Enhancing the quality of evidence, comparability, and reproducibility in brain arteriovenous malformations treated with open surgery research: a systematic review and proposal of a reporting guideline for surgical and clinical outcomes.

Brain Arteriovenous Malformations (bAVMs) are rare but high-risk developmental anomalies of the vascular system. Microsurgery through craniotomy is believed to be the mainstay standard treatment for many grades of bAVMs. However, a significant challenge emerges in the existing body of clinical studies on open surgery for bAVMs: the lack of reproducibility and comparability. This study aims to assess the quality of studies reporting clinical and surgical outcomes for bAVMs treated by open surgery and develop a reporting guideline checklist focusing on essential elements to ensure comparability and reproducibility. This is a systematic literature review that followed the PRISMA guidelines with the search in Medline, Embase, and Web of Science databases, for studies published between January 1, 2018, and December 1, 2023. Included studies were scrutinized focusing on seven domains: (1) Assessment of How Studies Reported on the Baseline Characteristics of the Patient Sample; (2) Assessment and reporting on bAVMs grading, anatomical characteristics, and radiological aspects; (3) Angioarchitecture Assessment and Reporting; (4) Reporting on Pivotal Concepts Definitions; (5) Reporting on Neurosurgeon(s) and Staff Characteristics; (6) Reporting on Surgical Details; (7) Assessing and Reporting Clinical and Surgical Outcomes and AEs. A total of 47 studies comprising 5,884 patients were included. The scrutiny of the studies identified that the current literature in bAVM open surgery is deficient in many aspects, ranging from fundamental pieces of information of methodology to baseline characteristics of included patients and data reporting. Included studies demonstrated a lack of reproducibility that hinders building cumulative evidence. A bAVM Open Surgery Reporting Guideline with 65 items distributed across eight domains was developed and is proposed in this study aiming to address these shortcomings. This systematic review identified that the available literature regarding microsurgery for bAVM treatment, particularly in studies reporting clinical and surgical outcomes, lacks rigorous scientific methodology and quality in reporting. The proposed bAVM Open Surgery Reporting Guideline covers all essential aspects and is a potential solution to address these shortcomings and increase transparency, comparability, and reproducibility in this scenario. This proposal aims to advance the level of evidence and enhance knowledge regarding the Open Surgery treatment for bAVMs.

Mutations in the postsynaptic density signaling hub TNIK disrupt PSD signaling in human models of neurodevelopmental disorders.

A large number of synaptic proteins have been recurrently associated with complex brain disorders. One of these proteins, the Traf and Nck interacting kinase (TNIK), is a postsynaptic density (PSD) signaling hub, with many variants reported in neurodevelopmental disorder (NDD) and psychiatric disease. While rodent models of TNIK dysfunction have abnormal spontaneous synaptic activity and cognitive impairment, the role of mutations found in patients with TNIK protein deficiency and TNIK protein kinase activity during early stages of neuronal and synapse development has not been characterized. Here, using hiPSC-derived excitatory neurons, we show that TNIK mutations dysregulate neuronal activity in human immature synapses. Moreover, the lack of TNIK protein kinase activity impairs MAPK signaling and protein phosphorylation in structural components of the PSD. We show that the TNIK interactome is enriched in NDD risk factors and TNIK lack of function disrupts signaling networks and protein interactors associated with NDD that only partially overlap to mature mouse synapses, suggesting a differential role of TNIK in immature synapsis in NDD.

Fetal Alcohol Spectrum Disorder: The Honey Bee as a Social Animal Model.

