In Canada, employment/education support is rarely embedded as a component of mental health service delivery. This study describes a supported education/employment program (SEP) that integrates both clinical and community mental health services. The main objectives were to estimate the feasibility of a 5-week SEP among youths aged 17–24 with mental illness and to estimate the extent to which participation in this program improved employment and mental health outcomes.This was a single cohort study. Feasibility outcomes assessed were demand, acceptability, practicality, integration, adaptation, and effectiveness. These were assessed through recruitment and retention rates, recording patterns of missing data, and examining differences between completers and non-completers. Appropriateness of the outcome measures was assessed through the strength of the association between the outcome measures at baseline. Effectiveness of the program was assessed through employment and as measured using MyLifetracker (MLT), Satisfaction with Life Scale (SWLS), and the Canadian Personal Recovery Outcome Measure (CPROM).A total of 110 youths with a mean age of 20.6 (SD: 2.2) were recruited. At 5 weeks, 82 (74.5%) of participants remained in the program. Of the people who completed the program, 56.1% were women, 76.6% were in stable housing and 64.1% had depression. Approximately 60% of non-completers used two or more services and were in at-risk housing. More than 25% of participants improved on the patient-reported outcomes. Scores on these measures were moderately to highly correlated with each other. Employment rates varied and corresponded to the waves of the COVID-19 pandemic in Canada.Results showed that this program was feasible and there was high demand for SEP during the COVID-19 pandemic but gaining employment remained difficult. Educational or employment outcomes, measured over a short period, may not be adequate. Instead, individualized and patient-reported outcome measures may be more appropriate for SEP programs. Employment shapes income, living conditions and access to resources, affects psychological functioning and identity, and influences health-related behaviors such as quality of diet, engagement in physical activity, tobacco use, and substance dependence  model , 14. IPSThis study had two objectives:  to estimThis study was a 16-week single cohort study assessing the effectiveness of the YESS program. This paper presents results based on data collected at three timepoints: baseline, 5-, and 16- weeks.This study was funded by a Service Canada grant to increase employment in youths with MHSU disorders. The funding was specifically catered to youths aged 17–24 years old who were neither employed nor in educational or training programs and the main outcome for this program was employment as set by the funder.This study was conducted in Vancouver, BC, Canada. The YESS program was conducted is an integrated youth service centre that provides psychiatric care, psychosocial rehabilitation and other services for youths aged 17–24 with mental health and substance use (MHSU) challenges in the Greater Vancouver Area. In this centre, all participants have access to mental health support services like counseling, substance use support, peer support, and psychiatric services.Participants were recruited at the centre. Eligibility criteria included the following: interested in pursuing employment, not employed or in school for <15 h per week, aged 17–24 years, and diagnosed with a mental illness  or substance use disorder. Eligible participants were contacted by center staff. All participants who expressed interest were recruited into the study since participation in the research study was a requirement for the YESS program. Recruitment occurred over a 13-month period from November 2019 to December 2020. During the COVID-19 pandemic, recruitment was done online through advertisements on Google and Instagram. Participants were screened for YESS program eligibility by staff at the center and a research coordinator. All participants provided written informed consent prior to any research procedures taking place. The study was approved by the University of British Columbia's Behavioral Research Ethics Board (H21-01510).For this feasibility study, we set out to recruit 100 participants for the 16-week duration of the study due to staff capacity and logistical reasons. After factoring in a 10% drop-out rate, we aimed to recruit 110 participants.The TiDier guidelines were used to describe this intervention . The YESUpon recruitment into the program, the team first assessed the participant's employment history, strengths, interests, and skills. When these were identified, the team worked together with the participant to explore different career options and select the relevant training courses needed for gainful employment. For participants who did not have a specific job in mind, the team worked with them to help with the job search and job application.Job matching to specific industries was facilitated by the IPS specialists. To enable a successful job matching, team members first did an environmental scan to identify and engage local businesses, educational and training programs in the Greater Vancouver Area. They also worked with the staff at the youth center to identify local businesses that had existing relationships with the centre. In addition, members of the team attended job fares, and employment programs networks to leverage resources. An updated list of job opportunities in the Greater Vancouver Area was sent to all participants on a bi-weekly basis.The whole duration of the YESS program was 5 weeks, with follow up support up to 16 weeks. As youths were recruited throughout the year, the 5-week intervention was offered every 3 months. During the first 5 weeks, the primary intervention was one to one work readiness and job matching support provided by the IPS specialists. Youth could also participate in small group training workshops if they were interested. Examples of these small group workshops include: Understanding Emotions, Mindfulness, Coping Strategies, Communication Skills, Motivation, Resumes and Job Searching techniques, Interview Skills, Disclosure and Accommodations, and Preparing for Workplace. These workshops were held twice a week and each session was an hour long. The workshops were delivered in person in small groups, however this format changed to virtual workshops due to the COVID-19 restrictions in March 2020 . One to one support was also changed to virtual sessions during the pandemic. Some participants also obtained additional training  as needed for their desired job. These courses ranged from a few days to more than a week. Lastly, participants could also do on job placements from 9 A.M. to 3 P.M. as part of the YESS intervention.After 5 weeks of training courses and job placements, participants were encouraged to apply for jobs. During the 11-week follow-up period, team members continued to provide one to one support to all participants when needed, in various areas like job application or peer support.via paper and pencil or using iPads provided at the centre. However, during the COVID-19 pandemic, due to lockdown restrictions, data was collected via an online survey. All data was entered into a secure database. Data collected were self-reported and included gender identity, age, ethnicity, sexual orientation, diagnosis, past educational attainment, housing status, current employment, and school attendance in the last 6 months.Demographic data were collected at baseline. Data collection was done in-person before the pandemic The aim of this feasibility study was to contribute evidence toward the implementation of a larger scale supported employment program in BC, we hoped to understand the factors that influenced fidelity and implementation of the YESS program . TherefoTo estimate the extent to which participation in the YESS program improved employment rate and mental health outcomes, we looked at limited efficacy testing , 23. LimThe primary outcome measure was the proportion of youth employed  after 5 weeks of intervention and at 16 week follow up.Secondary outcome measures included five patient reported outcome measures measured at 5 weeks and 16 weeks:The Canadian Personal Recovery Outcome Measure (CPROM), a 30-item scale developed for Canadians with mental illness living in the community, total scores on the CPROM were calculated by dividing the sum of all scores by 4, with higher scores reflecting better recovery .The MyLifeTracker (MLT), a 5-item mental health outcome measure designed for routine use. The five items cover five domains: general health, day to day activities, relationships with friends, relationship with family and coping. Total MLT scores were calculated by averaging across the five items, ranging from 0 to 100, with a higher score indicating a higher quality of life .The Satisfaction with Life Scale (SWLS), a 5-item scale measuring life satisfaction. Responses are denoted on a 7-point Likert scale ranging from strongly agree to strongly disagree. Total scores are calculated by summing all scores on the five items, with higher scores reflecting higher satisfaction .The General Anxiety Disorder (GAD-7), a 7-item screening tool for assessing generalized anxiety disorder. Each item is assigned a score of 0, 1, 2, and 3, corresponding to the response categories of “not at all,” “several days,” “more than half the days,” and “nearly every day,” respectively, total scores are obtained by adding together the scores for the seven questions .The Physical Health Questionnaire (PHQ-9), a 9-item scale that measures depressive symptoms. Each of the nine items are scored from “0”  to “3” (nearly every day). Total scores are calculated by summing all scores on the nine items .Distributional parameters were used to summarize baseline demographic variables. To estimate the limited efficacy of the YESS program among youths with mental health conditions, mean scores of all outcome measures at baseline and at week 5 were presented. Proportions of people who improved on these outcomes were presented at 5 and 16 weeks. Improvement on all measures refers to any increase in scores greater than the minimally clinically important change (MCID) score. For the GAD-7 and the PHQ-9, an improvement of four and five points, respectively, is clinically significant , 30. ForTo assess acceptability and demand of the program, the proportion of people who completed the program was computed. To assess adaptation, demographic characteristics of people who completed the program at week 5 were compared with non-completers. Adaptation of the program under COVID-19 restrictions was assessed by plotting the proportion of people employed over 1 year along with the timings of COVID-19 provincial-wide and nation-wide restrictions. Patterns of missing data in demographic and outcome variables were also identified.A total of 119 participants were recruited in the study but nine participants dropped out before baseline measurement see . ParticiThe correlations between demographic variables and outcome