Objective: The purpose of this study was to identify patient preferences for different components of a local diabetes prevention program that would improve reach.A secondary purpose was to determine if patient characteristics were related to program preferences. Methods: Participants were identified through electronic medical records from two family medicine clinics in Virginia. Participants completed a mailed survey addressing demographics, economic status, risk factors for diabetes, and preferences regarding diabetes prevention interventions—delivery mode, program length, and duration. Results: Twenty-nine percent of eligible participants responded (n = 142); 83% of participants were at risk for diabetes and 82% had a household income <$20,000.When presented with the choice between a class-based vs. a technology-based program, 83% preferred a technology-based program. Whites were less likely to choose the technology-based program, with no significant differences based on age, education, income, or gender. Conclusions: Contrary to beliefs that lower income individuals may not use technology-based interventions, lower socioeconomic patients indicated a preference for a technology- and telephone-supported diabetes prevention program over in-person class approaches. Findings provide formative data to support the design of a patient-centered, technology-enhanced diabetes prevention program in a real-world setting, thereby increasing potential participation and reach. With the ever quickening pace of life in modern societies, individuals are bombarded with information and choices. Additionally, given that human beings seek out pleasure, avoid pain, and are designed to do these things as efficiently as possible , it is iThis effort is particularly important because the predicted trends in the prevalence of type 2 diabetes (T2DM) pose an enormous public health concern. Approximately 8% of USA adults are currently diagnosed with T2DM with an additional 5% having undiagnosed T2DM. Estimates indicate that by 2050 one in three adults will have T2DM ,4. ConseHowever, prediabetes and T2DM do not equally affect geographies and populations across the USA . In VirgThe Diabetes Prevention Program (DPP) demonstrated that modest weight loss achieved through diet and exercise was superior to medication in delaying the onset of T2DM . The DPPSubsequently, many researchers have endeavored to translate the DPP into community and clinical settings ,20,21,22Laws and colleagues recently published a review of DPP interventions and concluded that the lack of reporting on external validity dimensions has significantly limited the ability to generalize findings  FurthermDiabetes prevention programs face several challenges including providing individual participants with the right mixture of intensity, personalization, and flexibility to maximize effect; reaching those at greatest risk; and delivering effective interventions in a sustainable format . IntensiPatients at risk for developing T2DM were identified through electronic medical records (EMR) of two family medicine clinics serving the Roanoke, VA area. A total of 490 patients were identified using the following ICD-9 diagnoses: prediabetes; glucose intolerance; hyperinsulinism; metabolic syndrome; obesity, morbid; simple Obesity; and/or abnormal weight gain .Identifip < 0.05.Participants were asked about their willingness to participate in two technology-based programs: (a) an educational DVD followed by automated interactive voice response (IVR) telephone calls, or (b) an in-person small group session followed by IVR calls. Additionally, participants were asked their preference for program length, the frequency and duration of IVR phone calls. The survey also included items from the diabetes risk assessment, which included height, weight, race, ethnicity, family diabetes history, and physical activity behaviors . AnalyseOne hundred and forty two surveys, 29% of those mailed, were returned. The average age of respondents was 52.7, with 77% female, 43% African-American, and 44% earning $10,000 or less over the last year .i.e., scored ≥ 5 on diabetes risk assessment [vs. 53.3%), black (42.5% vs. 35.0%), and less educated  (The average BMI was 39.7and 83% of respondents were at high risk for developing T2DM (sessment ). Compar. 36.1%) . Further. 36.1%) .vs. 31% 12+months, x2(5) = 14.363, p < 0.01) and those with no health insurance  = 9.721, p < 0.05) thought the frequency of calls should last longer. There were no differences according to disability status, education, income, or race. Finally, 85% of respondents indicated that call duration should be less than 10 minutes with no significant differences according to sex, insurance status, disability status, education, income, or race.Eighty-five percent of respondents were willing to participate in either of the two programs.Of those, over 75% indicated preference for weekly calls for the first 2–3 months, then bi-weekly calls for months 4–6, and then monthly calls through 12 months. Chi-Square tests revealed that male respondents  and those with a higher number of children living in the household  were less likely to be interested in participating. There were no differences in interest based on education, income, race, and sex . Of those that indicated a willingness to participate in either program, 83% preferred the DVD-based over the small group-based version. Logistic regression results demonstrated that whites were significantly less likely to choose the DVD option . There were no differences regarding age, education, income, and sex .i.e., income, education), suggesting that members of lower SES groups, who suffer from a disproportionate burden associated with T2DM, would be just as likely to participate in technology-based programs. Our study sample included a higher proportion of lower SES individuals indicating that technology-based programs could be a promising avenue for reaching this population.This project sought to determine participants’ preferences for technology-based diabetes prevention programs, and how demographic characteristics may be related to those choices. Current literature and growing epidemiological data has suggested that lower SES individuals are less likely to participate in such programs ,39. TechMost respondents willing to participate in a future program preferred a DVD and IVR-based program. Furthermore, there were no differences in program preference based on SES, which may not be surprising since the vast majority of participants had access to a telephone (98.6%) and a DVD player (90%). A large majority preferred a program lasting at least 12 months, with ongoing follow-up throughout the year. These results suggest patient preferences are consistent with the literature that recommends that programs last at least one year .i.e., participate in a program) has been shown to be predictors of future behavior  [The cross-sectional nature of the data does not allow for causal inferences to be made or whether these interventions would be effective. Further, the survey responses indicate a potential interest in future programs, but not actual participation in such programs. Nonetheless, intention to engage in a particular behavior (ipation) . Additioipation) .The findings from this investigation provide formative data to support the development and implementation of a patient-centered, technology-enhanced, diabetes prevention program within areal-world primary health care setting with the goal to increase the reach of such interventions.In particular, the high proportion of lower SES respondents provides important information regarding program characteristics that may be more attractive to them. In fact, potential participants appear to prefer brief follow-up phone calls, using a schedule that thins over the course of the program.The willingness of individuals from lower SES status, who are at high risk for developing T2DM to participate in technology-based programs also indicate that these strategies may be a viable alternative to traditional in-person diabetes prevention efforts. Finally, these interventions could be delivered at a lower cost using fewer clinical resources, thereby reducing the financial burden on both individuals and the health care system.


An additional grant from CAPES Foundation, Ministry of Education of Brazil was incorrectly omitted from the Funding Statement. The Funding Statement should read: "This study was supported by CAPES Foundation, Ministry of Education of Brazil [Postdoctoral Fellowship Program 3928/11-0 and Foreign Visiting Professor Program 115/2012]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."


