Peripherally-derived LGI1-reactive monoclonal antibodies cause epileptic seizures in vivo.

One striking clinical hallmark in patients with autoantibodies to leucine-rich glioma inactivated 1 (LGI1) is the very frequent focal seizure semiologies, including faciobrachial dystonic seizures (FBDS), in addition to the amnesia. Polyclonal serum IgGs have successfully modelled the cognitive changes in vivo but not seizures. Hence, it remains unclear whether LGI1-autoantibodies are sufficient to cause seizures. We tested this with the molecularly precise monoclonal antibodies directed against LGI1 (LGI1-mAbs), derived from patient circulating B cells. These were directed towards both major domains of LGI1, LRR and EPTP and infused intracerebroventricularly over 7 days into juvenile male Wistar rats using osmotic pumps. Continuous wireless EEG was recorded from a depth electrode placed in hippocampal CA3 plus behavioural tests for memory and hyperexcitability were performed. Following infusion completion (Day 9), post-mortem brain slices were studied for antibody binding and effects on Kv1.1. The LGI1-mAbs bound most strongly in the hippocampal CA3 region and induced a significant reduction in Kv1.1 cluster number in this subfield. By comparison to control-Ab injected rats video-EEG analysis over 9 days revealed convulsive and non-convulsive seizure activity in rats infused with LGI1-mAbs, with a significant number of ictal events. Memory was not impaired in the novel object recognition test. Peripherally-derived human LGI1-mAbs infused into rodent CSF provide strong evidence of direct in vivo epileptogenesis with molecular correlations. These findings fulfill criteria for LGI1-antibodies in seizure causation.

Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity.

Cannabidiol (CBD), a non-euphoric component of cannabis, reduces seizures in multiple forms of pediatric epilepsies, but the mechanism(s) of anti-seizure action remain unclear. In one leading model, CBD acts at glutamatergic axon terminals, blocking the pro-excitatory actions of an endogenous membrane phospholipid, lysophosphatidylinositol (LPI), at the G-protein-coupled receptor GPR55. However, the impact of LPI-GPR55 signaling at inhibitory synapses and in epileptogenesis remains underexplored. We found that LPI transiently increased hippocampal CA3-CA1 excitatory presynaptic release probability and evoked synaptic strength in WT mice, while attenuating inhibitory postsynaptic strength by decreasing GABAARγ2 and gephyrin puncta. LPI effects at excitatory and inhibitory synapses were eliminated by CBD pre-treatment and absent after GPR55 deletion. Acute pentylenetrazole-induced seizures elevated GPR55 and LPI levels, and chronic lithium-pilocarpine-induced epileptogenesis potentiated LPI's pro-excitatory effects. We propose that CBD exerts potential anti-seizure effects by blocking LPI's synaptic effects and dampening hyperexcitability.

Benchmarking framework for machine learning classification from fNIRS data.

Background: While efforts to establish best practices with functional near infrared spectroscopy (fNIRS) signal processing have been published, there are still no community standards for applying machine learning to fNIRS data. Moreover, the lack of open source benchmarks and standard expectations for reporting means that published works often claim high generalisation capabilities, but with poor practices or missing details in the paper. These issues make it hard to evaluate the performance of models when it comes to choosing them for brain-computer interfaces. Methods: We present an open-source benchmarking framework, BenchNIRS, to establish a best practice machine learning methodology to evaluate models applied to fNIRS data, using five open access datasets for brain-computer interface (BCI) applications. The BenchNIRS framework, using a robust methodology with nested cross-validation, enables researchers to optimise models and evaluate them without bias. The framework also enables us to produce useful metrics and figures to detail the performance of new models for comparison. To demonstrate the utility of the framework, we present a benchmarking of six baseline models [linear discriminant analysis (LDA), support-vector machine (SVM), k-nearest neighbours (kNN), artificial neural network (ANN), convolutional neural network (CNN), and long short-term memory (LSTM)] on the five datasets and investigate the influence of different factors on the classification performance, including: number of training examples and size of the time window of each fNIRS sample used for classification. We also present results with a sliding window as opposed to simple classification of epochs, and with a personalised approach (within subject data classification) as opposed to a generalised approach (unseen subject data classification). Results and discussion: Results show that the performance is typically lower than the scores often reported in literature, and without great differences between models, highlighting that predicting unseen data remains a difficult task. Our benchmarking framework provides future authors, who are achieving significant high classification scores, with a tool to demonstrate the advances in a comparable way. To complement our framework, we contribute a set of recommendations for methodology decisions and writing papers, when applying machine learning to fNIRS data.

