Effects of Cashew Nuts (Anacardium occidentale L.) and Cashew Nut Oil on Intestinal Permeability and Inflammatory Markers during an Energy-Restricted 8-Week Intervention: A Randomized Controlled Trial (Brazilian Nuts Study).

Cashew nuts can contribute to improving intestinal permeability and inflammation as they contain essential nutrients and bioactive compounds, but no clinical trials have evaluated these potential effects. This randomized trial aimed to assess the effects of cashew nuts and their oil on intestinal permeability and inflammatory markers. Sixty-four adults with overweight or obesity were allocated into three groups receiving energy restriction (-500 kcal/day): control (CT, free nuts), cashew nuts (CN, 30 g/day), or cashew nut oil (OL, 30 mL/day). Urine lactulose and mannitol, plasma zonulin and the lipopolysaccharide-binding protein (LBP), plasma interleukins (IL-6, TNF-α, IL-10, IL-1ß, IL-8, and IL-12p70), and C-reactive proteins were analyzed. Energy restriction reduced body fat and other indicators of adiposity without differences between the groups. Only the control group increased LBPs after an 8-week intervention. There were no statistically significant differences found between the groups in terms of intestinal permeability and inflammatory markers. In conclusion, incorporating cashew nuts or cashew nut oil into an energy-restricted 8-week dietary intervention did not change intestinal permeability and inflammatory markers. As studies evaluating cashew nuts on these markers remain scarce, further research is needed, perhaps with a longer study period and a higher concentration of cashew nuts and oil.

Microfiltered red-purple pitaya concentrate: A promising multifunctional food-derived colorant.

Red pitaya fruit has become a source of natural colorant, because it is rich in betalains, a pigment that imparts a red-purple color that interests the food and cosmetics industries. This fruit also possesses high nutritional value, with a range of bioactive compounds known to confer potential health benefits and prevent chronic diseases, such as diabetes, which makes it useful for use as pharmaceutical agents and dietary supplements. In order to improve its technological and biological effects, a concentration will be required. Thus, the microfiltration, followed by vacuum concentration, can be an interesting strategy for this purpose. This study aimed to explore tangential microfiltration to produce microfiltered material, which is an important step to obtain the microfiltered red-purple pitaya concentrate. Therefore, physicochemical and chemical characterization (including 1H NMR analysis) and biological properties (toxicity and diabetes) of this concentrate were assessed, using adult zebrafish as a model. The results show that microfiltration was carried out efficiently, with an average consumption of 95.75 ± 3.13 and 74.12 ± 3.58 kW h m-3, varying according to the material used ("unpeeled pitaya pulp" or "pitaya pulp with peel," respectively). The in vivo tests indicated non-toxicity and hypoglycemic effect of the concentrate, since the blood glucose levels were significantly lower in the zebrafish groups treated with this concentrate in comparison with that of control group. Thus, this study suggests the potential of microfiltered red-purple pitaya concentrate as a promising multifunctional food-derived colorant, exhibiting beneficial biological effects far beyond its attractive color. PRACTICAL APPLICATION: Hylocereus polyrhizus (F.A.C. Weber) Britton & Rose has attracted attention as a potential source of natural colorants because of its red-purple skin and flesh color. In addition, this fruit has a range of bioactive compounds, which make it a valuable resource for providing potential health benefits and preventing chronic diseases such as diabetes. In this paper, the microfiltered red-purple pitaya concentrate showed beneficial biological effects far beyond its attractive color. Thus, this product can be considered a promising multifunctional food-derived colorant to use in the food, pharmaceutical, or cosmetics industries.

Cashew nut (Anacardium occidentale L.) and cashew nut oil reduce cardiovascular risk factors in adults on weight-loss treatment: a randomized controlled three-arm trial (Brazilian Nuts Study).

