In Ghana, anaemia is a severe public health problem among adolescent girls. In an attempt to deal with this phenomenon, Ghana Ministry of Health in collaboration with other development partners developed and launched weekly iron and folic acid supplementation program for adolescent girls in Ghanaian junior high schools. Therefore, the main aim of this study was to determine the level of compliance with iron and folic acid supplementation (IFAS) and its associated factors among adolescent girls in the Tamale Metropolis of Ghana. p < 0.05.  A cross-sectional study was conducted among 424 randomly sampled adolescent girls in the Tamale Metropolis of Ghana from April to July 2019 using an interviewer-administered structured questionnaire. Twenty school health coordinators were purposively selected to answer questions on the challenges they face in implementing the IFAS program at the school level. Bivariate logistic regression and multivariate logistic regression were used to determine associations and strength of associations, respectively, at a significant threshold of p < 0.01), had good knowledge of anaemia  p=0.01), and had good knowledge of the IFAS program  p < 0.01) were significantly associated with compliance with the IFAS. The majority (60%) of the adolescent girls have ever missed taking the iron and folic acid (IFA) tablet because it was not issued to them by the teacher's concern while about 48.3% (169) of the adolescent girls are taking the tablet because it prevents anaemia. Adolescent girls perceiving the tablet as family planning medicine (88.8%) and unavailability of water in classrooms (18.8%) were cited as the major challenges by school health coordinators.  Compliance with the IFAS was low (26.2%). Adolescent girls who were aware of anaemia   Compliance with the IFAS among adolescent girls was low. Level of education and occupation of mothers of adolescent girls, awareness on anaemia, and good knowledge of anaemia and of the IFAS program were significant predictors of compliance with the IFAS. Educating the adolescent girls on anaemia and benefits of the IFAS, constant supply of the IFA tablet, and engaging parents of the adolescent girls on the program will help improve the compliance level of the adolescent girls with the IFAS. In developing countries, anaemia is a major public health problem of not only pregnant women or children but also adolescent girls . AdolescGlobally, anaemia is affecting about 1.62 billion people worldwide and approximately half of all anaemia can be attributed to iron deficiency. Children, pregnant women, and women of reproductive age are greatly affected . The numWorldwide, it is estimated that the absence of investment in prevention of anaemia would result in 265 million more cases of anaemia in women including adolescent girls by 2025 and nearly 800,000 more child deaths and 7,000–14,000 more maternal deaths [Anaemia, a direct indication of undernutrition and poor dietary intake of iron, is a serious public health problem among adolescent girls . AdolescAnaemia has serious consequences; it can lead to poor school performance among schoolchildren, impaired physical growth, and poor cognitive development, thereby hindering development socially and economically . AnaemiaIn Ghana, the prevalence of anaemia among adolescent girls is unacceptably high. Data from the Ghana Demographic Health Survey (GDHS) indicate a high prevalence of 48% among adolescent girls . Iron an2 [A cross-sectional study was conducted using quantitative data collection methods from April to July 2019 among adolescent girls in twenty selected junior high schools in the Tamale Metropolis of Ghana. Tamale Metropolis is geographically located between latitude 9° 16 and 9° 34 North and longitudes 0° 36 and 0° 57 West. Tamale Metropolis is one of the 14 Districts in the Northern Region. It is located in the central part of the region and shares boundaries with Sagnarigu, Mion, East Gonja, and Central Gonja districts. The Metropolis has a total estimated land size of 646.90180 km2 . Accordi2 .In Ghana, IFAS has been for only pregnant women neglecting adolescent girls . Weekly μg (0.4 mg) of folic acid) every Wednesday in a week at noon. Community health workers are expected to assist girls who are out of school to take the tablet [The IFAS program is in the pilot phase in four of the ten regions, namely, Northern Region, Brong Ahafo Region, and Upper West and Upper East regions with the main aim of contributing to the reduction of anaemia among adolescent girls. About 4,500 school health coordinators who are teachers in the participating schools and 3,000 health workers have been trained to support the implementation of the program . TeacherAll Adolescent girls attending junior high school in Tamale Metropolis were the source population. The study population consisted of randomly sampled girls who were attending junior high school in the study area in the third term of the 2018/2019 academic year. Girls who were absent and those who declined to answer the research questions were excluded from the study. School health coordinators of the 20 schools also participated in the study.N=(Z2  × p(1 − p))/d2 [N is the sample size, Z (statistic) = 1.96, p (compliance rate) = 0.5, and d (margin of error) = 0.05:The sample size was determined using Cochran's formula − p))/d2  with 95%The IFAS program is relatively a new program among adolescent girls in Ghana, hence the justification for the assumed compliance rate for the sample size calculation. The calculated sample size was therefore 385. After adding a 10% nonresponse rate, the final sample size obtained was 424 research participants.Simple random sampling was used to select the schools and the adolescent girls while purposive sampling was used to select the school health coordinators. Twenty schools were selected using lottery method. The names of all junior high schools in the metropolis were written on pieces of papers and placed in a bowl. With blind draw, the schools were randomly picked one by one without replacement until 20 schools were reached. The final sample size of 424 was proportionally allocated to the 20 schools based on the enrolment of girls in each school. The study participants were selected from each class through simple random sampling using random numbers generated for each class using the girls attendance register. Twenty school health coordinators in the selected schools were purposively sampled to participate in the study.The data collection tool used in collecting the research data was structured pretested questionnaires while data collection was done with the help of interviewer-assisted questionnaire administration. Pretesting of the data collection tool was done in Sagnerigu Municipality since it shares similar characteristics with the study area. The data collection tool was adapted and modified from similar published studies , 7, 20. A prior appointment was taken from headmasters and health coordinators of the selected schools. The questionnaires which were mostly closed-ended with multiple choice and dichotomous responses were divided into sections and administered to both adolescent girls and teachers. Section A consisted of 8 questions to elicit information on sociodemographic characteristics of the adolescent girls and section B was made of 9 questions to determine compliance level of the adolescent girls with the IFAS whereas section C consisted of 16 questions which sought to assess the level of knowledge of the adolescent girls of anaemia and of the IFAS program. Section C also sought to find out the side effects experienced by adolescent girls. Section D which was the only section administered to the teachers sought to determine the challenges faced by teachers in implementing the IFAS program at the school level. Data collection was done by two community health nurses and two masters students in public health nutrition. One-day training was organized for the data collectors by the principal investigator. They were trained on objectives of the study, how to ensure confidentiality of the data, and how to fill the questionnaires. They were also trained on how to initiate the interview process by reading the informed consent to every respondent for voluntary participation. After data collection, the principal investigator reviewed each questionnaire in order to ensure the accuracy and completeness of the data collected.The quantitative data were coded and analysed using STATA 14.1. Sociodemographic characteristics, level of compliance, and knowledge of anaemia and of the IFAS program were first presented in text, figures, and tables using descriptive statistics such as frequencies and percentages. Bivariate logistic regression test was done to determine the association between the sociodemographic characteristics and the outcome variables . Logistic regression analysis was also done to determine the effect of awareness of anaemia, knowledge of anaemia, and knowledge of the IFAS program on compliance level. Multivariate logistic regression was further done for variables that were statistically significant after the bivariate analysis. Crude and adjusted odds ratios with their respective confidence intervals (95%) were computed to determine the strength of association of each variable.IFAS compliance level was measured based on the number of tablets consumed in the past 7 weeks. Adolescent girls who consumed at least five tablets of the expected dose in the previous 7 weeks (1 tablet per week) which is equivalent to consuming 70% of the expected dose before the day of the data collection was considered compliant. Adolescent girls who consumed less than five tablets were considered noncompliant . RecordsKnowledge on anaemia was measured by summing up 19 relevant knowledge items on anaemia . A correct response was scored “1” and an incorrect response was scored “0” with a maximum score of 19. Those who scored above the median mark were considered as having good knowledge of anaemia while those who scored below the median mark were considered as having poor knowledge .Knowledge of the IFAS program was scored by summing up 15 relevant knowledge items on the IFAS program: one item on why they are given the tablet, 4 items on benefits of taking IFA tablet, 3 items on food that inhibits iron and folic acid absorption, 5 items on side effects of taking IFA tablets, and 2 items on why girls are given the iron and folic acid tablet. A correct answer was scored “1” and an incorrect answer was scored “0”. With a maximum score of 15, those who scored above the median mark were considered having good knowledge on the IFAS program while those who scored below the median mark were considered as having poor knowledge .Ethical clearance for the study was sought from the University for Development Studies. Approval letter for the study was granted by Ghana Health Service while permission to go into the school was obtained from the Tamale Metropolitan Education Office. Informed assent was obtained from underaged participants in their schools while informed consent was obtained from the parents of the girls. Selected girls were given informed consent forms for their parents to thumbprint/sign signalling their agreement for their child to participate in the study.The total number of respondents in this current study was 424 with a