Training, Pharmacological Ergogenic Aids, Dehydration, and Nutrition Strategies during a Peak Week in Competitive Brazilian Bodybuilders: An Observational Cross-Sectional Study in a Non-World Anti-Doping Agency Competitive Environment.

BACKGROUND: this observational and cross-sectional study aimed to describe training, pharmacological ergogenic aids, dehydration, and nutrition strategies during a peak week in competitive bodybuilders and monitor changes that occurred across this period. METHODS: Ten amateur bodybuilders were followed during a peak week phase and one day post-contest. Training, diet, dehydration protocol, anabolic steroid use, and nonsteroidal agents were recorded, prescribed, and supervised by the same coach in charge. Body composition, resting metabolic rate, and circumferences were assessed by the research team. RESULTS: Overall, during the peak week phase, the use of anabolic steroids, diuretics, and other pharmacological aids was high among athletes, and the dose and frequency were similar between competitors. Despite the use of supraphysiological doses of drugs, bodybuilders displayed a statistical reduction of lean mass markers, resting metabolic rate, and fat mass markers, possibly influenced by the performance of high volumes of aerobic exercise combined with dietary energy restriction. CONCLUSIONS: The main findings of this study display that the coach in charge of Brazilian bodybuilders applied the same anabolic steroid, diuretic, and other pharmacological protocols for all competitors. Moreover, the protocols employed by bodybuilders did not fully attenuate the loss of lean mass during the peak week period.

Perceptions of Cognitive Training Games and Assessment Technologies for Dementia: Acceptability Study With Patient and Public Involvement Workshops.

BACKGROUND: Cognitive training and assessment technologies offer the promise of dementia risk reduction and a more timely diagnosis of dementia, respectively. Cognitive training games may help reduce the lifetime risk of dementia by helping to build cognitive reserve, whereas cognitive assessment technologies offer the opportunity for a more convenient approach to early detection or screening. OBJECTIVE: This study aims to elicit perspectives of potential end users on factors related to the acceptability of cognitive training games and assessment technologies, including their opinions on the meaningfulness of measurement of cognition, barriers to and facilitators of adoption, motivations to use games, and interrelationships with existing health care infrastructure. METHODS: Four linked workshops were conducted with the same group, each focusing on a specific topic: meaningful improvement, learning and motivation, trust in digital diagnosis, and barriers to technology adoption. Participants in the workshops included local involvement team members acting as facilitators and those recruited via Join Dementia Research through a purposive selection and volunteer sampling method. Group activities were recorded, and transcripts were analyzed using thematic analysis with a combination of a priori and data-driven themes. Using a mixed methods approach, we investigated the relationships between the categories of the Capability, Opportunity, and Motivation-Behavior change model along with data-driven themes by measuring the φ coefficient between coded excerpts and ensuring the reliability of our coding scheme by using independent reviewers and assessing interrater reliability. Finally, we explored these themes and their relationships to address our research objectives. RESULTS: In addition to discussions around the capability, motivation, and opportunity categories, several important themes emerged during the workshops: family and friends, cognition and mood, work and hobbies, and technology. Group participants mentioned the importance of functional and objective measures of cognitive change, the social aspect of activities as a motivating factor, and the opportunities and potential shortcomings of digital health care provision. Our quantitative results indicated at least moderate agreement on all but one of the coding schemes and good independence of our coding categories. Positive and statistically significant φ coefficients were observed between several coding themes between categories, including a relatively strong positive φ coefficient between capability and cognition (0.468; P<.001). CONCLUSIONS: The implications for researchers and technology developers include assessing how cognitive training and screening pathways would integrate into existing health care systems; however, further work needs to be undertaken to address barriers to adoption and the potential real-world impact of cognitive training and screening technologies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1007/978-3-030-49065-2_4.

Multimodal electrophysiological analyses reveal that reduced synaptic excitatory neurotransmission underlies seizures in a model of NMDAR antibody-mediated encephalitis.

