Search

In 1995, a pioneering MD-PhD program was initiated in Brazil for the training of medical scientists in experimental sciences at the Federal University of Rio de Janeiro. The program's aim was achieved with respect to publication of theses in the form of papers with international visibility and also in terms of fostering the scientific careers of the graduates. The expansion of this type of program is one of the strategies for improving the preparation of biomedical researchers in Brazil. A noteworthy absence of interest in carrying out clinical research limits the ability of young Brazilian physicians to solve biomedical problems. To understand the students' views of science, we used qualitative and quantitative triangulation methods, as well as participant observation to evaluate the students' concepts of science and common sense. Subjective aspects were clearly less evident in their concepts of science. There was a strong concern about "methodology", "truth" and "usefulness". "Intuition", "creativity" and "curiosity" were the least mentioned thematic categories. Students recognized the value of intuition when it appeared as an explicit option but they did not refer to it spontaneously. Common sense was associated with "consensus", "opinion" and ideas that "require scientific validation". Such observations indicate that MD-PhD students share with their senior academic colleagues the same reluctance to consider common sense as a valid adjunct for the solution of scientific problems. Overcoming this difficulty may be an important step toward stimulating the interest of physicians in pursuing experimental research.

Abstract The escalating threat of climate change has placed global coastal communities at risk, with rising sea levels and intensified storm events presenting unprecedented challenges. Coastal vulnerability assessments, conducted every 3–5 years, are crucial. This empirical study assesses the Coastal Vulnerability Index (CVI) for the distinct coastal contexts of Dawlish, Happisburgh (England), and Aberystwyth (Wales). The CVI method consists of the Physical Coastal Vulnerability Index (PCVI) and the Economic Coastal Vulnerability Index (ECVI), which provide a multidimensional assessment of vulnerability for coastal zones. This integrated index allows for a nuanced evaluation of vulnerability, distinguishing between sites based on various factors. Additionally, this study conducted a correlation analysis to understand the associations between the parameters. The findings demonstrate that physical features like beach and dune widths significantly impact a location’s natural defences, and economic factors such as property values and population density are equally crucial in determining societal risks and potential financial repercussions. The Combined Coastal Vulnerability Index (CCVI) results confirm the effectiveness of incorporating a diverse range of variables. Despite its substantial economic value, it reveals that Dawlish requires targeted protective measures, whereas Happisburgh needs an increased focus on its most vulnerable sectors. Aberystwyth emerges as the area with the highest overall vulnerability, underscoring the need for comprehensive coastal management practices. The study’s conclusions emphasize the essential role of adaptive, integrated management strategies in enhancing coastal resilience against the complex threats posed by climate dynamics. Moving forward, the indices established herein advocate for their use in strategic planning and policymaking to strengthen coastal regions in the face of sea-level rise and climatic variability. This investigation lays the groundwork for future research, aimed at refining and expanding these methodologies, aspiring to develop a detailed national coastal vulnerability atlas, a critical tool for informed decision-making and safeguarding at-risk communities.

Abstract Colorectal cancer in Brazil is among the main public health concern. The burden of disease can be related to unhealthy lifestyle behavior and inequality in access to health services. The aim of this study was to identify the main factors associated with colorectal cancer mortality in Brazil. This is an ecological study that had the Brazilian Federal Units as the primary units of analysis. Colorectal cancer mortality data (ICD C18-C21) were obtained from Brazilian national mortality system to the year 2020. Prevalence of overweight, food consumption (fiber, whole grains and red meat), physical inactivity, smoke, alcohol consumption, the median of household income, years of study, rates of cancer treatment units and oncologist by Brazilian Federal Units were considered as factor associated to the colorectal cancer mortality. Quasipoisson Generalized Linear Models were used to associate CRC mortality and variables related to dietary intake, risk behavior, and access to health services. In 2020, there were 21,501 deaths by colorectal cancer (51% among women). Prevalence of overweight (men: IRR 1.03; CI: 1.01–1.04; women IRR 1.05; CI 1.02–1.08) and the density of oncologist (men: IRR 1.02; CI: 1.01–1.03; women IRR 1.02; CI 1.01–1.03) were the main factors associated with colorectal cancer mortality. Sociodemographic and food consumption characteristics were not statistically associated with CRC. Prevalence of overweight was the strongest factor associated with mortality from colorectal cancer in Brazil in 2020. Therefore, current public policies to reduce overweight and obesity should be prioritized and strengthened in Brazil.

Abstract The long-term effects of SARS-CoV-2 infection, and their determinants, are still unknown. This study aimed to assess symptoms one year after admission for COVID-19, according to the organ/system involved, and to identify factors. Cross-sectional study with retrospective data collection from March 2020 to February 2021. Inclusion criteria: aged ≥ 18 years and admitted for COVID-19. Exclusion criteria: death, not localized, refusal to participate, cognitive impairment or language barrier. A telephone survey was conducted on long COVID-related symptoms one year after hospital discharge. n = 486. The most frequent symptom groups were neurological (n = 225; 46.3%) and respiratory (n = 201; 41.4%). Multivariable analysis showed that a history of anxiety was significantly associated with psychiatric symptoms (ORa = 2.04, 95%CI = 1.02–4.06), fibromyalgia/chronic fatigue with general symptoms (ORa = 11.59, 95%CI = 1.47–9.34) and obesity with respiratory (ORa 1.90, 95%CI = 1.27–2.83) and musculoskeletal symptoms (ORa 1.96, 95%CI = 1.30–2.96). Male sex was associated with a significantly lower risk of neurological (ORa 0.64, 95%CI = 0.44–0.93), respiratory (ORa 0.45, 95%CI = 0.31–0.67), general (ORa 0.43, 95%CI = 0.29–0.63), psychiatric (ORa 0.34, 95%CI = 0.22–0.51), musculoskeletal (ORa 0.47, 95%CI = 0.32–0.70), dermatological (ORa 0.24, 95%CI = 0.14–0.42) and digestive (ORa 0.38, 95%CI = 0.20–0.73) symptoms. Advanced age (≥ 71 years) also had a protective effect against general (ORa 0.60, 95%CI = 0.39–0.95), psychiatric (ORa 0.39, 95%CI = 0.23–0.64), and dermatological (ORa 0.47, 95%CI = 0.24–0.92) symptoms. Patients admitted for SARS-CoV-2 infection frequently experience symptoms at one year, especially neurological and respiratory symptoms. Female sex, obesity, a history of anxiety and fibromyalgia/chronic fatigue were independent risk factors for presenting symptoms. Advanced age acted as a protective factor.

Abstract During the recent yellow fever (YF) epidemics in Brazil, human cases were attributed to spillover infections via sylvatic mosquito transmission. Despite YF virus (YFV) transmission in major urban centers with insufficient vaccination coverage and abundant populations of the domestic vector, Aedes aegypti, there was no evidence of human-amplified transmission. Furthermore, the historic absence of YF in Asia, despite abundant Ae. aegypti and an immunologically naive human population, is unexplained. We tested the hypothesis that pre-existing, heterologous flavivirus immunity, specifically from dengue (DENV) and Zika (ZIKV) viruses, limits YFV viremia and transmission by Ae. aegypti. We infected cynomolgus macaques with DENV or ZIKV, then challenged them 6–9 months later with YFV. We then measured viremia and disease and allowed Ae. aegypti mosquitoes to feed during peak macaque viremia. Although prior heterologous immunity had variable effects on disease, DENV and ZIKV immunity consistently suppressed YFV viremia. Despite no statistical difference due to a small sample size, the suppression in viremia led to a significant reduction in Ae. aegypti infection and a lack of transmission potential. These results support the hypothesis that, in DENV- and ZIKV-endemic regions such as South America and Asia, human flavivirus immunity suppresses YFV human amplification potential, reducing the risk of urban outbreaks.

