Search

Angola, a country grappling with prevalent tropical diseases such as malaria, is witnessing an alarming rise in cancer-related deaths. Despite the escalating significance of cancer globally and in Angola, the nation's medical schools lack compulsory oncology disciplines in their curricula. This absence compromises the comprehensive training of medical students, preventing the development of integrated perspectives and skills crucial for addressing the growing cancer burden. This article, authored by the Angolan Oncology Research Group (AORG), proposes an oncology program for undergraduate medical students in Angola, aiming to bridge the educational gap. The program outlines discipline objectives, topics to be covered, class formats, and workload considerations. [ABSTRACT FROM AUTHOR]

Hyptis suaveolens (L.) Poit is known for containing podophyllotoxin (PTOX), a natural lignan used as the lead compound in antitumor agent preparations, in its roots. The use of phloroglucinol (PHL) and indoleamines, such as melatonin (MEL) and serotonin (SER), in plant tissue culture is a promising alternative for eliciting rare and high-value secondary metabolites of medical importance. Aimed to evaluate the impact of different concentrations of PHL, either alone or in combination with MEL or SER, on the growth and accumulation of PTOX in H. suaveolens. Apical segments were vertically inoculated in MS medium containing different concentrations of MEL or SER (0; 0.25; 0.50; 1.00; 5.00 and 10.00 µM) and PHL (0 and 50 mg L-1). After 40 days, growth parameters, chlorophyll content and PTOX content were assessed. Plantlet rooting and root dry weight notably increased with the use of 0.5 µM MEL alongside PHL. Overall, treatments containing PHL showed superior results, except for chlorophyll content. SER supplementation was effective in increasing root growth, root number and leaf area. The combination of 1.0 µM MEL or SER and 50 mg L-1 PHL increased the production of PTOX in the roots of H. suaveolens by 2.0 and 1.6 times, respectively. In conclusion, the application of PHL and indoleamines demonstrated an eliciting effect on both growth and PTOX production in H. suaveolens roots, presenting a promising avenue for further research and application in eliciting targeted secondary metabolites.Key message: The application of phloroglucinol and indoleamines, such as melatonin (MEL) and serotonin (SER), demonstrated an eliciting effect on both growth and podophylotoxin production in Hyptis suaveolens roots. [ABSTRACT FROM AUTHOR]

This study investigates the impact of three key variables on the performance of nanoporous AM-3 and layered AM-4 titanosilicates in removing nine REEs (Y, La, Ce, Pr, Nd, Eu, Gd, Tb, and Dy) from natural mineral water and identifies optimal operational conditions using Response Surface Methodology (RSM). The experimental conditions were determined by a Box-Behnken Design of 3 factors-3 levels (pH 4, 6, and 8; sorbent dose 20, 100, and 180 mg/L; and element concentration 1, 3, and 5 μmol/L). Three-dimensional response surfaces were used to assess the linear, quadratic, and interaction influences of each factor on the REEs' removal percentage. The pH was the most significant factor in the removal process using AM-3, while the sorbent dose was more important for AM-4. The results highlighted the sorbents' strong capacity for REE removal. The optimal operating conditions obtained by RSM were applied to aqueous solutions with salinity 10 (common in coastal and transitional systems) and 30 (average seawater salinity). The results showed that AM-3 has a strong potential for removing REEs in solutions with salinity 10 and 30, while AM-4 was less efficient due to competition between REEs and other ions present in the solution. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) has been shown to affect a series of cognitive processes including memory, increasing the risk for dementia, particularly Alzheimer's disease (AD). Although increasing evidence has supported that both diseases share common features, the pathophysiological mechanisms connecting these two disorders remain to be fully elucidated. Herein, we used Drosophila melanogaster fed on a high-sugar diet (HSD) to mimic T2DM, and investigate its effects on memory as well as identify potential molecular players associated with the memory deficits induced by HSD. Flies hatched from and reared on HSD for 7 days had a substantial decrease in short-term memory (STM). The screening for memory-related genes using transcriptome data revealed that HSD altered the expression of 33% of memory genes in relation to the control. Among the differentially expressed genes (DEGs) with a fold change (FC) higher than two, we found five genes, related to synapse and memory trace formation, that could be considered strong candidates to underlie the STM deficits in HSD flies: Abl tyrosine kinase (Abl), bruchpilot (Brp), minibrain (Mnb), shaker (Sh), and gilgamesh (Gish). We also analyzed genes from the dopamine system, one of the most relevant signaling pathways for olfactory memory. Interestingly, the flies fed on HSD presented a decreased expression of the Tyrosine hydroxylase (Ple) and Dopa decarboxylase (Ddc) genes, signals of a possible dopamine deficiency. In this work, we present promising biomarkers to investigate molecular networks shared between T2DM and AD. [ABSTRACT FROM AUTHOR]

Hypoxia plays a significant role in the development of various cerebral diseases, many of which are associated with the potential risk of recurrence due to mitochondrial damage. Conventional drug treatments are not always effective for hypoxia-related brain diseases, necessitating the exploration of alternative compounds. In this study, we investigated the potential of diphenyl diselenide [(PhSe)2] to ameliorate locomotor impairments and mitigate brain mitochondrial dysfunction in zebrafish subjected to hypoxia. Additionally, we explored whether these improvements could confer resistance to recurrent hypoxia. Through a screening process, an appropriate dose of (PhSe)2 was determined, and animals exposed to hypoxia received a single intraperitoneal injection of 100 mg/kg of the compound or vehicle. After 1 h from the injection, evaluations were conducted on locomotor deficits, (PhSe)2 content, mitochondrial electron transport system, and mitochondrial viability in the brain. The animals were subsequently exposed to recurrent hypoxia to assess the latency time to hypoxia symptoms. The findings revealed that (PhSe)2 effectively crossed the blood–brain barrier, attenuated locomotor deficits induced by hypoxia, and improved brain mitochondrial respiration by modulating complex III. Furthermore, it enhanced mitochondrial viability in the telencephalon, contributing to greater resistance to recurrent hypoxia. These results demonstrate the beneficial effects of (PhSe)2 on both hypoxia and recurrent hypoxia, with cerebral mitochondria being a critical target of its action. Considering the involvement of brain hypoxia in numerous pathologies, (PhSe)2 should be further tested to determine its effectiveness as a potential treatment for hypoxia-related brain diseases. [ABSTRACT FROM AUTHOR]

