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Trata-se de uma reflexão sobre as ameaças aos direitos humanos, sobretudo à dignidade e à liberdade, e à essência humana geradas pelo avanço da biotecnologia. O foco de alerta e resgate da noção de cuidado de si perpassa a perspectiva de futuro de M. Foucault e usa como complemento e desfecho a noção de responsabilidade de H. Jonas para a manutenção da vida e para a realização do sentido do humano e das novas gerações - papel ético por excelência. O texto divide-se em duas partes: a primeira é inspirada em Foucault e a segunda, em Jonas. O leitor é convidado a refletir dentro de uma dupla consideração do tema

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive disorder marked by lipid accumulation, leading to steatohepatitis (MASH). A key feature of the transition to MASH involves oxidative stress resulting from defects in mitochondrial oxidative phosphorylation (OXPHOS). Here, we show that pathological alterations in the lipid composition of the inner mitochondrial membrane (IMM) directly instigate electron transfer inefficiency to promote oxidative stress. Specifically, mitochondrial cardiolipin (CL) was downregulated with MASLD/MASH in mice and in humans. Hepatocyte-specific CL synthase knockout (CLS-LKO) led to spontaneous and robust MASH with extensive steatotic and fibrotic phenotype. Loss of CL paradoxically increased mitochondrial respiratory capacity but also reduced the formation of I+III 2 +IV 1 respiratory supercomplex and interfered with the ability of coenzyme Q (CoQ) to transfer electrons to complex III. In turn, the bottleneck at complex III promoted electron leak primarily at site III Q0 as well as other upstream sites in the electron transport chain. Thus, reduction in mitochondrial CL promotes oxidative stress and contributes to pathogenesis of MASH.

Glyoxalase I (GLO1) is the primary enzyme for detoxification of the reactive dicarbonyl methylglyoxal (MG). Loss of GLO1 promotes accumulation of MG resulting in a recapitulation of diabetic phenotypes. We previously demonstrated attenuated GLO1 protein in skeletal muscle from individuals with type 2 diabetes (T2D). However, whether GLO1 attenuation occurs prior to T2D and the mechanisms regulating GLO1 abundance in skeletal muscle are unknown. GLO1 expression and activity were determined in skeletal muscle tissue biopsies from 15 lean healthy individuals (LH, BMI: 22.4 ± 0.7) and 5 individuals with obesity (OB, BMI: 32.4 ± 1.3). GLO1 protein was attenuated by 26 ± 0.3 % in OB compared to LH skeletal muscle (p = 0.019). Similar reductions for GLO1 activity were observed (p = 0.102). NRF2 and Keap1 expression were equivocal between groups despite a 2-fold elevation in GLO1 transcripts in OB skeletal muscle (p = 0.008). GLO1 knock-down (KD) in human immortalized myotubes promoted downregulation of muscle contraction and organization proteins indicating the importance of GLO1 expression for skeletal muscle function. SIRT1 KD had no effect on GLO1 protein or activity whereas, SIRT2 KD attenuated GLO1 protein by 28 ± 0.29 % (p < 0.0001) and GLO1 activity by 42 ± 0.12 % (p = 0.0150). KD of NAMPT also resulted in attenuation of GLO1 protein (28 ± 0.069 %, p = 0.003), activity (67 ± 0.09 %, p = 0.011) and transcripts (50 ± 0.13 %, p = 0.049). Neither the provision of the NAD + precursors NR nor NMN were able to prevent this attenuation in GLO1 protein. However, NR did augment GLO1 specific activity (p = 0.022 vs NAMPT KD). These perturbations did not alter GLO1 acetylation status. SIRT1, SIRT2 and NAMPT protein levels were all equivocal in skeletal muscle tissue biopsies from individuals with obesity and lean individuals. These data implicate NAD + -dependent regulation of GLO1 in skeletal muscle independent of altered GLO1 acetylation and provide rationale for exploring NR supplementation to rescue attenuated GLO1 abundance and activity in conditions such as obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Neuropsychiatric symptoms (NPS) in dementia can be reduced through music listening. Little has been reported on home-based listening, compilation processes, or individual responses that include biophysiological data. We aim to provide new insights from two home-based case studies focused on specific music selections. Participants were part of a larger study, co-designing an automated radio, diary reminder and personal playlist system for NPS management. Playlists were compiled that would have the best possible chance of achieving this, based on participants' autobiographical, narrative, heart rate (HR) and videoed responses. Participant's responses to their music aligned with the genre they chose - dancing to up-beat music, contrasting with subtle responses to Beethoven. Repeated listens may help to establish consistency of responses and allow time to communicate their genuine preferences, not those others suggested. If all of these data converge, then they could help confirm the suitability of music for NPS management., Competing Interests: Declaration of competing interest All the authors of this article declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Short sleep, physical inactivity, and being locked up are risk factors for weight gain. Objective: We evaluated weight gain according to sex, age, hours of sleep and physical activity in university students from 10 Latin American countries during the COVID-19 pandemic. Methods: Cross-sectional and multicenter study ( n  = 4880). Results: The average age was 22.5 ± 4.4 years. 60.2% were currently locked up. 73.6% were women, 48.2% increased their body weight, 66% reported insufficient sleep hours, and 65.9% were inactive. Women gained more weight than men (73.2%) and younger students gained more weight (85.1%). Those who had insufficient sleep hours gained most weight (67.6%). Inactive participants gained most weight (74.7%). Students who have insufficient sleep are 21% more likely to have changes in body weight compared to students who have optimal sleep. Conclusion: The increase in body weight and its risk factors during confinement should be considered as emerging from public health.

Quantum computing technology is developing at a fast pace. The impact of quantum computing on the music industry is inevitable. This paper maps the emerging field of quantum computer music. Quantum computer music investigates, and develops applications and methods to process music using quantum computing technology. The paper begins by contextualising the field. Then, it discusses significant examples of various approaches developed to date to leverage quantum computing to learn, process and generate music. The methods discussed range from rendering music using data from physical quantum mechanical systems and quantum mechanical simulations to computational quantum algorithms to generate music, including quantum AI. The ambition to develop techniques to encode audio quantumly for making sound synthesisers and audio signal processing systems is also discussed., (© 2024 IOP Publishing Ltd.)

Background: At hospital level, clinical nutritionists play a fundamental role in health recovery, contributing to shorter hospital stays and addressing hospital malnutrition. However, in Latin America no studies have been conducted on the activities of the nutritionist and the factors influencing their performance., Aims: to describe the activities of the clinical nutritionist in public and private hospital settings in Latin America and to determine the factors associated with disciplinary practice., Methods: A cross-sectional analytical, quantitative study was conducted. Participants consisted of hospital nutritionists from 13 Latin American countries who had participated in a previously validated online survey on the activities performed during their daily work, obtaining a Professional Activities Score (PAS)., Results: 1222 nutritionists participated. Of the activities associated with the professional role, the only ones who reached over 75 % of execution were: performing nutritional intervention; performing nutritional assessment and diagnosis; providing counseling and dietary prescription; developing nutritional care plans for patients with nutritional problems; and performing the monitoring and evaluation of results of priority patients. The least frequent activities were: university teaching and collaborating in research. Regarding the reasons for not performing activities: 34.0 % reported not being included in the activities, 24.5 % mentioned lack of time, and 13.6 % indicated that the activities were conducted by another professional. Variables positively associated with an increase in the PAS were: having spent more years exercising the profession (Beta: 0.028, 95 % CI: 0.004; 0.051), and having a greater number of specialties (4 or more, Beta: 2.294, 95 % CI: 1.031; 3.557). Working in lower-complexity facilities (Low: Beta: -1.037, 95 % CI: -1.443; -0.630), and having more reasons for not performing the activities (3 or more: Beta: -3.105, 95 % CI: -4.111; -2.099) were inversely associated. From the sample, 1.8 % held a doctorate in clinical nutrition, 43.9 % had a specialty, and 64.4 % had a diploma or postgraduate degree in clinical nutrition., Conclusion: None of the activities related to the nutritionist work was performed on a 100 % basis. In Latin America, Ministries of Health should standardize and regulate the functions of the clinical nutritionist, as well as quantifying understaffing and proposing solutions to alleviate the shortage of these professionals, acknowledging the positive impact that they have on the recovery of hospital patients., Competing Interests: Declaration of competing interest All authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To associate breakfast consumption frequency with self-reported nutritional status and dietary patterns of Latin American university students by human development., Material and Methods: This was a cross-sectional, multicenter observational study. University students from 11 Latin American countries (Argentina, Chile, Colombia, Costa Rica, Ecuador, Guatemala, Mexico, Peru, Paraguay, Panama and Uruguay) were invited to participate by answering an online self-administered questionnaire on food consumption and sociodemographic indicators, associations were investigated using logistic regression., Results: The logistic regression analysis showed significant associations between breakfast consumption and the crude model, models 2 and 3 in countries with very high and upper-middle/high human development. However, after adjustment in the most comprehensive model, the association is no longer statistically significant. In the fully adjusted model of the variables, a significant relationship was observed between breakfast consumption and both healthy and unhealthy dietary patterns. Specifically, students who typically consume breakfast exhibit greater consumption of oatmeal and fruits, as well as healthier dinner choices. Conversely, they exhibit lower consumption of fast food, sugary drinks, and juices. In particular, in highly developed countries, along with the mentioned foods, consumption of dairy was linked to breakfast consumption in a positive way, while alcohol consumption was negatively associated., Conclusion: University students who eat breakfast on a regular basis maintain a healthier diet in comparison to those who do not, irrespective of their country's level of human development.

