Digital screener of socio-motor agency balancing motor autonomy and motor control.

Dyadic social interactions evoke complex dynamics between two agents that, while exchanging unequal levels of body autonomy and motor control, may find a fine balance to synergize, take turns, and gradually build social rapport. To study the evolution of such complex interactions, we currently rely exclusively on subjective pencil and paper means. Here, we complement this approach with objective biometrics of socio-motor behaviors conducive to socio-motor agency. Using a common clinical test as the backdrop of our study to probe social interactions between a child and a clinician, we demonstrate new ways to streamline the detection of social readiness potential in both typically developing and autistic children by uncovering a handful of tasks that enable quantification of levels of motor autonomy and levels of motor control. Using these biometrics of autonomy and control, we further highlight differences between males and females and uncover a new data type amenable to generalizing our results to any social setting. The new methods convert continuous dyadic bodily biorhythmic activity into spike trains and demonstrate that in the context of dyadic behavioral analyses, they are well characterized by a continuous Gamma process that can classify individual levels of our thus defined socio-motor agency during a dyadic exchange. Finally, we apply signal detection processing tools in a machine learning approach to show the validity of the streamlined version of the digitized ADOS test. We offer a new framework that combines stochastic analyses, non-linear dynamics, and information theory to streamline and facilitate scaling the screening and tracking of social interactions with applications to autism.

Effects of mixed nuts as part of a Brazilian Cardioprotective diet on LDL-cholesterol in adult patients after myocardial infarction: a multicenter randomized controlled clinical trial.

BACKGROUND: Nuts consumption is related to cardioprotective effects on primary cardiovascular prevention, but studies conducted in secondary prevention are small, scarce and controversial. The objective of this trial was to evaluate the effects of a regional and sustainable cardioprotective diet added or not with an affordable mixed nuts on cardiometabolic features in patients with previous myocardial infarction. METHODS: DICA-NUTS study is a national, multi-center, and superiority-parallel randomized clinical trial. Males and females over 40 years old diagnosed with previous myocardial infarction in the last 2 to 6 months were included. Patients were allocated into two groups: the Brazilian Cardioprotective diet (DICA Br) supplemented with 30 g/day of mixed nuts (10 g of peanuts; 10 g of cashew; 10 g of Brazil nuts) (intervention group, n = 193); or only DICA Br prescription (control group, n = 195). The primary outcome was low-density lipoprotein cholesterol means (in mg/dL) after 16 weeks. Secondary outcomes were other lipid biomarkers, glycemic and anthropometric data and diet quality. RESULTS: After adjustment for baseline values, participating study site, time since myocardial infarction and statin treatment regimen (high potency, moderate and low potency/no statins), no significant difference was found between the groups in low-density lipoprotein cholesterol concentrations (intervention-control difference: 3.48 mg/dL [-3.45 to 10.41], P = 0.32). Both groups improved their overall diet quality at the end of the study without differences between them after 16 weeks (intervention-control difference: 1.05 (-0.9 to 2.99); P = 0.29). Other lipids, glycemic profile and anthropometrics were also not different between study groups at the end of the study. CONCLUSION: Adding 30 g/day of mixed nuts to the DICA Br for 16 weeks did not change lipid, glycemic and anthropometric features in the post-myocardial infarction setting. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov website under number NCT03728127 and its World Health Organization Universal Trial Number (WHO-UTN) is U1111-1259-8105.

Rats Exposed to Excess Sucrose During a Critical Period Develop Inflammation and Express a Secretory Phenotype of Vascular Smooth Muscle Cells.

BACKGROUND: Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Inflammation might contribute to changes during this period and could be associated with variations in the vascular smooth muscle (VSMC) phenotype. OBJECTIVE: We studied changes in inflammatory pathways that could underlie the expression of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP. METHODS: We analyzed histological changes in the aorta and the expression of the COX-2, TLR4, iNOS, eNOS, MMP-2 and -9, and ß- and α-actin, the quantities of TNF-α, IL-6, and IL-1ß using ELISA, and the levels of fatty acids using gas chromatography. RESULTS: The aortic wall presented disorganization, decellularization, and wavy elastic fibers and an increase in the lumen area. The α- and ß-actin expressions were decreased, while COX-2, TLR4, TNF-α, and the activity of IL-6 were increased. Oleic acid was increased in CP in comparison to the control group. CONCLUSIONS: There is transient hypertension at the end of the CP that is accompanied by inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the development of hypertension when animals reach adulthood.