Light is one of the factors that influence the growth, development and synthesis of secondary metabolites of different plant species in vitro. Origanum majorana is an aromatic plant belonging to a group of plants that produce arbutin, a substance of importance in the cosmetic industry. The objective of this study was to verify the effect of light intensity and wavelength on the growth and accumulation of arbutin in vitro in plantlets. Nodal segments were grown in MS culture medium under photon flux densities of 26, 51, 69, 94 and 130 µmol m−2 s−1. In the light spectrum, nodal segments were grown under different light-emitting diodes LED: red; blue; a combination of blue and red light (30% B:70% R; 50% B:50% R; 70% B:30% R); and white, yellow and green. After 40 days, the growth, photosynthetic pigments and arbutin accumulation were evaluated by HPLC-DAD. The lowest light intensity (26 µmol m−2 s−1) provided a higher content of photosynthetic pigments, and the intensity of 94 µmol m−2 s−1 increased dry biomass accumulation. Greater accumulation of arbutin was observed under a higher light intensity of 130 µmol m−2 s−1. Regarding the quality of light, different wavelengths did not significantly affect the number of shoots or shoot length. The white light spectrum stimulated a greater accumulation of dry biomass. The green light provided a greater accumulation of photosynthetic pigments. The amount of arbutin was influenced by the different light spectra. The red spectrum promoted the highest arbutin content, and the yellow inhibited.Key message: The intensity of 94 µmol m−2 s−1 increased dry biomass and 130 µmol m−2 s−1 increased arbutin accumulation. The red spectrum promoted the highest arbutin content, and the yellow inhibited. [ABSTRACT FROM AUTHOR]

Clarisia racemosa Ruiz & Pav is a neotropical species found in humid forests from southern Mexico to southern Brazil. There are few studies related to the ethnopharmacological use of C. racemosa. Our objective was to evaluate the hydroalcoholic extract of C. racemosa as a potential antiparasitic agent. For this, we performed in vitro assays against strains of Leishmania amazonensis, Trypanosoma cruzi, Plasmodium falciparum, and Schistosoma mansoni. At the same time, immunomodulatory activity tests were carried out. The results demonstrated that the extract was able to stimulate and activate immune cells. In preliminary antiparasitic tests, structural modifications were observed in the promastigote form of L. amazonensis and in adult worms of S. mansoni. The extract was able to inhibit the growth of trypomastigote form of T. cruzi and finally showed low antiparasitic activity against strains of P. falciparum. It is pioneering work and these results demonstrate that C. racemosa extract is a promising alternative and contributes to the arsenal of possible forms of treatment to combat parasites. [ABSTRACT FROM AUTHOR]

Worldwide, forests are vital in the regulation of the water cycle regulation and in water balance allocation. Knowledge of ecohydrological responses of production forests is essential to support management strategies, especially where water is already scarce. Shifting climatological patterns are expected to impact thermopluviometric regimes, water cycle components, hydrological responses, and plant physiology, evapotranspiration rates, crop productivity and land management operations. This work (1) assessed the impacts of different predicted climate conditions on water yield; (2) inferred the impacts of climate change on biomass production on eucalypt-to-eucalypt succession. To this end, the widely accepted Soil and Water Assessment Tool (SWAT) was run with the RCA, HIRHAM5 and RACMO climate models for two emission scenarios (RCP 4.5 and 8.5). Three 12-year periods were considered to simulate tree growth under coppice regime. The results revealed an overall reduction in streamflow and water yield in the catchment in line with the projected reduction in total annual precipitation. Moreover, HIRHAM5 and RACMO models forecast a slight shift in seasonal streamflow of up to 2 months (for 2024–2048) in line with the projected increase in precipitation from May to September. For biomass production, the extreme climate model (RCA) and severe emission scenario (RCP 8.5) predicted a decrease up to 46%. However, in the less extreme and more-correlated (with actual catchment climate conditions) climate models (RACMO and HIRHAM5) and in the less extreme emission scenario (RCP 4.5), biomass production increased (up to 20%), and the growth cycle was slightly reduced. SWAT was proven to be a valuable tool to assess climate change impacts on a eucalypt-dominated catchment and is a suitable decision-support tool for forest managers. [ABSTRACT FROM AUTHOR]

Information and Communication Technologies (ICT) is an important tool to reduce loneliness among older adults. One possibility for introducing them to ICT is via digital games (DG). To evaluate the effects of practicing DG during computer classes on loneliness among individuals older than 50 years. Longitudinal study, in which data from 36 students of an aging care center (72.22% female), aged between 51 and 87 years old (mean = 62.47 years old), enrolled in computer classes for beginners were analysed. Four games were used during intervention: Coincident Timing, Motor Skill Analyser, Labyrinth and Fitts. A characterization questionnaire and the short version of the Social and Emotional Loneliness Scale for Adults (SELSA-S), which comprises romantic, familial and social loneliness, were used. The statistical analysis compared the evolution in loneliness between three moments of data collection. The test ANOVA for repeated measures indicated differences between the moments of data collection for Romantic loneliness (F (1.64, 57.31) = 6.75, p = 0.004) and Friedman test for Familial loneliness (X2 = 21.46, p < 0.001) and SELSA-S total (X2 = 7.35, p = 0.025). No change was observed for Social loneliness. There was an increase in Romantic loneliness and a decrease in Familial loneliness along the three moment of data collection. For general loneliness, SELSA-S total score pointed a decrease in general loneliness after computer classes, followed by a slight increase after adding the DG.Computer classes reduced loneliness of individuals aged 50 and older, but practicing digital games during computer classes did not potentiate this effect. [ABSTRACT FROM AUTHOR]

