Accelerated Development of COVID-19 Vaccines: Technology Platforms, Benefits, and Associated Risks.

Multiple preventive COVID-19 vaccines have been developed during the ongoing SARS coronavirus (CoV) 2 pandemic, utilizing a variety of technology platforms, which have different properties, advantages, and disadvantages. The acceleration in vaccine development required to combat the current pandemic is not at the expense of the necessary regulatory requirements, including robust and comprehensive data collection along with clinical product safety and efficacy evaluation. Due to the previous development of vaccine candidates against the related highly pathogenic coronaviruses SARS-CoV and MERS-CoV, the antigen that elicits immune protection is known: the surface spike protein of SARS-CoV-2 or specific domains encoded in that protein, e.

Intracytoplasmic trapping of influenza virus by a lipophilic derivative of aglycoristocetin.

We report on a new anti-influenza virus agent, SA-19, a lipophilic glycopeptide derivative consisting of aglycoristocetin coupled to a phenylbenzyl-substituted cyclobutenedione. In Madin-Darby canine kidney cells infected with influenza A/H1N1, A/H3N2, or B virus, SA-19 displayed a 50% antivirally effective concentration of 0.60 μM and a selectivity index (ratio of cytotoxic versus antiviral concentration) of 112.

Human pluripotent stem cell-derived hepatocytes support complete replication of hepatitis C virus.

Background & Aims: Worldwide, about 180 million people are chronically infected with the hepatitis C virus (HCV). Current in vitro culture systems for HCV depend chiefly on human hepatoma cell lines. Although primary human hepatocytes support HCV infection in vitro, and immunodeficient mice repopulated with human hepatocytes support HCV infection in vivo, these models are limited because of shortage of human livers to isolate hepatocytes.

Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice.

Background: Ventricular expression of phosphodiesterase-5 (PDE5), an enzyme responsible for cGMP catabolism, is increased in human right ventricular hypertrophy, but its role in left ventricular (LV) failure remains incompletely understood. We therefore measured LV PDE5 expression in patients with advanced systolic heart failure and characterized LV remodeling after myocardial infarction in transgenic mice with cardiomyocyte-specific overexpression of PDE5 (PDE5-TG).

Methods And Results: Immunoblot and immunohistochemistry techniques revealed that PDE5 expression was greater in explanted LVs from patients with dilated and ischemic cardiomyopathy than in control hearts.

Immunohistochemistry using an antibody to unphosphorylated connexin 43 to identify human myometrial interstitial cells.

Background: Myometrial smooth myocytes contract as a result of electrical signalling via a process called excitation-contraction coupling. This process is understood in great detail at the cellular level but the generation and coordination of electrical signals throughout the myometrium are incompletely understood. Recent evidence concerning the vital role of interstitial cells of Cajal in tissue-level signalling in gastrointestinal tract, and the presence of similar cells in urinary tract smooth muscle may be relevant for future research into myometrial contractility but there remains a lack of evidence regarding these cells in the myometrium.

Reduced force generating capacity in myocytes from chronically ischemic, hibernating myocardium.

The contractile dysfunction of the hibernating myocardium in situ results from local environmental factors, but also from intrinsic cellular remodelling that may determine reversibility. Previous studies have suggested defects in myofilament Ca2+ responsiveness. We prepared single myocytes from control (CTRL, n(pigs)=7) and from hibernating myocardium (HIB, n(pigs)=8), removed the membranes and measured isometric force development during direct activation of the myofilaments.

Breast cancer resistance protein (BCRP/ABCG2) is expressed by progenitor cells/reactive ductules and hepatocytes and its expression pattern is influenced by disease etiology and species type: possible functional consequences.

Breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette transport protein that is expressed in several organs including the liver. Previous studies have shown that ABC transport proteins play an important pathophysiological role in several liver diseases. However, to date, expression pattern and possible role of BCRP in human liver diseases and animal models have not been studied in detail.

Cloning and characterization of a third isoform of corazonin in the honey bee Apis mellifera.