mean age (SD) of 14.4 (±1.7). Majority (79.7%) of the respondents had their ages ranging between 10 and 15 years with over half (53.5%) in junior high school two. Majority (67.9%) of the adolescent girls were Dagombas with 73.6% of them affiliated to the Islamic religion. Most (48.1%) of the respondents' mothers had no formal education while very few (14.2%) had tertiary education, and about half (51.9%) of the respondents' mothers were petty traders. Twenty-five percent of the respondents' fathers had tertiary education while most (44.8%) of them had no formal education with 46% of them being public/civil servants .Overall compliance with the IFAS in this current study was 26.2%. Only 26.2% (111) of the adolescent girls consumed 5 or more tablets in the past 7 weeks prior to the data collection. Majority (90.1%) of the adolescent girls took the IFA tablet on the first day it was given by the teachers. About 82.5% of the adolescent girls are still consuming the IFA tablet in school while the rest (17.4%) stopped consuming the IFA tablet. Among those currently taking the IFA tablet in school, most (48.3%) cited the prevention of anaemia as the reason for taking the IFA tablet while another 41.1% cited advice from their teacher. Among those who stopped taking the IFA tablet in school, 90.5% (67) cited the fact that their parents ask them not to take the tablet while another 5.4% (4) cited side effects as the reason for ceasing to take the IFA tablet. About 82.5% of the adolescent girls have ever missed taking the IFA tablet in school. Most (60%) of the adolescent girls have ever missed taking the IFA tablet because it was not issued to them by the teacher's concern while another 28.9% cited the fact that they were absent from school. Among those who have ever taken the tablet, 73.1% always take the tablet in the presence of the teacher .p < 0.05 established that the mother's level of education  and mother's occupation  were significantly associated with adolescent girls level of compliance (p=0.01). The odds of compliance with the IFAS among respondents whose mothers were traders were 56% times lower compared to those respondents whose mothers were unemployed  p=0.01) (p=0.01) and good knowledge of the IFAS program  p < 0.01) were also significant determinants of compliance with the IFAS. A logistic regression analysis found out that the odds of compliance with the IFAS were 3.6 times more likely among adolescent girls who were aware of anaemia compared to adolescent girls who were not aware of anaemia  p < 0.01) (A Pearson's chi-square test with a significant threshold of mpliance . Respond p=0.01) . Good kn < 0.01) .With multiple responses possible, majority (81.8%) of the adolescent girls cited regulation of menstruation as the benefit they have gotten from taking the IFA tablet and 77.8% thinks the IFA tablet has helped to improve their concentration and performance in class while over 18.2% cited reduced dizziness as the benefit they have gotten from taking the IFA tablet .About 247 (58.2%) of the respondents claimed they have ever heard of a disease where the affected person is said to have low blood level, and only 30.7% (130) were able to correctly mention anaemia as low blood level and hence were considered aware of anaemia. About 67.9% of the adolescent girls have never received education on anaemia. Those (32.1%) who have ever received education on anaemia cited teachers (85.3%) and health workers (14.7%) as their sources of anaemia education.p < 0.05 found no statistically significant association between respondent sociodemographic characteristics and knowledge on anaemia except for the occupation of fathers of the respondents . Respondents whose fathers were public/civil servants were found to be 4.4 times more likely to have good knowledge on anaemia as compared to those pupils whose fathers were unemployed  p=0.01)  of the adolescent girls had poor knowledge on anaemia while 43.2% had good knowledge of anaemia . Pearson p=0.01) .p < 0.05 found out that mother's level of education , mother's occupation , and father's occupation  of the respondents were statistically significant with adolescent girls' level of knowledge on the IFAS program (p=0.01). Again, respondents whose fathers were unemployed were 75% times less likely to have good knowledge of the IFAS program as compared to those respondents whose fathers were public/civil servants  p=0.03).Most (64.9%) of the adolescent girls were found to have poor knowledge of the IFAS program while 35.1% were found to have good knowledge of the IFAS program . Pearson program . Respondp=0.01)  p=0.01) .With multiple responses possible, most (78.8%) of the respondents reported that there were no side effects associated with the consumption of the IFA tablet. Some (10.9%) stated stomach/abdominal pains as the side effect they experienced with the consumption of the IFA tablet while few cited nausea (8.3%) .At the time of our visit, about 70% of the schools had IFA tablets in stock with school health coordinators (95%) in charge of issuing the IFA tablet to the adolescent girls. About 45% (9) of the school health coordinators have never educated the adolescent girls on anaemia and on the IFAS program. Among those who have never educated the adolescent girls on anaemia, 77.8% (7) cited limited time as one of the reasons for their inability to educate the adolescent girls on anaemia and on the IFAS program.A significant number  of the school health coordinators were not able to organize training for their colleague teachers with half  of them citing the fact that they can handle the work alone while another half reported there was no time to organize the training for colleague teachers. Fifty-five percent of the school health coordinators do not always supervise the adolescent girls to ingest the tablet with the majority 63.6% of them citing limited time for their inability to supervise them. Unavailability of water in the classroom (36.4%) was also cited as one of the reasons for their inability to always supervise the adolescent girls to ingest the tablet. About 80% of the school health coordinators admit the fact that they face challenges in implementing the IFAS program. Adolescent girls refusing to take the IFA tablet because they perceived it as family planning medicine and lack of water to swallow the tablet were some of the challenges opined by the school health coordinators. School health coordinators think educating parents and children on the IFAS program, providing incentives to school health coordinators, and ensuring the availability of water in classrooms could help solve some of these challenges.In this study, we sought to investigate the compliance level of adolescent girls with the IFAS and its influencing factors among adolescent girls in the Tamale Metropolis of Ghana. We included 424 adolescents girls with a mean age (SD) of 14.4 (±1.7) with the majority of the adolescent girls between 10 and 15 years.Compliance with the IFAS in this study was found to be low (26.2%). This finding is in variance with a similar study conducted in Iran  which foPrevention of anaemia and advice from teachers were found to be the motivating factors for consuming the IFA tablet by the adolescent girls. These findings agree with a cross-sectional study conducted by Dhikale et al.  which alIn this study, level of education and occupation of mothers of adolescent girls, awareness of anaemia, and good knowledge of anaemia and of the IFAS program were statistically associated with compliance with the IFAS. A similar study in Ethiopia also found good knowledge of anaemia and of the IFAS program as predictors of compliance . Lack ofAbout 90.5% (67) of the adolescent girls stopped taking the IFA tablet in school because their parents asked them not to take the IFA tablet. This finding agrees with a study conducted in India  which alAnaemia among adolescent girls can lead to problems such as decreased concentration, poor school performance, weakness, and irregular menstruation. Weekly IFAS is therefore indicated to improve the iron status of adolescent girls and to counteract the negative effects of iron deficiency anaemia . Most ofWe found a poor level of knowledge of the adolescent girls on anaemia. This finding means that adolescent girls' level of knowledge on meaning, causes, consequences, signs and symptoms, and prevention of anaemia altogether was inadequate. This was not surprising since the majority of the adolescent girls have never received education on anaemia. Our findings agree with studies conducted in Ethiopia (43.3%)  and DelhWe also found a poor level of knowledge of the adolescent girls on the IFAS program. A similar program evaluated in India also found poor knowledge of adolescent girls on IFAS pertaining to side effects of the IFA tablet (29%) and unawareness of benefits (32%) of taking the IFA tablet . Poor leMajority of the adolescent girl report no side effects associated with the consumption of the IFA tablet. However, popularly reported side effects were stomachache, nausea, and vomiting. Stomach ache, nausea, and vomiting are popularly reported as side effects associated with the consumption of IFA tablets in other studies , 26, 31.Unavailability of water in classrooms was seen as an obstacle for teachers to supervise the adolescent girls to ingest the tablet. This finding disagrees with a study conducted in Iran  where stAccording to the school health coordinators, the major challenge they face in implementing the IFAS program is the refusal of adolescent girls to take the IFA tablet as the perceived tablet as family planning medicine. This perception may be due to the poor engagement of the adolescent girls on the IFAS program. The fact that the program does not include adolescent boys might also contribute to this misconception about the IFAS. This calls for effective education on the IFAS program in order to enlighten the adolescent girls on its intended benefits and to also debunk the misconceptions the adolescent girls have about the IFA tablet.There was low compliance with the IFAS program among adolescent girls. Teachers not issuing the tablet to the adolescent girls and absenteeism on the part of the adolescent girls were seen as the major barriers to compliance. Mother's level of education, mother's occupation, awareness of anaemia, and good knowledge of both anaemia and the IFAS program were found to be significant determinants of compliance. Limited time on the part of the school health coordinators, unavailability of water in classrooms, adolescent girls perceiving the IFA tablet as family planning medicine, and irregular supply of IFA tablet were seen as the major challenges faced by school health coordinators. Educating the adolescent girls on anaemia and the IFAS program, engaging parents of the adolescent girls during PTAs meetings, ensuring unlimited access to water in classrooms and regular supply of the IFA tablet to the schools are recommended in order to ensure the success of the IFAS program in the schools.Most of the results in this study were self-reported by the adolescent girls. There is a possible tendency to recall bias and exaggeration. The result should be interpreted with caution. The study did not also measure Hb levels of the adolescent girls to determine the impact of the IFAS on their Hb levels.


