Azithromycin resistance in Escherichia coli and Salmonella from food-producing animals and meat in Europe.

OBJECTIVES: To characterize the genetic basis of azithromycin resistance in Escherichia coli and Salmonella collected within the EU harmonized antimicrobial resistance (AMR) surveillance programme in 2014-18 and the Danish AMR surveillance programme in 2016-19. METHODS: WGS data of 1007 E. coli [165 azithromycin resistant (MIC > 16 mg/L)] and 269 Salmonella [29 azithromycin resistant (MIC > 16 mg/L)] were screened for acquired macrolide resistance genes and mutations in rplDV, 23S rRNA and acrB genes using ResFinder v4.0, AMRFinder Plus and custom scripts. Genotype-phenotype concordance was determined for all isolates. Transferability of mef(C)-mph(G)-carrying plasmids was assessed by conjugation experiments. RESULTS: mph(A), mph(B), mef(B), erm(B) and mef(C)-mph(G) were detected in E. coli and Salmonella, whereas erm(C), erm(42), ere(A) and mph(E)-msr(E) were detected in E. coli only. The presence of macrolide resistance genes, alone or in combination, was concordant with the azithromycin-resistant phenotype in 69% of isolates. Distinct mph(A) operon structures were observed in azithromycin-susceptible (n = 50) and -resistant (n = 136) isolates. mef(C)-mph(G) were detected in porcine and bovine E. coli and in porcine Salmonella enterica serovar Derby and Salmonella enterica 1,4, [5],12:i:-, flanked downstream by ISCR2 or TnAs1 and associated with IncIγ and IncFII plasmids. CONCLUSIONS: Diverse azithromycin resistance genes were detected in E. coli and Salmonella from food-producing animals and meat in Europe. Azithromycin resistance genes mef(C)-mph(G) and erm(42) appear to be emerging primarily in porcine E. coli isolates. The identification of distinct mph(A) operon structures in susceptible and resistant isolates increases the predictive power of WGS-based methods for in silico detection of azithromycin resistance in Enterobacterales.

Influence of visceral adiposity on cardiovascular risk in patients with systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by systemic inflammation, endothelial dysfunction, generalized fibrosis and high cardiovascular mortality. The evaluation of cardiovascular risk through the visceral adiposity index (VAI) has been helpful due to its direct relationship to the body and visceral fat percentage. We evaluated the influence of body composition and anthropometrics on cardiovascular risk as measured by VAI in healthy controls (HC) and SSc. An analytical cross-sectional study of 66 participants (33 SSc and 33 HC), mean age 52.7 ± 10, 95% women, was conducted from August 2020 to January 2021. Inclusion criteria in cases were consecutive patients with SSc (ACR/EULAR 2013), 63.6% were diffuse cutaneous (dcSS) subtype, and 36.4 were limited cutaneous (lcSS) subtype. HC was matched by age and gender. Serum lipid profiles and InBody anthropometrics were analyzed and compared. We performed descriptive statistics, bivariate analysis with Student's t, or Mann-Whitney U, correlation and chi-square according to the variable type and distribution. Total cholesterol was significantly higher in SSc than HC (345 vs 194, p = < 0.001). The BMI was higher in HC (26.2 vs 28.9, p < 0.001). Kilograms of muscle (19.8 vs 28.9, p < 0.001) and total fat (23.4 vs 28.9, p < 0.001) were lower in SSc patients compared to HC. VAI was similar when BMI < 25, but significantly higher when BMI > 25 in SSc than in HC (3 vs 1.9, p = 0.030). The increase in BMI at overweight or obese in SSc is associated with a significant increase in cardiovascular risk.

Increased IL-12p70 and IL-8 Produced by Monocytes in Response to Streptococcus spp. and Actinomyces spp. Causals of Endodontic Primary Infections.

