3-Tetrazolyl-ß-carboline derivatives as potential neuroprotective agents.

3-Tetrazolyl-ß-carbolines were prepared by the Pictet-Spengler approach using a tryptophan analogue as building block, in which the carboxylic acid was replaced by the bioisosteric tetrazole group. Knowing that ß-carbolines are often associated with psychopharmacological effects, the study of the 3-tetrazolyl-ß-carbolines as potential neuroprotective agents against Parkinson's disease was investigated. The evaluation of neuroprotective effects against 1-methyl-4-phenylpyridin-1-ium (MPP+)-induced cytotoxicity allowed to identify compounds with relevant neuroprotective activity. One derivative, 3-(1-benzyl-1H-tetrazol-5-yl)-1-(p-dimethylaminophenyl)-ß-carboline, stood out for its low cytotoxicity and excellent performance, preventing cell death induced by this neurotoxin. The most promising compounds were also evaluated for their neuroprotective properties against iron (III)-induced cytotoxicity. However, only one 3-tetrazolyl-ß-carboline derivative slightly reduced iron-induced cytotoxicity. Overall, the neuroprotective properties of 3-tetrazolyl-ß-carbolines have been demonstrated and this finding may contribute to the development of new therapies for Parkinson's disease.

SOX9 keeps growth plates and articular cartilage healthy by inhibiting chondrocyte dedifferentiation/osteoblastic redifferentiation.

Cartilage is essential throughout vertebrate life. It starts developing in embryos when osteochondroprogenitor cells commit to chondrogenesis, activate a pancartilaginous program to form cartilaginous skeletal primordia, and also embrace a growth-plate program to drive skeletal growth or an articular program to build permanent joint cartilage. Various forms of cartilage malformation and degeneration diseases afflict humans, but underlying mechanisms are still incompletely understood and treatment options suboptimal. The transcription factor SOX9 is required for embryonic chondrogenesis, but its postnatal roles remain unclear, despite evidence that it is down-regulated in osteoarthritis and heterozygously inactivated in campomelic dysplasia, a severe skeletal dysplasia characterized postnatally by small stature and kyphoscoliosis. Using conditional knockout mice and high-throughput sequencing assays, we show here that SOX9 is required postnatally to prevent growth-plate closure and preosteoarthritic deterioration of articular cartilage. Its deficiency prompts growth-plate chondrocytes at all stages to swiftly reach a terminal/dedifferentiated stage marked by expression of chondrocyte-specific (Mgp) and progenitor-specific (Nt5e and Sox4) genes. Up-regulation of osteogenic genes (Runx2, Sp7, and Postn) and overt osteoblastogenesis quickly ensue. SOX9 deficiency does not perturb the articular program, except in load-bearing regions, where it also provokes chondrocyte-to-osteoblast conversion via a progenitor stage. Pathway analyses support roles for SOX9 in controlling TGFß and BMP signaling activities during this cell lineage transition. Altogether, these findings deepen our current understanding of the cellular and molecular mechanisms that specifically ensure lifelong growth-plate and articular cartilage vigor by identifying osteogenic plasticity of growth-plate and articular chondrocytes and a SOX9-countered chondrocyte dedifferentiation/osteoblast redifferentiation process.

Exploring uterine inflammation in postpartum primiparous precocious and conventional and multiparous Bos indicus beef cows.

This study aimed to compare the postpartum uterine dynamics of primiparous precocious (PP), primiparous conventional (PC) and multiparous conventional (MC) Bos indicus beef cows. For this purpose, PP (n = 8), PC (n = 18) and MC (n = 12) cows were enrolled in this study. These cows were evaluated at 20 and 10 days prepartum and weekly from parturition to 42 days postpartum (DPP). During this period, body weight (BW), subcutaneous fat thickness (SFT) and serum concentrations of glucose, ß-hydroxybutyrate, albumin and haptoglobin were measured. Proportion of polymorphonuclear (PMN) cells, and abundance of mRNA transcripts of genes involved in uterine inflammation and uterine health were evaluated. The PP cows had lower (p < .05) BW and SFT than that for PC and MC cows during the study period. The serum concentration of albumin after 35 DPP was lower (p < .05) in PP cows. The PP cows had the highest proportion of PMN on 28 and 35 DPP compared to PC and MC cows. The relative mRNA abundance of IL-1ß and IL-8 increased after 21 DPP in PP cows compared to the other groups. The PC had the highest, MC had an intermediate, and PP cows had the lowest relative abundance of IL10 mRNA. Overall, these findings indicated that uterine inflammation was more pronounced in PP cows. Moreover, based on the proportion of PMN and abundance of transcripts associated with inflammation in the uterus, PP cows may require a longer period to recover their uterine health after calving.

Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei.

Mycoses are one of the major causes of morbidity/mortality among immunocompromised individuals. Considering the importance of these infections, the World Health Organization (WHO) defined a priority list of fungi for health in 2022 that include Candida albicans as belonging to the critical priority group and Pichia kudriavzevii (Candida krusei) to the medium priority group. The existence of few available antifungal drugs, their high toxicity, the acquired fungal resistance, and the appearance of new species with a broader spectrum of resistance, points out the need for searching for new antifungals, preferably with new and multiple mechanisms of action. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 was previously tested against several fungi and revealed an interesting activity, with minimal inhibitory concentration (MIC) values of 8 µg/mL for C. krusei and of 128 µg/mL for C. albicans. The main objective of the present work was to deeply understand the mechanisms involved in its antifungal activity. The effects of the cyclam salt on yeast metabolic viability (resazurin reduction assay), yeast mitochondrial function (JC-1 probe), production of reactive oxygen species (DCFH-DA probe) and on intracellular ATP levels (luciferin/luciferase assay) were evaluated. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 induced a significant decrease in the metabolic activity of both C. albicans and C. krusei, an increase in Reactive Oxygen Species (ROS) production, and an impaired mitochondrial function. The latter was observed by the depolarization of the mitochondrial membrane and decrease in ATP intracellular levels, mechanisms that seems to be involved in the antifungal activity of H4[H2(4-CF3PhCH2)2Cyclam]Cl4. The interference of the cyclam salt with human cells revealed a CC50 value against HEK-293 embryonic kidney cells of 1.1 µg/mL and a HC10 value against human red blood cells of 0.8 µg/mL.

Lipid Metabolism Modulation during SARS-CoV-2 Infection: A Spotlight on Extracellular Vesicles and Therapeutic Prospects.

Extracellular vesicles (EVs) have a significant impact on the pathophysiological processes associated with various diseases such as tumors, inflammation, and infection. They exhibit molecular, biochemical, and entry control characteristics similar to viral infections. Viruses, on the other hand, depend on host metabolic machineries to fulfill their biosynthetic requirements. Due to potential advantages such as biocompatibility, biodegradation, and efficient immune activation, EVs have emerged as potential therapeutic targets against the SARS-CoV-2 infection. Studies on COVID-19 patients have shown that they frequently have dysregulated lipid profiles, which are associated with an increased risk of severe repercussions. Lipid droplets (LDs) serve as organelles with significant roles in lipid metabolism and energy homeostasis as well as having a wide range of functions in infections. The down-modulation of lipids, such as sphingolipid ceramide and eicosanoids, or of the transcriptional factors involved in lipogenesis seem to inhibit the viral multiplication, suggesting their involvement in the virus replication and pathogenesis as well as highlighting their potential as targets for drug development. Hence, this review focuses on the role of modulation of lipid metabolism and EVs in the mechanism of immune system evasion during SARS-CoV-2 infection and explores the therapeutic potential of EVs as well as application for delivering therapeutic substances to mitigate viral infections.

Antinociceptive and anti-inflammatory activities of Ayapana triplinervis essential oil rich in thymohydroquinone dimethyl ether from Brazil.

