Greenness and Hospitalization for Cardiorespiratory Diseases in Brazil.

BACKGROUND: The potential health benefits of exposure to vegetation, or greenness, are well documented, but there are few nationwide studies in Brazil, a country facing challenges related to land-use planning, deforestation, and environmental health risks. OBJECTIVES: In this study, we investigated the association between greenness and hospitalizations for cardiorespiratory diseases in Brazil. METHODS: We accessed hospital admissions data from 967,771 postal codes (a total of 26,724,624 admissions) covering Brazil for the period between 2008 and 2018. We used Normalized Difference Vegetation Index (NDVI) data from the Moderate Resolution Imaging Spectroradiometer (MODIS) to measure greenness at the postal-code level. First, we applied a quasi-Poisson regression model to estimate the association between greenness and hospitalizations for circulatory and respiratory diseases, adjusted for air pollution, weather variables, and area-level socioeconomic status. We stratified the analyzes by sex, age group, health outcome, and Brazilian regions. In the second stage, we performed a meta-analysis to estimate pooled effects across the Brazilian regions. RESULTS: The national meta-analysis for the whole population, incorporating both urban and nonurban areas, showed that higher levels of greenness were associated with a lower risk of hospitalizations for circulatory diseases. An interquartile range (IQR=0.18) increase in average NDVI was associated with a 17% (95% confidence interval: 8%, 27%) lower risk of cardiovascular admissions. In contrast, there was no association found between greenness and respiratory admissions. When specifically examining urban areas, the results remained consistent with the overall findings. However, the analyses of nonurban areas revealed divergent results, suggesting that higher levels of greenness in rural regions are associated with a lower risk of hospital admissions for both circulatory and respiratory diseases. DISCUSSION: The findings emphasize the importance of prioritizing the preservation and creation of green spaces in urban areas as a means of promoting cardiovascular health in Brazil. https://doi.org/10.1289/EHP13442.

Thermal stress and hospital admissions for cardiorespiratory disease in Brazil.

The growing body of scientific literature underscores the intricate relationship between meteorological conditions and human health, particularly in the context of extreme temperatures. However, conventional temperature-centric approaches often fall short in capturing the complexity of thermal stress experienced by individuals. Temperature alone, as a metric, fails to encompass the entirety of the thermal stress individuals face, necessitating a more nuanced understanding. In response to this limitation, climatologists have devised thermal indices-composite measures meticulously crafted to reflect the intricate interplay of meteorological factors influencing human perception of temperature. Recognizing the inadequacy of simplistic temperature-focused methodologies, our study aims to address the multifaceted nature of thermal stress. In this study, we explored the association between thermal indices and hospital admissions for circulatory and respiratory diseases in Brazil. We used an extensive dataset spanning 11 years (2008-2018) from the Brazilian Ministry of Health, encompassing a total of 23,791,093 hospitalizations for circulatory and respiratory diseases. We considered four distinct thermal indices-Discomfort Index (DI), Net Effective Temperature (NET), Humidex (H), and Heat Index (HI). We used an extension of the two-stage design with a case time series to assess this relationship. In the first stage, we applied a distributed lag non-linear modeling framework to create a cross-basis function. We next applied quasi-Poisson regression models adjusted by time-varying confounders. In the second stage, we applied meta-analysis with random effects to estimate the national relative risk (RR). Our findings suggest robust variations among the thermal indices under examination. These variations underscore the intricate nature of associations between temperature and health, with each index capturing distinct aspects of thermal conditions. Our results indicate that extreme thermal conditions, both at the low and high ends, are associated with increased risks of hospital admissions. The diverse impact observed among different indices emphasizes the complex interplay between various meteorological factors and their specific physiological consequences. This underscores the necessity for a comprehensive comprehension of temperature metrics to guide precise public health interventions, recognizing the multifaceted nature of temperature-health relationships.

Optimized Synthesis of Poly(Lactic Acid) Nanoparticles for the Encapsulation of Flutamide.