Evaluation of educational interventions is often focused on immediate and/or short-term metrics associated with knowledge and/or skills acquisition. We developed an educational intervention to support international medical graduates working in rural Victoria. We wanted an evaluation strategy that included participants' reactions and considered transfer of learning to the workplace and retention of learning. However, with participants in distributed locations and limited program resources, this was likely to prove challenging. Elsewhere, we have reported the outcomes of this evaluation. In this educational development report, we describe our evaluation strategy as a case study, its underpinning theoretical framework, the strategy, and its benefits and challenges. The strategy sought to address issues of program structure, process, and outcomes. We used a modified version of Kirkpatrick's model as a framework to map our evaluation of participants' experiences, acquisition of knowledge and skills, and their application in the workplace. The predominant benefit was that most of the evaluation instruments allowed for personalization of the program. The baseline instruments provided a broad view of participants' expectations, needs, and current perspective on their role. Immediate evaluation instruments allowed ongoing tailoring of the program to meet learning needs. Intermediate evaluations facilitated insight on the transfer of learning. The principal challenge related to the resource intensive nature of the evaluation strategy. A dedicated program administrator was required to manage data collection. Although resource-intensive, we recommend baseline, immediate, and intermediate data collection points, with multi-source feedback being especially illuminating. We believe our experiences may be valuable to faculty involved in program evaluations. Evaluation is an essential step in curriculum or program development. However, evaluation is often not given prominence during program development, as resources are directed towards implementation. There are benefits associated with evaluation strategies that evolve contemporaneously with program development. These include a clear focus on measurable program outcomes, and an educational design that may promote learning  and can be scheduled as part of the program.The program evaluation literature has extensively documented many approaches -8. ProgrIn this case study, we describe the development and implementation of the evaluation strategy for a program designed to support the international medical graduates (IMGs) working in rural Victoria, Australia. There are shortages of doctors working in rural practice and IMGs make a substantial contribution to healthcare services. Rural locations are often the first appointment for IMGs in Australia -11. OrieGIPSIE had three lead academic faculty  supported by several other academics , clinicians, and an administrator. Seventeen participants entered the GIPSIE program, which was implemented in 2008 and 2009. Fifteen participants completed GIPSIE and rated the program highly, especially the simulation-based activities with feedback and later audiovisual review on iPods and the GIPSIE website. However, suggestions were made for improving several aspects of the program. Participants reported increased knowledge, skills, and professionalism after the program. Although overall multi-source feedback (MSF) scores showed no statistically significant changes, there were positive directional changes for three items: technical, teaching, and communication skills. These developments were also supported by qualitative comments. Learning was reported to be sustained three months after the program.In this case study on educational development, we describe the development and implementation process of the evaluation, along with the benefits, and challenges of educational development with the goal of sharing our experiences of the process rather than the outcome of this approach to evaluation.Kirkpatrick  developeWe had several goals in the evaluation of GIPSIE. Using the adapted version of Kirkpatrick's model of training impact , we wantThere were eight instruments in the evaluation strategy and these are listed in Baseline data was collected in order to do the following: gain insight to our diverse participants, use this data to ensure a tailored educational program, and have a basis on which to compare outcome data.Participants completed a paper-based survey recording age, sex, experience of living and working in Gippsland, career goals, and experience with a range of educational methods. Responses included ratings of satisfaction and free text responses. The survey content was derived from our reading of the literature and issues we considered relevant to our region.Prior to commencing the program, participants were sent a paper-based form and asked to identify their expectations and learning goals for the GIPSIE program. Responses were in a free text format. The individual and collated content of the LNA were used to adjust the program content and personalize learning. The participants reviewed their LNA during and on completion of the program.The main outcome measure consisted of MSF (pre- and post-program). This is also known as peer assessment or 360 degree feedback. We used a validated instrument designed for workplace-based assessments that is easily integrated with clinical practice . Each IMThe process for collecting MSF data is presented in This data was collected to capture participants' experiences of GIPSIE including their perception of changes in knowledge and skills and the usefulness of the educational methods.After the weekend workshop, the participants were given a paper-based form and asked to rate the degree to which they met each prescriptive learning objective  and the educational methods . Participants were also asked to identify what worked well and what needed to be improved.Immediately after each evening session, participants were given a paper-based form and asked to rate the degree to which they met prescriptive learning objectives and the educational methods using the same scale described above. Participants identified what worked well and what needed to be improved. We also asked participants to record up to five things they learned in each session providing us with insight into what they valued and what might have been new to them.This data was compared with baseline data to measure the true impact of the GIPSIE program.A topic guide was used to explore participants' experiences of the program and the impact of those experiences on their work. The topic guide content was developed by program faculty to reflect GIPSIE goals and participant perceptions of the program content and educational methods. Detailed notes were made during the telephone interviews scheduled at a time to meet the needs of participants. These notes were read back to each participant as a process of validation. Some verbatim statements were recorded.User access information was recorded and collated. Participation in online quizzes and other web-based learning activities  were monitored through frequency of log-in, time online, and number of contributions.See instrument 3. Data from individuals was presented in a collated form so that they could monitor their progress from program commencement to completion. We used overall summary data to measure the impact of the GIPSIE program on participants' performance.The alignment of the evaluation strategy with Kirkpatrick is illustrated in Quantitative data was entered into SPSS ver 18.0  for analysis. Descriptive statistics were used to summarize the data. The relatively small sample meant that we used non-parametric statistics. Individual differences pre- and post-program were identified using the Wilcoxon signed rank test. Statistical significance was established at p<0.05.Qualitative data (free text comments and telephone interview data) were thematically analysed. Themes were identified independently and then agreement negotiated by the researchers . An external evaluator (CS) reviewed de-identified data to ensure rigorous evaluation.In this section we identify benefits and challenges of the instruments as we experienced them.The benefits of this approach included the ease with which data was collected. Participants readily shared their experiences. Collated data was used in an early session of the program ensuring personalized content. Participants appeared to value this approach, and it provided a platform to share both the highs and lows of living and working in Gippsland. By exploring positives and negatives, we conveyed to participants that we wanted to hear all views. Collection and analysis of data was relatively easy. There were no significant challenges with this instrument except ensuring that individual participants' personal experiences were not revealed without their permission. Sensitive questioning and prompting provided opportunities for further elaboration of relevant information from participants themselves.There were several benefits to using this instrument. The most obvious was that participants were encouraged to think deeply about what they wanted to achieve. It also provided us with insight into participants' perceptions of what they thought GIPSIE might be able to address. Learning needs outside the scope of GIPSIE could be clarified at the outset, an important aspect of matching program objectives with participant expectations. Data was easily recorded. The principal challenge (or weakness) was the quality of the information participants provided. On the form, we gave examples of learning needs in order to illustrate how they might be described. Most participants then reported issues similar to the examples we provided. However, some participants provided additional examples and on questioning, the needs appeared genuine.Instruments 3 & 8 are same but taken at different times. The main benefit of this instrument at the time of program commencement was that we were able to gain insight to the participants as their colleagues perceived them. Additionally, it conveyed to the participants' colleagues that they were enrolled in a prescribing training program. Although the numerical ratings were interesting, the free text comments were often more helpful, especially when they were detailed. However, the process of collecting the data was highly resource intensive. We collected the data prior to our personally meeting the program participants.Some participants found it difficult to identify more than eight assessors because they had a relatively short work exposure or worked in small organizations where they were not well known to colleagues outside their unit. The process of collecting the assessor forms required significant follow up and so a designated program manager was required. Despite these challenges, our response rates were satisfactory. Each participant had between two and eight returns at baseline with six the modal return number. After GIPSIE, each participant had five to nine MSF returns with six the modal value. Respondents seemed highly engaged in supporting their IMG colleagues.We asked IMGs to self assess using this instrument, which provided valuable insight to the participants as to how they viewed themselves in relation to their peers. Although there are issues associated with self-report, participants found the process insightful and sometimes confronting. We had to ensure that participants were supported in making sense of this data, which again, was labour-intensive but highly valued by participants as a learning experience.The benefit of these evaluations was that we received immediate insight into participants' experiences of the program. This helped us adjust subsequent learning objectives and educational methods. For example, in some educational methods, we needed to invest more time in orienting participants to their use . Because the evaluation data was collected immediately after the participants' experiences, we were able to adjust subsequent teaching methods. The challenges were associated with participants responding uncritically. Given the relatively small number of GIPSIE participants, there may have been a reluctance to share true feelings, especially if they were critical of the program. We tried to ensure that the completion of forms was a private event and that forms were returned anonymously.There were several benefits to this method, including the highly personalized nature of data collection. Although participants might have provided what they considered were 'socially desirable' responses, we felt reasonably confident that participants spoke quite freely. The participants seemed to be authentic in their responses. There were very few criticisms. They appreciated the attention and value we placed on their feedback. The challenges were again human-resource related because the interviews were time consuming and there were difficulties in scheduling. We also could not always be certain of where the participants chose to receive the telephone call. The settings might have impeded their freedom to share experiences.Although we planned this collection of data, we did not use it in the final evaluation report. This was mainly associated with the 'remote' management of the GIPSIE website and the relatively small numbers of participants. That is, the website management was commissioned externally, and this seemed to create some communication challenges. Some participants were also very slow to start using the GIPSIE website and with the small cohort size, we were confident that the participants' self-reporting was adequate to meet our evaluation needs.In order to evaluate the impact of a training program, a carefully planned and resourced strategy is essential. In health professional training, our goal is to ultimately improve the health services offered to patients. However, their direct involvement in evaluation is challenging. Further, programs are often offered by those distant to the workplaces of trainees. Ethical clearances make it difficult for the systematic collection of patient data.In the project, we sought to implement an evaluation strategy that addressed most levels of the modified Kirkpatrick framework.Based on our experience, we make the following recommendations:Encourage broad stakeholder involvement in the developmentof the strategy .Allocate adequate resourcing of administrative support, especially for MSF and booking telephone interviews.Incorporate evaluation data into educational content and process. That is, schedule evaluation activities as part of the curriculum. Use data collected to engage participants in a personalized program while ensuring relevance.If using MSF, then provide clear instructions to participants and assessors to minimize the encroachment on their time. Indicate that free text comments are highly valued if contextualized. Offer reassurance about confidentiality to assessors. Offer reassurance to participants that the results will not be used in any way to influence their employment with their health service.Incorporate participant feedback into ongoing program refinement and delivery to allow for personalization of education strategies as well as clarification of program objectives.Ensure externally commissioned contractual work is clearly articulated and include progress reports.