Ayapana triplinervis (M.Vahl) R.M.King & H.Rob. (Asteraceae), popularly known as japana, is a tropical, aromatic subshrub widely used as tea to combat some diseases. The essential oil was obtained from the leaves by hydrodistillation (3 h), and the chemical composition was analyzed by gas chromatography coupled to mass spectrometry. For in vivo assays, Mus musculus/Swiss mice were used to evaluate oral acute toxicological (at dose of 2000 mg/kg); peripheral and central analgesic for abdominal contortion (doses of 6.25, 12.5, 25, 50 and 100 mg/kg), hot plate test (12.5, 25, 50, and 100 mg/kg) and formalin (25, 50 and 100 mg/kg); open field test (100 mg/kg); and anti-inflammatory by ear swelling induced by xylene (6.25,12.5, 25, 50, and 100 mg/kg). The yield of A. triplinervis essential oil (AtEO) was 4.6%, and the oxygenated monoterpene 2,5-dimethoxy-p-cymene was the major compound in this study (63.6%). AtEO at a dose of 2,000 mg/kg orally did not change the behavior patterns or mortality of the animals; liver and kidney biochemical levels were similar to the control group, indicating no liver and kidney toxicity. Moreover, AtEO, at doses of 6.25, 12.5, 25, 50, and 100 mg/kg, reduced abdominal contortions by 21%, 54%, 91%, 58%, and 55%, respectively. In the hot plate test, AtEO showed a significant increase in latency time in the 60-min interval at doses of 25 mg/kg (11.3 ± 3.3 s) and 100 mg/kg (11.9 ± 0.9 s). In the first phase of the formalin test, AtEO decreased paw licking time at doses of 25, 50, and 100 mg/kg, with inhibition of 22%, 38%, and 83%; in the second phase, the same doses, decreased licking time with inhibition of 24%, 34%, and 76%. AtEO did not present a significant change in the spontaneous locomotor activity of the animals. Doses of 6.25, 12.5, 25, 50, and 100 mg/kg significantly reduced ear edema induced by topical application of xylene with percentages of 40%, 39%, 54%, 45%, and 45%, respectively. So, AtEO demonstrated low acute oral toxicity and exhibited significant antinociceptive and anti-inflammatory actions, consistent with the use of A. triplinervis in traditional medicine.

Matrix metalloproteinases -2 and -9 expression in dogs with visceral leishmaniasis: A systematic review.

The matrix metalloproteinases (MMPs) are engaged in the degradation and remodeling of the extracellular matrix and vessels, allowing the progression of pathological processes. Recent studies pointed that MMP -2 and -9 are promising visceral leishmaniasis biomarkers. Thus, the present studystudy aimed to review published scientific literature related to MMP-2 and -9 activity on canine visceral leishmaniasis (CVL). The review followed the PRISMA method, searching for articles in ScienceDirect, PubMed, Scopus, Lilacs, Medline and Google Scholar from inception until 20 March 2022 by employing the following terms: "dog", "matrix metalloproteinases" and "Visceral Leishmaniasis" or "Kala Azar". The selected articles were read in full and only those consistent with the eligibility criteria were included in the review. Of 238 articles from the initial search, only five were deemed eligible, which were conducted between 2010 and 2018. All studies were performed in Brazil. It was observed that there was a higher expression of proMMP-2 in cerebrospinal (CS) fluid and serum and active MMP-2 in different skin areas, mainly in high parasite load areas. As for MMP-9, the pro and active forms were both expressed in CS fluid, serum and different skin areas. The MMP-2 can be considered a biomarker of bad prognostic as it plays an inflammatory role with a greater release in the initial phase of the disease, where MMP-9 is perceived in the chronic phase of CVL. Future research on the subject with greater methodological rigor and bigger sample sizes are mandatory to clarify the role of MMPs on disease progression.

Uncertainty model for automated gunshot residue particle length measurements obtained from electron microscopy images.

Currently, the use of algorithms and computer vision systems for metrological purposes has increased in different areas of knowledge to reduce human error and process deviations, consequently increasing reliability and reducing measurement uncertainties. This study presents a model for estimating the uncertainty of Feret's diameter (DF ) measurements of scanning electron microscopy (SEM) images from regular and irregular gunshot residue (GSR) particles at different magnifications. The data were extracted using the automatic measurement algorithm developed by the Brazilian Institute of Metrology, Quality and Technology (Inmetro). The proposed uncertainty model was based on the recommendations of the guide to the expression of uncertainty in measurement (GUM). The gold standard technique to identify and detect GSR particles is the SEM coupled to energy dispersive X-ray spectroscopy (SEM/EDS), which was used in the study. The low uncertainty values obtained in this study are justified by the refinement of the measurements performed at each stage of digital image procedures. The proposed uncertainty model contributes in an innovative way to the metrological evaluation of regular and irregular GSR particles at different images magnifications. The correct morphometry definition of these particles allows to study their distinction from other possible sources of GSR and, above all, their correlation with the type of ammunition used when firing the firearm. These measurement uncertainty calculations can be applied to any object images acquired by SEM, which provides more confidence in the results of measurements of the object of interest.

Use of C-reactive protein to guide the antibiotic therapy in hospitalized patients: a systematic review and meta-analysis.