Seizures are a prominent feature in N-Methyl-D-Aspartate receptor antibody (NMDAR antibody) encephalitis, a distinct neuro-immunological disorder in which specific human autoantibodies bind and crosslink the surface of NMDAR proteins thereby causing internalization and a state of NMDAR hypofunction. To further understand ictogenesis in this disorder, and to test a potential treatment compound, we developed an NMDAR antibody mediated rat seizure model that displays spontaneous epileptiform activity in vivo and in vitro. Using a combination of electrophysiological and dynamic causal modelling techniques we show that, contrary to expectation, reduction of synaptic excitatory, but not inhibitory, neurotransmission underlies the ictal events through alterations in the dynamical behaviour of microcircuits in brain tissue. Moreover, in vitro application of a neurosteroid, pregnenolone sulphate, that upregulates NMDARs, reduced established ictal activity. This proof-of-concept study highlights the complexity of circuit disturbances that may lead to seizures and the potential use of receptor-specific treatments in antibody-mediated seizures and epilepsy.

Encephalitis patient-derived monoclonal GABAA receptor antibodies cause epileptic seizures.

Autoantibodies targeting the GABAA receptor (GABAAR) hallmark an autoimmune encephalitis presenting with frequent seizures and psychomotor abnormalities. Their pathogenic role is still not well-defined, given the common overlap with further autoantibodies and the lack of patient-derived mAbs. Five GABAAR mAbs from cerebrospinal fluid cells bound to various epitopes involving the α1 and γ2 receptor subunits, with variable binding strength and partial competition. mAbs selectively reduced GABAergic currents in neuronal cultures without causing receptor internalization. Cerebroventricular infusion of GABAAR mAbs and Fab fragments into rodents induced a severe phenotype with seizures and increased mortality, reminiscent of encephalitis patients' symptoms. Our results demonstrate direct pathogenicity of autoantibodies on GABAARs independent of Fc-mediated effector functions and provide an animal model for GABAAR encephalitis. They further provide the scientific rationale for clinical treatments using antibody depletion and can serve as tools for the development of antibody-selective immunotherapies.

Carbohydrate refeed does not modify GVT-performance following energy restriction in bodybuilders.

Bodybuilding is a sport in which competitors' physiques are judged on their muscular size, symmetry, and leanness, as displayed in a number of different poses. In the pre-competitive period, bodybuilders attempt to reduce body fat stores as much as possible while maintaining fat-free mass (FFM). This is achieved via a sustained negative energy balance, generally induced by a combination of decreased energy intake and increased energy expenditure. This study aimed to assess the ability of bodybuilders to resist fatigue during resistance exercise based German Volume Training (GVT), as well as the affective response after carbohydrate refeed following four weeks of moderate or severe energy restriction. Eleven male bodybuilders (28.4 ± 2.3 years old) with experience in competitions were randomized into two groups: Moderate Energy Restriction (MER; n = 6) or Severe Energy Restriction (SER; n = 5). On the 2nd day (during energy restriction) and 7th day (during refeed) of the fourth week, both groups completed two leg press protocols involving the GVT method. After the first and last workout protocol subjects were assessed for muscle soreness using the visual-analog scale (VAS), rating of perceived exertion (RPE), affective response, lactate, and creatine kinase. Anthropometric analysis indicated that a reduction of 3.7 and 3.2% in body mass corresponded to a loss of 16.0 and 17.6% of fat mass for the MER and SER groups, respectively, with both groups maintaining FFM. Blood CK and VAS values were reduced only in SER. Our results suggest that a carbohydrate refeed may help to attenuate the perception of muscle soreness and maintain exercise performance, especially when severe energy restriction is combined with an intense training protocol such as GVT.

The impact of quarantine on body image and lifestyle habits in resistance training practitioners / Impacto da quarentena sobre a percepção da imagem corporal e hábitos dos praticantes de musculação / Impacto de la cuarentena sobre la percepción de la imagen corporaly hábitos de los practicantes de musculación

ABSTRACT Introduction In order to curb the abrupt advance of "Coronavirus Disease 2019" (COVID-19) and prevent the collapse of the health system, authorities around the world have opted for social distancing strategies that include closing gyms, among other measures. Objectives This study analyzed the effect of social distancing on resistance training practitioners' quality of life and perception of body image in silhouette. Methods The volunteers were contacted through social media; data were collected between April 13 and 19, 2020, through a structured questionnaire, comprised of an Informed Consent Form, four questions about COVID-19 and restrictive measures; and twenty-nine questions designed to characterize the individuals' habits; as well as the Short Form Health Survey 36 questionnaire. All the questionnaires were applied over the Internet, using Google Forms®. After collection, the data were tabulated and interpreted using the software program AppleNumbers®, and subsequently presented as mean, standard deviation and percentiles. Results The results revealed changes in perception of body image and decreased frequency and satisfaction with training. There was also an increase in sedentary behavior, food intake, and amount of sleep; and a reduction in parameters related to health and quality of life. Conclusions The strategy of social distancing, adopted to curb the progress of COVID-19, has harmful consequences for resistance training practitioners, such as increased calorie intake, stress and anxiety, as well as possible psychological effects. These consequences, in turn, lead to changes in self-perception of body image and in the quality of training. Level of Evidence III; Cross-sectional study of non-consecutive patients; without uniformly applied reference standard.