The VA has invested in developing the skills of its primary care workforce through the longitudinal Geriatric Scholars Program. Now in its 11th year, the program has increased career satisfaction and job retention, standardized provider behaviors, improved clinical decision-making and reduced dispensing of potentially inappropriate medications. The program consists of: intensive coursework in geriatrics; workshop in quality improvement (QI); and initiation of a micro QI projects in the Scholar’s clinic. Electives enable learners to tailor the program to self-identified gaps in knowledge, skills and competencies. This presentation focuses on the sustainment and spread of these QI projects based on a recent survey of Scholars. Differences between rural and urban QI projects are compared. Commonality among rural QI projects is explored based on topic, team composition, and the types of efficiencies gained in clinical and/or organizational processes to improve care for older Veterans living in rural areas.


ARID1A that lead to inactivation or loss of expression are frequent and widespread across many cancer types including colorectal cancer (CRC). A tumor suppressor role of ARID1A has been established in a number of tumor types including CRC where the genetic inactivation of Arid1a alone led to the formation of invasive colorectal adenocarcinomas in mice. Mechanistically, ARID1A has been described to largely function through the regulation of enhancer activity.ARID1A (AT-rich interactive domain-containing protein 1A) is a subunit of the BAF chromatin remodeling complex and plays roles in transcriptional regulation and DNA damage response. Mutations in ARID1A gene in established colorectal cancer cell lines. We integrated gene expression analyses with genome-wide ARID1A occupancy and epigenomic mapping data to decipher ARID1A-dependent transcriptional regulatory mechanisms.To mimic ARID1A-deficient colorectal cancer, we used CRISPR/Cas9-mediated gene editing to inactivate the KRAS mutations are critically dependent on ARID1A function. In the absence of ARID1A, proliferation of these cell lines is severely impaired, suggesting an essential role for ARID1A in this context. Mechanistically, we showed that ARID1A acts as a co-factor at enhancers occupied by AP1 transcription factors acting downstream of the MEK/ERK pathway. Consistently, loss of ARID1A led to a disruption of KRAS/AP1-dependent enhancer activity, accompanied by a downregulation of expression of the associated target genes.Interestingly, we found that CRC cell lines harboring KRAS-mutated cells, enhancers that are co-occupied by ARID1A and the AP1 transcription factors become inactive, thereby leading to decreased target gene expression. Thus, targeting of the BAF complex in KRAS-mutated CRC may offer a unique, previously unknown, context-dependent therapeutic option in CRC.We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. Upon the loss of ARID1A in The online version of this article (10.1186/s13148-019-0690-5) contains supplementary material, which is available to authorized users. APC, KRAS, and TP53 represent a large fraction of the mutations prevalent in CRC. Notably, the KRAS oncogene is mutated in approximately 30% of CRC cases  [In 2018, colorectal cancer (CRC) was estimated to be the third most commonly occurring cancer and the second leading cause of cancer-related deaths [enomics) . These menomics) , 7.ARID1A gene is among the most frequently mutated genes in human CRC, where it is mutated in 10.9% of cases  [PTEN (6.4%)  [Followed by mutation of well-known tumor suppressor and oncogenes such as those listed above, the enomics) , 4. Inteenomics) , 4. ARIDenomics) , 9, whicenomics) . In vitrenomics) . The exaenomics) –17.ARID1A mutations are the most recurrent and widespread across many cancer types [ARID1A has been extensively described as a tumor suppressor in the literature [Arid1a in mice led to the formation of invasive adenocarcinomas in the colon [The deregulation of epigenetic modulation has been well established as a common occurrence in cancer. However, the extent of its involvement in the development and progression of cancer was underscored by genome- and exome-wide sequencing studies which revealed a close association between the epigenome and the pathogenesis of cancer. Most significantly, subunits of the mammalian BAF complex show an alteration frequency in over 20% of all cancers , 19. Amoer types . These mterature . Consisthe colon .ARID1A-deficient cells and accompanied by a loss of the active H3K27ac mark (acetylation of lysine 27 on histone 3) [While the BAF complex has also been shown to play a role in DNA damage repair , its pristone 3) . In thisARID1A in colorectal cancer patients. Analysis of several large datasets revealed an alteration frequency of up to ~ 12%  [ARID1A have been shown to lead to the loss of protein expression in tumors [ARID1A. These findings demonstrate that the loss of ARID1A protein expression is a frequent occurrence in rectal cancer patients.To begin with, we examined the mutation frequency for enomics) , 4 . These cell lines were specifically chosen because they expressed several BAF complex subunits to varying degrees  [. The guide RNAs utilized specifically target two intronic regions flanking exon 5 of ARID1A, resulting in a frameshift of any potentially transcribed and spliced product from the mutant allele  . The guiARID1A-deficient cell lines, we next sought to characterize them phenotypically. Surprisingly, in contrast to its described tumor suppressive role, we observed that the deletion of ARID1A led to a severe impairment in proliferation in two cell lines (HCT116 and DLD1) while proliferation in the other two cell lines (COLO320DM and HT29) was unaffected  displayed changes in gene expression associated with cardiac differentiation and Wnt pathway.To identify the gene regulatory networks responsible for the observed proliferation defects, we performed analyses of mRNA-sequencing data in HCT116 and DLD1 parental and  KO Fig. a. While KRAS gene. To further investigate whether ARID1A may preferentially promote the expression of downstream KRAS target genes, we compared three KRAS-mutated cell lines  to three wild-type counterparts  using the Morpheus tool [EREG, F3, and JAG1 as potential candidates that were particularly highly expressed in the KRAS-mutated cell lines compared to cell lines harboring wild-type KRAS  is a ligand for EGFR  which signals through the MEK/ERK pathway [F3 (tissue factor III) encodes a glycoprotein receptor for coagulation factor VII and initiates blood coagulation, but has also been implicated in cancer metastasis [KRAS-mutated CRC cell lines, EREG, F3, and JAG1 were all downregulated following trametinib treatment, thereby confirming that they are, indeed, MEK/ERK target genes  revealed that genes controlled by MEK/ERK pathway components  were specifically downregulated following ARID1A loss in HCT116  and DLD1 (KRAS) cells Fig. a. This feus tool . We iden pathway . One stu pathway . F3  displayed proliferation defects  in wild-type and ARID1A-deficient HCT116 cells. However, loss of ARID1A expression did not result in decreased phosphorylation of ERK in either HCT116  and presence in the same topology-associated domain. Using this approach, we identified 6,741 genes associated with the 3,061 potential enhancers. Further overlap of these genes with those downregulated following nes Fig. a. IntereLD1 Fig. b. The ChLD1 Fig. d and alsTo further confirm the link between the MEK/ERK signaling pathway and the loss of activity of enhancers, we attenuated the pathway using the clinical MEK1/2 inhibitor trametinib. ChIP-qPCR for JUND at these enhancers confirmed that the MEK/ERK pathway is essential for the maintenance of JUND AP1 transcription factor occupancy at these enhancers Fig. a. MoreovKRAS mutations are particularly dependent on ARID1A. In the absence of ARID1A, the proliferation of these cells is severely impaired, suggesting a tumor-supporting function in this context. Furthermore, we confirmed that ARID1A itself is, indeed, mainly localized at enhancers in colorectal cancer cells where it acts as a co-factor at regions bound by AP1 transcription factors, which act downstream of the MEK/ERK pathway. Consistently, we further showed that the attenuation of the MEK/ERK pathway leads to a disruption of this transcriptional network at enhancers as both ARID1A and H3K27ac are lost from these sites. This is accompanied by a downregulation in the expression of the associated target genes.The importance of epigenetic regulators in cancer has been widely recognized, and much of the current research is focused on deciphering the role of these regulators in driving oncogenic programs in cancer cells. As described in the previous sections, subunits of the BAF complex are among the most frequently mutated genes in cancer and are extensively described as tumor suppressors. In this study, we explored the role of ARID1A in transcriptional control of gene expression in colorectal cancer cells. We found that cell lines containing activating KRAS-mutated colorectal cancers, where an attenuation of the MEK/ERK pathway mimics the effects of ARID1A loss in these cells. Surprisingly, the primary function of ARID1A at these regions does not appear to be dependent upon the ability of the BAF complex to remodel chromatin since its loss had no effect on chromatin accessibility. This may be partially explained by other BAF complexes containing orthologues of ARID1A which may