In addition to medical intervention and counseling, patients with cardiovascular disease (CVD) need to manage their disease and its consequences by themselves in daily life.The aim of this paper is to describe the development of “Vascular View,” a comprehensive, multi-component, tailored, Web-based, self-management support program for patients with CVD, and how this program will be tested in an early randomized controlled trial (RCT).The Vascular View program was systematically developed in collaboration with an expert group of 6 patients, and separately with a group of 6 health professionals , according to the following steps of the intervention mapping (IM) framework: (1) conducting a needs assessment; (2) creating matrices of change objectives; (3) selecting theory-based intervention methods and practical applications; (4) organizing methods and applications into an intervention program; (5) planning the adaption, implementation, and sustainability of the program, and (6) generating an evaluation plan.The needs assessment (Step 1) identified 9 general health problems and 8 determinants  of self-managing CVD. By defining performance and change objectives (Step 2), 6 topics were distinguished and incorporated into the courses included in Vascular View (Steps 3 and 4): (1) Coping With CVD and its Consequences; (2) Setting Boundaries in Daily Life; (3) Lifestyle ; (4) Healthy Nutrition; (5) Being Physically Active in a Healthy Way; and (6) Interaction With Health Professionals. These courses were based on behavioral change techniques (BCTs) , which were incorporated in the courses through general written information: quotes from and videos of patients with CVD as role models and personalized feedback, diaries, and exercises. The adoption and implementation plan (Step 5) was set up in collaboration with the members of the two expert groups and consisted of a written and digital instruction manual, a flyer, bimonthly newsletters, and reminders by email and telephone to (re-)visit the program. The potential effectiveness of Vascular View will be evaluated (Step 6) in an early RCT to gain insight into relevant outcome variables and related effect sizes, and a process evaluation to identify intervention fidelity, potential working mechanisms, user statistics, and/or satisfaction.A comprehensive, multi-component, tailored, Web-based, self-management support program and an early RCT were developed in order to empower patients to self-manage their CVD.Nederlands Trial Register NTR5412; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5412 (Archived by WebCite at http://www.webcitation.org/6jeUFVj40) Cardio vascular disease (CVD) is the leading cause of death worldwide . In 2012CVD is predominantly caused by genetic and environmental factors, among which unhealthy lifestyle habits are the most important. Risk factors of CVD caused by atherosclerosis are divided into behavioral risk factors , metabolic risk factors , and other risk factors . Since all risk factors interact with each other and play a key role in decreasing the process of atherosclerosis, they must be considered in the treatment of CVD and secondary prevention .Health and social care services support patients with chronic diseases by providing specialized staff, medicines, and equipment to control symptoms. In addition to medical treatment and counseling, patients need to manage CVD and its consequences in daily life by themselves . Self-maSelf-management programs have the potential to decrease the load on health and social services, to lower the high costs of chronic care, and to improve patient quality of life. Self-management in chronic care appears to be effective, especially when focusing on behavioral change, supporting self-efficacy, and implemented in wider initiatives  . AlthougTo our knowledge, there are no comprehensive, multi-component, Web-based, self-management support programs that focus on behavior change and support self-efficacy in secondary care patients with CVD. Within such programs, the tailoring of the content to a patient’s profile is important in order to increase their level of understanding, information recall, and adherence to lifestyle interventions . TherefoThe aim of this paper is to describe (1) the development of the “Vascular View” (“Vaat in Zicht” in Dutch) program for patients with CVD, according to six steps of the intervention mapping (IM) framework ; and (2)IM is an iterative, 6-step process for developing theoretically-based behavior change interventions . The steThroughout the entire development process for the Vascular View program, two expert groups  explored and discussed, at each IM step, the specific issues (disease and treatment) that may influence self-management. The groups met up to three times to ensure that the program would be tailored to the perceived problems and needs that are important to patients with CVD and their health professionals. The patient expert group consisted of 1 female and 5 males with CVD . The professional expert group included a medical specialist in general and vascular medicine, a neurology nurse, a cardiology nurse, a vascular surgery nurse, a psychologist, a dietician, and a physical therapist. Two researchers (SPH and BvG) participated in both expert groups and SPH chaired each meeting. Before the start of each expert group meeting, the members were asked to prepare by reading information and finishing assignments on the themes of the meeting. The meetings were supported by PowerPoint presentations and the researchers emphasized the importance of the opinions and contributions of each member. This resulted in valuable discussions and agreements at the end of each meeting, which were audio recorded. After the meetings, the recordings were transcribed verbatim by a student. Analysis of all meetings took place by thematically verifying researcher’s (SPH) notes with the typed results of the audio recordings, in summary.The needs assessment focused on identifying perceived problems and (support) needs in the self-management of CVD using the Predisposing, Reinforcing, and Enabling Constructs in Educational/Environmental Diagnosis and Evaluation (PRECEDE) model . First, The aim of creating matrices of performance and change objectives was to provide a translation from needs to content in Vascular View. Behavioral and environmental conditions selected were related to self-management of the problems identified in Step 1. These were subdivided into performance objectives and combined with the important and modifiable determinants of the behavioral and environmental conditions based on the Integrated Change Model 2.0 (I-Change model 2.0) , and desThe purpose of Step 3 was to select theory-based intervention methods and practical applications based on the former steps. The Coding Manual for Behavior Change Techniques from de Bruin and colleagues  was usedThe aim of Step 4 was to develop and pretest the program components and materials of Vascular View. The program outcomes, the selected BCTs, and the practical applications from Steps 2 and 3 were starting points for the development and pretest of the program. All members of the two expert groups were asked what the ideal Vascular View program should look like, in line with the message , the channel (Internet), and the information sources . All patients from the expert group were also asked for the most valuable perceived advices that they received during their treatment and rehabilitation, how these advices looked like, and from whom these messages came. All health professionals were asked how they adapted their advice given to a patient and how they validated this adaptation. The research group prepared blueprints for the production of the different program materials and discussed this within the two expert groups in one meeting. Based on the outcomes of this meeting, the final content  was determined and developed by the research group and incorporated into the Vascular View program by Mind District Development BV (The Netherlands), the information and communication technology (ICT) partner. Finally, the program was pretested by the members of both expert groups individually and their feedback was gathered by open-ended questionnaires in which the members could describe their comments on each page. All patients and health professionals were asked to use the program for one week and give feedback about the importance and comprehensibility of the information, quotes, pictures, videos, diaries, and exercises, and their views of the layout of Vascular View and whether it was user-friendly. All of the feedback was collected, structured per training session and specific page, and incorporated into the final program. See also the results of Step 4.The focus of Step 5 was to make an implementation plan for Vascular View during the planned evaluation study. The adoption and implementation of Vascular View started in the development process with the involvement of patients and professionals by taking their expertise into account. In addition to their role in the development of the program, the two expert groups played an important role in the determination of facilitators for, and barriers to, the adoption and implementation of this intervention. For example, all members were asked, via questionnaires, what facilitates dissemination and exposure , in order to complete the different courses of Vascular View. The researchers also determined performance objectives for a patient’s first visit and re-visits to Vascular View and combined these with the relevant determinants into change objectives, and discussed these results in one meeting with the members of the two expert groups. The findings of dissemination and exposure were incorporated in the final Vascular View program. The performance and change objectives, and the corresponding determinants, were included in the adoption and implementation plan for Vascular View.The objective of the final step of IM was to design an evaluation study for Vascular View by conducting an early RCT to gain insight into relevant outcome variables and related effect sizes, and to perform a process evaluation to identify intervention fidelity, potential working mechanisms, and user satisfaction ,27.In this phase, we selected relevant measurable outcome variables related to the objectives of the Vascular View program, the defined performance outcomes, and whether the specific tailoring to changes in self-management behavior conformed to the applied I-Change Model 2.0. The process evaluation also includes a check of intervention fidelity (adherence to the program as proposed), incorporating outcomes compliant with the performance objectives and determinants as expressed in the matrix of change objectives in IM Step 2, as well as interviews with participants (program users and non-users) of the study, audio recordings of nursing visits with participating patients, and focus group interview(s) with health professionals.The involvement of the members of both expert groups for each IM step during the development of Vascular View is described in A literature search and three meetings with the two expert groups  elicitedThe second and third meetings provided the selected underlying behaviors and environmental conditions of these health problems and symptoms, which varied from having insufficient insight into CVD to having an unhealthy lifestyle, and being unsuccessful in setting boundaries, or inadequate interaction with health professionals . The folWe selected the three most important and modifiable determinants of self-managing CVD from the I-Change Model 2.0 : awareneIn one meeting, the members of the two expert groups  validateFor each selected determinant of self-management behavior , the BCTs were selected  and discIn translated these BCTs to practical applications, the parameters under which a given technique is most likely to be effective were taken into account. For example, self-reevaluation can use feedback and confrontation; however, raising awareness must be quickly followed by increase in problem-solving ability and self-efficacy. In one meeting, the two expert groups  emphasizThe course “Coping with CVD” addresses the determinants knowledge, awareness, risk perception, attitude, self-efficacy, subjective norm, intention, and action plans. The patient learns about dealing with CVD and its impact on daily life , relatives, social environment, and resuming activities.In the course “Setting Boundaries,” patients learn to clearly communicate with their social environment  about perceived boundaries in daily life and in resuming activities with respect to their current ability. This course addresses the determinants knowledge, awareness, attitude, self-efficacy, and subjective norm.The course “Lifestyle” addresses the determinants knowledge, awareness, attitude, self-efficacy, subjective norm, intention, habits, and skills, and consists of information about a healthy lifestyle , and information to support abstention from tobacco and alcohol use.In the courses “Healthy Nutrition” and “Being Physically Active in a Healthy Way,” patients gain insight into what they eat and drink, how physically active they are, and how to change their habits to healthier ones, step by step. These courses address the determinants knowledge, awareness, attitude, self-efficacy, subjective norm, intention, habits, and skills.The course “Interaction With Your Health Professional” teaches patients to effectively communicate with the health professional . This course addresses the determinants knowledge, awareness, attitude, self-efficacy, and subjective norm.The sessions in the courses are personalized and are supported by written information, quotes, pictures, videos, diaries, and exercises. In the courses “Healthy Nutrition” and “Being Physically Active in a Healthy Way,” two case studies involving two imaginary patients (a man and a woman) support the information and exercises offered through the sessions and courses .In all courses of Vascular View, tailoring was done using variables or factors related to behavior change (such as stage of change), or to relevance (such as culture or socioeconomic status) ,25. A paThe feedback of the pretest by all patients and health professionals of both expert groups  consisteAs a result of the first 4 Steps and one meeting with both expert groups , we deveThe members of the two expert groups also emphasized the importance of being motivated to use Vascular View by their health professionals, whether or not this was supported by a brochure. They added that health professionals should also be interested in the progress of a patient’s self-management behavior, and be able to answer questions during the study in order to show their involvement.The key persons in adoption and implementation are the medical specialists in Internal and Vascular Medicine, and the nurse specialists in Neurology, Cardiology, and Vascular Surgery, because of their crucial roles in the recruitment of patients. They also brought Vascular View to the attention of patients during regular consultations across the study period by asking about the program. Before the program started, the nurse specialists were instructed in how to support a patient’s use of Vascular View.A mixed-methods study design will be conducted with an early RCT and a process evaluation to (1) evaluate the potential effectiveness and effect size of Vascular View; (2) identify the outcome measures most likely to capture potential patient benefit; and (3) evaluate continued participation or withdrawal from Vascular View. The early RCT and the process evaluation will be performed at four outpatient clinics in one university hospital in the Netherlands .We will recruit 400 to 600 potential participants diagnosed with CVD, to allow the participation of 200 patients. Inclusion criteria are that patients (1) manifest atherosclerotic vascular disease, including ischemic heart disease, cerebrovascular disease , and peripheral artery disease , or a combination; (2) are aged 18 years or older; (3) can speak, read, and understand the Dutch language; and (4) have access to a computer, the Internet, and an email account. Exclusion criteria are patients with (1) comorbidities, which may hinder the use of Vascular View, as defined by the medical specialist; and (2) psychiatric disorders.The medical specialists will inform patients about the content and aim of the study via an information letter. After signing the informed consent and completing the baseline questionnaire (T0), patients will be included and randomized to an intervention group  and a control group . Randomization will take place at the individual level, will be stratified for diagnoses, and will be executed by a statistician who will use a computer program. Patient characteristics will be assessed at baseline via an online questionnaire (T0) and medical file research. Repeated measures will be conducted 6 months (T1) and 12 months (T2) after baseline. Semi-structured interviews will be performed with patients and focus group interview(s) will be conducted with health professionals at 12 months.This study has been improved by the Medical Ethical Research Committee of Arnhem - Nijmegen, Nijmegen, the Netherlands (registration number: 2015/1908), and is registered in the Netherlands Trial Registry (registration number: NTR5412).The quantitative data will be collected via an online questionnaire and medical file research. The online questionnaires consist of patient demographics and the following, described 11 measurements. Illness attribution will be assessed by one question in the Illness Perception Questionnaire (IPQ) . The heaTo investigate the factors that influence user statistics, intervention fidelity, and user satisfaction in the Vascular View program, a process evaluation will be performed based on the framework of Saunders et al . This isQuantitative and qualitative analyses will be performed. Patient outcome measures will be treated as dependent and continuous variables and will be analyzed on the basis of intention-to-treat. All variables will be presented in percentages or in means and standard deviations of the sum-scores. Repeated measures analyses will be performed to explore effect sizes and the responsiveness of outcome measures. Multilevel analyses will be applied to compensate for the clustered nature of the data using mixed linear modeling techniques. The qualitative data gathered in semi-structured interviews and the focus group interviews will be analyzed using content analyses.The aims of this paper are (1) to describe the development of the tailored, Web-based, self-management support program Vascular View for patients with CVD according to the 6 steps of the IM framework; and (2) to describe how the program will be evaluated. The 6 steps of IM provide a well-balanced processual guide for tailoring to the preferences and support needs of patients with CVD, by combining evidence and the perceived experiences of patients and their health professionals. A unique feature of the program is that it is based on the perceived problems of patients with CVD and that the corresponding determinants were combined with theory-based intervention methods into practical applications. This resulted in a Web-based program which may influence the relevant determinants—knowledge, awareness, attitude, self-efficacy, subjective norm, risk perception motivation (intention), habits, and maintenance—of self-management in patients with CVD by applying different methods through the courses. The Vascular View program was tailored to patient preferences, the level of elaborateness of the information, the content, factors related to behavior change, and relevance. To our knowledge, such a comprehensive, tailored, Web-based, self-management program for secondary care patients with CVD has not been previously developed; other programs have mainly focused on one or two risk factors or risk factor determinants only -15.A strength of the Vascular View program is the intensive cooperation of the two expert groups in every step of IM. The two expert groups ensured that the general information from the literature fitted the target group. Their knowledge, experiences, and visions led to the comprehensive, Web-based program developed.Vascular View was developed for a heterogeneous population of patients with manifest CVD, including, among others, ischemic heart disease, cerebrovascular disease, and peripheral artery disease. This diversity in patients and diagnoses required a well-balanced approach from the Web-based program. To overcome this possible limitation, we tailored the content of the courses to patient diagnoses and interests by using short questionnaires before or during a course and “read more” options within the courses.Despite the comprehensiveness of this Web-based program, Vascular View is limited in its influence over the different environmental factors of patients with CVDs. Different interpersonal , organizational , community , and societal  factors were incorporated in Vascular View because the program aimed to increase self-management behavior and the way patients living in this  environment are able to cope, via the patients themselves. However, we do not know how these different environmental factors interact in order to change behavior . In desiThis paper describes the systematic development of the comprehensive, tailored, Web-based self-management support program Vascular View for patients with CVD, according to the IM framework. Vascular View aims to increase self-management behavior in patients with CVD by influencing the risk factors of CVD and through an improvement in quality of life, via a unique combination of tailoring, personalizing, and behavior change, by influencing determinants  of self-management behavior. The proposed early RCT will indicate whether these aims can be achieved. Furthermore, this feasibility study will give insight into relevant outcome variables and related effect sizes and allow us to identify any flaws or technical difficulties. This information will be used to set up a larger RCT. A process evaluation will identify, amongst other things, patient experiences in using the program and at which level the Vascular View program is helpful in supporting self-managed CVD. This information will be used in the future development of the Vascular View program.


Participating in groups are a critical part of rehabilitation model in Early Psychosis Intervention. Effectiveness of intervention is dependent on the willingness of an individual to engage and remain engaged throughout the duration of the intervention. Approximately 30% of individuals with a first episode of psychosis disengage from services despite ongoing needs.On Track is a community based mental health outpatient program specialized in early assessment & treatment of psychosis. Client population includes individuals aged 16 to 35 years residing in the North East of Ontario, Canada.The program offers psychiatric follow up as well as unique group based interventions. Clients are required to be screened for group suitability & community safety prior to participation. Program evaluation highlighted challenges to engage clients. An open-ended, psycho-educational, drop in group called “The Café” was developed.Study used a mixed‐methods approach to evaluate the impact of the Café sessions on clients & their engagement in the program. Data was collected between December 2016 to June 2017. All clients were diagnosed with primary psychosis disorder. Patient experiences & engagement level were measured using a questionnaire & the Singh-O’Brien Level of Engagement Scale.43 clients participated in 29 Café sessions in seven months. Average number of participants per session was 7.3 (SD=3.05). Over 72% of clients participated in at least one to five sessions. Average age was 23.9 (SD=0.6). Participants were predominantly male (82%), white (42%), English speaking (93%), living with their parents (76.2%), no employment (69%), with some college or university degree (45.2%). Primary source of income were their families (47.6%). Over 59% of participants were in the program one year or less, 18.2 % & 22.7 % of participants have been in the program for two & three years, respectively.The engagement score among males did not differ significantly from females (t(42)=-0.94, p=0.35). There was no significant differences in engagement scores between ethnic groups (F(4)=2.84, p=0.062). There was a marginally significant difference in engagement score between program duration groups (F(2)=3.23, p=0.051); the engagement score for clients who have been enrolled in the program for over two years were slightly higher than one year clients.41% of clients attended Café before participating in any other groups; 4 of them joined other recreational & leisure groups. 3 clients later enrolled in a skill based group. 92% of respondents commented about the benefit of Café to their recovery as being “good” or “better”. Qualitative data identified socializing, coping with illness, & drop in nature of the Café as main themes contributing to recovery.In an attempt to increase opportunities for engagement, our program developed a drop in Café style group to provide client centered psycho-education group. The result of our intervention showed that the Café provided benefits to client’s engagement and recovery. The Café facilitated additional engagement in both recreational and leisure & skill based group streams. The drop in nature of the Café was advantageous to increasing engagement. Participation in the Café resulted in improvements in coping with the illness & socialization. Clients who had been enrolled in our program for 2 years reported higher levels of engagement compared to clients newly enrolled.Evaluating our intervention through collecting both qualitative & quantitative data provided us with a better understanding of the impact of the open- ended, drop in nature, psycho-education based group. Involvement of both client’s and families in the identification of the topics was another advantage of our study.


