• Eriksen Teague posted an update 3 days, 15 hours ago

    An urgent demand exists for the development of novel delivery systems that efficiently transport antibacterial agents across cellular membranes for the eradication of intracellular pathogens. In this study, the clinically relevant poorly water-soluble antibiotic, rifampicin, was confined within mesoporous silica nanoparticles (MSN) to investigate their ability to serve as an efficacious nanocarrier system against small colony variants of Staphylococcus aureus (SCV S. aureus) hosted within Caco-2 cells. The surface chemistry and particle size of MSN were varied through modifications during synthesis, where 40 nm particles with high silanol group densities promoted enhanced cellular uptake. Extensive biophysical analysis was performed, using quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) microscopy, to elucidate the mechanism of MSN adsorption onto semi-native supported lipid bilayers (snSLB) and, thus, uncover potential cellular uptake mechanisms of MSN into Caco-2 cells. Such studies revealed that MSN with reduced silanol group densities were prone to greater particle aggregation on snSLB, which was expected to restrict endocytosis. MSN adsorption and uptake into Caco-2 cells correlated well with antibacterial efficacy against SCV S. aureus, with 40 nm hydrophilic particles triggering a ~2.5-log greater reduction in colony forming units, compared to the pure rifampicin. Thus, this study provides evidence for the potential to design silica nanocarrier systems with controlled surface chemistries that can be used to re-sensitise intracellular bacteria to antibiotics by delivering them to the site of infection.Human adenoviruses (AdVs) are one of the most common causes of acute respiratory viral infections worldwide. Multiple AdV serotypes with low cross-reactivity circulate in the human population, making the development of an effective vaccine very challenging. In the current study, we designed a cross-reactive AdV vaccine based on the T-cell epitopes conserved among various AdV serotypes, which were inserted into the genome of a licensed cold-adapted live attenuated influenza vaccine (LAIV) backbone. We rescued two recombinant LAIV-AdV vaccines by inserting the selected AdV T-cell epitopes into the open reading frame of full-length NA and truncated the NS1 proteins of the H7N9 LAIV virus. We then tested the bivalent vaccines for their efficacy against influenza and human AdV5 in a mouse model. The vaccine viruses were attenuated in C57BL/6J mice and induced a strong influenza-specific antibody and cell-mediated immunity, fully protecting the mice against virulent influenza virus infection. The CD8 T-cell responses induced by both LAIV-AdV candidates were functional and efficiently killed the target cells loaded either with influenza NP366 or AdV DBP418 peptides. In addition, high levels of recall memory T cells targeted to an immunodominant H2b-restricted CD8 T-cell epitope were detected in the immunized mice after the AdV5 challenge, and the magnitude of these responses correlated with the level of protection against pulmonary pathology caused by the AdV5 infection. Our findings suggest that the developed recombinant vaccines can be used for combined protection against influenza and human adenoviruses and warrant further evaluation on humanized animal models and subsequent human trials.Metabolic syndrome (MetS) is a major public health challenge throughout the world, although studies on its association with the inflammatory potential of diet are inconsistent. The aim of this prospective study was to assess the association between the Dietary Inflammatory Index (DII®) and the risk of MetS and its components in a Korean population. click here Data from 157,812 Korean adults (mean age 52.8 years; 53,304 men and 104,508 women with mean follow-up of 7.4 years) collected by members of the Korean Genome and Epidemiology Study form the basis for this report. DII scores were calculated based on Semi-Quantitative Food-Frequency Questionnaire data. Multivariable-adjusted Cox proportional hazard models were used to estimate the association between DII scores and MetS. In women, higher DII scores (pro-inflammatory diet) increased the risk of MetS (hazard ratio [HR]quintile5 v. 1 1.43; 95% confidence interval (CI) 1.21-1.69; p for trend ≤ 0.0001) and its five components. A positive association was observed for postmenopausal women, with a 50% higher risk of developing MetS (HRquintile5 v. 1 1.50; 95% CI 1.23-1.83; p for trend = 0.0008) after fully adjusting for potential confounders. Irrespective of the menopausal status of women, higher DII (=Q5) scores were positively associated with all 5 components of MetS (p less then 0.05). In men, higher DII scores significantly increased the risk of low HDL cholesterol [HR]quintile5 v. 1 1.59 (1.27-1.99); p for trend = 0.0001], elevated waist circumferences [HR]quintile5 v. 1 1.28 (1.08-1.52); p for trend = 0.01], and high blood pressure [HR]quintile5 v. 1 1.17 (1.03-1.32); p for trend = 0.05]. These results indicate that diet with pro-inflammatory potential, as represented by higher DII scores, is prospectively associated with increased risk of MetS, and the relationship is stronger in women than in men.The current systematic review evaluated the effects of different pre-cooling techniques on sports performance in highly-trained athletes under high temperature conditions. PubMed/MEDLINE, EMBASE, Web of Science, CENTRAL, Scopus, and SPORTDiscus databases were searched from inception to December 2019. Studies performing pre-cooling interventions in non-acclimatized highly-trained athletes (>55 mL/kg/min of maximal oxygen consumption) under heat conditions (≥30 °C) were included. The searched reported 26 articles. Pre-cooling techniques can be external (exposure to ice water, cold packs, or cooling clothes), internal (intake of cold water or ice), or mixed. Cooling prior to exercise concluded increases in distance covered (1.5-13.1%), mean power output (0.9-6.9%), time to exhaustion (19-31.9%), work (0.1-8.5%), and mean peak torque (10.4-22.6%), as well as reductions in completion time (0.6-6.5%). Mixed strategies followed by cold water immersion seem to be the most effective techniques, being directly related with the duration of cooling and showing the major effects in prolonged exercise protocols.