RESUMO
The microRNAs encoded by the miR-17â¼92 polycistron are commonly overexpressed in cancer and orchestrate a wide range of oncogenic functions. Here, we identify a mechanism for miR-17â¼92 oncogenic function through the disruption of endogenous microRNA (miRNA) processing. We show that, upon oncogenic overexpression of the miR-17â¼92 primary transcript (pri-miR-17â¼92), the microprocessor complex remains associated with partially processed intermediates that aberrantly accumulate. These intermediates reflect a series of hierarchical and conserved steps in the early processing of the pri-miR-17â¼92 transcript. Encumbrance of the microprocessor by miR-17â¼92 intermediates leads to the broad but selective downregulation of co-expressed polycistronic miRNAs, including miRNAs derived from tumor-suppressive miR-34b/c and from the Dlk1-Dio3 polycistrons. We propose that the identified steps of polycistronic miR-17â¼92 biogenesis contribute to the oncogenic re-wiring of gene regulation networks. Our results reveal previously unappreciated functional paradigms for polycistronic miRNAs in cancer.
Assuntos
Carcinogênese/genética , MicroRNAs/genética , Processamento Pós-Transcricional do RNA/genética , Proteínas de Ligação ao Cálcio/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Iodeto Peroxidase/genética , Proteínas de Membrana/genética , MicroRNAs/biossíntese , Conformação de Ácido NucleicoRESUMO
BACKGROUND: There is a lack of patient-reported outcome measures (PROMs) with robust measurement properties to assess postoperative recovery and support patient-centered care after abdominal surgery. The aim of this study was to establish a conceptual framework of recovery after abdominal surgery to support the development of a conceptually relevant and psychometrically sound PROM. METHODS: Patients from four different countries (Canada, Italy, Brazil, and Japan) participated in qualitative interviews focusing on their lived experiences of recovery after abdominal surgery. Interviews were guided by a previously developed hypothesized conceptual framework established based on a literature review and expert consensus. Interviews were analyzed according to a modified grounded theory approach and transcripts were coded according to the International Classification of Functioning, Disability and Health (ICF). Codes for which thematic saturation was reached were classified into domains of health that are relevant to the process of recovery after abdominal surgery. These domains were organized into a structured diagram. RESULTS: 30 Patients with diverse demographics and surgical characteristics were interviewed (50% female, age 57 ± 18 years, 66% major or major extended surgery). 39 Unique domains of recovery emerged from the interviews, 17 falling under the ICF category of "Body Functions" and 22 under "Activities and Participation". These domains constitute the conceptual framework of recovery after abdominal surgery. CONCLUSIONS: This study provides comprehensive insight into patients' perspectives of the recovery process after abdominal surgery. This conceptual framework will support content validity and provide the pivotal basis for the development of a novel PROM to inform quality improvement initiatives and patient-centered research in abdominal surgery.
Assuntos
Abdome/cirurgia , Medidas de Resultados Relatados pelo Paciente , Psicometria/métodos , Qualidade de Vida/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The proportion of women in surgery has risen significantly yet there remains gender discrepancies in upper leadership positions in academia. Specialty societies play an important role in academic advancement but the progression of women in surgical societies has not been studied. The purpose of this study was to determine if there are gender differences in advancement within the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) leadership. METHODS: A retrospective audit of all SAGES committee members (CM) from 1992 to 2018 was performed. The overall membership gender distribution was available from 2010 to 2018. Leadership positions included Committee Chair/Co-chair, Board of Governors, and Executive Committee. Three phenomena were investigated: "pipeline," by determining the change in women CMs compared to overall membership over time; "sticky floors," by comparing advancement beyond CM by gender; "glass-ceiling," by analyzing the promotion trajectory and time to leadership positions between genders. Statistical analysis comparing trends over time was performed using Kendall-tau. RESULTS: There were 1546 surgeons who served on at least one committee during the study period. Women represented 21% of CMs, 18% of chairs/co-chairs, 16% of board members and 14% of executives, with one woman President. The proportion of women CMs has significantly increased over time from 3% in 1992 to 27% in 2018 (p-trend < 0.001). A similar proportion of women and men advanced beyond CM (17% vs. 14%, p = 0.194), with no difference in time to advancement. From 2010 to 2018, the increase in the proportion of women CMs and board members outpaced that of overall women members (p < 0.05). Women executives surpassed overall women members in 2018 (29% vs. 19%). A similar proportion of men and women "skipped ranks" to reach the Board/Executive (37% vs. 25%, p = 0.307). CONCLUSION: The proportion of women in leadership positions within SAGES is higher than in the overall membership. There were no gender differences in the advancement of CMs to leadership positions. While these data are encouraging, SAGES should continue to foster the advancement of women surgeons.