There are worrying trends and phenomena related to the development of adolescents in Hong Kong, such as the intensification of substance abuse and Internet addiction problems , 2. With Against the above background, The Hong Kong Jockey Club Charities Trust approved HK$400 million to launch a project entitled “P.A.T.H.S. to Adulthood: A Jockey Club Youth Enhancement Scheme” to promote adolescent development in junior secondary school students in Hong Kong in 2004. The word “P.A.T.H.S.” denotes Positive Adolescent Training through Holistic Social Programmes. The trust invited academics of five universities in Hong Kong to form a research team with The Hong Kong Polytechnic University as the lead institution to develop a multiyear universal positive youth development program to promote holistic adolescent development in Hong Kong, with the first author as the Principal Investigator. Besides developing the program, the research team also provides training for teachers and social workers who implement the program and carries out longitudinal evaluation of the project. Because of the overwhelming success of the project, it was extended for another cycle with an earmarked grant of HK$350 million in 2008. There are two tiers of programs (Tier 1 and Tier 2 Programs) in this project. The Tier 1 Program is a universal positive youth development program in which students in Secondary 1 to Secondary 3 participate, normally with 20 hours of curricular-based training in the school year at each grade. Because research findings suggest that roughly one-fifth of adolescents would need help of a deeper nature, the Tier 2 Program is provided generally for at least one-fifth of the students who have greater psychosocial needs at each grade .The project consists of two implementation phases—the Experimental Implementation Phase and the Full Implementation Phase. For the Experimental Implementation Phase (2005/06 to 2007/08 academic year), 52 secondary schools participated in the project with the objectives of accumulating experience in program implementation and familiarizing frontline workers with the program design and philosophy. In 2006/07 school year, the programs were implemented on a full scale at Secondary 1 level. In 2007/08 school year, the programs were implemented at Secondary 1 and Secondary 2 levels. In 2008/09 school year, the programs were implemented at Secondary 1, Secondary 2 and Secondary 3 levels. For the extension phase of the project, the program would be implemented from 2009/10 to 2011/12 school years.The overall objective of the Tier 1 Program is to promote holistic development among junior secondary school students in Hong Kong via the inclusion of positive youth development constructs in the program . The posSystematic and adequate training is another emphasis of the Project P.A.T.H.S. in Hong Kong . For eacIn view of the huge scope of the project, evaluation plays an important role in understanding the impact of the project. Adopting postpositivistic and pragmatic stands where multiple research methods are recognised, different evaluation strategies have been used to evaluate the Tier 1 Program. These strategies include the followingObjective Outcome Evaluation : in the Full Implementation Phase, 24 experimental schools and 24 control schools were randomly selected to participate in a randomized group trial in 2006/07 school year. Analyses of data collected at different time points using individual growth curve models controlling for differences between the two groups in terms of pretest scores, personal variables, and random effects of schools showed that participants in the experimental schools had significantly higher positive youth development levels than did participants in the control schools at posttest based on different indicators derived from the Chinese Positive Youth Development Scale. Students in the experimental schools also displayed less risk behavior than did students in the control schools. The findings based on the total eight waves of data are presented in a paper in this special issue .Subjective Outcome Evaluation (Tier 1 Program): both students and program implementers were invited to complete subjective outcome evaluation forms  after completion of the program to understand their perceptions of the program, the implementers and benefits of the program. Existing quantitative as well as qualitative findings generally showed that different stakeholders had positive views about the program and the program was beneficial to the participants. The subjective outcome evaluation findings were found to converge with objective outcome evaluation findings and the related changes. In the present special issue, two papers based on the perceptions of the program participants and implementers are included .Subjective Outcome Evaluation : to gain an in-depth understanding of the impact of the project, program implementers were invited to write down five conclusions regarding the project based on the Form A and Form B data. In separate studies, secondary data analyses of the conclusions drawn by the program implementers based on the Form A and Form B reports revealed that different stakeholders had positive views of the program and they perceived the program to be beneficial to the program participants. Integration of the secondary data analyses of the reports in all cohorts of students in the project revealed that the program was perceived to be beneficial to the program participants. The detailed findings can be seen in the paper in this special issue .Process Evaluation: in process evaluation, systematic observations were carried out by trained research assistants in randomly selected schools to understand the program implementation details. Several studies generally revealed that program adherence was high, with a mean adherence of over 80%. Besides, the findings generally showed that the program implementation quality in these schools was high. In this special issue, an integrative study analyzing all process evaluation data collected at different stages of the project was carried out. The findings showed that the overall program adherence and implementation quality was high .Interim Evaluation: to understand the process of implementation, interim evaluation was conducted by randomly interviewing roughly half of the participating schools in the Experimental Implementation Phase or the Full Implementation Phase. In this special issue, the data in all interim evaluation studies were integrated and analyzed. The findings generally showed that the participants and implementers perceived the merits and benefits of the program, although difficulties in implementing the program and recommendations for improving the program and the implementation process were observed .Qualitative Evaluation (Focus Groups Based on Students): focus groups involving students based on schools randomly selected from the participating schools were carried out in previous years. In this special issue, all focus group data based on previous studies were subject to secondary data analyses. With specific focus on how the informants described the program, results showed that the descriptors used were mainly positive in nature. When the informants were invited to name three metaphors that could stand for the program, the related metaphors were basically positive in nature. Finally, the program participants perceived many beneficial effects of the program in different psychosocial domains .Qualitative Evaluation (Focus Groups Based on Program Implementers): focus groups involving program implementers based on schools randomly selected from the participating schools were also conducted in the project. Secondary data analyses of the related data collected in the project revealed several observations. First, the program implementers identified strengths and positive features of the program. Second, they perceived the program to be beneficial to the development of the program participants. Third, they proposed suggestions on how the program could be improved. Generally speaking, the program implementers have positive evaluation of the program .Evaluation Based on Student Weekly Diaries: after completion of the Tier 1 Program, students were randomly selected from the participating schools to write a reflective journal in the form of weekly diary to reveal their perceptions and feelings regarding the Tier 1 Program and the related benefits. Secondary data analyses showed that most of the respondents had positive views on the program, had positive views on the instructors, and stated that they had acquired competencies at the societal, familial, interpersonal, and personal levels after joining the program .Evaluation Based on Repertory Grid Test: at the end of the Full Implementation Phase, students were randomly selected from schools to complete repertory grid tests to understand how the participants perceived changes in their identity at different points of time. The findings generally showed that the participants had improved self-representations after joining the program .Subjective Outcome Evaluation (Tier 2 Program): the participants were invited to complete subjective outcome evaluation forms (Form C) after completion of the Tier 2 Program to understand their perceptions of the program, the implementers, and benefits of the program. Existing quantitative as well as qualitative findings generally showed that different stakeholders had positive views about the program, the implementers, and benefits of the program. In the present special issue, one paper based on the perceptions of the program participants about the Tier 2 Program is included .Positive youth development programs in Chinese communities: where are we and where should we go?” by D. T. L. Shek and R. C. F. Sun) [There are several special features of the studies covered in this special issue. First, large sample sizes were involved in different evaluation studies. For example, 206,313 Tier 1 Program participants responded to the subjective outcome evaluation form (Form A), 7,926 Tier 1 Program implementers responded to the subjective outcome evaluation form (Form B), 60,241 Tier 2 Program participants responded to subjective outcome evaluation form (Form C), and 1,138 pieces of student diaries were collected. Second, data based on different cohorts of participants were integrated and analyzed in different studies covered in the papers reported in this special issue. The use of different cohorts can give an aggregated picture of evaluation findings over time. Third, based on the wide range of evaluation strategies used in the studies included in this special issue, the findings consistently showed that different stakeholders had positive perceptions of the Project P.A.T.H.S. and the two tiers of program were beneficial to the development of the program participants. Finally, this is the first known collection of evaluation studies of a positive youth development program in different Chinese contexts based on multiple evaluation strategies and longitudinal data (“ F. Sun) . It is o F. Sun) , 12.


