Comparison of Nasopharyngeal Samples for SARS‐CoV ‐2 Detection in a Paediatric Cohort

Aim: The diagnosis of coronavirus disease 2019 (COVID-19) depends on accurate and rapid testing. Choosing an appropriate sample may impact diagnosis. Naso-oropharyngeal swabs (NOS) are most frequently used, despite several limitations. Since studies suggest nasopharyngeal aspirate (NPA) as a superior alternative in children, we hypothesised collecting both nasopharyngeal swab and aspirate would improve our diagnostic accuracy. Methods: Observational, longitudinal, prospective study from 7 March to 7 May in a tertiary paediatric hospital in Lisbon. The objective was to compare the rate of detection of SARS-CoV-2 between NOS and NPA samples collected simultaneously. Results: A total of 438 samples collected from 85 patients with confirmed COVID-19. There were 47.7% overall positive specimens - 32% (70/219) positive NOS and 63.5% (139/219) positive NPA. The tests were 67.6% concordant (k = 0.45). 50.3% had positive NPA with negative NOS, while 1.3% had positive NOS with negative NPA. NPA proved to be more sensitive (98.6% with 95% confidence interval 91.2-99.9% vs. 49.6% with 95% confidence interval 41.1-58.2%, P < 0.001). Additionally, the difference between NPA and NOS positive samples was statistically significant across all population groups (age, health condition, clinical presentation, contact with COVID-19 patients or need for hospitalisation), meaning NPA is more sensitive overall. Conclusions: Nasopharyngeal aspirates had greater sensitivity than naso-oropharyngeal swabs in detecting SARS-CoV-2. Our results suggest paediatric patients would benefit from collecting nasopharyngeal aspirates in hospital settings, whenever feasible, to improve diagnosis of COVID-19.info:eu-repo/semantics/publishedVersio

Insights on the molecular mechanisms underlying the anticancer activity of lactoferrin in metastatic cancer cell lines

Lactoferrin (Lf) is an iron-binding protein derived from milk that is present in many tissues and biological fluids. It has been shown that this natural compound exihibits anticancer and anti-metastatic activities as well as cytotoxicity against several cancer cell lines. We have recently found that bovine lactoferrin (bLf) selectively triggers cell death in highly metastatic breast cancer cells through inhibition of the plasmalemmal proton pump V-H+-ATPase.1 In the present study we aim to determine whether this mechanism of action underlies the anticancer/anti-metastatic activity of bLf in metastatic cancer cells other than breast cancer cells. To this end, we assessed bLf-induced inhibition of cell proliferation and intracellular acidification of a prostate and an osteosarcoma metastatic cell line and compared it with the effects on the previously used metastatic breast cancer cell line. The possibility of a common molecular target/mechanism of action of bLf underpinning its anticancer/anti-metastatic activity will be discussed

Biological activity and cellular uptake of [Ru(eta(5)-C5H5)(PPh3)(Me(2)bpy)][CF3SO3] complex

Anticancer activity of the new [Ru(eta(5)-C5H5)(PPh3)(Me(2)bpy)][CF3SO3] (Me(2)bpy = 4,4'-dimethyl-2,2'-bipyridine) complex was evaluated in vitro against several human cancer cell lines, namely A2780, A2780CisR, HT29, MCF7, MDAMB231 and PC3. Remarkably, the IC50 values, placed in the nanomolar and sub-micromolar range, largely exceeded the activity of cisplatin. Binding to human serum albumin, either HSA (human serum albumin) or HSA(faf) (fatty acid-free human serum albumin) does not affect the complex activity. Fluorescence studies revealed that the present ruthenium complex strongly quench the intrinsic fluorescence of albumin. Cell death by the [Ru(eta(5)-C5H5)(PPh3)(Me(2)bpy)][CF3SO3] complex was reduced in the presence of endocytosis modulators and at low temperature, suggesting an energy-dependent mechanism consistent with endocytosis. On the whole, the biological activity evaluated herein suggests that the complex could be a promising anticancer agent. (C) 2013 Elsevier Inc. All rights reserved

A new family of iron(II)-cyclopentadienyl compounds shows strong activity against colorectal and triple negative breast cancer cells

