Unveiling the metabolites underlying the skin anti-ageing properties of Cytinus hypocistis (L.) L. through a biochemometric approach.

BACKGROUND: The genus Cytinus, recognised as one of the most enigmatic in the plant kingdom, has garnered attention for its bioactive potential, particularly its skin anti-ageing properties. Despite this recognition, much remains to be accomplished regarding deciphering and isolating its most active compounds. HYPOTHESIS: This study aimed to identify the compounds responsible for C. hypocistis skin anti-ageing potential. METHODS: Using multivariate analysis, a biochemometric approach was applied to identify the discriminant metabolites by integrating extracts' chemical profile (Liquid Chromatography-High-Resolution Mass Spectrometry, LCHRMS) and bioactive properties. The identified bioactive metabolite was structurally elucidated by 1D and 2D Nuclear Magnetic Resonance (NMR). RESULTS: Among the studied bioactivities, the anti-elastase results exhibited a significant variation among the samples from different years. After the biochemometric analysis, the compound 2,3:4,6-bis(hexahydroxydiphenoyl)glucose, with a molecular mass of 784.075 Da, was structurally elucidated as the discriminant feature responsible for the outstanding human neutrophil elastase inhibition. Remarkably, the subfraction containing this compound exhibited a tenfold improvement in neutrophil elastase inhibition efficacy compared to the crude extract; its effectiveness fell within the same range as SPCK, a potent irreversible neutrophil elastase inhibitor. Moreover, this subfraction displayed no cytotoxicity or phototoxicity and excellent efficacy for the tested anti-ageing properties. CONCLUSIONS: Hydrolysable tannins were confirmed as the metabolites behind C. hypocistis skin anti-ageing properties, effectively mitigating critical molecular mechanisms that influence the phenotypically distinct ageing clinical manifestations. Pedunculagin was particularly effective in inhibiting neutrophil elastase, considered one of the most destructive enzymes in skin ageing.

Stroke and Multiorgan Failure as the Initial Manifestations of Lupus.

Systemic lupus erythematosus (SLE) is a persistent autoimmune disorder that manifests across a spectrum ranging from mild to severe disease, often requiring hospitalization and critical care management. We present a severe case of systemic involvement at its onset. A young woman, with a background of arterial hypertension, presented to the emergency department exhibiting a total anterior circulation stroke and exuberant symmetric lower limb edema. Her condition rapidly deteriorated with neurological impairment, respiratory failure requiring mechanical ventilation, and acute kidney injury prompting her admission to the ICU. Following clinical investigation, a diagnosis of SLE was established, according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 and Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria. The patient underwent treatment involving high-dose corticosteroids, followed by the Euro-Lupus protocol, resulting in significant improvement, despite her severe neurological deficit at admission. Lupus is a complex disease that is often difficult to diagnose because of its potential to mimic various other conditions. Our report delves into a case of previously undiagnosed lupus leading the patient to the ICU. The clinical scenario described adds valuable insights to the understanding of lupus-related complications and their management through a multidisciplinary approach.

Emerging Approaches for Mitigating Biofilm-Formation-Associated Infections in Farm, Wild, and Companion Animals.

The importance of addressing the problem of biofilms in farm, wild, and companion animals lies in their pervasive impact on animal health and welfare. Biofilms, as resilient communities of microorganisms, pose a persistent challenge in causing infections and complicating treatment strategies. Recognizing and understanding the importance of mitigating biofilm formation is critical to ensuring the welfare of animals in a variety of settings, from farms to the wild and companion animals. Effectively addressing this issue not only improves the overall health of individual animals, but also contributes to the broader goals of sustainable agriculture, wildlife conservation, and responsible pet ownership. This review examines the current understanding of biofilm formation in animal diseases and elucidates the complex processes involved. Recognizing the limitations of traditional antibiotic treatments, mechanisms of resistance associated with biofilms are explored. The focus is on alternative therapeutic strategies to control biofilm, with illuminating case studies providing valuable context and practical insights. In conclusion, the review highlights the importance of exploring emerging approaches to mitigate biofilm formation in animals. It consolidates existing knowledge, highlights gaps in understanding, and encourages further research to address this critical facet of animal health. The comprehensive perspective provided by this review serves as a foundation for future investigations and interventions to improve the management of biofilm-associated infections in diverse animal populations.

