Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney

Tamm-Horsfall protein (THP), also known as uromodulin, is a kidney-specific protein produced by cells of the thick ascending limb of the loop of Henle. Although predominantly secreted apically into the urine, where it becomes highly polymerized, THP is also released basolaterally, toward the interstitium and circulation, to inhibit tubular inflammatory signaling. Whether, through this latter route, THP can also regulate the function of renal interstitial mononuclear phagocytes (MPCs) remains unclear, however. Here, we show that THP is primarily in a monomeric form in human serum. Compared with wild-type mice, THP-/- mice had markedly fewer MPCs in the kidney. A nonpolymerizing, truncated form of THP stimulated the proliferation of human macrophage cells in culture and partially restored the number of kidney MPCs when administered to THP-/- mice. Furthermore, resident renal MPCs had impaired phagocytic activity in the absence of THP. After ischemia-reperfusion injury, THP-/- mice, compared with wild-type mice, exhibited aggravated injury and an impaired transition of renal macrophages toward an M2 healing phenotype. However, treatment of THP-/- mice with truncated THP after ischemia-reperfusion injury mitigated the worsening of AKI. Taken together, our data suggest that interstitial THP positively regulates mononuclear phagocyte number, plasticity, and phagocytic activity. In addition to the effect of THP on the epithelium and granulopoiesis, this new immunomodulatory role could explain the protection conferred by THP during AKI

Billing by residents and attending physicians in family medicine: the effects of the provider, patient, and visit factors

BACKGROUND: Medical billing and coding are critical components of residency programs since they determine the revenues and vitality of residencies. It has been suggested that residents are less likely to bill higher evaluation and management (E/M) codes compared with attending physicians. The purpose of this study is to assess the variation in billing patterns between residents and attending physicians, considering provider, patient, and visit characteristics. METHOD: A retrospective cohort study of all established outpatient visits at a family medicine residency clinic over a 5-year period was performed. We employed the logistic regression methodology to identify residents' and attending physicians' variations in coding E/M service levels. We also employed Poisson regression to test the sensitivity of our result. RESULTS: Between January 5, 2009 and September 25, 2015, 98,601 visits to 116 residents and 18 attending physicians were reviewed. After adjusting for provider, patient, and visit characteristics, residents billed higher E/M codes less often compared with attending physicians for comparable visits. In comparison with attending physicians, the odds ratios for billing higher E/M codes were 0.58 (p = 0.01), 0.56 (p = 0.01), and 0.63 (p = 0.01) for the third, second, and first years of postgraduate training, respectively. In addition to the main factors of patient age, medical conditions, and number of addressed problems, the gender of the provider was also implicated in the billing variations. CONCLUSION: Residents are less likely to bill higher E/M codes than attending physicians are for similar visits. While these variations are known to contribute to lost revenues, further studies are required to explore their effect on patient care in relation to attendings' direct involvement in higher E/M-coded versus their indirect involvement in lower E/M-coded visits

The symmetry of charge order in cuprates

Charge-ordered ground states permeate the phenomenology of 3d-based transition metal oxides, and more generally represent a distinctive hallmark of strongly-correlated states of matter. The recent discovery of charge order in various cuprate families fueled new interest into the role played by this incipient broken symmetry within the complex phase diagram of high-Tc superconductors. Here we use resonant X-ray scattering to resolve the main characteristics of the charge-modulated state in two cuprate families: Bi2201 and YBCO. We detect no signatures of spatial modulations along the nodal direction in Bi2201, thus clarifying the inter-unit-cell momentum-structure of charge order. We also resolve the intra-unit-cell symmetry of the charge ordered state, which is revealed to be best represented by a bond-order with modulated charges on the O-2p orbitals and a prominent d-wave character. These results provide insights on the microscopic description of charge order in cuprates, and on its origin and interplay with superconductivity.Comment: A high-resolution version with supplementary material can be found at: http://www.phas.ubc.ca/~quantmat/ARPES/PUBLICATIONS/Articles/CDW_symmetry.pd

Plasma host protein biomarkers correlating with increasing Mycobacterium tuberculosis infection activity prior to tuberculosis diagnosis in people living with HIV

BACKGROUND: Biomarkers correlating with Mycobacterium tuberculosis infection activity/burden in asymptomatic individuals are urgently needed to identify and treat those at highest risk for developing active tuberculosis (TB). Our main objective was to identify plasma host protein biomarkers that change over time prior to developing TB in people living with HIV (PLHIV). METHODS: Using multiplex MRM-MS, we investigated host protein expressions from 2 years before until time of TB diagnosis in longitudinally collected (every 3-6 months) and stored plasma from PLHIV with incident TB, identified within a South African (SA) and US cohort. We performed temporal trend and discriminant analyses for proteins, and, to assure clinical relevance, we further compared protein levels at TB diagnosis to interferon-gamma release assay (IGRA; SA) or tuberculin-skin test (TST; US) positive and negative cohort subjects without TB. SA and US exploratory data were analyzed separately. FINDINGS: We identified 15 proteins in the SA (n=30) and 10 in the US (n=24) incident TB subjects which both changed from 2 years prior until time of TB diagnosis after controlling for 10% false discovery rate, and were significantly different at time of TB diagnosis compared to non-TB subjects (p<0.01). Five proteins, CD14, A2GL, NID1, SCTM1, and A1AG1, overlapped between both cohorts. Furthermore, after cross-validation, panels of 5 – 12 proteins were able to predict TB up to two years before diagnosis. INTERPRETATION: Host proteins can be biomarkers for increasing Mycobacterium tuberculosis infection activity/burden, incipient TB, and predict TB development in PLHIV. FUNDING: NIH/NIAID AI117927, AI146329, and AI127173 to JMA

Chaotic Amplification of Neutrino Chemical Potentials by Neutrino Oscillations in Big Bang Nucleosynthesis

We investigate in detail the parameter space of active-sterile neutrino oscillations that amplifies neutrino chemical potentials at the epoch of Big Bang Nucleosynthesis. We calculate the magnitude of the amplification and show evidences of chaos in the amplification process. We also discuss the implications of the neutrino chemical potential amplification in the Big Bang Nucleosynthesis. It is shown that with a $\sim 1$ eV \nue, the amplification of its chemical potential by active-sterile neutrino oscillations can lower the effective number of neutrino species at Big Bang Nucleosynthesis to significantly below 3.Comment: Revtex 20 pages, 7 postscript figures. Also by ftp://astro.queensu.ca/pub/shi/ . Submitted to PR

Statistical Analysis of Different Muon-antineutrino->Electron-antineutrino Searches

A combined statistical analysis of the experimental results of the LSND and KARMEN \numubnueb oscillation search is presented. LSND has evidence for neutrino oscillations that is not confirmed by the KARMEN experiment. This joint analysis is based on the final likelihood results for both data sets. A frequentist approach is applied to deduce confidence regions. At a combined confidence level of 36%, there is no area of oscillation parameters compatible with both experiments. For the complementary confidence of 1-0.36=64%, there are two well defined regions of oscillation parameters (sin^2(2th),Dm^2) compatible with both experiments.Comment: 25 pages, including 10 figures, submitted to Phys. Rev.