RESUMO Introdução Com o intuito de conter o avanço abrupto da "Coronavirus Disease 2019" (COVID-19) e evitar o colapso do sistema de saúde, autoridades mundiais optaram por estratégias de distanciamento social que compreendem o fechamento de academias, entre outras providências. Objetivos Este estudo analisou o efeito do distanciamento social sobre a qualidade de vida e a percepção da imagem corporal em silhueta de praticantes de treinamento de força. Métodos O contato com os voluntários foi realizado pelas mídias sociais e os dados foram coletados entre 13 e 19 de abril de 2020, por meio de um questionário estruturado, composto pelo Termo de consentimento livre e esclarecido, quatro questões sobre COVID-19 e medidas restritivas, vinte e nove questões destinadas à caracterização dos hábitos dos indivíduos, além do questionário Short Form Health Survey 36. Todos os questionários foram realizados no Google Forms®, com o auxílio da Internet. Depois da coleta, os dados foram tabulados e interpretados com o software AppleNumbers® e apresentados como média, desvio padrão e percentis. Resultados Os resultados revelaram alterações na percepção da imagem corporal, diminuição do volume e da satisfação com o treino. Ademais, foi observado um aumento do comportamento sedentário, da ingestão de alimentos e da quantidade de sono, além da redução dos parâmetros relacionados com a saúde e a qualidade de vida. Conclusões A estratégia de distanciamento social adotada para conter o avanço da COVID-19 revela consequências deletérias para os praticantes de treinamento de força, a saber, aumento da ingestão calórica, do estresse, da ansiedade, além de possíveis acometimentos de ordem psicológica. Essas consequências, por sua vez, promoveram alterações na percepção da autoimagem e na qualidade do treinamento. Nível de Evidência III; Estudo transversal de pacientes não consecutivos; sem padrão de referência aplicado uniformemente .

RESUMEN Introducción Con la intención de contener el avance abrupto de la "Coronavirus Disease 2019" (COVID-19) y evitar el colapso del sistema de salud, autoridades mundiales optaron por estrategias de distanciamiento social que comprenden el cierre de gimnasios, entre otras medidas. Objetivos Este estudio analizó el efecto del distanciamiento social sobre la calidad de vida y la percepción de la imagen corporal en silueta de practicantes de entrenamiento de fuerza. Métodos El contacto con los voluntarios fue realizado a través de las redes sociales y los datos fueron colectados entre el 13 y el 19 de abril de 2020, por medio de un cuestionario estructurado, compuesto por el Término de consentimiento libre y esclarecido, cuatro cuestiones sobre COVID-19 y medidas restrictivas, veintinueve cuestiones destinadas a la caracterización de los hábitos de los individuos, además del cuestionario Short Form Health Survey 36. Todos los cuestionarios fueron realizados en Google Forms®, con la ayuda de Internet. Después de la colecta, los datos fueron tabulados e interpretados con el software AppleNumbers® y presentados como promedio, desviación estándar y percentiles. Resultados Los resultados revelaron alteraciones en la percepción de la imagen corporal, disminución del volumen y de la satisfacción con el entrenamiento. Además, fue observado un aumento del comportamiento sedentario, de la ingestión de alimentos y de la cantidad de sueño; además de la reducción de los parámetros relacionados con la salud y la calidad de vida. Conclusiones La estrategia de distanciamiento social adoptada para contener el avance de la COVID-19 revela consecuencias deletéreas para los practicantes de entrenamiento de fuerza, tales como aumento de la ingestión calórica, estrés, ansiedad, además de posibles acometimientos de orden psicológico. Esas consecuencias, a su vez, promovieron alteraciones en la percepción de la autoimagen y en la calidad del entrenamiento. Nivel de evidencia III; Estudio transversal de pacientes no consecutivos; sin patrón de referencia aplicado uniformemente.