Abstract Pairing transition metals and heavier tetrylenes (Si, Ge, Sn, Pb) holds great potential for cooperative bond activation and catalysis. In this work, we investigate the reactivity of a low-coordinate Pt(0)/Ge(II) system that emerges from the reaction between the monoligated platinum(0) precursor [(PMe2ArDipp2)Pt(olefin)] with germylene dimer [ArDipp2GeCl]2 (where ArDipp2 = C6H3−2,6-(C6H3−2,6- i Pr2)2). The resulting complex reveals ability for cooperative bond activation. Stoichiometric reactions with dihydrogen, water, methanol, ammonia and alkynes unveil the formation of Pt(II)-germyl compounds, characterized by distinct isomeric forms, whose flexibility derives from the particularly low-coordination. We explore its catalytic potential in the hydrodehalogenation of aliphatic, aromatic and main-group halides under dihydrogen atmosphere using both thermal and photochemical conditions, demonstrating promising conversions even for more challenging alkyl chlorides.

Abstract Mapping the production of Ecosystem Services (ES) is imperative for sustainable ecosystem management. Likewise, incorporating expert knowledge enhances ES research. Here, we calculate eight multi-temporal ES indicators for mainland Portugal using a spatial modelling approach. These indicators are then integrated into the novel ASEBIO index—Assessment of Ecosystem Services and Biodiversity—which depicts a combined ES potential based on CORINE Land Cover, using a multi-criteria evaluation method with weights defined by stakeholders through an Analytical Hierarchy Process (AHP). Outputs from the modelling show how ES have changed in Portugal in relation to land use changes, including trade-offs between 1990 and 2018. The composed ASEBIO index is compared against the stakeholders’ valuation of ES potential for the year 2018. The results reveal a significant mismatch between the ES potential perceived by stakeholders and the models, with stakeholder estimates being 32.8% higher on average. All the selected ES were overestimated by the stakeholders. Drought regulation and erosion prevention have the highest contrasts, while water purification, food production and recreation are the most closely aligned among both approaches. Providing the first national overview about the status of multiple ES over a 28 year-period, our findings highlight potential disparities between data-driven and stakeholder-based evaluations. Therefore, we suggest the need for integrative strategies that consider scientific models with expert knowledge for more effective ES assessments and land-use planning. This approach could help bridge the gap between data-driven models and human perspectives, resulting in more balanced and inclusive decision-making.

Abstract High mobility group (HMG) proteins are intrinsically disordered nuclear non-histone chromosomal proteins that play an essential role in many biological processes by regulating the expression of numerous genes in eukaryote cells. HMGA proteins contain three DNA binding motifs, the “AT-hooks”, that bind preferentially to AT-rich sequences in the minor groove of B-form DNA. Understanding the interactions of AT-hook domains with DNA is very relevant from a medical point of view because HMGA proteins are involved in different conditions including cancer and parasitic diseases. We present here the first crystal structure (1.40 Å resolution) of the HMGA AT-hook 1 domain, bound to the minor groove of AT-rich DNA. In contrast to AT-hook 3 which bends DNA and shows a larger minor groove widening, AT-hook 1 binds neighbouring DNA molecules and displays moderate widening of DNA upon binding. The binding affinity and thermodynamics of binding were studied in solution with surface plasmon resonance (SPR)-biosensor and isothermal titration calorimetry (ITC) experiments. AT-hook 1 forms an entropy-driven 2:1 complex with (TTAA)2-containing DNA with relatively slow kinetics of association/dissociation. We show that N-phenylbenzamide-derived antikinetoplastid compounds (1–3) bind strongly and specifically to the minor groove of AT-DNA and compete with AT-hook 1 for binding. The central core of the molecule is the basis for the observed sequence selectivity of these compounds. These findings provide clues regarding a possible mode of action of DNA minor groove binding compounds that are relevant to major neglected tropical diseases such as leishmaniasis and trypanosomiasis.

Abstract NASH is characterized by hepatic lipid accumulation and inflammation; and JMJD2B—a histone demethylase—upregulation has been linked to its progression. Pirfenidone (PFD) is an antifibrotic agent with anti-inflammatory and antioxidant effects recognized to decrease NASH symptoms. Herein, our aim was to investigate PFD-induced epigenetics mechanisms involving JMJD2B and histone modifications in experimental NASH. Male C57BL/6J mice were fed with normo-diet, or high fat/carbohydrate diet (HF) for 16 weeks. A HF-subgroup was treated with PFD 300 mg/kg/d from week 8th to the end of protocol. Insulin tolerance test and liver and fat histological and biochemical analyses were carried out. Hepatic transcriptome was examined. Liver proteins were studied by western blot (WB) and Chromatin immunoprecipitation. In vitro, lipotoxicity was induced in HepG2 cells and proteins were evaluated using WB. Molecular docking was used to explore binding of PFD to JMJD2B. Mice treated with PFD reduced weight gain, epididymal fat and inflammatory nodules, and steatosis in liver tissue, as well as, improved biochemical test. PFD modified the expression of Jmjd2b, Pparg, Fasn and Srebp1, and restored JMJD2B protein and H3K9me3 repressive mark, both in animal and cell models. PFD increased hepatic enrichment of H3K9me2 and H3K9me3 at the promoter region of Fasn and Srebp1, and Pparg. In HepG2 cells, PFD reduced lipid vacuole accumulation. In silico, PFD interacted with JMJD2B catalytic site. PFD is an epigenetic regulator modifying JMJD2B activity, resulting in reduced NASH traits.

Abstract Prognostic tests and treatment approaches for optimized clinical care of prostatic neoplasms are an unmet need. Prostate cancer (PCa) and derived extracellular vesicles (EVs) proteome changes occur during initiation and progression of the disease. PCa tissue proteome has been previously characterized, but screening of tissue samples constitutes an invasive procedure. Consequently, we focused this study on liquid biopsies, such as urine samples. More specifically, urinary small extracellular vesicle and particles proteome profiles of 100 subjects were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC–MS/MS). We identified 171 proteins that were differentially expressed between intraductal prostate cancer/cribriform (IDC/Crib) and non-IDC/non-Crib after correction for multiple testing. However, the strong correlation between IDC/Crib and Gleason Grade complicates the disentanglement of the underlying factors driving this association. Nevertheless, even after accounting for multiple testing and adjusting for ISUP (International Society of Urological Pathology) grading, two proteins continued to exhibit significant differential expression between IDC/Crib and non-IDC/non-Crib. Functional enrichment analysis based on cancer hallmark proteins disclosed a clear pattern of androgen response down-regulation in urinary EVs from IDC/Crib compared to non-IDC/non-Crib. Interestingly, proteome differences between IDC and cribriform were more subtle, suggesting high proteome heterogeneity. Overall, the urinary EV proteome reflected partly the prostate pathology.