Bioactive compounds of peanut skin in prevention and adjunctive treatment of chronic non-communicable diseases.

The global prevalence of cancer continues to increase, so does its mortality. Strategies that can prevent/treat this condition are therefore required, especially low-cost and low-toxicity strategies. Bioactive compounds of plant origin have been presented as a good alternative. In this scenario, due to its abundant polyphenolic content (around 60 to 120 times greater than that of the grain), peanut skin by-products stand out as a sustainable source of food bioactives beneficial to human health. Investigated studies highlighted the importance of peanut skin for human health, its phytochemical composition, bioactivity and the potential for prevention and/or adjuvant therapy in cancer, through the advanced search for articles in the Virtual Health Library (VHL), Science direct and the Mourisco platform of the FioCruz Institute, from 2012 to 2022. Using the keywords, "peanut skin" AND "cancer" AND NOT "allergy", the words "peanut testa" and "peanut peel" were included replacing "peanut skin". 18 articles were selected from Plataforma Mourisco, 26 from Science Direct and 26 from VHL. Of these, 7 articles evaluated aspects of cancer prevention and/or treatment. Promising benefits were found in the prevention/treatment of chronic non-communicable diseases in the use of peanut and peanut skin extracts, such as cholesterolemia and glucose control, attenuation of oxidative stress and suppressive action on the proliferation and metabolism of cancer cells.

Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

BACKGROUND: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. OBJECTIVES: We asked whether high performance of an Immunochromatographic-test (ICT) could enable accurate, rapid diagnosis/treatment, establishing new, improved care-paradigms at point-of-care and clinical laboratory. METHODS: Data were obtained in 12 studies/analyses addressing: 1-feasibility/efficacy; 2-false-positives; 3-acceptability; 4-pink/black-line/all studies; 5-time/cost; 6-Quick-Information/Limit-of-detection; 7, 8-acute;-chronic; 9-epidemiology; 10-ADBio; 11,12-Commentary/Cases/Chronology. FINDINGS: ICT was compared with gold-standard or predicate-tests. Overall, ICT performance for 1093 blood/4967 sera was 99.2%/97.5% sensitive and 99.0%/99.7% specific. However, in clinical trial, FDA-cleared-predicate tests initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false-positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO REASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. CONCLUSIONS/SIGNIFICANCE: This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. TRIAL REGISTRATION: NCT04474132, https://clinicaltrials.gov/study/NCT04474132 ClinicalTrials.gov.

Overall diet quality, food groups and mental health disorders among Brazilians older than 15 years old: Brazilian National Health Survey - 2019.

BACKGROUND: Adherence to a nutrient-dense diet can have an impact on depression and other mental health issues. Little is known whether this is attributed to some or all components and how these differ in a country that is known to have a vast diversity of nutrient-dense foods. The aim was to examine whether there is a relationship between individual food groups with depression and other mental health disorders. METHODS: Data was from 89,955 Brazilians from the National Health Survey. Mental health and diet were accessed using a screener questionnaire. Descriptive statistics and regression analyses were calculated. RESULTS: Persons living with depression had significantly lower diet scores for vegetables/fruits (ß = -0.08, 95 % CI -0.13, -0.02), grains/roots (ß = -0.05; 95%CI (-0.07, -0.03)), beans (ß = -0.03; 95%CI (-0.04, -0.01)) and higher scores for sweetened beverages (ß = 0.04; 95%CI (0.01, 0.07)), sweets and sugars (ß = 0.03; 95%CI (0.01, 0.05) and high fat/sodium products (ß = 0.04; 9%CI (0.01, 0.07). Individuals living with other mental disorders showed lower scores for grains/roots (ß = -0.03; 95%CI (-0.06, -0.01)) and higher scores for sweets and sugars (ß = 0.06; 95%CI (0.03, 0.09)) and high fat/sodium products (ß = 0.05; 95%CI (0.01, 0.09)). CONCLUSION: People with mental health disorders are more likely to have an unhealthy diet. Relationships were slightly stronger with depression in particular food groups as other mental disorders. Further studies are needed to help in the prevention of these disorders.