Introduction: Cashew nut contains bioactive compounds that modulate satiety and food intake, but its effects on body fat during energy restriction remains unknown. This study aimed to assess the effects of cashew nut and cashew nut oil on body fat (primary outcome) as well as adiposity, cardiometabolic and liver function markers (secondary outcomes). Materials and methods: An eight-week (8-wk) randomized controlled-feeding study involved 68 adults with overweight/obesity (40 women, BMI: 33 ± 4 kg/m2). Participants were randomly assigned to one of the energy-restricted (-500 kcal/d) groups: control (CT, free-nuts), cashew nut (CN, 30 g/d), or cashew nut oil (OL, 30 mL/d). Body weight, body composition, and blood collection were assessed at the baseline and endpoint of the study. Results: After 8-wk, all groups reduced significantly body fat (CT: -3.1 ± 2.8 kg; CN: -3.3 ± 2.7 kg; OL: -1.8 ± 2.6 kg), body weight (CT: -4.2 ± 3.8 kg; CN: -3.9 ± 3.1 kg; OL: -3.4 ± 2.4 kg), waist (CT: -5.1 ± 4.6 cm; CN: -3.9 ± 3.9 cm; OL: -3.7 ± 5.3 cm) and hip circumferences (CT: -2.9 ± 3.0 cm; CN: -2.7 ± 3.1 cm; OL: -2.9 ± 2.3 cm). CN-group reduced liver enzymes (AST: -3.1 ± 5.3 U/L; ALT: -6.0 ± 9.9 U/L), while the OL-group reduced LDL-c (-11.5 ± 21.8 mg/dL) and atherogenic index (-0.2 ± 0.5). Both intervention groups decreased neck circumference (CN: -1.0 ± 1.2 cm; OL: -0.5 ± 1.2 cm) and apo B (CN: -6.6 ± 10.7 mg/dL; OL: -7.0 ± 15.3 mg/dL). Conclusion: After an 8-wk energy-restricted intervention, all groups reduced body fat (kg), weight, and some others adiposity indicators, with no different effect of cashew nut or cashew nut oil. However, participants in the intervention groups experienced additional reductions in atherogenic marker, liver function biomarkers, and cardiovascular risk factors (neck circumference and apo B levels), with these effects observed across the OL group, CN group, and both intervention groups, respectively.Clinical trial registration:https://ensaiosclinicos.gov.br/rg/RBR-8xzkyp2, identifier 8xzkyp2.

Contemporary open surgical approaches for the management of carotid stenosis: a comprehensive review.

This study aims to provide an overview on contemporary open surgical approaches for the management of carotid artery stenosis. A comprehensive literature search was performed to identify and categorize open surgery intervention techniques for the management of carotid artery stenosis, focusing on the benefits and drawbacks of each technique. Five surgical techniques for carotid endarterectomy (CEA) have been described: CEA with primary closure, CEA with patch closure, CEA by eversion technique, CEA by modified eversion technique and CEA by partial eversion. Evidence has reported significantly higher rates of perioperative complications after CEA with primary closure, including 30-days stroke rate and late restenosis. Although more recent techniques have been reported to provide superior outcomes, electing the best surgical technique is still a matter of debate. Also, CEA using a mini-skin incision has been associated to lower risk of cranial/cervical nerve injury and shorter length of hospital stay. The selection of the surgical intervention should be tailored and have into consideration individual patient characteristics, clinical considerations, surgeon preference and surgical team expertise. Further large-scale randomized clinical trials are needed to support more robust decisions on the choice of contemporary open surgical approaches to manage carotid stenosis.

Neural underpinnings of ethical decisions in life and death dilemmas in naïve and expert firefighters.

When a single choice impacts on life outcomes, faculties to make ethical judgments come into play. Here we studied decisions in a real-life setting involving life-and-death outcomes that affect others and the decision-maker as well. We chose a genuine situation where prior training and expertise play a role: firefighting in life-threatening situations. By studying the neural correlates of dilemmas involving life-saving decisions, using realistic firefighting situations, allowed us to go beyond previously used hypothetical dilemmas, while addressing the role of expertise and the use of coping strategies (n = 47). We asked the question whether the neural underpinnings of deontologically based decisions are affected by expertise. These realistic life-saving dilemmas activate the same core reward and affective processing network, in particular the ventromedial prefrontal cortex, nucleus accumbens and amygdala, irrespective of prior expertise, thereby supporting general domain theories of ethical decision-making. We found that brain activity in the hippocampus and insula parametrically increased as the risk increased. Connectivity analysis showed a larger directed influence of the insula on circuits related to action selection in non-experts, which were slower than experts in non rescuing decisions. Relative neural activity related to the decision to rescue or not, in the caudate nucleus, insula and anterior cingulate cortex was negatively associated with coping strategies, in experts (firefighters) suggesting practice-based learning. This shows an association between activity and expert-related usage of coping strategies. Expertise enables salience network activation as a function of behavioural coping dimensions, with a distinct connectivity profile when facing life-rescuing dilemmas.

