Pyocins and Beyond: Exploring the World of Bacteriocins in Pseudomonas aeruginosa.

Pseudomonas aeruginosa significantly induces health-associated infections in a variety of species other than humans. Over the years, the opportunistic pathogen has developed resistance against commonly used antibiotics. Since most P. aeruginosa strains are multi-drug resistant, regular antibiotic treatment of its infections is becoming a dire concern, shifting the global focus towards the development of alternate antimicrobial approaches. Pyocins are one of the most diverse antimicrobial peptide combinations produced by bacteria. They have potent antimicrobial properties, mainly against bacteria from the same phylogenetic group. P. aeruginosa, whether from clinical or environmental origins, produce several different pyocins that show inhibitory activity against other multi-drug-resistant strains of P. aeruginosa. They are, therefore, good candidates for alternate therapeutic antimicrobials because they have a unique mode of action that kills antibiotic-resistant bacteria by attacking their biofilms. Here, we review pseudomonas-derived antimicrobial pyocins with great therapeutic potential against multi-drug-resistant P. aeruginosa.

Trends in mortality related to kidney failure and diabetes mellitus in the United States: a 1999-2020 analysis.

BACKGROUND: Kidney failure ranks as the tenth leading cause of mortality in the United States (US), frequently arising as a complication associated with diabetes mellitus (DM). METHODS: Trends in DM and kidney failure mortality were assessed using a cross-sectional analysis of death certificates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. Crude and age-adjusted mortality rates (AAMR) per 100,000 people and annual percent change (APC) in age-adjusted mortality rate with 95% CI were obtained and measured across different demographic and geographic subgroups. RESULTS: Between 1999 and 2020, a total of 325,515 deaths occurred related to kidney failure and DM. The overall age-adjusted mortality rate showed no significant change between 1999 and 2012, after which it declined until 2015 - 64.8 (95% CI - 75.6 to - 44.8) and has been steadily increasing since. Men had consistently higher age-adjusted mortality rates than women throughout the study duration (overall age-adjusted mortality rate men: 8.1 vs. women: 5.9). Non-Hispanic (NH) Black or African American individuals had the highest overall age-adjusted mortality rate (13.9), followed by non-Hispanic American Indian or Alaskan Native (13.7), Hispanic or Latino (10.3), non-Hispanic Asian or Pacific Islander (6.1), and non-Hispanic White (6.0). Age-adjusted mortality rate also varied by region (overall age-adjusted mortality rate: West:7.5; Midwest: 7.1; South: 6.8; Northeast: 5.8), and non metropolitan areas had higher overall age-adjusted mortality rate (7.5) than small/medium (7.2) and large metropolitan areas (6.4). CONCLUSION: After an initial decline, mortality rose across all the demographic groups from 2015 to 2020, revealing notable disparities in gender, race, and region.

A bibliometric analysis of the 100 most-influential papers in the field of anti-diabetic drugs.

Aim: We analyzed the 100 most-cited articles on all anti-diabetic drugs. A comprehensive literature review found no bibliometrics on this. Methods: Two researchers independently extracted articles from Scopus and ranked them by citation count as the 'top 100 most-cited'. Results: The median number of citations is 1385.5. Most articles are from the USA (n = 59). Insulin has the most papers (n = 24). Majority (n = 76) were privately funded and contained at least one conflict of interest (n = 66). The New England Journal of Medicine has the most publications (n = 44). Male authors made majority of both first and last authorship positions. Conclusion: This study aims to aid in directing future research and in reducing biases.

Design and computational evaluation of a novel multi-epitope hybrid vaccine against monkeypox virus: Potential targets and immunogenicity assessment for pandemic preparedness.

Monkeypox is a type of DNA-enveloped virus that belongs to the orthopoxvirus family, closely related to the smallpox virus. It can cause an infectious disease in humans known as monkeypox disease. Although there are multiple drugs and vaccines designed to combat orthopoxvirus infections, with a primary focus on smallpox, the recent spread of the monkeypox virus to over 50 countries have ignited a mounting global concern. This unchecked viral proliferation has raised apprehensions about the potential for a pandemic corresponding to the catastrophic impact of COVID-19. This investigation explored the structural proteins of monkeypox virus as potential candidates for designing a novel hybrid multi-epitope vaccine. The epitopes obtained from the selected proteins were screened to ensure their non-allergenicity, non-toxicity, and antigenicity to trigger T and B-cell responses. The interaction of the vaccine with toll-like receptor-3 (TLR-3) and major histocompatibility complexes (MHCs) was assessed using Cluspro 2.0. To establish the reliability of the docked complexes, a comprehensive evaluation was conducted using Immune and MD Simulations and Normal Mode Analysis. However, to validate the computational results of this study, additional in-vitro and in-vivo research is essential.

