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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]

The decline in cognitive function associated with aging significantly impacts the well-being of elderly individuals and their families. This decline is a major recognized risk factor for neurodegenerative diseases, notably Alzheimer’s disease. Animal models of aging provide a platform for evaluating drugs concerning aspects like memory and oxidative stress. JM-20 has demonstrated protective effects on short-term memory acquisition and consolidation, along with antioxidant properties and modulation of Acetylcholinesterase activity. This study assesses the potential protective JM-20 against cognitive decline and age-related memory loss. For the study, aged mice exhibiting aging-associated damage were initially selected. Experimental groups were then formed, and the effect of 8 mg/kg of JM-20 was evaluated for 40 days on aging-related behavior, such as spatial memory, novelty recognition memory, ambulatory activity, and anxiety. Subsequently, animals were sacrificed, and the hippocampal region was extracted for redox studies and to assess acetylcholinesterase activity. Results indicated that JM-20 at 8 mg/kg reversed damage to spatial working and reference memory, exhibiting performance comparable to untreated young adult animals. Furthermore, JM-20 preserved the enzymatic activity of superoxide dismutase, catalase, and total sulfhydryl levels in age-related cognitive impairment in mice, indicating a potent protective effect against oxidative events at the brain level. However, only young, healthy animals showed decreased acetylcholinesterase enzyme activity. These findings provide preclinical pharmacological evidence supporting the neuroprotective activity of JM-20, positioning it as a promising therapeutic candidate for treating memory disorders associated with aging. [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]

Methylmercury (MeHg+) is a neurotoxicant abundantly present in the environment. The long-term effects of MeHg+ have been investigated in rodents, yet data on the long-term or persisted toxicity of MeHg+ in invertebrates is scanty. Here, we examined the acute, intermediate, and chronic effects upon dietary administration of MeHg+ in nymphs of Nauphoeta cinerea. Besides, the potential reversibility of the toxic effects of MeHg+ after a detoxification period was evaluated. Nymphs were exposed to diets containing 0 (control), 2.5, 25, and 100 μg MeHg+/g of diet for 10, 30, and 90 days. Additional groups of nymphs were fed with the same dose of MeHg+ for 30 days and then were subjected to a detoxification period for 60 days. The nymphs exposed to 100 μg MeHg+/g succumbed to a high mortality rate, along with multiple biochemical (increase of reactive oxygen species production and glutathione S-transferase activity, as well as decrease in the acetylcholinesterase activity) and behavioral alterations. We observed delayed mortality rate and behavioral alterations in nymphs exposed to 100 μg MeHg+/g for 30 days and subsequently subjected to 60 days of detoxification. However, the biochemical alterations did not persist throughout the detoxification period. In conclusion, our results established the persistent toxic effect of MeHg+ even after a prolonged detoxification period and evidenced the use of N. cinerea as an alternative model to study the toxicity of MeHg+. [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]

Treating fungal infections is challenging and frequently requires long-term courses of antifungal drugs. Considering the limited number of existing antifungal drugs, it is crucial to evaluate the possibility of repositioning drugs with antifungal properties and to revisit older antifungals for applications in combined therapy, which could widen the range of therapeutic possibilities. Undecanoic acid is a saturated medium-chain fatty acid with known antifungal effects; however, its antifungal properties have not been extensively explored. Recent advances indicate that the toxic effect of undecanoic acid involves modulation of fungal metabolism through its effects on the expression of fungal genes that are critical for virulence. Additionally, undecanoic acid is suitable for chemical modification and might be useful in synergic therapies. This review highlights the use of undecanoic acid in antifungal treatments, reinforcing its known activity against dermatophytes. Specifically, in Trichophyton rubrum, against which the activity of undecanoic acid has been most widely studied, undecanoic acid elicits profound effects on pivotal processes in the cell wall, membrane assembly, lipid metabolism, pathogenesis, and even mRNA processing. Considering the known antifungal activities and associated mechanisms of undecanoic acid, its potential use in combination therapy, and the ability to modify the parent compound structure, undecanoic acid shows promise as a novel therapeutic against fungal infections. [ABSTRACT FROM AUTHOR]

