A comprehensive guide on screening and selection of a suitable AMP against biofilm-forming bacteria.

Lately, antimicrobial resistance (AMR) is increasing at an exponential rate making it important to search alternatives to antibiotics in order to combat multi-drug resistant (MDR) bacterial infections. Out of the several antibacterial and antibiofilm strategies being tested, antimicrobial peptides (AMPs) have shown to give better hopes in terms of a long-lasting solution to the problem. To select a desired AMP, it is important to make right use of available tools and databases that aid in identification, classification, and analysis of the physiochemical properties of AMPs. To identify the targets of these AMPs, it becomes crucial to understand their mode-of-action. AMPs can also be used in combination with other antibacterial and antibiofilm agents so as to achieve enhanced efficacy against bacteria and their biofilms. Due to concerns regarding toxicity, stability, and bioavailability, strategizing drug formulation at an early-stage becomes crucial. Although there are few concerns regarding development of bacterial resistance to AMPs, the evolution of resistance to AMPs occurs extremely slowly. This comprehensive review gives a deep insight into the selection of the right AMP, deciding the right target and combination strategy along with the type of formulation needed, and the possible resistance that bacteria can develop to these AMPs.

The Molecular Basis of Wnt/ß-Catenin Signaling Pathways in Neurodegenerative Diseases.

Defective Wnt signaling is found to be associated with various neurodegenerative diseases. In the canonical pathway, the Frizzled receptor (Fzd) and the lipoprotein receptor-related proteins 5/6 (LRP5/LRP6) create a seven-pass transmembrane receptor complex to which the Wnt ligands bind. This interaction causes the tumor suppressor adenomatous polyposis coli gene product (APC), casein kinase 1 (CK1), and GSK-3ß (glycogen synthase kinase-3 beta) to be recruited by the scaffold protein Dishevelled (Dvl), which in turn deactivates the ß-catenin destruction complex. This inactivation stops the destruction complex from phosphorylating ß-catenin. As a result, ß-catenin first builds up in the cytoplasm and then migrates into the nucleus, where it binds to the Lef/Tcf transcription factor to activate the transcription of more than 50 Wnt target genes, including those involved in cell growth, survival, differentiation, neurogenesis, and inflammation. The treatments that are currently available for neurodegenerative illnesses are most commonly not curative in nature but are only symptomatic. According to all available research, restoring Wnt/ß-catenin signaling in the brains of patients with neurodegenerative disorders, particularly Alzheimer's and Parkinson's disease, would improve the condition of several patients with neurological disorders. The importance of Wnt activators and modulators in patients with such illnesses is to mainly restore rather than overstimulate the Wnt/ß-catenin signaling, thereby reestablishing the equilibrium between Wnt-OFF and Wnt-ON states. In this review, we have tried to summarize the significance of the Wnt canonical pathway in the pathophysiology of certain neurodegenerative diseases, such as Alzheimer's disease, cerebral ischemia, Parkinson's disease, Huntington's disease, multiple sclerosis, and other similar diseases, and as to how can it be restored in these patients.

Identification of naturally occurring compounds as alternatives to radiation therapy for treatment of small cell lung cancer.

Radiation resistance is one of the major problems in the treatment of small cell lung cancer (SCLC). Most of these patients are given radiation as first-line treatment and it was observed that the initial response in these patients is very good. However, they show relapse in a few months which is also associated with resistance to treatment. Thus, targeting the mechanism by which these cells develop resistance could be an important strategy to improve the survival chances of these patients. From the RNA-Seq data analysis, it was identified that CHEK1 gene was overexpressed. Chk1 protein which is encoded by the CHEK1 gene is an important protein that is involved in radiation resistance in SCLC. It is known to favour the cells to deal with replicative stress. CHEK1 is the major cause for developing radiation resistance in SCLC. Thus, natural compounds that could also serve as potential inhibitors for Chk1 were explored. Accordingly; the compounds were screened based on ADME, docking and MM-GBSA scores. MD simulations were performed for the selected protein-ligand complexes and the results were compared to the co-crystallised ligand, 3-(indol-2-yl)indazole. The results showed that compound INC000033832986 could be a natural alternative to the commercial ligand for the prevention of SCLC.Communicated by Ramaswamy H. Sarma.

More is not better: A scoping review of simulation in transition to residency programs.

