Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber–Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites

The link of biocompatibility to cytokine production

The link of biocompatibility to cytokine production. Recent studies suggest that chronic inflammation plays a role in the pathogenesis of cardiovascular disease. Cytokines released from jeopardized tissues stimulate the liver to synthesize acute phase proteins, including C-reactive protein (CRP). Baseline levels of CRP in apparently healthy persons or in persons with unstable angina constitute an independent risk factor for cardiovascular events. More recently, it has been suggested that CRP is useful not only as a marker of the acute phase response, but is also involved in the pathogenesis of the disease. CRP may, in fact, directly interact with the atherosclerotic vessels or ischemic myocardium by activation of the complement system, thereby promoting inflammation and thrombosis. Several studies in uremic patients have implicated CRP as a marker of malnutrition, resistance to erythropoietin, and chronic stimulation in hemodialysis. An increased cytokine production secondary to blood interaction with bioincompatible dialysis components has been reported by several studies; interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and mainly IL-6 are the three proinflammatory cytokines involved in the pathogenesis of hemodialysis-related disease. We have provided evidence for the occurrence of high CRP and IL-6 levels in chronic dialytic patients exposed to contaminate dialysate and suggest that backfiltration may induce a chronic, slowly developing inflammatory state that may be abrogated by avoiding backfiltration of contaminate dialysate. Therefore, CRP is implicated as a marker linking bioincompatibility associated with backfiltration and increased cytokine production with a clinical state of chronic inflammation

Sensory inflow manipulation induces learning-like phenomena in motor behavior

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Perceptual and goal-directed behaviors may be improved by repetitive sensory stimulations without practice-based training. Focal muscle vibration (f-MV) modulating the spatiotemporal properties of proprioceptive inflow is well-suited to investigate the effectiveness of sensory stimulation in influencing motor outcomes. Thus, in this study, we verified whether optimized f-MV stimulation patterns might affect motor control of upper limb movements. Methods: To answer this question, we vibrated the slightly tonically contracted anterior deltoid (AD), posterior deltoid (PD), and pectoralis major muscles in different combinations in forty healthy subjects at a frequency of 100 Hz for 10 min in single or repetitive administrations. We evaluated the vibration effect immediately after f-MV application on upper limb targeted movements tasks, and one week later. We assessed target accuracy, movement mean and peak speed, and normalized Jerk using a 3D optoelectronic motion capture system. Besides, we evaluated AD and PD activity during the tasks using wireless electromyography. Results: We found that f-MV may induce increases (p \u3c 0.05) in movement accuracy, mean speed and smoothness, and changes (p \u3c 0.05) in the electromyographic activity. The main effects of f-MV occurred overtime after repetitive vibration of the AD and PD muscles. Conclusion: Thus, in healthy subjects, optimized f-MV stimulation patterns might over time affect the motor control of the upper limb movement. This finding implies that f-MV may improve the individual’s ability to produce expected motor outcomes and suggests that it may be used to boost motor skills and learning during training and to support functional recovery in rehabilitation

Fluctuating velocity measurements in the turbulent wake of a wind turbine model

An experimental study of the turbulent wake of a wind turbine model was realized at the “Joaquim Blessmann” wind tunnel of the UFRGS. The turbine model was developed at the Universidade de Caxias do Sul and it represents a three blade turbine characterized by a NACA 4412 aerodynamic profile. Measurements of the velocity fluctuations were realized by hot wire anemometry. Complexity of the turbulent flow is evaluated by mean and fluctuating velocity profiles. The influence of the incident flow turbulence and the flow reconstructing process are analysed by the measurement results

SUBSTITUIÇÃO DOS GRÃOS SECOS DE MILHO PELA SILAGEM DE GRÃOS ÚMIDOS DE MILHO PARA VACAS DA RAÇA HOLANDESA EM LACTAÇÃO

RESUMO: Com o objetivo de avaliar os efeitos da substituição dos grãos secos de milho (GSM) pela silagem de grãos úmidos de milho (SGUM) sobre a produção e composição do leite, foram utilizadas cinco vacas da raça Holandesas, primíparas com média de 112 dias pós-parto, confinadas em Tie Stall, por 70 dias. Utilizou-se cinco rações de acordo com o NRC para 17,5% PB (MS) e 2,4 Mcal EM/kg MS, na relação 40:60 de volumoso e concentrado contendo farelo de soja, silagem de cana de açúcar e feno e níveis de substituição dos GSM pela SGUM nos tratamentos: 1) 0%; 2) 25%; 3) 50%; 4) 75% e 5) 100%. A produção de leite e o consumo de matéria seca (CMS) foram registrados diariamente. Os animais foram ordenhados diariamente 6:00 e 18:00 h, sendo as amostras de leite coletadas nas ordenhas consecutivas de cada fase experimental de 14 dias (quatro dias de coleta). O delineamento experimental utilizado foi o Quadrado Latino 5x5 e os dados analisados pelo programa estatístico SAS. O peso corporal (508 kg), produção de leite (23,6 kg), produção de leite corrigida (22,7 kg), CMS (17,13 kg), não apresentaram diferença significativas, porém os consumos de fibra em detergente neutro (6,67 kg), e em detergente ácido (3,39 kg), eficiência alimentar para produção de leite (1,41 kg leite/dia) o nitrogênio uréico (17,67 mg/dL) apresentaram diferença, indicando desta forma que a SGUM é mais eficiente que os GSM na dieta de vacas em lactação por não  alterar a produção e composição do leite