Abolishing spontaneous epileptiform activity in human brain tissue through AMPA receptor inhibition.

OBJECTIVE: The amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is increasingly recognized as a therapeutic target in drug-refractory pediatric epilepsy. Perampanel (PER) is a non-competitive AMPAR antagonist, and pre-clinical studies have shown the AMPAR-mediated anticonvulsant effects of decanoic acid (DEC), a major medium-chain fatty acid provided in the medium-chain triglyceride ketogenic diet. METHODS: Using brain tissue resected from children with intractable epilepsy, we recorded the effects of PER and DEC in vitro. RESULTS: We found resected pediatric epilepsy tissue exhibits spontaneous epileptic activity in vitro, and showed that DEC and PER inhibit this epileptiform activity in local field potential recordings as well as excitatory synaptic transmission. INTERPRETATION: This study confirms AMPAR antagonists inhibit epileptiform discharges in brain tissue resected in a wide range of pediatric epilepsies.

Oxidative stress, inflammation, psychological status, and severity of respiratory infections are negatively affected during the pre-contest period in amateur bodybuilders.

We examined whether off-season (OffS) and pre-contest (PreC) periods affect blood oxidative stress, inflammatory, immunological, and psychological markers in 20 bodybuilders. The athletes recorded their food intake (3-day record), physical activities, mood states (Profile of Mood States, POMS), recovery-stress (Recovery-Stress Questionnaire for Athletes, RESTQ-Sport), and upper respiratory symptoms (Wisconsin Upper Respiratory Symptom Survey, WURSS-21), and blood was obtained for biochemical analysis. Almost all athletes were in positive energy balance during OffS, while bodybuilders presented markedly restricted energy intake (∼45%) leading to loss of weight (-9%) and fat mass (-45%) with preservation of fat-free mass in PreC. Protein intake was high during both periods, while lipid and carbohydrate intakes were reduced ∼50% in PreC. Almost all athletes consumed 100% of the Recommended Dietary Allowance (RDA) for micronutrients in OffS, while 45% and 75% of the athletes had intakes below the RDA for vitamins A and E in PreC. Oxidative damage to lipids (thiobarbituric acid reactive substances, TBARS), protein carbonyls, and the TBARS/total antioxidant capacity ratio increased in PreC (32%, 27%, 60%), as did plasma tumor necrosis factor α (4-fold) and WURSS-21 scores (25%). There were no significant changes in serum catalase, glutathione reductase, and superoxide dismutase activities nor in interleukin 1ß and immunoglobulins. In PreC, POMS showed negative changes in vigor (-20%), fatigue (23%), and total mood disturbance (35%), and RESTQ-Sport showed alterations for general and sport stress (34% and 50%, respectively) and sport recovery (-23%). Thus, PreC negatively affects nutrient intake, which may worsen oxidative stress, inflammation, psychological status, and the severity of respiratory infections in bodybuilders.

Comparison of the acute effects of traditional versus high velocity resistance training on metabolic, cardiovascular, and psychophysiological responses in elderly hypertensive women.

OBJECTIVES: The aim of the present study was to compare the acute effects of traditional resistance training (RT) versus high velocity RT (HVRT) on metabolic, cardiovascular, and psychophysiological responses in elderly hypertensive women. METHODS: Fifteen elderly women (mean age ± standard deviation, 67.1±6.9 years) classified as having hypertension stage 1 or 2 were randomly allocated to complete traditional RT or HVRT; 1 week later, subjects allocated to RT completed the HVRT session and vice-versa. Heart rate, blood pressure, affective response, perceived effort, and blood samples analyzing lactate, nitrate, nitrite, oxidative damage (thiobarbituric acid reactive substances [TBARS]), and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid equivalent antioxidant capacity (TEAC) collected before and after training sessions were assessed. Nutritional counseling was provided regarding nutrients that could affect cardiovascular and nitrate/nitrite analysis. RESULTS: Systolic blood pressure was not statistically different (p>0.05) between conditions at the beginning and during 30 minutes after sessions. Diastolic blood pressure, rate pressure product, and heart rate were not statistically different (p>0.05) between conditions at the beginning and during 45 minutes after sessions. Nitric oxide was significantly higher (p<0.0005) for HVRT compared to RT after 30 minutes of exercise. TBARS and TEAC were significantly higher (p<0.05) for HVRT compared with RT only immediately after exercise. There were no differences for psychophysiological variables between protocols. CONCLUSION: The acute cardiovascular and metabolic responses, including oxidative stress, are transient and within normal values. Taken together with the positive affective responses, both HVRT and RT with this intensity and volume seem to be safe for elderly hypertensive women under medication.

