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1.
J Perinat Med ; 50(9): 1256-1263, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-35822724

RESUMO

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.


Assuntos
Recém-Nascido Prematuro , Neonatologistas , Recém-Nascido , Humanos , Idade Gestacional , Atitude do Pessoal de Saúde , Canadá , Ordens quanto à Conduta (Ética Médica)
2.
Am J Perinatol ; 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35554888

RESUMO

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..

3.
Med Teach ; 44(5): 551-558, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34860635

RESUMO

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.


Assuntos
Educação Médica , Estudantes de Medicina , Feminino , Humanos , Microagressão , Inquéritos e Questionários
4.
Adv Health Sci Educ Theory Pract ; 26(5): 1519-1535, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34152494

RESUMO

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.


Assuntos
Comunicação , Pessoal de Saúde , Emoções , Ocupações em Saúde , Humanos , Recém-Nascido , Pais , Pesquisa Qualitativa
5.
CMAJ ; 194(25): E879-E880, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35760432
6.
Med Educ ; 51(12): 1220-1231, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28984007

RESUMO

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.


Assuntos
Comunicação , Empatia , Relações Médico-Paciente , Médicos/psicologia , Atitude do Pessoal de Saúde , Educação de Pós-Graduação em Medicina , Teoria Fundamentada , Humanos , Terapia Intensiva Neonatal , Internato e Residência , Entrevistas como Assunto
7.
Proc Natl Acad Sci U S A ; 110(47): 18868-73, 2013 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-24191051

RESUMO

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.


Assuntos
Quebras de DNA de Cadeia Dupla , DNA Helicases/metabolismo , Reparo do DNA/fisiologia , Transferência Ressonante de Energia de Fluorescência/métodos , Complexos Multiproteicos/metabolismo , Hidrolases Anidrido Ácido , Proteínas de Ciclo Celular/metabolismo , Reparo do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Proteína Homóloga a MRE11 , Proteínas Nucleares/metabolismo
8.
9.
J Biol Chem ; 287(48): 40618-28, 2012 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-23055523

RESUMO

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.


Assuntos
Proteína BRCA1/deficiência , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Recombinação Homóloga , Ubiquitina-Proteína Ligases/metabolismo , Proteína BRCA1/genética , Linhagem Celular Tumoral , Reparo do DNA , Feminino , Inativação Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Domínios RING Finger , Proteína 1 de Ligação à Proteína Supressora de Tumor p53 , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/genética
10.
Cancer ; 119(10): 1838-44, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23436393

RESUMO

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.


Assuntos
DNA Viral/isolamento & purificação , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/virologia , Anticorpos Antivirais/sangue , Sudeste Asiático/epidemiologia , DNA Viral/sangue , Detecção Precoce de Câncer , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/epidemiologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco
11.
Nucleic Acids Res ; 39(14): 5935-44, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21459848

RESUMO

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.


Assuntos
Anáfase/genética , Segregação de Cromossomos , Reparo do DNA , Animais , Linhagem Celular , DNA Helicases/análise , Camundongos , Modelos Genéticos , Mutação , Rad51 Recombinase/genética
12.
Acad Med ; 98(11S): S65-S71, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37983398

RESUMO

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.


Assuntos
Internato e Residência , Médicos , Recém-Nascido , Humanos , Unidades de Terapia Intensiva Neonatal , Canadá , Comunicação
13.
J Biol Chem ; 286(49): 42470-42482, 2011 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-22027841

RESUMO

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.


