Protein misfolding has been linked to numerous inherited diseases. Loss‐ and gain‐of‐function mutations (common features of genetic diseases) may cause the destabilization of proteins, leading to ...alterations in their properties and/or cellular location, resulting in their incorrect functioning. Misfolded proteins can, however, be rescued via the use of proteostasis regulators and/or pharmacological chaperones, suggesting that treatments with small molecules might be developed for a range of genetic diseases. This work describes the potential of these small molecules in this respect, including for the treatment of congenital disorder of glycosylation (CDG) due to phosphomannomutase 2 deficiency (PMM2‐CDG).
Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited heterogeneous neurodegenerative rare disorders. These patients present with dystonia, spasticity, parkinsonism and ...neuropsychiatric disturbances, along with brain magnetic resonance imaging (MRI) evidence of iron accumulation. In sum, they are devastating disorders and to date, there is no specific treatment. Ten NBIA genes are accepted: PANK2, PLA2G6, C19orf12, COASY, FA2H, ATP13A2, WDR45, FTL, CP, and DCAF17; and nonetheless, a relevant percentage of patients remain without genetic diagnosis, suggesting that other novel NBIA genes remain to be discovered. Overlapping complex clinical pictures render an accurate differential diagnosis difficult. Little is known about the pathophysiology of NBIAs. The reported NBIA genes take part in a variety of pathways: CoA synthesis, lipid and iron metabolism, autophagy, and membrane remodeling. The next‐generation sequencing revolution has achieved relevant advances in genetics of Mendelian diseases and provide new genes for NBIAs, which are investigated according to 2 main strategies: genes involved in disorders with similar phenotype and genes that play a role in a pathway of interest. To achieve an effective therapy for NBIA patients, a better understanding of the biological process underlying disease is crucial, moving toward a new age of precision medicine.
Aim
To evaluate the antibiofilm activity of 2.5% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX), 2% alexidine (ALX) and 0.2% cetrimide (CTR) alone and in combination on mature polymicrobial root ...canal biofilms on human dentine using confocal laser scanning microscopy (CLSM).
Methodology
Twenty‐eight human dentine specimens were infected for 21 days with microbial samples collected from infected root canals of three volunteers. Antibiofilm activity of the irrigating solutions was evaluated after 3 min of contact time under CLSM. For quantification purposes, bioimage_L software was used. The variables evaluated were the log10 of total biovolume (μm3) and percentage of live cells (green) population. Statistical analysis of both variables was performed using an anova test and a post hoc Duncan test to determine significant clusters amongst groups. The variable green population percentage was previously subjected to the normalized Anscombe transformation.
Results
The NaOCl group had a total biovolume and percentage of live cells significantly lower than the other groups (P ˂ 0.001). The addition of 0.2% CTR significantly increased the antimicrobial effect of 2% CHX (P ˂ 0.001). There were no significant differences between 0.2% CTR, 2% ALX and the combination of both (P ˂ 0.05).
Conclusions
Overall, 2.5% NaOCl dissolved and killed bacteria significantly more efficiently when used against polymicrobial mature biofilm on human dentine. Cetrimide improved the antimicrobial activity of chlorhexidine and alexidine.
Quorum quenching decreases Pseudomonas aeruginosa virulence factors and biofilm formation, alleviating infections in animal models. Nevertheless, it is usually performed in laboratory strains such as ...PAO1 and PA14, and studies involving clinical or environmental isolates are scarce. In this work, the effects of ZnO nanoparticles, a potent quorum and virulence quencher for the PAO1 strain, were tested in six clinical strains from cystic fibrosis patients, a furanone C‐30 resistant clinical strain from urine, two PA14 gallium resistant mutants, a PA14 C‐30 resistant mutant and four environmental isolates. ZnO nanoparticles effectively decreased elastase, pyocyanin, and biofilm formation for most of the strains; regardless their origin or their resistance against the canonical quorum quencher C‐30 or the novel antimicrobial gallium. The data indicate ZnO nanoparticles may have a broad spectrum for the quorum quenching of relevant strains and that may be an alternative to treat Ps. aeruginosa recalcitrant infections.
Significance and Impact of the Study
Virulence inhibition by quorum quenchers in Pseudomonas aeruginosa is usually tested in laboratory strains and studies of their effects in relevant clinical and environmental strains are scarce. This study is significant as the effects of ZnO nanoparticles in QS‐dependent virulence factor production were tested in six clinical strains from cystic fibrosis patients, a C‐30 resistant clinical strain from urine, two PA14 gallium resistant mutants, a PA14 C‐30 resistant mutant, and four environmental isolates. ZnO nanoparticles decreased elastase, pyocyanin, and biofilms for most of the strains; indicating they have broad spectrum and may be an alternative to treat Ps. aeruginosa infections.
