DNA ligases play essential roles in DNA replication and repair. Bacteriophage T4 DNA ligase is the first ATP-dependent ligase enzyme to be discovered and is widely used in molecular biology, but its structure remained unknown. Our crystal structure of T4 DNA ligase bound to DNA shows a compact α-helical DNA-binding domain (DBD), nucleotidyl-transferase (NTase) domain, and OB-fold domain, which together fully encircle DNA. The DBD of T4 DNA ligase exhibits remarkable structural homology to the core DNA-binding helices of the larger DBDs from eukaryotic and archaeal DNA ligases, but it lacks additional structural components required for protein interactions. T4 DNA ligase instead has a flexible loop insertion within the NTase domain, which binds tightly to the T4 sliding clamp gp45 in a novel α-helical PIP-box conformation. Thus, T4 DNA ligase represents a prototype of the larger eukaryotic and archaeal DNA ligases, with a uniquely evolved mode of protein interaction that may be important for efficient DNA replication.

Purpose: Early exposure and surgical mentorship can augment interest in surgery. We evaluate the effect and feasibility of offering education and mentorship opportunities in surgery to premedical students at our institution through an undergraduate surgery interest group (USIG). Materials and Methods: We conducted a 1-year assessment of our USIG and reviewed its organizational structure, funding resources, media promotion, and educational activities. Our USIG hosted introductory-level surgical skills workshops, guest lectures by surgeons, and various facility tours. To assess participants’ interests, as well as the influences on them to pursue a surgical profession, we analyzed pre- and post-event questionnaires. Similar questionnaires were completed by medical students in our medical student surgery interest group to compare any differences in perception between premedical and medical students. Results: Our USIG currently has 378 undergraduate student members, with a higher proportion of women than in our medical student surgery interest group (P < 0.003). Neurosurgery was the most popular career choice among undergraduate participants. Participants reported the highest satisfaction with suturing and high-fidelity trauma surgery skills workshops. Undergraduate participants indicated that their intrinsic interest in the sciences is the highest motivation to pursue a surgical profession. Resident lifestyle and social obligations of a surgical career were actually positive influences for undergraduate participants; in contrast, medical students viewed those variables as negative factors. Conclusion: Our USIG was met with enthusiasm by premedical students and faculty alike. Participation strengthened premedical students’ interest in pursuing surgery and increased their understanding of the surgical profession. Early mentorship may positively influence premedical students’ perception of surgical careers. USIG is economically feasible and time-efficient; we encourage other academic institutions and educators to consider investing in similar interest groups.

Background: There are few data on sex differences in suspected cardiac sarcoidosis. Methods: Consecutive patients with histologically proven sarcoidosis and suspected cardiac involvement were studied. We investigated sex differences in presenting features, cardiac involvement, and the long-term incidence of a primary composite end point of all-cause death or significant ventricular arrhythmia and secondary end points of all-cause death and significant ventricular arrhythmia. Results: Among 324 patients, 163 (50.3%) were female and 161 (49.7%) were male patients. Female patients had a greater prevalence of chest pain (37.4% versus 23.6%; P =0.010) and palpitations (39.3% versus 26.1%; P =0.016) than male patients but not dyspnea, presyncope, syncope, or arrhythmias at presentation. Female patients had a lower prevalence of late gadolinium enhancement on cardiovascular magnetic resonance imaging (20.2% versus 35.4%; P =0.003) and less often met criteria for a clinical diagnosis of cardiac sarcoidosis (Heart Rhythm Society consensus criteria, 22.7% versus 36.0%; P =0.012 and 2016 Japanese Circulation Society guideline criteria, 8.0% versus 19.3%; P =0.005), indicating lesser cardiac involvement. However, the long-term incidence of all-cause death or significant ventricular arrhythmia was not different between female and male patients (23.2% versus 23.2%; P =0.46). Among the secondary end points, the incidence of all-cause death was not different between female and male patients (20.7% versus 14.3%; P =0.51), while female patients had a lower incidence of significant ventricular arrhythmia compared with male patients (4.3% versus 13.0%; P =0.022). On multivariable analyses, sex was not associated with the primary end point (hazard ratio for female patients, 1.36 [95% CI, 0.77–2.43]; P =0.29). Conclusions: We observed distinct sex differences in patients with suspected cardiac sarcoidosis. A paradox was identified wherein female patients had a greater prevalence of chest pain and palpitations than male patients, but lesser cardiac involvement, and a similar long-term incidence of all-cause death or significant ventricular arrhythmia.

