Almost half of the world's population is exposed to the risk of transmission of the four dengue virus serotypes (DENV 1-4), by mosquitoes of the genus Aedes. A dengue vaccine is effective if it induces prolonged protective immunity against all circulating viral strains, irrespective of the age and infection history of the vaccinated subject. An effective vaccine strategy against dengue is based on the injection of live attenuated viruses in a tetravalent formulation.
View Article and Find Full Text PDFIntroduction: Lung transplantation is associated with high proportion of transfusion. Monitoring of coagulopathy using viscoelastic tests could aid in the perioperative management of bleeding. The aim of the study was to assess the predictive cut-off values for thrombocytopenia and hypofibrinogenemia using the new thromboelastography analyzer, ClotPro.
View Article and Find Full Text PDFWe report the safety (primary endpoint) and efficacy (secondary endpoint) of a novel intracerebral gene therapy at 5.5 years of follow-up in children with Sanfilippo B. An uncontrolled, phase 1/2 clinical trial was performed in four patients aged 20, 26, 30, and 53 months.
View Article and Find Full Text PDFMucopolysaccharidosis type IIIB syndrome (Sanfilippo disease) is a rare autosomic recessif disorder caused by mutations in the α-N-acetylglucosaminidase (NAGLU) gene coding for a lysosomal enzyme, leading to neurodegeneration and progressive deterioration of cognitive abilities in affected children. To supply the missing enzyme, several recent human gene therapy trials relied on the deposit of adeno-associated virus (AAV) vectors directly into the brain. We reported safety and efficacy of an intracerebral therapy in a phase 1/2 clinical trial (https://clinicaltrials.
View Article and Find Full Text PDFZika virus (ZIKV) dramatically emerged in French Polynesia and subsequently in the Americas where it has been associated with severe neurological complications in adults and newborns, respectively. Although plasmacytoid dendritic cells (pDCs) are a key sensor of viral infection and are critical for initiating an antiviral response, little is known about the impact of ZIKV infection on pDCs. Here, we investigated the susceptibility of human pDCs to infection with multiple strains of ZIKV and further investigated the impact of infection on pDCs functions.
View Article and Find Full Text PDFBackground: Shigella remains in the top four pathogens responsible for moderate to severe diarrhoea in children below 5 years of age. The shigella O-specific polysaccharide (O-SP) is a promising vaccine target. We developed a conjugate vaccine prototype incorporating a unique well defined synthetic oligosaccharide hapten, chemically designed for optimal antigenic, conformational, structural, and functional mimicry of the O-SP from Shigella flexneri 2a (SF2a).
View Article and Find Full Text PDFUnderstanding the viral-host cell interface during HIV-1 infection is a prerequisite for the development of innovative antiviral therapies. Here we show that the suppressor of G2 allele of skp1 (SUGT1) is a permissive factor for human immunodeficiency virus (HIV)-1 infection. Expression of SUGT1 increases in infected cells on human brain sections and in permissive host cells.
View Article and Find Full Text PDFPurinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection. We found that NLRP3 acts as an inhibitory factor of viral entry that represses F-actin remodeling.
View Article and Find Full Text PDFEven though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism.
View Article and Find Full Text PDFTherapeutic strategies using drugs which cause Lysosomal Cell Death have been proposed for eradication of resistant cancer cells. In this context, nanotherapy based on Magnetic Intra-Lysosomal Hyperthermia (MILH) generated by magnetic nanoparticles (MNPs) that are grafted with ligands of receptors overexpressed in tumors appears to be a very promising therapeutic option. However, mechanisms whereby MILH induces cell death are still elusive.
View Article and Find Full Text PDFUnlabelled: For administration of multiple live attenuated vaccines, the Advisory Committee on Immunization Practices recommends either simultaneous immunization or period of at least 28days between vaccines, due to a possible reduction in the immune response to either vaccine. The main objective of this study was to compare the immune response to measles (alone or combined with mumps and rubella) and yellow fever vaccines among infants aged 6-24months living in a yellow fever non-endemic country who had receivedmeasles and yellow fever vaccines before travelling to a yellow fever endemic area.