Peri-Carotid Adipose Tissue and Atherosclerosis at Carotid Bifurcation.

Vulnerable carotid plaques are responsible for 20% of the ischemic strokes. The identification of these asymptomatic carotid plaques that will become symptomatic is essential but remains unclear. Our main goal was to investigate whether the amount of the peri-carotid adipose tissue, estimated by the extra-media thickness (EMT), is associated with the atherosclerotic characteristics at the carotid bifurcation in patients with PAD. An observational, prospective, single-center, longitudinal study was conducted. Overall, 177 patients were subjected to carotid Doppler ultrasound at the study admission. The following data were collected: EMT, intima-media thickness (IMT), the presence of carotid plaques, the area of the highest plaque, the presence of "acute culprit" carotid stenosis, and the grade of internal carotid stenosis. "Acute culprit" carotid stenosis was defined as a significant atherosclerotic plaque that leads to a neurologic event within 15 days. From each carotid bifurcation, a right and a left EMT were determined. We analyzed both the mean EMTs (calculated as the mean between the right and the left EMT) and the EMT ipsilateral to the carotid bifurcation. The presence of carotid plaques was associated with a higher mean EMT [Median = 1.14; IQR = 0.66 versus Median = 0.97; IQR = 0.40; p = 0.001]. A positive correlation was found between the mean EMT and IMT (right: ρ = 0.20; p = 0.010; left: ρ = 0.21; p = 0.007) and between the mean EMT and the area of the largest carotid plaque (right: ρ = 0.17; p = 0.036; left: ρ = 0.22; p = 0.004). Left carotid stenosis ≥ 70% was associated with higher ipsilateral EMT [Median = 1.56; IQR = 0.70 versus Median = 0.94; IQR = 0.42; p = 0.009]. Patients with "acute culprit" carotid stenosis had a higher ipsilateral EMT [left ipsilateral EMT: Median = 1.46; IQR = 0.63; "non-acute": Median = 0.94; IQR = 0.43; p = 0.009; right ipsilateral EMT: Median = 2.25; IQR = 0.62; "non-acute": Median = 1.00; IQR = 0.51; p = 0.015]. This difference was not found in the contra-lateral EMT. Six months after the neurologic event, EMT ipsilateral to an "acute culprit" carotid stenosis decreased (p = 0.036). The amount of peri-carotid adipose tissue, estimated with EMT, was associated with atherosclerosis at the carotid arteries. The mean EMT was associated with the features of chronic atherosclerosis lesions: the presence of carotid plaques, IMT, and the area of the highest plaque. Ipsilateral EMT was linked with "acute culprit" atherosclerotic plaque.

UPLC-QTOF-MSE based metabolomics and chemometrics study of the pitaya processing.

The search for knowledge related to the Pitaya (Hylocereus polyrhizus [F.A.C. Weber] Britton & Rose, family Cactaceae) is commonly due to its beneficial health properties e aesthetic values. But process to obtain pitaya pulp is a first and important step in providing information for the subsequent use of this fruit as colorant, for example. Therefore, the effects of the pulping process on the metabolomic and chemometric profile of non-volatile compounds of pitaya were assessed for the first time. The differences in metabolic fingerprints using UPLC-QTOF-MSE and multivariate modeling (PCA and OPLS-DA) was performed in the following treatments: treatment A, which consists of pelled pitaya and no ascorbic acid addition during pulping; treatment B, use of unpelled pitaya added of ascorbic acid during pulping; and control, unpelled pitaya and no ascorbic acid addition during pulping. For the metabolomic analysis, UPLC-QTOF-MSE shows an efficient method for the simultaneous determination of 35 non-volatile pitaya metabolites, including isorhamnetin glucosyl rhamnosyl isomers, phyllocactin isomers, 2'-O-apiosyl-phylocactin and 4'-O-malonyl-betanin. In addition, the chemometric analysis efficiently distinguished the metabolic compounds of each treatment applied and shows that the use of unpelled pitaya added of ascorbic acid during pulping has an interesting chemical profile due to the preservation or formation of compounds, such as those derived from betalain, and higher yields, which is desirable for the food industry.

