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

Bacterial transport of colloids in liquid crystalline environments † Soft Matter COMMUNICATION

We describe the controlled transport and delivery of non-motile eukaryotic cells and polymer microparticles by swimming bacteria suspended in nematic liquid crystals. The bacteria push reversibly attached cargo in a stable, unidirectional path (or along a complex patterned director field) over exceptionally long distances. Numerical simulations and analytical predictions for swimming speeds provide a mechanistic insight into the hydrodynamics of the system. This study lays the foundation for using cargo-carrying bacteria in engineering applications and for understanding interspecies interactions in polymicrobial communities. The manipulation of microscale structures is an unsolved challenge in microengineering and microtechnology. One approach has been to harness the mechanical work performed by cells, which takes advantage of their metabolism and motility machinery to convert chemical energy to motion in a wide range of chemical and physical environments. Bacteria have been the source of additional studies on microstructure transport as they are fast (velocities approaching E100 mm s À1 ) and adaptable, genetic tools are widely available for engineering their properties and behavior, and a range of mechanisms can be exploited to control their motion, including: concentration gradients of ions and chemicals, magnetic fields, light, heat, oxygen, and redox potential. 5,6 Many rod-shaped bacteria swim through fluids by rotating their flagella in a counterclockwise direction to form a bundle and &apos;run&apos;. Rotating a flagellum in the clockwise direction alters the structure of the bundle and reorients cells, which creates an event referred to as a &apos;tumble&apos;. Controlling the motion of many flagellated bacteria is complicated by run and tumble dynamics; 7 accordingly, bacteria-based motility of microscale objects is highly challenging, as it is difficult to place objects on cells without disrupting and inhibiting normal cell behavior. Applications relying on chemotaxis to move small cargo pose similar challenges due to spatial and temporal instability of chemical gradients. 9 A new method for directing bacterial motion without channels or gradients was recently developed, in which motile bacteria are suspended in solutions of nematic, lyotropic liquid crystals (LCs) consisting of disodium cromoglycate (DSCG). 13 In this Communication we describe the environmental relevance of the controlled transport and delivery of microparticles by swimming bacteria. We show that freely swimming P. mirabilis bacteria can push non-motile fungal cells in a stable, unidirectional path over long distances. By patterning a complex director profile in the fluid, the bacteria and cargo may be guided along a predefined path. Experiments with polymer microparticles, numerical simulations based on isotropi

Bacterial transport of colloids in liquid crystalline environments † Soft Matter COMMUNICATION

We describe the controlled transport and delivery of non-motile eukaryotic cells and polymer microparticles by swimming bacteria suspended in nematic liquid crystals. The bacteria push reversibly attached cargo in a stable, unidirectional path (or along a complex patterned director field) over exceptionally long distances. Numerical simulations and analytical predictions for swimming speeds provide a mechanistic insight into the hydrodynamics of the system. This study lays the foundation for using cargo-carrying bacteria in engineering applications and for understanding interspecies interactions in polymicrobial communities. The manipulation of microscale structures is an unsolved challenge in microengineering and microtechnology. One approach has been to harness the mechanical work performed by cells, which takes advantage of their metabolism and motility machinery to convert chemical energy to motion in a wide range of chemical and physical environments. Bacteria have been the source of additional studies on microstructure transport as they are fast (velocities approaching E100 mm s À1 ) and adaptable, genetic tools are widely available for engineering their properties and behavior, and a range of mechanisms can be exploited to control their motion, including: concentration gradients of ions and chemicals, magnetic fields, light, heat, oxygen, and redox potential. 5,6 Many rod-shaped bacteria swim through fluids by rotating their flagella in a counterclockwise direction to form a bundle and &apos;run&apos;. Rotating a flagellum in the clockwise direction alters the structure of the bundle and reorients cells, which creates an event referred to as a &apos;tumble&apos;. Controlling the motion of many flagellated bacteria is complicated by run and tumble dynamics; 7 accordingly, bacteria-based motility of microscale objects is highly challenging, as it is difficult to place objects on cells without disrupting and inhibiting normal cell behavior. Applications relying on chemotaxis to move small cargo pose similar challenges due to spatial and temporal instability of chemical gradients. 9 A new method for directing bacterial motion without channels or gradients was recently developed, in which motile bacteria are suspended in solutions of nematic, lyotropic liquid crystals (LCs) consisting of disodium cromoglycate (DSCG). 13 In this Communication we describe the environmental relevance of the controlled transport and delivery of microparticles by swimming bacteria. We show that freely swimming P. mirabilis bacteria can push non-motile fungal cells in a stable, unidirectional path over long distances. By patterning a complex director profile in the fluid, the bacteria and cargo may be guided along a predefined path. Experiments with polymer microparticles, numerical simulations based on isotropi