enable chromatin remodeling function [Smarcb1-deleted mouse embryonic fibroblasts, where H3K27ac is also globally lost from enhancers. Re-expression of Smarcb1 in that system restored H3K27ac, p300, BRD4, and Mediator binding in the chromatin fraction, supporting that enhancer activity could be restored [At the molecular level, ARID1A acts as a cofactor at sites occupied by AP1 transcription factors. Consistent with our findings, a direct interaction between ARID1A and FOS AP1 factors was previously reported . Our worfunction , but notrestored . In addiARID1A is a tumor suppressor, several research groups sought to model Arid1a-deficient cancer in mice. While these models confirmed its tumor suppressive role in various cancers, some striking observations were made which indicated that ARID1A could also play a pro-tumorigenic role in certain contexts. For example, in ovarian epithelial cancer (OEC), while Pten/Apc deletion led to the formation of poorly differentiated OECs in mice, the additional deletion of Arid1a caused tumor cells to have a less aggressive, more differentiated epithelial phenotype [Arid1a from otherwise wild-type mice protects against DEN (diethylnitrosamine)-induced hepatocellular carcinoma (HCC), while overexpression of Arid1a accelerated tumor initiation [Arid1a was shown to have very context-dependent roles [Arid1a in the background of Apc inactivation (which hyperactivates the Wnt pathway) blocked tumor formation [Smarca4 also attenuated Wnt-dependent tumorigenesis [KRAS mutation, the loss of ARID1A has an inhibitory effect on proliferation. This finding is further confirmed by the fact that mutations in KRAS and ARID1A are largely mutually exclusive in colorectal cancer patients. In future studies, it will be very interesting to decipher at which time point during transformation cancer cells lose ARID1A expression. In colorectal cancer, it appears that loss of ARID1A in wild-type backgrounds may promote early tumorigenesis while loss of ARID1A in the background of mutations in APC or KRAS may inhibit tumor progression  overnight at 4 °C. The next day, the slides were incubated with the boost-HRP secondary antibody  and stained using 3,3′-diaminobenzidine (DAB) (Medac) for 8 min at RT. Counterstaining was performed with hematoxylin. The slides were imaged using an Axioscope microscope (Carl Zeiss). The staining intensities of 164 biopsies were scored by a board-certified pathologist (P.S.).These experiments were performed according to the guidelines of the local ethics committee and with the requisite informed consent from all patients. Treatment naïve rectal cancer biopsies from 182 patients who were treated at the Department of General and Visceral Surgery, University Medical Center Göttingen, Germany, were collected and tissue microarrays were prepared. Immunohistochemistry for ARID1A was performed on these tissues. The slides were de-paraffinized, rehydrated, and then incubated for 6 min in a pressure cooker  with EDTA and Tween 20 pH 8. After cooling down, the slides were washed and incubated in 3% H2.HCT116 and HT29 cells were cultured in McCoy’s 5A medium (Gibco), and DLD1 and COLO320DM cells were cultured in RPMI 1640 (Gibco). All cells were tested to be mycoplasma free. All media were supplemented with 10% FBS, 1% glutamine, and 100 U/mL penicillin/streptomycin. Cells were maintained at 37 °C and 5% COFor proliferation assays, 5000–7500 cells were seeded in 24-well plates in multiple replicates. Cell proliferation was assessed by measuring confluence using a Celigo S Cell Imaging Cytometer (Nexcelom) every 24 h for 5 days, and plotted as relative confluence over time. The confluence in each well on each day was normalized with the confluence in that well on day one.For treatment with trametinib (Biomol GmbH), 20 nM of inhibitor was prepared in DMSO and diluted in media. As control, cells were treated with DMSO at a 1:1000 dilution.Different conditions were set up in a 24-well format, and cells were grown for 5–7 days. Once confluent, the wells were washed with PBS, fixed in 99% methanol for 10 min, and stained with 1% crystal violet prepared in 2% ethanol.2 (NEB), forward and reverse primers (Sigma), and Taq polymerase (Solis Biodyne). The reaction allowed 15 min of initial denaturation followed by 35 cycles of 30 s at 95 °C for denaturation, 45 s at 60 °C for annealing, and 60 s at 72 °C for elongation. Final elongation was carried out at 72 °C for 10 min. The PCR products were run on a 1% agarose gel at 100 V for 45 min and visualized using an INTAS imager.Each PCR reaction was conducted in a volume of 25 μL containing 10X buffer B (NEB), dNTPs (Jena Bioscience GmbH), MgCl® lysis reagent (Qiagen) according to the manufacturer’s instructions. One microgram of RNA was used for reverse transcription by MuMLV reverse transcriptase (NEB) to prepare cDNA. Quantitative real-time PCR was carried out using SYBR Green I (Roche Diagnostics GmbH) as a fluorophore with the following conditions: initial denaturation at 95 °C for 2 min followed by 40 cycles of denaturation at 95 °C for 10 s and annealing and extension at 60 °C for 30 s. qPCRs were analyzed using the standard curve method. For each gene, the expression was normalized to the expression of GAPDH [Total RNA was isolated in triplicate using the QIAzolof GAPDH . PrimersqPCR primers for ChIP were designed for the indicated enhancer regions. The following conditions were then used: initial denaturation at 95 °C for 2 min followed by 45 cycles of denaturation at 95 °C for 10 s and annealing and extension at 60 °C for 30 s. Primer sequences are indicated in Additional file w/v), 0.1% SDS (w/v), 1% NP-40 (v/v) containing protease inhibitors). The proteins were denatured by adding Laemmli buffer  and heating at 95 °C for 5 min. These were then resolved by SDS-PAGE and transferred to nitrocellulose membranes, incubated with primary antibodies . The deletion of the flanked exon (which contained a number of nucleotides not divisible by 3) was predicted to lead to a frameshift in any resulting spliced transcript, thereby leading to the loss of protein expression. The guide RNAs were cloned into a pSpCas9(BB)-2A-GFP (PX458) plasmid which was a gift from Feng Zhang  [ARID1A knockout. A single clone for each cell line was used for all experiments. Further information on the plasmid and gRNAs is provided in Additional file CRISPR/Cas9-mediated gene editing was used to generate e_48138) . PlasmidARID1A ChIP-seq was performed using a dual-crosslinking approach as described . Brieflyw/v), PIC). After allowing lysis, the SDS content was diluted to 0.5% SDS using 150–300 μL sonication buffer-2 , 20 nM NaF). The samples were sonicated in a Bioruptor Pico (Diagenode) for 15 cycles (30 s on/off). The soluble chromatin was pre-cleared with unconjugated sepharose. The chromatin was then diluted in dilution buffer  NP-40, 20 mMNaF 0.5% (w/v), sodium deoxycholate) and incubated overnight with primary antibodies . For ARID1A ChIP-qPCR, confluent cells in 15-cm plates were crosslinked in 2 mM EGS (Thermo Fischer Scientific) for 40 min at RT followed by crosslinking with 1% paraformaldehyde (Electron Microscopy Sciences) at 4 °C for 40 min. The samples were processed further as follows. Glycine (125 mM) was added to quench the formaldehyde/paraformaldehyde. The cells were harvested in nuclear preparation buffer . The nuclear pellet was isolated and resuspended in 150–300 μL sonication buffer-1  mRNA-sequencing were prepared using the Capture and Amplification by Tailing and Switching (CATS) RNA-seq kit (Diagenode) according to the manufacturer’s protocol using 50 ng total RNA as the starting material. For ChIP-seq libraries, the Diagenode MicroPlex Library Preparation Kit v2 was used according to the manufacturer’s instructions. Fifty bp single-end mRNA-sequencing was performed by Diagenode, Seraing, Belgium, on a HiSeq 2500. ChIP-seq libraries were sequenced by the Transcriptome and Genome Analysis Laboratory (TAL) of the University of Göttingen on the HiSeq 4000 (50 bp single-end). The concentrations of the libraries were measured using the Qubit 2.0 fluorimeter (Invitrogen), and fragment size was assessed using a Bioanalyzer (Agilent).ARID1A-deficient HCT116 cells) was downloaded from the NCBI GEO database  were called for histone modifications and narrow peaks for transcription factors and ATAC-seq data.Fastq files were obtained from the Transcriptome and Genome Analysis Laboratory (TAL) of the University Medical Center Göttingen (the data is deposited in ArrayExpress under the accession number E-MTAB-7792). Publicly available raw data were downloaded from NCBI GEO database  , 64. GenFastq files were downloaded from NCBI GEO . Mutual exclusivity of ARID1A and KRAS  mutations in the colorectal adenocarcinoma patient cohort from the TCGA PanCancer Atlas (b). Levels of pERK and JUND in Parental and ARID1A KO DLD1 cells (c). HSC70 was used as a loading control. The top 10 GO terms enriched for genes downregulated by ARID1A KO in the HCT116, DLD1, and COLO320 cell lines (d). Figure S2. Transcription factors that colocalize at all ARID1A-bound sites. These include several AP1 transcription factors (a). The AP1 binding motif is significantly enriched at all ARID1A-occupied regions (b). At all ARID1A-bound enhancers there is a reduction of SMARCA4 and SMARCC1 occupancy upon the loss of ARID1A (c). ATAC-seq signal remains unchanged and H3K27ac reduces significantly (c). (PDF 126 kb)Additional file 2:Tables S1–S4. (DOCX 31 kb)Supplementary tables. This file contains supplementary