Determinants of HIV late presentation among men who have sex with men in Portugal (2014-2019): who's being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

When the Lightning Strikes Twice: Navigating the Complex Terrain of Cerebral Tuberculosis.

Tuberculosis (TB), a Mycobacterium tuberculosis (Mtb) infection, remains a significant global health concern despite a declining incidence. This report highlights a complex case involving a 24-year-old patient from Angola who presented with a constellation of symptoms, including fever, weight loss, and neurological deficits. The patient had been on chronic corticosteroid therapy, a known risk factor for the reactivation of latent TB infection (LTBI). Her clinical course was marked by diagnostic challenges, such as a previous diagnosis of Kikuchi's disease and paradoxical progression despite appropriate tuberculostatic chemotherapy. Miliary TB, characterized by widespread dissemination of Mtb from the primary site of infection, can manifest in various extrapulmonary locations. Central nervous system (CNS) involvement, particularly TB meningitis, is the most severe form of TB, associated with significant morbidity and mortality. The diagnosis of miliary and CNS TB can be elusive due to nonspecific clinical presentations and imaging findings. This case underscores the importance of a high index of suspicion, especially in immunocompromised individuals, and the need for comprehensive microbiological analysis, including cerebrospinal fluid (CSF) examination, to confirm CNS involvement. Furthermore, this case illustrates the challenges associated with TB treatment, including the risk of drug toxicity, medication adherence, and the potential for drug resistance. Treatment duration for miliary TB is extended, typically lasting nine months to a year, and may require adaptation based on the patient's clinical response and drug penetration into the CNS. Corticosteroids play a critical role as adjuvant therapy, particularly in cases with perilesional edema or paradoxical reactions during treatment. This case underscores the complexity of diagnosing and managing miliary and CNS TB, emphasizing the importance of considering TB as a diagnostic possibility in patients with nonspecific symptoms and risk factors. Early identification, multidisciplinary collaboration, and tailored therapeutic strategies are essential for achieving optimal outcomes in such challenging cases. Additionally, screening for latent TB infection should be a priority for patients requiring immunosuppressive therapy to mitigate the risk of reactivation.

Structural and Functional Shifts in the Microbial Community of a Heavy Metal-Contaminated Soil Exposed to Short-Term Changes in Air Temperature, Soil Moisture and UV Radiation.

The interplay between metal contamination and climate change may exacerbate the negative impact on the soil microbiome and, consequently, on soil health and ecosystem services. We assessed the response of the microbial community of a heavy metal-contaminated soil when exposed to short-term (48 h) variations in air temperature, soil humidity or ultraviolet (UV) radiation in the absence and presence of Enchytraeus crypticus (soil invertebrate). Each of the climate scenarios simulated significantly altered at least one of the microbial parameters measured. Irrespective of the presence or absence of invertebrates, the effects were particularly marked upon exposure to increased air temperature and alterations in soil moisture levels (drought and flood scenarios). The observed effects can be partly explained by significant alterations in soil properties such as pH, dissolved organic carbon, and water-extractable heavy metals, which were observed for all scenarios in comparison to standard conditions. The occurrence of invertebrates mitigated some of the impacts observed on the soil microbial community, particularly in bacterial abundance, richness, diversity, and metabolic activity. Our findings emphasize the importance of considering the interplay between climate change, anthropogenic pressures, and soil biotic components to assess the impact of climate change on terrestrial ecosystems and to develop and implement effective management strategies.

A Comprehensive Ecotoxicity Study of Molybdenum Disulfide Nanosheets versus Bulk form in Soil Organisms.

