Acute gastroenteritis is one of the most common diseases worldwide. Ten to 70% of the outbreaks are food-borne seafood associated. However, no data has been collected to determine viral contamination ...in harvesting areas. We determined the occurrence of human enteric calicivirus (HECV) and AECV, in market oysters along the U.S. coasts during different seasons. Samples from bays approved for human consumption were positive for HuNoVs GII.4, and AECV (PoNoV, PoSaV, BoNoV). Different seasonal and state distributions were detected. Simultaneous detection of HECV and AECV strains raises concerns for possible human co-infection, favoring the opportunity for recombination and emergence of new strains.The major source of water and food contamination is the discharge of waste into waters. Causative agents of gastroenteritis are excreted by the fecal route from healthy or unhealthy animals. We determined the presence of swine enteric viruses in feces and evaluated 5 technologies (cESTs) for animal waste treatment. Porcine SaVs, PoNoVs, RV-A and RV-C were detected before treatment. After treatment infectious particles were not detected, nor were clinical signs or seroconversion detected in inoculated Gn pigs. This is the first study to evaluate the impact of cESTs on virus detection and viability in manure and suggest that infectious virus would not be present in the field after treatment. Different from RVs, HECV do not growth in cell culture except for PoSaV/Cowden strain and murine NoV. The PoSaV/Cowden growths in LLC-PK cells in presence of intestinal content (IC), from Gn pigs or bile acids. This requires down-regulation of STAT1/Interferon (IFN) by the PKA pathway. We measured gene expression of LLC-PK cells infected with PoSaV/Cowden in the presence of IC. Based on a threshold of 1.5-fold change, at 4h PI, 29 genes were up-regulated and, at 8h PI, 83 genes were up- and 7 were down-regulated in infected cells. Late up-regulation of immune response genes suggest block or delay of IFN response. Up-regulation of genes involved in apoptosis suggests that PoSaV/Cowden may trigger apoptosis for cell release or spread. Our study may serve as a foundation for further analysis to understand the mechanism of SaV infection and potentially NoVs.
It is well appreciated that autonomic neurons have a central role in the homeostatic regulation of organs and systems and participate to the pathogenesis of several disease conditions. As such, the ...function and signalling pathways activated by sympathetic neurons (SNs) in different cell types and organs have become a matter of intense investigation throughout the years of modern biomedical research. This review is focused on the methods used to address sympathetic innervation of cardiac and skeletal muscles which, quite surprisingly, has remained incompletely understood, mainly due to the technical limitations of the traditional methodologies. The current review provides a summary of the existing literature and, putting together the results obtained with different methodological approaches, provides a comprehensive view of the complexity of the SN network in striated muscles.
Abstract
In order to investigate safety and immunogenicity of SARS-CoV-2 vaccine third dose in people living with HIV (PLWH), we analyze anti-RBD, microneutralization assay and IFN-γ production in ...216 PLWH on ART with advanced disease (CD4 count <200 cell/mm
3
and/or previous AIDS) receiving the third dose of a mRNA vaccine (BNT162b2 or mRNA-1273) after a median of 142 days from the second dose. Median age is 54 years, median CD4 nadir 45 cell/mm
3
(20–122), 93% HIV-RNA < 50 c/mL. In 68% of PLWH at least one side-effect, generally mild, is recorded. Humoral response after the third dose was strong and higher than that achieved with the second dose (>2 log
2
difference), especially when a heterologous combination with mRNA-1273 as third shot is used. In contrast, cell-mediated immunity remain stable. Our data support usefulness of third dose in PLWH currently receiving suppressive ART who presented with severe immune dysregulation.
Thermosetting polymers have been widely used in many industrial applications as adhesives, coatings and laminated materials, among others. Recently, bisphenol A (BPA) has been banned as raw material ...for polymeric products, due to its harmful impact on human health. On the other hand, the use of aromatic amines as curing agents confers excellent thermal, mechanical and flame retardant properties to the final product, although they are toxic and subject to governmental restrictions. In this context, sugar-derived diepoxy monomers and anhydrides represent a sustainable greener alternative to BPA and aromatic amines. Herein, we report an "in-situ" sol-gel synthesis, using as precursors tetraethylorthosilicate (TEOS) and aminopropyl triethoxysilane (APTS) to obtain bio-based epoxy/silica composites; in a first step, the APTS was left to react with 2,5-bis(oxyran-2-ylmethoxy)methylfuran (BOMF) or diglycidyl ether of bisphenol A (DGEBA)monomers, and silica particles were generated in the epoxy in a second step; both systems were cured with methyl nadic anhydride (MNA). Morphological investigation of the composites through transmission electron microscopy (TEM) demonstrated that the hybrid strategy allows a very fine distribution of silica nanoparticles (at nanometric level) to be achieved within a hybrid network structure for both the diepoxy monomers. Concerning the fire behavior, as assessed in vertical flame spread tests, the use of anhydride curing agent prevented melt dripping phenomena and provided high char-forming character to the bio-based epoxy systems and their phenyl analog. In addition, forced combustion tests showed that the use of anhydride hardener instead of aliphatic polyamine results in a remarkable decrease of heat release rate. An overall decrease of the smoke parameters, which is highly desirable in a context of greater fire safety was observed in the case of BOMF/MNA system. The experimental results suggest that the effect of silica nanoparticles on fire behavior appears to be related to their dispersion degree.