BACKGROUND: C-reactive protein (CRP) is an inflammatory protein used in clinical practice to identify and monitor inflammatory and infectious processes. Recent data suggest CRP might be useful in guiding antibiotic therapy discontinuation among critical care patients. This meta-analysis analyzed the benefits and risks of CRP-guided protocols to guide antibiotic therapy in hospitalized patients in comparison with standard treatment. METHODS: Studies were searched in four databases: CENTRAL, Medline, Embase and LILACS. The search was performed until Jan 25th, 2023. The reference lists of the articles retrieved and related review studies were hand-screened to find eligible trials that might have been missed. Primary endpoints included the duration of antibiotic therapy for the index episode of infection. The secondary endpoint was the all-cause hospital mortality and infection relapses. The risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Random effects were used to pool the mean differences and odds ratio of individual studies. The protocol was registered in PROSPERO (CRD42021259977). RESULTS: The search strategy retrieved 5209 titles, out of which three studies met the eligibility criteria and were included in this meta-analysis. 727 adult patients were analyzed, of whom 278 were included in the intervention group and 449 were included in the control group. 55,7% of all patients were women. Meta-analysis indicated that experimental groups (CRP-guided) had a lower duration of antibiotic therapy (days) [MMD = -1.82, 95%IC -3.23; -0.40]; with no difference in mortality [OR = 1.19 95%IC 0.67-2.12] or in the occurrence of infection relapse [OR = 3.21 95%IC 0.85-12.05]. CONCLUSION: The use of CRP-guided protocol reduces the total amount of time required for antibiotic therapy when compared to standard protocols of treatment in hospitalized patients with acute bacterial infection. We did not observe statistical differences regarding mortality and infection relapse rates.

First record of Perkinsus marinus infecting Crassostrea sp. in Rio Grande do Norte, Brazil, using real-time PCR.

A pathogen with high virulence potential in some host species, Perkinsus marinus remains a challenge for the ecological integrity of marine ecosystems and the health of bivalve molluscs. This study investigates the occurrence of P. marinus in Crassostrea sp. in estuaries of the Potengi River and the Guaraíras lagoon in Rio Grande do Norte, Brazil. A total of 203 oyster samples that tested positive for Perkinsus sp. in Ray's fluid thioglycollate medium (RFTM) were subjected to species-specific quantitiative PCR, where 61 animals (30.05 %) presented amplification graphs with a melting temperature of 80.1 ± 0.6 °C matching the positive control. This was the first record of P. marinus in oysters in these estuaries using qPCR as a diagnostic tool.

Siparuna guianensis Essential Oil Antitumoral Activity on Ehrlich Model and Its Effect on Oxidative Stress.

This work aims to evaluate the chemical composition, in vitro antioxidant capacity, and in vivo antitumoral activity of S. guianensis essential oil against Ehrlich's ascitic carcinoma and the effects on oxidative stress. The animals (Mus musculus) received a daily dose of S. guianensis oil orally (100 mg/kg) for 9 days. The main constituents of essential oil were curzerenone (16.4±1.5 %), drimenol (13.7±0.2 %), and spathulenol (12.4±0.8 %). S. guianensis oil showed antioxidant activity, inhibiting 11.1 % of DPPH radicals (95.7 mgTE/g); and 15.5 % of the ß-carotene peroxidation. The group treated with S. guianensis showed a significant reduction in tumor cells (59.76±12.33) compared to the tumor group (96.88±19.15). Essential oil of S. guianensis decreased MDA levels and increased SOD levels in liver tissue. The essential oil of S. guianensis reduced oxidative stress, and showed antitumor and antioxidant activity, being characterized as a new chemical profile in the investigation of pathologies such as cancer.

Study Models of Drug-Drug Interactions Involving P-Glycoprotein: The Potential Benefit of P-Glycoprotein Modulation at the Kidney and Intestinal Levels.

P-glycoprotein (P-gp) is a crucial membrane transporter situated on the cell's apical surface, being responsible for eliminating xenobiotics and endobiotics. P-gp modulators are compounds that can directly or indirectly affect this protein, leading to changes in its expression and function. These modulators can act as inhibitors, inducers, or activators, potentially causing drug-drug interactions (DDIs). This comprehensive review explores diverse models and techniques used to assess drug-induced P-gp modulation. We cover several approaches, including in silico, in vitro, ex vivo, and in vivo methods, with their respective strengths and limitations. Additionally, we explore the therapeutic implications of DDIs involving P-gp, with a special focus on the renal and intestinal elimination of P-gp substrates. This involves enhancing the removal of toxic substances from proximal tubular epithelial cells into the urine or increasing the transport of compounds from enterocytes into the intestinal lumen, thereby facilitating their excretion in the feces. A better understanding of these interactions, and of the distinct techniques applied for their study, will be of utmost importance for optimizing drug therapy, consequently minimizing drug-induced adverse and toxic effects.