The increasing use of molybdenum disulfide (MoS2) nanoparticles (NPs) raises concerns regarding their accumulation in soil ecosystems, with limited studies on their impact on soil organisms. Study aim: To unravel the effects of MoS2 nanosheets (two-dimensional (2D) MoS2 NPs) and bulk MoS2 (156, 313, 625, 1250, 2500 mg/kg) on Enchytraeus crypticus and Folsomia candida. The organisms' survival and avoidance behavior remained unaffected by both forms, while reproduction and DNA integrity were impacted. For E. crypticus, the individual endpoint reproduction was more sensitive, increasing at lower concentrations of bulk MoS2 and decreasing at higher ones and at 625 mg/kg of 2D MoS2 NPs. For F. candida, the molecular endpoint DNA integrity was more impacted: 2500 mg/kg of bulk MoS2 induced DNA damage after 2 days, with all concentrations inducing damage by day 7. 2D MoS2 NPs induced DNA damage at 156 and 2500 mg/kg after 2 days, and at 1250 and 2500 mg/kg after 7 days. Despite affecting the same endpoints, bulk MoS2 induced more effects than 2D MoS2 NPs. Indeed, 2D MoS2 NPs only inhibited E. crypticus reproduction at 625 mg/kg and induced fewer (F. candida) or no effects (E. crypticus) on DNA integrity. This study highlights the different responses of terrestrial organisms to 2D MoS2 NPs versus bulk MoS2, reinforcing the importance of risk assessment when considering both forms.

Daphnia magna Multigeneration Exposure to Carbendazim: Gene Transcription Responses.

The world population is experiencing colossal growth and thus demand for food, leading to an increase in the use of pesticides. Persistent pesticide contamination, such as carbendazim, remains a pressing environmental concern, with potentially long-term impacts on aquatic ecosystems. In the present study, Daphnia magna was exposed to carbendazim (5 µg L-1) for 12 generations, with the aim of assessing gene transcription alterations induced by carbendazim (using a D. magna custom microarray). The results showed that carbendazim caused changes in genes involved in the response to stress, DNA replication/repair, neurotransmission, ATP production, and lipid and carbohydrate metabolism at concentrations already found in the environment. These outcomes support the results of previous studies, in which carbendazim induced genotoxic effects and reproduction impairment (increasing the number of aborted eggs with the decreasing number of neonates produced). The exposure of daphnids to carbendazim did not cause a stable change in gene transcription between generations, with more genes being differentially expressed in the F0 generation than in the F12 generation. This could show some possible daphnid acclimation after 12 generations and is aligned with previous multigenerational studies where few ecotoxicological effects at the individual and populational levels and other subcellular level effects (e.g., biochemical biomarkers) were found.

Exploring the α-amylase-inhibitory properties of tannin-rich extracts of Cytinus hypocistis on starch digestion.

Cytinus hypocistis(L.) L. is an edible parasitic plant that grows within the roots of its host. In addition to its use as famine food in the past, it is also tradidionally used for treating several illnesses such as intestinal problems, inflammations, tumors, and bleeding. This species is rich in hydrolysable tannins, compounds often associated with inhibiting starch digestion. Therefore, the present work investigated how effectively C. hypocistis tannin-rich extracts inhibited enzymes involved in starch digestion and if such effect also occurs in vivo. The latter premise was approached using the starch tolerance test in mice. Two optimized hydroethanolic extracts were used, a heat-assisted and an ultrasound-assisted extract, with known hydrolysable tannin content. Both extracts demonstrated potent inhibition of α-amylase. Inhibitions were of the mixed type with inhibitor constants in the 15 µg/mL range. The inhibition of the intestinal α-glucosidase was at least ten times less effective. The inhibition of the α-amylase was negatively affected by in vitro gastrointestinal digestion and bovine serum albumin. In vivo, both extracts inhibited starch digestion at doses between 100 and 400 mg/mL in healthy mice. The highest doses of the ultrasound and heat extracts diminished the peak glucose levels in the starch tolerance test by 46 and 59.3%, respectively. In streptozotocin diabetic mice, this inhibition occurred only at the dose of 400 mg/mL. Under this condition, diminution of the peak glucose concentration in the starch tolerance test was equal to 36.7% and 48.8% for the ultrasound and heat extracts, respectively. Maltose digestion was not inhibited by the C. hypocistis extracts. Qualitatively and quantitatively, thus, the actions of both extracts were similar. The results allow adding a new biological property to C. hypocistis, namely, the ability to decrease the hyper-glycemic excursion after a starch-rich meal, propitiating at the same time a diminished caloric intake.

Nanoplastics increase the toxicity of a pharmaceutical, at environmentally relevant concentrations - A mixture design with Daphnia magna.