Background: Delayed gastric emptying (DGE) is the most common postoperative complication following any pancreatic resection. The incidence and risk factors of DGE in patients undergoing distal pancreatic resection (DPR) is not well defined. We aimed to determine the incidence of DGE not associated with postoperative pancreatic fistula (POPF) in patients undergoing DPR and to identify predictors of DGE. Methods: ACS-NSQIP pancreatectomy database (2014-2017) was queried for patients with pancreatic adenocarcinoma undergoing DPR, excluding patients with POPF. A classification and regression tree (CART) analysis was performed to identify risk for DGE, defined by nasogastric/gastrostomy tube placed after postoperative day (POD) 7 or no oral intake by POD 14. Results: A total of 1626 patients underwent DPR without POPF; 59 had DGE (3.6%). Patients with DGE had a longer length of stay vs patients without DGE (median 15 vs 6 days, P < .001). CART analysis showed vascular resection and open surgery were predictors of DGE with a specificity of 98.3%. Patients requiring vascular resection had a 7.8% rate of DGE. Patients who did not undergo open surgery or vascular resection had a 1.8% rate of DGE. Conclusions: The rate of DGE in patients undergoing DPR without postoperative pancreatic fistula is low. Predictors of DGE include open surgical approach and vascular resection. These findings may be utilized to counsel patients and take precautions in those at greater risk of developing DGE. Further research can involve implementation of a scoring tool to help stratify patients at risk for DGE after DPR.

Colorectal peritoneal metastases portend a poor prognosis when compared to other isolated sites of metastatic disease. The advent of regional therapies, including cytoreductive surgery, have improved outcomes for patients with peritoneal carcinomatosis. However, these options are typically only available in patients deemed to have resectable disease. For patients with unresectable peritoneal disease, non-surgical regional therapy has only been studied in early-phase clinical trials. This represents a gap in therapy in a population with a desperate need. In this review, we highlight the current limited data, as well as postulate on the future direction of regional therapies in patients with unresectable peritoneal metastases from colorectal adenocarcinoma.

This research was presented at the American College of Surgeons Clinical Congress in Fall 2016 and at the University of Minnesota Undergraduate Research Symposium in Spring 2017. The work presented summarized the formation of the Undergraduate Surgery Interest Group as a novel educational platform for providing undergraduate students with meaningful exposure to the field of surgery.Early exposure to the field of surgery through workshops, lectures, and mentors may bolster and prolong interest in surgical careers for undergraduate students. An Undergraduate Surgery Interest Group (USIG) was started through the initiative of students, seeking to create more opportunities through which younger students could develop and explore their motivations for advancing toward surgical practices. This USIG has received advisorship, resources, and support from the University of Minnesota Medical School Department of Surgery. A group of students may work with the medical school and student government to develop a constitution defining the objectives and structure of the group, as well as create officer positions. Coordination with an advisor is recommended to aid navigation and networking within the medical school necessary for resources, events, and speakers. The group may then be publicized through social media, flyers, and various departments within the university to gain membership and participation. A USIG was created by a board of five undergraduate students under mentorship within the medical school. Each board member has a well-defined role and oversight by a USIG president. Weekly board meetings are held to coordinate bi-weekly events, which include surgical technique workshops, tours of medical labs, exposure to next-generation biomedical engineering devices, and discussions involving the history of surgery. This USIG was created in Fall 2015 and now has 260 active undergraduate participants. A Facebook page has been used to publicize events and workshops, currently with about 200 ‘Likes’. Short-term success of the group is routinely evaluated through member surveys and post-event questionnaires, and long-term impacts of the group will be evaluated through physicians citing the USIG as influential to their career. USIG provides unique opportunities for undergraduates to gain exposure and interest in the surgical field while promoting long-term commitment. In turn, advisers may discover students with valuable qualities, while medical students gain teaching opportunities which better prepare them for clinical rotations in surgery