A Modular Turn-On Strategy to Profile E2-Specific Ubiquitination Events in Living Cells.

A cascade of three enzymes, E1-E2-E3, is responsible for transferring ubiquitin to target proteins, which controls many different aspects of cellular signaling. The role of the E2 has been largely overlooked, despite influencing substrate identity, chain multiplicity, and topology. Here we report a method-targeted charging of ubiquitin to E2 (tCUbE)-that can track a tagged ubiquitin through its entire enzymatic cascade in living mammalian cells. We use this approach to reveal new targets whose ubiquitination depends on UbcH5a E2 activity. We demonstrate that tCUbE can be broadly applied to multiple E2s and in different human cell lines. tCUbE is uniquely suited to examine E2-E3-substrate cascades of interest and/or piece together previously unidentified cascades, thereby illuminating entire branches of the UPS and providing critical insight that will be useful for identifying new therapeutic targets in the UPS.

Expectant Management of Patients with Ventral Hernias: 3 Years of Follow-up.

BACKGROUND: The safety and effectiveness of expectant management (e.g., watchful waiting or initially managing non-operatively) for patients with a ventral hernia is unknown. We report our 3-year results of a prospective cohort of patients with ventral hernias who underwent expectant management. METHODS: A hernia clinic at an academic safety-net hospital was used to recruit patients. Any patient undergoing expectant management with symptoms and high-risk comorbidities, as determined by a surgeon based on institutional criteria, would be included in the study. Patients unlikely to complete follow-up assessments were excluded from the study. Patient-reported outcomes were collected by phone and mailed surveys. A modified activities assessment scale normalized to a 1-100 scale was used to measure results. The rate of operative repair was the primary outcome, while secondary outcomes include rate of emergency room (ER) visits and both emergent and elective hernia repairs. RESULTS: Among 128 patients initially enrolled, 84 (65.6%) completed the follow-up at a median (interquartile range) of 34.1 (31, 36.2) months. Overall, 28 (33.3%) patients visited the ER at least once because of their hernia and 31 (36.9%) patients underwent operative management. Seven patients (8.3%) required emergent operative repair. There was no significant change in quality of life for those managed non-operatively; however, substantial improvements in quality of life were observed for patients who underwent operative management. CONCLUSIONS: Expectant management is an effective strategy for patients with ventral hernias and significant comorbid medical conditions. Since the short-term risk of needing emergency hernia repair is moderate, there could be a safe period of time for preoperative optimization and risk-reduction for patients deemed high risk.

Gender Disparity in Authorship of Peer-Reviewed Medical Publications.

BACKGROUND: Women are underrepresented in medicine despite increases in the percentage of female physicians. It is unknown if academic productivity contributes to these differences. We sought to determine whether gender disparity exists in peer-reviewed literature authorship in the United States from 2000 to 2017. METHODS: Medical and surgical peer-reviewed research articles from the United States were retrospectively reviewed using PubMed from 2000 to 2017. Manuscripts were randomly selected within 4 different time periods: 2000-2005, 2006-2010, 2011-2015 and 2016-2017. The gender of the first and last authors was determined and the journal's impact factor recorded. The Accreditation Council for Graduate Medical Education (ACGME) and Association of American Medical Colleges (AAMC) databases were used to determine the percent of female residents, attendings and academic leadership positions. Primary outcome was the prevalence of female authors in peer-reviewed literature. Secondary aims were differences in disparity in medical versus surgical specialties, differences in publications' impact factor among gender and the association between gender and mentoring. RESULTS: Within 1,120 articles reviewed, 31.6% of first authors and 19.4% of last authors were women. Female first and last authors increased over time and authorship was proportional to the number of women in the studied specialties at that specific time period (P = 0.78). There was no difference in the journal's impact factors between gender (P = 0.64). On subgroup analysis of medical and surgical subspecialties, results remained unchanged. CONCLUSIONS: Women publish research at a rate proportional to the number of academic female physicians. Disparities in leadership roles are unlikely explained by differences in publications. While gender disparities in medicine have improved, substantial disparities in leadership persist.

Are online surgical discussion boards a safe and useful venue for surgeons to ask for advice? A review of the International Hernia Collaboration Facebook Group.