We sought to evaluate the effect of endodontic-causative microorganisms of primary infections on mononuclear cells such as CD14+, CD4+, CD8+, CD19+ and Tregs Foxp3+. Facultative anaerobic microorganisms were isolated from radicular conducts and peripheral blood samples, which were taken from patients with primary infections. Cellular cultures were performed with peripheral blood mononuclear cells (PBMC) with and without Actinomyces spp. and Streptococcus spp. during 48, 72, and 96 h of contact in culture (concentration 5 × 105 cells/well) in a round plate bound with 48 wells. Later, PBMC was collected for analysis by flow cytometry, with the monoclonal antibodies αCD14, αCD4, αCD8, αCD19 and αFoxp3, and acquired using an FACSCanto II cytometer. The supernatant of cellular cultures was analyzed for the quantification of inflammatory cytokines. Data analysis was performed in FlowJo v10.8.2 and FCAPArray software, and statistical analysis was performed using GraphPad v5.0. software. We observed an increase in the percentage of CD14+ cells in patients at different hours of cellular culture in the presence of both Actinomyces spp. and Streptococcus spp. microorganisms, compared to healthy controls. This study demonstrates the role played by the innate immune system in the pathogeny of endodontic primary infections, explaining the effects that generate the more common microorganisms in this oral pathology.

Antioxidant effects of phenolic extract from sugarcane straw and mannan extract from brewer's spent yeast on fresh-cut apples.

BACKGROUND: Fresh-cut fruit are convenient ready-to-eat products increasingly demanded by consumers, but highly susceptible to oxidation. To increase the shelf life of these products, this industry is currently facing the challenge of finding sustainable natural preservatives capable of maintaining fresh-cut fruit quality while meeting consumers' expectations regarding health and environmental concerns. RESULTS: In this work, fresh-cut apple slices were treated with two antioxidant extracts derived from industrial by-products: a phenolic-rich extract produced from sugarcane straw (PE-SCS) and applied at 15 g L-1 , and a mannan-rich extract obtained from brewer's spent yeast (MN-BSY) applied at two concentrations: 1 and 5 g L-1 . PE-SCS, having a brown color, imparted a brownish hue to the fruit and increased the browning rate during storage, and not even the initial robust antioxidant response (high superoxide dismutase, catalase, ascorbate peroxidase and guaiacol peroxidase activities), prevented oxidation. Fruit treated with MN-BSY extract at 5 g L-1 showed lower color loss rate and higher polyphenol oxidase inhibition, while at 1 g L-1 it showed lower firmness loss rate and lower lipid peroxidation after 6 days of storage. CONCLUSION: The results showed that PE-SCS triggers a potent antioxidant response in fresh-cut fruit and, despite it imparting a brown color to the fruit at 15 g L-1 , it may have potential for application at lower concentrations. Regarding MN-BSY, it generally decreased oxidative stress, but its effect on quality maintenance was dependent on the concentration and, thus, to confirm its potential as a fruit preservative more concentrations must be tested. © 2023 Society of Chemical Industry.

Disarranged neuroplastin environment upon aging and chronic stress recovery in female Sprague Dawley rats.

Chronic stress produces long-term metabolic changes throughout the superfamily of nuclear receptors, potentially causing various pathologies. Sex hormones modulate the stress response and generate a sex-specific age-dependent metabolic imprint, especially distinct in the reproductive senescence of females. We monitored chronic stress recovery in two age groups of female Sprague Dawley rats to determine whether stress and/or aging structurally changed the glycolipid microenvironment, a milieu playing an important role in cognitive functions. Old females experienced memory impairment even at basal conditions, which was additionally amplified by stress. On the other hand, the memory of young females was not disrupted. Stress recovery was followed by a microglial decrease and an increase in astrocyte count in the hippocampal immune system. Since dysfunction of the brain immune system could contribute to disturbed synaptogenesis, we analyzed neuroplastin expression and the lipid environment. Neuroplastin microenvironments were explored by analyzing immunofluorescent stainings using a newly developed Python script method. Stress reorganized glycolipid microenvironment in the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) hippocampal regions of old females but in a very different fashion, thus affecting neuroplasticity. The postulation of four possible neuroplastin environments pointed to the GD1a ganglioside enrichment during reproductive senescence of stressed females, as well as its high dispersion in both regions and to GD1a and GM1 loss in the CA1 region. A specific lipid environment might influence neuroplastin functionality and underlie synaptic dysfunction triggered by a combination of aging and chronic stress.

Current postbiotics in the cosmetic market-an update and development opportunities.

