Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions

Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV- 2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation, it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways, specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding end-organ tissue damage

Chemical Protection Studies of Activated Carbon Spheres based Permeable Protective Clothing Against Sulfur Mustard, a Chemical Warfare Agent

Technological advancements in the field of chemical threat have made it possible to create extremely dangerous chemical warfare agents (CWA). Hence, the effective protection of personnel is very important in a chemical warfare scenario amidst the current climate of terrorism awareness. In particular, body protection plays a substantial role in the chemical defence considering the urgency of situation in the nuclear, biological and chemical environment. Activated carbon spheres (ACS) based permeable chemical protective clothing (coverall) was developed for protection against CWA. The adsorbent material i.e, ACS used in this protective clothing provided higher adsorption capacity (1029 mg/g in terms of iodine) and low thermal burden (34 °C WBGT index) compared to earlier indigenously developed NBC suit. This article focuses on the extensive evaluation of chemical protective clothing against sulfur mustard (HD), a CWA. The results revealed that the developed protective clothing provided more than 24 h protection against HD. This chemical protective suit is light weight (< 2.75 kg for XL size). It also has higher air permeability (> 30 cm3/s/cm2) as well as less water vapour resistance (< 9.6 m2Pa/W). With continued innovations in materials and attention to key challenges it is expected that advanced, multifunction chemical protective suit will play a pivotal role in the CWA protection scenario

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

An interesting case report of vertebral artery dissection following polytrauma

Introduction: The authors present an interesting case of a 19-year-old male who presented as a polytrauma patient following a fall from a height. Presentation of case: He was initially managed on the intensive care unit with intracranial pressure bolt monitoring after being intubated and sedated and having his other traumatic injuries stabilized. Upon attempting to wean sedation and extubation a repeat CT scan of the head was undertaken and showed a new area suggested of cerebral infarction, this was a new finding. Further imaging found that he had a cervical vertebral artery dissection following this polytrauma mode of injury. Discussion: The incidence of vertebral artery dissection following generalized or local trauma is rising but routine imaging/screening in these patients is not undertaken. Conclusion: Our report displays select images related to this case report and emphasizes the consideration of routine imaging in head and neck traumatic injuries to diagnose internal carotid and/or vertebral artery dissections much earlier

Anxiolytic activity of Indian <i>Abies pindrow </i>Royle leaves in rodents: An experimental study

343-346Putative anxiolytic activity of ethanolic extract of Indian A. pindrow Royle leaf was investigated in rats using various experimental paradigms of anxiety viz. open field exploratory behaviour, elevated plus maze (EPM) and elevated zero maze (EZM) tests. Pilot studies indicated that single dose administration of extract had little to no acute behavioural effects, hence the extract was administered orally at different dose levels once daily for three consecutive days, while lorazepam (LR) (0.5 mg/kg, ip) was administered acutely. Ethanolic extract of A. pindrow (AP) leaves (50 and 100 mg/kg, po) showed significant anxiolytic effects on all the paradigms of anxiety. The results indicate that AP and LR induced a significant increase in open field ambulation and slight increase in rearings and activity in center, whereas grooming and faecal droppings remain unchanged. In EPM, significant augmentation of open arm entries, and time spent on open arms was noted in AP treated rats. In EZM test, significant increase in time spent on open arms and entries in open arms was observed, whereas slight increase in head dips and stretched attend postures was also observed. The AP extract showed consistent and significant anxiolytic activity in all the tests. The effects induced by ethanolic extract of AP were less marked than those of lorazepam were

Dimerization specificity of all 67 B-ZIP motifs in Arabidopsis thaliana: a comparison to Homo sapiens B-ZIP motifs

Basic region-leucine zipper (B-ZIP) proteins are a class of dimeric sequence-specific DNA-binding proteins unique to eukaryotes. We have identified 67 B-ZIP proteins in the Arabidopsis thaliana genome. No A.thaliana B-ZIP domains are homologous with any Homo sapiens B-ZIP domains. Here, we predict the dimerization specificity properties of the 67 B-ZIP proteins in the A.thaliana genome based on three structural properties of the dimeric α-helical leucine zipper coiled coil structure: (i) length of the leucine zipper, (ii) placement of asparagine or a charged amino acid in the hydrophobic interface and (iii) presence of interhelical electrostatic interactions. Many A.thaliana B-ZIP leucine zippers are predicted to be eight or more heptads in length, in contrast to the four or five heptads typically found in H.sapiens, a prediction experimentally verified by circular dichroism analysis. Asparagine in the a position of the coiled coil is typically observed in the second heptad in H.sapiens. In A.thaliana, asparagine is abundant in the a position of both the second and fifth heptads. The particular placement of asparagine in the a position helps define 14 families of homodimerizing B-ZIP proteins in A.thaliana, in contrast to the six families found in H.sapiens. The repulsive interhelical electrostatic interactions that are used to specify heterodimerizing B-ZIP proteins in H.sapiens are not present in A.thaliana. Instead, we predict that plant leucine zippers rely on charged amino acids in the a position to drive heterodimerization. It appears that A.thaliana define many families of homodimerizing B-ZIP proteins by having long leucine zippers with asparagine judiciously placed in the a position of different heptads