Abstract Age-related cataracts is a highly prevalent eye disorder that results in the clouding of the crystalline lens and is one of the leading causes of visual impairment and blindness. The disease is influenced by multiple factors including genetics, prolonged exposure to ultraviolet radiation, and a history of diabetes. However, the extent to which each of these factors contributes to the development of cataracts remains unclear. Our study identified 101 independent genome-wide significant loci, 57 of which are novel. We identified multiple genes and biological pathways associated with the cataracts, including four drug-gene interactions. Our results suggest a causal association between type 1 diabetes and cataracts. Also, we highlighted a surrogate measure of UV light exposure as a marker of cataract risk in adults.

Abstract The aim of this study was to build and validate an artificial neural network (ANN) algorithm to predict sleep using data from a portable monitor (Biologix system) consisting of a high-resolution oximeter with built-in accelerometer plus smartphone application with snoring recording and cloud analysis. A total of 268 patients with suspected obstructive sleep apnea (OSA) were submitted to standard polysomnography (PSG) with simultaneous Biologix (age: $$56\pm 11$$ 56 ± 11 years; body mass index: $$30.9\pm 4.6$$ 30.9 ± 4.6 $$\hbox {kg/m}^{2}$$ kg/m 2 , apnea-hypopnea index [AHI]: $$35\pm 30$$ 35 ± 30 events/h). Biologix channels were input features for construction an ANN model to predict sleep. A k-fold cross-validation method (k=10) was applied, ensuring that all sleep studies (N=268; 246,265 epochs) were included in both training and testing across all iterations. The final ANN model, evaluated as the mean performance across all folds, resulted in a sensitivity, specificity and accuracy of 91.5%, 71.0% and 86.1%, respectively, for detecting sleep. As compared to the oxygen desaturation index (ODI) from Biologix without sleep prediction, the bias (mean difference) between PSG-AHI and Biologix-ODI with sleep prediction (Biologix-Sleep-ODI) decreased significantly (3.40 vs. 1.02 events/h, p

Abstract A detailed assessment of a low energy demand, 1.5 ∘C compatible pathway is provided for Europe from a bottom-up, country scale modelling perspective. The level of detail enables a clear representation of the potential of sufficiency measures. Results show that by 2050, 50% final energy demand reduction compared to 2019 is possible in Europe, with at least 40% of it attributable to various sufficiency measures across all sectors. This reduction enables a 77% renewable energy share in 2040 and 100% in 2050, with very limited need for imports from outside of Europe and no carbon sequestration technologies. Sufficiency enables increased fairness between countries through the convergence towards a more equitable share of energy service levels. Here we show, that without sufficiency measures, Europe misses the opportunity to transform energy demand leaving considerable pressure on supply side changes combined with unproven carbon removal technologies.

Abstract How nicotine acts on developing neurocircuitry in adolescence to promote later addiction vulnerability remains largely unknown, but may hold the key for informing more effective intervention efforts. We found transient nicotine exposure in early adolescent (PND 21-28) male mice was sufficient to produce a marked vulnerability to nicotine in adulthood (PND 60 + ), associated with disrupted functional connectivity in dopaminergic circuits. These mice showed persistent adolescent-like behavioral and physiological responses to nicotine, suggesting that nicotine exposure in adolescence prolongs an immature, imbalanced state in the function of these circuits. Chemogenetically resetting the balance between the underlying dopamine circuits unmasked the mature behavioral response to acute nicotine in adolescent-exposed mice. Together, our results suggest that the perseverance of a developmental imbalance between dopamine pathways may alter vulnerability profiles for later dopamine-dependent psychopathologies.

Abstract The COVID-19 pandemic remains a significant global health threat, with uncertainties persisting regarding the factors determining whether individuals experience mild symptoms, severe conditions, or succumb to the disease. This study presents an NMR metabolomics-based approach, analysing 80 serum and urine samples from COVID-19 patients (34 intensive care patients and 46 hospitalized patients) and 32 from healthy controls. Our research identifies discriminant metabolites and clinical variables relevant to COVID-19 diagnosis and severity. These discriminant metabolites play a role in specific pathways, mainly “Phenylalanine, tyrosine and tryptophan biosynthesis”, “Phenylalanine metabolism”, “Glycerolipid metabolism” and “Arginine and proline metabolism”. We propose a three-metabolite diagnostic panel—comprising isoleucine, TMAO, and glucose—that effectively discriminates COVID-19 patients from healthy individuals, achieving high efficiency. Furthermore, we found an optimal biomarker panel capable of efficiently classify disease severity considering both clinical characteristics (obesity/overweight, dyslipidemia, and lymphocyte count) together with metabolites content (ethanol, TMAO, tyrosine and betaine).

Abstract Visceral leishmaniasis (VL) is an urgent public health concern in Brazil. We evaluated the spatiotemporal distribution of VL to better understand the effects of economic activities related to agriculture, livestock, and deforestation on its incidence in the Brazilian Legal Amazon (BLA). The data on newly confirmed cases of VL in Brazilian municipalities from 2007 to 2020 were extracted from the Brazilian Notifiable Diseases Information System (SINAN) and analyzed. The data on agricultural production (planted area in hectares) and livestock (total number of cattle) were obtained from the Brazilian Institute of Geography and Statistics (IBGE), whereas deforestation data (in hectares) were obtained from the Amazon Deforestation Estimation Project (PRODES). SatScan and the local indicators of spatial association (LISA) were used to identify the spatial and temporal patterns of VL and its relationships with economic and environmental variables. The cumulative incidence rate was found to be 4.5 cases per 100,000 inhabitants. Based on the LISA results, areas with a high incidence of VL and deforestation were identified in the states of Roraima, Pará, and Maranhão. Strengthening deforestation monitoring programs and environmental enforcement actions can help implement public policies to control illegal deforestation and mitigate the socio-environmental vulnerability in the BLA. Therefore, areas identified in this study should be prioritized for controlling VL.

Human societies face many challenges for which scientific knowledge is essential to gain a broader and in depth understanding of the problems and possible solutions and alternatives. However, fake news, anti-science claims and misinformation unbalance much-needed public debates on socio-scientific issues. Conversely, failure to convey a clear and transparent message about science can also contribute to the emergence or growth of controversies. There is no simple solution to such a complex problem, but the introduction of collaborative and participatory approaches to research, as a way of involving the public in the production of scientific knowledge, can be a powerful strategy for promoting trust in science, while integrating a critical view on research work. We recently proposed a new concept, engaged citizen social science, which aims to provide a theoretical framework for deeper engagement of citizens with science. This concept is being tested in a HE funded project that integrates social sciences and humanities in the development of a new biosensor technology. Biotechnology is a hot topic in socio-scientific debates, involving issues such as control, risks, access to data, democratisation of science or governance. By engaging in structured conversations with different publics, we are mapping these and other cultural and social perceptions, exploring dimensions of representation (ideas and cultural meanings about the technology) and identity (who the public is considering knowledge, proximity to the technology, and scientific information consumption). The results of these social dialogues influence the project’s research agenda and the production of the communication outputs, thus also having the potential to influence scientific policies in this area. Here we present the preliminary results of this mapping and discuss our findings in relation to our dialogical strategy.

