Cymensifin A: a promising pharmaceutical candidate to defeat lung cancer via cellular reactive oxygen species-mediated apoptosis.

Background: The upgrade of natural products for cancer treatment is essential since current anticancer drugs still pose severe side effects. Cymensifin A (Cym A) isolated from an orchid Cymbidium ensifolium has shown its potential to induce the death of several cancer cells; however, its underlying molecular mechanisms are hitherto unknown. Methods: Here, we conducted a set of in vitro preliminary tests to assess the cytotoxic effects of Cym A on non-small-cell lung cancer (NSCLC) cells (A549, H23, H292, and H460). A flow cytometry system and Western blot analyses were employed to unveil molecular mechanisms underlying cancer cell apoptosis caused by Cym A. Results: Cym A at 25-50 µM caused the death of all NSCLC cells tested, and its cytotoxicity was comparable to cisplatin, a currently used anticancer drug. The compound induced apoptosis of all NSCLC cells in a dose-dependent manner (5-50 µM), proven by flow cytometry, but H460 cells showed more resistance compared to other cells tested. Cym A-treated H460 cells demonstrated increased reactive oxygen species (ROS) and downregulated antioxidants (catalase, superoxide dismutase, and thioredoxin). The compound also upregulated the tumor suppressor P53 and the pro-apoptotic protein BAX but downregulated pro-survival proteins (BCL-2 and MCL-1) and deactivated survival signals (AKT and ERK) in H460 cells. Cym A was proven to trigger cellular ROS formation, but P53 and BAX were 2-fold more activated by Cym A compared to those treated with hydrogen peroxide. Our findings also supported that Cym A exerted its roles in the downregulation of nuclear factor erythroid 2-related factor 2 (a regulator of cellular antioxidant activity) and the increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase 3/7 during apoptosis. Conclusion: We propose that Cym A induces lung cancer cell death via ROS-mediated apoptosis, while the modulation of cellular ROS/antioxidant activity, the upregulation of P53 and BAX, the downregulation or deactivation of BCL-2, MCL-1, AKT, and ERK, and the increased cleavage of PARP and caspase 3/7, were the elucidated underlying molecular mechanisms of this phytochemical. The compound can be a promising candidate for future anticancer drug development.

Multi-activity 3D printed assistive technology in children: a case study.

Congenital limb defects occur when a limb does not develop normally during pregnancy. The quality of each person's everyday life is significantly impacted by any of these defects and there is no concrete treatment. 3D modeling and printing, enables the creation and customization of precise virtual and/or physical models, including models of the human anatomy. These technologies provide a novel method of producing new devices with optimized design and production time, improving adaptability, and incorporating functionality. To this end, we propose a method of designing and producing 3D printed assistive devices and we also present an example of an assistive device, done in the 3D Printing Center for Health, as well as its impact on the patient's daily life. With this device, the patient became able to play the guitar and hold a knife, thus helping on these two activities.

Hellebrigenin triggers death of promyelocytic leukemia cells by non-genotoxic ways.

Bufadienolides are digitalis-like aglycones mainly found in skin secretions of toads. Among their biological properties, the mechanisms of antiproliferative action on tumor cells remain unclear for many compounds, including against leukemia cells. Herein, it was evaluated the mechanisms involved in the antiproliferative and genotoxic actions of hellebrigenin on tumor cell lines and in silico capacity to inhibit the human topoisomerase IIa enzyme. Firstly, its cytotoxic action was investigated by colorimetric assays in human tumor and peripheral blood mononuclear cells (PBMC). Next, biochemical and morphological studies were detailed by light microscopy (trypan blue dye exclusion), immunocytochemistry (BrdU uptake), flow cytometry and DNA/chromosomal damages (Cometa and aberrations). Finally, computational modelling was used to search for topoisomerase inhibition. Hellebrigenin reduced proliferation, BrdU incorporation, viability, and membrane integrity of HL-60 leukemia cells. Additionally, it increased G2/M arrest, internucleosomal DNA fragmentation, mitochondrial depolarization, and phosphatidylserine externalization in a concentration-dependent manner. In contrast to doxorubicin, hellebrigenin did not cause DNA strand breaks in HL-60 cell line and lymphocytes, and it interacts with ATPase domain residues of human topoisomerase IIa, generating a complex of hydrophobic and van der Waals interactions and hydrogen bonds. So, hellebrigenin presented potent anti-leukemic activity at concentrations as low as 0.06 µM, a value comparable to the clinical anticancer agent doxorubicin, and caused biochemical changes suggestive of apoptosis without genotoxic/clastogenic-related action, but it probably triggers catalytic inhibition of topoisomerase II. These findings also emphasize toad steroid toxins as promising lead antineoplasic compounds with relatively low cytotoxic action on human normal cells.

