, Chinese policy-makers have put great emphasis on supply reduction and abstinence therapy to control illicit drug use . AccordiIn Kaiyuan, local public security brought attention to issues with the traditional rehabilitation model and implemented a pilot program called 'Yulu Shequ' at an existing compulsory detoxification institution run by the Department of Public Security. The program was developed with the understanding that most addicts do not live in healthy social and personal environments due to a lack of acceptance by mainstream society and sometimes a lack of family support. The pilot program aims to reduce relapse rates by providing a healthy social environment which will ultimately foster reintegration into mainstream society. Recently, this pilot program has gained a national reputation for successful rehabilitation and could be the seed for a new era in Chinese drug offender rehabilitation using a gentler approach that could be a stepping stone towards an integrated harm reduction approach within the overall Chinese detoxification treatment policy which is still largely focused on a "zero tolerance" approach . In factThe aim of this study was to describe this pilot program to the international public and to assess the program's effectiveness in terms of reducing illicit drug abuse relapse rates and costs to participants and public payers.To this end, we conducted 14 semi-structured interviews with key staff members of the Yulu Shequ program in Kaiyuan between January and March 2008, after permission for this study had been obtained from the Department of Public Security in Yunnan and from the Director of the Yulu Shequ program. The latter also nominated the staff members to be interviewed. Staff members included the head of the compulsory detoxification institution, supervisors, and nurses. The semi-structured interviews covered the following areas: 1) data on the infrastructure and on processes used in the program, 2) data on relapse rates and the definitions used for defining a relapse or a successful rehabilitation, 3) surveillance activities, 4) cost of rehabilitation to public payers and to addicts and their families, 5) data on successful reintegration into social life and employment, 6) health status data. Ethics approval (no.H-009-2008) for this study was obtained from the Human Research Ethics Committee at the University of Adelaide.The Yulu Shequ program has been set up as a drug-free community which consists of three components:1) In the community there is a clinic which provides free health care for every participant including treatment for common drug associated diseases such as hepatitis. Monthly health checks are offered and the clinic is also responsible for random drug testing. In addition, dieticians regularly visit the community and prepare nutritious meals for residents.2) Addicts are offered long-term psychological support in the community. A range of counselling sessions as well as sports and social activities are available for helping participants improve their social skills. For instance, there is a dance club and a basketball team to join. These help residents to develop friendships and explore other interests in life.3) The third part of the program is the most unique and important. Several different processing factories operate on site and members have the opportunity to become involved in these companies, for example making jewellery. The companies supply all equipment and training courses for residents. A suitable position is offered to participants depending on their physical and psychological condition. Some of the jobs on offer include polishing glass into fake diamonds, electric welding and carpentry. The program ensures that every resident has the opportunity to learn certain skills through professional training and to have a paid job in the community. Ultimately, it aims to prepare addicts for life in wider society by rebuilding their self-confidence and self-esteem in order to adapt to normal social life.There is no time limit for completing the Yulu Shequ program. Participants can live and work in the community as long as they want to and they can also withdraw at any time. The longest time a resident stayed in the community so far was 24 months. Furthermore, residents have some degree of freedom in the community, although they remain under supervision. They have the right to choose their roommates and to take holidays. They are able to leave the community to visit their families and friends after informing their supervisors. However, before they can re-enter the community routine drug tests are performed on every participant after an outside visit. This is flanked by a very strict policy to prevent illicit drugs from entering the community. The main types of drug tests used are urine and pupil tests which are used for testing cannabis, heroin, morphine and ice. Participants with a positive drug test are sent back to compulsory rehabilitation.Any participant completing compulsory rehabilitation in Kaiyuan is free to decide whether to leave rehabilitation or continue within the Yulu Shequ community. There are no further requirements or fees for entering the program. Since its inception in 2006, 555 people have participated in the Yulu Shequ program and 238 people were living the community in February 2008. Based on a retrospective analysis of routine institutional records by facility staff provided to the researchers, the illicit drug abuse relapse rate in the Yulu