Leptin Levels and Appetite Score in Patients on Hemodialysis Using High Flux or Medium Cutoff Membranes.

OBJECTIVES: Chronic kidney disease (CKD) patients on hemodialysis may have a modified appetite due to several factors including a lack of uremic toxins elimination. The use of medium cutoff (MCO) dialysis membranes has been suggested as an alternative to improve the removal of toxins, especially those of medium and high molecular weight. This study aimed to compare the effect of hemodialysis using MCO and high-flux membranes on the appetite and leptin levels of CKD patients. DESIGN AND METHODS: This is a predefined exploratory analysis of a randomized, open study, with a crossover design of 28 weeks of follow-up, which compared the effects of MCO and high-flux membranes in 32 CKD patients on hemodialysis. Appetite assessments were performed using the Appetite and Food Satisfaction Questionnaire. RESULTS: The MCO group had an appetite score of 3.00 (1.00-5.50) and 3.00 (1.00-5.00) at the beginning and at the end of the treatment period, respectively, while the high-flux group had 1.00 (0.25-6.00) and 2.00 (0.75-3.25). There were no effects of treatment (P = .573), time (P = .376), and interaction (P = .770) between the MCO and high-flux groups. Leptin levels, at the beginning and at the end of the treatment period, were 2,342.30 (1,156.50-4,091.50) and 2,571.50 (1,619.40-4,036.47) pg/mL in the MCO group, respectively, and 2,183.15 (1,550.67-3,656.50) and 2,685.65 (1,458.20-3,981.08) pg/mL in the high-flux group. There was a time effect (P = .014), showing an increase in leptin levels in both groups, while treatment (P = .771) or interaction (P = .218) effects were not observed. CONCLUSIONS: There is no difference between the effects of MCO or high-flux membranes on leptin levels or appetite of CKD patients on hemodialysis.

Fast Oscillatory Commands from the Motor Cortex Can Be Decoded by the Spinal Cord for Force Control.

Oscillations in the beta and gamma bands (13-30 Hz; 35-70 Hz) have often been observed in motor cortical outputs that reach the spinal cord, acting on motoneurons and interneurons. However, the frequencies of these oscillations are above the muscle force frequency range. A current view is that the transformation of the motoneuron pool inputs into force is linear. For this reason possible roles for these oscillations are unclear, since if this transformation is linear, the high frequencies in the motoneuron inputs (e.g., 20 Hz from pyramidal tract neurons) would be filtered out by the muscle and have no effect on force control. A biologically inspired mathematical model of the neuromuscular system was used to investigate the impact of high-frequency cortical oscillatory activity on force control. The model simulation results evidenced that a typical motoneuron pool has a nonlinear behavior that enables the decoding of a high-frequency oscillatory input. An input at a single frequency (e.g., beta band) leads to an increase in the steady-state force generated by the muscle. When the input oscillation was amplitude modulated at a given low frequency, the force oscillated at this frequency. In both cases, the mechanism relies on the recruitment and derecruitment of motor units in response to the oscillatory descending drive. Therefore, the results from this study suggest a potential role in force control for cortical oscillations at frequencies at or above the beta band, despite the low-pass behavior of the muscles. SIGNIFICANCE STATEMENT: The role of cortical oscillations in motor control has been a long-standing question, one view being that they are an epiphenomenon. Fast oscillations are known to reach the spinal cord, and hence they have been thought to affect muscle behavior. However, experimental limitations have hampered further advances to explain how they could influence muscle force. An approach for such a challenge was adopted in the present research: to study the problem through computer simulations of an advanced biologically compatible mathematical model. Using such a model, we found that the well-known mechanism of recruitment and derecruitment of the spinal cord motoneurons can allow the muscle to respond to cortical oscillations, suggesting that these oscillations are not epiphenomena in motor control.

Spinal mechanisms may provide a combination of intermittent and continuous control of human posture: predictions from a biologically based neuromusculoskeletal model.

