Antiangiogenic properties of BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom by VEGF pathway in endothelial cells.

Angiogenesis is a process that is controlled by a delicate combination of proangiogenic and antiangiogenic molecules and can be disrupted in various illnesses, including cancer. Non-cancerous diseases can also have an abnormal or insufficient vascular growth, inflammation and hypoxia, which exacerbate angiogenesis. These conditions include atherosclerosis, psoriasis, endometriosis, asthma, obesity and AIDS. Based on that, the present work assessed the in vitro and ex vivo antiangiogenic properties stemming from BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom, via the VEGF pathway. BthMP at a concentration of 5 and 40 µg/mL showed no toxicity to endothelial cells (HUVEC) in the MTT assay and was not able to induce necrosis and colony proliferation. Interestingly, BthMP inhibited adhesion, migration and invasion of HUVECs in Matrigel and arrested in vitro angiogenesis by reducing the average number of nodules in toxin-treated cells by 9.6 and 17.32 at 5 and 40 µg/mL, respectively, and the number of tubules by 15.9 at 5 µg/mL and 21.6 at 40 µg/mL in a VEGF-dependent way, an essential proangiogenic property. Furthermore, BthMP inhibited the occurrence of the angiogenic process in an ex vivo aortic ring test by decreasing new vessel formation by 52% at 5 µg/mL and by 66% at 40 µg/mL and by increasing the expression of an antiangiogenic gene, SFLT-1, and decreasing the expression of the proangiogenic genes VEGFA and ANGPT-1. Finally, this toxin reduces the production of nitric oxide, a marker that promotes angiogenesis and VEGF modulation, and decreases the protein expression of VEGFA in the supernatant of the HUVEC culture by about 30 %. These results suggest that BthMP has a promising antiangiogenic property and proves to be a biotechnological mechanism for understanding the antiangiogenic responses induced by snake venom metalloproteinases, which could be applied to a variety of diseases that exhibit an imbalance of angiogenesis mechanisms.

Venom Composition of Neglected Bothropoid Snakes from the Amazon Rainforest: Ecological and Toxinological Implications.

Snake venoms have evolved in several families of Caenophidae, and their toxins have been assumed to be biochemical weapons with a role as a trophic adaptation. However, it remains unclear how venom contributes to the success of venomous species for adaptation to different environments. Here we compared the venoms from Bothrocophias hyoprora, Bothrops taeniatus, Bothrops bilineatus smaragdinus, Bothrops brazili, and Bothrops atrox collected in the Amazon Rainforest, aiming to understand the ecological and toxinological consequences of venom composition. Transcriptomic and proteomic analyses indicated that the venoms presented the same toxin groups characteristic from bothropoids, but with distinct isoforms with variable qualitative and quantitative abundances, contributing to distinct enzymatic and toxic effects. Despite the particularities of each venom, commercial Bothrops antivenom recognized the venom components and neutralized the lethality of all species. No clear features could be observed between venoms from arboreal and terrestrial habitats, nor in the dispersion of the species throughout the Amazon habitats, supporting the notion that venom composition may not shape the ecological or toxinological characteristics of these snake species and that other factors influence their foraging or dispersal in different ecological niches.

Long-term impacts of 48-h water and feed deprivation on blood and performance responses of grazing Bos indicus Nellore heifers.

