Among the biopolymers from animal sources, keratin is one the most abundant, with a major contribution from side stream products from cattle, ovine and poultry industry, offering many opportunities ...to produce cost-effective and sustainable advanced materials. Although many reviews have discussed the application of keratin in polymer-based biomaterials, little attention has been paid to its potential in association with other polymer matrices. Thus, herein, we present an extensive literature review summarizing keratin's compatibility with other synthetic, biosynthetic and natural polymers, and its effect on the materials' final properties in a myriad of applications. First, we revise the historical context of keratin use, describe its structure, chemical toolset and methods of extraction, overview and differentiate keratins obtained from different sources, highlight the main areas where keratin associations have been applied, and describe the possibilities offered by its chemical toolset. Finally, we contextualize keratin's potential for addressing current issues in materials sciences, focusing on the effect of keratin when associated to other polymers' matrices from biomedical to engineering applications, and beyond.
The in vitro activity of the imidazolium salt C₁₆MImCl against planktonic and biofilm cells of multidrug‐resistant isolates of Candida tropicalis was evaluated, both in solution and applied on a ...commercial catheter surface. This was determined by inhibition and susceptibility assays of biofilm and planktonic cells. In both cases, C₁₆MImCl prevented in vitro biofilm formation of C. tropicalis strains, including multidrug‐resistant ones. Outstanding performances were observed, even at extremely low concentrations. Furthermore, this is the first report of the antifungal lock property of C₁₆MImCl, using a tracheal catheter as the test specimen to mimic a clinical in vivo condition. As such, C₁₆MImCl has been identified as a promising antimicotic pharmaceutical candidate for the treatment of candidiasis infections. SIGNIFICANCE AND IMPACT OF THE STUDY: The imidazolium salt 1‐n‐hexadecyl‐3‐methylimidazolium chloride (C₁₆MImCl) strongly prevents, in concentrations as low as 0·028 μg ml⁻¹, the biofilm formation of multidrug‐resistant Candida tropicalis isolates, either in solution or applied on the surface of commercial catheters. This presents an effective antimicotic candidate and alternative for invasive clinical procedure toolset asepsis.
Undeniably, new antifungal treatments are necessary against pathogenic fungi. Fungal infections have significantly increased in recent decades, being highlighted as important causes of morbidity and ...mortality, particularly in immunocompromised patients. Five main antifungal classes are used: (i) azoles, (ii) echinocandins, (iii) polyenes, (iv) allylamines and (v) pyrimidine analogues. Moreover, the treatment of mycoses has several limitations, such as undesirable side effects, narrow activity spectrum, a small number of targets and fungal resistance, which are still of major concern in clinical practice. The discovery of new antifungals is mostly achieved by the screening of natural or synthetic/semisynthetic chemical compounds. The most recent discoveries in drug resistance mechanism and their avoidance were explored in a review, focusing on different antifungal targets, as well as new agents or strategies, such as combination therapy, that could improve antifungal therapy.
Significance and Impact of the Study
The failure to respond to antifungal therapy is complex and is associated with microbiological resistance and increased expression of virulence in fungal pathogens. Thus, this review offers an overview of current challenges in the treatment of fungal infections associated with increased antifungal drug resistance and the formation of biofilms in these opportunistic pathogens. Furthermore, the most recent and potential strategies to combat fungal pathogens are explored here, focusing on new agents as well as innovative approaches, such as combination therapy between antifungal drugs or with natural compounds.
Significance and Impact of the Study: The failure to respond to antifungal therapy is complex and is associated with microbiological resistance and increased expression of virulence in fungal pathogens. Thus, this review offers an overview of current challenges in the treatment of fungal infections associated with increased antifungal drug resistance and the formation of biofilms in these opportunistic pathogens. Furthermore, the most recent and potential strategies to combat fungal pathogens are explored here, focusing on new agents as well as innovative approaches, such as combination therapy between antifungal drugs or with natural compounds.
Observational burden of illness studies are used in pharmacoepidemiology to address a variety of objectives, including contextualizing the current treatment setting, identifying important treatment ...gaps, and providing estimates to parameterize economic models. Methodologies such as retrospective chart review may be utilized in settings for which existing datasets are not available or do not include sufficient clinical detail. While specifying the number of charts to be extracted and/or determining whether the number that can feasibly extracted will be clinically meaningful is an important study design consideration, there is a lack of rigorous methods available for sample size calculation in this setting. The objective of this study was to develop recommended sample size calculations for use in such studies.
Calculations for identifying the optimal feasible sample size calculations were derived, for studies characterizing treatment patterns and medical costs, based on the ability to comprehensively observe treatments and maximize precision of resulting 95% confidence intervals. For cost outcomes, if the standard deviation is not known, the coefficient of variation cv can be used as an alternative. A case study of a chart review of advanced melanoma (MELODY) was used to characterize plausible values for cv in a real-world example.
Across sample sizes, any treatment given with greater than 1% frequency has a high likelihood of being observed. For a sample of size 200, and a treatment given to 5% of the population, the precision of a 95% confidence interval (CI) is expected to be ±0.03. For cost outcomes, for the median cv value observed in the MELODY study (0.72), a sample size of approximately 200 would be required to generate a 95% CI precise to within ±10% of the mean.
