Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.

Winery by-products are a rich source of polyphenols, which have proven to have several beneficial biological properties, such as, antioxidant and antimicrobial activities. Therefore, this study aimed the extraction of polyphenols from winery by-products of two Portuguese red grape varieties, Touriga Nacional and Preto Martinho, and evaluate their phenolic profile, antioxidant properties and antimicrobial activity against antibiotic resistant bacteria. The polyphenols were extracted from the grapes' skins, seeds and stems. Extracts were analysed for total phenolic, anthocyanin and tannin contents, and the polyphenol profile was determined by High Performance Liquid Chromatography. The antioxidant activity of the extracts was determined by ABTS + and DPPH methods. Antimicrobial susceptibility assay was performed using Kirby-Bauer disc diffusion method. Preto Martinho variety presented a higher polyphenolic content than Touriga Nacional. Malvidin 3-O-glucoside was the most abundant compound found in the skins extracts in both varieties. The main phenolic compound found in the seeds and stems extracts was catechin. From the several flavonols quantified, rutin was the most abundant. For both varieties, the seeds extracts showed the highest antioxidant and antimicrobial properties, followed by the stems extracts. The extracts showed antibacterial activity against all tested strains except on gram-negative bacteria Salmonella enteritidis, Escherichia coli and Pseudomonas aeruginosa. These results show that, natural products, such as polyphenols, may represent a source for the development of novel antimicrobials to combat gram-positive resistant bacteria and possibly be used as natural food preservatives. However, they were not effective against gram-negative resistant bacteria which shows that polyphenols, alone, might not substitute antibiotics.

BackgroundFactors associated with depression of medical students are poorly understood. The purpose of this study is to determine the prevalence of depression in medical students, its change during the course, if depression persists for affected students, what are the factors associated with depression and how these factors change over time.MethodsA prospective, longitudinal observational study was conducted at the Medical School of the University of Minho, Portugal, between academic years 2009–2010 to 2012–2013. We included students who maintained their participation by annually completing a questionnaire including Beck Depression Inventory (BDI). Anxiety and burnout were assessed using the State Trait Anxiety Inventory and Maslach Burnout Inventory. Surveys on socio-demographic variables were applied to evaluate potential predictors, personal and academic characteristics and perceived difficulties. ANOVA with multiple comparisons were used to compare means of BDI score. The medical students were organized into subgroups by K-means cluster analyses. ANOVA mixed-design repeated measurement was performed to assess a possible interaction between variables associated with depression.ResultsThe response rate was 84, 92, 88 and 81% for academic years 2009–2010, 2010–2011,2011-2012 and 2012/2013, respectively. Two hundred thirty-eight medical students were evaluated longitudinally. For depression the prevalence ranged from 21.5 to 12.7% (academic years 2009/2010 and 2012/2013). BDI scores decreased during medical school. 19.7% of students recorded sustained high BDI over time. These students had high levels of trait-anxiety and choose medicine for anticipated income and prestige, reported more relationship issues, cynicism, and decreased satisfaction with social activities. Students with high BDI scores at initial evaluation with low levels of trait-anxiety and a primary interest in medicine as a career tended to improve their mood and reported reduced burnout, low perceived learning problems and increased satisfaction with social activities at last evaluation. No difference was detected between men and women in the median BDI score over time.ConclusionsOur findings suggest that personal factors (anxiety traits, medicine choice factors, relationship patterns and academic burnout) are relevant for persistence of high levels of BDI during medical training. Medical schools need to identity students who experience depression and support then, as early as possible, particularly when depression has been present over time.

Escherichia coli are facultative, anaerobic Gram-negative rods with many facets. Within resistant bacterial populations, they play an important ecological role and can be used as a bioindicator of antimicrobial resistance. All animal species used for food production, as well as humans, carry E. coli in their intestinal tracts; plus, the genetic flexibility and adaptability of this bacteria to constantly changing environments allows it to acquire a great number of antimicrobial resistance mechanisms. Thus, the prevalence of antimicrobial resistance in these commensal bacteria (or others, such as enterococci) can be a good indicator for the selective pressure caused by the use of antimicrobial agents, providing an early warning of the emergence of antimicrobial resistance in pathogens. As many as 90% of E. coli strains are commensals inhabiting the intestinal tracts of humans and warm-blooded animals. As a commensal, it lives in a mutually beneficial association with its hosts and rarely causes diseases. However, E. coli also remains as one of the most frequent causes of several common bacterial infections in humans and animals. In humans, it is the prominent cause of enteritis, community- and hospital-acquired urinary tract infection (UTI), septicemia, postsurgical peritonitis, and other clinical infections, such as neonatal meningitis, while, in farm animals, it is more prominently associated with diarrhea. On a global scale, E. coli can be considered the most important human pathogen, causing severe infection along with other major bacterial foodborne agents, such as Salmonella spp. and Campylobacter. Thus, the importance of resistance in E. coli, typically considered a benign commensal, should not be underestimated.