Set Up to Fail? Barriers Impeding Resident Communication Training in Neonatal Intensive Care Units.

PURPOSE: Learning to navigate difficult clinical conversations is an essential feature of residency training, yet much of this learning occurs "on the job," often without the formative, multisource feedback trainees need. To generate insight into how on-the-job training influences trainee performance, the perspectives of parents and health care providers (HCPs) who engaged in or observed difficult conversations with Neonatal Intensive Care Unit (NICU) trainees were explored. METHOD: The iterative data generation and analysis process was informed by constructivist grounded theory. Parents (n = 14) and HCPs (n = 10) from 2 Canadian NICUs were invited to participate in semistructured interviews informed by rich pictures-a visual elicitation technique useful for exploring complex phenomena like difficult conversations. Themes were identified using the constant comparative approach. The study was conducted between 2018 and 2021. RESULTS: According to participants, misalignment between parents' and trainees' communication styles, HCPs intervening to protect parents when trainee-led communication went awry, the absence of feedback, and a culture of sole physician responsibility for communication all conspired against trainees trying to develop communication competence in the NICU. Given beliefs that trainees' experiential learning should not trump parents' well-being, some physicians perceived the art of communication was best learned by observing experts. Sometimes, already limited opportunities for trainees to lead conversations were further constricted by perceptions that trainees lacked the interest and motivation to focus on so-called "soft" skills like communication during their training. CONCLUSIONS: Parents and NICU staff described that trainees face multiple barriers against learning to navigate difficult conversations that may set them up to fail. A deeper understanding of the layered challenges trainees face, and the hierarchies and sociocultural norms that interfere with teaching, may be the start of breaking down multiple barriers trainees and their clinician supervisors need to overcome to succeed.

Extremely low gestational age neonates and resuscitation: survey on perspectives of Canadian neonatologists.

OBJECTIVES: Resuscitation care planning for extremely low gestational age neonates (ELGANs) is complex and ethically charged. Increasing survival at lower gestational ages has had a significant impact on this complexity. It also has an impact on healthcare resource utilization and policy development in Canada. This study sought to determine the current attitudes and practices of neonatologists in Canada, and to assess moral distress associated with resuscitation decisions in the ELGAN population. It also aimed to explore the perspectives of adopting a shared decision-making approach where further data with regard to best interests and prognosis are gathered in an individualized manner after birth. METHODS: Neonatologists in Canadian level III NICUs were surveyed in 2020. RESULTS: Amongst the 65 responses, 78% expressed moral distress when parents request non-resuscitation at 24 weeks. Uncertainty around long-term outcomes in an era with improved chances of morbidity-free survival was the most prominent factor contributing to moral distress. 70% felt less moral distress deciding goals of care after the baby's initial resuscitation and preferred an individualized approach to palliation decisions based on postnatal course and assessment. CONCLUSIONS: While most current guidelines still support the option of non-resuscitation for infants born at less than 25 weeks, we show evidence of moral distress among Canadian neonatologists that suggests the consideration of routine resuscitation from 24 weeks and above is a more ethical approach in the current era of improved outcomes. Canadian neonatologists identified less moral distress when goals of care are developed postnatally, with availability of more evidence for prognostication, instead of antenatally based primarily on gestational age.

Educational Impact of Targeted Neonatal Echocardiography and Hemodynamics Programs on Neonatal-Perinatal Medicine Fellows.

OBJECTIVE: Targeted neonatal echocardiography (TNE) is a real-time cardiac imaging modality used by a hemodynamics program to aid in diagnosis, treatment, and monitoring of neonatal cardiovascular illness. This study aimed to describe trainees' perspectives on existing hemodynamics education and perceived impacts of TNE and hemodynamics services on their education. STUDY DESIGN: This was a mixed quantitative and qualitative study that surveyed neonatal-perinatal medicine (NPM) fellow trainees in Canada and the United States, at programs both with and without a hemodynamics service. RESULTS: Ninety-two fellows responded to the survey, of whom 24 (26%) were enrolled in a program with an active hemodynamics service, 64 (70%) were training at a program without a hemodynamics service, and 4 (4%) were unsure. Trainees at centers with a hemodynamics service were more satisfied with their cardiovascular physiology education (91 vs. 69%, p = 0.040). Twenty-five percent of all trainees felt they do not have sufficient hemodynamics training to prepare them for independent practice. Areas of knowledge gaps were identified. Bedside teaching combined with didactic teaching was identified as useful means of teaching. CONCLUSION: Most trainees believed that TNE and a hemodynamics service are valuable educational assets. Thoughtful curriculum design for real-time and consolidation learning, with specific emphasis on content gaps, should be considered. KEY POINTS: · NPM Fellows perceive TNE & Neonatal Hemodynamics service as a valuable educational opportunity.. · Incorporation of TNE/Hemodynamics teaching into NPM curriculum can enrich trainee experience.. · Combining bedside and classroom teaching is key to successful cardiovascular training..