This study presents a formal guidance on sample size calculations for retrospective burden of illness studies. The approach presented here is methodologically rigorous and designed for practical application in real-world retrospective chart review studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, the structure, electrical and thermal properties of ten polymer compositions based on polylactic acid (PLA), low-cost industrial graphene nanoplates (GNP) and multi-walled carbon ...nanotubes (MWCNT) in mono-filler PLA/MWCNT and PLA/GNP systems with 0–6 wt.% filler content were investigated. Filler dispersion was further improved by combining these two carbon nanofillers with different geometric shapes and aspect ratios in hybrid bi-filler nanocomposites. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Raman spectroscopy exhibited uniform dispersion of nanoparticles in a polymer matrix. The obtained results have shown that for the mono-filler systems with MWCNT or GNP, the electrical conductivity increased with decades. Moreover, a small synergistic effect was observed in the GNP/MWCNT/PLA bi-filler hybrid composites when combining GNP and CNT at a ratio of 3% GNP/3% CNT and 1.5% GNP:4.5% CNT, showing higher electrical conductivity with respect to the systems incorporating individual CNTs and GNPs at the same overall filler concentration. This improvement was attributed to the interaction between CNTs and GNPs limiting GNP aggregation and bridging adjacent graphene platelets thus, forming a more efficient network. Thermal conductivity increases with higher filler content; this effect was more pronounced for the mono-filler composites based on PLA and GNP due to the ability of graphene to better transfer the heat. Morphological analysis carried out by electron microscopy (SEM, TEM) and Raman indicated that the nanocomposites present smaller and more homogeneous filler aggregates. The well-dispersed nanofillers also lead to a microstructure which is able to better enhance the electron and heat transfer and maximize the electrical and thermal properties. The obtained composites are suitable for the production of a multifunctional filament with improved electrical and thermal properties for different fused deposition modelling (FDM) 3D printing applications and also present a low production cost, which could potentially increase the competitiveness of this promising market niche.
There is a need to classify and standardize graphene-related materials giving the growing use of this materials industrially. One of the most used and more difficult to classify is graphene oxide ...(GO). Inconsistent definitions of GO, closely relating it to graphene, are found in the literature and industrial brochures. Hence, although they have very different physicochemical properties and industrial applications, commonly used classifications of graphene and GO definitions are not substantial. Consequently, the lack of regulation and standardization create trust issues among sellers and buyers that impede industrial development and progress. With that in mind, this study offers a critical assessment of 34 commercially available GOs, characterized using a systematic and reliable protocol for accessing their quality. We establish correlations between GO physicochemical properties and its applications leading to rationale for its classification.
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 intimately attaches to intestinal epithelial monolayers and produces attaching and effacing (A/E) lesions. In addition, EHEC infection causes ...disruptions of intercellular tight junctions, leading to clinical sequelae that include acute diarrhea, hemorrhagic colitis, and the hemolytic-uremic syndrome. Current therapy remains supportive since antibiotic therapy increases the risk of systemic complications. This study focused on the potential therapeutic effect of an alternative form of therapy, probiotic Lactobacillus rhamnosus strain GG, to attenuate EHEC-induced changes in paracellular permeability in polarized MDCK-I and T84 epithelial cell monolayers. Changes in epithelial cell morphology, electrical resistance, dextran permeability, and distribution and expression of claudin-1 and ZO-1 were assessed using phase-contrast, immunofluorescence, and transmission electron microscopy and macromolecular flux. This study demonstrated that pretreatment of polarized MDCK-I and T84 cells with the probiotic L. rhamnosus GG reduced morphological changes and diminished the number of A/E lesions induced in response to EHEC O157:H7 infection. With probiotic pretreatment there was corresponding attenuation of the EHEC-induced drop in electrical resistance and the increase in barrier permeability assays. In addition, L. rhamnosus GG protected epithelial monolayers against EHEC-induced redistribution of the claudin-1 and ZO-1 tight junction proteins. In contrast to the effects seen with the live probiotic, heat-inactivated L. rhamnosus GG had no effect on EHEC binding and A/E lesion formation or on disruption of the barrier function. Collectively, these findings provide in vitro evidence that treatment with the probiotic L. rhamnosus strain GG could prove to be an effective management treatment for preventing injury of the epithelial cell barrier induced by A/E bacterial enteropathogens.
Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have ...generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths.
We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days.
The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI eCI, 2.1-2.3) and 9.1 (95% eCI, 8.9-9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4-2.8) and 12.8 (95% eCI, 12.2-13.1) for every 1000 heart failure deaths, respectively.
Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day-and especially under a changing climate.
The European project PHASE aims to evaluate patterns of change in the temperature-mortality relationship and in the number of deaths attributable to heat in nine European cities in two periods, ...before and after summer 2003 (1996-2002 and 2004-2010). We performed age-specific Poisson regression models separately in the two periods, controlling for seasonality, air pollution and time trends. Distributed lag non-linear models were used to estimate the Relative Risks of daily mortality for increases in mean temperature from the 75th to 99th percentile of the summer distribution for each city. In the recent period, a reduction in the mortality risk associated to heat was observed only in Athens, Rome and Paris, especially among the elderly. Furthermore, in terms of heat-attributable mortality, 985, 787 and 623 fewer deaths were estimated, respectively, in the three cities. In Helsinki and Stockholm, there is a suggestion of increased heat effect. Noteworthy is that an effect of heat was still present in the recent years in all cities, ranging from +11% to +35%. In Europe, considering the warming observed in recent decades and population ageing, effective intervention measures should be promoted across countries, especially targeting vulnerable subgroups of the population with lower adaptive resources.
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