Suboptimal lifestyle factors in combination with genetic susceptibility contribute to cardiovascular disease and type 2 diabetes risk among Latinos. We describe a community–academic collaboration that developed and explored the feasibility of implementing a socioculturally tailored, healthy lifestyle intervention integrating genomics and family history education to reduce risk of cardiovascular disease and type 2 diabetes among Latinos.The community-based participatory research was conducted with communities in Kentucky, which has a rapidly growing Latino population. This growth underscores the need for socioculturally appropriate health resources.Su Corazon, Su Vida  is a Spanish-language, healthy lifestyle educational program to reduce cardiovascular disease and type 2 diabetes risk among Latinos. Twenty natural leaders from an urban Latino community in Kentucky participated in sociocultural tailoring of the program and development of a genomics and family history module. The tailored program was presented to 22 participants to explore implementation feasibility and assess appropriateness for community use. Preintervention and postintervention assessments of genomic knowledge and lifestyle behaviors and qualitative postintervention evaluations were conducted.Postintervention improvements in health-promoting lifestyle choices and genomic knowledge specific to cardiovascular disease and type 2 diabetes suggested that the program may be effective in reducing risk. Feedback indicated the program was socioculturally acceptable and responsive to community needs.These findings indicated that a tailored healthy lifestyle program integrating genomics and family history education was socioculturally appropriate and may feasibly be implemented to reduce cardiovascular disease and type 2 diabetes risk in a Latino community with limited health care resources. The project highlights contributions of community-based processes in tailoring interventions that are appropriate for community contexts. Cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) are leading causes of illness and death among US Latinos. In the United States in 2010, 13.2% of Latinos aged 18 or older had DM  is a promotores-facilitated educational program to reduce CVD risk among Latinos through healthy lifestyle promotion , more than doubled in size between 2000 and 2010, ranking fourth in the rate of growth in US states after South Carolina, Alabama, and Tennessee (12). Similar to the population nationally, most Kentucky Latino residents are from Mexico (61.3%) or other Latin American countries (22%); a smaller percentage are of Puerto Rican (6.4%) and Cuban (6.4%) origin . As a noTo address health needs of Kentucky’s Latino residents, a community–academic collaboration was established in 2008. The partnership originated from a longstanding relationship between the principal investigator  at the University of Kentucky and community leaders of the Latina Women’s Movement and La Casita Center in Louisville, Kentucky. The Latina Women’s Movement is a grassroots initiative dedicated to improving women’s well-being through programs that honor Latin American cultural traditions. La Casita Center is a community-based organization that provides services supporting Latino community development. Guided by principles of community-based participatory research (CBPR), the collaboration emerged from a mutually recognized need for a sustainable health promotion initiative, and a research team was formed that included the PI, the director of La Casita Center , and the founder of the Latina Women’s Movement (who was the project director).promotores-facilitated program would have greatest potential for sustainability with long-term health effects. Specific objectives of the collaboration were to 1) identify and tailor a healthy lifestyle intervention to reduce CVD and DM risk for use among Latino residents in urban Kentucky and 2) explore the feasibility of implementing the community intervention . This research was followed by exploratory examination of implementation feasibility and acceptability of the tailored curriculum conducted during 2010 (Study 2). Both studies were approved by the University of Kentucky institutional review board.promotores training sessions were also developed by community collaborators to complement the SCSV educational modules.Community partners were particularly interested in focusing on Latina women, whom they identified as more influential on family and community health behaviors than Latino men. It was decided to specifically engage Latinas in the sociocultural tailoring of the SCSV modules. Three Twenty Spanish-speaking Latinas identified by community partners as natural leaders participated. Natural leaders were defined as women who were representative of area Latinas, involved in community activities, and well respected by community members. Before study initiation, participants gave written informed consent.promotores training sessions and 8 SCSV educational modules were presented in Spanish during 11 two-hour sessions, with 1 module presented weekly. Participants provided feedback on the comprehensibility and sociocultural appropriateness of the modules. Each also participated in 1 of 4 focus group sessions conducted to guide the integration of culturally relevant family history and genomics education into the program. A final study session included summary review of the SCSV program with in-depth discussion of the potential value for promoting health in the community. All sessions were facilitated by the project director. To acknowledge their collaboration, participants received a gift card for sessions attended; childcare was also provided. The research team met regularly to review participant feedback and responses to modules. The iterative process of program tailoring was guided by individual and group feedback.The 3 fotonovelas  to allow time to discuss practical applications of information. For example, participants identified and shared healthy recipes for commonly enjoyed foods and suggested time be provided during each session for such activities. Including stress reduction techniques and using educational models to support learning were also suggested.Overall evaluation of the program was positive. Participants valued education about the physiologic bases of the diseases but were most interested in learning about risk factors and risk reduction. To enhance self-efficacy in reducing risk, participants suggested that specific, achievable health-promoting activities be identified early in the program and emphasized throughout. The women recommended omitting optional program activities such as Program adaptations in response to feedback included integration of time into each session for participants to identify and discuss context-specific health-promotion strategies. A psychiatric nurse practitioner with stress management expertise assisted with development of stress reduction techniques, including deep breathing and imagery exercises. Educational models complementing program modules were purchased, including a manipulable heart model and a visual display of sugar and salt content of foods commonly consumed in the Latino community.Feedback from focus group sessions supported the value of integrating genomics and family history education into the SCSV program. Further details on the focus groups have been previously reported . Participromotores-facilitated SCSV program could be successfully implemented in the community to improve health outcomes. However, participants suggested that both men and women be included in an educational initiative. Although there was agreement that women strongly influence family health behaviors, participants believed the support of male family members is vital to successful behavior change.There was enthusiastic consensus that the promotores training modules were not included in the final tailored program but were maintained as a separate training protocol for community development. An outline of the adapted SCSV modules and concepts covered is provided in To maintain fidelity to the SCSV program, we adhered to the original implementation framework and retained key educational components. The genomics and family history module was structured to complement SCSV, using a presentation format identical to that of other program modules. The promotores program. An uncontrolled preintervention/postintervention was designed with the following specific aims:For this study, we reached out to North Central Area Health Education Center (NC-AHEC), an organization with an extensive history of providing community education through a well-established Determine the feasibility of implementing the tailored SCSV program;Examine preliminary indicators of the effect of the program on healthy lifestyle choices and genomic knowledge related to CVD and DM;Gather evaluative feedback on sociocultural acceptability of the program.promotores and lay community members were important for evaluating program acceptability. We therefore extended verbal invitations to participate to 40 promotores with previous training from NC-AHEC. Lay community members were recruited through flyers posted at sites frequented by Latino community members. Inclusion criteria were being a Latino aged 18 years or older whose primary language was Spanish.This study was conducted in Lexington, Kentucky. Guided by participant feedback during the formative research, we decided to recruit both men and women. Perspectives of Two intervention groups were conducted: one at the NC-AHEC office and the other at a local library used for multiple community activities. Each site is easily accessible and familiar to Latino community members.Via a written survey, we assessed demographic characteristics by using individual items. Genomic knowledge of CVD and DM was measured using a 29-item Spanish-language instrument with true/false response options. Genomic knowledge refers to understanding disease risk in relation to genes, family history, and lifestyle behaviors. The instrument included 5 items related to genetic predisposition, 8 to family history, 9 to behavioral risk, and 7 to genetic and behavioral risk factors . The totpromotora with extensive experience conducting community-based health programs and with providing promotores training assisted the PI to collect baseline data. Educational modules were presented to each group in Spanish by the promotora during 8 weekly 2-hour sessions. The PI attended all sessions, taking field notes and evaluating protocol fidelity. A final session was used to collect postintervention data; feedback