Alteration of brain function and systemic inflammatory tone in older adults by decreasing the dietary palmitic acid intake.

Prior studies in younger adults showed that reducing the normally high intake of the saturated fatty acid, palmitic acid (PA), in the North American diet by replacing it with the monounsaturated fatty acid, oleic acid (OA), decreased blood concentrations and secretion by peripheral blood mononuclear cells (PBMCs) of interleukin (IL)-1ß and IL-6 and changed brain activation in regions of the working memory network. We examined the effects of these fatty acid manipulations in the diet of older adults. Ten subjects, aged 65-75 years, participated in a randomized, cross-over trial comparing 1-week high PA versus low PA/high OA diets. We evaluated functional magnetic resonance imaging (fMRI) using an N-back test of working memory and a resting state scan, cytokine secretion by lipopolysaccharide (LPS)-stimulated PBMCs, and plasma cytokine concentrations. During the low PA compared to the high PA diet, we observed increased activation for the 2-back minus 0-back conditions in the right dorsolateral prefrontal cortex (Broadman Area (BA) 9; p < 0.005), but the effect of diet on working memory performance was not significant (p = 0.09). We observed increased connectivity between anterior regions of the salience network during the low PA/high OA diet (p < 0.001). The concentrations of IL-1ß (p = 0.026), IL-8 (p = 0.013), and IL-6 (p = 0.009) in conditioned media from LPS-stimulated PBMCs were lower during the low PA/high OA diet. This study suggests that lowering the dietary intake of PA down-regulated pro-inflammatory cytokine secretion and altered working memory, task-based activation and resting state functional connectivity in older adults.

ACR Appropriateness Criteria® Headache: 2022 Update.

Headache is an ancient problem plaguing a large proportion of the population. At present, headache disorders rank third among the global causes of disability, accounting for over $78 billion per year in direct and indirect costs in the United States. Given the prevalence of headache and the wide range of possible etiologies, the goal of this document is to help clarify the most appropriate initial imaging guidelines for headache for eight clinical scenarios/variants, which range from acute onset, life-threatening etiologies to chronic benign scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Functional capacity and quality of life in children and adolescents with sickle cell anemia.

OBJECTIVE: To evaluate the functional and exercise capacity, lung function, quality of life of children and adolescents with sickle cell anemia (SCA HbSS) and to test the reproducibility of functional capacity tests in this population. METHOD: Cross-sectional study with volunteers with SCA Hb-SS (SCAG), aged 6-18 years matched in age and gender to the control group (CG) with healthy individuals. Spirometry, 5-repetition sit-to-stand test (5STS-test), modified shuttle test (MST), and Pediatric Quality of Life Questionnaire (PedsQL) were performed. The reproducibility of 5STS-test and MST was evaluated: RESULTS: Forty eight volunteers of SCAG and 48 of CG were evaluated. Lung function of SCAG (FVC: 92 ± 15% pred.; FEV1 /FVC: 84 ± 8% pred.) was worse than the CG (104 ± 15% pred.; FEV1 /FVC: 90 ± 6% pred.) p < 0.05. SCAG had worse functional capacity registered by distance walked: 576 m (515-672 m) and 5STS-test: 8 s (7.4-8.9 s) compared with the CG who showed distance walked: 1010 m (887-1219 m) and 5STS-test: 7 s (7.0-8.1 s), p < 0.001. SCAG had worse quality of life compared to CG, p < 0.05. The reproducibility of MST (ICC 0.99 (0.98-0.99 IC-95%)) and 5STS-test (ICC 0.80 (0.69-0.88) was considered good, p < 0.001. CONCLUSION: Children and adolescents with sickle cell anemia presented worse capacity to walk or run, and to perform sit-to-stand test when compared with their control peers. Additionally, they have poorer quality of life. The MST and 5STS-test showed good reproducibility to be applied in pediatric individuals with SCA.

