Cmv-specific cell-mediated immunity in immunocompetent adults with primary cmv infection: A case series and review of the literature

Cytomegalovirus-specific cell-mediated immunity (CMV-CMI) in actively infected healthy immunocompetent hosts has been poorly investigated. Conversely, correlates of maternal protective immunity for the fetus after primary infection in pregnancy continue to be studied. The kinetics and magnitude of CMV-specific CMI in immunocompetent primary CMV-infected adults are described. A literature review on CMV-CMI in primarily infected pregnant women and its correlation to the risk of vertical virus transmission is included. Immunological measurements after infection were performed by enzyme-linked ImmunoSPOT assay enumerating IFN-γ secreting CMV-specific T cells, at a single cell level, upon in vitro stimulation with viral antigens. Simultaneously, serological and virological profiles of infected patients were investigated. Patients displayed mild-to-moderate clinical and laboratory profiles for infection, and all showed positive EliSpot results in the early stage of infection (<20 days after onset). The virus-CMI was strong in the majority of patients (58.8%) in which the lowest CMV-DNAemia levels (<300 copies/mL) were detected. Significantly higher viral loads were observed in patients with weak CMV-CMI at the same time-point post-infection (up to 15,104 copies/mL; p < 0.001). T cell response magnitudes to IE-1 and pp65-UL83 peptides were overlapping and stable over time. In these case series, the early presence of CMV-CMI was probably pivotal in controlling viral replication and led to spontaneous viral clearance

Virological and Immunological Monitoring of Human Cytomegalovirus Infection in Heart and Small Bowel/Multivisceral Transplantation

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Shape optimization of a curved duct with Free Form Deformations

The Free Form Deformation method was applied to a S-duct geometry to reduce total pressure losses and flow distortion. The deformation method was coupled with a multiobjective genetic algorithm to optimize the shape of a diffusing S-duct, which was previously investigated, both numerically and experimentally. During the optimization process, 200 deformed shapes were tested with steady-state CFD simulations and the performances were evaluated both in terms of total pressure losses and swirl angle at the outlet. It was obtained a Pareto front with a maximum total pressure losses reduction of 20% and a maximum swirl reduction of 10%. The two extreme points of the Pareto front were further investigated by transient Detached Eddy Simulations to assess also the impact of the optimization on the flow instability. Surprisingly, one of the solutions showed stable and stationary vortical structures. This is in strong contrast with the previous investigations of the flow field time history of the baseline configuration, which outlined strong oscillations of the flow field combined with a high increase of the distortion parameters in comparison with the time-averaged flow field

Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance

The growing global epidemic of obesity and type 2 diabetes mellitus has de-termined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the West-ern world and a leading cause of liver transplan-tation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close as-sociation between insulin resistance (IR), dys-biosis, and steatosis. However, all the mecha-nisms that lead to impaired permeability, inflam- mation, and fibrosis have not been fully clari- fied. Recently, new possible treatment modali- ties have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (poly -phenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NA-FLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the thera-peutic strategies currently in use

A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation

Background: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5(+)) to counteract white adipogenesis by promoting WAT browning. Methods: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5(+), or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. Results: A5(+) administration significantly reduced lipids' accumulation in adipocytes when compared to control cells (p < 0.005). Similarly, A5(+) inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (p < 0.0001). We also found that A5(+) significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (p < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (p < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. Conclusion: Overall, these results demonstrated that the synergistic effect of compounds contained in A5(+) may be able to counteract adipogenesis and then obesity by inducing fat browning