Abstract Wastewater is a geospatially- and temporally-linked microbial fingerprint of a given population, making it a potentially valuable tool for tracking public health across locales and time. Here, we integrate targeted and bulk RNA sequencing (N = 2238 samples) to track the viral, bacterial, and functional content over geospatially distinct areas within Miami Dade County, USA, from 2020-2022. We used targeted amplicon sequencing to track diverse SARS-CoV-2 variants across space and time, and we found a tight correspondence with positive PCR tests from University students and Miami-Dade hospital patients. Additionally, in bulk metatranscriptomic data, we demonstrate that the bacterial content of different wastewater sampling locations serving small population sizes can be used to detect putative, host-derived microorganisms that themselves have known associations with human health and diet. We also detect multiple enteric pathogens (e.g., Norovirus) and characterize viral diversity across sites. Moreover, we observed an enrichment of antimicrobial resistance genes (ARGs) in hospital wastewater; antibiotic-specific ARGs correlated to total prescriptions of those same antibiotics (e.g Ampicillin, Gentamicin). Overall, this effort lays the groundwork for systematic characterization of wastewater that can potentially influence public health decision-making.

Abstract SARS-CoV-2 caused the pandemic situation experienced since the beginning of 2020, and many countries faced the rapid spread and severe form of the disease. Mechanisms of interaction between the virus and the host were observed during acute phase, but few data are available when related to immunity dynamics in convalescents. We conducted a longitudinal study, with 51 healthy donors and 62 COVID-19 convalescent patients, which these had a 2-month follow-up after symptoms recovery. Venous blood sample was obtained from all participants to measure blood count, subpopulations of monocytes, lymphocytes, natural killer cells and dendritic cells. Serum was used to measure cytokines, chemokines, growth factors, anti-N IgG and anti-S IgG/IgM antibodies. Statistic was performed by Kruskal–Wallis test, and linear regression with days post symptoms and antibody titers. All analysis had confidence interval of 95%. Less than 35% of convalescents were anti-S IgM+, while more than 80% were IgG+ in D30. Anti-N IgG decreased along time, with loss of seroreactivity of 13%. Eosinophil count played a distinct role on both antibodies during all study, and the convalescence was orchestrated by higher neutrophil-to-lymphocyte ratio and IL-15, but initial stages were marked by increase in myeloid DCs, B1 lymphocytes, inflammatory and patrolling monocytes, G-CSF and IL-2. Later convalescence seemed to change to cytotoxicity mediated by T lymphocytes, plasmacytoid DCs, VEGF, IL-9 and CXCL10. Anti-S IgG antibodies showed the longest perseverance and may be a better option for diagnosis. The inflammatory pattern is yet present on initial stage of convalescence, but quickly shifts to a reparative dynamic. Meanwhile eosinophils seem to play a role on anti-N levels in convalescence, although may not be the major causative agent. We must highlight the importance of immunological markers on acute clinical outcomes, but their comprehension to potentialize adaptive system must be explored to improve immunizations and further preventive policies.

In recent years, research on normatively positive social tipping dynamics in response to the climate crisis has produced invaluable insights. In contrast, relatively little attention has been given to the potentially negative social tipping processes that might unfold due to an increasingly destabilized Earth system and to how they might in turn reinforce social and ecological destabilization dynamics and/or impede positive social change. In this paper, we discuss selected potential negative social tipping processes (anomie, radicalization and polarization, displacement, conflict, and financial destabilization) linked to Earth system destabilization. We draw on related research to understand the drivers and likelihood of these negative tipping dynamics, their potential effects on human societies and the Earth system, and the potential for cascading interactions (e.g. food insecurity and displacement) contributing to systemic risks. This first attempt to provide an explorative conceptualization and empirical account of potential negative social tipping dynamics linked to Earth system destabilization is intended to motivate further research into an under-studied area that is nonetheless crucial for our ability to respond to the climate crisis and for ensuring that positive social tipping dynamics are not averted by negative ones.

Abstract Cervical cancer screening in Brazil is opportunistic, based on cytology and offered for women aged 25–64 years, with low coverage (30%) and 70% of cancer diagnoses done in advanced stages, without impact on mortality. The current study reports 5-year first-round results of a population-based DNA-HPV testing screening program in a Brazilian city, which intended to be a model for transition to a more efficient program. Program flowchart is simple and current, indicating repetition of a negative test after five years. The first-round (October 2017-September 2022) screened 20,551 women by DNA-HPV testing with 58.7% coverage and 99.4% compliance with the program's targeted age range. Coverage increases to 77.8% when excluding the ‘pandemic period’. The DNA-HPV testing was 87.2% negative with 6.2% colposcopy referrals and 84.8% colposcopies performed. A total of 258 high-grade precursor lesions and 29 cervical cancers (mean age = 41.4 years, 83% Stage I) were detected. As a reference, 41,387 cytology tests from the previous program (2012–2016) detected 36 cervical cancers (mean age = 52.0 years, p = 0.0005), with 67% in advanced stages (p

Abstract The objective was to evaluate the biosolids as an alternative source of nutrients in the production of chrysanthemums by adding increasing doses to the cultivation substrate. The experimental design was in blocks with 6 treatments and 5 replications. The treatments consisted of the mixture (commercial substrate + biosolid) at the concentrations: 20%, 40%, 60% and 80% of biosolid + two controls (100% of biosolid and 100% of substrate). The experiment was conducted in a greenhouse for 90 days. Physiological parameters, number of flower buds, dry biomass and nutrient accumulation were evaluated. Physiological parameters were evaluated using the Infrared Gas Analyzer. The number of flower buds was evaluated by counting. Biomass was determined after drying the structures and then calculated the accumulation of nutrients. A total of 90 plants were evaluated. Concentrations of up to 40% of biosolid promoted a greater number of flower buds, dry biomass and nutrient accumulation. Concentrations above 60% lower number of buds, biomass increment and nutrient accumulation. It is concluded that the biosolid has potential as an alternative source of nutrients in the cultivation of chrysanthemums, indicating concentrations of up to 40% and the nutrient content of each batch generated must be verified.

Abstract To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia. Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

En el Programa Universidad en el Campo (UNICAM), se realizan prácticas extensionistas con la finalidad de promover el intercambio de conocimientos entre la universidad y la comunidad, así como abordar desafíos específicos relacionados con la producción ganadera. Los estudiantes ejecutaron las prácticas pecuarias para compartir conocimiento con productores de las comunidades de su entorno, además de visualizar problemáticas en el hato ganadero, dando soluciones a estas, tomando en cuenta la experiencia in situ que posee el productor. El objetivo general de la sistematización es el de documentar experiencia sobre las prácticas pecuarias de la carrera Desarrollo Rural Sostenible, del programa Universidad en el campo (UNICAM), con estudiantes de la sede Empalme Morrito / Morrito, con una población de 13 unidades productivas; el instrumento que se aplicó fue la observación directa, al realizar el examen físico se evaluó el estado nutricional, logrando identificar deficiencias de vitaminas y minerales, encontrando un peso entre de 401 kg a 600 kg un 66 %, un 22 % se encuentran menos 400 kg y un 12 % está entre 801 kg a más, sin embargo no se encontró déficit nutricional por el tipo de categoría del ganado.

