Interactions between commensal Enterococcus faecium and Enterococcus lactis and clinical isolates of Enterococcus faecium.

Enterococcus faecium (Efm) is a versatile pathogen, responsible for multidrug-resistant infections, especially in hospitalized immunocompromised patients. Its population structure has been characterized by diverse clades (A1, A2, and B (reclassified as E. lactis (Ela)), adapted to different environments, and distinguished by their resistomes and virulomes. These features only partially explain the predominance of clade A1 strains in nosocomial infections. We investigated in vitro interaction of 50 clinical isolates (clade A1 Efm) against 75 commensal faecal isolates from healthy humans (25 clade A2 Efm and 50 Ela). Only 36% of the commensal isolates inhibited clinical isolates, while 76% of the clinical isolates inhibited commensal isolates. The most apparent overall differences in inhibition patterns were presented between clades. The inhibitory activity was mainly mediated by secreted, proteinaceous, heat-stable compounds, likely indicating an involvement of bacteriocins. A custom-made database targeting 76 Bacillota bacteriocins was used to reveal bacteriocins in the genomes. Our systematic screening of the interactions between nosocomial and commensal Efm and Ela on a large scale suggests that, in a clinical setting, nosocomial strains not only have an advantage over commensal strains due to their possession of AMR genes, virulence factors, and resilience but also inhibit the growth of commensal strains.

Expression of the locus of enterocyte effacement genes during the invasion process of the atypical enteropathogenic Escherichia coli 1711-4 strain of serotype O51:H40.

Atypical enteropathogenic Escherichia coli (aEPEC) is a significant cause of diarrhea in developing countries. Some aEPEC strains, including the Brazilian representative strain of serotype O51:H40 called aEPEC 1711-4, can use flagella to attach to, invade, and persist in T84 and Caco-2 intestinal cells. They can even translocate from the gut to extraintestinal sites in a rat model. Although various aspects of the virulence of this strain were studied and the requirement of the T3SS for the efficiency of the invasion process was demonstrated, the expression of the LEE genes during the invasion and intracellular persistence remains unclear. To address this, the expression of flagella and the different LEE operons was evaluated during kinetic experiments of the interaction of aEPEC 1711-4 with enterocytes in vitro. The genome of the strain was also sequenced. The results showed that flagella expression remained unchanged, but the expression of eae and escJ increased during the early interaction and invasion of aEPEC 1711-4 into Caco-2 cells, and there was no change 24 hours post-infection during the persistence period. The number of pedestal-like structures formed on HeLa cells also increased during the 24-hour analysis. No known gene related to the invasion process was identified in the genome of aEPEC 1711-4, which was shown to belong to the global EPEC lineage 10. These findings suggest that LEE components and the intimate adherence promoted by intimin are necessary for the invasion and persistence of aEPEC 1711-4, but the detailed mechanism needs further study.

Radiation Therapy Skin Marking with Lancets Versus Electric Marking Pen (COMFORTATTOO)-6 Months Results on Cosmesis, Fading, and Patients' Satisfaction From a Randomized, Double-Blind Trial.

Purpose: Most of radiation oncology centers rely on set-up skin markings for patient setup during treatment delivery. Permanent dark-ink tattooing is the most popular marking method. COMFORTATTOO is a unicentric, randomized trial testing 2 permanent methods: lancets against an electric marking pen (Comfort Marker 2.0, CM). One substudy was undertaken to test if using the CM translates into a cosmesis, fading, or satisfaction benefit compared with the lancets. Methods and Materials: Patients aged 18 years or older referred to our department to receive RT were recruited. They were randomly assigned, in a 1:1 ratio, to receive set-up markings using lancets or CM. This substudy aimed to recruit all the living participants included in the main study. The primary endpoints were tattoos cosmesis, tattoos fading, and patients' satisfaction 6 months after finishing the RT. Cosmetic and fading assessments were scored on a 5-point ascending scale and patients' satisfaction on a 10-point ascending scale. The trial is registered at ClinicalTrials.gov (number NCT05371795). Results: Between April and September 2022, 92 patients were enrolled (45 assigned to lancets and 47 to CM) and assessed for the outcomes. Patients receiving CM had significantly better cosmetic markings, with a median score of 4.4 (vs 3.7 for lancets, P<.001). On the fading assessment, the CM was associated with lower scores compared with the lancets (median score of 1.3 and 3.3, respectively; P<.001). No differences in patients' satisfaction were observed with either method (median score of 10 for both arms, P=.952). Conclusions: Our substudy results demonstrated that, 6 months after the end of RT, the CM produces better cosmetic markings with less fading compared with the lancets. These differences didn't translate into patients' satisfaction superiority toward any method.

