Estimated quantification of residual volume in vaccines supplies and its impact on the Brazilian health system.

Between 2017 and 2021, the Brazilian Unified Health System (BUHS) administered a total of 527,903,302 doses of immunizations. Each immunization results in the presence of a residual volume (RV) due to syringe dead space (DS). The International Organization for Standardization 7886-1 allows a DS of up to 0.07mL in sterile single-use hypodermic syringes with volumes less than 5mL. This study aims to quantify the DS of immunization devices used in Brazil, study the best combinations of needles and syringes to minimize RV, estimate the number of wasted doses from 2017 to 2021, and evaluate the impact on the BUHS. Pneumococcal 10 vaccine with a 25x6mm needle and a regular 1mL syringe exhibited a significantly higher average RV (0.0826mL) and waste rate (14.42%). It was observed that for some intramuscular vaccines, there is less waste when using a 20x5.5mm needle compared to a 25x6mm needle. The use of syringes with plunger stoppers that penetrate the syringe barrel, denoted as low dead space syringes, results in less RV and an estimated difference in the waste rate of approximately 10% compared to the regular syringe. The estimated number of wasted doses from 2017 to 2021 by BUHS is approximately 32 million doses.

Reference values and drivers of diversity for South Brazilian grassland plant communities.

The South Brazilian grasslands (Campos Sulinos) form the dominant vegetation in southern Brazil. They are species-rich ecosystems that occur under distinct geomorphological and climatic conditions but spatial variation of plant species diversity remains understudied. Here, we present a detailed description of plant communities across the region. Our data were obtained in 1080 plots, representing well-preserved grasslands in different ecological systems. Apart from describing alpha and beta diversity, we investigated the relations of plant communities with environmental features. We identified 759 plant species and found clear differences in community composition across the region. Northern and Southern highland grasslands, humid and dry coastal grasslands and the mesic Pampa grassland were clearly distinct, related to climatic and edaphic features. While species abundance distribution was markedly uneven, local species richness was high, above 20 species/m2, especially in the highlands and in mesic Pampa sites, on shallow soils. The predominant component of beta diversity was species turnover, which suggests that a network of well-conserved grasslands distributed across the region would be the best strategy to protect plant diversity. Our results establish regionalized reference values for richness and diversity that can be useful for initiatives of restoration and conservation of these grasslands.

Nanoplastics Decrease the Toxicity of a Complex PAH Mixture but Impair Mitochondrial Energy Production in Developing Zebrafish.

Plastics are recognized as a worldwide threat to the environment, possibly affecting human health and wildlife. Small forms of plastics such as micro- and nanoplastics can interact with other organic contaminants, potentially acting as chemical carriers and modulating their toxicity. In this study, we investigated the toxicity of polystyrene nanoparticles (Nano-PS) and a real-world environmental PAH mixture (Elizabeth River Sediment Extract, ERSE, comprised of 36 detected PAHs) to zebrafish embryos and larvae. Embryos were exposed to Nano-PS (0.1-10 ppm) or ERSE (0.1-5% v/v, equivalent to ΣPAH 5.07-25.36 ppb) or coexposed to a combination of both. Larvae exposed to Nano-PS did not exhibit developmental defects, while larvae exposed to ERSE (2-5%) showed classic signs of PAH toxicity such as heart malformation and deformities in the jaw, fin, and tail. ERSE (5%) also impaired vascular development in the brain. When coexposed, Nano-PS decreased the developmental deformities and impaired vascular development caused by ERSE. This was strongly correlated to the lower PAH bioaccumulation detected in the coexposed animals (whole larvae, as well as the yolk sac, brain, and heart). Our data suggest that PAHs are sorbing to the surface of the Nano-PS, decreasing the concentration, uptake, and toxicity of free PAHs during the exposure. Such sorption of PAHs increases the agglomeration rate of Nano-PS during the exposure time, potentially decreasing the uptake of Nano-PS and associated PAHs. Despite that, similar induction of EROD activity was detected in animals exposed to ERSE in the presence or not of Nano-PS, suggesting that enough PAHs were accumulated in the organisms to induce cellular defense mechanisms. Nano-PS exposure (single or combined with ERSE) decreased the mitochondrial coupling efficiency and increased NADH production, suggesting an impairment on ATP production accompanied by a compensatory mechanism. Our data indicate that nanoplastics can sorb contaminants and potentially decrease their uptake due to particle agglomeration. Nanoplastics also target and disrupt mitochondrial energy production and act as vectors for the mitochondrial uptake of sorbed contaminants during embryonic and larval stages. Such negative effects of nanoplastics on energy metabolism and efficiency could be detrimental under multiple-stressors exposures and energy-demanding scenarios, which remains to be validated.