After bonding with the different luting agents, only 30% remained as 2M1: specifically, 22% of the thinner discs and 37.3% of the thicker discs. In general, the effect of bonding increased the value and the chroma of the shade to a significant extent. Regression analyses revealed that the most significant predictor for all color parameters was cement shade, the thinner disc group bonded with −3 cement being the most unstable subgroup. According to the 3D Master System, the shade of the luting agent was the main predictor of the final color. However, the final color seems to be somewhat unpredictable, at least according to the modulating factors evaluated in the present study.The final color of a ceramic restoration is influenced by both the ceramic thickness and the cement shade. This study aims to evaluate the color stability according to the 3D Master System of e.max ceramic discs after bonding with different shades of luting agents. A total of 120 e.max.Press 2M1 HT ceramic discs (60 discs of 1‐mm thick and 60 discs of 0.5 mm thick) and three different values of Variolink Veneer cement were used  for the cementation process. An Easyshade compact device was used to measure color shade tabs, according to the 3D Master System, on the discs both before and after the cementation protocols. Bivariate and multivariate analyses were carried out with the  Color is undoubtedly one of the parameters with the greatest weight when patients judge the quality of their restorations, above all in the anterior region of the mouth , that is, three distinct shades between both the thinner and thicker ceramic subgroups. The −3 and +3 shades are assumed to alter the final brightness value of the ceramic, that is, +3 high‐value pastes allow the restoration to appear lighter , whereas low‐value −3 impart a darker or more yellowish character to the ceramic restoration. All specimens were placed on a middle‐grey background , with the ceramic surface always facing the measurement side.One hundred and twenty ceramic discs simulating veneer thickness were prepared from A2 HT (high translucent) shades of IPS e.max Press  of 0.5‐mm (60 discs) and 1.0‐mm thickness (60 discs) with a diameter of 8.0 mm. The ceramics were divided into three groups according to the shade  of the Variolink Veneer luting agent from the same manufacturer. Thus, each of the six experimental subgroups contained 20 specimens (n = 20). We also used the digital caliper to estimate cement thickness.All discs were of the all‐ceramic lithium disilicate type (IPS e.max.PressA2 HT). According to the manufacturer, the true color of the ceramic ingot was A2, this being equivalent to 2 M1 in the Master 3D system. The specimens were prepared according to the manufacturer's instructions. The thickness of the specimens was measured three times with a digital caliper , and the specimen means were within the 0.50 ± 0.06 and 1.00 ± 0.01 mm range. The specimens were cleaned ultrasonically for 10 min before cementation and were divided into six thickness and Variolink Veneer shade groups . The spectrophotometer used was a Vita Easyshade Compact . After the probe tip calibration, the Easyshade compact probe was placed in contact with and perpendicular to the middle of the top surface of the discs. All discs were recorded in the “Single Tooth” mode. The probe tip has 19 optic fibres measuring 1 mm in diameter. The outer ring is formed by 12 packets of fibres and is used to illuminate the 5 mm diameter of the probe tip (from 0° to 30°).To analyze color change, the luting agents were bonded to the initially colored 2M1 ceramic discs. On each disc, the area designated for contact with the cement material was prepared with 5% hydrofluoric acid in gel applied for 1 min, rinsed with water for 30 sec, and dried with oil‐free air. Following this, a monocomponent silane was applied for 1 min and then dried for 3 sec with oil‐free air. Bonding was performed using Heliobond for the Variolink Veneers, following the manufacturer's instructions .2 for 40 sec. For all specimens, color was measured immediately after curing process using the Vita Easyshade compact, and the first result that coincided twice was recorded. This provided results coded according to the 3D‐Master System. To perform comparisons regarding the color change, we used the baseline color of all specimens as controls.Resin cements were applied directly from a syringe to the unglazed area of the ceramic surfaces. We used the same amount of cement for both discs thickness. Following this, a clean glass slide was placed onto the resin mixture and a manual pressure of approximately 500 grs was applied to it for 5 sec to simulate clinical conditions. Then, a light‐emitting diode was applied in direct perpendicular contact with the top surfaces  with a power of 1100 nW/cmt‐tests for independent samples and step‐wise linear regression analyses). Step‐wise linear regression analysis was conducted to measure the relative weight of the independent variables in predicting the color parameters. All analyses were performed with the spss v.21 .Bivariate and multivariate analyses were carried out to assess the influence of the thickness of the ceramic and the value and thickness of the cement on the resulting shade, using both paired non‐parametric (Wilcoxon Rank Tests) and parametric tests  of the 1.0‐mm‐thick group. Moreover, 95% of the 1.0‐mm‐thick discs and 62.3% of the 0.5‐mm discs became lighter when cemented with the +3 shade luting agent. The greatest variability in colors after cementing was obtained for the 0.5‐mm ceramic discs cemented with −3 shade luting agent, observing values ranging between 1M2 up to 2M3, passing through tones of different hue, chroma, and value, although most of them ended at 1L1.5 (35%) or the original color of 2M1 (20%).Table Dentistry faces the challenge of quantifying, predicting, and controlling the color changes inherent to treatment with laminate veneers. This is because color is one of the most influential factors in patient acceptance of a tooth restoration and at the same time is very difficult to achieve. The clinical impact lies in the fact that if there is a mistake when choosing the shade tab of the 3D Master Toothguide, there will very probably be an unacceptable color difference from a clinical point of view. This fact causes an evident alteration in esthetic restorations, which may end in patient rejection . In a try to simulate clinical conditions, the cement thickness was not standardized using spacers. In fact, in spite of using the same amount of luting cement for both ceramic thicknesses, the cement thickness for the 0.5‐mm discs was almost twice the thickness of the 1 mm discs. This may be a technical‐related event, that is, the operator should exert a higher manual pressure onto the thicker discs than onto the thinner discs, because of the higher weakness of the latter. Anyway, because we were well aware that this continuous variable should significantly modulate the color changes, it was introduced as a potential predictor within the linear regression models Table , resultiThe cement thickness obtained in this study was the result of a luting process carried out by a single operator, and hence, the variability in concentration and meticulousness during the procedural steps may have partially altered our results. However, the magnitude of the marginal fit reported here is clearly lower than that reported in several clinical trials  in 85% of the cases with thicknesses of 0.5 mm and in 35% of the cases with thicknesses of 1 mm. Hence, special caution should be exercised when cementing thin veneers (0.5 m) with 0 neutral shade luting agents because the value of the final shade would be increased. By contrast, the difficulty involved in darkening or decreasing the final lightness of restorations, even with minimum thicknesses, using the −3 Variolink luting agent shade should be noted, as reported by Chang et al. These observations should be taken with caution, because cement thickness, which is directly correlated with the shade of a resin‐based cement, was almost double in the 0.5‐mm discs than in the 1.0‐mm discs  were clinically perceptible, exceeding the dentistry threshold of ΔEIt should be taken into account that the shade changes reported here do not necessarily have to be homogeneous if the study is reproduced with another baseline ceramic shade or a ceramic from another manufacturer. For example, Leucite‐reinforced feldspathic ceramics  have generally been found to be less yellow and darker than glass‐infiltrated aluminum oxide  (Lee et al. Regarding ceramic thickness, in consonance with most authors, we conclude that the thinner the ceramic, the greater the influence of the underlying shade (Chang et al. It would be interesting to perform further studies with different ceramic shades, with different luting agent shades from different manufacturers and with different ceramic thicknesses and then measure the results according to the Vitapan classical and 3D Master systems.Although ceramic thickness modulated the chroma of the final shade of the laminates, the major predictor was cement shade, which is able to alter all the shade parameters to a significant extent.The authors declare that they have no conflict of interest.


