Identification of human circulating factors following remote ischemic conditioning (RIC): Potential impact on stroke.

Remote ischemic conditioning (RIC) is a procedure consisting of short cycles of ischemia applied in a limb that activates endogenous protection in distant organs, such as the brain. Despite the promising outcomes of RIC, the biochemical factors governing inter-organ communication remain largely unexplored, particularly in humans. A pilot study on 20 healthy humans was performed to identify potential circulating biochemical factors involved in RIC signalling. Blood was collected before and immediately, 4 and 22 h after the end of RIC. To characterize the responses triggered by RIC, a combination of biochemical and proteomic analysis, along with functional in vitro tests in human cells, were performed. RIC did not alter the levels of nitric oxide, bilirubin and cell-free mitochondrial DNA. In contrast, carboxyhaemoglobin levels increased following RIC at all time points and young subset, suggesting endogenous production of carbon monoxide that is a cytoprotective gasotransmitter. Additionally, the levels of glutathione and cysteinylglycine bound to proteins also increased after RIC, while glutathione catabolism decreased. Plasma proteomic analysis identified overall 828 proteins. Several steps of statistical analysis (Student's t-test, repeated measures ANOVA, with Holm corrected pairwise p-values <0.05 threshold and fold change higher or lower than 100 %) leaded to the identification of 9 proteins with altered circulating levels in response to RIC at 4h and 22h. All 9 proteins are from extracellular space or exosomes, being involved in inflammation, angiogenesis or metabolism control. In addition, RIC-conditioned plasma from young subjects protected microglial cell culture against inflammatory stimuli, indicating an anti-inflammatory effect of RIC. Nevertheless, other functional tests in neurons or endothelial cells had no effect. Overall, we present some evidence for RIC-induced anti-inflammatory and antioxidant responses in healthy human subjects, in particular in young subjects. This study is a first step towards the disclosure of signalling factors involved in RIC-mediated inter-organ communication.

Validation of a bioanalytical HPLC-UV method to quantify Α-Bisabolol in rat plasma applied to pharmacokinetic pilot study with the drug nanoemulsion.

α-Bisabolol (α-BIS) is a sesquiterpene alcohol present in chamomile essential oil [Chamomilla recutita (L.) Rauschert]. Despite its numerous pharmacological effects, its pharmacokinetics remain understudied. An analytical method capable of quantifying α-BIS in plasma is crucial to enable pharmacokinetic analysis. Presently, only one study has quantified it using mass spectrometry. Administering α-BIS requires a nanoemulsion for intravenous injection. This study aimed to develop and validate a bioanalytical method using high-performance liquid chromatography with an ultraviolet detector to quantify α-BIS in rat plasma. The method employed acetonitrile and ultrapure water (80:20, v/v) as the mobile phase, with a flow rate of 1 ml/min and concentrations ranging from 465 to 29.625 µg/ml. All US Food and Drug Administration-designated assays were successful, indicating the method's precision, accuracy, sensitivity and linearity in determining α-BIS in rat plasma. The developed nanoemulsion, assessed through dynamic light scattering analysis, the ensemble collection of particles and polydispersity index evaluation, proved safe and effective for intravenous administration. The pharmacokinetic parameters such as volume of distribution, clearance and half-life indicated that α-BIS tends to persist in the body. This study provides a foundation for further research to explore α-BIS's potential pharmaceutical applications in the future.

PLA2-MjTX-II from Bothrops moojeni snake venom exhibits antimetastatic and antiangiogenic effects on human lung cancer cells.

Phospholipases A2 (PLA2s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA2 isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.

Fetal hemodynamics and placental histopathology in Down syndrome.