Shequ program in 2007 was 60% compared to 96% for the compulsory rehabilitation program run by the same institution. Because of the sequential order of the two programs and a selection bias due to the voluntary adherence to the Yulu Shequ program and the compulsory attendance of the basic rehabilitation program, no other comparator to evaluate relapse rates is available. Data on successful reintegration into social life and employment or on the health status of participants were not accessible.Annual average costs to public payers of CNY4800 (US$700) per program participant were largely offset by income earned through on-site labour by participants totalling CNY4600 (US$670). Approximately one third of costs were spent on the provision of medical care. Cost data were provided by the finance manager of the Kaiyuan Department of Public Security and could not be scrutinised independently.The Yulu Shequ program seems to achieve a far lower rate of relapse than the traditional, compulsory drug rehabilitation program alone. It needs to be emphasised that Yulu Shequ participants are a highly selected population as entry into the program is contingent on them having completed the standard compulsory detoxification program and participation is voluntary. Therefore direct comparisons of relapse rates with other first-line rehabilitation programs cannot be made. Because of its labour component the Yulu Shequ program appears to be largely cost-neutral to public payers. Possible additional benefits of reduced relapse rates include the reintegration of successfully rehabilitated addicts into society and a positive impact on drug-related crime. The Department of Public Security Yulu Shequ approach differs in many respects from the "rehabilitation through-labour" units run by the Department of Justice. In contrast to the latter, it is characterised by a more participative, gentler approach to drug addict rehabilitation, in many respects similar to therapeutic communities in western countries  with theQL and CAG planned the study. QL collected, analysed and synthesized the data; and wrote the first draft of the article. CAG assisted in data analysis and synthesis, and contributed to the writing of the article. All authors read and approved the final manuscript.The authors declare that they have no competing interests.


BackgroundA major destructive earthquake is predicted to shake the Tehran city in the near future. To mitigate the damage from such earthquakes, it is necessary to assess the preparedness of people and find the related risk factors.MethodsA cross-sectional study was conducted in Tehran city among people aged 15 years or older in 2009. 1195 of Tehran's residents were interviewed using a questionnaire. Pearson chi-square test and binary logistic regression were used in order to evaluate the factors associated with preparedness against an earthquake.ResultsThe analysis showed that 1076 (90.0%), 1160 (97.1%), and 490 (41.0%) of the participants achieved half of the possible scores for the knowledge, attitude, and practice components, respectively. Furthermore, in multivariate analysis low knowledge (p<0.001), having a high-school (p=0.033) or lower education (p<0.001) and living in Northern high-risk regions (p<0.001) of the Tehran were identified as risk factors for taking precautionary measures against earthquake. For low knowledge, lack of previous experience (p<0.001), and working as labor, businessman, employee (p=0.001) or being housewife (p=0.002) were related risk factors. In addition, people in the Southern high risk regions were significantly more knowledgeable (OR=0.618 compared to people in low risk regions) about earthquakes.ConclusionsIt is suggested that preparedness programs should target people with lower educational level and people in high risk regions especially the Northern districts of the city and aim at increasing public knowledge about earthquakes.Address for correspondence: Ali Ardalan, No. 78, Italia Ave, Department of Disaster Public Health, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Email: aardalan@gmail.com or aardalan@tums.ac.irCitation: Ostad Taghizadeh A, Hosseini M, Navidi I, Mahaki AA, Ammari H, Ardalan A. Knowledge, Attitude and Practice of Tehran’s Inhabitants for an Earthquake and Related Determinants. PLOS Currents Disasters. 2012 Aug 6 Although they constitute a small share among the number of disasters, earthquakes are the major cause of death (55.7%) and cause US$232,070 million worth of damage (22%) comparing to other natural phenomena.Based on the observations since 1900, one earthquake of magnitude 8 or greater, 15 earthquakes of magnitude 7-7.9 and 134 earthquakes of magnitude 6-6.9 on the Richter scale are expected each year, worldwide.Tehran, the capital city and the most inhabited city of Iran, is located in a high seismic zone that is the result of its location in the main part of Alpine-Himalayan orogenic belt. The city has recorded many earthquakes during its history.The Bam earthquake was the latest major earthquake in Iran, this shook the Bam city and a large area of the Kerman province on December 26, 2003.This disaster made the Iranians more cautious about the same event in the capital city of Tehran, to an extent that the Iranian government considered moving the capital to another cityTo mitigate the damage from the earthquakes, some precautionary actions can be taken, such as earthquake insurance or fixing high furniture securely; however, people in