BACKGROUND: Social media is a growing medium for disseminating information among surgeons. The International Hernia Collaboration Facebook Group (IHC) is a widely utilized social media platform to share ideas and advice on managing patients with hernia-related diseases. Our objective was to assess the safety and utility of advice provided. METHODS: Overall, 60 consecutive de-identified clinical threads were extracted from the IHC in reverse chronological order. A group of three hernia specialists evaluated all threads for unsafe posts, unhelpful comments, and if an established evidence-based management strategy was provided. Positive and negative controls for safe and unsafe answers were included in seven threads and reviewers were blinded to their presence. Reviewers were free to access all online and professional resources (except the IHC). RESULTS: There were 598 unique responses (median 10, 1-26 responses per thread) to the 60 clinical threads/scenarios. The review team correctly identified all seven positive and negative controls. Most responses were safe (96.6%) but some were unhelpful (28.4%). For sixteen threads, the reviewers believed there was an established evidence-based answer; however, only six were provided. In addition, 14 responses were considered unsafe, but only four were corrected. CONCLUSIONS: The vast majority of responses were considered helpful; however, evidence-based management is typically not provided and unsafe recommendations often go uncontested. While the IHC allows wide dissemination of hernia-related surgical advice/discussions, surgeons should be cautious when using the IHC for clinical advice. Mechanisms to provide evidence-based management strategies and to identify unsafe advice are needed to improve quality within online forums and to prevent patient harm.

Is non-operative management warranted in ventral hernia patients with comorbidities? A case-matched, prospective 3 year follow-up, patient-centered study.

BACKGROUND: We hypothesized that long-term quality of life (QoL) is improved among patients with ventral hernias (VHs) and comorbid conditions managed operatively than with non-operative management. METHODS: This was the 3-year follow-up to a prospective observational study of patients with comorbid conditions and VHs. Primary outcome was change in QoL measured utilizing the modified Activities Assessment Scale (AAS), a validated, hernia-specific survey. Outcomes were compared using: (1)paired t-test on matched subset and (2)multivariable linear regression on the overall cohort. RESULTS: In the matched cohort (n = 80; 40/group), the operative group experienced a significantly greater improvement in QoL compared to the non-operative group (28.4 ±â€¯27.1 vs. 11.8 ±â€¯23.8,p = 0.005). The operative group, had 10 (25.0%) reported recurrences while the non-operative group, reported 4/15 (26.7%) recurrences among the 15 (37.5%) patients that underwent repair. On multivariable analysis of the whole cohort (n = 137), operative management was associated with a 19.5 (95% CI7.0-31.9) point greater improvement in QoL compared to non-operative management. CONCLUSIONS: This is the first long term prospective study showing the benefits of operative as opposed to non-operative management of patients with comorbid conditions and VHs.

Gender Disparity in Surgery: An Evaluation of Surgical Societies.

Background: The percentage of female surgeons and surgery residents has increased slowly to 24% and 35%, respectively. However, women remain under-represented in surgical leadership positions (<20%). Society awards and leadership positions are used for hiring and promoting surgeons. We hypothesized that within the Surgical Infection Society (SIS), females are under-represented. Methods: The SIS website and databases were consulted for the number of female members, awardees, and leaders. Representation was divided into four time periods: 2000-2005, 2006-2010, 2011-2015, and 2016-2017 and compared for changes over time utilizing a Χ2 test. In addition, we reviewed the council members of five other surgical societies and compared the percentage of female representation in leadership positions. Results: Since the SIS was founded, there have been 587 members of whom only 135 (23%) are female. There has been an increase in female membership over time (p < 0.001). The number of female awardees rose from 37% during the first two study periods to more than 50% in the last two periods (p = 0.002). However, female representation in leadership positions decreased from 26% in 2000-2005 to less than 15% in the last three study periods (p = 0.234). Similar disparities emerged when comparing the SIS with other surgical societies: Women have represented only 24% (range 8%-42%) of leaders and 4% (range 0-11%) of society presidents. Conclusions: Female surgeons are under-represented in the SIS membership and leadership positions. Whereas the number of female surgeons and residents has increased, these trends have not occurred with council membership and leadership within the SIS. There is a need to address this gender disparity.