Several models have been employed to study human postural control during upright quiet stance. Most have adopted an inverted pendulum approximation to the standing human and theoretical models to account for the neural feedback necessary to keep balance. The present study adds to the previous efforts in focusing more closely on modelling the physiological mechanisms of important elements associated with the control of human posture. This paper studies neuromuscular mechanisms behind upright stance control by means of a biologically based large-scale neuromusculoskeletal (NMS) model. It encompasses: i) conductance-based spinal neuron models (motor neurons and interneurons); ii) muscle proprioceptor models (spindle and Golgi tendon organ) providing sensory afferent feedback; iii) Hill-type muscle models of the leg plantar and dorsiflexors; and iv) an inverted pendulum model for the body biomechanics during upright stance. The motor neuron pools are driven by stochastic spike trains. Simulation results showed that the neuromechanical outputs generated by the NMS model resemble experimental data from subjects standing on a stable surface. Interesting findings were that: i) an intermittent pattern of muscle activation emerged from this posture control model for two of the leg muscles (Medial and Lateral Gastrocnemius); and ii) the Soleus muscle was mostly activated in a continuous manner. These results suggest that the spinal cord anatomy and neurophysiology (e.g., motor unit types, synaptic connectivities, ordered recruitment), along with the modulation of afferent activity, may account for the mixture of intermittent and continuous control that has been a subject of debate in recent studies on postural control. Another finding was the occurrence of the so-called "paradoxical" behaviour of muscle fibre lengths as a function of postural sway. The simulations confirmed previous conjectures that reciprocal inhibition is possibly contributing to this effect, but on the other hand showed that this effect may arise without any anticipatory neural control mechanism.

Determination of the pubertal growth spurt by artificial intelligence analysis of cervical vertebrae maturation in lateral cephalometric radiographs.

OBJECTIVE: This study aimed to assess the performance of a convolutional neural network (CNN) model in detecting the pubertal growth spurt by analyzing cervical vertebrae maturation (CVM) in lateral cephalometric radiographs (LCRs). STUDY DESIGN: In total, 600 LCRs of patients from 6 to 17 years old were selected. Three radiologists independently and blindly classified the maturation stages of the LCRs and defined the difficulty of each classification. Subsequently, the stage and level of difficulty were determined by consensus. LCRs were distributed between training, validation, and test datasets across 4 CNN-based models. The models' responses were compared with the radiologists' reference standard, and the architecture with the highest success rate was selected for evaluation. Models were developed using full and cropped LCRs with original and simplified maturation classifications. RESULTS: In the simplified classification, the Inception-v3 CNN yielded an accuracy of 74% and 75%, with recall and precision values of 61% and 62%, for full and cropped LCRs, respectively. It achieved 61% and 62% total success rates with full and cropped LCRs, respectively, reaching 72.7% for easy-to-classify cropped cases. CONCLUSION: Overall, the CNN model demonstrated potential for determining the maturation status regarding the pubertal growth spurt through images of the cervical vertebrae. It may be useful as an initial assessment tool or as an aid for optimizing the assessment and treatment decisions of the clinician.

Influences of premotoneuronal command statistics on the scaling of motor output variability during isometric plantar flexion.

This study focuses on neuromuscular mechanisms behind ankle torque and EMG variability during a maintained isometric plantar flexion contraction. Experimentally obtained torque standard deviation (SD) and soleus, medial gastrocnemius, and lateral gastrocnemius EMG envelope mean and SD increased with mean torque for a wide range of torque levels. Computer simulations were performed on a biophysically-based neuromuscular model of the triceps surae consisting of premotoneuronal spike trains (the global input, GI) driving the motoneuron pools of the soleus, medial gastrocnemius, and lateral gastrocnemius muscles, which activate their respective muscle units. Two types of point processes were adopted to represent the statistics of the GI: Poisson and Gamma. Simulations showed a better agreement with experimental results when the GI was modeled by Gamma point processes having lower orders (higher variability) for higher target torques. At the same time, the simulations reproduced well the experimental data of EMG envelope mean and SD as a function of mean plantar flexion torque, for the three muscles. These results suggest that the experimentally found relations between torque-EMG variability as a function of mean plantar flexion torque level depend not only on the intrinsic properties of the motoneuron pools and the muscle units innervated, but also on the increasing variability of the premotoneuronal GI spike trains when their mean rates increase to command a higher plantar flexion torque level. The simulations also provided information on spike train statistics of several hundred motoneurons that compose the triceps surae, providing a wide picture of the associated mechanisms behind torque and EMG variability.

Effect of rosuvastatin and sevelamer on the progression of coronary artery calcification in chronic kidney disease: a pilot study.

