One-step synthesis of amphiphilic copolymers PDMS-b-PEG using tris(pentafluorophenyl)borane and subsequent study of encapsulation and release of curcumin.

A series of amphiphilic block copolymer (BCP) micelles based on poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) (PEG) were synthesized by a one-step reaction in the presence of tris(pentafluorophenyl)borane (BCF) as a catalyst. The structural composition of PDMS-b-PEG (PR11) and PEG-b-PDMS-b-PEG (PR12) was corroborated by FTIR, 29Si NMR, and TGA. The BCPs were assembled in an aqueous solution, obtaining micelles between 57 and 87 nm in size. PR11 exhibited a higher (2.0 g L-1) critical micelle concentration (CMC) than PR12 (1.5 g L-1) due to the short chain length. The synthesized nano micelles were used to encapsulate curcumin, which is one of three compounds of turmeric plant 'Curcuma longa' with significant biological activities, including antioxidant, chemoprotective, antibacterial, anti-inflammatory, antiviral, and anti-depressant properties. The encapsulation efficiency of curcumin was 60% for PR11 and 45% for PR12. Regarding the release study, PR11 delivered 53% curcumin after five days under acidic conditions (pH of 1.2) compared to 43% at a pH of 7.4. The degradation products of curcumin were observed under basic conditions and were more stable at acidic pH. In both situations, the release process is carried out by breaking the silyl-ether bond, allowing the release of curcumin. PR11 showed prolonged release times, so it could be used to reduce ingestion times and simultaneously work as a nanocarrier for other hydrophobic drugs.

Decoding medical educators' perceptions on generative artificial intelligence in medical education.

Generative AI (GenAI) is a disruptive technology likely to generate a major impact on faculty and learners in medical education. This work aims to measure the perception of GenAI among medical educators and to gain insights into its major advantages and concerns in medical education. A survey invitation was distributed to medical education faculty of colleges of allopathic and osteopathic medicine within a single university during the fall of 2023. The survey comprised 12 items, among those assessing the role of GenAI for students and educators, the need to modify teaching approaches, GenAI's perceived advantages, applications of GenAI in the educational context, and the concerns, challenges, and trustworthiness associated with GenAI. Responses were obtained from 48 faculty. They showed a positive attitude toward GenAI and disagreed on GenAI having a very negative effect on either the students' or faculty's educational experience. Eighty-five percent of our medical schools' faculty responded to had heard about GenAI, while 42% had not used it at all. Generating text (33%), automating repetitive tasks (19%), and creating multimedia content (17%) were some of the common utilizations of GenAI by school faculty. The majority agreed that GenAI is likely to change its role as an educator. A perceived advantage of GenAI in conducting more effective background research was reported by 54% of faculty. The greatest perceived strengths of GenAI were the ability to conduct more efficient research, task automation, and increased content accessibility. The faculty's major concerns were cheating in home assignments in assessment (97%), tendency for blunder and false information (95%), lack of context (86%), and removal of human interaction in important feedback processes (83%). The majority of the faculty agrees on the lack of guidelines for safe use of GenAI from both a governmental and an institutional policy. The main perceived challenges were cheating, the tendency of GenAI to make errors, and privacy concerns.The faculty recognized the potential impact of GenAI in medical education. Careful deliberation of the pros and cons of GenAI is needed for its effective integration into medical education. There is general agreement that plagiarism and lack of regulations are two major areas of concern. Consensus-based guidelines at the institutional and/or national level need to start to be implemented to govern the appropriate use of GenAI while maintaining ethics and transparency. Faculty responses reflect an optimistic and favorable outlook on GenAI's impact on student learning.

Igniting children's enthusiasm for microbes with an origami paper microscope.

The COVID-19 pandemic has underscored the urgent need for microbiology literacy in society. Microbiology knowledge, and its dissemination, can help inform and increase the objectivity of important decisions, such as treatment or vaccination. A microbiology learning experience titled "What you can't see can hurt you" was delivered as part of a larger outreach event where children were exposed to various aspects of medicine and health care fields. The activity involved an introduction to and a discussion of bacteria of clinical importance and the use of a smartphone-attachable paper-based foldable microscope. To explore the impact of this activity on participants' interest in science and microbiology, a pre- and post-activity survey of five questions on an emoji-based Likert scale was completed by the participants. A statistically significant increase in their interest in microbes and where to find them, as well as in microscopy, was observed after the event. Making microbes visible to children and allowing them to capture images of microbes exposes them directly and personally to microscopy and microbiology. An affordable low-cost paper-based microscope can become an alternative approach to teaching and learning to deliver clinical microbiology information to a wide audience range.

