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Abstract Unhealthy lifestyles risk factors, such as smoking, alcohol consumption, physical inactivity, poor diet, and obesity, have been associated with a higher risk of all-cause and cause-specific mortality. However, composite score of these unhealthy behaviours has not been considered, particularly in Latin American populations. Herein, we examined the association of lifestyle risk factors score with all-cause and cause-specific mortality in Mexican adults. A total of 159,517 adults from the Mexico City Prospective Study (MCPS) were included. Data on sociodemographic, lifestyle risk factors and medical histories was collected through a self-reported baseline questionnaire in a census-style door-to-door interviews. Lifestyle risk factors assessment was based on five modifiable lifestyle risk factors and their respective cut-off points according to current health recommendations, including obesity, physical inactivity, tobacco, alcohol consumption and fruits and vegetables intake. Multivariable Cox regression models were used to estimate the associations of lifestyle risk factor score (ranging from 0 to 5) with all-cause and cause-specific mortality (cardiovascular disease, renal or hepatobiliary diseases, diabetes, respiratory diseases, cancer and all-cause mortality). We excluded the first 2, 5, 10, and 15 years of follow-up to account for reverse causation bias. We found a high prevalence (77%) of Mexican adults, with two or more lifestyle risk factors. Hazard ratio for respiratory diseases and renal or hepatobiliary diseases were 1.86 (95%CI: 1.45–2.39) and 2.00 (95%CI: 1.60–2.52) comparing participants with 4–5 lifestyle risk factors vs. those with none. For all-cause mortality, participants with 4–5 lifestyle risk factors had a 49% (HR: 1.49; 95%CI: 1.03–2.16) higher risk as compared to participants with none. The magnitude of the associations increased as the exclusion of follow-up time increased after 2, 5, 10 and 15 years. There was a positive association between the number of lifestyle risk factors and all-cause and cause-specific mortality, showing the highest rate of respiratory, renal or hepatobiliary and all-cause mortality among participants with 4–5 lifestyle risk factors. After accounting for reverse causation, associations were stronger.

With the rapid spread and evolution of SARS-CoV-2, the ability to monitor its transmission and distinguish among viral lineages is critical for pandemic response efforts. The most commonly used software for the lineage assignment of newly isolated SARS-CoV-2 genomes is pangolin, which offers two methods of assignment, pangoLEARN and pUShER. PangoLEARN rapidly assigns lineages using a machine-learning algorithm, while pUShER performs a phylogenetic placement to identify the lineage corresponding to a newly sequenced genome. In a preliminary study, we observed that pangoLEARN (decision tree model), while substantially faster than pUShER, offered less consistency across different versions of pangolin v3. Here, we expand upon this analysis to include v3 and v4 of pangolin, which moved the default algorithm for lineage assignment from pangoLEARN in v3 to pUShER in v4, and perform a thorough analysis confirming that pUShER is not only more stable across versions but also more accurate. Our findings suggest that future lineage assignment algorithms for various pathogens should consider the value of phylogenetic placement.

Endocrine-disrupting chemicals (EDCs) are chemical substances that can interfere with any hormone action. They are categorized according to origin and use, such as industrial chemicals like polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs), plastics like bisphenol A (BPA), plasticizers like phthalates, pesticides like dichlorodiphenyltrichloroethane (DDT), fungicides like vinclozolin, and pharmaceuticals like diethylstilbestrol (DES). Natural EDCs, such as phytoestrogens, are present in the diet of both humans and animals. Polyphenols are a large group of natural compounds derived from plants and are found in beverages and food. They are grouped based on their chemical structure into flavonoids and nonflavonoids and are reported to have many beneficial effects on health, including, but not limited to, anticancer, antioxidant, and anti-inflammatory effects. Moreover, polyphenols have both pro- and antioxidant characteristics, and due to their antioxidant and anti-inflammatory potential, they presumably have a protective effect against damage induced by EDCs. However, polyphenols may act as EDCs. In this review, we report that polyphenols regulate the activity of EDCs, having both positive and negative effects. Hence, a better understanding of the associations between EDCs and polyphenols will allow the establishment of improved approaches to protect human health from EDCs.

The objective of this study was to present the main factors responsible for falls in older adults, measures for assessing risk, and prevention strategies. This is a qualitative study, developed from the international and national gerontology literature. Two models were created, one including the main fall risk factors and another including common assessment and prevention measures. Five types of intervention procedures were identified: educational, physical, cognitive, exergames and exercise programs. It was concluded that early identification of fall risk is important. The most appropriate intervention methodologies for preventing falls in the elderly include periodic dual and multi-task physical training followed by educational measures. In addition, exercise programs and exergames are effective in preventing falls, especially in congregate housing.