OBJECTIVE: To evaluate the association between Doppler patterns in fetuses with Down syndrome (DS) and their placental histopathologic findings. METHODS: A retrospective cross-sectional study was performed by collecting data from medical records of singleton pregnancies between January 2014 and January 2022, whose fetuses had a confirmed diagnosis of DS either prenatally or postnatally. Placental histopathology, maternal characteristics, and prenatal ultrasound (biometric parameters and umbilical artery [UA] Doppler) were evaluated. RESULTS: Of 69 eligible pregnant women, 61 met the inclusion and exclusion criteria. In the sample, 15 fetuses had an estimated fetal weight < 10th percentile for gestational age (GA) and were considered small for gestational age (SGA). Thirty-eight fetuses had increased resistance on the UA Doppler. Histologic changes were detected in 100% of the placentas, the most common being delayed villous maturation, alterations associated with poor fetal vascular perfusion, and villous dysmorphism. More than 50% of the placentas showed alterations related to placental insufficiency. We did not observe a statistically significant association between UA Doppler examination and placental alterations. All placentas analyzed in the SGA subgroup showed findings compatible with placental insufficiency. CONCLUSION: We found no statistically significant association between placental histopathologic findings and UA Doppler abnormalities in fetuses with DS. The placental alterations identified were delayed villous maturation, alterations associated with poor fetal vascular perfusion, and villous dysmorphism.

Tratamento percutâneo da insuficiência tricúspide funcional grave com implante de TricValve® em pacientes de alto risco cirúrgico / Percutaneous treatment of severe functional tricuspid insufficiency with TricValve® implantation in patients at high surgical risk

INTRODUÇÃO: A reoperação para tratamento de Insuficiência Tricúspide (IT) importante funcional isolada está associada à alta morbimortalidade. Considerando este cenário, esforços são direcionados para pesquisas envolvendo tratamento por via percutânea da valva tricúspide em pacientes de alto risco cirúrgico. Uma das soluções propostas é o TricValve®, dispositivo composto por valvas autoexpansíveis implantadas na veia cava superior e inferior, com o objetivo de reduzir a congestão venosa sistêmica e melhorar a qualidade de vida. MATERIAL E MÉTODO: Estudo prospectivo, observacional, unicêntrico, realizado entre 2022 e 2024. Critérios de inclusão: pacientes com IT importante, funcional, com insuficiência cardíaca direita refratária ao tratamento medicamentoso otimizado e sem indicação de intervenção do lado esquerdo do coração. CRITÉRIOS DE EXCLUSÃO: disfunção grave do ventrículo direito (VD) e pressão de artéria pulmonar ≥ 65mmHg. Os pacientes foram avaliados com ecocardiograma transtorácico e tomografia computadorizada. O implante do TricValve® foi realizado por veia femoral, com o dispositivo implantado nas veias cava inferior e superior, sob anestesia geral e monitorização com ecocardiograma transesofágico e fluoroscopia. RESULTADOS: Foram incluídos cinco pacientes, três mulheres e dois homens, com idade entre 59 e 79 anos, um deles com prótese mitral, dois mitroaórticos e dois transplantados do coração. Ocorreu uma complicação imediata: paralisia do nervo frênico direito confirmado por exame de imagem. Não houve mortalidade hospitalar. No seguimento médio de 15 meses (8 a 20 meses) todos os pacientes estão vivos e em quatro deles (80%) houve melhora importante da classe funcional (NYHA de III para I). O grau da IT manteve-se importante em todos os casos, houve melhora da função ventricular direita em dois pacientes (FAC de 29% para 37% e de 31% para 35%) e remodelamento do átrio direito em um paciente. CONCLUSÃO: Em um seguimento médio de 15 meses, o implante de TricValve® dedicado à IT funcional grave foi seguro e efetivo em melhorar a classe funcional dos pacientes. A melhora da função ventricular direita foi observada em metade dos casos.

Mental health during ecological crisis: translating and validating the Hogg Eco-anxiety Scale for Argentinian and Spanish populations.