The study investigated the effects of 48-h water and feed deprivation on blood and the performance of grazing Nellore (Bos indicus) heifers. Twenty-four Nellore heifers (initial body weight [BW] = 238 ±â€…10 kg; age = 16 ±â€…2 mo), were ranked by initial BW and age and randomly assigned to one of the two treatments: (1) grazing animals with free access to pasture, water, and mineral-mix (CON; n = 12), or (2) the same grazing conditions but deprived of pasture, water, and mineral-mix for 48 h (DPR; n = 12). The paddocks consisted of Urochloa brizantha cv. Marandu, using a continuous and fixed stocking rate. The experiment lasted 225 d, with the first 14 d considered as the adaptation period (days -14 to -1) and the subsequent 211 d as the evaluation period (days 0 to 211). From days 0 to 2, treatments were applied by keeping the DPR heifers in pens and reintegrating them into the experimental area after a 48-h water and feed deprivation. Individual full BW was recorded on days -14, -13, -1, before (day 0) and after (day 2) treatment application, and on days 6, 11, 12, 41, 42, 210, and 211. Blood samples were collected in the morning on days 0, 2, 6, 12, and 211. A treatment effect was detected (P < 0.001) for shrink BW from days 0 to 2, which was greater (P < 0.001) in DPR vs. CON heifers. Subsequently, DPR animals were lighter (P < 0.001) compared with CON heifers by the end of the deprivation period (day 2). From days 4 to 211, DPR was lighter (P < 0.001) compared with CON heifers after treatment application and for the entire experimental period. In the first 10 d after treatment application (days 2 to 12), DPR heifers showed a partial compensatory average daily gain (ADG; P < 0.001) compared with CON heifers, while no significant differences were observed in ADG between the treatments from days 12 to 42 and 42 to 211 (P > 0.420). Overall ADG (days 2 to 211) was greater (P < 0.001) for DPR vs. CON heifers. All serum variables, except AST, were higher (P < 0.001) in DPR than in CON heifers on day 2 after treatment application. Our study demonstrates that grazing Nellore heifers subjected to 48-h water and feed deprivation experienced significant alterations in their blood metabolites and BW immediately after the stressful event. Although the deprived heifers partially compensated for their BW loss in the early days post-deprivation, they remained 12 kg lighter than the non-deprived animals throughout the production cycle.

Effect of Different Herbage Allowances from Mid to Late Gestation on Nellore Cow Performance and Female Offspring Growth until Weaning.

This study evaluated different herbage allowances from mid to late pregnancy on pre- and postpartum physiological responses, milk production, and the performance of Nellore cows and the preweaning growth of their female offspring. Sixty multiparous Nellore cows were blocked by their body weight (BW; 425 ± 36 kg) and body condition score (BCS; 3.67 ± 0.23, scale 1-5) and randomly allocated to twelve pastures. Treatments consisted of two different herbage allowances (HA) during pregnancy: low HA (LHA; 2.80 kg DM/kg of BW) and high HA (HHA; 7.60 kg DM/kg of BW). Both treatment groups were fed 1 g/kg BW of a protein supplement. After calving, all cow-calf pairs were combined in a single group. The effects of maternal treatment × day of the study were detected for herbage mass and allowance, the stocking rate and forage crude protein, and for cow BW, BCS, and carcass measures (p < 0.01). Milk yield corrected to 4% fat, while the levels of fat total solids and cow plasma IGF-1 and urea were different (p ≤ 0.04) between treatments. HHA offspring was heavier (p ≤ 0.05) at 120 days and at weaning. A high herbage allowance can be implemented from mid-gestation until calving to increase cow prepartum performance, post-partum milk yield and composition, and positively modulate female offspring preweaning growth.

Venom composition of neglected Bothropoid snakes from the Amazon Rainforest: ecological and toxinological implications

Snake venoms have evolved in several families of Caenophidae, and their toxins have been assumed to be biochemical weapons with a role as a trophic adaptation. However, it remains unclear how venom contributes to the success of venomous species for adaptation to different environments. Here we compared the venoms from Bothrocophias hyoprora, Bothrops taeniatus, Bothrops bilineatus smaragdinus, Bothrops brazili, and Bothrops atrox collected in the Amazon Rainforest, aiming to understand the ecological and toxinological consequences of venom composition. Transcriptomic and proteomic analyses indicated that the venoms presented the same toxin groups characteristic from bothropoids, but with distinct isoforms with variable qualitative and quantitative abundances, contributing to distinct enzymatic and toxic effects. Despite the particularities of each venom, commercial Bothrops antivenom recognized the venom components and neutralized the lethality of all species. No clear features could be observed between venoms from arboreal and terrestrial habitats, nor in the dispersion of the species throughout the Amazon habitats, supporting the notion that venom composition may not shape the ecological or toxinological characteristics of these snake species and that other factors influence their foraging or dispersal in different ecological niches.

