Mucin1 expression and gustatory function in postmenopausal females : a case-control observational study

Investigating possible relationship between Mucin1 expression levels in saliva, gustatory function, and taste perception in postmenopausal females. Using whole mouth taste test, twenty-five post-menopausal females (51.35 ± 5.22 years) and twenty-five p

Evaluation of the safety and antioxidant activities of Crocus sativus and Propolis ethanolic extracts

AbstractThe possible toxicological effects and in vitro antioxidant activity of the ethanolic extracts of Crocus sativus and Propolis were investigated. Both extracts did not cause any mortalities or signs of toxicity in mice when administered orally at doses up to 5g/kgb.wt. In the sub-chronic study; the tested extracts did not produce any significant change in liver and kidney functions of rats, following oral administration for 8 successive weeks at doses of 500mg/kgb.wt. of each. Propolis showed remarkable in vitro antioxidant activity at concentrations of (40–100mg/ml). In contrast, the ethanolic extract of C. sativus ethanolic extract showed weak antioxidant activity in concentrations of (1–10mg/ml) while at concentrations of (20–100mg/ml) failed to exhibit any antioxidant activity. It was concluded that: both extracts were non-toxic, as they did not cause any mortalities or signs of toxicity in mice when administered orally at doses up to 5g/kgb.wt. Daily oral administration of C. sativus, Propolis ethanolic extracts alone or in combination for 8 successive weeks to rats was quiet safe and didn't cause any toxic changes in liver and kidney. Antioxidant study showed that Propolis ethanolic extract was a more potent antioxidant than C. sativus extract

Precise Cerebrovascular Segmentation

© 2020 IEEE. Analyzing cerebrovascular changes using Time-of-Flight Magnetic Resonance Angiography (ToF-MRA) images can detect the presence of serious diseases and track their progress, e.g., hypertension. Such analysis requires accurate segmentation of the vasculature from the surroundings, which motivated us to propose a fully automated cerebral vasculature segmentation approach based on extracting both prior and current appearance features that capture the appearance of macro and micro-vessels. The appearance prior is modeled with a novel translation and rotation invariant Markov-Gibbs Random Field (MGRF) of voxel intensities with pairwise interaction analytically identified from a set of training data sets, while the current appearance is represented with a marginal probability distribution of voxel intensities by using a Linear Combination of Discrete Gaussians (LCDG) whose parameters are estimated by a modified Expectation-Maximization (EM) algorithm. The proposed approach was validated on 190 data sets using three metrics, which revealed high accuracy compared to existing approaches

In depth characterisation of the biomolecular coronas of polymer coated inorganic nanoparticles with differential centrifugal sedimentation

Advances in nanofabrication methods have enabled the tailoring of new strategies towards the controlled production of nanoparticles with attractive applications in healthcare. In many cases, their characterisation remains a big challenge, particularly for small-sized functional nanoparticles of 5 nm diameter or smaller, where current particle sizing techniques struggle to provide the required sensitivity and accuracy. There is a clear need for the development of new reliable characterisation approaches for the physico-chemical characterisation of nanoparticles with significant accuracy, particularly for the analysis of the particles in the presence of complex biological fluids. Herein, we show that the Differential Centrifugal Sedimentation can be utilised as a high-precision tool for the reliable characterisation of functional nanoparticles of different materials. We report a method to correlate the sedimentation shift with the polymer and biomolecule adsorption on the nanoparticle surface, validating the developed core–shell model. We also highlight its limit when measuring nanoparticles of smaller size and the need to use several complementary methods when characterising nanoparticle corona complexes

Computational mutagenesis reveals the role of active-site tyrosine in stabilising a boat conformation for the substrate:QM/MM molecular dynamics studies of wild-type and mutant xylanases

Molecular dynamics simulations have been performed for non-covalent complexes of phenyl b-xylobioside with the retaining endo-b-1,4-xylanase from B. circulans (BCX) and its Tyr69Phe mutant using a hybrid QM/MM methodology. A trajectory initiated for the wild-type enzyme–substrate complex with the proximal xylose ring bound at the –1 subsite (adjacent to the scissile glycosidic bond) in the 4C1 chair conformation shows spontaneous transformation to the 2,5B boat conformation, and potential of mean force calculations indicate that the boat is ~30 kJ mol-1 lower in free energy than the chair. Analogous simulations for the mutant lacking one oxygen atom confirm the key role of Tyr69 in stabilizing the boat in preference to the 4C1 chair conformation, with a relative free energy difference of about 20 kJ mol-1, by donating a hydrogen bond to the endocyclic oxygen of the proximal xylose ring. QM/MM MD simulations for phenyl b-xyloside in water, with and without a propionate/propionic acid pair to mimic the catalytic glutamate/glutamic acid pair of the enzyme, show the 4C1 chair to be stable, although a hydrogen bond between the OH group at C2 of xylose and the propionate moiety seems to provide some stabilization for the 2,5B conformatio

Aqueous Stable Gold Nanostar/ZIF‐8 Nanocomposites for Light‐Triggered Release of Active Cargo Inside Living Cells