Neurochemical differences in core regions of the autistic brain: a multivoxel 1H-MRS study in children.

Autism spectrum disorder (ASD) is a neurodevelopmental condition which compromises various cognitive and behavioural domains. The understanding of the pathophysiology and molecular neurobiology of ASD is still an open critical research question. Here, we aimed to address ASD neurochemistry in the same time point at key regions that have been associated with its pathophysiology: the insula, hippocampus, putamen and thalamus. We conducted a multivoxel proton magnetic resonance spectroscopy (1H-MRS) study to non-invasively estimate the concentrations of total choline (GPC + PCh, tCho), total N-acetyl-aspartate (NAA + NAAG, tNAA) and Glx (Glu + Gln), presenting the results as ratios to total creatine while investigating replication for ratios to total choline as a secondary analysis. Twenty-two male children aged between 10 and 18 years diagnosed with ASD (none with intellectual disability, in spite of the expected lower IQ) and 22 age- and gender-matched typically developing (TD) controls were included. Aspartate ratios were significantly lower in the insula (tNAA/tCr: p = 0.010; tNAA/tCho: p = 0.012) and putamen (tNAA/tCr: p = 0.015) of ASD individuals in comparison with TD controls. The Glx ratios were significantly higher in the hippocampus of the ASD group (Glx/tCr: p = 0.027; Glx/tCho: p = 0.011). Differences in tNAA and Glx indices suggest that these metabolites might be neurochemical markers of region-specific atypical metabolism in ASD children, with a potential contribution for future advances in clinical monitoring and treatment.

Unveiling Lung Adenocarcinoma: Non-bacterial Thrombotic Endocarditis as the Debut Sign.

Non-bacterial thrombotic endocarditis (NBTE) involves the deposition of fibrin and platelets on heart valves, frequently leading to systemic embolism. The association between NBTE and cancer demands thorough investigation in cases lacking an evident cause. This case report elucidates the clinical course of a nonsmoking woman in her sixties with NBTE linked to pulmonary adenocarcinoma. The patient, who had a history of multiple sclerosis (MS) and was receiving dimethyl fumarate treatment, presented to the emergency department with stroke-like symptoms. Diagnostic challenges arose due to preexisting motor sensory impairment from MS. Initial evaluations revealed hypocapnia and elevated inflammatory markers. Blood cultures were obtained twice, and imaging confirmed pneumonia, left pleural effusion, and chronic pulmonary embolism while excluding acute vascular events or intracranial hemorrhage. The first transthoracic echocardiogram (TTE) indicated no cardiac abnormalities. Treatment encompassed parenteral antibiotics, systemic anticoagulation, and admission to medical floors. Although the initial treatment yielded a positive clinical response, subsequent complications emerged. On the tenth day, the patient required additional interventions, including broad-spectrum antibiotics and supplemental oxygen. A follow-up chest X-ray revealed persistent pneumonia and pleural effusion, and blood cultures upon admission returned negative. A subsequent head MRI confirmed an embolic stroke and displayed evidence of MS progression. Around the twentieth day, empirical treatment for infective endocarditis was initiated, and an 8 mm vegetation on the aortic valve was identified via transesophageal echocardiography (TOE). Acute pulmonary edema prompted a transfer to the intermediate care unit. Further investigations, including left thoracocentesis and CT, unveiled exudate and metastatic lesions in the liver, ilium, and kidney. Unfortunately, on the twenty-fifth day, the patient experienced acute myocardial infarction, right leg ischemia, disseminated intravascular coagulation, and shock. Pleural fluid analysis revealed malignant cells suggestive of lung adenocarcinoma. This case underscores the pivotal role of timely NBTE recognition and the search for malignancy when workup for infective endocarditis and autoimmune panels is negative. Moreover, it emphasizes the significance of vigilant monitoring, particularly in immunocompromised individuals or those with preexisting neurological deficits, especially when new neurological symptoms manifest. These insights significantly contribute to the comprehension of NBTE management and its implications for analogous patient cohorts.