Sarcosaprophagous dipterans are well known due to their forensic and medical-sanitary importance, as they are possible vectors of pathogens and cause myiasis. However, their potential as bioindicators of anthropogenic actions is still little explored, especially in environments with high human interference (e.g., coastal environments). Thus, this work aims to compare the abundance and frequency of dipteran of forensic importance between two mangrove landscapes with different human impact levels: i) Baía Formosa, characterized as less anthropized, and ii) Extremoz, as a more anthropized mangrove. Adult flies were collected by using suspended traps containing decomposing animal tissue (chicken liver) as baits. A diverse assemblage of sarcosaprophagous Diptera was registered in the two mangroves, consisting of 18 species from four families: Calliphoridae (n = 1,738; S = 4), Sarcophagidae (n= 214; S = 9), Muscidae (n = 46; S = 3) and Fanniidae (n = 26; S = 2). Chrysomya megacephala was the most abundant species in Baía Formosa and Oxysarcodexia intona in Extremoz. In addition, this study reveals that human impact levels can modulate the structure and composition of flies’ assemblages in mangrove environments.

Abstract Humoral response to SARS-CoV-2 has been studied, predominantly the classical IgG and its subclasses. Although IgE antibodies are typically specific to allergens or parasites, a few reports describe their production in response to SARS-CoV-2 and other viruses. Here, we investigated IgE specific to receptor binding domain (RBD) of SARS-CoV-2 in a Brazilian cohort following natural infection and vaccination. Samples from 59 volunteers were assessed after infection (COVID-19), primary immunization with vectored (ChAdOx1) or inactivated (CoronaVac) vaccines, and booster immunization with mRNA (BNT162b2) vaccine. Natural COVID-19 induced IgE, but vaccination increased its levels. Subjects vaccinated with two doses of ChAdOx1 exhibited a more robust response than those immunized with two doses of CoronaVac; however, after boosting with BNT162b2, all groups presented similar IgE levels. IgE showed intermediate-to-high avidity, especially after the booster vaccine. We also found IgG4 antibodies, mainly after the booster, and they moderately correlated with IgE. ELISA results were confirmed by control assays, using IgG depletion by protein G and lack of reactivity with heterologous antigen. In our cohort, no clinical data could be associated with the IgE response. We advocate for further research on IgE and its role in viral immunity, extending beyond allergies and parasitic infections.

Abstract The increasing prevalence of gut colonization with CTX-M extended-spectrum β-lactamase- and/or DHA plasmid-mediated AmpC-producing Escherichia coli is a concern. Here, we evaluate Nanopore-shotgun metagenomic sequencing (Nanopore-SMS) latest V14 chemistry to detect bla CTX-M and bla DHA genes from healthy stools. We test 25 paired samples characterized with culture-based methods (native and pre-enriched). Antimicrobial resistant genes (ARGs) are detected from reads and meta-assembled genomes (MAGs) to determine their associated genetic environments (AGEs). Sensitivity and specificity of native Nanopore-SMS are 61.1% and 100%, compared to 81.5% and 75% for pre-enriched Nanopore-SMS, respectively. Native Nanopore-SMS identifies only one sample with an AGE, whereas pre-enriched Nanopore-SMS recognizes 9/18 plasmids and 5/9 E. coli chromosomes. Pre-enriched Nanopore-SMS identifies more ARGs than native Nanopore-SMS (p

Abstract Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.

Abstract Information about the morphology of the intracranial pressure waveform, as well as the variations in intracranial pressure (ICP) and compliance in pediatric patients are essential to diagnose and predict the progression of various neurological conditions. However, there is no information on the morphology of the IP waveform in neurologically healthy pediatric patients. In the present study, intracranial compliance was therefore analyzed in neurologically healthy patients with the aid of a noninvasive device. The study was an observational, cross-sectional study. Fifty-five neurologically healthy participants were included. Data on intracranial compliance with the patient in two positions, lying down (0°) and seated (45°), were collected with a noninvasive extracranial sensor, which allowed the intracranial pressure waveforms to be recorded. The values of the ratio P2/P1 were then analyzed. A questionnaire (with a scale from zero to ten, where ten corresponds to the highest level of satisfaction) was applied for patients to evaluate their satisfaction with the sensor. Patients were 10 years old (average), and most of them were (58%). Mean P2/P1 ratio was 0.94 (sd = 0.14) in the supine position and 0.91 (sd = 0.15) in the seated position. Participants were satisfied with the length of time for which the equipment was used (9.8, sd = 0.71). The device did not cause any discomfort. The noninvasive method used was well accepted by the patients. Intracranial compliance values were determined by analysis of the P2/P1 ratio in neurologically healthy pediatric population. Trial registration: Brazilian Registry of Clinical Trials Identifier: RBR-5j74ddg.

Abstract Skyrmions are topologically protected, vortex-like structures found in various condensed-matter systems including helical ferromagnets and liquid crystals, typically arising from chiral interactions. Using extensive particle-based simulations, we demonstrate that non-chiral hard banana-shaped particles, governed solely by excluded-volume interactions, spontaneously stabilize skyrmion structures through the bend-flexoelectric effect. Under thin confinement, we observe the formation of quasi-2D layers of isolated skyrmions or dense skyrmion lattices. These structures, comprising a racemic mixture of left- and right-handed skyrmions, show resilience against thermal fluctuations while remaining responsive to external fields, offering intriguing possibilities for manipulation. We also find that the size of these skyrmions can be adjusted by the dimensions and curvature of the banana-shaped particles. In the absence of geometric frustration due to confinement, a blue phase III may emerge, characterized by a 3D network of chiral skyrmion filaments of the nematic director field within an isotropic background. Our findings provide valuable insights into stabilizing skyrmion lattices and blue phases, showcasing non-Gaussian fluid-like dynamics in systems of achiral hard particles. Furthermore, they highlight the remarkable capacity of these complex fluids in designing advanced functional materials with diverse applications in photonics and memory devices.

Abstract T-box riboswitches are noncoding RNA elements involved in genetic regulation of most Gram-positive bacteria. They regulate amino acid metabolism by assessing the aminoacylation status of tRNA, subsequently affecting the transcription or translation of downstream amino acid metabolism-related genes. Here we present single-molecule FRET studies of the Mycobacterium tuberculosis IleS T-box riboswitch, a paradigmatic translational T-box. Results support a two-step binding model, where the tRNA anticodon is recognized first, followed by interactions with the NCCA sequence. Furthermore, after anticodon recognition, tRNA can transiently dock into the discriminator domain even in the absence of the tRNA NCCA-discriminator interactions. Establishment of the NCCA-discriminator interactions significantly stabilizes the fully bound state. Collectively, the data suggest high conformational flexibility in translational T-box riboswitches; and supports a conformational selection model for NCCA recognition. These findings provide a kinetic framework to understand how specific RNA elements underpin the binding affinity and specificity required for gene regulation.