The Commonwealth of Pennsylvania is implementing a mandatory Medicaid managed Long-Term Services and Supports (LTSS) program that covers people age 21 and older who are fully eligibly for both Medicare and Medicaid, living in a nursing facility paid for by Medicaid, or in an aged or physical disability home and community based services (HCBS) waiver. The overall program goals are to: Enhance Opportunities for Community Living; Improve Service Coordination; Enhance Quality and Accountability; Advance Program and Innovation; and Increase Efficiency. The program will be administered by 3 managed care organizations (MCOs) that are obligated to coordinate with Medicare Advantage and D-SNP plans. This major policy change affects the traditional roles and responsibilities of the aging network by shifting the locus of control to insurance companies. This presentation will describe the policy change, the implications for the aging network, and the multi-method evaluation designed to assess the implementation and outcomes.


Anesthesiologists returning to clinical practice pose unique challenges for licensing and credentialing boards. Few institutions provide re-education. We describe the physician refresher/re-entry program at our College of Medicine.  We launched the physician re-entry program in 2006. This individualized program re-educates physicians who left clinical practice for any reason and are seeking to return. We report results achieved for 12 anesthesiologists who successfully completed the course between August 2012 and February 2018.  Seven men and five women left their practices for various reasons, which included relocation, family or medical reasons, substance use, and burnout. None left practice for medical negligence. Range away from clinical activity was 0–10 years. Five had active licenses. Seven were US graduates and five were international. Nine of 12 achieved their goals. Of the 3 others, 1 did not pursue her goal, another did not obtain a residency, and the other just finished the program. Seven out of 9 (78%) achieved their goal within 1 year of course completion.  Despite our small sample size, our experience to successfully return inactive physicians to the workforce adds to the scant literature and experience in refreshing inactive physicians. Our trainees return to practice serving communities across the country and are now a pivotal part of the anesthesiology workforce. Thus, this program not only services individual physicians, but the whole community affected by their absence. Practicing physicians leave medicine for multiple reasons including illness, family responsibilities, career dissatisfaction or change, substance use, and early retirement , 2. RetuFew programs address the professional and educational needs of inactive physicians, especially in anesthesiology . In geneIn 1968, the Medical College of Pennsylvania was among the first universities to initiate a re-entry program for nonpracticing physicians returning to clinical practice , 8. SuccUpon initial contact, the program director and returning anesthesiologist discuss relevant career background, anticipated future practice scope, reasons for leaving and returning, organizational requirements, and specific goals or expectations. Then, if the physician desires, the program director communicates with referring groups to further identify parameters for the physician's individualized re-education. All initial application review is by the director, steering committee, and then specialty-specific preceptor. The director and preceptor further conduct phone interviews with trainees to assure that goals can be met. Accepted trainees are enrolled in 6-week blocks  for 6, 12, or more weeks depending upon the individualized goals and recommendations. To optimize focused attention, in the anesthesiology department, one re-entry physician is accepted at any one time.The distinct outcome of this re-entry program is the refresher and update of skills are necessary to practice anesthesia as the American Board of Anesthesiology would deem fit. This includes sufficient knowledge base, application of knowledge to develop sound plan, and reinsertion into CME cycle requisites. Re-entering physicians, each with their own specific obstacles and needs seek a refresher; we ask them to identify their primary goals. Ascertaining said goals helps to further personalize the program, address each learner's individual needs, and fine-tune interactions with preceptors. We believe that going beyond the textbook and organizational needs to address the varied backgrounds of participants is crucial to fostering a constructive, successful environment.The program director, physician trainee, preceptor, and program coordinator develop an individualized curriculum. Several components of the program are mandatory; however, within the mandatory components, the individual cases and days can be adapted based on the physician's career goals. This process is informed by an initial needs assessment, during week 1, over a 2-day period, including Post Licensure Assessment System (PLAS) multiple-choice examinations, oral discussions of clinical scenarios, three standardized patient evaluations and their documentations. The information from the needs assessment is reviewed with the student over a two-day long feedback didactic session in a group setting. Concepts are reinforced, or new concepts introduces, as trainees learn from one another as well as the faculty. This allows trainees to contribute to each other's experiences and expand learning from everyone's topics and issues. The re-entry physician also completes a clinical interest survey to communicate their focus of interest for program scheduling. While trainees all follow the overall structure of the preceptorship, there is flexibility based on needs and goals within each component. For instance, all trainees receive formative feedback on their standardized patients' evaluations. If a trainee needs more practice with communication skills versus medical content, then cases for practice are selected to meet their individual needs. Another example is in the self-selection of the anesthesia cases among all operating rooms, based on the physicians' individual goals. Trainees keep a daily patient/case log to assure a wide range of clinical exposures that meet their specific future work goals. Trainees also write pre/postop notes for practice, on encountered patients in a word document , which they review weekly with their preceptor for summative feedback. Preceptors together observe the trainee's recorded standardized patient scenarios  using a communication skill and medical content checklist to identify strengths and potentials for improvement. Updating computer, presentation, and peer teaching skills are other aspects of training.Similar to the program at Mt. Sinai, this program does not provide a hands-on experience for inactive returning anesthesiologists . Our proIn a tertiary academic center in an urban setting, physicians are exposed to an all-encompassing variety of real patient cases highly beneficial to a re-entering physician, who are seeking to update their skills and regain their confidence. Re-entering physicians choose from a myriad of available cases to suit their individual needs based on their self-assessed and practical future goals, similar to adult learning models. Candidates do not perform hands-on procedures but have direct interaction with the patients in the perioperative setting. Day-to-day discussions of comorbidity and subsequent anesthetic plans are reinforced by preceptors at the bedside. Re-entry physicians follow these patients into the operating room and witness their entire induction, maintenance, and emergence. They witness the assessment and recovery process in the postoperative care unit. Throughout this process, they are expected to actively interact, question, and learn from the perioperative team. We have learned that after applying didactic learning to such experiences, physicians are confident and academically up-to-date to enter a clinical setting where their employers often then provide an initial short supervised period.Two to three times during each 6-week period , physicians evaluate standardized patients for formative and summative feedback. Cases have been written by Drexel physicians ; there is access to a large variety of scenarios, both for communication and clinical content. The cases and checklists are standardized, identical to ones used for Drexel medical students, residents, and physician re-entry trainees. The level of the re-entry anesthesiologist is different from that of the other learners, but the content still proves useful. After the evaluations, as a group in an interactive setting where all contribute, learners, and faculty review the recorded evaluations, provide feedback, and are scored based on standardized checklists. The checklists measure interviewing skills as well as content medical knowledge. The content medical knowledge lists questions a physician should ask to elaborate a focused history of the specific chief complaint and elicit/narrow its differential diagnoses. The interviewing skills measure data gathering, interpersonal, information giving, and organizational skills as well as standardized patient satisfaction. As such, physicians first practice, learn, and improve in a safe and controlled environment.https://dxrgroup.com/healthcare-education-products/dxr-clinician/, Doc.comhttps://doc.com/, and Aquafer https://www.aquifer.org/). Each