Animal models have been essential for advancing research of fetal alcohol spectrum disorder (FASD) in humans, but few animal species effectively replicate the behavioural and clinical signs of FASD. The honey bee (Apis mellifera) is a previously unexplored research model for FASD that offers the distinct benefit of highly social behaviour. In this study, we chronically exposed honey bee larvae to incremental concentrations of 0, 3, 6, and 10% ethanol in the larval diet using an in vitro rearing protocol and measured developmental time and survival to adult eclosion, as well as body weight and motor activity of newly emerged adult bees. Larvae reared on 6 and 10% dietary ethanol demonstrated significant, dose-responsive delays to pupation and decreased survival and adult body weight. All ethanol-reared adults showed significantly decreased motor activity. These results suggest that honey bees may be a suitable social animal model for future FASD research.

Long-term studies on West Antarctic Peninsula phytoplankton blooms suggest range shifts between temperate and polar species.

The Western Antarctic Peninsula (WAP) experiences one of the highest rates of sea surface warming globally, leading to potential changes in biological communities. Long-term phytoplankton monitoring in Potter Cove (PC, King George Island, South Shetlands) from the 1990s to 2009 revealed consistently low biomass values, and sporadic blooms dominated by cold-water microplankton diatoms. However, a significant change occurred between 2010 and 2020, marked by a notable increase in intense phytoplankton blooms in the region. During this period, the presence of a nanoplankton diatom, Shionodiscus gaarderae, was documented for the first time. In some instances, this species even dominated the blooms. S. gaarderae is recognized for producing blooms in temperate waters in both hemispheres. However, its blooming in the northern Southern Ocean may suggest either a recent introduction or a range shift associated with rising temperatures in the WAP, a phenomenon previously observed in experimental studies. The presence of S. gaarderae could be viewed as a warning sign of significant changes already underway in the northern WAP plankton communities. This includes the potential replacement of microplankton diatoms by smaller nanoplankton species. This study, based on observations along the past decade, and compared to the previous 20 years, could have far-reaching implications for the structure of the Antarctic food web.

Mean-field method for generic conductance-based integrate-and-fire neurons with finite timescales.

The construction of transfer functions in theoretical neuroscience plays an important role in determining the spiking rate behavior of neurons in networks. These functions can be obtained through various fitting methods, but the biological relevance of the parameters is not always clear. However, for stationary inputs, such functions can be obtained without the adjustment of free parameters by using mean-field methods. In this work, we expand current Fokker-Planck approaches to account for the concurrent influence of colored and multiplicative noise terms on generic conductance-based integrate-and-fire neurons. We reduce the resulting stochastic system through the application of the diffusion approximation to a one-dimensional Langevin equation. An effective Fokker-Planck is then constructed using Fox Theory, which is solved numerically using a newly developed double integration procedure to obtain the transfer function and the membrane potential distribution. The solution is capable of reproducing the transfer function and the stationary voltage distribution of simulated neurons across a wide range of parameters. The method can also be easily extended to account for different sources of noise with various multiplicative terms, and it can be used in other types of problems in principle.

Human cerebellar organoids with functional Purkinje cells.

Research on human cerebellar development and disease has been hampered by the need for a human cell-based system that recapitulates the human cerebellum's cellular diversity and functional features. Here, we report a human organoid model (human cerebellar organoids [hCerOs]) capable of developing the complex cellular diversity of the fetal cerebellum, including a human-specific rhombic lip progenitor population that have never been generated in vitro prior to this study. 2-month-old hCerOs form distinct cytoarchitectural features, including laminar organized layering, and create functional connections between inhibitory and excitatory neurons that display coordinated network activity. Long-term culture of hCerOs allows healthy survival and maturation of Purkinje cells that display molecular and electrophysiological hallmarks of their in vivo counterparts, addressing a long-standing challenge in the field. This study therefore provides a physiologically relevant, all-human model system to elucidate the cell-type-specific mechanisms governing cerebellar development and disease.

The greening-causing agent alters the behavioral and electrophysiological responses of the Asian citrus psyllid to a putative sex pheromone.