Primary or Delayed Repair for Complete Atrioventricular Septal Defect, Tetralogy of Fallot, and Ventricular Septal Defect: Relationship to Country Economic Status.

OBJECTIVE: Primary repair in the first six months of life is routine for tetralogy of Fallot, complete atrioventricular septal defect, and ventricular septal defect in high-income countries. The objective of this analysis was to understand the utilization and outcomes of palliative and reparative procedures in high versus middle-income countries. METHODS: The World Database of Pediatric and Congenital Heart Surgery identified patients who underwent surgery for: tetralogy of Fallot, complete atrioventricular septal defect, and ventricular septal defect. Patients were categorized as undergoing primary repair, repair after prior palliation, or palliation only. Country economic status was categorized as lower middle, upper middle, and high, defined by the World Bank. Multiple logistic regression models were utilized to identify independent predictors of hospital mortality. RESULTS: Economic categories included high (n = 571, 5.3%), upper middle (n = 5,342, 50%), and lower middle (n = 4,793, 49.7%). The proportion of patients and median age with primary repair were: tetralogy of Fallot, 88.6%, 17.7 months; complete atrioventricular septal defect, 83.4%, 7.7 months; and ventricular septal defect, 97.1%, ten months. Age at repair was younger in high income countries (P < .0001). Overall mortality after repair was lowest in high income countries. Risk factors for hospital mortality included prematurity, genetic syndromes, and urgent or emergent operations (all P < .05). CONCLUSIONS: Primary repair was selected in >90% of patients, but definitive repair was delayed in lower and upper middle income countries compared with high-income countries. Repair after prior palliation versus primary repair was not a risk factor for hospital mortality. Initial palliation continues to have a small but important role in the management of these three specific congenital heart defects.

Antimicrobial effect of chamomile-containing over-the-counter ear and eye drops.

Chamomile (Matricaria chamomilla) is a plant with known antimicrobial, anti-inflammatory, and analgesic properties. Homeopathic drops containing chamomile extract are often used for ear pain and chronic ear infections. We aimed to evaluate the antimicrobial effect of over-the-counter eardrops containing chamomile against organisms causing bacterial conjunctivitis and otitis externa. Liquid cultures of Streptococcus aureus and Pseudomonas aeruginosa were exposed to increasing concentrations of eardrops containing chamomile extract. Liquid cultures of S. aureus and Streptococcus pneumoniae were exposed to increasing concentrations of chamomile eye drops for 5, 10, 15, and 45 min. Colony forming units (CFUs) were assessed after 18 h. Viability assays for these organisms were performed using the resazurin microdilution assay. We observed a reduction in the number of P. aeruginosa CFUs when the bacteria were exposed to any of the three concentrations of the chamomile drops as early as 5 min, with maximal reduction upon exposure to the 30% concentration at 45 min. Reduction in S. aureus CFUs, on the other hand, was observed for all three concentrations as maximal in the 5 min of exposure. We observed a marked reduction in the number of S. aureus CFUs upon exposure to any of the three preparations of chamomile-containing eye drops, which was almost immediate at 10% concentration. Streptococcus pneumoniae reduction happened at 5 min and continued through the 45-min observation period for all three concentrations. Our findings suggest that over-the-counter ear drops containing chamomile extract could potentially be used as a non-prescription treatment for mild cases of otitis externa and bacterial conjunctivitis.

Bacille-Calmette-Guerin modulates human macrophage and dendritic cell response to SARS-CoV-2 S-glycoprotein.

Background: Given that epidemiological evidence suggests a potential protective role for Bacille-Calmette-Guerin against COVID-19, we aimed to explore whether pre-exposure of human monocyte-derived macrophages and dendritic cells to BCG could modulate their response to SARS-CoV-2 S-glycoprotein. Methods: Dual THP-1 cells containing 2 reporter plasmids for transcription factors NF-κB, and IRF were differentiated into macrophages over 3 days using phorbol 12-myristate 13-acetate, or into dendritic cells over 6 days using commercial monocyte-dencritic cell differentiation media and matured with recombinant tumor necrosis factor-α. Cells were exposed to BCG for 24 h and then stimulated with SARS-CoV-2 S-glycoprotein for 24 hours. Results: Pre-exposure of human macrophages and DCs to BCG increased IRF and NF-kb activation in response to the SARS-CoV-2 S-glycoprotein. Conclusions: Our results showed that pre-exposure of both types of cells to BCG exhibited an increase in inflammatory transcription factors upon stimulation with S-glycoprotein. BCG-induced trained immunity may be an important tool for reducing susceptibility to SARS-CoV-2 infection and severity of COVID-19. Our findings help in the design of future BCG-based therapeutic approaches in the treatment of diseases caused by viral infections.