Assuntos
Cromossomos/genética , Quebras de DNA de Cadeia Dupla , Enzimas Reparadoras do DNA/química , Proteína Quinase Ativada por DNA/metabolismo , Proteínas de Ligação a DNA/química , DNA/química , Transcrição Gênica , Hidrolases Anidrido Ácido , Animais , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Dano ao DNA , Proteínas de Ligação a DNA/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Histonas/metabolismo , Humanos , Camundongos , Modelos Genéticos , Regiões Promotoras Genéticas , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo
14.
PLoS Genet ; 5(10): e1000683, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19834534

RESUMO

To characterize the repair pathways of chromosome double-strand breaks (DSBs), one approach involves monitoring the repair of site-specific DSBs generated by rare-cutting endonucleases, such as I-SceI. Using this method, we first describe the roles of Ercc1, Msh2, Nbs1, Xrcc4, and Brca1 in a set of distinct repair events. Subsequently, we considered that the outcome of such assays could be influenced by the persistent nature of I-SceI-induced DSBs, in that end-joining (EJ) products that restore the I-SceI site are prone to repeated cutting. To address this aspect of repair, we modified I-SceI-induced DSBs by co-expressing I-SceI with a non-processive 3' exonuclease, Trex2, which we predicted would cause partial degradation of I-SceI 3' overhangs. We find that Trex2 expression facilitates the formation of I-SceI-resistant EJ products, which reduces the potential for repeated cutting by I-SceI and, hence, limits the persistence of I-SceI-induced DSBs. Using this approach, we find that Trex2 expression causes a significant reduction in the frequency of repair pathways that result in substantial deletion mutations: EJ between distal ends of two tandem DSBs, single-strand annealing, and alternative-NHEJ. In contrast, Trex2 expression does not inhibit homology-directed repair. These results indicate that limiting the persistence of a DSB causes a reduction in the frequency of repair pathways that lead to significant genetic loss. Furthermore, we find that individual genetic factors play distinct roles during repair of non-cohesive DSB ends that are generated via co-expression of I-SceI with Trex2.


Assuntos
Quebra Cromossômica , Quebras de DNA de Cadeia Dupla , Mutagênese , Animais , Células Cultivadas , Reparo do DNA , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Camundongos , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
15.
J Biol Chem ; 285(21): 15739-45, 2010 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-20348101

RESUMO

Homologous recombination (HR) provides an efficient mechanism for error-free repair of DNA double-strand breaks (DSBs). However, HR can be also harmful as inappropriate or untimely HR events can give rise to lethal recombination intermediates and chromosome rearrangements. A critical step of HR is the formation of a RAD51 filament on single-stranded (ss)DNA, which mediates the invasion of a homologous DNA molecule. In mammalian cells, several DNA helicases have been implicated in the regulation of this process. RECQ5, a member of the RecQ family of DNA helicases, interacts physically with the RAD51 recombinase and disrupts RAD51 presynaptic filaments in a reaction dependent on ATP hydrolysis. Here, we have precisely mapped the RAD51-interacting domain of RECQ5 and generated mutants that fail to interact with RAD51. We show that although these mutants retain normal ATPase activity, they are impaired in their ability to displace RAD51 from ssDNA. Moreover, we show that ablation of RECQ5-RAD51 complex formation by a point mutation alleviates the inhibitory effect of RECQ5 on HR-mediated DSB repair. These findings provide support for the proposal that interaction with RAD51 is critical for the anti-recombinase attribute of RECQ5.


Assuntos
Pareamento Cromossômico/fisiologia , Quebras de DNA de Cadeia Dupla , Reparo do DNA/fisiologia , Rad51 Recombinase/metabolismo , RecQ Helicases/metabolismo , Recombinação Genética/fisiologia , Linhagem Celular , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , Humanos , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Rad51 Recombinase/genética , RecQ Helicases/genética
16.
PLoS Genet ; 4(6): e1000110, 2008 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-18584027

