The diagnosis of frailty is usually subjective, which calls for objective biomarkers in clinical medicine. 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGsn) and 8-oxo-7, 8-dihydroguanosine (8-oxoGsn) in urine are two aging biomarkers that have not been explored deeply in cases of frailty. A total of 508 elderly patients with cardiovascular disease (mean age 75.0 ± 6.5 years, 50.8% males) were enrolled consecutively. Frailty was assessed by the Fried phenotype (robust 0 score; pre-frail 1-2 scores; frail 3-5 scores). The concentrations of 8-oxoGsn and 8-oxodGsn in urine were measured by improved ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Urinary creatinine (Cre) was tested to correct the 8-oxoGsn and 8-oxodGsn levels. According to the Fried phenotype score, the proportions of robust, pre-frail, and frail subjects were 20.5% (104/508), 53.9% (274/508), and 25.6% (130/508), respectively. The urinary 8-oxoGsn/Cre (P  less then  0.001) differed significantly among these 3 groups, but the urinary 8-oxodGsn/Cre (P = 0.600) showed no marked difference. Univariate and multivariate logistic regression showed that the age (odds ratio [OR] = 1.090, P  less then  0.001), systolic blood pressure (OR = 0.981, P = 0.008), 8-oxoGsn/Cre (OR = 1.203, P = 0.007), hemoglobin (OR = 0.980, P = 0.007), and sodium (OR = 0.915, P = 0.044) were independently associated with frailty. The sensitivity and specificity to identify frailty were 53.08% and 71.96%, respectively, for 8-oxoGsn/Cre at the optimal cut-off value of 3.879 μmol/mol according to the maximal Youden index. Urinary 8-oxoGsn, as a recognized biomarker of RNA oxidation, is independently associated with frailty in elderly patients with cardiovascular disease. However, the urinary 8-oxodGsn shows no obvious correlation with frailty. To obtain a better diagnostic performance for frailty, more biomarkers from different pathophysiological pathways should be explored in the future. Daily phagocytosis of shed photoreceptor outer segments (POS) by the retinal pigment epithelium (RPE) is required to sustain the visual function. Recent reports revealed that POS phagocytosis is progressed with LC3-associated manner. Patients with age-related macular degeneration (AMD) had impaired autophagic degradation in the RPE. Nrf2 is a key antioxidant transcriptional regulator that ameliorates oxidative stress which is another contributor to AMD pathogenesis. Nrf2 activation also induces the autophagy receptor protein, p62. However, the role of the Nrf2-p62 pathway in LC3-associated phagocytosis of POS is poorly understood. Here, we investigated the relationships between Nrf2 activation and POS phagocytosis progression. A triterpenoid Nrf2 activator, RS9, facilitated POS uptake into phagolysosomes in RPE cells. RS9 also induced the expression of the autophagy-related proteins, LC3-II and p62, as well as phase-2 antioxidant enzymes. The effect of RS9 on POS phagocytosis was abolished by autophagy inhibition. Unexpectedly, p62 knockdown did not inhibit the effect of RS9 on POS phagocytosis, although, RS9-mediated LC3-II induction by RS9 was inhibited in p62 knockdown RPE cells. We also found that RS9 activated the AMPKα-mTOR signaling pathway earlier than p62 induction. Knockdown of AMPKα1, but not α2, inhibited the RS9-mediated activation of LC3-associated phagocytosis and RS9-mediated induction of LC3-II. Furthermore, intravitreal treatment of RS9 to adult mice decreased the size of POS phagolysosomes after light exposure. Collectively, these results showed that RS9-mediated activation of POS phagocytosis was mainly ascribed to the enhancement of autophagy via AMPKα1 activation. Our findings reveal novel effects of Nrf2 and AMPK α1 activation that contribute to the maintenance of the RPE function via LC3-associated POS phagocytosis. BACKGROUND Recurrence after hiatal hernia repair is common. The causes are uncertain. Our observation is the site of recurrence is primarily the non-sutured or non-reinforced anterior-left lateral portion of the hiatus. Our aim was to assess the distribution of hiatal hernia recurrence location as a basis for developing a theory of recurrence. METHODS Consecutive patients who underwent repair of recurrent hiatal hernias from 3/2012 to 12/2019 were reviewed. Data gleaned included age, sex, date of operation, location of hiatal hernia recurrence, operative approach, method of hiatal hernia repair, fundoplication performed, need for gastrectomy, and additional procedures. RESULTS 108 consecutive patients were studied. The distribution of recurrence locations anterior 67%, posterior 12%, and circumferential 21%. Foreshortened esophagus was a contributing factor in 12%. The median time (with interquartile range) in years from the original repair to recurrence was 1.5 (0.9 – 3.75) years for posterior recurrences, 2.75 (1.15- 8.5) years for circumferential recurrences, and 3.25 (1.38 – 10) years for anterior recurrences. Recurrences were repaired in a variety of techniques depending on the clinical circumstances. CONCLUSION Hiatal hernia recurrences due to failure of the crural closure were less common, but early recurrences. The majority of recurrences were due to stretching of the hiatus anterior and to the left of the esophagus. We theorize that the pathophysiology of late hiatal hernia recurrence is widening of the anterior and left lateral portion of the hiatus secondary to repeated stress from differential pressures that eventually overcomes the tensile strength of the hiatus. BACKGROUND Cefazolin is the first-line prophylactic antibiotic used to prevent surgical site infections (SSIs) in cardiac surgery. Patients with a history of penicillin allergy often receive less effective second-line antibiotics, which is associated with an increased SSI risk. OBJECTIVE We aimed to describe the impact of pre-operative penicillin allergy evaluation on peri-operative cefazolin use in cardiac surgery patients. METHODS We performed a retrospective cohort study of