BMI-matched normal- (NGT, n = 10, 41 ± 4y, 35.6 ± 3.0 kg/m 2 ) and abnormal-glucose-tolerant (AGT, n = 16, 51 ± 3y, 34.3 ± 1.5 kg/m 2 ) participants were evaluated for body composition, metabolic health (oral glucose tolerance test [OGTT]), and VO 2 max. Participants also completed a treadmill walking test at 65% VO 2 max for 30 min. Total sRAGE, esRAGE, sTLR2, and sTLR4 were assessed via ELISA, and cRAGE was calculated. AGT exhibited greater (p < 0.05) body fat % (+24%), fasting plasma glucose (+37%), OGTT AUC (+59%), and HOMA-IR (+55%) and lower (p < 0.05) VO 2 max (-24%). sTLR2 was 33% lower in AGT than NGT (main effect, p = 0.034). However, sTLR2 did not change (p > 0.05) following AE. sTLR4 tended to be 36% lower in AGT than NGT (main effect, p = 0.096) and did not change following AE (p > 0.05). Total sRAGE and isoforms were similar (p > 0.05) between groups and did not change following AE (p > 0.05). sTLR2 was correlated with (p < 0.05) basal BG (r = -0.505) and OGTT AUC (r = -0.687). sTLR4 was correlated with basal BG (p < 0.10, r = -0.374) and OGTT AUC (p < 0.05, r = -0.402). Linear regressions were predictive of sTLRs in the basal state (sTLR2: R 2  = 0.641, p = 0.01; sTLR4: R 2  = 0.566, p = 0.037) and after acute exercise state (sTLR2: R 2  = 0.681, p = 0.004, sTLR4: R 2  = 0.568, p = 0.036).These findings show circulating sTLR profiles are disrupted in AGT and acute AE minimally modulates their levels., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Obesity prevalence in the US has nearly tripled since 1975 and a parallel increase in prevalence of type 2 diabetes (T2D). Obesity promotes a myriad of metabolic derangements with insulin resistance (IR) being perhaps the most responsible for the development of T2D and other related diseases such as cardiovascular disease. The precarious nature of IR development is such that it provides a valuable target for the prevention of further disease development. However, the mechanisms driving IR are numerous and complex making the development of viable interventions difficult. The development of metabolic derangement in the context of obesity promotes accumulation of reactive metabolites such as the reactive alpha-dicarbonyl methylglyoxal (MG). MG accumulation has long been appreciated as a marker of disease progression in patients with T2D as well as the development of diabetic complications. However, recent evidence suggests that the accumulation of MG occurs with obesity prior to T2D onset and may be a primary driving factor for the development of IR and T2D. Further, emerging evidence also suggests that this accumulation of MG with obesity may be a result in a loss of MG detoxifying capacity of glyoxalase I. In this review, we will discuss the evidence that posits MG accumulation because of GLO1 attenuation is a novel target mechanism of the development of metabolic derangement. In addition, we will also explore the regulation of GLO1 and the strategies that have been investigated so far to target GLO1 regulation for the prevention and treatment of metabolic derangement., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Nearly 40% of Americans have obesity and are at increased risk for developing type 2 diabetes. Skeletal muscle is responsible for >80% of insulin-stimulated glucose uptake that is attenuated by the inflammatory milieu of obesity and augmented by aerobic exercise. The receptor for advanced glycation endproducts (RAGE) is an inflammatory receptor directly linking metabolic dysfunction with inflammation. Circulating soluble isoforms of RAGE (sRAGE) formed either by proteolytic cleavage (cRAGE) or alternative splicing (esRAGE) act as decoys for RAGE ligands, thereby counteracting RAGE-mediated inflammation. We aimed to determine if RAGE expression or alternative splicing of RAGE is altered by obesity in muscle, and whether acute aerobic exercise (AE) modifies RAGE and sRAGE. Young (20-34 yr) participants without [ n = 17; body mass index (BMI): 22.6 ± 2.6 kg/m 2 ] and with obesity ( n = 7; BMI: 32.8 ± 2.9 kg/m 2 ) performed acute aerobic exercise (AE) at 40%, 65%, or 80% of maximal aerobic capacity (V̇o 2max ; mL/kg/min) on separate visits. Blood was taken before and 30 min after each AE bout. Muscle biopsy samples were taken before, 30 min, and 3 h after the 80% V̇o 2max AE bout. Individuals with obesity had higher total RAGE and esRAGE mRNA and RAGE protein ( P < 0.0001). In addition, RAGE and esRAGE transcripts correlated to transcripts of the NF-κB subunit P65 ( P < 0.05). There was no effect of AE on total RAGE or esRAGE transcripts, or RAGE protein ( P > 0.05), and AE tended to decrease circulating sRAGE in particular at lower intensities of exercise. RAGE expression is exacerbated in skeletal muscle with obesity, which may contribute to muscle inflammation via NF-κB. Future work should investigate the consequences of increased skeletal muscle RAGE on the development of obesity-related metabolic dysfunction and potential mitigating strategies. NEW & NOTEWORTHY This study is the first to investigate the effects of aerobic exercise intensity on circulating sRAGE isoforms, muscle RAGE protein, and muscle RAGE splicing. sRAGE isoforms tended to diminish with exercise, although this effect was attenuated with increasing exercise intensity. Muscle RAGE protein and gene expression were unaffected by exercise. However, individuals with obesity displayed nearly twofold higher muscle RAGE protein and gene expression, which positively correlated with expression of the P65 subunit of NF-κB.

In this paper, we present a bespoke brain-computer interface (BCI), which was developed for a person with severe motor-impairments, who was previously a Violinist, to allow performing and composing music at home. It uses steady-state visually evoked potential (SSVEP) and adopts a dry, low-density, and wireless electroencephalogram (EEG) headset. In this study, we investigated two parameters: (1) placement of the EEG headset and (2) inter-stimulus distance and found that the former significantly improved the information transfer rate (ITR). To analyze EEG, we adopted canonical correlation analysis (CCA) without weight-calibration. The BCI for musical performance realized a high ITR of 37.59 ± 9.86 bits min -1 and a mean accuracy of 88.89 ± 10.09%. The BCI for musical composition obtained an ITR of 14.91 ± 2.87 bits min -1 and a mean accuracy of 95.83 ± 6.97%. The BCI was successfully deployed to the person with severe motor-impairments. She regularly uses it for musical composition at home, demonstrating how BCIs can be translated from laboratories to real-world scenarios.