In aquatic environments, nanoplastics (NPls) can adsorb pharmaceuticals. However, throughout the scientific community, there is scarce knowledge about the interactive effects of the mixture nanoplastics (NPls) with pharmaceuticals to aquatic organisms. Therefore, this study aimed to investigate if the pharmaceutical diphenhydramine (DPH) toxicological effects alters when in presence of polystyrene NPls (PSNPls). To achieve this, Daphnia magna immobilization and different biochemical biomarkers (48-hours exposure) were assessed. Synergistic interactions occurred at environmentally relevant concentrations, PSNPls+DPH induced oxidative damage, whereas no effect was observed at single exposures. With the increase of PSNPls concentration, the DPH concentration causing 50% of effect (EC50) for organisms' immobilization decreased to 0.001 mg/L. In silico analysis suggested that the DPH toxicity to D. magna occurs via the sodium-dependent serotonin transporter. The results showed interactive effects between PSNPls and DPH (implying harmful effects on D. magna), allowing more thoughtful decisions by society and policymakers regarding plastics and pharmaceuticals.

Skin pigmentation as landmark for arteriovenous fistula cannulation in hemodialysis.

BACKGROUND: The cannulation of the arteriovenous fistula (AVF) for hemodialysis (HD) has traditionally depended on the nurse's tactile sensation, which has been associated with suboptimal needle placement and detrimental effects on vascular access (VA) longevity. While the introduction of ultrasound (US) has proven beneficial in mapping the AVF outflow vein and assisting in cannulation planning, aneurysmal deformations remain a common occurrence resulting from various factors, including inadequate cannulation techniques. Within this context, the utilization of skin pigmentation as a clinical landmark has emerged as a potential approach to enhance cannulation planning in HD. METHODS: A prospective longitudinal study was undertaken to investigate the correlation between the occurrence of venous morphological deformations and the cannulation technique guided by skin pigmentation after a 2-month period of implementation. RESULTS: Thirty patients were enrolled in the study with 433 cannulations being described within the first 2 months of AVF use. The overall rate of cannulation-related adverse events was 21.9%. Comparative analysis demonstrated a statistically significant relationship (p < 0.001) between aneurysmal deformation and non-compliance with the proposed cannulation technique, resulting in cannulation outside the designated points. Non-compliance was primarily attributed to nurse's decision (57.1%). CONCLUSION: The integration of US mapping of the AVF outflow vein and the utilization of skin pigmentation as a guiding tool have shown promising results in enhancing cannulation planning over time. Consistent adherence to a cannulation technique other than the area technique has been found to reduce the risk of AVF morphological deformation. These findings underscore the potential benefits of incorporating skin pigmentation as a clinical landmark in cannulation practices, highlighting its ability to impact positively cannulation outcomes.

Safety and Efficacy of Triple Therapy With Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors in Treatment-Naive Human Immunodeficiency Virus Type 2 Patients: Results From a 48-Week Phase 2 Study.

BACKGROUND: Integrase strand transfer inhibitor-based regimens are recommended for first-line therapy in human immunodeficiency virus type 2 (HIV-2). Nonetheless, dolutegravir (DTG) clinical trial data are lacking. METHODS: We conducted a phase 2, single-arm, open-label trial to evaluate the safety and efficacy of a triple therapy regimen that included DTG in persons with HIV-2 (PWHIV-2) in Portugal. Treatment-naive adults receive DTG in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs). Treatment efficacy was evaluated by the proportion of patients who achieved a plasma viral load (pVL) <40 copies/mL and/or by the change from baseline in CD4+ T-cell count and in CD4/CD8 ratio at week 48. RESULTS: A total of 30 patients were enrolled (22 women; median age, 55 years). At baseline, 17 (56.7%) individuals were viremic (median, pVL 190 copies/mL; interquartile range [IQR], 99-445). The median CD4 count was 438 cells/µL (IQR, 335-605), and the CD4/CD8 ratio was 0.8. Three patients discontinued the study. At week 48, all participants (27) had pVL <40 copies/mL. No virological failures were observed. Mean changes in CD4 count and CD4/CD8 ratio at week 48 were 95.59 cells/µL (95% confidence interval [CI], 28-163) and 0.32 (95% CI, .19 to .46). The most common drug-related adverse events were headache and nausea. One participant discontinued due to central nervous system symptoms. No serious adverse events were reported. CONCLUSIONS: DTG plus 2 NRTIs is safe and effective as first-line treatment for PWHIV-2 with a tolerability profile previously known. No virological failures were observed that suggest a high potency of DTG in HIV-2 as occurs in HIV-1. CLINICAL TRIALS REGISTRATION: M NCT03224338.

