In vivo Bioimaging as a Novel Strategy to Detect Doxorubicin-Induced Damage to Gonadal Blood Vessels

INTRODUCTION: Chemotherapy may induce deleterious effects in normal tissues, leading to organ damage. Direct vascular injury is the least characterized side effect. Our aim was to establish a real-time, in vivo molecular imaging platform for evaluating the potential vascular toxicity of doxorubicin in mice. METHODS: Mice gonads served as reference organs. Mouse ovarian or testicular blood volume and femoral arterial blood flow were measured in real-time during and after doxorubicin (8 mg/kg intravenously) or paclitaxel (1.2 mg/kg) administration. Ovarian blood volume was imaged by ultrasound biomicroscopy (Vevo2100) with microbubbles as a contrast agent whereas testicular blood volume and blood flow as well as femoral arterial blood flow was imaged by pulse wave Doppler ultrasound. Visualization of ovarian and femoral microvasculature was obtained by fluorescence optical imaging system, equipped with a confocal fiber microscope (Cell-viZio). RESULTS: Using microbubbles as a contrast agent revealed a 33% (P<0.01) decrease in ovarian blood volume already 3 minutes after doxorubicin injection. Doppler ultrasound depicted the same phenomenon in testicular blood volume and blood flow. The femoral arterial blood flow was impaired in the same fashion. Cell-viZio imaging depicted a pattern of vessels' injury at around the same time after doxorubicin injection: the wall of the blood vessels became irregular and the fluorescence signal displayed in the small vessels was gradually diminished. Paclitaxel had no vascular effect. CONCLUSION: We have established a platform of innovative high-resolution molecular imaging, suitable for in vivo imaging of vessels' characteristics, arterial blood flow and organs blood volume that enable prolonged real-time detection of chemotherapy-induced effects in the same individuals. The acute reduction in gonadal and femoral blood flow and the impairment of the blood vessels wall may represent an acute universal doxorubicin-related vascular toxicity, an initial event in organ injury

GROWTH on S190425z: Searching Thousands of Square Degrees to Identify an Optical or Infrared Counterpart to a Binary Neutron Star Merger with the Zwicky Transient Facility and Palomar Gattini-IR

The third observing run by LVC has brought the discovery of many compact binary coalescences. Following the detection of the first binary neutron star merger in this run (LIGO/Virgo S190425z), we performed a dedicated follow-up campaign with the Zwicky Transient Facility (ZTF) and Palomar Gattini-IR telescopes. The initial skymap of this single-detector gravitational wave (GW) trigger spanned most of the sky observable from Palomar Observatory. Covering 8000 deg2 of the initial skymap over the next two nights, corresponding to 46% integrated probability, ZTF system achieved a depth of ≈21 m AB in g- and r-bands. Palomar Gattini-IR covered 2200 square degrees in J-band to a depth of 15.5 mag, including 32% integrated probability based on the initial skymap. The revised skymap issued the following day reduced these numbers to 21% for the ZTF and 19% for Palomar Gattini-IR. We narrowed 338,646 ZTF transient "alerts" over the first two nights of observations to 15 candidate counterparts. Two candidates, ZTF19aarykkb and ZTF19aarzaod, were particularly compelling given that their location, distance, and age were consistent with the GW event, and their early optical light curves were photometrically consistent with that of kilonovae. These two candidates were spectroscopically classified as young core-collapse supernovae. The remaining candidates were ruled out as supernovae. Palomar Gattini-IR did not identify any viable candidates with multiple detections only after merger time. We demonstrate that even with single-detector GW events localized to thousands of square degrees, systematic kilonova discovery is feasible

GROWTH on GW190425: Searching thousands of square degrees to identify an optical or infrared counterpart to a binary neutron star merger with the Zwicky Transient Facility and Palomar Gattini IR

The beginning of the third observing run by the network of gravitational-wave detectors has brought the discovery of many compact binary coalescences. Prompted by the detection of the first binary neutron star merger in this run (GW190425 / LIGO/Virgo S190425z), we performed a dedicated follow-up campaign with the Zwicky Transient Facility (ZTF) and Palomar Gattini-IR telescopes. As it was a single gravitational-wave detector discovery, the initial skymap spanned most of the sky observable from Palomar Observatory, the site of both instruments. Covering 8000 deg$^2$ of the inner 99\% of the initial skymap over the next two nights, corresponding to an integrated probability of 46\%, the ZTF system achieved a depth of $\approx$\,21 $m_\textrm{AB}$ in $g$- and $r$-bands. Palomar Gattini-IR covered a total of 2200 square degrees in $J$-band to a depth of 15.5\,mag, including 32\% of the integrated probability based on the initial sky map. However, the revised skymap issued the following day reduced these numbers to 21\% for the Zwicky Transient Facility and 19\% for Palomar Gattini-IR. Out of the 338,646 ZTF transient "alerts" over the first two nights of observations, we narrowed this list to 15 candidate counterparts. Two candidates, ZTF19aarykkb and ZTF19aarzaod were particularly compelling given that their location, distance, and age were consistent with the gravitational-wave event, and their early optical lightcurves were photometrically consistent with that of kilonovae. These two candidates were spectroscopically classified as young core-collapse supernovae. The remaining candidates were photometrically or spectroscopically ruled-out as supernovae. Palomar Gattini-IR identified one fast evolving infrared transient after the merger, PGIR19bn, which was later spectroscopically classified as an M-dwarf flare. [abridged

Atherosclerosis: current concepts on pathogenesis and interventional therapies

Atherosclerosis, the primary pathological condition accounting for most stroke syndromes, has been the intense focus of epidemiological, basic, and clinical investigations. Since these studies have direct bearing on the prevention of atherothrombotic brain infarction, this review emphasizes those advances in treatment resulting from their findings. The two most prominent theories on the pathogenesis of atherosclerosis relate to aberrations in lipoprotein metabolism and to enhanced proliferation of smooth muscle cells; likely, the theories are complementary. As a practical guideline for preventive therapy, the importance of using the total cholesterol level is stressed, although finer distinctions must rely on the low-density and high-density lipoprotein concentrations and their normalization. Since prevention of stroke may ultimately be its most effective therapy, consideration of cholesterol level, akin to strategies for preventing coronary heart disease, and efforts to avert platelet adhesion or aggregation and coagulation are warranted