RESUMO

Characterizing the functional overlap and mutagenic potential of different pathways of chromosomal double-strand break (DSB) repair is important to understand how mutations arise during cancer development and treatment. To this end, we have compared the role of individual factors in three different pathways of mammalian DSB repair: alternative-nonhomologous end joining (alt-NHEJ), single-strand annealing (SSA), and homology directed repair (HDR/GC). Considering early steps of repair, we found that the DSB end-processing factors KU and CtIP affect all three pathways similarly, in that repair is suppressed by KU and promoted by CtIP. In contrast, both KU and CtIP appear dispensable for the absolute level of total-NHEJ between two tandem I-SceI-induced DSBs. During later steps of repair, we find that while the annealing and processing factors RAD52 and ERCC1 are important to promote SSA, both HDR/GC and alt-NHEJ are significantly less dependent upon these factors. As well, while disruption of RAD51 causes a decrease in HDR/GC and an increase in SSA, inhibition of this factor did not affect alt-NHEJ. These results suggest that the regulation of DSB end-processing via KU/CtIP is a common step during alt-NHEJ, SSA, and HDR/GC. However, at later steps of repair, alt-NHEJ is a mechanistically distinct pathway of DSB repair, and thus may play a unique role in mutagenesis during cancer development and therapy.


Assuntos
Quebra Cromossômica , Cromossomos de Mamíferos/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Animais , Antígenos Nucleares/genética , Antígenos Nucleares/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Endodesoxirribonucleases , Endonucleases/genética , Endonucleases/metabolismo , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Autoantígeno Ku , Camundongos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , Proteína Rad52 de Recombinação e Reparo de DNA/genética , Proteína Rad52 de Recombinação e Reparo de DNA/metabolismo , Proteínas de Saccharomyces cerevisiae
17.
Can Med Educ J ; 12(3): 105-112, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34249196

RESUMO

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.

18.
J Grad Med Educ ; 11(5): 513-517, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31636818

RESUMO

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.


Assuntos
Centros Comunitários de Saúde/estatística & dados numéricos , Ginecologia/educação , Internato e Residência/estatística & dados numéricos , Obstetrícia/educação , Feminino , Humanos , Gravidez , Inquéritos e Questionários , Estados Unidos
19.
Paediatr Child Health ; 12(5): 373-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-19030388

RESUMO

BACKGROUND: Adderall XR (Shire BioChem Inc, Canada), a medication used to treat attention deficit hyperactivity disorder, was withdrawn from the Canadian market in February 2005 due to concerns of possible cardiotoxicity and cerebral vascular events among a small number of individuals who had taken the medication. OBJECTIVE: The primary objective of the present study was to investigate the degree to which the physician's relationship with the families of the patients to whom the medication was prescribed was affected by the withdrawal of Adderall XR from the Canadian market. The study sought to explore the perceptions of caregivers of patients who took Adderall XR to the drug recall. As a secondary objective, the study also assessed the differences in perception of caregivers toward physicians compared with their perception of other agencies involved with the recall. METHODS: Questionnaires were sent to the caregivers of 123 patients who had been taking the drug at the time of the withdrawal. RESULTS AND CONCLUSIONS: Of the 53 (43%) completed questionnaires, 89% of respondents indicated that they were concerned when informed of the withdrawal, while 58% indicated that they were frightened. Despite the concerns, only a modest degree of anger was expressed. Thirty per cent of respondents reported anger directed at Health Canada, 24% reported anger directed at the manufacturer, while no caregiver reported anger directed at their physician. Only three families (5.7%) indicated a decrease in confidence in the physician following the event. Fifty-eight per cent indicated a willingness to resume taking Adderall XR, if it was deemed safe by Health Canada. These results offer insight into patient and family perspectives following an unexpected medication recall. While caregivers were generally concerned and often frightened by this event, the present data do not suggest that the parent-physician relationship was greatly affected.

20.
Can J Gastroenterol Hepatol ; 2016: 1910292, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28101498

RESUMO

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.


Assuntos
Asiático/psicologia , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Hepatite B/psicologia , Estigma Social , Adulto , Idoso , Portador Sadio/diagnóstico , Portador Sadio/epidemiologia , Chicago/epidemiologia , Feminino , Culpa , Educação em Saúde , Hepatite B/diagnóstico , Hepatite B/prevenção & controle , Hepatite B/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Vergonha , Inquéritos e Questionários , Vacinação , Vietnã/etnologia
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