both developing and developed countries do not utilize these actions.The question "Why some people become prepared for natural hazards but not all?" or in other words "What motivates people to take precautionary actions in order to mitigate damage from the hazards?" has been addressed abundantly in the literature. The answers are varied depending on the type of hazard and the region studied. The findings show that the income and economic levelOnly a few researches have studied the factors associated with earthquake preparedness in Iran. As indicated above, the factors may vary between regions. The latest published research studied the factors using a KAP study with data from 2007.After the Bam earthquake, the Iranian government has executed several preparedness programs. It is thus necessary to assess the efficiency of these programs and to identify the social groups that are in most need of related interventions. We also considered it necessary to reevaluate the population preparedness for earthquake and identify differences among different social groups. In addition, we aimed to estimate the associated factors using statistical methods.Sample and Procedure. A cross-sectional survey conducted by the Social and Cultural Studies Department, Tehran Municipality employed a questionnaire of 80 questions. This study focused on 31 of those questions, which included the participants' demographic characteristics, their knowledge about earthquakes and their attitude toward earthquakes and uptake of precautiounary measures.21-α/2×p×(1-p))/d2 with p=0.50 for each component considering α=0.05 and the precision of 3% (d=0.03) which yielded a total number of 1067 to be a reasonable for the aims of this study. However, using a random stratified-systematic sampling method, 1195 records were finally sampled.The target population included residents of Tehran 15 years of age or older, staying in Tehran in the year of 2009. Initially, the sample size for the estimation of components of interest  was calculated using n= Low risk regions: These districts are not on active seismic faults . (II) Southern high-risk regions  and (III) Northern high-risk regions : The Southern and Northern districts of Tehran which were on active seismic faults. Distinguishing the Northern and Southern high-risk districts (regions) was due to different socio-economic characteristics of these regions. In addition, previous studies have shown that buildings in the Northern districts are less vulnerable to the earthquake than those in the Southern area.Knowledge about earthquake preparedness. Ten questions were asked to evaluate the participants' knowledge of safety measures during an earthquake. Each question asked about safe places during an earthquake. Participants got 1 score for each correct answer and 0 for an incorrect one . The sum of the scores was used as the knowledge score for each participant. The median of the score of all participants was calculated and any participant with a score lower than the median, was regarded as a participant with low knowledge.Attitude toward earthquake preparedness. Three questions were asked to assess the attitude of the participants toward the earthquake. Questions like "Earthquakes can be avoided by praying" were in this section. A score from 1 through 5 was set to each question in which 1 stands for the lowest attitude and 5 for the highest. The sum of these three questions was assumed as the attitude score (Cronbach's α=0.65). Any participant with an attitude score lower than median was regarded as participant with low attitude.Taking precautionary actions (Practice component). Nine yes/no questions were asked by interviewers to evaluate the measure of precautionary actions for each participant. The questions were about the precautionary actions that can mitigate the damages of earthquakes such as "Does your house have an earthquake insurance?". The sum of yes answers considered as the practice score (Cronbach's α=0.74). The median for this score which considered as cut-off point was 3, thus any participant with practice score lower than 3 considered as participant with low practice.Analysis. SPSS 11.5 have been used in order to record and analyze the data. All demographic variables were assumed as categorical variables. To avoid the effect of missing values, for each of knowledge, attitude and practice (KAP) components, the summation based on the mean of answered questions was assumed as the score. For example if three questions out of ten of the knowledge component were missing, the mean of the seven remained questions multiplied by 10 assigned as the score of knowledge for that observation.The score of the KAP components were analyzed and median used as the cut off point for categorizing these components, such that if an observation's knowledge score was bellow the median, that observation was considered as having low knowledge. The same applied to the attitude and practice components and three new binary variables extracted.We used frequency tables to present the characteristics of study population. As the "other" group in the marital status category and the "military" group in the occupation category had a small number of observations, we removed them from further analysis in this study. Cross-tabulation was used in order to present the distribution of the answers based on the factor variables for each component and chi-square test applied to test whether the components and demographic variable were independent