The Asian Citrus Psyllid (ACP), Diaphorina citri, is a vector of the pathological bacterium Candidatus Liberibacter asiaticus (CLas), which causes the most devastating disease to the citrus industry worldwide, known as greening or huanglongbing (HLB). Earlier field tests with an acetic acid-based lure in greening-free, 'Valencia' citrus orange groves in California showed promising results. The same type of lures tested in São Paulo, Brazil, showed unsettling results. During the unsuccessful trials, we noticed a relatively large proportion of females in the field, ultimately leading us to test field-collected males and females for Wolbachia and CLas. The results showed high rates of Wolbachia and CLas infection in field populations. We then compared the olfactory responses of laboratory-raised, CLas-free, and CLas-infected males to acetic acid. As previously reported, CLas-uninfected males responded to acetic acid at 1 µg. Surprisingly, CLas-infected males required 50 × higher doses of the putative sex pheromone, thus explaining the failure to capture CLas-infected males in the field. CLas infection was also manifested in electrophysiological responses. Electroantennogram responses from CLas-infected ACP males were significantly higher than those obtained with uninfected males. To the best of our knowledge, this is the first report of a pathogen infection affecting a vector's response to a sex attractant.

Spider venom neurotoxin based bioinsecticides: A novel bioactive for the control of the Asian citrus psyllid Diaphorina citri (Hemiptera).

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is a key vector of the phloem-limited bacteria Candidatus Liberibacter asiaticus (CLas) associated with huanglongbing (HLB), the most serious and currently incurable disease of citrus worldwide. Here we report the first investigation into the potential use of a spider venom-derived recombinant neurotoxin, ω/κ-HxTx-Hv1h (hereafter HxTx-Hv1h) when delivered alone or when fused to snowdrop lectin (Galanthus nivalis agglutinin; GNA) to control D. citri. Proteins, including GNA alone, were purified from fermented transformed yeast Pichia pastoris cultures. Recombinant HxTx-Hv1h, HxTx-Hv1h/GNA and GNA were all orally toxic to D. citri, with Day 5 median lethal concentrations (LC50) derived from dose-response artificial diet assays of 27, 20 and 52 µM, respectively. Western analysis of whole insect protein extracts confirmed that psyllid mortality was attributable to protein ingestion and that the fusion protein was stable to cleavage by D. citri proteases. When applied topically (either via droplet or spray) HxTx-Hv1h/GNA was the most effective of the proteins causing >70 % mortality 5 days post treatment, some 2 to 3-fold higher levels of mortality as compared to the toxin alone. By contrast, no significant mortality or phenotypic effects were observed for bumble bees (Bombus terrestris L.) fed on the recombinant proteins in acute toxicity assays. This suggests that HxTx-Hv1h/GNA has potential as a novel bioinsecticide for the management of D. citri offering both enhanced target specificity as compared to chemical pesticides and compatibility with integrated pest management (IPM) strategies.

Non-synaptic function of the autism spectrum disorder-associated gene SYNGAP1 in cortical neurogenesis.

Genes involved in synaptic function are enriched among those with autism spectrum disorder (ASD)-associated rare genetic variants. Dysregulated cortical neurogenesis has been implicated as a convergent mechanism in ASD pathophysiology, yet it remains unknown how 'synaptic' ASD risk genes contribute to these phenotypes, which arise before synaptogenesis. Here, we show that the synaptic Ras GTPase-activating (RASGAP) protein 1 (SYNGAP1, a top ASD risk gene) is expressed within the apical domain of human radial glia cells (hRGCs). In a human cortical organoid model of SYNGAP1 haploinsufficiency, we find dysregulated cytoskeletal dynamics that impair the scaffolding and division plane of hRGCs, resulting in disrupted lamination and accelerated maturation of cortical projection neurons. Additionally, we confirmed an imbalance in the ratio of progenitors to neurons in a mouse model of Syngap1 haploinsufficiency. Thus, SYNGAP1-related brain disorders may arise through non-synaptic mechanisms, highlighting the need to study genes associated with neurodevelopmental disorders (NDDs) in diverse human cell types and developmental stages.