The following is available online, Figure S1—1H NMR spectrum of complexes 6, in acetone-d6, Table S1. Bond lengths [Å] and angles [°] for [Fe(η5-Cp)(CO)(PhCN)(PPh3)][CF3SO3] 1, [Fe(η5-Cp)(CO)(p-NCPhNH2)(PPh3)][CF3SO3] 4 and [Fe(η5-Cp)(CO)(p-NCPhBr)(PPh3)][CF3SO3] 5, Table S2. Relevant TD-DFT (PBE0) excitation energies (λ), oscillator strengths (f) and compositions (only those > 5% are shown), for complexes 1–6, compared with experimental data (λexp). Both calculated and experimental values were obtained in dichloromethane, Figure S2—UV-Vis spectra of complexes 1–6 in DMSO along the 24 h study, Figure S3—UV-Vis spectra of complexes 1–6 in DMSO/DMEM mixture along the 24 h study and its variation plot (%) (bottom), Figure S4. ‘FeCp’ compounds affect the colony formation ability of SW480 cell line. Analysis of the colony formation ability, after 48 h of incubation with 1/4 IC50 and IC50, in SW480 cell line. Representative images of colony formation assay in SW480 cell line, Figure S5. ‘FeCp’ compounds induce apoptosis colorectal cancer-derived cell line. Apoptotic cell death was analyzed by Annexin V fluorescein isothiocyanate (AV-FITC) and propidium iodide (PI) assay in SW480 cells, after incubation with IC50 and 2×IC50 concentrations for 48 h. Representative histograms of SW480 cell line double stained with AV and PI, Table S4. Crystal data and structure refinement for [Fe(η5-Cp)(CO)(PhCN)(PPh3)][CF3SO3] 1, [Fe(η5-Cp)(CO)(p-NCPhNH2)(PPh3)][CF3SO3] 4 and [Fe(η5-Cp)(CO)(p-NCPhBr)(PPh3)][CF3SO3] 5.A family of compounds with the general formula [Fe(η5-C5H5)(CO)(PPh3)(NCR)]+ has been synthesized (NCR = benzonitrile (1); 4-hydroxybenzonitrile (2); 4-hydroxymethylbenzonitrile (3); 4-aminobenzonitrile (4); 4-bromobenzonitrile (5); and, 4-chlorocinnamonitrile (6)). All of the compounds were obtained in good yields and were completely characterized by standard spectroscopic and analytical techniques. Compounds 1, 4, and 5 crystallize in the monoclinc P21/c space group and packing is determined by short contacts between the phosphane phenyl rings and cyclopentadienyl (compounds 1 and 4) or π-π lateral interactions between the benzonitrile molecules (complex 5). DFT and TD-DFT calculations were performed to help in the interpretation of the experimental UV-Vis. data and assign the electronic transitions. Cytotoxicity studies in MDA-MB-231 breast and SW480 colorectal cancer-derived cell lines showed IC50 values at a low micromolar range for all of the compounds in both cell lines. The determination of the selectivity index for colorectal cells (SW480 vs. NCM460, a normal colon-derived cell line) indicates that the compounds have some inherent selectivity. Further studies on the SW480 cell line demonstrated that the compounds induce cell death by apoptosis, inhibit proliferation by inhibiting the formation of colonies, and affect the actin-cytoskeleton of the cells. These results are not observed for the hydroxylated compounds 2 and 3, where an alternative mode of action might be present. Overall, the results indicate that the substituent at the nitrile-based ligand is associated to the biological activity of the compounds.Centro de Química Estrutural acknowledges Fundação para a Ciência e Tecnologia (FCT) for the Project UIDB/00100/2020. This work was also funded in the scope of the project PTDC/QUI-QIN/28662/2017 (FCT) and by the strategic program UID/BIA/04050/2019 (FCT). A. Pilon and Ana Rita Brás thank FCT for their Ph.D. Grants (SFRH/BD/139412/2018 and SFRH/BD/139271/2018, respectively). A. Valente acknowledges the CEECIND 2017 Initiative (CEECIND/01974/2017). P. J Costa thank FCT for Investigador FCT Program IF/00069/2014, exploratory project IF/00069/2014/CP1216/CT0006, and strategic project UID/MULTI/04046/2019. P. J. Costa also acknowledges FCT, Programa Operacional Regional de Lisboa (Lisboa 2020), Portugal 2020, FEDER/FN, and the European Union for project LISBOA-01-0145-FEDER-028455 / PTDC/QUI-QFI/28455/2017