Plants with medicinal properties play an increasingly important role in food and pharmaceutical industries for their functions on disease prevention and treatment. This study characterizes the phenolic composition and antioxidant activity of seven medicinal and food plants, including the leaves of Salvia officinalis L., Rosmarinus officinalis L., Olea europaea L., and Punica granatum L., as well as the leaves and young stems of Ruta graveolens L., Mentha piperita L., and Petroselinum crispum, Mill., by using colorimetric, chromatographic, and spectrophotometric assays. Results revealed that the hydro-methanolic leaf extracts of P. granatum (pomegranate) displayed the highest content of total phenols (199.26 mg gallic acid per gram of plant dry weight), ortho-diphenols (391.76 mg gallic acid per gram of plant dry weight), and tannins (99.20 mg epicatechin per gram of plant dry weight), besides a higher content of flavonoids (24 mg catechin per gram of plant dry weight). The highest antioxidant capacity measured by ABTS, DPPH, and FRAP (2.14, 2.27, and 2.33 mM Trolox per gram of plant dry weight, respectively) methods was also obtained in pomegranate leaf extracts, being 4–200 times higher than the other species. Such potent antioxidant activity of pomegranate leaves can be ascribed to the presence of different types of phenolic compounds and the high content in tannins, whilst phenolic acids and flavonoids were found to be the dominant phenolic classes of the other six plants. Consequently, despite the well-known antioxidant properties of these plant species, our study suggests pomegranate leaf can stand out as a relatively more valuable plant source of natural bioactive molecules for developing novel functional food-pharma ingredients, with potential for not only promoting human health but also improving bio-valorization and environment. [ABSTRACT FROM AUTHOR]

Background: Patients who undergo Roux-en-Y gastric bypass (RYGB) have significant weight loss, and abdominoplasty is an effective corrective surgery for removing excess skin. This study aimed to evaluate the impact of the weight of removed tissue on the development of postoperative complications in patients undergoing abdominoplasty without lipoaspiration after gastric bypass at the Federal District North Wing Regional Hospital, Brasília, Brazil. Methods: Data were analyzed from a prospective registry of patients who underwent abdominoplasty without lipoaspiration after gastric bypass from January 2011 to December 2018. The variables examined included body mass index (BMI) before RYGB and before plastic surgery, weight loss, weight of the excised abdominal flap, comorbidities, and medical complications. Analysis of the role of the weight of the removed tissue after abdominoplasty was performed to assess outcome measures. Results: One hundred sixty-three patients were included. The mean age of the patients was 42 years. Their BMI at the time of abdominoplasty was 27.49 kg/m2, and the average weight loss before abdominoplasty was 47.13 kg. The preweight loss BMI was 45.27 kg/m2, and the ∆BMI was 17.78 kg/m2. The overall complication rate was 29.4%. An amount of removed tissue from the abdomen ≥ 2000 g significantly increased the rates of postoperative complications (46.7% vs. 19.4%; p = 0.002; OR = 3.13). Conclusions: Removal of ≥ 2000 g of tissue from the abdomen led to significantly more complications in patients who underwent abdominoplasty after gastric bypass. In addition, this group of patients was significantly associated with the presence of higher anthropometric variable values (BMI, weight loss, max BMI, and ∆BMI) and not associated with the presence of comorbidities. [ABSTRACT FROM AUTHOR]

Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins. [ABSTRACT FROM AUTHOR]