Biopolymeric nanoparticles (NPs) have gained significant attention in several areas as an alternative to synthetic polymeric NPs due to growing environmental and immunological concerns. Among the most promising biopolymers is poly(lactic acid) (PLA), with a reported high degree of biocompatibility and biodegradability. In this work, PLA NPs were synthesized according to a controlled gelation process using a combination of single-emulsion and nanoprecipitation methods. This study evaluated the influence of several experimental parameters for accurate control of the PLA NPs' size distribution and aggregation. Tip sonication (as the stirring method), a PLA concentration of 10 mg/mL, a PVA concentration of 2.5 mg/mL, and low-molecular-weight PLA (Mw = 5000) were established as the best experimental conditions to obtain monodisperse PLA NPs. After gelification process optimization, flutamide (FLU) was used as a model drug to evaluate the encapsulation capability of the PLA NPs. The results showed an encapsulation efficiency of 44% for this cytostatic compound. Furthermore, preliminary cell viability tests showed that the FLU@PLA NPs allowed cell viabilities above 90% up to a concentration of 20 mg/L. The comprehensive findings showcase that the PLA NPs fabricated using this straightforward gelification method hold promise for encapsulating cytostatic compounds, offering a novel avenue for precise drug delivery in cancer therapy.

Ecological consequences when organisms avoid a contaminated environment: A study evaluating the toxicity of fipronil.

The ability of aquatic organisms to sense the surrounding environment chemically and interpret these signals correctly is crucial to their survival and ecological niche. This study applied the Heterogenous Multi-Habitat Assay System - HeMHAS to evaluate the avoidance potential of Daphnia magna to detect fipronil-contaminated habitats in a connected landscape after a short (48 h), previous, forced exposure to an environmentally relevant concentration of the same insecticide. The swimming of daphnids was also analyzed by recording the total distance covered. D. magna preferred areas with less contamination, although the effect of fipronil on their swimming ability (a decrease) was observed for all the concentrations tested. The application of non-forced multi-compartment exposure methodologies is a recent trend and is ecologically relevant as it is based on how contamination can really produce changes in an organism's habitat selection. Finally, we consider the importance of more non-forced exposure approaches where Stress Ecology can be aggregated to improve systemic understanding of the risk that contaminants pose to aquatic ecosystems from a broader landscape perspective.

Organellar-genome analyses from the lycophyte genus Isoetes L. show one of the highest frequencies of RNA editing in land plants.

RNA editing is a post-transcriptional process that challenges the central dogma of molecular biology by modifying RNA sequences, introducing nucleotide changes at specific sites, and generating functional diversity beyond the genomic code, especially when it concerns organellar transcripts. In plants, this phenomenon is widespread, but its extent varies significantly among species and organellar genomes. Among land plants, the heterosporous lycophytes (i.e., Isoetes and Selaginella) stand out for their exceptionally high numbers of RNA-editing sites, despite their morphological stasis and ancient lineage. In this study, we explore the complete set of organellar protein-coding genes in the aquatic plant group Isoetes, providing a detailed analysis of RNA editing in both the mitochondrial and plastid genomes. Our findings reveal a remarkable abundance of RNA editing, particularly in the mitochondrial genome, with thousands of editing sites identified. Interestingly, the majority of these edits result in non-silent substitutions, suggesting a role in fine-tuning protein structure and function. Furthermore, we observe a consistent trend of increased hydrophobicity in membrane-bound proteins, supporting the notion that RNA editing may confer a selective advantage by preserving gene functionality in Isoetes. The conservation of highly edited RNA sequences over millions of years underscores the evolutionary significance of RNA editing. Additionally, the study sheds light on the dynamic nature of RNA editing, with shared editing sites reflecting common ancestry whereas exclusive edits matching more recent radiation events within the genus. This work advances our understanding of the intricate interplay between RNA editing, adaptation, and evolution in land plants and highlights the unique genomic features of Isoetes, providing a foundation for further investigations into the functional consequences of RNA editing in this enigmatic plant lineage.

Physiological responses on the reproductive, metabolism and stress endpoints of Astyanax lacustris females (Teleostei: Characiformes) after diclofenac and ibuprofen exposure.

