RESUMO
INTRODUCTION: We assessed students' perception of the impact of the pandemic on their well-being, education, academic achievement, and whether grit and resilience alter students' ability to mitigate the stress associated with disruptions in education. We hypothesized that students would report a negative impact, and those with higher grit and resilience scores would be less impacted. METHODS: A multidisciplinary team of educators created and distributed a survey to medical students. Survey results were analyzed using descriptive statistics, ANOVA, and multivariate linear regressions. A p-value <.05 was considered statistically significant. RESULTS: A total of 195 students were included in the study. Approximately 92% reported that clinical education was negatively affected, including participants with higher grit scores. Students with higher resilience scores were more optimistic about clinical education. Those with higher resilience scores were less likely to report anxiety, insomnia, and tiredness. CONCLUSION: More resilient students were able to manage the stress associated with the disruption in their education. Resiliency training should be year-specific, and integrated into the UME curriculum due to the different demands each year presents.
Assuntos
COVID-19 , Educação Médica , Estudantes de Medicina , COVID-19/epidemiologia , Currículo , Humanos , PandemiasRESUMO
BACKGROUND: Surgical endoscopy (SE), the official journal of the Society of American Gastrointestinal and Endoscopic Surgeons and the European Association for Endoscopic Surgery, is an important source of new evidence pertaining to surgical education in the field. However, qualitative deficiencies in medical education research have prompted medical education leaders to advocate for increased methodological rigor. The purpose of this study is to review the quality of education-focused research published through SE. METHODS: A PubMed search examining all SE articles categorized as education-related research from 2010 to 2019 was conducted; studies not meeting inclusion criteria were excluded. Remaining publications were independently reviewed, classified, and scored by 7 raters using the medical education research study quality instrument (MERSQI). Intraclass correlation was calculated and data were examined with descriptive statistics. RESULTS: A total of 227 studies met inclusion criteria. There was no significant difference in number of publications by year (average 25.88 [SD 5.6]); 60% were conducted outside of the United States, and 47% (n = 106) were funded. The average MERSQI was 12.5 (SD 2). Most studies used two-group non-random (42%, n = 96) or post/cross-sectional designs (29%, n = 65). Thirty-six (16%) were randomized controlled trials. Multi-institutional studies comprised 24% (n = 54). Of the manuscripts, 96% (n = 217) reported at least one measure of validity evidence and 28% (n = 67) described three levels of validity evidence. Studies primarily reported changes in skills or knowledge (45%, n = 103) or satisfaction or general facts (44%, n = 99), while patient-related outcomes encompassed 3% (n = 6) of studies. ICC between raters was 0.93 (CI 0.90-0.93, p < 0.001). CONCLUSIONS: Based on publications to date, this journal's peer review process appears to facilitate the dissemination of education-related studies of moderate to good quality. However, there were uncovered deficits, ranging from validity evidence to study designs and level of outcomes. This journal's breadth of viewership offers a potential venue to advance education-related research.
Assuntos
Pesquisa Biomédica , Educação Médica , Humanos , Estudos Transversais , Projetos de Pesquisa , EndoscopiaRESUMO
OBJECTIVE: General surgery training prepares residents for the autonomous practice of surgery; however, assessment for readiness for independent practice presents several challenges. The simulation lab offers a safe and standardized environment for assessing the technical skills of a resident in the absence of numerous confounders of the real operating room. We describe our experience with evaluation and remediation of chief resident assessments in a porcine simulation lab. DESIGN: Operative skill assessment of surgical residents was conducted using anesthetized porcine models. Procedure's representative of basic and complex operative skill was chosen for the assessment. Faculty assessed the residents using a checklist for the completion of all critical operative steps. A "failing" score or "critical fail" on a given procedure determined mandatory remediation. For remediation, faculty provided immediate post-procedure feedback on all errors, and residents were offered supervised practice. Residents were then retested to demonstrate competency. SETTING: Large animal research center at Indiana University School of Medicine, Indianapolis, IN PARTICIPANTS: From 2017 to 2020, thirty-seven PGY5 residents participated in the porcine lab over a 4-year period. These general surgery residents were assessed at the beginning of their chief year. RESULTS: There were a total of 6 residents that failed 1 or more procedures. There were no failures in the cholecystectomy, 3 failures for Nissen, 4 failures for Hand sewn anastomosis, and 1 failure for stapled anastomosis. Two residents failed 2 procedures. All residents received remediation with a faculty member and were subsequently able to perform the procedure competently. CONCLUSIONS: A formal simulation-based assessment of procedural competence can identify technical performance deficiencies even at the chief resident level. Combined with a formal remediation program, such deficiencies can be addressed well in advance of residency graduation. Determining the relationship of such simulation-based assessments with operative performance is currently underway.
