A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults.

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively.

Cold and distant: structural features of the nucleoprotein complex of a cold-adapted influenza A virus strain.

Two influenza A nucleoprotein variants (wild-type: G102R; and mutant: G102R and E292G) were studied with regard to macro-molecular interactions in oligomeric form (24-mers). The E292G mutation has been previously shown to provide cold adaptation. Molecular dynamics simulations of these complexes and trajectory analysis showed that the most significant difference between the obtained models was distance between nucleoprotein complex strands.

Non-Mouse-Adapted H1N1pdm09 Virus as a Model for Influenza Research.

The number of lung-adapted influenza viruses is limited. Most of them are not antigenically related to current circulating viruses. Viruses similar to recent strains are required for screening modern antiviral compounds and studying new vaccine candidates against novel influenza viruses.

Study of Neuraminidase-Inhibiting Antibodies in Clinical Trials of Live Influenza Vaccines.

Background: Currently, the immunogenicity of influenza vaccines is assessed by detecting an increase of hemagglutination inhibition (HI) antibodies. As neuraminidase (NA)-based immunity may be significant in protecting against influenza infection, detection of neuraminidase inhibiting (NI) antibodies may improve the assessment of the immunogenicity of influenza vaccines.

Methods: We investigated the immune response to NA in people after immunization with live influenza vaccines (LAIVs).

The effect of galanin gene polymorphism rs948854 on the severity of multiple sclerosis: A significant association with the age of onset.

Background: Data on genetic markers that determine the prognosis of multiple sclerosis (MS) is still limited. The association between galanin gene polymorphism rs948854 and prognosis of MS had been demonstrated earlier.

Objectives: To confirm earlier findings in a distinct from the previously studied cohort of patients, and to further characterized the rs948854 polymorphism as one of the candidates for the risk stratification in patients with MS.

A common genetic variant rs2821557 in KCNA3 is linked to the severity of multiple sclerosis.

The rate of symptom accumulation distinguishes between slowly and rapidly progressing forms of multiple sclerosis (MS). Given that a patient's genetics can affect the rate of disease progression, identification of genetic variants associated with rapid disease progression should provide valuable information for timely prognosis and development of optimal treatment plans. We hypothesized that the polymorphism rs2821557 in the human KCNA3 gene encoding a voltage-gated potassium channel Kv1.

Receptor expression by JEG-3 trophoblast cells in the presence of placenta secreted factors.

Preeclampsia still remains one of the most severe pregnancy complications and is an actual problem in the obstetrics practice. At present, the joint impact of cytokines and other placenta secreted factors on trophoblast cell functional activity during preeclampsia complicated pregnancy remains unclear. The aim of the study is to estimate the surface receptors expression by trophoblast cells in the presence of placenta secreted factors during physiological pregnancy and at preeclampsia.

Mucosal vaccine based on attenuated influenza virus and the group B Streptococcus recombinant peptides protected mice from influenza and S. pneumoniae infections.

Although many influenza-related deaths are attributable to secondary bacterial infection with S. pneumoniae, vaccines that simultaneously protect against influenza and pneumococcal infection are currently not developed. The aim of our study was to evaluate the possibility to prevent post-influenza pneumococcal infection using an associated vaccine based on live influenza vaccine (LAIV) combined with recombinant polypeptides derived from superficial factors of Group B streptococcus (GBS) determining pathogenicity.

Factors of early protective action of live influenza vaccine combined with recombinant bacterial polypeptides against homologous and heterologous influenza infection.

We are developing an associated vaccine based on live influenza vaccine (LAIV) and streptococcal recombinant peptides. The recombinant group B streptococcus (GBS) peptides P6 and ScaAB demonstrated a distinguished immunomodulating effect in THP-1 cells. The increase in IFN 1-alpha expression after ScaAB inoculation was similar to that against LAIV.

Changing times: Fluorescence-lifetime analysis of amyloidogenic SF-IAPP fusion protein.

In a number of conformational diseases, intracellular accumulation of proteins bearing non-native conformations occurs. The search for compounds that are capable of hindering the formation and accumulation of toxic protein aggregates and fibrils is an urgent task. Present fluorescent methods of fibrils' detection prevent simple real-time observations.

Nasal immunization with recombinant chimeric pneumococcal protein and cell wall from immunobiotic bacteria improve resistance of infant mice to Streptococcus pneumoniae infection.

Respiratory tract infections and invasive disease caused by Streptococcus pneumoniae in high-risk groups are a major global health problem. Available human vaccines have reduced immunogenicity and low immunological memory in these populations, as well as high cost as a public health strategy in poor communities. In addition, no single pneumococcal protein antigen has been able to elicit protection comparable to that achieved using protein-polysaccharide conjugate vaccines.

Basics of CD8 T-cell immune responses after influenza infection and vaccination with inactivated or live attenuated influenza vaccine.

Introduction: One of the essential mechanisms of virus infection control is cell-mediated cytotoxicity, which can act in an antibody-dependent or -independent fashion and is provided by different effector cells. The role of CD8 T-cells in infection control and in affecting the pathological outcome of different types of infection has been demonstrated in numerous animal studies. Despite this, their role in controlling human influenza infection is not fully understood.