The MEDITAGING study: protocol of a two-armed randomized controlled study to compare the effects of the mindfulness-based stress reduction program against a health promotion program in older migrants in Luxembourg.

BACKGROUND: Migration is a phenomenon worldwide, with older migrants, particularly those with fewer socioeconomic resources, having an increased risk of developing adverse cognitive and health outcomes and social isolation. Therefore, it is of utmost importance to validate interventions that promote healthy aging in this population. Previous studies have shown a positive impact of mindfulness based-stress reduction (MBSR) on outcomes such as cognition and sleep. However, only a few studies verified its potential in older adults, especially with vulnerable populations such as migrants. This article presents the protocol of the MEDITAGING study, which is the first to investigate the MBSR effects in migrants aged ≥55 in comparison to a health promotion program. METHODS: MEDITAGING is a two-arm randomized, double-blinded, controlled study, which will include older Portuguese-speaking migrants (n = 90). Participants are randomized to the MBSR or a health promotion program. Both interventions are conducted in groups over a total of 8 weeks, incorporating weekly meetings, an additional 4-hour class, and extra at-home tasks. The health promotion program has the same structure as the MBSR but comprises different activities related to dementia prevention, healthy habits, cognitive stimulation, sleeping, nutrition, watercolor painting, and physical activity. The assessment of executive functioning, physiological stress measures, self-reported questionnaires, and qualitative interviews are conducted at baseline, after 8 weeks (post-intervention), and at a follow-up session (from one to 3 months thereafter). Analyzes will be conducted using a modified intention-to-treat approach (all participants with at least 3 days of participation in the group-sessions and one post-intervention observation). DISCUSSION: This study will test effects of a mindfulness-based intervention against an active control condition in older adult migrants, which few studies have addressed. TRIAL REGISTRATION: ClinicalTrials.gov NCT05615337 (date of registration: 27 September 2022; date of record verification: 14 November 2022).

Influence of Age on the Diagnostic Value of Coronary Artery Calcium Score for Ruling Out Obstructive Coronary Disease in Symptomatic Patients.

Concerns have been raised about the added diagnostic value of coronary artery calcium score (CACS) of 0 for reducing the likelihood of obstructive coronary artery disease (CAD) in younger patients. Our study aimed to assess the influence of age on the value of CAC = 0 in symptomatic patients who underwent coronary computed tomography angiography (CCTA). We conducted a 2-center retrospective study assessing symptomatic patients with suspected CAD who underwent CACS and CCTA. Pretest probability was calculated according to the Juarez-Orozco method and obstructive CAD was defined as ≥50% luminal stenosis. The diagnostic likelihood ratios and negative predictive values were used to assess the diagnostic value of a CACS of 0 to rule out obstructive CAD. A total of 2,043 patients (mean age 60 ± 11 years, 60% women, 48.5% CACS of 0) were analyzed. The pretest probability of obstructive CAD increased with age, whereas the proportion of patients with a CACS of 0 decreased with age. The added diagnostic value of a CACS of 0 was lower in younger patients (negative likelihood ratios ranging from 0.36 for <50 years to 0.10 for ≥70 years). However, the prevalence of obstructive CAD in patients with a CACS of 0 was low in all age groups. In a cohort of symptomatic patients who underwent CCTA for suspected CAD, the added diagnostic value of a CACS of 0 decreases significantly at younger ages. However, it is offset by their lower pretest probabilities, yielding high negative predictive values independently of age.

Antiulcer mechanisms of the hydroalcoholic extract from Aztec marigolds' medicinal and edible flowers (Tagetes erecta L.).

