We present a measurement study of wireless experience in a diverse set of home environments by deploying an infrastructure, we call WiSe. Our infrastructure consists of OpenWrt-based Access Points (APs) that have been given away to residents for free to be installed as their primary wireless access mechanism. These APs are configured with our specialized measurement and monitoring software that communicates with our measurement controller through an open API. We have collected wireless performance traces from 30 homes for a period in excess of 6 months. To analyze the characteristics of these home wireless environments, we have also developed a simple metric that estimates the likely TCP throughput different clients can expect based on current channel and environmental conditions. With this infrastructure, we provide multiple quantitative observations, some of which are anecdotally understood in our community. For example, while a majority of links performed well most of the time, we observed cases of poor client experience about 2.1% of the total time.
Lactoferrin-binding protein B (LbpB) is a lipoprotein present on the surface of Neisseria that has been postulated to serve dual functions during pathogenesis in both iron acquisition from lactoferrin (Lf), and in providing protection against the cationic antimicrobial peptide lactoferricin (Lfcn). While previous studies support a dual role for LbpB, exactly how these ligands interact with LbpB has remained unknown. Here, we present the structures of LbpB from N. meningitidis and N. gonorrhoeae in complex with human holo-Lf, forming a 1:1 complex and confirmed by size-exclusion chromatography small-angle X-ray scattering. LbpB consists of N- and C-lobes with the N-lobe interacting extensively with the C-lobe of Lf. Our structures provide insight into LbpB’s preference towards holo-Lf, and our mutagenesis and binding studies show that Lf and Lfcn bind independently. Our studies provide the molecular details for how LbpB serves to capture and preserve Lf in an iron-bound state for delivery to the membrane transporter LbpA for iron piracy, and as an antimicrobial peptide sink to evade host immune defenses.
92 Background: Abiraterone (AA) and Enzalutamide (ENZ) are both hormone therapies used in the treatment of metastatic castrate resistant prostate cancer (mCRPC). Due to a lack of large comparative studies, they are currently used interchangeably, but may have different adverse outcomes in patients with comorbid conditions. In this study, we aim to identify adverse events that lead to hospitalization in patients treated with ENZ versus AA. Methods: Patients treated with AA or ENZ between September 10, 2014 and June 3, 2017 were identified in the Veterans Health Administration and followed until April 2020. We obtained ICD 9/10 codes using the Veterans Health Administration Informatics and Computing Infrastructure (VINCI) platform among VA hospitalizations. We used the top 3 ICD 9/10 codes at discharge to ascertain causation of hospitalization. Infections were defined by ICD 9 and ICD 10 codes falling into 3 categories: pneumonia (ICD9: 480.x-486.x, ICD10: J13.x-J18.x), urinary tract infection (ICD9: 599.0, ICD10: N39.0), and sepsis (ICD9: 995.91, 995.92, ICD10: A40.x-A41.x, R65.20, R65.21). Results: 5,822 patients were identified for the cohort. The mean age of the patients was 75.3 years old, with a mean Charlson comorbidity index of 4.2. Patients first treated with enzalutamide were older (75.8 vs 75.0 years, p = 0.002) with a higher mean Charlson comorbidity score (4.4 vs 4.1, p < 0.001). There were no significant differences in time from initial diagnosis of PCa to treatment with AA or ENZ. Of the 5,822 patients, 2504 (43.0%) were initially treated with ENZ, and 3,318 (57.0%) with AA. Total hospitalization rate in events/person-years was 1.52 and 1.29 for the abiraterone and enzalutamide cohorts respectively, with an incidence rate difference (IDR) of 0.23 (p < 0.0001, CI: 0.14-0.32), indicating a statistically significant increase in hospitalizations among the abiraterone cohort. Of the total hospitalizations, 1/4th of them were caused by infections defined as pneumonia, sepsis, or UTI. The incidence in events/person-years for the combined infections in the AA and ENZ cohort was 0.99 and 0.86 (IDR = 0.13, p = 0.06) respectively, 0.97 and 0.86 (IDR = 0.11, p = 0.26) for UTI; 0.76 and 0.74 (IDR = 0.021, p = 0.82) for sepsis; and 0.82 and 0.71 (IDR = 0.12, p = 0.22) for pneumonia. This shows no statistical difference in infection rate between the two treatments. Conclusions: The increase in incidence rate of hospitalizations of 0.23 events/person-years among the abiraterone group, despite greater age and comorbidities in the enzalutamide group, suggests an increased risk of adverse events requiring hospitalization in patients started on abiraterone initially. However, no difference was seen in incidence of the three most common infections between cohorts. This suggests that the difference in mechanism of action and use of prednisone with AA may not be of clinical significance with regards to risk for infection.