Developmental methylmercury (MeHg) exposures cause latent neurotoxic effects in adults; however, the mechanisms underlying the latent neurotoxicity are not fully understood. In the current study, we used C. elegans as an animal model to investigate the latent neurotoxic effects of developmental MeHg exposures on glutamatergic neurons. The young larvae stage 1 worms were exposed to MeHg (0.05 ~ 5 µM) for 48 h. The morphological and behavioral endpoints of glutamatergic neurons were compared when worms reached to adult stages including the young adult stage (day 1 adult) and the old adult stage (day 10 adult). Here, we showed that C. elegans glutamatergic neurons were morphologically intact following low or medium MeHg exposures (0.05 ~ 0.5 µM). The morphological damage of glutamatergic neurons appeared to be pronounced in day 10 adults developmentally exposed to 5 µM MeHg. Behavioral assays also showed an age-dependent latent effect of MeHg. In the nose touch response assay, only day 10 adult worms exhibited a functional decline following prior 5 µM MeHg exposure. Moreover, the disruption of NaCl memory appeared only in day 1 adults following MeHg exposures but not in day 10 adults. The expression of C. elegans homologs of mammalian vesicular glutamate transporter (eat-4) was repressed in day 1 adults, while the glutamate receptor homolog (glr-1) was upregulated in day 10 adults with 5 µM MeHg. In the comparison of age-dependent changes in the insulin-like pathway (daf-2/age-1/daf-16) following MeHg exposures, we showed that the daf-2/age-1/daf-16 pathway was mobilized in day 1 adults but repressed in day 10 adults. Collectively, our data supports a conclusion that MeHg-induced glutamatergic neurotoxicity exhibits an age-dependent pattern, possibly related to the prominent changes in age-dependent modulation in the glutamatergic neurotransmission and metabolic pathways. [ABSTRACT FROM AUTHOR]

Backgroud: Peripheral arterial disease can progress to critical limb ischemia, which requires revascularization. The endovascular approach is associated with a lower long-term patency due to restenosis resulting from neointimal hyperplasia. Statins offer significant advantages in patients undergoing percutaneous interventions. However, there are few studies on statin therapy associated with improved clinical outcomes after endovascular treatment in this patients. Aim: This systematic review and meta-analysis examined the effects of statins (in comparison with no statin) on outcomes of lower-limb arterial angioplasty by evaluating patency, amputation and mortality. Method: We searched MEDLINE, Academic Search Premier and CINAHL using a predetermined search strategy from inception to September 21, 2022. Study selection (first by title and abstract and then by full text) and data extraction was conducted by two independent reviewers. Risk of bias was assessed using the Newcastle-Ottawa Scale. According to data availability, we conducted meta-analysis using RevMan v.5.4. Results: The search identified 841 relevant articles and included 10 studies with 43,543 patients. Statin use in patients before undergoing lower-limb arterial angioplasty was associated with improved primary patency at 12 (12.57%, 95% confidence interval [CI] 6.86–18.28, p < 0.0001) and 24 months (7.19%, 95% CI 1.02–13.37, p = 0.02), decreased mortality in 39% at 12 months (relative risk (RR): 0.61, 95% CI 0.55–0.74, p < 0.00001) and decreased limb loss in 23% in the studied patients (RR: 0.77, 95% CI 0.65–0.91, p = 0.003). Conclusion: Statin therapy before the procedure was associated with significantly improved patency and overall survival and decreased limb loss after lower-limb arterial angioplasty. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 proteases Mpro and PLpro are important targets for the development of antivirals against COVID-19. The functional group 1,2,4-thiadiazole has been indicated to inhibit cysteinyl proteases, such as papain and cathepsins. Of note, the 1,2,4-thiadiazole moiety is found in a new class of cephalosporin FDA-approved antibiotics: ceftaroline fosamil, ceftobiprole, and ceftobiprole medocaril. Here we investigated the interaction of these new antibiotics and their main metabolites with the SARS-CoV-2 proteases by molecular docking, molecular dynamics (MD), and density functional theory (DFT) calculations. Our results indicated the PLpro enzyme as a better in silico target for the new antibacterial cephalosporins. The results with ceftaroline fosamil and the dephosphorylate metabolite compounds should be tested as potential inhibitor of PLpro, Mpro, and SARS-CoV-2 replication in vitro. In addition, the data here reported can help in the design of new potential drugs against COVID-19 by exploiting the S atom reactivity in the 1,2,4-thiadiazole moiety. [ABSTRACT FROM AUTHOR]