INTRODUCTION: Coronary artery calcification (CAC) is highly prevalent among chronic kidney disease (CKD) patients and its strong association with mortality has been recognized early in the course of CKD. The aim of the present study was to test the effect of rosuvastatin and sevelamer hydrochloride on the progression of CAC in nondialyzed CKD patients. METHODS: An open-label, randomized and controlled pilot study was conducted including 117 CKD patients (62% men, 56.9 ± 11.2 years, eGFR 36 ± 16.5 ml/min). Patients were randomly assigned to rosuvastatin (n = 38; 10 mg/day), to sevelamer hydrochloride (n = 38; 2,400 mg/day) and to control (n = 41) groups. CAC (by multislice computed tomography) and biochemical analyses were performed at baseline and after 24 months. RESULTS: At baseline, CAC was observed in 55%, 58% and 61% of patients in the rosuvastatin, sevelamer hydrochloride and control groups, respectively (p = 0.87). Calcium score at baseline as well as its absolute and relative changes during 24 months were similar among the groups. Low density lipoprotein cholesterol (LDL-c) was higher and decreased significantly in the rosuvastatin group (p < 0.01). The analysis adjusting for LDL-c showed that the drug regimens were not associated with the progression of CAC (drug effect p = 0.85; time-effect p < 0.001; interaction p = 0.76). CONCLUSIONS: Treatment with rosuvastatin and sevelamer hydrochloride may not delay the progression of CAC in non-dialysis dependent CKD patients.

The effects of medium cut-off and high-flux membranes on activated clotting time of patients on hemodialysis.

Introduction: The interaction between blood and dialysis membrane increases the risk of clot formation. Membrane properties can interfere with coagulation activation during dialysis. Heparin is usually used to ensure anticoagulation, which can be monitored by the Activated Clotting Time (ACT) test. The purpose of this study was to compare the ACT of patients with chronic kidney disease (CKD) undergoing hemodialysis with high-flux (HF) and medium cut-off (MCO) membranes. Methods: This is a prospective, randomized, crossover study in which 32 CKD patients were dialyzed for 12 weeks with each membrane. Blood clotting measured by ACT was evaluated at the beginning, 2nd, and 4th hour of the dialysis session. Throughout the study, there were no changes in the dose or administration method of heparin. Results: Patients mainly were middle-aged, non-black males on hemodialysis for eight years. Before randomization, ACT values were 132 ± 56, 195 ± 60, and 128 ± 32 seconds at pre-heparinization, 2nd and 4th hour, respectively. After 12 weeks, ACT values in HF and MCO groups were 129 ± 17, 205 ± 65 and 139 ± 38 seconds, and 143 ± 54, 219 ± 68 and 142 ± 45 seconds, respectively. An ANOVA model adjusted and unadjusted for repeated measures showed a significant time but no treatment or interaction effects. In an additional paired-sample analysis, no difference between ACT values of HF and MCO Groups was observed. Discussion and Conclusion: There was no difference regarding the ACT test during dialysis therapy using HF or MCO membranes. This data suggests that no adjustment in the dose or administration method of heparin is necessary with the use of MCO dialysis membranes.

The association between coronary artery calcification progression and loss of bone density in non-dialyzed CKD patients.

BACKGROUND: Coronary artery calcification (CAC) and low bone density are coexisting deleterious conditions commonly shared by chronic kidney disease (CKD) patients. In the present study, we aimed to investigate whether the progression of CAC was associated with overtime reduction in bone density in non-dialyzed CKD patients. METHODS: This is a prospective study of 24 months including 72 non-dialyzed CKD patients Stages 2 - 4 (age 57.6 ± 10.3 years, 62% male, 22% diabetics). CAC and vertebral bone density (VBD) were measured by computed tomography. RESULTS: At baseline, 46% of the patients had CAC (calcified group) and calcification was not identified in 54% of the patients (non-calcified group). The calcified group was older, predominantly male, and had lower VBD in comparison to non-calcified group. CAC progression was observed only in the calcified group (91% of the patients increased calcium score). The multiple regression analysis revealed loss of VBD as the independent determinant of CAC progression in these patients. CONCLUSIONS: CAC progression was associated with loss of VBD in non-dialyzed CKD patients.

A worldwide comparison of long-distance running training in 2019 and 2020: associated effects of the COVID-19 pandemic.

