RSV: Available Prophylactic Options and Vaccines in Clinical Trials

Respiratory syncytial virus (RSV) is the leading cause of serious lower respiratory infection (ALRI)-related hospitalization in children worldwide, and a source of morbidity and mortality in high-risk adults. There are strong associations between RSV, persistent wheezing and childhood asthma. Despite extensive research, no effective treatment is available aside from supportive care. The trial of a formalin-inactivated RSV vaccine in the 1960s resulted in priming the severe illness upon natural infection. Palivizumab, a monoclonal antibody approved for RSV prophylaxis in high-risk infants, has only moderately decreased hospital admissions due to RSV infection. Live-attenuated, vector, and protein-based vaccine candidates are being investigated in many clinical trials. Developing a vaccine remains challenging due to finding the right balance between adequate immunogenicity and attenuation of vaccine. Here we review the clinical significance of RSV in infants, young children, high-risk adults, elderly population, pregnant women; clinical manifestations and consequences of RSV infection; the pharmacologic strategies currently available, the current stages of RSV vaccine clinical trials, different strategies, and major hurdles in the development of an effective RSV vaccine

Neurotrophins Regulate Bone Marrow Stromal Cell IL-6 Expression through the MAPK Pathway

The host's response to infection is characterized by altered levels of neurotrophins and an influx of inflammatory cells to sites of injured tissue. Progenitor cells that give rise to the differentiated cellular mediators of inflammation are derived from bone marrow progenitor cells where their development is regulated, in part, by cues from bone marrow stromal cells (BMSC). As such, alteration of BMSC function in response to elevated systemic mediators has the potential to alter their function in biologically relevant ways, including downstream alteration of cytokine production that influences hematopoietic development.In the current study we investigated BMSC neurotrophin receptor expression by flow cytometric analysis to determine differences in expression as well as potential to respond to NGF or BDNF. Intracellular signaling subsequent to neurotrophin stimulation of BMSC was analyzed by western blot, microarray analysis, confocal microscopy and real-time PCR. Analysis of BMSC Interleukin-6 (IL-6) expression was completed using ELISA and real-time PCR.BMSC established from different individuals had distinct expression profiles of the neurotrophin receptors, TrkA, TrkB, TrkC, and p75(NTR). These receptors were functional, demonstrated by an increase in Akt-phosphorylation following BMSC exposure to recombinant NGF or BDNF. Neurotrophin stimulation of BMSC resulted in increased IL-6 gene and protein expression which required activation of ERK and p38 MAPK signaling, but was not mediated by the NFkappaB pathway. BMSC response to neurotrophins, including the up-regulation of IL-6, may alter their support of hematopoiesis and regulate the availability of inflammatory cells for migration to sites of injury or infection. As such, these studies are relevant to the growing appreciation of the interplay between neurotropic mediators and the regulation of hematopoiesis

Pediatric patient with systemic lupus erythematosus & congenital acquired immunodeficiency syndrome: An unusual case and a review of the literature

The coexistence of systemic lupus erythematosus (SLE) in patients with congenital human immunodeficiency virus (HIV) infection is rare. This is a case report of a child diagnosed with SLE at nine years of age. She initially did well on non-steroidal anti-inflammatory agents, hydroxychloroquine, and steroids. She then discontinued her anti-lupus medications and was lost to follow-up. At 13 years of age, her lupus symptoms had resolved and she presented with intermittent fevers, cachexia, myalgias, arthralgias, and respiratory symptoms. Through subsequent investigations, the patient was ultimately diagnosed with congenitally acquired immunodeficiency syndrome (AIDS)

Vitamin D3 protects against respiratory syncytial virus-induced barrier dysfunction in airway epithelial cells via PKA signaling pathway

