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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Role of lipids in the control of autophagy and primary cilium signaling in neurons

The brain is, after the adipose tissue, the organ with the greatest amount of lipids and diversity in their composition in the human body. In neurons, lipids are involved in signaling pathways controlling autophagy, a lysosome-dependent catabolic process essential for the maintenance of neuronal homeostasis and the function of the primary cilium, a cellular antenna that acts as a communication hub that transfers extracellular signals into intracellular responses required for neurogenesis and brain development. A crosstalk between primary cilia and autophagy has been established; however, its role in the control of neuronal activity and homeostasis is barely known. In this review, we briefly discuss the current knowledge regarding the role of autophagy and the primary cilium in neurons. Then we review the recent literature about specific lipid subclasses in the regulation of autophagy, in the control of primary cilium structure and its dependent cellular signaling in physiological and pathological conditions, specifically focusing on neurons, an area of research that could have major implications in neurodevelopment, energy homeostasis, and neurodegeneration

CD43 Promotes Cells Transformation by Preventing Merlin-Mediated Contact Inhibition of Growth

<div><p>In normal tissues, strict control of tissue size is achieved by regulating cell numbers. The mechanism that controls total cell number is known as contact inhibition of growth and it depends on the NF2/Merlin pathway. Negative regulation of this pathway by deleterious mutations or by oncogenes results in cell transformation and tumor progression. Here we provide evidence that the CD43 sialomucin cooperates with oncogenic signals to promote cell transformation by abrogating the contact inhibition of growth through a molecular mechanism that involves AKT-dependent Merlin phosphorylation and degradation. Accordingly, inhibition of endogenous CD43 expression by RNA interference in lung, cervix and colon human cancer cells impaired tumor growth <i>in vivo</i>. These data underscore a previously unidentified role for CD43 in non-hematopoietic tumor progression. </p> </div

CD43 expression confers tumoral fitness to human tumor-derived cells.

<p>A549 lung (<b>A</b>), CasKi cervix (<b>B</b>) or DLD-1 colon (<b>C</b>) tumor cells containing the empty pSuper (pSup) vector or expressing the CD43 specific RNAi (RNAi) were cultured to confluence, the monolayer was then wounded and healing was evaluated (upper panel). Cells were also cultured in soft agar as indicated in material and methods, after three weeks colonies were counted (middle panel). Cells (1X10⁶ for A549, 3X10⁶ for CasKi or DLD-1) were injected subcutaneously into nu/nu mice; one month later, animals were sacrificed and tumor weight was evaluated (lower panel). Data represents the average ± SD of four independent experiments performed with four independent pSup or RNAi clones for each cell line. *p < 0.05, **p < 0.01 vs pSup.</p

CD43 signaling targets the Merlin pathway.

<p>A549 clones containing the empty pSuper (pSup) vector or expressing the CD43 specific RNAi (RNAi) were grown to confluence (t=0) and further cultured for the indicated time points. At each time total cell extracts were prepared and the phosphorylation levels of STAT3 (p-STAT3), AKT (p-AKT), and GSK3β (p-GSK3) (<b>A</b>) as well as total Merlin levels (<b>B</b>) were determined by immunoblot, using specific antibodies. ERK protein levels were determined as loading control. <b>C</b>) Total cell extracts from A549 lung tumor cells cultured to confluence (t=0) or further cultured for 48 hrs in the absence (-) or presence of 20 μM LY294002 were resolved by SDS-PAGE and Merlin protein levels (Merlin) or phosphorylated AKT (pAKT) were evaluated by immunoblot with specific antibodies. ERK protein levels were used as loading control. <b>D</b>) A549 clones containing the empty pSuper (pSup) vector or expressing the CD43 specific RNAi (RNAi) were grown to confluence (t=0) and cultures were maintained for the indicated time points. Total cell extracts were prepared and the phosphorylation levels of YAP (p-YAP), ERK protein levels (loading control) were determined by immunoblot using specific antibodies. <b>E</b>) A549 clones expressing the empty pSuper (pSup) vector or the CD43 specific RNAi (RNAi) were grown to confluence and cultures were maintained in the absence or presence of 20 μM LY294002 (+LY) for 48 hrs. Cells were then harvested and counted. The graph represents the average cell number ± SD of three independent experiments using at least three independent clones. *p < 0.05, **p < 0.01 vs pSup.</p

Merlin mediates the inhibition of A549 cell proliferation by cell-cell contact.