Abstract Background Brazil is one of the countries with the highest rates of caesarean sections (CS), reaching almost 90% of births in the private sector. A quality improvement project called “Adequate Childbirth Project (PPA)” was conceived to reduce CS in the private sector. This project consisted of four primary components: “Governance”, “Participation of Women”, “Reorganization of Care” and “Monitoring”. This paper aims to evaluate: (1) which specific activities of the PPA had the largest effect on the probability of a woman having a vaginal delivery; (2) which primary component of the PPA had the largest effect on the probability of vaginal delivery and (3) which scenarios combining the implementation of different activities planned in the PPA had a higher effect on the probability of vaginal delivery. Methods A sample of 12 private hospitals participating in the PPA was evaluated. We used a Bayesian Network (BN) to capture both non-linearities and complex cause-effect relations. The BN integrated knowledge from experts and data from women to estimate 26 model parameters. The PPA was evaluated in 2473 women belonging to groups 1–4 of the Robson classification, who were divided into two groups: those participating or not participating in the PPA. Results The probability of a woman having a vaginal delivery was 37.7% higher in women participating in the PPA. The most important component of the project that led to an increase in the probability of vaginal delivery was “Reorganization of Care”, leading to a 73% probability of vaginal delivery among women in labor. The activity that had the greatest effect on the type of delivery was access to best practices during labor, with a 72% probability of vaginal delivery. Considering the 12 scenarios combining the different activities of the PPA, the best scenarios included: a non-scheduled delivery, access to information about best practices, access to at least 4 best practices during labor and respect of the birth plan, with an 80% probability of vaginal delivery in the best combinations. Conclusion PPA has been shown to be an effective quality improvement program, increasing the likelihood of vaginal delivery in private Brazilian hospitals.

Human Hsp70-escort protein 1 (hHep1) is a cochaperone that assists in the function and stability of mitochondrial HSPA9. Similar to HSPA9, hHep1 is located outside the mitochondria and can interact with liposomes. In this study, we further investigated the structural and thermodynamic behavior of interactions between hHep1 and negatively charged liposomes, as well as interactions with cellular membranes. Our results showed that hHep1 interacts peripherally with liposomes formed by phosphatidylserine and cardiolipin and remains partially structured, exhibiting similar affinities for both. In addition, after being added to the cell membrane, recombinant hHep1 was incorporated by cells in a dose-dependent manner. Interestingly, the association of HSPA9 with hHep1 improved the incorporation of these proteins into the lipid bilayer. These results demonstrated that hHep1 can interact with lipids also present in the plasma membrane, indicating roles for this cochaperone outside of mitochondria.

Phylogenetics has been foundational to SARS-CoV-2 research and public health policy, assisting in genomic surveillance, contact tracing, and assessing emergence and spread of new variants. However, phylogenetic analyses of SARS-CoV-2 have often relied on tools designed for de novo phylogenetic inference, in which all data are collected before any analysis is performed and the phylogeny is inferred once from scratch. SARS-CoV-2 data sets do not fit this mold. There are currently over 14 million sequenced SARS-CoV-2 genomes in online databases, with tens of thousands of new genomes added every day. Continuous data collection, combined with the public health relevance of SARS-CoV-2, invites an "online" approach to phylogenetics, in which new samples are added to existing phylogenetic trees every day. The extremely dense sampling of SARS-CoV-2 genomes also invites a comparison between likelihood and parsimony approaches to phylogenetic inference. Maximum likelihood (ML) and pseudo-ML methods may be more accurate when there are multiple changes at a single site on a single branch, but this accuracy comes at a large computational cost, and the dense sampling of SARS-CoV-2 genomes means that these instances will be extremely rare because each internal branch is expected to be extremely short. Therefore, it may be that approaches based on maximum parsimony (MP) are sufficiently accurate for reconstructing phylogenies of SARS-CoV-2, and their simplicity means that they can be applied to much larger data sets. Here, we evaluate the performance of de novo and online phylogenetic approaches, as well as ML, pseudo-ML, and MP frameworks for inferring large and dense SARS-CoV-2 phylogenies. Overall, we find that online phylogenetics produces similar phylogenetic trees to de novo analyses for SARS-CoV-2, and that MP optimization with UShER and matOptimize produces equivalent SARS-CoV-2 phylogenies to some of the most popular ML and pseudo-ML inference tools. MP optimization with UShER and matOptimize is thousands of times faster than presently available implementations of ML and online phylogenetics is faster than de novo inference. Our results therefore suggest that parsimony-based methods like UShER and matOptimize represent an accurate and more practical alternative to established ML implementations for large SARS-CoV-2 phylogenies and could be successfully applied to other similar data sets with particularly dense sampling and short branch lengths.