The papain-like protease (PLpro) from SARS-CoV-2 is an important target for the development of antivirals against COVID-19. The safe drug disulfiram (DSF) presents antiviral activity inhibiting PLpro in vitro, and it is under clinical trial studies, indicating to be a promising anti-COVID-19 drug. In this work, we aimed to understand the mechanism of PLpro inhibition by DSF and verify if DSF metabolites and derivatives could be potential inhibitors too. Molecular docking, DFT, and ADMET techniques were applied. The carbamoylation of the active site cysteine residue by DSF metabolite (DETC-MeSO) is kinetically and thermodynamically favorable (ΔG‡ = 3.15 and ΔG = − 12.10 kcal mol-1, respectively). Our results strongly suggest that the sulfoxide metabolites from DSF are promising covalent inhibitors of PLpro and should be tested in in vitro and in vivo assays to confirm their antiviral action. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) neurotoxicity exhibits age-dependent effects with a latent and/or persistent neurotoxic effect on aged animals. Individual susceptibility to MeHg neurotoxicity is governed by both exposure duration and genetic factors that can magnify or mitigate the pathologic processes associated with this exposure. We previously showed the G2019S mutation of leucine-rich repeat kinase 2 (LRRK2) modulates the response of worms to high levels of MeHg, mitigating its effect on neuronal morphology in pre-vesicles in cephalic (CEP) dopaminergic neurons. Here we sought to better understand the long-term effects of MeHg exposure at low levels (100-fold lower than that in our previous report) and the modulatory role of the LRRK2 mutation. Worms exposed to MeHg (10 or 50 nM) at the larval stage (L1 stage) were compared at adult stages (young age: day 1 adult; middle age: day 5 adult; old age: day 10 adult) for the swimming speeds in M9 buffer, moving speeds during locomotion on an OP50-seeded plate, and the numbers of CEP dopaminergic pre-vesicles, vesicular structures originating from the dendrites of CEP for exportation of cellular content. In addition, the expression levels of Caenorhabditis elegans homologs of dopamine transporter (dat-1) and tyrosine hydroxylase (cat-2) were also analyzed at these adult stages. Our data showed that swimming speeds were reduced in wild-type worms at the day 10 adult stage at 50 nM MeHg level; yet, reduced swimming speeds were noted in the G2019S LRRK2 transgenic line upon MeHg exposures as low as 10 nM. Compared to locomotor speeds, swimming speeds appear to be more sensitive to the behavioral effects of developmental MeHg exposures, as the locomotor speeds were largely intact and indistinguishable from controls following MeHg exposures. Furthermore, we showed an age-dependent modulation of dat-1 and cat-2 expressions, which could also be modified by the LRRK2 mutation. Although MeHg exposures did not change the number of pre-vesicles, the LRRK2 mutation was associated with increased numbers of pre-vesicles in aged worms. Our data suggest that the latent behavioral effects of MeHg are sensitized by the G2019S LRRK2 mutation, and the underlying mechanism likely involves age-dependent changes in dopaminergic signaling. [ABSTRACT FROM AUTHOR]

The molecular mechanisms underlying circuit re-wiring in the mature brain remains ill-defined. An eloquent example of adult circuit remodelling is the hippocampal mossy fiber (MF) sprouting found in diseases such as temporal lobe epilepsy. The molecular determinants underlying this retrograde re-wiring remain unclear. This may involve signaling system(s) controlling axon specification/growth during neurodevelopment reactivated during epileptogenesis. Since adenosine A2A receptors (A2AR) control axon formation/outgrowth and synapse stabilization during development, we now examined the contribution of A2AR to MF sprouting. A2AR blockade significantly attenuated status epilepticus(SE)-induced MF sprouting in a rat pilocarpine model. This involves A2AR located in dentate granule cells since their knockdown selectively in dentate granule cells reduced MF sprouting, most likely through the ability of A2AR to induce the formation/outgrowth of abnormal secondary axons found in rat hippocampal neurons. These A2AR should be activated by extracellular ATP-derived adenosine since a similar prevention/attenuation of SE-induced hippocampal MF sprouting was observed in CD73 knockout mice. These findings demonstrate that A2AR contribute to epilepsy-related MF sprouting, most likely through the reactivation of the ability of A2AR to control axon formation/outgrowth observed during neurodevelopment. These results frame the CD73-A2AR axis as a regulator of circuit remodeling in the mature brain. [ABSTRACT FROM AUTHOR]

The effects of sumac, cumin, black pepper and red pepper diethyl ether extracts on the growth of eight foodborne pathogens (FBP) and their biogenic amine (BA) production were investigated in histidine decarboxylase broth. The antimicrobial effect was determined by the minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations. Sumac extract showed the highest antimicrobial activity against FBP. Enterococcus faecalis and Aeromonas hydrophila were the most susceptible strains to sumac extract. The MBC of spice extracts on the FBP was generally above 50 mg/mL. Cumin extract was the most effective in decreasing bacterial loads, inhibiting significantly the microbial growth of Staphylococcus aureus, Pseudomonas aeruginosa, Campylobacter jejuni and A. hydrophila. Histamine production ranged from 0.14 (Yersinia enterocolitica) to 39.29 mg/L (S. aureus). Cumin extract significantly inhibited the histamine formation by S. aureus and Salmonella paratyphi A. Black and red pepper extracts promoted the histamine formation by most of FBP under scrutiny. Red pepper extract generally increased formation of BA, while sumac and cumin extracts proved to be the most effective antimicrobials and BA formation inhibitors. This research study allowed to conclude that sumac and cumin extracts can be used as natural preservatives in the agro-food industry. [ABSTRACT FROM AUTHOR]

