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More than 98% of reported human listeriosis cases are caused by specific serotypes within genetic lineages I and II. The genome sequence of Listeria monocytogenes lineage III strain HCC23 (serotype 4a) enables whole genomic comparisons across all three L. monocytogenes lineages. Protein cluster analysis indicated that strain HCC23 has the most unique protein pairs with nonpathogenic species Listeria innocua. Orthology analysis of the genome sequences of representative strains from the three L. monocytogenes genetic lineages and L. innocua (CLIP11262) identified 319 proteins unique to nonpathogenic strains HCC23 and CLIP11262 and 58 proteins unique to pathogenic strains F2365 and EGD-e. BLAST comparison of these proteins with all the sequenced L. monocytogenes and L. innocua revealed 126 proteins unique to serotype 4a and/or L. innocua; 14 proteins were only found in pathogenic serotypes. Some of the 58 proteins unique to pathogenic strains F2365 and EGD-e were previously published and are already known to contribute to listerial virulence.

Background and Objective: Considering the rapidly evolving treatment landscape of renal cell carcinoma (RCC), recent descriptions of the RCC population in the UK are lacking, as are real-world data on treatment and patient outcomes. To analyse the demographic and clinical characteristics, treatment patterns, and overall survival of patients with RCC using national data sets in England., Patients and Methods: This was a retrospective cohort study of patients diagnosed with RCC (all stages) between 2014-2018 using demographic, clinical, cancer registration, and treatment data. Patients were followed until death or study end (December 31, 2020). Treatments administered in each line were described to understand treatment sequencing. Kaplan-Meier methods were used for time-to-event analyses. Factors associated with discontinuation and survival were identified using Cox proportional hazard models., Results and Limitations: Among 32,577 included patients, the median age at diagnosis was 66 years, 63.4% were male, and 6,786 (20.8%) had metastatic RCC at diagnosis. Tyrosine kinase inhibitor (TKI) monotherapy was the most common treatment class across lines. Over three quarters of patients (78.5% [95% CI: 78.0-78.9]) were alive one year after diagnosis (93.2% in the non-metastatic at diagnosis subgroup and 37.1% among patients with metastases at diagnosis). At three years post initial diagnosis, 18.0% patients were alive in the metastatic at diagnosis subgroup. Rapid evolution of the treatment landscape limits the results regarding lines of therapy., Conclusion: This large-scale study provides insight on characteristics of patients with RCC, and it highlights the need for better treatment options to improve survival., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Research years during medical school are becoming increasingly common amongst applicants to competitive residency programs. As many of these positions are unpaid, it is important to consider the financial implications of these experiences and the feasibility of participation from students of all backgrounds. This study aims to quantify the cost of a research year during medical school., Design/setting: We identified the top 50 NIH-funded medical schools of 2022 and obtained cost-of-living information for each of their respective counties. Estimated loan interest accrual resulting from a research year was calculated using information on the cost of attendance to medical school and annual interest rates for federal education loans. Cost-of-living calculations were stratified by geographic region, and interest accrual calculations by timing of research year and attendance at public versus private medical schools., Results: Top 50 NIH-funded medical schools in the West are located in counties with the highest mean and median costs of living, each approaching nearly $45,000 per year. Medical schools in the Midwest are located in counties with the lowest mean and median cost of living, at less than $36,000 annually. Estimated loan interest accrual resulting from a research year ranges from $3177 to $17,789, depending on timing of the research year and type of medical school attended., Conclusions: This study exemplifies the significant financial burden that a research year can impose on medical students. As more residency applicants pursuing competitive specialties opt for research years during medical school, it is important to consider the associated financial implications. Many research year opportunities are unpaid or underpaid, which may prevent interested individuals from participating; this is especially the case for those who are from lower socioeconomic backgrounds. Moving forward, it is imperative that we ensure the availability of equitable and funded research year opportunities for students of all backgrounds., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Tramadol is a commonly used opioid analgesic in dogs, particularly in dogs with a compromised immune system. An opioid may be selected for its immunomodulatory effects. Consequently, the objective of this study was to investigate the effects of tramadol on immune system function by evaluating the effect of tramadol and o-desmethyltramadol (M1) on the function of canine leukocytes in vitro. The hypothesis was that tramadol and M1 would not alter polymorphonuclear leukocyte (PMN) phagocytosis, PMN oxidative burst, or stimulated leukocyte cytokine production capacity of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10., Study Design: In vitro pharmacodynamic study., Animals: Six healthy dogs., Methods: Blood from six dogs was obtained and incubated with various concentrations of tramadol and M1. Phagocytosis and oxidative burst were assessed using flow cytometry, and lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PG)-stimulated leukocyte production of TNF, IL-6, and IL-10 were measured using a canine specific multiplex assay., Results: No differences were detected in phagocytosis or oxidative burst with any drug concentration. Tramadol did not alter leukocyte cytokine production, however, M1 significantly blunted IL-10 production., Conclusions: Tramadol and its metabolite M1 were sparing to PMN phagocytosis and oxidative burst in dogs in vitro. Tramadol did not alter leukocyte cytokine production, however, M1 blunted IL-10 production at clinically achievable concentrations suggesting that M1 may promote a proinflammatory shift., Clinical Relevance: These data suggest that tramadol has minimal effect on phagocytosis and oxidative burst, and may promote a proinflammatory shift. Therefore, tramadol may be an ideal opioid analgesic in dogs at high risk of infection. Further investigation in vivo is warranted., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

In 8 patients undergoing routine coronary-artery bypass surgery, monophasic action potentials (MAPs) were measured by means of a hand-held pressure contact electrode to provide an index of local ischaemic changes. 4 patients received left internal mammary anastomoses (LIMA), and there were a total of 27 saphenous vein grafts (SVG). After completion of all grafts blood-flow to the myocardium was reduced for 90 s by means of different permutations of SVG and LIMA occlusion, either on or off bypass. In all patients MAPs indicated typical ischaemic changes. The high sensitivity of the method enables the study to be completed quickly and without hazard to the patient. The technique provides a new means to assess local ischaemia, the viability of specific areas of myocardium, and the efficiency of individual grafts during surgery.