or not. Instead of chi-square p-value, the p-value of Fisher Exact test is reported wherever it was possible to use this test.To assess the relationship of demographic factors and KAP components by adjusting other factors, multiple binary logistic regression was used. For each regression model, the significance level and odd ratio and its 95% confidence interval are reported. Factors which were significant (at α≤0.2 level) at previous univariate tests entered in the regression model and the forward likelihood ratio method was used to dismiss the effect of non-significant factors. As low knowledge and attitude toward earthquake were significant factors for practice components, we entered these two component as well as other significant factors into the regression model for low practice. P-value < 0.05 was supposed as significant for all logistic regressions and 0.05 assigned as entry probability for the stepwise method.Between June and October 2009, 1195 Tehran's residents were interviewed in Tehran, Iran. The characteristics of the study population are shown in Table I. Of the participants, 717 (60.1%) were aged 21-45 years old and the ratio of male to female was nearly 1. In addition, 322 (27.0%) had received education lower than high school or were or illiterate and about 30% of the participants were single. Furthermore, 959 (79.9%) of the participants had faced an earthquake at least once in the past and 1014 (90.9%) of them had been living in Tehran for more than ten years. Besides, 1076 (90.0%), 1160 (97.1%), and 490 (41.0%) achieved half of the possible scores for knowledge, attitude and practice components, respectively.Table II displays the results of univariate analysis of the factors affecting KAP components as well as the association between knowledge and attitude components with practice.Results from Table II show that low knowledge about earthquake was significantly associated with higher age groups and lack of previous earthquake experience, and had a significant association with the occupation and region of the participant. Lower attitude was significantly associated with increasing age, length of residence and being married. The attitude component also had a significant negative association with educational level and was associated with sex, region and occupation of the participant. Furthermore, there was a significant association between the practice component and previous earthquake experience, region of the participant, low knowledge about earthquake and low attitude toward earthquake, and there was a significant negative relation between educational level and practice component. It should be noted that this results are tested independently; it means that the associations found here might be confounded by the effect of other factors.In order to adjust for the effect of possible confounders, a multiple binary logistic regression method was used. Table III shows the result of logistic regression of knowledge component on factors using forward method. The result of this analysis shows that lack of previous earthquake experience, region and occupation of the participants remained as significant predictors for low knowledge.Older age and lower educational level remained as risk factors on low attitude toward earthquake (Table IV). In addition, low practice was significantly linked to lower levels of education, low knowledge and region of the participants when educational level, previous earthquake experience, region of the participant, low knowledge and low attitude were entered in a multivariate logistic regression, as shown in Table V.Our findings showed that people with a lower educational level are at higher risk of unpreparedness than people with a higher education. People in the Northern high-risk regions are less prepared than people in low-risk regions. The analysis also showed that low knowledge can cause low preparedness. Low knowledge, however, is affected by previous earthquake experience, the region and occupation by itself. Furthermore, the attitude component was also affected by the educational level and age group.et al. Our study showed that people in high-risk regions are less prepared than people in low risk regions. The reason for this might be the reliance of people in Northern vulnerable regions on their secure buildingsIn the latest study conducted in TehranIn our study, the attitude toward earthquake was not a significant factor for taking precautionary actions against an earthquake after multivariate analysis, however, Tekeli‐Yeşil et al.As in other cities around the world, different regions of Tehran have different socio-economic characteristics . If we consider the region in our study as a socio-economic factor, our findings replicate the effect of economic level and social classes on the practice component which was shown in the USAet al. have distinguished the survival and mitigate types of preparedness Although we tried to assess the effect of all the factors used by previous studies, we did not have data on some of them, such as the risk perception which was employed previously.Our findings show that general education, region and knowledge about earthquakes are the factors which can influence the behavior of Tehran residents during an earthquake. Therefore, in order to mitigate the damage from future earthquakes, it will be importnat to increase the population's general education as well as their knowledge about earthquakes, especially for those in high-risk regions.