Efficacy and safety of mavacamten in treatment of hypertrophic cardiomyopathy: a systematic review and meta-analysis.

Aim: This meta-analysis was performed to assess the efficacy and safety of mavacamten in patients with hypertrophic cardiomyopathy. Methods & materials: A search was conducted using PubMed, Cochrane, and Scopus up to August 2022 for randomized studies reporting our pre-specified outcomes. Results: It was observed that mavacamten significantly improved New York Heart Association class (p < 0.009), Clinical Summary Score of the Kansas City Cardiomyopathy Questionnaire (p = 0.02), post-exercise left ventricular outflow tract gradient (p < 0.00001), functional end point (p = 0.05), and lowered septal reduction therapy rates (p < 0.00001). However, there were no significant differences in the ≥1 severe adverse events, ≥1 treatment-emergent adverse events, left ventricular volume index, left ventricular filling pressure, left ventricular end-diastolic volume index, and peak oxygen uptake (pVO2). Conclusion: Future large-scale trials are required to confirm our results and determine the long-term benefits and risks of mavacamten use in these patients.

Mavacamten is a recently introduced medication that relaxes the heart muscle and is indicated for patients with hypertrophic cardiomyopathy (a disease in which parts of the heart become thick and stiff). To determine the effectiveness and safety of this drug, the results of clinical trials were combined in order to produce an overall estimate. Overall, it was observed that mavacamten improved most functional parameters related to the heart and demonstrated no significant increases in the number of side effects. This suggests the effectiveness and safety of mavacamten, although further trials are needed to confirm our results.

A call to action; national survey of teaching radiology curriculum to medical students.

Objectives: Radiology and medical imaging are important yet often an underrepresented facet of medical education. Notably, there is concern among radiologists that students do not receive enough radiology exposure and that they struggle to interpret image findings on entering residency. Therefore, this survey aims to identify how medical students perceive the radiology curriculum and to determine gaps in delivery. Material and Methods: Students were recruited from United States (US) medical schools and given a 21-question survey assessing their perception of the radiology curriculum as well as asking about their confidence levels regarding medical imaging. The inclusion criteria were age >18 and enrolled in US medical school. The surveys were completed in April-July 2020 by students across the US. Objective parameters were measured as percentage correct, while subjective parameters used a 4-point Likert scale. Results: A total of 472 medical students across 31 medical schools completed the surveys with a response rate of 69%. Responses represented all class years within medical schools and showed equal distribution among the future career plans. Students responded that didactic lectures were the most common teaching method and that radiologists were their primary teachers during preclinical education. Students were unfamiliar with the American College of Radiology appropriateness criteria with 65% responding they had never heard of it and 33% reporting that they have heard of it but never used it. In assessing students' perceptions of radiology education, 72% of students responded that they received too little, and 28% of students responded, "Just right." <1% of students responded that there was "Too much" radiology in their curriculum. Conclusion: Radiologists are increasing their educational representation in medical school curricula. Despite this, radiology continues to be under-represented with students desiring more exposure to medical imaging. Integrating the student's perceptions with existing curricula suggests that efforts should focus on increasing awareness of which studies are appropriate and teaching students how to systematically interpret an image.

Acing the Fundamentals of Radiology: An Online Series for Medical Students and Interns.