Postbiotics are a new class of health-promoting molecules that derive from probiotics. These new cosmetic and dermatological ingredients are defined as a 'preparation of inanimate microorganisms and/or their components that confers a health benefit on the host'. This review focuses on what is presently known of these compounds, the benefits of using them, the main postbiotics products available in the market and players, the production key trends and available production methods. The main advantages identified for the use of postbiotics are related to their higher specificity of action on resident microbiota as of interaction with cells of the host compared to probiotics. Postbiotics can be produced/obtained especially through fermentative processes, but most of companies industrial processes are patented. Most of these compounds are usually derived from lactic acid bacteria, Lactobacillus genera and/or yeasts, especially Saccharomyces cerevisiae. Postbiotics go from metabolites like teichoic acids to polysaccharides among others and exhibit important biological properties such as antioxidant, anti-inflammatory, anti-proliferative and immunomodulatory-the reason why their use in cosmetic formulations must be considered. Besides that, when compared to probiotics, postbiotics have longer shelf life and greater safety and do not require viability in the topical formulation which turns them into an innovative approach within the cosmetic ingredients market. The main players are companies that operate in several areas, such as the chemical industry, food innovation, pharmaceutical and cosmetic industries, and the critical trends for production of these compounds include energy efficiency, emission-free mobility, conservation of finite resources and renewable raw material utilization. KEY POINTS: • Postbiotics are mainly derived from lactic acid bacteria and S. cerevisiae. • Postbiotics exhibit several biological properties. • Postbiotics present several advantages over probiotics.

Risk Factors and Outcomes for COVID-19 in Autoimmune Inflammatory Diseases during the SARS-CoV-2 Pandemic: A Comparative Study.

BACKGROUND: Patients with autoimmune disease (AID) and coronavirus disease 2019 (COVID-19) could have higher mortality due to the co-morbidity and the use of immunosuppressive therapy. OBJECTIVES: To analyze the risk factors and outcomes of patients with AID and COVID-19 versus a control group. METHODS: A prospective cohort study included patients with and without AID and COVID-19. Patients were paired by age and sex. Clinical, biochemical, immunological treatments, and outcomes (days of hospital stay, invasive mechanical ventilation [IMV], oxygen at discharge, and death) were collected. RESULTS: We included 226 COVID-19 patients: 113 with AID (51.15 ± 14.3 years) and 113 controls (53.45 ± 13.3 years). The most frequent AIDs were Rheumatoid arthritis (26.5%), systemic lupus erythematosus (21%), and systemic sclerosis (14%). AID patients had lower lactate dehydrogenas, C-reactive protein, fibrinogen, IMV (P = 0.027), and oxygen levels at discharge (P ≤ 0.0001) and lower death rates (P ≤ 0.0001). Oxygen saturation (SaO2) ≤ 88% at hospitalization provided risk for IMV (RR [relative risk] 3.83, 95% confidence interval [95%CI] 1.1-13.6, P = 0.038). Higher creatinine and LDH levels were associated with death in the AID group. SaO2 ≤ 88% and CO-RADS ≥ 4 were risk factors for in-hospital mortality (RR 4.90, 95%CI 1.8-13.0, P = 0.001 and RR 7.60, 95%CI 1.4-39.7, P = 0.016, respectively). Anticoagulant therapy was protective (RR 0.36, 95%CI 0.1-0.9, P = 0.041). CONCLUSIONS: Patients with AID had better outcomes with COVID-19 than controls. Anticoagulation was associated with a lower death in patients with AID.

Effects of Dietary n-3 LCPUFA Supplementation on the Hippocampus of Aging Female Mice: Impact on Memory, Lipid Raft-Associated Glutamatergic Receptors and Neuroinflammation.