Diclofenac (DCF) and ibuprofen (IBU) are pharmaceutical compounds frequently detected in aquatic compartments worldwide. Several hazard effects including developmental abnormalities and redox balance impairment have been elucidated in aquatic species, but multiple endocrine evaluations are scarce. Therefore, the present study aimed to assess the disruptive physiological effects and toxicity of DCF and IBU isolated and combined, using females of the native freshwater teleost Astyanax lacustris. In regards to NSAIDs bioavailability, the results showed absence of degradation of IBU and DCF after 7 days of exposure. IBU LC50 for A. lacustris was 137 mgL-1 and females exposed to IBU isolated increased thyroxine (T4) concentration at 24 h and decreased after 96 h; DCF exposure decreased triiodothyronine (T3) concentration at 96 h. Circulating levels of 17ß-estradiol (E2), cortisol (F) and testosterone (T) were not affected by any treatment. HPG and HPI axis genes fshß, pomc and vtg were upregulated after 24 h of IBU exposure, and dio2 was downregulated in DCF fish exposed group after 96 h compared to the mixture. Protein concentration was reduced in muscle and increased in the liver by DCF and mixtures exposures at 24 h; while liver lipids were increased in the mixture groups after 96 h. The study point out the capacity of NSAIDs to affect endocrine endpoints in A. lacustris females and induce changes in energetic substrate content after acute exposure to isolated and mixed NSAIDs treatments. Lastly, the present investigation brings new insights into the toxicity and endocrine disruptive activity of NSAIDs in Latin America teleost species and the aquatic environment.

Ecological Implications on Aquatic Food Webs Due to Effects of Pesticides on Invertebrate Predators in a Neotropical Region.

Predation presents specific behavioral characteristics for each species, and the interaction between prey and predator influences the structuring of the food web. Concerning insects, predation can be affected in different ways, such as exposure to chemical stressors, e.g., pesticides. Therefore, analyses were carried out of the effects of exposure to insecticide fipronil and the herbicide 2,4-D on predation, parameters of food selectivity, and the swimming behavior of two neotropical predatory aquatic insects of the families Belostomatidae (giant water bugs) and larvae of Libellulidae (dragonfly). These predatory insects were exposed for 24 h to a commercial formulation of the chlorophenoxy herbicide, 2,4-D at nominal concentrations of 200, 300, 700, and 1400 µg L-1, and to a commercial formulation of the phenylpyrazole insecticide, fipronil at nominal concentrations of 10, 70, 140, and 250 µg L-1. In a control treatment, the insects were placed in clean, unspiked water. At the end of the exposure, the maximum swimming speed of the predators was evaluated. Afterward, the predators were placed in clean water in a shared environment for 24 h with several prey species, including the cladoceran Ceriodaphnia silvestrii, larvae of the insect Chironomus sancticaroli, the amphipod Hyalella meinerti, the ostracod Strandesia trispinosa, and the oligochaete Allonais inaequalis for 24 h. After this period, the consumed prey was counted. The results reveal that predators from both families changed prey consumption compared with organisms from the control treatment, marked by a decrease after exposure to fipronil and an increase in consumption caused by 2,4-D. In addition, there were changes in the food preferences of both predators, especially when exposed to the insecticide. Exposure to fipronil decreased the swimming speed of Belostomatidae individuals, possibly due to its neurotoxic effect. Exposure to the insecticide and the herbicide altered prey intake by predators, which could negatively influence the complex prey-predator relationship and the functioning of aquatic ecosystems in contaminated areas.

The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.

The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.

Congenital syphilis: the re-emergence of a forgotten disease.

A preterm newborn presented at birth with generalised oedema, disseminated bullous and desquamative exanthema with palmoplantar involvement and hepatomegaly, admitted to the neonatal intensive care unit with severe multisystemic disease, haemodynamic instability and respiratory distress. The mother had a history of treated latent syphilis before pregnancy. Venereal Disease Research Laboratory screening was negative in the first trimester, titre 1:2 in second trimester and 1:32 in the third trimester, a result only available to the medical team at birth. The mother's rapid plasma reagin (RPR) titre was 1:64 at birth. The newbon's RPR titre was 1:256, confirming the diagnosis of early congenital syphilis. The newborn was treated with aqueous penicillin G, with clinical and laboratorial progressive recovery. Congenital syphilis is a preventable disease, but despite prenatal screening programmes, it remains a significant public health issue worldwide with high morbidity and mortality.

Environmentally Relevant Concentrations of the Insecticide Fipronil Modulated Molecular Response in Chironomus riparius.