Assuntos
Cirurgia Geral , Internato e Residência , Anastomose Cirúrgica , Animais , Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Retroalimentação , Cirurgia Geral/educação , Humanos , Salas Cirúrgicas , SuínosRESUMO
OBJECTIVE: To demonstrate the feasibility of implementing a CBE curriculum within a general surgery residency program and to evaluate its effectiveness in improving resident skill. SUMMARY OF BACKGROUND DATA: Operative skill variability affects residents and practicing surgeons and directly impacts patient outcomes. CBE can decrease this variability by ensuring uniform skill acquisition. We implemented a CBE LC curriculum to improve resident performance and decrease skill variability. METHODS: PGY-2 residents completed the curriculum during monthly rotations starting in July 2017. Once simulator proficiency was reached, residents performed elective LCs with a select group of faculty at 3 hospitals. Performance at curriculum completion was assessed using LC simulation metrics and intraoperative operative performance rating system scores and compared to both baseline and historical controls, comprised of rising PGY-3s, using a 2-sample Wilcoxon rank-sum test. PGY-2 group's performance variability was compared with PGY-3s using Levene robust test of equality of variances; P < 0.05 was considered significant. RESULTS: Twenty-one residents each performed 17.52 ± 4.15 consecutive LCs during the monthly rotation. Resident simulated and operative performance increased significantly with dedicated training and reached that of more experienced rising PGY-3s (n = 7) but with significantly decreased variability in performance ( P = 0.04). CONCLUSIONS: Completion of a CBE rotation led to significant improvements in PGY-2 residents' LC performance that reached that of PGY-3s and decreased performance variability. These results support wider implementation of CBE in resident training.
Assuntos
Colecistectomia Laparoscópica , Cirurgia Geral , Internato e Residência , Humanos , Competência Clínica , Estudos de Coortes , Currículo , Cirurgia Geral/educaçãoRESUMO
OBJECTIVE: To define criteria for robotic credentialing using expert consensus. BACKGROUND: A recent review of institutional robotic credentialing policies identified significant variability and determined current policies are largely inadequate to ensure surgeon proficiency and may threaten patient safety. METHODS: Twenty-eight national robotic surgery experts were invited to participate in a consensus conference. After review of available institutional policies and discussion, the group developed a 91 proposed criteria. Using a modified Delphi process the experts were asked to indicate their agreement with the proposed criteria in three electronic survey rounds after the conference. Criteria that achieved 80% or more in agreement (consensus) in all rounds were included in the final list. RESULTS: All experts agreed that there is a need for standardized robotic surgery credentialing criteria across institutions that promote surgeon proficiency. Forty-nine items reached consensus in the first round, 19 in the second, and 8 in the third for a total of 76 final items. Experts agreed that privileges should be granted based on video review of surgical performance and attainment of clearly defined objective proficiency benchmarks. Parameters for ongoing outcome monitoring were determined and recommendations for technical skills training, proctoring, and performance assessment were defined. CONCLUSIONS: Using a systematic approach, detailed credentialing criteria for robotic surgery were defined. implementation of these criteria uniformly across institutions will promote proficiency of robotic surgeons and has the potential to positively impact patient outcomes.
Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgiões , Competência Clínica , Consenso , Credenciamento , Técnica Delphi , Humanos , Procedimentos Cirúrgicos Robóticos/educaçãoRESUMO
BACKGROUND: Non-technical skills impact trauma resuscitation time. Crisis resource management teaches non-technical skills required for effective teamwork in a crisis. We developed a simulation-based multidisciplinary trauma team training, with an emphasis on crisis resource management and a goal of improving residents' non-technical skills. METHODS: Twenty-five post-graduate year-1 general surgery and emergency medicine residents were divided into multidisciplinary teams with embedded nurse participants. Teams underwent 3 trauma resuscitation scenarios followed by a crisis resource management debrief. Additionally, a Just-In-Time crisis resource management didactic was delivered before 1 scenario. Teams' non-technical skills in each scenario were assessed by expert raters using non-technical skills scale for trauma and scenario scores before and after the Just-In-Time didactic were compared. Multiple linear-regression calculating the impact of clinical scenario, case order, and timing relative to the Just-In-Time didactic on a teams' non-technical skills scale for trauma score was performed. RESULTS: Seventy-four team T-NOTECHS ratings were completed. T-NOTECHS total score was significantly higher on the third training case regardless of clinical scenario or timing relative to the Just-In-Time didactic (pre = 15.58 vs post = 18.11, P = .117). Teams scored an average of 15.44 on the first scenario of the day, 16.63 on the second, and 19.04 on the last (P < .001). CONCLUSION: Crisis resource management-focused multidisciplinary team training significantly improves residents' non-technical skills in the simulated environment. Case repetition followed by crisis resource management focused debriefings outweighed the effect of a single Just-In-Time crisis resource management didactic.
Assuntos
Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Recursos em Saúde , Internato e Residência/métodos , Equipe de Assistência ao Paciente/organização & administração , Treinamento por Simulação/métodos , Traumatologia/educação , Currículo , HumanosRESUMO
BACKGROUND: Excessive stress negatively impacts surgical residents' technical performance. The effect of stress on trainee nontechnical skills, however, is less well studied. Given that nontechnical skills are known to impact clinical performance, the purpose of this study was to assess the relationship between residents' perceived stress and nontechnical skills during multidisciplinary trauma simulations. METHODS: First-year surgery and emergency medicine residents voluntarily participated in this study. Residents participated in 3 trauma simulations across 2 training sessions in randomly assigned teams. Each team's nontechnical skills were evaluated by faculty using the Trauma Nontechnical Skills scale. The Trauma Nontechnical Skills scale consists of 5 items: leadership, cooperation, communication, assessment, and situation awareness/coping with stress. After each scenario, residents completed the 6-item version of the State-Trait Anxiety Inventory and the Surgery Task Load Index to detail their perceived stress and workload during scenarios. Linear regressions were run to assess relationships between stress, workload, and nontechnical skills. RESULTS: Twenty-five residents participated in the first simulation day, and 24 residents participated in the second simulation day. Results from regressions revealed that heightened stress and workload predicted significantly lower nontechnical skills performance during trauma scenarios. In regard to specific aspects of nontechnical skills, residents' heightened stress and workload predicted statistically significant lower situation awareness and decision-making during trauma scenarios. CONCLUSION: Residents' perceived stress and workload significantly impaired their nontechnical skills during trauma simulations. This finding highlights the need to offer stress management and performance-optimizing mental skills training to trainees to lower their stress and optimize nontechnical skills performance during challenging situations.
