ABL1 is primarily known as a leukemia-related oncogene due to translocation, but about 2.2% of ABL1 mutations have been identified in bladder cancer, and high expression in solid cancer has also been detected.ABL1 breakpoint region and to identify the variable number of tandem repeats (VNTR). To investigate the relationship between ABL1-MS1 and bladder cancer, a case-controlled study was conducted in 207 controls and 197 bladder cancer patients. We also examined the level of transcription of the reporter gene driven by the ABL1 promoter to determine if the VNTR region affects gene expression.Here, we used the NCBI database, UCSC genome browser gateway and Tandem repeat finder program to investigate the structural characterization of the ABL1, and was named ABL1-MS1. In the control group, only two common alleles  were detected, but an additional two rare alleles  were detected in bladder cancer. A statistically significant association was identified between the rare ABL1-MS1 allele and bladder cancer risk: P = 0.013. Investigating the level of transcription of the reporter gene driven by the ABL1 promoter, VNTR showed inhibition of ABL1 expression in non-cancer cells 293 T, but not in bladder cancer cells. In addition, ABL1-MS1 was accurately passed on to offspring according to Mendelian inheritance through meiosis.In our study, one VNTR was identified in the breakpoint region, the intron 1 region of ABL1-MS1 region can affect ABL1 expression of bladder cancer. This study provides that ABL1-MS1 can be used as a DNA fingerprinting marker. In addition, rare allele detection can predict susceptibility to bladder cancer.Therefore, the The online version contains supplementary material available at 10.1186/s12920-021-00968-1. ABL1) encodes a kinase and is activated by several switch kinases such as receptor tyrosine kinase (RTK) and cyclic AMP (cAMP), and is involved in various cellular processes including cell growth, division, differentiation and migration [ABL1 presents at 9q34.12 on chromosome 9, translocate with the breakpoint cluster region (BCR) gene on chromosome 22 to form the Philadelphia chromosome, the cause of chronic myelogenous leukemia [ABL1 contains retrotransposon repeats, a DNA sequence that can be rearranged within the genome, and satellite DNA, a short repeat sequence. It is known that the high density of these repeated sequences can lead to disease-causing genomic structural instability [ABL1, it has recently been reported that the ABL1 gene may have an effect on the onset of solid cancer. In particular, an association with bladder cancer in the BCR region of ABL1 has also been reported [The Abelson murine leukemia virus oncogene homolog 1  marker that may affect the recurrence of bladder cancer [Bladder cancer is largely divided into non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) . At the patients . And it patients . In addir cancer .ABL1, and one VNTR in the ABL1 intron 1 belonging to the BCR region was identified in this study. The VNTR belonging to SSLP can be used as a DNA typing marker. Thus, it can be used as a paternity marker and is also used as a susceptibility marker for diseases such as Huntington's chorea and cancer [ABL1, VNTR was not reported in previous studies, so this study focused on the association between VNTR in the BCR region and bladder cancer.The occurrence of LOH in genomic DNA has been reported in many cases due to the instability of the repeat sequence . Reportsd cancer –20. AlthABL1-MS1 allele is polymorphic was investigated, and a case–control study was conducted using genomic DNA samples from male controls and male bladder cancer patients. In addition, family genomic DNA samples were used to confirm whether this region could be used as a paternity marker. We also investigated the effect of the ABL1-MS1 allele on gene expression identified in control and bladder cancer patients. The functional potential of ABL1-MS1, according to the results, will be discussed in this paper.First, whether the https://www.ncbi.nlm.nih.gov/gene) and the UCSC genome browser gateway (https://genome.ucsc.edu/cbi-bin/hgGateway) were used to analyze the genome structure of the BCR region in ABL1. The repeat regions were also analyzed using the RepeatMasker (www.repeatmasker.org) program and the Tandem repeat finder program (http://www.tandem.bu.edu/trf/trf.html). For selecting the VNTR region among SSLP, we identified a VNTR with a repeat unit length of 10–100 bp and a program algorithm score of 1000 or more. The primers’ construction for amplifying the selected VNTR region was made using the Primer 3 program (http://www.bioinfo.ut.ee/primer3-0.4.0/) and the Primer-BLAST program (http://www.ncbi.nlm.nih.gov/tools/primer-blast). Primer sequences used in this study are as follows: ABL1-MS1 primers (Forward 5′-GGAATGGAAGGGGTGTTGGG-3′ and Reverse 5′-ACCCACTTCTCCACCTCCTC-3′).The NCBI database  under the following conditions: 94 °C for 2 min, 30 cycles of 94 °C for 30 s, 68 °C for 20 s, 72 °C for 3 min and a final extension step at 72 °C for 7 min. PCR products were visualized by 2% SeaKem LE agarose  ethidium bromide gel electrophoresis in TAE buffer at 60 V for 16 h.PCR analysis of human DNA samples was performed using the Coregen Taq polymerase  with 100 ng genomic DNA. Genomic DNA was amplified using primers (forward and reverse) in addition to a standard PCR mixture of 50 mM KCl, 10 mM Tris–HCl (pH 9.0), 3 mM MgClABL1 5'-promoter region, a fragment was amplified from normal male genomic DNA containing the ABL1 genomic sequence by PCR and inserted into the NheI/HindIII site of the luciferase reporter vector pGL3-Basic . To confirm the effect of ABL1-MS1 on ABL1 expression, two common (TR13 and TR15) alleles and two rare alleles (TR14 and TR16) were amplified from genomic DNA derived from control and case and inserted into the HpaI/SalI sites of the p2000 fragment to generate the reporter plasmids p2000 + TR13, p2000 + TR14, p2000 + TR15, and p2000 + TR16  and UM-UC3 (bladder cancer cell line). For the luciferase assay, cells (4 × 104) were seeded in 24-well plates, cultured overnight and transfected with the ABL1 promoter-luciferase plasmids (0.3 μg per well) using the jetPrime transfection reagent  at a ratio of DNA/jetPrime of 1:3. Analysis of the cells was performed using a dual-luciferase reporter assay system (Promega) 24 h after completion of the transfection procedure. Firefly luciferase activities were normalized to Renilla luciferase activity, and activity was expressed in relative luciferase units to reflect the promoter activity. Triplicate transfections of each construct were tested for each experiment, and the final results were calculated from four independent experiments.The following human cell lines were tested for the effect of ABL1-MS1 were calculated for each minisatellite. To examine the extent of sequence divergence, the pairwise distance was calculated using a modified Kimura’s two-parameter model with MEGA3 software [Nucleotide diversities of each repeat unit of the software , 22. We software  with Kimsoftware .https://www.socscistatistics.com/tests/fisher/default2.aspx) with the Fisher exact test [P < 0.05 considered statistically significant.Regression analysis was used to determine odd ratios (ORs) for the association between alleles of the VNTR region and the risk of bladder cancer incidence among the control group and bladder cancer patient groups. 95% confidence intervals (CIs) for OR were calculated using logarithms of OR and standard error (SE). The difference was considered to be CI 95% significant. The data were examined using R statistical software  and UCSC genome browser gateway database (http://genome.ucsc.edu/cgi-bin/hgGateway?org=human).  was present at the highest frequency, and many repetitive sequences such as long interspersed nuclear element (LINE), long terminal repeat (LTR), and simple repeats were identified , an area within intron 1 that belongs to the BCR area was analyzed, and one VNTR area  was identified. We named it ABL1-MS1 and the repeat unit of this VNTR was 76 bp, and the expected PCR product size was 1194 bp .To confirm the polymorphism of ABL1-MS1 with two alleles containing 13- or 15-repeats, 1113 bp and 1265 bp in length  when comparing the bladder cancer group and the control group   , and a group diagnosed at an older age can be divided into an old group (≥ 65 years). The frequency of rare alleles was higher in younger cases (2.92%) than in older cases (0.46%) Table . In younABL1-MS1 alleles during meiosis, we selected family groups of two and three generations  , and the transmission of alleles from parent to child in six families was traced , and new ABL1-MS1 alleles were not observed during this analysis.To examine the meiotic segregation of ly) Fig. . Genomicced Fig. . The resABL1-MS1  of http://www.gene-regulation.com/pub/databases.html), which found several putative binding sites for the transcription factor GR-alpha, GR-beta [EBF [C/EBPbeta [NF-1 [FOXP3 [Pax-5 [p53 [STAT4 [TFII-I [ABL1-MS1 . Four reporter vectors  were constructed by inserting TRs with four different lengths into the enhancer region of the ABL1-promoter vector (p2000)   was identified in the intron 1 region of ABL1.leukemia –48. There region , 50. Amoe region –20. TherABL1-MS1 region was detected, and each ABL1-MS1 allele was found to be accurately transmitted from parent to the next generation. In a case–control study using genomic DNA from 207 cancer-free controls and 197 bladder cancer patients, rare alleles  with a frequency of less than 1% were identified only in bladder cancer. The rare alleles identified only in bladder cancer showed a statistically significant association with cancer risk (P = 0.013). In addition, as a result of comparing the frequency of rare alleles by age based on the age of bladder cancer at 65, there was an increased tendency for association in the younger group (P = 0.061). These results suggest that rare ABL1-MS1 allele may be genetically related to bladder cancer.In this study, the polymorphism of the ABL1 has been reported in solid cancers including bladder cancer [ABL1 was investigated. First, four TRs (TR13–TR16) identified in this study were sequenced, and analyzed the putative transcription factors using Transfac software. The following transcription factors that appear to be involved in the development and progression of cancer have been identified as being present within the repeat sequence: GR-alpha, GR-beta [EBF [C/EBPbeta [NF-1 [FOXP3 [Pax-5 [p53 [STAT4 [TFII-I [In addition, since abnormal expression of r cancer –8, 26–29 GR-beta , EBF [33/EBPbeta , NF-1 [3ta [NF-1 , FOXP3 [1 [FOXP3 , Pax-5 [3 [Pax-5 , 38, p53x-5 [p53 , STAT4 [3 [STAT4  and TFII [TFII-I .GR-alpha and GR-beta, and it is known as a transcription factor involved in the expression of genes involved in cell cycle arrest and apoptosis, and it has been reported that low expression of GR is related to bladder cancer [EBF) is a DNA-binding transcription factor involved in the differentiation and maturation of various cell lineages. It has been reported that deletion of the EBF gene contributes to leukemia recurrence and, when inactivated, contributes to tumor formation [C/EBP beta) is involved in various cellular processes and has recently been reported as an essential mediator of breast cancer development [NF-1) is a tumor suppressor gene that inhibits RAS-GTP activation, and it has recently been reported that NF-1 mutations are associated with cancer [FOXP3) is a