Evaluation of a Standardized Extract Obtained from Cashew Apple (Anacardium occidentale L.) Bagasse in DSS-Induced Mouse Colitis.

Inflammatory bowel diseases (IBD) include Crohn's disease and ulcerative colitis. Several studies relate eating habits to different aspects of IBD, such as progression and worsening of the clinical condition. Therefore, many natural products (NPs) such as polyphenols and carotenoids have been identified as promising agents in supporting IBD. An interesting source for obtaining bioactive NPs is the by-products of the food industry. The present study evaluated the potential beneficial effect of a standardized extract (CAE) obtained from cashew apple bagasse in the dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice. This was the first time that CAE had been evaluated in this experimental model. Chemical evaluation of CAE identified carotenoids (96.28 ± 0.15 mg/100 g), phenolic compounds (37.49 ± 0.64 mg/100 g), and a mixture of anacardic acids (C15:3 = 94.2 ± 0.6 mg/100 g; C15:2 = 108.4 ± 0.1 mg/100 g; C15:1 = 214.8 ± 0.2 mg/100 g). Administration of CAE (500 mg/kg, 4 days, p.o.) after DSS challenge was more effective in delaying disease progression compared with prior treatment (500 mg/kg, 30 days, p.o.), according to the disease activity index. However, no treatment strategy with CAE was able to prevent or inhibit disease progression, since all parameters evaluated (macroscopic, biochemical, and histopathological) in CAE-treated animals were similar to those observed in DSS-challenged animals. Despite the high dose (500 mg/kg), the standardized extract (CAE) did not result in an effective concentration of carotenoids. Furthermore, as some anacardic acids have been reported as histone acetyltransferases inhibitors, there could be a possible antagonistic relationship between carotenoids and anacardic acids. Complementary research will be necessary to test the hypothesis of antagonism. Thus, an optimized extract, with an even higher concentration of carotenoids, obtained from cashew apple bagasse, can be developed as a possible adjuvant food supplement for inflammatory bowel diseases.

Intra-Amniotic Administration of Cashew Nut (Anacardium occidentale L.) Soluble Extract Improved Gut Functionality and Morphology In Vivo (Gallus gallus).

Cashew nuts are rich in dietary fibers, monounsaturated fatty acids, carotenoids, tocopherols, flavonoids, catechins, amino acids, and minerals that offer benefits for health. However, the knowledge of its effect on gut health is lacking. In this way, cashew nut soluble extract (CNSE) was assessed in vivo via intra-amniotic administration in intestinal brush border membrane (BBM) morphology, functionality, and gut microbiota. Four groups were evaluated: (1) no injection (control); (2) H2O injection (control); (3) 10 mg/mL CNSE (1%); and (4) 50 mg/mL CNSE (5%). Results related to CNSE on duodenal morphological parameters showed higher Paneth cell numbers, goblet cell (GC) diameter in crypt and villi, depth crypt, mixed GC per villi, and villi surface area. Further, it decreased GC number and acid and neutral GC. In the gut microbiota, treatment with CNSE showed a lower abundance of Bifidobacterium, Lactobacillus, and E. coli. Further, in intestinal functionality, CNSE upregulated aminopeptidase (AP) gene expression at 5% compared to 1% CNSE. In conclusion, CNSE had beneficial effects on gut health by improving duodenal BBM functionality, as it upregulated AP gene expression, and by modifying morphological parameters ameliorating digestive and absorptive capacity. For intestinal microbiota, higher concentrations of CNSE or long-term intervention may be necessary.

Impact of different kernel grades on volatile compounds profile, fatty acids and oxidative quality of cashew nut oil.