Assuntos
Educação de Pós-Graduação em Medicina/métodos , Comunicação Interdisciplinar , Internato e Residência/métodos , Procedimentos Ortopédicos/educação , Treinamento por Simulação/métodos , Estresse Psicológico/psicologia , Traumatologia/educação , Adulto , Competência Clínica , Avaliação Educacional , Feminino , Humanos , Liderança , Masculino , Projetos PilotoRESUMO
Introduction: Recent endeavors from governing bodies such as the AAMC have formally recognized the importance of aseptic technique. AAMC guidelines include activities that all graduating physicians should be able to perform with minimum indirect supervision and were developed to recognize these needs. For example, the skills necessary for aseptic technique include daily safety habits and general physician procedures. Methods: We developed a scrub training curriculum and evaluated the program through a quasi-experimental study with a pre- and posttest design. Questions were developed to examine students' perceived knowledge and skills as related to the objectives of the course and to their anxieties, concerns, and future training needs. Results: Between February 2020 and March 2020, 44 students completed the curriculum. Students indicated that self-efficacy significantly increased in all aspects of the curricular goals following curriculum completion. Students identified understanding OR etiquette as the most anxiety-provoking element associated with scrub training. They felt that more time could be spent elucidating this etiquette. On the other hand, tasks such as surgical hand hygiene were the least anxiety-inducing. Discussion: We share this multimodal scrub training curriculum, mapped to the AAMC's guidelines, to reduce variability in teaching strategies and skills acquisition through a standardized curriculum. Also, we effectively imparted these skills and instilled a sense of confidence in learners as they worked to provide their best in patient care and safety.
Assuntos
Estudantes de Medicina , Currículo , Humanos , Conhecimento , Assistência ao Paciente , AutoeficáciaRESUMO
BACKGROUND: Robotic surgery has seen unprecedented growth, requiring hospitals to establish or update credentialing policies regarding this technology. Concerns about verification of robotic surgeon proficiency and the adequacy of current credentialing criteria to maintain patient safety have arisen. The aim of this project was to examine existing institutional credentialing requirements for robotic surgery and evaluate their adequacy in ensuring surgeon proficiency. METHODS: Robotic credentialing policies for community and academic surgery programs were acquired and reviewed. Common criteria across institutions related to credentialing and recredentialing were identified and the average, standard deviation, and range of numeric requirements, if defined, was calculated. Criteria for proctors and assistants were also analyzed. RESULTS: Policies from 42 geographically dispersed US hospitals were reviewed. The majority of policies relied on a defined number of proctored cases as a surrogate for proficiency with an average of 3.24 ± 1.69 and a range of 1-10 cases required for initial credentialing. While 34 policies (81%) addressed maintenance of privileges requirements, there was wide variability in the average number of required robotic cases (7.19 ± 3.28 per year) and range (1-15 cases per year). Only 11 policies (26%) addressed the maximum allowable time gap between robotic cases. CONCLUSION: Significant variability in credentialing policies exists in a representative sample of US hospitals. Most policies require completion of a robotic surgery training course and a small number of proctored cases; however, ongoing objective performance assessments and patient outcome monitoring was rarely described. Existing credentialing policies are likely inadequate to ensure surgeon proficiency; therefore, development and wide implementation of robust credentialing guidelines is recommended to optimize patient safety and outcomes.
Assuntos
Credenciamento , Procedimentos Cirúrgicos Robóticos/educação , Competência Clínica , Credenciamento/normas , Hospitais , Humanos , Política Organizacional , Procedimentos Cirúrgicos Robóticos/normas , Cirurgiões , Estados UnidosRESUMO
BACKGROUND: The global COVID-19 pandemic has placed tremendous physical and mental strain on the US healthcare system. Studies examining the effects of outbreaks have demonstrated both an increased prevalence and long-term development of Post-Traumatic Stress Disorder (PTSD) symptoms in healthcare providers. We sought to assess the impact of the COVID-19 pandemic on the psychological well-being of medical providers, medical trainees, and administrators at a large academic center to identify stressors and moderators to guide future mental health and hospital-system interventions. METHODS: A 42-item survey examining specific stressors, grit, and resilience was widely distributed to physicians, residents, fellows, and administrators a large academic institution for departmental distribution. Survey results were analyzed using descriptive statistics, ANOVA, and multivariate linear regressions. A p-value <0.05 was considered statistically significant. RESULTS: A total of 785 participants completed the survey. The majority of respondents rated their stress to be significantly increased during the pandemic. Respondents' fear of transmitting the virus to their family members was a significant stressor. Higher resilience was associated with lower stress, anxiety, fatigue, and sleep disturbances. Overall, respondents felt supported by their departments and institution and felt contingency plans and personal protective equipment were adequate. CONCLUSIONS: Healthcare workers have increased resilience in the face of heightened stress during a pandemic. Higher resilience and grit were protective factors in managing personal and system-level stressors at the peak of the COVID-19 pandemic in our institution. Implementing an intervention designed to enhance healthcare workers' resilience in response to the COVID-19 pandemic is warranted.