protein involved in the immune system response, and the expression of FOXP3 has been reported to be associated with poor prognosis in several cancers [Pax-5) gene is a family of nuclear transcription factors [p53 is a tumor suppressor gene and plays an important role in cell death and genomic stability, mutations in the p53 gene cause cancer [STAT4) play an important role in development, proliferation, and immune defense, but overexpression can lead to several cancers [TFII-I was originally a transcription factor capable of binding to two separate promoter elements, a pyrimidine-rich initiator and the recognition site (E-box) of upstream factor 1. Recently, it has been reported that it acts as an activator of other factors and affects breast and liver cancer [ABL1-MS1 region may influence ABL1 activity.Glucocorticoid receptor (GR) is expressed in various isotypes such as r cancer . Early Bormation . CCAAT eelopment . Neurofih cancer . Forkhea cancers . The Pai factors , has bee factors . Althouge cancer . Signal  cancers . TFII-I r cancer . TherefoABL1-MS1 region on the expression, four ABL1-promoter vectors with TRs inserted into the enhancer region was constructed. When transfected with 293 T, suppression of the luciferase activity by TR was observed, but not in bladder cancer cells. Therefore, this influence on the expression of the TR region suppresses the expression of ABL1 in non-cancer cells, but does not suppress the expression of ABL1 in cancer cells. Although we could not find a statistically significant difference based upon TRs length, we identified the potential of ABL1-MS1 in ABL1 expression regulation. We hypothesized that the ABL1-MS1 polymorphism loses its ability to suppress the ABL1 expression during tumor formation.In order to investigate the effect of the ABL1-MS1 region on control and bladder cancer patients. In the future, studies on samples of various cases of bladder cancer patients are needed, and studies on how the influence of transcription factors related to the ABL1 promoter region can affect ABL1-MS1 in bladder cancer is needed.Our study used a limited number of samples to investigate the effect of repeat sequences in the ABL1 breakpoint region, identified one variable number of tandem repeats (VNTR) present in Intron 1 and named it ABL1-MS1. Two rare alleles  were detected in bladder cancer, and a statistically significant association was confirmed between the rare ABL1-MS1 allele and bladder cancer risk: P = 0.013. We also examined the transcription level of the reporter gene driven by the ABL1 promoter to determine if the VNTR region influenced gene expression, and that VNTR showed inhibition of ABL1 expression in non-cancer cells 293 T, but not in bladder cancer cells. In addition, it was confirmed that ABL1-MS1 is accurately transmitted to offspring according to Mendelian inheritance through meiosis. Therefore, it is suggested that the ABL1-MS1 region may affect the regulation of ABL1 expression in bladder cancer, and the identification of rare alleles of the ABL1-MS1 may suggest predictability as a susceptibility marker for bladder cancer.We investigated the structural characterization of the Additional file 1. Figure S1. Analysis of repeat sequence distribution of ABL1 breakpoint cluster region. (a) Schematic diagram of repeat sequence within ABL1 breakpoint region. The black horizontal line represents the ABL1 breakpoint region and the vertical bar represents the position of the repeat sequence. All repeat sequences were analyzed through Repeatmasker and the UCSC database. (b) The diagram represents the number of different repeat sequences within the ABL1 breakpoint area. Figure S2. Analysis of distances between repeat units and identification of putative binding sites for transcription factors of four minisatellites in the ABL1-MS1 region. (a) Phylogenic trees for the repeat units within each allele of ABL1-MS1. Numbers above branches represent bootstrap value (%) for the clades with 1000 replicates. (b) Composition of putative transcriptional factors on each minisatellite of the ABL1-MS1 region.Additional file 2: Supplementary Table S1. Homology comparison of repeat sequences in the ABL1-MS1 region.


Resistance Training for Teens (RT for Teens) program.Physical activity guidelines recommend young people engage in regular muscle-strengthening activities . However, few school-based physical activity interventions have been delivered at-scale or promoted RT. The aim of this study was to evaluate the reach, effectiveness, adoption, implementation and maintenance of the Reach: number and characteristics of students estimated to be exposed to the program; (ii) Effectiveness: impact of the program on student-level outcomes measured in a subsample of 750 students from 17 schools; (iii) Adoption: number and representativeness of schools with one or more teachers trained to deliver the program; (iv) Implementation: extent to which the program was delivered as intended; and (v) Maintenance: extent to which the program was sustained in schools.Data were collected between August 2015 and October 2020. RE-AIM was operationalized as: (i) The estimated program reach was ~ 10,000 students, out of a total student population of ~ 200,000 (~ 5%). Students were from diverse socioeconomic and ethnic backgrounds. Improvements in muscular fitness, RT self-efficacy, perceived cardiorespiratory fitness and flexibility, and participation in muscle-strengthening physical activities were documented. A total of 30 workshops were delivered, involving 468 teachers from 249 schools from diverse geographical regions. Implementation varied considerably, with teachers adapting the program to suit the context of their school and student cohorts. However, RT skill development and the promotion of muscular fitness were the session components delivered most during sessions. Teachers’ adherence to the SAAFE  teaching principles was high. Approximately 30% of teachers (144/476) registered to use the RT for Teens app. At the school-level, 37% (93/249) of schools had at least one registered user (teacher and/or student). A total of 2,336 workouts and 3,116 fitness tests were completed by registered users. Of the 249 schools represented, 51 (20.5%) sent an additional (previously untrained) teacher to a second workshop.RT for Teens program had broad reach and adoption. However, intervention delivery varied considerably across schools and additional support strategies are required to optimize intervention implementation and maintain program delivery over time. Future studies will benefit from the utilization of accepted frameworks, recommendations and guidelines for implementation research.The st February 2021.Australian New Zealand Clinical Trials Registry (ACTRN12621000352808), retrospectively registered 1The online version contains supplementary material available at 10.1186/s12966-021-01195-8. The health benefits of muscular fitness for adults  and youtSecondary schools are well-positioned to introduce young people to RT as they have the access and curriculum to target health behaviors. They are also uniquely placed with personnel, such as physical education (PE) teachers, who may have the expertise to deliver RT programs. Unfortunately, there are notable barriers to the delivery of RT in schools, including lack of appropriate facilities, equipment, teacher confidence, and time , 17. AddThe need for widespread rollout of successful physical activity interventions has been well documented –25. HoweNutrition and Enjoyable Activity for Teen (NEAT) Girls [Active Teen Leaders Avoiding Screen-time (ATLAS) [Resistance Training for Teens’ (RT for Teens) program.The T) Girls  and Acti (ATLAS)  were two (ATLAS) , muscula (ATLAS) , and RT  (ATLAS) , as well (ATLAS) , 33. Des (ATLAS) . Followi (ATLAS) , as well (ATLAS)  the inteRT for Teens intervention was designed to improve muscular fitness and provide adolescents with the knowledge, motivation, skills, and confidence to engage in RT. The scalability of the intervention was optimized [The multi-component ptimized  through RT for Teens was initially evaluated via a cluster randomized controlled trial (RCT) [RT for Teens program followed a comprehensive pathway to scale-up, flowing through all four stages described by Indig and colleagues [RT for Teens cluster RCT [RT for Teens dissemination trial . Program development and rationale [RT for Teens program.al (RCT) . At the al (RCT) . Improveal (RCT) . Notablyal (RCT) . The RT lleagues . These flleagues  and ATLAlleagues  programsster RCT , 38); anationale –41, and ationale , 33 and ationale , 38 haveRT for Teens study as it balances internal and external validity, with the versatility to be used across all stages of research (from pilot to dissemination). Additionally, RE-AIM includes dimensions related to both outcome assessment and implementation quality [RT for Teens was evaluated in two phases. The first phase  took place in mid-2015 (ACTRN126150003605167). The second phase,  commenced in late 2015 and was retrospectively registered (ACTRN12621000352808).A type 2 hybrid effectiveness-implementation trial design  was used quality , which a quality . Mixed m quality . Ethics  quality . RT for RT for Teens program. One strategy was the training of teachers to deliver the program, during a professional learning workshop delivered by the research team. This workshop was an accredited one-day training opportunity , for teachers of any specialization. The workshop included practical and theoretical components designed to provide teachers with the knowledge, skills and competence to deliver the RT for Teens program. The workshop was adapted from the original RCT workshop to include the following content: (1) Program rationale including importance of muscular fitness, secular trends and RT guidelines, (2) Findings from the RT for Teens RCT, (3) Introduction to the RT for Teens program components, and (4) Motivating students using the SAAFE teaching principles. The final section did not highlight the physical limitations of specific groups . Instead it focused on delivering the RT for Teens program using autonomy supportive teaching practices. For example, students could choose to do push-ups on their knees or toes depending upon their perceived level of muscular fitness. Similarly, students were discouraged from comparing themselves to their peers, with the focus on self-improvement rather than competition. Teacher professional learning workshops (N = 30) were delivered from August 2015 until December 2019, with final data for the evaluation collected in October 2020. As an adjunct to the training, and to support program delivery, teachers were also provided with resources, including circuit cards  to attend professional learning workshops. As such, the decision to ‘adopt’ the RT for Teens professional learning workshop from 2015–2019, we conservatively estimate that the program reached ~ 10,000 students. This estimate is based on the assumption that teachers who attended training delivered the program to at least one class of 23 students (representing the average class size in NSW government secondary schools) [RT for Teens dissemination cohort, except schools within the effectiveness sub-sample had slightly larger enrollment numbers (~ 150 more students). Data available from NSW DoE specifies that 49% of school students are female [RT for Teens dissemination cohort, effectiveness sub-sample school cohort, and effectiveness sub-sample student cohort . NSW