PRAME was conducted to compare protein and transcriptional expression levels. We demonstrated a robust proof-of-concept for PRAME targeting in vivo by radiolabeling MPA1 with zirconium-89 (89Zr-DFO-MPA1) and demonstrating high specific uptake in PRAME expressing tumors. To our knowledge, this is the first time a cancer testis antigen has been targeted using conventional antibody technologies. Thus, PRAME can be exploited for multiple clinical applications, including targeted therapy, diagnostic imaging and treatment guidance in a wide-range of malignancies, with minimal off-target toxicity.Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen that is overexpressed in a broad range of malignancies, while absent in most healthy human tissues, making it an attractive diagnostic cancer biomarker and therapeutic target. Although commonly viewed as an intracellular protein, we have demonstrated that PRAME has a membrane bound form with an external epitope targetable with conventional antibodies. We generated a polyclonal antibody  against an extracellular peptide sequence of PRAME. Binding of MPA1 to recombinant PRAME was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). Flow cytometry and confocal immunofluorescence microscopy of MPA1 was performed on multiple tumor cell lines. Reverse Transcription Polymerase Chain Reaction (RT-PCR) for  PRAME has been shown to be overexpressed in an array of solid and hematological malignancies [PRAME has displayed particularly high expression in Acute Myeloid Leukemia (AML), Acute Lymphoid Leukemia (ALL) and Chronic Myeloid Leukemia (CML) in blast crisis [Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen initially isolated from melanoma cells . PRAME hgnancies , 2. Exprgnancies . In hemat crisis   and thereby antagonize the antiproliferative and cytotoxic effects of Retinoic Acid (RA) . Its preet al. previously reported that PRAME, apart from being associated with cytoplasmic and nuclear-associated protein, was detectable as a membrane protein [in vitro using flow cytometry and high magnification confocal microscopy. To investigate the in vivo targeting properties of MPA1, we constructed an immuno-PET radiotracer by labeling the antibody with zirconium-89, a positron-emitting radioisotope with a 3.3 day half-life, which is well suited for studying antibodies in vivo. Our results demonstrate that a PRAME targeting approach has considerable potential to effect targeted imaging and therapy of multiple cancers.Proto-Siqueira  protein . The comTo determine if MPA1, developed against a domain of PRAME, binds to PRAME efficiently, we performed an ELISA. The results showed specific binding of MPA1 to a PRAME-Fc fusion protein consisting of amino acids 23–407  and liquid  tumor cell lines using an extracellular staining protocol Figure  and 3C. s Figure  and 3D. Cellular localization of PRAME by immuno-fluorescence microscopy showed binding of the MPA1 antibody to the cellular membrane of K562 and THP-1 (PRAME positive), while BLCL (PRAME negative) showed no binding Figure . Median PRAME in AML cell lines [To further evaluate the specificity of MPA1, we investigated if staining increased with PRAME induction. Inhibition of DNA methylation has been shown to augment ll lines , 12, 13.89Zr-DFO-MPA1 was blotted (1 μL) on silica-impregnated paper and a solution of 50 mM diethylenetriaminepentaacetic acid was used as a mobile phase  for 89Zr-DFO-MPA1 in a competitive binding assay with unlabeled MPA1 in THP-1 cells  radiolabeled antibody conjugate for noninvasive imaging. Radiopurity was assessed by radio-instant thin layer chromatography. Briefly, e Figure . All labs Figure , demonstin vivo in order to characterize cell surface expression of PRAME in multiple cancer models we performed classic organ biodistribution assays. Maximum tumor-associated activity of 89Zr-DFO-MPA1 was observed 24 hours post injection (p.i.) in K562 models  and 48 hours p.i. for THP-1 , respectively  in PRAME-negative BLCL compared to PRAME positive liquid tumor models . We did not note a high spleen uptake in BALB/c (nu/nu) based models , which also showed a lower uptake in general.To utilize this novel imaging probe y Figure . Uptake ls Table . Similart Figure  and 2B. 89Zr-DFO-MPA1 construct also enables noninvasive longitudinal evaluation through positron emission tomography (PET) imaging. In the K562 xenograft model, we evaluated the organ pharmacokinetics and tumor uptake over the course of 72 h. The studies showed a region of focal uptake in K562 tumors, recapitulating the biodistribution data  against amino acid region 310-331 of PRAME, which we predicted to be extracellular. Flow cytometry showed binding of MPA1 to PRAME positive, but not to PRAME negative cell lines, ensuring MPA1 target specificity in vitro. To abrogate binding to intracellular PRAME, we used an extracellular staining protocol, without a permeabilization step to prevent MPA1 from interfering prior to cell fixation.In this work, we demonstrate, in multiple tumor models, that PRAME can be targeted In comparison to PRAME mRNA levels, flow cytometry of MPA1 on THP-1 was disproportionately higher than in K562. However, disproportionality between transcription and mature protein is a commonly occurring biological phenomenon , 18, 19.We showed that MPA1 binding increases significantly after PRAME expressing cells were treated with 5-AZA, which is known to induce PRAME expression. This demonstrates that membrane bound PRAME is representative of intra-cellular PRAME, and that MPA1 can be used to report changes in PRAME expression levels following pharmacological stimulation. To further our understanding of the biology of PRAME, we investigated if expression of membrane bound PRAME was correlated to certain phases of the cell cycle. Our results showed that PRAME was constituently expressed on the cell surface and not associated with a specific cell cycle phase. This increases the possibility of successful development of immunotheranostic targeting of membrane bound PRAME.in vivo immuno-PET and ex vivo biodistribution showed accumulation of 89Zr-DFO-MPA1 that was significantly higher in PRAME positive, compared to PRAME negative, mouse models of disease. Binding specificity was further validated by our blocking study in which unlabeled antibody successfully blocked tumor uptake of 89Zr-DFO-MPA1 in THP-1 xenograft. Off-target uptake was mainly restricted to liver, spleen and bone, while blood-bearing organs such as heart and lungs showed a decrease rate matching blood clearance. The non-decreasing liver uptake is likely a result of the well-known fact of immunoglobulin retention and processing in the liver, and the increasing bone uptake is likely caused by free 89Zr4+ ion, which has high affinity for bone, released from metabolic degradation of the tracer [89Zr4+ bone deposition is lower in humans [In order to study and evaluate PRAME as a cancer specific target with translational capability, we synthesized a radiolabeled MPA1. Both e tracer . Translan humans .Unexpectedly, we noted that all three NSG based models of liquid tumors had a high spleen uptake. In the K562 tumor model, the higher spleen uptake is most likely associated with the nature of the malignancy and has been previously described in this model . HoweverWith these encouraging proof-of-principle results in hand, we have begun to study applications of PRAME targeting. We are currently generating monoclonal antibodies that target the same extracellular epitope domain that MPA1 targets; in residues 310–331 of PRAME. These monoclonals would then be ideally suited for examining therapeutic potential and off-target binding, with the overarching long-term goal to develop a therapeutic selective for PRAME positive cancers. Since many malignancies overexpress PRAME, the potential applications are manifold, from diagnostic imaging and therapy to treatment guidance.Computational transmembrane analysis of PRAME predicted that amino acid region 310-331 could be extracellular. A polyclonal IgG rabbit antibody, denominated MPA1 was obtained in collaboration with Innovagen AB, Lund, Sweden. A peptide consisting of this 22 amino acid long sequence was produced, conjugated to Keyhole Limpet Hemocyanin (KLH), and used as immunogen in rabbits. Antibodies were purified from serum by Protein G chromatography followed by affinity purification with the peptide previously used as immunogen.Para-Nitrophenylphosphate (pNPP) was used as detection substrate and added at 1 mg/mL in pNPP-buffer . The plate was read immediately for background optical absorbance and after incubation, at 405 nm in a Multiskan EX microplate spectrophotometer .A Nunc Maxisorp 96 MicroWell plate  was coated with a PRAME-Fc fusion protein consisting of amino acids 23-407 , 1 μg/ml in PBS, at 4° C overnight. The plate was then washed with PBS-Tween 0.05% and blocking solution , was added to each well. The plate was covered and placed on a shaker for 1 hour at room temperature, and then washed again. MPA1 was serially diluted from 20 μg/mL to 0.00122 μg/mL and added to the plate, followed by shaking incubation for 1 hour at room temperature. A goat-anti rabbit antibody conjugated to alkaline phosphatase  was used as secondary antibody for detection. The antibody was diluted 1:2000 in the blocking solution and incubated in the wells for 1 hour at room temperature, preceded and followed by washing of the plate. HL60, THP-1, K562, NK92, KG-1, BT474, OVCAR, RPMI1795, and PA1 were purchased from American Type Culture Collection . LNCaP-AR was a kind gift from the Sawyers laboratory. BJAB was kindly provided by Scheinberg laboratory. K562 is a CML cell line in blast crisis and THP-1, HL60 and KG-1 are AML cell lines. BJAB and NK92 are lymphoma cell lines, Burkitt and non-Hodgkin, respectively. OVCAR and PA-1 are ovarian cancer cell lines, while RPMI-7951 and LNCaP-AR are lymph node metastases of melanoma and prostate cancer, respectively. BT474 is a ductal breast carcinoma. All cell lines were cultured according to the manufacturer’s instructions. 5-Azacytidine (Sigma), 0.05 nM/ml 5-AZA, was added to the cell media to inhibit of DNA methylation. Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell line (BLCL) was obtained through transformation with EBV virus of healthy donor B-cells collected by Ficoll density centrifugation. The donor cells were collected after informed consent according to Memorial Sloan Kettering Cancer Center Institutional Review Board.6 cells per cell line were harvested, washed in phosphate-buffered saline (PBS) and incubated with MPA1 (10 μg/mL) for 20 minutes at 4° C. Alexa 488 Goat anti-Rabbit polyclonal IgG (Abcam Biotechnology) was used as secondary antibody and cells were stained for 15 minutes at 4° C (10 μg/mL). Flow cytometry data was collected on a BD FACSCalibur  and analyzed with FlowJo 9.4.8 software. When investigating correlations between PRAME expression (by quantifying MPA1 binding) and cell cycle phases, cells were washed and fixed with 4% PFA (Thermo Scientific) for 15 minutes at room temperature (RT), spun down for 5 minutes, and permeabilized with PBS with 0.5% Triton X-100 (Fisher Scientific) at RT for 15 min, followed by two washes before adding DAPI . Samples were acquired on a LSR Fortessa  and analyzed with FCS Express 6 software.Approximately 0.5 × 106 cells per cell line were harvested, pelleted and frozen prior to the assay. RNA was extracted using the RNeasy Mini Kit (250)  and cDNA was generated using High-Capacity cDNA Reverse Transcription Kit , both according to the manufacturers’ instructions. PRAME specific primers were obtained from Qiagen and DNA amplification was performed using the RT2 SYBR Green fluor qPCR Mastermix  and the CFX96 Touch™ Real-Time PCR Detection System . All data was obtained in triplicate and the mRNA expression levels were analyzed and normalized to HTB78, BLCLs and BT474 cells, (a cell lines with very low PRAME expression), and presented as fold change.2 × 106 cells/mL in PBS. Cells were transferred to 4 well chamber slides, 2 × 105 cells per well. The slides were centrifuged at 1000 RPM and 4° C for 5 minutes. 200 μL of 4% paraformaldehyde was added to each well, already containing 200 μL of PBS. The slides were centrifuged again for 2 minutes (1000 RPM and 4° C). The supernatants were carefully poured off and 500 μL of PBS were added and removed by pipetting. The chambers were removed and the slides were dipped in PBS and allowed to air-dry followed by oven drying at 60° C for 30 minutes. The chambers were put back on and the fixed cells were incubated with goat Anti-Rabbit IgG Alexa 568  in darkness at room temperature for 45 minutes, followed by three washes with PBS. Chambers were removed and coverslips were mounted using Vectashield Hardset Mounting Media with DAPI .Cells were transferred from culture to 15 mL centrifuge tubes  and washed three times with cold phosphate-buffered saline (PBS). The pellets were resuspended in 100 μL of cold PBS and put on ice. The cells were incubated with MPA1 (70 μg/mL) for 90 minutes, kept on ice to prevent internalization, followed by three washes with PBS and pellet resuspension to a concentration of 1 × 10Confocal laser scanning microscopy was performed using the Leica TCS SP8 X confocal microscope  in the Molecular Cytology Core Facility at MSKCC. Images were rendered using Fiji and Imaris software.para-isothiocyanatobenzyl DFO  as follows. To the buffer exchanged antibody  was added three aliquots of 5 μL p-SCN-Bn-DFO  with brief, gentle vortexing after each addition; this was incubated for 45 min at 37° C. The DFO-conjugated MPA1 was buffer exchanged into pH 7.5 0.5 M HEPES four times in an Amicon spin-filter in the same manner as above. The total IgG concentration was measured before and after DFO conjugation with a yield typically exceeding 80%. The DFO conjugate could be stored at this point, and was typically used in <24h.MPA1 was used as received from Innovagen AB, Lund, Sweden. Buffers and reagents used prior to and during radiolabeling were treated with metal scavenging resin at 5% wt/vol overnight . Protein concentrations were determined by UV-vis spectroscopy (NanoDrop 2000). MPA1 was buffer-exchanged four times in pH 8.5 0.5M HEPES using a 50 kDa cutoff spin filter . MPA1 was concentrated to a volume of 200μL, transferred and an additional 100μL of buffer was used to rinse the membrane. MPA1 was then derivatized with 89Zr) in 1 M oxalic acid was used as supplied in a microfuge tube . The 89Zr stock was neutralized by adding small aliquots of 1M Na2CO3 until neutral by narrow range pH paper. After each addition of base, the solution was mixed gently by pipetting; after completion, the tube was left a few minutes to allow oxalate salts to precipitate. This was transferred to a microfuge tube filter , and the salts were removed at low-speed for 1-2min in a minifuge. The clear 89Zr solution was added to the DFO-MPA1 conjugate, mixed gently by pipetting and incubated at room temperature for 1 hour. Radio-instant thin-layer chromatography (Radio-ITLC) in 50mM DTPA was performed to confirm consumption of free 89Zr. DTPA  was added to the reaction mixture to chelate any remaining free Zr-89. Crude 89Zr-DFO-MPA1 was purified by size exclusion chromatography on a PD-10 column . The column was equilibrated with 20 mL of sterile 0.9% saline by gravity elution. The labeling reaction was loaded to the column in its entirety, typically in a volume of 600-800 μL. The 89Zr-DFO-MPA1 was eluted with saline in 0.5 mL fractions, pooled and evaluated by radio-ITLC for radiochemical purity. The radiolabeling yield ranged from 75.5 to 87.5% with a final specific activity between 1.36 and 2.59 mCi/mg of antibody. The mass of 89Zr-DFO-MPA1 was assumed to be proportional to radioactivity for yield and specific activity calculations.Zirconium-89 (6 THP-1 cells each. 89Zr-DFO-MPA1 (1 μCi) in 50 μl of RPMI 1640, 1% BSA, was added to each vial. The vials containing cells, unlabeled antibody and radiolabeled antibody were incubated for 1 hour at 4°C. The cells were then harvested by centrifugation  and washed in cold washing buffer . The remaining cell-bound radioactivity was measured on a Wizard 3 1480 automatic gamma counter . Three unharvested vials were counted and served as standards. Non-specific binding was measured by harvesting and counting three vials incubated without cells; the average CPM was subtracted from the data, which was expressed as cell/media CPM. The data was fit to a single-site isotherm (nonlinear regression) model using Prism 7 GraphPad software  and an IC50 was calculated.Unlabeled (non-radioactive) MPA1 antibody was serially diluted in RPMI 1640 with 1% BSA, from 900 nM to 0.03 nM in triplicate set of vials. The unlabeled antibody dilutions were transferred to vials containing 1 × 106 cells suspended in a 1:1 v/v mixture of media and Matrigel . Male NSG mice (NOD.Cg-Prkdc SCID IL2rgtm1Wjl/SzJ), 8-10 weeks old, obtained from the Memorial Sloan Kettering Animal Breeding Facility, were used for K562, THP-1, or BLCL tumors, while LNCaP-AR and BT474 were inoculated in 6-8 weeks old BALB/c (nu/nu) obtained from Charles River Laboratories. Tumors appeared in approximately 2-4 weeks and growth was followed by caliper measurements.All animal experiments were conducted in compliance with institutional guidelines at Memorial Sloan Kettering Cancer Center. Subcutaneous tumors were grafted by injection of 200 μL 1.0-3.0 ×10In vivo uptake of 89Zr-DFO-MPA1 was evaluated in multiple solid  and liquid tumor  models with varying degree of PRAME expression. The radiotracer was administered by tail-vein injection  and 4–5 animals were euthanized by CO2 asphyxiation at 4, 24, 48 and 72 hours post injection (p.i.). An additional time-point (120 hours p.i.) was added to the study in K562 xenografts (n=5). BLCL mice (n = 4) served as PRAME negative liquid tumor model and were euthanized at 72 hours post injection. To further evaluate in vivo targeting specificity a group of THP-1 mice (n = 4) were co-administered with a 20-fold excess of unlabeled MPA1 and euthanized at 24 hours p.i. 14 tissues were collected from all animals, rinsed in water, dried in air, weighted and counted on a Wizard 3 1480 automatic gamma counter  for accumulation of 89Zr-radioactivity . The count data were background and decay corrected and compared to the total administered dose; expressed as percentage of injected dose per gram .89Zr-DFO-MPA1  through tail vein injection. About 5 min before recording PET images, mice were anesthetized by inhalation of 2% isoflurane /oxygen gas mixture and placed on the scanner bed. PET images of K562 xenografts were recorded at 4, 24, 48 and 72 hours post injection, while BLCL xenografts were imaged at 72 hours. List mode data were acquired using a γ-ray energy window of 350 to 750 keV and a coincidence timing window of 6 ns. PET image data were correlated for detector non-uniformity, dead time, random coincidences, and physical decay. No partial volume correction or attenuation correction was applied to the data (in our experience not necessary for quantitative murine imaging). For all images scan time was adjusted to ensure > 20 million recorded events. Sinogram data was reconstructed with a filtered back projection. The images were evaluated by manually delineated volumes of interest (VOIs) applied to the axial views of the data sets .Small-animal PET imaging was performed on a microPET Focus 120 Scanner . Mice were administered t test with a 95% confidence interval. In all cases, differences in results were considered to be statistically significant when the computed P value was less than 0.05. All analyses were performed using Prism 7 GraphPad software .Testing for statistical significance was performed using a two-tailed unpaired Student’s


The overall impact findings were that the intervention had no significant effect on maternal or perinatal mortality or maternal morbidity, despite having positive effects on essential birth practices.In the article “The BetterBirth Program: Pursuing Effective Adoption and Sustained Use of the WHO Safe Childbirth Checklist Through Coaching-Based Implementation in Uttar Pradesh, India” by Nabihah Kara, Rebecca Firestone, Tapan Kalita, et al., which appeared in the June 2017 issue  of GHSP, the authors describe the BetterBirth program and lessons learned as the program was tested in a cluster-randomized controlled trial conducted in Uttar Pradesh, India. The trial assessed whether use of a safe childbirth checklist could improve birth attendants' adherence to essential birth practices and maternal and newborn health outcomes. At the time of publication of this article, we noted at the end of the Abstract field that we would update this article by including a reference to the impact findings of the intervention, which were pending publication in another journal. Those impact findings have now been published in the These impact findings are now referenced at the end of the Abstract.


Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration  Colorectal cancer (CRC) is the third most common cancer worldwide and remains a leading cause of cancer-related deaths. Although surgical techniques and adjuvant therapy have improved, the overall survival of patients with CRC has not improved dramatically –4. ThereDecoy receptor 3 (DcR3), also known as TNFRSF6B or M68, is a soluble receptor belonging to the tumor necrosis factor receptor (TNFR) superfamily . Dysreguin vitro and in tumorigenesis and metastasis in vivo. Interestingly, DcR3 mediated TGF-β3/SMAD-induced epithelial-mesenchymal transition (EMT) in CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with overall survival and survival time in CRC patients. Our study has identified a novel mechanism by which DcR3 regulates CRC tumorigenesis and metastasis.In this study, we found that both transcriptional expression and post-transcriptional DcR3 expression DcR3 expression were significantly up-regulated in CRC tissues. Moreover, the expression of DcR3 was significantly correlated with the clinicopathologic characteristics and overall survival of CRC patients. By manipulating DcR3 expression in CRC cells, DcR3 was found to be playing a critical role in CRC proliferation and migration At the cellular level, the expression of DcR3 protein and mRNA was detected in seven different CRC cells. Our results revealed that SW480/M5, SW480 and HCT116 cells exhibited much higher DcR3 expression levels than other cells Figure , whereasIHC was used to detect the expression level of DcR3 in 86 cases paraffin-embedded CRC tissue samples. The results showed that the expression of DcR3 increased markedly in 62/86 CRC tissues Figure . MoreoveTo determine the role of DcR3 in CRC tumorigenesis and progression, stable DcR3 expressed cell lines RKO/DcR3 and HT29/DcR3 were made Figure . The colin vitro, we performed lentiviral vector-mediated shRNA knockdown of DcR3 in SW480/M5 and HCT116 cells  to inhibit smad2/3 phosphorylation in RKO and HT29 cells treated with TGF-β3. As shown in Figure Notably, inhibition of smad2/3 phosphorylation by SB431542 (SB) also blocked TGF-β3-induced DcR3 protein expression Figure . We therTo analyze the correlation between DcR3 expression and TGF-β3/SMAD signaling in CRC tissues, we analyzed the association between DcR3 expression and the TGF-β3/SMAD pathway in a public clinical microarray dataset of 177 CRC tissues . We foun(−) and N-cadherin(+), DcR3(+) and N-cadherin(+) and DcR3(+) and E-cadherin(−) patients had shorter overall survival times than E-cadherin(+) and N-cadherin(−), DcR3(−) and N-cadherin(−) and DcR3(−) and E-cadherin(+) patients, suggesting that cooperation between DcR3 and EMT-related protein expression was strongly correlated with survival and survival time of patients  patients exhibiting activated TGF-β3/SMAD signaling-related protein expression had a poorer prognosis  patients exhibiting inactivated TGF-β3/SMAD signaling-related protein expression, and patients with an activated TGF-β3/SMAD signaling pathway exhibited shorter overall survival times  patients with activated TGF-β3/SMAD-EMT signaling-related protein expression faced poorer prognoses than other CRC patients  patients exhibiting activated TGF-β3/SMAD signaling-related protein expression had a poorer prognosis. Thus, DcR3 was essential for TGF-β3/SMAD-mediated CRC metastasis.Transforming growth factor-β comprises three isoforms, TGF-β1, TGF-β2 and TGF-β3, which can regulate the growth, differentiation, and migration of nearly all cell types –37. SeveIn conclusion, our study demonstrated that DcR3 enhanced tumorigenes and metastasis in patients with CRC. The function of DcR3 may be partially facilitated by activation of the TGF-β3/SMAD signaling pathway, resulting in EMT in CRC cells. Because DcR3 expression was associated with tumor differentiation, tumor infiltration depth, tumor metastasis, and lower survival, DcR3may be useful as a biomarker for making early diagnoses, predicting prognoses, and improving disease management in patients with CRC.The use of 86 archived, formalin-fixed paraffin-embedded human colorectal carcinoma tissues for this study was approved by the ethics committee of Nanfang Hospital, Southern Medical University, China. Before using these clinical materials for research purposes, we obtained informed consent from all the patients. None of the patients in question had received any preoperative chemotherapy or radiotherapy.2 at 37 °C.CRC cell lines SW480, HCT116, LS174T, SW620, RKO and HT29 were obtained from the American Type Culture Collection (ATCC). SW480/M5 was established at our laboratory . All celTotal RNA was extracted from tissues or cells using TRIzol reagent , according to the manufacturer's instructions. RNA was reverse transcribed to cDNA with a Reverse Transcription Kit (Takara). Quantitative real-time PCR (qRT-PCR) analysis was performed using SYBR Green Master Mix (Takara), and the analysis was performed in triplicate. The results were normalized to the expression of GAPDH. The DcR3 primers were as follows: (forward) 5′-GTA CGC GGA GTG GCA GAA A-3′ and (reverse) 5′-CAG AGG ACG TTG CAG TAG C-3′ (206bp). The GAPDH primers were as follows: (forward) 5′-ACA GTC AGC CGC ATC TTC TT-3′ and (reverse) 5′-GAC AAG CTT CCC GTT CTC AG-3′ (351bp).Proteins were extracted using lysis buffer and quantified by bicinchoninic acid (BCA) protein quantitative assay . Protein lysates were separated using 10% SDS-PAGE and transferred onto PVDF membranes . Then, the membranes were incubated with specific antibodies against DcR3 , p-Smad2, p-Smad3, E-cadherin, N-cadherin and vimentin , followed byincubation with the appropriate second antibodies. Finally, the membranes were detected using an enhanced chemiluminescence (ECL) detection system , according to the manufacturer's instructions.According to the manufacturer's instructions, lentiviral constructs containing the indicated DcR3-repressing shRNA sequence (TCATCGACTTTGTGGCTTT) purchased from Gene Pharma  were used to establish cell lines constitutively repressing DcR3. Lentiviral constructs not repressing any known human genes were used to establish a control cell line. The DcR3 sequence was synthesized and subcloned into a GV358 vector . Lentiviral vector encoding the human DcR3 gene was designated LV-DcR3. An empty vector was used as a control and designated LV-control. Antibiotic-resistant transfected cells were selected via 5 ug/ml puromycin  administration in the culture medium. DcR3 transfection efficiency was examined by western blotting.Following fixation and embedding, surgical specimens were cut into 5 μm-thicksections. According to the specifications of the S-P kit, tissue sections were retrieved with citrate buffer, incubated with an anti-DcR3 primary antibody , and then detected with an avidin-biotin complex with 3, 3′-diaminobenzidine. The degree of staining was observed and scored independently by two pathologists. Cytoplasmic immune staining intensity was rated as follows: 0(no staining), 1, 2  and 3. DcR3 staining quality was rated as follows: 0(no staining), 1(<30%), 2(30%-70%) and 3(>70%). Tumor tissue intensity was scored via summation as follows: 0-1 (−), 2–3 (+), 4 (++), and 5–6 (+++). Tissues scored 0-1 (−)/2-3 (+) were classified into the low-expression group, and tissues scored 4 (++)/5-6 (+++) were classified into the high-expression group .After being fixed with 4% paraformaldehyde for 30 min and permeabilized with 0.5% Triton X-100 for 10 min at room temperature, cells seeded on confocal dishes were incubated with primary antibodies at 4 °C overnight. Then, the cells were washed with PBS and incubated with the appropriate fluorescent secondary antibody in the dark at room temperature for 1 h. Finally, the confocal dishes were mounted using an anti-fade mounting solution containing 4, 6-diamidino-2-phenylindole (DAPI) and washed with PBS. Staining was examined, and images were captured using an Olympus FV1200 confocal laser scanning microscope.3/well). Cell proliferation was evaluated by Cell Counting Kit-8  assay, according to the manufacturer's protocols. Briefly, 10 μl of CCK-8 solution was added to the culture medium and incubated for 2 h in 5% CO2 at 37 °C. Then, the absorbance at 450 nm was measured. The cell proliferation assay was performed on days 1, 2, 3, 4 and 5.Cells were seeded in 96-well plates . After being cultured for two weeks, the cells were washed twice with PBS, fixed with 4% paraformaldehyde, and then stained with hematoxylin for 30 minutes. Finally, the number of colonies containing more than 50 cells under was counted under a microscope. All experiments were repeated three times.5 cells in 200 μl of serum-free medium were placed into the top chamber of a transwell chamber , which featured a pore size of 8 μm. The matched lower chamber contained 500 μl of 10% FBS medium, which served as a chemoattractant. After incubating for the appropriate time, the cells were fixed with formaldehyde and stained with hematoxylin for 30 minutes. Then, the cells that migrated to the basal portion of the membrane in the lower compartment of the chamber were counted in 5 random visual fields using a light microscope (×200).Cell migration ability was assessed by the wound healing assay and the migration assay. For the wound healing assay, artificial wounds were scratched on a confluent cell monolayer using sterile