Objective: The goal of the present study was to investigate possible effects of the COVID-19 pandemic on long-distance running training. Methods: This is a retrospective study with a within-subject design. We analyzed 10,703,690 records of running training during 2019 and 2020, from 36,412 athletes from around the world. The records were obtained through web scraping of a large social network for athletes on the internet. A potential long-distance runner was defined as a user of the social network who had a record of running at least one of the six World Marathon Majors by 2019. Results: In 2020, compared with 2019, in total there was a 3.6% decrease in the number of athletes running, a 7.5% decrease in the distance and 6.7% in the duration of running training. There were large variations in these variables throughout 2020, reaching 16% fewer athletes running weekly and 35% lower running distance (Cohen's d = 0.34, p < 0.001) and 33% lower running duration (Cohen's d = 0.30, p < 0.001) in September 2020. The beginning of the decrease in running training in the first quarter of 2020 coincides with the beginning of the adoption of measures to restrict the COVID-19 pandemic; but as of the second quarter of 2020, running training appears to have undergone variations unrelated to the preventive measures. Among the ten most represented countries in the dataset, running training in Brazil appears to have been the most affected by the COVID-19 pandemic and restriction measures. Conclusion: The wide variations in long-distance running training throughout 2020 are likely related to the COVID-19 pandemic. As for the total volume, the observed decreases of up to 7.5% in the outcome variables related to running training in 2020 could also be attributed to the COVID-19 pandemic, but other factors such as injury, illness or lack of interest, may also have contributed to these decreases.

Electrophysiological and functional signs of Guillain-Barré syndrome predicted by a multiscale neuromuscular computational model.

Objective.The diagnosis of nerve disorders in humans has relied heavily on the measurement of electrical signals from nerves or muscles in response to electrical stimuli applied at appropriate locations on the body surface. The present study investigated the demyelinating subtype of Guillain-Barré syndrome using multiscale computational model simulations to verify how demyelination of peripheral axons may affect plantar flexion torque as well as the ongoing electromyogram (EMG) during voluntary isometric or isotonic contractions.Approach.Changes in axonal conduction velocities, mimicking those found in patients with the disease at different stages, were imposed on a multiscale computational neuromusculoskeletal model to simulate subjects performing unipodal plantar flexion force and position tasks.Main results.The simulated results indicated changes in the torque signal during the early phase of the disease while performing isotonic tasks, as well as in torque variability after partial conduction block while performing both isometric and isotonic tasks. Our results also indicated changes in the root mean square values and in the power spectrum of the soleus EMG signal as well as changes in the synchronization index computed from the firing times of the active motor units. All these quantitative changes in functional indicators suggest that the adoption of such additional measurements, such as torques and ongoing EMG, could be used with advantage in the diagnosis and be relevant in providing extra information for the neurologist about the level of the disease.Significance.Our findings enrich the knowledge of the possible ways demyelination affects force generation and position control during plantarflexion. Moreover, this work extends computational neuroscience to computational neurology and shows the potential of biologically compatible neuromuscular computational models in providing relevant quantitative signs that may be useful for diagnosis in the clinic, complementing the tools traditionally used in neurological electrodiagnosis.

Bone mass measurement by DXA should be interpreted with caution in the CKD population with vascular calcification.

BACKGROUND: KDIGO guidelines suggest the use of dual-energy X-ray absorptiometry (DXA) to assess bone mineral density (BMD) in patients with CKD 3a-5D. Previous studies have demonstrated an association between trabecular bone mass loss and coronary artery calcification (CAC) progression. This study aimed to prospectively investigate the relationship between BMD changes, quantified by DXA, and CAC progression in the non-dialyzed CKD population. METHODS: In this post hoc study, BMD by DXA was measured at the lumbar spine and total hip at baseline and 12-months. Patients were categorized according to BMD changes into 3 different groups: LOSS, UNCHANGED and GAIN. CAC quantification was obtained by multislice computed tomography at baseline and 12-months. RESULTS: 87 patients (55.6 ± 10.7 years, 62% males, 30% diabetic, eGFR = 39.2 ± 18.1 mL/min/1.73m2) were enrolled. CAC was found in 41 (47%) of the patients at baseline and CAC progression in 25 (64%) of them. Considering the lumbar spine and total hip BMD changes together, 24%, 48%, and 25% of the patients were in the LOSS, UNCHANGED and GAIN groups, respectively. Compared to the UNCHANGED or LOSS groups, the GAIN group had an increase in calcium score (p = 0.04) and a higher proportion of patients with CAC progression (p = 0.01). In the logistic regression analysis, CAC progression was 4.5 times more likely to be in the GAIN group. CONCLUSIONS: The association between the increase in BMD values and the progression of vascular calcification was the result of two concomitant processes overlapping, leading to a misinterpretation of DXA results. Thus, the use of DXA for the evaluation of bone mass, especially at the lumbar spine, must be applied with restraint and its results very carefully interpreted in CKD patients.