Resistance training-induced gains in muscle strength, body composition, and functional capacity are attenuated in elderly women with sarcopenic obesity.

OBJECTIVES: The purpose of this study was to compare the effects of resistance training (RT) on body composition, muscle strength, and functional capacity in elderly women with and without sarcopenic obesity (SO). METHODS: A total of 49 women (aged ≥60 years) were divided in two groups: without SO (non-SO, n=41) and with SO (n=8). Both groups performed a periodized RT program consisting of two weekly sessions for 16 weeks. All measures were assessed at baseline and postintervention, including anthropometry and body composition (dual-energy X-ray absorptiometry), muscle strength (one repetition maximum) for chest press and 45° leg press, and functional capacity (stand up, elbow flexion, timed "up and go"). RESULTS: After the intervention, only the non-SO group presented significant reductions in percentage body fat (-2.2%; P=0.006), waist circumference (-2.7%; P=0.01), waist-to-hip ratio (-2.3; P=0.02), and neck circumference (-1.8%; P=0.03) as compared with baseline. Muscle strength in the chest press and biceps curl increased in non-SO only (12.9% and 11.3%, respectively), while 45° leg press strength increased in non-SO (50.3%) and SO (40.5%) as compared with baseline. Performance in the chair stand up and timed "up and go" improved in non-SO only (21.4% and -8.4%, respectively), whereas elbow flexion performance increased in non-SO (23.8%) and SO (21.4%). Effect sizes for motor tests were of higher magnitude in the non-SO group, and in general, considered "moderate" compared to "trivial" in the SO group. CONCLUSION: Results suggest that adaptations induced by 16 weeks of RT are attenuated in elderly woman with SO, compromising improvements in adiposity indices and gains in muscle strength and functional capacity.

Aerobic exercise training rescues protein quality control disruption on white skeletal muscle induced by chronic kidney disease in rats.

We tested whether aerobic exercise training (AET) would modulate the skeletal muscle protein quality control (PQC) in a model of chronic kidney disease (CKD) in rats. Adult Wistar rats were evaluated in four groups: control (CS) or trained (CE), and 5/6 nephrectomy sedentary (5/6NxS) or trained (5/6NxE). Exercised rats were submitted to treadmill exercise (60 min., five times/wk for 2 months). We evaluated motor performance (tolerance to exercise on the treadmill and rotarod), cross-sectional area (CSA), gene and protein levels related to the unfolded protein response (UPR), protein synthesis/survive and apoptosis signalling, accumulated misfolded proteins, chymotrypsin-like proteasome activity (UPS activity), redox balance and heat-shock protein (HSP) levels in the tibialis anterior. 5/6NxS presented a trend towards to atrophy, with a reduction in motor performance, down-regulation of protein synthesis and up-regulation of apoptosis signalling; increases in UPS activity, misfolded proteins, GRP78, derlin, HSP27 and HSP70 protein levels, ATF4 and GRP78 genes; and increase in oxidative damage compared to CS group. In 5/6NxE, we observed a restoration in exercise tolerance, accumulated misfolded proteins, UPS activity, protein synthesis/apoptosis signalling, derlin, HSPs protein levels as well as increase in ATF4, GRP78 genes and ATF6α protein levels accompanied by a decrease in oxidative damage and increased catalase and glutathione peroxidase activities. The results suggest a disruption of PQC in white muscle fibres of CKD rats previous to the atrophy. AET can rescue this disruption for the UPR, prevent accumulated misfolded proteins and reduce oxidative damage, HSPs protein levels and exercise tolerance.

Maintenance of exercise training benefits is associated with adequate milk and dairy products intake in elderly hypertensive subjects following detraining.