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Effects of scapular retraction/protraction position and scapular elevation on shoulder girdle muscle activity during glenohumeral abduction

According to scapulohumeral rhythm, shoulder abduction is followed through scapular upward rotation to ensure joint mobility and stability. Of interest, the shoulder abduction can be performed holding the scapula in different positions and in association with scapular elevation, with possible effects on shoulder muscle activity. Therefore, the aim of the study was to analyze the activity of relevant shoulder muscles and the activity ratios between the scapulothoracic muscles, during shoulder abduction performed in different combinations of scapular position (neutral, retracted, protracted) and scapular elevation. The electromyographic activity of middle deltoid, serratus anterior, upper, middle and lower fibers of trapezius was recorded during shoulder abduction movements executed holding the scapula in neutral, retracted and protracted position, and subsequently a shoulder elevation movement. The activation of each muscle and the scapulothoracic muscles activity ratios were determined every 15 degrees, from 15° to 120° of abduction. Scapular retraction led to higher activation of the entire trapezius muscle, whereas protraction induced higher upper trapezius, middle deltoid and serratus anterior activity, along with lower activity of middle and lower trapezius. Shoulder elevation led to higher activity of the upper trapezius and middle deltoid. Moreover, it induced lower activation of the serratus anterior and middle and lower trapezius, thus leading to high ratios between the upper trapezius and the other scapulothoracic muscles, especially between 15 and 75 degrees of abduction. This study highlights that shoulder abduction performed with scapular protraction and in combination with scapular elevation leads to increased activity of the middle deltoid and upper trapezius, resulting in imbalances between the scapulothoracic muscles that could hamper the optimal scapulohumeral rhythm. The abduction performed in the aforementioned scapular conditions also induce potential reciprocal inhibition effects between the movers and stabilizers muscles of scapula, suggesting different motor control strategies of integrating a common shoulder movement with various modification of the scapular position

Mechanisms of modulation of automatic scapulothoracic muscle contraction timings

Erected posture provides humans a large shoulder mobility that requires complex automatic muscle synergies to accomplish joint stability needs. This is evident in shoulder abduction, wherein the voluntary activation of glenohumeral muscles is coupled with an automatic recruitment of scapulothoracic muscles. Here, we investigated whether volitional modification of the scapular position, and dynamic scapular elevation, modulate the contraction timing of five shoulder muscles (middle deltoid, upper, middle and lower fiber of the trapezius, serratus anterior) during shoulder abduction. The results show matched contraction timings of the deltoid and upper trapezius across the scapular positions, whereas the contraction timings of the middle and lower fibers of the trapezius change secondary to the scapular position. These results might reflect different central strategies to coordinate the automatic sequences of contraction of the scapulothoracic muscles. This suggest a flexible and adaptable predisposition of the motor control system in exploring alternative solutions to accomplish the functional movement needs, such as the fulfillment of unconstrained movements. Intriguingly, the shoulder abduction may represent a powerful, non-invasive, and straightforward tool to deepen the understanding of the neural basis underlying the voluntary motor command modulation of the out-of-volition automatic muscle contractions

Joint torques and tibiofemoral joint reaction force in the bodyweight "wall squat" therapeutic exercise

This study provides a biomechanical analysis of the bodyweight wall-squat exercise considering four exercise variants: knee angle; horizontal hip-ankle distance (d); shift between the rearfoot and forefoot of the centre of pressure (xGR) of the ground reaction force; back supported via the scapular or pelvic zone. The ankle and hip angles corresponding to a given knee angle can be modulated, changing the distance d, to manage limitation in lumbopelvic and ankle mobility. The knee-extensor muscles can be overloaded (250 Nm muscle torque) with knees flexed at 90°, back supported through the pelvic zone, and feet away from the wall (d = 50 cm). Scapular support, xGR at forefoot, and d = 50 cm, yield a higher level of muscle-torque for hip-extension (130 Nm) and knee-flexion (65 Nm), with knees at 90° of flexion or near full extension, respectively. Ankle-dorsiflexion (plantarflexion) muscle torque up to 40 Nm is reached with xGR at the forefoot (rearfoot). This study may aid trainers and therapists to finely modulate the muscle torques (up to the above-mentioned levels) by an appropriate selection of exercise variants for training or rehabilitation purposes. Low levels (60 N) of anterior tibial pull may occur near 25° of knee flexion with xGR at the rearfoot

De novo synthesized estradiol: a role in modulating the cerebellar function

The estrogen estradiol is a potent neuroactive steroid that may regulate brain structure and function. Although the effects of estradiol have been historically associated with gonadal secretion, the discovery that this steroid may be synthesized within the brain has expanded this traditional concept. Indeed, it is accepted that de novo synthesized estradiol in the nervous system (nE2) may modulate several aspects of neuronal physiology, including synaptic transmission and plasticity, thereby influencing a variety of behaviors. These modulations may be on a time scale of minutes via non-classical and often membrane-initiated mechanisms or hours and days by classical actions on gene transcription. Besides the high level, recent investigations in the cerebellum indicate that even a low aromatase expression can be related to the fast nE2 effect on brain functioning. These pieces of evidence point to the importance of an on-demand and localized nE2 synthesis to rapidly contribute to regulating the synaptic transmission. This review is geared at exploring a new scenario for the impact of estradiol on brain processes as it emerges from the nE2 action on cerebellar neurotransmission and cerebellum-dependent learning