Generation of Biologically Contained Marburg Virus.

Wild-type Marburg virus (MARV) can only be handled in biosafety level 4 facilities. By removing an essential gene from the virus genome, deficient virus particles can be generated that are only capable of replication if the missing gene product is provided in trans. As a result, these viruses are restricted to specific cell lines, making them safe to handle at lower biosafety levels.

Cellular electrical impedance to profile SARS-CoV-2 fusion inhibitors and to assess the fusogenic potential of spike mutants.

Despite the vaccination campaigns for COVID-19, we still cannot control the spread of SARS-CoV-2, as evidenced by the ongoing circulation of the Omicron variants of concern. This highlights the need for broad-spectrum antivirals to further combat COVID-19 and to be prepared for a new pandemic with a (re-)emerging coronavirus. An interesting target for antiviral drug development is the fusion of the viral envelope with host cell membranes, a crucial early step in the replication cycle of coronaviruses.

Structural insights into TRAP association with ribosome-Sec61 complex and translocon inhibition by a CADA derivative.

During cotranslational translocation, the signal peptide of a nascent chain binds Sec61 translocon to initiate protein transport through the endoplasmic reticulum (ER) membrane. Our cryo-electron microscopy structure of ribosome-Sec61 shows binding of an ordered heterotetrameric translocon-associated protein (TRAP) complex, in which TRAP-γ is anchored at two adjacent positions of 28 ribosomal RNA and interacts with ribosomal protein L38 and Sec61α/γ. Four transmembrane helices (TMHs) of TRAP-γ cluster with one C-terminal helix of each α, β, and δ subunits.

Development and optimization of biologically contained Marburg virus for high-throughput antiviral screening.

Comparable to the related Ebola virus, Marburg virus is an emerging zoonotic pathogen that causes hemorrhagic fever with a high mortality rate. Therefore, handling of Ebola virus and Marburg virus is limited to biosafety level 4 facilities, of which only a limited number exists worldwide. However, researchers have developed several virus alternatives that are safe to handle in lower biosafety settings.

Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern.

agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UDA as a broad-spectrum antiviral agent against SARS-CoV-2.

SARS-CoV-2 Permissive glioblastoma cell line for high throughput antiviral screening.

Despite the great success of the administered vaccines against SARS-CoV-2, the virus can still spread, as evidenced by the current circulation of the highly contagious Omicron variant. This emphasizes the additional need to develop effective antiviral countermeasures. In the context of early preclinical studies for antiviral assessment, robust cellular infection systems are required to screen drug libraries.

Intracellular flow cytometry complements RT-qPCR detection of circulating SARS-CoV-2 variants of concern.

Basic and antiviral research on SARS-CoV-2 rely on cellular assays of virus replication . In addition, accurate detection of virus-infected cells and released virus particles is needed to study virus replication and to profile new candidate antiviral drugs. Here, by flow cytometry, we detect SARS-CoV-2 infection at single cell level and distinguish infected Vero E6 cells from uninfected bystander cells.

Identification of novel Ebola virus inhibitors using biologically contained virus.

Despite recent advancements in the development of vaccines and monoclonal antibody therapies for Ebola virus disease, treatment options remain limited. Moreover, management and containment of Ebola virus outbreaks is often hindered by the remote nature of the locations in which the outbreaks originate. Small-molecule compounds offer the advantage of being relatively cheap and easy to produce, transport and store, making them an interesting modality for the development of novel therapeutics against Ebola virus disease.

A Proteomic Study on the Membrane Protein Fraction of T Cells Confirms High Substrate Selectivity for the ER Translocation Inhibitor Cyclotriazadisulfonamide.

Cyclotriazadisulfonamide (CADA) inhibits the cotranslational translocation of type I integral membrane protein human CD4 (huCD4) across the endoplasmic reticulum in a signal peptide (SP)-dependent way. Previously, sortilin was identified as a secondary substrate for CADA but showed reduced CADA sensitivity as compared with huCD4. Here, we performed a quantitative proteomic study on the crude membrane fraction of human T-cells to analyze how many proteins are sensitive to CADA.