This is the peer reviewed version of the following article: C. Carrillo-Carrión, R. Martínez, M. F. Navarro Poupard, B. Pelaz, E. Polo, A. Arenas-Vivo, A. Olgiati, P. Taboada, M. G. Soliman, Ú. Catalán, S. Fernández-Castillejo, R. Solà, W. J. Parak, P. Horcajada, R. A. Alvarez-Puebla, P. del Pino, Angew. Chem. Int. Ed. 2019, 58, 7078, which has been published in final form at https:// doi.org/10.1002/anie.201902817. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsA plasmonic core–shell gold nanostar/zeolitic‐imidazolate‐framework‐8 (ZIF‐8) nanocomposite was developed for the thermoplasmonic‐driven release of encapsulated active molecules inside living cells. The nanocomposites were loaded, as a proof of concept, with bisbenzimide molecules as functional cargo and wrapped with an amphiphilic polymer that prevents ZIF‐8 degradation and bisbenzimide leaking in aqueous media or inside living cells. The demonstrated molecule‐release mechanism relies on the use of near‐IR light coupled to the plasmonic absorption of the core gold nanostars, which creates local temperature gradients and thus, bisbenzimide thermodiffusion. Confocal microscopy and surface‐enhanced Raman spectroscopy (SERS) were used to demonstrate bisbenzimide loading/leaking and near‐IR‐triggered cargo release inside cells, thereby leading to DNA stainingThis work has received financial support from the MINECO‐Spain (MAT2016‐80266‐R, MAT2015‐74381‐JIN, CTQ2017‐88648R, ENE2016‐79608‐C2‐1‐R, CTQ2017‐89588‐R, RYC‐2014‐15039, RYC‐2014‐16962), the Xunta de Galicia, Centro singular de investigación de Galicia accreditation 2016–2019 (ED431G/09), the Agrupación Estratégica de Materiales Action (ED431E 2018/08), the Generalitat de Cataluña (2017SGR522, 2017SGR883, SLT002/16/00239), the URV (2017PFR‐URV‐B2‐02), the German Research Society (DFG PA 794‐21‐1), and the European Union (European Regional Development Fund—ERDF, H2020‐MSCA‐IF‐2016, project 749667). M.F.N.P acknowledges the CONACYT PhD fellowship programS

Genomic characterization of SARS-CoV-2 in Egypt: insights into spike protein thermodynamic stability

The overall pattern of the SARS-CoV-2 pandemic so far has been a series of waves; surges in new cases followed by declines. The appearance of novel mutations and variants underlie the rises in infections, making surveillance of SARS-CoV-2 mutations and prediction of variant evolution of utmost importance. In this study, we sequenced 320 SARS-CoV-2 viral genomes isolated from patients from the outpatient COVID-19 clinic in the Children’s Cancer Hospital Egypt 57357 (CCHE 57357) and the Egypt Center for Research and Regenerative Medicine (ECRRM). The samples were collected between March and December 2021, covering the third and fourth waves of the pandemic. The third wave was found to be dominated by Nextclade 20D in our samples, with a small number of alpha variants. The delta variant was found to dominate the fourth wave samples, with the appearance of omicron variants late in 2021. Phylogenetic analysis reveals that the omicron variants are closest genetically to early pandemic variants. Mutation analysis shows SNPs, stop codon mutation gain, and deletion/insertion mutations, with distinct patterns of mutations governed by Nextclade or WHO variant. Finally, we observed a large number of highly correlated mutations, and some negatively correlated mutations, and identified a general inclination toward mutations that lead to enhanced thermodynamic stability of the spike protein. Overall, this study contributes genetic and phylogenetic data, as well as provides insights into SARS-CoV-2 viral evolution that may eventually help in the prediction of evolving mutations for better vaccine development and drug targets

Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients

BACKGROUND: Colorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been shown to be of prognostic significance in colorectal cancer. METHODS: The expression of cyclin D1, cyclin A, histone H3 and Ki-67 was examined in 60 colorectal cancer cases for co-regulation and impact on overall survival using immunohistochemistry, southern blot and in situ hybridization techniques. Immunoreactivity was evaluated semi quantitatively by determining the staining index of the studied proteins. RESULTS: There was a significant correlation between cyclin D1 gene amplification and protein overexpression (concordance = 63.6%) and between Ki-67 and the other studied proteins. The staining index for Ki-67, cyclin A and D1 was higher in large, poorly differentiated tumors. The staining index of cyclin D1 was significantly higher in cases with deeply invasive tumors and nodal metastasis. Overexpression of cyclin A and D1 and amplification of cyclin D1 were associated with reduced overall survival. Multivariate analysis shows that cyclin D1 and A are two independent prognostic factors in colorectal cancer patients. CONCLUSIONS: Loss of cell cycle checkpoints control is common in colorectal cancer. Cyclin A and D1 are superior independent indicators of poor prognosis in colorectal cancer patients. Therefore, they may help in predicting the clinical outcome of those patients on an individual basis and could be considered important therapeutic targets

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London