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Background: Scientific writing is a core component of academic hospital medicine, and yet finding time to engage in deeply focused writing is difficult in part due to the highly clinical, 24/7 nature of the specialty that can limit opportunities for writing-focused collaboration and mentorship., Objective: Our objective was to develop and evaluate an academic writing retreat program., Methods: We drafted a set of key retreat features to guide implementation of a 3-day, 2-night retreat program held within a 2 h radius of our hospital. Agendas included writing blocks ranging from 45 to 90 min interspersed with breaks and opportunities for feedback, exercise, and preparing meals together. After each retreat, we distributed an evaluation with multiple choice and free text response options to characterize retreat helpfulness and later gathered data on the status of each paper and grant worked on., Results: We held 4 retreats between September 2022 and October 2023, engaging 18 faculty and fellows at a cost of $296 per attendee per retreat. In evaluations, nearly 80% reported that the retreat was extremely helpful, and comments praised the highly mentored environment, enriching community of colleagues, and release from commitments that get in the way of writing. Of the 24 papers attendees worked on, 12 have been accepted and 6 are under review. Of the 4 grant proposals, 2 are under review., Conclusions: We implemented a low-cost, productive writing retreat program that attendees reported was helpful in supporting deep work and represented a meaningful step toward building a community centered around academic writing., (© 2024 Society of Hospital Medicine.)

Objective: In 2006 the Association of American Medical Colleges recommended standardization of documentation of the contributions of medical educators and guidelines for their academic promotion. The authors characterized current United States (US) medical school promotion guidelines for medical educators., Methods: Authors collected publicly available data from medical school promotion websites from March through July 2022 after determining categories by traditional-set domains as well as peer-reviewed standards. Extracted data were analyzed using descriptive and inferential statistics, and frequencies were calculated for nominal and categorical data., Results: Of 155 medical schools identified, promotion criteria were publicly available for 143 (92%) schools. Ninety-one (64%) schools identified a distinct educator track. Of those with a defined educator track, 44 (48%) schools consider workshops or other media when evaluating candidates for promotion, and only 52 (57%) of schools with a specified educational track require additional documentation of teaching or education as part of their promotion process. Notably, 34 (37%) of the 91 schools with an educator track specifically require an Educational Portfolio, compared to 27 (52%) of the 52 schools that do not have a specific educator track for promotion., Conclusion: This study describes the current lack of clarity and consistency of the promotion criteria for medical educators and indicates that the guidelines proposed by the Association of American Medical Colleges over 15 years ago have not been widely adopted. These data amplify previous calls for a more objective set of criteria for evaluating and recognizing the contributions of medical educators., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objective: To perform a qualitative content analysis of learning and assessment strategies that pediatric subinterns describe in Individualized Learning Plans (ILPs) and to explore barriers and facilitators to their learning., Methods: We analyzed ILPs from medical students enrolled in pediatric subinternships at 10 US medical schools that utilized a standardized curriculum and were recruited to reflect diversity in geographic location, funding, and enrollment. Students used an ILP to record 3 or more selected learning objectives, rationale for selection, and reflection on learning and assessment strategies. Investigators used the constant comparative method to perform a content analysis of the ILPs, grouping codes into themes, and verifying relationships between codes within themes., Results: Two hundred and four ILPs that included student reflections on 850 learning objectives were analyzed. Content was analyzed in 5 categories: rationale for selecting objectives, learning strategies, assessment strategies, challenges to learning, and facilitators of learning. Students showed strong commitment to individualized, self-directed learning, developed a wide range of creative learning strategies, and relied heavily on self-reflection to assess their progress. The learning environment both helped and hindered students' ability to make and assess progress on their selected learning objectives., Conclusions: Through ILP-guided reflection and a formal curriculum, students can choose well-justified learning objectives and demonstrate resourcefulness and independence in developing self-directed learning and assessment strategies. The strategies that students identified in this study provide a menu of learning and assessment options for subinterns. Identified challenges and facilitators of learning provide guidance for educators who seek to enhance the clinical learning environment., Competing Interests: Declaration of Competing Interest The authors have no potential conflicts of interest or corporate sponsors to disclose. We had no funding for this study., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Some pediatric residents report experiencing less autonomy when working clinically with pediatric hospital medicine (PHM) fellows than with attendings alone. We sought to explore pediatric senior resident (SR) experiences working clinically with PHM fellows, with a focus on characterizing fellow behaviors that could impact perceived resident autonomy., Methods: In this qualitative study, we conducted virtual semistructured interviews with pediatric SRs. We recorded, deidentified, and transcribed interviews for codebook thematic analysis, making iterative adjustments to our codebook and themes until reaching thematic sufficiency., Results: We conducted 17 interviews. A subanalysis identified key components of the resident mental model of autonomy, including independent clinical decision-making with 3 core qualifiers: 1) plan follow-through, 2) availability of a safety net, and 3) ownership. Our primary analysis identified 4 key themes (with a total of 7 contributory subthemes) describing resident experiences of autonomy, scaffolded based on an organizing framework adapted from Bronfenbrenner's ecological model including 1) microsystem factors (based on direct resident-fellow or resident-leadership team interactions), 2) mesosystem factors (based on fellow-attending interactions), 3) exosystem factors (based on fellow-intrinsic characteristics), and 4) macrosystem factors (cultural values, norms, and policies governing academic pediatrics)., Conclusions: Many factors impact perceived resident autonomy on PHM fellow-inclusive teams. Although some are related to direct resident-fellow interactions, many others are more complex and may reflect resident interactions with the leadership team, attending-fellow dynamics, and the influence of cultural context. Based on our analysis, we propose several best-practice recommendations directed at fellows, attendings, the fellow-attending dyad, and Graduate Medical Education programs overall., Competing Interests: Declaration of Competing Interest The authors have no relevant conflicts of interest to declare., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objectives: Individuals who prefer to communicate about health care in a language other than English (LOE) experience poorer quality medical care and challenges when communicating with health care providers. The objective of this study was to elucidate how caregivers who prefer an LOE perceive communication with their physicians on an inpatient general pediatrics service., Methods: Caregivers of patients admitted to the general pediatrics service at our urban freestanding children's hospital whose preferred language for medical care was Spanish, Arabic, Brazilian Portuguese, or Mandarin were eligible for this qualitative study. Semistructured interviews using video interpreter services were conducted to explore the participants' experiences communicating with their physicians. Interview transcripts were analyzed using conventional content analysis., Results: We interviewed 15 participants representing 7 countries of origin and 4 non-English languages: Spanish, Arabic, Brazilian Portuguese, and Mandarin. Three main domains emerged, including: (1) use of interpreter services, (2) overall communication experience with physician providers, and (3) suggestions for improvement in physician communication. Salient themes included early identification of the need for an interpreter is essential and physicians' use of body language in combination with an interpreter enhances successful communication., Conclusions: This project fills a gap in existing literature by describing the perspectives of caregivers who prefer an LOE, including those speaking languages other than Spanish, as they communicate with inpatient pediatricians. In addition to ensuring appropriate use of interpreter services, physicians can focus on using plain language and gestures during encounters, helping to facilitate communication and provide culturally competent care for this population., (Copyright © 2023 by the American Academy of Pediatrics.)