Instrumentation time and effectiveness of hand and rotary files in a prototyped second mandibular primary molar: A micro-CT study.

BACKGROUND: Eccentric instruments have been proposed as more effective and less time-consuming for endodontic instrumentation. AIM: To compare biomechanical outcomes of different instrumentation systems and time undertaken for instrumentation in resin prototypes. DESIGN: Sixty standardized prototypes of mandibular second primary molars were instrumented according to the following systems: K-files, ProTaper Next (PTN), XP-endo Shaper (XPS), XP-endo Finisher (XPF), XP-Clean (XPC), and Sequence Baby File (SBF; n = 10/each). Irrigation was performed with saline with simultaneous aspiration, and time spent was recorded. The prototypes were micro-CT-scanned before and after the instrumentation, and image sets were reconstructed and registered. Non-instrumented areas, accumulated debris, removed root material volume, and canal transportation were quantified. Data were analyzed through ANOVA, the Kruskal-Wallis test, and the Wilcoxon signed-rank test (α = 5%). RESULTS: K-files and SBF resulted in more instrumentation time (p < .05). SBF, XPC and PTN removed less root dentine (p < .05), but PTN left more untouched areas (p < .05). Accumulated debris were lower for XPC and SBF (p < .05). Canal transportation was similar among the groups. CONCLUSION: Rotary systems reduced instrumentation time, whereas SBF and XPC resulted in more conservative instrumentation, with less debris accumulation and non-instrumented areas. A dedicated paediatric endodontic system (SBF) outperformed eccentric instruments in terms of effectiveness.

Safety climate in the surgical center during the Covid-19 pandemic: mixed-method study.

CONTEXT: The gradual impact of the Covid-19 pandemic had important effects on routines in surgical environments. In order to cope with the impact and re-establish anaesthesiology and surgery procedures, it was imperative to pursue in-depth studies with a view to ensuring safe surgical care, reducing hazards, as well as protecting the health, safety and wellbeing of the health personnel involved. The purpose of this study was to evaluate quantitative and qualitative approaches to domains of safety climate among multi-professional staffs of surgical centres during the Covid-19 pandemic and to identify intersections. METHODS: This mixed-method project employed a concomitant triangulation strategy on a quantitative approach in an exploratory, descriptive, cross-sectional study, as well as a qualitative approach by way of a descriptive study. Data were collected using the validated, self-applicable Safety Attitudes Questionnaire/Operating Room (SAQ/OR) questionnaire and a semi-structured interview script. The 144 participants were the surgical, anaesthesiology, nursing and support teams working in the surgical centre during the Covid-19 pandemic. RESULTS: The study found an overall safety climate score of 61.94, the highest-scoring domain being 'Communication in the surgical environment' (77.91) and the lowest, 'Perception of professional performance' (23.60). On integrating the results, a difference was found between the domains 'Communication in the surgical environment' and 'Working conditions'. However, there was intersection by the 'Perception of professional performance' domain, which permeated important categories of the qualitative analysis. CONCLUSIONS: For care practice, it is hoped to encourage improved patient safety, educational interventions to strengthen the patient safety climate and promote in-job wellbeing on the job for health personnel working in surgical centres. It is suggested that further studies explore the subject in greater depth among several surgical centres with mixed methods, so as to permit future comparisons and to monitor the evolving maturity of safety climate.

Use of Teriparatide in Hyperphosphatemic Familial Tumor Calcinosis: Evaluating the Interaction Between FGF23 and PTH on the Phosphaturic Effect.