Mechanical Genomic Studies Reveal the Role of d-Alanine Metabolism in Pseudomonas aeruginosa Cell Stiffness

The mechanical properties of bacteria are important for protecting cells against physical stress. The cell wall is the best-characterized cellular element contributing to bacterial cell mechanics; however, the biochemistry underlying its regulation and assembly is still not completely understood. Using a unique high-throughput biophysical assay, we identified genes coding proteins that modulate cell stiffness in the opportunistic human pathogen Pseudomonas aeruginosa. This approach enabled us to discover proteins with roles in a diverse range of biochemical pathways that influence the stiffness of P. aeruginosa cells. We demonstrate that d-Ala—a component of the peptidoglycan—is tightly regulated in cells and that its accumulation reduces expression of machinery that cross-links this material and decreases cell stiffness. This research demonstrates that there is much to learn about mechanical regulation in bacteria, and these studies revealed new nonessential P. aeruginosa targets that may enhance antibacterial chemotherapies or lead to new approaches.The stiffness of bacteria prevents cells from bursting due to the large osmotic pressure across the cell wall. Many successful antibiotic chemotherapies target elements that alter mechanical properties of bacteria, and yet a global view of the biochemistry underlying the regulation of bacterial cell stiffness is still emerging. This connection is particularly interesting in opportunistic human pathogens such as Pseudomonas aeruginosa that have a large (80%) proportion of genes of unknown function and low susceptibility to different families of antibiotics, including beta-lactams, aminoglycosides, and quinolones. We used a high-throughput technique to study a library of 5,790 loss-of-function mutants covering ~80% of the nonessential genes and correlated P. aeruginosa individual genes with cell stiffness. We identified 42 genes coding for proteins with diverse functions that, when deleted individually, decreased cell stiffness by >20%. This approach enabled us to construct a “mechanical genome” for P. aeruginosa. d-Alanine dehydrogenase (DadA) is an enzyme that converts d-Ala to pyruvate that was included among the hits; when DadA was deleted, cell stiffness decreased by 18% (using multiple assays to measure mechanics). An increase in the concentration of d-Ala in cells downregulated the expression of genes in peptidoglycan (PG) biosynthesis, including the peptidoglycan-cross-linking transpeptidase genes ponA and dacC. Consistent with this observation, ultraperformance liquid chromatography-mass spectrometry analysis of murein from P. aeruginosa cells revealed that dadA deletion mutants contained PG with reduced cross-linking and altered composition compared to wild-type cells

Divin: A Small Molecule Inhibitor of Bacterial Divisome Assembly

Bacterial cell division involves the dynamic assembly of division proteins and coordinated constriction of the cell envelope. A wide range of factors regulates cell divisionincluding growth and environmental stressesand the targeting of the division machinery has been a widely discussed approach for antimicrobial therapies. This paper introduces divin, a small molecule inhibitor of bacterial cell division that may facilitate mechanistic studies of this process. Divin disrupts the assembly of late division proteins, reduces peptidoglycan remodeling at the division site, and blocks compartmentalization of the cytoplasm. In contrast to other division inhibitors, divin does not interact with the tubulin homologue FtsZ, affect chromosome segregation, or activate regulatory mechanisms that inhibit cell division indirectly. Our studies of bacterial cell division using divin as a probe suggest that dividing bacteria proceed through several morphological stages of the cell envelope, and FtsZ is required but not sufficient to compartmentalize the cytoplasmic membrane at the division site. Divin is only moderately toxic to mammalian cells at concentrations that inhibit the growth of clinical pathogens. These characteristics make divin a useful probe for studying bacterial cell division and a starting point for the development of new classes of therapeutic agents

Divin: A Small Molecule Inhibitor of Bacterial Divisome Assembly

Bacterial cell division involves the dynamic assembly of division proteins and coordinated constriction of the cell envelope. A wide range of factors regulates cell divisionincluding growth and environmental stressesand the targeting of the division machinery has been a widely discussed approach for antimicrobial therapies. This paper introduces divin, a small molecule inhibitor of bacterial cell division that may facilitate mechanistic studies of this process. Divin disrupts the assembly of late division proteins, reduces peptidoglycan remodeling at the division site, and blocks compartmentalization of the cytoplasm. In contrast to other division inhibitors, divin does not interact with the tubulin homologue FtsZ, affect chromosome segregation, or activate regulatory mechanisms that inhibit cell division indirectly. Our studies of bacterial cell division using divin as a probe suggest that dividing bacteria proceed through several morphological stages of the cell envelope, and FtsZ is required but not sufficient to compartmentalize the cytoplasmic membrane at the division site. Divin is only moderately toxic to mammalian cells at concentrations that inhibit the growth of clinical pathogens. These characteristics make divin a useful probe for studying bacterial cell division and a starting point for the development of new classes of therapeutic agents