The chromatographic constitution of andiroba oil and his healing effects, compared to the LLLT outcomes, in oral mucositis induced in golden Syrian hamsters: a new treatment option.

The oral mucositis is a mucosal alteration that usually arises from oncological treatments, such as chemotherapy, and it is characterized as an inflammatory process. The aim of this study is to demonstrate the chromatographic constitution of Andiroba oil, comparing and evaluating Andiroba oil and laser scarring efficiency in treatments of oral mucositis in hamsters. These animals were submitted to 5-Fluorouracil. A total of 122 animals were used, randomized and divided into the following groups: (a) positive control; (b) laser associated to andiroba oil; (c) laser; (d) andiroba oil; (e) negative control; (f) cyclophosphamide (genotoxicity control). The induction of oral mucositis occurred by the administration of intraperitoneal Fluorouracila (60 mg/kg) and trauma to the mucosa. The laser protocol was performed once a day and the andiroba oil applied 3 times a day (1,5 ml/day). The mucosae were photographed and removed for clinical and histopathological analysis on day 4, 8, 12 and 15. The analysis was based in OM severity, in specific scoring for the clinical and histopathological aspect. Toxicity was evaluated on day 15 using comet assay and it was performed by variant DNA damage parameters. The data were analysed using analysis of variance (ANOVA) Tukey post-test and Kruskal-Wallis Dunn post-test. The "andiroba oil" and "laser" groups presented better results when compared to the control groups and the treatment associations. The andiroba oil presented the best scarring results, even considering its efficiency proximity to the laser treatment. Andiroba and laser, separately, did not present genotoxicity, however their association evidences damage to DNA.

Effectiveness of Physical Therapy Interventions in Children with Brachial Plexus Birth Injury: A Systematic Review.

AIM: To systematically review the effectiveness of physical therapy interventions in infants, children and adolescents with brachial plexus birth injury (BPBI). METHODS: Systematic review of randomized controlled trials including patients under 18 years old with BPBI was conducted on Medline, Cochrane, Embase, Amed and Pedro databases. Methodological quality was assessed by the PEDro score and quality of evidence by the GRADE system. The primary outcomes measured were range of motion, muscle strength and bone mineral density. RESULTS: Seven studies were included, two in infant and 5 in children, of 932 title and abstracts screened. The interventions, characteristics of the participants and outcomes were diverse. The largest effect was found when other intervention was combined with conventional physical therapy in the primary outcomes, with low quality of evidence. CONCLUSION: Physical therapy interventions alone or in combination with other treatment modalities are effective in improving short-term disabilities in children with BPBI.

Mechanical performance and bioactivation of 3D-printed PEEK for high-performance implant manufacture: a review.