data specifies that 6% of students identify as Aboriginal or Torres Strait Islander [RT for Teens groups indicates a slightly higher mean percentage of Indigenous students across these cohorts. Across the dissemination, effectiveness sub-sample school, and effectiveness sub-sample student cohorts, 10%, 8% and 7% reported Indigenous heritage, respectively.Based on the attendance of 468 classroom teachers at the schools) . Characte female . This prIslander . Data frA total of 750 students from 17 schools located in a major city and inner regional areas provided effectiveness data. The characteristics of students in this sub-sample are presented in Table RT for Teens represent almost half of all Government secondary schools in NSW [nd to 99th percentile. In addition to teachers from the aforementioned schools, eight employees from the NSW DoE School Sport Unit and the NSW Health Population Health research team attended workshops. This brings the total number of trained individuals to 476. Of these individuals, 429 (90%) completed a survey prior to attendance at the workshop to collect baseline demographic characteristics. Baseline characteristics of workshop attendees are presented in Supplementary Table Between August 2015 and November 2019, 30 workshops were delivered, with 468 teachers from 249 schools in attendance. The characteristics of these schools are presented in Table s in NSW . Almost RT for Teens app showed that of the 93 schools using the app, 48 used the workout function and 48 completed fitness testing. Thirty-five of the schools used both functions. In total, 2,336 workouts and 3,113 fitness tests were completed via the app.During the dissemination evaluation, 22 lesson observations were conducted at the 17 schools within the effectiveness sub-sample. The level of implementation varied considerably across schools and is presented in Table Fifty-one of the 249 schools sent at least one additional teacher to a RT for Teens workshop , demonstrating that these schools were engaged with the program and wanted to “upskill” additional staff members.RT for Teens program. Our conservative estimate suggests ~ 10,000 students were exposed to the program, representing substantial reach. Regarding effectiveness, the program improved muscular fitness, RT self-efficacy, perceived CRF and flexibility, and participation in muscle-strengthening physical activities in a sub-sample of students who completed the assessments. Adoption was high, with 468 teachers from 249 schools trained to deliver the program. These 249 schools include almost half of the Government secondary schools in NSW. Implementation varied considerably across schools, however, resources usage and adherence to the SAAFE principles was evident in most sessions. A fifth of schools sent one or more teachers to subsequent workshops for training, indicating potential program maintenance in schools. To our knowledge, this is the first study focusing on the state-wide dissemination of a school-based RT program.The objective of our study was to evaluate the reach, effectiveness, adoption, implementation and maintenance  of the RRT for Teens program to any of their classes, others may have delivered the program to multiple classes over a number of years since receiving the training (which commenced in 2015). As such, our estimate is likely to be an underestimation of actual student reach. Findings from semi-structured interviews conducted with teachers [Previous studies have utilized a variety of methods to calculate the ‘potential’ reach of school-based physical activity interventions . Similarteachers  support RT for Teens program was also included in the Physical Activity 4 Everyone (PA4E1) whole-school intervention (as the enhanced school sport component) [RT for Teens training [RT for Teens for 10-weeks to at least one full grade level of students [Of note, the mponent) . At leastraining   was comparable to the 49% of female students reported across the NSW DoE [RT for Teens groups indicates a slightly higher mean percentage of Indigenous students across the dissemination, effectiveness sub-sample school, and effectiveness sub-sample student cohorts. These cohorts reported 10%, 8% and 7% students of Indigenous heritage, respectively, compared to 6% of NSW students identify as being of Aboriginal or Torres Strait Islander descent [RT for Teens program in schools with representative female and Indigenous student cohorts, however assumptions are preliminary, and limited due to available data.Within the reach domain, it is also important to assess the characteristics of participants, to describe the representativeness of the population and thus the generalizability of findings . This is NSW DoE . Additio descent . As suchThere is considerable variability in the reporting of effectiveness data in programs delivered at-scale, with the majority reporting effectiveness from a prior study . In the RT for Teens professional learning workshop. A total of 468 teachers from 249 schools, including 213 Government secondary schools, had at least one RT for Teens trained teacher. Similar school numbers have been seen in previous successful school-based programs delivered at-scale, including SPARK PE [RT for Teens in almost half of NSW government secondary schools [RT for Teens workshop was provided as accredited professional learning in partnership with the NSW DoE, with teachers gaining hours towards their mandated training requirements. In addition to this social influence, the partnership with the NSW DoE also allowed for co-creation of the adapted program. The research team utilized feedback from the DoE when adapting RT for Teens from the previous NEAT Girls [ATLAS [We operationalized adoption as the number of schools with at least one teacher who had participated in the SPARK PE . A recenSPARK PE  highligh schools . The RT AT Girls  and ATLAs [ATLAS  programss [ATLAS . It is iRT for Teens program components. The necessary focus on muscular fitness [There was noticeable variation in implementation across schools. Of note, the overall session score within the dissemination 5/10) was lower than observed within the RCT (7/10) . Despite fitness  remained0 was low fitness . Variati fitness . It is l fitness . NonetheRT for Teens app was also a useful intervention resource, including fitness testing and workout functions. The current version of the app was only released in mid-2018, created in response to the reported barriers experienced with the earlier web-based version of the app [RT for Teens RCT [The  the app . Whilst eens RCT , as resoRT for Teens was designed and developed, there has been rapid increase in the publication of recommendations and guidelines for implementation research [RT for Teens dissemination study was conceived.Whilst there are a number of promising findings related to implementation, there is considerable room for improvement. Although our study was designed using an established scale-up evaluation framework , we did not use an existing implementation framework   or scaleresearch . ResearcRT for Teens, the lack of support following program training was a limitation. Our key learning from this study is that standalone professional learning workshops are not sufficient to support the high-quality implementation of physical activity programs in schools. External support from change agents is needed to overcome commonly faced barriers and enhance program implementation. The failure to provide on-going support may explain why ‘voltage drop’ occurs when interventions progress from small-scale projects with high levels of researcher support to larger-scale effective and dissemination studies with minimal researcher support. For example, one of the implementation strategies included within a recent school-based policy was to provided teachers with ongoing support [Quality implementation of programs is linked with improved outcomes , so it i support . This wa support . Finding support , 80, 81.RT for Teens program). Following interest, and incorporation of RT for Teens into one teachers’ practice, there arose a need to train additional teachers to sustain program delivery. At the very least this is an indication of teachers’ satisfaction with the workshop, and their belief that it would be of value to other staff members at their school. Interview findings support this assumption [For the purpose of this study, maintenance was operationalized at the setting-level. School-level maintenance, or the integration of the program into practice , indicasumption , with tesumption . Individsumption , with muRT for Teens app. According to our usage data, participants completed 2,336 workouts and 3,116 fitness tests. These numbers are much lower than our estimated reach . Fourth, implementation findings were determined using data from a subset of participating teachers. Fifth, program acceptance data was not collected from students and teachers in the dissemination phase. However, findings from our RCT suggest that teachers were highly satisfied with the program (4.8/5) [Strengths of this study include the extensive involvement of the NSW DoE School Sport Unit. This partnership allowed for greater dissemination of the program throughout NSW secondary schools. The mixed methods of data collection, including interviews, also allowed for the utilization of a variety of data sources to evaluate dissemination. Rather than relying on single sources of information, the multiple methods allowed for a more in-depth exploration of program impact across RE-AIM domains. Evaluation of program effectiveness via the RCT, prior to at-scale dissemination, also contributed to the strength of this study. This data allowed for findings from the dissemination phase (where there was no control group) to be compared against outcome improvements from the rigorous RCT. Whilst this study had many strengths, it is not without limitations. Firstly, little implementation support was provided to teachers following the workshop, which may have hindered implementation efforts. Second, this lack of support/contact with schools also presented as a barrier to determine implementation quality and maintenance. Third, not all schools used the  (4.8/5) . StudentRT for Teens is the first school-based RT program to be delivered at-scale. Our study provides an in-depth account of the journey of the program through scale-up and describes the impact of the program across RE-AIM dimensions. The RT for Teens program had large potential reach and high levels of adoption, however, implementation varied considerably across schools. External support from change agents may be needed to overcome barriers and optimize intervention implementation in schools, including the documentation of adaptations that may have been made to increase implementation success. Future studies, guided by accepted frameworks, recommendations and guidelines [Given the need to implement effective physical activity programs at-scale –25, our idelines , 75–77 fAdditional file 1: Supplementary Table 1. Proposed RT for Teens session structure.Additional file 2: Supplementary Table 2. Characteristics of workshop attendees.Additional file 3: The TIDieR (Template for Intervention Description and Replication) Checklist*.Additional file 4: Supplementary Figure 1a. RT for Teens session observation checklist . Supplementary Figure 1b. RT for Teens session observation checklist .Additional file 5: Supplementary Figure 2. RT for Teens exercise library examples (from App).


