GENESIS-Guidance, Education, Networking, and Empowerment-based Smart Initiative for Students research in health care: A research modeling experience from a newly established medical college.

The importance of undergraduate medical research has been undermined in Indian medical education. Various studies show there is a drastic difference between the research output of Indian medical graduates in comparison to Western counterparts. With all the challenges identified, a student-oriented research committee was formed -Guidance, Education, Networking, and Empowerment-based Smart Initiative for Students (GENESIS) research in health care - A research modeling experience from a newly established medical college. The structure was established to serve the needs of students in the field of research. Problems were identified with the help of a survey, and steps were taken to address the issues through its 4-pronged strategy that includes conducting regular journal clubs. Journal clubs follow a peer-to-peer learning strategy and provide an open stage for discussion. Second, a research tracker which helps in increasing the sustainability of a research project. The third strategy includes a research live matchmaker which helps in bridging the gap between the students and the faculties. Lastly, involving alumni in the initiative will help students get guidance and acts as a gateway to opportunities at the national level. For maintaining the integrity and sustainability of the initiative, the involvement of students from all the batches is made sure. Inputs from faculties and administration are taken on a regular basis. Interinstitutional collaborations and regular assessment and evaluation are done to ensure positive outcomes. With its focus on peer-to-peer mentoring and attempt to eliminate the barriers for research enthusiasts, GENESIS has the potential to make a lasting impact in promoting research culture in colleges.

Inhibition of c-Rel expression in myeloid and lymphoid cells with distearoyl -phosphatidylserine (DSPS) liposomal nanoparticles encapsulating therapeutic siRNA.

c-Rel, a member of the nuclear factor kappa B (NF-κB) family, is preferentially expressed by immune cells and is known to regulate inflammation, autoimmune diseases and cancer. However, there is a lack of therapeutic intervention to specifically inhibit c-Rel in immune cells. Recent success with Pfizer and Moderna mRNA lipid-encapsulated vaccines as well as FDA approved medicines based on siRNA prompted us to test a lipid nanoparticle-based strategy to silence c-Rel in immune cells. Specifically, we encapsulated c-Rel-targeting siRNA into distearoyl-phosphatidylserine (DSPS)-containing nanoparticles. DSPS is a saturated phospholipid that serves as the "eat-me" signal for professional phagocytes such as macrophages and neutrophils of the immune system. We demonstrated here that incorporation of DSPS in liposome nanoparticles (LNP) improved their uptake by immune cells. LNP containing high concentrations of DSPS were highly effective to transfect not only macrophages and neutrophils, but also lymphocytes, with limited toxicity to cells. However, LNP containing low concentrations of DSPS were more effective to transfect myeloid cells than lymphoid cells. Importantly, DSPS-LNP loaded with a c-Rel siRNA were highly effective to inhibit c-Rel expression in several professional phagocytes tested, which lasted for several days. Taken together, our results suggest that DSPS-LNP armed with c-Rel siRNA could be exploited to target immune cells to limit the development of inflammatory diseases or cancer caused by c-Rel upregulation. In addition, this newly developed DSPS-LNP system may be further tested to encapsulate and deliver other small molecule drugs to immune cells, especially macrophages, neutrophils, and lymphocytes for the treatment of diseases.

Vps501, a novel vacuolar SNX-BAR protein cooperates with the SEA complex to regulate TORC1 signaling.

The sorting nexins (SNX), constitute a diverse family of molecules that play varied roles in membrane trafficking, cell signaling, membrane remodeling, organelle motility and autophagy. In particular, the SNX-BAR proteins, a SNX subfamily characterized by a C-terminal dimeric Bin/Amphiphysin/Rvs (BAR) lipid curvature domain and a conserved Phox-homology domain, are of great interest. In budding yeast, many SNX-BARs proteins have well-characterized endo-vacuolar trafficking roles. Phylogenetic analyses allowed us to identify an additional SNX-BAR protein, Vps501, with a novel endo-vacuolar role. We report that Vps501 uniquely localizes to the vacuolar membrane and has physical and genetic interactions with the SEA complex to regulate TORC1 inactivation. We found cells displayed a severe deficiency in starvation-induced/nonselective autophagy only when SEA complex subunits are ablated in combination with Vps501, indicating a cooperative role with the SEA complex during TORC1 signaling during autophagy induction. Additionally, we found the SEACIT complex becomes destabilized in vps501Δsea1Δ cells, which resulted in aberrant endosomal TORC1 activity and subsequent Atg13 hyperphosphorylation. We have also discovered that the vacuolar localization of Vps501 is dependent upon a direct interaction with Sea1 and a unique lipid binding specificity that is also required for its function. This article is protected by copyright. All rights reserved.