Hospital Mortality and Adverse Events Following Repair of Congenital Heart Defects in Developing Countries.

BACKGROUND: Mortality associated with the correction of congenital heart disease has decreased to approximately 2% in developed countries and major adverse events are uncommon. Outcomes in developing countries are less well defined. The World Database for Pediatric and Congenital Heart Surgery was utilized to compare mortality and adverse events in developed and developing countries. METHODS: A total of 16,040 primary procedures were identified over a two-year period. Centers that submitted procedures were dichotomized to low/middle income (LMI) and high income (HI) by the Gross National Income per capita categorization. Mortality was defined as any death following the primary procedure to discharge or 90 days inpatient. Multiple logistic regression models were utilized to identify independent predictors of mortality. RESULTS: Of the total number of procedures analyzed, 83% (n = 13,294) were from LMI centers. Among all centers, the mean age at operation was 2.2 years, with 36% (n = 5,743) less than six months; 85% (n = 11,307) of procedures were STAT I/II for LMI centers compared with 77% (n = 2127) for HI centers (P < .0001). Overall mortality across the cohort was 2.27%. There was a statistical difference in mortality between HI centers (0.55%) versus LMI centers (2.64%) (P < .0001). After adjustment for other risk factors, the risk of death remained significantly higher in LMI centers (odds ratio: 2.36, 95% confidence interval: 1.707-3.27). CONCLUSION: Although surgical expertise has increased across the globe, there remains a disparity with some outcomes associated with the correction of congenital heart disease between developing and developed countries. Further studies are needed to identify specific opportunities for improvement.

The future of CRISPR in Mycobacterium tuberculosis infection.

Clustered Regularly Interspaced Short Palindromic repeats (CRISPR)-Cas systems rapidly raised from a bacterial genetic curiosity to the most popular tool for genetic modifications which revolutionized the study of microbial physiology. Due to the highly conserved nature of the CRISPR locus in Mycobacterium tuberculosis, the etiological agent of one of the deadliest infectious diseases globally, initially, little attention was paid to its CRISPR locus, other than as a phylogenetic marker. Recent research shows that M. tuberculosis has a partially functional Type III CRISPR, which provides a defense mechanism against foreign genetic elements mediated by the ancillary RNAse Csm6. With the advent of CRISPR-Cas based gene edition technologies, our possibilities to explore the biology of M. tuberculosis and its interaction with the host immune system are boosted. CRISPR-based diagnostic methods can lower the detection threshold to femtomolar levels, which could contribute to the diagnosis of the still elusive paucibacillary and extrapulmonary tuberculosis cases. In addition, one-pot and point-of-care tests are under development, and future challenges are discussed. We present in this literature review the potential and actual impact of CRISPR-Cas research on human tuberculosis understanding and management. Altogether, the CRISPR-revolution will revitalize the fight against tuberculosis with more research and technological developments.

Multidrug-Resistant Enterococcal Infection in Surgical Patients, What Surgeons Need to Know.

Enterococci are organisms that can be found in the normal intestinal and skin microbiota and show remarkable ability to acquire antibiotic resistance. This is an enormous challenge for surgeons when faced with surgical site infections caused by multidrug-resistant (MDR) Enterococci. Due to an increase in the prevalence of MDR Enterococcus within the last few decades, there has been a major decrease in therapeutic options, because the majority of E. faecium isolates are now resistant to ampicillin and vancomycin and exhibit high-level resistance to aminoglycosides, traditionally three of the most useful anti-enterococcal antibiotics. There is limited data regarding the magnitude and pattern of multidrug resistance among the enterococcal genus causing surgical site infections in hospitalized patients. The scope of the review is to summarize the most recent findings in the emergence of postoperative MDR Enterococci and discuss recent mechanisms of resistance and the best treatment options available.

Development of an Online SARS-CoV-2/COVID-19 Elective Course for Fourth-Year Medical Students.

As a result of the COVID-19 pandemic, the Paul L. Foster School of Medicine incorporated supplementary online learning for 4th year medical students who were unable to participate in clinical activities due to clinical site restrictions to reduce SARS-CoV-2 transmission. An online elective was developed aimed to increase student knowledge of COVID-19: "COVID-19: Utilizing basic sciences to implement what you need to know as a physician." This course required students to further their understanding of SARS-CoV-2 and COVID-19 through directed self-study to identify and summarize the latest scientific literature followed by presenting an online seminar to peers and faculty.