program has its own learning objectives. Participants are expected to complete 1-2 modules  per week in each program and encouraged to redo modules as reinforcement, for practice in a virtual and safe setting. Didactic learning is assessed via multiple-choice or short-answer exam questions with feedback. Trainees report that these resources are invaluable for their learning and often voluntarily complete more modules than their weekly assignments.To assure reentering physicians' re-education parallels current up-to-date medical education, which may have been different from the physician's early medical education, we incorporate technology as a learning tool. In addition to in-person didactics and discussions in anesthesia conferences, the curriculum includes web-based interactive programs for focused learning and assessment on medical knowledge, communication skills, and clinical reasoning. Three distinct sources provide these online annotated video and virtual patients  format to reinforce documentation skills, which they review through case logs with preceptor weekly. The templates are from the EHR, copied as pdf file where trainees may write their notes, but they are neither online nor part of the patient's permanent records; the documentations provide room for practice and learning. Trainees could participate in further EHR training with administrators, based on their individual needs.Trainees participate in grand rounds, clinical cases, and conferences. Trainees learn within a multidisciplinary team with the entire anesthesiology staff  and self-select to work closely with faculty who share their interest. Each physician regularly meets one-on-one with a designated anesthesiology mentor for two hours for further individualized learning. These meetings include oral presentations, discussion of daily OR cases, review of notes, and summative performance evaluation.Trainees participate in simulated scenarios in a multidisciplinary setting alongside nurses and other healthcare providers using the same simulations used to teach anesthesiology residents. These sessions include trained individuals as simulated patients to create realistic patient encounters, including but not limited too medical history obtain, consenting, conflict resolution, and ultrasound training. Robotic models that display changeable vital signs, can be “administered” medication, and be subjected to procedures which mimic acute scenarios. Sessions take place in the simulation center and are designed to benefit all learners involved; anesthesia trainees gain personal and interdisciplinary experience in this fashion. Learners are able to participate as the primary clinical provider and observe others. Each trainee has at least one simulation session during the re-entry period. These sessions are followed by debriefing sessions where the scenarios are discussed in detail for learning opportunities.During the orientation week, students meet with the science librarian for information technology skill sessions to learn evidence-based medicine research skills for continued self-improvement after the program. Trainees are expected to use these skills during their presentations; they are required to make one formal presentation on any self-chosen topic to their peers as well as volunteer for informal self-selected clinical presentations.Most re-entry physicians confront emotional, personal, career, and financial barriers when returning to practice. The continuing medical education department provides hours of career and emotional support before, during, and after the program. We advocate on trainees' behalf by writing letters, brainstorming career options, providing networking and employment introductions, and speaking to committees/employers.Weekly evaluations monitor achieved learning goals. We regularly seek trainees' written and verbal feedback, review gaps, and adjust schedules. Faculty provides summative feedback weekly on trainees' clinical knowledge, communication skills, professionalism, history taking and documentation skills, and formative feedback using evaluation forms also used for medical students. Since all faculties participate in teaching medical students and residents, they use these evaluation forms regularly. Each trainee receives a minimum of 1 evaluation per week of the course. Upon completion, each trainee receives a detailed evaluation letter and certificate explaining their accomplishments and assessments; individual faculty feedback is listed, as well. The letters do not endorse competency for practice; rather they report on physicians' accomplishments.Results reflect 6-year data from anesthesiology department re-entry physician trainees, from August 2012 to February 2018. Twelve physicians began and completed the anesthesiology re-entry program. Trainee demographics are in Each physician noted their specific goals after program completion . Nine ofReturning physicians bring unique backgrounds, needs, skills, and knowledge from their nonclinical experiences. Inactive physicians face difficulty returning to work for various reasons. Increasingly, they are asked to gain re-education. A re-entry program should provide flexible individualized re-education to meet physicians' varying needs. Assessment is important for ongoing improvement, and a re-entry program is an effective way by which physicians can seek assessment and improve their professional skills , 10, 11.We seek physician feedback for constant improvement; thus, we have learned important lessons. A multidisciplinary team of faculty, resident, and nursing support is critical to trainee re-education. Clinician-educators are best suited for re-entry physicians, as they are at the forefront of education. Re-education is best among a community of learners alongside fellows, residents, and students. The university provides undergraduate and graduate medical education; anesthesiology re-entry physicians learn alongside a variety of learners. This variety of knowledge distribution strengthens clinical skills and promotes the learning process. Interactions within this structure help to boost confidence and teaching skills. The re-entering anesthesiologist contributes to the learning of others by bringing nonclinical experiences.We explain choices available to trainees and obstacles they may face during or after the course. After hours of career and personal counseling, some may opt not to pursue re-entry, as with one of the trainees. Randomly, some trainees maintain close contact with us years later, reaching out for news or even guidance. We have expanded our career advisory roles, as trainees return for networking and advice long after program completion. We have an alumni association, where current trainees communicate (online or in person) with alumni for questions and support. Despite challenges of re-entry, participants are eager to regain proficiency and as evident in our program, the majority has succeeded in achieving their anticipated goals.The re-entry program has been a part of the College of Medicine since 1968, yet challenges still persist. While the re-entering physicians may learn in one department, resource utilization in other departments  requires timely coordination. While an academic setting is ideal for education and patient scenario variety, at the same time there are many learners  which necessitate clever and planned space coordination. Costs are significant in time and personnel due to the need for dedicated staff and faculty . Two proFollow-up with re-entry physicians to ascertain goal completion in short term is achieved via direct contact with participants. These individuals often keep informal contact with the program to share their success and positivity. As years progress, it becomes difficult to maintain contact and ensure long-term achievement. Further program improvement includes developing dedicated means to contact destination sites to ascertain trainee status and provide long-term support.This paper reflects 12 physicians' experiences; there is clear need for continued program evaluation. Our general re-entry program originally began in 1968; the anesthesiology track was developed in 2012. While this physician cohort, with representation from all regions and backgrounds, has had a 75% success in reaching their individual goals, we reflect short-term data upon program completion. Although our results are encouraging, there are more questions that need further investigation. Of specific note, areas of interest for future study could include which learning activities were of most use, if coaching support was beneficial, or if supervision upon reinstitution to practice helped support reintegration. For instance, it would be interesting to note if re-entering physicians more readily leave medicine again; or if they left for medical reasons, is relapse common; or do they enter advocacy fields to help colleagues maintain practice. Even as such, this anesthesiology physician re-entry program can provide a useful service to the community.A multidisciplinary team of faculty, resident, and nursing support is critical to trainee re-education.Clinician-educators are best suited for re-entry physicians, as they are at the forefront of education, and this is best accomplished among a community of learners alongside fellows, residents, and students.The re-entering anesthesiologist contributes to the multidisciplinary variety of knowledge and strengthens clinical skill that accelerates the learning process along with a boost of confidence.