Equity in medical education: Addressing microaggressions and discrimination on the wards.

PURPOSE: Existing frameworks to address instances of microaggressions and discrimination in the clinical environment have largely been developed for faculty and resident physicians, creating a lack of resources for medical students. METHODS: We implemented a workshop to prepare pre-clinical medical/dental students to recognize and respond to microaggressions. Participants in three cohorts from 2018 to 2020 completed pre- and post-workshop surveys assessing the prevalence of exposure to clinical microaggressions and the workshop's effect on mitigating commonly perceived barriers to addressing microaggressions. RESULTS: Of 461 first-year medical and dental students who participated, 321 (69.6%) provided survey responses. Over 80% of students reported experiencing microaggressions, with women and URM students over-represented. After the workshop, participants reported significant reductions in barriers to addressing microaggressions and discrimination, including recognizing incidents, uncertainty of what to say or do, lack of allies, lack of familiarity with institutional policies, and uncertainty of clinical relevance. The workshop was similarly effective in-person and virtual formats. CONCLUSIONS: Most medical/dental student respondents reported experiencing microaggressions in the clinical setting, particularly female and URM students. Our workshop mitigated most perceived challenges to responding to microaggressions. Future interventions across institutions should continue to equip students with the tools they need to address and respond to microaggressions.

Rehearsal simulation for antenatal consults.

BACKGROUND: Rehearsal simulations are patient-specific case- matched tasks performed immediately prior to the actual task, with the objective of improving performance. OBJECTIVE: How does rehearsal simulation for antenatal consults impact how residents learn to engage in difficult conversations with families? STUDY DESIGN: Residents in the NICU performed case-matched video recorded rehearsal simulations, followed by actual antenatal consults. The purpose of antenatal consults is to prepare parents expecting a complication with their baby before birth. Questionnaires assessed changes in resident confidence and self-assessment of communication skills. Residents were interviewed for qualitative data to explore the overall impact of rehearsal simulation on their learning and performance. RESULTS: Thirteen residents participated. Rehearsal simulation improved confidence with a more organized approach of medical content and better communication techniques, allowing for a shift of focus from a checklist approach to building rapport and displaying empathy. CONCLUSIONS: While rehearsal simulation did not prepare residents for unexpected parent responses, trainees' increased confidence with medical content organization and communication techniques created space for reflection-in-action and compassionate approaches.

CONTEXTE: Les simulations préparatoires correspondent à des cas spécifiques de patients et elles sont effectuées immédiatement avant l'intervention réelle, dans le but d'améliorer la performance. OBJECTIF: Comment la simulation préparatoire pratiquée avant une consultation prénatale influence-t-elle la manière dont les résidents apprennent à engager une conversation difficile avec les familles? MÉTHODES: Les résidents de l'unité de soins intensifs néonatals ont effectué des simulations préparatoires adaptées à la situation clinique à venir, qui ont été filmées. Ils ont par la suite effectué les consultations prénatales réelles. L'objet des consultations prénatales est de préparer les parents lorsque des complications sont anticipées, et ce avant la naissance de leur bébé. Nous avons évalué les changements au niveau de la confiance des résidents et l'autoévaluation par ces derniers de leurs compétences en communication par le biais de questionnaires. Les résidents ont participé à une entrevue, qui a fourni les données qualitatives afin d'explorer l'impact global de la simulation sur leur apprentissage et leur performance. RÉSULTATS: Treize résidents ont participé à l'étude. La simulation préparatoire a rehaussé leur confiance en eux, car elle les a aidés à adopter une approche plus organisée du contenu médical et de meilleures techniques de communication, permettant de passer d'une approche par « cases à cocher ¼ à une approche basée sur l'établissement d'un lien avec les parents et à la manifestation d'empathie. CONCLUSIONS: Bien que la simulation préparatoire n'ait pas préparé les résidents aux réactions inattendues des parents, la confiance accrue des stagiaires en leur capacité à organiser le contenu médical et en leurs techniques de communication a laissé place à la réflexion dans l'action et aux approches compatissantes.