Most pharmacological studies concerning the beneficial effects of organoselenium compounds have focused on their ability to mimic glutathione peroxidase (GPx). However, mechanisms other than GPx-like activity might be involved on their biological effects. This study was aimed to investigate and compare the protective effects of two well known [(PhSe)2 and PhSeZnCl] and two newly developed (MRK Picolyl and MRK Ester) organoselenium compounds against oxidative challenge in cultured neuronal HT22 cells. The thiol peroxidase and oxidase activities were performed using the glutathione reductase (GR)-coupled assay. In order to evaluate protective effects of the organoselenium compounds against oxidative challenge in neuronal HT22 cells, experiments based on glutamate-induced oxytosis and SIN-1-mediated peroxynitrite generation were performed. The thiol peroxidase activities of the studied organoselenium compounds were smaller than bovine erythrocytes GPx enzyme. Besides, (PhSe)2 and PhSeZnCl showed higher thiol peroxidase and lower thiol oxidase activities compared to the new compounds. MRK Picolyl and MRK Ester, which showed lower thiol peroxidase activity, showed higher thiol oxidase activity. Both pre- or co-treatment with (PhSe)2, PhSeZnCl, MRK Picolyl and MRK Ester protected HT22 cells against glutamate-induced cytotoxicity. (PhSe)2 and MRK Picolyl significantly prevented peroxinitrite-induced dihydrorhodamine oxidation, but this effect was observed only when HT22 were pre-treated with these compounds. The treatment with (PhSe)2 increased the protein expression of antioxidant defences (Prx3, CAT and GCLC) in HT22 cells. Taking together, our results suggest that the biological effects elicited by these compounds are not directly related to their GPx-mimetic and thiol oxidase activities, but might be linked to the up-regulation of endogenous antioxidant defences trough their thiol-modifier effects. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of (+)-catechin, a polyphenolic compound, on orofacial dyskinesia (OD) induced by reserpine in mice. The potential modulation of monoaminoxidase (MAO) activity, tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD67) immunoreactivity by catechin were used as biochemical endpoints. The interaction of catechin with MAO-A and MAO-B was determined in vitro and in silico. The effects of catechin on OD induced by reserpine (1 mg/kg for 4 days, subcutaneously) in male Swiss mice were examined. After, catechin (10, 50 or 100 mg/kg, intraperitoneally) or its vehicle were given for another 20 days. On the 6th, 8th, 15th and 26th day, vacuous chewing movements (VCMs) and locomotor activity were quantified. Biochemical markers (MAO activity, TH and GAD67 immunoreactivity) were evaluated in brain structures. In vitro, catechin inhibited both MAO isoforms at concentrations of 0.34 and 1.03 mM being completely reversible for MAO-A and partially reversible for MAO-B. Molecular docking indicated that the catechin bound in the active site of MAO-A, while in the MAO-B it interacted with the surface of the enzyme in an allosteric site. In vivo, reserpine increased the VCMs and decreased the locomotor activity. Catechin (10 mg/kg), decreased the number of VCMs in the 8th day in mice pre-treated with reserpine without altering other behavioral response. Ex vivo, the MAO activity and TH and GAD67 immunoreactivity were not altered by the treatments. Catechin demonstrated a modest and transitory protective effect in a model of OD in mice. [ABSTRACT FROM AUTHOR]