Cuidadores familiares de pessoas com demência: Tradução, adaptação e validação da Escala de Limites Ambíguos / Family caregivers of people with dementia: Translation, adaptation, and validation of the Boundary Ambiguity Scale / Cuidadores familiares de personas con demencia: Traducción, adaptación y validación de la Escala de Límites Ambiguos

Resumo Enquadramento: Cuidar de pessoas com demência (PcD) é gerador de stresse entre cuidadores familiares (CF). Uma das situações geradoras desse stresse é a perda ambígua (PA). Objetivos: Traduzir, adaptar e validar a Escala de Limites Ambíguos (ELA) para português europeu e determinar as caraterísticas psicométricas da ELA. Metodologia: Estudo metodológico a partir de uma amostra de 88 CF de PcD. A consistência interna (CI) avaliada com o Coeficiente de Ômega de McDonald ((), a validade de constructo através da análise fatorial exploratória (AFE) e a validade de critério com a Escala de Perceção de Stresse (EPS). Resultados: A ELA apresentou validade conteúdo excelente. A AFE determinou um modelo de dois fatores, explicando 44% da variância, ( de 0,72. Os CF que residem com a PcD apresentam maior PA (t = 2,823, p < 0,01). Correlação significativa positiva e moderada entre a ELA e a EPS (r s = 0,578, p < 0,01). Conclusão: A ELA é um instrumento com propriedade psicométrica de CI e validade aceitáveis para a avaliação da PA.

Abstract Background: Caring for people with dementia generates stress among family caregivers. One of these stressor events is ambiguous loss. Objectives: To translate, adapt, and validate the Boundary Ambiguity Scale (BAS) into European Portuguese and assess its psychometric properties. Methodology: Methodological study with a sample of 88 family caregivers of people with dementia. Internal consistency was assessed using McDonald's omega coefficient ((). Construct validity was assessed through exploratory factor analysis (EFA) and criterion validity through the Perceived Stress Scale (PSS). Results: The BAS showed excellent content validity. The EFA revealed a two-factor model, explaining 44% of variance, and a ( of 0.72. Family caregivers who live with people with dementia had greater ambiguous loss (t = 2.823, p < 0.01). A statistically significant moderate positive correlation was found between the BAS and the PSS (r s = 0.578, p < 0.01). Conclusion: The BAS has acceptable validity and internal consistency for assessing ambiguous loss.

Resumen Marco contextual: El cuidado de personas con demencia (PcD) genera estrés entre los cuidadores familiares (CF). Una de las situaciones que generan este estrés es la pérdida ambigua (PA). Objetivos: Traducir, adaptar y validar la Escala de Límites Ambiguos (ELA) al portugués europeo y determinar las características psicométricas de la ELA. Metodología: Estudio metodológico basado en una muestra de 88 CF de PcD. La consistencia interna (CI) se evaluó mediante el coeficiente omega de McDonald ((), la validez de constructo mediante el análisis factorial exploratorio (AFE) y la validez de criterio mediante la Escala de Percepción del Estrés (EPS). Resultados: La ELA presentó una validez de contenido excelente. El AFE determinó un modelo de dos factores, que explican el 44% de la varianza, ( de 0,72. Los CF que residen con PcD presentan mayor PA (t = 2,823, p < 0,01). Correlación significativa positiva y moderada entre la ELA y la EPS (r s = 0,578, p < 0,01). Conclusión: La ELA es un instrumento con propiedades psicométricas de CI y validez aceptables para la evaluación de la PA.

HIV testing among immigrant men who have sex with men in Brazil.