The benefits of exercise involve skeletal muscle redox state alterations of nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD). We determined the fiber-specific effects of acute exercise on the skeletal muscle redox state in healthy adults. Muscle biopsies were obtained from 19 participants (11 M, 8 F; 26 ± 4 yr) at baseline (fasted) and 30 min and 3 h after treadmill exercise at 80% maximal oxygen consumption (V̇o 2max ). Muscle samples were probed for autofluorescence of NADH (excitation at 340-360 nm) and oxidized flavoproteins (Fp; excitation at 440-470 nm) and subsequently, fiber typed to quantify the redox signatures of individual muscle fibers. Redox state was calculated as the oxidation-to-reduction redox ratio: Fp/(Fp + NADH). At baseline, pair-wise comparisons revealed that the redox ratio of myosin heavy chain (MHC) I fibers was 7.2% higher than MHC IIa ( P = 0.023, 95% CI: 5.2, 9.2%) and the redox ratio of MHC IIa was 8.0% higher than MHC IIx ( P = 0.035, 95% CI: 6.8, 9.2%). MHC I fibers also displayed greater NADH intensity than MHC IIx ( P = 0.007) and greater Fp intensity than both MHC IIa ( P = 0.019) and MHC IIx ( P < 0.0001). Fp intensities increased in all fiber types (main effect, P = 0.039) but redox ratios did not change (main effect, P = 0.483) 30 min after exercise. The change in redox ratio was positively correlated with capillary density in MHC I (rho = 0.762, P = 0.037), MHC IIa fibers (rho = 0.881, P = 0.007), and modestly in MHC IIx fibers (rho = 0. 771, P = 0.103). These findings support the use of redox autofluorescence to interrogate skeletal muscle metabolism. NEW & NOTEWORTHY This study is the first to use autofluorescent imaging to describe differential redox states within human skeletal muscle fiber types with exercise. Our findings highlight an easy and efficacious technique for assessing skeletal muscle redox in humans.

Background: Deterioration in the health-related quality of life (HRQoL) and healthy eating behavior due to the effect of COVID-19 lockdown has been reported. The aim of this study was to associate eating habits and HRQoL with physical activity behavior in Latin American university students during COVID-19 pandemic. Methods: Measured 4,859 university students with a mean age of 22.4 years and they were mostly female (73.7%) from 10 Latin American countries (Argentina, Chile, Colombia, Costa Rica, Ecuador, Guatemala, Mexico, Panama, Paraguay and, Peru). Eating habits were measured using a survey validated with other university students, HRQoL was assessments using the short version of the World Health Organization (WHOQOL-BREF) scale and physical activity behavior with a dicotomous question based on the international recommendations for physical activity. Results: There is a higher complaince for all the international recommendations for healthy foods intake in the physically active group of students ( p  < 0.01), with the exception of alcohol and salt. In addition, physically active students presented a significantly higher HRQoL ( p  < 0.001) in all the dimensions analyzed when compared to physically inactive students. Conclusions: Latin American university students who are physically active are more likely to have a healthier eating behavior and a lower risk of a decreased HRQoL during COVID-19 pandemic.

Reactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength. Here, we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by deletion of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner. In young and old mice, genetic and pharmacological neutralization of LOOH or their secondary reactive lipid aldehydes robustly prevented muscle atrophy and weakness, indicating that LOOH-derived carbonyl stress mediates age- and disuse-induced muscle dysfunction. Our findings provide novel insights for the role of LOOH in sarcopenia including a therapeutic implication by pharmacological suppression., Competing Interests: HE, JS, PS, ZM, PF, AL, JM, AP, AV, JJ, AS, JP, EM, EA, SB, QR, JC, MD, KF No competing interests declared, MP is affiliated with Sciex. The author has no financial interests to declare, (© 2023, Eshima, Shahtout et al.)

Significance: Accumulation of reactive oxygen species (ROS) is known to promote cellular damage in multiple cell types. In skeletal muscle, ROS has been implicated in disuse-induced muscle atrophy. However, the molecular origin and mechanism of how disuse promotes ROS and muscle dysfunction remains unclear. Recent Advances: Recently, we implicated membrane lipids of mitochondria to be a potential source of ROS to promote muscle atrophy. Critical Issues: In this review, we discuss evidence that changes in mitochondrial lipids represent a physiologically relevant process by which disuse promotes mitochondrial electron leak and oxidative stress. Future Directions: We further discuss lipid hydroperoxides as a potential downstream mediator of ROS to induce muscle atrophy. Antioxid. Redox Signal . 38, 338-351.

Objective: The goal of this investigation was to evaluate circulating and skeletal muscle inflammatory biomarkers between maintenance hemodialysis (MHD) and demographic-matched control subjects (CON) before and after ingestion of a protein-rich meal., Design and Methods: CON (n = 8; 50 ± 2 years; 31 ± 1 kg/m 2 ) and MHD patients (n = 8; 56 ± 5 years; 32 ± 2 kg/m 2 ) underwent a basal blood draw and muscle biopsy and serial blood draws after the ingestion of a mixed meal on a nondialysis day. Plasma advanced glycation end products (AGEs) and markers of oxidation were assessed via liquid chromatography-tandem mass spectrometry before and after the meal (+240 min). Circulating inflammatory cytokines and soluble receptors for AGE (sRAGE) isoforms (endogenous secretory RAGEs and cleaved RAGEs) were determined before and after the meal (+240 min). Basal muscle was probed for inflammatory cytokines and protein expression of related signaling components (RAGE, Toll-like receptor 4, oligosaccharyltransferase subunit 48, TIR-domain-containing adapter-inducing interferon-β, total IκBα, and pIκBα)., Results: Basal circulating AGEs were 7- to 343-fold higher (P < .001) in MHD than those in CON, but only MG-H1 increased in CON after the meal (P < .001). There was a group effect (MHD > CON) for total sRAGEs (P = .02) and endogenous secretory RAGEs (P < .001) and a trend for cleaved RAGEs (P=.09), with no meal effect. In addition, there was a group effect (MHD < CON; P < .05) for circulating fractalkine, interleukin (IL)10, IL17A, and IL1β and a trend (P < .10) for IL6 and macrophage inflammatory protein 1 alpha, whereas tumor necrosis factor alpha was higher in MHD (P < .001). In muscle, Toll-like receptor 4 (P = .03), TIR-domain-containing adapter-inducing interferon-β (P = .002), and oligosaccharyltransferase subunit 48 (P = .02) expression was lower in MHD than that in CON, whereas IL6 was higher (P = .01) and IL8 (P = .08) tended to be higher in MHD., Conclusion: Overall, MHD exhibited an exaggerated, circulating, and skeletal muscle inflammatory biomarker environment, and the meal did not appreciably affect the inflammatory status., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