Trypanosoma cruzi Mexican Strains Differentially Modulate Surface Markers and Cytokine Production in Bone Marrow-Derived Dendritic Cells from C57BL/6 and BALB/c Mice.

Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in the immune response against Trypanosoma cruzi, the causative agent of Chagas disease. In vitro and in vivo studies have shown that the modulation of these cells by this parasite can directly affect the innate and acquired immune response of the host in order to facilitate its biological cycle and the spreading of the species. Many studies show the mechanisms by which T. cruzi modulates DCs, but the interaction of these cells with the Mexican strains of T. cruzi such as Ninoa and INC5 has not yet been properly investigated. Here, we evaluated whether Ninoa and INC5 strains evaded the immunity of their hosts by modulating the biology and function of murine DCs. The CL-Brener strain was used as the reference strain. Herein, it was demonstrated that Ninoa was more infective toward bone marrow-derived dendritic cells (BMDCs) than INC5 and CL-Brener strains in both BMDCs of BALB/c and C57BL/6 mice. Mexican strains of T. cruzi induced different cytokine patterns. In BMDCs obtained from BALB/c mice, Ninoa strain led to the reduction in IL-6 and increased IL-10 production, while in C57BL/6 mice Ninoa strain considerably increased the productions of TNF-α and IL-10. Also, Ninoa and INC5 differentially modulated BMDC expressions of MHC-II, TLR2, and TLR4 in both BALB/c and C57BL/6 mice compared to Brazilian strain CL-Brener. These results indicate that T. cruzi Mexican strains differentially infect and modulate MHC-II, toll-like receptors, and cytokine production in DCs obtained from C57BL/6 and BALB/c mice, suggesting that these strains have developed particular modulatory strategies to disrupt DCs and, consequently, the host immune responses.

Transcriptional effects in the estuarine guppy Poecilia vivipara exposed to sanitary sewage in laboratory and in situ.

The urban growth has increased sanitary sewage discharges in coastal ecosystems, negatively affecting the aquatic biota. Mangroves, one of the most human-affected coastal biomes, are areas for reproduction and nursing of several species. In order to evaluate the effects of sanitary sewage effluents in mangrove species, this study assessed the hepatic transcriptional responses of guppy fish Poecilia vivipara exposed to sanitary sewage 33% (v:v), using suppressive subtraction hybridization (SSH), high throughput sequencing of RNA (Ion-proton) and quantification of transcript levels by qPCR of some identified genes in fish kept in a sewage-contaminated environment. Genes identified are related predominantly to xenobiotic biotransformation, immune system and sexual differentiation. The qPCR results confirmed the induction of cytochrome P450 1A (CYP1A), glutathione S transferase A-like (GST A-like) methyltransferase (MET) and UDP glycosyltransferase 1A (UDPGT1A), and repression of complement component C3 (C3), doublesex and mab-3 related transcription factor 1 (DMRT1), and transferrin (TF) in the laboratory experiment. In the field exposure, the transcript levels of CYP1A, DMRT1, MET, GST A-like and UDPGT1A were higher in fishes exposed at the contaminated sites compared to the reference site. Chemical analysis in fish from the laboratory and in situ experiments, and surface sediment from the sewage-contaminated sites revealed relevant levels of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyl (PCBs) and linear alkylbenzenes (LABs). These data reinforce the use of P. vivipara as a sentinel for monitoring environmental contamination in coastal regions.

Salivary Gland Extract of Kissing Bug, Triatoma lecticularia, Reduces the Severity of Intestinal Inflammation through the Modulation of the Local IL-6/IL-10 Axis.