Forming the Hematology-Oncology Collaborative Videoconferencing (CO-VID) Learning Initiative: Experiential Lessons Learned From a Novel Trainee-Led Multidisciplinary Virtual Learning Platform.

PURPOSE: COVID-19 challenged medical practice and graduate medical education. Building on previous initiatives, we describe and reflect on the formative process and goals of the Hematology-Oncology Collaborative Videoconferencing Learning Initiative, a trainee-led multi-institutional virtual COVID-19 learning model. METHODS: Clinical fellows and faculty from 13 US training institutions developed consensus needs, goals, and objectives, recruited presenters, and generated a multidisciplinary COVID-19 curriculum. Weekly Zoom conferences consisted of two trainee-led instructional segments and a trainee-moderated faculty Q&A panel. Hematology-oncology training program faculty and trainees were the targeted audience. Leadership evaluations consisted of anonymized baseline and concluding mixed methods surveys. Presenter evaluations consisted of session debriefs and two structured focus groups. Conference evaluations consisted of attendance, demographics, and pre- or postmultiple-choice questions on topic learning objectives. RESULTS: In 6 weeks, the initiative produced five conferences: antivirals, anticoagulation, pulmonology, provider resilience, and resource scarcity ethics. The average attendance was 100 (range 57-185). Among attendees providing both pre- and postconference data, group-level knowledge appeared to increase: antiviral (n = 46) pre-/postcorrect 82.6%/97.8% and incorrect 10.9%/2.2%, anticoagulation (n = 60) pre-/postcorrect 75%/93.3% and incorrect 15%/6.7%, and pulmonary (n = 21) pre-/postcorrect 66.7%/95.2% and incorrect 33.3%/4.8%. Although pulmonary management comfort appeared to increase, comfort managing of antivirals and anticoagulation was unchanged. At the conclusion of the pilot, leadership trainees reported improved self-confidence organizing multi-institutional collaborations, median (interquartile range) 58.5 (50-64) compared with baseline 34 (26-39), but did not report improved confidence in other educational or leadership skills. CONCLUSION: During crisis, trainees built a multi-institutional virtual education platform for the purposes of sharing pandemic experiences and knowledge. Accomplishment of initiative goals was mixed. Lessons learned from the process and goals may improve future disaster educational initiatives.

First Analysis of Same-day Pegfilgrastim Use with Concurrent Capecitabine-based Regimens in Patients with Gastrointestinal Malignancies.

BACKGROUND: Pegfilgrastim is administered 24 hours. after chemotherapy to reduce risks of myelosuppression. This requires an additional clinic visit, which can be difficult for some patients (pts) due to work and transportation issues. In GI malignancies, patients receiving capecitabine-based regimens also require pegfilgrastim to reduce myelotoxicity. We present here the first study to analyze safety and efficacy of administering pegfilgrastim on the same day as capecitabine-based regimens in patients with GI malignancies. METHODS: We evaluated 157 patients with GI malignancies who received a capecitabine-based chemotherapy regimen, including XELOX, EOX, ECX, XELIRI, MIXE, gemcitabine-capecitabine and same-day pegfilgrastim (6 mg) within 1 hr of completion of systemic agents. As per institutional guidelines, patients were counseled on risks of same-day pegfilgrastim prior to its administration. Patients were followed to determine the degree of neutropenia and toxicity. RESULTS: A total of 914 chemotherapy cycles in 157 patients were analyzed. Median ANC nadir for all cycles was 5634/uL (range: 450 - 23800). Grade 1 and 2 neutropenia developed in 11 of 914 cycles. Bone pain reported in 9 pts. There was 1 episode of grade >3 neutropenia resulting in infection and antibiotic use. No other patient required dose reductions, chemotherapy delays, or hospitalizations. No increased toxicity of capecitabine was noticed. CONCLUSIONS: We believe our study is the first in GI malignancies to report that same-day pegfilgrastim administration with capecitabine-based regimens may be as effective and safe as next-day administration. Additionally, given the absence of CD in human bone marrow, it appears capecitabine can be used concurrently with pegfilgrastim. Prospective studies should be done to further investigate, as this practice can benefit patients clinically, decrease office visits, increase patient's satisfaction and reduce healthcare costs.