Discovery of Novel miRNAs in Colorectal Cancer: Potential Biological Roles and Clinical Utility.

Deregulated miRNAs are associated with colorectal cancer (CRC), with alterations depending on the tumor location. Novel tissue-specific miRNAs have been identified in different tumors and are associated with cancer. We used miRMaster to identify novel miRNAs in CRC from the TCGA and GEO data (discovery and validation groups). We used TCGA data from five tissues to analyze miRNA tissue specificity. miRDB was used to predict miRNA targets, and the UCSC Xena Browser was used to evaluate target expression. After successive analyses, we identified 15 novel miRNAs with the same expression patterns in CRC in both the discovery and validation groups. Four molecules (nov-miR-13844-5p, nov-miR-7154-5p, nov-miR-5035-3p, and nov-miR-590-5p) were differentially expressed in proximal and distal CRC. The nov-miR-3345-5p and nov-miR-13172-3p, which are upregulated in tumors, are only expressed in colorectal tissues. These molecules have been linked to a worse prognosis in right-sided colon and rectal carcinomas. An analysis revealed an association between eight novel miRNAs and 81 targets, mostly cancer-related genes, with varying expression based on tumor location. These findings provide new miRNAs with potential biological relevance, molecular biomarkers, and therapeutic targets for CRC treatment.

Use of ergogenic aids among Brazilian athletes: a cross-sectional study exploring competitive level, sex and sports.

Was investigated ergogenic aids (EAs) used by Brazilian athletes and their association with performance, sex, sports classification, and modality. It identified the main purposes of EAs and their prescription. Methods: 239 athletes of 15 modalities, ranging from regional to international level, answered a survey online. Results: Highly competitive athletes consumed nutritional and mechanical aids more (OR = 1.96 CI 95% [1.28-2.9]; OR = 1.79 CI 95% [1.29-2.47]), while the use of psychological EAs decreased [OR = 1.66 95% CI (1.18-2.94); p = 0.001]. Male athletes [OR = 1.44 CI 95% (1.11-2.88)] and individual sports practitioners [OR = 1.78 CI 95% (1.02-3.11)] used nutritional aids more. Triathlon athletes had higher nutritional EA use, while soccer athletes had lower. Combat sports athletes had higher pharmacological EA use. Conclusion: Athletes use nutritional and pharmacological aids more to improve performance and gain lean body mass. Mechanical aids were used for recovery and psychological aids for motivation. Self-prescription is common, especially for pharmacological aids.

Antioxidant Interactions between Citrus Fruit Carotenoids and Ascorbic Acid in New Models of Animal Cell Membranes.

The regular consumption of citrus fruits by humans has been associated with lower incidence of chronic-degenerative diseases, especially those mediated by free radicals. Most of the health-promoting properties of citrus fruits derive from their antioxidant content of carotenoids and ascorbic acid (ASC). In the current work we have investigated the scavenging (against hydroxyl radical) and quenching capacities (against singlet oxygen) of four different carotenoid extracts of citrus fruits in the presence or absence of ASC (µM range) in organic solvent, aqueous solution, micelles and in an innovative biomimicking liposomal system of animal cell membrane (AML). The fruits of four varieties of citrus were selected for their distinctive carotenoid composition (liquid chromatography characterization): 'Nadorcott' mandarin and the sweet oranges 'Valencia late', 'Ruby Valencia' and 'Pinalate' mutant. The quenching activity of citrus carotenoids strongly depended on the biological assemblage: freely diffusible in organic solvent, 'Ruby Valencia' carotenoids (containing lycopene) showed the highest quenching activity, whereas 'Nadorcott' mandarin extracts, rich in ß-cryptoxanthin, prevailed in micellar systems. Interestingly, the addition of 10 µM ASC significantly increased the quenching activity of all citrus extracts in micelles: 'Valencia' orange (+53%), 'Pinalate' (+87%), 'Ruby' (4-fold higher) and 'Nadorcott' mandarins (+20%). Accurate C11-BODIPY581/591 fluorescence assays showed solid scavenging activities of all citrus extracts against AML oxidation: 'Valencia' (-61%), 'Pinalate' (-58%) and 'Ruby' oranges (-29%), and 'Nadorcott' mandarins (-70%). Indeed, all four citrus extracts tested here have balanced antioxidant properties; extracts from the 'Nadorcott' mandarin slightly prevailed overall, due, at least in part, to its high content of ß-cryptoxanthin. This study depicts some of the antioxidant interactions between citrus fruit carotenoids and ascorbic acid in models of animal cell membranes and reinforces the contribution of them in promoting health benefits for humans.