The antiulcer mechanisms of the dry extract of T. erecta flowers (DETe) were studied here. The acute ulcers induced by acidified ethanol or indomethacin were reproduced in mice pretreated with DETe (3 - 300 mg/kg). The antiulcer activity of DETe was also verified in mice pretreated with NEM, L-NAME, indomethacin, or yohimbine. The antisecretory effect of DETe was verified in rats, and its anti-Helicobacter pylori activity was determined in vitro. DETe (300 mg/kg, p.o) reduced the ethanol- or indomethacin-induced ulcer by 49 and 93%, respectively. The pre-treatment with L-NAME, NEM or yohimbine abolished the gastroprotective effect of DETe. However, DETe did not change the volume, acidity, or peptic activity in rats and did not affect H. pylori. This study expands knowledge about the antiulcerogenic potential of DETe, evidencing the role of nitric oxide, non-protein sulfhydryl groups, α2 adrenergic receptors, and prostaglandins, but not antisecretory or anti-H. pylori properties.

Correction: Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.

[This corrects the article DOI: 10.1371/journal.pmed.1004036.].

Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.

BACKGROUND: Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. METHODS AND FINDINGS: We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. CONCLUSIONS: This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.

Fate and Trophic Transfer of Rare Earth Elements in a Tropical Estuarine Food Web.

We sampled abiotic and food web components in an impacted estuarine system to assess the transfer and fate of rare earth elements (REE). REE (based on dry weight) were measured in sediments, suspended particulate matter (SPM), and organisms from different trophic levels. The highest ∑REE concentrations were measured in sediments (180 ± 4.24 mg kg-1) and SPM (163 ± 12.6 mg kg-1). Phytoplankton (45.7 ± 5.31 mg kg-1), periphyton (51.6 ± 1.81 mg kg-1), and zooplankton (68.5 ± 1.27 mg kg-1) are the major sources of exposure and transfer of REE to the food web. REE concentrations were several orders of magnitude lower in bivalves, crustaceans, and fish (6.01 ± 0.11, 1.22 ± 0.18, and 0.059 ± 0.003 mg kg-1, respectively) than in plankton. The ∑REE declined as a function of the trophic position, as determined by functional feeding groups and δ15N, indicating that REE were subject to trophic dilution. Our study suggests that the consumption of seafood is unlikely to be an important source of REE for humans. However, given the numerous sources of dietary introduction of REE, they should be monitored for a possible harmful cumulative effect. This study provides new key information on REE's baseline concentrations and trophic transfers and patterns.

Examining the effects of emotional valence and arousal on source memory: A meta-analysis of behavioral evidence.

The current meta-analysis examined the effects of valence and arousal on source memory accuracy, including the identification of variables that moderate the magnitude and direction of those effects. Fifty-three studies, comprising 85 individual experiments (N = 3,040 participants), were selected. Three separate analyses focusing on valence effects (valence-based: negative-neutral; positive-neutral; negative-positive) and other three focusing exclusively on arousal (arousal-based: high-low; medium-low; high-medium) were considered. Effect sizes varied from very small to medium. For the valence-based analyses, source memory accuracy was impaired for emotional compared with neutral stimuli (dunb = -.14 for negative-neutral; dunb = -.11 for positive-neutral), with a similar performance found for the negative-positive comparison (dunb = -.04). In the case of arousal-based analyses, source memory was improved for stimuli with high and medium arousal versus low arousal (dunb = .27, dunb = .49, respectively), with no statistically significant difference between high and medium arousal stimuli (dunb = -.12). Emotion effects on source memory were modulated by methodological factors. These factors may account for the variety findings typically found in emotion-related source memory research and could be systematically addressed in future studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Virulence Profile, Antibiotic Resistance, and Phylogenetic Relationships among Escherichia coli Strains Isolated from the Feces and Urine of Hospitalized Patients.