Triatomines are known for their role as vectors of the causative agent of Chagas disease. The occurrence of an arsenal of molecules in their saliva is able to suppress vertebrate immune responses. Thus, it is reasonable to assume that the presence of molecules with therapeutic potential in their saliva is able to constrain inflammation in immune-mediated diseases. Thus, mice were exposed to dextran sulfate sodium (DSS) in drinking water uninterruptedly during 6 consecutive days and treated with T. lecticularia salivary gland extract (SGE) (3, 10, or 30 µg) or vehicle (saline) (n = 6/group). At the highest dose (30 µg), an improvement in clinical outcome and macroscopic aspects of the intestine were observed. This observation was followed by amelioration in histopathological aspects in the colon especially when the doses of 10 and 30 µg were used. Regardless of the concentration used, treatment with T. lecticularia SGE significantly reduced the levels of the inflammatory cytokine IL-6 in the intestine. The production of the anti-inflammatory cytokine IL-10 was positively impacted by the concentrations of 3 and 30 µg. Our results suggest that the presence of molecules in the T. lecticularia SGE is able to attenuate clinical outcome and colon shortening and improve intestinal architecture besides reducing the production of IL-6 and inducing a local production of IL-10 in the intestine.

How important are glutathione and thiol reductases to oyster hemocyte function?

Bivalves are animals with worldwide distribution. Although they play key roles in economic activities, human feeding and environmental studies, there is a considerable lack of knowledge about the relationship between their immune system and antioxidant defenses. Here, we performed an in vitro experiment where Crassostrea gigas hemocytes were exposed to the electrophilic compound 1-chloro-2,4-dinitrobenzene (CDNB, 0.1-50 µM) for one hour. CDNB treatment clearly disturbed thiol homeostasis, causing a concentration-dependent decrease in the glutathione (GSH) content and a decrease in the activity of two thiol reductases, glutathione reductase (GR - 2.5 and 50 µM CDNB) and thioredoxin reductase (TrxR - only 50 µM CDNB). The MTT reduction assay showed that none of the CDNB concentrations tested significantly altered cell viability. However, there was a decrease in the hemocyte's ability to uptake the neutral red dye, which indicates lysosomal impairment (≥12.5 µM CDNB). Cellular immunocompetence was further investigated and, despite the lower GSH content, GR activity and impairment in lysosome integrity, hemocyte functions (adhesion capacity, phagocytosis of latex beads and laminarin-induced ROS production) were preserved in the 2.5 and 12.5 µM CDNB treatments. These results suggest a minor importance of thiol pools and GR activity in C. gigas hemocyte's immunocompetence, in an in vitro acute exposure model. The 50 µM CDNB treatment, however, significantly compromised all the measured hemocyte functions. This response was associated with TrxR inhibition, increased lysosome impairment, decreased GSH content, and lower GR activity. Therefore, it seems that TrxR may be particularly important for the hemocyte function, or, alternatively, it is only affected when a deeply aggravated scenario in thiol homeostasis is set up. Such findings point out the need for further studies towards a better understanding of antioxidant and immune defenses interactions in bivalve cellular systems.

Phenolic content and ferric reducing-antioxidant power of cow's milk produced in different pasture-based production systems in southern Brazil.

BACKGROUND: Phenolic compounds are widely present in forage. However, few studies have been carried out to investigate the presence of these compounds in animal products such as milk. In this study, the total phenolic content (TPC) and ferric reducing-antioxidant power (FRAP) of milk produced under agroecological and conventional management systems in southern Brazil were determined. Three systems were compared: (a) agroecological, with intensive rotational grazing, also known as Voisin grazing (ECO); (b) semi-intensive conventional (SIC); and (c) conventional grazing (CGR) (n = 8 per group). Pastures with distinct and more diverse botanical composition were observed on the ECO farms. RESULTS: Significantly (P < 0.05) lower amounts of TPC were found in agroecologically produced milk in autumn and summer and the CGR system showed the highest FRAP value (P < 0.05) for the samples collected in autumn. Positive correlations where found between the TPC and FRAP values obtained for the milk samples (0.198, P < 0.05), milk FRAP and forage TPC values (0.344, P < 0.05), and the TPC and FRAP values obtained for the forage (0.70, p < 0.01). PCA applied to the UV spectra dataset (200-350 nm) clearly distinguished the samples collected from the ECO system in the winter. CONCLUSION: Our results revealed that, under the conditions prevalent in southern Brazil, since the cows were allowed to graze in all of the systems, the TPC and antioxidant capacity of the milk samples showed minimal variation. However, since the forage TPC and FRAP values for the milk were correlated, TPC appears to be a promising variable for the purpose of monitoring forage prior to its selection aimed at enhancing the antioxidant activity of milk.