In this study, the impact of kernel grade on the physicochemical quality, fatty acids, and volatile compounds of cashew nut oil was assessed. The oil samples were obtained from different classifications of nuts and analyzed for acid and peroxide values, color, fatty acids and volatile compounds. The broken kernel oils showed similar or superior quality to the whole kernel oil (LW3), especially samples B3 (batoque) and P3 (large piece), with acid, peroxide and color values equal to the one in LW3. The oils from less intact nuts showed high proportions of monounsaturated fatty acids (MUFA), with acid ratios higher than the ones in LW3 (64.47 to 65.28 %, while the latter displayed 63.33 %). Sample P3 showed higher proportions of volatile compounds not derived from oxidation. This study expands the possibility of valorizing lower commercial value cashew nuts by producing oil with adequate quality for consumption.

Assessment of metabolic, mineral, and cytotoxic profile in pineapple leaves of different commercial varieties: A new eco-friendly and inexpensive source of bioactive compounds.

Pineapple is among the most produced and consumed fruits worldwide, and consequently, its agroindustrial production/processing generates high amounts of agricultural waste, which are routinely discarded. Thus, it is crucial to seek alternatives to reuse this agricultural waste that are in high availability. Therefore, this work aims to evaluate the chemical composition of a specific residue (leaves) of seven commercial varieties of pineapples, to attribute high added value uses, and to evaluate its potential as a source of secondary metabolites and minerals. Thereby, twenty-eight metabolites were annotated by UPLC-QTOF-MSE, including amino acids, organic acids, and phenolic compounds. The following minerals were quantitatively assessed by ICP-OES: Zn (5.30-19.77 mg kg-1), Cr, Cd, Mn (50.80-113.98 mg kg-1), Cu (1.05-4.01 mg kg-1), P (1030.77-6163.63 mg kg-1) and Fe (9.06-70.17 mg kg-1). In addition, Cr and Cd (toxic materials) present concentration levels below the limit of quantification of the analytical method (LOQCr and LOQCd = 0.02 mg kg-1) for all samples. The multivariate analysis was conceived from the chemical profile, through the tools of PCA (principal component analysis) and HCA (hierarchical cluster analysis). The results show that pineapple leaves have similarities and differences concerning their chemical composition. In addition, the cytotoxicity assays of the extracts against tumor and non-tumor strains shows that the extracts were non-toxic. This fact can corroborate and enhance the prospection of new uses and applications of agroindustrial co-products from pineapple, enabling the evaluation and use in different types of industries, such as pharmacological, cosmetic, and food, in addition to the possibility of being a potential source of bioactive compounds.

Previous gut microbiota has an effect on postprandial insulin response after intervention with yacon syrup as a source of fructooligosaccharides: a randomized, crossover, double-blind clinical trial.

OBJECTIVES: The use of prebiotics has an effect on postprandial glucose and insulin concentrations; however, the interaction between the previous profile of the intestinal microbiota and the effect of supplementation with prebiotics is not clear. Our objective was to evaluate the effect of previous intestinal microbiota profile on the postprandial insulin response to yacon syrup, used as a source of fructooligosaccharides (FOSs), in young women. The product presents high levels of FOS. METHODS: In this double-blind, crossover, randomized clinical trial, 40 adult women were allocated to receive a breakfast containing 40 g of yacon syrup (14 g FOS, intervention A) or a breakfast containing 40 g of placebo (intervention B). On each intervention day, after 12 h of fasting, an aliquot of blood was collected for insulin analysis at 0, 15, 30, 45, 60, 90, and 120 min. The fecal sample was collected before the beginning of the interventions, and the DNA was extracted and quantified, with subsequent amplification of the 16S region, next-generation sequencing, and analysis of sequencing data. RESULTS: The glucose and insulin concentrations were reduced after ingestion of yacon syrup compared with placebo, specifically at the 30 min to insulin. After the receiver operating characteristic analysis, six volunteers who did not respond to the yacon consumption intervention were identified. The abundance of the phylum Actinobacteria (P = 0.021) and the order Bifidobacteriales (P = 0.013) were positively associated with better insulin response. Other main phyla were not associated with intervention response. CONCLUSIONS: The previous profile of the intestinal microbiota has an effect on the postprandial insulin response to FOSs, mainly in the phylum Actinobacteria and Bifidobacteriales order.

The impact of cathodal tDCS on the GABAergic system in the epileptogenic zone: A multimodal imaging study.