Objective: To describe the sociodemographic characteristics, access to sexual and reproductive health (SRH) care, including contraceptives and to assess menstrual poverty of migrant Venezuelan adult women of childbearing age at the northwestern border between Venezuela and Brazil., Methods: Cross-sectional study coordinated by the Department of Obstetrics and Gynecology, University of Campinas, Campinas, SP, Brazil, conducted in Boa Vista, Roraima between January 18 and 24, 2021. We invited women aged 18 to 49 years to participate. A semi-structured self-response questionnaire was applied. The survey covered issues relating to SRH services, knowledge, access, and use of SRH services for women. We also applied a questionnaire regarding access to and quality of hygiene kits and toilets, and an open-ended question on " what does menstruation mean to you" ? We excluded illiterate women and those with amenorrhea, those who had undergone hysterectomy or tubal ligation, and those with partners who had undergone vasectomy., Findings: The age (mean ± SD) of the 177 respondent women was 28 ± 6.8 years, 32.2% reported that they had more than three children, 38.4% referred at least one unplanned pregnancy, and 52.5% of the women indicated an intention to become pregnant in the near future. Furthermore, 40 (29.8%) women sought a healthcare service because they wanted a contraceptive method; among them, 16 did not receive the contraceptive that they chose, and 15 women wanted to use a contraceptive implant. Regarding menstrual poverty, 64 women stated that the menstrual hygiene products provided by humanitarian organizations were not enough for their needs, and 44 women claimed being unable to wash their hands anytime they wanted to., Conclusions: The vulnerabilities of this cohort of Venezuelan migrant women in Brazil who lived mainly out of the official shelters further increase when they struggle with no knowledge of how to access SRH services, lack of provision of LARC methods, risk of unplanned pregnancy, and inappropriate access to menstrual hygiene products and sanitary services. There are several challenges to be overcome to ensure SRH care for migrant women in Brazil., Competing Interests: The authors have declared that no competing interests exist., (© 2022 The Authors. Published by Elsevier Ltd.)

Interprofessional teamwork provides unique opportunities for improving patient care. This study used Social Identity Theory as a conceptual framework to characterize the relationships between the social identities of pediatric hospitalists and their perceptions of interprofessional teamwork. We used qualitative methods including free-listing and semi-structured interviews to examine these relationships. We identified five key themes: (a) Pediatric hospitalists' identities fall along a spectrum ranging from profession-centered to team-centered; (b) Familiarity is conducive to formation of team identity; (c) Co-creation of a shared vision and practice of creating shared mental models strengthens sense of team; (d) Institutional culture acts as both a facilitator for and barrier to formation of team identity; (e) High-functioning teams often epitomize the concept of "flexible leadership." We conclude that Social Identity Theory can be a useful theoretical lens for examining interprofessional teamwork in healthcare settings, including among pediatric hospitalists.

Children with medical complexity make up a small portion of the pediatric population but utilize a large percentage of health care time and spending. The medical needs of children with medical complexity are highly variable and the education of healthcare providers in the care of these children has taken on more significance. Designing curricula and educational innovations related to the care of children with medical complexity can be challenging. Familiarity with the sociocultural theory, the zone of proximal development, Kolb's experiential learning model, and the educational resources that already exist allow for more ease in developing a curriculum that fits the needs of learners who may have a wide range of exposure to children with medical complexity. Flipped classroom models, simulations, asynchronous modules, and home and community experiences are all useful learning modalities to provide a varied and important curriculum. Taking advantage of the knowledge and skills of the many different members of the multi-disciplinary team caring for children with medical complexity is an important educational strategy that provides benefits to the learners and can enhance interprofessional education., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Planning for and responding to happenstance is an important but rarely discussed part of the professional development of medical students. We noted this gap while conducting a study of career inflection points of 24 physicians who frequently mentioned how luck had shaped their unfolding careers. A review of the career counseling literature led us to a body of work known as Planned Happenstance Learning Theory (PHLT). PHLT focuses on the attitudes and skills to make happenstance a positive force in one's life. We found no reference to this work in the medical education literature and resolved to address this gap., Methods: We created resources for an interactive, 90-minute faculty development workshop. In the workshop, the facilitator used a PowerPoint presentation, vignettes of happenstance, a student testimonial, and a reflection worksheet. We presented and formally evaluated the workshop at three national meetings for health science educators., Results: Workshop participants, mostly faculty ( N = 45), consistently expressed positive regard for the workshop content, organization, and instructional methods, especially the opportunity for guided reflection. A retrospective pre/postevaluation revealed a meaningful increase in knowledge about PHLT attitudes and skills, as well as a commitment to use these skills in promoting professional development., Discussion: The skills and attitudes of PHLT are relevant to students' career development. A workshop designed to introduce PHLT skills and attitudes to faculty advisors and mentors can help prepare faculty to promote students' awareness and use of these attitudes and skills., (© 2021 Vo et al.)