Drawing on experience: exploring the pedagogical possibilities of using rich pictures in health professions education.

In both clinical and health professions education research, rich pictures, or participant-generated drawings of complex phenomena, are gaining recognition as a useful method for exploring multifaceted and emotional topics in medicine. For instance, two recent studies used rich pictures to augment semi-structured interviews exploring trainees', health care professionals' (HCPs), and parents' experiences of difficult conversations in the Neonatal Intensive Care Unit (NICU)-an environment in which communication is often challenging, anxiety-provoking, and emotionally distressing. In both studies, participants were invited to draw a picture depicting how they experienced a difficult conversation in this setting. As part of the interview process, participants were asked to both describe how they engaged with rich pictures, and to share their perceptions about the affordances and limitations of this research method. Here, their perspectives are reported and the possibilities of using rich pictures to inform pedagogical innovations in health professions education and research are considered.

Community Health Center Engagement and Training During Obstetrics and Gynecology Residency.

BACKGROUND: Community health centers (CHCs) and federally qualified health centers (FQHCs) are critical health care access points for medically underserved areas in the United States. They also provide opportunities for residents to learn about health system challenges, including workforce shortages, social determinants of health, and health equity. OBJECTIVE: We sought to describe current obstetrics and gynecology (OB-GYN) resident engagement and training in community health settings. METHODS: We conducted a website review and survey to identify the prevalence and types of OB-GYN resident exposure to CHCs, including FQHCs. We reviewed 241 program websites to identify community health electives or rotations. We then surveyed program administrators regarding departmental affiliations with CHCs, types of resident involvement, and barriers to resident rotations at CHCs. RESULTS: The website review revealed that 18% (44 of 241) of programs offered a community health rotation. Of the 241 programs surveyed, 78 program administrators responded (32%). Forty-three programs (55%) had at least 1 affiliated CHC, and 34 programs (44%) allowed residents to rotate at a CHC. The most common barrier to resident rotations at a CHC was inadequate resident coverage of hospital-based clinical responsibilities. Respondents reported that among 782 graduating residents in the 2016-2017 and 2017-2018 academic years, 76 (10%) planned to pursue a position at a CHC. CONCLUSIONS: According to their websites, a small percentage of US OB-GYN residency programs offered a CHC rotation. Of programs responding to a survey on the topic, less than half offered CHC rotations and less than 1 in 10 residents planned to work in CHCs after graduation.

Navigating difficult conversations: the role of self-monitoring and reflection-in-action.

CONTEXT: Clinicians draw upon experiential knowledge to manoeuvre difficult conversations, using tacit knowledge that is difficult to explicitly teach. Instead, learners are taught to communicate through role-play and checklists, both of which are approaches that may fail during moments of clinical complexity. We know that difficult conversations may provoke anxiety in learners, but we know little about how they learn to navigate them. Without a deeper understanding, we may fail to equip learners with the skills to manoeuvre these conversations in practice. METHODS: Using constructivist grounded theory, we applied the sensitising concepts of self-monitoring and reflection-in-action both to explore the process in which trainees engage to navigate difficult conversations and to expand understanding about these theories. We situated our research in the neonatal intensive care unit (NICU), in which difficult conversations are ubiquitous. Fifteen resident and fellow trainees drew rich pictures about difficult conversations, and shared their drawings and experiences during semi-structured interviews. Interview transcripts were analysed using constant comparative analysis. RESULTS: Participants described how they responded when checklist approaches became ineffective during moments of unexpected uncertainty and complexity. For participants, these indeterminate zones of practice triggered a process of seeing families differently and then pausing to understand problems that arose with the checklist-based approach. Throughout this process, learners actively observed others' communication approaches, negotiated their roles within difficult conversations, and abandoned the checklist to engage differently with families. CONCLUSIONS: Our findings suggest links between the theories of self-monitoring and reflection-in-action, and describe the engagement of both processes in the context of NICU conversations. Self-monitoring may lead to the realisation of an indeterminate zone of practice, after which trainees may respond through reflection-in-action. We recognise that training programmes may need to teach a checklist-based approach as a starting point. We suggest that trainees also be given purposeful opportunities and support to depart from checklists in order to compassionately and flexibly navigate difficult conversations with families.

Hepatitis B Stigma and Knowledge among Vietnamese in Ho Chi Minh City and Chicago.