Historical view of medical Spanish instruction in a medical school at the US-Mexico border region.

With a growing speaking Spanish population in the USA, it is necessary to help meet their healthcare needs. The Paul L. Foster School of Medicine is located in El Paso at the US-Mexico border. The medical Spanish curriculum is required for all medical students and begins on their first day of medical school, with conversational Spanish and medical Spanish through the preclerkship years. One of the key elements to the success of this course is the use of instructors with expertise in language instruction with an emphasis on task-based instruction. In addition to language instruction, this course also emphasizes instruction and experience in the culture of the US-Mexico border region. While taught medical Spanish, students are also prompted to understand when their skills are not adequate for the situation, in which case they need to enlist a skilled translator. Students report that, on a daily basis, they productively use what they learned in this preclerkship curriculum.

Breakthrough SARS-CoV-2 infections after COVID-19 immunization.

As no vaccines are 100% effective at preventing illness, COVID-19 vaccine breakthrough cases are expected. We here aim to review the most recent literature on COVID-19 vaccine breakthrough infections. SARS-CoV-2 breakthrough infections are, in general, rare. Age may still be a factor in SARS-CoV-2 infections in immunized individuals.

Antibodies Against SARS-CoV-2 in Human Breast Milk After Vaccination: A Systematic Review and Meta-Analysis.

Background: CDC guidelines have recommended coronavirus disease-19 (COVID-19) vaccination for all people 5 years and older, including people who are breastfeeding. Breast milk has shown to be a valuable source of protection for immune-immature neonates. It has been shown that breast milk from mothers who have received vaccinations can transfer antibodies. Aim/Objective: This systematic review and meta-analysis investigate the presence of antibodies to SARS-CoV-2 in human breast milk after vaccination. Methods: Studies that evaluated immunoglobulins in breast milk of women receiving a SARS-CoV-2 vaccination were included. PubMed, Embase, Web of Science were searched for articles published between December 1, 2019 and September 30, 2021. Data from relevant articles were extracted manually or by WebPlotDigitizer version 4.1 to obtain the numeric values of antibody levels on peak days and the peak day then condensed into Excel. Additional raw data and information were supplied by corresponding authors. Results: One hundred ninety-two articles were obtained from the search. After excluding duplicates, screening titles and abstracts, 18 cohort studies were identified. For the rate of SARS-CoV-2 antibodies in breast milk after the first vaccine dose but before the second vaccine dose, we found 64% (95% CI 51-78%) were positive for IgA and 30% (95% CI 13.1-46%) were positive for IgG. For the rate for SARS-CoV-2 antibodies in breast milk after the second vaccine dose, we found 70% (95% CI 55-86%) were positive for IgA and 91% (95% CI 80-103%) were positive for IgG. Conclusions: Our analysis of the data published worldwide showed high rates of positivity for antibodies in breast milk following COVID-19 immunizations. Further research is necessary to find if the rate of positivity of IgA and IgG against SARS-CoV-2 in breast milk persists months after the full immunization, and their impact on the prevention of SARS-CoV-2 infection in infants.

Examining the Efficacy of Antimicrobial Therapy in Preventing the Development of Postinfectious Glomerulonephritis: A Systematic Review and Meta-Analysis.

Postinfectious glomerulonephritis (PIGN) is an immune-mediated acute glomerulonephritis classically seen weeks after infection with Streptococcus pyogenes, although other infectious etiologies have emerged. While it has become increasingly rare in industrialized regions, it continues to affect children in developing countries. There has been debate as to why incidence rates are declining, including the possibility of improved initial treatment of bacterial infections. The ability of antimicrobial therapy in preventing PIGN as infectious sequelae, however, has not been comprehensively assessed. As varying evidence from published studies exists, the objective of this meta-analysis is to determine if antimicrobial therapy utilized to treat an initial infection has an effect in reducing the development of PIGN in humans. EMBASE, MEDLINE, and CENTRAL were searched using a comprehensive terminology strategy. From an initial search that returned 337 publications, 9 articles were included for analysis. Eight studies showed an incidence of PIGN after antimicrobial use ranging from 0.05% to 10% with a mean standardized difference (MSD) of 0.03 (0.01-0.06). Three studies showed an occurrence of PIGN without antibiotic use ranging from 1% to 13% with an MSD of 0.06 (-0.09-0.21). Our findings suggest that antimicrobial treatment for the initial infection may help diminish the development of PIGN. Although Streptococcus pyogenes infections are generally treated aggressively to prevent rheumatic fever, these findings may help further support the early treatment of bacterial infections to prevent postinfectious sequelae, especially as we consider other infectious etiologies of PIGN antimicrobial resistance.