Purpose: Difficulty in recruiting and retaining community preceptors for medical student education has been described in the literature. Yet little, if any, information is known about community outpatient preceptors who have stopped or decreased teaching time with students. This study aimed to examine these preceptors' perspectives about this phenomenon., Method: Using a phenomenology framework, this multi-institutional qualitative study used semistructured interviews with community pediatric preceptors who had stopped or reduced teaching time with medical students. Interviews were conducted between October 2017 and January 2018 and transcribed verbatim. Interviews explored factors for engaging in teaching, or decreasing or ceasing teaching, that would enable future teaching. An initial code book was developed and refined as data were analyzed to generate themes., Results: Twenty-seven community pediatricians affiliated with 10 institutions participated. Thirty-seven codes resulted in 4 organizing themes: evolution of health care, personal barriers, educational system, and ideal situations to recruit and retain preceptors, each with subthemes., Conclusions: From the viewpoints of physicians who had decreased or stopped teaching students, this study more deeply explores previously described reasons contributing to the decline of community preceptors, adds newly described barriers, and offers strategies to help counter this phenomenon based on preceptors' perceptions. These findings appear to be manifestations of deeper issues including the professional identify of clinical educators. Understanding the barriers and strategies and how they relate to preceptors themselves should better inform education leaders to more effectively halt the decline of community precepting and enhance the clinical precepting environment for medical students.

Objective: Boot camps are being developed and implemented by a growing number of medical schools to facilitate medical students' transition to internship. However, there is limited conceptual understanding of how this facilitation occurs., Methods: We developed and piloted a 1-week pediatric boot camp in 2015, then significantly revised and evaluated the program in 2016-2017 using a conceptual framework of self-efficacy. Consistent with this framework, the revised boot camp focuses on enhancing practical skills that can ease medical students' transition to internship. Observations and course evaluations informed process evaluation, whereas learner assessments immediately after and at 6 months after the boot camp informed outcomes evaluation in terms of both perceived self-efficacy and confidence., Results: Medical students valued sessions that were "hands on," and program improvements were made to include a variety of interactive curricular activities. Data from course evaluations provided evidence of increased perceived self-efficacy. Learner assessment showed a medium to large effect size for confidence in nearly all specific skills that were queried and a positive, albeit attenuated, effect on perceived self-efficacy at 6 months., Conclusions: Program evaluation of a pediatric boot camp informed by a conceptual framework of self-efficacy shed light on how it might facilitate medical students' transition to internship. A similar conceptual framework may be useful for other trainee preparatory courses., (Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Low-value health care is pervasive in the United States, and clinicians need to be trained to be stewards of health care resources. Despite a mandate by the Accreditation Council for Graduate Medical Education to educate trainee physicians on cost awareness, only 10% of pediatric residency programs have a high-value care (HVC) curriculum. To meet this need, we set out to develop and evaluate the impact of High-Value Pediatrics, an open-access HVC curriculum. High-Value Pediatrics is a 3-part curriculum that includes 4 standardized didactics, monthly interactive morning reports, and an embedded HVC improvement project. Curriculum evaluation through an anonymous, voluntary survey revealed an improvement in the self-reported knowledge of health care costs, charges, reimbursement, and value ( P < .05). Qualitative results revealed self-reported behavior changes, and HVC improvement projects resulted in higher-value patient care. The implementation of High-Value Pediatrics is feasible and reveals improved knowledge and attitudes about HVC. HVC improvement projects augmented curricular knowledge gains and revealed behavior changes. It is imperative that formal high-value education be taught to every pediatric trainee to lead the culture change that is necessary to turn the tide against low-value health care. In addition, simultaneous work on faculty education and attention to the hidden curriculum of low-value care is needed for sustained and long-term improvements., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Objective: Electronic health record (EHR) simulation with realistic test patients has improved recognition of safety concerns in test environments. We assessed if simulation affects EHR use patterns in real clinical settings., Materials and Methods: We created a 1-hour educational intervention of a simulated admission for pediatric interns. Data visualization and information retrieval tools were introduced to facilitate recognition of the patient's clinical status. Using EHR audit logs, we assessed the frequency with which these tools were accessed by residents prior to simulation exposure (intervention group, pre-simulation), after simulation exposure (intervention group, post-simulation), and among residents who never participated in simulation (control group)., Results: From July 2015 to February 2017, 57 pediatric residents participated in a simulation and 82 did not. Residents were more likely to use the data visualization tool after simulation (73% in post-simulation weeks vs 47% of combined pre-simulation and control weeks, P <. 0001) as well as the information retrieval tool (85% vs 36%, P < .0001). After adjusting for residents' experiences measured in previously completed inpatient weeks of service, simulation remained a significant predictor of using the data visualization (OR 2.8, CI: 2.1-3.9) and information retrieval tools (OR 3.0, CI: 2.0-4.5). Tool use did not decrease in interrupted time-series analysis over a median of 19 (IQR: 8-32) weeks of post-simulation follow-up., Discussion: Simulation was associated with persistent changes to EHR use patterns among pediatric residents., Conclusion: EHR simulation is an effective educational method that can change participants' use patterns in real clinical settings.