Redox control of antioxidants, metabolism, immunity, and development at the core of stress adaptation of the oyster Crassostrea gigas to the dynamic intertidal environment.

This review uses the marine bivalve Crassostrea gigas to highlight redox reactions and control systems in species living in dynamic intertidal environments. Intertidal species face daily and seasonal environmental variability, including temperature, oxygen, salinity, and nutritional changes. Increasing anthropogenic pressure can bring pollutants and pathogens as additional stressors. Surprisingly, C. gigas demonstrates impressive adaptability to most of these challenges. We explore how ROS production, antioxidant protection, redox signaling, and metabolic adjustments can shed light on how redox biology supports oyster survival in harsh conditions. The review provides (i) a brief summary of shared redox sensing processes in metazoan; (ii) an overview of unique characteristics of the C. gigas intertidal habitat and the suitability of this species as a model organism; (iii) insights into the redox biology of C. gigas, including ROS sources, signaling pathways, ROS-scavenging systems, and thiol-containing proteins; and examples of (iv) hot topics that are underdeveloped in bivalve research linking redox biology with immunometabolism, physioxia, and development. Given its plasticity to environmental changes, C. gigas is a valuable model for studying the role of redox biology in the adaptation to harsh habitats, potentially providing novel insights for basic and applied studies in marine and comparative biochemistry and physiology.

An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish.

Human exposure to polycyclic aromatic hydrocarbons (PAH) is a significant and growing public health problem. Frequent, high dose exposures are likely to increase due to a warming climate and increased frequency of large-scale wildfires. Here, we characterize an epigenetic memory at the cytochrome P450 1A (CYP1A) gene in a population of wild Fundulus heteroclitus that has adapted to chronic, extreme PAH pollution. In wild-type fish, CYP1A is highly induced by PAH. In PAH-tolerant fish, CYP1A induction is blunted. Since CYP1A metabolically activates PAH, this memory protects these fish from PAH-mediated cancer. However, PAH-tolerant fish reared in clean water recover CYP1A inducibility, indicating that blunted induction is a non-genetic memory of prior exposure. To explore this possibility, we bred depurated wild fish from PAH-sensitive and - tolerant populations, manually fertilized exposure-naïve embryos, and challenged them with PAH. We observed epigenetic control of the reversible memory of generational PAH stress in F1 PAH-tolerant embryos. Specifically, we observed a bivalent domain in the CYP1A promoter enhancer comprising both activating and repressive histone post-translational modifications. Activating modifications, relative to repressive ones, showed greater increases in response to PAH in sensitive embryos, relative to tolerant, consistent with greater gene activation. Also, PAH-tolerant adult fish showed persistent induction of CYP1A long after exposure cessation, which is consistent with defective CYP1A shutoff and recovery to baseline. Since CYP1A expression is inversely correlated with cancer risk, these results indicate that PAH-tolerant fish have epigenetic protection against PAH-induced cancer in early life that degrades in response to continuous gene activation.

Effects of tire particles and associated-chemicals on the Pacific oyster (Magallana gigas) physiology, reproduction and next-generation.

By 2040, tire particles (TP) are expected to dominate marine plastic contamination, raising concerns about their effects on marine animals. This study employed a multidisciplinary and multigenerational approach on the Pacific oyster Magallana gigas to investigate the effects of TP and their leachates (LEA). Effects were analyzed at the individual scale, from cellular, molecular, and microbiota changes to reproductive outputs and offspring performance. Microbiota characterization revealed potential dysbiosis in oysters treated with high concentration of both TP and LEA. RNA-seq analyses highlighted the activation of energy metabolism and stress responses in the LEA treatment. Additionally, transcriptional changes in oocytes and the reduction of motile spermatozoa suggested potential effects on gamete quality. Notably, possible oyster resilience was pointed out by the lack of significant ecophysiological modifications in adults and impacts on the growth and reproductive outputs of the offspring. Overall, the implications of the observed oyster resilience under our experimental setting are discussed in relation to available toxicity data and within a comprehensive view of coastal ecosystems, where a higher diversity of plastic/rubber materials and harsher environmental conditions occur.

Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents.

Leishmaniasis is a group of parasitic diseases with the potential to infect more than 1 billion people; however, its treatment is still old and inadequate. In order to contribute to changing this view, this work consisted of the development of complexes derived from MI metal ions with thioureas, aiming to obtain potential leishmanicidal agents. The thiourea ligands (HLR) were obtained by reactions of p-toluenesulfohydrazide with R-isothiocyanates and were used in complexation reactions with AgI and AuI, leading to the formation of complexes of composition [M(HLR)2]X (M = Ag or Au; X = NO3- or Cl-). All compounds were characterized by FTIR, 1H NMR, UV-vis, emission spectroscopy and elemental analysis. Some representatives were additionally studied by ESI-MS and single-crystal XRD. Their properties were further analyzed by DFT calculations. Their cytotoxicity on Vero cells and the extracellular leishmanicidal activity on Leishmania infantum and Leishmania braziliensis cells were evaluated. Additionally, the interaction of the complexes with the Old Yellow enzyme of the L. braziliensis (LbOYE) was examined. The biological tests showed that some compounds present remarkable leishmanicidal activity, even higher than that of the standard drug Glucantime, with different selectivity for the two species of Leishmania. Finally, the interaction studies with LbOYE revealed that this enzyme could be one of their biological targets.

Intertidal limits shape covariation between metabolic plasticity, oxidative stress and telomere dynamics in Pacific oyster (Crassostrea gigas).

In intertidal zones, species such as sessile shellfish exhibit extended phenotypic plasticity to face rapid environmental changes, but whether frequent exposure to intertidal limits of the distribution range impose physiological costs for the animal remains elusive. Here, we explored how phenotypic plasticity varied along foreshore range at multiple organization levels, from molecular to cellular and whole organism acclimatization, in the Pacific oyster (Crassostrea gigas). We exposed 7-month-old individuals for up to 16 months to three foreshore levels covering the vertical range for this species, representing 20, 50 and 80% of the time spent submerged monthly. Individuals at the upper range limit produced energy more efficiently, as seen by steeper metabolic reactive norms and unaltered ATP levels despite reduced mitochondrial density. By spending most of their time emerged, oysters mounted an antioxidant shielding concomitant with lower levels of pro-oxidant proteins and postponed age-related telomere attrition. Instead, individuals exposed at the lower limit range near subtidal conditions showed lower energy efficiencies, greater oxidative stress and shorter telomere length. These results unraveled the extended acclimatization strategies and the physiological costs of living too fast in subtidal conditions for an intertidal species.

Inflammatory Response and Activation of Coagulation after COVID-19 Infection.

SARS-CoV-2 (COVID-19) infection is responsible for causing a disease with a wide spectrum of clinical presentations. Predisposition to thromboembolic disease due to excessive inflammation is also attributed to the disease. The objective of this study was to characterize the clinical and laboratory aspects of hospitalized patients, in addition to studying the pattern of serum cytokines, and associate them with the occurrence of thromboembolic events. METHODOLOGY: A retrospective cohort study with 97 COVID-19 patients hospitalized from April to August 2020 in the Triângulo Mineiro macro-region was carried out. A review of medical records was conducted to evaluate the clinical and laboratory aspects and the frequency of thrombosis, as well as the measurement of cytokines, in the groups that presented or did not present a thrombotic event. RESULTS: There were seven confirmed cases of thrombotic occurrence in the cohort. A reduction in the time of prothrombin activity was observed in the group with thrombosis. Further, 27.8% of all patients had thrombocytopenia. In the group that had thrombotic events, the levels of IL1b, IL-10, and IL2 were higher (p < 0.05). CONCLUSIONS: In the studied sample, there was an increase in the inflammatory response in patients with thrombotic events, confirmed by the increase in cytokines. Furthermore, in this cohort, a link was observed between the IL-10 percentage and an increased chance of a thrombotic event.

