Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Producción enzimática de ésteres de citronelol.

The citronellol esters are component of the essential oils with diverse uses in the pharmaceutical, cosmetic and food industry. These compounds can be obtained by alcoholysis using chemical catalysts or biocatalysts. In this investigation the enzymatic synthesis of the same ones is evaluated starting from vegetable oils and citronellol, being carried out a screening with four commercial lipases in two different reaction systems.Los ésteres de citronelol son componentes de los aceites esenciales con diversos usos en la industria farmacéutica, cosmética y alimenticia. Estos compuestos pueden obtenerse por alcoholisis usando catalizadores químicos o biocatalizadores. En esta investigación se evalúa la síntesis enzimática de los mismos a partir de aceites vegetales y citronelol, realizándose un screening con cuatro lipasas comerciales en dos sistemas de reacción diferentes

N-terminal region is responsible for mHv1 channel activity in MDSCs

Voltage-gated proton channels (Hv1) are important regulators of the immunosuppressive function of myeloid-derived suppressor cells (MDSCs) in mice and have been proposed as a potential therapeutic target to alleviate dysregulated immunosuppression in tumors. However, till date, there is a lack of evidence regarding the functioning of the Hvcn1 and reports on mHv1 isoform diversity in mice and MDSCs. A computational prediction has suggested that the Hvcn1 gene may express up to six transcript variants, three of which are translated into distinct N-terminal isoforms of mHv1: mHv1.1 (269 aa), mHv1.2 (269 + 42 aa), and mHv1.3 (269 + 4 aa). To validate this prediction, we used RT-PCR on total RNA extracted from MDSCs, and the presence of all six predicted mRNA variances was confirmed. Subsequently, the open-reading frames (ORFs) encoding for mHv1 isoforms were cloned and expressed in Xenopus laevis oocytes for proton current recording using a macro-patch voltage clamp. Our findings reveal that all three isoforms are mammalian mHv1 channels, with distinct differences in their activation properties. Specifically, the longest isoform, mHv1.2, displays a right-shifted conductance–voltage (GV) curve and slower opening kinetics, compared to the mid-length isoform, mHv1.3, and the shortest canonical isoform, mHv1.1. While mHv1.3 exhibits a V0.5 similar to that of mHv1.1, mHv1.3 demonstrates significantly slower activation kinetics than mHv1.1. These results suggest that isoform gating efficiency is inversely related to the length of the N-terminal end. To further explore this, we created the truncated mHv1.2 ΔN20 construct by removing the first 20 amino acids from the N-terminus of mHv1.2. This construct displayed intermediate activation properties, with a V0.5 value lying intermediate of mHv1.1 and mHv1.2, and activation kinetics that were faster than that of mHv1.2 but slower than that of mHv1.1. Overall, these findings indicate that alternative splicing of the N-terminal exon in mRNA transcripts encoding mHv1 isoforms is a regulatory mechanism for mHv1 function within MDSCs. While MDSCs have the capability to translate multiple Hv1 isoforms with varying gating properties, the Hvcn1 gene promotes the dominant expression of mHv1.1, which exhibits the most efficient gating among all mHv1 isoforms.Fil: Peña Pichicoi, Antonio. Universidad de Valparaíso; ChileFil: Fernández, Miguel. Universidad de Valparaíso; ChileFil: Navarro Quezada, Nieves. Universidad de Valparaíso; ChileFil: Alvear Arias, Juan José. Universidad de Valparaíso; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Carrillo, Christian A.. Universidad de Valparaíso; ChileFil: Carmona, Emerson M.. Texas Tech University Health Sciences Center; Estados UnidosFil: Gárate, José Antonio. Universidad de Valparaíso; Chile. Universidad San Sebastián; ChileFil: Lopez Rodriguez, Angelica M.. Universidad Juárez del Estado de Durango; MéxicoFil: Neely, Alan. Universidad de Valparaíso; ChileFil: Hernández Ochoa, Erick O.. University of Maryland; Estados UnidosFil: González, Carlos. Universidad de Valparaíso; Chile. University of Miami; Estados Unido

Definition and classification of individual interventions (coverage) (based on [22]).