Injury is a major cause of mortality and morbidity of young people and the cost-effectiveness of many injury prevention programs remains uncertain. This study aimed to analyze the costs and benefits of an injury awareness education program, the P.A.R.T.Y. (Prevent Alcohol and Risk-related Trauma in Youth) program, for juvenile justice offenders in Western Australia.Costs and benefits analysis based on effectiveness data from a linked-data cohort study on 225 juvenile justice offenders who were referred to the education program and 3434 who were not referred to the program between 2006 and 2011.During the study period, there were 8869 hospitalizations and 113 deaths due to violence or traffic-related injuries among those aged between 14 and 21 in Western Australia. The mean length of hospital stay was 4.6 days, a total of 320 patients (3.6%) needed an intensive care admission with an average length of stay of 6 days. The annual cost saved due to serious injury was $3,765 and the annual net cost of running this program was $33,735. The estimated cost per offence prevented, cost per serious injury avoided, and cost per undiscounted and discounted life year gained were $3,124, $42,169, $8,268 and $17,910, respectively. Increasing the frequency of the program from once per month to once per week would increase its cost-effectiveness substantially.The P.A.R.T.Y. injury education program involving real-life trauma scenarios was cost-effective in reducing subsequent risk of committing violence or traffic-related offences, injuries, and death for juvenile justice offenders in Western Australia. Injury is responsible for two-thirds of deaths in those under the age of 24 in Australia and is also associated with a significant number of hospitalizations, disability and costs . In WestMany assaults, motor vehicle accidents and physical injury in developed countries are related to risk-taking behaviors involving alcohol and drug use ,8. HealtOur recent study showed that participation in an injury education program involving real-life trauma scenarios was associated with a reduced subsequent risk of committing violence or traffic-related offences, injuries, and death for juvenile justice offenders . We hypoThe P.A.R.T.Y. (Prevent Alcohol and Risk-related Trauma in Youth) program is a one-day youth injury prevention program developed in 1986 by the Regional Trauma Centre at Sunnybrook and Women’s College Health Sciences Centre in Toronto, Canada. The program provides relevant information to young people to improve their awareness of injury-producing situations, make informed prevention-oriented choices, and adopt behaviours and actions to minimize risk of injuries. Royal Perth Hospital was the first hospital in Australia that initiated the P.A.R.T.Y. education program in 2006.Although the main focus of this program was on high school students (between grade 10 and 12), this program was also provided to traffic-related juvenile justice offenders (aged between 14 and 18 years old) who were referred to this program by juvenile justice court magistrates on an ad hoc basis. Currently this education program takes part once per week for high school students and once per month for juvenile justice offenders. The participants of this program spend a day following the admission of an imaginary major trauma patient. After attending talks on pre-hospital care and the vulnerability of the brain and spinal cord to injuries, participants visit the Emergency Department, Intensive Care Unit (ICU), and Trauma wards. The participants are shown why and when a serious injury is more likely to occur and are given the opportunity of talking to trauma patients about their experiences and attempting to mobilize using a wheelchair and crutches, giving them an insight into previously unconsidered consequences of risk-taking behaviour.ad hoc basis by the discretion of the court magistrates as part of the juvenile justice offenders’ rehabiliation program. All those who were referred to the program had attended the program. Among a total of 3659 juvenile justice offenders who were sentenced by court magistrates during the study period, 225 were referred to the P.A.R.T.Y. education program. A substantial proportion of the participants of the program (57%) stated that the program would modify their attitude on risk-taking behaviors and also expressed very positive comments about the values of the program  =1.6%, 95% confidence interval [CI] 1.2%-2.1%; number needed to benefit = 62) was significantly lower for those who had attended the program compared to those who had not  and $17,910, respectively. The estimated cost per offence prevented was $3,124 .By increasing the frequency of the education program to once per week, the program would be even more cost-effective. We estimated that the cost per offence prevented would be $781 , the cost per serious injury avoided would be $10,542 (3.2 major injuries prevented), and cost per life year gained discounted at 3% would be $4478.If we included the post-hospitalization costs of injuries, the net cost of running the program would be $19,726. We estimated that the cost per offence prevented would be $1826, the cost per serious injury avoided would be $24,658, and cost per life year gained discounted at 3% would be $10,472. Even using a higher discounted rate, at 4% or 5%, for future life years gained, the program remained reasonably cost-effective  if we included all private and public costs such as rehabilitation, occupational therapy, and home services [First, a recent Access Economic report on economics of road trauma showed that the average cost of a person hospitalized due to motor vehicle accident was much higher than the figure we used in this cost-effectiveness analysis , Department of Health of Western Australia (2011/2), and Western Australia Police (00000FV001). Informed consent was waived by the ethics committees because of the extreme difficulty in obtaining direct contact with juvenile justice offenders and their families, observational nature of the study and the use of deidentified data.ARR: Absolute risk reduction; CI: Confidence interval; IRSD: Index of Relative Socioeconomic Advantage and Disadvantage; ICU: Intensive Care Unit; IQR: interquartile range; P.A.R.T.Y.: Prevent Alcohol and Risk-related Trauma in Youth.The authors declare that they have no competing interests'.KMH initiated the study, analyzed the data and drafted the manuscript. EG was responsible for analyzing and interpreting the economic data. MG initiated the idea of the P.A.R.T.Y. education program at Royal Perth Hospital and interpreted the data. MB was responsible for collecting the outcome data and interpreting the data. SR was responsible for initiating the P.A.R.T.Y. education program and interpreting the data. All authors agreed with the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/12/279/prepub