The resulting whey from cheese manufacture consists mainly of water and lactose, a sugar with little sweetening and fermentable power and low commercial value. Aiming at valorizing the whey and faced with the challenge to reduce and treat an industrial wastewater present at high volumes and composed of high organic load, several ways to enhance the commercial value lactose have been sought. Thanks to the functional and technological traits of lactose and to the biotechnological advances, several applications have been proposed either for direct use or for the production and application of chemical and enzymatic derivatives or by-products from microbiological processes. Nowadays, lactose has numerous potential applications in food, feed, nutraceutical, pharmaceutical and cosmetic industry, an overview of which is given in this review. On the other hand, many compounds of high added value are produced from lactose, such as oligosaccharides with prebiotic properties, lactobionic acid with antioxidant properties, lactitol as sweetener with dietetic and prebiotic functions, and lactulose as prebiotic ingredient. Nevertheless, the implementation of industrial processes for whey collection and lactose recovery and valorization faces practical difficulties, particularly of logistical and financial investment nature. This communication aims at giving an overview with respect to the problems associated with the high volumes of whey produced in the dairy industry and some of the foremost technological routes for its commercial exploitation through the use of lactose and its derivatives. It also presents a set of considerations regarding the main bottlenecks to overcome towards the creation and implementation of integrated systems tailored for collecting and processing cheese whey in an efficient, sustainable and cost-effective approach. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CPF) is a neurotoxic organophosphorus (OP) insecticide widely used for agricultural purposes. CPF-mediated neurotoxicity is mainly associated with its anticholinesterase activity, which may lead to a cholinergic syndrome. CPF metabolism generates chlorpyrifos-oxon (CPF-O), which possesses higher anticholinesterase activity and, consequently, plays a major role in the cholinergic syndrome observed after CPF poisoning. Recent lines of evidence have also reported non-cholinergic endpoints of CPF- and CPF-O-induced neurotoxicities, but comparisons on the non-cholinergic toxic properties of CPF and CPF-O are lacking. In this study, we compared the non-cholinergic toxicities displayed by CPF and CPF-O in cultured neuronal cells, with a particular emphasis on their pro-oxidant properties. Using immortalized cells derived from mouse hippocampus (HT22 line, which does present detectable acetylcholinesterase activity), we observed that CPF-O was 5-fold more potent in decreasing cell viability compared with CPF. Atropine, a muscarinic acetylcholine receptor antagonist, protected against acetylcholine (ACh)-induced toxicity but failed to prevent the CPF- and CPF-O-induced cytotoxicities in HT22 cells. CPF or CPF-O exposures significantly decreased the levels of the antioxidant glutathione (GSH); this event preceded the significant decrease in cell viability. Pretreatment with N-acetylcysteine (NAC, a GSH precursor) protected against the cytotoxicity induced by both CPF and CPF-O. The present study indicates that GSH depletion is a non-cholinergic event involved in CPF and CPF-O toxicities. The study also shows that in addition of being a more potent AChE inhibitor, CPF-O is also a more potent pro-oxidant molecule when compared with CPF, highlighting the role of CPF metabolism (bioactivation to CPF-O) in the ensuing non-cholinergic toxicity. [ABSTRACT FROM AUTHOR]

Summary: Background: Hereditary diffuse gastric cancer is an autosomal dominant cancer susceptibility syndrome characterized by increased risk for gastric cancer and lobular breast cancer and mainly caused by germline alterations in the CDH1 gene. Methods: This was an observational, retrospective, and unicentric study. Clinical data from patients with hereditary diffuse gastric cancer who had risk-reducing total gastrectomy between June 2005 and January 2018 were collected. A thorough histopathological analysis of gastrectomy specimens was performed, according to the current recommendations of the International Gastric Cancer Linkage Consortium. Results: In 59 families fulfilling the clinical criteria for CDH1 testing, we identified the same CDH1 missense pathogenic variant in five families. Thirty-nine CDH1 carriers were identified. Four CDH1 carriers died with advanced diffuse gastric cancer, 19 chose risk-reducing total gastrectomy, and 16 opted for endoscopic surveillance, despite being duly informed of the limited utility of periodic gastric endoscopy in this context. The 19 asymptomatic CDH1 carriers undergoing surgery had an age range of 14–63 years (median, 39 years) and the median hospital stay was 6 days. Laparoscopic total gastrectomy was performed on four of 19 CDH1 carriers. There were no cases of mortality or major morbidity in this procedure. The range of weight loss in our series was 13%. Histopathological examination of the entirety of gastric mucosa revealed intramucosal gastric carcinoma foci (pT1a) in 17 of 19 (89.5%) total gastrectomy specimens. No lymph node metastases were detected (pN0). Conclusion: Risk-reducing total gastrectomy remains the best clinical management for patients with hereditary diffuse gastric cancer harboring a germline, pathogenic CDH1 variant. In our series, intramucosal carcinoma foci were found in the great majority (89.5%) of CDH1 carriers. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) is a global pollutant and potent neurotoxin. In humans, MeHg damages the central nervous system (CNS), causing irreversible neuronal shrinkage, and neuronal loss. Most chelators for clinical mercury detoxification are thiol-containing agents. N,N 'bis-(2-mercaptoethyl) isophthalamide (NBMI) is a lipophilic thiol agent synthesized from natural chemicals. NBMI has high affinity for mercury, cadmium and lead, and can decrease their concentrations in polluted water. However, the efficacy of NBMI for MeHg toxicity has yet to be evaluated in intact animals. Here we used the nematode Caenorhabditis elegans (C. elegans) to test the efficacy of NBMI in attenuating MeHg toxicity in vivo in the whole organism. The results showed that NBMI reduced both the acute toxicity (125 μM MeHg, 1 h) and chronic (5 μM MeHg, 24 h) MeHg toxicity. Co-treatment with NBMI achieved maximal efficacy against MeHg toxicity, however delayed treatment 6 days after initiation of exposure was also effective at reducing neurotoxicity. Co-treatment of NBMI reduced the worms' death rate, structural damage in DAergic neurons, and restored antioxidant response levels. While this study provides proof of principle for the therapeutic value of NBMI in MeHg toxicity, future studies are needed to address the cellular and molecular mechanisms and translatability of these effects to humans and other animals. [ABSTRACT FROM AUTHOR]