Maintained activity in ankylosing spondylitis patients treated with TNFi and/or NSAID for at least 12 weeks: a cross-sectional study in Brazil.

BACKGROUND: The aim of this study was to evaluate disease activity among patients with axial spondyloarthritis (AS) treated with tumor necrosis factor inhibitors (TNFi) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 12 weeks in private outpatient settings in Brazil. METHODS: This was a cross-sectional, real-world study conducted in 17 Brazilian private health care institutes. Patients were selected if diagnosed with AS or axial radiographic spondyloarthritis (AxSpA) and treated with NSAIDs or TNFi for at least 12 weeks within the last 26 weeks prior to enrollment. The data were collected from interviewed-based and self-administered questionnaires from patients and physicians. Disease activity was defined as active (≥ 4), low /suboptimal (≥ 2 and < 4) and inactive (< 4) by Bath AS Disease Activity Index (BASDAI) and/or very high (≥ 3.5), high (≥ 2.1 to < 3.5), low (≥ 1.3 to < 2.1), and inactive (< 1.3) by AS Disease Activity Score (ASDAS-CRP). Both patients and physicians' perceptions of disease control were assessed using a numeric rating scale (NRS; 0-inactive to 10-very active disease). RESULTS: The cohort included 378 patients with a mean age of 46 years, and the median time since diagnosis until enrollment was 5.4 years (interquartile range 2.7-10.5). Most patients were treated with TNFi alone (74%), followed by TNFi in combination with NSAID (15%), and NSAID alone (11%). About half AS patients showed active disease and 24% of patients showed low activity/suboptimal disease control despite having been treated for at least 12 weeks. Although TNFi showed better disease control than NSAID, inactive disease was experienced by few patients. The NRS (mean [standard deviation]) score for disease perception was 4.24 (3.3) and 2.85 (2.6) for patients and physicians, respectively. CONCLUSION: This real-world study showed that most AS patients on TNFi and/or NSAID had not achieved an adequate disease control, as almost 75% of them exhibited active disease or low activity/suboptimal disease control. There remains a need for improved disease management among patients with AS.

Effects of spermidine and p-cresol on polymorphonuclear cell apoptosis and function.

Polymorphonuclear leukocytes (PMNs) from chronic kidney disease (CKD) patients display accelerated apoptosis and dysfunction, which may predispose CKD patients to infections. In this study, we investigated the effect of spermidine and p-cresol on apoptosis and function on PMN from healthy subjects. We measured the effect of spermidine and p-cresol on apoptosis, ROS production unstimulated and stimulated (S. aureus and PMA) and expression of CD95, caspase 3, and CD11b on PMN. After incubation with p-cresol and spermidine, we did not observe any changes in apoptosis, viability or expression of caspase 3 and CD95 in PMN from healthy subjects. PMN incubated for 10 minutes with spermidine demonstrated a significant reduction in spontaneous, S. aureus and PMA-stimulated ROS production. p-cresol induced a decrease in PMA-stimulated ROS production. Spermidine and p-cresol also induced a decrease in the expression of CD11b on PMN. Spermidine and p-cresol decreased the expression of CD11b and oxidative burst of PMN from healthy subjects and had no effect on PMN apoptosis and viability.

[Hemoglobin levels in hemodialysis patients treated with epoetin: a Brazilian experience]. / Variação dos níveis de hemoglobina de pacientes em hemodiálise tratados com eritropoetina: uma experiência brasileira.