Abstract The Continuous Visual Attention Test (CVAT) is a test that detects visuomotor reaction time (RT, alertness), variability of reaction time (VRT, sustained attention), omission errors (OE, focused attention), and commission errors (CE, response inhibition). The standard test takes 15 min, while the ultrafast version only 90 s. Besides overall task length, the two versions differ by target probability (20% and 80% in the 15-min vs. only 80% in the 90-s test) and stimulus-onset asynchrony (SOA) (1, 2, and 4 s in the 15-min vs. only 1 s in the 90-s test. We aimed to analyze the effect of target probability, SOA, and time length on the CVAT variables across the 15-min task and to verify correlations and agreements between the 15-min and the 90-s CVATs. 205 healthy participants performed the two CVATs on the same day. Considering the 15-min task, RT and CE were strongly affected by target probability. Conversely, VRT was not affected. When the 15-min task was compared to the 90-s task, we found no significant difference in the VRT variable. Additionally, a significant agreement between the two tasks was found for the VRT variable. We concluded that sustained attention can be measured with the 90-s CVAT.

Abstract The compositional nutrient diagnosis—CND method is a standard tool for evaluating plant nutritional status. Adjustments are crucial to elevate accuracy. The effectiveness of such methodological refinements should be rigorously assessed through accuracy tests that are benchmarked against the prescient diagnostic analysis—PDA methodology. The objective of this investigation was to refine the CND technique for a more precise evaluation of N, P, and B nutrient status in cotton. The study’s database encompasses 144 data points pertaining to crop yield and foliar nutrient concentrations from cotton plantations in the Cerrado biome of Brazil. Subsequently, the CND norms were established through rigorous calibration. Three separate nutrient-dose trials, each featuring four levels of N, P and B, were carried out to assess plant true nutritional status. Adjustments were made to the nutrient responsiveness range—NRr (0.5 and 1.0), while yield response—YR were scrutinized at threshold levels (5% and 10%). The prerequisites for achieving high diagnostic accuracy were nutrient specific. For N, maximal accuracy was linked only to the YR parameter (YR = 10%). For P, the most precise outcomes were attained with a NRr = 0.5 and YI = 5%. For B, highest diagnostic accuracy when the NRr = 1.0 and YI = 10%. These insights highlight the need to fine-tune the CND method for reliable nutritional evaluations and cotton crop productivity optimization.

Abstract Despite their ancient past and high diversity, African populations are the least represented in human population genetic studies. In this study, uniparental markers (mtDNA and Y chromosome) were used to investigate the impact of sociocultural factors on the genetic diversity and inter-ethnolinguistic gene flow in the three major Nigerian groups: Hausa (n = 89), Yoruba (n = 135) and Igbo (n = 134). The results show a distinct history from the maternal and paternal perspectives. The three Nigerian groups present a similar substrate for mtDNA, but not for the Y chromosome. The two Niger–Congo groups, Yoruba and Igbo, are paternally genetically correlated with populations from the same ethnolinguistic affiliation. Meanwhile, the Hausa is paternally closer to other Afro-Asiatic populations and presented a high diversity of lineages from across Africa. When expanding the analyses to other African populations, it is observed that language did not act as a major barrier to female-mediated gene flow and that the differentiation of paternal lineages is better correlated with linguistic than geographic distances. The results obtained demonstrate the impact of patrilocality, a common and well-established practice in populations from Central-West Africa, in the preservation of the patrilineage gene pool and in the affirmation of identity between groups.

Abstract Although validated and reliable psychophysical tests of olfactory function are available, an easy-to-use and feasible test has yet to be developed. This study aimed to design a digital odour identification test, evaluate its validity, assess its reliability, establish a normative curve, and explore the impact of demographic factors. The odour identification test was presented with the Multiscent-20, a hand-held, tablet-like digital scent device that features an integrated odour digital delivery system. The identification performance on the 20 odours was assessed using item response theory (IRT). The normative curve was established by administering the test to a large sample of participants (n = 1299). The mean identification score was 17.5 (SD = 2.1). The two-parameter logistic IRT model provided the best fit, revealing variation in item discrimination and difficulty parameters. Educational attainment influenced performance, with primary education associated with lower scores. Additionally, sex was not found to be associated with performance. This study provides initial evidence supporting the validity and reliability of use of the Multiscent-20 as a digital odour identification test. The test’s automation and portability enable the standardized delivery of olfactory stimuli and efficient automatic recording and scoring of responses.

Abstract The Ediacaran-Cambrian transition documents a critical stage in the diversification of animals. The global fossil record documents the appearance of cloudinomorphs and other shelled tubular organisms followed by non-biomineralized small carbonaceous fossils and by the highly diversified small shelly fossils between ~ 550 and 530 Ma. Here, we report diverse microfossils in thin sections and hand samples from the Ediacaran Bocaina Formation, Brazil, separated into five descriptive categories: elongate solid structures (ES); elongate filled structures (EF); two types of equidimensional structures (EQ 1 and 2) and elongate hollow structures with coiled ends (CE). These specimens, interpreted as diversified candidate metazoans, predate the latest Ediacaran biomineralized index macrofossils of the Cloudina-Corumbella-Namacalathus biozone in the overlying Tamengo Formation. Our new carbonate U–Pb ages for the Bocaina Formation, position this novel fossil record at 571 ± 9 Ma (weighted mean age). Thus, our data point to diversification of metazoans, including biomineralized specimens reminiscent of sections of cloudinids, protoconodonts, anabaritids, and hyolithids, in addition to organo-phosphatic surficial coverings of animals, demonstrably earlier than the record of the earliest known skeletonized metazoan fossils.

Abstract Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a double-blinded cluster-randomized controlled trial on 380 Cambodian schoolchildren, we characterize the impact of six months consumption of two types of rice fortified with different levels of vitamins and minerals on pre-specified outcomes. We investigate the association between the faecal microbiota (16SrRNA sequencing) and age, sex, nutritional status (underweight, stunting), micronutrient status (iron, zinc and vitamin A deficiencies, anaemia, iron deficient anaemia, hemoglobinopathy), inflammation (systemic, gut), and parasitic infection. We show that the faecal microbiota is characterised by a surprisingly high proportion of Lactobacillaceae. We discover that deficiencies in specific micronutrients, such as iron and vitamin A, correlate with particular microbiota profiles, whereas zinc deficiency shows no such association. The nutritional intervention with the two rice treatments impacts both the composition and functions predicted from compositional analysis in different ways. (ClinicalTrials.gov (Identifier: NCT01706419))

Abstract To examine the association between levels of physical fitness, parameters of body composition and phase angle (PhA) amongst adolescents. A total of 152 adolescents (84 girls) aged 11–16 years were included in this study. Weight and height were measured and the body mass index (BMI) was calculated. Bioelectrical impedance analysis (BIA) provided resistance and reactance parameters to calculate fat-free mass (FFM), PhA and fat mass (%FM). The following physical fitness variables were analysed: flexibility, abdominal muscular endurance, upper and lower limb explosive strength, agility, speed and cardiorespiratory fitness. Generalized Linear Models were applied to verify differences across sexes. Stepwise linear regression was used to establish an association between the variables studied. The study established an association between PhA and weight, FFM, BMI, FM, %FM and medicine ball throw (MBT) for girls. As for the boys, an association was verified between PhA and weight, FFM, BMI, standing long jump (SLJ), MBT and the three allometric VO2peak variables analyzed. An association was found between PhA and the boys’ 4-m shuttle run test (4SRT) and 20-m sprint test (20SRT). Boys showed a greater phase angle than girls; In girls, BMI and %FM, were determinant of 32.4% (r = 0.57). PhA variability which is influenced by physical fitness, body composition and, therefore, the tissues electrical conductivity. Furthermore, boys’ height, FFM, upper limb strength, and agility account for 58.4% (r = 0.76) PhA variability. There was a positive correlation between the physical fitness tests and the PhA.