Assuntos
COVID-19/terapia , Pessoal de Saúde/psicologia , Pneumonia Viral/terapia , Resiliência Psicológica , Transtornos de Estresse Pós-Traumáticos/prevenção & controle , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: Over one third of general surgery residents interrupt their clinical training to pursue dedicated research time (DRT), which has financial implications for programs and residents. Studies have examined the impact of DRT on academic outcomes, but little is known about why residents pursue DRT. Therefore, this study aimed to examine resident motivations regarding DRT in order to gain an understanding of resident goals and challenges surrounding this phase of training. DESIGN: Surgical residents currently participating in DRT and residents considering completing DRT were recruited to participate. Members of the research team at each institution conducted interviews and focus groups, which were recorded and transcribed. Data was analyzed using the qualitative method of open and focused coding. Identified themes guided the development of a conceptual framework. SETTING: Interviews and focus groups were held at three geographically diverse US academic health centers. PARTICIPANTS: Twenty-one surgery residents participated. RESULTS: Reasons for pursuing DRT fell into 1 of 3 themes: strategic career planning, professional development, and personal rejuvenation. Residents described the perceived need for publications or networking to enhance future competitiveness for desired fellowships or academic appointments. Residents also expressed the desire to have time for career exploration and to cultivate mentorship for their professional career. The need to take time off for more personal reasons, including burnout, was pervasive. Additionally, many in DRT felt under-supported in developing their research skills and expressed a desire for more formal instruction and guidance from mentors. CONCLUSIONS: General surgery residents' motivations to pursue DRT are multifactorial. Professional development is a pervasive motivation and includes learning skills that can be applied to future research. Current DRT programs may be inadequate in supporting residents to achieve this goal. These results can be used to inform programmatic efforts to optimize DRT for residents and mentors alike.
Assuntos
Cirurgia Geral , Internato e Residência , Escolha da Profissão , Bolsas de Estudo , Grupos Focais , Cirurgia Geral/educação , Humanos , Mentores , MotivaçãoRESUMO
OBJECTIVES: Knot tying is a fundamental surgical skill. Existing knot tying models assess tying efficiency and errors but do not address respect for tissue. Development of a model that assesses tissue displacement during knot tying may provide a good surrogate for respect for tissue, allow detection of expertise, and offer an improved training platform for skill acquisition. This study aimed to develop a novel, low-cost, knot tying board (KTB) that collects objective, automated metrics of knot displacement, and assesses knot displacement by level of surgical expertise. DESIGN: The novel KTB was developed in collaboration between engineering students and surgical educators. Joystick potentiometers were incorporated on 2 parallel rubber tubes to measure vertical and horizontal displacement while tying. Participants used a standardized technique to tie 1- and 2-handed knots. Differences in time and tubing displacement were compared among junior residents (postgraduate year 1-2), senior residents (postgraduate year 3-5), and attending surgeons; p < 0.05 was considered statistically significant. SETTING: This study was conducted at the Indiana University Surgical Skills Center in Indianapolis, IN. PARTICIPANTS: Forty-seven residents and faculty participated in the study (26 juniors, 14 seniors, 7 attendings). RESULTS: KTB development required 100 hours and $70.00. The attending surgeons tied 2-handed knots faster and with significantly more vertical tubing displacement than residents. Senior residents tied knots significantly faster but with similar tubing displacement as juniors. Similar trends were found for 1-handed knots. CONCLUSIONS: A novel, low-cost KTB was developed to measure knot displacement as a surrogate for tissue handling. The new performance metric of vertical knot displacement proved more sensitive in detecting performance differences among groups compared with horizontal knot displacement. This board and its novel metrics may promote the development of robust knot tying skill by residents.