Objective: Effective self-directed educational tools are invaluable. Our objective was to determine whether a self-directed, web-based oral case presentation module would improve medical students' oral case presentations compared to usual curriculum, and with similar efficacy as structured oral presentation faculty feedback sessions., Methods: We conducted a pragmatic multicenter cluster randomized controlled trial among medical students rotating in pediatric clerkships at 7 US medical schools. In the clerkship's first 14 days, subjects were instructed to complete an online Computer-Assisted Learning in Pediatrics Program (CLIPP) oral case presentation module, an in-person faculty-led case presentation feedback session, or neither (control). At the clerkship's end, evaluators blinded to intervention status rated the quality of students' oral case presentations on a 10-point scale. We conducted intention-to-treat multivariable analyses clustered on clerkship block., Results: Study participants included 256 CLIPP (32.5%), 263 feedback (33.3%), and 270 control (34.2%) subjects. Only 51.1% of CLIPP subjects completed the assigned presentation module, while 98.5% of feedback subjects participated in presentation feedback sessions. Compared to controls, oral presentation quality was significantly higher in the feedback group (adjusted difference in mean quality, 0.28; 95% confidence interval, 0.08, 0.49) and trended toward being significantly higher in the CLIPP group (0.19; 95% confidence interval, -0.006, 0.38). The quality of presentations in the CLIPP and feedback groups was not significantly different (-0.10; 95% confidence interval, -0.31, 0.11)., Conclusions: The quality of oral case presentations delivered by students randomized to complete the CLIPP module did not differ from faculty-led presentation feedback sessions and was not statistically superior to control., (Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Providing and learning from feedback are essential components of medical education, and typically described as resistant to change. But given a decade of change in the clinical context in which feedback occurs, the authors asked if, and how, perceptions of feedback and feedback behaviors might have changed in response to contextual affordances., Methods: In 2017, the authors conducted a follow-up, ethnographic study on 2 general pediatric floors at the same children's hospital where another ethnographic study on a general pediatric floor was conducted in 2007. Data sources included (1) 21 and 34 hours of observation in 2007 and 2017, respectively, (2) 35 and 25 interviews with general pediatric attending physicians and residents in 2007 and 2017, respectively, and (3) a review of 120 program documents spanning 2007 to 2017. Data were coded and organized around 3 recommendations for feedback that were derived from 2007 data and served as standards for assessing change in 2017., Results: Data revealed progress in achieving each recommendation. Compared with 2007, participants in 2017 more clearly distinguished between feedback and evaluation; residents were more aware of in-the-moment feedback, and they had shifted their orientation from evaluation and grades to feedback and learning. Explanations for progress in achieving recommendations, which were derived from the data, pointed to institutional and national influences, namely, the pediatric milestones., Conclusions: On the basis of follow-up, ethnographic data, changes in the clinical context of pediatric education may afford positive change in perceptions of feedback and feedback behavior and point to influences within and beyond the institution., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Purpose: The recruitment and retention of community preceptors to teach medical students is difficult. The authors sought to characterize the underlying motivational factors for becoming a preceptor and to identify strategies for recruiting and retaining community-based pediatric preceptors., Method: This multicenter qualitative action study included semistructured interviews with community-based pediatric preceptors affiliated with 12 institutions from August to December 2015. Only active preceptors were included, and participating institutions were diverse with respect to geographic location and class size. Interviews were conducted over the telephone and transcribed verbatim. Six investigators used deidentified transcripts to develop a codebook. Through a constant comparative method, codes were revised as data were analyzed and disagreements were resolved through discussion. All investigators organized the themes into dimensions., Results: Fifty-one preceptors were interviewed. Forty-one themes coalesced into four dimensions: (1) least liked aspects of teaching, (2) preparation to teach, (3) inspiration to teach, and (4) ways to improve recruitment and retention. Time constraints and patient care demands were the most commonly cited deterrents to teaching. Successful preceptors balanced their clinical demands with their desire to teach using creative scheduling. External rewards (e.g., recognition, continuing medical education credit) served as incentives. Internal motivation inspired participants to share their enthusiasm for pediatrics and to develop longitudinal relationships with their learners., Conclusions: Changes in health care delivery have imposed more time constraints on community-based preceptors. However, this study identified underlying factors motivating physicians to volunteer as preceptors. Strategies to recruit new and retain current preceptors must be collaborative.

Purpose: To investigate evidence for validity of faculty members' pediatric milestone (PM) ratings of interns (first-year residents) and subinterns (fourth-year medical students) on nine subcompetencies related to readiness to serve as a pediatric intern in the inpatient setting., Method: The Association of Pediatric Program Directors Longitudinal Educational Assessment Research Network (APPD LEARN) and the National Board of Medical Examiners collaborated to investigate the utility of assessments of the PMs for trainees' performance. Data from 32 subinterns and 179 interns at 17 programs were collected from July 2012 through April 2013. Observers used several tools to assess learners. At each site, a faculty member used these data to make judgments about the learner's current developmental milestone in each subcompetency. Linear mixed models were fitted to milestone judgments to examine their relationship with learner's rank and subcompetency., Results: On a 5-point developmental scale, mean milestone levels for interns ranged from 3.20 (for the subcompetency Work effectively as a member of a team) to 3.72 (Humanism) and for subinterns from 2.89 (Organize and prioritize care) to 3.61 (Professionalization). Mean milestone ratings were significantly higher for the Professionalism competency (3.59-3.72) for all trainees compared with Patient Care (2.89-3.24) and Personal and Professional Development (3.33-3.51). Mean intern ratings were significantly higher than mean subintern ratings for all nine subcompetencies except Professionalization, Humanism, and Trustworthiness., Conclusions: The PMs had a coherent internal structure and could distinguish between differing levels of trainees, which supports their validation for documenting developmental progression of pediatric trainees.

Background: To develop the capacity for rapid-cycle improvement at the unit level, a large freestanding children's hospital designated 2 inpatient units with normal patient loads and workforce as pilot "Innovation Units" where frontline staff was trained to lead rigorous improvement portfolios., Methods: Frontline staff received improvement training, and interdisciplinary teams brainstormed ideas for tests of change. Ideas were prioritized using an impact-effort evaluation and an assessment of how they aligned with high-level goals. A template for each test summarized the following: the opportunity for improvement, the test being conducted, dates for the tests, driver diagrams, metrics to measure effects, baseline data, results, findings, and next steps. Successful interventions were implemented and disseminated to other units., Results: Multidisciplinary staff generated 150 improvement ideas and Innovation Units collectively ran >40 plan-do-study-act cycles. Of the 10 distinct improvement projects, elements of all 10 were deemed "successful" and fully implemented on the unit, and elements from 8 were spread to other units. More than 3 years later, elements of all of the successful improvements are still in practice in some form on the units, and each unit has tested >20 additional improvement ideas, using multiple plan-do-study-act cycles to refine them., Conclusions: The Innovation Unit model successfully engaged frontline staff in improvement work and established a sustainable system and framework for managing rigorous improvement portfolios at the unit level. Other hospitals and health care delivery settings may find our quality improvement approach helpful, especially because it is rooted in the microsystem of care delivery., (Copyright © 2016 by the American Academy of Pediatrics.)