Cellular and transcriptional responses of Crassostrea gigas hemocytes exposed in vitro to brevetoxin (PbTx-2).

Hemocytes mediate a series of immune reactions essential for bivalve survival in the environment, however, the impact of harmful algal species and their associated phycotoxins upon bivalve immune system is under debate. To better understand the possible toxic effects of these toxins, Crassostrea gigas hemocytes were exposed to brevetoxin (PbTx-2). Hemocyte viability, monitored through the neutral red retention and MTT reduction assays, and apoptosis (Hoechst staining) remained unchanged during 12 h of exposure to PbTx-2 in concentrations up to 1000 µg/L. Despite cell viability and apoptosis remained stable, hemocytes incubated for 4 h with 1000 µg/L of PbTx-2 revealed higher expression levels of Hsp70 (p < 0.01) and CYP356A1 (p < 0.05) transcripts and a tendency to increase FABP expression, as evaluated by Real-Time quantitative PCR. The expression of other studied genes (BPI, IL-17, GSTO, EcSOD, Prx6, SOD and GPx) remained unchanged. The results suggest that the absence of cytotoxic effects of PbTx-2 in Crassostrea gigas hemocytes, even at high concentrations, allow early defense responses to be produced by activating protective mechanisms associated to detoxification (CYP356A1 and possibly FABP) and stress (Hsp70), but not to immune or to antioxidant (BPI, IL-17, EcSOD, Prx6, GPx and SOD) related genes.

Nanoplastics in Aquatic Environments: Impacts on Aquatic Species and Interactions with Environmental Factors and Pollutants.

Plastic production began in the early 1900s and it has transformed our way of life. Despite the many advantages of plastics, a massive amount of plastic waste is generated each year, threatening the environment and human health. Because of their pervasiveness and potential for health consequences, small plastic residues produced by the breakdown of larger particles have recently received considerable attention. Plastic particles at the nanometer scale (nanoplastics) are more easily absorbed, ingested, or inhaled and translocated to other tissues and organs than larger particles. Nanoplastics can also be transferred through the food web and between generations, have an influence on cellular function and physiology, and increase infections and disease susceptibility. This review will focus on current research on the toxicity of nanoplastics to aquatic species, taking into account their interactive effects with complex environmental mixtures and multiple stressors. It intends to summarize the cellular and molecular effects of nanoplastics on aquatic species; discuss the carrier effect of nanoplastics in the presence of single or complex environmental pollutants, pathogens, and weathering/aging processes; and include environmental stressors, such as temperature, salinity, pH, organic matter, and food availability, as factors influencing nanoplastic toxicity. Microplastics studies were also included in the discussion when the data with NPs were limited. Finally, this review will address knowledge gaps and critical questions in plastics' ecotoxicity to contribute to future research in the field.

Role of Cytokines, Chemokines and IFN-γ+ IL-17+ Double-Positive CD4+ T Cells in Patients with Multiple Sclerosis.

Multiple sclerosis is mediated by self-reactive myelin T and B cells that lead to axonal and myelin damage. The immune response in multiple sclerosis involves the participation of CD4+ T cells that produce cytokines and chemokines. This participation is important to find markers for the diagnosis and progression of the disease. In our work, we evaluated the profile of cytokines and chemokines, as well as the production of double positive CD4+ T cells for the production of IFNγ IL-17 in patients with multiple sclerosis, at different stages of the disease and undergoing different treatments. We found that relapsing-remitting patients had a significant increase in IL-12 production. About IL-5, its production showed significantly higher levels in secondarily progressive patients when compared to relapsing-remitting patients. IFN-γ production by PBMCs from secondarily progressive patients showed significantly higher levels. This group also had a higher percentage of CD4+ IFNγ+ IL-17+ T cells. The combination of changes in certain cytokines and chemokines together with the presence of IFNγ+ IL-17+ double positive lymphocytes can be used to better understand the clinical forms of the disease and its progression.

Development of Ag-ZnO/AgO Nanocomposites Effectives for Leishmania braziliensis Treatment.

Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania. Leishmania braziliensis (L.b) is one of the most clinically relevant pathogens that affects the skin and mucosa, causing single or multiple disfiguring and life-threatening injuries. Even so, the few treatment options for patients have significant toxicity, high dropout rates, high cost, and the emergence of resistant strains, which implies the need for studies to promote new and better treatments to combat the disease. Zinc oxide nanocrystals are microbicidal and immunomodulatory agents. Here, we develop new Ag-ZnO/xAgO nanocomposites (NCPs) with three different percentages of silver oxide (AgO) nanocrystals (x = 49%, 65%, and 68%) that could act as an option for tegumentary leishmaniasis treatment. Our findings showed that 65% and 68% of AgO inhibit the extra and intracellular replication of L.b. and present a high selectivity index. Ag-ZnO/65%AgO NCPs modulate activation, expression of surface receptors, and cytokine production by human peripheral blood mononuclear cells toward a proinflammatory phenotype. These results point to new Ag-ZnO/AgO nanocomposites as a promising option for L. braziliensis treatment.

Clinical-Epidemiology Aspect of Inpatients With Moderate or Severe COVID-19 in a Brazilian Macroregion: Disease and Countermeasures.

COVID-19, also known as coronavirus disease 2019, is an infectious viral disease caused by SARS-CoV-2, a novel coronavirus. Since its emergence, its epidemiology has been explored; however, for some regions of the world, COVID-19's behavior, incidence, and impact remain unclear. In continental nations like Brazil, this lack of knowledge results in nonuniform control, prevention, and treatment measures, which can be controversial in some locations. This study aimed to describe the epidemiological profile of patients with COVID-19 in the macroregion of Triângulo Sul in the state of Minas Gerais (MG), Brazil. Between March 25 and October 21, 2020, data were collected and statistically analyzed from 395 hospitalized patients in the city of Uberaba, MG, suspected to have moderate or severe forms of the disease. Of the 395 suspected cases, 82% were confirmed to be positive for COVID-19. The mean age of positive patients was 58.4 years, and 60.76% were male. Following these patients throughout their hospitalization, a mortality rate of 31.3% was observed. In the population positive for COVID-19, the risk of death increased by 4% for each year of the patient's age. Likewise, the older the patient, the longer their hospitalization and the higher the risk of developing acute respiratory failure. Among the treatments tested in patients, heparin was associated with protection against mortality, and the absence of anticoagulant use was linked to a more than six times greater risk of death. Finally, comorbidities in patients with COVID-19 were positively correlated with increased hospitalization time. In summary, this study revealed that age, presence of comorbidities, length of hospitalization, and drug treatment considerably altered COVID-19's lethality. To understand infection rates and the factors involved in COVID-19's lethality, knowledge of the local epidemiology is necessary.

The organophosphate insecticide diazinon and aging: Neurobehavioral and mitochondrial effects in zebrafish exposed as embryos or during aging.

Organophosphate (OP) compounds comprise one of the most widely used classes of insecticides worldwide. OPs have been shown to have negative human health impacts, particularly developmental neurotoxicity. However, neurotoxic impacts in later adulthood and during the aging process are relatively uncharacterized. The present study examined diazinon (DZN), an OP, to determine the neurobehavioral consequences, in addition to mitochondrial dysfunction on a macroscale (whole organism basal respiration) and on a microscale (whole organ mitochondrial respiration), using zebrafish (ZF) as a model. One group of 14-month-old adult ZF were exposed acutely as adults (0.4, 1.25, and 4.0 µM) for five days and tested as adults, and another group was exposed developmentally 5-120 h post-fertilization (70, 210, and 700 nM) and tested at larval, adolescent, adult, and aging life stages. ZF exposed acutely as adults did not display many significant neurobehavioral impacts or mitochondrial dysfunction. Conversely, the embryonically exposed ZF showed altered behavioral functions at each stage of life which emerged and attenuated as fish transitioned from each developmental stage to the next. Mitochondrial oxygen consumptions measurement results for developmentally DZN exposed ZF showed significant increases in the low and middle dose groups in organs such as the brain and testes. Overall, there is an indication that early developmental exposure to DZN had continuing adverse neurobehavioral and cellular consequences throughout their lives well into adulthood and aging periods.