Ileo-colonic lymphoma: presentation, diagnosis, and management.

PURPOSE OF REVIEW: The gut-associated lymphoid tissue (GALT), the bulk of which is located in the ileo-colonic region comprises the lymphoid cells of the gastrointestinal tract and confers specific immunological responses. Repetitive antigenic stimulation of these cells predispose to a monoclonal proliferation of this tissue and the eventual development of lymphoma. The gastrointestinal tract is the most commonly involved site of extranodal lymphomas. This review will focus primarily on lymphomas of the ileo-colonic region (defined as the terminal ileum, the colon, and the rectum). We will discuss the epidemiology, pathogenesis, and presentation as well as current practices in diagnosis and management. RECENT FINDINGS: Despite the majority of the GALT to be located in the ileo-colonic region of the gut, the lymphomas in this location are relatively rare. However, the overall annual incidence of ileo-colonic lymphomas is steadily increasing. This entity has a varied spectrum of clinical presentations. Ileo-colonoscopy with adequate targeted biopsies can serve as a gold standard for definitive diagnosis. Ileo-colonic lymphomas may be managed with chemotherapy alone while surgery is reserved for highly aggressive tumors or clinical emergencies. Radiation is not a preferred adjuvant treatment for lymphomas in this location of the gut. Adequate endoscopic surveillance measures and tools to potentially prevent recurrence and improve the overall prognosis of this disease are lacking. SUMMARY: Ileo-colonic lymphomas are rare and can present with varied symptoms and signs. Endoscopy with adequate sampling can aid in making a definitive diagnosis. Chemotherapy can be highly effective in management while surgery is indicated for emergency presentations. Adequate endoscopic surveillance tools are lacking, yet imperative to prevent recurrence and improve prognosis.

Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer.

BACKGROUND: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. METHODS: Patients aged >65 years with chemo-naïve APC with Eastern Cooperative Oncology Group performance status ⩽2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan-Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles. RESULTS: A total of 73 patients (median age: 73 years; range: 66-93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade ⩾3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively. CONCLUSION: In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy.

Efficacy of quality improvement and patient safety workshops for students: a pilot study.

BACKGROUND: While the Association of American Medical Colleges encourages medical schools to incorporate quality improvement and patient safety (QI/PS) into their curriculum, medical students continue to have limited QI/PS exposure. To prepare medical students for careers that involve QI/PS, the Institute for Healthcare Improvement chapter at an allopathic medical school and school of allied health professions initiated self-directed learning by offering student-led workshops to equip learners with skills to improve the quality and safety of healthcare processes. METHODS: In this prospective cohort study, workshops were hosted for medical students between 2015 and 2018 on five QI/PS topics: Process Mapping, Root-Cause Analysis (RCA), Plan-Do-Study-Act (PDSA) Cycles, Evidence Based Medicine (EBM), and Patient Handoffs. Each workshop included a hands-on component to engage learners in practical applications of QI/PS skills in their careers. Change in knowledge, attitudes, and behaviors was assessed via pre- and post-surveys using 5-point Likert scales, and analyzed using either the McNemar test or non-parametric Wilcoxon signed-rank test. Surveys also gathered qualitative feedback regarding strengths, future areas for improvement, and reasons for attending the workshops. RESULTS: Data was collected from 88.5% of learners (n = 185/209); 19.5% of learners reported prior formal instruction in these topics. Statistically significant improvements in learners' confidence were observed for each workshop. Additionally, after attending workshops, learners felt comfortable teaching the learned QI/PS skill to colleagues (mean pre/post difference 1.96, p < 0.0001, n = 139) and were more likely to pursue QI/PS projects in their careers (mean pre/post difference 0.45, p < 0.0001, n = 139). Lastly, learners demonstrated a statistically significant increase in knowledge in four out of five skills workshop topics. CONCLUSION: Few medical students have formal instruction in QI/PS tools. This pilot study highlights advantages of incorporating an innovative, student-directed modified 'flipped classroom' methodology, with a focus on active experiential learning and minimal didactic instruction.