BACKGROUND: Eco-anxiety is increasingly recognized as a shared experience by many people internationally, encompassing fear of environmental catastrophe and anxiety about ecological crises. Despite its importance in the context of the changing climate, measures for this construct are still being developed in languages other than English. METHODS: To contribute to global eco-anxiety research, we translated the Hogg Eco-Anxiety Scale (HEAS) into Spanish, creating the HEAS-SP. We validated this measure in samples from both Argentina (n = 990) and Spain (n = 548), performing measurement invariance and confirmatory factor analyses. Internal consistency of the scale and score stability over time were investigated through reliability analyses. Differences in eco-anxiety across sociodemographic variables were explored through Student's t-tests and Pearson's r tests. RESULTS: The four-factor model of the HEAS-SP comprising affective and behavioural symptoms, rumination, and anxiety about personal impact demonstrated excellent model fit. We found good internal consistency for each subscale, and established measurement invariance between Spanish and Argentine samples, as well as across genders and participants' age. Spanish participants reported higher scores on the affective symptoms and personal impact anxiety factors compared to the Argentinian sample. Also, men reported lower levels than women on the subscales of affective symptoms, rumination, and personal impact anxiety. It was found that the relationship between both age and personal impact anxiety and age and affective symptoms varies significantly depending on the gender of the individuals. Younger participants tended to report higher scores on most dimensions of eco-anxiety. CONCLUSIONS: These findings enhance the global initiative to investigate, explore and therefore comprehend eco-anxiety by introducing the first valid and reliable Spanish-language version of this psychometric instrument for its use within Spanish and Argentinian populations. This study augments the body of evidence supporting the robust psychometric properties of the HEAS, as demonstrated in prior validations for Australian, Turkish, Portuguese, German, French, and Italian populations.

The socioeconomic epidemiology of inherited retinal diseases in Portugal.

BACKGROUND: Inherited retinal diseases (IRDs) are a group of rare degenerative disorders of the retina that can lead to blindness from birth to late middle age. Knowing the target population and its resources is essential to better plan support measures. The aim of this study was to evaluate the socioeconomic characteristics of regions in Portugal where IRD patients reside to inform the planning of vision aid and rehabilitation intervention measures. RESULTS: This study included 1082 patients from 973 families, aged 3 to 92 years, with a mean age of 44.8 ± 18.1 years. Patients living with an IRD were identified in 190 of the 308 municipalities. According to this study, the estimated IRD prevalence in Portugal was 10.4 per 100,000 inhabitants, and by municipalities, it ranged from 0 to 131.2 per 100,000 inhabitants. Overall, regions with a higher prevalence of IRD have a lower population density (r=-0.371, p < 0.001), a higher illiteracy rate (r = 0.404, p < 0.001) and an overall older population (r = 0.475, p < 0.001). Additionally, there is a lower proportion of doctor per capita (r = 0.350, p < 0.001), higher social security pensions beneficiaries (r = 0.439, p < 0.001), worse water quality for human consumption (r=-0.194, p = 0.008), fewer audiences at the cinema (r=-0.315, p < 0.001) and lower proportion of foreign guests in tourist accommodations (r=-0.287, p < 0.001). CONCLUSION: The number of identified patients with IRD varied between regions. Using data from national statistics (PORDATA), we observed differences in socioeconomic characteristics between regions. Multiple targeted aid strategies can be developed to ensure that all IRD patients are granted full clinical and socioeconomic support.

Detection of elusive DNA copy-number variations in hereditary disease and cancer through the use of noncoding and off-target sequencing reads.

Copy-number variants (CNVs) play a substantial role in the molecular pathogenesis of hereditary disease and cancer, as well as in normal human interindividual variation. However, they are still rather difficult to identify in mainstream sequencing projects, especially involving exome sequencing, because they often occur in DNA regions that are not targeted for analysis. To overcome this problem, we developed OFF-PEAK, a user-friendly CNV detection tool that builds on a denoising approach and the use of "off-target" DNA reads, which are usually discarded by sequencing pipelines. We benchmarked OFF-PEAK on data from targeted sequencing of 96 cancer samples, as well as 130 exomes of individuals with inherited retinal disease from three different populations. For both sets of data, OFF-PEAK demonstrated excellent performance (>95% sensitivity and >80% specificity vs. experimental validation) in detecting CNVs from in silico data alone, indicating its immediate applicability to molecular diagnosis and genetic research.