Alterations in mRNA expression of glutamate receptor subunits and excitatory amino acid transporters following pilocarpine-induced seizures in rats.

Temporal lobe epilepsy is the most prevalent form of complex partial seizure, and it is frequently triggered by an initial brain-damaging insult. The prevention of epileptogenesis after a primary event could be a key innovative approach to epilepsy treatment. Therefore, it is critical to understand the pathogenic mechanisms of this process in detail.

A double-edged sword: supramolecular complexes of triazavirine display multicenter binding effects which influence aggregate formation.

Communicated by Ramaswamy H. Sarma.

Anti-neuraminidase antibodies against pandemic A/H1N1 influenza viruses in healthy and influenza-infected individuals.

The main objective of the study was to evaluate neuraminidase inhibiting (NI) antibodies against A/H1N1pdm09 influenza viruses in the community as a whole and after infection. We evaluated NI serum antibodies against A/California/07/09(H1N1)pdm and A/South Africa/3626/2013(H1N1)pdm in 134 blood donors of different ages using enzyme-linked lectin assay and in 15 paired sera from convalescents with laboratory confirmed influenza. The neuraminidase (NA) proteins of both A/H1N1pdm09 viruses had minimal genetic divergence, but demonstrated different enzymatic and antigenic properties.

The amyloidogenicity of the influenza virus PB1-derived peptide sheds light on its antiviral activity.

The influenza virus polymerase complex is a promising target for new antiviral drug development. It is known that, within the influenza virus polymerase complex, the PB1 subunit region from the 1st to the 25th amino acid residues has to be is in an alpha-helical conformation for proper interaction with the PA subunit. We have previously shown that PB1(6-13) peptide at low concentrations is able to interact with the PB1 subunit N-terminal region in a peptide model which shows aggregate formation and antiviral activity in cell cultures.

The anti-SLAMF7 antibody elotuzumab mediates NK cell activation through both CD16-dependent and -independent mechanisms.

Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16).

Prevention of Influenza A(H7N9) and Bacterial Infections in Mice Using Intranasal Immunization With Live Influenza Vaccine and the Group B Streptococcus Recombinant Polypeptides.

We investigate the protective effect of combined vaccination based on live attenuated influenza vaccine (LAIV) and group B streptococcus (GBS) recombinant polypeptides against potential pandemic H7N9 influenza infection followed by GBS burden. Mice were intranasally immunized using 107 50% egg infectious dose (EID) of H7N3 LAIV, the mix of the 4 GBS peptides (group B streptococcus vaccine [GBSV]), or combined LAIV + GBSV vaccine. The LAIV raised serum hemagglutination-inhibition antibodies against H7N9 in higher titers than against H7N3.

Regulation of the Functions of Natural Cytotoxicity Receptors by Interactions with Diverse Ligands and Alterations in Splice Variant Expression.

The natural cytotoxicity receptor (NCR) family is constituted by NKp46, NKp44, and NKp30 in humans, which are expressed mainly on natural killer (NK) cells and are encoded by the , and genes, respectively. NCRs have classically been defined as activating receptors that trigger cytotoxicity and cytokine responses by NK cells upon engaging with ligands on tumor cells. Several new findings, however, have challenged this model and identified alternative mechanisms regulating the function of NCRs.

Evaluation in Mouse Model of Combined Virus-bacterial Vaccine Based on Attenuated Influenza A(H7N3) Virus and the Group B Streptococcus Recombinant Polypeptides.

Background: Secondary bacterial influenza complications are a common cause of excesses morbidity and mortality, which determines the need to develop means for specific prophylaxis. Group B streptococcal infection is especially common cause of pneumonia among children and the elderly with underlying conditions. Here we investigate in a mouse model the effects of combined intranasal immunization using live attenuated influenza vaccine and recombinant polypeptides based on group B surface proteins.

Individual Differences in Behavioural Despair Predict Brain GSK-3beta Expression in Mice: The Power of a Modified Swim Test.

While deficient brain plasticity is a well-established pathophysiologic feature of depression, little is known about disorder-associated enhanced cognitive processing. Here, we studied a novel mouse paradigm that potentially models augmented learning of adverse memories during development of a depressive-like state. We used a modification of the classic two-day protocol of a mouse Porsolt test with an additional session occurring on Day 5 following the initial exposure.

Radiofrequency ablation or stripping of large-diameter incompetent great saphenous varicose veins with C2 or C3 disease.

Objective: The objectives of this study were to compare the results of radiofrequency ablation (RFA) and stripping for large-diameter varicose target veins for the period of 1 year, based on a composite end point; to analyze the pain severity on a digital rating scale for 7 days after RFA and stripping; and to detect the factors affecting the level of postoperative pain using the cluster analysis.

Methods: This was a multicenter retrospective cohort study. Two groups, stripping ≥14 mm and RFA ≥14 mm, of 129 varicose vein disease patients underwent surgical treatment in three specialized clinics.

Injured Nerve Regeneration using Cell-Based Therapies: Current Challenges.

This paper reviews the recent research progress in the past several years on promoting peripheral nerve recovery using stem and progenitory cells. The emphasis is placed on studies aimed at assessing various stem cells capable of expressing neurotrophic and growth factors and surviving after implantation in the nerve or a conduit. Approaches to improving nerve conduit design are summarized.