patients with a documented penicillin allergy who underwent cardiac surgery at the Massachusetts General Hospital from September 2015 through December 2018. We describe penicillin allergy evaluation assessment and outcomes. We evaluated the relation between preoperative penicillin allergy evaluation and first-line peri-operative antibiotic use using a multivariable logistic regression model. RESULTS Of 3,802 cardiac surgical patients, 510 (13%) had a documented penicillin allergy; 165 (33%) were referred to Allergy/Immunology. Of 160 (31%) patients who underwent penicillin allergy evaluation (i.e., penicillin skin testing and, if negative, an amoxicillin challenge), 154 (97%) were found not to have a penicillin allergy. Patients who underwent pre-operative penicillin allergy evaluation were more likely to receive the first-line peri-operative antibiotic (92% vs 38%, p less then 0.001). After adjusting for potential confounders, patients who underwent pre-operative penicillin allergy evaluation had higher odds of first-line peri-operative antibiotic use (adjusted odds ratio 26.6 [95% CI 12.8, 55.2]). CONCLUSION Integrating penicillin allergy evaluation into routine pre-operative care ensured that almost all cardiac surgery patients evaluated received first-line antibiotic prophylaxis, a critical component of SSI risk reduction. Further efforts are needed to increase access to pre-operative allergy evaluation. OBJECTIVE The high burden associated with respiratory syncytial virus (RSV), has made the development of RSV vaccine(s) a global health high priority. This review summarizes the journey to an RSV vaccine, the different strategies and challenges associated with the development of preventive strategies for RSV, and the diverse products that are undergoing clinical testing. DATA SOURCES Studies on RSV biology, immunology, epidemiology and monoclonal antibodies and vaccines were searched using MEDLINE. We also searched https//path.org and ClinicalTrials.gov for updated information regarding the status of RSV vaccines and monoclonal antibodies undergoing clinical trials. STUDY SELECTIONS We selected relevant studies conducted in infants and young children, pregnant women and the elderly for the prevention of RSV infection. RESULTS Identification of a safe and immunogenic vaccine has been an important but elusive initiative for over 60 years for different reasons including the legacy of formalininactivated vaccine, our limited understanding of the immune response to RSV and how it relates to clinical disease severity or the need for different endpoints according to the different vaccine platforms. Nevertheless, there are currently 39 vaccines and monoclonal antibodies under development and 19 undergoing clinical trials CONCLUSION Over the past decade there have been significant advances in our knowledge of RSV molecular and structural biology, and in understanding the human immune response to RSV. Despite the barriers, there are several promising monoclonal antibodies and RSV vaccines undergoing clinical trials that hope to offer protection to the most vulnerable populations. Keratocytes synthesize stromal proteins and participate in wound healing through successive differentiation into corneal fibroblasts and myofibroblasts. Cultured keratocytes or corneal fibroblasts are also known as non-professional phagocytes and innate immune cells. However, whether the corneal fibroblasts phagocytize their dead cells and whether the associated innate immunity is enhanced remains unknown. We initially characterized immortalized corneal fibroblast cells with the expression of specific genes. The corneal fibroblasts strongly expressed extracellular matrix molecules (FN and COL1A1) and low or medium levels of macrophage markers (CD14, CD68, and CD36), inflammatory cytokines (IL1A, IL1B, and IL6), and chemokines (IL8 and CCL2), but not CD11b, suggesting that corneal fibroblasts are macrophage-like fibroblasts. We confirmed the phagocytic activity of the corneal fibroblasts with fluorescent dye labeled-dead E. coli and S. aureus bacteria using confocal microscopy and flow cytometry. To test corneal fibroblast phagocytosis of apoptotic and necrotic cells we co-cultured corneal fibroblasts with fluorescent dye labeled-apoptotic and -necrotic cells and analyzed their uptake using fluorescence and confocal microscopy. We observed that corneal fibroblasts can engulf digested or processed cellular debris and entire dead cells. Co-cultured dying and dead cells strongly enhanced the expression of cytokine (IL1A, IL1B, and IL6), chemokine (CCL2, CCL5, CCL20, IL8, and CXCL10), and MMP (MMP1, MMP3, and MMP9) genes through the NF-κB signaling pathway. Our findings suggest that dying and dead cells stimulate corneal fibroblasts to further induce inflammatory factors and that corneal fibroblasts contribute to the clearing of cell debris as non-professional phagocytes. Welding fume exposure has been associated with structural brain changes and a wide variety of clinical and sub-clinical outcomes including cognitive, behavioral and motor abnormalities. Respirator use has been shown to decrease exposure to welding fumes; however, the associations between respirator use and health outcomes, particularly neurologic health, have been understudied. In this preliminary study, we used diffusion tensor imaging (DTI) to investigate the effectiveness of respirator use in protecting workers’ white matter (WM) from the harmful effects related to welding fume exposure. Fractional anisotropy (FA), a common DTI measurement of water diffusion properties, was used as a marker of WM microstructure integrity. We hypothesized that FA in brain regions involved in motor and neurocognitive functions would differ between welders reporting respirator use compared to those not using a respirator. We enrolled a pilot cohort of 19 welders from labor unions in the New York City area. All welders completed questionnaires to assess welding history and occupational health.