Stigma regarding viral hepatitis and liver disease has psychological and social consequences including causing negative self-image, disrupting relationships, and providing a barrier to prevention, testing, and treatment. The aim of this study was to characterize and compare HBV knowledge and stigma in Vietnamese in Ho Chi Minh City and Chicago and to begin to evaluate the cultural context of HBV stigma. Methods. A written survey including knowledge questions and a validated HBV stigma questionnaire was distributed to Vietnamese in Ho Chi Minh City and Chicago. 842 surveys from Ho Chi Minh City and 170 from Chicago were analyzed. Results. Vietnamese living in Chicago had better understanding of HBV transmission and that HBV can cause chronic infection and liver cancer. Vietnamese in Chicago had higher stigma scores on a broad range of items including guilt and shame about HBV and were more likely to feel that persons with HBV can bring harm to others and should be isolated. Conclusions. Vietnamese in Ho Chi Minh City and Chicago have knowledge deficits about HBV, particularly regarding modes of transmission. Persons in Ho Chi Minh City expressed lower levels of HBV stigma than Vietnamese living in Chicago, likely reflecting changing cultural attitudes in Vietnam. Culturally appropriate educational initiatives are needed to address the problem of HBV stigma.

A Survey Study of Pregnant Women and Healthcare Practitioners Assessing the Knowledge of Attitudes and Practices of Hepatitis B Management at a Teaching Hospital in Kumasi, Ghana, West Africa.

Hepatitis B virus (HBV) infection is a major global health problem, with sub-Saharan Africa (SSA), including West Africa, bearing a large proportion of cases. Mother-to-child and early childhood horizontal transmission, the most common mechanisms of disease spread in West Africa, lead to a high rate of chronic infection. Although these transmission mechanisms are preventable through vaccine and hepatitis B immunoglobulin, they are not routinely used due to limited resources. Antiviral therapy in pregnant women who are HBV positive is another option to reduce transmission. We conducted a survey study of pregnant women and clinicians at a teaching hospital in West Africa to determine the knowledge base about HBV and willingness to implement measures to reduce HBV transmission. Pregnant women had limited knowledge about HBV and the common transmission mechanisms. Clinicians identified cost and time as the major barriers to implementation of HBV prevention measures. Both pregnant women and clinicians were largely willing to implement and use measures, including antivirals, to help reduce HBV transmission.

Sources of input to the rostromedial tegmental nucleus, ventral tegmental area, and lateral habenula compared: A study in rat.

Profound inhibitory control exerted on midbrain dopaminergic neurons by the lateral habenula (LHb), which has mainly excitatory outputs, is mediated by the GABAergic rostromedial tegmental nucleus (RMTg), which strongly innervates dopaminergic neurons in the ventral midbrain. Early reports indicated that the afferent connections of the RMTg, excepting its very strong LHb inputs, do not differ appreciably from those of the ventral tegmental area (VTA). Presumably, however, the RMTg contributes more to behavioral synthesis than to simply invert the valence of the excitatory signal coming from the LHb. Therefore, the present study was done to directly compare the inputs to the RMTg and VTA and, in deference to its substantial involvement with this circuitry, the LHb was also included in the comparison. Data indicated that, while the afferents of the RMTg, VTA, and LHb do originate within the same large pool of central nervous system (CNS) structures, each is also related to structures that project more strongly to it than to the others. The VTA gets robust input from ventral striatopallidum and extended amygdala, whereas RMTg biased inputs arise in structures with a more direct impact on motor function, such as deep layers of the contralateral superior colliculus, deep cerebellar and several brainstem nuclei, and, via a relay in the LHb, the entopeduncular nucleus. Input from the ventral pallidal-lateral preoptic-lateral hypothalamus continuum is strong in the RMTg and VTA and dominant in the LHb. Axon collateralization was also investigated, providing additional insights into the organization of the circuitry of this important triad of structures.

Visualization of local DNA unwinding by Mre11/Rad50/Nbs1 using single-molecule FRET.

The Mre11/Rad50/Nbs1 (MRN) complex initiates and coordinates DNA repair and signaling events at double-strand breaks. The interaction between MRN and DNA ends is critical for the recruitment of DNA-processing enzymes, end tethering, and activation of the ATM protein kinase. Here we visualized MRN binding to duplex DNA molecules using single-molecule FRET, and found that MRN unwinds 15-20 base pairs at the end of the duplex, holding the branched structure open for minutes at a time in an ATP-dependent reaction. A Rad50 catalytic domain mutant that is specifically deficient in this ATP-dependent opening is impaired in DNA end resection in vitro and in resection-dependent repair of breaks in human cells, demonstrating the importance of MRN-generated single strands in the repair of DNA breaks.

Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia. Over the last decade, plasma Epstein-Barr virus (EBV) DNA has been developed as a tumor marker for NPC. In this study, the authors investigated whether plasma EBV DNA analysis is useful for NPC surveillance. METHODS: In total, 1318 volunteers ages 40 to 60 years were prospectively recruited. Plasma EBV DNA and serology for viral capsid antigen immunoglobulin A (IgA) were measured. Participants who had detectable plasma EBV DNA or positive IgA serology underwent nasal endoscopic examination and a follow-up plasma EBV DNA analysis in approximately 2 weeks. All participants were followed for 2 years to record the development of NPC. RESULTS: Three individuals with NPC were identified at enrolment. All of them were positive for EBV DNA and remained positive in follow-up analysis. Only 1 of those patients was positive for EBV serology. In 1 patient who had NPC with a small tumor confined to the mucosa, the tumor was not detectable on endoscopic examination. Because of a 2-fold increase in plasma EBV DNA on the follow-up analysis, that patient underwent magnetic resonance imaging, which revealed the tumor. Among the participants who did not have NPC but had initially positive plasma EBV DNA results, approximately 66% had negative EBV DNA results after a median of 2 weeks. CONCLUSIONS: Plasma EBV DNA analysis proved useful for detecting early NPC in individuals without a clinical suspicion of NPC. Repeating the test in those who had initially positive results differentiated those with NPC from those who had false-positive results. Cancer 2013. © 2013 American Cancer Society.

On lateral septum-like characteristics of outputs from the accumbal hedonic "hotspot" of Peciña and Berridge with commentary on the transitional nature of basal forebrain "boundaries".

Peciña and Berridge (2005; J Neurosci 25:11777-11786) observed that an injection of the µ-opioid receptor agonist DAMGO (D-ala(2) -N-Me-Phe(4) -Glycol(5) -enkephalin) into the rostrodorsal part of the accumbens shell (rdAcbSh) enhances expression of hedonic "liking" responses to the taste of an appetitive sucrose solution. Insofar as the connections of this hedonic "hotspot" were not singled out for special attention in the earlier neuroanatomical literature, we undertook to examine them. We observed that the patterns of inputs and outputs of the rdAcbSh are not qualitatively different from those of the rest of the Acb, except that outputs from the rdAcbSh to the lateral preoptic area and anterior and lateral hypothalamic areas are anomalously robust and overlap extensively with those of the lateral septum. We also detected reciprocal interconnections between the rdAcbSh and lateral septum. Whether and how these connections subserve hedonic impact remains to be learned, but these observations lead us to hypothesize that the rdAcbSh represents a basal forebrain transition area, in the sense that it is invaded by neurons of the lateral septum, or possibly transitional neuronal forms sharing properties of both structures. We note that the proposed transition zone between lateral septum and rdAcbSh would be but one of many in the basal forebrain and conclude by reiterating the longstanding argument that the transitional nature of such boundary areas has functional importance, of which the precise nature will remain elusive until the neurophysiological and neuropharmacological implications of such zones of transition are more generally acknowledged and better addressed.

RING finger nuclear factor RNF168 is important for defects in homologous recombination caused by loss of the breast cancer susceptibility factor BRCA1.

BACKGROUND: RNF168 promotes chromosomal break localization of 53BP1 and BRCA1; 53BP1 loss rescues homologous recombination (HR) in BRCA1-deficient cells. RESULTS: RNF168 depletion suppresses HR defects caused by BRCA1 silencing; RNF168 influences HR similarly to 53BP1. CONCLUSION: RNF168 is important for HR defects caused by BRCA1 loss. SIGNIFICANCE: Although RNF168 promotes BRCA1 and 53BP1 localization to chromosomal breaks, RNF168 affects HR similarly to 53BP1. The RING finger nuclear factor RNF168 is required for recruitment of several DNA damage response factors to double strand breaks (DSBs), including 53BP1 and BRCA1. Because 53BP1 and BRCA1 function antagonistically during the DSB repair pathway homologous recombination (HR), the influence of RNF168 on HR has been unclear. We report that RNF168 depletion causes an elevated frequency of two distinct HR pathways (homology-directed repair and single strand annealing), suppresses defects in HR caused by BRCA1 silencing, but does not suppress HR defects caused by disruption of CtIP, RAD50, BRCA2, or RAD51. Furthermore, RNF168-depleted cells can form ionizing radiation-induced foci of the recombinase RAD51 without forming BRCA1 ionizing radiation-induced foci, indicating that this loss of BRCA1 recruitment to DSBs does not reflect a loss of function during HR. Additionally, we find that RNF168 and 53BP1 have a similar influence on HR. We suggest that RNF168 is important for HR defects caused by BRCA1 loss.