Expression, Purification, and Liposome Binding of Budding Yeast SNX-BAR Heterodimers.

SNX-BAR proteins are an evolutionarily conserved class of membrane remodeling proteins that play key roles in sorting and trafficking of protein and lipids during endocytosis, sorting within the endosomal system, and autophagy. Central to SNX-BAR protein function is the ability to form homodimers or heterodimers that bind membranes using highly conserved phox-homology (PX) and BAR (Bin/Amphiphysin/Rvs) domains. In addition, oligomerization of SNX-BAR dimers on membranes can elicit the formation of membrane tubules and vesicles and this activity is thought to reflect their functions as coat proteins for endosome-derived transport carriers. Researchers have long utilized in vitro binding studies using recombinant SNX-BAR proteins on synthetic liposomes or giant unilamellar vesicles (GUVs) to reveal the precise makeup of lipids needed to drive membrane remodeling, thus revealing their mechanism of action. However, due to technical challenges with dual expression systems, toxicity of SNX-BAR protein expression in bacteria, and poor solubility of individual SNX-BAR proteins, most studies to date have examined SNX-BAR homodimers, including non-physiological dimers that form during expression in bacteria. Recently, we have optimized a protocol to overcome the major shortcomings of a typical bacterial expression system. Using this workflow, we demonstrate how to successfully express and purify large amounts of SNX-BAR heterodimers and how to reconstitute them on synthetic liposomes for binding and tubulation assays.

Bacterial contamination of medical providers' white coats and surgical scrubs: A systematic review.

BACKGROUND: Horizontal transmission of bacteria, especially multidrug-resistant organisms (MDROs), remains an important concern in hospitals worldwide. Some studies have implicated provider attire in the transmission of organisms within hospitals, whereas others have suggested that evidence supporting this notion is limited. METHODS: PubMed was searched for publications between 1990 and 2018 to identify studies of bacterial contamination of, or dissemination of, bacteria from physician, nursing, or trainee attire, with a specific focus on white coats and surgical scrubs. A total of 214 articles were identified. Of these, 169 were excluded after abstract review and 33 were excluded after in-depth full manuscript review. RESULTS: Twenty-two articles were included: 16 (73%) cross-sectional studies, 4 (18%) randomized controlled trials, and 2 (9%) cohort studies. Results are organized by microbial contaminants, antibiotic resistance, types of providers, fabric type, antimicrobial coating, and laundering practices. Provider attire was commonly colonized by MDROs, with white coats laundered less frequently than scrubs. Studies revealed considerable differences among fabrics used and laundering practices. CONCLUSIONS: Findings suggest that provider attire is a potential source of pathogenic bacterial transmission in health care settings. However, data confirming a direct link between provider attire and health care-associated infections remain limited. Suggestions outlined in this article may serve as a guideline to reduce the spread of bacterial pathogens, including MDROs, that have the potential to precipitate hospital-acquired infections.

Influence of Cationic meso-Substituted Porphyrins on the Antimicrobial Photodynamic Efficacy and Cell Membrane Interaction in Escherichia coli.

Photodynamic inactivation (PDI) is a non-antibiotic option for the treatment of infectious diseases. Although Gram-positive bacteria have been shown to be highly susceptible to PDI, the inactivation of Gram-negative bacteria has been more challenging due to the impermeability properties of the outer membrane. In the present study, a series of photosensitizers which contain one to four positive charges (1⁻4) were used to evaluate the charge influence on the PDI of a Gram-negative bacteria, Escherichia coli (E. coli), and their interaction with the cell membrane. The dose-response PDI results confirm the relevance of the number of positive charges on the porphyrin molecule in the PDI of E. coli. The difference between the Hill coefficients of cationic porphyrins with 1⁻3 positive charges and the tetra-cationic porphyrin (4) revealed potential variations in their mechanism of inactivation. Fluorescent live-cell microscopy studies showed that cationic porphyrins with 1⁻3 positive charges bind to the cell membrane of E. coli, but are not internalized. On the contrary, the tetra-cationic porphyrin (4) permeates through the membrane of the cells. The contrast in the interaction of cationic porphyrins with E. coli confirmed that they followed different mechanisms of inactivation. This work helps to have a better understanding of the structure-activity relationship in the efficiency of the PDI process of cationic porphyrins against Gram-negative bacteria.