Long-chain polyunsaturated fatty acids (LCPUFA), essential molecules whose precursors must be dietary supplied, are highly represented in the brain contributing to numerous neuronal processes. Recent findings have demonstrated that LCPUFA are represented in lipid raft microstructures, where they favor molecular interactions of signaling complexes underlying neuronal functionality. During aging, the brain lipid composition changes affecting the lipid rafts' integrity and protein signaling, which may induce memory detriment. We investigated the effect of a n-3 LCPUFA-enriched diet on the cognitive function of 6- and 15-months-old female mice. Likewise, we explored the impact of dietary n-3 LCPUFAs on hippocampal lipid rafts, and their potential correlation with aging-induced neuroinflammation. Our results demonstrate that n-3 LCPUFA supplementation improves spatial and recognition memory and restores the expression of glutamate and estrogen receptors in the hippocampal lipid rafts of aged mice to similar profiles than young ones. Additionally, the n-3 LCPUFA-enriched diet stabilized the lipid composition of the old mice's hippocampal lipid rafts to the levels of young ones and reduced the aged-induced neuroinflammatory markers. Hence, we propose that n-3 LCPUFA supplementation leads to beneficial cognitive performance by "rejuvenating" the lipid raft microenvironment that stabilizes the integrity and interactions of memory protein players embedded in these microdomains.

Root canal microorganisms and their antibiotic susceptibility in patients with persistent endodontic infections, with and without clinical symptoms.

Secondary/persistent infections are present in teeth with previous root canal treatment, and a great variety of anaerobic microorganisms has been observed in these infections. The antibiotics prescription is occasional; however, in some cases, it is essential, particularly when the general health condition of the patient is compromised. The aims of this study were to identify the associated microorganisms in diagnosis of persistent or secondary apical periodontitis and to evaluate the susceptibility level to the antibiotics most used. Fifteen patients with persistent or secondary apical periodontitis requiring endodontic re-treatment were included. Microbiological samples were taken from the root canals and incubated in thioglycollate under anaerobic conditions. Anaerobic CDC agar (formulated by the Center for Disease Control and Prevention) was employed as a culture medium and the microorganisms were identified using the API system. The microorganisms were subjected to antibiograms with three different antibiotics. Twenty-six microorganisms were identified, the most common genus was Enterococcus (26.8%), Streptococcus (19.22%), Aerococcus (19.1%), and Clostridium (11.4%). 48% of them were susceptible to amoxicillin, with 28% of resistance. For clavulanic acid/amoxicillin, the susceptibility occurred in 32%, with 28% of resistance; and for clindamycin, the susceptibility was present in 40%, with 52% of resistance. The most frequently detected associated microorganism for secondary infections was genus Enterococcus, which exhibited high resistance to the studied antibiotics.

FLTX2: A Novel Tamoxifen Derivative Endowed with Antiestrogenic, Fluorescent, and Photosensitizer Properties.

Tamoxifen is the most widely used selective modulator of estrogen receptors (SERM) and the first strategy as coadjuvant therapy for the treatment of estrogen-receptor (ER) positive breast cancer worldwide. In spite of such success, tamoxifen is not devoid of undesirable effects, the most life-threatening reported so far affecting uterine tissues. Indeed, tamoxifen treatment is discouraged in women under risk of uterine cancers. Recent molecular design efforts have endeavoured the development of tamoxifen derivatives with antiestrogen properties but lacking agonistic uterine tropism. One of this is FLTX2, formed by the covalent binding of tamoxifen as ER binding core, 7-nitrobenzofurazan (NBD) as the florescent dye, and Rose Bengal (RB) as source for reactive oxygen species. Our analyses demonstrate (1) FLTX2 is endowed with similar antiestrogen potency as tamoxifen and its predecessor FLTX1, (2) shows a strong absorption in the blue spectral range, associated to the NBD moiety, which efficiently transfers the excitation energy to RB through intramolecular FRET mechanism, (3) generates superoxide anions in a concentration- and irradiation time-dependent process, and (4) Induces concentration- and time-dependent MCF7 apoptotic cell death. These properties make FLTX2 a very promising candidate to lead a novel generation of SERMs with the endogenous capacity to promote breast tumour cell death in situ by photosensitization.

ResFinder 4.0 for predictions of phenotypes from genotypes.

