Secondary hyperparathyroidism in HIV-infected patients: relationship with bone remodeling and response to vitamin D supplementation

Purpose of the study: Secondary hyperparathyroidism (SH) is frequent in HIV-infected patients. However, the causes and consequences are not well established. The aim of our study was to determine the relationship between parathyroid hormone (PTH), vitamin D and bone mineral density (BMD) in HIV-infected patients, and the effect of vitamin D replacement on PTH levels. Methods: Prospective study of 506 patients with at least two sequential serum determinations of PTH and 25-hydroxyvitamin D levels. In all cases, a bone dual X-ray absorptiometry (DEXA) was performed at inclusion. Hyperparathyroidism was defined as a PTH level above 65 pg/ml. Summary of results: Mean age was 44 yrs (24–78), and 75% were male. Mean BMI was 23.7 (17.97–33.11), and only 3% were of black race. Median nadir CD4+ was 200 cells/µL (9–499), and median time of HIV infection was 15.3 yrs (1.7–25.2). At inclusion, 488 patients (86%) were on HAART (31% TDF+PI, 44% TDF+NNRTI, 25% non-TDF based regimen) for a median of 929.5 days (154–1969), and 40% were HCV-coinfected. Median eGFR was 97.9 ml/min (62.14–134.08). Overall, mean serum PTH was 56.3 pg/mL (27.2–95.07). SH was observed in 27% of cases, with a marked influence of seasonality (from 44% in January to 10% in August). Mean levels of vitamin D were 17.45 ng/mL (7.6–40.78), with 16% below 10 ng/ml, 59%<20 ng/ml (deficiency), 85%<30 ng/ml (insufficiency). SH was related to vitamin D deficiency (relative risk, RR, 2.44), age (RR 1.04 per year), and a higher decrease in eGFR (RR 1.03 per ml/min), after adjustment by season, antiretroviral therapy, GFR at baseline, and HCV coinfection. DEXA scan showed 18% osteoporosis and 54% osteopenia, and there was an inverse correlation between PTH levels and T and Z score in femoral neck (r=−0.14, p<0.01), higher in those patients below 40 yrs. Vitamin D supplementation in 181 patients produced a significant decrease in serum PTH (57.2 if not treated vs 50.5 pg/ml, p=0.02, 23% continues with SH) and the only factor associated with lack of response was persistent vitamin D deficiency. Conclusion: SH is relatively frequent in HIV patients, in close relation with vitamin D deficiency. It is associated with bone resorption, especially in the femoral neck. The use of vitamin D supplementation improves SH when levels above 20 ng/ml are achieved

Bloqueo atrioventricular completo en un perro : tratamiento mediante la implantación de un marcapasos endovenosos permanente

Una perra Labrador Retriever presentaba una historia de síncopes, fatiga e intolerancia al ejercicio debida a un bloqueo atrioventricular completo. Debido a que no respondía a la terapia médica (terbutalina, teofilina y posteriormente atropina), fue remitida al Hospital Clínico Veterinario de la Universidad de Murcia con el fin de considerar la implantación de un marcapasos. Las radiografías de tórax mostraron aumento global de la silueta cardiaca y la ecocardiografía puso de manifiesto, además, ligera regurgitación de válvulasatrioventriculares. Se le implantó un marcapasos endovenoso permanente unipolar con modo VVI bajo anestesia general, guiando el cable hacia el ventrículo derecho mediante fluoroscopia con amplificador de imagen. Ocho meses después de la implantación, no se han producido complicaciones y el marcapasos funciona según los parámetros programados.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study - A Randomized Clinical Trial

Background: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. Animals: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio >= 1.6, normalized left ventricular internal diameter in diastole >= 1.7, and vertebral heart sum >10.5. Methods: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. Results: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). Conclusions and Clinical Importance: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit

The high-energy emission from HD 93129A near periastron

We conducted an observational campaign towards one of the most massive and luminous colliding wind binaries in the Galaxy, HD~93129A, close to its periastron passage in 2018. During this time the source was predicted to be in its maximum of high-energy emission. Here we present our data analysis from the X-ray satellites \textit{Chandra} and \textit{NuSTAR} and the γ-ray satellite \textit{AGILE}. High-energy emission coincident with HD~93129A was detected in the X-ray band up to ∼18~keV, whereas in the γ-ray band only upper limits were obtained. We interpret the derived fluxes using a non-thermal radiative model for the wind-collision region. We establish a conservative upper limit for the fraction of the wind kinetic power that is converted into relativistic electron acceleration, fNT,e0.3~G. We also argue a putative interpretation of the emission from which we estimate fNT,e≈0.006 and BWCR≈0.5~G. We conclude that multi-wavelength, dedicated observing campaigns during carefully selected epochs are a powerful tool for characterising the relativistic particle content and magnetic field intensity in colliding wind binaries

Design, characterization and installation of the NEXT-100 cathode and electroluminescence regions

NEXT-100 is currently being constructed at the Laboratorio Subterr\'aneo de Canfranc in the Spanish Pyrenees and will search for neutrinoless double beta decay using a high-pressure gaseous time projection chamber (TPC) with 100 kg of xenon. Charge amplification is carried out via electroluminescence (EL) which is the process of accelerating electrons in a high electric field region causing secondary scintillation of the medium proportional to the initial charge. The NEXT-100 EL and cathode regions are made from tensioned hexagonal meshes of 1 m diameter. This paper describes the design, characterization, and installation of these parts for NEXT-100. Simulations of the electric field are performed to model the drift and amplification of ionization electrons produced in the detector under various EL region alignments and rotations. Measurements of the electrostatic breakdown voltage in air characterize performance under high voltage conditions and identify breakdown points. The electrostatic deflection of the mesh is quantified and fit to a first-principles mechanical model. Measurements were performed with both a standalone test EL region and with the NEXT-100 EL region before its installation in the detector. Finally, we describe the parts as installed in NEXT-100, following their deployment in Summer 2023.Comment: 35 pages, 25 Figures, update includes accepted version in JINS

A Compact Dication Source for Ba2+^{2+} Tagging and Heavy Metal Ion Sensor Development

We present a tunable metal ion beam that delivers controllable ion currents in the picoamp range for testing of dry-phase ion sensors. Ion beams are formed by sequential atomic evaporation and single or multiple electron impact ionization, followed by acceleration into a sensing region. Controllability of the ionic charge state is achieved through tuning of electrode potentials that influence the retention time in the ionization region. Barium, lead, and cobalt samples have been used to test the system, with ion currents identified and quantified using a quadrupole mass analyzer. Realization of a clean $\mathrm{Ba^{2+}}$ ion beam within a bench-top system represents an important technical advance toward the development and characterization of barium tagging systems for neutrinoless double beta decay searches in xenon gas. This system also provides a testbed for investigation of novel ion sensing methodologies for environmental assay applications, with dication beams of Pb$^{2+}$ and Cd$^{2+}$ also demonstrated for this purpose

Strategies to reengage patients lost to follow up in HIV care in high income countries, a scoping review

Background: Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90-90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. Methods: A scoping review was done following Arksey & O'Malley's methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. Results: Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. Conclusions: This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied

Design, construction and operation of the ProtoDUNE-SP Liquid Argon TPC

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber (LArTPC) that was constructed and operated in the CERN North Area at the end of the H4 beamline. This detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment (DUNE), which will be constructed at the Sandford Underground Research Facility (SURF) in Lead, South Dakota, USA. The ProtoDUNE-SP detector incorporates full-size components as designed for DUNE and has an active volume of $7\times 6\times 7.2$~m$^3$. The H4 beam delivers incident particles with well-measured momenta and high-purity particle identification. ProtoDUNE-SP's successful operation between 2018 and 2020 demonstrates the effectiveness of the single-phase far detector design. This paper describes the design, construction, assembly and operation of the detector components