OBJECTIVE: To evaluate the prevalence of non-testing for HIV among immigrant men who have sex with men (MSM) residing in Brazil and identify associated factors. DESIGN: An analytical web-survey study was conducted across all Brazilian states from January 2020 to May 2021. SAMPLE: The study included 804 MSM immigrants from Portuguese-speaking countries. MEASUREMENTS: Odds ratio (OR) and adjusted Odds Ratio (AOR) were utilized to determine the strength of the association between non-HIV testing and associated factors. RESULTS: Among the participants, 63.7% had never undergone HIV testing. Multivariate analysis revealed several factors associated with a higher likelihood of not being tested for HIV: having a steady/monogamus partner (AOR: 1.5; 95%CI: 1.1-2.3) or both casual and steady partners (AOR: 1.8; 95%CI: 1.2-3.4), not engaging in bareback sex (AOR: 1.91; 95%CI: 3-3.5), being an immigrant in the country for less than 12 months (AOR: 3.7; 95%CI: 2.5-9.7), and having a preference for insertive (AOR: 1.5; 95%CI: 1.1-2.5) or receptive (AOR: 2.9; 95%CI: 1.4-5.7) roles. However, practicing chemsex was found to be a protective factor for testing (AOR: 4). CONCLUSION: To enhance HIV prevention strategies, it is crucial to implement specific measures that ensure accessibility, confidentiality, and a reduction in stigma associated with HIV testing.

Performance, Intake, Feed Efficiency, and Carcass Characteristics of Young Nellore Heifers under Different Days on Feed in the Feedlot.

Two studies evaluated the productive characteristics of young Nellore heifers receiving different days on feed (DOF) to determine the biological slaughter endpoint. In Experiment 1 (Exp. 1), fifty-one Nellore heifers [324 ± 19.3 kg of body weight (BW); 16 ± 1 months] were split into three DOF lengths (45, 75, or 105 days), while in Experiment 2 (Exp. 2), thirty-six Nellore heifers (362 ± 25.5 kg of BW; 18 ± 1 months of age) were split into three DOF lengths (45, 90, or 135 days). In both studies, all animals were distributed in complete randomized blocks according to initial BW and stratified via carcass ultrasound. The diet was supplied ad libitum, allowing 3% of refusals. The point at which the animals achieved 25% of ether extract of shrunk body weight (EESBW) was defined as the biological endpoint. Thus, relationships were made between some characteristics obtained in both studies. Positive linear relationships were found between backfat thickness (BFT) vs. EESBW (p < 0.001, r = 0.84) and BFT vs. body weight (p < 0.001, r = 0.77). Our results suggest that the biological slaughter endpoint for young Nellore heifers is 6.97 mm of backfat thickness or 402 kg shrunk body weight, corresponding to around 75 DOF.

The Venom Composition of the Snake Tribe Philodryadini: 'Omic' Techniques Reveal Intergeneric Variability among South American Racers.

Snakes of the Philodryadini tribe are included in the Dipsadidae family, which is a diverse group of rear-fanged snakes widespread in different ecological conditions, including habitats and diet. However, little is known about the composition and effects of their venoms despite their relevance for understanding the evolution of these snakes or even their impact on the occasional cases of human envenoming. In this study, we integrated venom gland transcriptomics, venom proteomics and functional assays to characterize the venoms from eight species of the Philodryadini tribe, which includes the genus Philodryas, Chlorosoma and Xenoxybelis. The most abundant components identified in the venoms were snake venom metalloproteinases (SVMPs), cysteine-rich secretory proteins (CRISPs), C-type lectins (CTLs), snake endogenous matrix metalloproteinases type 9 (seMMP-9) and snake venom serinoproteinases (SVSPs). These protein families showed a variable expression profile in each genus. SVMPs were the most abundant components in Philodryas, while seMMP-9 and CRISPs were the most expressed in Chlorosoma and Xenoxybelis, respectively. Lineage-specific differences in venom composition were also observed among Philodryas species, whereas P. olfersii presented the highest amount of SVSPs and P. agassizii was the only species to express significant amounts of 3FTx. The variability observed in venom composition was confirmed by the venom functional assays. Philodryas species presented the highest SVMP activity, whereas Chlorosoma species showed higher levels of gelatin activity, which may correlate to the seMMP-9 enzymes. The variability observed in the composition of these venoms may be related to the tribe phylogeny and influenced by their diets. In the presented study, we expanded the set of venomics studies of the Philodryadini tribe, which paves new roads for further studies on the evolution and ecology of Dipsadidae snakes.