Discovery of TRPA1 Antagonist GDC-6599: Derisking Preclinical Toxicity and Aldehyde Oxidase Metabolism with a Potential First-in-Class Therapy for Respiratory Disease.

Transient receptor potential ankyrin 1 (TRPA1) is a nonselective calcium ion channel highly expressed in the primary sensory neurons, functioning as a polymodal sensor for exogenous and endogenous stimuli, and has been implicated in neuropathic pain and respiratory disease. Herein, we describe the optimization of potent, selective, and orally bioavailable TRPA1 small molecule antagonists with strong in vivo target engagement in rodent models. Several lead molecules in preclinical single- and short-term repeat-dose toxicity studies exhibited profound prolongation of coagulation parameters. Based on a thorough investigative toxicology and clinical pathology analysis, anticoagulation effects in vivo are hypothesized to be manifested by a metabolite─generated by aldehyde oxidase (AO)─possessing a similar pharmacophore to known anticoagulants (i.e., coumarins, indandiones). Further optimization to block AO-mediated metabolism yielded compounds that ameliorated coagulation effects in vivo, resulting in the discovery and advancement of clinical candidate GDC-6599, currently in Phase II clinical trials for respiratory indications.

Irregularity of instantaneous gamma frequency in the motor control network characterize visuomotor and proprioceptive information processing.

Objective.The study aims to characterize movements with different sensory goals, by contrasting the neural activity involved in processing proprioceptive and visuo-motor information. To accomplish this, we have developed a new methodology that utilizes the irregularity of the instantaneous gamma frequency parameter for characterization.Approach.In this study, eight essential tremor patients undergoing an awake deep brain stimulation implantation surgery repetitively touched the clinician's finger (forward visually-guided/FV movement) and then one's own chin (backward proprioceptively-guided/BP movement). Neural electrocorticographic recordings from the motor (M1), somatosensory (S1), and posterior parietal cortex (PPC) were obtained and band-pass filtered in the gamma range (30-80 Hz). The irregularity of the inter-event intervals (IEI; inverse of instantaneous gamma frequency) were examined as: (1) auto-information of the IEI time series and (2) correlation between the amplitude and its proceeding IEI. We further explored the network connectivity after segmenting the FV and BP movements by periods of accelerating and decelerating forces, and applying the IEI parameter to transfer entropy methods.Main results.Conceptualizing that the irregularity in IEI reflects active new information processing, we found the highest irregularity in M1 during BP movement, highest in PPC during FV movement, and the lowest during rest at all sites. Also, connectivity was the strongest from S1 to M1 and from S1 to PPC during FV movement with accelerating force and weakest during rest.Significance. We introduce a novel methodology that utilize the instantaneous gamma frequency (i.e. IEI) parameter in characterizing goal-oriented movements with different sensory goals, and demonstrate its use to inform the directional connectivity within the motor cortical network. This method successfully characterizes different movement types, while providing interpretations to the sensory-motor integration processes.

Total Outflow of High-Density Lipoprotein-Cholesteryl Esters from Plasma Is Decreased in a Model of 3/4 Renal Mass Reduction.

(1) Background: Previous studies have enriched high-density lipoproteins (HDL) using cholesteryl esters in rabbits with a three-quarter reduction in functional renal mass, suggesting that the kidneys participate in the cholesterol homeostasis of these lipoproteins. However, the possible role of the kidneys in lipoprotein metabolism is still controversial. To understand the role of the kidneys in regulating the HDL lipid content, we determined the turnover of HDL-cholesteryl esters in rabbits with a three-quarter renal mass reduction. (2) Methods: HDL subclass characterization was conducted, and the kinetics of plasma HDL-cholesteryl esters, labeled with tritium, were studied in rabbits with a 75% reduction in functional renal mass (Ntx). (3) Results: The reduced renal mass triggered the enrichment of cholesterol, specifically cholesteryl esters, in HDL subclasses. The exchange of cholesteryl esters between HDL and apo B-containing lipoproteins (VLDL/LDL) was not significantly modified in Ntx rabbits. Moreover, the cholesteryl esters of HDL and VLDL/LDL fluxes from the plasmatic compartment tended to decrease, but they only reached statistical significance when both fluxes were added to the Nxt group. Accordingly, the fractional catabolic rate (FCR) of the HDL-cholesteryl esters was lower in Ntx rabbits, concomitantly with its accumulation in HDL subclasses, probably because of the reduced mass of renal cells requiring this lipid from lipoproteins.

