Recurrent bacterial infections are a significant burden worldwide, and prior history of infection is often a significant risk factor for developing new infections. For urinary tract infection (UTI), a history of two or more episodes is an independent risk factor for acute infection. However, mechanistic knowledge of UTI pathogenesis has come almost exclusively from studies in naive mice. Here we show that, in mice, an initial Escherichia coli UTI, whether chronic or self-limiting, leaves a long-lasting molecular imprint on the bladder tissue that alters the pathophysiology of subsequent infections, affecting host susceptibility and disease outcome. In bladders of previously infected versus non-infected, antibiotic-treated mice, we found (1) an altered transcriptome and defects in cell maturation, (2) a remodelled epithelium that confers resistance to intracellular bacterial colonization, and (3) changes to cyclooxygenase-2-dependent inflammation. Furthermore, in mice with a history of chronic UTI, cyclooxygenase-2-dependent inflammation allowed a variety of clinical E. coli isolates to circumvent intracellular colonization resistance and cause severe recurrent UTI, which could be prevented by cyclooxygenase-2 inhibition or vaccination. This work provides mechanistic insight into how a history of infection can impact the risk for developing recurrent infection and has implications for the development of therapeutics for recurrent UTI.

SUMMARY The urothelium is an epithelia barrier lined by a luminal layer of binucleated, octoploid, superficial cells. Superficial cells are critical for production and transport of uroplakins, a family of proteins that assemble into a waterproof crystalline plaque that helps protect against infection and toxic substances. Adult urothelium is nearly quiescent, but rapidly regenerates in response to injury. Yet the mechanism by which binucleated, polyploid, superficial cells are produced remains unclear. Here, we show that superficial cells are likely to be derived from a population of binucleated intermediate cells, which are produced from mononucleated intermediate cells via incomplete cytokinesis. We show that binucleated intermediate and superficial cells increase DNA content via endoreplication, passing through S phase without entering mitosis. The urothelium can be permanently damaged by repetitive or chronic injury or disease. Identification of the mechanism by which superficial cells are produced may be important for developing strategies for urothelial repair.

Men and women sustained a significant number of UE injuries playing collegiate ice hockey during the period studied, with acromioclavicular joint sprain being the most common UE injury and the one that most frequently led to significant time loss. These data may provide insight for future injury prevention and guide improvements in training.

Objective To characterize the relationship between objective tympanogram values and patient-reported symptoms and associations with common comorbid conditions. Study Design Cross-sectional study with prospective data collection. Setting Tertiary medical center. Methods Patients undergoing routine audiometric evaluation between October 2018 and June 2019 were included. Participants with temporomandibular joint dysfunction, inner ear hydrops, and similar conditions were excluded. Symptoms were assessed with the 7-item Eustachian Tube Dysfunction Questionnaire. Demographics and medical comorbidities were recorded from the medical record. Analysis of tympanometric peak pressure (TPP), demographics, and comorbidities was performed to determine associations with clinically significant eustachian tube dysfunction (ETD) symptoms. Results A total of 250 patients were included with similar demographics: 101 (40.4%) in the asymptomatic group and 149 (59.6%) in the symptomatic group. The median (interquartile range) TPP was –10 (20) daPa and –25 (100) daPa in the asymptomatic and symptomatic groups, respectively. A diagnosis of rhinitis was more likely to be associated with significant ETD symptoms (adjusted odds ratio, 2.61; 95% CI, 1.23-5.63). A subgroup analysis revealed that symptomatic patients with normal TPP values were negatively skewed as compared with asymptomatic patients. This symptomatic group had a higher prevalence of rhinitis and chronic rhinosinusitis than the asymptomatic group. Conclusion Patients with symptoms of ETD may have a TPP within a range typically considered normal per conventional standards. This suggests that the currently accepted interpretation of tympanometry findings may be insensitive for the diagnosis of less severe cases of ETD.

Purpose: The aim of this study is to further examine the associations of race, socioeconomic factors, and comorbidity with COVID-19 health outcomes. Methods: This is a retrospective cohort study of 309 PCR confirmed COVID-19 positive adults who presented to Tulane Medical Center in New Orleans, LA, from March 9 to May 29, 2020. The primary outcomes investigated were need for invasive mechanical ventilation (IMV) and in-hospital mortality. A multivariate analysis was performed to determine socioeconomic and medical risk factors for IMV and in-hospital mortality. Results: Compared to white patients, Black patients were more likely to present younger, female, obese, unemployed, and underinsured. However, when controlled for common risk factors, Black and white patients had similar risk for IMV and mortality. Increased age (≥65 years), obesity, and increased comorbidity were associated with increased risk for IMV and mortality. Conclusions: Race and socioeconomic factors may increase risk for COVID-19 infection but did not affect health outcomes within the hospital setting. Therefore, the higher rates of COVID-19 infection and mortality in vulnerable populations may be better explained by lower socioeconomic status, with subsequent higher comorbidity, in these populations. Community health initiatives should be prioritized in response to the COVID-19 pandemic.