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.

Genetic profile of syndromic retinitis pigmentosa in Portugal.

PURPOSE: Retinitis pigmentosa (RP) comprises a genetically and clinically heterogeneous group of inherited retinal degenerations, where 20-30% of patients exhibit extra-ocular manifestations (syndromic RP). Understanding the genetic profile of RP has important implications for disease prognosis and genetic counseling. This study aimed to characterize the genetic profile of syndromic RP in Portugal. METHODS: Multicenter, retrospective cohort study. Six Portuguese healthcare providers identified patients with a clinical diagnosis of syndromic RP and available genetic testing results. All patients had been previously subjected to a detailed ophthalmologic examination and clinically oriented genetic testing. Genetic variants were classified according to the American College of Medical Genetics and Genomics; only likely pathogenic or pathogenic variants were considered relevant for disease etiology. RESULTS: One hundred and twenty-two patients (53.3% males) from 100 families were included. Usher syndrome was the most frequent diagnosis (62.0%), followed by Bardet-Biedl (19.0%) and Senior-Løken syndromes (7.0%). Deleterious variants were identified in 86/100 families for a diagnostic yield of 86.0% (87.1% for Usher and 94.7% for Bardet-Biedl). A total of 81 genetic variants were identified in 25 different genes, 22 of which are novel. USH2A and MYO7A were responsible for most type II and type I Usher syndrome cases, respectively. BBS1 variants were the cause of Bardet-Biedl syndrome in 52.6% of families. Best-corrected visual acuity (BCVA) records were available at baseline and last visit for 99 patients (198 eyes), with a median follow-up of 62.0 months. The mean BCVA was 56.5 ETDRS letters at baseline (Snellen equivalent ~ 20/80), declining to 44.9 ETDRS letters (Snellen equivalent ~ 20/125) at the last available follow-up (p < 0.001). CONCLUSION: This is the first multicenter study depicting the genetic profile of syndromic RP in Portugal, thus contributing toward a better understanding of this heterogeneous disease group. Usher and Bardet-Biedl syndromes were found to be the most common types of syndromic RP in this large Portuguese cohort. A high diagnostic yield was obtained, highlighting current genetic testing capabilities in providing a molecular diagnosis to most affected individuals. This has major implications in determining disease-related prognosis and providing targeted genetic counseling for syndromic RP patients in Portugal.

PLA2-MjTX-II from Bothrops moojeni snake venom exhibits antimetastatic and antiangiogenic effects on human lung cancer cells

Phospholipases A2 (PLA2s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA2 isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.

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.

Loneliness, Social Support, and Cognitive Reserve of Older Adults in the COVID-19 Pandemic / Solidão, Apoio Social e Reserva Cognitiva em Pessoas Idosas na Pandemia da COVID-19 / Soledad, Apoyo Social y Reserva Cognitiva en Adultos Mayores en la Pandemia del COVID-19

Abstract: The COVID-19 pandemic significantly affected the quality of life of older Brazilian adults. This study aimed to investigate the level of loneliness and social support of older adults during the COVID-19 pandemic and its relation with cognitive reserve, sociodemographic data, daily habits, and perceived health. An online cross-sectional study was conducted. The final sample consisted of 116 Brazilians aged over 60 years. The following instruments were used: sociodemographic questionnaire, questionnaire on the everyday habits during the pandemic, CRIq, Revised UCLA Loneliness Scale and MOS-SSS. The results showed a significant association between loneliness and social support. The regression models demonstrate the influence of perceived health and different forms of social contact in predicting social support and loneliness. These results evince the importance of the evaluation of factors related to the quality of life of older Brazilian adults during and after the COVID-19 pandemic.