The StrongerMemory program is a brain health intervention targeting older adults with mild cognitive impairment (MCI). Approximately 20% of individuals over 65 years old have MCI and 38% will potentially develop dementia after 5 years of MCI onset. Participants in the 16-week StrongerMemory program practice exercises involving math, writing, and reading aloud for 20-30 minutes a day, stimulating the prefrontal cortex of the brain, which governs the brain’s ability to retrieve memories. The current research exploring participants’ experiences with the StrongerMemory program was approved by the University’s Institutional Review Board. A semi-structured interview was implemented with each participant and the interviews took about 15 to 30 minutes to complete. There was a total of 24 respondents associated with a local continuing care retirement community, each providing their verbal consent to be interviewed and recorded over Zoom. The respondents were mostly female ranging in age from 65 to 90. Most respondents reported having advanced degrees and were participating in the program on their own, with a spouse or friend. Each interview transcript was coded by at least two members of the Mason research team. Participants reported being motivated to participate in the program due to fearing memory loss because of experiences of family members and friends and others wanted to remain “cognitively fit.” Codes and themes representing participants’ perceptions and reactions to exercises and their challenges and lessons learned from their participation will be discussed, including participants feelings of being “less foggy” and better able to remember information.


Herein, a water-soluble rhodamine-poly (ethylene glycol) conjugate (DRF-PEG), as a dual responsive colorimetric and fluorescent polymeric sensor for Fe3+ detection with high biocompatibility, was first synthesized through Schiff base reaction between rhodamine 6G hydrazide and benzaldehyde-functionalized polyethylene glycol. As expected, the introduction of PEG segment in DRF-PEG significantly improved the water solubility of rhodamine derivatives and resulted in a good biosensing performance. The detection limit of DRF-PEG for Fe3+ in pure water is 1.00 μM as a fluorescent sensor and 3.16 μM as a colorimetric sensor at pH 6.5. The specific sensing mechanism of DRF-PEG toward Fe3+ is proposed based on the intramolecular charge transfer (ICT) mechanism, in which the O and N atoms in rhodamine moiety, together with the benzene groups from benzaldehyde-modified PEG segment, participate in coordination with Fe3+. Furthermore, DRF-PEG was applied for the ratiometric imaging of Fe3+ in HeLa cells and showed the potential for quantitative determination of Fe3+ in fetal bovine serum samples. This work provides insights for the design of water-soluble chemosensors, which can be implemented in iron-related biological sensing and clinical diagnosis.Quantitative and accurate determination of iron ions play a vital role in maintaining environment and human health, but very few polymeric chemosensors were available for the detection of Fe Among the numerous detection assays, such as atomic absorption  (PEG) is commonly used in biomedical research . By virtand Al3+ . However2) of Rh and the aldehyde group (−CHO) of di-benzaldehyde terminated poly (ethylene glycol) (DF-PEG). The rhodamine moiety of DRF-PEG serves as a sensing fluorophore in detecting metal ions, while the PEG segment improves the sensor’s water solubility and biocompatibility. DRF-PEG is highly sensitive and selective for Fe3+ in water with dual-responsive fluorescent and colorimetric response. MTT assay suggests that DRF-PEG possesses low cytotoxicity and good biocompatibility, which can be utilized for intracellular imaging. Furthermore, the detection performance of DRF-PEG for Fe3+ is evaluated in fetal bovine serum. This work provides a facial and typical model for designing polymeric sensors with high biocompatibility and water solubility, which can be applied in living cell imaging or metal ion detection in biological systems.Herein, rhodamine 6G hydrazide (Rh) is selected as the fluorescent/colorimetric sensing receptor, and PEG segment is chosen as the hydrophilic segment. The polymeric sensor (DRF-PEG) containing both PEG chain and rhodamine moiety is synthesized through a facile Schiff base reaction between the amine group , hydrazine monohydrate (50%), silver nitrate, chloride salts of K+, Na+, Mg2+, Ca2+, Cu2+, Hg2+, Co2+, Cd2+, Zn2+, Ni2+, Mn2+, Al3+, Cr3+, and Fe3+ were purchased from Sinopharm Chemical Reagent Co. Ltd. MTT (thiazolyl blue tetrazolium bromide) was obtained from Thermo Fisher Scientific (China). Ultrapure water (18.2 MΩ cm) was obtained from the Milli-Q system and applied throughout the experiment. Other solvents and chemicals were of analytical reagent grade and used without further treatment.Rhodamine 6G (95%), 1,3-dicyclohexylcarbodiimide , N,N-dimethylpyridin-4-amine , and 4-carboxybenzaldehyde (98%) were obtained from Aladdin Chemistry Co. Ltd. . Polyethylene glycol . FT-IR spectra were obtained on a TENSOR II FTIR routine spectrometer from Bruker (Germany) after pelleting samples with KBr. The UV-Vis absorption measurement was carried out on a Hitachi U-4100 UV/Vis/NIR spectrometer (Japan). Fluorescence spectra were performed on a FluoroMax-4 high efficiency integrated fluorescence spectrometer (Horiba. United States), and each measurement was repeated three times. The pH of the solution was measured by a Mettler Toledo SevenCompact pH meter S210. Confocal laser scanning microscopy (CLSM) images were recorded on a Leica TCS SP8 lighting confocal microscope (Germany).Rhodamine 6G hydrazide was prepared through the reduction of rhodamine 6G by hydrazine monohydrate using the reported procedure .4000  in dry THF was mixed with 4-formylbenzoic acid  and DMAP (0.09 g). After complete dissolution of all the compounds by sonication, DCC (1.65 g) in 50 ml of THF was added. The mixture was thoroughly stirred at 25°C for 48 h and then filtered. Filtrates were dried through vacuum rotary evaporation and precipitated by ethyl ether three times. The obtained precipitate was dried under vacuum for 2 days to give DF-PEG as a white waxy solid. Yield: 6.4 g (75%). 1H NMR  δ: 3.40–3.90 , 4.48–4.53 , 7.95 , 8.21 , 10.10 .DF-PEG was synthesized by following the previously reported method . Under a1H NMR  δ: 1.20 , 1.85 , 3.06–3.17 , 3.40–3.80 , 4.40–4.46 , 5.01 , 6.16 , 6.21 , 6.94–6.99 , 7.48–7.53 , 7.76–7.81 , 8.06 , 8.16 , 10.12 .The solution of R6G hydrazide  in 20 ml of acetone was slowly added into 30 ml of acetone with DF-PEG . After refluxed at 58°C for 8 h and cooled overnight, the mixture was then filtered. The obtained filtrate was concentrated under vacuum to give DRF-PEG as a purple solid. Yield: 1.0 g (80%). 3+ and other metal ions (1.0 × 10–3 mol/L) were prepared by dissolving the related inorganic salts in Milli-Q water for the fluorescence and absorption experiment. Stock solution of DRF-PEG was prepared in Milli-Q water with a concentration of 1.0 mg/ml. All the spectral experiments were conducted in an aqueous solution except for the absorption test related to Rh because of its poor water solubility. For the absorption and fluorescence selectivity experiment, DRF-PEG solution (0.1 mg/ml) was mixed with different metal ions (10–4 M). For the sensitivity experiment, DRF-PEG solution (0.1 mg/ml) was mixed with different concentrations of Fe3+. The fluorescence emission spectra of DRF-PEG were collected from 520–680 nm with an excitation wavelength of 500 nm. The quartz cuvette with a 1-cm path length was used for the absorption and emission studies. For the pH test, the pH of the tested solution was adjusted by using 0.1 mol/L of HCl, and 0.1 mol/L of NaOH solutions at 25°C.Stock solutions of FeThe cytotoxicity of DRF-PEG was evaluated by a standard MTT assay on HeLa cells  obtained from Shanghai EK-Bioscience Biotechnology Co., Ltd.4 cells/well and cultured in DMEM medium with 1% antibiotic and 10% FBS . After cell attachment, the cells were incubated with different concentrations of DRF-PEG  and maintained at 37°C under 5% CO2 for 24 h. After washing with PBS buffer three times, fresh culture medium containing MTT  was added and incubated for another 4 h. Then the culture medium was removed and washed with PBS buffer. The samples were then dissolved in 150 μl of DMSO and shook for 10 min. Compared with the control sample, the cell viability was estimated through the optical density of the mixture at 450 nm.HeLa cells were seeded at a density of 1 × 104 cells/well) were first cultured in DMEM medium at 37°C with 10% FBS for 24 h under 5% CO2. Then the culture medium was removed, and fresh medium containing 0.1 mg/ml DRF-PEG was added. Following incubation for 0.5 h, the samples were washed with PBS buffer to remove the residual DRF-PEG in the culture medium. Subsequently, cell culture media with different concentrations of Fe3+  were added and cultured for another 30 min to allow effective uptake of Fe3+. Before imaging, the cells were rinsed with PBS buffer three times to remove the residual Fe3+ in the culture medium. CLSM images of the cells were captured at ambient temperature under an excitation wavelength of 488 nm, and the fluorescent signals were collected between 500 and 600 nm.HeLa cells , the fluorescent emission signals of serum samples were recorded.Fetal bovine serum obtained from Gibco (Germany) was used to investigate the potential application of DRF-PEG in biosystems. To reduce background interference, bovine serum lipids were removed with chloroform–methanol mixture before the test by referring to the reported procedure . Stock svia Schiff base  linkages. The synthetic route of DRF-PEG is illustrated in 1H NMR spectra (The rhodamine-derived polymeric sensor (DRF-PEG) was facilely synthesized through Schiff base reaction between DF-PEG and Rh with a reaction ratio of 1:2. DF-PEG was synthesized through esterification reaction among poly (ethylene glycol) and 4-carboxybenzaldehyde acid in the presence of DCC/DMAP at ambient temperature. PEG chain in DF-PEG contributes to improve the water solubility of DRF-PEG, while the terminal benzaldehyde group acts as a connecting bridge and will react with amine groups in rhodamine 6G hydrazide. One DF-PEG molecule is covalently bonded with two Rh molecules  spectra .