on the program was provided during an audiotaped discussion held with each group. Participants received a gift card and childcare was provided during each session.A t tests. This analysis was completed using SAS version 9.3 ; an α level of .05 was used. Discussion session recordings were transcribed verbatim and transcriptions reviewed by the PI and promotora to identify salient themes.Comparisons of genomic knowledge and HPLP II scales and subscales from preintervention to postintervention were conducted using paired promotores training. One participant attended all sessions but was unable to attend the final assessment; a second attended several sessions but a work schedule change precluded completing the intervention. Two participants did not attend after the first meeting. Eighteen participants (82%) completed the postintervention assessment. Of those who completed the assessment, 14 attended all 8 educational sessions; 8 attended 6 to 7 sessions.Twenty-two participants, which included 1 group of 5 participants and a second group of 17, were enrolled and completed baseline assessments; 10 had previous The average age of participants in Study 2 was 44.5 years (standard deviation [SD] = 15.3 y). Men participated in each group but most participants were female (73%). Participants were from Mexico (59%) and South (36.4%) and Central (4.6%) America. Most participants were married (77%). More than half had some postsecondary education (52%); most were not employed (64%). Most reported their health to be “good,” “very good,” or “excellent,” the highest 3 ratings of a 5-level self-rated health assessment (68%). Most did not have health insurance (67%) or a health care provider (71%).P = .03). The overall score on the HPLP II scale was 2.45 (SD = 0.37) at preintervention and 2.68 (SD = 0.37) at postintervention (P = .009). There was a significant increase in the HPLP II subscale scores for health responsibility (P = .04), physical activity (P = .003), interpersonal relations (P = .04), and stress management (P = .03); change over time was not significant for nutrition or spiritual growth  to postintervention (20.50, SD = 10.22; l growth .Responses to program adaptations indicated that these were of benefit. Participants in both groups enthusiastically engaged in discussions on practical strategies for healthy lifestyles. During presentation of the genomic and family history module, participants expressed much interest in the topic. Several commented that they had heard of genes and associations with health but better understood this information after the presentation. Comments regarding positive experiences using relaxation techniques in response to daily stressors and appreciation of the educational models used to support learning indicated the benefit of each.During the postintervention discussion, participants commonly expressed that the program had influenced their behaviors. Several shared that positive health effects, particularly weight loss, had occurred during the course of the program. Participants in both groups stated they were more aware of unhealthy eating habits. One participant said that she now read food labels when grocery shopping. Many talked about sharing educational materials and information with family members and stated that family members were engaging in more healthful behaviors as a result. More global comments on the program included positive feedback regarding the format and pace of the educational presentations.A difficulty noted by several participants was that, although they were generally aware of the health status of first-degree relatives, they were less aware of that of their second-degree relatives. Several participants were hesitant to communicate with family members about health history because of privacy concerns. They thought family health discussions should occur naturally rather than information sought directly but agreed that increased family history awareness would encourage future discussions.Study results indicate that the socioculturally tailored SCSV program integrating genomic and family history education is feasible and appropriate to implement in a community setting among Latinos in a nontraditional area of residence. Outcomes also suggest that the program has potential to improve health behaviors and increase knowledge of genomics and family history of CVD and DM.promotora with the organization were essential to successful program implementation.Program tailoring was guided by CBPR principles that included building on and extending community-academic relationships; mutual identification of community health needs and approaches to address these; and sociocultural tailoring, implementation, and evaluation of a risk-reduction program. Community partners were crucial to identifying health needs and guiding development of the research program. The academic component of the partnership was important in guiding scientific aspects of research. Participant collaborators in the formative research provided feedback critical for tailoring the SCSV program and informing development of the genomics and family history educational module. Strategizing with NC-AHEC representatives and the collaborative efforts of a Community–academic collaboration foundational to CBPR presents both unique opportunities and challenges, both of which were experienced during this study. Effective communication among partners is vital to successful collaboration. In our study, collaborative processing, brainstorming, and problem-solving provided a solid foundation for relationship building and maintenance. Flexibility is also essential, as highlighted by study protocol changes guided by community partners. These resulted in improved outcomes but required significant cooperation and mutual engagement in the research process.There were several study limitations. First, Study 1 was conducted with Latinas; inclusion of Latino males may have provided differences in program tailoring. However, outcomes from the exploratory study indicate the tailored intervention is appropriate for use with men and women. Second, although the small sample size for Study 2 was sufficient to indicate sociocultural appropriateness of the program, demonstrating effective CVD and DM risk reduction will necessitate conducting the intervention in a larger sample with more diverse representation of Latino countries of origin, a more rigorous research design, and a longer follow-up assessment period.The outcomes of this study provide preliminary indication that the tailored healthy lifestyle intervention, including integration of genomic and family history education, is socioculturally appropriate and may provide a foundation for a sustainable program of health promotion for Latinos in a community with limited culturally and linguistically suitable health care resources. As important, the CBPR process used in program tailoring may provide guidance for addressing the health needs of Latino community members in other nontraditional areas of residence.


During summer 2010, 262 human cases including 35 deaths from West Nile virus (WNV) infection were reported from Central Macedonia, Greece. Evidence from mosquitoes, birds and blood donors demonstrated that the epidemic was caused by WNV lineage 2, which until recently was considered of low virulence. We conducted a household seroprevalence study to estimate the spread of infection in the population during the epidemic, ascertain the relationship of infection to clinical disease, and identify risk factors for infection.We used a two-stage cluster design to select a random sample of residents aged ≥18 years in the outbreak epicentre. We collected demographic, medical, and risk factor data using standard questionnaires and environmental checklists, and tested serum samples for presence of WNV IgG and IgM antibodies using ELISA.Overall, 723 individuals participated in the study, and 644 blood samples were available. Weighted seropositivity for IgG antibodies was 5.8% . We estimated that about 1 in 130 (1:141 to 1:124) infected individuals developed WNV neuroinvasive disease, and approximately 18% had clinical manifestations attributable to their infection. Risk factors for infection reflected high exposure to mosquitoes; rural residents were particularly at risk .This study adds to the evidence that WNV lineage 2 strains can cause significant illness, demonstrating ratios of infection to clinical disease similar to those found previously for WNV lineage 1. Culex mosquitoes. Wild birds are the natural host, while horses and humans are dead-end hosts , and <1% go on to develop WNND ,18, and -22, withThe study population was defined as the adult population (≥ 18 years) resident in 84 townships (towns or villages) in the lowland areas of Imathia and Pella prefectures, Central Macedonia, where the highest incidence of WNND had occurred during the 2010 outbreak  . We usedSelected households were recruited into the study by fieldwork coordinators. In case of non-inhabitation, non-answer, or refusal to participate, the clockwise neighbouring household was approached as a substitute. At least three visits at different times of the day were made to selected households prior to substitution. Fieldwork was undertaken by trained field researchers between November 25 and December 22, 2010, 14–18 weeks after the epidemic peak and 7–11 weeks after the last case was reported.All participants were interviewed at their household using a standard questionnaire concerning demographic characteristics, medical history, and exposure to potential risk or protective factors. One participant per household answered a second questionnaire concerning household-level characteristics, such as presence of screens on windows and potential sources of standing water. We tested the questionnaires through a pilot study involving 20 purposively selected persons from the study area. For rural  and semi-urban  areas, we collected additional information regarding local environmental characteristics through structured observation using checklists. Participants were asked to provide a 3ml blood sample on the day of interview. Standard precautions were taken regarding phlebotomy, transport and cold storage of samples. Serum samples were tested for WNV-specific IgM and IgG using ELISA  using cut-offs according to the manufacturer’s instructions. An avidity test using urea 6M was performed in the IgG-positive samples for probable differentiation between acute and non-acute infection; avidity index higher than 40% was suggestive of non-acute (>3 months) infection. Positive samples were also tested for