Resumo: A pandemia da COVID-19 afetou significativamente a qualidade de vida das pessoas idosas brasileiras. O objetivo deste estudo foi analisar o nível de apoio social e de solidão de pessoas idosas durante a pandemia do COVID-19 e sua relação com variáveis como a reserva cognitiva, dados sociodemográficos, hábitos diários e a saúde percebida. Foi conduzido um estudo transversal, online, com uma amostra de 116 brasileiros com mais de 60 anos. Os seguintes instrumentos foram aplicados: Questionário sociodemográfico, Questionário sobre hábitos na pandemia, CRIq, Revised UCLA Loneliness Scale e MOS-SSS . Foi observada uma associação significativa entre a solidão e o apoio social. Os modelos de regressão demonstram a influência da percepção da saúde, e de diferentes meios de comunicação na predição do apoio social e da solidão. Os resultados apresentados demonstram a importância de avaliar fatores psicossociais relacionados à qualidade de vida das pessoas idosas brasileiras durante e após a pandemia de COVID-19.

Resumen: La pandemia del COVID-19 ha afectado significativamente a la calidad de vida de los adultos mayores brasileños. El objetivo de este estudio fue investigar el nivel de apoyo social y la soledad en los adultos mayores durante la pandemia del covid-19 y su relación con las variables como reserva cognitiva, datos sociodemográficos, hábitos diarios y salud percibida. Se realizó un estudio transversal en línea con una muestra de 116 participantes con más de 60 años de edad. Se utilizaron los instrumentos: Cuestionario sociodemográfico, cuestionario sobre hábitos en la pandemia, CRIq , Revised UCLA Loneliness Scale y MOS-SSS . Se encontró una correlación significativa entre la soledad y el apoyo social. Los modelos de regresión encontrados demuestran la influencia de la percepción del estado de salud y de diferentes medios en la predicción del apoyo social y la soledad. Los resultados presentados muestran la importancia de evaluar los factores psicosociales relacionados con la calidad de vida de los adultos mayores brasileños durante y después de la pandemia del COVID-19.

Antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, on Leishmania (Leishmania) amazonensis.

BACKGROUND: Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs. OBJECTIVES: We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis. METHODS: Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays. FINDINGS: Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism. MAIN CONCLUSIONS: γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment.

Validating a measure for eco-anxiety in Portuguese young adults and exploring its associations with environmental action.

BACKGROUND: Worsening environmental conditions may amplify people's emotional responses to an environmental crisis (eco-anxiety). In Portugal, young people seem to be especially concerned about climate change. However, this phenomenon needs to be interpreted using accurate instruments. Thus, this study aimed to validate the Portuguese version of the Hogg Eco-Anxiety Scale (HEAS) in young adults and examine the associations among eco-anxiety, sociodemographic characteristics, and pro-environmental behaviours. METHODS: A survey was administered to 623 Portuguese university students aged between 18 and 25 years. The survey included our Portuguese translation of the HEAS (obtained through a back-translation and pretesting process), a sociodemographic assessment, and questions related to pro-environmental behaviours. Confirmatory factor analysis was conducted to assess the construct validity of the Portuguese version of the HEAS, and global fit indices were used to assess whether the original four-dimensional structure of the scale was reproduced. The reliability of the Portuguese version of the HEAS was evaluated by Cronbach's alpha and the intraclass correlation coefficient. Measurement invariance examined sex differences in scale interpretation. Linear regressions were used to detect whether sociodemographic variables predict eco-anxiety and whether eco-anxiety predicts pro-environmental behaviours. RESULTS: The factorial structure of the original scale was replicated in the Portuguese version of the HEAS, showing good internal consistency, reliability over time and strict invariance between men and women. A higher paternal education level predicted greater eco-anxiety in children. Two dimensions of eco-anxiety-namely, rumination and anxiety about personal impacts on the environment-predicted higher engagement in pro-environmental behaviours. CONCLUSIONS: The translated scale is an appropriate tool to measure eco-anxiety in the Portuguese context and should be used to collect evidence to drive environmental and health policies. An individual's education level should be considered a determinant of their emotional response to environmental conditions. Importantly, eco-anxiety can act as a protective emotional response to preserving the planet.