OBJECTIVE: To investigate whether maintenance of exercise training benefits is associated with adequate milk and dairy products intake in hypertensive elderly subjects after detraining. METHODS: Twenty-eight elderly hypertensive patients with optimal clinical treatment underwent 16 weeks of multicomponent exercise training program followed by 6 weeks of detraining, and were classified according to milk and dairy products intake as low milk (<3 servings) and high milk (≥3 servings) groups. RESULTS: After exercise training, there was a significant reduction (p<0.001) in body weight, systolic, diastolic and mean blood pressure, an increase in lower and upper limb strength (chair-stand test and elbow flexor test) as well as in aerobic capacity (stationary gait test) and functional capacity (sit down, stand up, and move around the house) in both groups. However, in the Low Milk Intake Group significant changes were observed: body weight (+0.5%), systolic, diastolic and mean blood pressure (+0.9%,+1.4% and +1.1%, respectively), lower extremity strength (-7.0%), aerobic capacity (-3.9%) and functional capacity (+5.4) after detraining. These parameters showed no significant differences between post-detraining and post-training period in High Milk Intake Group. CONCLUSION: Maintenance of exercise training benefits related to pressure levels, lower extremity strength and aerobic capacity, is associated with adequate milk and dairy products intake in hypertensive elderly subjects following 6 weeks of detraining.

Maintenance of exercise training benefits is associated with adequate milk and dairy products intake in elderly hypertensive subjects following detraining / A preservação dos benefícios do treinamento físico está associada à ingestão adequada de leite e produtos lácteos em idosos hipertensos após destreino

ABSTRACT Objective To investigate whether maintenance of exercise training benefits is associated with adequate milk and dairy products intake in hypertensive elderly subjects after detraining. Methods Twenty-eight elderly hypertensive patients with optimal clinical treatment underwent 16 weeks of multicomponent exercise training program followed by 6 weeks of detraining, and were classified according to milk and dairy products intake as low milk (<3 servings) and high milk (≥3 servings) groups. Results After exercise training, there was a significant reduction (p<0.001) in body weight, systolic, diastolic and mean blood pressure, an increase in lower and upper limb strength (chair-stand test and elbow flexor test) as well as in aerobic capacity (stationary gait test) and functional capacity (sit down, stand up, and move around the house) in both groups. However, in the Low Milk Intake Group significant changes were observed: body weight (+0.5%), systolic, diastolic and mean blood pressure (+0.9%,+1.4% and +1.1%, respectively), lower extremity strength (-7.0%), aerobic capacity (-3.9%) and functional capacity (+5.4) after detraining. These parameters showed no significant differences between post-detraining and post-training period in High Milk Intake Group. Conclusion Maintenance of exercise training benefits related to pressure levels, lower extremity strength and aerobic capacity, is associated with adequate milk and dairy products intake in hypertensive elderly subjects following 6 weeks of detraining.

RESUMO Objetivo Investigar se a preservação dos benefícios do treinamento físico está associada à ingestão adequada de leite/produtos lácteos em idosos hipertensos após destreino. Métodos Vinte e oito idosos hipertensos em tratamento clínico otimizado submetidos a 16 semanas de treinamento físico multicomponente, seguidas por 6 semanas de destreino, foram classificados segundo a ingestão de leite e produtos lácteos como baixo consumo (<3 porções/dia) e alto consumo (≥3 porções/dia). Resultados Após o treinamento físico, houve redução significativa (p<0,001) em peso corporal, pressão arterial sistólica, diastólica e média, aumento na força de membros inferiores e superiores (testes sentar-levantar e flexão de cotovelos, respectivamente), capacidade aeróbica (teste da marcha estacionária) e capacidade funcional (sentar, levantar-se e mover-se pela casa) em ambos os grupos. Entretanto, no Grupo Baixo Consumo de Lácteos, observaram-se alterações significativas em peso corporal (+0,5%), pressão arterial sistólica, diastólica e média (+0,9%, +1,4% e +1,1%, respectivamente), força de membros inferiores (-7,0%), capacidade aeróbica (-3,9%) e capacidade funcional (+5,4) após o destreino. Estes parâmetros não apresentaram diferenças significativas entre o destreino e o período pós-treinamento no Grupo Alto Consumo de Lácteos. Conclusão A preservação dos benefícios do treinamento físico em relação a pressão arterial, força de membros inferiores e capacidade aeróbia esteve associada com ingestão adequada de leite e produtos lácteos em idosos hipertensos após 6 semanas de destreino.

Dexamethasone-induced cardiac deterioration is associated with both calcium handling abnormalities and calcineurin signaling pathway activation.