BACKGROUND: Transition to residency programs frequently use simulation to promote clinical skills but place limited emphasis on non-clinical skills. We conducted a scoping review to determine how simulation is being used in transition to residency programs and the key non-clinical skills addressed by simulation activities and tools in these programs. METHODS: We searched PubMed, Scopus, and Embase to identify articles addressing transition to residency, simulation, and non-clinical skills/attributes. Two authors independently screened all abstracts and full-text articles and identified non-clinical attributes elicited in each study. Using descriptive statistics, we characterized the simulation activities and tools and the number and type of non-clinical attributes captured in the programs. Using analysis of variance, we compared the number of non-clinical attributes elicited based on the number of simulation activities used and compared the number of non-clinical attributes elicited based on the number of simulation tools used. RESULTS: We identified 38 articles that met the study criteria. We characterized simulation activities as mock paging (37%), case-based scenarios (74%), and/or procedural skills training (39%). We found that the most common simulation tools were standardized patients (64.8%), and the most elicited non-clinical attributes were communication skills, critical thinking, and teamwork. Using more simulation activity categories or simulation tools did not increase the number of non-clinical skills elicited. CONCLUSION: Simulation is used broadly in transition to residency programs but provides training in a few of the non-clinical skills required for a successful transition. Incorporating more simulation activities or tools does not increase the number of non-clinical attributes elicited, illustrating the importance of developing more targeted simulation activities to promote non-clinical skills more effectively.

Thriving as a Surgical Intern: Three Tips From the Collaboration of Surgical Education Fellows (CoSEF).

We are the multi-institutional organization known as the Collaboration of Surgical Education Fellows (CoSEF). We've collectively reflected on our range of experiences across the country and identified 3 principles which promote a successful intern experience: (1) Own your patients; (2) Treat people like people; and (3) Take care of yourself.

The domino effect: the impact of gender on operative self-efficacy.

BACKGROUND: Studies suggest that there are key differences in operative experience based on a trainee's gender. A large-scale self-efficacy (SE) survey, distributed to general surgery residents after the American Board of Surgery In-Training Examination in 2020, found that female gender was associated with decreased SE in graduating PGY5 residents for all 4 laparoscopic procedures included on the survey (cholecystectomy, appendectomy, right hemicolectomy, and diagnostic laparoscopy). We sought to determine whether these differences were reflected at the case level when considering operative performance and supervision using an operative assessment tool (SIMPL OR). METHODS: Supervision and performance data reported through the SIMPL OR platform for the same 4 laparoscopic procedures included in the SE survey were aggregated for residents who were PGY5s in 2020. Independent t-tests and multiple linear regression were used to determine the relationship between trainee gender and supervision/performance ratings. RESULTS: For laparoscopic cases in aggregate (n = 2708), male residents rated their performance higher than females (3.57 vs. 3.26, p < 0.001, 1 = critical deficiency, 5 = exceptional performance) and reported less supervision (3.15 vs. 2.85, p < 0.001, 1 = show and tell, 4 = supervision only); similar findings were seen when looking at attending reports of resident supervision and performance. A multiple linear regression model showed that attending gender did not significantly predict resident-reported supervision or performance levels, while case complexity and trainee gender significantly affected both supervision and performance (p < 0.001). DISCUSSION: Female residents perceive themselves to be less self-efficacious at core laparoscopic procedures compared to their male colleagues. Comparison to more case-specific data confirm that female residents receive more supervision and lower performance ratings. This may create a domino effect in which female residents receive less operative independence, preventing the opportunity to establish SE. Further research should identify opportunities to break this cycle and consider gender identity beyond the male/female construct.

We Need to Do Better: A Scoping Review of Wellness Programs In Surgery Residency.