Chronic pain predicts a worse response to depression treatment, regardless of thyroid function or psychotropics prescribed.

BACKGROUND: Chronic pain (CP) and thyroid hormones' (TH) abnormalities are associated with depression, but the impact of pain and TH fluctuation on the response to depression treatment is uncertain. METHODS: Eighty-eight patients with major depression were evaluated before and after 6 months of specific treatment, through scales of symptoms' severity (HAM-D-17), psychomotor disturbance (CORE), and quality of life (WHOQOL-Bref). We reviewed psychiatric medications and measured TSH, T3 and T4. We used Generalized Estimating Equations to assess the interaction effect between CP and treatment time on depression severity and TH levels, and Bonferroni to compare means. RESULTS: 47.7 % of the patients had CP. Patients with and without CP did not differ at baseline. At follow-up, those with CP experienced a more modest decrease in symptoms' severity and no improvement in any domain of psychomotor disturbance, contrasting with a decrease of over 40 % from the baseline values of CORE in patients without CP (non-CP). Initial and final scores were respectively: HAM-D CP 24.06 and 19.3, Δ = -4.75; HAM-D non-CP 22.92 and 14.7, Δ = -8.21; CORE CP 5.36 and 5.24, Δ = -0.12; CORE non-CP 5.8 and 3.22, Δ = -2.57. There was no interaction with TH or life quality. Model adjustments for psychotropic drugs received and sensitivity analysis excluding somatic symptoms from severity scales did not impact the results. LIMITATIONS: Findings may not replicate in mildly depressed patients from primary care. Pain scales were not applied. CONCLUSIONS: Individuals with chronic pain showed a suboptimal response to depression treatment, regardless of the medications used or TH levels.

Empowering frail older adults: multicomponent elastic-band exercises and BCAA supplementation unleash physical health and preserve haematological biomarkers.

The effectiveness of Branched Chain Amino Acids (BCAAs) supplementation on enhancing exercise performance in both young and older adults remains a topic of debate. Recent research suggests that BCAAs combined with regular exercise might have an impact on human erythropoiesis, blood dynamics, and iron homeostasis. Given the increasing longevity of the global population, it is crucial to investigate the potential benefits of BCAA supplementation and regular exercise as non-pharmacological interventions for improving the overall health of frail older adults. To assess the influence of a 40-week multicomponent exercise intervention (MEP) combined BCCA supplementation on the haematological indicators of frail older adults (83-93 years old) residing in nursing homes. A prospective, naturalistic, controlled clinical trial employing an intervention-washout-intervention was conducted for this purpose. The study included four experimental groups: MEP plus BCAA supplementation (MEP + BCAA, n = 8), MEP only (n = 7), BCAA supplementation only (n = 7), and control group non exercising (CG, n = 13). Fried's physical frailty (PF) protocol was employed to stratify the participants. Additionally, the assessment included the evaluation of nutritional status, comorbidities, and anthropometric measurements. Among the several haematological markers examined, only mean cellular Haemoglobin Concentration (MCH) [F = 4.09; p < 0.03] and Mean Cell haemoglobin Concentration (MCHC) [F = 10, 323; p < 0,0001] showed significant effects of time group. Our findings demonstrate that a long-term intervention with BCAA plus MEP did not lead to significant alterations in the haematological profile. An 8-week withdrawal from interventions did not affect the frailty status in the MEP and MEP + BCAA groups, whereas the control group exhibited an increase in PF status. The findings, demonstrating the potential pro-immune effect and maintenance of MCH and MCHC levels, highlight the relevance of incorporating exercise and nutritional strategies to promote healthy aging. This study contributes to the achievement of the United Nations Sustainable Development Goals 3 (good health and well-being) and 10 (reduced Inequalities) for all.