Purpose: To report on the development of content and user feedback regarding the assessment process and utility of the workplace-based assessment instruments of the Pediatrics Milestones Assessment Pilot (PMAP)., Method: One multisource feedback instrument and two structured clinical observation instruments were developed and refined by experts in pediatrics and assessment to provide evidence for nine competencies based on the Pediatrics Milestones (PMs) and chosen to inform residency program faculty decisions about learners' readiness to serve as pediatric interns in the inpatient setting. During the 2012-2013 PMAP study, 18 U.S. pediatric residency programs enrolled interns and subinterns. Faculty, residents, nurses, and other observers used the instruments to assess learner performance through direct observation during a one-month rotation. At the end of the rotation, data were aggregated for each learner, milestone levels were assigned using a milestone classification form, and feedback was provided to learners. Learners and site leads were surveyed and/or interviewed about their experience as participants., Results: Across the sites, 2,338 instruments assessing 239 learners were completed by 630 unique observers. Regarding end-of-rotation feedback, 93% of learners (128/137) agreed the assessments and feedback "helped me understand how those with whom I work perceive my performance," and 85% (117/137) agreed they were "useful for constructing future goals or identifying a developmental path." Site leads identified several benefits and challenges to the assessment process., Conclusions: PM-based instruments used in workplace-based assessment provide a meaningful and acceptable approach to collecting evidence of learner competency development. Learners valued feedback provided by PM-based assessment.

There is evidence that both smartphone and tablet integration into medical education has been lacking. At the same time, there is a niche for augmented reality (AR) to improve this process through the enhancement of textbook learning. Gunner Goggles is an attempt to enhance textbook learning in shelf exam preparatory review with augmented reality. Here we describe our initial prototype and detail the process by which augmented reality was implemented into our textbook through Layar. We describe the unique functionalities of our textbook pages upon augmented reality implementation, which includes links, videos and 3D figures, and surveyed 24 third year medical students for their impression of the technology. Upon demonstrating an initial prototype textbook chapter, 100% (24/24) of students felt that augmented reality improved the quality of our textbook chapter as a learning tool. Of these students, 92% (22/24) agreed that their shelf exam review was inadequate and 19/24 (79%) felt that a completed Gunner Goggles product would have been a viable alternative to their shelf exam review. Thus, while students report interest in the integration of AR into medical education test prep, future investigation into how the use of AR can improve performance on exams is warranted.

Objective: To document the prevalence of simulation-based education (SBE) for third- and fourth-year medical students; to determine the perceived importance of SBE; to characterize the barriers associated with establishing SBE., Methods: A 27-item survey regarding simulation was distributed to members of the Council on Medical Student Education in Pediatrics (COMSEP) as part of a larger survey in 2012., Results: Seventy-one (48%) of 147 clerkship directors (CD) at COMSEP institutions responded to the survey questions regarding the use of SBE. Eighty-nine percent (63 of 71) of CDs reported use of SBE in some form: 27% of those programs (17 of 63) reported only the use of the online-based Computer-Assisted Learning in Pediatrics Program, and 73% (46 of 63) reported usage of other SBE modalities. Fifty-four percent of CDs (38 of 71) agreed that SBE is necessary to meet the requirements of the Liaison Committee on Medical Education (LCME). Multiple barriers were reported in initiating and implementing an SBE program., Conclusions: SBE is commonly used for instruction during pediatric undergraduate medical education in North American medical schools. Barriers to the use of SBE remain despite the perception that it is needed to meet requirements of the LCME., (Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Pharmaceutical compounds such as ketoprofen, diclofenac and atenolol are frequently detected at relatively high concentrations in secondary effluents from wastewater treatment plants. Therefore, it is important to assess their transformation kinetics and intermediates in subsequent disinfection processes, such as direct ultraviolet (UV) irradiation. The photodegradation kinetics of these compounds using a medium pressure (MP) lamp was assessed in pure water, as well as in filtered and unfiltered treated wastewater. Ketoprofen had the highest time- and fluence-based rate constants in all experiments, whereas atenolol had the lowest values, which is consistent with the corresponding decadic molar absorption coefficient and quantum yield. The fluence-based rate constants of all compounds were evaluated in filtered and unfiltered wastewater matrices as well as in pure water. Furthermore, transformation products of ketoprofen, diclofenac and atenolol were identified and monitored throughout the irradiation experiments, and photodegradation pathways were proposed for each compound. This enabled the identification of persistent transformation products, which are potentially discharged from WWTP disinfection works employing UV photolysis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose of Review: Nonaccidental trauma and neglect continue to be major problems for children, families, and the providers who care for them. Whereas prevention is the key to ending child abuse and neglect, diagnosis and treatment continue to be the mainstays of practice. This article will briefly review the epidemiology, diagnosis, sequelae, and prevention of abuse and neglect in today's world., Recent Findings: The latest statistics estimate that more than 900000 children are victims of child maltreatment. Abuse occurs at all ages but is most common in younger children. Child abuse may manifest as skin injuries, skeletal trauma, head injury, or many other forms. Information on abusive head trauma has been published in large amounts in the past year and is reviewed in further depth. The long-term consequences, the keys to prevention, and the role for pediatric providers are also reviewed., Summary: Whereas great strides have been made in diagnosing and treating child abuse, our work has been cut out for us in preventing child abuse. Pediatric clinicians must continue to screen patients and families, recognize signs and symptoms of abuse and neglect, and find time to advocate for home visits, early intervention programs, and education on this very important topic.

We report the case of a 55-year-old man with neurosyphilis that presented with features of herpes simplex encephalitis. Neurosyphilis is easily diagnosed and treated and should be included in the differential diagnosis of herpes simplex encephalitis.

Purpose: To determine the following: (1) the feasibility of combining the antiretroviral didanosine (ddl) with a 96-hour continuous intravenous (IV) infusion of cyclophosphamide (800 mg/m2), doxorubicin (50 mg/m2), and etoposide (240 mg/m2) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma (NHL) associated with human immunodeficiency virus (HIV) infection; (2) the effect of ddl on CDE-induced myelosuppression and CD4 lymphopenia; and (3) the effect of CDE on serum p24 antigen and quantitative HIV blood cultures., Methods: Twenty-five patients with HIV-related NHL received CDE every 28 or more days. Consecutive patients were assigned in an alternating fashion to group A (ddl given at a standard dose during cycles one, two, five, and six) or group B (ddl given during cycles three, four, five, and six)., Results: ddl use was associated with less leukopenia (mean nadir, 3.33 v 1.49 x 10(3)/microL; p = .03), neutropenia (2.38 v 1.07 x 10(3)/microL; p = .03), and thrombocytopenia (76 v 48 x 10(3)/microL; p = .059), and fewer RBC (1.6 v 3.1 per cycle; p < .01) and platelet transfusions (0.7 v 1.5 per cycle; p < .01), but had no significant effect on CD4 lymphopenia. Furthermore, lymphomatous bone marrow involvement and low CD4 count were associated with significantly greater myelosuppression. Although there was no substantial change in serum p24 antigen, the HIV blood culture became quantitatively more positive or converted from negative to positive in seven patients (64%). Complete response (CR) occurred in 58% of patients (95% confidence interval, 38% to 78%), median CR duration exceeded 18 months, tumor-related mortality was 20%, and median survival was 18.4 months., Conclusion: Our results suggest that the CDE and filgrastim regimen is tolerable and effective for patients with HIV-associated NHL, and that combination with ddl is feasible and may result in less myelosuppression.