measures are presented in Altogether, 82 (74.5%) participants completed the whole 5-week program. Over the last year, the number of participants who were employed in our study corresponded with the timing of the COVID-19 restrictions in BC see . EmploymThe objectives of this study were to estimate the feasibility of the YESS program and the extent to which participation in the YESS program improved employment and mental health outcomes among youths with MHSU disorders. Our results showed that the YESS program was feasible, and ~33% of participants gained employment after the program and ~25% of the participants made improvements across all mental health outcomes, especially on outcomes measuring life satisfaction, and quality of life. However, due to the COVID-19 pandemic restrictions, only a small proportion of participants were employed after the 5-week program.In general, on most outcome measures, more than 30% of participants made improvements with the biggest proportion reported on the SWLS and the MLT. The main outcome measure of the YESS program was obtaining employment, and only 33.3% of people secured employment at the end of the follow-up period. Due to the pandemic, certain industries  were shut down and job opportunities were limited. Thus, unemployment rates were high and participants were competing with other more qualified candidates for the few available jobs, leading to decreased opportunities. In addition, some participants were hesitant to work during the pandemic. Most participants were youths with depression and anxiety, which were heightened during the pandemic. As such, many participants wanted to ease into employment and make sure they could handle the workload and being in a new environment, while others were happy to attend courses and training during this period.The effectiveness of the YESS program could also be associated with the outcomes used in this study. Appropriateness of the outcome measures was assessed as part of implementation. Many of the outcome measures were moderately to highly correlated with each other. The strongest association was found between the GAD-7 & PHQ-9 (0.78) and the CPROM and MLT (0.76). Consistent with literature, strong associations between scores on the PHQ-9 and the GAD-7 were reported indicating a strong convergent validity between the two scales but this could also indicate that the measures may be measuring the same underlying construct , 32. WhiThe high association between the CPROM and the MLT was also expected, as some items on the CPROM like general wellbeing are similar to the MLT. The CPROM measures the construct of recovery while the MLT measures quality of life and these two constructs are very closely associated in mental health research . InteresAt the end of the 5 and 16 weeks, about 20–30% of participants made improvement. Results showed improvements on the self-reported measures like a decrease in depressive and anxiety symptoms , 37. WhiOther aspects of feasibility were also examined. The study commenced in November 2019 and a total of 110 participants were recruited at the end of recruitment in December 2020. All eligible participants who were interested in the program were recruited. The participants in this study were from diverse backgrounds and more than 50% identified as women. Despite the COVID-19 pandemic, the demand in this program remained consistent throughout the study period. While recruitment was affected by the initial COVID-19 restrictions, the number of participants recruited steadily increased until December 2020, indicating that there is a demand for the program among youths in BC. The switch to online recruitment could also have helped maintain recruitment rates. Online recruitment appears to be an effective way to recruit people and reach out to people in need of services during the pandemic. However, all responses to our online advertisement had to be screened as not everyone met the eligibility criteria. This demand for our program could also be driven by the COVID-19 pandemic. Based on baseline results, our participants reported moderate depression and anxiety, and most were slightly dissatisfied with their lives. For people with existing mental health issues, the impact of this pandemic might be more acute and therefore extra efforts should be made to ensure that there is continued access to mental health and employment services .The retention rate of the YESS program was ~75%, with an attrition rate of 25%, which is a better result than most youth mental health programs where the average drop-out rate of youth mental health programs ranged from 28% to 78% . The proIn terms of practicality of the program, patterns of missing data were examined. Missing data was more prevalent with demographic variables than outcome measures. More than 10% of data was missing from demographic variables on housing situation and number of services used. There were also more missing data on questions related to diagnosis, symptoms, and hospitalization. This might be due to the sensitive nature of the questions. For people who are in at-risk or precarious housing situations, their situation might be constantly evolving, making it difficult to answer questions on their housing situation. Questions regarding diagnosis and symptoms might also be difficult to answer and many youths often suffer from more than one mental disorder at any one point in time . To incrSome limitations existed in this study. As the YESS program was unique to one Canadian urban centre, transferability of the study findings is limited to this context. Additionally, due to the COVID-19 pandemic, recruitment took a longer than expected time. We also did not collect data on participants' diagnoses and medication, which would have given us a clearer picture of the description of participants and the relationship between these factors and employment. Qualitative data was also not collected in this study due to the uncertainty around the COVID-19 pandemic and emerging ethical protocols for how to conduct one on one interviews. Qualitative data from participants and members of the team would have helped to better understand experiences in the program, and feasibility outcomes.Overall, the results showed that the YESS program was feasible, even within the context of the global COVID-19 pandemic. However, employment, as for many youths across Canada, was difficult to achieve. Engagement in this program brought about unexpected benefits that go beyond employment such as improved mental health and recovery outcomes. An individualized approach to treatment and measurement is recommended for future implementation of the YESS program. Results of this study have affirmed that a supported employment program can be integrated and implemented on a larger scale within an integrated youth service network in BC.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the University of British Columbia's Behavioral Research Ethics Board (H21-01510). Written informed consent for participation was not provided by the participants' legal guardians/next of kin because: Written informed consent is needed only for children aged 14 years and below in British Columbia, Canada. We did not have any participants who were minors and therefore written consent from legal guardians was not required. All participants were 17 years old and older and able to provide written consent independently.NO: conceptualization, data curation, formal analysis, methodology, project administration, investigation, and writing-original draft. KM and KG: writing-review and editing and visualization. DA: conceptualization, data curation, and writing-review and editing. SM: conceptualization, funding acquisition, and resources. SB: conceptualization, funding acquisition, methodology, validation, resources, supervision, project administration, and writing-review and editing. All authors contributed to the article and approved the submitted version.This study was funded by Canadian Institute Health Research Project (Grant Number: 156191).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immune profile of human livers during NMP.Six human livers were placed on a NMP device. Tissue and perfusate samples were obtained during cold storage prior to perfusion and at 1, 3, and 6 hours of perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines in the perfusate and within the liver tissue. Mean values between baseline and time points were compared by Student’s t-test.Within circulating perfusate, significantly increased frequencies of CD4 T cells, B cells and eosinophils were detectable by 1 hour of NMP and continued to increase at 6 hours of perfusion. On the other hand, NK cell frequency significantly decreased by 1 hour of NMP and remained decreased for the duration of perfusion. Within the liver tissue there was significantly increased B cell frequency but decreased neutrophils detectable at 6 hours of NMP. A transient decrease in intermediate monocyte frequency was detectable in liver tissue during the middle of the perfusion run. Overall, no significant differences were detectable in tissue resident T regulatory cells during NMP. Significantly increased levels of pro-inflammatory and anti-inflammatory cytokines were seen following initiation of NMP that continued to rise throughout duration of perfusion.Time-dependent dynamic changes are seen in individual leukocyte cell-types within both perfusate and tissue compartments of donor livers during NMP. This suggests a potential role of NMP in altering the immunogenicity of donor livers prior to transplant. These data also provide insights for future work to recondition the intrinsic immune profile of donor livers during NMP prior to transplantation. Liver normothermic machine perfusion (NMP) systems have gained clinical approval following recent clinical trials and are now in wider use . These dLiver NMP may also serve as a platform to condition organs prior to transplantation to minimize rejection or optimize organ function , 9. The ex vivo lung perfusion demonstrated removal of passenger non-classical monocytes from perfusates, suggesting altered immunogenicity of transplant lungs with ex vivo perfusion  and two were donation after brain death donors (DBD). Donors with history of hepatitis B or C infection and DCD donors who took longer than 90 minutes to expire after withdrawal of care were excluded from our study  medium  containing 5% bovine serum albumin, with an eventual hematocrit goal of 10-15%.Normothermic machine perfusion (NMP) of liver was performed using a circuit design compatible with existing clinical NMP devices . Another 10 mL perfusate sample was collected hourly downstream of the organ for complete blood count and comprehensive metabolic panel including liver enzyme levels.th hour. During perfusion, perfusate samples (about 300 mL) and tissue samples (about 3 g) were obtained at each time point . Perfusate samples were spun down at 400G and treated with ammonium-chloride-potassium buffer  to lyse remaining red blood cells. Liver tissue was mechanically disrupted and enzymatically digested at 37°C for 90 minutes using 100U/mL of