Assuntos
Liderança , Médicas/estatística & dados numéricos , Sociedades Médicas/organização & administração , Cirurgiões/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos , Distribuição por Sexo , SexismoRESUMO
BACKGROUND: We initiated a research program to develop a novel patient-reported outcome measure (PROM) to assess postoperative recovery from the perspective of abdominal surgery patients. In light of FDA recommendations, the first stage of our program aimed to, based on previous literature and expert input, develop a hypothesized conceptual framework portraying the health domains that are potentially relevant to the process of recovery after abdominal surgery. METHODS: This study was conducted in three phases: (1) systematic review to identify PROMs with measurement properties appraised in the context of recovery after abdominal surgery, (2) content analysis to categorize the health domains covered by the PROMs according to the ICF, and (3) two-round Delphi study to gain expert input regarding which of these health domains are relevant to the process of recovery. Participants were experts in perioperative care identified through two major surgical societies (35 invited). RESULTS: The systematic review identified 19 PROMs covering 66 ICF domains. 23 experts (66%) participated in the Delphi process. After Round 2, experts agreed that 22 health domains (8 body functions, 14 activities and participation) are potentially relevant to the process of recovery after abdominal surgery. These domains were organized into a diagram, representing our hypothesized conceptual framework. CONCLUSIONS: This hypothesized conceptual framework is an important first step in our research program and will be further refined based on in-depth qualitative interviews with patients. The sound methodological approach used to derive this framework may be valuable for studies aimed to develop PROMs according to FDA standards.
Assuntos
Abdome/cirurgia , Medidas de Resultados Relatados pelo Paciente , Recuperação de Função Fisiológica , Técnica Delphi , Humanos , Período Pós-OperatórioRESUMO
Importance: Postoperative recovery is difficult to define or measure. Research addressing interventions aimed to improve recovery after abdominal surgery often focuses on measures such as duration of hospital stay and complication rates. Although these clinical parameters are relevant, understanding patients' perspectives regarding postoperative recovery is fundamental to guiding patient-centered care. Objective: To elucidate the meaning of recovery from the perspective of patients undergoing abdominal surgery. Design, Setting, and Participants: This international qualitative study involved semistructured interviews with patients recovering from abdominal surgery from October 2016 to November 2018 in tertiary hospitals in 4 countries (Canada, Italy, Brazil, and Japan). A purposive maximal variation sampling method was used to ensure the recruitment of patients with varying demographic, clinical, and surgical characteristics. Data on race were not collected. Each interview lasted between 1 and 2 hours. Interviews were recorded and then transcribed verbatim. Transcripts were then analyzed using an inductive thematic analysis approach. Data analysis was conducted from July 2019 to September 2019. Main Outcomes and Measures: The qualitative analysis revealed themes reflecting the meaning of recovery from the perspective of patients undergoing abdominal surgery. Results: Thirty patients recovering from abdominal surgery were interviewed (15 [50%] female; mean [SD] age, 57 [18] years; 10 [33%] underwent major surgery; 16 [53%] underwent laparoscopic surgery). The interviews revealed that for patients undergoing abdominal surgery, the meaning of recovery embodied 5 overarching themes: (1) returning to habits and routines, (2) resolution of symptoms, (3) overcoming mental strains, (4) regaining independence, and (5) enjoying life. Themes associating the meaning of recovery to traditional parameters, such as earlier hospital discharge or absence of complications, were not identified in the interviews. Conclusions and Relevance: This qualitative study suggests that the meaning of recovery from the perspective of patients undergoing abdominal surgery goes beyond traditional clinical parameters. The elements of recovery identified in this study should be taken into account in patient-surgeon discussions about recovery and when developing patient-centered strategies to improve postoperative outcomes.