Dexamethasone is a potent and widely used anti-inflammatory and immunosuppressive drug. However, recent evidences suggest that dexamethasone cause pathologic cardiac remodeling, which later impairs cardiac function. The mechanism behind the cardiotoxic effect of dexamethasone is elusive. The present study aimed to verify if dexamethasone-induced cardiotoxicity would be associated with changes in the cardiac net balance of calcium handling protein and calcineurin signaling pathway activation. Wistar rats (~400 g) were treated with dexamethasone (35 µg/g) in drinking water for 15 days. After dexamethasone treatment, we analyzed cardiac function, cardiomyocyte diameter, cardiac fibrosis, and the expression of proteins involved in calcium handling and calcineurin signaling pathway. Dexamethasone-treated rats showed several cardiovascular abnormalities, including elevated blood pressure, diastolic dysfunction, cardiac fibrosis, and cardiomyocyte apoptosis. Regarding the expression of proteins involved in calcium handling, dexamethasone increased phosphorylation of phospholamban at threonine 17, reduced protein levels of Na+/Ca2+ exchanger, and had no effect on protein expression of Serca2a. Protein levels of NFAT and GATA-4 were increased in both cytoplasmic and nuclear faction. In addition, dexamethasone increased nuclear protein levels of calcineurin. Altogether our findings suggest that dexamethasone causes pathologic cardiac remodeling and diastolic dysfunction, which is associated with impaired calcium handling and calcineurin signaling pathway activation.

Resistance training minimizes catabolic effects induced by sleep deprivation in rats.

Sleep deprivation (SD) can induce muscle atrophy. We aimed to investigate the changes underpinning SD-induced muscle atrophy and the impact of this condition on rats that were previously submitted to resistance training (RT). Adult male Wistar EPM-1 rats were randomly allocated into 1 of 5 groups: control, sham, SD (for 96 h), RT, and RT+SD. The major outcomes of this study were muscle fiber cross-sectional area (CSA), anabolic and catabolic hormone profiles, and the abundance of select proteins involved in muscle protein synthesis and degradation pathways. SD resulted in muscle atrophy; however, when SD was combined with RT, the reduction in muscle fiber CSA was attenuated. The levels of IGF-1 and testosterone were reduced in SD animals, and the RT+SD group had higher levels of these hormones than the SD group. Corticosterone was increased in the SD group compared with the control group, and this increase was minimized in the RT+SD group. The increases in corticosterone concentrations paralleled changes in the abundance of ubiquitinated proteins and the autophagic proteins LC3 and p62/SQSTM1, suggesting that corticosterone may trigger these changes. SD induced weight loss, but this loss was minimized in the RT+SD group. We conclude that SD induced muscle atrophy, probably because of the increased corticosterone and catabolic signal. High-intensity RT performed before SD was beneficial in containing muscle loss induced by SD. It also minimized the catabolic signal and increased synthetic activity, thereby minimizing the body's weight loss.

Impact of leucine supplementation on exercise training induced anti-cardiac remodeling effect in heart failure mice.

Leucine supplementation potentiates the effects of aerobic exercise training (AET) on skeletal muscle; however, its potential effects associated with AET on cardiac muscle have not been clarified yet. We tested whether leucine supplementation would potentiate the anti-cardiac remodeling effect of AET in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α2A/α2CARKO). Mice were assigned to five groups: wild type mice treated with placebo and sedentary (WT, n = 11), α2A/α2CARKO treated with placebo and sedentary (KO, n = 9), α2A/α2CARKO treated with leucine and sedentary (KOL, n = 11), α2A/α2CARKO treated with placebo and AET (KOT, n = 12) or α2A/α2CARKO treated with leucine and AET (KOLT, n = 12). AET consisted of four weeks on a treadmill with 60 min sessions (six days/week, 60% of maximal speed) and administration by gavage of leucine (1.35 g/kg/day) or placebo (distilled water). The AET significantly improved exercise capacity, fractional shortening and re-established cardiomyocytes' diameter and collagen fraction in KOT. Additionally, AET significantly prevented the proteasome hyperactivity, increased misfolded proteins and HSP27 expression. Isolated leucine supplementation displayed no effect on cardiac function and structure (KOL), however, when associated with AET (KOLT), it increased exercise tolerance to a higher degree than isolated AET (KOT) despite no additional effects on AET induced anti-cardiac remodeling. Our results provide evidence for the modest impact of leucine supplementation on cardiac structure and function in exercised heart failure mice. Leucine supplementation potentiated AET effects on exercise tolerance, which might be related to its recognized impact on skeletal muscle.