Objectives: We aimed to investigate the antiepileptic effects of cathodal transcranial direct current stimulation (c-tDCS) and mechanisms of action based on its effects on the neurotransmitters responsible for the abnormal synchrony patterns seen in pharmacoresistant epilepsy. This is the first study to test the impact of neurostimulation on epileptiform interictal discharges (IEDs) and to measure brain metabolites in the epileptogenic zone (EZ) and control regions simultaneously in patients with pharmacoresistant epilepsy. Methods: This is a hypothesis-driven pilot prospective single-blinded repeated measure design study in patients diagnosed with pharmacoresistant epilepsy of temporal lobe onset. We included seven patients who underwent two sessions of c-tDCS (sham followed by real). The real tDCS session was 20 min in duration and had a current intensity of 1.5 mA delivered via two surface electrodes that had dimensions of 3 × 4 cm. The cathode electrode was placed at FT7 in the center whereas the anode at Oz in the center. After each session, we performed electroencephalographic recording to count epileptiform IEDs over 30 min. We also performed magnetic resonance spectroscopy (MRS) to measure brain metabolite concentrations in the two areas of interest (EZ and occipital region), namely, gamma-aminobutyric acid (GABA), glutamate (Glx), and glutathione. We focused on a homogenous sample where the EZ and antiepileptic medications are shared among patients. Results: Real tDCS decreased the number of epileptiform IEDs per min (from 9.46 ± 2.68 after sham tDCS to 5.37 ± 3.38 after real tDCS), p = 0.018, as compared to sham tDCS. GABA was decreased in the EZ after real c-tDCS stimulation as compared to sham tDCS (from 0.129 ± 0.019 to 0.096 ± 0.018, p = 0.02). The reduction in EZ GABA correlated with the reduction in the frequency of epileptiform IED per min (rho: 0.9, p = 0.003). Conclusion: These results provide a window into the antiepileptic mechanisms of action of tDCS, based on local and remote changes in GABA and neural oscillatory patterning responsible for the generation of interictal epileptiform discharges.

Cortical inhibition in neurofibromatosis type 1 is modulated by lovastatin, as demonstrated by a randomized, triple-blind, placebo-controlled clinical trial.

Neurofibromatosis type 1 (NF1) is associated with GABAergic dysfunction which has been suggested as the underlying cause of cognitive impairments. Previous intervention trials investigated the statins' effects using cognitive outcome measures. However, available outcome measures have led to inconclusive results and there is a need to identify other options. Here, we aimed at investigating alternative outcome measures in a feasibility trial targeting cortical inhibition mechanisms known to be altered in NF1. We explored the neurochemical and physiological changes elicited by lovastatin, with magnetic resonance spectroscopy and transcranial magnetic stimulation (TMS). Fifteen NF1 adults participated in this randomized, triple-blind, placebo-controlled crossover trial (Clinicaltrials.gov NCT03826940) composed of one baseline and two reassessment visits after lovastatin/placebo intake (60 mg/day, 3-days). Motor cortex GABA+ and Glx concentrations were measured using HERMES and PRESS sequences, respectively. Cortical inhibition was investigated by paired-pulse, input-output curve, and cortical silent period (CSP) TMS protocols. CSP ratios were significantly increased by lovastatin (relative: p = 0.027; absolute: p = 0.034) but not by placebo. CSP durations showed a negative correlation with the LICI 50 ms amplitude ratio. Lovastatin was able to modulate cortical inhibition in NF1, as assessed by TMS CSP ratios. The link between this modulation of cortical inhibition and clinical improvements should be addressed by future large-scale studies.

Motor Cortex Excitation/Inhibition Imbalance in Young Adults With Autism Spectrum Disorder: A MRS-TMS Approach.