<p><b>A</b>) A549 clones expressing the CD43 specific RNAi (RNAi) were transfected with non-specific (Ctl) or Merlin specific siRNAs (Merlin). 48 hrs after cells reached confluence total cell extract were prepared and Merlin protein levels (Merlin) as well as phosphorylated Yap levels (p-YAP) were evaluated by immunobloting using specific antibodies. Actin levels were used as loading control. <b>B</b>) The proliferation capacity of A549 clones expressing the CD43 specific RNAi (RNAi) transfected with non-specific (Ctl) or Merlin specific siRNA (Merlin) was evaluated at the indicated time points after cells reached confluence. Data represent the average of three independent experiments using two different clones.</p

CD43 signaling cooperates with oncogenic signals to promote cell transformation.

<p>In epithelial cells, upon interaction with putative ligand(s) present on the cell surface of neighboring cells or in the extracellular matrix, CD43 activates the PI3K/AKT pathway that results in the inhibition of the Hippo pathway by a mechanism involving Merlin phosphorylation and degradation, thus favoring cell survival and proliferation. Depending of the cellular context, signaling from intracellular CD43 located either on membrane vesicles or the nuclear membrane may also contribute to cellular transformation. Nonetheless, this might not be sufficient to overcome the anti-proliferative and death effects resulting from the activation of the ARF-p53 pathway also induced by CD43 [24]. However, in transformed cells with an impaired p53 pathway resulting from oncogenic signals like those provided by the E6 oncoprotein from HPV16, CD43 signaling promotes cells proliferation and tumor formation. </p

CD43 intracellular domain is required to promote cell transformation.

<p>Total cell extracts from A549 lung tumor cells stably containing the empty pFNeo vector (pFNeo) or expressing CD43 lacking the intracellular domain (ΔIC) were resolved on SDS-PAGE and transferred to nitrocellulose membranes. CD43 expression levels were determined by immunoblot using anti-CD43 specific antibodies (<b>A</b>). The arrowhead indicates the endogenous wild-type CD43 molecule; the bracket, the CD43 mutant lacking the intracellular domain. A549 lung tumor cells were grown to confluence, the monolayer was then wounded and healing was evaluated by light microscopy (<b>B</b>) or were grown in soft agar as described in material and methods and three weeks later colonies formed were counted (<b>C</b>). The data represents the average ± SD of three independent experiments. *p < 0.05, **p < 0.01 vs pFNeo.</p

CD43 signaling cooperates with oncogenic signals to promote cell transformation.

<p>NIH-3T3-hEGFR (<b>A</b>) or E6/E7 transgenic mouse fibroblasts (<b>C</b>) carrying the pFNeo empty vector (pFNeo), expressing wild-type CD43 (Wt) or CD43 lacking the intracellular domain (ΔIC) were grown to confluence; the monolayer was then wounded (t=0) and healing was evaluated by light microscopy at the indicated time points. NIH-3T3-hEGFR fibroblasts were grown in soft agar as described in material and methods; after three weeks, colonies were counted (<b>B</b>). E6 transgenic mouse fibroblasts stably transfected with the indicated constructs were grown to confluence for three weeks; foci were stained with Giemsa and counted (<b>D</b>). 3X10⁶ E6/E7 fibroblasts stably transfected were injected subcutaneously into nu/nu mice; one month later, animals were sacrificed and tumor mass was weighed (<b>E</b>). Data shown are representative of at least four independent experiments performed with at least four independent pFNeo, Wt or ΔIC clones from each cell line. Graphs represent the average cell number ± SD of three independent experiments using at least 3 independent clones. *p < 0.05 vs pFNeo.</p