Interplay Between the Immune and Nervous Cognitive Systems in Homeostasis and in Malaria.

The immune and nervous systems can be thought of as cognitive and plastic systems, since they are both involved in cognition/recognition processes and can be architecturally and functionally modified by experience, and such changes can influence each other's functioning. The immune system can affect nervous system function depending on the nature of the immune stimuli and the pro/anti-inflammatory responses they generate. Here we consider interactions between the immune and nervous systems in homeostasis and disease, including the beneficial and deleterious effects of immune stimuli on brain function and the impact of severe and non-severe malaria parasite infections on neurocognitive and behavioral parameters in human and experimental murine malaria. We also discuss the effect of immunization on the reversal of cognitive deficits associated with experimental non-severe malaria in a model susceptible to the development of the cerebral form of the illness. Finally, we consider the possibility of using human vaccines, largely exploited as immune-prophylactics for infectious diseases, as therapeutic tools to prevent or mitigate the expression of cognitive deficits in infectious and chronic degenerative diseases.

Food insecurity in a Brazilian transgender sample during the COVID-19 pandemic.

Transgender people often live with social vulnerability, largely promoted by gender-based prejudice. Our aim in this article was to raise preliminary data on how the COVID-19 pandemic and perceived prejudice have contributed to the problem of food and food insecurity in the transgender communities in Brazil. We conducted a web-based cross-sectional study, in which 109 transgender people from all regions of Brazil participated. We used the Chi-Square test and Poisson regression modeling with robust variance to estimate the association between food insecurity and the investigated factors. In our sample, 68.8% of transgender people experienced food insecurity, of these, 20.2% experienced severe food insecurity. Our results showed that the difficulties in purchasing food in the transgender community predate the COVID-19 pandemic, yet that the restrictive measures adopted have also impacted overall access to quality food. However, the main explanations for food insecurity were income and employment. In predicting food insecurity, the experiences of prejudice must be considered, and give rise to the hypothesis that specific conditions to which transgender people are exposed explain, to some degree, their vulnerability to food insecurity.

Immunomodulation through vaccination as a promising therapeutic strategy to mitigate malaria-related neurocognitive sequelae.

Malaria, an ancient infectious parasitic disease, is caused by protozoa of the genus Plasmodium, whose erythrocytic cycle is accompanied by fever, headache, sweating and chills and a systemic inflammation that can progress to severe forms of disease, including cerebral malaria. Approximately 25% of survivors of this syndrome develop sequelae that may include neurological, neurocognitive, behavioral alterations and poor school performance. Furthermore, some outcomes have also been recorded following episodes of non-severe malaria, which correspond to the most common clinical form of the disease worldwide. There is a body of evidence that neuroinflammation, due to systemic inflammation, plays an important role in the neuropathogenesis of malaria culminating in these cognitive dysfunctions. Preclinical studies suggest that vaccination with type 2 immune response elicitors, such as the tetanus-diphtheria (Td) vaccine, may exert a beneficial immunomodulatory effect by alleviating neuroinflammation. In this viewpoint article, vaccination is proposed as a therapy approach to revert or mitigate neurocognitive deficits associated with malaria.