Polyetheretherketone (PEEK) has stood out as the leading high-performance thermoplastic for the replacement of metals in orthopaedic, trauma and spinal implant applications due to its high biocompatibility and mechanical properties. Despite its potential for custom-made medical devices, 3D-printed PEEK's mechanical performance depends on processing parameters and its bioinertness may hinder bone opposition to the implant. Concerning these challenges, this review focuses on the available literature addressing the improvement of the mechanical performance of PEEK processed through "fused filament fabrication" (FFF) along with literature on bioactivation of PEEK for improved osseointegration. The reviewed research suggests that improvements can be achieved in mechanical performance of 3D-printed PEEK with adequate FFF parametrization while different bioactivation techniques can be used to improve the bioperformance of 3D-printed PEEK. The adequate approaches towards these procedures can increase PEEK's potential for the manufacture of high-performance custom-made implantable devices that display improved bone-implant integration and prevent stress shielding of the treated bone.

Prediction equation of peak oxygen uptake for the modified shuttle test in healthy adolescents / Equação de predição do consumo máximo de oxigênio para o shuttle test modificado em adolescentes saudáveis / Ecuación de predicción del consumo máximo de oxígeno para el shuttle test modificado en adolescentes sanos

ABSTRACT Given the gap in the literature regarding the peak of oxygen consumption (VO2peak) for adolescents of both sexes, this study aimed to propose an equation to predict the VO2peak in healthy adolescents using the Modified Shuttle Test (MST). This is a cross-sectional study with 84 healthy adolescents between 12 and 18 years old, female and male. The MST is an external paced test, in which the speed increases at each minute. Two MST were performed with at least 30 minutes of rest between them. The test with the longest walked distance was considered for analysis. VO2 was directly monitored by an open circuit spirometry. Mean age was 14.67±1.82 and the walked distance was 864.86±263.48m. Variables included in the prediction equation were walked distance and sex, explaining the VO2peak variability of 53% during MST performance. The prediction equation for VO2peak with the MST was: predicted VO2peak=18.274+(0.18×Distance Walked, meters)+(7.733×Sex); R2=0.53 and p<0.0001 (sex: 0 for girls, 1 for boys). This MST equation, proposed to predict VO2peak in healthy adolescents of both sexes, can be used as a reference to assess exercise capacity in healthy adolescents and to investigate cardiopulmonary function in adolescents with reduced functional capacity.

RESUMO Dada a lacuna na literatura quanto à equação de predição do pico de consumo de oxigênio (VO2) para adolescentes de ambos os sexos, o objetivo deste estudo é propor uma equação para predizer o VO2pico em adolescentes saudáveis utilizando o shuttle test modificado (MST). Trata-se de um estudo transversal realizado com 84 adolescentes saudáveis entre 12 e 18 anos, do sexo feminino e masculino. O MST é um teste de campo ditado por um sinal sonoro que indica o aumento da velocidade a cada minuto. Dois MSTs foram realizados com pelo menos 30 minutos de descanso entre eles. O teste com a maior distância percorrida foi o considerado para análise. O VO2 foi monitorado diretamente por uma espirometria de circuito aberto. A média de idade foi de 14,67±1,82 anos, e a de distância percorrida foi de 864,86±263,48m. As variáveis incluídas na equação de predição foram distância percorrida e sexo, que explicaram 53% da variabilidade do VO2pico durante a realização do MST. A equação de referência para o VO2pico previsto com o MST foi VO2pico predito=18,274+(0,18×Distância percorrida, em metros)+(7,733×Sexo); R2=0,53 e p<0,0001 (sexo: 0 para meninas, 1 para meninos). A equação do MST proposta para predizer o VO2pico em adolescentes saudáveis de ambos os sexos pode ser usada como referência para avaliar a capacidade de exercício em adolescentes saudáveis e investigar a função cardiopulmonar em adolescentes com capacidade funcional reduzida.