Toxicity assessment of binary mixtures of BP3 with 4-MBC (UV-filters), and BP3 with DEET (insect repellent) using the aquatic midge Chironomus riparius.

Personal care products have various organic ultraviolet filters (UV filters) in their composition to increase protection against ultraviolet radiation. Some of these products also contain insect repellents in their formulations. Consequently, these compounds reach freshwater ecosystems, exposing aquatic organisms to a cocktail of anthropogenic contaminants. In this study, the joint effects of two most frequently detected UV filters (Benzophenone - 3 (BP3) and Enzacamene (4-MBC)) and joint effects of BP3 combined with an insect repellent (N, N diethyl-3-methylbenzamide - DEET) were evaluated using life-history traits of the aquatic midge Chironomus riparius such as emergence rate, time to emergence and imagoes body weight. The results showed synergistic effects between BP3 and 4-MBC for C. riparius emergence rate. Regarding the effects of BP3 and DEET mixture, our analysis suggests synergism in the case of males but antagonism in the case of females' time to emergence. Our results imply that the effects of UV filters present in sediments within chemical mixtures are complex and that the evaluation of effects using different life-history traits can yield different patterns of responses. This study demonstrates the importance of assessing the combined effects of pollutants used/found concomitantly in aquatic systems for a more accurate risk assessment, as individual chemical testing can underestimate the toxicity of organic UV filters.

Toxicokinetics and bioaccumulation of silver sulfide nanoparticles in benthic invertebrates in an indoor stream mesocosm.

Mesocosms allow the simulation of environmentally relevant conditions and can be used to establish more realistic scenarios of organism exposure to nanoparticles. An indoor mesocosm experiment simulating an aquatic stream ecosystem was conducted to assess the toxicokinetics and bioaccumulation of silver sulfide nanoparticles (Ag2S NPs) and AgNO3 in the freshwater invertebrates Girardia tigrina, Physa acuta and Chironomus riparius, and determine if previous single-species tests can predict bioaccumulation in the mesocosm. Water was daily spiked at 10 µg Ag L-1. Ag concentrations in water and sediment reached values of 13.4 µg Ag L-1 and 0.30 µg Ag g-1 in the Ag2S NP exposure, and 12.8 µg Ag L-1 and 0.20 µg Ag g-1 in the AgNO3. Silver was bioaccumulated by the species from both treatments, but with approximately 1.5, 3 and 11 times higher body Ag concentrations in AgNO3 compared to Ag2S NP exposures in snails, chironomids and planarians, respectively. In the Ag2S NP exposures, the observed uptake was probably of the particulate form. This demonstrates that this more environmentally relevant Ag nanoform may be bioavailable for uptake by benthic organisms. Interspecies interactions likely occurred, namely predation (planarians fed on chironomids and snails), which somehow influenced Ag uptake/bioaccumulation, possibly by altering organisms´ foraging behaviour. Higher Ag uptake rate constants were determined for AgNO3 (0.64, 80.4 and 1.12 Lwater g-1organism day-1) than for Ag2S NPs (0.05, 2.65 and 0.32 Lwater g-1organism day-1) for planarians, snails and chironomids, respectively. Biomagnification under environmentally realistic exposure seemed to be low, although it was likely to occur in the food chain P. acuta to G. tigrina exposed to AgNO3. Single-species tests generally could not reliably predict Ag bioaccumulation in the more complex mesocosm scenario. This study provides methodologies/data to better understand exposure, toxicokinetics and bioaccumulation of Ag in complex systems, reinforcing the need to use mesocosm studies to improve the risk assessment of environmental contaminants, specifically NPs, in aquatic environments.

Toxicokinetics of Ag from Ag2S NP exposure in Tenebrio molitor and Porcellio scaber: Comparing single-species tests to indoor mesocosm experiments.