OBJECTIVES: WGS-based antimicrobial susceptibility testing (AST) is as reliable as phenotypic AST for several antimicrobial/bacterial species combinations. However, routine use of WGS-based AST is hindered by the need for bioinformatics skills and knowledge of antimicrobial resistance (AMR) determinants to operate the vast majority of tools developed to date. By leveraging on ResFinder and PointFinder, two freely accessible tools that can also assist users without bioinformatics skills, we aimed at increasing their speed and providing an easily interpretable antibiogram as output. METHODS: The ResFinder code was re-written to process raw reads and use Kmer-based alignment. The existing ResFinder and PointFinder databases were revised and expanded. Additional databases were developed including a genotype-to-phenotype key associating each AMR determinant with a phenotype at the antimicrobial compound level, and species-specific panels for in silico antibiograms. ResFinder 4.0 was validated using Escherichia coli (n = 584), Salmonella spp. (n = 1081), Campylobacter jejuni (n = 239), Enterococcus faecium (n = 106), Enterococcus faecalis (n = 50) and Staphylococcus aureus (n = 163) exhibiting different AST profiles, and from different human and animal sources and geographical origins. RESULTS: Genotype-phenotype concordance was ≥95% for 46/51 and 25/32 of the antimicrobial/species combinations evaluated for Gram-negative and Gram-positive bacteria, respectively. When genotype-phenotype concordance was <95%, discrepancies were mainly linked to criteria for interpretation of phenotypic tests and suboptimal sequence quality, and not to ResFinder 4.0 performance. CONCLUSIONS: WGS-based AST using ResFinder 4.0 provides in silico antibiograms as reliable as those obtained by phenotypic AST at least for the bacterial species/antimicrobial agents of major public health relevance considered.

Autoimmune/inflammatory syndrome induced by methylmethacrylate associated to seronegative antiphospholipid syndrome and diffuse large B-cell non-Hodgkin's lymphoma.

BACKGROUND: Autoimmune/inflammatory syndrome induced by adjuvants has been associated with different substances used for cosmetic purposes; for example, silicone, methylmethacrylate, autoimmune disorders and cancer. DISCUSSION: A 40-year-old man with a prior history of methylmethacrylate injection in the buttocks for aesthetic purposes 8 years ago, presented with deep venous thrombosis in the left leg 6 months ago, accompanied with inflammation, hardening, changes in colour, ulceration in the buttocks, arthritis, myalgias and fever. Weak and moderate lupus anticoagulant and low levels of anticardiolipin antibodies were present. Thoracoabdominal tomography showed hepatosplenomegaly and a pulmonary nodule, the biopsy of which showed chronic granulomatous inflammation. After a month, a new chest tomography showed multiple nodular pulmonary lesions. The new pulmonary biopsy showed a diffuse large B-cell non-Hodgkin's lymphoma which was treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab for four cycles, with good response of the autoimmune/inflammatory syndrome, but partial response of the diffuse large B-cell non-Hodgkin's lymphoma. CONCLUSION: We describe the first case of seronegative antiphospholipid syndrome and lymphoma associated with methylmethacrylate in a patient with autoimmune/inflammatory syndrome.

Aerobic and anaerobic microorganisms and antibiotic sensitivity of odontogenic maxillofacial infections.

This study aimed to identify the aerobic and anaerobic causal microorganisms of odontogenic infections and their antibiotic sensitivity. Purulent exudates were taken from patients with odontogenic infections by transdermal puncture, and aerobic and anaerobic microorganisms were identified using biochemical tests. Susceptibility to antibiotics was tested using the Kirby-Bauer method; the inhibition halos were measured according to NCCLS, and based on the results, the microorganisms were classified as susceptible, intermediate or resistant to each antibiotic. Frequencies of species and percentages of resistance were calculated. The microorganisms associated with odontogenic infections were principally anaerobic (65.3% anaerobic vs. 35.7% aerobic), and the susceptibility to antibiotics was higher in anaerobic than in aerobic microorganisms. The majority of isolated microorganisms (82%) showed susceptibility to amoxicillin/clavulanic acid. The causal agents of odontogenic infections were anaerobic microorganisms, which exhibited high resistance to antibiotics.

[Effectiveness of an intervention strategy in the biosimilar glargine prescription pattern in primary care]. / Efectividad de una estrategia de intervención en el patrón de prescripción del biosimilar glargina en atención primaria.