−1 originated from the stretching vibration of a carbonyl (–C=O) comes from the benzaldehyde groups or the newly formed ester groups in DF-PEG. Compared with the FT-IR spectrum of PEG, newly emerged peaks below 900 cm−1 were observed in DF-PEG, which can be ascribed to the characteristic absorption of benzene rings due to the introduction of benzaldehyde groups (−1) appear on the FT-IR spectrum (blue line). The transmission band at 1,419 cm−1 is caused by the C–N deformation of rhodamine moieties, and the peak at 1,519 cm−1 can be assigned to the deformation of aromatic rings  in DRF-PEG  was very weak at 543 nm. The addition of Hg2+ and Cr3+, and Al3+ gave rise to a slight increase in fluorescence intensity (4.5- to 6.7-fold) at 553 nm, and a bathochromic shift was observed, whereas the presence of Fe3+ induced the most prominent fluorescence enhancement (15-fold) at 555 nm and the largest bathochromic shift (12 nm), suggesting the selective and specific recognition of DRF-PEG toward Fe3+. The affinity between Fe3+ and DRF-PEG should be the strongest, which has a relationship with the metal-ion radius and ligand configuration . Both the fluorescence emission and absorption enhancement of DRF-PEG in the presence of Fe3+ were not influenced by all the investigated interfering ions. These results reveal that DRF-PEG shows high selectivity and anti-interference capability for detection of Fe3+ over other metal ions. DRF-PEG can serve as a dual-responsive fluorescence turn-on and colorimetric chemosensor for detection of Fe3+ with high selectivity in pure aqueous solution. This application of DRF-PEG does not need the assistance of organic solvent, which makes the detection of Fe3+ convenient, environmental friendly, and demonstrating great potential in practical environmental and industrial monitoring.Anti-interference ability of DRF-PEG to Fet pH 6.5 . Competi3+ can be explained by the strong coordination ability of rhodamine moieties toward Fe3+ based on our previous reports  in rhodamine moiety, resulting in the ring opening of spirolactam structure and strong fluorescence emission . Based on the titration curves, the detection limit of DRF-PEG to Fe3+ can be calculated separately from the fluorescence and absorption data through the following equation , SD is the standard deviation of blank DRF-PEG solution, and S is the slope of regression line of the titration curve   . Similar3+ is checked in the pH range of 2.0–13.3 (3+ suggests that DRF-PEG can be applied for the recognition of Fe3+ in this pH range. It is proposed that the existence of H+ will restrain the coordination of Fe3+ with DRF-PEG. The fluorescence/absorption intensity first decreased with the increase in pH (5 < pH < 7), then increased when the amount of H+ is very few because the interference from hydrogen ions disappeared (7 < pH < 10). At pH >10, a large amount of Fe3+ would be precipitated by OH− according to the solubility product rule, so the fluorescence/absorption intensity of DRF-PEG decreases dramatically since pH 10. As shown in 3+ in the pH range of 3.0–10.0 and served as a colorimetric sensor for Fe3+ in the pH range of 3.2–13.3. Therefore, DRF-PEG has great tolerance to the solution pH, suggesting the diverse applications of DRF-PEG in metal ion detection.For the efficient detection of metal ions in practical applications, sensors should possess the ability to be operated in a broad pH range. Namely, the fluorescent/absorption response of the sensor should take place and not be affected by the solution pH . The eff2.0–13.3 . Hydroge2.0–13.3 . At pH 3in vitro tests.Biocompatibility and cytotoxicity are important criteria to assess the potential application of chemical sensors in biological and medical studies . The cyt3+ and bio-imaging capability of DRF-PEG are tested in living HeLa cells by CLSM. HeLa cells were first incubated with 0.1 mg/ml DRF-PEG for 30 min, washed by PBS buffer, and then cultured with different concentrations of Fe3+ for another 30 min. As shown in 3+ display faint fluorescence emission because of a trace amount of free iron or non-transferrin-bound ions in the culture medium, while bright and strong green fluorescence is observed for HeLa cells incubated with extra Fe3+ from 5 to 100 μM. The fluorescent signals are specifically located in the intracellular areas suggesting that DRF-PEG possesses good cell membrane permeability and can be used for the monitoring of Fe3+ in living cells without any transfection agents. Intracellular fluorescence emission intensity of HeLa cells is enhanced with the amount of Fe3+ added (3+ is low (5 μM), the fluorescence is mainly concentrated in the cytoplasm area of HeLa cells. With the increase in Fe3+, intracellular uptake of Fe3+ increases, and fluorescent signals start to spread over the whole cell area. Obviously, HeLa cells incubated with 100 μM of Fe3+ exhibit the strongest fluorescent emission after the same incubation period (30 min) with bright green fluorescence in the nucleus. According to the distribution of fluorescence signals, DRF-PEG can be implemented to monitor the intracellular absorption path of Fe3+, showing enormous potential in intracellular imaging and visually monitor Fe3+ in living systems.Encouraged by the biocompatibility and high sensing performance of DRF-PEG, intracellular detection of Fe3+ added . When th3+ in fetal bovine serum is examined. As shown in 3+ in the range of 100–1,000 μM, and the minimum responsive concentration of Fe3+ is 100 μM. The biosensing performance of DRF-PEG toward Fe3+ can be ascribed to the anti-fouling properties of PEG chains from benzaldehyde-modified PEG segments. Results showed that the DRF-PEG possesses sensing capability toward Fe3+ in biological samples, implying its potential applications to serve as a bio-sensor in biomedical fields. In comparison with the recent rhodamine-based chemosensors for Fe3+  for the detection of Fe


Cutaneous T-cell lymphomas (CTCLs) are rare tumors with no established markers that can reliably distinguish between benign and malignant lesions. Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen that is found in many solid and hematologic malignancies. PRAME overexpression typically portends a poor prognosis and lower chemotherapeutic response. To date, no studies have established a role for PRAME in CTCL. An analysis was performed on 47 cases definitively diagnosed as CTCL: 25 cases of mycosis fungoides, 2 of Sezary syndrome, 5 of CD30+ lymphoproliferative disorder, 7 of primary cutaneous anaplastic large T-cell lymphoma, 3 of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, 1 of subcutaneous panniculitis-like T-cell lymphoma, and 4 of angiocentric T-cell lymphoma. PRAME immunohistochemistry was completely negative in all cases. PRAME expression was not found in any CTCL subtypes, suggesting that the pathogenesis of CTCL is not mediated by PRAME. Further study is required to identify biomarkers that might aid in the diagnosis and prognostication of CTCLs. Cutaneous T-cell lymphomas (CTCLs) are a rare class of tumors with an annual incidence of approximately 0.5 in 100,000 . While mPreferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen (CTA). The CTA family comprises a number of genes whose expression is typically restricted to only male germ cells. These antigens are abnormally re-expressed in a variety of solid and hematologic malignancies ,28,29,30To date, no studies have established a role for PRAME in the diagnosis and prognosis of CTCLs. We hypothesized that PRAME might be a useful marker to assist in the diagnosis of CTCLs and to differentiate between indolent and aggressive lesions.This is a retrospective analysis utilizing pre-existing tissue from patients with a definitive diagnosis of CTCL by biopsy. For MF in particular, tumors at either the patch stage or more advanced stages  were included. Patients younger than 18 years old or with concomitant malignancy of the skin at other sites were excluded. Specimens were obtained from the surgical pathology archive of a tertiary medical center over a 10-year span. Unstained recuts were obtained from the original formalin-fixed paraffin-embedded tissue (FFPET) blocks. Hematoxylin and eosin (H&E) staining and immunohistochemistry for PRAME  with red chromogen were performed on recut slides.All cases were reviewed by two independent investigators to confirm the diagnoses and evaluate PRAME expression. The following parameters were evaluated: percentage of PRAME expression, nuclear/cytoplasmic expression, and intensity and extent of staining. Melanoma and sebaceous glands were used as external and internal positive controls, respectively. The results were tabulated and compared utilizing statistical software in Excel and SPSS. A chi-squared test was used to compare differences in PRAME expression between malignant T cells in CTCL and adjacent normal sebaceous glands or melanoma tissue as a control group.The study consisted of 47 CTCLs from patients aged 26 to 91 years with an average age of 59.2, with 31 male (66.0%) and 16 female (34.0%) patients. There were 28 white (59.6%), 8 black (17.0%), 2 Asian (4.3%), 2 other non-Hispanic (4.3%), and 7 patients of unknown ethnicity (14.9%).The sample included 25 cases of mycosis fungoides (53.2%), 2 of Sezary Syndrome (4.3%), 5 of CD30+ lymphoproliferative disorder (10.6%), 7 of primary cutaneous anaplastic large T-cell lymphoma (14.9%), 3 of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (6.4%), 4 of angiocentric T-cell lymphoma  (8.5%), and 1 of subcutaneous panniculitis-like T-cell lymphoma (2.1%). Of the 25 MFs, all stages  were represented, including 3 cases with large cell transformation (12.0%), 2 with the CD8 immunophenotype (8.0%), and 1 with blast cell transformation (4.0%). PRAME immunohistochemical staining was strongly and diffusely positive in both the external positive control—melanoma tissue—and the internal positive control—benign sebaceous glands, whereas the stain was completely negative in all malignant T cells . The bacThe function of PRAME in normal and tumor cells is not completely understood, although a role in the regulation of retinoic acid signaling and immune evasion has been proposed. The regulation of PRAME gene expression is also poorly understood, and thus the molecular basis of its expression in malignancies is largely unknown. While PRAME is absent or expressed at very low levels in most normal tissues, high levels of PRAME mRNAs are encountered in certain types of malignant cells. PRAME expression has been described in a variety of hematologic malignancies, including both acute and chronic myeloid and lymphocytic leukemias, hairy cell leukemia, Hodgkin’s lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, and multiple myeloma. PRAME overexpression in these tumors generally portends a poor prognosis with shorter overall survival and progression-free survival and lower chemotherapeutic response ,32,33,34While most cases of CTCL have an indolent clinical course, some subtypes have a very aggressive course. For instance, MF is typically a slow-growing tumor, but a small subset of cases can progress quickly to large cell or blast cell transformation, which is associated with worse prognosis. In 2018, Masson D et al. found that in CTCLs—particularly MF—a tumor clone frequency >25% (measured by high-throughput sequencing of the TCRB gene) is an independent predictor of early disease progression and death . HoweverThis study had several limitations that should be acknowledged. Firstly, only one PRAME clone was used in the study; the results may have differed if another clone were used due to variable immunohistochemical staining patterns among different PRAME clones. Secondly, we did not stain all subtypes of CTCLs, with the notable omission of primary cutaneous gamma-delta T-cell lymphoma, primary cutaneous acral CD8+ T-cell lymphoma, and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma due to the extreme rarity of these entities. As such, the results of this study cannot be generalized to all subtypes of CTCL.In summary, our study suggests that the pathogenesis of CTCL is not mediated by PRAME. Further study is required to identify additional biomarkers that might aid in the diagnosis and prognostication of CTCL.