Pesticides employed worldwide for crop protection easily reach aquatic systems, which act as the main reservoirs, and become a risk factor for aquatic fauna. Fipronil is a broad-spectrum insecticide acting on the insect nervous system; however, other effects and systems unrelated to this mechanism could be affected in non-target organisms. Thus, the present study aimed to assess the impact of fipronil on the suborganismal response (gene expression and enzymatic activity) of Chironomus riparius larvae as a model organism in ecotoxicology. To this end, short-term toxicity tests were carried out with fourth-instar larvae exposed to 0.001, 0.01, and 0.1 µg L-1 of fipronil for 24 and 96 h. Messenger RNA levels of 42 genes related to diverse metabolic pathways were analyzed by real-time polymerase chain reaction, complemented with catalase (CAT), glutathione S-transferase (GST), and acetylcholinesterase (AChE) activities. Few effects were observed at 24 h; however, after longer exposure (96 h), genes involved in the endocrine, detoxification, stress, and immune response pathways were altered. Moreover, fipronil at 96 h increased CAT and GST activity at 0.01 µg L-1 and AChE at the highest concentrations. The results demonstrate that even low environmentally relevant fipronil concentrations can modulate the molecular response of several cellular pathways in C. riparius after short-term exposure. These results bring new information about the underlying response of fipronil and its mode of action on a key aquatic invertebrate. Despite no effects on mortality, strong modulation at the suborganismal level emphasizes the advantage of biomarkers as early damage responses and the harmful impact of this pesticide on freshwater organisms. Environ Toxicol Chem 2024;43:405-417. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

rAAV-compatible human mini promoters enhance transgene expression in rat retinal ganglion cells.

Recombinant adeno-associated viral vectors (rAAV) are the safest and most effective gene delivery platform to drive the treatment of many inherited eye disorders in well-characterized animal models. The use in rAAV of ubiquitous promoters derived from viral sequences such as CMV/CBA (chicken ß-actin promoter with cytomegalovirus enhancer) can lead to unwanted side effects such as pro-inflammatory immune responses and retinal cytotoxicity, thus reducing therapy efficacy. Thus, an advance in gene therapy is the availability of small promoters, that potentiate and direct gene expression to the cell type of interest, with higher safety and efficacy. In this study, we used six human mini-promoters packaged in rAAV2 quadruple mutant (Y-F) to test for transduction of the rat retina after intravitreal injection. After four weeks, immunohistochemical analysis detected GFP-labeled cells in the ganglion cell layer (GCL) for all constructs tested. Among them, Ple25sh1, Ple25sh2 and Ple53 promoted a widespread reporter-transgene expression in the GCL, with an increased number of GFP-expressing retinal ganglion cells when compared with the CMV/CBA vector. Moreover, Ple53 provided the strongest levels of GFP fluorescence in both cell soma and axons of retinal ganglion cells (RGCs) without any detectable adverse effects in retina function. Remarkably, a nearly 50-fold reduction in the number of intravitreally injected vector particles containing Ple53 promoter, still attained levels of transgene expression similar to CMV/CBA. Thus, the tested MiniPs show great potential for protocols of retinal gene therapy in therapeutic applications for retinal degenerations, especially those involving RGC-related disorders such as glaucoma.

Systematic review of reverse vaccinology and immunoinformatics data for non-viral sexually transmitted infections.

Sexually Transmitted Infections (STIs) are a public health burden rising in developed and developing nations. The World Health Organization estimates nearly 374 million new cases of curable STIs yearly. Global efforts to control their spread have been insufficient in fulfilling their objective. As there is no vaccine for many of these infections, these efforts are focused on education and condom distribution. The development of vaccines for STIs is vital for successfully halting their spread. The field of immunoinformatics is a powerful new tool for vaccine development, allowing for the identification of vaccine candidates within a bacterium's genome and allowing for the design of new genome-based vaccine peptides. The goal of this review was to evaluate the usage of immunoinformatics in research focused on non-viral STIs, identifying fields where research efforts are concentrated. Here we describe gaps in applying these techniques, as in the case of Treponema pallidum and Trichomonas vaginalis.

Milk and Fresh Cheese Quality of Crossbred Cows Supplemented with Phytogenic Additives and Managed under Thermal Stress.