Research has indicated that depression prevention programs attenuate the development of symptoms of depression in adolescents. To implement these programs on a large scale, implementation in a school setting with teachers providing the programs is needed. In the present study, the effectiveness of the Dutch depression prevention program Op Volle Kracht (OVK) provided by school teachers during school hours with adolescents from high risk neighborhoods will be tested. The mediating effects of cognitive distortions and alexithymia will be evaluated as well. We hypothesize that the OVK program will prevent or decrease reported depressive symptoms, and that this association will be mediated by cognitive distortions and alexithymia.Schools with at least 30% of their pupils living in low income areas in the Netherlands are invited to participate in the study. Classes from vocational training up to pre-university level are eligible and 1324 adolescents (11-14 years) will be participating in the study. Randomisation will be done at class level, randomly assigning participants to an intervention group (OVK) and a control group , stratifying by school level (high versus low). Trained school teachers will be delivering the program, which covers cognitive-behavioral and social problem-solving skills. Longitudinal data will be collected with self-report measurements administered in the school setting at baseline, post intervention and at two follow ups (at 6 and 12 months). Primary outcome is the level of depressive symptoms, and secondary outcomes include: cognitive errors, response style, attributional style, alexithymia, stressful life events, substance use, happiness, and school grades.If the OVK program proves to be effective when it is provided by school teachers, a structural implementation of the program in the school curriculum will enhance the quality of the lives of adolescents and their families and will reduce costs in health care. In addition, the results of the study advances current knowledge on the underlying mechanisms of the development of depression and may aid the improvement of depression prevention programs in general.NTR3110Dutch Trial Register  Research pointing to the importance of cognitive distortions in the etiology and maintenance of depressive feelings has led to the development of cognitive behavioral interventions for youth. These interventions are not only used for the treatment of existing disorders, but also for the prevention of new cases. Recent meta-analyses suggest that preventive interventions can significantly reduce depressive symptoms or risk for future depressive symptoms compared to control groups -3. More One of the best studied depression prevention programs is the Penn Resiliency Program (PRP) . PRP is Selective prevention implies focusing on a population whose risk is deemed to be above average to develop symptoms of a given disorder. This type of prevention has been found to be more effective than universal prevention ,7. Commoprevent youth from developing depression symptoms, a structural, easily accessible implementation on a large scale is needed to reach early adolescents who have not developed clinical depressive symptoms yet. This will be achieved by implementing the program in the regular school curriculum. No stigmatization will occur as a result of singling out individuals to receive the program. In addition, we expect the effects of the class-based program to be more easily consolidated because the classmates will interact and learn from each other in day-to-day experiences. For a feasible implementation of the program in the school curriculum, the following pragmatic and logistic arguments and costs have to be taken into account. Because hiring external professionals for providing the program is too expensive for most schools, it is important that school teachers are able to deliver the program. It is therefore pivotal to study if school teachers can provide the program as effectively as clinicians and/or the developers of the program, and to evaluate practical implementation challenges and difficulties. Meta-analyses of the PRP program show significant effect sizes regardless of group leader type [Since the purpose of the OVK program is to der type , althougder type ,4,11.In addition to studying the main effects of this program on symptoms of depression, the mechanisms and possible factors underlying the effects of the program are of great interest. To this end, the mediating effects of two specific concepts will be examined in the current study: distorted cognitions and alexithymia. Distorted cognitions are important determinants of depressive feelings. Three central theories explain the etiology and maintenance of depressive feelings with the role of cognitions: Beck's cognitive theory of depression , the hopAnother theoretical concept we expect to be highly relevant in relation to depression prevention programs is alexithymia. Alexithymia refers to difficulties in experiencing and verbalizing emotions and difficulties in emotional self-regulation . An impaThe first goal of the current study is to test if the OVK program prevents symptoms of depression when the program is delivered by teachers during school hours to a whole class of adolescents. The second goal is to study the mechanisms and possible factors underlying the effects of the program.The present longitudinal study involves a