Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients.

BACKGROUND: CD28(neg) T cells, which display functional characteristic of oligoclonally expanded cytotoxic memory T lymphocytes, are believed to be pathologically relevant in rheumatoid arthritis manifestation. The CD28 co-stimulation blockade by abatacept can prevent the generation of CD28(neg) T-cell populations in these patients. METHODS: Samples were obtained before and after 12 months of abatacept therapy. T-cell phenotype and T-cell receptor diversity were evaluated by flow cytometry and complementarity-determining region-3 spectratyping, respectively, while telomerase reverse-transcriptase gene level was measured by real-time PCR. RESULTS: Abatacept induces a decrease of the percentage and number of CD4(+)CD28(neg) T cells and a reduction of T-cell repertoire restrictions; these features are directly correlated. Thymic output and telomerase activity are not modified by the therapy. CONCLUSIONS: Abatacept-induced decrease of peripheral T-cell repertoire restrictions can due to a reduced generation of senescent, chronically stimulated CD4(+)CD28(neg) T cells

Classificação macroscópica dos graus de atrofia dos cornetos na rinite atrófica dos suínos.

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Midwest Pharmacists\u27 Familiarity, Experience, and Willingness to Provide Pre-Exposure Prophylaxis (PrEP) for HIV

INTRODUCTION: Pharmacist provision of pre-exposure prophylaxis (PrEP) through collaborative practice agreements with physicians could expand access to people at risk for HIV. We characterized pharmacists\u27 familiarity with and willingness to provide PrEP services in Nebraska and Iowa. METHODS: An invitation to complete an 18-question survey was emailed to 1,140 pharmacists in Nebraska and Iowa in June and July of 2016. Descriptive analyses and Pearson chi-square tests were used to determine to what extent demographics, familiarity and experience were associated with respondent willingness to provide PrEP. Wilcoxon rank-sum tests compared ages and years of experience between groups of respondents. RESULTS: One hundred forty pharmacists (12.3%) responded. Less than half were familiar with the use of PrEP (42%) or the CDC guidelines for its use (25%). Respondents who were older (p = .015) and in practice longer (p = .005) were less likely to be familiar with PrEP. Overall, 54% indicated they were fairly or very likely to provide PrEP services as part of a collaborative practice agreement and after additional training. While familiarity with PrEP use or guidelines did not affect respondents\u27 willingness to provide PrEP, respondents were more likely to provide PrEP with prior experience counseling HIV-infected patients on antiretroviral therapy (OR 2.43; p = 0.023) or PrEP (OR 4.67; p = 0.013), and with prior HIV-related continuing education (OR 2.77; p = 0.032). CONCLUSIONS: Pharmacist respondents in Nebraska and Iowa had limited familiarity and experience with PrEP, but most indicated willingness to provide PrEP through collaborative practice agreements after additional training. Provision of PrEP-focused continuing education may lead to increased willingness to participate in PrEP programs

Observing Ultra High Energy Cosmic Particles from Space: SEUSO, the Super Extreme Universe Space Observatory Mission

The experimental search for ultra high energy cosmic messengers, from $E\sim 10^{19}$ eV to beyond $E\sim 10^{20}$ eV, at the very end of the known energy spectrum, constitutes an extraordinary opportunity to explore a largely unknown aspect of our universe. Key scientific goals are the identification of the sources of ultra high energy particles, the measurement of their spectra and the study of galactic and local intergalactic magnetic fields. Ultra high energy particles might, also, carry evidence of unknown physics or of exotic particles relics of the early universe. To meet this challenge a significant increase in the integrated exposure is required. This implies a new class of experiments with larger acceptances and good understanding of the systematic uncertainties. Space based observatories can reach the instantaneous aperture and the integrated exposure necessary to systematically explore the ultra high energy universe. In this paper, after briefly summarising the science case of the mission, we describe the scientific goals and requirements of the SEUSO concept. We then introduce the SEUSO observational approach and describe the main instrument and mission features. We conclude discussing the expected performance of the mission

Deadly Puppy Infection Caused by an MDR Escherichia coli O39 blaCTX–M–15, blaCMY–2, blaDHA–1, and aac(6)-Ib-cr – Positive in a Breeding Kennel in Central Italy

