Opposing Effects of Prior Infection versus Prior Vaccination on Vaccine Immunogenicity against Influenza A(H3N2) Viruses

Prior vaccination can alternately enhance or attenuate influenza vaccine immunogenicity and effectiveness. Analogously, we found that vaccine immunogenicity was enhanced by prior A(H3N2) virus infection among participants of the Ha Nam Cohort, Viet Nam, but was attenuated by prior vaccination among Australian Health Care Workers (HCWs) vaccinated in the same year. Here, we combined these studies to directly compare antibody titers against 35 A(H3N2) viruses spanning 1968–2018. Participants received licensed inactivated vaccines containing A/HongKong/4801/2014 (H3N2). The analysis was limited to participants aged 18–65 Y, and compared those exposed to A(H3N2) viruses circulating since 2009 by infection (Ha Nam) or vaccination (HCWs) to a reference group who had no recent A(H3N2) infection or vaccination (Ha Nam). Antibody responses were compared by fitting titer/titer-rise landscapes across strains, and by estimating titer ratios to the reference group of 2009–2018 viruses. Pre-vaccination, titers were lowest against 2009–2014 viruses among the reference (no recent exposure) group. Post-vaccination, titers were, on average, two-fold higher among participants with prior infection and two-fold lower among participants with 3–5 prior vaccinations compared to the reference group. Titer rise was negligible among participants with 3–5 prior vaccinations, poor among participants with 1–2 prior vaccinations, and equivalent or better among those with prior infection compared to the reference group. The enhancing effect of prior infection versus the incrementally attenuating effect of prior vaccinations suggests that these exposures may alternately promote and constrain the generation of memory that can be recalled by a new vaccine strain.     

Wire Arc Additive Manufacturing of Al-Mg Alloy with the Addition of Scandium and Zirconium

The proposed paper considers the opportunity of expanding the application area of wire arc additive manufacturing (WAAM) method by means of increasing the strength properties of deposited material, due to the implementation of aluminum wire with the addition of scandium and zirconium. For the experimental research, the welding wire 1575 of the Al-Mg-Sc-Zr system containing 0.23% Sc and 0.19% Zr was selected. The optimal welding parameters, ensuring the defect-free formation of deposited material with low heat input, were used. Porosity level was estimated. The thermal state was estimated by finite element simulation. Simulated thermal state was verified by comparison with thermocouples data. Post-heat treatment parameters that lead to maximum strength with good plasticity were determined. The maximum yield strength (YS) of 268 MPa and ultimate strength (UTS) of 403 MPa were obtained, while the plasticity was determined at least 16.0% in all WAAM specimens.     

Alzheimer amyloid beta inhibition of Eg5/kinesin 5 reduces neurotrophin and/or transmitter receptor function

The mechanism by which amyloid beta (Aβ) causes neuronal dysfunction and/or death in Alzheimer's disease (AD) is unclear. Previously, we showed that Aβ inhibits several microtubule-dependent kinesin motors essential for mitosis and also present in mature neurons. Here, we show that inhibition of kinesin 5 (Eg5) by Aβ blocks neuronal function by reducing transport of neurotrophin and neurotransmitter receptors to the cell surface. Specifically, cell-surface NGF/NTR(p75) and NMDA receptors decline in cells treated with Aβ or the kinesin 5 inhibitor monastrol, or expressing APP. Aβ and monastrol also inhibit NGF-dependent neurite outgrowth from PC12 cells and glutamate-dependent Ca++ entry into primary neurons. Like Aβ, monastrol inhibits long-term potentiation, a cellular model of NMDA-dependent learning and memory, and kinesin 5 activity is absent from APP/PS transgenic mice brain or neurons treated with Aβ. These data imply that cognitive deficits in AD may derive in part from inhibition of neuronal Eg5 by Aβ, resulting in impaired neuronal function and/or survival through receptor mislocalization. Preventing inhibition of Eg5 or other motors by Aβ may represent a novel approach to AD therapy.     

Increasing the Efficiency of a Spintronic THz Emitter Based on WSe2/FeCo

We report an increase in terahertz (THz) radiation efficiency due to FeCo/WSe₂ structures in the reflection geometry. This can be attributed to an absorption increase in the alloy FeCo layer at the input FeCo/WSe₂ interface due to constructive interference, as well as to the backward transport of hot carriers from FeCo to WSe₂. In contrast to the transmission geometry, the THz generation efficiency in the reflection is much less dependent on the magnetic layer thickness. Our results suggest a cheap and efficient way to improve the characteristics of THz spintronic emitters with the conservation of a full set of their important properties.     

Brain white matter morphological structure correlation with its optical properties estimated from optical coherence tomography (OCT) data

A pilot post-mortem study identifies a strong correlation between the attenuation coefficient estimated from the OCT data and some morphological features of the sample, namely the number of nuclei in the field of view of the histological image and the fiber structural parameter introduced in the study to quantify the difference in the myelinated fibers arrangements. The morphological features were identified from the histopathological images of the sample taken from the same locations as the OCT images and stained with the immunohistochemical (IHC) staining specific to the myelin. It was shown that the linear regression of the IHC quantitative characteristics allows adequate prediction of the attenuation coefficient of the sample. This discovery opens the opportunity for the usage of the OCT as a neuronavigation tool.     