A clinical nutritionist (CN) is a university-educated professional trained to perform preventive and recovery functions in the health of patients. The actions of these professionals, both worldwide and in Latin America, may face barriers and opportunities that require careful identification and examination. The main objective of this study is to identify the most important barriers and opportunities for the clinical nutritionist in 13 Latin American countries. A qualitative study was carried out; the initial phase involved conducting in-depth individual interviews with 89 informants, experienced CNs from 13 Latin American countries. After calculating the mean and standard deviation, we ranked the top 10 most frequently reported barriers by assigning a score ranging from 1 to 10. Additionally, 3 opportunities were identified with a lower score from 1 to 3. Means and standard deviation were calculated to sort the responses. Results: the most important barrier was the absence of public policies that regulate and/or monitor compliance with the staffing of CNs according to the number of hospital beds, while the most important opportunity was the advances in technology such as software, body analysis equipment and other tools used in Nutritional Care. The identified barriers can interfere with the professional performance of CNs and, moreover, make it difficult to monitor the good nutritional status of patients. It is recommended to consider the barriers identified in this study, as well as the opportunities, with a view to improving the quality of hospital services with an adequate supply of nutritionists., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: SARS-CoV-2, a newly identified coronavirus responsible for the COVID-19 pandemic, has challenged health services and profoundly impacted people's lifestyles. The objective of the present study was to evaluate the effect of confinement during the COVID-19 pandemic on food consumption patterns and body weight in adults from 12 Ibero-American countries., Methods: Multicentric, cross-sectional study. Data was collected using an online survey disseminated by social networks. The sample included 10 552 people from Spain and 11 Latin American countries who were selected by snowball sampling., Results: While 38.50% of the sample reported weight gain, 16.90% reported weight lost. Weight change was associated with sex, age, country of residence, and education level. People who were not confined more often reported having maintained their weight in comparison to people who were confined. All Latin American countries showed an increased consumption of sweetened drinks, pastry products, fried foods, and alcoholic beverages during confinement. Consumption of eggs and dairy products was independent from body weight change. People who consumed more fruits and vegetables during confinement more often reported having lost weight. In contrast, body weight gain during confinement was associated with increased intake of sugary drinks, baked goods and pastries, pizza, fried foods, and alcoholic beverages., Conclusion: During COVID-19 confinement, the Latin American countries included in this study showed a change in their consumption patterns toward less healthy diets, which in turn was associated with an increase in the body weight of their population., Competing Interests: Declaration of competing interest BMC has received fees, consulting payments, and unrestricted research funding from government and non-profit sources. He has also received consulting fees from biotechnology, pharmaceutical, and food and beverage companies. None of the above entities had any role in the design or preparation of this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Cathepsin B (CTSB) and brain derived neurotrophic factor (BDNF) are increased with aerobic exercise (AE) and skeletal muscle has been identified as a potential source of secretion. However, the intensity of AE and the potential for skeletal muscle contributions to circulating CTSB and BDNF have not been fully studied in humans., Objective: Determine the effects of AE intensity on circulating and skeletal muscle CTSB and BDNF expression profiles., Methods: Young healthy subjects ( n  = 16) completed treadmill-based AE consisting of VO 2 max and calorie-matched acute AE sessions at 40%, 65% and 80% VO 2 max. Fasting serum was obtained before and 30-minutes after each bout of exercise. Skeletal muscle biopsies ( vastus lateralis ) were taken before, 30-minutes and 3-hours after the 80% bout. Circulating CTSB and BDNF were assayed in serum. CTSB protein, BDNF protein and mRNA expression were measured in skeletal muscle tissue., Results: Serum CTSB increased by 20±7% ( p  = 0.02) and 30±18% ( p  = 0.04) after 80% and VO 2 max AE bouts, respectively. Serum BDNF showed a small non-significant increase (6±3%; p  = 0.09) after VO 2 max. In skeletal muscle tissue, proCTSB increased 3 h-post AE (87±26%; p  < 0.01) with no change in CTSB gene expression. Mature BDNF protein decreased (31±35%; p  = 0.03) while mRNA expression increased (131±41%; p  < 0.01) 3 h-post AE. Skeletal muscle fiber typing revealed that type IIa and IIx fibers display greater BDNF expression compared to type I ( p  = 0.02 and p  < 0.01, respectively)., Conclusions: High intensity AE elicits greater increases in circulating CTSB compared with lower intensities. Skeletal muscle protein and gene expression corroborate the potential role of skeletal muscle in generating and releasing neuroprotective exerkines into the circulation.NEW AND NOTEWORTHY: 1) CTSB is enriched in the circulation in an aerobic exercise intensity dependent manner. 2) Skeletal muscle tissue expresses both message and protein of CTSB and BDNF. 3) BDNF is highly expressed in glycolytic skeletal muscle fibers., Competing Interests: The authors have no conflict of interest to report., (© 2022 – The authors. Published by IOS Press.)

Background and Objectives: The confinement by COVID-19 has affected the food chain and environments, which added to factors such as anxiety, frustration, fear and stress have modified the quality of the diet in the population around the world. The purpose of this study was to explore diet quality during the COVID-19 pandemic in 11 Latin American countries., Methodology: Multicentric, cross-sectional study. An online survey was applied to residents of 11 Latin-American countries, during April and May 2020, when confinement was mandatory. Diet quality was evaluated using a validated questionnaire., Result: 10,573 people participated in the study. The quality of the food by country shows that Colombia presented the best quality, while Chile and Paraguay presented the lowest. When comparing the overall results of diet quality by gender, schooling and age, women, people with more schooling and people under 30 years of age, presented better diet quality. The regression model showed that the variables associated with diet quality were: age (df = 3, F = 4. 57, p < 0.001), sex (df = 1, F = 131.01, p < 0.001), level of education (df = 1, F = 38.29, p < 0.001), perception of weight change (df = 2, F = 135.31, p < 0.001), basis services (df = 1, F = 8.63, p = 0.003), and quarantine (df = 1, F = 12.14, p = 0.001)., Conclusion: It is necessary for governments to intervene to reverse these indicators, considering that inadequate feeding favors the appearance of no communicable diseases, which favor a higher risk of infection and worse prognosis with COVID-19., (© 2022. The Author(s).)

Introduction: This study aimed to determine the relationship between symptoms of anxiety and/or anhedonia (inability to feel pleasure) and diet quality during confinement due to COVID-19 in rural populations in Latin America., Methods: This was a multicentric, cross-sectional study. An online survey was applied, which included the Beck Anxiety Inventory, Snaith-Hamilton Pleasure Scale for assessing the presence of anhedonia, the Food Intake Questionnaire and sociodemographic questions., Results: The study included 10 552 people from 11 countries; 708 participants were living in rural areas. More than half of the participants were quarantined at the time of the survey. Diet quality was inversely associated with anhedonia (p<0.001) and anxiety (p=0.003). In addition, a healthier diet was associated with being female (p=0.030), having a higher level of education (p=0.008) and country of residence (p=0.001)., Conclusion: Among the rural population during the COVID pandemic, this study found a worse diet quality was associated with symptoms of anhedonia and anxiety, as well as lower level of education and being male. Proposals to improve the quality of the diet could include interventions aimed at people's mental health.

Thioredoxin-interacting protein (TXNIP) negatively effects the redox state and growth signaling via its interactions with thioredoxin (TRX) and regulated in development and DNA damage response 1 (REDD1), respectively. TXNIP expression is downregulated by pathways activated during aerobic exercise (AE), via posttranslational modifications (PTMs; serine phosphorylation and ubiquitination). The purpose of this investigation was to determine the effects of acute AE on TXNIP expression, posttranslational modifications, and its interacting partners, REDD1 and TRX. Fifteen healthy adults performed 30 min of aerobic exercise (80% V̇o 2max ) with muscle biopsies taken before, immediately following, and 3 h following the exercise bout. To explore potential mechanisms underlying our in vivo findings, primary human myotubes were exposed to two models of exercise, electrical pulse stimulation (EPS) and palmitate-forskolin-ionomycin (PFI). Immediately following exercise, TXNIP protein decreased, but returned to preexercise levels 3 h after exercise. These results were replicated in our PFI exercise model only. Although not statistically significant, there was a trending main effect in serine-phosphorylation status of TXNIP ( P = 0.07) immediately following exercise. REDD1 protein decreased 3 h after exercise. AE had no effect on TRX protein expression, gene expression, or the activity of its reducing enzyme, thioredoxin reductase. Consequently, AE had no effect on the TRX: TXNIP interaction. Our results indicate that AE leads to acute reductions in TXNIP and REDD1 protein expression. However, these changes did not result in alterations in the TRX: TXNIP interaction and could not be entirely explained by alterations in TXNIP PTMs or changes in TRX expression or activity. NEW & NOTEWORTHY Aerobic exercise is an effective tool in the prevention and treatment of several chronic metabolic diseases. However, the mechanisms through which these benefits are conferred have yet to be fully elucidated. Our data reveal a novel effect of aerobic exercise on reducing the protein expression of molecular targets that negatively impact redox and insulin/growth signaling in skeletal muscle. These findings contribute to the expanding repository of molecular signatures provoked by aerobic exercise.

Competing Interests: BMC is currently the Head of Sciences at Health Care Pediatrics, at Nutricia Argentina. All other authors declare that they have no conflict of interest.