Antimicrobial consumption in veterinary medicine has led to the spread of multi drug-resistance in clinically important bacteria, with the companion animals and their environment involved as emerging reservoirs. While CTX-M-15 and CMY-2 acquired β-lactamases have been widely detected in the bacterial population of companion and breeding animals in European area, DHA-1 enzymes have been rarely reported in veterinary medicine. The aim of the study was to characterize the Escherichia coli associated with mortality of a litter of Bulldog puppies in a breeding kennel located in Pesaro area, Central Italy. The E. coli strains O39 serotype were resistant to 3rd/4th generation cephalosporins, chloramphenicol, aminoglycosides, trimethoprim-sulfamethoxazole, and ciprofloxacin, retaining susceptibility to carbapenems, colistin, fosfomycin, and levofloxacin (by Microscan Autoscan4, EUCAST clinical breakpoints). Pulse field gel electrophoreses (PFGE-XbaI) on five E. coli strains revealed the presence of a single profile. Whole genome sequencing (WGS) analysis revealed a complex resistome, harboring blaTEM–1b, blaCTX–M–15, blaOXA–1, aph(6)-Ib, aac(6′)Ib-cr, aac(3)-Ila, aph(6)-Id, aadA1, qnrB1, sul2, catA1, catB3, tetA, and dfrA14 genes located on a 302597 bp IncHI2/HI2A plasmid. Moreover, blaDHA–1, qnrB4, mph(A), sul1, and dfrA17 determinants were carried on an 83,429 bp IncFII plasmid. A blaCMY–2 determinant was carried on a 90,249 bp IncI1 plasmid. Two IncX1 and IncX4 plasmids without antimicrobial resistance genes were also detected. The presence of lpfA, iss, astA, and gad virulence factors was highlighted. This is the first report in Italy on an invasive infection in eight 2-weeks old dogs caused by the same MDR E. coli O39 blaCTX–M–15, blaCMY–2, blaDHA–1, and aac(6′)-Ib-cr positive strain. The above MDR E. coli clone caused the death of the entire litter, despite amoxicillin-clavulanate and enrofloxacin administration. The tank for storage of the water used to prepare the milk-based meal for the litter was the suspected reservoir

EUSO science

EUSO is a mission to explore the extreme universe by the probe of Ultra High Energy Cosmic Rays (UHECRs) and UHE neutrinos. EUSO monitors a gigantic volume of atmosphere from Space and measures showers induced by UHECRs and UHE neutrinos. Scientifically, it is important to measure the energy spectrum of UHECRs well beyond GZK energy with high statistics. EUSO ensures the observation of UHECRs up to 10$^{21}$eV even in the case of GZK mechanism working, and gives us a clear picture of the existence / non-existence of the GZK effect and the behavior of the spectrum beyond GZK energy, which represents the contributions from nearby sources. The anisotropy study of UHECR arrival directions in a small scale angle above GZK energy may allow us to identify individual source, because of the limited propagation distance and the high rigidity of particles. If event clusters observed by AGASA are real, it is expected from Monte Carlo simulation that EUSO will see ~100 particles from individual brightest sources and will give us a good opportunity to test the relativity in high precision. The UHE neutrino is a unique channel to explore the universe much deeper than UHECRs. EUSO essentially can measure UHE neutrinos free from background proton showers. The number of GZK neutrino events in a EUSO three years' mission is expected to be only a few. Nevertheless, it is a definitely conceivable opportunity to begin UHE neutrino astrophysics at GZK energy

Propagation of ultra-high energy protons in the nearby universe

We present a new calculation of the propagation of protons with energies above $10^{19}$ eV over distances of up to several hundred Mpc. The calculation is based on a Monte Carlo approach using the event generator SOPHIA for the simulation of hadronic nucleon-photon interactions and a realistic integration of the particle trajectories in a random extragalactic magnetic field. Accounting for the proton scattering in the magnetic field affects noticeably the nucleon energy as a function of the distance to their source and allows us to give realistic predictions on arrival energy, time delay, and arrival angle distributions and correlations as well as secondary particle production spectra.Comment: 12 pages, 9 figures, ReVTeX. Physical Review D, accepte

Extreme Energy Cosmic Rays (EECR) Observation Capabilities of an "Airwatch from Space'' Mission

The longitudinal development and other characteristics of the EECR induced atmospheric showers can be studied from space by detecting the fluorescence light induced in the atmospheric nitrogen. According to the Airwatch concept a single fast detector can be used for measuring both intensity and time development of the streak of fluorescence light produced by the atmospheric shower induced by an EECR. In the present communication the detection capabilities for the EECR observation from space are discussed.Comment: 3 pages (LaTeX). To appear in the Proceedings of TAUP'9

Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria

Background: To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations. Methods and Findings: From 2004–2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for 24 months. Patients developed a median of 0.6 (IQR: 0–1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir. Conclusions: This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access