The role of interleukin DNA polymorphisms in gastric cancer

Gastric carcinoma is one of the most widespread malignancies worldwide. Interleukins are the key group of cytokines which may have tumor-promoting or tumor-suppressing effect, and receptors for them, of course, have the same importance in this context. However, mechanisms of their impact on tumor are not fully understood up to date. Numerous studies provide conflicting data, that makes picture more confusing and complicated. It is known that single nucleotide polymorphisms in interleukin genes may dramatically affect on protein expression level, or alter its functions, which may lead to gastritis or ulcer, and eventually promote cancer occurrence. Furthermore, some of these genetic polymorphisms may serve as predictive factors for cancer prognosis and prevention. In order to understand the impact of each genetic polymorphism, the review of IL-1B, IL-4, IL-6, IL-8, IL-10, IL17A, IL-17F DNA polymorphisms on gastric carcinoma was done, and risk alleles were recommended for further research.     

AAV delivery of wild-type rhodopsin preserves retinal function in a mouse model of autosomal dominant retinitis pigmentosa

Autosomal dominant retinitis pigmentosa (ADRP) is frequently caused by mutations in RHO, the gene for rod photoreceptor opsin. Earlier, a study on mice carrying mutated rhodopsin transgenes on either RHO?+?/?+ or RHO?+?/- backgrounds suggested that the amount of wild-type rhodopsin affected survival of photoreceptors. Therefore, we treated P23H RHO transgenic mice with adeno-associated virus serotype 5 (AAV5) expressing a cDNA clone of the rhodopsin gene (RHO301) that expressed normal opsin from the mouse opsin promoter. Analysis of the electroretinogram (ERG) demonstrated that increased expression of RHO301 slowed the rate of retinal degeneration in P23H mice: at 6 months, a-wave amplitudes were increased by 100% and b-wave amplitudes by 79%. In contrast, nontransgenic mice injected with AAV5 RHO301 demonstrated a decrease in the ERG, confirming the damaging effect of rhodopsin overproduction in normal photoreceptors. In P23H mice, the increase in the ERG amplitudes was correlated with improvement of retinal structure: the thickness of the outer nuclear layer in RHO301-treated eyes was increased by 80% compared with control eyes. These findings suggest that the wild-type RHO gene can be delivered to rescue retinal degeneration in mice carrying a RHO mutation and that increased production of normal rhodopsin can suppress the effect of the mutated protein. These findings make it possible to treat ADRP caused by different mutations of RHO with the expression of wild-type RHO.     

Central line placement in patients with and without prophylactic plasma

Central line placement (CLP) is a common life-saving intervention in critically ill patients, and patients with coagulation abnormalities as identified by an abnormal international normalized ratio (INR) may receive prophylactic plasma transfusion before the procedure despite previously published data that such a practice is not efficacious. Over a 14-month period, 287 CLPs were performed in the intensive care unit. The use of plasma preprocedure in patients with an elevated INR was generally discouraged but left to the discretion of the operator. A total of 100 lines were placed in patients with a preprocedure INR greater than 1.5, 27 of whom received prophylactic fresh frozen plasma. Only 1 case of bleeding was observed in a patient with an INR of 3.9, who received fresh frozen plasma preprocedure (0/73 vs 1/27; P = .6). The occurrence of bleeding was very low overall with CLP (0.3%; 95% confidence interval, 0%-2%), and no benefit of prophylactic plasma was observed.     

Strength and Fracture Mechanism of an Ultrafine-Grained Austenitic Steel for Medical Applications

In this paper, we study the corrosion-resistant austenitic steel Fe-0.02C-18Cr-8Ni for medical applications. The microstructure and mechanical properties (tensile mechanical properties, torsional strength, impact toughness, and static and cyclic crack resistance) under different types of loading of the steel are investigated. The results are compared for the two states of the steel: the initial (coarse-grained) state and the ultrafine-grained state produced by severe plastic deformation processing via equal-channel angular pressing. It is demonstrated that the ultrafine-grained steel 0.08C-18Cr-9Ni has essentially better properties and is very promising for the manufacture of medical products for various applications that experience various static and cyclic loads during operation.     

Mechanisms of NMDA receptor inhibition by diarylamidine compounds

Pentamidine, diminazene and 4′,6‐diamidino‐2‐phenylindole (DAPI) are antiprotozoal diarylamidine compounds. In the present work, we have studied their action on native N‐methyl‐D‐aspartate (NMDA) receptors in rat hippocampal pyramidal neurons. All three compounds inhibited NMDA receptors at ?80 mV holding voltage with IC₅₀ of 0.41 ± 0.08, 13 ± 3 and 3.1 ± 0.6 μM, respectively. The inhibition by pentamidine was strongly voltage‐dependent, while that of DAPI was practically voltage‐independent. Inhibition by diminazene had both voltage‐dependent and voltage‐independent components. Diminazene and DAPI demonstrated tail currents and overshoots suggesting “foot‐in‐the‐door” mechanism of action. In contrast, pentamidine was partially trapped in the closed NMDA receptor channels. Such difference in the mechanism of action can be explained by the difference in the 3D structure of compounds. In the pentamidine molecule, two benzamidine groups are connected with a flexible linker, which allows the molecule to fold up and fit in the cavity of a closed NMDA receptor channel. Diminazene and DAPI, in contrast, have an extended form and could not be trapped.