Improving Integration of Basic Science into Clinical Medicine: Vertical Integration into Clinical Education (VICE) Activity.

The integration of basic science into clinical clerkships continues to be a challenge in medical curricula. We developed an integrated session for 3rd year medical students enrolled in OB-Gyn/Pediatric Block. The session focused on transplacental and perinatal infections, and consisted of a student-driven pedagogy activity in which students were required to explain the basic science principles behind the pathophysiology of the clinical presentations, the work-up, and the treatment of the infections. This approach helps students understand how basic science knowledge informs clinical practice and potential increase clerkship-level students' confidence as it makes them serve as leaders of active learning modules. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01485-7.

Methods of Blood Pressure Measurement to Predict Hypertension-Related Cardiovascular Morbidity and Mortality.

PURPOSE OF REVIEW: As the evidence on different blood pressure phenotypes and their cardiovascular risks evolve, it is imperative to evaluate the reliability of office blood pressure (OBP), ambulatory blood pressure (ABP), and home blood pressure (HBP) measurements and their associations with cardiovascular morbidity and mortality. RECENT FINDINGS: HBP is more reliable in diagnosis of hypertension than OBP or ABP. HBP correlates better with left ventricular mass index (LVMI). Increasing systolic HBP is associated with a higher risk of all-cause mortality, cardiovascular mortality, and cardiovascular events. An elevated systolic ABP is also associated with a higher risk of cardiovascular events and mortality. ABP is a better predictor of cardiovascular events than OBP in diabetics. ABP and HBP furnish additional information beyond OBP. They correlate better with cardiovascular outcomes and are more helpful with monitoring therapy than OBP. Comparative effectiveness studies of all three methods associating with cardiovascular outcomes are warranted.

Multiple Sclerosis-associated Bacterial Ligand 654.

BACKGROUND AND AIMS: Many endogenous and exogenous risk factors are associated with multiple sclerosis (MS), but recent studies suggest that microbiome-derived ligands, play a role in the disease process. The goal of this study was to characterize the cellular response elicited in human microglia upon treatment with IFN-ß and Fingolimod, two first line medications for the management of MS, and determine whether these treatments affect the response of microglial cells to an MS-associated bacterial ligand, Lipid 654. MATERIALS AND METHODS: HMC3 human microglial cells were treated with IFN-ß or Fingolimod. Cytokine secretion was evaluated using a multiplex system, and microglia polarization was assessed by flow cytometry. RESULTS: We observed that treatment with IFN-ß or Fingolimod induced differential secretion of various pro-inflammatory cytokines. Upon cell stimulation with Lipid 654, we observed that IFN-ß and Fingolimod decreased the secretion of M1-associated cytokines. Using flow cytometry, we observed that the decrease in inflammatory cytokine secretion was likely due to a containment of M1 phenotype of microglia after stimulation with Lipid 654. CONCLUSIONS: Our findings provide new clues of still unknown mechanisms of action of IFN-ß and Fingolimod in human microglia, which will prompt new avenues of research on the use of these therapies in the regulation of the inflammatory response in MS.

Human macrophage polarization in the response to Mycobacterium leprae genomic DNA.

Infection with Mycobacterium leprae, the causative organism of leprosy, is still endemic in numerous parts of the world including the southwestern United States. The broad variation of symptoms in the leprosy disease spectrum range from the milder tuberculoid leprosy (paucibacillary) to the more severe and disfiguring lepromatous leprosy (multibacillary). The established thinking in the health community is that host response, rather than M. leprae strain variation, is the reason for the range of disease severity. More recent discoveries suggest that macrophage polarization also plays a significant role in the spectrum of leprosy disease but to what degree it contributes is not fully established. In this study, we aimed to analyze if different strains of M. leprae elicit different transcription responses in human macrophages, and to examine the role of macrophage polarization in these responses. Genomic DNA from three different strains of M. leprae DNA (Strains NHDP, Br4923, and Thai-53) were used to stimulate human macrophages under three polarization conditions (M1, M1-activated, and M2). Transcriptome analysis revealed a large number of differentially expressed (DE) genes upon stimulation with DNA from M. leprae strain Thai-53 compared to strains NHDP and Br4923, independent of the macrophage polarization condition. We also found that macrophage polarization affects the responses to M. leprae DNA, with up-regulation of numerous interferon stimulated genes. These findings provide a deeper understanding of the role of macrophage polarization in the recognition of M. leprae DNA, with the potential to improve leprosy treatment strategies.