Determining the potential for accumulation of Ag from Ag2S NPs as an environmentally relevant form of AgNPs in different terrestrial organisms is an essential component of a realistic risk assessment of AgNP emissions to soils. The objectives of this study were first to determine the uptake kinetics of Ag in mealworms (Tenebrio molitor) and woodlice (Porcellio scaber) exposed to Ag2S NPs in a mesocosm test, and second, to check if the obtained toxicokinetics could be predicted by single-species bioaccumulation tests. In the mesocosms, mealworms and woodlice were exposed together with plants and earthworms in soil columns spiked with 10 µg Ag g-1 dry soil as Ag2S NPs or AgNO3. The total Ag concentrations in the biota were measured after 7, 14, and 28 days of exposure. A one-compartment model was used to calculate the Ag uptake and elimination rate constants. Ag from Ag2S NPs appeared to be taken up by the mealworms with significantly different uptake rate constants in the mesocosm compared to single-species tests (K1 = 0.056 and 1.66 g dry soil g-1 dry body weight day-1, respectively), and a significant difference was found for the Ag bioaccumulation factor (BAFk = 0.79 and 0.15 g dry soil g-1 dry body weight, respectively). Woodlice did not accumulate Ag from Ag2S NPs in both tests, but uptake from AgNO3 was significantly slower in mesocosm than in single-species tests (K1 = 0.037 and 0.26 g dry soil g-1 dry body weight day-1, respectively). Our results are of high significance because they show that single-species tests may not be a good predictor for the Ag uptake in mealworms and woodlice in exposure systems having greater levels of biological complexity. Nevertheless, single-species tests could be used as a fast screening approach to assess the potential of a substance to accumulate in biota before more complex tests are conducted.

Shewanella algae, an Emerging Human Pathogen: A Series of Four Cases From a Portuguese Hospital.

Shewanella algae is a rod-shaped, Gram-negative bacterium that is considered an emerging human pathogen. Traditionally associated with warmer climates, S. algae has now been isolated from patients worldwide, and reports of infection are increasing. In a regional hospital on the outskirts of Lisbon, Portugal, four cases have been detected in the past 10 years. Two of the patients were migrants from African countries with daily contact with water; the other two patients were Portuguese, and no epidemiological risk factors were found among them. These are the first cases reported in Portugal. Risk factors associated with S. algae infection in patients discussed in this paper include the following: human immunodeficiency virus (HIV) infection, chronic venous insufficiency, lower limb ulcers, chronic kidney disease, diabetes, arterial hypertension, dilated cardiomyopathy, atrial fibrillation, chronic hepatic disease, and chronic pancreatitis. One patient died in the intensive care unit with septic shock and disseminated intravascular coagulation from a fulminant infection secondary to S. algae bacteraemia. The four clinical cases presented in this case series highlight the clinical features of this infection so that other physicians can successfully identify and treat S. algae infections.

Potential of plant extracts in targeting SARS-CoV-2 main protease: an in vitro and in silico study.

The deaths caused by the covid-19 pandemic have recently decreased due to a worldwide effort in vaccination campaigns. However, even vaccinated people can develop a severe form of the disease that requires ICU admission. As a result, the search for antiviral drugs to treat these severe cases has become a necessity. In this context, natural products are an interesting alternative to synthetic medicines used in drug repositioning, as they have been consumed for a long time through traditional medicine. Many natural compounds found in plant extracts have already been shown to be effective in treating viral and bacterial diseases, making them possible hits to exploit against covid-19. The objective of this work was to evaluate the antiviral activity of different plant extracts available in the library of natural products of the Universidade Estadual de Maringá, by inhibiting the SARS-CoV-2 main protease (Mpro), and by preventing viral infection in a cellular model. As a result, the extract of Cytinus hypocistis, obtained by ultrasound, showed a Mpro inhibition capacity greater than 90%. In the infection model assays using Vero cells, an inhibition of 99.6% was observed, with a selectivity index of 42.7. The in silico molecular docking simulations using the extract compounds against Mpro, suggested Tellimagrandin II as the component of C. hypocistis extract most likely to inhibit the viral enzyme. These results demonstrate the potential of C. hypocistis extract as a promising source of natural compounds with antiviral activity against covid-19.Communicated by Ramaswamy H. Sarma.

Is there a time window for MRI in Wernicke encephalopathy - a decade of experience from a tertiary hospital.