This article introduces GeMS, a system for music composition informed by synthetic biology. GeMS generates music with simulations of genetic processes, such as transcription, translation, and protein folding, with which biological systems render chains of amino acids from DNA strands. The system comprises the following components: the Miranda machine , the rhythmator , and the pitch processor . The Miranda machine is an abstract Turing-machine-like processor, which manipulates a sequence of DNA symbols according to a set of programming instructions. This process generates a pool of new DNA strands, which are subsequently translated into rhythms. GeMS represents the musical equivalent of amino acids in terms of rhythms, referred to as rhythmic codons. This enables the rhythmator to convert DNA sequences into rhythmic sequences. The pitch processor generates pitches for such rhythmic sequences. It is inspired by the phenomenon of protein folding. The pitch processor considers orientation information of DNA instructions yielded by the Miranda machine in order to activate algorithms for generating pitches. A musical composition, entitled Artibiotics , for percussion ensemble and electronic instruments, is presented to demonstrate the system.

The ability of music to evoke activity changes in the core brain structures that underlie the experience of emotion suggests that it has the potential to be used in therapies for emotion disorders. A large volume of research has identified a network of sub-cortical brain regions underlying music-induced emotions. Additionally, separate evidence from electroencephalography (EEG) studies suggests that prefrontal asymmetry in the EEG reflects the approach-withdrawal response to music-induced emotion. However, fMRI and EEG measure quite different brain processes and we do not have a detailed understanding of the functional relationships between them in relation to music-induced emotion. We employ a joint EEG - fMRI paradigm to explore how EEG-based neural correlates of the approach-withdrawal response to music reflect activity changes in the sub-cortical emotional response network. The neural correlates examined are asymmetry in the prefrontal EEG, and the degree of disorder in that asymmetry over time, as measured by entropy. Participants' EEG and fMRI were recorded simultaneously while the participants listened to music that had been specifically generated to target the elicitation of a wide range of affective states. While listening to this music, participants also continuously reported their felt affective states. Here we report on co-variations in the dynamics of these self-reports, the EEG, and the sub-cortical brain activity. We find that a set of sub-cortical brain regions in the emotional response network exhibits activity that significantly relates to prefrontal EEG asymmetry. Specifically, EEG in the pre-frontal cortex reflects not only cortical activity, but also changes in activity in the amygdala, posterior temporal cortex, and cerebellum. We also find that, while the magnitude of the asymmetry reflects activity in parts of the limbic and paralimbic systems, the entropy of that asymmetry reflects activity in parts of the autonomic response network such as the auditory cortex. This suggests that asymmetry magnitude reflects affective responses to music, while asymmetry entropy reflects autonomic responses to music. Thus, we demonstrate that it is possible to infer activity in the limbic and paralimbic systems from pre-frontal EEG asymmetry. These results show how EEG can be used to measure and monitor changes in the limbic and paralimbic systems. Specifically, they suggest that EEG asymmetry acts as an indicator of sub-cortical changes in activity induced by music. This shows that EEG may be used as a measure of the effectiveness of music therapy to evoke changes in activity in the sub-cortical emotion response network. This is also the first time that the activity of sub-cortical regions, normally considered "invisible" to EEG, has been shown to be characterisable directly from EEG dynamics measured during music listening.

The purpose of this investigation was to evaluate the effects of experimental hyperglycemia on oxidative damage (OX), advanced glycation end products (AGEs), and the receptor for AGEs (RAGE) through an in vivo approach. Obese subjects ( n = 10; 31.2 ± 1.2 kg·m -2 ; 56 ± 3 years) underwent 24 h of hyperglycemic clamp (+5.4 mM above basal), where plasma at basal and after 2 h and 24 h of hyperglycemic challenge were assayed for OX (methionine sulfoxide, MetSO, and aminoadipic acid, AAA) and AGE-free adducts (N e -carboxymethyllysine, CML; N e -carboxyethyllysine, CEL; glyoxal hydroimidazolone-1, GH-1; methylglyoxal hydroimidazolone-1, MG-H1; and 3-deoxyglucosone hydroimidazolone, 3DG-H) via liquid chromatography⁻tandem mass spectrometry (LC⁻MS/MS). Urine was also analyzed at basal and after 24 h for OX and AGE-free adducts and plasma soluble RAGE (sRAGE) isoforms (endogenous secretory RAGE, esRAGE, and cleaved RAGE, cRAGE), and inflammatory markers were determined via enzyme-linked immunosorbent assay (ELISA). Skeletal muscle tissue collected via biopsy was probed at basal, 2 h, and 24 h for RAGE and OST48 protein expression. Plasma MetSO, AAA, CEL, MG-H1, and G-H1 decreased (-18% to -47%; p < 0.05), while CML increased (72% at 24 h; p < 0.05) and 3DG-H remained unchanged ( p > 0.05) with the hyperglycemic challenge. Renal clearance of MetSO, AAA, and G-H1 increased (599% to 1077%; p < 0.05), CML decreased (-30%; p < 0.05), and 3DG-H, CEL, and MG-H1 remained unchanged ( p > 0.05). Fractional excretion of MetSO, AAA, CEL, G-H1, and MG-H1 increased (5.8% to 532%; p < 0.05) and CML and 3DG-H remained unchanged ( p > 0.05). Muscle RAGE and OST48 expression, plasma sRAGE, IL-1β, IL-1Ra, and TNFα remained unchanged ( p > 0.05), while IL-6 increased (159% vs. basal; p > 0.05). These findings suggest that individuals who are obese but otherwise healthy have the capacity to prevent accumulation of OX and AGEs during metabolic stress by increasing fractional excretion and renal clearance.

Advanced glycation end products (AGEs) promote the development of diabetic complications through activation of their receptor (RAGE). Isoforms of soluble RAGE (sRAGE) sequester AGEs and protect against RAGE-mediated diabetic complications. We investigated the effect of an overnight fast on circulating metabolic substrates, hormones, AGEs, and sRAGE isoforms in 26 individuals with type 1 diabetes (T1DM). Blood was collected from 26 young (18⁻30 years) T1DM patients on insulin pumps before and after an overnight fast. Circulating AGEs were measured via LC-MS/MS and sRAGE isoforms were analyzed via ELISA. Glucose, insulin, glucagon, and eGFR cystatin-c decreased while cortisol increased following the overnight fast ( p < 0.05). AGEs (CML, CEL, 3DG-H, MG-H1, and G-H1) decreased (21⁻58%, p < 0.0001) while total sRAGE, cleaved RAGE (cRAGE), and endogenous secretory RAGE (esRAGE) increased (22⁻24%, p < 0.0001) following the overnight fast. The changes in sRAGE isoforms were inversely related to MG-H1 ( rho = -0.493 to -0.589, p < 0.05) and the change in esRAGE was inversely related to the change in G-H1 ( rho = -0.474, p < 0.05). Multiple regression analyses revealed a 1 pg/mL increase in total sRAGE, cRAGE, or esRAGE independently predicted a 0.42⁻0.52 nmol/L decrease in MG-H1. Short-term energy restriction via an overnight fast resulted in increased sRAGE isoforms and may be protective against AGE accumulation.