The precursor of the insect hormone corazonin has been cloned from the honey bee Apis mellifera. The precursor predicts a novel isoform of corazonin, pQTFTYSHGWTNamide, which was confirmed by tandem mass spectrometry. Although Apis corazonin differs only by a glutamine/threonine substitution from [His7]-corazonin, it is considerably less active in the dark color inducing assay on albino locusts.

Vitrectomy with peeling of the inner limiting membrane for treating diabetic macular edema.

Purpose: to evaluate the results of pars plana vitrectomy with peeling of the inner limiting membrane (ILM stained with infracyanine green (IfCG) in 26 patients with diabetic macular edema, and to identify which factors are associated with a better postoperative visual outcome.

Patients And Methods: 26 patients with diabetic macular edema were included in the study. A pars plana vitrectomy with ILM peeling stained with IfCG was performed, in some cases combined with cataract surgery.

Lead exposure by drinking water: an epidemiologial study in Hamburg, Germany.

Study objective was to investigate the extent of lead exposure via tap water in Hamburg and the relevance of preventive strategies. Two hundred and forty-eight non-smoking young women participated in the cross-sectional study program and 52 women completed the intervention program. In the cross-sectional study program most women (N = 178) didn't know anything about the material of the plumbing system at their homes.

Fraenkel's pupariation factor identified at last.

Thirty-five years ago, Zdarek and Fraenkel demonstrated that nervous tissue extracts influenced development by accelerating pupariation in the grey flesh fly, Neobellieria bullata. We have now identified this pupariation factor as SVQFKPRLamide, designated Neb-pyrokinin-2 (Neb-PK-2). To achieve this, the central nervous system of N.

SIFamide is a highly conserved neuropeptide: a comparative study in different insect species.

Neb-LFamide or AYRKPPFNGSLFamide was originally purified from the grey flesh fly Neobellieria bullata as a myotropic neuropeptide. We studied the occurrence of this peptide and its isoforms in the central nervous system of different insect species by means of whole mount fluorescence immunohistochemistry, mass spectrometry, and data mining. We found that both sequence and immunoreactive distribution pattern are very conserved in the studied insects.

Potent, selective and cell-mediated inhibition of human herpesvirus 6 at an early stage of viral replication by the non-nucleoside compound CMV423.

CMV423 (2-chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide) is a new antiviral agent with potent and selective in vitro activity against the beta-herpesvirus human cytomegalovirus (HCMV), but not against alpha- or gamma-herpesviruses. Here we report that its activity also extends to human herpesvirus 6 (HHV-6) and 7 (HHV-7). When compared in vitro to ganciclovir and foscarnet (the standard drugs recommended for treatment of HHV-6 infections), CMV423 showed a superior selectivity, due to its high activity (antiviral IC(50): 53nM) and low cytotoxicity (CC(50): 144microM), both in continuous cell lines and in CBLCs infected with HHV-6.

Expression of a novel neuropeptide, NVGTLARDFQLPIPNamide, in the larval and adult brain of Drosophila melanogaster.

Advances in mass spectrometry and the availability of genomic databases made it possible to determine the peptidome or peptide content of a specific tissue. Peptidomics by nanoflow capillary liquid chromatography tandem mass spectrometry of an extract of 50 larval Drosophila brains, yielded 28 neuropeptides. Eight were entirely novel and encoded by five not yet annotated genes; only two genes had a homologue in the Anopheles gambiae genome.

Double vital staining using trypan blue and infracyanine green in macular pucker surgery.

Aims: To study the clinical properties of double vital staining in premacular fibrosis, facilitating complete removal of all epiretinal tissue.

Methods: In a two step surgery, the epiretinal pucker was removed after staining with trypan blue, whereafter the inner limiting membrane was peeled after staining with infracyanine green.

Results: In all 30 patients, a separate epiretinal layer and inner limiting membrane were removed from the macular area.

Impact of direct virus-induced neuronal dysfunction and immunological damage on the progression of flavivirus (Modoc) encephalitis in a murine model.

Flavivirus encephalitis is believed to be the result of two main mechanisms: (i) direct damage to and dysfunction of neurons as a result of viral replication and (ii) destruction of the brain tissue by an inflammatory response. The differential impact of both mechanisms on the progression of flavivirus encephalitis has not been clearly determined. We have now studied the encephalitis caused by Modoc virus (MODV) infection in (i) severe combined immunodeficiency (SCID) mice, (ii) immunocompetent NMRI mice, and (iii) NMRI mice under varying immunosuppressive treatment regimens.