Glioblastoma (GBM) is the most frequent and lethal brain tumor, whose therapeutic outcome - only partially effective with current schemes - places this disease among the unmet medical needs, and ...effective therapeutic approaches are urgently required. In our attempts to identify repositionable drugs in glioblastoma therapy, we identified the neuroleptic drug chlorpromazine (CPZ) as a very promising compound. Here we aimed to further unveil the mode of action of this drug. We performed a supervised recognition of the signal transduction pathways potentially influenced by CPZ via Reverse-Phase Protein microArrays (RPPA) and carried out an Activity-Based Protein Profiling (ABPP) followed by Mass Spectrometry (MS) analysis to possibly identify cellular factors targeted by the drug. Indeed, the glycolytic enzyme PKM2 was identified as one of the major targets of CPZ. Furthermore, using the Seahorse platform, we analyzed the bioenergetics changes induced by the drug. Consistent with the ability of CPZ to target PKM2, we detected relevant changes in GBM energy metabolism, possibly attributable to the drug's ability to inhibit the oncogenic properties of PKM2. RPE-1 non-cancer neuroepithelial cells appeared less responsive to the drug. PKM2 silencing reduced the effects of CPZ. 3D modeling showed that CPZ interacts with PKM2 tetramer in the same region involved in binding other known activators. The effect of CPZ can be epitomized as an inhibition of the Warburg effect and thus malignancy in GBM cells, while sparing RPE-1 cells. These preclinical data enforce the rationale that allowed us to investigate the role of CPZ in GBM treatment in a recent multicenter Phase II clinical trial.
The impact of malting on the profile of the phenolic compounds and the antioxidant properties of tartary buckwheat (Fagopyrum tataricum L. Gaertn.) was investigated. A considerable increase in total ...phenolic compounds and higher antioxidant activity were observed after 88 h of germination. The highest relative increases in phenolic compounds were observed for quercetin, orientin, and vitexin, which are consequently major inducible phenolic compounds during malting. Only a minor relative increase was observed for the most abundant phenolic compound, rutin. Formulations of gluten-free cookies based on rice flour and buckwheat malt or flour in ratios 70:30, have been produced. In the raw material and cookies the proximate composition, starch, resistant starch, total polyphenols, profile of polyphenols, antioxidant activity and expected glycemic index were determined. Gluten-free cookies made with rice flour and buckwheat malt exhibited significantly higher total phenolic and quercetin contents. Comparing to control cookies higher antioxidant activity and lower glycemic index (p < 0.05) was found.
•Composition of phenolics in tartary buckwheat malt was studied.•Major inducible phenolics were quercetin orientin, vitexin, and rutin.•Antioxidant capacity of buckwheat seeds was positively affected by malting.•Tartary Malt Cookies (TMC) 70:30 rice flour and buckwheat malt were produced.•TMC have a higher phenols content, antioxidant capacity, and lower glycemic index.
Abstract
Background
Data on SARS-CoV-2 vaccine immunogenicity in PLWH are currently limited. Aim of the study was to investigate immunogenicity according to current CD4 T-cell count
Methods
PLWH on ...ART attending a SARS-CoV-2 vaccination program, were included in a prospective immunogenicity evaluation after receiving BNT162b2 or mRNA-1273. Participants were stratified by current CD4 T-cell count (poor CD4 recovery, PCDR: <200/mm3; intermediate CD4 recovery, ICDR: 200–500/mm3; high CD4 recovery, HCDR: >500/mm3). RBD-binding IgG, SARS-CoV-2 neutralizing antibodies (nAbs) and IFN-γ release were measured. As control group, HIV-negative healthcare workers (HCWs) were used
Findings
Among 166 PLWH, after 1 month from the booster dose, detectable RBD-binding IgG were elicited in 86.7% of PCDR, 100% of ICDR, 98.7% of HCDR, and a neutralizing titre ≥1:10 elicited in 70.0%, 88.2%, and 93.1%, respectively. Compared to HCDR, all immune response parameters were significantly lower in PCDR. After adjusting for confounders, current CD4 T-cell <200/mm3 significantly predicted a poor magnitude of anti-RDB, nAbs and IFN-γ response. As compared with HCWs, PCDR elicited a consistently reduced immunogenicity for all parameters, ICDR only a reduced RBD-binding antibody response, whereas HCDR elicited a comparable immune response for all parameters
Conclusion
Humoral and cell-mediated immune response against SARS-CoV-2 were elicited in most of PLWH, albeit significantly poorer in those with CD4 T-cell <200/mm3 versus those with >500 cell/mm3 and HIV-negative controls. A lower RBD-binding antibody response than HCWs was also observed in PLWH with CD4 T-cell 200–500/mm3, whereas immune response elicited in PLWH with a CD4 T-cell >500/mm3 was comparable to HIV-negative population
Humoral and cell-mediated immune-response against SARS-CoV-2 were elicited in PLWH, significantly poorer in those with CD4 T-cell <200/mm3vs those with >500 cell/mm3and HIV-negative controls; immune response in PLWH with a CD4 T-cell >500/mm3 was comparable to HIV-negative population.
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