Oxalate (dys)Metabolism: Person-to-Person Variability, Kidney and Cardiometabolic Toxicity.

Oxalate is a metabolic end-product whose systemic concentrations are highly variable among individuals. Genetic (primary hyperoxaluria) and non-genetic (e.g., diet, microbiota, renal and metabolic disease) reasons underlie elevated plasma concentrations and tissue accumulation of oxalate, which is toxic to the body. A classic example is the triad of primary hyperoxaluria, nephrolithiasis, and kidney injury. Lessons learned from this example suggest further investigation of other putative factors associated with oxalate dysmetabolism, namely the identification of precursors (glyoxylate, aromatic amino acids, glyoxal and vitamin C), the regulation of the endogenous pathways that produce oxalate, or the microbiota's contribution to oxalate systemic availability. The association between secondary nephrolithiasis and cardiovascular and metabolic diseases (hypertension, type 2 diabetes, and obesity) inspired the authors to perform this comprehensive review about oxalate dysmetabolism and its relation to cardiometabolic toxicity. This perspective may offer something substantial that helps advance understanding of effective management and draws attention to the novel class of treatments available in clinical practice.

Vitamin D deficiency and hyperglycemia in male rotating shift workers: A disturbed circadian rhythms influence.

BACKGROUND: Shift work is related to several negative impacts on the health of workers. This study aimed to evaluate the association between vitamin D deficiency (VDD) and hyperglycemia in shift workers. METHODOLOGY: This cross-sectional study included male rotating shift workers in an iron ore extraction company. Participants were classified as VDD when 25(OH)D < 20 ng/mL for a healthy population and 25(OH)D < 30 ng/mL for groups at risk for VDD. Hyperglycemia was classified when fasting glucose ≥100 mg/dL or HbA1c ≥ 5.7%. Data were compared using chi-square analysis with Cramer's V as effect size, and Bonferroni correction. Multivariate logistic regression, from a model of determination, was performed to investigate whether VDD was associated with hyperglycemia. RESULTS: The study evaluated 1411 workers, most workers were aged 30-39 years (53.2%), and 77.5% self-declared as black, brown, with up to complete high school (71.4%) and working alternate shifts for more than 5 years (76.1%). Regarding glucose and vitamin D, 32.0% and 29.1% of the workers had hyperglycemia and VDD, respectively. In multivariate analysis, controlled for confounding factors, workers with VDD had a 119% increased chance of hyperglycemia (OR: 2.19; IC95%: 1.56-3.08). Furthermore, vitamin D levels in distribution quintiles showed a dose-response gradient in relation to hyperglycemia, where increased vitamin D values were associated with a reduction in the occurrence of hyperglycemia. CONCLUSION: Rotating shift workers with vitamin D deficiency are more likely to have hyperglycemia.

Beyond Angiogenesis: The Multitasking Approach of the First PEGylated Vascular Endothelial Growth Factor (CdtVEGF) from Brazilian Rattlesnake Venom.

A pioneering study regarding the isolation, biochemical evaluation, functional assays and first PEGylation report of a novel vascular endothelial growth factor from Crotalus durissus terrificus venom (CdtVEGF and PEG-CdtVEGF). CdtVEGF was isolated from crude venom using two different chromatographic steps, representing 2% of soluble venom proteins. Its primary sequence was determined using mass spectrometry analysis, and the molecule demonstrated no affinity to heparin. The Brazilian crotalid antivenom recognized CdtVEGF. Both native and PEGylated CdtVEGF were able to induce new vessel formation and migration, and to increase the metabolic activity of human umbilical endothelial vascular cells (HUVEC), resulting in better wound closure (~50% within 12 h) using the native form. CdtVEGF induced leukocyte recruitment to the peritoneal cavity in mice, with a predominance of neutrophil influx followed by lymphocytes, demonstrating the ability to activate the immune system. The molecule also induced a dose-dependent increase in vascular permeability, and PEG-CdtVEGF showed less in vivo inflammatory activity than CdtVEGF. By unraveling the intricate properties of minor components of snake venom like svVEGF, this study illuminates the indispensable significance of exploring these molecular tools to unveil physiological and pathological processes, elucidates the mechanisms of snakebite envenomings, and could possibly be used to design a therapeutic drug.