Hyperphosphatemic familial tumor calcinosis (HFTC) is a rare disease characterized by hyperphosphatemia and calcium and phosphorus crystal deposition. It occurs due to the loss of function of FGF23. Herein, we report a case of a 50-year-old woman diagnosed with HFTC (homozygous variant in the GALNT3 gene, c.803_804 C insertion) with a history of ectopic calcifications in the past 30 years. Laboratory tests on admission were as follows: phosphate (P) 7.1 mg/dL (Normal range (NR) 2.5-4.5 mg/dL), FGF23 c-terminal 2050 RU/mL (NR < 150 RU/mL), and intact FGF23 (iFGF23) 18.93 pg/mL (NR 12.0-69.0 pg/mL). Treatment with acetazolamide, sevelamer, and a phosphorus-restricted diet was started, but phosphatemia remained high and calcifications continued to progress. In an attempt to further decrease P, a 36-day cycle of teriparatide (TPTD) 20 mcg twice daily was added, decreasing P from 6.2 to 5.2 mg/dL and increasing the 1.25(OH)2 vitamin D by 34.2%. As urinalysis was not feasible at the end of the 36-day cycle, a second cycle was performed for another 28 days, producing a similar decrease in P (from 6.4 to 5.5 mg/mL) and an evident decrease in the rate of tubular reabsorption of P (from 97.2 to 85.3%), however, accompanied by a worrying increase in calciuria. The use of TPTD 20 mcg twice daily in a patient with genetic resistance to FGF23 (HFTC) was associated with consistent increase in phosphaturia and reduction in phosphatemia, in addition to an increase in calcitriol. The resulting hypercalciuria precludes the therapeutic use of TPTD in HFTC and suggests an important role of FGF23, not only in phosphate homeostasis but also in avoiding any excess of calcitriol.

Genomic, biochemical, and phylogenetic evaluation of bacteria isolated from deep-sea sediment harboring methane hydrates.

Over half of the organic carbon on Earth's surface is trapped in marine sediment as methane hydrates. Ocean warming causes hydrate dissociation and methane leakage to the water column, rendering the characterization of microbes from hydrate depositions a pressing matter. Through genomic, phylogenetic, and biochemical assays, we characterize the first microorganisms isolated from the Rio Grande Cone (Brazil), reservoir responsible for massive methane releases to the water column. From sediment harboring rich benthic communities, we obtained 43 strains of Brevibacillus sp., Paenibacillus sp. and groups of Bacillus sp. Methane-enriched samples yielded strains of the Pseudomonas fluorescens complex, exhibiting fluorescent siderophore production and broad multi-carbon catabolism. Genomic characterization of a novel Pseudomonas sp. strain indicated 32 genes not identified in the closest related type-species, including proteins involved with mercury resistance. Our results provide phylogenetic and genomic insights on the first bacterial isolates retrieved from a poorly explored region of the South Atlantic Ocean.

Pro-Oxidant and Cytotoxic Effects of Tucum-Do-Cerrado (Bactris setosa Mart.) Extracts in Colorectal Adenocarcinoma Caco-2 Cells.

Colorectal cancer is one of the most common types of cancer. Bioactive natural compounds can act in cancer chemoprevention as tumor growth inhibitors. Tucum-do-cerrado (Bactris setosa Mart.) is a Brazilian fruit that contains several phenolic compounds. This study investigated the effect of tucum aqueous extract in Caco-2 cells in comparison to primary human intestinal organoids and fibroblasts. Cells were exposed to 0.5 and 1 mg/ml of tucum aqueous extract for 24 h. ROS production, mRNA levels for SOD1 and SOD2, CAT, GPX1, NFE2L2, HIF1A and NOS2 were evaluated in Caco-2 cells exposed to tucum extract. Cell viability of Caco-2 cells was decreased upon tucum extract exposure. Mitochondrial ROS levels increased in Caco-2 cells exposed to tucum extract. The mRNA levels of SOD1, SOD2, CAT, GPX, NFE2L2 and HIF1A were downregulated in Caco-2 cells exposed to tucum extract, while NOS2 mRNA levels remained unchanged. Protein levels of SOD2, CAT and NRF2 remained unchanged in Caco-2 cells treated with tucum extract, indicating that catalase and SOD2 cellular functions may be unaffected by the tucum extract at 24 h, of exposure. Aqueous extract of tucum-do-cerrado may induce cellular toxicity in a cancer cell-specific manner, possibly through increased mitochondrial ROS production and gene expression regulation.

Biochemical features and early adhesion of marine Candida parapsilosis strains on high-density polyethylene.