RESUMEN Dada una laguna en la literatura con respecto a la ecuación para predecir el consumo máximo de oxígeno (VO2) en adolescentes de ambos sexos, el objetivo de este estudio es proponer una ecuación para predecir el VO2máximo en adolescentes sanos usando el shuttle test modificado (MST). Se trata de un estudio transversal, realizado con 84 adolescentes sanos con edades entre 12 y 18 años, de ambos sexos. El MST es una prueba de campo dictada por una señal sonora que indica el aumento de velocidad cada minuto. Se realizaron dos MST con al menos 30 minutos de descanso entre ellos. Para el análisis se consideró la prueba con mayor distancia recorrida. El monitoreo del VO2 fue realizado directamente por espirometría de circuito abierto. La edad media fue de 14,67±1,82 años; y la distancia recorrida, de 864,86±263,48m. Las variables incluidas en la ecuación de predicción fueron la distancia recorrida y el sexo, que explicaron el 53% de la variabilidad del VO2máximo durante la realización del MST. La ecuación de referencia para el VO2máximo predicho con el MST fue VO2máximo previsto=18,274+(0,18×Distancia recorrida, en metros)+(7,733×Sexo); R2=0,53 y p<0,0001 (sexo: 0 para chicas, 1 para chicos). La ecuación MST propuesta para predecir el VO2máximo en adolescentes sanos de ambos sexos puede utilizarse como una referencia para evaluar la capacidad de ejercicio en adolescentes sanos y para investigar la función cardiopulmonar en adolescentes con capacidad funcional reducida.

High-Cycle Fatigue Behaviour of Polyetheretherketone (PEEK) Produced by Additive Manufacturing.

Polyetheretherketone (PEEK) is the leading high-performance thermoplastic biomaterial that can be processed through material extrusion (ME) additive manufacturing (AM), also known as three-dimensional (3D) printing, for patient-specific load-bearing implant manufacture. Considering the importance of cyclic loading for load-bearing implant design, this work addresses the high-cycle fatigue behaviour of 3D-printed PEEK. In this work, printed PEEK specimens are cyclically loaded under stress-controlled tension-tension using different stress levels between 75% and 95% of printed PEEK's tensile strength. The experimental results are used to document 3D-printed PEEK's fatigue behaviour using Basquin's power law, which was compared with previous fatigue research on bulk PEEK and other 3D-printing materials. As a pioneering study on its fatigue behaviour, the results from this work show that 3D-printed PEEK exhibits an above-average fatigue strength of 65 MPa, corresponding to about 75% of its tensile strength. Fracture surface analysis suggests that a transition can occur from ductile to brittle fracture with maximum stresses between 85% and 95% of the tensile strength. Evidence of crack propagation features on fracture surfaces under scanning electron microscope (SEM) observation suggests crack initiation in void defects created by printing deposition that propagates longitudinally through line bonding interfaces along layers. Considering this, 3D-printed PEEK's fatigue behaviour can be strongly related to printing conditions. Further research on the fatigue behaviour of 3D-printed PEEK is necessary to support its use in load-bearing implant applications.

Cytotoxic and mutagenic effects of the food additive tartrazine on eukaryotic cells.

BACKGROUND: Among the food additives used in the food industry, food dyes are considered the most toxic. For instance, tartrazine (TRZ) is a food colorant commercially available with conflicting data regarding its cytotoxic, genotoxic, and mutagenic effects. Therefore, this study aimed to evaluate the cytotoxic and mutagenic potential of TRZ using different eukaryotic cells (in vitro). METHODS: This study employed 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), brine shrimp lethality, Allium cepa and Saccharomyces cerevisiae tests. Different concentrations of TRZ and different exposure times were used in this study. RESULTS: The results demonstrate that TRZ induced a concentration-dependent toxic effect on the test systems. It also exerted cytotoxicity in fibroblasts and human gastric cells. In addition, TRZ showed mutagenic effects on the A. cepa test system. However, its toxicogenic effects may not relate to the oxidizing activity, which was confirmed by the S. cerevisiae test model. CONCLUSION: Taken together, TRZ exerted toxicogenic effects on the test systems. Therefore, it may be harmful to health, especially its prolonged use may trigger carcinogenesis.

Moderators of ayahuasca's biological antidepressant action.