Background and Aims: The receptor for advanced glycation end products (RAGE) is implicated in obesogenesis. Conversely, soluble RAGE (sRAGE) competitively inhibits RAGE. Our aim was to determine the effects of weight-loss via alternate day fasting (ADF) on sRAGE isoforms and evaluate potential relationships with body composition., Methods and Results: 42 obese participants were randomized to control (CON) or ADF. For 24 weeks, the ADF group consumed 25% or 125% of their caloric requirements on alternating days while the CON group did not change their diet. Body fat was measured via DXA, visceral fat (VAT) via MRI and subcutaneous fat (SAT) was derived by subtracting VAT from total fat. sRAGE isoforms were measured via ELISAs. After 24 weeks, ADF -6.8 (-9.5, -3.5)kg (Median, IQR) lost more weight than CON -0.3 (-1.9, 1.0)kg (p < 0.05). The change in endogenous secretory RAGE (esRAGE) was different between ADF 15 (-30, 78)pg/mL and CON -21 (-72, 16)pg/mL after 24 weeks (p < 0.05). To examine the effect of changes in body composition, the cohort was stratified by median weight-, fat-, SAT-, and VAT-loss. The changes in all sRAGE isoforms were different between those above and below median weight-loss (p < 0.05) with sRAGE isoforms tending to decrease in individuals below the median. Changes in total sRAGE and esRAGE were different between individuals above compared to below median fat- and SAT-loss (p < 0.05). Those above median fat-loss increased esRAGE by 29 (-5, 66)pg/mL (p < 0.05)., Conclusion: Improvements in body composition are related to increased sRAGE isoforms, implicating sRAGE as a potential target for the treatment of obesity., Clinical Trial Registration: NCT00960505., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

A high-fat diet can induce inflammation and metabolic diseases such as diabetes and atherosclerosis. The receptor for advanced glycation endproducts (RAGE) plays a critical role in metabolic disease pathophysiology and the soluble form of the receptor (sRAGE) can mitigate these effects. However, little is known about RAGE in the postprandial condition and the effect of exercise in this context. Thus, we aimed to determine the effects of a single high-fat meal (HFM) with and without prior exercise on peripheral blood mononuclear cell (PBMC) RAGE biology. Healthy males (n = 12) consumed a HFM on two occasions, one without prior exercise and one 16-18 hours following acute aerobic exercise. Total soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) were determined via ELISA and cleaved RAGE (cRAGE) was calculated as the difference between the two. Isolated PBMCs were analyzed for RAGE, ADAM10, TLR4, and MyD88 protein expression and ADAM10 activity. The HFM significantly (P < 0.01) attenuated sRAGE, esRAGE, and cRAGE by 9.7%, 6.9%, and 10.5%, respectively. Whereas, the HFM increased PBMC RAGE protein expression by 10.3% (P < 0.01), there was no meal effect on PBMC TLR4, MYD88, or ADAM10 protein expression, nor ADAM10 activity. There was also no exercise effect on any experimental outcomes. These findings suggest that PBMC RAGE and soluble RAGE may be important in the postprandial response to a HFM, and that prior aerobic exercise does not alter these processes in young healthy adult males. The mechanisms by which a HFM induces RAGE expression and reduces circulating soluble RAGE isoforms requires further study., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

The objective was to evaluate the inclusion of macaúba seed cake (MSC) meal in diets for growing rabbits by assessing their growth and slaughtering performance, haematological traits, nutritional contribution of caecotrophs, in vitro digestibility, degradability and fermentation parameters. A total of 88 rabbits were distributed to four groups with 22 animals each and fed diets containing 0, 50, 100 and 150 g/kg of MSC, respectively. The in vitro assays were conducted employing cecum inoculum on the same dietary treatments. The inclusion of MSC yielded a quadratic effect on in vitro dry matter digestibility (p < 0.001). The maximum amount of produced gas was raised linearly with the inclusion of MSC (p = 0.016). MSC linearly reduced several variables as the nutritional contribution of caecotrophs in dry matter (p = 0.017) and crude protein (p = 0.014), live weight at 51 d (p = 0.024), body weight gain (p = 0.039), average daily feed intake (ADFI) (p = 0.001) and feed conversion ratio (FCR) (p = 0.007) in the first period evaluated (30-50 d); furthermore the ADFI and FCR the second (51-72 d) and whole period (30-72 d) (p < 0.001). MSC addition caused a quadratic effect on white blood cells count (p = 0.026) and a linear decrease of eosinophils (p = 0.045). In conclusion, the inclusion of up to 150 g/kg of MSC improves the in vitro digestibility and fermentation potential of the diets, reflecting on the ADFI and FCR of the animals, although adverse effects are observed on the weight of the commercial carcass and nutritive contribution of the caecotrophs.

Although there is evidence for metabolic dysfunction and chronic inflammation in Alzheimer's disease (AD), circulating levels of soluble receptor for advanced glycation end products (sRAGE) and the receptor for advanced glycation end products (RAGE) ligand S100B have not been characterized. sRAGE is an important mediator in disease as it can act as a ligand decoy for RAGE and attenuate downstream inflammatory signaling. Cognitively healthy elderly and AD participants with and without type 2 diabetes ( n = 135) were stratified according to the clinical dementia rating (CDR; 0 = normal cognition (NC); ≥0.5 = AD). Total serum sRAGE, endogenous secretory RAGE (esRAGE), and S100B were assayed via ELISAs, and cleaved RAGE (cRAGE) and the cRAGE : esRAGE ratio were calculated. cRAGE : esRAGE was lower in AD compared to NC ( p < 0.05). Metabolic substratifications were used to investigate the factors that influence sRAGE pathology in AD. Stratification by BMI classification, median fat mass, median HOMA-IR, median insulin, and median amylin were all metabolic or anthropometric factors which significantly interacted with sRAGE profiles within AD subjects. There were no significant differences in serum S100B between groups. These characterizations of sRAGE contribute evidence to the link between impaired metabolism and cognitive decline due to AD.

Skeletal muscle insulin resistance is a hallmark of Type 2 diabetes (T2DM) and may be exacerbated by protein modifications by methylglyoxal (MG), known as dicarbonyl stress. The glyoxalase enzyme system composed of glyoxalase 1/2 (GLO1/GLO2) is the natural defense against dicarbonyl stress, yet its protein expression, activity, and regulation remain largely unexplored in skeletal muscle. Therefore, this study investigated dicarbonyl stress and the glyoxalase enzyme system in the skeletal muscle of subjects with T2DM (age: 56 ± 5 yr.; BMI: 32 ± 2 kg/m 2 ) compared with lean healthy control subjects (LHC; age: 27 ± 1 yr.; BMI: 22 ± 1 kg/m 2 ). Skeletal muscle biopsies obtained from the vastus lateralis at basal and insulin-stimulated states of the hyperinsulinemic (40 mU·m -2 ·min -1 )-euglycemic (5 mM) clamp were analyzed for proteins related to dicarbonyl stress and glyoxalase biology. At baseline, T2DM had increased carbonyl stress and lower GLO1 protein expression (-78.8%), which inversely correlated with BMI, percent body fat, and HOMA-IR, while positively correlating with clamp-derived glucose disposal rates. T2DM also had lower NRF2 protein expression (-31.6%), which is a positive regulator of GLO1, while Keap1 protein expression, a negative regulator of GLO1, was elevated (207%). Additionally, insulin stimulation during the clamp had a differential effect on NRF2, Keap1, and MG-modified protein expression. These data suggest that dicarbonyl stress and the glyoxalase enzyme system are dysregulated in T2DM skeletal muscle and may underlie skeletal muscle insulin resistance. Whether these phenotypic differences contribute to the development of T2DM warrants further investigation.

The soluble receptor for advanced glycation end products (sRAGE) may be protective against inflammation associated with obesity and type 2 diabetes (T2DM). The aim of this study was to determine the distribution of sRAGE isoforms and whether sRAGE isoforms are associated with risk of T2DM development in subjects spanning the glucose tolerance continuum. In this retrospective analysis, circulating total sRAGE and endogenous secretory RAGE (esRAGE) were quantified via ELISA, and cleaved RAGE (cRAGE) was calculated in 274 individuals stratified by glucose tolerance status (GTS) and obesity. Group differences were probed by ANOVA, and multivariate ordinal logistic regression was used to test the association between sRAGE isoform concentrations and the proportional odds of developing diabetes, vs. normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). When stratified by GTS, total sRAGE, cRAGE, and esRAGE were all lower with IGT and T2DM, while the ratio of cRAGE to esRAGE (cRAGE:esRAGE) was only lower ( P < 0.01) with T2DM compared with NGT. When stratified by GTS and obesity, cRAGE:esRAGE was higher with obesity and lower with IGT ( P < 0.0001) compared with lean, NGT. In ordinal logistic regression models, greater total sRAGE (odds ratio, 0.91; P < 0.01) and cRAGE (odds ratio, 0.84; P < 0.01) were associated with lower proportional odds of developing T2DM. Reduced values of sRAGE isoforms observed with both obesity and IGT are independently associated with greater proportional odds of developing T2DM. The mechanisms by which each respective isoform contributes to obesity and insulin resistance may reveal novel treatment strategies for diabetes., (Copyright © 2017 the American Physiological Society.)