Human exposure to the neurotoxin methylmercury (MeHg) poses a significant health risk to the development of the nervous system. The mechanisms of MeHg-induced neurotoxicity are associated with the disruption of cellular homeostasis, and include oxidative stress, loss of calcium homeostasis, and impaired protein quality control. The stress inducible protein 1 (STI-1) is involved in the regulation of protein quality control by acting as a protein cochaperone to maintain optimal protein unfolding and refolding. Here, we utilized the Caenorhabditis elegans (C. elegans) model of MeHg toxicity to characterize the role of the sti-1 gene in MeHg-induced toxicity. We showed that lifespan and developmental milestone timings were significantly altered in sti-1 knockout (KO) animals with MeHg exposure. However, knocking down sti-1 by RNAi did not result in an analogous effect for lifespan, but did still sensitize to delays in developmental milestone progression by acute MeHg, suggesting that insufficiency of sti-1 does not recapitulate all phenotypes of the null mutation. Furthermore, inhibition of ATP levels by MeHg exposure was modulated by sti-1. Considering that the skn-1/gst-4 pathway is highly involved in metal's toxicity, such pathway was also explored in our model. We showed that sti-1 mutant worms exhibited impaired capacity to upregulate the antioxidant genes skn-1/gst-4, highlighting a central role of sti-1 in modulating antioxidant response. Lastly, we showed that loss-of-function mutation in the rrf-3 gene, which encodes a putative RNA-directed RNA polymerase, has significant effect in altering MeHg-induced toxicity by potentiating the animal's detoxification system. Altogether, our novel data show an indispensable role of protein quality control in the defense against MeHg toxicity. [ABSTRACT FROM AUTHOR]

Populations of Culex quinquefasciatus Say, 1823 (Diptera: Culicidae) have shown resistance to insecticides of the carbamate and organophosphate classes. The objective of this study was to assess the susceptibility of C. quinquefasciatus larvae to essential oils from leaves of Eugenia uniflora L., Melaleuca armillaris (Sol. ex Gaertn.) Sm., and Schinus molle L and C. quinquefasciatus larvae's biochemical responses after their exposure to these leaves. The essential oils were chemically analyzed by GC and GC/MS. First, the lethal concentration for 50% (LC50) values was estimated using different concentrations of essential oils and probit analysis. The larvae were exposed for 1 h at the LC50 estimated for each essential oil. The susceptibility of the larvae to essential oils was evaluated using the following biochemical parameters: concentrations of total protein and reduced glutathione; levels of production of hydrogen peroxide and lipid peroxidation; and the activity of the enzyme acetylcholinesterase (AChE). The main chemical constituents in E. uniflora were E-β-ocimene, curzerene, germacrene B, and germacrone; in M. armillaris were 1,8-cineole and terpinolene; and in S. molle were sabinene, myrcene, and sylvestrene. The essential oils had LC50 values between 31.52 and 60.08 mg/L, all of which were considered effective. All of them also promoted changes in biochemical parameters when compared to the control treatment. The essential oils of S. molle and E. uniflora inhibited the activity of the AChE enzyme, and the essential oil of M. armillaris increased it. All essential oils had larvicidal activity against C. quinquefasciatus, but the essential oil of E. uniflora was the most efficient. Thus, the findings of the present study suggest that the essential oil of E. uniflora can be considered promising for the development of botanical larvicides. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) is a global pollutant, which can cause damage to the central nervous system at both high-acute and chronic-low exposures, especially in vulnerable populations, such as children and pregnant women. Nowadays, acute-high poisoning is rare. However, chronic exposure to low MeHg concentrations via fish consumption remains a health concern. Current therapeutic strategies for MeHg poisoning are based on the use of chelators. However, these therapies have limited efficacy. Ghrelin is a gut hormone with an important role in regulating physiologic processes. It has been reported that ghrelin plays a protective role against the toxicity of several xenobiotics. Here, we explored the role of ghrelin as a putative protector against MeHg-induced oxidative stress. Our data show that ghrelin was able to ameliorate MeHg-induced reactive oxygen species (ROS) production in primary neuronal hypothalamic and hippocampal cultures. An analogous effect was observed in mouse hypothalamic neuronal GT 1–7 cells. Using this model, our novel findings show that antioxidant protection of ghrelin against MeHg is mediated by glutathione upregulation and induction of the NRF2/NQO1 pathway. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in parkin is associated with onset of juvenile Parkinson's disease (PD). Resveratrol is a polyphenolic stilbene with neuroprotective activity. Here, we evaluated the rescue action of resveratrol in parkin mutant D. melanogaster. The control flies (w1118) received diet-containing 2% ethanol (vehicle), while the PD flies received diets-containing resveratrol (15, 30 and 60 mg/kg diet) for 21 days to assess survival rate. Consequently, similar treatments were carried out for 10 days to evaluate locomotor activity, oxidative stress and antioxidant markers. We also determined mRNA levels of Superoxide dismutase 1 (Sod1, an antioxidant gene) and ple, which encodes tyrosine hydroxylase, the rate-limiting step in dopamine synthesis. Our data showed that resveratrol improved survival rate and climbing activity of PD flies compared to untreated PD flies. Additionally, resveratrol protected against decreased activities of acetylcholinesterase and catalase and levels of non-protein thiols and total thiols displayed by PD flies. Moreover, resveratrol mitigated against parkin mutant-induced accumulations of hydrogen peroxide, nitric oxide and malondialdehyde. Resveratrol attenuated downregulation of ple and Sod1 and reduction in mitochondrial fluorescence intensity displayed by PD flies. Overall, resveratrol alleviated oxidative stress and locomotor deficit associated with parkin loss-of-function mutation and therefore might be useful for the management of PD. [ABSTRACT FROM AUTHOR]