Assuntos
Internato e Residência , Cirurgiões , Competência Clínica , Humanos , Indiana , Técnicas de SuturaRESUMO
Surgical educators face many challenges on the path toward ensuring surgical trainee technical-skill acquisition. We present effective intraoperative teaching techniques and discuss the utilization of simulation to improve technical skills outside of the operating room. Adjuncts, including coaching, mental skills, and nontechnical-skill assessments, are also reviewed. Finally, an example of a clinical curriculum that incorporates best practices in teaching technical surgery is presented.
RESUMO
BACKGROUND: Fundamentals of Endoscopic Surgery (FES) has become a board certification requirement for general surgery residents. While the FES program provides a robust didactic curriculum, an endoscopic skills curriculum is lacking for this high stakes assessment. The aims of this study were to develop a proficiency-based endoscopic skills curriculum and assess its effectiveness on success in the FES exam. METHODS: Endoscopy experts developed a multiple-choice questionnaire based on the FES online didactics. Five training cases from the GI Mentor II simulator were selected, and expert performance defined proficiency levels for each case. Participating surgery residents were required to review online didactics and achieve proficiency twice on selected simulator cases. The multiple-choice questionnaire, simulator-generated metrics of two endoscopy cases, Global Assessment of Gastrointestinal Endoscopic Skills (GAGES), NASA-Task Load Index (TLX), and the manual portion of the FES exam were used for assessment before and after training. The curriculum was implemented either alongside a clinical endoscopy rotation or independent of the rotation. Clinical endoscopic skills of participants with a dedicated rotation were assessed using GAGES. RESULTS: Twenty-eight general surgery residents (PGY 2-5) participated in the study, of which 25 (89%) completed the curriculum. Scores of the multiple-choice questionnaire and all simulator-generated metrics improved in the post-training assessment, with the exception of the percentage of mucosal surface examined, which was slightly decreased. Simulated and clinical GAGES scores and the NASA-TLX score improved after training. Performance scores on four of five FES exam tasks were significantly improved. CONCLUSIONS: The proficiency-based endoscopic skills curriculum was successfully implemented both alongside the clinical endoscopy rotation and independent of the rotation. Participating residents acquired skills to pass the FES exam. This curriculum will be valuable to general surgery residency programs.
Assuntos
Currículo/tendências , Avaliação Educacional/métodos , Endoscopia , Cirurgia Geral/educação , Internato e Residência , Competência Clínica/normas , Endoscopia/educação , Endoscopia/métodos , Humanos , Internato e Residência/métodos , Internato e Residência/tendênciasRESUMO
Pregnancy and parturition are intricately regulated to ensure successful reproductive outcomes. However, the factors that control gestational length in humans and other anthropoid primates remain poorly defined. Here, we show the endogenous retroviral long terminal repeat transposon-like human element 1B (THE1B) selectively controls placental expression of corticotropin-releasing hormone (CRH) that, in turn, influences gestational length and birth timing. Placental expression of CRH and subsequently prolonged gestational length were found in two independent strains of transgenic mice carrying a 180-kb human bacterial artificial chromosome (BAC) DNA that contained the full length of CRH and extended flanking regions, including THE1B. Restricted deletion of THE1B silenced placental CRH expression and normalized birth timing in these transgenic lines. Furthermore, we revealed an interaction at the 5' insertion site of THE1B with distal-less homeobox 3 (DLX3), a transcription factor expressed in placenta. Together, these findings suggest that retroviral insertion of THE1B into the anthropoid primate genome may have initiated expression of CRH in placental syncytiotrophoblasts via DLX3 and that this placental CRH is sufficient to alter the timing of birth.