Significance and Impact of the Study: Virulence inhibition by quorum quenchers in Pseudomonas aeruginosa is usually tested in laboratory strains and studies of their effects in relevant clinical and environmental strains are scarce. This study is significant as the effects of ZnO nanoparticles in QS‐dependent virulence factor production were tested in six clinical strains from cystic fibrosis patients, a C‐30 resistant clinical strain from urine, two PA14 gallium resistant mutants, a PA14 C‐30 resistant mutant, and four environmental isolates. ZnO nanoparticles decreased elastase, pyocyanin, and biofilms for most of the strains; indicating they have broad spectrum and may be an alternative to treat Ps. aeruginosa infections.
In this paper, we address the problem of the ranking of companies based on their diversity and financial performance. The addressed problem is a multiple criteria decision‐making problem where a ...composite measure needs to be obtained to rank firms. Taking as a reference the methodological approach followed by Refinitiv in the construction of their Diversity and Inclusion Index, we propose an alternative ranking framework that overcomes some of the problems identified in the methodological approach of Refinitiv. In particular, the proposed method in this work does not require the a priori establishment of a weighting scheme and is able to incorporate the past behavior of the companies in terms of diversity in their workplaces.
•The proposed FE model shows to be promising to detect expansion to date in concrete structures.•Scattering between measured and calculated data ranged from 3 to 30% depending on the member.•The ...proposed FE model is able to match cracking orientation, intensity and main locations.•Results indicate that ASR affected RBC bridge was near global failure after 50 years in service.•Parameters such as leaching, creep and shrinkage should be further evaluated to improve the model.
Modeling alkali-silica reaction (ASR) induced expansion and damage in reinforced concrete structures is quite complex, yet necessary to obtain accurate predictions of the structural responses of distressed concrete members. In order to predict the expansion and damage at the structural (macroscopic) scale, a new simple yet reliable finite element (FE) approach was developed and validated by the authors. It accounts for the most important parameters affecting ASR through an engineering-based approach, without the need for non-technical guesses or to “fit” model parameters. In this work, the proposed modelling approach is used to analyze the Robert-Bourassa/Charest overpass (Quebec City, Canada), which was demolished in 2010 due to severe structural distress induced by ASR. Results show that the proposed FE approach is capable of properly performing the condition assessment of the structure at the time of demolition based only on simple measurable parameters, thus proving its applicability to simulate ASR in slender reinforced concrete structures.
The use of orange wastes, generated in the orange juice industry, for removing cadmium from aqueous solutions has been investigated. The material was characterized by Fourier transform infrared ...spectroscopy and batch experiments were conducted to determine the adsorption capacity of the biomass. A strong dependence of the adsorption capacity on pH was observed, the capacity increasing as pH value rose. Kinetics and adsorption equilibrium were studied at different pH values (4–6). The adsorption process was quick and the equilibrium was attained within 3
h. The maximum adsorption capacity of orange waste was found to be 0.40, 0.41 and 0.43
mmol/g at pH 4–6, respectively. The kinetic data were analysed using various kinetic models – pseudo-first order equation, pseudo-second order equation, Elovich equation and intraparticle diffusion equation – and the equilibrium data were tested using four isotherm models – Langmuir, Freundlich, Sips and Redlich–Peterson. The data were fitted by non-linear regression and five error analysis methods were used to evaluate the goodness of the fit. The Elovich equation provides the greatest accuracy for the kinetic data and the Sips model the closest fit for the equilibrium data.
The use of edible films and coatings is an environmentally friendly technology that offers substantial advantages for shelf-life increase of many food products including fruits and vegetables. The ...development of new natural edible films and coatings with the addition of antimicrobial compounds to preserve fresh and minimally processed fruits and vegetables is a technological challenge for the industry and a very active research field worldwide. Antimicrobial agents have been successfully added to edible composite films and coatings based on polysaccharides or proteins such as starch, cellulose derivatives, chitosan, alginate, fruit puree, whey protein isolated, soy protein, egg albumen, wheat gluten, or sodium caseinate. This paper reviews the development of edible films and coatings with antimicrobial activity, typically through the incorporation of antimicrobial food additives as ingredients, the effect of these edible films on the control of target microorganisms, the influence of antimicrobial agents on mechanical and barrier properties of stand-alone edible films, and the effect of the application of antimicrobial edible coatings on the quality of fresh and fresh-cut fruits and vegetables.
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