Type II collagenase  in Hank’s Balanced Salt Solution  prior to filtration through 100-micron filters . Samples were then washed and resuspended in phosphate-buffered saline.Before initiation of perfusion, perfusate samples from retrograde flush with cold phosphate-buffered saline (about 300 mL) and tissue samples from wedge biopsies (about 3 g) were obtained. The samples collected prior to initiation of perfusion were labeled as 0Flow cytometry was used to determine the donor leukocyte profile in both the graft and perfusate compartments. Isolated cells were washed and stained with Zombie UV viability dye  in phosphate-buffered saline and then stained with the following markers: anti-CD3 Alexa Fluor 700 (Biolegend), anti-CD4 Alexa Fluor 488 (Biolegend), anti-CD8 Brilliant Violet 785 (Biolegend), anti-CD14 Brilliant Violet 650 (Biolegend), anti-CD16 Brilliant Violet 570 (Biolegend), anti-CD19 Brilliant Violet 510 (Biolegend), anti-CD45 Alexa Fluor 532 , anti-CD56 PE-Vio770 , and anti-CD66b PE-dazzle (Biolegend) (th hour) and at the end of perfusion (6th hour). Tissue samples were fixed in 10% neutral buffered formalin  for 24-36 hours prior to embedding in paraffin. Sections were stained with hematoxylin and eosin for qualitative evaluation for sinusoidal and portal triad structural integrity.About 300 mg of tissue samples were taken as wedge biopsy prior to perfusion , CD4 , DAPI  and FOXP3  .3mL of perfusate downstream from the organ were collected in ethylenediaminetetraacetic acid coated tube prior to perfusion and at 1st hour, 3rd hour, or 6th hour) relative to 0th hour (cold storage) was calculated.Using flow cytometry, the frequency each immune cell type based on the total number of CD45+ cells was calculated in both perfusate and liver tissue. To illustrate the time dependent, dynamic effect of NMP on each individual cell type in either compartment, percentage change of each cell type frequency at various time points  of each cytokine at each time were calculated for all organs. Student’s t-test was used to determine if concentration changes between time points were significant.th hour and 6th hour. A mean regulatory T cell frequency was assigned to each organ for each time point by averaging all ROI values. Paired Student’s t-test was used to compare regulatory T cell frequencies of all organs between time points 0th hour and 6th hour.Using immunohistochemistry, the percentage of regulatory T cells out of total number of CD3+ T cells were calculated for all ROI’s from each tissue slide taken from 0th h: 7.41 ± 2.58 versus 6th h: 2.53 ± 1.01, P = 0.009)  , classical monocytes (10.0 ± 4.2%), and macrophages (9.9 ± 7.3%). By contrast, the composition of leukocytes within the perfusate consisted of predominantly neutrophils (55.6 ± 16.3), NK cells (13.1 ± 6.5%), and eosinophils (7.7 ± 10.8%) . The second and third most abundant cells types in the liver tissues were macrophages (13.1 ± 10.0%) and NK cells (10.3 ± 7.1%). Similar to analysis of the tissue resident leukocytes, neutrophils were the most abundant leukocytes in the perfusate following 6 hours of NMP, with a lower percentage of neutrophils detected at 6 hours compared to prior to initiation of NMP (36.4 ± 24.5%). The second most abundant cell type were eosinophils (32.6 ± 22.6%), while CD4 T cells constituted a greater relative population following NMP (10.7 ± 4.7%)  (th hour of NMP (-24.5 ± 21.3%) (st hour (-30.7 ± 19.7%). By the third hour of perfusion, the frequency of tissue intermediate monocyte was similar to baseline  and continued to increase at the 6th hour (+472.6 ± 172.5%). Perfusate B cell frequency likewise increased throughout duration of NMP, starting at the 1st hour (+147.4 ± 127.5%) and continuing to the 6th hour (+288.5 ± 189.2%) (st hour of perfusion and remained decreased at the 6th hour of perfusion (-70.7 ± 9.8%) (th hour of NMP (-56.8 ± 28.5%)  at the 6th hour , and remained decreased throughout NMP  at the 1Given that FoxP3, a critical marker for regulatory T cells (Treg cells), is a transcription factor, immunohistochemistry was used to identify tissue Treg cells. At baseline, 4.1 ± 2.5% of tissue CD3+ T cells were Treg cells. At the end of perfusion, 2.5 ± 2.2% of tissue CD3+ T cells were Treg cells. Compared to baseline, there was no significant T reg cell frequency change at end of perfusion  demonstrate a rapid increase in perfusate monocytes at onset of perfusion with abundant non-classical monocytes attached to the leukocyte filter at end of EVLP, suggesting EVLP may remove passenger non-classical monocytes  . All livIn summary, our study demonstrates changes to the intrinsic immune profile of liver donor-livers during NMP. Furthermore, the changes in immune profiles of the perfusate and the organ don’t seem to mirror each other. Given that the organ is transplanted while the perfusate is discarded, our findings may be important in future NMP studies to address this. The results of our study have important implications on future work on novel targeted therapies to recondition donor livers using NMP to expand the organ donor poor, prevent delayed graft failure and induce tolerance.The original contributions presented in the study are included in the article/AL - study design, data acquisition, data analysis, and writing of manuscript. AE - data acquisition and writing of manuscript. ML- data acquisition and writing of manuscript. VM - data acquisition and writing of manuscript. AS - data acquisition and writing of manuscript. LJ - data acquisition, data analysis, and writing of manuscript. RP - data acquisition. RR - data acquisition. JH - data acquisition. BA - data acquisition. MJ - data acquisition. JM - study design, supervision, and manuscript revision. JD - acquisition of funding and supervision. MM - acquisition of funding, study design, and supervision. RB - acquisition of funding and supervision. DS - acquisition of funding and supervision. KS - acquisition of funding, study design, supervision, and manuscript revision. JF - acquisition of funding, supervision, and manuscript revision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Pulmonary rehabilitation (PR) is an integral part of the management of patients with chronic respiratory diseases. However, there is limited information available on the effectiveness and practice of PR in Africa. This study was conducted to examine the prevalence, structure, and organization of PR in Africa, as well as its substance and claimed efficacy. We conducted a multimethod study involving systematic review of PR studies  and a web-based survey of African healthcare professionals engaged in PR (using a standardized questionnaire). The review included papers on at least one component of PR in Africa and excluded those on PR from other continents or assessing pulmonary disorders in general without PR, cardio-rehabilitation, or physiotherapy practice in general in Africa. The Cochrane risk of bias and the Newcastle Ottawa scale instruments were used to assess the quality of included studies. We narratively synthesised data across the studies to produce a holistic picture. Of the 14 studies included for qualitative synthesis, seven were randomized controlled trials on the effectiveness of PR treatments with a total number of 333 participants. Of the 39 surveys mailed to health professionals working in Africa, only 14 (35.8%) were returned. We found aerobic exercise and breathing exercises were the most used technique and that quality of life, exercise capacity, and lung function improved significantly after PR treatments. There were differences in the duration, frequency, and length of the programs across the continent. Half of the respondents indicated that their institutions had one or more PR programs for inpatient, outpatient, maintenance, and/or home-based programs. Additionally, aerobic activities, upper and lower extremity strength training were the most frequently used exercise modalities in PR programs, followed by breathing exercises. Pulmonary rehabilitation is understudied in Africa, but it has been linked to improved lung function, exercise capacity, and quality of life. There is a need to invest in techniques tailored to the continent to enhance the implementation of pulmonary rehabilitation in Africa. In developing countries, public health is facing the impact of chronic respiratory diseases (CRDs) which is challenging because of their frequency, severity, projected trends and economic impact . In low The management of COPD is multidisciplinary  and pulmWe conducted a multimethod study combining a systematic review of the literature and a cross-sectional study among health workers involved in PR practice in Africa.Search strategy and selection criteria: we searched the following electronic databases: PubMed, Google scholar, Cochrane. In general, databases were searched with a combination of terms (respiratory OR pulmonary) AND (rehabilitation OR exercise OR physiotherapy) AND (Africa OR Afrique) and derived keywords, including variations of the following terms: “chronic obstructive pulmonary disease OR COPD”, “asthma”, “tuberculosis”, “physiotherapy”, “exercise”, “rehabilitation”, “Africa”, “Afrique” or North Africa or “sub-Saharan-Africa”. No language restriction was applied; the timeframe of the search included all records from the electronic database inception December 2018 to September 30, 2020, and an update was realisedend of January 2021. In addition, grey literature was searched, and individual authors or organization were contacted for data completeness. The PR definition was described as “comprehensive intervention based on thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behaviour change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviours” [aviours” . We consData analysis: we performed a narrative synthesis and produced summary tables of findings of included papers because methodological heterogeneity in exposure and outcome assessment precluded meta-analyses. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline [uideline .Risk of bias: two reviewers (AB and PK) independently assessed the papers' risk of bias and then debated the appropriate interpretation. In case of discrepancies, a third reviewer (JK) was asked to provide the final judgment. The Cochrane risk of bias instrument was used to assess the risk of bias in randomized trials studies, while the Newcastle Ottawa scale was utilized for observational studies.Study design, population, and settings: a cross-sectional study (from December 2018 to February 2020) was conducted using the questionnaire from a Canadian survey of 2005 published by Brooks et al. [s et al. . We obtaStatistical analysis: data were collected via Microsoft Excel spreadsheet. SPSS statistical program was used to perform statistical analysis. Descriptive statistics such as the mean (standard deviation) and median (interquartile ranges) were calculated for data summary. The distribution of PR programs was calculated by expressing the number of facilities  per city and presenting the number of rehabilitation programs available per city. All programs mentioned in the survey  and online support (other program) were present in different facilities in South Africa. Ethical approval: we obtained the ethical approval from the National Health Ethical Committee of Democratic Republic of Congo (amendment n°258/CNES/BN/PMMF/2021).Characteristics of included studies: as shown in the PRISMA flow diagram  were returned  from which seven health professionals  reported having at least one or more PR programs in their facilities such as inpatient, outpatient, maintenance and/or home-based programs. One respondent (from South Africa) reported online support via an email/Skype program. The remaining seven respondents from South Africa, Senegal, Niger, Angola, Nigeria, and DRC reported the absence of a program in their facilities. The others 25 health professionals never answer to the mail.Program characteristic, components, follow-up, and health worker: in- and outpatient programs were the most reported programs with a duration of 60 minutes (for each session) in general for three (outpatient program) or six (inpatient program) days per week with a length of six (inpatient program) or eight (outpatient program) weeks per session (Annex 2). Aerobic exercises, mostly walking (100% of in- and outpatient programs) and strength training of upper and lower extremities (100% of in- and outpatient programs) were the most used exercise modalities in PR programs, followed by breathing exercises (100% of in- and outpatient programs) (Annex 2). Home exercise prescription was provided for outpatient (86%) and for inpatient (80%) programs. There was little use of education  and psychological support (20% of inpatient and 43% of outpatient programs) reported in PR programs. The distribution of follow-up components is summarized in Annex 2. Follow-up was added as part of the pulmonary rehabilitation program in all facilities that reported having a PR program in this study. Reassessment was the most used follow-up component (80% of inpatient and 100% of outpatient programs) and supervised exercises the least (0% of inpatient and 28% of outpatient programs). Pulmonologist, physiatrist, internist, and physical therapist were the most represented health professionals , while social worker (14% of outpatient program) and psychologist (28% of outpatient) were the least represented (Annex 2). Nurse and spiritual leader were absent in the reported programs. Other healthcare professionals, i.e., resuscitator/anaesthetist, thoracic surgeon, paediatrician was part of the PR program team in the Kinshasa facilities.Outcome measures: outcome measures are shown in (Annex 3). The 6-minute walking test was the most frequently used measure (100% of in- and outpatient programs) followed by St Georges Respiratory Questionnaire (100% of in- and outpatient programs) and simple spirometry with bronchodilator response (100% of in- and outpatient programs). The Chronic Respiratory Disease Questionnaire, constant work rate test, 12-minute walking test and shuttle walk test were not used.The interest of this review and survey was to investigate the current evidence and practice of PR in Africa (North and Sub-Saharan Africa). In the systematic review, 14 studies were included and showed a disparate existence of structured PR in some African facilities indicated for COPD patients, asthma, pulmonary tuberculosis and post-tuberculosis lung disease patients, surgical patients, ICU patients and HIV/AIDS patients. The improvement of quality of life of CRDs patients was also shown.A web-based survey yielded a very limited response rate despite several reminders and thus reduces the generalizability of our survey´ findings. Additionally, due to the significant level of heterogeneity, we were unable to do meta-analyses. The interpretation of the results must therefore be made with caution.Nevertheless, from the respondents, we noted that despite the high burden of CRDs in the continent , PR as aThe systematic review found that programs take 10 to 30 minutes, 2 or 3 time per week for 6 to 8 weeks. The British Thoracic Society guideline on PR also recommended PR program 2 to 3 time per week for 6 to 12 weeks and is in line with current literature . MoreoveFurthermore, breathing exercise was among the most used component for PR practice in Africa and this was also reported in both inpatient and outpatient program in our survey. This type of exercise aims at modifying respiratory muscle recruitment and reduces dyspnoea in COPD patients . HoweverUnfortunately, despite its well-known importance as PR component  and evidFrequently measured outcomes included 6MWT  wLung function measurement was mostly evaluated with simple spirometry with bronchodilator response in inpatient (100%) and outpatient (86%) programs in the survey study. Though some studies reported statistically and clinically significant improvements in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), FEV1/FVC ratio in patients with asthma, pulmonary tuberculosis and COPD in the review, it is known that a short-term improvement of lung function in COPD patients after a PR program is unexpected . In accoAll pulmonary rehabilitation programs have the same essential characteristics, but the resources available, the program setting, structure, staff and duration vary considerably from one health system to another . CurrentConsequently, further studies on PR are warranted to accelerate the adaptation of guidelines in Africa while considering health system constraints especially during COVID-19 era. PR programs delivery was severely impacted by the coronavirus disease 19 (COVID-19) pandemic what prompted to review the methods of application of exercises . As teleDespite the relative presence of pulmonary rehabilitation in Africa, its practice is still limited across many countries with high disparities within countries. Considering, the high burden of chronic respiratory diseases in Africa, there is a necessity to conduct robust studies testing local practices  to help engineering adapted PR guidelines for easy implementation in poor resource settings where more chronic respiratory diseases are reported.Pulmonary rehabilitation increases the quality of life of patients with chronic respiratory disease;Pulmonary rehabilitation works in occidental settings but given the difference in resources and trained personnel in Africa, it is important to understand the existing evidence for pulmonary rehabilitation in the continent.Pulmonary rehabilitation is underutilized in North and Sub-Saharan Africa;Pulmonary rehabilitation program varies in African countries but generally respects guideline of occidental societies which do not have same realities with African countries in general.


Seeking spatiotemporal patterns about how citizens interact with the urban space is critical for understanding how cities function. Such interactions were studied in various forms focusing on patterns of people’s presence, action, and transition in the urban environment, which are defined as human-urban interactions in this paper. Using human activity datasets that utilize mobile positioning technology for tracking the locations and movements of individuals, researchers developed stochastic models to uncover preferential return behaviors and recurrent transitional activity structures in human-urban interactions. Ad-hoc heuristics and spatial clustering methods were applied to derive meaningful activity places in those studies. However, the lack of semantic meaning in the recorded locations makes it difficult to examine the details about how people interact with different activity places. In this study, we utilized geographic context-aware Twitter data to investigate the spatiotemporal patterns of people’s interactions with their activity places in different urban settings. To test consistency of our findings, we used geo-located tweets to derive the activity places in Twitter users’ location histories over three major U.S. metropolitan areas: Greater Boston Area, Chicago, and San Diego, where the geographic context of each location was inferred from its closest land use parcel. The results showed striking spatial and temporal similarities in Twitter users’ interactions with their activity places among the three cities. By using entropy-based predictability measures, this study not only confirmed the preferential return behaviors as people tend to revisit a few highly frequented places but also revealed detailed characteristics of those activity places. As the world is undergoing rapid urbanization cities become the main human settlements. Citizens navigate through the landscape of urban environments for various types of daily activities, such as staying at home, traveling to work/school, and shopping at grocery stores or malls. Understanding the spatiotemporal characteristics of citizens’ interactions with the urban environments helps gain valuable insights into how cities function and reveal the city image and its elements Lynch, . The repOn the one hand, human behaviors in interacting with urban space are complex and are expected to vary in different spatial, temporal, and even cultural urban settings  or geolocation-enabled mobile applications. In comparison, the locations of social media users are collected when users post social media messages with the geolocation feature turned on or by tagging a message with geolocation, such as geo-located tweets and check-ins. Both data sources were used to explore population dynamics across large spatial scales. For example, mobile phone location data were used for dynamic population mapping  is associated with an address or a named place , work , school , leisure , among others . A geo-located tweet is a regular tweet tagged with a real-world geographic location. Such a location is represented by a pair of latitude and longitude coordinates, which are usually derived from location-based service enabled smartphones via integrated GPS and Wi-Fi positioning. The geographic locations are considered to have high spatial resolution down to 10 m , Chicago , and San Diego . Because the data collection was carried out at the city level, it did not exceed the data volume limit  mentioned in . As the geo-located tweets were collected in 2014, we extract land use parcels from the same year. The details of the parcel-level land use maps for Greater Boston and Chicago can be found in  only those land use parcels with the tweets counts above the average number of tweets in a user’s trajectory will be considered as activity places (2) the popularity of those activity places are ranked by the number of tweets at each parcel. Essentially, this approach serves as a de-facto spatial clustering method without arbitrarily using the geometry of a spatial cluster as a place. Note that most tweeted activity places are not necessarily users’ home places. In this study, we are not fixated to identify Twitter users’ “home” places but simply focusing on understanding the characteristics of those activity places. At this stage, the land use parcel  of the activity sequences. To do so, we used the entropy-based measures developed by Song et al.  to quantg et al.  utilizedEvery citizen is a unique