Abstract The purpose of this study was to evaluate the fatigue survival of 5Y-PSZ zirconia infiltrated with an experimental glass and bonded onto dentin analogues. Disc-shaped specimens of a 5Y-PSZ (Katana UTML Kuraray Noritake) were cemented onto dentin analogs (NEMA G10) and divided into four groups (n = 15): Zctrl Group (control, without infiltration); Zglz Group (Glaze, compression surface); Zinf-comp Group (Experimental Glass, compression surface); Zinf-tens Group (Experimental Glass, tension surface). Surface treatments were varied. Cyclic fatigue loading, oblique transillumination, stereomicroscope examination, and scanning electron microscopy were performed. Fatigue data were analyzed (failure load and number of cycles) using survival analysis (Kaplan–Meier and Log-Rank Mantel–Cox). There was no statistically significant difference in fatigue survival between the Zglz, Zctrl, and Zinf-comp groups. The Zinf-tens group presented a significantly higher failure load when compared to the other groups and exhibited a different failure mode. The experimental glass effectively infiltrated the zirconia, enhancing structural reliability, altering the failure mode, and improving load-bearing capacity over more cycles, particularly in the group where the glass was infiltrated into the tensile surface of the zirconia. Glass infiltration into 5Y-PSZ zirconia significantly enhanced structural reliability and the ability to withstand loads over an increased number of cycles. This approach has the potential to increase the durability of zirconia restorations, reducing the need for replacements and save time and resources, promoting efficiency in clinical practice.

Abstract As age increases, a decline in lower extremity strength leads to reduced mobility and increased fall risks. This decline outpaces the age-related reduction in muscle mass, resulting in mobility limitations. Older adults with varying degrees of mobility-disability use different stepping strategies. However, the link between functional lower extremity strength and stepping strategy is unknown. Therefore, understanding how age-related reductions in functional lower extremity strength influence stepping strategy is vital to unraveling mobility limitations. Twenty participants (17F, 72 ± 6 years) were recruited and tested at a local community event. Participants were outfitted with inertial measurement units (IMU) and walked across a pressurized walkway under single and dual motor task conditions (walking with and without carrying a tray with water) at their usual and fast speeds. Participants were dichotomized into normal (11) or low functional strength groups (9) based on age-specific normative cutoffs using the instrumented 5-repetition Sit-to-Stand test duration. Our study reveals that older adults with normal strength prefer adjusting their step time during walking tasks, while those with reduced strength do not exhibit a preferred stepping strategy. This study provides valuable insights into the influence of functional lower extremity strength on stepping strategy in community-dwelling older adults during simple and complex walking tasks. These findings could aid in diagnosing gait deviations and developing appropriate treatment or management plans for mobility disability in older adults.

Abstract We use complex systems science to explore the emergent behavioral patterns that typify eusocial species, using collective ant foraging as a paradigmatic example. Our particular aim is to provide a methodology to quantify how the collective orchestration of foraging provides functional advantages to ant colonies. For this, we combine (i) a purpose-built experimental arena replicating ant foraging across realistic spatial and temporal scales, and (ii) a set of analytical tools, grounded in information theory and spin-glass approaches, to explore the resulting data. This combined approach yields computational replicas of the colonies; these are high-dimensional models that store the experimental foraging patterns through a training process, and are then able to generate statistically similar patterns, in an analogous way to machine learning tools. These in silico models are then used to explore the colony performance under different resource availability scenarios. Our findings highlight how replicas of the colonies trained under constant and predictable experimental food conditions exhibit heightened foraging efficiencies, manifested in reduced times for food discovery and gathering, and accelerated transmission of information under similar conditions. However, these same replicas demonstrate a lack of resilience when faced with new foraging conditions. Conversely, replicas of colonies trained under fluctuating and uncertain food conditions reveal lower efficiencies at specific environments but increased resilience to shifts in food location.

Abstract Changes in dietary patterns and body weight have become a focus of research in undergraduate students. This study compared breakfast consumption, intake of foods high in saturated fat, and BMI between medical and non-medical students. A comparative cross-sectional study was conducted in 4,561 Peruvian university students, of whom 1,464 (32.1%) were from the medical field and 3,097 (67.9%) from the non-medical field. We compared the frequency of breakfast consumption (categorized as regular: 6 to 7 days/week; occasional: 3 to 5 days/week; and rarely or never: 0 to 2 days/week) and the frequency of consumption of foods high in saturated fat. We created simple and multiple linear and Poisson regression models with robust variance to evaluate the association of the mentioned variables with academic fields. Non-medical students (Adjusted Prevalence Ratio [PR] = 0.92, 95% CI 0.86–0.99; p = 0.008) were less likely to eat breakfast regularly compared to medical students. Likewise, consumption of foods high in saturated fats was higher in non-medical students (B = 1.47, 95% CI 0.91–2.04; p

Microgliosis plays a critical role in diet-induced hypothalamic inflammation. A few hours after a high-fat diet (HFD), hypothalamic microglia shift to an inflammatory phenotype, and prolonged fat consumption leads to the recruitment of bone marrow-derived cells to the hypothalamus. However, the transcriptional signatures and functions of these cells remain unclear. Using dual-reporter mice, this study reveals that CX3CR1-positive microglia exhibit minimal changes in response to a HFD, while significant transcriptional differences emerge between microglia and CCR2-positive recruited myeloid cells, particularly affecting chemotaxis. These recruited cells also show sex-specific transcriptional differences impacting neurodegeneration and thermogenesis. The chemokine receptor CXCR3 is emphasized for its role in chemotaxis, displaying notable differences between recruited cells and resident microglia, requiring further investigation. Central immunoneutralization of CXCL10, a ligand for CXCR3, resulted in increased body mass and decreased energy expenditure, especially in females. Systemic chemical inhibition of CXCR3 led to significant metabolic changes, including increased body mass, reduced energy expenditure, elevated blood leptin, glucose intolerance, and decreased insulin levels. This study elucidates the transcriptional differences between hypothalamic microglia and CCR2-positive recruited myeloid cells in diet-induced inflammation and identifies CXCR3-expressing recruited immune cells as protective in metabolic outcomes linked to HFD consumption, establishing a new concept in obesity-related hypothalamic inflammation.

Summary: The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use.We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions.We found that continuous intravenous administration of rGOT within the first 8 h after ischemic onset significantly reduced the infarct size in both severe (30%) and mild lesions (48%). Cerebrospinal fluid and proteomics analysis, in combination with positron emission tomography imaging, indicated that rGOT can reach the brain and induce cytoprotective autophagy and induce local protection by alleviating neuronal apoptosis.Our results suggest that rGOT can be safely used immediately in patients suspected of having a stroke. This study requires further validation in clinical stroke populations.