OBJECTIVE: Correction of anemia using epoetin decreases morbidity and increases survival and quality of life in end-stage renal disease. Maintaining hemoglobin levels within the range proposed by guidelines has become a major challenge, with hemoglobin cycling affecting more than 90% of patients undergoing hemodialysis. The variability of hemoglobin levels over time was assessed in our patients. METHODS: Data were retrospectively collected on 249 patients undergoing hemodialysis over a 3-year period at seven centers in Brazil. Hemoglobin was measured at least monthly, and target levels were those between 10.5 g/dL and 12.5 g/dL. Patients were grouped into six categories of variability consistently low (<10.5 g/dL), consistently target range (10.5 to 12.5 g/dL), consistently high (>12.5 g/dL), low amplitude fluctuation with low hemoglobin levels, low amplitude fluctuation with high hemoglobin levels and high amplitude fluctuation. None of the patients maintained stable hemoglobin levels for the entire 36-month period. RESULTS: The mean monthly proportion of patients that had hemoglobin levels within the target range was 50% (range, 42% to 61%). Mean levels above the target (30%) were more frequent than those below it (20%). During 6, 12, and 36 months, proportions of patients with consistently low levels of hemoglobin decreased from 3.6% to 0%, from 31.7% to 2.8% for those with consistently high, from 7.6% to 0% for those with low amplitude fluctuation with low hemoglobin levels and from 41.3% to 8.3% for those with low amplitude fluctuation with high hemoglobin levels. However, the proportions of patients with high amplitude fluctuation increased from 21.5% to 88.9%. CONCLUSION: Maintaining hemoglobin levels within the target range is difficult, especially for longer periods of time. Missing the target seems more often due to levels above it, but high-amplitude fluctuations eventually occur in the majority of patients.

Hyperkalemia in chronic kidney disease.

Hyperkalemia is a frequent finding in patients with chronic kidney disease (CKD). This increase in serum potassium levels is associated with decreased renal ion excretion, as well as the use of medications to reduce the progression of CKD or to control associated diseases such as diabetes mellitus and heart failure. Hyperkalemia increases the risk of cardiac arrhythmia episodes and sudden death. Thus, the control of potassium elevation is essential for reducing the mortality rate in this population. Initially, the management of hyperkalemia includes orientation of low potassium diets and monitoring of patients' adherence to this procedure. It is also important to know the medications in use and the presence of comorbidities to guide dose reduction or even temporary withdrawal of any of the potassium retention-related drugs. And finally, the use of potassium binders is indicated in both acute episodes and chronic hyperkalemia.

An Open Data Set of Inertial, Magnetic, Foot-Ground Contact, and Electromyographic Signals From Wearable Sensors During Walking.

This study describes an open data set of inertial, magnetic, foot-ground contact, and electromyographic signals from wearable sensors during walking at different speeds. These data were acquired from 22 healthy adults using wearable sensors and walking at self-selected comfortable, fast and slow speeds, and standing still. All data are publicly available in the Internet (https://doi.org/10.6084/m9.figshare.7778255). In total, there are data of 9,661 gait strides. This data set also contains files with the instants of the gait events identified using the foot-ground contact sensors and notebooks exemplifying how to access and visualize the data. This data set gives the opportunity to all interested researchers to work with such data, for example, making tests of algorithms for gait event estimation against a common reference, possible.

Effects of age and speed on the ankle-foot system's power during walking.

Structural and functional changes in the foot have been associated with age-related changes in gait mechanics, but walking speed may be a confounding factor in this relationship. The aim of this study was to investigate the effect of aging and speed on the ankle-foot power output during level walking. The effects of speed and aging on features of the mechanical power and work of the ankle and foot were quantified with a gait analysis of 24 young and 16 older individuals walking at different speeds. We observed gait speed having a significant effect on all the investigated features: peak power and positive and negative work of the ankle, foot, and sum of the ankle and foot (average effect size: 0.64 ± 0.22, from 0.26 to 0.87). We observed age having no effect on these same features (average effect size: 0.23 ± 0.12, from 0.03 to 0.39), with the exception of age's effect when combined with speed on the negative work of the foot. We performed additional analysis to illustrate how the speed can become a confounding factor to the understanding of the age effect on the gait biomechanics. Based on the influence of gait speed on the mechanical power of the ankle-foot system, it is essential that studies control for the effect of gait speed if there is interest in understanding age-related effects, particularly when studying frail older individuals.

Impact of dialyzer membrane on apoptosis and function of polymorphonuclear cells and cytokine synthesis by peripheral blood mononuclear cells in hemodialysis patients.