The complexation of carvedilol by RAMEB significantly increased the drug’s photochemical stability in aqueous solution. These results might constitute a first step towards the development of a novel oral formulation of carvedilol.We studied the effect of several CDs on carvedilol’s solubility and chemical stability in various aqueous media. Our present results show that it is possible to achieve a carvedilol concentration of 5 mg/mL (12.3 mM) in the presence of 5 eq of γCD or RAMEB in an aqueous medium with an acceptable acid pH (between 3.5 and 4.7). Carvedilol formed 1:1 inclusion complexes but those with RAMEB appear to be stronger (K = 317 M Carvedilol a is a noFrom a pharmaceutical point of view, carvedilol is a racemic compound with low aqueous solubility (ranging from 0.01 to 1 mg/mL depending on the pH) . It is p2O/ethanol before evaporation . Un. Un18]. 10 mM CD was the concentration of carvedilol dissolved in the presence of 10 mM CD, and (carvedilol)No CD was the concentration of carvedilol dissolved in the absence of the CD. The addition of αCD did not significantly change the dissolution of carvedilol in any of the media, as illustrated by the R values close to 1 , or hydrochloric acid . To investigate the CDs’ ability to increase the solubility of carvedilol in various media, we calculated the R ratio: ose to 1 .Carvedilol’s solubility in all the studied media was greater in the presence of βCD and γCD derivatives in general and RAMEB, γCD and HPγCD in particular. It should be noted that γCD and HPγCD were only less effective than βCD derivatives in citrate buffer. The greatest R ratios were obtained in acetate buffer, with values of between 4.78 and 5.10 (reaching the target of 12.3 mM) in the presence of 10 mM γCD, HPγCD and RAMEB. These findings are in line with literature reports on the greater impact of acetic acid on carvedilol solubilization by HPβCD, relative to phosphoric acid at pH 3.7 .Likewise, a positive impact of citric acid on carvedilol solubilization by 2 mM βCD has been reported previously, however, this impact decreased at citric acid concentrations above 2 mM and the pH was not described . Our stuLastly, we found that HCl increased the solubilization of carvedilol less than acetate but more than citrate. To reach the target carvedilol concentration (12.3 mM), γCD was selected due to its European pharmacopeia presence and RAMEB for its better solubilizing effect. Then, 12.3 mM Carvedilol was added in 13 mM HCl aqueous solution containing 61.5 mM (5 eq) CD, leading to clear solutions for both CDs at pH ~3.5 as displayed on 1H NMR spectra of carvedilol in acetate-buffered D2O were very similar to those in D2O with HCl pH adjustment .2O, using conventional 2D NMR (COSY and phase-sensitive HSQC). The spectral features of the aliphatic moiety were similar to those reported in the literature [1H and COSY spectra are provided as We first characterized 5 mM carvedilol in 0.1 M acetate-buffered Dterature . The che1H NMR titration experiments .As mentioned above, carvedilol is an amphiphilic compound at acidic pH. Its potential self-aggregation properties should be investigated before carvedilol/CD interactions are studied. More precisely, the threshold concentration for carvedilol self-aggregation  should be estimated before ITC is performed. Self-association phenomenon is a concentration-dependent process that competes with the formation of inclusion complexes; this potentially leads to discrepancies and misinterpretations of the ITC and NMR data . As show1H NMR experiments were first carried out in acetate or hydrochloride solutions ) and carvedilol, olutions . We comp1H NMR spectra of carvedilol solutions in acetate buffer  increased with the CD concentration  and 3.5 × 10−10 m2/s with the larger γCD  is illustrated in Lastly, strong interactions were observed between the OCH1H NMR titration experiments [r coefficient ranged from 0 to 1. We produced a Job plot of the observed Δδ·(CD) vs. r  vs. r b. It shoIn order to evaluate the thermodynamic parameters of carvedilol/CD complexes, we used ITC to investigate the interaction between carvedilol and γCD or RAMEB in acetate buffer. As low wiseman “c” parameters  were expThe theoretical and experimental isotherms showed a high level of agreement-confirming that the 1:1 stoichiometry used in the data treatment correctly described the interaction of carvedilol with both γCD and RAMEB. The corresponding thermodynamic parameters are described in −1, under our experimental conditions), as could be expected from the solubility studies. Even though the corresponding low wiseman “c” parameters, the degree of uncertainty was moderate and thus validated our experimental approach. Furthermore, both systems exhibit favorable inclusion enthalpy, which was partially compensated by an unfavorable inclusion entropy. This type of thermodynamic profile is often observed for CD inclusion compounds [−1·K−1 for γCD and −25 J·mol−1·K−1 for RAMEB). This might indicate that the relative contributions of hydrophobic forces vs. interaction forces differ for these systems, with a stronger contribution from water reorganization [The formation of carvedilol/γCD and carvedilol/RAMEB complexes was a spontaneous process, with negative values for ΔG°. The affinity was moderate (below 500 Mompounds  and is gnization  for γCD.m/z corresponding to the complex compared to the m/z (carvedilol + H)+ or (CD + Na)+. As illustration on It should be noted that some mass spectrometry and UV-Vis experiments were also carried out in addition to gain deeper information. It is well-known that ESI ionization is a soft ionization method used to investigate inclusion complexes stability . With βCIn addition, UV spectra of carvedilol did not show any variation of λ in absence of CDs or in presence of 10 equivalents of γCD or RAMEB in 13 mM HCl . Only sm2O2 7.5% v/v) conditions [The photochemical stability of 5 mg/mL (12.3 mM) carvedilol was investigated in the presence or absence of 5 eq of γCD or RAMEB in aqueous HCl solution. In water, carvedilol is reported to be stable under neutral or acidic (HCl 1.0 N) conditions but sensible to basic (NaOH 1.0 N) or oxidative  in acetonitrile, γCD and RAMEB solutions, respectively .−6 days−1 (p < 0.001), 85.2 × 10−6 days−1 (p < 0.001) and 73.1 × 10−6 days−1 (p < 0.001) for acetonitrile, γCD, RAMEB solutions, respectively). We found that CDs slowed the degradation of light-exposed vials of aqueous acidic carvedilol solutions. The first-order kinetic constants were 144.6 × 102O mixture. Studies of the degradation mechanisms inhibited by CDs are now warranted and occurring.It has been reported that CDs can protect drugs from photo-oxidation and that the hydroxyl substituents’ electron-donating tendency may dampen this protective effect ,31. In c−1 at 298 K) than that with γCD (K = 225 M−1 at 298 K). The complexation of carvedilol by RAMEB significantly increased the drug’s photochemical stability in aqueous solution. These results might constitute a first step towards the development of a novel oral formulation of carvedilol.Our present results show that it is possible to achieve a carvedilol concentration of 5 mg/mL (12.3 mM) in the presence of 5 eq of γCD or RAMEB in an aqueous medium with an acceptable acid pH (pH ~3.5). In both cases, carvedilol formed a 1:1 inclusion complex. The complex with RAMEB appears to be stronger (K = 317 M


To identify preferred burnout interventions within a resident physician population, utilizing the Nominal Group Technique. The results will be used to design a discrete choice experiment study to inform the development of resident burnout prevention programs.Three resident focus groups met (10–14 participants/group) to prioritize a list of 23 factors for burnout prevention programs. The Nominal Group Technique consisted of three steps: an individual, confidential ranking of the 23 factors by importance from 1 to 23, a group discussion of each attribute, including a group review of the rankings, and an opportunity to alter the original ranking across participants.The total number of residents (36) were a representative sample of specialty, year of residency, and sex. There was strong agreement about the most highly rated attributes which grouped naturally into themes of autonomy, meaning, competency and relatedness. There was also disagreement on several of the attributes that is likely due to the differences in residency specialty and subsequently rotation requirements.This study identified the need to address multiple organizational factors that may lead to physician burnout. There is a clear need for complex interventions that target systemic and program level factors rather than focus on individual interventions. These results may help residency program directors understand the specific attributes of a burnout prevention program valued by residents. Aligning burnout interventions with resident preferences could improve the efficacy of burnout prevention programs by improving adoption of, and satisfaction with, these programs. Physician burnout is a work-related syndrome characterized by emotional exhaustion, depersonalization, and a sense of reduced personal accomplishment . Burnout It often takes a tragedy like the one suffered at a New York City hospital where two first-year residents died by suicide within four days, to draw attention to the seriousness of the problem . A 2017 Existing research on burnout prevention among residents focuses primarily on physician-directed interventions, such as building personal resiliency  and pracDiscrete choice experiment (DCE) research can be used to understand how stakeholders value specific components of possible programs or interventions. For example, this approach was used to model the physician preferences regarding a pay-for performance incentive program,  adherencThree resident focus groups (consisting of 10–14 participants/session) were conducted in July and August 2020, in three medical centers in California to prioritize resident preferences for burnout intervention attributes. We purposely chose programs based at diverse healthcare organizations. The first program was based at a university with 900 resident physicians across all medical specialties. Residents rotated at both the university hospital and the affiliated Veterans Affairs Medical Center. The second program was based at a large (476 beds) not-for-profit medical center with family medicine, internal medicine, and emergency medicine residency programs . The third program was based at a community teaching hospital with 14 residents enrolled in a family medicine residency program.All residents were emailed an invitation to participate in a focus group at a predetermined time. Anyone who presented the day of the focus group could participate. Due to the COVID-19 pandemic, two focus groups had to meet via Zoom, while one group met in person. Participants were considered eligible for inclusion in the study if they were currently part of a residency program at one of these three centers. They were purposely selected to represent the full program spectrum of age, sex, specialty, type of hospital, and year of residency.The moderator had no reporting relationships with residents or faculty in any participating program, and a neutral note-taker was present during each focus group. Participants provided oral informed consent before discussions began. Focus groups were audio-recorded and transcribed; all identifiers were removed before analysis. After each focus group, participants were provided with information on available resources for addressing burnout. The Loma Linda University institutional review board approved the study as expedited.NGT was selected as a strategy for identifying relevant attributes and relative ranking of importance. NGT is a qualitative exploratory research method often used in situations that require complex problem solving, decision-making, priority-setting, and consensus reaching . It is dNGT combines quantitative and qualitative data collection in a group setting while avoiding the issues of group dynamics present in other group methods such as Delphi methods or brainstorming. Additional advantages of NGT over other group methods include reduced researcher bias due to the structured nature of the process, expedient achievement of data saturation, and its ability to simultaneously address problem identification, development of solutions, and establishing priorities for action. This