Assuntos
Hormônio Liberador da Corticotropina/genética , Placenta/metabolismo , Primatas/genética , Retroelementos/genética , Animais , Sequência de Bases , Sistemas CRISPR-Cas/genética , Cromossomos Artificiais Bacterianos/genética , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Redes Reguladoras de Genes , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Camundongos Transgênicos , Mutagênese Insercional/genética , Parto , Gravidez , Ligação Proteica , Deleção de Sequência , Especificidade da Espécie , Sequências Repetidas Terminais/genética , Fatores de Transcrição/metabolismo , Trofoblastos/metabolismoRESUMO
Nematodes represent a diverse phylum of both free living and parasitic species. While the species Caenorhabditis elegans is a valuable model organism, parasitic nematodes or helminths pose a serious threat to human health. Indeed, helminths cause many neglected tropical diseases that afflict humans. Nematode glycoconjugates have been implicated in evasive immunomodulation, a hallmark of nematode infections. One monosaccharide residue present in the glycoconjugates of several human pathogens is galactofuranose (Galf). This five-membered ring isomer of galactose has not been detected in mammals, making Galf metabolic enzymes attractive therapeutic targets. The only known pathway for biosynthetic incorporation of Galf into glycoconjugates depends upon generation of the glycosyl donor UDP-Galf by the flavoenzyme uridine 5'-diphosphate (UDP) galactopyranose mutase (UGM or Glf). A putative UGM encoding gene (glf-1) was recently identified in C. elegans. We sought to assess the catalytic activity of the corresponding gene product (CeUGM). CeUGM catalyzes the isomerization of UDP-Galf and UDP-galactopyranose (UDP-Galp). In the presence of enzyme, substrate, and a hydride source, a galactose-N5-FAD adduct was isolated, suggesting the CeUGM flavin adenine dinucleotide (FAD) cofactor serves as a nucleophile in covalent catalysis. Homology modeling and protein variants indicate that CeUGM possesses an active site similar to that of prokaryotic enzymes, despite the low sequence identity (â¼15%) between eukaryotic and prokaryotic UGM proteins. Even with the primary sequence differences, heterocyclic UGM inhibitors developed against prokaryotic proteins also inhibit CeUGM activity. We postulate that inhibitors of CeUGM can serve as chemical probes of Galf in nematodes and as anthelmintic leads. The available data suggest that CeUGM facilitates the biosynthetic incorporation of Galf into nematode glycoconjugates through generation of the glycosyl donor UDP-Galf.
Assuntos
Caenorhabditis elegans/enzimologia , Transferases Intramoleculares/química , Animais , Cristalografia por Raios X , Humanos , Transferases Intramoleculares/isolamento & purificaçãoRESUMO
CONTEXT: Although more than 7 million athletes participate in high school sports in the United States, to date no nationally representative studies of rare injuries and conditions (RICs) exist. Rare injuries and conditions include eye injuries, dental injuries, neck and cervical injuries, and dehydration and heat illnesses. OBJECTIVE: To describe the epidemiology of RICs sustained by high school athletes during the 2005-2006 and 2006-2007 school years. DESIGN: Prospective cohort study. SETTING: A nationally representative sample of 100 US high schools using an injury surveillance system, High School Reporting Information Online. PATIENTS OR OTHER PARTICIPANTS: Athletes participating in football, boys' soccer, girls' soccer, volleyball, boys' basketball, girls' basketball, wrestling, baseball, or softball at one of the 100 participating high schools. MAIN OUTCOME MEASURE(S): We reviewed all RICs to calculate injury rates and to identify potential risk factors and preventive measures. RESULTS: A total of 321 RICs were sustained during 3 550 141 athlete-exposures (AEs), for an injury rate of 9.04 RICs per 100 000 AEs. This represents an estimated 84 223 RICs sustained nationally. The RICs accounted for 3.5% of all high school athletes' injuries. The most common diagnoses were neck and cervical injuries (62.0%, n = 199) and dehydration and heat illnesses (18.7%, n = 60). Football had the highest RIC rate per 100 000 AEs (21.2), followed by wrestling (15.2) and baseball (7.60). The RICs occurred at a higher rate in boys (12.4) than in girls (2.51) (rate ratio = 4.93; 95% confidence interval = 3.39, 7.18). The majority of RICs (67.3%, n = 216) permitted athletes to return to play within 1 week of diagnosis. CONCLUSIONS: The RIC injury rates varied by sport and sex and represented almost 100 000 potentially preventable injuries to high school athletes. Because of the potentially serious consequences, future researchers must develop and implement more effective preventive measures to aid certified athletic trainers in decreasing the RIC incidence among high school athletes.