Extra-intestinal pathogenic Escherichia coli (ExPEC) may inhabit the human gut microbiota without causing disease. However, if they reach extra-intestinal sites, common cystitis to bloodstream infections may occur, putting patients at risk. To examine the human gut as a source of endogenous infections, we evaluated the E. coli clonal diversity of 18 inpatients' guts and their relationship with strains isolated from urinary tract infection (UTI) in the same hospital. Random amplified polymorphic DNA evaluated the clonal diversity, and the antimicrobial susceptibility was determined by disk diffusion. One isolate of each clone detected was sequenced, and their virulome and resistome were determined. Overall, 177 isolates were screened, among which 32 clones were identified (mean of two clones per patient), with ExPEC strains found in over 75% of the inpatients' guts. Endogenous infection was confirmed in 75% of the cases. ST10, ST59, ST69, ST131, and ST1193 clones and critical mobile drug-resistance encoding genes (blaCTX-M-15, blaOXA-1, blaDHA-1, aac(6')-lb-cr, mcr-1.26, qnrB4, and qnrB19) were identified in the gut of inpatients. The genomic analysis highlighted the diversity of the fecal strains, colonization by lactose-negative E. coli, the high frequency of ExPEC in the gut of inpatients without infections, and the presence of ß-lactamase producing E. coli in the gut of inpatients regardless of the previous antibiotics' usage. Considering that we found more than one ExPEC clone in the gut of several inpatients, surveillance of inpatients' fecal pathogens may prevent UTI caused by E. coli in the hospital and dissemination of risk clones.

Distinction between Enterococcus faecium and Enterococcus lactis by a gluP PCR-Based Assay for Accurate Identification and Diagnostics.

It was recently proposed that Enterococcus faecium colonizing the human gut (previous clade B) actually corresponds to Enterococcus lactis. Our goals were to develop a PCR assay to rapidly differentiate these species and to discuss the main phenotypic and genotypic differences from a clinical perspective. The pan-genome of 512 genomes of E. faecium and E. lactis strains was analyzed to assess diversity in genes between the two species. Sequences were aligned to find the best candidate gene for designing species-specific primers, and their accuracy was tested with a collection of 382 enterococci. E. lactis isolates from clinical origins were further characterized by whole-genome sequencing (Illumina). Pan-genome analysis resulted in 12 gene variants, with gene gluP (rhomboid protease) being selected as the candidate for species differentiation. The nucleotide sequence of gluP diverged by 90 to 92% between sets, which allowed species identification through PCR with 100% specificity and no cross-reactivity. E. lactis strains were greatly pan-susceptible and not host specific. Hospital E. lactis isolates were susceptible to clinically relevant antibiotics, lacked infection-associated virulence markers, and were associated with patients presenting risk factors for enhanced bacterial translocation. Here, we propose a PCR-based assay using gluP for easy routine differentiation between E. faecium and E. lactis that could be implemented in different public health contexts. We further suggest that E. lactis, a dominant human gut species, can cross the gut barrier in severely ill, immunodeficient, and surgical patients. Knowing that bacterial translocation may be a sepsis promoter, the relevance of infections caused by E. lactis strains, even if they are pan-susceptible, should be explored. IMPORTANCE Enterococcus faecium is a WHO priority pathogen that causes severe and hard-to-treat human infections. It was recently proposed that E. faecium colonizing the human gut (previous clade B) actually corresponds to Enterococcus lactis; therefore, some of the human infections occurring globally are being misidentified. In this work, we developed a PCR-based rapid identification method for the differentiation of E. faecium and E. lactis and discussed the main phenotypic and genotypic differences of these species from a clinical perspective. We identified the gluP gene as the best candidate, based on the phylogenomic analysis of 512 published pan-genomes, and validated the PCR assay with a comprehensive collection of 382 enterococci obtained from different sources. Further detailed analysis of clinical E. lactis strains showed that they are highly susceptible to antibiotics and lack the typical virulence markers of E. faecium but are able to cause severe human infections in immunosuppressed patients, possibly in part due to gut barrier translocation.

Occurrence and contents of trace metals and rare earth elements on plastic pellets.

We determined the occurrence of pellets (2-5 mm) and their composition in terms of trace metals and rare earth elements (REE) on nine sandy beaches of the coast of Bahia, northeastern Brazil. We compared the occurrence of pellets between oceanic and sheltered beaches and the effect of fluvial contribution on the occurrence of these microplastics. The number of pellets found was surprisingly low (i.e., max 45 pellets per m2 in an oceanic beach without fluvial river inputs). Thus, the studied beaches exhibited a very low pollution index. Concentrations of ∑REE in pellets varied between 0.36 and 1.74 mg kg-1 and were ~5-fold higher in white/transparent pellets than in brown pellets. The sum of trace metals (i.e., Fe, Cd, Cu, Ni, Pb, and Zn) was also highest in the white pellets (357 ± 12 mg kg-1). Plastic pellets are a potentially important vector of REE exposition to biota.