OBJECTIVES: To examine the effects of specific interventions on biosimilar glargine insulin (BGI) prescribing in general practices and to analyse the influence of prescriber and economic impact. DESIGN: Non randomized controlled study. SETTING: General practices in 2 health areas of Seville, intervention and control group. PARTICIPANTS: 220 general practices (intervention group) and 100 general practices (control group). INTERVENTION: Intervention group received educational seminars on biosimilar drugs, pharmacotherapeutic bulletin and prescribing feedback. The study was carried out from the biosimilar commercialization, October-2015, to February-2016 (pre-intervention) and from February to August 2016 (intervention). MAIN MEASUREMENTS: Percentage of patients and DDD with BGI respect to total glargine before and during intervention for both areas were analysed. Physicians have been analysed by subgroups of age, sex, training, type of contract, years of experience and quota. MAIN RESULTS: Both indicators for intervention group were significantly greater than for control group (P<.0005), with a 95% confidence interval (2.5-4.7). The ratio of the percentage of cumulative increase of both variables between areas was 3.73 times higher after the intervention. No differences were found for the evaluated categories of physicians in the intervention group. CONCLUSIONS: Intervention strategies aimed at training and information, as well as monitoring health professionals, influence the pattern of prescription and can have an economic impact. Our results have not been influenced by the profile of the prescriber.

Metabolic syndrome, autoimmunity and rheumatic diseases.

Metabolic syndrome (MetS) is a cluster of metabolic and cardiovascular (CV) risk factors including obesity and visceral adiposity, insulin resistance, dyslipidemia and hypertension contributing to CV mortality. The interface between the metabolic and immune systems has been of great interest recently. These interactions are regulated through genetics, nutritional status, and the intestinal microbiome. Alterations in the immune-metabolic cross-talk contribute to the development of autoimmune diseases. Adipokines exert a variety of metabolic activities contributing to the ethiopathogenesis of MetS and are involved in the regulation of both inflammatory processes and autoimmunity occurring in rheumatic diseases. Patients with autoinflammatory disease such as gout and those with autoimmune rheumatic diseases (ARD), such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, ankylosing spondylitis and vasculitis among others, have increased prevalence of MetS. Despite recent advances in treatment of ARD, incidence of CVD remains high. MetS and altered secretion patterns of proinflammatory adipokines could be the link between CVDs and ARD. In addition, in ARD the activation of proinflammatory signalling pathways results in the induction of several biological markers of chronic inflammation contributing to CVD. In the present paper, we review recent evidences of the interactions between MetS and ARD, as well as novel therapeutic targets.

A field evaluation of an isothermal DNA amplification assay for the detection of Theileria annulata infection in cattle.

A loop-mediated isothermal amplification (LAMP) assay was evaluated for the detection of Theileria annulata infection in cattle. The results were compared with a real-time PCR used for the quantification of T. annulata parasitaemia. One hundred bovine blood samples from 16 cattle farms were tested with LAMP and real-time PCR, with T. annulata DNA being detected in 66% and 67% of the samples, respectively. The results showed that the LAMP assay detects a parasitaemia as low as 0.00025%, indicating a high analytical sensitivity of LAMP for clinical diagnosis of bovine theileriosis.

Antimicrobial efficacy of orthodontic primer added with silver nanoparticles. Cross-sectional in vitro study. / Eficacia antimicrobiana del primer ortodóncico adicionado con nanopartículas de plata. Estudio transversal in vitro.

The antimicrobial efficacy of the silver nanoparticles (NPsAg), incorporated into the adhesive (primer) placed in the enamel adjacent to fixed orthodontic appliances (brackets), was evaluated. An experimental study was performed on 40 premolars in vitro, which were divided into two groups with brackets, one cemented with conventional primer and another added with NPsAg, placed in culture media previously inoculated with Streptococcus mutans, and sampled for culturing and counting colony forming units (UFC) on days 1, 15 and 30. A decrease in the presence of Streptococcus mutans in the samples after 15 days with nanoparticle aggregation was observed, and a reduction in the effect of said nanoparticles after 30 days. This reduction of the nanoparticles effects can be due to the absence of mechanical cleaning, which favored the bacterial aggregation on the biofilm, affecting its antimicrobial effect. This suggest the need for realizing studies in "vivo" which will allow the observation of the behavior of the biometals on the buccal medium. The NPsAg added to the primer are an effective tool to prevent the demineralization of the enamel around the fixed orthodontic appliances.