OBJECTIVE: Burnout, depression, and fatigue are common among surgical residents. Most published wellness studies in surgery only focus on a cross-sectional view of attitudes and perceptions around wellness in training. While much of this literature calls for interventions and presents strategies for improving resident well-being, there is a paucity of published wellness initiatives, and even fewer with programmatic evaluation. DESIGN: A scoping review was designed to address: (1) What wellness initiatives are used in surgery residency programs? (2) Which wellness domains do these programs address? and (3) How are program outcomes evaluated? A formal literature search was conducted using PubMed, Embase, and Scopus databases to identify English-language studies conducted in the United States that described wellness-focused initiatives for surgery residents. Two authors independently screened all abstracts and full texts for inclusion. Data were extracted including wellness domain(s) and outcomes evaluation methods with associated Kirkpatrick level(s) (1-reaction, 2-learning, 3-behavior, 4-results). Study quality was examined using the medical education research study quality index (MERSQI) score. RESULTS: A total of 2237 abstracts were screened with 115 full texts reviewed for eligibility. Fifty-one studies were included in the final analysis, representing 39 distinct wellness programs. The most common domains of wellness addressed were emotional (19/39, 48.7%), occupational (17/39, 43.6%), and physical (16/39, 41.0%). Of the 51 studies reviewed, 8 (15.7%) did not conduct any program evaluation, 27 (52.9%) evaluated level 1, 30 (58.8%) evaluated level 2, 3 (5.9%) evaluated level 3, and none evaluated level 4 outcomes. The mean MERSQI score was 9.16 (SD 1.8). CONCLUSIONS: Wellness is an established problem in surgical training. This review reveals a small number of published wellness interventions and even fewer that incorporate programmatic evaluation at the level of behavior and results change. Effective change will require rigorous and deliberate programming that addresses multiple domains and evaluation levels.

An assessment of the strategy and status of COVID-19 vaccination in India.

The COVID-19 disease continues to cause devastation for almost 3 years of its identification. India is one of the leading countries to set clinical trials, production, and administration of COVID-19 vaccination. Recent COVID-19 vaccine tracker record suggests that 12 vaccines are approved in India, including protein subunit, RNA/DNA, non-replicating viral vector, and inactivated vaccine. Along with that 16 more vaccines are undergoing clinical trials to counter COVID-19. The availability of different vaccines gives alternate and broad perspectives to fight against viral immune resistance and, thus, viruses escaping the immune system by mutations. Using the recently published literature on the Indian vaccine and clinical trial sites, we have reviewed the development, clinical evaluation, and registration of vaccines trial used in India against COVID-19. Moreover, we have also summarized the status of all approved vaccines in India, their associated registered clinical trials, manufacturing, efficacy, and their related safety and immunogenicity profile.

The Program Director Perspective: Perceptions of PGY5 Residents' Operative Self-Efficacy and Entrustment.

INTRODUCTION: A 2020 survey of post-graduate year 5 (PGY5) general surgery residents linked to the American Board of Surgery In-Training Examination (ABSITE) revealed significant deficits in self-efficacy (SE), or personal judgment of one's ability to complete a task, for 10 commonly performed operations. Identifying whether this deficit is similarly perceived by program directors (PDs) has not been well established. We hypothesized that PDs would perceive higher levels of operative SE compared to PGY5s. METHODS: A survey was distributed through the Association of Program Directors in Surgery listserv; PDs were queried about their PGY5 residents' ability to perform the same 10 operations independently and their accuracy of patient assessments and operative plans for components of several core entrustable professional activities (EPAs). Results of this survey were compared to PGY5 residents' perception of their SE and entrustment based on the 2020 post-ABSITE survey. Chi-squared tests were used for statistical analysis. RESULTS: 108 responses were received, representing ∼32% (108/342) of general surgery programs. Perceptions from PDs of PGY5 residents' operative SE were highly concordant with resident perceptions; no significant differences were observed for 9 of 10 procedures. Both PGY5 residents and PDs perceived adequate levels of entrustment; no significant differences were observed for 6 of 8 EPA components. CONCLUSIONS: These findings show concordance between PDs and PGY5 residents in their perceptions of operative SE and entrustment. Though both groups perceive adequate levels of entrustment, PDs corroborate the previously described operative SE deficit, illustrating the importance of improved preparation for independent practice.

Complication to consider: delayed traumatic hemothorax in older adults.

