Evaluation of potential miRNA sponge effects of SARS genomes in human

: To date the coronavirus family is composed of seven different viruses which were commonly known as cold viruses until the appearance of the severe acute respiratory coronavirus (SARS-CoV) in 2002, the middle east respiratory syndrome coronavirus (MERS) in 2012 and the severe acute respiratory coronavirus 2 (SARS-CoV-2) which caused the COVID-19 global pandemic in 2019. Using bioinformatic approaches we tested the potential interactions of human miRNAs, expressed in pulmonary epithelial cells, with the available coronavirus genomes. Putative miRNA binding sites were then compared between pathogenic and non pathogenic virus groups. The pathogenic group shares 6 miRNA binding sites that can be potentially involved in the sequestration of miRNAs already known to be associated with deep vein thrombosis. We then analysed ∼100k SARS-CoV-2 variant genomes for their potential interaction with human miRNAs and this study highlighted a group of 97 miRNA binding sites which is present in all the analysed genomes. Among these, we identified 6 miRNA binding sites specific for SARS-CoV-2 and the other two pathogenic viruses whose down-regulation has been seen associated with deep vein thrombosis and cardiovascular diseases. Interestingly, one of these miRNAs, namely miR-20a-5p, whose expression decreases with advancing age, is involved in cytokine signaling, cell differentiation and/or proliferation. We hypothesize that depletion of poorly expressed miRNA could be related with disease severity

Experimental Assessment of Cuff Pressures on the Walls of a Trachea-Like Model Using Force Sensing Resistors: Insights for Patient Management in Intensive Care Unit Settings

The COVID-19 outbreak has increased the incidence of tracheal lesions in patients who underwent invasive mechanical ventilation. We measured the pressure exerted by the cuff on the walls of a test bench mimicking the laryngotracheal tract. The test bench was designed to acquire the pressure exerted by endotracheal tube cuffs inflated inside an artificial model of a human trachea. The experimental protocol consisted of measuring pressure values before and after applying a maneuver on two types of endotracheal tubes placed in two mock-ups resembling two different sized tracheal tracts. Increasing pressure values were used to inflate the cuff and the pressures were recorded in two different body positions. The recorded pressure increased proportionally to the input pressure. Moreover, the pressure values measured when using the non-armored (NA) tube were usually higher than those recorded when using the armored (A) tube. A periodic check of the cuff pressure upon changing the body position and/or when performing maneuvers on the tube appears to be necessary to prevent a pressure increase on the tracheal wall. In addition, in our model, the cuff of the A tube gave a more stable output pressure on the tracheal wall than that of the NA tube

Autologous bone marrow mononuclear cells (Bmmcs) for the treatment of uncomplicated grade 2 ununited anconeal process (uap) in six dogs: Preliminary results

The aim of this study was to report the results of autologous bone marrow mononuclear cell (BMMC) transplantation as a minimally invasive treatment for grade 2 UAP in dogs. This was an observational case series on six German shepherd dogs affected by grade 2 UAP as defined according to their clinical condition as well as radiographic and CT findings. Bone marrow was collected from the iliac crest and the mononuclear fraction was separated with density gradient centrifugation. Cells were suspended in fibrin glue before BMMC administration and implanted via transcutaneous injection under IB or CT guidance, using a spinal needle directly inserted into the ossification centre between the anconeal process and the olecranon. Clinical and radiographic follow-up was performed for up to 6 months. Microradiographic assessment was performed on one dog that died of other causes. A progressive reduction of pain within 3 weeks after BMMC administration was observed in all dogs, with gradually increased weight bearing on the affected limb. Radiographic and CT follow-up revealed the progressive fusion of the ossification centre at 90 days without any signs of secondary OA. The examination of microradiographs showed newly formed bone tissue in which a residue of calcified cartilage was present at the site of BMMC implantation. On the basis of these results, BMMC therapy for grade 2 UAP may be considered to be an effective and minimally invasive treatment option for dogs

Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan

Jugular vein distensibility predicts fluid responsiveness in septic patients

Introduction: The purpose of the study was to verify the efficacy of using internal jugular vein (IJV) size and distensibility as a reliable index of fluid responsiveness in mechanically ventilated patients with sepsis. Methods: Hemodynamic data of mechanically ventilated patients with sepsis were collected through a radial arterial indwelling catheter connected to continuous hemodynamic monitoring system (Most Care®, Vytech Health, Padova, Italy), including cardiac index (CI) (L/min/M2), heart rate (beats/min), mean arterial pressure (MAP) (mmHg), central venous pressure (CVP) (mmHg) and arterial pulse pressure variation (PPV), coupled with ultrasound evaluation of IJV distensibility (%), defined as a ratio of the difference between IJV maximal antero-posterior diameter during inspiration and minimum expiratory diameter to minimum expiratory diameter x100. Patients were retrospectively divided into two groups; fluid responders (R), if CI increase of more than or equal to 15% after a 7 ml/kg crystalloid infusion, and non-responders (NR) if CI increased more than 15%. We compared differences in measured variables between R and NR groups and calculated receiver-operator-characteristic (ROC) curves of optimal IJV distensibility and PPV sensitivity and specificity to predicting R. We also calculated a combined inferior vena cava distensibility-PPV ROC curve to predict R. Results: We enrolled 50 patients, of these, 30 were R. Responders presented higher IJV distensibility and PPV before fluid challenge than NR (P <0.05). An IJV distensibility more than 18% prior to volume challenge had an 80% sensitivity and 85% specificity to predict R. Pairwise comparison between IJV distensibility and PPV ROC curves revealed similar ROC area under the curve results. Interestingly, combining IJV distensibility more than 9.7% and PPV more than 12% predicted fluid responsiveness with a sensitivity of 100% and specificity of 95%. Conclusion: IJV distensibility is an accurate, easily acquired non-invasive parameter of fluid responsiveness in mechanically ventilated septic patients with performance similar to PPV. The combined use of IJV distensibility with left-sided indexes of fluid responsiveness improves their predictive value

Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study

PURPOSE: Ventricular–arterial (V–A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV). METHODS: After at least 24 h of hemodynamic optimization, 45 septic shock patients, with an HR ≥95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) ≥65 mmHg, received a titrated esmolol infusion to maintain HR between 80 and 94 bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis, and norepinephrine requirements, were obtained at baseline and at 4 h after commencing esmolol. RESULTS: Esmolol reduced HR in all patients and this was associated with a decrease in Ea (2.19 ± 0.77 vs. 1.72 ± 0.52 mmHg l−1), arterial dP/dtmax (1.08 ± 0.32 vs. 0.89 ± 0.29 mmHg ms−1), and a parallel increase in SV (48 ± 14 vs. 59 ± 18 ml), all p < 0.05. Cardiac output and ejection fraction remained unchanged, whereas norepinephrine requirements were reduced (0.7 ± 0.7 to 0.58 ± 0.5 µg kg−1 min−1, p < 0.05). CONCLUSIONS: HR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V–A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock

Early and late improvement of global and regional left ventricular function after transcatheter aortic valve implantation in patients with severe aortic stenosis: an echocardiographic study.

The recent development of transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) treatment offers a viable option for high-risk patient categories. Our aim is to evaluate whether 2D strain and strain rate can detect subtle improvement in global and regional LV systolic function immediately after TAVI. 2D conventional and 2D strain (speckle analysis) echocardiography was performed before, at discharge and after three months in thirty three patients with severe AS. After TAVI, we assessed by conventional echocardiography an immediate reduction of transaortic peak pressure gradient (p<0.0001), of mean pressure gradient (p<0.0001) and a concomitant increase in aortic valve area (AVA: 1.08±0.31 cm(2)/m(2); p<0.0001). 2D longitudinal systolic strain showed a significant improvement in all patients, both at septal and lateral level, as early as 72 h after procedure (septal: -14.2±5.1 vs -16.7±3.7%, p<0.001; lateral: -9.4±3.9 vs -13.1±4.5%, p<0.001; respectively) and continued at 3 months follow-up (septal: -18.1±4.6%, p<0.0001; lateral: -14.8±4.4%, p<0.0001; respectively). Conventional echocardiography after TAVI proved a significant reduction of LV end-systolic volume and of LV mass with a mild improvement of LV ejection fraction (EF) (51.2±11.8 vs 52.9±6.4%; p<0.02) only after three months. 2D strain seems to be able to detect subtle changes in LV systolic function occurring early and late after TAVI in severe AS, while all conventional echo parameters seem to be less effective for this purpose. Further investigations are needed to prove the real prognostic impact of these echocardiographic findings

Natural ventilation in urban areas : results of the European Project URBVENT Part 1: urban environment

The application of natural ventilation is more difficult in urban than in rural environment, especially in street canyons due to reduced wind velocity, urban heat island, noise and pollution, which are considered to be important barriers to the application of natural ventilation. The wind, temperature, noise attenuation and outdoor-indoor pollution transfer were measured in a large range of variation and various types of urban configuration. The models obtained can be used in the initial stages of building design in order to assess the viability of natural ventilation in urban environment, especially in street canyons

Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives

The anteroposterior axial identity of motor neurons (MNs) determines their functionality and vulnerability to neurodegeneration. Thus, it is a crucial parameter in the design of strategies aiming to produce MNs from human pluripotent stem cells (hPSCs) for regenerative medicine/disease modelling applications. However, the in vitro generation of posterior MNs corresponding to the thoracic/lumbosacral spinal cord has been challenging. Although the induction of cells resembling neuromesodermal progenitors (NMPs), the bona fide precursors of the spinal cord, offers a promising solution, the progressive specification of posterior MNs from these cells is not well defined. Here, we determine the signals guiding the transition of human NMP-like cells toward thoracic ventral spinal cord neurectoderm. We show that combined WNT-FGF activities drive a posterior dorsal pre-/early neural state, whereas suppression of TGFβ-BMP signalling pathways promotes a ventral identity and neural commitment. Based on these results, we define an optimised protocol for the generation of thoracic MNs that can efficiently integrate within the neural tube of chick embryos. We expect that our findings will facilitate the comparison of hPSC-derived spinal cord cells of distinct axial identities