The venom composition of the snake tribe Philodryadini: ‘Omic’ techniques reveal intergeneric variability among South American racers

Snakes of the Philodryadini tribe are included in the Dipsadidae family, which is a diverse group of rear-fanged snakes widespread in different ecological conditions, including habitats and diet. However, little is known about the composition and effects of their venoms despite their relevance for understanding the evolution of these snakes or even their impact on the occasional cases of human envenoming. In this study, we integrated venom gland transcriptomics, venom proteomics and functional assays to characterize the venoms from eight species of the Philodryadini tribe, which includes the genus Philodryas, Chlorosoma and Xenoxybelis. The most abundant components identified in the venoms were snake venom metalloproteinases (SVMPs), cysteine-rich secretory proteins (CRISPs), C-type lectins (CTLs), snake endogenous matrix metalloproteinases type 9 (seMMP-9) and snake venom serinoproteinases (SVSPs). These protein families showed a variable expression profile in each genus. SVMPs were the most abundant components in Philodryas, while seMMP-9 and CRISPs were the most expressed in Chlorosoma and Xenoxybelis, respectively. Lineage-specific differences in venom composition were also observed among Philodryas species, whereas P. olfersii presented the highest amount of SVSPs and P. agassizii was the only species to express significant amounts of 3FTx. The variability observed in venom composition was confirmed by the venom functional assays. Philodryas species presented the highest SVMP activity, whereas Chlorosoma species showed higher levels of gelatin activity, which may correlate to the seMMP-9 enzymes. The variability observed in the composition of these venoms may be related to the tribe phylogeny and influenced by their diets. In the presented study, we expanded the set of venomics studies of the Philodryadini tribe, which paves new roads for further studies on the evolution and ecology of Dipsadidae snakes.

Dynamics and immunomodulation of cognitive deficits and behavioral changes in non-severe experimental malaria.

Data recently reported by our group indicate that stimulation with a pool of immunogens capable of eliciting type 2 immune responses can restore the cognitive and behavioral dysfunctions recorded after a single episode of non-severe rodent malaria caused by Plasmodium berghei ANKA. Here we explored the hypothesis that isolated immunization with one of the type 2 immune response-inducing immunogens, the human diphtheria-tetanus (dT) vaccine, may revert damages associated with malaria. To investigate this possibility, we studied the dynamics of cognitive deficits and anxiety-like phenotype following non-severe experimental malaria and evaluated the effects of immunization with both dT and of a pool of type 2 immune stimuli in reversing these impairments. Locomotor activity and long-term memory deficits were assessed through the open field test (OFT) and novel object recognition task (NORT), while the anxiety-like phenotype was assessed by OFT and light/dark task (LDT). Our results indicate that poor performance in cognitive-behavioral tests can be detected as early as the 12th day after the end of antimalarial treatment with chloroquine and may persist for up to 155 days post infection. The single immunization strategy with the human dT vaccine showed promise in reversal of long-term memory deficits in NORT, and anxiety-like behavior in OFT and LDT.

Differences in PLA2 Constitution Distinguish the Venom of Two Endemic Brazilian Mountain Lanceheads, Bothrops cotiara and Bothrops fonsecai.

Interspecific differences in snake venom compositions can result from distinct regulatory mechanisms acting in each species. However, comparative analyses focusing on identifying regulatory elements and patterns that led to distinct venom composition are still scarce. Among venomous snakes, Bothrops cotiara and Bothrops fonsecai represent ideal models to complement our understanding of the regulatory mechanisms of venom production. These recently diverged species share a similar specialized diet, habitat, and natural history, but each presents a distinct venom phenotype. Here, we integrated data from the venom gland transcriptome and miRNome and the venom proteome of B. fonsecai and B. cotiara to better understand the regulatory mechanisms that may be acting to produce differing venom compositions. We detected not only the presence of similar toxin isoforms in both species but also distinct expression profiles of phospholipases A2 (PLA2) and some snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) isoforms. We found evidence of modular expression regulation of several toxin isoforms implicated in venom divergence and observed correlated expression of several transcription factors. We did not find strong evidence for miRNAs shaping interspecific divergence of the venom phenotypes, but we identified a subset of toxin isoforms whose final expression may be fine-tuned by specific miRNAs. Sequence analysis on orthologous toxins showed a high rate of substitutions between PLA2s, which indicates that these toxins may be under strong positive selection or represent paralogous toxins in these species. Our results support other recent studies in suggesting that gene regulation is a principal mode of venom evolution across recent timescales, especially among species with conserved ecotypes.