In vitro toxicity of fine and coarse particulate matter on the skin, ocular and lung microphysiological cell-culture systems.

Particulate matter (PM) has been associated with adverse effects on human health, causing allergies, skin and eye irritation and corrosion, respiratory tract irritation, headaches, bronchoconstriction, cardiopulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, reproductive problems, premature deaths, and epigenetic changes that lead to a wide variety of cancers, among other health conditions. The air quality in the Medellín - Colombia presents fluctuations that oscillate between the maximum permissible levels established at the national level and by the WHO, which represents a latent risk to people's health. Although important efforts have been made to quantify the different levels of pollution and administrative measures have been established to mitigate air pollution, little research work has been done to establish the relationship between these levels of pollutants and the effects on biological systems. The objective of the present research was to make a morphological and chemical characterization of particulate matter (PM) captured with a commercial air filter and a electrospun nanofiber membrane and evaluate the cytotoxicity of the each PM extracts in monolayer and co-culture models which recreate microphysiological systems of lung, skin and cornea and propose the possible cellular interactions that lead the cytotoxic response of the chemical compounds found in particulate matter in cities. The morphology and elemental chemical characterization were done with scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM - EDS). For the polycyclic aromatic hydrocarbons detection was made with a chromatographic method accoupled to mass spectrometer. Finally, the cytotoxicity was made in monolayers of A549, HEK001, and SIRC cell lines and microphysiological systems consisting of two-cell layer construct to resemble the interaction between fibroblast and epithelial cells that comprises naturally the corneal, skin and lung tissue. We performed three different cocultures models with BALB/3T3 clone A31 as a feeder layer, using porous Transwell® inserts in the in-contact and non-contact way. Monolayer and co-culture models were exposed to coarse and fine PM (1, 2, and 5 mg/mL) and the cell viability was evaluated at 24 h using an MTT assay. The electrospun nanofibers membranes demonstrates higher efficiency to capture PM with different sizes and high concentration of polycyclic aromatic hydrocarbons, heavy metals, and other chemical compounds responsible of many human diseases. Cytotoxic effects of MP were observed in all models at higher concentration; however, models exposed to fine PM exhibited a significant reduction in cell viability compared to those exposed to coarse PM. In addition, multilayer models are more resistant to PM exposure than monolayer models. Furthermore, the study indicated that, depending on the seeding strategy, different results might be observed: the non-contact model showed higher resistance to PM exposure than in-contact for SIRC and HEK001, but A549 monolayers showed the highest viability response. This study demonstrates the usefulness of applying co-culture models to assess environmental pollutant toxicity, in addition to being a potential alternative method to animal testing for risk assessment.

Inflammation and Oxidative Stress Induced by Obesity, Gestational Diabetes, and Preeclampsia in Pregnancy: Role of High-Density Lipoproteins as Vectors for Bioactive Compounds.

Inflammation and oxidative stress are essential components in a myriad of pathogenic entities that lead to metabolic and chronic diseases. Moreover, inflammation in its different phases is necessary for the initiation and maintenance of a healthy pregnancy. Therefore, an equilibrium between a necessary/pathologic level of inflammation and oxidative stress during pregnancy is needed to avoid disease development. High-density lipoproteins (HDL) are important for a healthy pregnancy and a good neonatal outcome. Their role in fetal development during challenging situations is vital for maintaining the equilibrium. However, in certain conditions, such as obesity, diabetes, and other cardiovascular diseases, it has been observed that HDL loses its protective properties, becoming dysfunctional. Bioactive compounds have been widely studied as mediators of inflammation and oxidative stress in different diseases, but their mechanisms of action are still unknown. Nonetheless, these agents, which are obtained from functional foods, increase the concentration of HDL, TRC, and antioxidant activity. Therefore, this review first summarizes several mechanisms of HDL participation in the equilibrium between inflammation and oxidative stress. Second, it gives an insight into how HDL may act as a vector for bioactive compounds. Third, it describes the relationships between the inflammation process in pregnancy and HDL activity. Consequently, different databases were used, including MEDLINE, PubMed, and Scopus, where scientific articles published in the English language up to 2023 were identified.