In an in vivo crossover trial, we compared a cellulosic with a synthetic dialyzer with respect to polymorphonuclear cells (PMN) function and apoptosis, cytokine serum levels and synthesis by peripheral blood mononuclear cells (PBMC), and complement activation. Twenty hemodialysis (HD) patients were assigned in alternate order to HD with cellulose acetate (CA) or polysulfone (PS) dialyzer. After 2 weeks, patients were crossed over to the second dialyzer and treated for another 2 weeks. Apoptosis was assessed by flow cytometry in freshly isolated PMN. Phagocytosis and production of peroxide by PMN were studied by flow cytometry in whole blood. PBMC were isolated from blood samples and incubated for 24 h with or without lipopolysaccharide (LPS). There was no impact of dialyzer biocompatibility on PMN apoptosis and function, cytokine synthesis by PBMC or on their serum levels, serum levels of C3a, and terminal complement complex (TCC). Nevertheless, after HD, serum levels of complement correlated negatively with PMN phagocytosis and peroxide production, and positively with PMN apoptosis and cytokine production by PBMC. Although the results did not show a dialyzer advantage on the immunologic parameters, complement activation may have modulated cell function and apoptosis after HD.

Nonlinear Frequency-Domain Analysis of the Transformation of Cortical Inputs by a Motoneuron Pool-Muscle Complex.

Corticomotor coherence in the beta and/or gamma bands has been described in different motor tasks, but the role of descending brain oscillations on force control has been elusive. Large-scale computational models of a motoneuron pool and the muscle it innervates have been used as tools to advance the knowledge of how neural elements may influence force control. Here, we present a frequency domain analysis of a NARX model fitted to a large-scale neuromuscular model by the means of generalized frequency response functions (GFRF). The results of such procedures indicated that the computational neuromuscular model was capable of transforming an oscillatory synaptic input (e.g., at 20 Hz) into a constant mean muscle force output. The nonlinearity uncovered by the GFRFs of the NARX model was responsible for the demodulation of an oscillatory input (e.g., a beta band oscillation coming from the brain and forming the input to the motoneuron pool). This suggests a manner by which brain rhythms descending as command signals to the spinal cord and acting on a motoneuron pool can regulate a maintained muscle force. In addition to the scientific aspects of these results, they provide new interpretations that may further neural engineering applications associated with quantitative neurological diagnoses and robotic systems for artificial limbs.

Maintained activity in ankylosing spondylitis patients treated with TNFi and/or NSAID for at least 12 weeks: a cross-sectional study in Brazil

Abstract Background The aim of this study was to evaluate disease activity among patients with axial spondyloarthritis (AS) treated with tumor necrosis factor inhibitors (TNFi) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 12 weeks in private outpatient settings in Brazil. Methods This was a cross-sectional, real-world study conducted in 17 Brazilian private health care institutes. Patients were selected if diagnosed with AS or axial radiographic spondyloarthritis (AxSpA) and treated with NSAIDs or TNFi for at least 12 weeks within the last 26 weeks prior to enrollment. The data were collected from interviewed-based and self-administered questionnaires from patients and physicians. Disease activity was defined as active (≥ 4), low /suboptimal (≥ 2 and < 4) and inactive (< 4) by Bath AS Disease Activity Index (BASDAI) and/or very high (≥ 3.5), high (≥ 2.1 to < 3.5), low (≥ 1.3 to < 2.1), and inactive (< 1.3) by AS Disease Activity Score (ASDAS-CRP). Both patients and physicians' perceptions of disease control were assessed using a numeric rating scale (NRS; 0—inactive to 10—very active disease). Results The cohort included 378 patients with a mean age of 46 years, and the median time since diagnosis until enrollment was 5.4 years (interquartile range 2.7-10.5). Most patients were treated with TNFi alone (74%), followed by TNFi in combination with NSAID (15%), and NSAID alone (11%). About half AS patients showed active disease and 24% of patients showed low activity/suboptimal disease control despite having been treated for at least 12 weeks. Although TNFi showed better disease control than NSAID, inactive disease was experienced by few patients. The NRS (mean [standard deviation]) score for disease perception was 4.24 (3.3) and 2.85 (2.6) for patients and physicians, respectively. Conclusion This real-world study showed that most AS patients on TNFi and/or NSAID had not achieved an adequate disease control, as almost 75% of them exhibited active disease or low activity/suboptimal disease control. There remains a need for improved disease management among patients with AS.