Advancing Marburg virus antiviral screening: Optimization of a novel T7 polymerase-independent minigenome system.

Marburg virus (MARV) is the only known pathogenic filovirus not belonging to the genus Ebolavirus. Minigenomes have proven a useful tool to study MARV, but all existing MARV minigenomes are dependent on the addition of an exogenous T7 RNA polymerase to drive minigenome expression. However, exogenous expression of a T7 polymerase is not always feasible and can act as a confounding factor in compound screening assays.

Cocaine-Induced Pneumopericardium: Safe for Discharge? A Case Report and Literature Review.

A 29-year-old male presented at the Emergency Department (ED) with chest pain and neck tenderness after intranasal cocaine usage. Physical exam of the patient demonstrated moderate subcutaneous emphysema on the right side of his neck. The ECG did not demonstrate any changes associated with cocaine-induced cardiac ischemia, and blood analysis was normal (negative troponins).

Smartphone Application Monitoring of Acceleration Forces During Pneumatic Tube System Transport of Emergency Department Patient Samples.

Background: The use of pneumatic tube system (PTS) transport has gained considerable popularity in modern hospitals but is also associated with sample hemolysis. The potential contribution of PTS-associated acceleration forces to high hemolysis rates observed in the emergency department (ED) has not been investigated before and can be easily examined nowadays using smartphone applications. The first aim of our study was to investigate whether our PTS induces hemolysis of patient samples obtained from our ED.

High anion gap metabolic acidosis induced by cumulation of ketones, L- and D-lactate, 5-oxoproline and acute renal failure.

Introduction: Frequent causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis and impaired renal function. In this case report, a HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5-oxoproline is discussed.

Case Presentation: A 69-year-old woman was admitted to the emergency department with lowered consciousness, hyperventilation, diarrhoea and vomiting.

Schoolchildren as BLS instructors for relatives and friends: Impact on attitude towards bystander CPR.

Introduction: We investigated the impact of Cardio-Pulmonary Resuscitation (CPR) instruction by children on the attitude of people to perform bystander CPR.

Methods: In 2012, children from primary and secondary school (age span 11–13 years) received a free individual CPR training package containing an inexpensive manikin and a training video. After a CPR training session by their class teacher, they were invited to teach their relatives and friends.

The effect of anti-L-selectin (aselizumab) in multiple traumatized patients--results of a phase II clinical trial.

Objective: The objectives of this study were to evaluate safety (primary) and clinical efficacy (secondary) of the humanized monoclonal anti-L-selectin antibody aselizumab in severely injured patients.

Design: Prospective phase II, parallel group, double-blind, randomized, placebo-controlled clinical trial.

Setting: Fourteen medical intensive care units or trauma units in level I trauma centers in Belgium, Germany, and Poland.

Survey of non-invasive ventilation for acute exacerbation of chronic obstructive pulmonary disease patients in emergency departments in Belgium.

A study was undertaken to assess the availability and use of non-invasive ventilation (NIV) for the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) in emergency departments in Belgium. A questionnaire was sent to the head physicians of 145 emergency departments (EDs) found in the list of the Belgian College of Emergency Physicians (BeCEP). Ninety eight questionnaires were analysed (representing 68% of the questionnaires sent).

High cervical pain and impairment of skull mobility as the only symptoms of an occipital condyle fracture. Case report.

Occipital condyle fractures are rarely reported in survivors of trauma. Most cases involve patients with a major head trauma, lower cranial nerve palsy, and/or suspected lesions demonstrated on plain x-ray films of the skull or cervical spine. The authors describe a traffic-accident victim in whom an atlanto-occipital joint lesion was suspected based only on mobility investigation of the skull.

Occipital condyle fracture must be considered in the pediatric population: case report.

To our knowledge, no case of occipital condyle fracture after minor head trauma in the pediatric population has been published. We report the case of a 12-year-old girl with a Jefferson's fracture detected on x-ray films. Axial high resolution computed tomography and coronal reconstruction images demonstrated the additional occipital condyle fracture.