Our research is aimed at gaining a better understanding of the electronic properties of organisms in order to engineer novel bioelectronic systems and computing architectures based on biology. This specific paper focuses on harnessing the unicellular slime mold Physarum polycephalum to develop bio-memristors (or biological memristors) and bio-computing devices. The memristor is a resistor that possesses memory. It is the 4th fundamental passive circuit element (the other three are the resistor, the capacitor, and the inductor), which is paving the way for the design of new kinds of computing systems; e.g., computers that might relinquish the distinction between storage and a central processing unit. When applied with an AC voltage, the current vs. voltage characteristic of a memristor is a pinched hysteresis loop. It has been shown that P. polycephalum produces pinched hysteresis loops under AC voltages and displays adaptive behavior that is comparable with the functioning of a memristor. This paper presents the method that we developed for implementing bio-memristors with P. polycephalum and introduces the development of a receptacle to culture the organism, which facilitates its deployment as an electronic circuit component. Our method has proven to decrease growth time, increase component lifespan, and standardize electrical observations.

Beat perception is fundamental to how we experience music, and yet the mechanism behind this spontaneous building of the internal beat representation is largely unknown. Existing findings support links between the tempo (speed) of the beat and enhancement of electroencephalogram (EEG) activity at tempo-related frequencies, but there are no studies looking at how tempo may affect the underlying long-range interactions between EEG activity at different electrodes. The present study investigates these long-range interactions using EEG activity recorded from 21 volunteers listening to music stimuli played at 4 different tempi (50, 100, 150 and 200 beats per minute). The music stimuli consisted of piano excerpts designed to convey the emotion of "peacefulness". Noise stimuli with an identical acoustic content to the music excerpts were also presented for comparison purposes. The brain activity interactions were characterized with the imaginary part of coherence (iCOH) in the frequency range 1.5-18 Hz (δ, θ, α and lower β) between all pairs of EEG electrodes for the four tempi and the music/noise conditions, as well as a baseline resting state (RS) condition obtained at the start of the experimental task. Our findings can be summarized as follows: (a) there was an ongoing long-range interaction in the RS engaging fronto-posterior areas; (b) this interaction was maintained in both music and noise, but its strength and directionality were modulated as a result of acoustic stimulation; (c) the topological patterns of iCOH were similar for music, noise and RS, however statistically significant differences in strength and direction of iCOH were identified; and (d) tempo had an effect on the direction and strength of motor-auditory interactions. Our findings are in line with existing literature and illustrate a part of the mechanism by which musical stimuli with different tempi can entrain changes in cortical activity.

Insulin resistance promotes vascular endothelial dysfunction and subsequent development of cardiovascular disease. Previously we found that skeletal muscle arteriolar flow-induced dilation (FID) was reduced following a hyperinsulinemic clamp in healthy adults. Therefore, we hypothesized that hyperinsulinemia, a hallmark of insulin resistance, contributes to microvascular endothelial cell dysfunction via inducing oxidative stress that is mediated by NADPH oxidase (Nox) system. We examined the effect of insulin, at levels that are comparable with human hyperinsulinemia on 1) FID of isolated arterioles from human skeletal muscle tissue in the presence and absence of Nox inhibitors and 2) human adipose microvascular endothelial cell (HAMECs) expression of nitric oxide (NO), endothelial NO synthase (eNOS), and Nox-mediated oxidative stress. In six lean healthy participants (mean age 25.5±1.6 y, BMI 21.8±0.9), reactive oxygen species (ROS) were increased while NO and arteriolar FID were reduced following 60min of ex vivo insulin incubation. These changes were reversed after co-incubation with the Nox isoform 2 (Nox2) inhibitor, VAS2870. In HAMECs, insulin-induced time-dependent increases in Nox2 expression and P47 phox phosphorylation were echoed by elevations of superoxide production. In contrast, phosphorylation of eNOS and expression of superoxide dismutase (SOD2 and SOD3) isoforms showed a biphasic response with an increased expression at earlier time points followed by a steep reduction phase. Insulin induced eNOS uncoupling that was synchronized with a drop of NO and a surge of ROS production. These effects were reversed by Tempol (SOD mimetic), Tetrahydrobiopterin (BH4; eNOS cofactor), and VAS2870. Finally, insulin induced nitrotyrosine formation which was reversed by inhibiting NO or superoxide generation. In conclusions, hyperinsulinemia may reduce FID via inducing Nox2-mediated superoxide production in microvascular endothelial cells which reduce the availability of NO and enhances peroxynitrite formation. Therefore, the Nox2 pathway should be considered as a target for the prevention of oxidative stress-associated endothelial dysfunction during hyperinsulinemia., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Previous studies have shown the anti-inflammatory and antioxidant properties of phenolic compounds of virgin olive oil (VOO). However, the effect of bioavailable phenolic compounds on the vascular endothelium is unknown. We aimed to evaluate the effect of the consumption of virgin olive oil rich in phenolic compounds on the vascular endothelium., Methods: We treated HUVEC with human serum obtained in fasting state and after the intake of a breakfast prepared with VOO with a high or low content of phenolic compounds., Results: Treatment of HUVEC with serum obtained 2 h after the intake of the high-phenol VOO-based breakfast decreased p65 and MCP-1 gene expression (p < 0.001 and p = 0.002, respectively) and increased MT-CYB, SDHA and SOD1 gene expression (p = 0.004, p = 0.012 and p = 0.001, respectively), as compared with the treatment of HUVEC with the serum obtained 2 h after the intake of the low-phenol VOO-based breakfast. The treatment with serum obtained 4 h after the intake of the high-phenol VOO-based breakfast decreased MCP-1 and CAT gene expression (p < 0.001 and p = 0.003, respectively) and increased MT-CYB gene expression (p < 0.001), as compared to the treatment with serum obtained 4 h after the intake of the low-phenol VOO-based breakfast., Conclusion: Our results suggest that the consumption of virgin olive oil rich in phenolic compounds may reduce the risk of atherosclerosis development by decreasing inflammation and improving the antioxidant profile in the vascular endothelium.

Objective: To evaluate the fatty infiltration and atrophy of the supraespinatus in the pre- and postoperative of a rotator cuff lesion (RCL), by MRI., Methods: Ten patients with full-thickness rotator cuff tears who had undergone surgical arthroscopic rotator cuff repair between September and December 2011 were included. This is a prospective study, with analysis and comparison of fatty infiltration and atrophy of the supraespinatus. The occupation ratio was measured using the magic selection tool in Adobe Photoshop CS3((r)) on T1 oblique sagittal Y-view MRI. Through Photoshop, the proportion occupied by the muscle belly regarding its fossae was calculated., Results: There was a statistically significant increase in the muscle ratio (p=0.013) comparing images pre and postoperative, analyzed by the Wilcoxon T test., Conclusion: The proportion of the supraspinal muscle above the pit increases in the immediate postoperative period, probably due to the traction exerted on the tendon at the time of repair. Level of Evidence II, Cohort Study.