New iron(II) cyclopentadienyl derivative complexes: synthesis and antitumor activity against human leukemia cancer cells

A new family of 'FeII(h5-C5H5)' half sandwich compounds bearing a N-heteroaromatic ligand coordinated to the iron center by a nitrile functional group has been synthesized and fully characterized by NMR and UVeVis spectroscopy. X-ray analysis of single crystal was achieved for complexes 1 and 3, which crystallized in the monoclinic P21/c and monoclinic P21/n space groups, respectively. Studies of interaction of these five new complexes with plasmid pBR322 DNA by atomic force microscopy showed very strong and different types of interaction. Antiproliferative tests were examined on human leukemia cancer cells (HL-60) using the MTT assay, and the IC50 values revealed excellent antiproliferative activity compared to cisplatin

Asymmetric introgression between sympatric molestus and pipiens forms of Culex pipiens (Diptera: Culicidae) in the Comporta region, Portugal

<p>Abstract</p> <p>Background</p> <p><it>Culex pipiens </it>L. is the most widespread mosquito vector in temperate regions. This species consists of two forms, denoted molestus and pipiens, that exhibit important behavioural and physiological differences. The evolutionary relationships and taxonomic status of these forms remain unclear. In northern European latitudes molestus and pipiens populations occupy different habitats (underground <it>vs</it>. aboveground), a separation that most likely promotes genetic isolation between forms. However, the same does not hold in southern Europe where both forms occur aboveground in sympatry. In these southern habitats, the extent of hybridisation and its impact on the extent of genetic divergence between forms under sympatric conditions has not been clarified. For this purpose, we have used phenotypic and genetic data to characterise <it>Cx. pipiens </it>collected aboveground in Portugal. Our aims were to determine levels of genetic differentiation and the degree of hybridisation between forms occurring in sympatry, and to relate these with both evolutionary and epidemiological tenets of this biological group.</p> <p>Results</p> <p>Autogeny and stenogamy was evaluated in the F1 progeny of 145 individual <it>Cx. pipiens </it>females. Bayesian clustering analysis based on the genotypes of 13 microsatellites revealed two distinct genetic clusters that were highly correlated with the alternative traits that define pipiens and molestus. Admixture analysis yielded hybrid rate estimates of 8-10%. Higher proportions of admixture were observed in pipiens individuals suggesting that more molestus genes are being introgressed into the pipiens form than the opposite.</p> <p>Conclusion</p> <p>Both physiological/behavioural and genetic data provide evidence for the sympatric occurrence of molestus and pipiens forms of <it>Cx. pipiens </it>in the study area. In spite of the significant genetic differentiation between forms, hybridisation occurs at considerable levels. The observed pattern of asymmetric introgression probably relates to the different mating strategies adopted by each form. Furthermore, the differential introgression of molestus genes into the pipiens form may induce a more opportunistic biting behaviour in the latter thus potentiating its capacity to act as a bridge-vector for the transmission of arboviral infections.</p

Empirical Investigation of Data Analytics Capability and Organizational Flexibility as Complements to Supply Chain Resilience

Supply chain resilience and data analytics capability have generated increased interest in academia and among practitioners. However, existing studies often treat these two streams of literature independently. Our study model reconciles two different streams of literature: data analytics capability as a means to improve information-processing capacity and supply chain resilience as a means to reduce a ripple effect in supply chain or quickly recover after disruptions in the supply chain. We have grounded our theoretical model in the organisational information processing theory (OIPT). Four research hypotheses are tested using responses from 213 Indian manufacturing organisations collected via a pre-tested survey-based instrument. We further test our model using variance-based structural equation modelling, popularly known as PLS-SEM. All of the hypotheses were supported. The findings of our study offer a unique contribution to information systems (IS) and operations management (OM) literature. The findings further provide numerous directions to the supply chain managers. Finally, we note our study limitations and provide further research directions

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.info:eu-repo/semantics/publishedVersio