Subjects And Methods: A retrospective, multicenter case-control study was carried out in 7 travel clinics in the Paris area from February 1st 2011 to march 31, 2015.
Two bismuth oxalates, namely, Bi(CO)·7HO and Bi(CO)OH, were studied in terms of synthesis, structural characterization, particle morphology, and thermal behavior under several atmospheres. The oxalate powders were produced by chemical precipitation from bismuth nitrate and oxalic acid solutions under controlled pH, then characterized by X-ray diffraction (XRD), temperature-dependent XRD, IR spectroscopy, scanning electron microscopy, and thermogravimetric differential thermal analyses. New results on the thermal decomposition of bismuth oxalates under inert or reducing atmospheres are provided.
View Article and Find Full Text PDFBackground: Mucopolysaccharidosis type IIIB syndrome (also known as Sanfilippo type B syndrome) is a lysosomal storage disease resulting in progressive deterioration of cognitive acquisition after age 2-4 years. No treatment is available for the neurological manifestations of the disease. We sought to assess the safety and efficacy of a novel intracerebral gene therapy.
View Article and Find Full Text PDFBackground: This study aimed to assess the effect of walking with Nordic Walking (NW) poles on postural stability and gait spatial-temporal characteristics in individuals with PD and to determine the cognitive load associated operating the poles.
Methods: Twelve individuals with PD (age: 61.6±11.
J Aging Phys Act
January 2018
We investigated the impact of Nordic walking (NW) on gait patterns in individuals with Parkinson's disease (PD) following a 6-week NW familiarization. Twelve participants with PD and 12 healthy older adults took part in a gait analysis walking with and without poles (NP). Results showed larger knee power (knee extensor: K2) on the most affected leg in NW compared to NP (P = .
View Article and Find Full Text PDFBackground: HIV-associated neurocognitive disorders (HAND) persist in the post-HAART era, characterized by asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorders (MND). High mobility group box 1 (HMGB1) is a non-histone chromosomal protein widely expressed in the nucleus of all eukaryotic cells, including brain cells, which acts as a potent proinflammatory cytokine when actively secreted from immune cells. Recent reports suggested that HMGB1 acts on microglial cells to promote neuroinflammation.
View Article and Find Full Text PDFIn the era of highly active antiretroviral therapy (HAART), HIV-1-associated neurocognitive disorders (HAND) persist in infected individuals with adequate immunological and virological status. Risk factors for cognitive impairment include hepatitis C virus co-infection, host genetic factors predisposing to HAND, the early establishment of the virus in the CNS and its persistence under HAART; thus, the CNS is an important reservoir for HIV. Microglial cells are permissive to HIV-1, and NLRP3 inflammasome-associated genes were found expressed in brains of HIV-1-infected persons, contributing to brain disease.
View Article and Find Full Text PDFPlasmacytoid dendritic cells (pDCs) are innate sensors of viral infections and important mediators of antiviral innate immunity through their ability to produce large amounts of IFN-α. Moreover, Toll-like receptor 7 (TLR7) and 9 (TLR9) ligands, such as HIV and CpG respectively, turn pDCs into TRAIL-expressing killer pDCs able to lyse HIV-infected CD4+ T cells. NK cells can regulate antiviral immunity by modulating pDC functions, and pDC production of IFN-α as well as cell-cell contact is required to promote NK cell functions.
View Article and Find Full Text PDFThe immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs).
View Article and Find Full Text PDFBackground And Aims: Data on the efficacy and safety of seasonal influenza vaccines in patients with inflammatory bowel disease (IBD) remain scarce. The aim of the study was to evaluate the impact of immunosuppressive (IS) therapeutics on serological response to 2-year influenza vaccination in IBD adults.
Methods: A multicentre prospective study performed in 255 IBD adults (18-64 years) receiving the trivalent influenza vaccine in the years 2009-2010 and 2010-2011.