Optimizing the synthesis of dimeric peptides: influence of the reaction medium and effects that modulate kinetics and reaction yield.

Peptides are remarkably interesting alternatives to several applications. In particular, antimicrobial sequences have raised major interest of the scientific community due to the resistance acquired by commonly used antibiotics. Amongst these, some dimeric peptides have shown very promising characteristics as strong biological activities and resistance against degradation by peptidases. However, despite such promising characteristics, a relatively small number of studies address dimeric peptides, mainly due to the synthesis-related obstacles in their production, whereas the well-implemented routines of solid phase peptide synthesis-which includes the possibility of automation-makes life significantly easier. Here, we present kinetic investigations of the dimerization of a cysteine-containing sequence to obtain the homodimeric antimicrobial peptide homotarsinin. Based on the structural and membrane interaction data already available for the dimer and its monomeric chain, we have proposed distinct dimerization protocols in selected environments, namely, aqueous buffer, TFE:H2O and micellar solutions. The experimental results were adjusted by a theoretical model. Both the kinetic profiles and the reaction yields are dependent on the reaction medium, clearly indicating that aggregation, peptide structure, and peptide-membrane interactions play major roles in the formation of the disulfide bond. Finally, the rationalization of the different aspects addressed here is expected to contribute to research and applications that demand the obtainment of dimeric peptides.

Are visual assessments of the single-leg squat valid to be used in clinical practice? A systematic review of measurement properties based on the COSMIN guideline.

OBJECTIVE: Evaluate the discriminative and convergent validity of visual scales for the assessment of movement quality in the single-leg squat. METHODS: Searches performed in CINAHL, Cochrane, Embase, PubMed, SPORTDiscus and Web of Science databases. Studies evaluating discriminative and convergent validity of movement quality visual assessments in single-leg squats were included. The COSMIN risk of bias checklist was used to assess the risk of bias, and certainty of evidence was assessed by the GRADE modified version. RESULTS: Ten studies evaluating three different methods of visual assessment of the single-leg squat (Crossley scale; Whatman score and Medial knee displacement) were included. Very low certainty evidence suggests that the Crossley scale had sufficient discriminative validity for patient-centred outcomes. Very low to moderate certainty evidence suggests that the three visual methods of assessment of the single-leg squat had insufficient discriminative validity for surrogate outcomes and groups. None of the three methods had the convergent validity assessed. CONCLUSION: The Crossley scale exhibited sufficient discriminative validity for patient-centred outcomes, although the evidence supporting this conclusion is of very low certainty. Visual scales for the assessment of the single-leg squat movement quality should be used with caution in clinical practice as most methods had insufficient discriminative validity and no reports of convergent validity.

Comparison of individual and pooled sampling methods for estimation of Vairimorpha (Nosema) spp. levels in experimentally infected honey bee colonies.