African eggplant (Solanum macrocarpon L) (AE) and Black Nightshade (Solanum nigrum L) (BN) leaves are green leafy vegetables with nutritional and ethnobotanical values. We have previously characterized the vegetables via HPLC/LC-MS to reveal notable phenolic acids, flavonoids and alkaloids. In this present study, we addressed the efficacy of the two vegetables in mitigating mercuric chloride (HgCl2)-induced neurotoxicity and memory impairment in Drosophila melanogaster. Flies were exposed to HgCl2 (0.30 mg/g) alone or in combination with the vegetables (0.1 and 1.0%) of both samples in their diets for seven days. The results showed that HgCl2 (Hg)-exposed flies had significantly reduced survival rate and memory index, which were ameliorated in the Hg-exposed flies fed AE or BN. This was accompanied by increased reactive oxygen species (ROS) levels, reduced total thiol, as well as catalase, glutathione transferase (GST) and acetylcholine esterase (AChE) activities in Hg-exposed fly heads, but ameliorated in Hg-exposed flies fed dietary inclusions of the vegetables. In addition, the Hg-induced alterations in SOD, NF-ҝB/Relish, Dronc and Reaper mRNA levels were statistically indistinguishable from controls in Hg-treated flies fed diets containing AE or BN. Normalization of cnc/Nrf2 and FOXO were observed only in Hg-treated flies fed BN. These findings suggest that dietary AE or BN leaves offer protection against Hg-induced memory impairment and neurotoxicity in D. melanogaster, and further justify them as functional foods with neuroprotective properties. [ABSTRACT FROM AUTHOR]

Predictive maintenance techniques allow monitoring machines without the need to interrupt its operation, reducing the frequency of corrective maintenance interventions. This work proposes a noninvasive vibration detection system to analyze the state of a three-phase electric powered centrifugal pumps using a micro-electro-mechanical system sensor composed of three-axial accelerometer and gyroscope. The structural analysis is used to extracting time domain signal characteristics. Classification experiments were performed in order to analyze the signal discrimination power for different machine conditions. The results show that using the signals from accelerometers and gyroscopes improves the performance of the classifiers, achieving more than 98% correct condition classification and 100% pump classification. In addition, using the SCM structural analysis method as feature extraction is fast and produces a relative small feature dimension enabling it to be used in embedded systems. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) is a ubiquitous environmental neurotoxicant whose mechanisms of action involve oxidation of endogenous nucleophilic groups (mainly thiols and selenols), depletion of antioxidant defenses, and disruption of neurotransmitter homeostasis. Diphenyl diselenide—(PhSe)2—a model diaryl diselenide, has been reported to display significant protective effects against MeHg-induced neurotoxicity under both in vitro and in vivo experimental conditions. In this study, we compared the protective effects of (PhSe)2 with those of RC513 (4,4′-diselanediylbis(2,6-di-tert-butylphenol), a novel diselenide-probucol-analog) against MeHg-induced toxicity in the neuronal (hippocampal) cell line HT22. Although both (PhSe)2 and RC513 significantly mitigated MeHg- and tert-butylhydroperoxide (t-BuOOH)-cytotoxicity, the probucol analog exhibited superior protective effects, which were observed earlier and at lower concentrations compared to (PhSe)2. RC513 treatment (at either 0.5 µM or 2 µM) significantly increased glutathione peroxidase (GPx) activity, which has been reported to counteract MeHg-toxicity. (PhSe)2 was also able to increase GPx activity, but only at 2 µM. Although both compounds increased the Gpx1 transcripts at 6 h after treatments, only RC513 was able to increase mRNA levels of Prx2, Prx3, Prx5, and Txn2, which are also involved in peroxide detoxification. RC513 (at 2 µM) significantly increased GPx-1 protein expression in HT22 cells, although (PhSe)2 displayed a minor (nonsignificant) effect in this parameter. In agreement, RC513 induced a faster and superior capability to cope with exogenously-added peroxide (t-BuOOH). In summary, when compared to the prototypical organic diaryl diselenide [(PhSe)2], RC513 displayed superior protective properties against MeHg-toxicity in vitro; this was paralleled by a more pronounced upregulation of defenses related to detoxification of peroxides, which are well-known MeHg-derived intermediate oxidant species. [ABSTRACT FROM AUTHOR]

This paper presents the C-ORAL-ESQ corpus project, which is dedicated to the study of the speech of individuals with schizophrenia. The main aim of the project is to investigate cognitive aspects of individuals with schizophrenia. This investigation is carried through the compilation of a spontaneous speech corpus and its study, which focuses mainly on the analysis of information structuring and its prosodic correlates. The paper mainly deals with the methodological aspects of the corpus compilation and reports its present stage: it informs about the environment and the setting of the sound file recordings, the medical and ethical criteria for the selection of the participants, the corpus aimed dimensions and the present stage of compilation, as well as its design and compilation criteria, which include attention to prosodic annotation, and metadata related to the participants' characteristics. Additionally, the theory adopted for the study of information structure is summarized, focusing on those aspects that can better address cognitive processes of individuals with schizophrenia and their prosodic correlates. Finally, the perspectives for future studies and resource compilations are presented. [ABSTRACT FROM AUTHOR]

High-speed railway bridges are subjected to normative limitations concerning maximum permissible deck accelerations. For the design of these structures, the European norm EN 1991-2 introduces the high-speed load model (HSLM)—a set of point loads intended to include the effects of existing high-speed trains. Yet, the evolution of current trains and the recent development of new load models motivate a discussion regarding the limits of validity of the HSLM. For this study, a large number of randomly generated load models of articulated, conventional, and regular trains are tested and compared with the envelope of HSLM effects. For each type of train, two sets of 100,000 load models are considered: one abiding by the limits of the EN 1991-2 and another considering wider limits. This comparison is achieved using both a bridge-independent metric (train signatures) and dynamic analyses on a case study bridge (the Canelas bridge of the Portuguese Railway Network). For the latter, a methodology to decrease the computational cost of moving loads analysis is introduced. Results show that some theoretical load models constructed within the stipulated limits of the norm can lead to effects not covered by the HSLM. This is especially noted in conventional trains, where there is a relation with larger distances between centres of adjacent vehicle bogies. [ABSTRACT FROM AUTHOR]