Differences in PLA2 constitution distinguish the venom of two endemic brazilian mountain lanceheads, Bothrops cotiara and Bothrops fonsecai

Interspecific differences in snake venom compositions can result from distinct regulatory mechanisms acting in each species. However, comparative analyses focusing on identifying regulatory elements and patterns that led to distinct venom composition are still scarce. Among venomous snakes, Bothrops cotiara and Bothrops fonsecai represent ideal models to complement our understanding of the regulatory mechanisms of venom production. These recently diverged species share a similar specialized diet, habitat, and natural history, but each presents a distinct venom phenotype. Here, we integrated data from the venom gland transcriptome and miRNome and the venom proteome of B. fonsecai and B. cotiara to better understand the regulatory mechanisms that may be acting to produce differing venom compositions. We detected not only the presence of similar toxin isoforms in both species but also distinct expression profiles of phospholipases A2 (PLA2) and some snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) isoforms. We found evidence of modular expression regulation of several toxin isoforms implicated in venom divergence and observed correlated expression of several transcription factors. We did not find strong evidence for miRNAs shaping interspecific divergence of the venom phenotypes, but we identified a subset of toxin isoforms whose final expression may be fine-tuned by specific miRNAs. Sequence analysis on orthologous toxins showed a high rate of substitutions between PLA2s, which indicates that these toxins may be under strong positive selection or represent paralogous toxins in these species. Our results support other recent studies in suggesting that gene regulation is a principal mode of venom evolution across recent timescales, especially among species with conserved ecotypes.

Uma revisão de escopo de revisões sistemáticas sobre exposição humana ao mercúrio / A scoping review of systematic reviews on human exposure to mercury

Resumo: Introdução: a promulgação da Convenção de Minamata no Brasil em 2018 incentivou o cumprimento dos seus objetivos em reduzir o uso e a poluição por mercúrio. Objetivo: caracterizar a produção científica sobre exposição humana ao mercúrio e identificar lacunas de conhecimento a fim de subsidiar a tomada de decisão em saúde. Métodos: revisão de escopo de revisões sistemáticas e metanálises, sem restrição de idioma ou data de publicação, utilizando as bases PubMed, BVS e Cochrane Library. Resultados: 71 estudos atenderam aos critérios de elegibilidade, com 40 revisões sistemáticas, 30 metanálises e 1 overview. Amálgama dentário e contaminação alimentar e ambiental por atividades que utilizam mercúrio foram as fontes de exposição mais mencionadas. Os temas mais estudados contaram com transtornos mentais e comportamentais, assim como uso de biomarcadores e testes neurocomportamentais relacionados à exposição ao mercúrio. Discussão: lacunas como a exposição ocupacional ao mercúrio, uso em práticas tradicionais e em cosméticos apontam para a necessidade de mais estudos. As revisões identificadas podem oferecer subsídios para sínteses de evidências e protocolos de atenção à saúde de populações expostas, assim como para a elaboração de políticas públicas que visem o controle do uso e da exposição ao mercúrio.

Abstract: Introduction: in 2018, the promulgation of the Minamata Convention in Brazil encouraged compliance with its goals of reducing mercury use and pollution. Objective: to characterize the scientific production and identify the knowledge gaps to subsidize decision-making in healthcare on human exposure to mercury. Methods: a scoping review was carried out of systematic reviews and metanalysis, without language and publication date restriction, retrieved from the PubMed, BVS, and Cochrane Library databases. Results: a total of 71 studies met the eligibility criteria, of which 40 were systematic reviews, 30 meta-analyses, and one overview. Dental amalgam as well as food and environmental contamination by mercury-based activities were the most cited sources of exposure. Most studies focused on mental and behavioral disorders, as well as the use of biomarkers and neurobehavioral tests related to mercury exposure. Discussion: knowledge gaps on occupational exposure to mercury, mercury use in both traditional practices and cosmetics point to the need for further studies. The reviews identified could provide data for evidence synthesis and healthcare protocols for affected populations, as well as for elaborating public policies aimed at controlling mercury use and exposure.