OBJECTIVE: Wernicke encephalopathy (WE) is a neuropsychiatric syndrome caused by thiamine deficiency. Despite its low sensitivity, brain magnetic resonance imaging (MRI) is the most useful diagnostic technique. Our aim was to investigate whether the timing of the imaging study, and thiamine replacement can influence brain MRI findings in these patients. METHODS: Retrospective observational study of hospitalized patients between January/2008 and December/2020 with a clinical diagnosis of WE. Data from clinical presentation, diagnostic features, therapeutic approach, and outcomes were collected. RESULTS: We identified 41 patients (55 ± 13.3 years) with WE. Brain MRI was performed in 36 patients, and one third had T2/FLAIR hyperintensities suggestive of WE. We found an association between a history of poor diet and periventricular hyperintensities (p = 0.023), especially on the ventral surface of the thalamus and the periaqueductal region. It was found that the odds of having a typical imaging of WE decreased by 5.3% for each additional unit (100 mg) of thiamine administered (p = 0.046) (95% CI [0.89, 0.99]). On the other hand, the number of days from clinical presentation was not found to be a viable predictor (p = 0.254) (95% CI [0.88, 1.03]) Recovery was positively correlated with the total dose of thiamine received until discharge (p = 0.020). CONCLUSIONS: MRI hyperintensities seem to be dependent on the timing of thiamine correction and, particularly, on the thiamine dosage prescribed at admission. Nevertheless, thiamine replacement should not be delayed, as its timely prescription is associated with a better prognosis at discharge.

Ecotoxicological effects of fluvial eroded bitumen sediments from the Alberta oil sands to model aquatic species.

To fully understand the ecological and cumulative effects of mining activities on the surrounding aquatic systems of the Canadian oil sands region, it is essential to understand the consequences of exposure to bitumen-containing soils/sediment from natural geomorphological processes. Both physical and chemical stress on aquatic biota can potentially result from exposure to natural bitumen, resulting from hillslope erosional processes and slumping of bankside soils into the rivers, affecting both riverbed habitat and water quality. The magnitude and duration of bitumen-containing soil's fluvial soils/erosional input into receiving watersheds depends on the interannual variability in the regional hydroclimatology and related seasonal and extreme flow events. The primary objective of this study was to evaluate the potential ecotoxicological effects associated with erosional input of riverbank bitumen soils using controlled exposures. A series of integrated, laboratory-based ecotoxicological bioassays were conducted using organisms with different ecological and functional traits (Daphnia magna (Cladocera), Physa acuta (Gastropoda), and Aliivibrio fischeri (Bacteria)). All model organisms were exposed to elutriates produced from natural bitumen from four different regional rivers: fresh bitumen from shoreline outcrops at the Steepbank River upper and lower reaches (STB-CF and STB-MF, respectively) and the lower-Ells River (EL-MF) and aged, fluvially processed/weathered bitumen from the shoreline of the Athabasca River (ATB-MF). All tested organisms responded negatively to STB-MF and EL-MF elutriates. Low toxicity was also observed in the STB-CF and ATB-MF samples. These results follow the chemical analysis of the parental material and elutriates, where higher levels of metals, polycyclic aromatic compounds and naphthenic acids were detected in the EL-MF sample. In summary, this study shows that eroded and transported bitumen-containing soils and sediments could be a natural source of contaminant exposure to aquatic biota. This fluvial pathway should be considered when assessing background toxicity and the toxicological and ecological effects of oil sands mining activities.

Four diterpenes identified in silico were isolated from Hyptidinae and demonstrated in vitro activity against Mycobacterium tuberculosis.

Plants of Hyptidinae subtribe (Lamiaceae - family), as Mesosphaerum sidifolium, are a source of bioactive molecules. In the search for new drug candidates, we perform chemical characterization of diterpenes isolated from the aerial parts of M. sidifolium was carried out with uni- and bidimensional NMR spectral data, and evaluate in silico through the construction of a predictive model followed by in vitro testing Mycobacterium tuberculosis and Mycobacterium smegmatis. Resulted in the isolation of four components: Pomiferin D (1), Salviol (2), Pomiferin E (3) and 2α-hydroxysugiol (4), as well as two phenolic compounds, rosmarinic and caffeic acids. In silico model identified 48 diterpenes likely to have biological activity against M. tuberculosis. The diterpenes isolated were tested in vitro against M. tuberculosis demonstrating MIC = 125 µM for 4 and 1, while 2 and 3 -MIC = 250 µM. These compounds did not show biological activity at these concentrations for M. smegmatis.