Objective: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia., Design: A randomized, double-blind study., Setting: 24 U.S. academic medical centers., Patients: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less., Intervention: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone., Measurements: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions., Results: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P=0.2), therapeutic failure (P>0.2), or a complete course of therapy (P>0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P>.02). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P=0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P=0.01)., Conclusions: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

The VitaCuff catheter, a specialized central venous catheter (CVC) with an attached silver-impregnated cuff, is designed to permit percutaneous placement and prolonged venous access. A prospective randomized study was undertaken comparing the VitaCuff with standard triple lumen catheters to determine if the VitaCuff reduces infection during extended use. All consenting patients underwent percutaneous placement of subclavian lines. By study design, control and VitaCuff catheters could remain in site for up to 7 and 14 days, respectively. Cultures were obtained from the preinsertion skin site, and upon removal, from the skin, hubs, infusates, CVC tip, and cuff. Statistical methods included chi 2, the Student t test, and the log-rank test on Kaplan-Meier estimates. Of 133 patients completing this study, 64 patients (48.1%) underwent VitaCuff placement and 69 patients (51.8%) served as controls. In 124 patients (93.2%), the indication for catheter placement was for perioperative care. Overall, 67 patients (50.4%) required central venous access > 7 days, necessitating > or = 1 additional line in 29 patients (21.8%). The incidence of pneumothorax per patient from the initial central line insertion was 4/104 (3.85%), significantly lower than the 4/29 (13.8%) incidence during secondary catheter placement (P = 0.046). Culture results upon catheter removal demonstrated a reduction in colonization of skin sites and hubs for the VitaCuff patients, but not for catheter tips or infusates. Regardless of the type of catheter used, colonization was dependent upon duration of insertion. The incidence of catheter-related sepsis was 6.8%, and did not differ significantly between the study groups. Multiple CVC insertions increase the incidence of pneumothorax. Because VitaCuff catheters permit extended access up to 14 days without increasing the incidence of sepsis, we recommend their use in patients who require prolonged CVC access.

A variety of mycobacterial organisms may infect patients with acquired immunodeficiency syndrome. A patient with acquired immunodeficiency syndrome, lymphoma, and sporotrichoid Mycobacterium marinum is described. The patient responded completely to antimycobacterial therapy but relapsed when he discontinued his medications six months into his course. Disease persistence in spite of therapy had been noted in other immunocompromised states but not previously in acquired immunodeficiency syndrome. Patients with acquired immunodeficiency syndrome may require prolonged treatment or suppressive therapy for Mycobacterium marinum infections.

The increase in the number of human immunodeficiency virus-1 (HIV-1)-infected children is a direct consequence of the heterosexual spread of the disease to women and the growing number of HIV-positive i.v. drug users. It is not known how the majority of infants born to HIV-1-infected women escape HIV-1 infection, and, for those infected, the timing of HIV-1 transmission has yet to be determined. In addition, the role of maternal antibodies in the prevention of HIV-1 transmission to the fetus is unclear. We have previously demonstrated a correlation between vertical transmission and the absence of high-affinity/avidity antibodies to a peptide, KRI-HIGPGRAFYT, which corresponds to a region of the primary neutralizing domain of the gp120 V3 loop of HIVMN (MN-PND). The present study examines the correlation between the presence of these high affinity antibodies in women completing a pregnancy or undergoing an elective abortion and the detection of HIV-1 infection in their aborted fetuses. In several instances, transmission occurred despite high-affinity antibodies to the MN-PND. We have, therefore, evaluated the reactivity of sera to different MN-PND variants. In one infant born to a mother with high-affinity/avidity antibodies to KRI-HIGPGRAFYT (classic MN-PND), the infected baby developed antibodies to an MN-PND variant peptide against which his mother did not mount a humoral immune response during pregnancy. This finding indicates that fetal infection with MN-PND escape mutants arising during pregnancy may occur during a period when the mother is serologically negative.

Pediatric AIDS is increasing in frequency due to a rise in the number of human immunodeficiency virus type 1 (HIV-1)-infected women of childbearing age. Because outcome studies reveal that most children infected peripartum manifest HIV-1-related disease in the first year of life, intrauterine infection has been suspected. Fetal tissues from 23 second-trimester abortuses were examined. The presence of HIV-1 nucleic acid sequences was determined by the polymerase chain reaction and used to define infection of the fetus. By analysis of available tissues, 7 of 23 fetuses were infected, while control fetal tissue was negative. In situ hybridization for HIV-1 DNA showed that only 1 of 8 infected abortuses was positive, while all samples of noninfected tissues revealed no HIV-1 DNA. These studies indicate that maternofetal transmission of HIV-1 may occur in 30% of pregnancies (7/23) by the end of the second trimester.