individual. Intuitively, the activity places people interacted with on a daily basis or over time should vary drastically by individuals as well. It may be the case when we took a first glance at the number of activity places in each Twitter user’s activity sequence. Yet, when plotting the probability density function of the number of visited activity places over the three cities in 2014, there is a clear bimodal distribution that divides the user base into two distinct groups  at different times of the day to get a better sense of the temporal characteristics of people’s activities in the urban environment. The weekday hourly distribution of tweets volumes at Twitter users’ activity places classified by different land use types is shown in Fig. The results provide insights into the connections between human activities and the geospatial setting of the urban environment. Importantly, a remarkable resemblance of the temporal characteristics of the activity places is observed across all three cities. However, there are some apparent discrepancies in the temporal signals derived from using geo-located Twitter data. First, the inference of Twitter users’ whereabouts is strongly influenced by varying human behaviors. For example, there are significantly fewer activities observed in the early morning. It does not mean people are not staying at home (or other places), but simply are not posting tweets. In the case of work activities peaking around mid-day, it seems that the signals from tweet volumes are delayed because people are less likely to tweet during early working hours but during breaks .The calculation of real entropy k et al. .The probability density functions It is the rhythm in everyday citizens’ daily activities that forms the heartbeat of the city. The ability to capture and understand how citizens interact with the urban space can provide important insights to reveal how cities function. With the increasing availability of various forms of human activity data, such as surveys, mobile phone location data, and geo-located social media data, many studies have been conducted to seek different types of human activity patterns in the urban environment. However, specific to citizens’ interactions with the urban space, most of the existing studies have focused on seeking patterns either from the human aspect or from the urban space aspect of the interactions. In this connection, we proposed a new concept, namely human-urban interaction, which takes the literal meaning of the term “interaction” to encapsulate the interactions as people’s presence (visitation), action (activity), and transition (mobility) in urban space. Using this concept, this study aims to gain insights into the interplays between human activities and the geospatial settings of urban environments.Abundant research efforts have utilized mobile phone location data and geo-located social media data for tracking the locations and movements of individuals to study human activities in the urban environment. However, the actual places that people interact with were often overlooked, where the activity places were inferred by applying ad-hoc heuristics and spatial clustering methods. The inability to identify different types of activity places from single-layered location data is mainly attributed to the absence of geographic context in the recorded locations. In this study, we utilized geographic context-aware Twitter data to investigate the spatiotemporal characteristics of people’s interactions with their activity places in different urban settings. Specifically, we used geo-located tweets and parcel-level detailed land use maps to derive activity places from their location history and constructed activity sequences over three major U.S. metropolitan areas from the East Coast to Midwest and the West Coast: Greater Boston, Chicago, and San Diego.The results showed remarkable spatial and temporal similarities and consistencies in Twitter users’ interactions with their activity places across three different cities. First, the identified bimodal distribution in the number of activity places in Twitter users’ activity sequences divided the user base into two distinct groups. Second, Twitter users’ behaviors in returning to the same activity place exhibited a clear periodical shift with approximately a 24-h interval, which supported the existence of preferential return behaviors in human-urban interactions. Further, we examined the detailed characteristics of Twitter users’ activity places. By decomposing the top 10 most frequently visited activity places in the three cities, we found that Twitter users do tweet regularly or substantially at a diverse collection of urban places. Each type of activity place seems to show an almost unique signal to reflect the corresponding human activity in the urban environment. Using the temporal signals as indicators to understand the urban environment is very much in alinement with the concept of social sensing  or missing signals . More importantly, neither mobile phone data nor geo-located Twitter data can track user locations continuously, which means the intermediate user locations between two tweets may not be recorded. This will significantly affect our ability to derive actual or timely movements from users’ location history, which is demonstrated by calculating the real entropy value of Twitter users’ activity sequences. Although the Twitter user base in this study covers different groups of people in the urban environment, studies have shown that there is a mismatch between the Twitter user population and the real population. Particularly, the Twitter user population is skewed toward younger users (Greenwood et al.,


Ito) and the ultrarapid delayed rectifier potassium current (IKur) are major potassium currents involved in the repolarization process of sinoatrial node cells (SNCs).  The transient outward potassium current , steady-state activation (SSA), steady-state inactivation (SSI), and recovery from inactivation (RFI) curves were plotted, respectively. Compared to the control group, both the peak current density and the current density at the voltage of Ito and IKur decreased obviously in SNCs after simulated I/R, the SSA curves moved right, and the SSI curves moved left. After TYHX was added to the extracellular solution of SNCs, both the peak current density and the current density at the voltage of Ito and IKur increased significantly, the SSA curves moved left, and the SSI curves moved right with a significant difference of V1/2. The recovery from the IKur RFI curves was slightly restored, and the Ito curves did not change.  The SNCs of neonatal rats were divided into control, ischemia/reperfusion (I/R), I/R+blank serum, and Tongyang Huoxue recipe (TYHX) serum groups. Ito and IKur. This may be the mechanism of TYHX in shortening the action potential duration of repolarization, which accelerates spontaneous pulsation. TYHX increases the peak current density, accelerates the activation, and decreases the inactivation of the  The sinoatrial node (SAN) is the primary cardiac pacemaker and the source of internal electrical stimulation driving the coordinated rhythmic contraction of the heart . The SANIf), potassium currents (IK), calcium currents (ICa), and sodium-calcium exchange current (INCX) ), where y is the normalized current, Vm is the membrane potential, V1/2  is the voltage at midpoint of the available channels which are activated or inactivated, and k is the slope factor of curves. The curves of recovery from inactivation were obtained by fitting the time course data to a simple exponential function.The t test. Steady-state activation and inactivation curves were fit with the Boltzmann function to obtain slope factor (k) and midpoint (V1/2 ). The time-dependent recovery from the inactivation was fit using a first-order exponential function. p values less than 0.05 were considered statistically significant.The data obtained were processed using Clampfit version 10.4 (Axon Instruments) and Origin version 8.0 , and the measured data are expressed as mean ± SD. Multigroup comparisons were performed using one-way analysis of variance (ANOVA), and continuous univariate data were analyzed using a Student's Ito of SNC was found. To explore the effects of TYHX on the potassium current of SNC, we applied blank serum and TYHX-medicated serum to SNC. A significant reduction in the Ito current can be observed in the I/R group at the peak density  from a holding potential of -80 mV. The Ito values corresponding to the above voltages were measured in each group, and I-V curves were constructed. The results showed (p < 0.05) compared with the control group. The current densities of 100 μL TYHX serum under each voltage increased to different degrees, especially between the voltages of +10 mV and +70 mV with statistical significance (p < 0.05) compared to the I/R group. There was no statistical difference between the blank serum group and the I/R group. The results indicated that the TYHX recipe-medicated serum could voltage dependently increase the current density of the Ito in SNCs.s showed  that theIto channel in the I/R group moved right of the depolarization direction. Besides, k value (the steepness of the Boltzmann curve) was changed to 12.10 ± 0.95 from the 11.66 ± 1.93 . No significant difference in SSA curve, V1/2,act, and k value was observed between the I/R group and 100 μL blank serum. After adding 100 μL TYHX serum, the SSA curve moved left   was 10.67 ± 1.43 with no difference (p > 0.05)  ; however > 0.05) . The resp < 0.01) and the half-maximal inactivation voltage  was changed from −39.54 ± 0.61 mV to −53.93 ± 0.89 mV (p < 0.01). There was no significant difference in SSI and V1/2,inact change between the I/R group and blank serum. TYHX serum produced a statistically significant right shift   . The slom groups . Ito chaIto was increased in TYHX application, we observed no difference in recovery from inactivation between all groups  (IKur in the SAN cells. The TYHX recipe can increase the peak current density of the IKur in damaged SAN cells and reverse I/R-induced IKur changes in SAN cells.The current of as shown . The peaHX serum . No sign < 0.05) . The aboIKur current recorded after stimulation between voltages of -40 mV and +70 mV (10 mV depolarizing steps) from a holding potential of -80 mV. The results showed (p < 0.05) compared with the control group. After adding 100 μL TYHX serum, we found that all current densities under each voltage increased to different degrees, especially between voltages of +20 mV and +70 mV, with statistical significance (p < 0.05) compared to the I/R group. Nevertheless, there was no statistical difference between the blank serum group and the I/R group. The results indicated that I/R leads to decreased current density. The TYHX serum could increase the current density of the IKur in the SNCs with a voltage-dependent manner.s showed  that theIKur channel moved right   was changed from −13.6 ± 1.9 mV to −9.53 ± 1.57 mV (p < 0.05)   , and the < 0.05)  with the Figures . The resIKur   . The datectively . The resIKur channel function. We