Body Composition, Sarcopenia and Physical Performance After Bariatric Surgery: Differences Between Sleeve Gastrectomy and Roux-En-Y Gastric Bypass.

PURPOSE: Evaluate the differences between surgical techniques in the modifications of body composition and the interference in skeletal muscle health, risk of sarcopenia, and reduced physical performance. MATERIALS AND METHODS: This is a cross-sectional prospective study. A total of 71 patients, who underwent sleeve gastrectomy (SG) or underwent Roux-en-Y gastric bypass (RYGB). Both groups underwent anthropometric, laboratory analysis, body composition assessment, presence of sarcopenia, and physical performance tests. RESULTS: The study found a higher percentage of weight loss and lower BMI in RYGB compared to SG. The other assessments of sarcopenia and physical performance showed similarity between the surgical models. Baumgartner index (7.9 kg/m2 vs. 7.3 kg/m2), FNIH (9.0 vs. 3.0), handgrip strength (27.3 kg vs. 25.2 kg), and SPPB (9.5 vs. 9.3). Leptin in the general SG group was higher than in RYGB (14.2 ng/ml vs. 8.0 ng/ml). CONCLUSION: RYGB and SG have a similar presence of sarcopenia and physical performance. However, SG allows greater preservation of bone and muscle mass and is associated with higher values of leptin, which may represent protection from long-term postoperative complications.

Involvement of Anti-Inflammatory and Stress Oxidative Markers in the Antidepressant-like Activity of Aloysia citriodora and Verbascoside on Mice with Bacterial Lipopolysaccharide- (LPS-) Induced Depression.

Aloysia citriodora Palau is popularly used to treat nervous disorders. Experimental evidence has indicated that verbascoside (VBS) isolated from A. citriodora has pharmacological potential. In this study, we evaluated the antidepressant-like effects of a hydroalcoholic extract of A. citriodora (HEAc) and VBS against lipopolysaccharide- (LPS-) induced depressive-like behavior in mice. In the pretreatment protocol (performed to evaluate the preventive potential), mice were pretreated with HEAc (3, 30, or 300 mg/kg) or VBS (30 mg/kg) before the administration of LPS. In the posttreatment protocol (performed to evaluate the therapeutic potential), mice were initially administered LPS and were subsequently given HEAc (3, 30, or 300 mg/kg) or VBS (30 mg/kg). In both treatments, the mice were submitted to an open-field test and tail suspension test (TST) at 6 and 24 h after LPS administration. The posttreatment evaluation revealed that HEAc (30 or 300 mg/kg) and VBS produced an antidepressant-like effect, as indicated by a reduction in the time spent with no movement in the TST. Moreover, HEAc (30 or 300 mg/kg) was found to reduce interleukin-6 (IL-6) levels and N-acetyl-glycosaminidase activity in the hippocampus, increase glutathione (GSH) levels in the hippocampus and cortex, and enhance IL-10 in the cortex and, at a dose of 300 mg/kg, reduced myeloperoxidase activity in the cortex. Contrastingly, no comparable effects were detected in mice subjected to the pretreatment protocol. Administration of VBS similarly reduced the levels of IL-6 in the hippocampus and increased GSH levels in the cortex. Our observations indicate that both HEAc and VBS show promising antidepressant-like potential, which could be attributed to their beneficial effects in reducing neuroinflammatory processes and antioxidant effects in the central nervous system.

Neuronal Activity Reporters as Drug Screening Platforms.