Kinetochores accelerate centrosome separation to ensure faithful chromosome segregation.

At the onset of mitosis, cells need to break down their nuclear envelope, form a bipolar spindle and attach the chromosomes to microtubules via kinetochores. Previous studies have shown that spindle bipolarization can occur either before or after nuclear envelope breakdown. In the latter case, early kinetochore-microtubule attachments generate pushing forces that accelerate centrosome separation. However, until now, the physiological relevance of this prometaphase kinetochore pushing force was unknown. We investigated the depletion phenotype of the kinetochore protein CENP-L, which we find to be essential for the stability of kinetochore microtubules, for a homogenous poleward microtubule flux rate and for the kinetochore pushing force. Loss of this force in prometaphase not only delays centrosome separation by 5-6 minutes, it also causes massive chromosome alignment and segregation defects due to the formation of syntelic and merotelic kinetochore-microtubule attachments. By contrast, CENP-L depletion has no impact on mitotic progression in cells that have already separated their centrosomes at nuclear envelope breakdown. We propose that the kinetochore pushing force is an essential safety mechanism that favors amphitelic attachments by ensuring that spindle bipolarization occurs before the formation of the majority of kinetochore-microtubule attachments.

Biomimicking Atherosclerotic Vessels: A Relevant and (Yet) Sub-Explored Topic.

Atherosclerosis represents the etiologic source of several cardiovascular events, including myocardial infarction, cerebrovascular accidents, and peripheral artery disease, which remain the leading cause of mortality in the world. Numerous strategies are being delineated to revert the non-optimal projections of the World Health Organization, by both designing new diagnostic and therapeutic approaches or improving the interventional procedures performed by physicians. Deeply understanding the pathological process of atherosclerosis is, therefore, mandatory to accomplish improved results in these trials. Due to their availability, reproducibility, low expensiveness, and rapid production, biomimicking physical models are preferred over animal experimentation because they can overcome some limitations, mainly related to replicability and ethical issues. Their capability to represent any atherosclerotic stage and/or plaque type makes them valuable tools to investigate hemodynamical, pharmacodynamical, and biomechanical behaviors, as well as to optimize imaging systems and, thus, obtain meaningful prospects to improve the efficacy and effectiveness of treatment on a patient-specific basis. However, the broadness of possible applications in which these biomodels can be used is associated with a wide range of tissue-mimicking materials that are selected depending on the final purpose of the model and, consequently, prioritizing some materials' properties over others. This review aims to summarize the progress in fabricating biomimicking atherosclerotic models, mainly focusing on using materials according to the intended application.

Protocatechuic acid as an inhibitor of lipid oxidation in meat.

Lipid oxidation is the principal driver of meat and meat product deterioration during shelf life, causing the loss of fresh meat color, flavor, and aroma. Currently, synthetic antioxidants are used to prevent oxidation, but increasing consumer demand for natural ones leaves the industry with few alternatives. In this study, protocatechuic acid (PCA), known to have high antioxidant activity, was evaluated as a potential inhibitor of meat lipid oxidation. For this purpose, the antioxidant capacity and lipoxygenase (LOX) inhibitory activity of PCA were evaluated in vitro, and a set of four experiments was conducted, treating minced meat with water (control), lactic acid (LA), rosmarinic acid (RA) and PCA, at different concentrations (1-12 mg mL-1), depending on the experiment. The potential antioxidant effect of PCA when applied to meat cubes was also evaluated, as well as the potential of carboxymethyl cellulose (CMC) as a delivery system for PCA. The in vitro results showed that PCA is a potent antioxidant and an effective LOX inhibitor at 1 mg mL-1. PCA effect on meat lipid oxidation prevention was dose-dependent, and at 2 mg mL-1, it inhibited color change by 50% and lipid peroxidation by up to 70% when compared to water-treated samples, performing better than RA at 0.25 mg mL-1. These results suggest that PCA is a promising molecule to the meat industry as a natural preservative for meat and meat products directly or in a formulation.