Excitatory/inhibitory imbalance has been suggested as a neurobiological substrate of the cognitive symptomatology in Autism Spectrum Disorder (ASD). Studies using magnetic resonance spectroscopy (MRS) attempted to characterize GABA and Glutamate brain levels in ASD. However mixed findings have been reported. Here, we characterize both neurochemical and physiological aspects of GABA system in ASD by implementing a more comprehensive approach combining MRS and transcranial magnetic stimulation (TMS). A group of 16 young ASD adults and a group of 17 controls participated in this study. We employed one MRS session to assess motor cortex GABA+ and Glutamate+Glutamine (Glx) levels using MEGAPRESS and PRESS sequences, respectively. Additionally, a TMS experiment was implemented including paired-pulse (SICI, ICF and LICI), input-output curve and cortical silent period to probe cortical excitability. Our results showed a significantly increased Glx, with unchanged GABA+ levels in the ASD group compared with controls. Single TMS measures did not differ between groups, although exploratory within-group analysis showed impaired inhibition in SICI5ms, in ASD. Importantly, we observed a correlation between GABA levels and measures of the input-output TMS recruitment curve (slope and MEP amplitude) in the control group but not in ASD, as further demonstrated by direct between group comparisons. In this exploratory study, we found evidence of increased Glx levels which may contribute to ASD excitatory/inhibitory imbalance while highlighting the relevance of conducting further larger-scale studies to investigate the GABA system from complementary perspectives, using both MRS and TMS techniques.

The Neurophysiological Impact of Subacute Stroke: Changes in Cortical Oscillations Evoked by Bimanual Finger Movement.

INTRODUCTION: To design more effective interventions, such as neurostimulation, for stroke rehabilitation, there is a need to understand early physiological changes that take place that may be relevant for clinical monitoring. We aimed to study changes in neurophysiology following recent ischemic stroke, both at rest and with motor planning and execution. MATERIALS AND METHODS: We included 10 poststroke patients, between 7 and 10 days after stroke, and 20 age-matched controls to assess changes in cortical motor output via transcranial magnetic stimulation and in dynamics of oscillations, as recorded using electroencephalography (EEG). RESULTS: We found significant differences in cortical oscillatory patterns comparing stroke patients with healthy participants, particularly in the beta rhythm during motor planning (p = 0.011) and execution (p = 0.004) of a complex movement with fingers from both hands simultaneously. Discussion. The stroke lesion induced a decrease in event-related desynchronization in patients, in comparison to controls, providing evidence for decreased disinhibition. CONCLUSIONS: After a stroke lesion, the dynamics of cortical oscillations is changed, with an increasing neural beta synchronization in the course of motor preparation and performance of complex bimanual finger tasks. The observed patterns may provide a potential functional measure that could be used to monitor and design interventional approaches in subacute stages.

Brazil and cashew nuts intake improve body composition and endothelial health in women at cardiometabolic risk (Brazilian Nuts Study): a randomized controlled trial.

Several mechanisms have been proposed for the beneficial effect of nuts on health. However, Brazil and cashew nuts remain the least studied. We aim to evaluate the effect of these nuts within an energy-restricted diet on body weight, body composition, cardiometabolic markers, and endothelial function in cardiometabolic risk women. Brazilian nuts study is a randomized controlled parallel 8-week dietary intervention trial. Forty women were randomly allocated to 1) Control group: Energy-restricted diet without nuts, n= 19 or, 2) Brazil and cashew nuts group (BN-Group): Energy-restricted diet containing daily 45 g of nuts (15 g of Brazil nuts + 30g of cashew nuts), n= 21. At the beginning and final intervention, anthropometry, body composition, and blood pressure were measured. Fasting blood sampling was obtained to evaluate lipid profile, glucose homeostasis, and endothelial function markers. After 8-week, plasma selenium concentration increased in BN-group (∆ = + 31.5 ± 7.8 µg/L; p= 0.001). Brazil and cashew nuts intake reduced total body fat (-1.3 ± 0.4 %) parallel to improvement of lean mass percentage in BN-group compared to the control. Besides, the soluble adhesion molecule VCAM-1 decreased (24.03 ± 15.7 pg/mL vs. -22.2 ± 10.3 pg/mL; p= 0.019) after Brazil and cashew nuts intake compared to the control. However, lipid and glucose profile markers, apolipoproteins, and blood pressure remained unchanged after the intervention. Thus, the addition of Brazil and cashew nuts to an energy-restricted diet can be a healthy strategy to improve body composition, selenium status, and endothelial inflammation in cardiometabolic risk women.