AIMS: Plastic debris are constantly released into oceans where, due to weathering processes, they suffer fragmentation into micro- and nanoplastics. Diverse microbes often colonize these persisting fragments, contributing to their degradation. However, there are scarce reports regarding the biofilm formation of eukaryotic decomposing microorganisms on plastics. Here, we evaluated five yeast isolates from deep-sea sediment for catabolic properties and early adhesion ability on high-density polyethylene (HDPE). METHODS AND RESULTS: We assessed yeast catabolic features and adhesion ability on HDPE fragments subjected to abiotic weathering. Adhered cells were evaluated through Crystal Violet Assay, Scanning Electron Microscopy, Atomic Force Microscopy and Infrared Spectroscopy. Isolates were identified as Candida parapsilosis and exhibited wide catabolic capacity. Two isolates showed high adhesion ability on HDPE, consistently higher than the reference C. parapsilosis strain, despite an increase in fragment roughness due to weathering. Isolate Y5 displayed the most efficient colonization, with production of polysaccharides and lipids after 48 h of incubation. CONCLUSION: This work provides insights on catabolic metabolism and initial yeast-HDPE interactions of marine C. parapsilosis strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings represent an essential contribution to the characterization of early interactions between deep-sea undescribed yeast strains and plastic pollutants found in oceans.

Local understandings of PTSD and complex PTSD among health professionals working with adolescents in violent neighbourhoods of São Paulo city, Brazil.

BACKGROUND: Adolescents in low-resource urban settings in Brazil are often exposed to high levels of trauma that can result in post-traumatic stress disorder (PTSD). However, preliminary evidence indicates that PTSD tends to be under-reported in Brazilian health services, despite the high prevalence of trauma. Additionally, little is known about the perceived applicability among clinicians of the new ICD-11 diagnosis of complex PTSD (CPTSD), despite its potential relevance for contexts of chronic trauma. The current study investigated local understandings of PTSD and CPTSD among health professionals working with adolescents in violent neighbourhoods of São Paulo city. METHODS: Semi-structured interviews were conducted with 58 health professionals working at both the primary care and specialized mental health levels in two areas of São Paulo city with high levels of community violence. RESULTS: Most participants knew about PTSD, but most did not know about CPTSD. There were mixed views concerning the commonality of PTSD among adolescents exposed to community violence. Many participants reported having no experience working with patients with the PTSD diagnosis. According to some, community violence was normalized by adolescents and health professionals, and did not result in PTSD. Others highlighted how they did not use psychiatric diagnoses in their practice, had critical perspectives towards psychiatric diagnoses and/or PTSD, or simply knew little about PTSD. Furthermore, many highlighted how the chronic nature of multiple traumas experienced by adolescents often resulted in complex clinical presentations characterised by many symptoms beyond PTSD. The diagnosis of CPTSD was considered appropriate to the context by many participants as it captured the complex traumatic histories and symptom presentations of adolescents exposed to community violence in Brazil. CONCLUSIONS: These findings have important implications for the assessment and treatment of mental health among adolescents exposed to community violence in Brazil.

Cognitive impairment and markers of optical neurodegeneration in early multiple sclerosis.

INTRODUCTION: Cognitive impairment and retinal atrophy have been proposed as two potential markers of neurodegeneration in multiple sclerosis (MS). We aimed at assessing the relation between peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer (mGCL) atrophy and cognitive performance in early MS. METHODS: This is a multicenter cross-sectional study on patients with early MS (clinically isolated syndrome and relapsing-remitting MS), with an EDSS score ≤ 3.0. Patients with previous optic neuritis, other ocular diseases, psychiatric illness, or recent relapse were excluded. All patients underwent standardized optical coherence tomography (OCT) and neuropsychological evaluation with validated tests for MS patients. Cognitive impairment was defined as having two cognitive tasks below age- and education-adjusted norms. RESULTS: We recruited 52 patients with early MS, with an average age of 37 years (SD = 10.5), an average disease duration of 3.69 years (SD = 2.3), and a median EDSS of 1.0 (IQR = 0.5). In this sample, 15/52 patients presented cognitive impairment. Regarding OCT measurements, 7/52 patients had an average pRNFL below the 5th percentile and 2/52 had an average mGCL below the 5th percentile. The average pRNFL thickness was comparable in cognitively impaired and cognitively preserved patients (100.3 µm vs 103.1 µm, p = 0.52); the average mGCL thickness had also similar values between groups (50.5 µm vs 53 µm, p = 0.38). CONCLUSIONS: Cognitive impairment was frequent in our sample of early MS. However, no association with reduced pRNFL or mGCL thickness was found. When compared to OCT, cognitive assessment could provide an earlier marker of neurodegeneration in MS.