Abstract High-intensity physical activity is a non-pharmacological intervention that has been tested as a treatment for Parkinson’s disease (PD). The objective of the study was to investigate the benefits of high-intensity physical exercise on the number of neurons and astrocytes in a a rat model of Parkinson’s disease submitted to training before and after the inducing injury. Seventy Wistar rats were used, distributed as follows: nine rats trained before PD induction (DP-Exa), nine trained after PD induction (DP-Exd), 10 trained before and after PD induction (DP-Exad), and nine sedentary rats (DP-Sed). There were also the same groups but with the rats exposed to the sham surgery (control). High-intensity physical exercise on a vertical ladder was performed before and/or after PD induction for 5 days/week, 30-45 min a day, for 4 weeks. PD was induced with an electrolytic lesion (AP -4.9, ML 1.7, and DV 8.1). At the end of the experiment, the brain was removed for Nissl staining and immunohistochemistry of glial fibrillary acidid protein (GFAP) in the substantia nigra and striatum. The DP-Exa, Sham-Exa, DP-Exad, and Sham-Exad groups showed a greater number of neurons and higher expression of GFAP in the substantia nigra and stiatum compared with the the DP-Exd, Sham-Exd, DP-Sed, and Sham-Sed groups. Thus, rats that performed high-intensity training before or before and after PD induction had higher densities of neurons and astrocytes.

Abstract Ganoderma lingzhi is widely reported for its medicinal properties, presenting several bioactive substances with potential pharmaceutical and industrial application. This study aimed to evaluate the production of mycelial biomass, extracellular enzymes and antioxidant compounds by G. lingzhi under submerged fermentation. G. lingzhi was cultured in Polysaccharide (POL) and Melin-Norkrans (MNM) media for 7 days. The cellulases, xylanases, pectinases, laccases, and proteases activities were quantified in the culture broth, while the antioxidant potential was evaluated for the mycelial biomass. G. lingzhi showed higher biomass production in MNM. However, it exhibited similar microstructural characteristics in both culture media. In the POL there was greater activity of CMCase (0.229 U/mL), xylanase (0.780 U/mL), pectinase (0.447 U/mL) and proteases (16.13 U/mL). FPase did not differ (0.01 U/mL), and laccase was detected only in MNM (0.122 U/mL). The biomass water extract from MNM showed high levels of phenolic compounds (951.97 mg AGE/100 g). DPPH• inhibition (90.55%) and reducing power (0.456) were higher in MNM medium, while ABTS•+ inhibition (99.95%) and chelating ability (54.86%) were higher in POL. Thus, the MNM medium was more favorable to the production of mycelial biomass and phenolic compounds, while the POL medium favored the synthesis and excretion of hydrolytic enzymes.

Dental restoration materials are susceptible to bacterial biofilm formation, which damages the restorations and causes oral health problems. Therefore, to overcome this, silver nanoparticles (AgNPs) are studied widely due to their antimicrobial, anti-inflammatory and healing properties. The purpose of this study was to develop a strategy for incorporating AgNPs onto the surface of bisacrylic resin (Bis) to evaluate its antibiofilm effects using Streptococcus sanguinis and Actinomyces naeslundii. AgNPs with an average size of 25 nm at two different concentrations were dispersed on the Bis surface (Bis-AgNPs) by mechanical deposition. Ag release was quantified until 7 days of incubation. Bacterial growth was assessed using a viability assay kit and observed using confocal microscopy. The biofilm biomass was quantified using arbitrary fluorescence units. Cell viability was evaluated using an MTT assay. The results showed that Bis-AgNPs significantly inhibited biofilm formation along with a significant difference in the viability of human gingival fibroblasts. The quantification confirmed a decrease in Ag release over time, and elemental mapping showed AgNP penetration up to 10 µm from the surface. Therefore, it was concluded that Bis-AgNPs presented enhanced antibiofilm properties, even at a concentration with no adverse effects. Therefore, this nanocomposite may be a promising alternative for biofilm control in temporary restorative materials.

This study aims to investigate the impact of national quality programs in mammography and technological advances in digital mammography units on the radiation doses delivered to women in Brazil. Radiation dose assessments in mammography units were conducted through a mail-based dosimetric system. For each unit of facilities that applied to one of the two national quality programs, a postal dosimetric system is dispatched, comprising an optically stimulated luminescent dosimeter (OSL) attached to the surface of a 4.0 cm thick polymethyl methacrylate (PMMA) phantom, simulating a compressed breast with 4.5 cm thickness. Testing instructions to expose the dosimetric phantom for assessing the mean glandular dose (MGD) are provided. Between 2012 and 2023, the programs evaluated the MGD in 1,687 mammography units of computed radiography (CR) and direct digital radiography (DR) technologies from 1,399 facilities located in all Brazilian regions. A total of 1,660 (70.5%) evaluations were carried out on CR technology mammography units and 696 (29.5%) on DR units, totaling 2,356 MGD evaluations. The overall average MGD was 1.60 ± 0.80 mGy, with 1.68 ± 0.83 mGy for CR technology and 1.42 ± 0.68 mGy for DR technology. A comparison of average MGD between the periods 2012 - 2018 and from 2019 onwards shows a dose reduction of 8.6% for CR systems and of 26.0% for DR systems (p = 0.000). As CR systems use analog mammography units, which did not undergo technological advances between the two periods, the reduction in doses observed is due to the actions of national quality certification programs and by using image plates for dual-sided reading or needle-based image plates. The reduction observed in DR systems is due to both national quality programs and technological advances in mammography units, especially the use of radiation beams generated by X-ray tubes with tungsten targets.

Abstract Cardiovascular diseases, resulting from the deposition of clots in blood vessels, are the leading cause of death worldwide. Fibrinolytic enzymatic activity can catalyze blood clot degradation. Findings show that 36 fungal isolates recovered from Caatinga soils have the potential to produce fibrinolytic protease under submerged conditions. About 58 % of the isolates displayed fibrinolytic activity above 100 U/mL, with Mucor subtilissimus UCP 1262 being the most active. The protease was biochemically and biophysically characterized, showing that the enzyme had a high affinity for SAApNA substrate and was significantly inhibited by fluoride methyl phenyl sulfonyl-C7H7FO2S, suggesting that it is a chymotrypsin-like serine protease. The highest enzyme activity was detected at pH 5.0 and 28 °C. This fibrinolytic protease’s far-UV circular dichroism (CD) showed that its secondary structure was primarily α-helical. The purified fibrinolytic enzyme may represent a novel therapeutic agent for treating thrombosis. At temperatures above 65 °C, the enzyme lost all its secondary structure. Its melting temperature was 58.1 °C, the denaturation enthalpy 85.1 kcal/mol, and the denaturation entropy 0.26 kcal/K∙mol.

Abstract According to a biopsychosocial framework, personal and environmental factors might be mediators or facilitators/barriers, respectively, to functioning. However, it is not known how these factors can impact independence in household chores in children/adolescents with Down syndrome (DS). This study explored whether and how personal/environmental factors are associated with the independence level in household chores of children/adolescents with DS in Brazil. Caregivers of twenty-eight children/adolescents with DS were interviewed using the CHORES and a standardized questionnaire about personal (child’s age and sex) and environmental (socioeconomic level and maternal schooling) factors. Multiple linear regression analysis identified if/how these factors are associated with level of independence. For CHORES self-care and CHORES total, sex was a significant variable explaining 21.8% and 15.8%, respectively, of the variation in the outcomes. For the outcome CHORES family care none of the variables was significant. Female sex was associated with a lower need for assistance. We conclude that only the personal factor assessed related to female sex in children with DS was associated with the independence level in household chores. This finding highlights the importance of health care providers and families to encourage the independence in chores regardless of sex and promote opportunities for both boys and girls.