randomized controlled trial (RCT) with two conditions (intervention versus control) . Participants do not receive incentives for filling out questionnaires. A low attrition rate is expected, because the measurements are administered during the regular school hours. The teachers will be motivated to keep complying to the protocol through personal email contact with the research team in which they receive results about the assessments on school level.th and 8th grade (range 11 to 14 years old) are selected. Two weeks after approaching the school by means of a written invitation, they will be contacted by telephone. If they are interested in participating in the study, a personal visitation will follow and classes will be selected. From the participating classes, none of the pupils will be excluded, to avoid stigmatization and social exclusion. With support from the schools, all parents will receive a letter to inform them about the content and aim of the program as well as the procedures of the study. Permission from the parents for their child's participation will be obtained through informed passive consent. If parents do not give permission for participation in the study, the adolescents will still attend the OVK program because it is taught in the regular school curriculum, but no data will be collected from them. To protect confidentiality of the data provided by the participating adolescents a unique code will be assigned to each participant. The Ethical Committee of the Faculty of Social Sciences at the Radboud University Nijmegen approved the study's protocol.All the secondary schools in the Netherlands that meet the criterion of having at least 30% of their pupils inhabiting low income areas will be approached for participation in the study. In the Netherlands, this information can be obtained from the Dutch Ministry of Education, Culture and Science and it is based on the average income in the postal code area in which the pupils live. The eligible schools are predominantly situated in urban areas. Two other selection criteria are the educational level and age: pupils from vocational training up to pre-university level and from the 7The classes will be randomly assigned to two conditions (intervention or control). An independent researcher will perform the allocation before the baseline assessment will be administered. Randomization will be carried out centrally on class-level and within schools to control for school characteristics, using a computerized random number generator with blocked randomization scheme (block size 2) and stratified by level of education (high versus low).Power analysis (G-power) was conducted based on a 12-month effect size of .20. Although the expected effect size for a depression prevention program for high-risk youth is .40  , which hSecondary outcomes are stressful life events, substance use, happiness, and school grades. The Adolescent Life Events Questionnaire - Revised  is used Data will be analyzed in accordance with the intent-to-treat principle but will also be analyzed separately for the completers only. Multiple imputations will be used for missing observations at follow-ups. The hypotheses will be tested with regression analyses for dichotomous and linear outcome measures in MPLUS 5.1 . We willThe aim of the study is to test the effectiveness and mechanisms of change of a Dutch school-based universal depression prevention program 'Op Volle Kracht' for adolescents with high risk background. As we know very little yet about the mechanisms of change underlying effective CBT-based programs, we aim to test these mediating processes ,41.One of the strengths of this study concerns the rigorous research design of a randomised controlled trial with a large sample N = 1,324) to analyse the underlying mechanisms and the sequence of change in the parameters. Another strength is the assessment of the cognitive distortions as possible mediators of symptoms of depression, which are based on three well-established cognitive theories -15. Furt,324 to aOn the other hand, several limitations of this study exist. First, probably primarily motivated schools will join in the study, which may limit generalizability of the results to all schools. Second, by using a within-school design (as opposed to a between-schools design), contamination effects between the experimental and the control group could occur, although we expect to minimize these effects by delivering the program to entire classes instead of parts of classes. Third, the measurements are solely based on self-reports. Nevertheless, with respect to internalizing problems, it has been shown that adolescents are probably better informants compared to their parents or teachers . At lastIf the OVK program proves to be effective in preventing elevated levels of depressive symptoms in adolescence, the study has strong practical relevance as the quality of life of the adolescents and their families will be enhanced and the costs for society and health care on the long term might be reduced. Because teachers are intensively trained, they are more likely to generalize their skills and knowledge to other parts of the curriculum. Moreover, they are expected to be more sensitive to signals of students with subclinical or clinical symptoms of depression and professional help could be consulted earlier. A structural implementation of the program in the school curriculum could be considered. In addition, the results of the study enable us to better understand the underlying mechanisms of development of depression and to improve depression prevention programs.CNCEQ-R: Childrens Negative Cognitive Errors Questionnaire Revised; OVK: Op Volle Kracht; PRP: Penn Resiliency Program; RCT: Randomized Controlled Trial.The authors declare that they have no competing interests.All authors contributed to the design of this study. KK is responsible for the data collection and data analysis, as well as for reporting the study results. RvZ and RE are supervisors and principal investigators. All authors contributed to the writing of the manuscript. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/12/212/prepub