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection in infants and young children globally and is responsible for hospitalization and mortality in the elderly population. Virus-induced airway epithelial barrier damage is a critical step during RSV infection, and emerging studies suggest that RSV disrupts the tight junctions (TJs) and adherens junctions (AJs) between epithelial cells, increasing the permeability of the airway epithelial barrier. The lack of commercially available vaccines and effective antiviral drugs for RSV emphasizes the need for new management strategies. Vitamin D3 is a promising intervention for viral infection due to its critical role in modulating innate immune responses. However, there is limited evidence on the effect of vitamin D3 on RSV pathogenies. Here, we investigated the impact of vitamin D3 on RSV-induced epithelial barrier dysfunction and the underlying mechanisms. We found that pre-incubation with 1,25(OH)2D3, the active form of vitamin D3, alleviated RSV-induced epithelial barrier disruption in a dose-dependent manner without affecting viability in 16HBE cells. 1,25(OH)2D3 induced minor changes in the protein expression level of TJ/AJ proteins in RSV-infected cells. We observed increased CREB phosphorylation at Ser133 during 1,25(OH)2D3 exposure, indicating that vitamin D3 triggered protein kinase A (PKA) activity in 16HBE. PKA inhibitors modified the restoration of barrier function by 1,25(OH)2D3 in RSV-infected cells, implying that PKA signaling is responsible for the protective effects of vitamin D3 against RSV-induced barrier dysfunction in airway epithelial cells. Our findings suggest vitamin D3 as a prophylactic intervention to protect the respiratory epithelium during RSV infections

Dispersing of Petroleum Asphaltenes by Acidic Ionic Liquid and Determination by UV-Visible Spectroscopy

Nowadays, constructing a mechanism to prevent the aggregation petroleum asphaltenes by the use of new acidic ionic liquids has become of fundamental importance. In this research, 3-(2-carboxybenzoyl)-1-methyl-1H-imidazol-3-ium chloride ([CbMIM] [Cl]) and other ionic liquids such as [CbMIM]BF4, [HMIM]Cl, [BMIM]Br, and [HMIM]HSO4 were tested. It should be noted that during the experiment the presence of the acidic ionic liquid moiety enhanced interactions between asphaltenes and acidic ionic liquids and it greatly limited asphaltene aggregation. We considered parameters such as temperature, amount of dispersant, effect of water: toluene ratio, the stirring time and effects of other ionic liquids, and determination of concentration of petroleum asphaltenes after dispersing by acidic ionic liquid under various parameters using UV-Visible spectroscopy

Very Deep Convolutional Neural Networks for Complex Land Cover Mapping Using Multispectral Remote Sensing Imagery

Despite recent advances of deep Convolutional Neural Networks (CNNs) in various computer vision tasks, their potential for classification of multispectral remote sensing images has not been thoroughly explored. In particular, the applications of deep CNNs using optical remote sensing data have focused on the classification of very high-resolution aerial and satellite data, owing to the similarity of these data to the large datasets in computer vision. Accordingly, this study presents a detailed investigation of state-of-the-art deep learning tools for classification of complex wetland classes using multispectral RapidEye optical imagery. Specifically, we examine the capacity of seven well-known deep convnets, namely DenseNet121, InceptionV3, VGG16, VGG19, Xception, ResNet50, and InceptionResNetV2, for wetland mapping in Canada. In addition, the classification results obtained from deep CNNs are compared with those based on conventional machine learning tools, including Random Forest and Support Vector Machine, to further evaluate the efficiency of the former to classify wetlands. The results illustrate that the full-training of convnets using five spectral bands outperforms the other strategies for all convnets. InceptionResNetV2, ResNet50, and Xception are distinguished as the top three convnets, providing state-of-the-art classification accuracies of 96.17%, 94.81%, and 93.57%, respectively. The classification accuracies obtained using Support Vector Machine (SVM) and Random Forest (RF) are 74.89% and 76.08%, respectively, considerably inferior relative to CNNs. Importantly, InceptionResNetV2 is consistently found to be superior compared to all other convnets, suggesting the integration of Inception and ResNet modules is an efficient architecture for classifying complex remote sensing scenes such as wetlands