Chiral Analysis of Pesticides and Drugs of Environmental Concern: Biodegradation and Enantiomeric Fraction

The importance of stereochemistry for medicinal chemistry and pharmacology is well recognized and the dissimilar behavior of enantiomers is fully documented. Regarding the environment, the significance is equivalent since enantiomers of chiral organic pollutants can also differ in biodegradation processes and fate, as well as in ecotoxicity. This review comprises designed biodegradation studies of several chiral drugs and pesticides followed by enantioselective analytical methodologies to accurately measure the enantiomeric fraction (EF). The enantioselective monitoring of microcosms and laboratory-scale experiments with different environmental matrices is herein reported. Thus, this review focuses on the importance of evaluating the EF variation during biodegradation studies of chiral pharmaceuticals, drugs of abuse, and agrochemicals and has implications for the understanding of the environmental fate of chiral pollutants.The authors wish to thank Fundação para a Ciência e Tecnologia—FCT for financial support under the project Fluoropharma PTDC/EBB-EBI/111699/2009, the PhD grant attributed to Alexandra S. Maia SFRH/BD/86939/2012, QREN-POPH, European Social Fund, MCTES, PEst FCOMP-01-0124-FEDER-022718; PEst-OE/EQB/LA0016/2011, PEst-OE/SAU/UI4040/2014. This research was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT—Fundação para a Ciência e Tecnologia and European Regional Development Fund (ERDF), in the framework of the program PT2020 and by CESPU (ChiralDrugs_CESPU_2017

Tribomechanical Comparison between PVA Hydrogels Obtained Using Different Processing Conditions and Human Cartilage

Designing materials for cartilage replacement raises several challenges due to the complexity of the natural tissue and its unique tribomechanical properties. Poly(vinyl alcohol) (PVA) hydrogels have been explored for such purpose since they are biocompatible, present high chemical stability, and their properties may be tailored through different strategies. In this work, the influence of preparation conditions of PVA hydrogels on its morphology, water absorption capacity, thermotropic behavior, mechanical properties, and tribological performance was evaluated and compared with those of human cartilage (HC). The hydrogels were obtained by cast-drying (CD) and freeze-thawing (FT), in various conditions. It was found that the method of preparation of the PVA hydrogels critically affects their microstructure and performance. CD gels presented a denser structure, absorbed less water, were stiffer, dissipated less energy, and withstood higher loads than FT gels. Moreover, they led to friction coefficients against stainless steel comparable with those of HC. Overall, CD hydrogels had a closer performance to natural HC, when compared to FT ones.info:eu-repo/semantics/publishedVersio

The chick chorioallantoic membrane model: A new in vivo tool to evaluate breast cancer stem cell activity

The high plasticity of cancer stem-like cells (CSCs) allows them to differentiate and proliferate, specifically when xenotransplanted subcutaneously into immunocompromised mice. CSCs are highly tumorigenic, even when inoculated in small numbers. Thus, in vivo limiting dilution assays (LDA) in mice are the current gold standard method to evaluate CSC enrichment and activity. The chick embryo chorioallantoic membrane (CAM) is a low cost, naturally immuneincompetent and reproducible model widely used to evaluate the spontaneous growth of human tumor cells. Here, we established a CAM-LDA assay able to rapidly reproduce tumor specificities— in particular, the ability of the small population of CSCs to form tumors. We used a panel of organotropic metastatic breast cancer cells, which show an enrichment in a stem cell gene signature, enhanced CD44+/CD24-/low cell surface expression and increased mammosphere-forming efficiency (MFE). The size of CAM-xenografted tumors correlate with the number of inoculated cancer cells, following mice xenograft growth pattern. CAM and mice tumors are histologically comparable, displaying both breast CSC markers CD44 and CD49f. Therefore, we propose a new tool for studying CSC prevalence and function—the chick CAM-LDA—a model with easy handling, accessibility, rapid growth and the absence of ethical and regulatory constraints.This work was funded by FEDER—Fundo Europeu de Desenvolvimento Regional— funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior under the projects PestC/SAU/LA0003/2013, NORTE-01-0145-FEDER-000029, SAICTPAC/0022/2015 and FCT/02/SAICT/2017/030625. FCT funded the research grant of RC (SFRH/BD/135831/2018). IPATIMUP integrated the i3S Research Unit, which was partially supported by FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145FEDER-007274)

City size and the spreading of COVID-19 in Brazil

The current outbreak of the coronavirus disease 2019 (COVID-19) is an unprecedented example of how fast an infectious disease can spread around the globe (especially in urban areas) and the enormous impact it causes on public health and socio-economic activities. Despite the recent surge of investigations about different aspects of the COVID-19 pandemic, we still know little about the effects of city size on the propagation of this disease in urban areas. Here we investigate how the number of cases and deaths by COVID-19 scale with the population of Brazilian cities. Our results indicate that large cities are proportionally more affected by COVID-19, such that every 1% rise in population is associated with 0.57% increase in the number of cases per capita and 0.25% in the number of deaths per capita. The difference between the scaling of cases and deaths indicates the case fatality rate decreases with city size. The latest estimates show that a 1% increase in population associates with a 0.14% reduction in the case fatality rate of COVID-19; however, this urban advantage has decreased over time. We interpret this to be due to the existence of proportionally more health infrastructure in the largest cities and a lower proportion of older adults in large urban areas. We also find the initial growth rate of cases and deaths to be higher in large cities; however, these growth rates tend to decrease in large cities and to increase in small ones during the long-term course of the pandemic