antibodies to two other flaviviruses, tick-borne encephalitis virus (TBEV)  and dengue fever virus (DENV)  to rule out these infections.We performed statistical analysis adjusting for cluster design and weighting by age and area of residence, as younger age-groups and people living in cities were under-represented in the sample compared to 2001 census data . We analWe calculated seroprevalence estimates for both IgG and IgM. To determine the ratio of WNND to infection, we compared the number of cases reported from the study area during the epidemic to the estimated number of infections given the IgG seroprevalence we found and the population size in the study area according to 2001 census data ,25. To eSensitivity analysis: we repeated the calculation of IgG seroprevalence and WNND-to-infection ratio classifying as IgG-negative persons who were IgG-positive/IgM-negative and had low outlier values of IgG index n=4, .To investigate the relationship between seropositivity and WNF, we categorised participants according to whether or not they had experienced at least three of the following WNF indicator symptoms during the same episode (from June to September 2010): (1) fever, (2) chills, (3) headache, (4) myalgia or arthralgia, (5) skin rash, (6) generalised weakness, and (7) ocular pain . The weiTo explore associations between exposure variables and IgG seropositivity, we calculated prevalence ratios (PR) from the weighted proportions in the exposed and unexposed groups. We included exposure variables with a PR>2 or <0.5 or a p-value <0.05 in a logistic regression analysis. To simplify the models, variables were removed one at a time depending on significance testing (p<0.05) using the likelihood ratio test. We then used binomial regression to derive adjusted PRs using all the variables of the final logistic regression model. Potential interactions were also examined. We additionally performed a sub-analysis of the rural and semi-urban data to include the environmental variables from these areas. All participants provided written informed consent. Ethical approval was obtained from The Bioethics Committee of the National School of Public Health, Greece.A total of 360 households participated in the study; 216 (60%) were those initially selected, and 144 (40%) were substitutions. Approximately two thirds of substitutions (69%) were due to non-inhabitation or non-answer of the original household, and one third (31%) due to refusal to participate. Of 850 eligible residents, 723 (85%) participated, and 644 (76%) provided a suitable blood sample.Local environmental information was available for all 234 households in rural and semi-urban areas, corresponding to 586 eligible residents, and 491 (84%) study participants; blood results were available for 443 (76%) of these partcipants.WNV IgG antibodies were detected in 41 out of 644 persons tested ; in 15 of them WNV IgM antibodies were also detected . Seroprevalence was highest in residents of rural areas, and IgG-positive as well as IgM-positive participants tended to be older than those who were seronegative .The mean IgG avidity index was 75% (range 43%–100%), and there was no difference in the pattern of the avidity index distribution between IgG-positive/IgM-positive and IgG-positive/IgM-negative persons (supporting information The ratio of WNND patients to infected persons was found to be 1:141 (95% CI: 1:209–1:92). This ratio increased with age, and was considerably higher in persons aged 70 years or older ; it was After sensitivity analysis, the seroprevalence we found was 5.1% (95% CI: 3.5–7.4) and the WNND-to-infection ratio 1:124 (95% CI: 1:179–1:85) in all ages, 1:241 (95% CI: 1:366–1:155) in persons aged 18–69, and 1:27 (95% CI: 1:51–1:14) in those aged ≥70 see also . In thisOf the 41 IgG-positive persons, 20.2% reported experiencing three or more WNF indicator symptoms, as opposed to 3.7% of the 603 seronegative persons; this corresponds to an attributable risk of 16.5%. A similar pattern was seen for two or more symptoms . Combining these two estimates, we deduced that approximately 18% of persons infected with WNV developed symptomatic disease .Several factors were found to be associated with IgG seropositivity on univariable analysis  among alTo our knowledge, this study is the first population seroprevalence survey following a WNV L2 epidemic. Our results show that the impact of the epidemic was much larger than suggested by the 262 cases notified to the public health authorities. The seroprevalence we found in the study area was 5.1–5.8%, and we estimated that 24,000–28,000 infections occurred nationally. We concluded that about 1 in 130 (1:141 to 1:124) infected persons of all ages developed WNND, and approximately 18% experienced symptoms typical of WNF. The outbreak had a rural character in the study area, with people living in less populated areas at an eight times higher risk for infection.WNV IgG and IgM antibodies were detected in 15 participants, while another 26 had only IgG antibodies. The absence of IgM antibodies can be explained by the fact that the study was conducted 14–18 weeks after the epidemic peak, and the IgM antibodies had probably disappeared. This is in accordance with results of a recent study among Greek patients with WNV infection, which found that on average the IgM index becomes negative 164 (95% CI: 99–236) days after symptom onset . The detThis is supported by evidence that WNV L2 was recently introduced to Greece  and the Ixodes ricinus ticks among 3,144 Ixodidae ticks collected during 2003–2006 from goats and sheep in rural areas of northern Greece, indicating limited circulation [Cross-reactivity in serology is common among flaviviruses. We found low-titre cross-reactivity in IgG antibodies between WNV and DENV, and to a lesser degree between WNV and TBEV, similar to findings of previous studies . All WNVculation . These dOn univariable analysis, we found that seropositive persons tended to be older than seronegative ones, but age did not remain an independent risk factor for infection in the final multivariable model . This prIn the present study, estimates of WNND-to-infection ratios were based on a considerable number of WNND cases reported during the outbreak from the study area (n=80), unlike the respective estimates elsewhere . This gaOur study demonstrated that approximately 18% of persons with WNV infection manifested symptoms attributable to this infection. Other surveys conducted after WNV L1 outbreaks have shown the respective proportion to be 20–25% ,18. The Culex mosquitoes, may be implicated in the higher risk of people with water repositories on their property, and of rural/semi-urban residents living close to an irrigation drainage ditch. As in previous WNV L1 studies ,21-23, tIn conclusion, the present study demonstrates that a WNV L2 strain prompted an epidemic essentially similar to previous WNV L1 outbreaks in terms of virulence, disease-to-infection ratio, and risk factors. Given the historic propensity for rapid geographical spread of WNV ,16, and Figure S1Comparison of IgG index distribution in West Nile virus (WNV) IgG-positive/IgM-positive and IgG-positive/IgM-negative study participants.Lower IgG indices can be expected in IgG-positive/IgM-negative participants compared to those who were IgM-positive, due to waning immunity in the former group. However, this tendency was not statistically significant in our data set, although within the IgG-positive/IgM-negative group there were four participants with low outlier values of IgG index. When these four outlier values are disregarded, minimum, 25th percentile, and median IgG indices in the IgM-negative group are in fact higher than in the IgM-positive group (see figure), with the minimum value (3.8) being substantially higher than the cut-off for a positive result (1.5). In the sensitivity analysis (table S3), we classified these four individuals with outlier IgG indices as IgG-negative. Note that: (1) Box depicts inter-quartile range (IQR); Adjacent values (whiskers) represent most extreme values within IQRx1.5 from the nearest quartile; Line within box represents median; Circles depicts outlier observations; (2) The criterion for positive result was IgG index >1.5; (3) Comparison of IgG index in the two groups: IgG index in the IgM-positive group is not significantly higher than in the IgM-negative group (Wilcoxon rank-sum (Mann-Whitney) test, one-tailed, p= 0.477).(TIF)Click here for additional data file.Figure S2Comparison of West Nile virus (WNV) IgG avidity distribution in IgG-positive/IgM-positive and IgG-positive/IgM-negative study participants.High avidity indices (>40%) were found in all cases, indicating that infection occurred more than 3 months before drawing blood samples. This can be explained by the long interval between epidemic and study implementation (14–18 weeks after the epidemic peak and 7–11 weeks after the last case was reported). Avidity indices in IgM-negative individuals were not higher that in those who were IgM-positive.Note that: (1) Box represents inter-quartile range (IQR); Adjacent values (whiskers) represent most extreme values within IQRx1.5 from the nearest quartile; Line within box depicts median; Circles depict outlier observations; (2) The criterion for recent infection (i.e. less than 3 months) was IgG avidity index <40%; (3) Comparison of IgG avidity in the two groups: IgG avidity in the IgM-negative group is not significantly higher than in the IgM-positive group (Wilcoxon rank-sum (Mann-Whitney) test, one-tailed, p= 0.339).(TIF)Click here for additional data file.Table S1Demographic characteristics of study participants and respective data for study area from census, 2001.(DOCX)Click here for additional data file.Table S2Mean age in different groups according to West Nile virus IgG and IgM status.In the present study, WNV IgG-positive participants tended to be older than those who were IgG-negative (main text (DOCX)Click here for additional data file.Table S3Sensitivity analysis: West Nile virus IgG seroprevalence and ratio of West Nile neuroinvasive disease to infection by age group.(DOCX)Click here for additional data file.Table S4West Nile fever indicator symptoms in seropositive and seronegative study participants, prevalence ratios, and attributable risks.Zou et al [ou et al  identifi(DOCX)Click here for additional data file.Table S5Factors associated with IgG seropositivity for West Nile virus on univariable analysis.(DOCX)Click here for additional data file.Table S6Personal, household and local environmental information collected.(DOCX)Click here for additional data file.