The time is ripe for the renaissance of autism treatments: evidence from clinical practitioners.

Introduction: Recent changes in diagnostics criteria have contributed to the broadening of the autism spectrum disorders and left clinicians ill-equipped to treat the highly heterogeneous spectrum that now includes toddlers and children with sensory and motor issues. Methods: To uncover the clinicians' critical needs in the autism space, we conducted surveys designed collaboratively with the clinicians themselves. Board Certified Behavioral Analysts (BCBAs) and developmental model (DM) clinicians obtained permission from their accrediting boards and designed surveys to assess needs and preferences in their corresponding fields. Results: 92.6% of BCBAs are open to diversified treatment combining aspects of multiple disciplines; 82.7% of DMs also favor this diversification with 21.8% valuing BCBA-input and 40.6% neurologists-input; 85.9% of BCBAs and 85.3% of DMs advocate the use of wearables to objectively track nuanced behaviors in social exchange; 76.9% of BCBAs and 57.0% DMs feel they would benefit from augmenting their knowledge about the nervous systems of Autism (neuroscience research) to enhance treatment and planning programs; 50.0% of BCBAs feel they can benefit for more training to teach parents. Discussion: Two complementary philosophies are converging to a more collaborative, integrative approach favoring scalable digital technologies and neuroscience. Autism practitioners seem ready to embrace the Digital-Neuroscience Revolutions under a new cooperative model.

In Vitro Digestion of Peanut Skin Releases Bioactive Compounds and Increases Cancer Cell Toxicity.

Peanut skin is a rich source of bioactive compounds which may be able to reduce the risk factors associated with metabolic syndromes. This study aimed to characterize bio-compounds from peanut skin (Arachis hypogaea) and their bioactivity (antioxidant activity, inhibition of lipase, and carbohydrase enzymes) and to evaluate their anti-proliferative properties in colorectal cancer cells (HCT116) upon in vitro digestion. Peanut skin was digested in two sequential phases, and the final content, named phase-1 (P1) and phase-2 (P2) extracts, was evaluated. Several bioactive compounds were positively identified and quantified by liquid chromatography, including quinic acid, released especially after in vitro digestion. The total phenolic content and, regardless of the method, the antioxidant activity of P1 was higher than P2. P1 also showed a lower enzyme inhibitory concentration IC50 than P2, lipase, and α-glucosidase. For cell viability in HCT116 cells, lower concentrations of P1 were found for IC50 compared to P2. In conclusion, bioactive compounds were released mainly during the first phase of the in vitro digestion. The digested samples presented antioxidant activity, enzyme inhibitory activity, and cancer cell cytotoxicity, especially those from the P1 extract. The potential applications of such a by-product in human health are reported.

CD8+ T-cell Exhaustion Phenotype in Human Asymptomatic and Ocular Toxoplasmosis.

This work analyzed exhaustion markers in CD8+ T-cell subpopulations in 21 samples of peripheral blood mononuclear cells (PBMCs) from individuals with ocular toxoplasmosis (n = 9), chronic asymptomatic toxoplasmosis (n = 7), and non-infected people (n = 5) by using RT-qPCR and flow cytometry techniques. The study found that gene expression of PD-1 and CD244, but not LAG-3, was higher in individuals with ocular toxoplasmosis versus individuals with asymptomatic infection or uninfected. Expression of PD1 in CD8+ central memory (CM) cells was higher in nine individuals with toxoplasmosis versus five uninfected individuals (p = .003). After ex vivo stimulation, an inverse correlation was found between the exhaustion markers and quantitative clinical characteristics (lesion size, recurrence index, and number of lesions). A total exhaustion phenotype was found in 55.5% (5/9) of individuals with ocular toxoplasmosis. Our results suggest that the CD8+ exhaustion phenotype is involved in the pathogenesis of ocular toxoplasmosis.