Intracranial arterial stenosis is a frequently misdiagnosed cause of ischemic stroke, associated with high rates of recurrence under medical therapy alone. Endovascular intracranial angioplasty and stenting has increasingly been used worldwide for treatment of symptomatic intracranial stenoses, despite controversial results of the first randomized trials. Lesion morphology and etiology must be considered during endovascular treatment planning. Complex morphologies can lead to serious complications during the endovascular procedure. We present a case of a symptomatic complex middle cerebral artery stenosis that was successfully treated with a double stenting in T configuration, using a safety micro-guidewire technique. During follow-up, intracranial Doppler revealed a non-significant residual stenosis and the patient remained asymptomatic. [ABSTRACT FROM AUTHOR]

Alfalfa (Medicago sativa L.) is a forage legume of great interest because of its role in milk production schemes. Although it has the potential to be cultivated in different edaphoclimatic regions, the fodder production in tropical regions is limited. The objectives of this study were to perform phenotypic and molecular characterization of alfalfa germplasm, to examine the relationship between dissimilarity based on phenotypic and molecular information and to identify the germplasm with potential to generate base populations adapted to tropical conditions. The genetic values of nine traits from seventy-seven alfalfa accessions of a genetic background amenable to a temperate climate were obtained to characterize phenotypic diversity, and microsatellite markers were used to assess molecular diversity. Phenotypic information based on joint deviance analysis revealed the presence of genetic diversity. The correlation between the dissimilarity matrices of genetic values and molecular data was low. Based on phenotypic and molecular data, a great base population would be composed of Pro INTA Patricia, Pro INTA Super Monarca, Mecha, Magna 601, WL 525, ACA 900, Bacana, CUF 101, Crioula, and Ruano. These populations have at least 50 distinct parents, presented high dry matter yield, besides favorable alleles for regrowth ability, biomass yield, and persistence. The genetic variability observed for most traits indicates a high potential for the development of alfalfa base populations adapted to the tropical condition. Once adapted synthetic alfalfa populations are selected, they may be integrated into breeding programs in other tropical regions of the world. [ABSTRACT FROM AUTHOR]