tips, and wound healing images were taken at the appropriate time. For the migration assay, 1×10Four to six-week-old athymic BALB/c nude mice were obtained from the Experimental Animal Centre of Southern Medical University (permission number: SCXK2011-0015). All animal experiments were conducted such that the animals received ethical and humane treatment, in accordance with a license from the Guangdong Provincial Bureau of Science, and all procedures were approved by the Institutional Animal Care and Use Committee of Southern Medical University.in vivo tumor growth assay, after being re-suspended in serum-free medium, 5×106 cells were injected subcutaneously into the left or right flank of nude mice (n=6 per group). Twenty five days later, tumors were removed and measured. For the metastasis model, 2×106 cells were injected into the tail veins of six-week-old athymic BALB/c nude mice (n=6 per group). Eight weeks later, the mice were sacrificed via cervical dislocation, and all organs were removed and formalin-fixed for histological analysis.For the The clinical data sets reanalyzed in this study came from the GEO database (GSE17538).2test. Survival curves were plotted using the Kaplan–Meier method and compared by the log-rank test using SPSS 13.0 software. Differences were considered significant if P<0.05*; P<0.01**; P<0.001***.The quantitative results of all experiments are expressed as the mean ± SD. Differences among/between sample groups were analyzed by one-way ANOVA or the independent-samples t test. Relationships between DcR3 expression and clinicopathologic characteristics were tested using Pearson x


Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a useful and less invasive procedure for the definitive diagnosis of mediastinal and hilar lymph nodes. However, infectious complications can occur after EBUS-TBNA, although they are extremely rare.A 66-year-old man with necrotic and swollen lower paratracheal lymph nodes underwent EBUS-TBNA. A mediastinal abscess developed 9 days post-procedure. Surgical drainage and debridement of the abscess were performed along with lymph node biopsy followed by daily washing of the thoracic cavity. Surgical treatment was effective, leading to remission of the abscess. Biopsy revealed that the tumor was squamous cell carcinoma with no radiologically detected cancer elsewhere in the body. Mediastinal lung cancer was thus confirmed. Subsequent chemoradiotherapy led to the remission of the tumor.Mediastinitis after EBUS-TBNA is rare but should be considered, particularly if the target lymph nodes are necrotic. Mediastinitis can lead to serious and rapid deterioration of the patient’s condition, for which surgical intervention is the treatment of choice. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method that is now being widely performed to obtain specimens from mediastinal and hilar lesions . It is aA 66-year-old man was referred to our hospital for examination of swollen mediastinal lymph nodes. He was a current smoker with no significant past medical history. Computed tomography (CT) showed swelling of the lower paratracheal lymph nodes, with a maximum diameter of 48 mm; however, there were no pulmonary lesions Fig. . EBUS-TBStreptococcus pneumoniae was isolated from multiple culture specimens of the debridement material. The patient’s general condition gradually improved, and he was discharged on antibiotics at 24 days post-procedure.Seven days after EBUS-TBNA, the patient experienced high fever and returned to our hospital. On admission, his symptoms included wheezing, right chest pain, and rapid breathing. The blood test results indicated infection: white cell count 9000/μL, C-reactive protein 33.58 mg/dL, and procalcitonin 50.76 ng/dL. The tumor markers, squamous cell carcinoma antigen (SCC) and cytokeratin-19 fragments (Cyfla), were elevated, being 5.2 and 3.9 ng/mL, respectively. Chest CT revealed right pleural effusion, enlargement of the lower paratracheal lymph nodes, and a multiloculated mediastinal abscess with gas production Fig. ; therefoPathological examination of the specimen revealed squamous cell carcinoma Fig. , and theEBUS-TBNA is a recently introduced, promising alternative to mediastinoscopy, which has been considered the standard technique in mediastinal lymph node biopsy , 16. EBUTo date, only 16 cases of infective mediastinitis after EBUS-TBNA have been reported (Table Klebsiella pneumonia [Actinomyces [Streptococcus [Streptococcus intermedius [Surgery was performed in 12 of the 16 cases, and in 9 of these cases, thoracotomy was required. The most common treatment is thoracotomy with chest tube drainage and intravenous antibiotics , 13–15. neumonia , Actinomermedius . No bactS. pneumoniae, a common oropharynx contaminant, was identified as the culprit pathogen in the present case. In contrast, mediastinoscopy via a percutaneous approach is thought to be unlikely to cause infection with oropharyngeal bacteria. However, mediastinoscopy may be associated with other potentially catastrophic complications, such as bleeds due to major vessel damage, tracheobronchial injury, and esophageal trauma [The presumed mechanism underlying the infectious complications is the introduction of oropharyngeal bacteria into deep mediastinal tissues during the transbronchial or transtracheal passage of the needle , 22. In l trauma . Severall trauma –25.Matsuoka et al. suggested that biopsy needle puncture increases the risk of mediastinitis . InfectiBecause mediastinitis after EBUS-TBNA is rare, the diagnosis is sometimes difficult. However, mediastinitis should be considered in the differential diagnosis because of its potentially fatal course. Mild mediastinitis is treatable with antibiotics alone, whereas surgical intervention should be considered without delay in more serious cases . In our The present case underscores the risk of infectious complications after EBUS-TBNA. Close monitoring for the development of signs and symptoms of infection following EBUS-TBNA is essential. Surgery is the treatment of choice for an intractable mediastinal abscess, such as the case reported here.


To the Editor:JACMP and agree it raises some very important issues in relation to the over‐supply of MS medical physics graduate students attempting to gain entry to clinical medical physics residencies. We concur this is a problem and acknowledge the plight of graduating MS students who find themselves in this position.We read with interest the editorial in Volume 16, issue number 2 of the In the editorial, candidate #1 suggests graduate programs should be accountable to CAMPEP for their rates of enrolment being similar to the rates at which their graduates are successful at being placed into residency programs. This would imply there are no other viable opportunities for MS graduates other than entry into clinical residency programs. We believe, however, that placement into other forms of nonclinical medical physics employment or starting a PhD degree program are also valid outcomes following MS graduation. Whilst we certainly agree that individual graduate program directors should pay attention to such rates and be transparent with all applicants to MS degree programs by providing them with available data  and candid advice, we do not believe that CAMPEP is the appropriate authority to enforce limits on enrolment, except for very specific reasons related to the quality of education and training.The mission statement from the CAMPEP website reads as follows: “To promote consistent quality education of medical physicists by evaluating and accrediting Graduate, Residency, and Continuing Education programs that meet high standards established by CAMPEP in collaboration with its sponsoring organizations.”It is clear from this that CAMPEP's mandate is limited to assessment of the quality of education that programs provide, and does not extend to having influence over numbers of students in any given program. The exception would be if a program has too many students or residents for the number of faculty available to adequately support them.CAMPEP recently introduced its own standards to be met by all accredited programs. For graduate programs, standard 2.11(1) states:We encourage students considering entering any MS degree program to look for this information and suggest they only consider applying to programs where it is clear from the publicly disclosed information there is reasonable chance of successful placement into a residency, further degree, or other employment opportunity. If the program does not post the destination information of its graduates on their Web site, then directly ask the Program Director about it.This advice, unfortunately, may not benefit the current crop of enrolled MS degree students, but hopefully (given this oversupply situation) prospective students will take advantage of it as they research programs to which they apply and ultimately matriculate for pursuit of a terminal MS degree. Students would be well advised to avoid programs that do not exhibit a favorable success rate of its graduates finding desired postgraduation destinations .The statements made above are those of the authors. Whilst the authors believe the above information also reflects the opinions of others on the CAMPEP Board based on prior discussions, this letter should not be interpreted as an official CAMPEP position on this matter.