The microsporidian pathogens Vairimorpha apis and V. ceranae are known to cause intestinal infection in honey bees and are associated with decreased colony productivity and colony loss. The widely accepted method for determining Vairimorpha colony infection level for risk assessment and antibiotic treatment is based on spore counts of 60 pooled worker bees using light microscopy. Given that honey bee colonies consist of as many as 1,000 times more individuals, the number of bees collected for Vairimorpha detection may significantly impact the estimated colony infection level, especially in the case of uneven distribution of high- and low-infected individuals within a hive. Hence, we compared the frequency and severity of Vairimorpha infection in individual bees to pooled samples of 60, 120, and 180 bees, as well as compared the Vairimorpha spp. prevalence in pooled samples of 60 and 180 bees. Overall, we did not find significant differences in spore counts in pooled samples containing incremental numbers of bees, although we observed that, in less-infected colonies, a low frequency of highly infected individuals influenced the estimated colony infection level. Moreover, Vairimorpha spp. prevalence did not differ significantly among the pooled bee samples tested. Increasing the number of pooled bees from the recommended 60 bees to 180 bees did not yield a more accurate representation of colony infection level for highly infected colonies, but the clinical importance of a low frequency of highly infected individuals in less-infected colonies needs to be addressed in future studies.

The high salt intake in adults with metabolic syndrome is related to increased waist circumference and blood pressure: the Brazilian Longitudinal Study of Adult Health study (ELSA-Brasil).

OBJECTIVES: The association between metabolic syndrome (MetS), a cluster of cardiometabolic risk factors, and salt consumption has fed intense debate in recent years, although it is yet to be fully elucidated. We aimed to evaluate whether individuals with MetS have a high salt consumption and to identify which components of the MetS diagnosis could be independently related to high salt consumption. METHODS: We analyzed data from 11 982 adults, ages 35 to 74 y, from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort study, from which clinical and anthropometric data were assessed, and a validated 12-h overnight urine collection was used to estimate salt intake. MetS was defined according to the Adult Treatment Panel III criteria. RESULTS: Salt intake was increased in individuals with MetS compared with individuals without MetS, regardless of sex (men: 14.3 ± 6.4 g/d versus 12.2 ± 5.5 g/d, P < 0.001; women: 10.6 ± 4.9 g/d versus 8.9 ± 4.0 g/d, P < 0.001) and increased progressively as the MetS criteria accumulated. The high salt intake in MetS participants, however, was observed only in the presence of elevated waist circumference and/or blood pressure and not with the other MetS criteria (reduced high-density lipoprotein, increased triglycerides, and impaired fasting blood glucose), regardless of the presence of MetS. When diabetes was incorporated as a MetS criterion, increased salt intake was observed in men but not in women. CONCLUSIONS: Salt intake should be reduced worldwide, but strategies must be more intense in people with elevated blood pressure and waist circumference, regardless of MetS diagnosis, to avoid the associated morbidity and mortality.

Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem.

Propentofylline (PROP) is a methylated xanthine compound that diminishes the activation of microglial cells and astrocytes, which are neuronal cells strongly associated with many neurodegenerative diseases. Based on previously observed remyelination and neuroprotective effects, PROP has also been proposed to increment antioxidant defenses and to prevent oxidative damage in neural tissues. Since most neurodegenerative processes have free radicals as molecular pathological agents, the aim of this study was to evaluate the antioxidant effects of 12.5 mg·kg-1·day-1 PROP in plasma and the brainstem of Wistar rats exposed to the gliotoxic agent 0.1% ethidium bromide (EB) for 7-31 days. The bulk of the data here demonstrates that, after 7 days of EB treatment, TBARS levels were 2-fold higher in the rat CNS than in control, reaching a maximum of 2.4-fold within 15 days. After 31 days of EB treatment, lipoperoxidation in CNS was still 65% higher than that in the control. Clearly, PROP treatment limited the progression of lipoperoxidation in EB-oxidized CNS: it was, for example, 76% lower than in the EB-treated group after 15 days. Most of these effects were associated with PROP-induced activity of glutathione reductase in the brainstem: the EB + PROP group showed 59% higher GR activity than that of the EB or control groups within 7 days. In summary, aligning with previous studies from our group and with literature about MTXs, we observed that propentofylline (PROP) improved the thiol-based antioxidant defenses in the rat brainstem by the induction of the enzymatic activity of glutathione reductase (GR), which diminished lipid oxidation progression and rebalanced the redox status in the CNS.