The genus Cynodon includes species that have huge potential to produce high-quality fodder, for grazing and hay production. In perennial forage breeding, selection should be performed based on repeated measurements in the same individual over time, which maximizes the selective efficiency. Thus, the objectives of this study were to estimate the coefficients of repeatability and optimal number of measures for the genetic selection of Cynodon spp. clones. We evaluated 202 clones, being five checks, during four harvests, in augmented block design. A mixed model methodology (REML/BLUP) was used to estimate the variance components and predict the genotypic values. The repeatability coefficient for plant height, green weight, dry matter, and plant vigor were equal to 0.50, 0.67, 0.25, and 0.73, respectively. The accuracies obtained by performing m repeated measures revealed that 5, 2, 13, and 2 measurements are required to attain an accuracy ≥ 90% in genetic gain from the selection for plant height, green weight, dry matter, and plant vigor, respectively. Furthermore, the efficiency of performing four measurements compared with that of performing only one measurement was 27%, 15%, 51%, and 12% for plant height, green weight, dry matter, and vigor, respectively. In addition, the additive index, adopting a 10% selection intensity, was used in simultaneous selection, leading to desirable genetic gains for plant height, green weight, and plant vigor. In conclusion, the use of the repeatability coefficient suggests performing three measurements to obtain a high accuracy and good efficiency on the selection of superior genotypes of Cynodon spp. [ABSTRACT FROM AUTHOR]

In common bean breeding programs, experiments are conducted in different environments to select plants with high potential for inbred lines extraction and/or recombination. The occurrence of genetic and/or statistical unbalance is common in these experiments. Moreover, there may be (co)variance between genetic and non-genetic effects when treatments are assessed in different environments. Our aim was to (1) test different (co)variance structures between seasons for genetic and non-genetic effects; (2) choose the model with the highest predictive capacity of the genotypic value; and (3) select the superior progenies to mitigate the effects of genotype-by-environment interactions. To this end, two experiments were conducted in the 2015 drought and winter seasons. The grain yield and grain aspect were assessed. Model 4, with an unstructured (co)variance for genetic effects, homogeneous block variance, and heterogeneous residual diagonal variance, was the model that best fit the data. The heritability estimates and their accuracy differed between the different adjusted models, with the most accurate estimates observed in model 4. The genetic correlation between the drought and winter seasons was of low magnitude (− 0.04) for grain yield, which corroborates the strong genotype by environment interaction. The average gain predicted with the recombination of the selected progenies in model 4 was 2.97% for grain yield. The modeling of different (co)variance structures for genetic and non-genetic effects could be applicable for analyses involving statistical unbalance and the assessment of progenies in different environments, with the aim of selecting those with high potential for recombination. [ABSTRACT FROM AUTHOR]

Reaction norms fitted through random regression models are a powerful tool to identify and quantify the genotype × environment (G × E) interaction and they represent a promising alternative in forest tree breeding for analysis of multi-environment trials. Thus, the objective of this study was to compare random regression models with the compound symmetry model in Eucalyptus breeding for analysis of multi-environment trials. To this end, a data set with 215 Eucalyptus clones of different species and hybrids evaluated in four environments for diameter at breast height and Pilodyn penetration was used. The random regression models provided a better fit for both traits. Results showed that there was genotypic variability among Eucalyptus clones and that the reaction norms over the environmental gradients identified the G × E interaction. The compound symmetry model and the random regression models are highly correlated in terms of genotype ranking for both traits. The main advantage of random regression models over the compound symmetry model is the ability to predict genotypic performance in environments where a genotype has not been evaluated. Thus, our results suggest that reaction norms fitted through random regression models can be successfully used in forest tree breeding for analysis of multi-environment trials. [ABSTRACT FROM AUTHOR]