Metal ion content of internal organs in the calorically restricted Wistar rat.

BACKGROUND: Despite the agreed principle that access to food is a human right, undernourishment and metal ion deficiencies are public health problems worldwide, exacerbated in impoverished or war-affected areas. It is known that maternal malnutrition causes growth retardation and affects behavioral and cognitive development of the newborn. Here we ask whether severe caloric restriction leads per se to disrupted metal accumulation in different organs of the Wistar rat. METHODS: Inductively coupled plasma optical emission spectroscopy was used to determine the concentration of multiple elements in the small and large intestine, heart, lung, liver, kidney, pancreas, spleen, brain, spinal cord, and three skeletal muscles from control and calorically restricted Wistar rats. The caloric restriction protocol was initiated from the mothers prior to mating and continued throughout gestation, lactation, and post-weaning up to sixty days of age. RESULTS: Both sexes were analyzed but dimorphism was rare. The pancreas was the most affected organ presenting a higher concentration of all the elements analyzed. Copper concentration decreased in the kidney and increased in the liver. Each skeletal muscle responded to the treatment differentially: Extensor Digitorum Longus accumulated calcium and manganese, gastrocnemius decreased copper and manganese, whereas soleus decreased iron concentrations. Differences were also observed in the concentration of elements between organs independently of treatment: The soleus muscle presents a higher concentration of Zn compared to the other muscles and the rest of the organs. Notably, the spinal cord showed large accumulations of calcium and half the concentration of zinc compared to brain. X-ray fluorescence imaging suggests that the extra calcium is attributable to the presence of ossifications whereas the latter finding is attributable to the low abundance of zinc synapses in the spinal cord. CONCLUSION: Severe caloric restriction did not lead to systemic metal deficiencies but caused instead specific metal responses in few organs.

Eicosapentaenoic and Docosahexaenoic Acid Supplementation Increases HDL Content in n-3 Fatty Acids and Improves Endothelial Function in Hypertriglyceridemic Patients.

High-density lipoproteins (HDLs) are known to enhance vascular function through different mechanisms, including the delivery of functional lipids to endothelial cells. Therefore, we hypothesized that omega-3 (n-3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content of HDLs would improve the beneficial vascular effects of these lipoproteins. To explore this hypothesis, we performed a placebo-controlled crossover clinical trial in 18 hypertriglyceridemic patients without clinical symptoms of coronary heart disease who received highly purified EPA 460 mg and DHA 380 mg, twice a day for 5 weeks or placebo. After 5 weeks of treatment, patients followed a 4-week washout period before crossover. HDLs were isolated using sequential ultracentrifugation for characterization and determination of fatty acid content. Our results showed that n-3 supplementation induced a significant decrease in body mass index, waist circumference as well as triglycerides and HDL-triglyceride plasma concentrations, whilst HDL-cholesterol and HDL-phospholipids significantly increased. On the other hand, HDL, EPA, and DHA content increased by 131% and 62%, respectively, whereas 3 omega-6 fatty acids significantly decreased in HDL structures. In addition, the EPA-to-arachidonic acid (AA) ratio increased more than twice within HDLs suggesting an improvement in their anti-inflammatory properties. All HDL-fatty acid modifications did not affect the size distribution or the stability of these lipoproteins and were concomitant with a significant increase in endothelial function assessed using a flow-mediated dilatation test (FMD) after n-3 supplementation. However, endothelial function was not improved in vitro using a model of rat aortic rings co-incubated with HDLs before or after treatment with n-3. These results suggest a beneficial effect of n-3 on endothelial function through a mechanism independent of HDL composition. In conclusion, we demonstrated that EPA and DHA supplementation for 5 weeks improved vascular function in hypertriglyceridemic patients, and induced enrichment of HDLs with EPA and DHA to the detriment of some n-6 fatty acids. The significant increase in the EPA-to-AA ratio in HDLs is indicative of a more anti-inflammatory profile of these lipoproteins.