ABSTRACT Klebsiella pneumoniae is a significant healthcare-associated pathogen, notable for its diverse virulence and antibiotic resistance profiles. This study aimed to characterize the genotypic and phenotypic diversity of K. pneumoniae isolates and evaluate their virulence using the Galleria mellonella model. Biomass production, metabolic activity, capsule formation, and siderophore production were assessed in 27 K. pneumoniae isolates from hospital-associated infections. Lethality curves were generated using the G. mellonella model, with survival monitored hourly from 16 to 48 hours. The most common sequence types (ST) identified were the high-risk clones ST307 (N = 10), ST512 (N = 8), ST101 (N = 7), and ST661 (N = 2). These STs were associated with distinct K-locus, including KL102, KL107, KL17, and KL39. Most isolates belonged to the O2afg locus (N = 18), with the K. pneumoniae carbapenemase genotype detected in 96.3% of strains. None of the isolates were classified as hypervirulent. Phenotypically, ST661 exhibited the highest biomass production despite showing similar metabolic activity to other STs. A positive correlation was observed between biomass and siderophore production, while capsule production was inversely correlated with biomass. In the G. mellonella model, ST661 demonstrated the highest virulence, resulting in 100% mortality by 48 hours, compared to survival rates of 21.4% for ST101, 38.0% for ST307, and 31.2% for ST512. These findings underscore the pathogenic potential of ST661 isolates with enhanced biofilm production. The G. mellonella model may serve as an effective in vivo system for evaluating the virulence of emerging K. pneumoniae lineages.IMPORTANCEWe demonstrate that the Galleria mellonella model is a useful tool to analyze the virulence of carbapenem-resistant Klebsiella pneumoniae strains. Our findings highlight the pathogenicity of carbapenem-resistant K pneumoniae isolates, particularly the role of the ST661 that, despite being a rare lineage, harbors the blaVIM gene and is associated with high biofilm production and the highest mortality rates.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder exacerbated by Staphylococcus aureus colonization. The specific factors that drive S. aureus overgrowth and persistence in AD remain poorly understood. This study analyzed skin barrier functions and microbiome diversity in lesional (LE) and non-lesional (NL) forearm sites of individuals with severe AD compared to healthy control subjects (HS). Notable differences were found in transepidermal water loss, stratum corneum hydration, and microbiome composition. Cutibacterium was more prevalent in HS, while S. aureus and S. lugdunensis were predominantly found in AD LE skin. The results highlighted that microbial balance depends on inter-species competition. Specifically, network analysis at the genus level demonstrated that overall bacterial correlations were higher in HS, indicating a more stable microbial community. Notably, network analysis at the species level revealed that S. aureus engaged in competitive interactions in NL and LE but not in HS. Whole-genome sequencing (WGS) showed considerable genetic diversity among S. aureus strains from AD. Despite this variability, the isolates exhibited convergence in key phenotypic traits such as adhesion and biofilm formation, which are crucial for microbial persistence. These common phenotypes suggest an adaptive evolution, driven by competition in the AD skin microenvironment, of S. aureus and underscoring the interplay between genetic diversity and phenotypic convergence in microbial adaptation.

Mitochondrial quality control is critical for cardiac homeostasis as these organelles are responsible for generating most of the energy needed to sustain contraction. Dysfunctional mitochondria are normally degraded via intracellular degradation pathways that converge on the lysosome. Here, we identified an alternative mechanism to eliminate mitochondria when lysosomal function is compromised. We show that lysosomal inhibition leads to increased secretion of mitochondria in large extracellular vesicles (EVs). The EVs are produced in multivesicular bodies, and their release is independent of autophagy. Deletion of the small GTPase Rab7 in cells or adult mouse heart leads to increased secretion of EVs containing ubiquitinated cargos, including intact mitochondria. The secreted EVs are captured by macrophages without activating inflammation. Hearts from aged mice or Danon disease patients have increased levels of secreted EVs containing mitochondria indicating activation of vesicular release during cardiac pathophysiology. Overall, these findings establish that mitochondria are eliminated in large EVs through the endosomal pathway when lysosomal degradation is inhibited.

