Proteoglycan 4 (PRG4)/Lubricin and the Extracellular Matrix in Gout

Proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes, released into synovial fluid, and adsorbed on cartilage and synovial surfaces. PRG4′s roles include cartilage boundary lubrication, synovial homeostasis, immunomodulation, and suppression of inflammation. Gouty arthritis is mediated by monosodium urate (MSU) crystal phagocytosis by synovial macrophages, with NLRP3 inflammasome activation and IL-1β release. The phagocytic receptor CD44 mediates MSU crystal uptake by macrophages. By binding CD44, PRG4 limits MSU crystal uptake and downstream inflammation. PRG4/CD44 signaling is transduced by protein phosphatase 2A, which inhibits NF-κB, decreases xanthine oxidoreductase (XOR), urate production, and ROS-mediated IL-1β secretion. PRG4 also suppresses MSU crystal deposition in vitro. In contrast to PRG4, collagen type II (CII) alters MSU crystal morphology and promotes the macrophage uptake of MSU crystals. PRG4 deficiency, mediated by imbalance in PRG4-degrading phagocyte proteases and their inhibitors, was recently implicated in erosive gout, independent of hyperuricemia. Thus, dysregulated extracellular matrix homeostasis, including deficient PRG4 and increased CII release, may promote incident gout and progression to erosive tophaceous joint disease. PRG4 supplementation may offer a new therapeutic option for gout

Photon-number-resolution with sub-30-ps timing using multi-element superconducting nanowire single photon detectors

A photon-number-resolving detector based on a four-element superconducting nanowire single photon detector is demonstrated to have sub-30-ps resolution in measuring the arrival time of individual photons. This detector can be used to characterize the photon statistics of non-pulsed light sources and to mitigate dead-time effects in high-speed photon counting applications. Furthermore, a 25% system detection efficiency at 1550 nm was demonstrated, making the detector useful for both low-flux source characterization and high-speed photon-counting and quantum communication applications. The design, fabrication and testing of this detector are described, and a comparison between the measured and theoretical performance is presented.Comment: 13 pages, 5 figure

Treatment utilization and outcomes in elderly patients with locally advanced esophageal carcinoma: A review of the National Cancer Database

For elderly patients with locally advanced esophageal cancer, therapeutic approaches and outcomes in a modern cohort are not well characterized. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment type. Variables associated with treatment utilization were evaluated using logistic regression and survival evaluated using Cox proportional hazards analysis. Propensity matching (1:1) was performed to help account for selection bias. A total of 21,593 patients were identified. Median and maximum ages were 77 and 90, respectively. Treatment included palliative therapy (24.3%), chemoradiation (37.1%), trimodality therapy (10.0%), esophagectomy alone (5.6%), or no therapy (12.9%). Age ≥80 (OR 0.73), female gender (OR 0.81), Charlson-Deyo comorbidity score ≥2 (OR 0.82), and high-volume centers (OR 0.83) were associated with a decreased likelihood of palliative therapy versus no treatment. Age ≥80 (OR 0.79) and Clinical Stage III (OR 0.33) were associated with a decreased likelihood, while adenocarcinoma histology (OR 1.33) and nonacademic cancer centers (OR 3.9), an increased likelihood of esophagectomy alone compared to definitive chemoradiation. Age ≥80 (OR 0.15), female gender (OR 0.80), and non-Caucasian race (OR 0.63) were associated with a decreased likelihood, while adenocarcinoma histology (OR 2.10) and high-volume centers (OR 2.34), an increased likelihood of trimodality therapy compared to definitive chemoradiation. Each treatment type demonstrated improved survival compared to no therapy: palliative treatment (HR 0.49) to trimodality therapy (HR 0.25) with significance between all groups. Any therapy, including palliative care, was associated with improved survival; however, subsets of elderly patients with locally advanced esophageal cancer are less likely to receive aggressive therapy. Care should be taken to not unnecessarily deprive these individuals of treatment that may improve survival

Sensemaking and Success in the Transition from Community Colleges to University IS/CS/CE Programs

Increasing the enrollment of women, minority, and other underrepresented populations in undergraduate information systems and computing programs is an important social issue. We explore ways of attracting and retaining community college transfer students—an important source of underrepresented students —by examining their sensemaking efforts as they transition to four-year universities. We conducted a qualitative study to test sensemaking theory and develop recommendations for retaining community college transfer students in undergraduate information systems, computer science, and computer engineering programs

Implementation Research for the Prevention of Mother-to-Child HIV Transmission in Sub-Saharan Africa: Existing Evidence, Current Gaps, and New Opportunities

Tremendous gains have been made in the prevention of mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Ambitious goals for the “virtual elimination” of pediatric HIV appear increasingly feasible, driven by new scientific advances, forward-thinking health policy, and substantial donor investment. To fulfill this promise, however, rapid and effective implementation of evidence-based practices must be brought to scale across a diversity of settings. The discipline of implementation research can facilitate this translation from policy into practice; however, to date, its core principles and frameworks have been inconsistently applied in the field. We reviewed the recent developments in implementation research across each of the four “prongs” of a comprehensive PMTCT approach. While significant progress continues to be made, a greater emphasis on context, fidelity, and scalability – in the design and dissemination of study results – would greatly enhance current efforts and provide the necessary foundation for future evidence-based programs

Moderators of the Relationship between Exercise and Mood Changes: Gender, Exertion Level, and Workout Duration

ABSTRACT Although the role of exercise in improving mood is well established, less is known about moderators of this effect, particularly outside of the laboratory. The current study examined the effect of gender, type of exercise, level of exertion, and duration of workout on the exercisemood relationship in a naturalistic setting. One hundred and thirty five participants (64 females) either engaged in weight training (n=52) or cardiovascular (n=83) exercise. Pre-and postexercise assessments of mood were collected and changes in two types of mood, negative mood and exhaustion, were examined. Overall, participants reported improved mood after exercise in both domains. Workout duration and level of exertion significantly moderated the relationship of exercise to mood improvement (i.e., an increase in either corresponded to greater improved mood, ps < 0.05). Overall, women showed more improved mood than men in the domain of exhaustion (p=0.001)

The Chlamydomonas reinhardtii BBSome is an IFT cargo required for export of specific signaling proteins from flagella

In humans, seven evolutionarily conserved genes that cause the cilia-related disorder Bardet-Biedl syndrome (BBS) encode proteins that form a complex termed the BBSome. The function of the BBSome in the cilium is not well understood. We purified a BBSome-like complex from Chlamydomonas reinhardtii flagella and found that it contains at least BBS1, -4, -5, -7, and -8 and undergoes intraflagellar transport (IFT) in association with a subset of IFT particles. C. reinhardtii insertional mutants defective in BBS1, -4, and -7 assemble motile, full-length flagella but lack the ability to phototax. In the bbs4 mutant, the assembly and transport of IFT particles are unaffected, but the flagella abnormally accumulate several signaling proteins that may disrupt phototaxis. We conclude that the BBSome is carried by IFT but is an adapter rather than an integral component of the IFT machinery. C. reinhardtii BBS4 may be required for the export of signaling proteins from the flagellum via IFT