Oocyte donation is one of the assisted reproductive techniques that can undermine the mental health of the women donor. As such, the aim of this study is to design a mental health promotion program for oocyte donors.This is an exploratory mixed methods study  that consists of three phases. In the first phase, a qualitative study will be conducted to identify the needs and strategies of the mental health promotion program for the women donors. In this phase, the participants will be selected using purposeful sampling method and the data will be collected through semi-structured interviews. In the second phase, the initial draft of the program is designed and validated in the panel of experts and using the classic Delphi technique and, then, the program is finalized. In the third phase, the designed program will be implemented as a quasi-experimental study in two groups of program recipients (intervention) and control, and the effectiveness of the intervention program will be evaluated.In order to design a documentation-based mental health promotion program for the oocyte donors, their experience during the process of oocyte donation should be evaluated. Doing so, the program will be developed based on the specific circumstances of the target population and their social and cultural context and, hence, will have the highest impact. Oocyte donation is both psychologically and morally so challenging for the donors. Given the mental complications caused by oocyte donation and considering ethical principles in assisted reproductive treatments, an intervention program seems necessary to maintain, provide and promote the mental health of the donors. The present research will provide some comprehensive information regarding the needs and strategies for improving the psychological health in the oocyte donors. Using an exploratory mixed method, this study will be conducted in three phases. In the first phase, a qualitative study will be conducted to extract the needs and strategies of the mental health program for the oocyte donors. The participants in this phase will be selected using purposive sampling method and the data will be collected using semi-structured interviews and taking notes in the field. The data will be analyzed using the conventional content analysis method. In the second phase, using the information obtained from the previous phase and review of the literature, the initial draft of the mental health program for the oocyte donors will be prepared. Then, using classic Delphi technique, the program will be validated and finalized in the panel of experts based on the priorities. In the third phase, the designed program will be implemented using a quantitative approach, and the effectiveness of the program will be evaluated comparing the mental health status of the two groups of donors before and after the implementation of the program. As such, this program designed based on a qualitative study and review of the literature and the newest information, can improve the mental health of the oocyte donors.The use of donated oocyte in assisted reproductive technology (ART) is an accepted method in the treatment of the couples who cannot be pregnant through autologous oocyte . The useIn this method, the whole processes of the ovarian stimulation, ovarian response monitoring and the oocyte retrieval are performed on the oocyte donors and, after in vitro fertilization or intracytoplasmic sperm injection procedure, the resulted embryo or embryos are transferred to the uterus of the recipient woman . In thisThis experience had not been satisfying for many donors . In addiMaterialistic use of the body for gaining financial benefits is another related issue . AnotherPrevious studies also show a decline in the mental health of the donors during this process , 12, 13.Among the Muslim countries, Iran is the only country in which using a third-party and oocyte donation is allowed in the process of reproduction , and manThis study approved by the Ethics Committee of Isfahan University of Medical Sciences in Isfahan, Iran (IR.MUI.RESEARCH.REC.1398.492), and will be conducted in the centers for providing ART services in Isfahan. Informed consent will be obtained from the participants at all phases of the research. The design of the program will be based on the Talbot and Verrinder model and will be implemented in three phases.The first step of this programing pattern includes the analysis of the needs and determination of a specific subject for programing. The draft of the program will be designed in the second step; then, the finalization of the program, its implementation, monitoring of the implementation and evaluation of the effectiveness of the program will be performed in the third to sixth steps respectively . In the In the second phase, in line with the second and third steps of the pattern, the initial draft of the mental health program for the oocyte donors is designed and validated using the panel of experts and the classic Delphi technique. In the third phase, in line with fourth to sixth steps of the Talbot and Verrinder programing pattern, the program will be implemented and whose effectiveness will be evaluated.Using in-depth interviews, the qualitative study will be conducted to explain the needs and strategies of the program. The setting of this phase of the research is the centers for providing ART services in Isfahan. All of the interviews will be conducted in a private place selected based on the preference of the participants. The providers of ART services will also interviewed in their workplaces. After analyzing the qualitative data by the content analysis method, the proposed needs and strategies of the program will be extracted.The participants of the qualitative phase of this research consist of the oocyte donors, the providers of ART services  and the family members of the oocyte donors who are willing to take part in the study. The participants will be selected using purposeful sampling method and considering the diversity of the age, education, number of their oocyte donation, and the motivation for entering the process of donation. After evaluating their inclusion criteria and obtaining their informed consent, the participants will be interviewed. The interviews will be continued until the repetition of the data and the feeling of reaching data saturation.In the qualitative phase of the research, the data will be collected using in-depth interviews, taking notes in the field and reading the notebooks of the women donors. To observe ethical considerations, the participants are explained about the aims of the study and their informed consent will be obtained for recoding their voice. The setting and the length of the interviews will be specified based on the preferences of the participants. Data analysis will be performed using the conventional content analysis . To assuIn the qualitative study, Iranian oocyte donors that a maximum of 6 months have passed from their entrance to the process of donation will be included in the study. Other inclusion criteria include no history of hospitalization or the use of medicine because of mental disorders, absence of stress, anxiety and severe depression in them, no history of ovarian hyper-stimulation syndrome in previous donations, and no legal problem related to donation. The inclusion criteria for the providers of donation services will be at least 2 years of work experience.In this phase of the study, the priorities of the program will be developed based on the results of the first phase and the extracted strategies. Using review of the literature, the objectives and the operational program for achieving each objective are developed, and the validity of the program will be evaluated through using Delphi method in a study.In this stage, in order to design the final version of the program and obtain the experts’ consensus of opinion, the initial draft of the program is designed and, then the classic Delphi technique is used for validating the program and determining its priorities. The members of the panel will consist of reproductive health specialists, planning experts, gynecologists, psychiatrists, sociologists, psychiatric nurses, psychologists, lawyers, and midwives. The electronic version of the program (and the hard copy if needed), together with open questions, will be sent to the members of the panel. These questions are to obtain the written opinion of the panel experts about the components of the program. After collecting the written opinion of the experts, content analysis will be performed and applying their opinions, the corrected version together with the assessment checklist is given to the experts. Then, collecting their opinions, the corrected version will be given to the experts. It is predicted that the program will be finalized during four rounds.In this phase, the quantitative study as a multi-stage, two-group and field trial will be conducted on 72 oocyte donors.The setting of the research is the centers for providing ART services in Isfahan. Infertility and Shahid Beheshti fertility centers in Isfahan will consider as a research environment. The target population of the study consists of the oocyte donors at the time of the oocyte donation during the process of assisted reproductive treatment. Convenience sampling method will be used to select the subjects of the study.Inclusion criteria at this phase of the study will include the absence of a known and under treatment physical illness, no oocyte donation during the past year, and no exposure to significant stressors during the past year based on Holmes and Rahe checklist (< 200 score); and if the ovulation induction is stopped because of the request of the recipient, the sample will be excluded from the study.Before the implementation of the intervention group, the sampling process will be performed for the control group; then, the program is implemented and the sampling process will be done for the intervention group. The variables considered in this study will include depression, anxiety and stress levels in both groups during the three stages before the start of the oocyte donation, on the eighth day of the menstrual cycle (the time of the first follicle growth monitoring after ovulation induction) and after oocyte pick-up. To this end, the self-report DASS-21 questionnaire will be used. The DASS-21 questionnaire is a 21-item self-report tool in which each of the depression, anxiety and stress levels are assessed using seven items . Each ofThe collected data will be analyzed using SPSS19 as well as descriptive and inferential statistical methods. Kolmogorov–Smirnov test will be used to evaluate the normality of the data. To compare quantitative baseline characteristics in the two groups of the control and intervention, independent t-test will be used, and for the comparison of the qualitative baseline characteristics, Mann-Whitney test will be used. Moreover, to compare nominal qualitative variables, chi-square will be used. Finally, repeated measures multivariate analysis of variance will be used to compare the mean of the mental health scores between the intervention and control group at the three measurement times.The process of oocyte donation confronts the donors with social and ethical challenges that endanger their mental health. However, supportive programs can prevent the psychological injuries caused by such confrontations , 22. OocHowever, the present program will be designed based on the socio-cultural and religious context of Iran and will provide robust information about the needs and strategies of the mental health promotion program for the women donors. As such, this program seems to be suitable for countries with similar characteristics such as the South Asian countries. Nonetheless, many of the obtained strategies may be applicable to other societies including Westerns countries. Thus, efforts will be made to develop strategies in such a way to be used in infertility centers, especially in countries with a socio-cultural structure like that of Iran. We hope that the designed program will have the capacity for being integrated into the instructions of ART service centers to take a step forward towards improving the mental health of the oocyte donors.