Background and Aims: Biocrusts are found on soil surface resulting from an association between soil particles and microorganisms. Photoautotrophic cyanobacteria and microalgae are pioneers on biocrusts formation, promoting soil stability, nutrients availability and water retention, leading to the development of other communities. This work aimed at isolating and characterizing cyanobacteria/microalgae from biocrusts (Central Portugal) and to assess their potential as plant biostimulants, as well as obtaining an insight into their mechanism(s) of action. Methods: Microorganisms were isolated through successive spread plating/serial dilutions and characterized using genetical analysis/morphological traits. An initial screening was performed using exudates from each microorganism and two plant species, Arabidopsis thaliana and Lolium multiflorum. Subsequently, the selected microorganisms were tested as a consortium in hydroponic systems. Biometric and biochemical parameters were evaluated for both plant species. Results: The consortium microorganisms belong to genera often found in soils/biocrusts: Trichocoleus, Nodosilinea, Microcoleus (filamentous cyanobacteria), Nostoc (diazotrophic heterocystous cyanobacteria), and Klebsormidium (filamentous microalga), and some of them have the capacity to produce phytohormones and/or siderophores. The consortium showed biostimulant potential in hydroponic cultures, promoting plant growth and enhancing physiological productivity related parameters. Stress related parameters revealed that the microorganisms did not lead to a stressful situation. However, a significant increase in proline was observed, endorsing a role of this molecule in this process. Conclusion: This study contributes to the knowledge on the biodiversity of cyanobacteria and microalgae from Portuguese soils and highlights their potential as biostimulants, constituting a step forward towards understanding the molecular mechanisms behind this effect. [ABSTRACT FROM AUTHOR]

The Graded Prognostic Assessment (GPA) score has the best accuracy among prognostic scales for patients with brain metastases (BM). A wide range of GPA-derived scales have been established to different types of primary tumor BM. However, there is a high variability between them, and their characteristics have not been described altogether yet. We aim to summarize the features of the existent GPA-derived scales and to compare their predictor factors and their uses in clinical setting. Medline was searched from inception until January 2023 to identify studies related to the development, update, or validation of GPA. The initial search yielded 1,083 results. 16 original studies and 16 validation studies were included, comprising a total of 33,348 patients. 13 different scales were assessed, including: GPA, Diagnosis-Specific GPA, Extracranial Score, Lung-molGPA, Updated Renal GPA, Updated Gastrointestinal GPA, Modified Breast GPA, Integrated Melanoma GPA, Melanoma Mol GPA, Sarcoma GPA, Hepatocellular Carcinoma GPA, Colorectal Cancer GPA, and Uterine Cancer GPA. The most prevalent prognostic predictors were age, Karnofsky Performance Status, number of BM, and presence or absence of extracranial metastases. Treatment modalities consisted of whole brain radiation therapy, stereotactic radiosurgery, surgery, cranial radiotherapy, gamma knife radiosurgery, and BRAF inhibitor therapy. Median survival rates with no treatment and with a specific treatment ranged from 6.1 weeks to 33 months and from 3.1 to 21 months, respectively. Original GPA and GPA-derived scales are valid prognostic tools, but with heterogeneous survival results when compared to each other. More studies are needed to improve scientific evidence of these scales. [ABSTRACT FROM AUTHOR]

A collaborative project in different areas of Spain and Portugal was designed to find out the variables that influence the mortality after discharge and develop a prognostic model adapted to the current healthcare needs of chronic patients in an internal medicine ward. Inclusion criteria were being admitted to an Internal Medicine department and at least one chronic disease. Patients' physical dependence was measured through Barthel index (BI). Pfeiffer test (PT) was used to establish cognitive status. We conducted logistic regression and Cox proportional hazard models to analyze the influence of those variables on one-year mortality. We also developed an external validation once decided the variables included in the index. We enrolled 1406 patients. Mean age was 79.5 (SD = 11.5) and females were 56.5%. After the follow-up period, 514 patients (36.6%) died. Five variables were identified as significantly associated with 1 year mortality: age, being male, lower BI punctuation, neoplasia and atrial fibrillation. A model with such variables was created to estimate one-year mortality risk, leading to the CHRONIBERIA. A ROC curve was made to determine the reliability of this index when applied to the global sample. An AUC of 0.72 (0.7–0.75) was obtained. The external validation of the index was successful and showed an AUC of 0.73 (0.67–0.79). Atrial fibrillation along with an advanced age, being male, low BI score, or an active neoplasia in chronic patients could be critical to identify high risk multiple chronic conditions patients. Together, these variables constitute the new CHRONIBERIA index. [ABSTRACT FROM AUTHOR]

Machine learning algorithms are being increasingly used in healthcare settings but their generalizability between different regions is still unknown. This study aims to identify the strategy that maximizes the predictive performance of identifying the risk of death by COVID-19 in different regions of a large and unequal country. This is a multicenter cohort study with data collected from patients with a positive RT-PCR test for COVID-19 from March to August 2020 (n = 8477) in 18 hospitals, covering all five Brazilian regions. Of all patients with a positive RT-PCR test during the period, 2356 (28%) died. Eight different strategies were used for training and evaluating the performance of three popular machine learning algorithms (extreme gradient boosting, lightGBM, and catboost). The strategies ranged from only using training data from a single hospital, up to aggregating patients by their geographic regions. The predictive performance of the algorithms was evaluated by the area under the ROC curve (AUROC) on the test set of each hospital. We found that the best overall predictive performances were obtained when using training data from the same hospital, which was the winning strategy for 11 (61%) of the 18 participating hospitals. In this study, the use of more patient data from other regions slightly decreased predictive performance. However, models trained in other hospitals still had acceptable performances and could be a solution while data for a specific hospital is being collected. [ABSTRACT FROM AUTHOR]