method can be implemented within a narrow timeframe, and it is easily understood by participants. Responses are weighted by participants, and the process is transparent, inclusive and can be easily replicated. NGT promotes even participation and facilitates representation of the implicit views of the group –26.We conducted a literature search to identify systematic reviews of interventions to reduce burnout in groups of physicians . Both individual and organization directed interventions were included. We restricted our review of existing studies to a time limit of 10 years and found eight systematic reviews , 27–32. Twenty-three potential important attributes of intervention programs were established from this literature review. The NGT process consisted of three steps. After a welcome from the facilitator, participants were asked to introduce themselves, including specialty and year of residency. The facilitator then described the purpose of the study, the process, and the survey list of potential attributes with a description of each attribute. These attributes were displayed in Google Sheets for all participants to view in real-time. Participants were then asked to complete the survey, ranking each potential attribute from 1–23 with one being the most important and twenty-three being the least. Ranking occurred anonymously using Google Sheets. Each participant was assigned an individual sheet displaying the list of attributes in one column and the drop-down list of ranking values (1–23) in the adjacent column. Participants ranked each attribute, assigning only one number per attribute. The aggregate ranking of each attribute was instantly updated on a separate summary sheet available to the group facilitator. The summary sheet displayed individual anonymous rankings of each group member  together with the list of attributes sorted according to the rank order at the group level.During a second step . Next highest agreement, attribute 20 –communication skills training–with participants agreeing that it is not a useful intervention (4.87). The highest prioritized intervention was attribute 1 –flexible scheduling–with participants agreeing that this is the most wanted intervention, though with a higher standard deviation (4.91). The highest disagreement among participants with the resulting highest standard deviation was attribute 21, spiritual nurturing and care (7.51), followed by attribute 10, mindfulness and self-care training (7.40) and attribute 5, enforcing sensible patient censuses (6.71). This disagreement can be attributed to the differences in residency programs and types of hospital settings. One setting was a faith-based organization and some residents spent more time in outpatient versus inpatient settings that require the consideration of a patient census limit for trainees.“Using the direct rating method,” we calculated mean importance scores and standard deviations for each program attribute. The mean importance score was calculated by dividing the total points awarded per attribute by the total number of residents participating in the focus groups. The mean scores show the group aggregate rank, whereas standard deviation show the spread, i.e., disagreement of the group’s responses around that result. Based on the mean importance score and calculated standard deviations, we made the ranking of attributes from most (lowest mean) to least (highest mean) important . SimilarWe review the top 10 priority interventions and provide participants’ quotes to help contextualize the ratings in the following sections.This attribute was identified as the essential aspect of the burnout prevention programs. In all three focus groups, residents prioritized time for personal and professional needs as the most critical aspect of burnout prevention. Residents talked about their time constraints preventing them from practicing self-care, mindfulness, or meaningful learning. Time off work and flexibility in scheduling was discussed as a baseline for any other wellness intervention. When on-call schedules do not allow residents to meet basic needs such as sleep and self-care, any additional intervention to prevent burnout is meaningless.Scheduling is so important. This is a change that doesn’t take much work to implement and will have a real, immediate impact. It is no stretch of the imagination to think working fewer days in a row could mean a better quality of life. More rest between shifts means a better quality of life. More time-off requests granted means more of us are happier in the long-term. This is the most immediate and tangible solution instead of stress management or meditation promoted by some programs.”“Residents discussed the importance of fatigue as a precursor to burnout. They talked about how long hours, heavy workloads, and constant pressure are emotionally taxing. Participants emphasized the ability to spend time away from work to reenergize, engage in activities that can prevent burnout, and maintain a life outside of work.Having shorter shifts means I have time either before or after my shift to spend time with my family, work out, cook meals, and be a normal person outside of the hospital.”““Having a shorter shift structure would let me recover sooner after night shifts. You are not completely wiped out at the end of your shift.”Residents described the protective mechanisms of physical fitness and exercise. Participants spoke about the benefits of exercise not only for physical, but also for their mental health and well-being. There was a discrepancy in ranking this intervention. University hospital residents ranked it lower than the other two programs, possibly due to their easy access to a state-of-the-art recreation and wellness center.Exercise is the best way for me to sweat off stress and anxiety. I keep talking to my patients about the importance of physical activity, yet my schedule is so hectic that I cannot find enough time to exercise regularly. It takes about 20 minutes to get to the gym, and I feel like our minutes are precious. I am struggling to integrate exercise into my routine.”“Despite the work hours restrictions, it remains challenging to get enough sleep while in residency. Residents linked sleep deprivation to burnout and discussed this issue as requiring system change rather than individual attention. They mentioned difficulties in noticing and addressing their sleep deprivation, exacerbated by an “I can handle it” mentality.“Once I ended up being on call for six days in a row. Near the end, I was so tired that I stopped smiling. I was so tired of running on no sleep. During that time, we were getting late-night calls from the ER, but you are expected to see patients during the day as well. So, you are running on no sleep. At the end of the sixth day, I developed a fever and had to call in sick.”Residents articulated the distinction between hours worked per shift and the number of admissions during the shift. Because of work hour restrictions by accreditation policies,  programs“I can have several long shifts scheduled back-to-back but uneventful and still feel fine. Sometimes my shifts are more staggered and seem more manageable, but I end up caring for a lot more patients or dealing with many end-of-life situations and feel much more run down. It is not only about how many hours I spent in the hospital, but also what happens during those hours that matters for burnout.”Meaningful learning experiences are essential during residency. Participants emphasized the fact that residency is an educational experience. They work long hours for minimal pay in exchange for the benefits of clinical education. For residents to receive the most benefit from their training, programs need to prioritize their learning by securing uninterrupted educational time. This protected time would show residents that hospitals value their personal growth and training over their service.“It is refreshing to have an opportunity to invest in your education and improvement as a physician. At least in part, my burnout experience was connected to a feeling of not being prepared to face some of the more challenging clinical situations. One solution is taking some time away from chaos, turning off your pager, and having a meaningful learning experience. I listen better, ask more questions, and learn more when I can have no responding duties during educational conferences.”According to a recent study, the average physician spends 28 hours on clinical documentation during nights and weekends each month . Residen“At times, I feel like EHR robs me of everything that gives me meaning in my profession–it makes me less efficient, less able to spend time with my patients. It is very disruptive to the flow of my work.”Residents identified programs’ unresponsiveness to residents’ feedback as one of the factors contributing to burnout. Residents perceived themselves as being at the bottom of the hospital hierarchy and rarely having control over their hours, schedule, and work environment. Having a sense of control and being able to influence change can moderate the intensity of workload and burnout. Residents prioritized the ability to have a forum where they can voice concerns and see them addressed.“Giving residents a voice as much as possible is a great way to sustain our motivation and prevent apathy. Let us tell you what works and what interventions are effective (or not). We are the ones on the frontlines.”Participants discussed multiple ways in which residency programs and healthcare practice can lead to a sense of isolation and loneliness, resulting in burnout. They talked about many hours spent in front of their computers working on medical records, high case workload, and online learning, leading to reduced face-to-face interactions. They highlighted the connection between social support and reduced burnout.“One of my priorities as of late is to invest in relationships. Residency can be lonely and isolated. This sense of isolation can lead to burnout. I believe we need more personal, human interaction beyond quick, professional exchanges. We need opportunities to talk with each other about our work and lives. We need to vent about bad stuff, to talk about meaningful experiences at work, to share tips about surviving this place without losing our sanity.”Some residents found mindfulness useful for combating stress and burnout. They talked about the importance of self-awareness and positive self-reinforcement to reduce their emotional response to stressors.“I’ve been focusing on self-care and fostering my sense of connection, not only to family and friends, but to myself. I am figuring out what really inspired me, what really motivated me. This practice of mindfulness can be very cathartic or Zen.”However, there was a high level of disagreement between the usefulness of mindfulness and stress-management classes to reduce burnout. Residents at the community hospital ranked this intervention remarkably high, while residents at the university hospital ranked it exceptionally low.