Extracellular cAMP functions as a primary ligand for cell surface cAMP receptors throughout Dictyostelium discoideum development, controlling chemotaxis and morphogenesis. The developmental consequences of cAMP signaling and the metabolism of cAMP have been studied in great detail, but it has been unclear how cells export cAMP across the plasma membrane. Here we show pharmacologically and genetically that ABC transporters mediate cAMP export. Using an evolutionary-developmental biology approach, we identified several candidate abc genes and characterized one of them, abcB3, in more detail. Genetic and biochemical evidence suggest that AbcB3 is a component of the cAMP export mechanism in D. discoideum development., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We investigated the molecular mechanisms by which phenolic compounds (phenols) in virgin olive oil reduce the postprandial inflammatory response with the aim of identifying the transcription factor involved and the downstream effects. Olive oil-based breakfasts prepared with virgin olive oil (VOO) with high (398 ppm), intermediate (149 ppm) and low (70 ppm) phenol content were administered to 49 metabolic syndrome patients following a randomized crossover design. The consumption of a high-phenol VOO-based breakfast limited the increase of lipopolysaccharide plasma levels, TLR4, and SOCS3 proteins (p<0.001, p=0.041 and p=0.008, respectively), the activation of NF-κB (p=0.016) and the IL6 (p=0.007 and p=0.048, low and intermediate oil, respectively), IL1B (p=0.002, intermediate oil), and CXCL1 (p=0.001) postprandial gene expression, in peripheral blood mononuclear cells, as compared with the consumption of a breakfast prepared with the same oil but with low or intermediate phenol content. Virgin olive oil phenolic compounds reduce the postprandial inflammatory response in association with postprandial plasma lipopolysaccharide levels., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We have investigated whether dietary fat modifies the postprandial oxidative stress in adipose tissue of elderly people. Twenty participants received three diets for 4 weeks each: SFA-rich diet, Mediterranean (Med) diet enriched in MUFA with virgin olive oil, and a low-fat, high-carbohydrate diet enriched in n-3 PUFA (α-linolenic acid from plant origin) (CHO-PUFA diet). After 12 h of fasting, volunteers received a breakfast reflecting the fatty acid composition of the diet ingested in the preceding dietary period. Med diet induced higher postprandial SOD2 and TrxR mRNA levels, and CHO-PUFA diet induced higher GPx1 and TrxR mRNA levels compared with SFA-rich diet. Med and CHO-PUFA breakfasts induced a postprandial increase in plasma reduced glutathione (GSH), and a greater postprandial GSH/oxidized glutathione ratio compared to the SFA-rich diet. Our study suggests that the consumption of Med and CHO-PUFA diets may reduce postprandial oxidative stress compared to an SFA-rich diet, which may be due to higher antioxidant enzymes gene expression in adipose tissue.

ATP-binding cassette (ABC) transporters can translocate a broad spectrum of molecules across the cell membrane including physiological cargo and toxins. ABC transporters are known for the role they play in resistance towards anticancer agents in chemotherapy of cancer patients. There are 68 ABC transporters annotated in the genome of the social amoeba Dictyostelium discoideum. We have characterized more than half of these ABC transporters through a systematic study of mutations in their genes. We have analyzed morphological and transcriptional phenotypes for these mutants during growth and development and found that most of the mutants exhibited rather subtle phenotypes. A few of the genes may share physiological functions, as reflected in their transcriptional phenotypes. Since most of the abc-transporter mutants showed subtle morphological phenotypes, we utilized these transcriptional phenotypes to identify genes that are important for development by looking for transcripts whose abundance was unperturbed in most of the mutants. We found a set of 668 genes that includes many validated D. discoideum developmental genes. We have also found that abcG6 and abcG18 may have potential roles in intercellular signaling during terminal differentiation of spores and stalks.

Background: Amoebae and bacteria interact within predator-prey and host-pathogen relationships, but the general response of amoeba to bacteria is not well understood. The amoeba Dictyostelium discoideum feeds on, and is colonized by, diverse bacterial species, including Gram-positive [Gram(+)] and Gram-negative [Gram(-)] bacteria, two major groups of bacteria that differ in structure and macromolecular composition., Results: Transcriptional profiling of D. discoideum revealed sets of genes whose expression is enriched in amoebae interacting with different species of bacteria, including sets that appear specific to amoebae interacting with Gram(+) or with Gram(-) bacteria. In a genetic screen utilizing the growth of mutant amoebae on a variety of bacteria as a phenotypic readout, we identified amoebal genes that are only required for growth on Gram(+) bacteria, including one that encodes the cell-surface protein gp130, as well as several genes that are only required for growth on Gram(-) bacteria, including one that encodes a putative lysozyme, AlyL. These genes are required for parts of the transcriptional response of wild-type amoebae, and this allowed their classification into potential response pathways., Conclusions: We have defined genes that are critical for amoebal survival during feeding on Gram(+), or Gram(-), bacteria that we propose form part of a regulatory network that allows D. discoideum to elicit specific cellular responses to different species of bacteria in order to optimize survival., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Transcriptional profiling methods have been utilized in the analysis of various biological processes in Dictyostelium. Recent advances in high-throughput sequencing have increased the resolution and the dynamic range of transcriptional profiling. Here we describe the utility of RNA sequencing with the Illumina technology for production of transcriptional profiles. We also describe methods for data mapping and storage as well as common and specialized tools for data analysis, both online and offline.

Objective: To compare the chronological age and bone age among cerebral palsy patients in the outpatient clinic and its correlation with the type of neurological involvement, gender and functional status., Methods: 401 patients with spastic cerebral palsy, and ages ranging from three months to 20 years old, submitted to radiological examination for bone age and analyzed by two independent observers according Greulich & Pyle., Results: In the topographic distribution, there was a significant delay (p<0.005) in tetraparetic (17.7 months), hemiparetic (10.1 months), and diparetic patients (7.9 months). In the hemiparetic group, the mean bone age in the affected side was 96.88 months and the uncompromised side was 101.13 months (p<0.005). Regarding functional status, the ambulatory group showed a delay of 18.73 months in bone age (p<0.005). Comparing bone age between genders, it was observed a greater delay in males (13.59 months) than in females (9.63 months), but not statistically significant (p = 0.54)., Conclusion: There is a delay in bone age compared to chronological age influenced by the topography of spasticity, functional level and gender in patients with cerebral palsy. Level of Evidence IV, Case Series.

Most HIV-1 broadly neutralizing antibodies are directed against the gp120 subunit of the env surface protein. Native env consists of a trimer of gp120-gp41 heterodimers, and in contrast to monomeric gp120, preferentially binds CD4 binding site (CD4bs)-directed neutralizing antibodies over non-neutralizing ones. Some cryo-electron tomography studies have suggested that the V1V2 loop regions of gp120 are located close to the trimer interface. We have therefore designed cyclically permuted variants of gp120 with and without the h-CMP and SUMO2a trimerization domains inserted into the V1V2 loop. h-CMP-V1cyc is one such variant in which residues 153 and 142 are the N- and C-terminal residues, respectively, of cyclically permuted gp120 and h-CMP is fused to the N-terminus. This molecule forms a trimer under native conditions and binds CD4 and the neutralizing CD4bs antibodies b12 with significantly higher affinity than wild-type gp120. It binds non-neutralizing CD4bs antibody F105 with lower affinity than gp120. A similar derivative, h-CMP-V1cyc1, bound the V1V2 loop-directed broadly neutralizing antibodies PG9 and PG16 with ∼20-fold higher affinity than wild-type JRCSF gp120. These cyclic permutants of gp120 are properly folded and are potential immunogens. The data also support env models in which the V1V2 loops are proximal to the trimer interface.

Background: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy with indolent clinical course and good prognosis. Brain metastases are extremely rare and the average survival time after diagnosis has been reported to be around 12 months., Summary: We here report a 69-year-old patient who was admitted to the emergency room in January 2000 with progressive dizziness, headache, and vomiting. Five years before admission the patient underwent partial thyroidectomy for goiter. On admission, a diagnostic evaluation that included brain magnetic resonance imaging showed multiple brain lesions, and a stereotactic biopsy demonstrated a metastatic carcinoma from primary PTC, with the neoplastic cells staining for thyroglobulin. Total thyroidectomy was then performed, which showed colloid goiter and a PTC metastasis on a cervical lymph node. The patient received 200 mCi of radioactive iodine ((131)I) with suppressive therapy with l-thyroxine thereafter. Subsequently, serial whole-body scanning and magnetic resonance imaging showed multiple brain metastases and the patient received further (131)I treatment, with a total dose of 1.2 Ci in a 10-year span. She also underwent partial surgical resection of brain metastases because complete resection was not feasible. Thereafter, the patient was subjected to whole-brain body radiotherapy with a dose of 44 Gy, followed by two brain gamma knife radiosurgeries (15 Gy each). To date, biochemical tests are within the normal range and the patient remains asymptomatic., Conclusions: To our knowledge, this is the first report of a 10-year-survival case of brain metastases from PTC, despite this being a bad prognostic factor. A combined approach of surgical excision, (131)I, whole-brain radiotherapy, and gamma knife radiosurgery was successful to treat metastases derived from primary tumor.