Categorization of terms/concepts/constructs that allows for better understanding and comparison of public health interventions is often lacking in program implementation and evaluation. A classification system such as a lexicon, when used appropriately, can help address this need. The present narrative describes a lexicon of policy, systems, and environmental change strategies (PSEs) that was developed and prototyped to aid local implementation of Supplemental Nutrition Assistance Program Education (SNAP-Ed) interventions in obesity prevention. The lexicon was reviewed and refined by a panel of experts who provided iterative feedback on the system's scope and utility. To develop the lexicon, a team from the local health department: (i) conducted an inventory (community context scan) of SNAP-Ed PSEs implemented in Los Angeles County during 2010–2015; (ii) assessed commonalities among PSEs that were translated into “index factors” to contextualize terms/concepts/constructs relevant to SNAP-Ed services planning; and (iii) convened a panel of experts to review and test the classification system for quality and usability. In the latter activity, the panel reviewed the terms/concepts/constructs within the context of two geographical areas and by the selected PSEs. The final version of the lexicon organized the terms/concepts/constructs of the local SNAP-Ed PSEs into overarching categories, so they can be compared/assessed by type, content, and/or impact. The goal of the project was to create a classification system that can help facilitate meaningful communications among program implementers, evaluators, and community stakeholders. The lexicon has practical implications and potential applications for other jurisdictions interested in reducing obesity rates through SNAP-Ed PSEs. •Policy, systems, and environmental changes (PSEs) in prevention can vary widely.•Comparison of PSE strategies is limited by a lack of standard categorization.•A lexicon can improve communications among PSE implementers and evaluators.•A lexicon can enhance data comparability and help shape PSE designs/evaluations. StandarThe lexicon developed and presented in this narrative is specific to public health interventions focused on obesity prevention, a priority area that is well-characterized in the literature . The nar22.1Healthy, Hunger-Free Kids Act, the federal United States Department of Agriculture (USDA) SNAP-Ed program adopted a socioecological framework to guide service delivery of nutrition education and related health promotion resources (With passage of the esources . A benefesources . Under tesources .During the latest SNAP-Ed funding cycle (2013–2016), planners of the Los Angeles County effort recognized, early on, that a common language describing the SNAP-Ed interventions may be necessary to facilitate meaningful communications and coordinated actions among implementers, evaluators, and community stakeholders. They understood that such a classification system  should be constructed based on data and information from a landscape analysis of regional policies and programming before and after the start of the latest cycle of SNAP-Ed funding, an accurate assessment of population health burden, and qualitative input from experts who have extensive knowledge and experience in implementing PSEs.2.2To develop the lexicon, the project team utilized data derived from several program sources, including: (1) a community context scan, (2) a health indicators project that synthesized health data by geographical region, and (3) a convening of an expert panel, using the modified Delphi method to pilot test and refine the classification system. The Delphi method is an iterative process framework based on multiple rounds of queries, typically asking experts to reach consensus or to explore areas of future thinking that goes beyond what is currently known . The itehealthy food and beverage standards, community gardens, healthy retail makeover, and farmers markets.(i)Community context scanThe lexicon groupings were referred to as “index factors” in this project, representing observed commonalities or identified patterns of PSEs that are organized or contextualized in a meaningful, consistent way. To group and assign terms/concepts/constructs to these index factors, data were obtained and synthesized for four key SNAP-Ed PSE strategy interventions implemented in two of the eight Service Planning Areas (SPAs) in LAC –Metropolitan (SPA 4) and South Los Angeles (SPA 6). Both SPAs covered geographic areas where there were high densities of low-income, SNAP-Ed eligible households. SNAP-Ed eligibility is determined primarily based on census tracts where at least 50% of the population have income at or below 185% of the Federal Poverty Level (FPL). The four selected interventions (focus areas) included: (ii)Health indicators projectThe community context scan, developed in partnership with Ad Lucem Consulting, included an initial review of relevant obesity prevention efforts in Los Angeles County during 2010–2015. The resulting database cataloged obesity prevention activities in the region for the past 5 years. It included information derived from a series of 51 key informant interviews with leaders of various sectors such as academia, non-profit, government, community clinics, and the private sector . Special focus was placed on capturing a snapshot of target areas of SPAs 4 and 6 where many residents were poor and were eligible for SNAP-Ed services. The context scan provided qualitative and quantitative data that aided the development of the lexicon, including information on type, setting, reach, factors associated with program implementation, and sustainability of key PSE strategy interventions. The scan was not an exhaustive review of all PSEs in LAC during 2010–2015.Communities of Excellence in Nutrition, Physical Activity, and Obesity Prevention (CX3) project contained pertinent neighborhood-level data that were acquired using the recommended community assessment tool developed by the California Department of Public Health. In combination, this information provided context and contributed to the methodology that was used to categorize and operationalize the health elements (terms and constructs) of SNAP-Ed interventions and services implemented in LAC.(iii)Panel of expertsPopulation-level health indicators for SPAs 4 and 6 were assessed in parallel to the community context scan during the 2010–2015 time period using the California Health Interview Survey (CHIS). CHIS data were broken down by SPA designations; for comparison, data for SPA designations other than 4 and 6 were also included. To explore differences in the health indicator by selected geography and demographics, several statistical analyses were conducted to describe the associations between the indicators and known risks of obesity and nutrition-related diseases . When feasible, these indicators and other existing sources of data were used to inform and select key terms/concepts/constructs for inclusion in the lexicon. For example, data sources such as the Using a modified Delphi method, the lexicon categories that were derived from the community context scan and the health indicators project were further contextualized with input from a panel of experts convened by DPH. The panel of experts (there were four of them) comprised members with expertise in PSE implementation and community design. As a condition of participation and to preserve confidentiality, each member's organizational affiliation(s) were not disclosed. These experts' input allowed for selective testing/prototyping of terms/concepts/constructs identified in the first two phases of the lexicon development process. The overall Delphi process took approximately 6 months to complete – two rounds of surveys, one group discussion, and the synthesis of data gathered.3Using the community context scan results , Table 2In the convening of the panel of experts, the terms/concepts/constructs derived from these first two phases of lexicon development were pilot tested and further refined for quality and usability – i.e., how the terms/concepts/constructs should be interpreted and applied in real world situations; under which context should they be used to plan and/or inform action , Table 6distribution or receptivity of PSE strategies or programming in the field or in each community/region that may correlate with the reach and/or impact of a program or PSE activity in that community.The results of the modified Delphi allowed the project team (representing the SNAP-Ed project in LAC) to fine-tune several of the terms/concepts/constructs in the lexicon. For example, “intervention spread” became more multi-dimensional with added complexity based on inputs from the panel. The term or concept was ultimately defined as the Because the overarching categorization approach was not intended to be exhaustive , they should be interpreted within the context of continuous learning and application of best practices using data from the most available evidence base. The lexicon ultimately serves as a starting point for facilitating a more standardized dialogue among program implementers, evaluators, and community stakeholders; these groups are responsible for making the various SNAP-Ed interventions a success across the county. It has been estimated that during 2010–2015, >150 PSE strategy interventions were successfully implemented throughout LAC .4Despite consensus on how to improve nutrition and related health behaviors, little is known about which mix of strategies is optimal for preventing these obesity risk factors in different settings . This laSystematic naming or classification of intervention parameters and related index factors can provide greater opportunities to standardize data collection and analysis. Over time, having commonalities in information management and synthesis terminology can lead to more reliable and accurate longitudinal tracking of progress in program implementation. This in turn can lead to better designs of program improvement efforts; not to mention greater confidence in the validity of the information being gathered, communicated, and used. More specific intervention descriptors and classification protocols can enhance surveillance and allow for greater ease in replicating interventions because of reduced guesswork in the definition and application of what is/are effective in a specific community. The capacity to generate and use this type of iterative process can, if done meaningfully, help lower the overall cost of intervention selection and implementation, and may help facilitate quicker diffusion of innovations .The lexicon is intended to address these and other issues about program implementation and evaluation. By categorizing a broad range of factors that could be considered within each PSE type, the system ultimately aims to help program implementers, evaluators, and community stakeholders communicate their vision and roadmap for program implementation, using a consistent vocabulary to describe, execute, and evaluate PSEs. The need for clear delineations within and between the selected strategy interventions was apparent during the modified Delphi discussion. The panel of experts was given an opportunity to pilot test or prototype  several key terms/concepts/constructs within the context of implementation nuances for each of the selected strategies. The resulting inputs were invaluable for refining the lexicon – e.g., variations among communities around safety, gentrification, organizational capacities, political will, and density of eligible populations within eligible census tracts became added considerations in the construction of the system.The present narrative describes the development and refinement of a lexicon that can be used to better understand PSEs in their “real world” context, especially as they relate to the growing obesity epidemic in LAC. The classification system (a tool) is proposed as an iterative approach for program planning and implementation, with built-in flexibility for ongoing adjustments and updates. By organizing PSEs into lexicon categories, the present project sought to establish a usable framework for improving local program communication and implementation of SNAP-Ed strategies. Future efforts should consider adapting and optimizing this lexicon for use by other LHDs that are interested in streamlining or improving SNAP-Ed delivery across the United States.5Public health practice is driven by an ongoing process of systematic surveillance, data collection, analysis, and interpretation of results. The value of these outputs depends on their comparability, application, and how they are communicated among program implementers, evaluators, and community stakeholders. Current PSE categories are generally too broad or amorphous to allow for meaningful, consistent comparisons or documentation of program progress/impact. A lexicon on intervention type, content, and impact, based on agreed upon terms/concepts/constructs, can help address this gap in public health practice. During a time of heightened scrutiny of public health programs, the need for meaningful categorization of program interventions is critical. In the case of SNAP-Ed in LAC, a lexicon of PSE strategy interventions appeared to confer added value for addressing this accountability process in social and health services delivery.The authors report no financial disclosures or conflicts of interest.