“Our program focuses a lot on this. Pretty much every retreat we go through, that is the one thing they do. And I am so glad to see the agreement that this is not helpful.”Although burnout during residency training has been widely acknowledged, there is less consensus regarding ways to address this problem , 17. Litcontrol over their work and learning environment and have a voice and ability to influence change. Residents wanted their programs to cultivate meaning in residency training by bringing them back to patient care . They talked about addressing the reasons why they are pulled away from the bedside, such as high patient census and high volume of administrative tasks. Participants referred to time as the priority for interventions to reduce burnout–limiting durations of shifts to allow for self-care and protecting sleep time. Finally, they mentioned the importance of social connectivity and practicing within a work environment that fosters a sense of belonging.The study results suggest that residents prioritize interventions targeting systemic and program-level factors contributing to burnout over the individual interventions. This finding is in line with several recently published studies –38. PartResidents prioritized several individual-level interventions such as physical exercise programs and mindfulness training. However, these interventions were on the list of the attributes with the highest disagreement among participants. Residents of one program were dissatisfied with the sole focus of their program administration on boosting physicians’ resilience as the best strategy for dealing with burnout. It is also worth mentioning the contextual differences between programs that factored into residents’ preferences. While a physical exercise program was highly prioritized by medical center and community hospital residents, it was scored lower by the university hospital residents who had easy access to an on-site, state-of-the-art wellness center that remained open in the pandemic with classes outdoors. Stress management and mindfulness training were a high priority for community hospital residents, and a low priority for medical center and university hospital residents who had this incorporated by their programs and realized it was not helpful.autonomy , meaning , competence , and relatedness .The results of our study support the need for interventions to address multiple organizational factors leading to burnout as opposed to addressing a single issue such as workload or shift patterns. There is a need for complex interventions that will target several systemic and program level factors , 40 whilThe literature has not clarified guidance on NGT sample size, and this study, like others before, used a small number of focus groups. We were aware that the restriction of our project timeframe to conduct focus groups may have led to limited depth of discussion of each attribute. Subsequent groups may have been able to broadened the scope and breadth. We used eight systematic literature reviews of interventions, both individual and institutional, for prevention of burnout, to develop the list of 23 attributes. In addition, we spoke with experts to refine our list. However, we cannot rule out other burnout program attributes that are important to some residents or that additional groups of residents may have added other attributes not mentioned in the current study methods. In addition, the samples for the focus groups contained a relatively high proportion of internal medicine and family medicine residents but a limited representation of several other specialties. Participants also represented three diverse healthcare centers. Some might consider our selection of participants to be less generalizable to all residency programs and medical specialties. Future studies could do this procedure on each medical speciality and compare and contrast the program attribute rankings in interesting ways. A further limitation is that we have not compared the attributes derived from NGT with other approaches . Head-to-head comparisons of different techniques could help to assess and understand strengths and weaknesses between approaches.This study identified and ranked burnout prevention preferences in a resident population, showing that there is a need to address multiple organizational factors leading to burnout. There is also a need for complex interventions that will target several systemic and program level factors. While there was variability about attributes the groups perceived to be less important, as well as variability between healthcare centers, there was strong agreement about the most highly rated attributes. The attributes group naturally into themes of autonomy, meaning, competency, and relatedness. The next steps in this process will enable the researchers to refine the methods to determine measures for each attribute. The results of this study may help residency program directors understand what specific attributes of a burnout prevention program residents will value. The results will also be used to design a DCE study that would model residents’ burnout prevention program preferences. This may advance understanding and support for evidence-based, best practices as well as increase residents participation in, and adoption of, burnout prevention programs resulting in a potential decrease in rates of resident burnout. These same attributes could also be explored with physicians across specialities to determine whether the four themes of autonomy, meaning, competency, and relatedness also apply after board certification and across specialties.S1 Annex(DOCX)Click here for additional data file.


Over 450,000 individuals are hospitalized with burns annually and roughly 35% are scald burns. Children younger than 5 years of age are at the greatest risk of scald burn injury. Caregiver burn prevention programs have been found to reduce the prevalence of injuries in young children; however, low-income and underserved populations seldomly have access to these programs. The impact of scald burn prevention programs in underserved populations remains unexplored. The objective of the current study was to evaluate the efficacy of a scald burn prevention program at a Level One Pediatric Trauma Center in a low-income, underserved community.t-test.Our hospital developed a one-hour scald burn prevention program for caregivers with children 5 years of age or younger. The program educated caregivers on ways to prevent scald burns and create safeguards in their home. Caregivers completed a pre-post survey to measure their ability to identify hot or cold objects, as well as respond to items about their perceptions of the program’s utility, their willingness to share it with others, and the likelihood that they would use the information in the future. Data was analyzed using a paired N = 269) caregivers participated in the program. Before the program, caregivers could identify potentially hot objects 83.17% of the time, and after the program, they were able to identify these items 92.31% of the time: t (268) = 12.46, p < .001, d = 1.07. Additionally, 95% of caregivers indicated that the program was helpful, 99% stated that they were likely to share this information with others, and 100% indicated that they would use the information from the program.Two-hundred and sixty-nine (Education is a critical component to prevent scald burns. Results indicate that a hospital-led scald burn prevention program can positively impact a caregiver’s ability to identify possible scald-burn risks. Providing education to caregivers who typically do not receive this information could lower the prevalence of scald burns not only institutionally, but in communities that are disproportionately impacted by this mechanism of injury. According to the American Burn Association (ABA), approximately 450,000 individuals are hospitalized from burns annually . The hospital’s Injury Prevention and Research Coordinators developed a one-hour scald burn prevention program that invited caregivers who had children 5 years or younger to participate from 2018 to 2019. Caregivers were referred to the program by various hospital staff members such as social workers, physicians, nursing staff, and the Injury Prevention Coordinator. Caregivers that attended the hospital-based program were from a variety of locations, including in-patient and out-patient facilities, community referrals, and individuals with children presenting to the hospital’s Emergency Department. Caregivers were invited to the scald burn prevention course held at the hospital. Each session had 5–10 caregivers in attendance to ensure caregivers were able to receive one-on-one attention from the instructor, feel comfortable asking questions, and participate in hands-on activities.The course began with a pre-test survey asking the caregivers to identify 16-items as ‘hot or not’  the utility of the program, (2) willingness to share the program’s information with others, and (3) if they will use the information they learned. For completing the program, caregivers were provided with prevention items such as temperature safety ducks to assist parents to test water, reading packets, no-spill travel mugs, infant bathtubs, plug-ins, cabinet locks, suction bowls and child safety gates to create safer home environments. These items can be useful in preventing common scald burns and were introduced with descriptions of appropriate use in the demonstration from the injury prevention coordinator.t-test was utilized to display group differences from pre to post survey on the ‘hot or not’ activity. Effect size (Cohen’s d) was calculated to identify the magnitude of the change. Statistical analyses were performed using R Studio  and composite scores were compared from pre-post. The post survey items regarding the utility, willingness to share the information, and likelihood to use the program’s content were represented by group mean scores (in percentages). A paired SD = 1.66; 83.17%). After the program, caregivers were able to identify 14.77 . The difference in mean scores from pre to post was statistically significant: t (268) = 12.46, p < .001, d = 1.07. Additionally, 95% of caregivers indicated that the program was helpful, 99% stated that they were likely to share this information with others, and 100% indicated that they would use the information from the program.Over the two-year program, 269 caregivers participated and over 700 prevention items were distributed. Before the program, caregivers were able to correctly identify 13.31 hot objects out of 16  received standard medical care or were being treated for their burn. While scald burn programs are often offered at community centers, there are often transportation and/or childcare barriers, which may limit attendance (Hodkinson et al. The current study is not without limitations. Most notably, due to this being a quality assurance project, the author’s Institutional Review Board prohibited the collection of identifying information beyond initials to link pre-post responses. This limited the present study’s ability to accurately depict the sample; however, the general geographical location and hospital’s surroundings were included to provide some background of the population that is usually served. First, the current study displayed that a hospital-led program could increase caregiver knowledge in a generally low-income community, yet it did not show if the program reduced rates of scald burns in the hospital’s patient population. This was hospital-based at a single center; thus, this program should be replicated at other facilities to understand if it is generalizable. The current project utilized the same, unvalidated, survey for English and non-English speakers, however, due to lack of resources to translate the other survey questions, data was not able to be included for this population in the present sample. Lastly, participants could have perhaps stated that the program was more helpful than they actually found it due to providing socially desirable answers. Qualitative feedback could perhaps reduce these confounding factors and specifically understand what was helpful for each participant.The results from the current study expand literature and could inform future research. As such, future work should investigate if the implementation of scald burns programs at a hospital decrease scald burn occurrences longitudinally at an institution. Along similar lines, longitudinal designs would allow for researchers to test the durability and long-term improvement of knowledge gained from the program. Additionally, understanding and following-up with caregivers to assure that they were able to implement the tools that were distributed in their home would be helpful to understand if the program truly taught them how to utilize these resources. Moreover, future work could attempt to create a validated knowledge assessment to specifically target scald burn knowledge items and assure their validity. Further, future research should try to establish if the program is impactful to Spanish or non-English speaking caregivers, even just through instructor demonstrations. Lastly, future research should attempt to garner community partnerships to have interconnected prevention programs that offer the same information at hospital and community settings.The present study found that a one-hour hospital-led scald burn prevention course significantly increased caregiver knowledge and that caregivers found the program useful. Moreover, caregivers reported that they were extremely likely to use the materials they received and that they planned to share this information with others. The results from the current study show that a simple scald burn program can assist caregivers, regardless of their background, in understanding potential scald burn risks while providing useful materials to attempt to prevent future burns.