Dengue virus (DENV) is the most important human virus transmitted by mosquitos. Dengue pathogenesis is characterized by a large induction of proinflammatory cytokines. This cytokine induction varies among the four DENV serotypes (DENV1 to 4) and poses a challenge for live DENV vaccine design. Here, we identify a viral mechanism to limit NF-κB activation and cytokine secretion by the DENV protein NS5. Using proteomics, we found that NS5 binds and degrades the host protein ERC1 to antagonize NF-κB activation, limit proinflammatory cytokine secretion, and reduce cell migration. We found that ERC1 degradation involves unique properties of the methyltransferase domain of NS5 that are not conserved among the four DENV serotypes. By obtaining chimeric DENV2 and DENV4 viruses, we map the residues in NS5 for ERC1 degradation, and generate recombinant DENVs exchanging serotype properties by single amino acid substitutions. This work uncovers a function of the viral protein NS5 to limit cytokine production, critical to dengue pathogenesis. Importantly, the information provided about the serotype-specific mechanism for counteracting the antiviral response can be applied to improve live attenuated vaccines.

Objectives: The present study aims to address the psychological motivations behind social media use, focusing on its under-explored regulatory function in the context of coping strategies and emotional regulation among teachers. This exploratory research explores the relationship between social media engagement and its impact on educators’ stress management and emotional regulation mechanisms. Methods: To investigate this relationship, the study utilized two key instruments: The coping inventory for stressful situations and the Italian version of the difficulties in emotion regulation scale. These tools were administered to a sample of 214 Italian teachers, predominantly female (90.7%), with ages ranging from 25 to 65 years (Mean±SD 47.19±9.02 years). The study employed correlation analysis to assess the associations between social media use in addition to various coping and emotional regulation strategies. Results: The correlation analysis revealed a nuanced relationship between the usage of certain social media platforms and a higher inclination toward a problem-oriented coping style, alongside a decreased sense of a lack of negative emotional control. Accordingly, while social media can serve as a tool for problem-oriented coping, it may also hinder the ability to disengage from negative emotional states. Discussion: The results of this study shed light on the potential of social media as a resource and a challenge in the emotional and professional lives of teachers. By identifying specific coping strategies that are positively and negatively associated with social media use, the research points toward possible interventions that could mitigate the adverse effects of social media. This could include developing targeted support mechanisms to enhance teachers’ ability to manage stress and regulate emotions effectively, thereby optimizing their use of social media in a way that supports their psychological well-being.

Summary: Background: Carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) are listed by World Health Organization (WHO) as priority antimicrobial-resistant bacteria. Data on WHO Priority Antimicrobial resistance Phenotype (WPAP) bacteria from low- and middle-income countries are scarce. In this study, we investigated the occurrence of WPAP in healthcare-associated bloodstream infections (BSI) in Brazil, an upper-middle-income country in South America. Methods: ASCENSION was a prospective, multicentre, observational study conducted in 14 hospitals from four of five Brazilian regions. Enterobacterales, A. baumannii, P. aeruginosa, S. aureus and E. faecium BSIs in hospitalised patients were analysed. The primary outcome was the frequency of WPAP among all bacteria of interest. Secondary outcomes were incidence-density of bacteria isolates in hospitalised patients, WPAP proportions within bacterial species, and 28-day mortality. PCR for carbapenemase genes was performed in carbapenem-resistant Gram-negative bacteria. Findings: Between August 15, 2022, and August 14, 2023, 1350 isolates (1220 BSI episodes) were included. WPAP accounted for 38.8% (n = 524; 95% Confidence Interval 32.0–46.1) of all isolates, with CRE (19.3%) as the most frequent, followed by CRAB (9.6%), MRSA (4.9%), VRE (2.7%), and CRPA (2.4%). Incidence-density of all and WPAP isolates were 1.91 and 0.77/1000 patients-day, respectively. Carbapenem-resistant Klebsiella pneumoniae (CRKP) was the most common CRE, corresponding to 14.2% of all BSIs. A. baumannii isolates presented the highest proportion of WPAP (87.8%). Mortality rates were higher in patients with BSIs by WPAP than non-WPAP isolates. KPC (64.4%) was the predominant carbapenemase in CRE, followed by NDM (28.4%) and KPC + NDM co-production (7.1%). OXA-23 was the most frequent in CRAB. Interpretation: A high frequency of WPAP bacteria, particularly CRKP and CRAB, were found in healthcare-associated BSIs in Brazil, posing them as a major public health problem in this country. Funding: National Council for Scientific and Technological Development, Brazil.