Introduction: The understanding of biological responses to psychedelics with antidepressant potential is imperative. Here we report how a set of acute parameters, namely emotional (depressive symptoms), cognitive (psychedelic experience), and physiological (salivary cortisol), recorded during an ayahuasca dosing session, modulated serum brain-derived neurotrophic factor (BDNF), serum cortisol (SC), serum interleukin 6 (IL-6), plasma C-reactive protein (CRP), and salivary cortisol awakening response (CAR). Methods: Results were analyzed 2 days after the psychedelic intervention (ayahuasca) versus placebo in both patients with treatment-resistant depression and healthy volunteers. These measures were assessed as part of a randomized double-blinded, placebo-controlled trial (n = 72). Results: Results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients. Whereas lesser changes in salivary cortisol levels during the ayahuasca intervention were related to higher BDNF levels in patients with a larger clinical response in the reduction in depressive symptoms. No moderator was found for patient's CAR, IL-6, and CRP responses to ayahuasca and for all biomarker responses to ayahuasca in healthy controls and in the placebo group. Discussion: In summary, some specific emotional and physiological parameters during experimental ayahuasca session were revealed as critical moderators of the improvement of major depression biomarkers, mainly BDNF and SC two days after ayahuasca intake. These findings contribute to paving the way for future studies investigating the biological antidepressant response to psychedelic therapy.

Prophylactic action of ayahuasca in a non-human primate model of depressive-like behavior.

Observational studies of long-term users of ayahuasca, an Amazonian psychedelic brew, suggest an increase in resilience via improvements in emotion and cognition. Ayahuasca has also demonstrated clinical antidepressant effects in human and animal studies; however, its potential prophylactic action in depression has not been previously studied. Therefore, this experimental study sought to evaluate the potential prophylactic effects of repeated and long-term ayahuasca use, via the modulation of resilience, in a non-human primate animal model, Callithrix jacchus, subjected to a protocol for induction of depressive-like behavior. For the formation of the study groups, some juvenile marmosets were kept in their family groups (GF = 7), while for the two experimental groups, the animals were removed from the family and kept socially isolated. Then, part of the isolated animals made up the group in which ayahuasca was administered (AG, n = 6), while for others, no intervention was made (IG, n = 5). AG animals took ayahuasca (1.67 mL/300g body weight) at weeks 4 (before isolation), 8, and 12 (during isolation) of the study. More adaptive stress response was observed for the AG when compared to the IG. The AG showed higher cortisol reactivity and fecal cortisol levels than IG, while both measures were similar to FG. Moreover, AG animals showed no signs of anhedonia and no increase in chronic stress-related behaviors, which were expressed by the IG. Thus, ayahuasca seems to promote the expression of resilient responses, indicating a prophylactic action, buffering the emergence of depressive-like behaviors and cortisol alterations associated with major depression. These results are encouraging for further research on the prophylactic use of psychedelics to prevent psychopathologies associated with chronic stress.

Neurosarcoidosis: Phenotypes, Approach to Diagnosis and Treatment.

PURPOSE OF REVIEW: The aim of this review is to provide an update of clinical presentation, diagnosis, differential diagnoses, and treatment according to recent evidence. RECENT FINDINGS: Neurosarcoidosis remains a diagnosis of exclusion, with infectious and malignant etiologies recognized as important mimickers. Corticosteroids remain as first-line therapy. In recent years, however, studies have demonstrated the effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in the treatment of neurosarcoidosis, leading to improved outcomes. Neurosarcoidosis is a granulomatous disease with protean manifestations that may affect any part of the central and peripheral nervous system. It has many mimickers, and potentially devastating complications necessitating long-term follow-up. Early initiation of treatment, particularly with anti-TNF therapy, may lead to better outcomes and fewer relapses. There is an unmet need for randomized controlled trials that provide robust data to guide therapy and the long-term management of neurosarcoidosis patients.