In the majority of adult and pediatric patients with AIDS, hematologic abnormalities including leukopenia, anemia, and thrombocytopenia are commonly observed. In addition to these findings, changes in hematopoietic progenitor cells occur, including a reduction of multipotential-forming units, granulocyte-macrophages, macrophage as well as eosinophil colony-forming units, and bone marrow erythroid burst-forming units. This study examined alterations in human fetal liver hematopoiesis in 2nd trimester abortuses from human immunodeficiency virus (HIV)-seropositive women. The differentiation and growth potential of hematopoietic cells in vitro were monitored. Upon initial isolation, some populations of liver hematopoietic cells from abortuses of HIV-seropositive women were significantly decreased when compared to age-matched samples from fetuses of normal females including the percentage of early T cells [cluster of differentiation (CD)2], B cells (CD19), and early monocytes (CD14). A decrease in multipotent progenitors (CD34), myelomonocytes (CD33), and panleukocytes (CD45) was also observed. In contrast, after 21 d in culture, cells from HIV abortuses demonstrated an increase in the percentage of CD14 cells when stimulated with erythropoietin and granulocyte-monocyte colony-stimulating factor, as well as an increase in CD45 phenotype after exposure to granulocyte-monocyte colony-stimulating factor alone. These samples showed a persistence of erythropoietic elements (transferrin and CD36 phenotype) when compared to normal controls. No significant difference in the in vitro growth of hematopoietic progenitors (bone marrow erythroid burst-forming units, granulocyte-macrophage colony-forming units, and multipotential forming units) between these samples and normal controls was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Some neonates with congenital human immunodeficiency virus type 1 (HIV-1) infection exhibit immune dysregulation. This suggests that fetal CD4+ cells, possibly thymocytes, may be infected during gestation. If thymocytes are infected, this may result in a disruption of T-cell differentiation. To examine this hypothesis, normal human fetal thymocytes were established in tissue culture, characterized, and then exposed to HIV-1. On initial isolation, fetal thymocytes were analyzed for phenotypic markers by flow cytometry and assessed for T-cell function by mitogen-stimulated thymidine incorporation. The thymocytes comprised greater than 70% double positive (CD4+, CD8+) cells and responded to T- but not to B-cell mitogens. Thereafter, thymocytes were incubated in either tissue culture medium containing infectious HIV-1 or in control (HIV-free) medium. Infection of fetal thymocytes was determined by light and electron microscopy in combination with immunocytochemistry, molecular hybridization, and an infectious cell center (ICC) assay. After 1 week in culture, the thymocytes exposed to HIV-1 were positive by immunocytochemistry for the HIV-1-associated protein gp41. In addition, the presence of HIV-1 DNA was detected by molecular hybridization confirming infection of these cells. The ICC assay demonstrated the production of infectious HIV-1 particles and budding of mature virions was observed by electron microscopy. These studies demonstrate that human fetal thymocytes can be infected with HIV-1 in vitro and that this infection results in production of infectious virions. These results support the hypothesis that vertical transmission of HIV-1 in vivo may result in the infection of fetal thymocytes, which may contribute to postnatal HIV-1-associated pathologic conditions.

Passive immunity is conferred to the fetus by maternal antibodies, the majority of which are transported across the placenta during the third trimester of pregnancy. To determine the placental transport of anti-HIV-1 antibodies, serum from 5 women infected with human immunodeficiency virus (HIV) and their abortuses were examined for anti-HIV-1 antibodies. The gestational age of the abortuses ranged from 18 to 24 weeks and following polymerase chain reaction amplification, HIV-1 gag DNA was detected in tissue from 2 of the abortuses. The concentration of total IgG antibodies present in cord blood ranged from 2.9% to 12.5% of maternal levels. Antibodies directed against the envelope proteins, gp160 and gp120, the reverse transcriptase protein, p66, and the capsular protein, p24, were present in fetal and maternal serum. Although IgG1 was the predominant subclass antibody generated in response to HIV-1 proteins, IgG2, IgG3, and IgG4 directed against HIV-1 proteins were also detected. There were large differences in the antigens recognized by the antibodies produced in the mothers, and the IgG subclasses of the antibodies produced. HIV-1 proteins recognized by antibodies present in cord blood were similar to those recognized by paired maternal serum and IgG1, IgG2, IgG3 recognizing HIV-1 proteins were detected in fetal serum. However, there was a dichotomy in placental transport of IgG subclass antibodies to HIV-1 proteins. The role of these antibodies in prevention of vertical transmission of HIV-1 has yet to be determined.

The central nervous system (CNS) of 221 adults and 31 infants or children with the acquired immunodeficiency syndrome (AIDS) was examined with immunocytochemistry for infectious agents and for human immunodeficiency virus-1 (HIV-1) antigen (gp41). Since the major risk factor in this population was intravenous drug abuse, there were more female and pediatric patients than in other neuropathology autopsy series. Although children had a different spectrum of pathologic changes, including less frequent opportunistic infections, women did not differ from men in terms of types or incidence of opportunistic infections, vascular disease, neoplasia, and subacute AIDS encephalitis (SAE). Subacute AIDS encephalitis was detected in 26% of adult and 48% of pediatric brains. Immunocytochemical analysis of 100 adult and 20 pediatric brains revealed gp41 immunoreactivity in 78% and 40%, respectively. Virtually all adult brains with SAE had gp41 immunoreactivity in macrophages and microglia. Even brains with no significant pathology had frequent gp41 immunoreactivity, especially in the basal ganglia. In pediatric brains, including cases with SAE, gp41 immunoreactivity was less abundant, suggesting the possibility of latent infection or viral clearance. Spinal cords with vacuolar myelopathy or corticospinal tract degeneration had only rare gp41-positive cells. Brains from 16 aborted fetuses from HIV-1-seropositive women were all negative for gp41 immunoreactivity, but 12 brains were positive for HIV-1 by the polymerase chain reaction. These results may indicate that HIV-1 infection in fetal brains is below the limits of detection of immunocytochemistry. The differences noted between adults and children suggest that adults more often have productive CNS HIV-1 infection.

Vancomycin instilled in an Ommaya reservoir was used to treat a reservoir-associated infection. Vancomycin concentrations in cerebrospinal fluid (CSF) were measured, and derivation of pharmacokinetic parameters allowed tailoring of dosing. First-order kinetics were observed. The calculated half-life of 3.52 h was less than reported by others, and the apparent volume of distribution (60 ml) was less than anticipated. The elimination constant was 0.197 h-1. Empiric dosing based on schedules suggested in the literature would have led to high peak and low mean concentrations of intrareservoir vancomycin. Patients with reservoir-associated infections have a variety of pathophysiologic conditions that can result in alteration of normal CSF dynamics. Pharmacokinetic analysis is useful to individualize dosing and to optimize therapy with intrareservoir vancomycin.