Understanding how neuronal activity changes and detecting such changes in both normal and disease conditions is of fundamental importance to the field of neuroscience. Neuronal activity plays important roles in the formation and function of both synapses and circuits, and dysregulation of these processes has been linked to a number of debilitating diseases such as autism, schizophrenia, and epilepsy. Despite advances in our understanding of synapse biology and in how it is altered in disease, the development of therapeutics for these diseases has not advanced apace. Many neuronal activity assays have been developed over the years using a variety of platforms and approaches, but major limitations persist. Current assays, such as fluorescence indicators are not designed to monitor neuronal activity over a long time, they are typically low-throughput or lack sensitivity. These are major barriers to the development of new therapies, as drug screening needs to be both high-throughput to screen through libraries of compounds, and longitudinal to detect any effects that may emerge after continued application of the drug. This review will cover existing assays for measuring neuronal activity and highlight a live-cell assay recently developed. This assay can be performed with easily accessible lab equipment, is both scalable and longitudinal, and can be combined with most other established methods.

Intradermal Immunization of SARS-CoV-2 Original Strain Trimeric Spike Protein Associated to CpG and AddaS03 Adjuvants, but Not MPL, Provide Strong Humoral and Cellular Response in Mice.

Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the intradermal route has been studied around the globe as a strong candidate for immunization against SARS-CoV-2. Adjuvants have shown to be essential vaccine components that are capable of driving robust immune responses and increasing the vaccination efficacy. In this work, our group aimed to develop a vaccination strategy for SARS-CoV-2 using a trimeric spike protein, by testing the best route with formulations containing the adjuvants AddaS03, CpG, MPL, Alum, or a combination of two of them. Our results showed that formulations that were made with AddaS03 or CpG alone or AddaS03 combined with CpG were able to induce high levels of IgG, IgG1, and IgG2a; high titers of neutralizing antibodies against SARS-CoV-2 original strain; and also induced high hypersensitivity during the challenge with Spike protein and a high level of IFN-γ producing CD4+ T-cells in mice. Altogether, those data indicate that AddaS03, CpG, or both combined may be used as adjuvants in vaccines for COVID-19.

Prevalence of dementia in Latin America and Caribbean countries: Systematic review and meta-analyses exploring age, sex, rurality, and education as possible determinants.

BACKGROUND: Studies have shown that the prevalence of dementia in Latin America and the Caribbean (LAC) may be higher than in high-income countries. Thus, we sought to systematically analyse the prevalence of dementia and explore possible drivers that lead to this disparity in LAC countries. METHOD: We searched Pubmed, Web of Knowledge, Scopus, Lilacs, and SciELO for studies on dementia in LAC countries published in English, Spanish, and Portuguese. Random-effects model was applied. RESULTS: Thirty-one studies from 17 LAC countries were included. Pooled prevalence of all-cause dementia was 10.66%. Further analyses with studies providing raw prevalence by sex, area, and educational level showed a higher prevalence for women (8.97%) than for men (7.26%). Also, dementia prevalence was higher for rural than urban residents (7.71% vs 8.68%, respectively). Participants without formal education presented more than double the prevalence of dementia (21.37%) compared to those with at least one year of formal education (9.88%). Studies with more recent data collection showed higher dementia prevalence. CONCLUSION: Our findings suggest a high global dementia prevalence in LAC countries and an unequal burden of dementia for women, lower-educated, and rural residents. Secular increases in dementia prevalence call for greater public health efforts for preventative actions.

Immunogenicity of SARS-CoV-2 Trimeric Spike Protein Associated to Poly(I:C) Plus Alum.

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid [Poly(I:C)] adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2 in vitro by neutralization assay, after two or three immunizations. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+ and CD8+ T cells producing interferon-gamma were equivalent, demonstrating that the Alum + Poly(I:C) combination supported a Th1 profile. Based on the high neutralizing titers, we evaluated B cells in the germinal centers, which are specific for receptor-binding domain (RBD) and spike, and observed that more positive B cells were induced upon the Alum + Poly(I:C) combination. Moreover, these B cells produced antibodies against both RBD and non-RBD sites. We also studied the impact of this vaccination preparation [spike protein with Alum + Poly(I:C)] in the lungs of mice challenged with inactivated SARS-CoV-2 virus. We found a production of IgG, but not IgA, and a reduction in neutrophil recruitment in the bronchoalveolar lavage fluid (BALF) of mice, suggesting that our immunization scheme reduced lung inflammation. Altogether, our data suggest that Alum and Poly(I:C) together is a possible adjuvant combination for vaccines against SARS-CoV-2 by the intradermal route.