Yoga is increasingly popular, though little data regarding its implementation in healthcare settings is available. Similarly, telehealth is being utilized more frequently to increase access to healthcare; however we know of no research on the acceptability or effectiveness of yoga delivered through telehealth. Therefore, we evaluated the feasibility, acceptability, and patient-reported effectiveness of a clinical yoga program at a Veterans Affairs Medical Center and assessed whether these outcomes differed between those participating in-person and those participating via telehealth.Veterans who attended a yoga class at the VA Palo Alto Health Care System were invited to complete an anonymous program evaluation survey.p = .40), or improvement in any of 16 specific health problems.64 Veterans completed the survey. Participants reported high satisfaction with the classes and the instructors. More than 80% of participants who endorsed a problem with pain, energy level, depression, or anxiety reported improvement in these symptoms. Those who participated via telehealth did not differ from those who participated in-person in any measure of satisfaction, overall improvement (Delivering yoga to a wide range of patients within a healthcare setting appears to be feasible and acceptable, both when delivered in-person and via telehealth. Patients in this clinical yoga program reported high levels of satisfaction and improvement in multiple problem areas. This preliminary evidence for the effectiveness of a clinical yoga program complements prior evidence for the efficacy of yoga and supports the use of yoga in healthcare settings. Over the past two decades, yoga has gained in popularity as an adjunct mind-body treatment for a range of mental and physical health issues . While aA rigorous review concluded that there is generally insufficient research to support the use of yoga as a stand-alone intervention for many conditions, though there is more significant empirical support for its treatment of chronic low back pain , 6. TherYoga may be suitable for Veterans with multiple comorbid conditions as similar yoga programs have been associated with diverse positive impacts . FurtherSecond, with large numbers of Veterans returning from recent conflicts, there is an increased need for cost-effective interventions that can treat this growing population . For exaThird, new information technologies are revolutionizing healthcare and offer large potential benefits to Veterans and other patients. Telehealth is one such technology with potential benefits that include improved access to healthcare, especially those with limited mobility or those living in rural areas, decreased travel time to a clinic, and the containment of treatment costs. The Office of Telehealth Services in the VA has focused on four applications of telehealth including Telemental Health, Telerehabilitation, Teleretinal screening, and Primary Care Telehealth Outreach Clinics. Across these programs, telehealth has been growing steadily since 2005, and over 140,000 unique patients were projected to receive services via telehealth in 2012 –27.The War Related Illness and Injury Study Center (WRIISC) program at the VA Palo Health Care System has provided a yoga program to Veterans at its Palo Alto location since 2010. A Clinical Video Telehealth  component was added beginning in 2012. Referrals to both programs have increased each year bringing the cumulative number of referrals to more than 2300 as of 2016. Telehealth involves the use of a secure real-time interactive video conferencing system that links the patient(s) at an outlying clinic to a provider at another location. In the WRIISC yoga program, an instructor located in the Palo Alto Division provides yoga instruction to students who are in the same room. These classes are often simultaneously broadcast via the videoconferencing system to students at outlying community-based outpatient clinics. Many students report enjoying and benefitting from the classes. However, little empirical evidence for the effectiveness of the program exists. Therefore, in order to assess the feasibility, acceptability, and self-reported effectiveness of the program here we report students’ satisfaction with the program and their self-rated improvement in physical and mental health. We also compared these outcomes between those who attended in-person and those who attended via telehealth.The yoga program currently offers 13 classes per week - eight classes are open drop-in outpatient classes  and five additional classes that are restricted to patients in a specific setting . Attendees report being motivated to attend by a wide variety of health conditions and/or to enhance well-being. Outpatient students are referred by VA staff and receive clearance from a medical provider and, when applicable, a mental health care provider. Students in residential or inpatient programs are cleared to participate in yoga classes by the program’s medical providers. Some students request a referral from their provider while others attend on the recommendation of their providers. Classes are taught by five different Yoga Alliance-certified instructors with a minimum of 200 h of teaching experience who have training in different lineages of hatha yoga, in addition to in-house training on teaching yoga to the Veteran population. Most of the yoga instructors have additional training and teaching experience. All instructors utilize a standard WRIISC protocol which incorporates meditation, intention setting, controlled breath practices, postures emphasizing alignment, synchronization of breath and movement, and relaxation/meditation. Classes are one-hour long and utilize equipment such as mats, blocks, straps, blankets and chairs to adapt postures to the needs of each student.All classes are taught at the Palo Alto Division. During the classes enhanced with the videoconference connection to the outlying clinics, the instructor can see the students at the outlying clinics on a screen and provide appropriate feedback. Students at the outlying clinics can see the instructor on their screen. For safety reasons, classes offered as simultaneous in-person and telehealth classes are limited to chair-based yoga. In these classes the students sit on chairs for the meditation, warm-up, and final relaxation portion of the class and have the option to sit or stand for the more active portion of class.Students are free to attend as many of the open outpatient classes as they wish and some students attend between 2 and 4 classes per week. The telehealth classes are provided to patients at six remote clinics within the VA Palo Alto Health Care System and are available up to 3 days/week .To assess students’ satisfaction and symptom improvement, all participants who attended any class within a two week period in March 2015 were invited to complete a self-report survey. Students are not limited to a fixed number of sessions. Therefore, this evaluation includes data from participants who have been attending WRIISC yoga classes for months or years as well as participants for whom this is a first yoga class and all cases in-between. In order to facilitate candid reporting, identifying information such as respondents’ names was not collected.The anonymous survey data was collected for program management and evaluation purposes. Therefore, consistent with policy at the university which provides ethics review for the program site, no ethics review of the survey was conducted.The survey included multiple choice items assessing Veterans’ demographics, their satisfaction with the classes they attended, and the extent to which they noticed improvements in various aspects of their health. To preserve anonymity, the only demographics that were collected were gender and the era in which they served in the military. A survey item assessed the number of WRIISC yoga classes the respondent has taken. Answer options were defined in order to capture the range of student experience. Items assessing satisfaction included ‘Overall, how would you rate the quality of your yoga class?”, ‘How would you rate the quality of the yoga classroom and equipment?’ and ‘Did your yoga teacher explain things in a way that was easy to understand?’ These items were rated on a four point scale ranging from ‘poor’ to ‘excellent’ or ‘not at all’ to ‘yes, completely.’ Items assessing improvement in symptoms included one item assessing global health improvement and 16 items assessing improvement in specific symptoms, such as back pain, trouble falling asleep, and anxiety. The five answer options for these 16 items were; “not applicable”, ‘no improvement’, ‘not very much’, ‘yes, somewhat’ and ‘yes, completely.’Frequencies of demographic and satisfaction variables were tabulated. The 16 symptom-improvement variables were dichotomized: ‘no improvement’ and ‘not very much’ .were counted as not improved and ‘yes, somewhat’ and ‘yes, completely’ were counted as improved. The proportions of Veterans who reported improvement in each symptom were computed. Veterans who reported not having a particular problem were not included in the summary statistics for that symptom. Whether the percent improved was statistically significantly greater than a threshold was tested. Since the intervention is low cost, it may be an appropriate activity even if only a moderate proportion of Veterans improve through their participation. Therefore a low comparison threshold of >33% improvement was selected and tested using a nonparametric one-sample binomial test.To compare satisfaction and improvement between in-person and telehealth modalities, independent samples nonparametric tests or chi-square analyses were conducted, as appropriate. Following convention, a primary alpha of .05 was chosen. Given the 16 problem areas assessed for improvement, a Bonferroni correction was used to set a secondary alpha = .003 .n = 29) and via telehealth (n = 30). Of the 64 Veterans who completed the survey, almost three quarters were male (n = 47). About half of the Veterans served in the military during the Vietnam war era (n = 29). About one-fifth served during the recent conflicts in Iraq and Afghanistan . The number of WRIISC yoga classes Veterans attended ranged widely, with 40% of the sample having attended five or fewer classes, and 29% having attended 21 or more classes. Gender, era of military service and number of yoga classes completed did not differ statistically significantly between groups. However, a trend was observed, with Vietnam era Veterans slightly more likely to attend via telehealth and Iraq and Afghanistan war Veterans slightly more likely to attend in-person.In 2015, the year in which the survey was administered, 719 Veterans attended at least one WRIISC yoga class, which represented about 1.4% of all Veterans served by the VA Palo Alto Health Care System. Table Table p < .05 level and for 11 out of the 16 problem areas at the Bonferroni-corrected p < .003 level.In response to the item assessing overall improvement in symptoms, 12 respondents (26%) indicated complete improvement, 29 (62%) reported partial improvement and only 6 13%) reported no improvement. Figure % reporteTable p = .97). Table n = 22, p = .18 and n = 18, p = .09, respectively).Veterans’ responses to the item assessing their overall symptom improvement since starting yoga classes did not differ between groups. Eighty eight percent of those participating in-person reported at least some improvement overall, as compared to 89% of those participating via telehealth (Few studies have focused on the feasibility, acceptability and effectiveness of yoga programs within real-world hospital or community clinic settings. Overall, students in a clinical yoga program at our VA Medical Center were highly satisfied with the program, and 88% of respondents reported some degree of subjective symptom improvement. While yoga is available at many VA sites  there isParticipants’ reports of high levels of satisfaction support the conclusion that the yoga program was feasible and well-accepted by patients, whether delivered in-person or via telehealth. Feasibility is further demonstrated by the increasing demand for classes and the ensuing robust schedule of 13 classes per week as well as the rarity of adverse events. According to the commonly accepted definition of serious adverse events , no studPrior randomized controlled trials have demonstrated yoga to be efficacious in treating a variety of medical and mental health conditions , 3, 32. There is minimal published research on telehealth yoga, and to our knowledge this is the first report on this modality in Veterans. One recent study evaluated the feasibility of an eight-week Tele-Yoga program for participants recovering from heart failure and chronic obstructive pulmonary disease . The stuNevertheless, limitations of telehealth modalities should be considered. First, technological problems such as poor video quality or streaming can interfere with the ability to provide care . This coSeveral limitations require that these program evaluation results be viewed as preliminary. No control group was used, and as such it cannot be concluded that the improvements seen were due to the yoga program. Another limitation is that patients were not randomly assigned to in-person or telehealth conditions. A research study in which participants were randomly assigned to modality could more precisely assess for differences between modalities. The evaluations were subjective ratings rather than validated clinical measures. In this regard, it should be noted that participants in other yoga studies have reported subjective positive experiences and perceived changes even when measured changes were not significant . The preIn sum, respondents’ ratings of satisfaction and symptom improvement provide preliminary evidence for the acceptability, feasibility and effectiveness of incorporating yoga into clinical programming for Veterans with a wide variety of physical and mental health problems. These findings provide preliminary support for the continued development and evaluation of yoga programs within healthcare systems. Ongoing clinical yoga programs should conduct feasibility and effectiveness studies to inform future programming’s development, dissemination and evaluation. Delivering yoga via telehealth appears to be acceptable and feasible. While doing so, issues such as risk management and treatment individualization should be carefully considered.