Neurological disease is a common finding in children with AIDS and in others without signs of disease but with evidence of congenital HIV-1 infection. To investigate the possibility that HIV-1 can infect fetal central nervous system (CNS) tissue and therefore possibly serve as the substrate for the abnormal neurodevelopment characteristic of pediatric AIDS, eight abortus CNS samples (one set of twins) from seven HIV-1-seropositive intravenous drug users (IVDUs) and eight control abortus CNS samples from eight HIV-1-seronegative IVDUs were analyzed for HIV-1 infection. HIV-1 nucleic acid was detected only after the use of polymerase chain reaction (PCR) in three of eight CNS samples from HIV-seropositive IVDUs but not in samples from seronegative subjects. In situ hybridization confirmed that HIV-1 DNA sequences were in cells in the CNS parenchyma of two of the three positive samples. This study demonstrates that HIV-1 can infect human fetal CNS tissue in vivo, but that the use of PCR may be necessary for its detection.

The Fv-1 murine gene controls predominantly the replication of leukemia viruses of murine cells. Forced passage by B-tropic Friend leukemia virus in the restrictive host cells (NIH, Fv-1n/n) results in viral progeny capable of replicating efficiently in murine cells of any Fv-1 type, which are denoted as NB-tropic virus. We have studied the RNase T1-resistant oligonucleotide pattern of a series of NB-tropic Friend virus isolates and have been able to show changes from the parental B-tropic virus which occur at the 5' end of the genome. Cloned NB-tropic virus falls into three classes, demonstrating either four, one, or no apparent changes in the genome. These results suggest the possibility that conversion to NB tropism occurs by a recombination mechanism but, since change to NB tropism can occur without any observable oligonucleotide alteration, they do not confirm that any single oligonucleotide is diagnostic of NB tropism.

Following injection of Crohn's disease tissue filtrates, lymphomas and hyperplastic lymph nodes developed in 16% of athymic nude (nu/nu) mice; whereas only 4% of control nude mice developed lymphadenopathy (p less than 0.025). One hundred forty coded sera from 111 patients (Crohn's disease = 36, ulcerative colitis = 28, diarrheal and other controls = 47) were assayed by indirect immunofluorescence for immunoreactivity with the lymphomas and hyperplastic lymph nodes. Coded sections were examined by two observers and scored on a 0 to 3 + scale. Fifty-four percent of the sera from patients with Crohn's disease were reactive with the Crohn's disease induced lymphoma by this assay. Eighty percent of sera from patients with symptomatic Crohn's disease were positive, whereas 22% of sera from patients in remission were positive. Sixty-six percent of sera from patients with symptomatic Crohn's disease reacted against hyperplastic lymph nodes induced by Crohn's disease filtrates. In contrast, only one control serum (from a patient with ulcerative colitis) reacted with the lymphomas or hyperplastic lymph nodes. Lymphomas induced by other means or arising spontaneously did not show immunofluorescence with Crohn's disease or control sera. Electron microscopy revealed C-type viral particles in five lymphomas induced by Crohn's disease filtrates and in one control lymphoma, but not in five hyperplastic lymph nodes and five control lymph nodes. Absorption of Crohn's disease sera with control lymphoma or with murine leukemia virus infected fibroblasts did not diminish immunoreactivity, whereas similar absorption with lymphomas induced by Crohn's disease filtrates abolished the immunofluorescence. These studies indicate that Crohn's disease tissue, when injected into athymic nude mice, induces lymphoid hyperplasia and lymphomas that contain an antigen(s) recognized by Crohn's disease sera.

The regulation of expression of the Friend virus complex (FV) was studied in clones of H-2 congenic erythroleukemia cell lines. Molecular probes specific for each of the two FV components were generated and hybridized to RNA extracted from clones differing with respect to virus production or viral envelope antigen expression. Sequences representing the defective component of FV continued to be transcribed in cells regardless of virus production. The presence of helper virus-specific sequences, however, was shown to be directly related to virus expression. Molecular hybridization with cytoplasmic and nuclear RNA extracted from the H-2 congenic clones representing various stages of viral expression demonstrated a direct correlation between the level of transcription of FMuLV-specific sequences and the degree of virus expression. These data suggest that regulation of FV expression is primarily related to the cessation of helper virus transcription in the cell lines studied. In this paper we provide further evidence that the defective viral components is responsible for the rapid malignancy associated with Friend disease.

The fate of input Friend leukemia virus RNA was studied using labeled input virus. The appearance of nuclear RNA-DNA hybrid molecules and the apparent integration of input virion RNA with host cell DNA was studied using a series of inhibitors of DNA or protein synthesis, cell growth conditions, and an intercalating agent. Under all these conditions of infection, little to no viral-specific RNA-DNA hybrid molecules were formed. These data demonstrate that the formation of such RNA-DNA hybrid structures requires conditions of infection that allow provirus synthesis and integration. Furthermore, they suggest that at least a fraction of input virion RNA may transiently become integrated with host cell DNA.

Fv-1 gene-mediated host restriction of Friend leukemia virus replication was investigated in terms of coat protein synthesis. By using the assay of pseudotype formation with vesicular stomatitis virus. it was shown that under restricting growth conditions the availablity of leukemia virus coat protein for pseudotype formation was decreased. These studies appear to eliminate a pure assembly defect as the mechanism of Fv-1 host restriction.

The murine gene Fv-1 exerts a major control over the replication of Friend murine leukemia virus (F-MuLV). An effect of the gene product has been determined to be at the level of accumulation and integration of viral DNA. Aphidicolin, an inhibitor of eucaryotic DNA polymerase alpha, was studied in murine cells infected either permissively or nonpermissively with regard to the Fv-1 genotype. Results indicated that inhibition of DNA polymerase alpha did not affect the accumulation of form III viral DNA in either permissive or nonpermissive cells. However, the normal accumulation of circular form I DNA in permissive cells was inhibited. The block in the accumulation of form I DNA resembled that occurring in some F-MuLV Fv-1-nonpermissive infections. Additionally, aphidicolin treatment resulted in the accumulation of novel low-molecular-weight viral DNA species, normally detectable in a nonpermissive infection of NIH cells with B-tropic F-MuLV. These data suggest that the Fv-1 gene product may interact with host DNA polymerase alpha to prevent viral replication.