Parenteral nutrition (PN) is a therapy that delivers essential nutrients intravenously to patients who are unable to meet their nutrition requirements via standard enteral feeding. This methodology is often referred to as PN when accompanied by minimal or no enteral nutrition (EN). Although PN is lifesaving, significant complications can arise, such as intestinal failure–associated liver disease and gut‐mucosal atrophy. The exact mechanism of injury remains ill defined. This review was designed to explore the available literature related to the drivers of injury mechanisms. The Farnesoid X receptor and fibroblast growth factor 19 signaling pathway seems to play an important role in gut‐systemic signaling, and its alteration during PN provides insights into mechanistic links. Central line infections also play a key role in mediating PN‐associated injury. Although lipid reduction strategies, as well as the use of multicomponent lipid emulsions and vitamin E, have shown promise, the cornerstone of preventing injury is the early establishment of EN.
116 Background: In metastatic castrate resistant prostate cancer (mCRPC), the oral treatments of enzalutamide (ENZ) and abiraterone (AA) are used interchangeably because there are few large-scale comparative studies of the therapies. However, both drugs have different mechanisms of action, AA being an androgen biosynthesis inhibitor and ENZ being an androgen receptor inhibitor, so there may be therapeutic variance between the two drugs based on their interactions with comorbid conditions like obesity. Obesity not only increases the risk of other comorbidities, like heart disease, diabetes, and stroke, but has also been implicated in the development of CRPC. Methods: Patients treated with abiraterone or enzalutamide from September 10, 2014 to June 2, 2017 in the Veterans Health Administration were identified via pharmacy records. Among this population, patients were separated into body mass index (BMI) categories for underweight ( < 18.5), normal (18.5 to < 25), overweight (25 to < 30), and obese ( > 30). Age, Charlson Comorbidity Index and mCRPC treatments were collected and analyzed for the primary outcome of survival via the Kaplan-Meier method. A multivariate Cox proportional hazard model was performed with the following variables: BMI, Charlson Comorbidity Index, age, Black race, treatment with bone-directed therapy, and baseline PSA. Results: In patients with BMI > 25, there was a significantly improved overall survival for treatment with ENZ (n = 1623) over AA (n = 2159), with medians of 30.0 and 27.0 months respectively (p = 0.002). There was no significant difference in survival for patients with BMI < 25 (p = 0.48), with median survival of 17.7 months for ENZ (n = 589) and 16.1 months for AA (n = 860). The overall survival difference between underweight (n = 113), normal (n = 1336), overweight (n = 1879), and obese (n = 1903) groups shows significant increase in survival with increasing BMI, with the median survival durations of 9.2, 15.9, 23.9, and 29.8 months respectively (p < 0.001). This finding was corroborated by the Cox proportional hazard model, with the data indicating an increased risk of death (aHR = 1.58; 95% CI: 1.29, 1.94; p < 0.001) with the underweight group and decreased risk with the overweight (aHR = 0.75; 95% CI: 0.69, 0.81; p < 0.001) and obese (aHR = 0.64; 95% CI: 0.59, 0.70; p < 0.001) groups. Conclusions: Treatment with ENZ was associated with longer survival for mCRPC patients with overweight and obesity (BMI > 25) over AA. Otherwise, for normal and underweight patients (BMI < 25), there was no significant difference in overall survival between the two drugs. Higher BMI is associated with improved survival, suggesting a protective effect of obesity in mCRPC patients. While the reason for this finding warrants further investigation, similar findings have been seen in obese patients in some hormone driven cancers, like breast cancer and myeloma.
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