Development of a composite diffusion tensor imaging score correlating with short-term neurological status in neonatal hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal acquired brain injury. Although conventional MRI may predict neurodevelopmental outcomes, accurate prognostication remains difficult. As diffusion tensor imaging (DTI) may provide an additional diagnostic and prognostic value over conventional MRI, we aimed to develop a composite DTI (cDTI) score to relate to short-term neurological function. Sixty prospective neonates treated with therapeutic hypothermia (TH) for HIE were evaluated with DTI, with a voxel size of 1 × 1 × 2 mm. Fractional anisotropy (FA) and mean diffusivity (MD) from 100 neuroanatomical regions (FA/MD *100 = 200 DTI parameters in total) were quantified using an atlas-based image parcellation technique. A least absolute shrinkage and selection operator (LASSO) regression was applied to the DTI parameters to generate the cDTI score. Time to full oral nutrition [short-term oral feeding (STO) score] was used as a measure of short-term neurological function and was correlated with extracted DTI features. Seventeen DTI parameters were selected with LASSO and built into the final unbiased regression model. The selected factors included FA or MD values of the limbic structures, the corticospinal tract, and the frontotemporal cortices. While the cDTI score strongly correlated with the STO score (rho = 0.83, p = 2.8 × 10-16), it only weakly correlated with the Sarnat score (rho = 0.27, p = 0.035) and moderately with the NICHD-NRN neuroimaging score (rho = 0.43, p = 6.6 × 10-04). In contrast to the cDTI score, the NICHD-NRN score only moderately correlated with the STO score (rho = 0.37, p = 0.0037). Using a mixed-model analysis, interleukin-10 at admission to the NICU (p = 1.5 × 10-13) and tau protein at the end of TH/rewarming (p = 0.036) and after rewarming (p = 0.0015) were significantly associated with higher cDTI scores, suggesting that high cDTI scores were related to the intensity of the early inflammatory response and the severity of neuronal impairment after TH. In conclusion, a data-driven unbiased approach was applied to identify anatomical structures associated with some aspects of neurological function of HIE neonates after cooling and to build a cDTI score, which was correlated with the severity of short-term neurological functions.

Vortex-assisted matrix solid-phase dispersion: An eco-friendly alternative for the determination of halogens in edible seaweed.

Edible seaweed has been widely consumed around the world through oriental cuisine and it is important to monitor the levels of some elements, especially halogens. This study proposes, for the first time, the development of an analytical method using the vortex-assisted matrix solid-phase dispersion (VA-MSPD) combined with alkaline extraction of halogens (F, Cl, Br, and I) in edible seaweed for further determination by ion chromatography. The proposed method was evaluated using edible seaweed of the Nori (Porphyra spp.) type and applied to samples of the Wakame (Undaria pinnatifida), Kombu (Laminaria ochroleuca), and Hijiki (Hizikia fusiformis) types. Important VA-MSPD parameters were investigated and using 0.1 g sample, 1 g sea sand as solid support, 50 mmol L-1 (NH4)2CO3 as extraction solution, and 5 min of maceration, higher extraction efficiencies were obtained. The method was linear within the evaluated range (R2 > 0.99) for all elements and no matrix effect was observed. The detection limits of the method were 27, 26, 19, and 28 µg g-1 for F, Cl, Br, and I, respectively. The accuracy was evaluated by a recovery test (ranging from 92 to 108%) and analysis of certified reference materials for apple leaves (NIST 1515) and peach leaves (NIST 1547), which had a good agreement (ranging from 97 to 101%) with the certified values. Comparing the results with those obtained by inductively coupled plasma-mass spectrometry after microwave-induced combustion, no significant difference was found between the results, and the relative standard deviations were lower than 12%. The proposed method proved to be efficient for the determination of halogens in different algae species, showing advantages such as simplicity and low cost, combined to the use of a material from renewable sources (sea sand) as a solid support, contributing to the principles of Green Analytical Chemistry.