This investigation aimed to assess the physiological parameters and quality of milk and fresh cheeses produced by cows that were housed in paddocks, either with or without shade, and supplemented with a phytogenic additive. Sixteen crossbred cows were allocated in a 4 × 4 Latin square design, dividing them into paddocks with or without shade, and providing or not providing a phytogenic additive in their feed. This resulted in a total of four treatment groups and sixteen experimental plots, each containing four animals, over four periods of 21 days. Various parameters were examined, including haematology, rectal and skin temperature, respiratory rate, milk yield and composition, serum parameters, and cheese yield and quality. It is worth noting that the temperature and humidity, as measured by a black globe thermometer, did not display significant variations between the different environments and exhibited minimal fluctuations throughout the day. Additionally, the supplementation of the phytogenic additive led to a reduction in haematocrit levels (p = 0.011). Furthermore, the analysis showed that whey obtained from cheese production had a higher fat content when cows were without access to shade (p = 0.005). Notably, there was an interaction between factors in relation to the total dry extract content, which was lower when cows had access to shade and received the additive (p = 0.010). In summary, the provision of a phytogenic additive and the presence or absence of shade did not bring about significant changes in milk production and quality or in the yield and quality of fresh cheese.

Probiogenomics of Leuconostoc Mesenteroides Strains F-21 and F-22 Isolated from Human Breast Milk Reveal Beneficial Properties.

Bacteria of the Leuconostoc genus are Gram-positive bacteria that are commonly found in raw milk and persist in fermented dairy products and plant food. Studies have already explored the probiotic potential of L. mesenteroides, but not from a probiogenomic perspective, which aims to explore the molecular features responsible for their phenotypes. In the present work, probiogenomic approaches were applied in strains F-21 and F-22 of L. mesenteroides isolated from human milk to assess their biosafety at the molecular level and to correlate molecular features with their potential probiotic characteristics. The complete genome of strain F-22 is 1.99 Mb and presents one plasmid, while the draft genome of strain F-21 is 1.89 Mb and presents four plasmids. A high percentage of average nucleotide identity among other genomes of L. mesenteroides (≥ 96%) corroborated the previous taxonomic classification of these isolates. Genomic regions that influence the probiotic properties were identified and annotated. Both strains exhibited wide genome plasticity, cell adhesion ability, proteolytic activity, proinflammatory and immunomodulation capacity through interaction with TLR-NF-κB and TLR-MAPK pathway components, and no antimicrobial resistance, denoting their potential to be candidate probiotics. Further, the strains showed bacteriocin production potential and the presence of acid, thermal, osmotic, and bile salt resistance genes, indicating their ability to survive under gastrointestinal stress. Taken together, our results suggest that L. mesenteroides F-21 and F-22 are promising candidates for probiotics in the food and pharmaceutical industries.

How natural and anthropogenic factors should drive microplastic behavior and fate: The scenario of Brazilian urban freshwater.

Brazil maintains its position at the top of the global ranking of plastic producers, yet recycling efforts have been incipient. Recent data reveals an annual production of approximately 14 million tons of plastic waste, not accounting for the surge in the usage of plastic masks and related materials due to the COVID-19 pandemic. However, what remains largely unreported is that over half of post-consumer plastic packaging in Brazil is managed without any monitoring, and it remains unclear how this will contribute to the occurrence of plastic waste and microplastics in Brazilian freshwaters. This scenario requires the consideration of several other crucial factors. Studies have been carried out mainly in marine and estuarine waters, while data on freshwaters are lacking. Brazil has continental dimensions and the highest water availability on the planet, yet the demand for water is greatest in regions with medium to low supply. Many densely populated Brazilian urban areas face chronic flood problems, possess inadequate levels of wastewater treatment, and display inadequate solid waste management practices. Consequently, urban freshwater with tropical characteristics in Brazil presents an intriguing scenario and is complementary to the most commonly studied marine environments. In this study, we explore the nuances of pollution in Brazilian urban freshwater and discuss how various parameters, such as organic matter, suspended solids, temperature, and pH, among others, influence the behavior of microplastics and their interactions with organic and inorganic contaminants. Furthermore, we address how microplastic conditions, such as biofouling, the type of plastic, or degradation level, may impact their behavior. By analyzing how these conditions change, we propose priority themes for investigating the occurrence of microplastics in Brazilian urban freshwater systems under different degrees of human impact. Ultimately, this study aims to establish a network dedicated to standardized monitoring of microplastic pollution in Brazilian urban freshwaters.

Impact of yarn compositions, loop length, and float stitches on the mechanical behavior of knitted fabrics via full factorial design and RSM.