In Brazil, the CNPq (National Council for Scientific and Technological Development) provides grants, funds and fellowships to productive scientists to support their investigations. They are ranked and categorized into four hierarchical levels ranging from PQ 1A (the highest) to PQ 1D (the lowest). Few studies, however, report and analyse scientific productivity in different sub-fields of Biomedical Sciences (BS), e.g., Biochemistry, Pharmacology, Biophysics and Physiology. In fact, systematic comparisons of productivity among the PQ 1 categories within the above sub-fields are lacking in the literature. Here, the scientific productivity of 323 investigators receiving PQ 1 fellowships (A to D levels) in these sub-fields of BS was investigated. The Scopus database was used to compile the total number of articles, citations, h-index values and authorship positions (first-, co- or last-listed author) in the most cited papers by researchers granted CNPq fellowships. We found that researchers from Pharmacology had the best performance for all of the parameters analysed, followed by those in Biochemistry. There was great variability in scientific productivity within the PQ 1A level in all of the sub-fields of BS, but not within the other levels (1B, 1C and 1D). Analysis of the most cited papers of PQ 1(A–D) researchers in Pharmacology revealed that the citations of researchers in the 1C and 1D levels were associated with publications with their senior supervisors, whereas those in the 1B level were less connected with their supervisors in comparison to those in 1A. Taken together, these findings suggest that the scientific performance of PQ 1A researchers in BS is not homogenous. In our opinion, parameters such as the most cited papers without the involvement of Ph.D. and/or post-doctoral supervisors should be used to make decisions regarding any given researcher's fellowship award level. [ABSTRACT FROM AUTHOR]

Copper is a transition metal that exists in different chemical forms (e.g., Cu2+,Cu+, and Cu0) and at high concentrations it is toxic. Here, we investigated the Cu2+-induced toxicity in Drosophila melanogaster, evaluating the survival, locomotion, and the activity of acetylcholinesterase (AChE) and glutathione S-transferase (GST) enzymes. Flies were exposed to Cu2+(0.1–1 mmol CuSO4/kg of diet or approximately 0.1–1 mM Cu2+) and allowed to mate during 24 h. GST and AChE enzymes were evaluated in the larvae and in the head and the body (thorax + abdomen) of the adult male and females flies. The total number of adult females (0.4–1 mM) and males (0.75 and 1 mM) was decreased by CuSO4. The climbing ability was hampered in flies exposed to 1 mM Cu2+. In larvae, Cu2+(0.4–1 mM) increased AChE activity (P < 0.002). In males' heads, 0.4 mM Cu2+ increased the AChE activity (P < 0.01). In adults' bodies, Cu2+inhibited the activity in both sexes, but with greater effectiveness in males (0.1 to 1 mM) than in females (1 mM). Regarding GST activity, 0.1 mM Cu2+increased, but 1 mM decrease GST in larvae. In the head of flies, Cu2+decreased the GST activity at intermediate (0.4 mM) and increased GST at the highest concentration (1 mM) in males. In the bodies, the effect of Cu2+was similar. In conclusion, Cu2+exposure in D. melanogaster disrupted locomotion and enzymatic parameters that can be related to changes in AChE and in the detoxifying GST enzyme. [ABSTRACT FROM AUTHOR]

Mammalian δ-aminolevulinate dehydratase (δ-ALA-D) is a metalloenzyme, which requires Zn(II) and reduced thiol groups for catalytic activity, and is an important molecular target for the widespread environmental toxic metals. The δ-ALA-D inhibition mechanism by metals of Group 10 (Ni, Pd, and Pt) and 11 (Cu, Ag, and Au) of the periodic table has not yet been determined. The objective of this study was to characterize the molecular mechanism of δ-ALA-D inhibition caused by the elements of groups 10 and 11 using in vitro (δ-ALA-D activity from human erythrocytes) and in silico (docking simulations) methods. Our results showed that Ni(II) and Pd(II) caused a small inhibition (~ 10%) of the δ-ALA-D. Pt(II) and Pt(IV) significantly inhibited the enzyme (75% and 44%, respectively), but this inhibition was attenuated by Zn(II) and dithiothreitol (DTT). In group 11, all metals inhibited δ-ALA-D with great potency (~ 70-90%). In the presence of Zn(II) and DTT, the enzyme activity was restored to the control levels. The in silico molecular docking data suggest that the coordination of the ions Pt(II), Pt(IV), Cu(II), Ag(I), and Au(III) with thiolates groups from C135 and C143 residues from the δ-ALA-D active site are crucial to the enzyme inhibition. The results indicate that a possible mechanism of inhibition of δ-ALA-D by these metals may involve the replacement of the Zn(II) from the active site and/or the cysteinyl residue oxidation. [ABSTRACT FROM AUTHOR]