Correct end use during end joining of multiple chromosomal double strand breaks is influenced by repair protein RAD50, DNA-dependent protein kinase DNA-PKcs, and transcription context.

During repair of multiple chromosomal double strand breaks (DSBs), matching the correct DSB ends is essential to limit rearrangements. To investigate the maintenance of correct end use, we examined repair of two tandem noncohesive DSBs generated by endonuclease I-SceI and the 3' nonprocessive exonuclease Trex2, which can be expressed as an I-SceI-Trex2 fusion. We examined end joining (EJ) repair that maintains correct ends (proximal-EJ) versus using incorrect ends (distal-EJ), which provides a relative measure of incorrect end use (distal end use). Previous studies showed that ATM is important to limit distal end use. Here we show that DNA-PKcs kinase activity and RAD50 are also important to limit distal end use, but that H2AX is dispensable. In contrast, we find that ATM, DNA-PKcs, and RAD50 have distinct effects on repair events requiring end processing. Furthermore, we developed reporters to examine the effects of the transcription context on DSB repair, using an inducible promoter. We find that a DSB downstream from an active promoter shows a higher frequency of distal end use, and a greater reliance on ATM for limiting incorrect end use. Conversely, DSB transcription context does not affect end processing during EJ, the frequency of homology-directed repair, or the role of RAD50 and DNA-PKcs in limiting distal end use. We suggest that RAD50, DNA-PKcs kinase activity, and transcription context are each important to limit incorrect end use during EJ repair of multiple DSBs, but that these factors and conditions have distinct roles during repair events requiring end processing.

Inputs to the midbrain dopaminergic complex in the rat, with emphasis on extended amygdala-recipient sectors.

The midbrain dopaminergic neuronal groups A8, A9, A10, and A10dc occupy, respectively, the retrorubral field (RRF), substantia nigra compacta (SNc), ventral tegmental area (VTA), and ventrolateral periaqueductal gray (PAGvl). Collectively, these structures give rise to a mixed dopaminergic and nondopaminergic projection system that essentially permits adaptive behavior. However, knowledge is incomplete regarding how the afferents of these structures are organized. Although the VTA is known to receive numerous afferents from cortex, basal forebrain, and brainstem and the SNc is widely perceived as receiving inputs mainly from the striatum, the afferents of the RRF and PAGvl have yet to be assessed comprehensively. This study was performed to provide an account of those connections and to seek a better understanding of how afferents might contribute to the functional interrelatedness of the VTA, SNc, RRF, and PAGvl. Ventral midbrain structures received injections of retrograde tracer, and the resulting retrogradely labeled structures were targeted with injections of anterogradely transported Phaseolus vulgaris leucoagglutinin. Whereas all injections of retrograde tracer into the VTA, SNc, RRF, or PAGvl produced labeling in many structures extending from the cortex to caudal brainstem, pronounced labeling of structures making up the central division of the extended amygdala occurred following injections that involved the RRF and PAGvl. The anterograde tracing supported this finding, and the combination of retrograde and anterograde labeling data also confirmed reports from other groups indicating that the SNc receives robust input from many of the same structures that innervate the VTA, RRF, and PAGvl.

The relative efficiency of homology-directed repair has distinct effects on proper anaphase chromosome separation.

Homology-directed repair (HDR) is essential to limit mutagenesis, chromosomal instability (CIN) and tumorigenesis. We have characterized the consequences of HDR deficiency on anaphase, using markers for incomplete chromosome separation: DAPI-bridges and Ultra-fine bridges (UFBs). We show that multiple HDR factors (Rad51, Brca2 and Brca1) are critical for complete chromosome separation during anaphase, while another chromosome break repair pathway, non-homologous end joining, does not affect chromosome segregation. We then examined the consequences of mild versus severe HDR disruption, using two different dominant-negative alleles of the strand exchange factor, Rad51. We show that mild HDR disruption is viable, but causes incomplete chromosome separation, as detected by DAPI-bridges and UFBs, while severe HDR disruption additionally results in multipolar anaphases and loss of clonogenic survival. We suggest that mild HDR disruption favors the proliferation of cells that are prone to CIN due to defective chromosome separation during anaphase, whereas, severe HDR deficiency leads to multipolar divisions that are prohibitive for cell proliferation.