This article presents a study on the tensile properties of knitted fabrics commonly employed in polymeric matrix textile composites. The key mechanical parameters investigated include stress (Pa), strain, Young's modulus (Pa), and work of rupture (J). The knitted fabrics were developed using the Cixing Knitting System software and subsequently manufactured using a double jersey (electronic) flat knitting machine. The primary objective of this research was to explore the impact of various factors on the mechanical behavior of these knitted fabrics. The factors studied were wale and course directions, float stitch density, loop length (cm), and the type of synthetic knitting yarns used (100% polyester and 100% polyamide) along with different combinations of knitting yarns (100% cotton and 67% polyester/33% cotton hybrid). The adopted ASTM D 5034 standard, Response Surface Methodology (RSM), and Analysis of Variance (ANOVA) were employed to evaluate the mechanical performance of these fabric structures. The findings of the study revealed that the statistical adjustment of the data set for stress, strain, Young's modulus, and work of rupture in knitted fabric structures significantly reduced the standard deviations for mechanical responses. This information holds particular significance as it pertains to the frequent use of these knitted fabric structures as reinforcement in textile-reinforced composite materials. Overall, this study sheds light on the mechanical behavior in structures of knitted fabrics used in polymeric matrix composites, providing valuable insights for the design and optimization of advanced textile-based materials.

Occurrence of contaminants of emerging concern and their risks to the Pantanal Sul-Mato-Grossense aquatic biota, Brazil.

The Aquidauana River is an important ecological corridor in the Pantanal biome. However, the growth of agricultural and urban areas along its banks has contributed to the deterioration of its water quality, consequently putting the aquatic biota at risk. Our objectives were to evaluate: 1) the composition of the landscape around six sampling sites located in the Aquidauana River middle section; and 2) the quality of its water by determining limnological parameters, concentrations of contaminants of emerging concern (CECs), and the risks to native aquatic biota. Water samples were collected in November 2020. We observed the conversion of native riparian vegetation to extensive pasture areas and anthropic occupation around the sampling sites. We observed that the chlorophyll and total ammoniacal nitrogen values were above the standards established by Brazilian legislation in all samples. Studies focused on the quantification of CECs in the Pantanal waters are scarce, and to the best of our knowledge, this is the first study that investigated the presence of pharmaceuticals in the Aquidauana River. All 30 CECs analyzed were detected in at least one water sample. Eleven CECs were quantified with eight pesticides (atrazine, diuron, hexazinone, tebuthiuron, azoxystrobin, carbendazim, tebuconazole, and fipronil) and one atrazine degradation product (atrazine-2-hydroxy), caffeine, and bisphenol A. The concentrations of atrazine herbicide observed in the water samples pose risks for protecting aquatic biota (RQs >1). Therefore, the native biota of the Pantanal biome is vulnerable to several types of toxic contaminants observed in the water, which can cause the disappearance of native and endemic species in this region. Establishing a monitoring program, improving sanitation infrastructure, and intensifying good agricultural practices are essential for reducing and controlling the entry of CECs into the Aquidauana River and the Pantanal water system.

Telemedicine Support for Primary Care Providers versus Usual Care in Patients with Heart Failure: Protocol of a Pragmatic Cluster Randomised Trial within the Brazilian Heart Insufficiency with Telemedicine (BRAHIT) Study.

Heart failure is a prevalent condition and a frequent cause of hospital readmissions and poor quality of life. Teleconsultation support from cardiologists to primary care physicians managing patients with heart failure may improve care, but the effect on patient-relevant outcomes is unclear. We aim to evaluate whether collaboration through a novel teleconsultation platform in the Brazilian Heart Insufficiency with Telemedicine (BRAHIT) project, tested on a previous feasibility study, can improve patient-relevant outcomes. We will conduct a parallel-group, two-arm, cluster-randomised superiority trial with a 1:1 allocation ratio, with primary care practices from Rio de Janeiro as clusters. Physicians from the intervention group practices will receive teleconsultation support from a cardiologist to assist patients discharged from hospitals after admission for heart failure. In contrast, physicians from the control group practices will perform usual care. We will include 10 patients per each of the 80 enrolled practices (n = 800). The primary outcome will be a composite of mortality and hospital admissions after six months. Secondary outcomes will be adverse events, symptoms frequency, quality of life, and primary care physicians' compliance with treatment guidelines. We hypothesise that teleconsulting support will improve patient outcomes.