Three new species of Mimosa endemic to the Brazilian Cerrado biodiversity hotspot are described and illustrated. Mimosa cavalcantina, M. gustavoi and M. venosa are assigned to subser. Polycephalae for having its diagnotic morphology, including unarmed branches, leaves with a pair of pinnae, a fimbriate paleaceous calyx, and filaments shortly monadelpous at the base. We summarize geographic distributions, habitats, phenology, and conservation status for each of the new species, compare them with morphologically similar congeners, and discuss their systematic positions. [ABSTRACT FROM AUTHOR]

Monitoring human exposure to polycyclic aromatic hydrocarbons (PAHs) is a public health concern. Children are a vulnerable subgroup of the population with limited human biomonitoring data worldwide. Thus, this study aimed to measure the levels of seven PAH metabolites in urine from Brazilian children and provide risk assessment values for this exposure. Our data show naphthalene was the major contributor to children's exposure to PAHs, with a 100% detection rate. Children in urban regions presented higher exposure to PAHs, with higher concentrations of 2-naphthol in the southeast (1.09 ng/mL, p < 0.05). Furthermore, the highest concentration of 2-naphthol was found in older children (p = 0.02), suggesting a possible difference in dietary habits. Exposure to the carbaryl insecticide is suggested based on the high concentrations of 1-naphthol (1.29 ng/mL) and considering the ratio 1-naphthol/2-naphthol (1.78). Moreover, the positive correlation between the metabolites of fluorine and pyrene also suggests exposure to PAHs by petrol combustion. The risk assessment of the PAH exposure was evaluated using the estimated daily intake (EDI) for two naphthalene metabolites in the study with a 100% detection rate. The EDI was 14.47 ng/kg BW/day. The risk assessment to the PAH exposure revealed a non-carcinogenic risk profile, with a hazard quotient of 0.71. To the best of our knowledge, this study is the first to provide levels of PAHs in Brazilian children. [ABSTRACT FROM AUTHOR]

Background: Although abnormal movements and postures are the hallmark of dystonia, non-motor symptoms (NMS) are common and negatively affect quality of life. Objectives: The aim of this study was to screen dystonia patients for NMS and analyze their association with clinical parameters, including motor disability. Methods: Adult patients with idiopathic isolated dystonia were interviewed and examined. Dystonia severity was evaluated with the Fahn-Marsden Dystonia Rating Scale and the presence of NMS was assessed using a list of 29 complaints. Results: A hundred and two patients (63.7% female) were enrolled. Dystonia began after 20 years of age in 61.8% and was focal or segmental in 82.8% of patients. Only eight patients (7.8%) had no NMS and 59.8% reported more than five. The most prevalent NMS were pain (72.5%) and anxiety (63.7%), followed by difficulty recalling information (44.1%), sadness/anhedonia (41.2%), and difficulty falling asleep (38.2%). No correlation was found between the total number of NMS and dystonia severity (p = 0.18) or regular botulinum toxin use (p = 0.66). The majority of NMS domains correlated with each other. Conclusions: Our results confirm a high prevalence of NMS among dystonia patients, even in those with mild motor disability. The pathophysiology of NMS in dystonia remains to be completely understood. [ABSTRACT FROM AUTHOR]

The presence of cadmium in the environment requires attention, due to its carcinogenic and bioaccumulative power. To remedy water bodies contaminated with trace metal, different materials are reported in the literature. This work describes a method able to remove 10–25% of Cd2+ from aqueous solutions in a single batch using layered and cationic exchanger cerium hydrogenphosphate (CeP) material. In the present study, this material was obtained in three forms after hydrothermal treatment for 4 h, 16 h and 24 h. Powder X-rays diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, 31P nuclear magnetic resonance (31P NMR) and thermogravimetric analysis evidenced that CeP 24 h had a surface-like sorption in contrast to CeP 4 h. SEM visualizations showed a much pronounced fibrillar morphology for CeP 24 h. Also, we studied the Cd sorption mode by each material either applying agitation (dynamic) or not (static). Considering all this, the best results were obtained for Cd adsorption using CeP 24 h in dynamic mode according to ion adsorption capacity% values calculated from atomic absorption data. This is in contrast to data in the literature that mostly applies CeP 4 h as the metal ion sorptive material. [ABSTRACT FROM AUTHOR]

Exposure to environmental stressors, an increasingly recurring event in natural communities due to anthropogenic-induced environmental change, profoundly impacts disease emergence and spread. One mechanism through which this occurs is through stress-induced immunosuppression increasing disease susceptibility, prevalence, intensity and reactivation in hosts. We experimentally evaluated how exposure to stressors affected both the physiology of avian hosts and the prevalence of the zoonotic bacteria Borrelia burgdorferi sensu lato (s.l.), in two model species—the blackbird Turdus merula and the robin Erithacus rubecula captured in the wild, using xenodiagnoses and analysis of skin biopsies and blood. Although exposure to stressors in captivity induced physiological stress in birds (increased the number of circulating heterophils), there was no evidence of increased infectivity to xenodiagnostic ticks. However, Borrelia detection in the blood for both experimental groups of blackbirds was higher by the end of the captivity period. The infectivity and efficiency of transmission were higher for blackbirds than robins. When comparing different methodologies to determine infection status, xenodiagnosis was a more sensitive method than skin biopsies and blood samples, which could be attributed to mild levels of infection in these avian hosts and/or dynamics and timing of Borrelia infection relapses and redistribution in tissues. [ABSTRACT FROM AUTHOR]