BACKGROUND: Emerging evidence suggests older adults may experience subtle hemothoraces that progress over several days. Delayed progression and delayed development of traumatic hemothorax (dHTX) have not been well characterized. We hypothesized dHTX would be infrequent but associated with factors that may aid prediction. METHODS: We retrospectively reviewed adults aged ≥50 years diagnosed with dHTX after rib fractures at two level 1 trauma centers (March 2018 to September 2019). dHTX was defined as HTX discovered ≥48 hours after admission chest CT showed either no or 'minimal/trace' HTX. Two blinded, board-certified radiologists reviewed inpatient chest imaging and classified injury patterns according to Chest Wall Injury Society (CWIS) taxonomy. Descriptive analysis was performed for demographic and hospitalization characteristics. RESULTS: We identified 14 patients with pooled dHTX rate of 1.3%. After initial chest CT negative for concerning hemothoraces, the patients did not undergo follow-up imaging until new symptoms (shortness of breath, chest pain) developed: eight (57%) were not diagnosed until after discharge from initial hospitalization (mean (range): 9 (2-20) days after discharge). Aspirin and/or anticoagulants were involved in fewer than half of cases (43%). According to CWIS taxonomy, all patients had a series of posterolateral fractures with at least one offset or displaced fracture, and an average of six consecutive rib fractures. All patients underwent tube thoracostomy and six patients (42%)-all aged <65-underwent operative interventions. DISCUSSION: Preliminary data suggest older adults with rib fractures may be at risk of experiencing delayed progression of trace hemothoraces or a delayed presentation of hemothoraces. Asymptomatic progression or readmission to other services/hospitals likely occurs and true dHTX rates are likely higher. Our preliminary findings suggest a possible anatomic explanation for severe chest wall injury patterns' association with dHTX. Further characterization and capturing the true incidence of dHTX first requires wider recognition of this complication.

Safety of Foregoing Operation for Small Bowel Obstruction in the Virgin Abdomen: Systematic Review and Meta-Analysis.

Our objective was to assess the safety of foregoing surgery in patients without abdominopelvic surgery history presenting with small bowel obstruction (SBO). Classic dogma has counseled early surgical intervention for SBO in the virgin abdomen-patients without abdominopelvic surgery history-given their presumed higher risk of malignant or potentially catastrophic etiologies compared with those who had undergone previous abdominal operations. The term virgin abdomen was coined before widespread use of CT, which now elucidates many SBO etiologies. Despite recent efforts to re-evaluate clinical management standards, the prevalence of SBO etiologies in the virgin abdomen and the current management landscape (nonoperative vs operative) in these patients remain unclear. Our random-effects meta-analysis of 6 studies including 442 patients found the prevalence of malignant etiologies in patients without abdominopelvic surgery history presenting with SBO varied from 7.7% (95% CI 3.0 to 14.1) to 13.4% (95% CI 7.6 to 20.3) on sensitivity analysis. Most malignant etiologies were not suspected before surgery. De novo adhesions (54%) were the most common etiology. More than half of patients underwent a trial of nonoperative management, which often failed. Subgroups of patients likely have variable risk profiles for underlying malignant etiologies, yet no study had consistent follow-up data and we did not find convincing evidence that foregoing operative management altogether in this population can be generally recommended.

Holding Hands.

[Full article available at http://rimed.org/rimedicaljournal-2017-10.asp].

Sjögren Syndrome and Cryoglobulinemic Glomerulonephritis.

We report the case of a 53-year-old woman with Sjögren syndrome and cryoglobulinemia. The patient presented with nephrotic syndrome, hematuria, and reduced estimated glomerular filtration rate. The kidney biopsy revealed diffuse endocapillary proliferation and leukocyte exudation with focal intraluminal hyaline thrombi, prominent tubulointerstitial inflammation, and vasculitis. Diffuse granular mesangial and segmental to global capillary wall staining was observed on immunofluorescence with antisera to C3 and immunoglobulin M (IgM), with less intense staining indicative of IgG and κ and λ light chains. A biopsy diagnosis of Sjögren syndrome-related cryoglobulinemic membranoproliferative glomerulonephritis and vasculitis was rendered. Subsequent investigations revealed the presence of circulating type II cryoglobulins with cryocrit of 9%. Although rare, Sjögren syndrome is the most common cause of non-hepatitis C virus-related mixed cryoglobulinemia. We discuss the possible pathogenic mechanisms involved in the development of mixed cryoglobulinemia and its evolution to lymphoma, as best described in the setting of hepatitis C virus infection. Although the specific antigen involved is unknown, it is likely that the mixed cryoglobulinemia in Sjögren syndrome is triggered by the long-term B-cell stimulation, resulting in clonal proliferation of B cells. Additional chromosomal aberrations and cytokine milieu alterations, as seen in hepatitis C virus infection, may result in prolonged B-cell survival and progression to non-Hodgkin lymphoma.