a<p>Endocrine therapy consists of 20 mg tamoxifen per day for 5 years.</p>b<p>Down-staging interventions cause a shift in stage distribution and are only modeled in combination with treatment of all stages (I–IV).</p>c<p>BAR was excluded as a standalone intervention in Costa Rica and Mexico.</p>d<p>Palliative care interventions are only applied to stage IV patients, and substitutes stage IV treatment.</p>e<p>The (neo)adjuvant chemotherapy combination regimen consists of 7 cycles of Epirubicin, Fluorouracil and cyclophosphamide (FEC regimen) Given on an outpatient basis.</p>f<p>Radiotherapy includes a standard dose of 50 Gy given in 25 fractions of 2 Gy on an outpatient basis.</p>g<p>Trastuzumab is given for 8 months.</p

Costa Rica - Results of sensitivity analysis on average cost-effectiveness ratio (ACER).

a<p>Alternative stage distribution: 9.4% stage I, 14.2% stage II, 58.0% stage III, 18.4% stage IV <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095836#pone.0095836-Groot1" target="_blank">[7]</a>.</p>b<p>Alternative Case Fatality rates; 0,0174 stage I, 0,0284 stage II, 0,0832 stage III, 0,2855 stage IV <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095836#pone.0095836-Ortiz1" target="_blank">[24]</a>.</p>c<p>Mechanical equipment (e.g. mammography machines, CT, X-ray).</p>d<p>Alternative assumptions on effectiveness of awareness interventions (−25%), sensitivity of CBE, and stage shifts of CBE screening.</p

Graphical representation of the model showing the relationships between the different health states through the incidence rates of breast cancer (Ix1–Ix4), the different stage specific case fatality rates (Fx1–4), and the background mortality (M) [7].

<p>Stage specific relapse rates to stage IV were used to correct health state valuations only (Rx1–Rx3).</p

Costa Rica - Average costs (US$), effects and cost-effectiveness of breast cancer control scenarios per year.

a<p>All costs in this table are in 2009 US$(1CRC = 0,001784 US$).</p>b<p>DALYs, disability-adjusted life-years (age weighted, discounted).</p>c<p>ACER: Average cost-effectiveness ratio compared to the do nothing-scenario (US$per DALY averted).</p>d<p>ICER: Incremental cost effectiveness ratio, ratio of additional cost per additional life-year saved when next intervention is added to a mix on the intervention path (additional US$ per additional DALY saved).</p

Mexico- Results of sensitivity analysis on average cost-effectiveness ratio (ACER).

a<p>Unidad de Análisis Económico - 8.4% stage I, 38.5% stage II, 42.5% stage III, 10.6% stage IV <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095836#pone.0095836-Comisin1" target="_blank">[42]</a>.</p>b<p>9.7% stage I, 52.7% stage II, 34.8% stage III, 2.8% stage IV <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095836#pone.0095836-FloresLuna1" target="_blank">[41]</a>.</p>c<p>9.4% stage I, 14.2% stage II, 58.0% stage III, 18.4% stage IV <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095836#pone.0095836-Groot1" target="_blank">[7]</a>.</p>d<p>Alternative Case Fatality rates: 0,013 stage I, 0,042 stage II, 0,102 stage III, 0,266 stage IV <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095836#pone.0095836-Salomon1" target="_blank">[35]</a>.</p>e<p>Mechanical equipment (e.g. mammography machines, CT, X-ray).</p>f<p>Alternative assumptions on effectiveness of awareness interventions (−25%), sensitivity of CBE, and stage shifts of CBE screening.</p

Average utilization of diagnosis and treatment ingredients and unit costs per patient.

a<p>Based on estimates by Costa Rican CCSS.</p>b<p>Unit costs WHO-CHOICE database in 2000 US. Corrected for inflation: 2000–2009 (2.81 in CR & 1.66 in MX). 2009 exchange rates were used (560.45 CRC/US & 13.06 MXN/US$).</p>c<p>Based on values of IMSS.</p>d<p>Based on communication with Unidad de Análisis Económico of MoH.</p>e<p>Based on Norum et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095836#pone.0095836-Norum1" target="_blank">[61]</a>.</p>f<p>Based on Knaul et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095836#pone.0095836-Knaul1" target="_blank">[11]</a>.</p>g<p>palliative care (substitutes stage IV treatment).</p>h<p>50 Gy given in 25 fractions of 2 Gy.</p>i<p>daily dose of 20 mg. Tamoxifen for 5 years.</p>j<p>7 cycles of Epirubicin, Fluorouracil and cyclophosphamide (FEC regimen).</p>k<p>1 fraction of 10 Gy.</p>l<p>40 ml/54 s days.</p>m<p>35 mg/54 days.</p>n<p>8 mg/day.</p>o<p>751mg/day.</p>p<p>5 mg/day.</p