Pulmonary neuroendocrine cells (PNEC) and neuroepithelial bodies (NEB): chemoreceptors and regulators of lung development.

The airway and alveolar epithelia contain pulmonary neuroendocrine cells whose structure indicates an endocrine function. They are also in contact with sensory nerve fibres. These cells often aggregate into distinct corpuscles-neuroepithelial bodies-and carry membrane receptors sensitive to a number of stimuli, including hypoxia and nicotine.

Sulphated and sulphonated polymers inhibit the initial interaction of hepatitis B virus with hepatocytes.

The initial step during hepatitis B virus (HBV) infection is the specific attachment of the virus to the hepatocyte. Here we studied whether the binding of HBV to hepatocytes can, as is the case with most other enveloped viruses, be blocked by polyanionic compounds. Viral particles produced by HepAD38 cells were used as inoculum and HBV-negative HepG2 cells, as well as primary human hepatocytes, as target cells.

Valved jugular vein segments for right ventricular outflow tract reconstruction in young sheep.

Objective: This study was undertaken to investigate the degeneration and calcification of valved bovine jugular vein segments for right ventricular outflow tract reconstruction in juvenile sheep.

Methods: Seven valved bovine jugular vein conduits (Contegra model 220; VenPro Corporation, Irvine, Calif) and 3 control conduits (MH100; Medtronic, Inc, Minneapolis, Minn) were implanted in the pulmonary artery in young sheep. After 20 weeks the conduits were explanted and qualitatively analyzed by epicardial echocardiography, gross examination, x-ray analysis, light microscopy, and transmission electron microscopy.

Occurrence of toxigenic Aspergillus versicolor isolates and sterigmatocystin in carpet dust from damp indoor environments.

Over the past decade, there has been growing concern regarding the role of toxigenic fungi in damp indoor environments; however, there is still a lack of field investigations on exposure to mycotoxins. The goal of our pilot study was to quantify the proportion of toxigenic Aspergillus versicolor isolates in native carpet dust from damp dwellings with mold problems and to determine whether sterigmatocystin can be detected in this matrix. Carpet dust samples (n = 11) contained from <2.

Infection of SCID mice with Montana Myotis leukoencephalitis virus as a model for flavivirus encephalitis.

We have established a convenient animal model for flavivirus encephalitis using Montana Myotis leukoencephalitis virus (MMLV), a bat flavivirus. This virus has the same genomic organization, and contains the same conserved motifs in genes that encode potential antiviral targets, as flaviviruses that cause disease in man (N. Charlier et al.

Immunocytochemical localization of a diuretic hormone of the beetle Tenebrio molitor, Tenmo-DH(37), in nervous system and midgut.

Although the mealworm Tenebrio molitor inhabits very dry environments, it has at least two diuretic peptides, which increase fluid secretion by the free portions of the Malpighian tubules. Unlike other insect corticotropin-releasing factor (CRF)-related peptides isolated to date, these are non-amidated peptides. The immunocytochemical localization of Tenmo-DH(37) was investigated using antisera raised against this hormone.

Trypan blue staining of epiretinal membranes in proliferative vitreoretinopathy.

Objective: To determine whether trypan blue staining facilitates epiretinal membrane (ERM) removal in proliferative vitreoretinopathy.

Methods: In 10 patients undergoing vitrectomy for proliferative vitreoretinopathy, ERM peeling was performed without staining the tissue, until no additional ERMs were clearly visible. Then, after a fluid-air exchange, 0.

Sleeve-related thrombosis: a new form of catheter-related thrombosis.

In a detailed study of central venous catheter-related sleeve and thrombosis in experimental animals, a new form of thrombosis was detected and termed sleeve-related thrombosis. A silastic catheter was placed in the jugular vein and the anterior vena cava of 22 rabbits and 54 rats. After intervals of 1, 3, 7 days, 2, 3, 4 weeks and 1, 2, 4, 6 months the veins were examined by light microscopy and by transmission electron microscopy.