Effect of a parenteral fish-oil-containing lipid emulsion on liver lipid perioxidation and antioxidative defenses in Lewis rats.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), naturally abundant in fish oil (FO), are known for their anti-inflammatory and potential antioxidant properties. The aim in this article is to evaluate the effect of the infusion of a parenteral FO-containing lipid emulsion on markers of liver lipid peroxidation and oxidative stress in rats undergoing central venous catheterization (CVC). METHODS: After 5-day acclimatization, adult Lewis rats (n = 42) receiving a 20-g/day AIN-93M oral diet were randomly subdivided into four groups: (1) basal control (BC) (n = 6), without CVC or LE infusion; (2) SHAM (n = 12), with CVC but without LE infusion; (3) soybean oil (SO)/medium-chain triglyceride (MCT) (n = 12), with CVC and receiving LE without FO (4.3 g/kg fat); and (4) SO/MCT/FO (n = 12), with CVC and receiving LE containing 10% FO (4.3 g/kg fat). Animals from the BC group were euthanized immediately after acclimatization. The remaining groups of animals were euthanized after 48 or 72 h of surgical follow-up to assess profiles of liver and plasma fatty acids by gas chromatography, liver gene transcription factor Nrf2, F2-isoprostane lipid peroxidation biomarker, and the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) by enzyme-linked immunosorbent assay. R program (version 3.2.2) was utilized for data analysis. RESULTS: Compared with the other groups, liver EPA and DHA levels were higher in the SO/MCT/FO group, which also showed the highest liver Nrf2, GPx, SOD, and CAT levels and lower liver F2-isoprostane (P < 0.05). CONCLUSION: Experimental delivery of FO via EPA and DHA sources in a parenteral LE was associated with a liver antioxidant effect.

Sensing echoes: temporal misalignment in auditory brainstem responses as the earliest marker of neurodevelopmental derailment.

Neurodevelopmental disorders are on the rise worldwide, with diagnoses that detect derailment from typical milestones by 3 to 4.5 years of age. By then, the circuitry in the brain has already reached some level of maturation that inevitably takes neurodevelopment through a different course. There is a critical need then to develop analytical methods that detect problems much earlier and identify targets for treatment. We integrate data from multiple sources, including neonatal auditory brainstem responses (ABR), clinical criteria detecting autism years later in those neonates, and similar ABR information for young infants and children who also received a diagnosis of autism spectrum disorders, to produce the earliest known digital screening biomarker to flag neurodevelopmental derailment in neonates. This work also defines concrete targets for treatment and offers a new statistical approach to aid in guiding a personalized course of maturation in line with the highly nonlinear, accelerated neurodevelopmental rates of change in early infancy.

Temporal changes in the systemic concentrations of retinoids in pregnant and postpartum women.

Retinoids and vitamin A are essential for multiple biological functions, including vision and immune responses, as well as the development of an embryo during pregnancy. Despite its importance, alterations in retinoid homeostasis during normal human pregnancy are incompletely understood. We aimed to characterize the temporal changes in the systemic retinoid concentrations across pregnancy and postpartum period. Monthly blood samples were collected from twenty healthy pregnant women, and plasma concentrations of retinol, all-trans-retinoic acid (atRA), 13-cis-retinoic acid (13cisRA), and 4-oxo-retinoic acids were measured using liquid chromatography-tandem mass spectrometry. Significant decreases in 13cisRA concentrations over the pregnancy were observed, with rebound increases in retinol and 13cisRA levels after delivery. Of note, atRA concentrations exhibited a unique temporal pattern with levels peaking at mid-pregnancy. While the 4-oxo-atRA concentration was below the limit of quantification, 4-oxo-13cisRA was readily detectable, and its temporal change mimicked that of 13cisRA. The time profiles of atRA and 13cisRA remained similar after correction by albumin levels for plasma volume expansion adjustment. Together, the comprehensive profiling of systemic retinoid concentrations over the course of pregnancy provides insights into pregnancy-mediated changes in retinoid disposition to maintain its homeostasis.