Dimeric IgG1 Fc tail-based fusion proteins are popular reagents in immunology. They are used for receptor activation, by mimicking ligands, and for meas-uring binding of proteins to receptors on cells. Using IgG fusion proteins, only those interactions with dissociation constants in the μM range or lower appear to be detected. Multimeric molecules, such as trimers, tetramers, and pentamers, have increased avidity but can be difficult to prepare and may have limited flexibility . MultimeIn searching for a highly multimeric and flexible reagent for flow cytometry and immunoassays, we developed IgM-based fusion proteins –4. IgM mWe coupled the extracellular domains of proteins to Ig domains 3–5 of the human IgM heavy chain. Domains 4 and 5 of the human IgM heavy chain contain cysteine residues that form disulfide bonds, required for the formation of multimers –8. The iWe assessed by flow cytometry and immunoassay whether co-expression of the J-chain influences binding of IgM-based heavy chain fusions to antigen. We also compared the binding of IgG-based and IgM-based fusion proteins by immunoassay.+ vectors (R&D Systems). The complementary deoxyribonucleic acid (cDNA) for mouse PD-L1 was from OpenBiosystems . The J-chain DNA sequence was from cDNA from the human B-cell line Raji, cloned into pCIPac DNA plasmid [We used a human IgM DNA sequence encoding the heavy chain domains 3–5, which Fukuda's laboratory used to detect binding partners of L-selectin and E-selectin by fluorescence microscopy . IgG1a f plasmid . The DNA plasmid . Fusion + primary mouse T cells which express its ligand PD-1 when activated. PD-L1 binds PD-1 with a dissociation constant of 0.77 μM, and B7–1 of 1.4 μM [+ primary T cells and bound weakly to CD3+ primary T cells which had been activated for 3 days using 1 μg/ml anti-CD3 and 0.5 μg/ml anti-CD28 (+ T cells increased (+ primary T cells even after activation. When the J-chain was co-expressed with the BTN2A2-IgM fusion protein, significant binding to the surface of activated CD3+ T cells was detected. Since the expression of the J-chain increased binding of IgM-based fusion proteins, we developed HEK-293 cell lines that were stably double-transfected with the respective IgM fusion plasmid, and the J-chain plasmid.To assess the advantage of IgM + J-chain constructs by flow cytometry, we monitored binding of mouse PD-L1 molecule to CD3f 1.4 μM . We alsof 1.4 μM . First, nti-CD28 A. PD-L1-ncreased A. As shoTo assess further the influence of the J-chain, a PerkinElmer DELFIA™ time-resolved fluorescence immunoassay system was used. First, the contribution of the J-chain to the binding of PD-L1-IgM fusion protein to plate-bound PD-1 was measured by immunoassay A. About In addition, the binding to plate-bound PD-1 of dilutions of cell culture supernatant containing either PD-L1-IgG or PD-L1-IgM + J-chain was compared by immunoassay. When the PD-L1-IgM + J-chain complexes were used at 6 μg/ml, signals for bound PD-L1-IgM fusion protein exceeded, at high PD-1-rCD4 concentrations, the maximal detection limit of the immunoassay system, visible in When comparing the binding of supernatants with either 6 μg/ml PD-L1-IgG or PD-L1-IgM fusion protein and J-chain, a shift of the binding curve toward lower concentrations of PD-1 was observed B. To quaIn principle, IgM-based fusion proteins have advantages over IgG-, as they are more flexible and form higher multimers, promoted by the J-chain. We showed that co-expression of the J-chain increased binding of PD-L1-hIgM to PD-1 by approximately 2.5-fold. Compared with IgG, IgM + J-chain enabled detection of approximately tenfold lower amounts of binding partner. When we compared binding of different concentrations of fusion protein, we found that the IgM backbone strongly increased binding to plate-bound PD-1 by approximately 100-fold compared with IgG. A possible mechanism that could facilitate binding or reduce dissociation might be the higher valency of the IgM-backbone. In conclusion, IgM-based fusion proteins co-expressed with the J-chain appear to be useful reagents to characterize weak receptor–ligand interactions. In addition, our data indicate a function of the J-chain in facilitating IgM binding. It remains to be elucidated how coupling the IgM backbone and the J-chain facilitates formation of receptor–ligand interactions.


N = 66) were assessed before and after the yoga program and at three- and six-month follow-ups. Decreases in mood disturbance and stress symptoms and improvements in HRQL were observed upon program completion. Improvements in mood disturbance and stress symptoms were maintained at the three- and six-month follow-ups. HRQL exhibited further improvement at the three-month follow-up, which was maintained at the six-month follow-up. Improvements in measures of well-being were predicted by initial positive yoga beliefs and concurrently assessed affective and mindfulness predictor variables. Previous yoga experience, affect, mindfulness, and HRQL were related to yoga practice maintenance over the course of the study.Little attention has been paid to the psychological determinants by which benefits are accrued via yoga practice in cancer-related clinical settings. Using a longitudinal multilevel modeling approach, associations between affect, mindfulness, and patient-reported mental health outcomes, including mood disturbance, stress symptoms, and health-related quality of life (HRQL), were examined in an existing seven-week yoga program for cancer survivors. Participants ( Receiving a cancer diagnosis, undergoing treatment, and the subsequent recovery takes a great toll on many cancer survivors. Psychosocial distress stemming from the cancer experience is a significant problem for up to half of all cancer patients, and many survivors experience lowered overall health-related quality of life (HRQL) during and following active treatment . RegardlWithin the larger field of exercise and cancer, yoga is often considered a gentle, low-intensity form of exercise . The unihow yoga leads to clinically significant outcomes is the next step in understanding the ability of yoga to target desired outcomes. Recommendations from the UK Medical Research Council . Small significant increases from baseline in moderate-to-vigorous PA were observed at the three- and six-month follow-ups. A small significant increase in total physical activity (LSI) was also observed over time   = 11.98, P < .001]. Small decreases in tiredness after-program were not maintained at the 3-month follow-up but again improved at the 6-month follow-up . Small decreases in tension were observed after-program, and were not maintained at the three-month follow-up, but again improved at the six-month follow-up . There were no changes in patient-reported calmness over time  = 9.46, P < .001]. Small increases in participants' ability to be nonjudgmental of inner experience were observed after-program that were maintained at the three- and six-month follow-up . No significant changes in nonreaction were observed after-program but small significant improvements were observed at the three- and six-month follow-up   = 5.72, P < .001]. A moderate decrease in stress symptoms was observed from baseline to after program that was maintained at both the three- and six-month follow-ups . A small statistically significant improvement in HRQL was observed after program. However, HRQL significantly improved at the three-month follow-up and was maintained at the six-month follow-up  . R2 value suggests inclusion of these variables reduced error in predicting mood disturbance by 31% . Upon initiation of the current study, 48% (32 participants) reported previous yoga practice experience either through the Yoga Thrive program, community classes, home practice, or combinations thereof. At the end of the seven-week yoga program, 96% were still practicing yoga in various settings, a significant increase of 48% from baseline. At the three-month follow-up yoga practice had dropped, with 69% of participants were still practicing yoga in various settings, a significant 20% increase from baseline. At the six-month follow-up there was a slight increase in participation rates, with 76% of participants reporting continued yoga practice in various settings, a significant 27% increase from baseline see .Follow-up GEE logistic regression analyses were performed to examine what participant characteristics predicted ongoing yoga practice (objective 2b). In examining associations between yoga practice at each time point and predictor variables, there was an initial positive linear effect for time, reflecting the increased rate of participants reporting yoga practice before-after program. The quadratic trend reflects a significant decline postintervention completion in yoga practice at three- and six-months. Those who reported more frequent participation in the Yoga Thrive program at each time had a greater chance of continuing their yoga practice for each time they completed the Yoga Thrive program. In addition, those who reported higher energy at each time point were more likely to maintain a yoga practice, as were those who reported a greater ability to be nonreactive to inner experience. Finally, those with higher self-reported HRQL at each time point had a greater chance of continuing yoga practice see .Despite an emerging body of evidence highlighting the benefits of yoga for cancer survivors, little work has been done to bridge these clinical findings with theoretical predictors of change. The current research sought to bridge this gap between determining clinical benefits and describing predictors of these improvements in mood disturbance, stress symptoms and HRQL. Using the Circumplex Model of Affect as it has been applied in exercise settings  and emerCurrent study results suggest a linear increase in energy over time. These findings concur with research in the area of aerobic training  which suLongitudinal findings suggest participants reported improved ability to act with awareness, a mindfulness facet closely related to one's ability to concentrate . ParticiBaseline positive yoga beliefs were consistently associated with lower mood disturbance, stress symptoms, and higher HRQL at all time points. Sohl et al.  suggest core affect [The present research ascribed to Russell's (2003) thesis that when affective dimensions are examined longitudinally, they are no longer tied to a specific context as in acute exercise settings, where the temporal proximity to an exercise session is evident. Rather, these measures become reflective of what Russell (2003) has termed prolonged, objectless e affect . It coule affect , 74, 75.Higher reported ability to act with awareness was associated with lower mood disturbance and stress symptoms at all times. Higher reported nonjudgment of inner experiences was related to lower stress symptoms and higher HRQL. These improvements may reflect an accepting attention strategy in which participants find alternate ways to respond to stressful situations . These fThe present research is congruent with previous work suggesting yoga's effectiveness in reducing psychological distress and improving HRQL in cancer survivors , 9. ContPrevious participation in the Yoga Thrive program was a significant predictor of yoga practice maintenance at all time points. This finding is similar to Speed-Andrews and colleagues' finding that yoga experience over the past year was significantly related to current yoga adherence in a cancer setting . PositivThose reporting higher energy at each time point were also more likely to continue yoga practice. This relationship between positive affect and adherence has been widely reported in the literature , 19. It Results suggesting those higher in non-reactivity were more likely to adhere to yoga practice are also supported in the literature. Nonreaction refers specifically to the ability to remain calm in the face of distressing thoughts and emotions. This ability to be nonreactive to inner experience has salutary effects and seems to be a key facet of mindfulness as well as one of the facets most affected by contemplative training . ResearcResults from the current study suggest a reciprocal relationship in which higher HRQL is associated with yoga practice maintenance. Higher HRQL has been associated with increasing individual self-efficacy to adhere and maintain exercise programs . MaintenTaken together these results suggest previous yoga experience coupled with higher energy, a greater ability to be nonreactive to inner experience and higher HRQL interact to improve the likelihood participants will maintain yoga practice, arguably further engendering the benefits of these practices. If affect and mindfulness are both associated with improved mental health outcomes and HRQL and cited as leading to increased program adherence, it behooves clinicians to consider developing approaches that focus more exclusively on the inherent psychological benefits of exercise, including yoga , 80.The use of an observational research design, including 48% of study participants who had already completed the program, added complexity to the current analyses. Without a comparison group, it is impossible to determine whether positive program effects were related to the yoga program, or due to the simple passage of time, among other factors. Also, given the high degree of previous yoga experience within the study sample, these findings are not generalizable to a general cancer survivor population. Despite these limitations, a comparison group was not utilized. Rather, the researchers elected to conduct the research in a “real-world” clinical setting given the Yoga Thrive programs' broad community-based implementation and the researchers' stated goal of identifying and developing theory to examine likely predictors of change in participant-reported outcomes . HoweverBefore yoga can be broadly applied within oncology, carefully designed and executed research that convincingly evaluates not only the effectiveness of yoga in clinical settings but also posits potential predictors of program outcomes are required. Despite the aforementioned limitations, longitudinal multilevel analyses allowed for the integration of theory to develop a novel research design able to examine mental health outcomes, contextual factors, and interactions thereof, within an existing community-based yoga program for cancer survivors. This combined knowledge can be translated directly back into the community to further develop innovative yoga programs and best practices with the express aim of improving mental health and HRQL in cancer survivors, soothing both mind and body.