observed slower recovery from inactivation in the I/R group compared to the control group, especially in the time of the former 3000 ms. The application of TYHX showed much faster deinactivation than the I/R group and blank group  is an organic disease of SAN and its surrounding tissues, which leads to a series of clinical manifestations caused by pacing and impulsive efferent disturbance. It is a significant clinical refractory cardiovascular disease, manifested as bradycardia and conduction block, that can lead to the inadequate blood supply to the heart, brain, kidney, and other vital organs. The prevalence of SSS has been reported to be 1/1000 in adults over 45 years  and 1/60If current density in a voltage-dependent manner [Natural products have been globally recognized for having broad clinical application prospects in light of their advantages with respect to multitargets, efficacy advantages, and safety. With the rapid advances of modern technology, such as the patch clamp, we can evaluate a variety of Chinese antiarrhythmic medicines or their effective ingredients. Natural compounds are widely used in traditional Chinese medicine and have been verified to act on ion channels to alter ion channel gating against arrhythmia . Previout manner . Componet manner . These ct manner , 27. In t manner –30.Ito and IKur current density or the process of activation and inactivation compared to the I/R group. Therefore, we used the method of serum pharmacology in vitro experiments and observed the effect of mediated serum on the regulation of Ito and IKur.The serum pharmacology method has been frequently used to study the effects and mechanisms of Chinese drugs in vitro, as it eliminates the interferences of the physical and chemical characteristics of crude herbs in the experimental process and provides similar experimental conditions to the in vivo environment. The results showed that blank serum from rats does not significantly affect the Ito and IKur are critical currents involved in action potential repolarization of SNCs [Ito and IKur affect the action potential duration and then affect the frequency of pulsation, which is of great significance to the regulation of action potential in SNCs. Ito in mammalian ventricular and atrial cells has been shown to be generated by K+ outward ions that largely contribute to the formation of the AP during the early repolarization phase (phase 1) [Ito, including Kv1.4, Kv4.2, and Kv4.3 channels. Some researchers have suggested that phase 1 of the AP in SAN cannot be identified. However, other studies showed that Ito significantly promoted the repolarization of rabbit sinoatrial node cells [Ito-sensitive blocker 4-aminopyridine (4-AP) blocked Ito [IKur also leads to rapid repolarization of the action potential and balances the inward depolarization current of Na + and L-type Ca2+ channels [IKur results in a 39% prolongation of the AP and a 27% increase in cycle length [IKur [The abnormality of SNCs' ion channels and currents can lead to SSS , in whic of SNCs . Changesphase 1) . A host de cells , and actcked Ito . IKur alchannels . Block oe length . Kv1.5 (th [IKur , locatedth [IKur . An age-th [IKur , which mth [IKur .Ito and IKur play an important role in regulating spontaneous cardiac rhythms and heart rate. The results of the present study show that TYHX increased the Ito and IKur current density in the damaged SAN cells in a voltage-dependent manner. The SSA curve of the Ito and IKur channels was shifted to the left, indicating that the TYHX treatment accelerated channel activation. The SSI curve of the Ito and IKur channel was shifted to the right, which illustrates TYHX slows the inactivation of Ito and IKur channel. The result estimated the possibility of TYHX in shorting the depolarization phase of the action potential and improving the autorhythmicity of SAN cells.Our research elucidates the mechanism of TYHX in treating SSS from the aspect of cell electrophysiology. Combining with previous studies, our group systematically and intensely studied the clinical efficacy and mechanism of TYHX in the treatment of SSS from different levels, such as theoretical basis, animal experiment, holistic effect, cell molecule, and gene expression. It proved that TYHX has multiple goals and ways, playing an essential role in providing a scientific basis for the research methods and ideas for the treatment of diseases with TCM, which can deepen the scientific connotation of famous TCM experiences.


Performance on the certifying examinations such as the American Board of Internal Medicine Certification Exam (ABIM-CE) is of great interest to residents and their residency programs. Identification of factors associated with certification exam result may allow residency programs to recognize and intervene for residents at risk of failing. Despite this, residency programs have few evidence-based predictors of certification exam outcome. The change to pass-or-fail score reporting of the USA Medical Licensing Exam (USMLE) Step 1 removes one such predictor.We performed a retrospective study of residents from a medium-sized internal medicine residency program who graduated from 1998 through 2017. We used univariate tests of associations between ABIM-CE result and various demographic and scholastic factors.P = 0.01); lower percentile rank on the Internal Medicine In-Training Examination (IM-ITE) in each of the first, second, and third years of training ; and lower scores on the USMLE Steps 1, 2 Clinical Knowledge, and 3 . No association was seen between a variety of other scholastic or demographic factors and first-attempt ABIM-CE result.Of 166 graduates, 14 (8.4%) failed the ABIM-CE on the first attempt. Failing the first attempt of the ABIM-CE was associated with older median age on entering residency (29 vs 27 years; Although USMLE step 1 has changed to a pass-or-fail reporting structure, there are still other characteristics that allow residency programs to identify residents at risk of ABIM-CE first time failure and who may benefit from intervention. Passing a certification exam – commonly referred to as a board exam or simply ‘the Boards’ – is an important milestone for the residency program graduate. Residency program staff also have an abiding interest in their graduates’ board exam performance. For example, beyond wanting graduates to succeed, residency programs must achieve specific aggregate certifying exam pass rates to meet the Common Program Requirements of the Accreditation Council for Graduate Medical Education (ACGME) . For intThere is a gap between which factors educators expect to be linked to board exam performance and which associations have empirical evidence to support such a linkage. For example, in a 2013 survey, residency program directors proposed links between internal medicine board exam performance and various factors such as ACGME work hour requirements, performance on other standardized tests, teaching conference attendance, and competing personal obligations  and the Within internal medicine, research regarding associations between passing the ABIM-CE and participation in specific clinical experiences is inconclusive ,19,20, wSingle-center studies on this topic have examined associations over a short time span, and multicenter studies have tested for associations in only 1 year. Instruments used by faculty members to assess resident performance  have changed over time, and certain factors such as the content, frequency and length of required educational conferences vary by institution. The current study aimed to use data from a longitudinal sample to identify factors durably associated with first-attempt ABIM-CE performance among internal medicine residents from a medium-sized residency program in the USA.We performed a retrospective study of all residents who graduated from the Internal Medicine Residency Program at Mayo Clinic in Arizona from 1998 through 2017. The program has full ACGME accreditation, and its size gradually increased from an initial 6 residents per class to its current 12 residents per class. The program is affiliated with a tertiary care hospital in a large metropolitan area in the Southwest USA. Residents in the program during the study period were provided access to ABIM-CE preparation resources, including the Medical Knowledge Self-Assessment Program, MedStudy Internal Medicine Board Review, and the opportunity to participate in a funded, off-site ABIM-CE preparatory course. Residents with IM-ITE performance below a prespecified score were enrolled in an individualized education plan with access to another question bank and check-ins from an associate program director. The study protocol was approved by the Institutional Review Board of the Mayo Clinic in Arizona (application 13–000080). The Board conducted a risk-benefit analysis, determined the study constituted minimal risk research, and waived the requirement to obtain informed consent.Residency program coordinators, the principal investigator, and a nonmedical volunteer abstracted demographic and scholastic data from archived files of all program graduates into a digital spreadsheet. Information was deidentified by these abstractors through substitution of a number for the graduate’s name, the key for which was kept by the principal investigator. Information collected and subsequently coded as binary variables included gender, marital status, primary language, medical degree type , off-cycle residency graduation, Alpha Omega Alpha (AOA) Honor Medical Society membership, childrearing or childbearing in residency, graduation from a medical school outside the USA, graduate or professional degrees earned before starting residency, completing a rotation at the program’s institution before starting residency, board review course completion, a gap of at least 1 year between completion of medical school and starting residency, area of program director concern during residency, and publication of an article or abstract during residency. Information collected on work hour requirements was coded as a categorical variable, with specific requirements noted in P < 0.05 was the threshold for statistical significance. R Statistical Software version 3.6.2 was used to conduct the analysis.We used univariate analysis to test associations between various resident factors and first-attempt ABIM-CE results classified as pass or fail. Binary and categorical variables are presented as counts and percentages. Continuous variables are presented as median (range or interquartile range). Associations were tested by using Fisher’s exact test for categorical variables and Wilcoxon rank sum test for continuous variables, and correlations were estimated with the Pearson correlation coefficient. Among 167 residents, 1 did not graduate and was excluded from analysis. Data from 166 graduates were included for analysis. One resident restarted the residency program after a leave of absence, and data from work before the leave of absence were excluded. The overall first-attempt board exam failure rate of graduates was 8.4% (n = 14). Resident demographic characteristics are summarized in P = 0.01)  . There w = 0.01) .P < 0.001 for all) (P = 0.02), Step 2 Clinical Knowledge , and Step 3 . There were no between-group differences in other scholastic performance factors evaluated , second (71 vs 32), and third (69 vs 24.5) years of residency  . Similarvaluated .Table 3r = −0.19; P = 0.02), postgraduate year 3 IM-ITE score , and USMLE Step 3 score .We next analyzed the correlation between age and IM-ITE and USMLE scores. Pearson correlation coefficients ranged from −0.07 to −0.22 . The corIn our study population, residents who passed the ABIM-CE on the first attempt had higher performance on the USMLE and IM-ITE than did peers who failed the ABIM-CE. This is in line with findings of other investigators . Unlike P = 0.47). Furthermore, there was no significant difference in the proportion of residents with such additional family commitments who passed the first-attempt ABIM-CE and those who failed . Future research with larger sample sizes and wider-ranging demographic data collection could help determine why an association might exist between certifying examination performance and age at residency entry.We hypothesized that among residents in our study population, those entering residency at younger ages may have different average test scores than those entering at older ages. Further analysis identified a small negative correlation between age and some of the IM-ITE and USMLE scores. This suggests that those who were younger on entering residency had slightly higher exam scores during residency than did those who started residency at older ages. Residents who were older may be more likely to have more family commitments – marriage, childbearing, childrearing, or aging family members with caregiver needs – and competing time demands outside of work. However, those who were married, who bore children or who raised children were not significantly older on average than residents who were single and did not bear or raise children . Future studies with dedicated measurement of burnout would be valuable to determine whether an association exists between burnout and certifying exam performance.Burnout is associated with adverse physician and perhaps even patient outcomes , but datAdditional factors that may potentially associate with board passage include AOA membership and post-residency fellowship pursuit. Of residents who passed the ABIM-CE in our cohort, a higher proportion were AOA members (19.1% vs. 0.0%), and a lower proportion pursued subspecialty practice after residency graduation (57.9% vs. 78.6%), though these differences were not statistically significant. Horn and colleagues  in radioOur study’s strength was in inclusion of novel factors not examined in the existing internal medicine literature. These included AOA membership, completion of an audition rotation at our hospital while in medical school, and an estimate of commute distance. It also included results from data collected over a longer period than in other studies, a characteristic that might mitigate potentially confounding effects of broader changes in residency training and the ABIM-CE over time. Finding differences that do – or do not – endure over time may make those findings more reliable or externally valid.We acknowledge study limitations, including the size of the study. With the given ABIM-CE pass rate, the study was not powered to reach statistical significance for between-group differences of small magnitudes. The study is exploratory in nature, and to reduce type II error, no corrections were made for multiple. All findings require validation. Another limitation is that the study population includes residents at only 1 center. Residents in our residency program may not be representative of those in another, or of those in other specialties. Importantly, we did not collect data that reflected the program’s active efforts to increase the ABIM-CE pass rate. These efforts included implementing interventions such as medical knowledge enhancement opportunities for residents whose IM-ITE scores were concerning for failing the boards, and programs to systematically ensure all residents’ review of relevant topics. For instance, in 2019, the residency program created and offered protected time for third-year residents to attend a program-created weekly review of medicine topics and practice tests for those in the last six months of residency, with a 100% first-attempt ABIM-CE pass rate in the three years since.In addition, other than including the updated ACGME work hour rules, our study does not account for institutional factors that may influence resident performance. As examples, investigators have found possible associations between resident-specific ABIM-CE results and timing of certain clinical experiences , number Lastly, as illustrated by the change in USMLE Step 1 score reporting, some of these variables may not be useful in the future. Critical appraisal of current assessment methods and markers of achievement may identify systemic issues, even if explanations for such issues can only be theorized. As an example, in the Summary Report and Preliminary Recommendations from the March 2019 Invitational Conference on USMLE Scoring (InCUS), Barone and others  noted raThe USMLE Step 1 score reporting has changed from a numeric score to pass or fail. Over ti


Nano- and microplastics (NMPs) are a group of contaminants that cause concern due to their abundance in the environment, high persistence, and interaction with other contaminants. This review aims to understand the role of NMP in the bioaccumulation of environmental contaminants. For that, a comprehensive literature search was conducted to identify publications that compared the uptake of contaminants in the presence and absence of NMP. In this part I, twenty-eight publications of the terrestrial compartment were analyzed. Two main taxonomic groups were studied, namely, earthworms and terrestrial plants. In earthworms, most studies observed an increase in the bioaccumulation of the contaminants, while in plants, most studies observed a decrease in the bioaccumulation. Changes in bioavailable fractions of contaminants due to NMP presence was the main reason pointed out by the authors for their outcomes. Moreover, biological aspects were also found to be important in defining how NMPs affect bioaccumulation. Dermal damage and changes in contaminant-degrading bacteria in the gut of earthworms caused an increase in bioaccumulation, and root pore blockage was a common reason for the decrease in the bioaccumulation of contaminants in plants. Nevertheless, such effects were mainly observed at high, unrealistic NMP concentrations. Finally, knowledge gaps were identified, and the limitations of this systematic review were presented. Nano- and microplastics (NMPs) are one of the main pollutants of concern nowadays for several reasons. Firstly, NMPs are abundantly found in the environment, and reports of their presence have been made worldwide . This isThere is a great body of literature on NMP interaction with contaminants, especially via sorption/desorption processes ,12. The Bioaccumulation, hereby defined as the increase in contaminant levels in an organism’s body, is the first step of possible toxic effects. It results from the net uptake and elimination rates of the contaminant and is a critical process, defining the potential of a contaminant to trigger adverse effects. The uptake of contaminants can occur via different routes in the environmental medium , including ingestion and dermal uptake in biota and rhizofiltration in plants. NMP may change the processes involved in bioaccumulation. Firstly, NMP may be a new route of exposure to environmental contaminants, for example, via the ingestion of contaminated NMP. Moreover, NMP may affect the internal processes of uptake/elimination in the organisms, affecting the overall bioaccessibility of contaminants. Considering the increasing levels of NMP in the environment and their interaction with contaminants, it is crucial to understand if NMPs are likely to affect the bioaccumulation of contaminants. The number of studies on the joint exposure of NMP and contaminants has been gradually increasing over the years ,11. WhilThis paper covers a systematic scoping review of the literature, concerning the impact of NMP exposures on the bioaccumulation of toxic compounds in terrestrial organisms. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this review aims to find evidence on the interaction of NMP–chemicals–bioaccumulation and identify knowledge gaps on this topic. We aim to answer the question: how does NMP’s presence affect the bioaccumulation of contaminants? For that, only publications that compared treatments with or without NMP were included. After the literature selection, the articles were separated into three main groups to make the systematic review as comprehensive as possible: namely, terrestrial, freshwater, and marine. This review focuses on the terrestrial publications retrieved from our literature search. Soils are an important sink for NMP , and morThis review followed the guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-) . A comprAn inclusion criterion was used during the title and abstract screening. Only original research articles published in English were considered. Other publications, such as reviews, book or book chapters, and conference papers, were not included. Moreover, studies that did not explicitly indicate the joint exposure to nano/microplastics and contaminants or the use of environmentally important species  were excluded.The studies included in the final selection had their data extracted into a table in excel. Information on the study characteristics included the exposure route (soil or hydroponic medium) and spiking procedure. Three spiking procedures were included: NMP and contaminant added to the medium at the beginning of the experiment (freshly spiked), NMP and contaminant added to the medium and incubated before exposure (pre-incubation), or NMP contaminated with the contaminant in water before being added to the exposure medium (pre-contamination). The characteristics of NMP were included . The studies were further classified, using particle size, as microplastic (MP) experiments, for particles between 1 µm and 5 mm, and nanoplastic (NP) experiments, for particles below 1 µm ,23. MoreThe number of publications in each phase of the literature search and selection can be found in Some publications used more than one type of NMP or test species. Therefore, we found it necessary to distinguish between the number of publications and the number of experiments. For example, a publication with two types of NMP  was counted as two experiments. The 28 publications resulted in a total of 36 experiments. The selected studies were published between 2017 and 2022, with almost 90% published from 2020 to 2022 . MicroplThe contaminants were classified into major chemical groups, considering both chemical properties and use. Metals were the most studied group (51.2%), followed by polycyclic aromatic hydrocarbons (PAHs) (18.6%), polychlorinated biphenyls (PCBs) (9.3%), and nanoparticles (4.7%). Pesticides, phthalates, and per- and polyfluoroalkyl substances (PFASs) were used in 4.7% of the experiments each, and pharmaceuticals and personal care products (PPCPs) in 2.3% each.In most experiments (80.6%), organisms were exposed to soil or hydroponic medium freshly spiked with NMP . Pre-incEisenia fetida and E. andrei were used in 90% of the experiments, while Lumbricus terrestris and Metaphire californica were used in 5% of the experiments each. Regarding the bioaccumulation of contaminants, diverged outcomes were observed. The characteristics of NMP and contaminants are shown in Soil was the exposure medium used in all studies with oligochaetes. The earthworms More than half of the experiments (52.2%) observed an increase in the bioaccumulation of contaminants when NMPs were added to the soils. Microplastics and nanoplastics, composed of different polymer types, were either pre-incubated with contaminants or were freshly spiked to the soils. The presence of NMP increased the bioaccumulation of both metals and PAHs in 17.4% of experiments, pesticides in 8.7%, and nanoparticles and PFASs in 4.3% each. A decrease in bioaccumulation was observed in 39.1% of the experiments with earthworms. MP and NP, composed of PS, PE, and PVC, were either pre-incubated or freshly spiked. Metals’ and PCBs’ bioaccumulation decreased in 13% of experiments each, PAHs in 8.7%, and nanoparticles in 4.3%. One study found that NMP did not influence the bioaccumulation of Zn in earthworms . It was Enchytraeus crypticus, was only used in one experiment, which did not find differences in bioaccumulation of Ag, as nanoparticles or AgNO3, when exposed along with PET MP [The potworm, h PET MP .Brassica napus, Glycine max, Pisum sativum, Lactuca sativa, Lolium perenne, Oryza sativa, Triticum aestivum, and Zea mays. The characteristics of NMP, contaminants, and experiments are found in Eight terrestrial plants were tested in total, namely, The bioaccumulation of metals was the only one found to increase in the presence of NMP, representing 18.8% of the experiments with plants. All experiments were conducted in a freshly spiked medium. No influence of NMP on metal bioaccumulation was observed in 25% of the experiments.This systematic review aimed to answer one central question: whether NMP affected the bioaccumulation of contaminants by comparing the co-exposure of contaminants and NMP versus the single exposure to the contaminant. For that, only publications that had these two treatments  under the same conditions were included. Our results showed that NMP affected bioaccumulation in over 91% and 76% of the studies using earthworms and plants, respectively. NMP concentration seems to play an important role, as many studies observed that effects on bioaccumulation were increased or decreased with increasing NMP levels. More specifically, contaminant bioaccumulation decreased in seven experiments ,29,30,31Several reasons were attributed to increased contaminant bioaccumulation in earthworms and plants. One common explanation given by the authors was that NMP presence could increase the bioavailability of contaminants ,33,35,36Other explanations for the bioaccumulation increase were related to the biological characteristics or traits of the studied organisms. In earthworms, the ingestion of contaminated NMP caused an increase in contaminant levels ,37,38,39The presence of NMP could also decrease the bioaccumulation of contaminants, as shown by many studies. Similarly, NMP affected the bioavailable fraction of contaminants, but in this case, decreased the bioaccumulation in both earthworms ,29,45,46The studies, which found that NMP did not affect bioaccumulation, were all conducted with metals in earthworms and plants. This could be explained by the fact that metals normally have lower adsorption coefficients for NMP than hydrophobic compounds . An exceAn overview of the mechanisms affecting the bioaccumulation of contaminants caused by NMP presence is given in The role of NMP as a vector of contaminants is intrinsically related to biological and chemical processes, as follows: adsorption of contaminant from medium to NMP, uptake of contaminated NMP by the organism by the organism, desorption of the contaminant in the body or rhizosphere followed by absorption into the vascular system or transfer of contaminated NMP into the vascular system. Considering the contaminants’ concentration in the environmental matrix is higher than in the NMP, the transfer of the contaminant from the medium to the NMP occurs. The adsorption is highly dependent not only on the chemical properties of NMP and contaminant but also on several environmental factors and may be a rather complex process . While sHowever, whether the NMP adsorbed with contaminants will enter the organism’s body depends on the organism’s traits, such as feeding behavior . If the NMP may also present indirect effects on bioaccumulation. One interesting fact observed in the studies included in this review is that NMP can also affect the environmental behavior of contaminants by either increasing or decreasing, for example, porewater concentrations . If NMP presence increases the porewater concentrations of a contaminant, it can result in a higher dermal/oral uptake in soil invertebrates or root uptake in plants of the contaminant from the medium, independent of the uptake of NMP by the organisms.Finally, there are also mechanisms related to bioaccessibility, which is the contaminant fraction that crosses the biological barrier . This meAlthough there is an increasing number of publications on this topic, this systematic review identified several knowledge gaps. The first observation was the low number of different taxonomic groups studied. The terrestrial ecosystem comprises organisms living in different habitats and diverse traits. Particularly, there was a lack of studies with soil invertebrates other than oligochaetes.Regarding the NMP characteristics, PS accounted for about 55% of the polymer type studied, and the spherical-shaped ones comprised almost 45%. Nevertheless, PE accounts for most plastic waste in the environment ,65,66. FToxicokinetic studies on chemicals comparing treatments with and without NMP were unavailable for soil organisms. Few publications assessed chemical uptake over time ,41, and The evidence of NMP affecting bioaccumulation under a realistic scenario is limited. Extremely high NMP concentrations were used in many studies included in this review, and effects on contaminants’ bioaccumulation occurred mainly at ≥500 mg/kg. Testing high levels of NMP contamination is important to observe extreme exposure scenarios. However, in most studies, the effects on bioaccumulation were observed at unrealistically high concentrations . Moreover, a high percentage of studies did not provide basic information on the NMP characteristics. For example, 21% of the publications reported herein did not inform the shape of the NMP used in their experiments. It is imperative for publications to include this information in the methodology section and to take it into account when discussing their results because the size and shape of NMP ultimately determine interaction and/or internalization by organisms. -Research is moving towards smaller particles, with an increasing number of publications using NP.-In plants, most studies observed a decrease in contaminants’ bioaccumulation. In earthworms, on the other hand, an increase in contaminant bioaccumulation was observed in most of the experiments.-In general, change in the bioavailable forms of the contaminants, either water or soil, was a major reason for the NMP to affect the contaminants’ bioaccumulation. This was valid for both plants and earthworms, even though the route of exposure differs between these two taxonomic groups.-Little consistency was found regarding NMP characteristics. This could be caused by the specific relation between NMP characteristics and the overall study design (from spiking methodology to contaminant used and its concentrations). Still, this topic should be better explored. For example, there is still inconsistency among studies on the NMP size that can enter the plant root.-Effects on bioaccumulation were more visible at high NMP concentrations, with few exceptions using realistic low concentrations. Future studies should focus on environmentally realistic concentrations.The main findings of this systematic review are synthesized below:


Crohn’s disease (CD) is a chronic inflammatory condition which can affect the entire gastrointestinal tract with a wide variety of potential complications which may require endoscopic or surgical interventions. Small bowel CD beyond the reach of standard endoscopy poses a diagnostic obstacle and relies on cross sectional imaging ─ such as computed tomography enterography (CTE) ─ and balloon assisted endoscopy (BAE). BAE is the current diagnostic gold standard allowing for direct mucosal visualization as well as therapeutic capabilities; however, remains limited by access, cost, and requires specialized training. Alternatively, CTE in small bowel in CD is widely available, and less invasive than BAE. The diagnostic accuracy of CTE against the gold standard of BAE remains unclear.We aim to assess the sensitivity and specificity of CTE vs BAE in the diagnosis and evaluation of small bowel CD.Patients with an established diagnosis of Crohn’s disease who underwent a CTE and a BAE within 6 months between 2011 and 2018 were reviewed. Relevant findings of active inflammation , long-segment disease (≥ 15 cm active disease), skip-segments, number of strictures, and presence of high-grade strictures  were extracted from both reports and images of CTE and BAE by two independent reviewers. Sensitivity and specificity for each finding on CTE was calculated using BAE as the gold-standard diagnostic test.A total of 42 patients with 65 corresponding CTE and BAE were identified between 2011 and 2018. CTE was found to be most sensitive for assessing presence of active inflammation and number of strictures at 75.6%  and 71.4% , respectively. CTE was highly specific for findings of long-segment inflammation, skip lesions, number of strictures, and high-grade stricture with a specificity of 89.3% , 74.1% , 100% , and 84.4%  respectively. CTE showed poor specificity for active inflammation 45.0% [23.1-68.5%], and poor sensitivity for high grade strictures 54.5% [36.4-71.9] and skip lesions 54.5% [23.4-83.3]CTE is relatively sensitive in detecting active inflammation and number of strictures compared to BAE, but showed suboptimal sensitivity in detecting long segment inflammation, skip lesions, and high-grade strictures. CTE showed high specificity in identification of long segment inflammation, number of strictures, and high-grade strictures, but not active inflammation overall. CTE and BAE are complementary to one another and based utilized in combination to improve diagnostic accuracy. Future directions include prospective validation prospective studies to validate the results of this study looking at a broader population of Crohn’s disease patients.NoneNone Declared