Mental health training programs for non-health professionals and volunteers working with asylum-seekers and refugees: scoping review.

OBJECTIVE: To identify and describe the mental health training programs for non-health professionals and volunteers who work, have worked, or would work with asylum seekers and/or refugees. METHOD: Scoping review following JBI methodology. Search carried out in MEDLINE, CINAHL, ERIC, SCOPUS, PsycINFO, Psychology & Behavioral Sciences Collection, RCAAP, ProQuest, and websites of Clinical Trials, UNHCR, International Organization for Migration, WHO, Save the Children, International Migration, Integration and Social Cohesion in Europe, and International Federation of Red Cross and Red Crescent Societies. Studies written in English, Portuguese, French, Spanish and Swedish. RESULTS: Of the 8954 articles identified, 16 were included reporting on 11 training programs: Mind-Spring, PM+, MHFA, Cognitive-Behavioral Training for Community and Religious Leaders, EmpaTeach, Suicide Prevention Education Program, Teaching Recovery Techniques, Handbook for Teachers of Vietnamese Refugee Students, PFA, Psychosocial support of volunteers and CBP&MHPSS. CONCLUSION: Training programs from scientific literature focus on mental health disorders, while non-governmental organizations' documents focus on resilience and self-care. The current mental health training programs might be insufficient.

The pro-resolving lipid mediator Maresin 1 ameliorates pain responses and neuroinflammation in the spared nerve injury-induced neuropathic pain: A study in male and female mice.

Specialized pro-resolving mediators (SPMs) have recently emerged as promising therapeutic approaches for neuropathic pain (NP). We evaluated the effects of oral treatment with the SPM Maresin 1 (MaR1) on behavioral pain responses and spinal neuroinflammation in male and female C57BL/6J mice with spared nerve injury (SNI)-induced NP. MaR1, or vehicle, was administered once daily, on post-surgical days 3 to 5, by voluntary oral intake. Sensory-discriminative and affective-motivational components of pain were evaluated with von Frey and place escape/avoidance paradigm (PEAP) tests, respectively. Spinal microglial and astrocytic activation were assessed by immunofluorescence, and the spinal concentration of cytokines IL-1ß, IL-6, IL-10, and macrophage colony-stimulating factor (M-CSF) were evaluated by multiplex immunoassay. MaR1 treatment reduced SNI-induced mechanical hypersensitivity on days 7 and 11 in both male and female mice, and appeared to ameliorate the affective component of pain in males on day 11. No definitive conclusions could be drawn about the impact of MaR1 on the affective-motivational aspects of pain in female mice, since repeated suprathreshold mechanical stimulation of the affected paw in the dark compartment did not increase the preference of vehicle-treated SNI females for the light side, during the PEAP test session (a fundamental assumption for PAEP's validity). MaR1 treatment also reduced ipsilateral spinal microglial and astrocytic activation in both sexes and marginally increased M-CSF in males, while not affecting cytokines IL-1ß, IL-6 and IL-10 in either sex. In summary, our study has shown that oral treatment with MaR1 (i) produces antinociception even in an already installed peripheral NP mouse model, and (ii) this antinociception may extend for several days beyond the treatment time-frame. These therapeutic effects are associated with attenuated microglial and astrocytic activation in both sexes, and possibly involve modulation of M-CSF action in males.