CARD15 that encodes NOD2 are linked to Crohn’s disease or Blau’s syndrome. Genome-wide association studies (GWASs) have identified a number of risk alleles encompassing NLR genes in a host of diseases including allergic rhinitis, multiple sclerosis, inflammatory bowel disease, asthma, multi-bacillary leprosy, vitiligo, early-onset menopause, and bone density loss in elderly women. Animal models have allowed the characterization of underlying effector mechanisms in a number of cases. In this review, we highlight the functions of NLRs in health and disease and discuss how the characterization of their molecular mechanisms provides new insights into therapeutic strategies for the management of inflammatory pathologies.Nucleotide-binding and oligomerization domain NOD-like receptors (NLRs) are highly conserved cytosolic pattern recognition receptors that perform critical functions in surveying the intracellular environment for the presence of infection, noxious substances, and metabolic perturbations. Sensing of these danger signals by NLRs leads to their oligomerization into large macromolecular scaffolds and the rapid deployment of effector signaling cascades to restore homeostasis. While some NLRs operate by recruiting and activating inflammatory caspases into inflammasomes, others trigger inflammation via alternative routes including the nuclear factor-κB, mitogen-activated protein kinase, and regulatory factor pathways. The critical role of NLRs in development and physiology is demonstrated by their clear implications in human diseases. Mutations in the genes encoding NLRP3 or NLRP12 lead to hereditary periodic fever syndromes, while mutations in  The mammalian immune system encompasses an ancient genome-encoded innate immune system and a more recently acquired adaptive immune system capable of combating pathogens with exquisite specificity and long-term memory. The innate immune system remains a pivotal player in controlling host resistance. This system is equipped with an arsenal of pattern recognition receptors (PRRs) that translate microbial and danger sensing into immediate host defenses as well as provides signals to prime the adaptive immune response for long-lasting protection , 2. NuclThe characteristic feature of NLRs is a central NOD (or NACHT) domain, required for oligomerization, an N-terminal homotypic protein–protein interaction domain and a C-terminal series of leucine-rich repeats (LRRs) involved in agonist sensing or ligand binding. Mammalian NLRs are sub-divided into four subfamilies based on the variation in their N-terminal domain: NLRA or Class II transactivator (CIITA) contains an acid transactivation domain, NLRBs or neuronal apoptosis inhibitor proteins (NAIPs) possess a baculovirus inhibitor of apoptosis protein repeat (BIR), NLRCs have a caspase-recruitment domain (CARD), and NLRPs a pyrin domain (PYD). NLRX1 contains a CARD-related X effector domain Figure , 14. NLRNLRP3 (CIAS1)  or anti-IL-1β antibodies (canakinumab), to cure patients inflicted with hereditary periodic fever syndromes . ConcurBacillus anthracis which activates murine NLRP1b  have shown a significant association of polymorphic variants in the extended promoter and/or coding regions of vitiligo , 29, celvitiligo , Addisonvitiligo , 32, autvitiligo , systemivitiligo , systemivitiligo , 36, convitiligo , rheumatvitiligo , and Alzvitiligo   process significantly greater amounts of pro-IL-1β into mature IL-1β under basal conditions. It was thus proposed that the enhanced production of IL-1β predisposes carriers to a wide spectrum of autoimmune diseases  at the steady state, which rendered them cytopenic , which are a group of rare hereditary auto-inflammatory diseases including familial cold urticaria, MWS, and neonatal onset multisystem inflammatory disease [reviewed in Ref.  activation, suggesting that NLRP6 may suppress TLR pathways after the recognition of pathogens to prevent amplified inflammatory pathology   secreted significantly lower levels of IL-1β and TNF in response to LPS despite high intracellular levels of pro-IL-1β and unimpaired pro-IL-1β processing. The authors concluded that NLRP7 might play a role in cytokine trafficking and secretion from the cell  , 95–97. d N913S)  and endod N913S)  cancers.the cell . Conversthe cell , 101. Mothe cell . Thus, fYersinia pestis infection, where NLRP12-deficient mice were more susceptible to infection compared to the controls . A recent study by Vladimer et al. has shown that the NLRP12 inflammasome has a key role in controlling IL-1β and IL-18 production after controls . Other pathology .While many of the functions and activators of NLRP12 remain unknown, mutations in the NLRP12 gene have been associated with auto-inflammatory diseases such as atopic dermatitis  and hereNlrp12−/−mice were found to be more susceptible to colitis and colon cancer, and polyps isolated from these mice showed significantly higher non-canonical activation of NF-κB with an increased expression of inflammation and cancer-related genes  and MDP from Gram-negative and Gram-positive bacteria –132. DesCARD4 and CARD15 genes respectively, and as NLRCs, both contain the shared NOD and LRR domains in addition to an amino-terminal CARD. Despite the strong similarities between the two receptors, differences exist; NOD1 contains one CARD domain, while NOD2 contains two   . Like NOoly(I:C) , 212 andoly(I:C) . Recentloly(I:C) , 215. Hocontrols –219. In controls , 218. Zhcontrols . Lastly,controls . These fOne of the newest additions to the NLR family, NLRC5 has been shown to have a similar structure to other NLRs, although the CARD domain has been found to be structurally distinct from CARD domains expressed in other NLRs. The protein is most similar to CIITA, both in structure and activity. NLRC5 has been shown to be able to enter the nucleus, and its main function is believed to be as a MHC Class I transactivator, forming the basis of an enhanceosome for MHC Class I transcription . AccordiL. monocytogenes. Interestingly, NLRC5 deficiency also seemed to result in a decrease in NLRP3 inflammasome activation, suggesting that NLRC5 may play a role in the regulation of this pathway , a disease characterized by severe immunodeficiency due to a lack of MHC Class II expression . Its detCIITA-BX648577 gene fusion product in the KM-H2 Hodgkin lymphoma cell-line which was associated with decreased HLA Class II expression and increased programed cell death 1 (PDL1) on the surface of affected cells , and have the ability to initiate and support robust immune responses through the formation of inflammasomes and the activation of NF-κB, IRF, and MAPK pathways. Functions such as the enhancement of MHC transcription and presentation implicate NLRs in adaptive immunity, and their roles in reproduction, indicate a broader responsibility of this gene family than previously suspected. The potency of NLRs in inducing immune defenses is vital for the host, but can also provide serious problems when dysregulation or malfunction occurs. GWAS have found many SNPs in NLR genes associated with a plethora of inflammatory and autoimmune pathologies. Research is vastly expanding contemporary knowledge on the functions and roles of NLRs, but several NLRs still remain poorly characterized and understood. Specifically, it remains unclear how NLRs can interact with various and structurally diverse ligands. It is hypothesized that upstream receptors or effectors dictate the activation of NLRs. Alternatively, NLRs might employ co-receptors or dimerize with additional sensors to achieve their functions. Further description of the roles of NLRs in initiating and perpetuating human disease, as well as the role of NLRs at the steady state, will prove vital to gaining a comprehensive understanding of many human pathologies and will provide novel targets and therapies for patients afflicted with these diseases.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.