Orbital Exenteration for Eyelid Skin Carcinoma

Exenteration of the orbit is a disfiguring and destructive procedure; it is generally performed for orbital malignancies and often provides a significant reconstructive challenge. Our purpose was to evaluate the clinical indications for orbital exenteration in a tertiary referral center and to assess the reconstructive options employed. A retrospective nonrandomized analysis was performed, selecting all patients undergoing orbital exenteration over a 5-year period, between January 2005 and January 2010. Patient demographics, tumor characteristics, and reconstructive techniques used were evaluated. Twenty patients with a mean age of 76.5 years underwent total orbital exenteration. Basal cell carcinoma was the main operative indication (45%), followed by squamous cell carcinoma (15%). Reconstructive techniques included cover of the raw orbital cavity with a temporal muscular flap in all cases followed with split skin grafting (25%), bilaterally pedicle V-Y advancement flap (10%) and a fasciocutaneous island flap of the retroauricular region (65%). Twenty percent of patients had local complications and all were treated in a satisfactory fashion. Eyelid skin tumors remain an important cause of orbital exenteration. Temporal muscle flap is a reliable and stable reconstructive solution after orbital exenteration and additional aid is supplied with skin grafts or local flaps. This technique ensures a good aesthetic outcome and better situation for later complementary treatments and minimal associated donor site morbidity

Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in Staphylococcus aureus with Divergent Resistance Phenotypes

Healthcare-associated methicillin-resistant Staphylococcus aureus infections represent extremely high morbidity and mortality rates worldwide. We aimed to assess the antimicrobial potential and synergistic effect between Epigalocatenin-3-gallate (EGCG) and different antibiotics in S. aureus strains with divergent resistance phenotypes. EGCG exposure effects in epigenetic and drug resistance key modulators were also evaluated. S. aureus strains (n = 32) were isolated from infected patients in a Lisbon hospital. The identification of the S. aureus resistance phenotype was performed through automatized methods. The antibiotic synergistic assay was performed through disk diffusion according to EUCAST guidelines with co-exposure to EGCG (250, 100, 50 and 25 µg/mL). The bacteria's molecular profile was assessed through FTIR spectroscopy. The transcriptional expression of OrfX, SpdC and WalKR was performed by using qRT-PCR. FTIR-spectroscopy analysis enabled the clear discrimination of MRSA/MSSA strains and the EGCG exposure effect in the bacteria's molecular profiles. Divergent resistant phenotypes were associated with divergent transcriptional expression of the epigenetic modulator OrfX, particularly in MRSA strains, as well as the key drug response modulators SpdC and WalKR. These results clearly demonstrate that EGCG exposure alters the expression patterns of key epigenetic and drug response genes with associated divergent-resistant profiles, which supports its potential for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms.info:eu-repo/semantics/publishedVersio

Cadherin expression and emt: A focus on gliomas

Cadherins are calcium-binding proteins with a pivotal role in cell adhesion and tissue homeostasis. The cadherin-dependent mechanisms of cell adhesion and migration are exploited by cancer cells, contributing to tumor invasiveness and dissemination. In particular, cadherin switch is a hallmark of epithelial to mesenchymal transition, a complex development process vastly described in the progression of most epithelial cancers. This is characterized by drastic changes in cell polarity, adhesion, and motility, which lead from an E-cadherin positive differentiated epithelial state into a dedifferentiated mesenchymal-like state, prone to metastization and defined by N-cadherin expression. Although vastly explored in epithelial cancers, how these mechanisms contribute to the pathogenesis of other non-epithelial tumor types is poorly understood. Herein, the current knowledge on cadherin expression in normal development in parallel to tumor pathogenesis is reviewed, focusing on epithelial to mesenchymal transition. Emphasis is taken in the unascertained cadherin expression in CNS tumors, particularly in gliomas, where the potential contribution of an epithelial-to-mesenchymal-like process to glioma genesis and how this may be associated with changes in cadherin expression is discussed.This work was funded by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT—Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Ensino Superior under the project FCT/02/SAICT/2017/030625

A quartz tube atomizer with tungsten coil: a new system for vapor atomization in atomic absorption spectrometry

A quartz tube atomizer with a tungsten coil (QTAW) is described for the determination of arsenic in a flow injection hydride generation system. The flow injection system includes a Nafion(R) membrane that continuously dries the gaseous species, allowing removal of 4.2 mg min(-1) of water, corresponding to an efficiency of 92.7%. The application of this system to the determination of arsenic, using the optimized conditions, shows considerable stability with time, without loss of sensitivity, and it was possible to obtain a calibration curve with a wide range (up to 500 mg l(-1)), with R-2 = 0.9998, a limit of detection of 1.5 mg l(-1) and an analytical frequency of 60 determinations per hour. The determination of arsenic in samples of mineral and sea-waters, sediment and biological materials, shows good accuracy and precision between the results obtained and the certified values for the recovery of arsenic, with RSD values less than 6%.17111516152

CDH3 (Cadherin 3, Type 1, P-Cadherin (Placental))

Review on CDH3 (Cadherin 3, Type 1, P-Cadherin (Placental)), with data on DNA, on the protein encoded, and where the gene is implicated