Can risk of sarcopenia predict poorer quality of life in hemodialysis patients? / Risco de sarcopenia pode predizer pior qualidade de vida entre pacientes em hemodiálise?

Background: Sarcopenia and low quality of life (QOL) are widely found among hemodialysis (HD) patients. We aimed to verify whether risk of sarcopenia can predict QOL level in patients submitted to HD. Methods: The sample was formed by 147 chronic kidney disease patients undergoing HD in October 2020 at a single dialysis center.  Demographic and clinical data were collected. Risk of sarcopenia was classified using the SARC-F questionnaire. QOL was evaluated by the Brazilian version of the SF-36. QOL scores were compared between patients with and without risk of sarcopenia. Multivariate linear regression was performed to test risk of sarcopenia as an independent predictor of QOL scores. Results: There were 62 (42.2%) patients classified as having risk of sarcopenia. In the comparison of QOL scores between patients with and without risk of sarcopenia, scores of seven dimensions were significantly lower among patients with sarcopenia risk, the only exception being role-emotional. Risk of sarcopenia was an independent predictor of six dimensions of QOL, except for role-emotional and mental health. Conclusion: We found risk of sarcopenia to be an independent predictor of QOL among HD patients. Our results point to the possibility of improving patients' QOL by intervening to minimize the risk of sarcopenia.

Introdução: Sarcopenia e baixa qualidade de vida (QV) são amplamente encontradas entre pacientes em hemodiálise (HD). Nosso objetivo foi verificar se o risco de sarcopenia prediz o nível de QV nesta população. Métodos: A amostra foi formada por 147 pacientes em HD em outubro de 2020 em um único centro de diálise. Dados demográficos e clínicos foram coletados. O risco de sarcopenia foi classificado pelo questionário SARC-F. A QV foi avaliada pela versão brasileira do SF-36. Os escores de QV foram comparados entre pacientes com e sem risco de sarcopenia. A regressão linear multivariada foi realizada para testar o risco de sarcopenia como preditor independente dos escores de QV. Resultados: Havia 62 (42,2%) pacientes classificados como tendo risco de sarcopenia. Comparando os escores de QV entre pacientes com e sem risco de sarcopenia, os escores de 7 dimensões foram significativamente menores entre os pacientes com risco de sarcopenia, exceto aspectos emocionais. O risco de sarcopenia foi um preditor independente de 6 dimensões da QV, exceto para aspectos emocionais e saúde mental. Conclusão: O risco de sarcopenia é um preditor independente de QV entre os pacientes em HD. Nossos resultados apontam para a possibilidade de melhorar a QV dos pacientes intervindo para minimizar o risco de sarcopenia.

Observation of Bothrops atrox Snake Envenoming Blister Formation from Five Patients: Pathophysiological Insights.

In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds.

Immune system challenge improves recognition memory and reverses malaria-induced cognitive impairment in mice.

The immune system plays a role in the maintenance of healthy neurocognitive function. Different patterns of immune response triggered by distinct stimuli may affect nervous functions through regulatory or deregulatory signals, depending on the properties of the exogenous immunogens. Here, we investigate the effect of immune stimulation on cognitive-behavioural parameters in healthy mice and its impact on cognitive sequelae resulting from non-severe experimental malaria. We show that immune modulation induced by a specific combination of immune stimuli that induce a type 2 immune response can enhance long-term recognition memory in healthy adult mice subjected to novel object recognition task (NORT) and reverse a lack of recognition ability in NORT and anxiety-like behaviour in a light/dark task that result from a single episode of mild Plasmodium berghei ANKA malaria. Our findings suggest a potential use of immunogens for boosting and recovering recognition memory that may be impaired by chronic and infectious diseases and by the effects of ageing.