PURPOSE: The current undergraduate radiology education predominantly integrates radiology with other disciplines during preclerkship years and is often taught by nonradiologists. Early exposure to radiology and profound understanding of scientific fundamentals of imaging modalities and techniques are essential for a better understanding and interest in the specialty. Furthermore, the COVID-19 pandemic-related impact on in-person medical education aggravated the need for alternative virtual teaching initiatives to provide essential knowledge to medical students. METHODS: The authors designed an online 7-session course on the principles of imaging modalities for medical students and fresh graduates in the United States and abroad. The course was delivered online and taught by radiologists from different US institutions. Pretests and posttests were delivered before and after each session, respectively, to assess change in knowledge. At the end of the course, a survey was distributed among students to collect their assessment and feedback. RESULTS: A total of 162 students and interns initially enrolled in the program by completing a sign-up interest form. An average of 65 participants attended each live session, with the highest attendance being 93 live attendees. An average of 44 attendees completed both the pretest and posttest for each session. There was a statistically significant increase in posttest scores compared with pretest scores ( P < 0.01) for each session; on average, the posttest scores were 48% higher than the pretest scores. A total of 84 participants answered the end-of-course survey. A total of 11% of the respondents described themselves as first year, 17% as second year, 18% as third year, 21% as fourth year, and 33% as "other." Attendees were enrolled in medical schools across 21 different countries with 35% of the respondents studying medicine in the United States. More than 76% of the respondents stated that they "strongly agree" that the program increased their understanding of radiology, increased their interest in radiology, and would be useful in their clinical practice in the future. Eighty-three percent of the respondents stated that they "strongly agree" that "this course was a worthwhile experience." Particularly, more than 84% of the respondents stated that among the most important components in enhancing their understanding of radiology were "the interpretation of normal imaging" and "interpretation of clinical cases." Ninety-two percent of the respondents stated that "the amount of effort to complete the requirements for this program was just right." Participants were also asked to rate each of the 8 sessions using the following scale: poor = 1 point, fair = 2, good = 3, and excellent = 4. The average rating for all 8 sessions was 3.61 points (SD = 0.55), which translates to 96% of the sessions being rated good or excellent. Eighty percent of the participants reported that the topics presented in the program were "excellent and clinically important to learn," and 20% of the participants reported that the topics presented were "good and somewhat important to learn." The participants were asked to evaluate their confidence regarding basic radiology skills before and after the program using the following scale: not confident at all = 1 point, somewhat confident = 2, moderately confident = 3, and very confident = 4. Figure 2 summarizes the responses of the participants. CONCLUSIONS: An online course to teach the fundamentals of imaging modalities could be delivered through a webinar format to medical students and interns in several countries to address the potential gaps in radiology education, therefore increasing their understanding of the different imaging modalities and their proper use in medicine.

Clozapine Intoxication in a Patient on Chronic Use With a Short-Term Noncompliance.

Clozapine has been associated with various adverse effects at both subtherapeutic and standard doses. These adverse effects are most commonly seen during the initiation of therapy in treatment-naïve patients. However, reports of intoxication in patients with long-term use of clozapine are yet to be documented. We highlight the case of a 42-year-old gentleman who had been on long-term clozapine use and presented with an altered mental status after being resumed on full standard doses without careful titration of clozapine after a short period of medication noncompliance. His workup in the hospital was largely unremarkable, and his presentation was attributed to the resumption of clozapine without medication titration. This is the first case to demonstrate the necessity of careful titration regardless of previous treatment history and highlights that patients should be started on clozapine at low levels to avoid the possibility of acute intoxication.

Multidisciplinary Approach in Teaching Diagnostic Radiology to Medical Students: The Development, Implementation, and Evaluation of a Virtual Educational Model.

PURPOSE: The aim of this study was to develop, implement, and evaluate the effectiveness of an online multidisciplinary approach for teaching diagnostic radiology to medical students. METHODS: An online 10-session case-based learning course was designed and taught by a multidisciplinary team of radiologists, surgeons, and internists. Session topics included common clinical case scenarios for different systems and were hosted on a videoconferencing platform. Students from six medical schools across Texas enrolled in the course. The effectiveness of each session was evaluated using a pretest-posttest design. Students completed a final survey after the course to evaluate their experience. RESULTS: An average of 108 attended the live sessions, with attendance peaking at 220. On average, 75 students completed both the pretest and posttest of each session. Posttest scores were an average of 46% higher than pretest scores. A total of 109 students completed the final survey; more than 90% of participants agreed that the program was relevant, that its multidisciplinary approach was valuable, and that it increased their knowledge of imaging as a diagnostic tool. Seventy-four percent said that the program increased their interest in radiology. Almost all participants said that the topics presented were thought to be "excellent and clinically important to learn" by most of the students (70%). Participants reported increased confidence in basic radiology skills after completion of the program. CONCLUSIONS: An online multidisciplinary approach can be feasibly implemented to address the radiology education needs of a large number of medical students across a group of medical schools.