Central Nervous System Control Research Articles

Investigation of copeptin levels in foetal congenital central nervous system anomalies

Copeptin has been shown to be associated with central nervous system pathologies. The aim of this study was to investigate the relationship between serum CCP levels and central nervous system (CNS) anomalies. In this case-control study, those at 9–14 weeks of gestation serum levels of copeptin, were assessed in pregnant women whose foetuses subsequently developed CNS anomalies (group 1: n = 60) and compared with gestational age-matched pregnant women who exhibited normal pregnancy outcomes (group 2: n = 48). The mean copeptin levels were 1.58 ± 0.40 ng/mL and 1.11 ± 0.36 ng/mL in the CNS anomalies and control groups, respectively (p < .0001). An increased level of copeptin independently predicts development of CNS anomalies, suggesting that copeptin can be used for prediction and discrimination of CNS anomalies in normal pregnancies at 9–14 weeks of gestation. Impact statement What is already known on this subject? There is no test or method to diagnose CNS anomalies in the first trimester of pregnancy. This study presents the first and new information on the relationship between serum copeptin levels and central nervous system anomalies in pregnant women whose foetuses subsequently developed CNS anomalies. What do the results of this study add? I have strongly demonstrated differences in maternal CPP levels between CNS anomalous pregnancies and healthy controls. What are the implications of these findings for clinical practice and/or further research? It has been thought that copeptin appears to be an ideal marker for central nervous system anomaly prediction at 9–14 weeks of gestational age and if confirmed in larger prospective studies. Finally, these results could not be used as parameters for prenatal CNS screening. Advanced studies, well-structured and conducted on larger populations are needed to investigate the issue further.

Towards an Understanding of Control of Complex Rhythmical "Wavelike" Coordination in Humans.

How does the human neurophysiological system self-organize to achieve optimal phase relationships among joints and limbs, such as in the composite rhythms of butterfly and front crawl swimming, drumming, or dancing? We conducted a systematic review of literature relating to central nervous system (CNS) control of phase among joint/limbs in continuous rhythmic activities. SCOPUS and Web of Science were searched using keywords “Phase AND Rhythm AND Coordination”. This yielded 1039 matches from which 23 papers were extracted for inclusion based on screening criteria. The empirical evidence arising from in-vivo, fictive, in-vitro, and modelling of neural control in humans, other species, and robots indicates that the control of movement is facilitated and simplified by innervating muscle synergies by way of spinal central pattern generators (CPGs). These typically behave like oscillators enabling stable repetition across cycles of movements. This approach provides a foundation to guide the design of empirical research in human swimming and other limb independent activities. For example, future research could be conducted to explore whether the Saltiel two-layer CPG model to explain locomotion in cats might also explain the complex relationships among the cyclical motions in human swimming.

Clinical Outcomes in Patients with Renal Cell Carcinoma Metastases to the Choroid Plexus

Intraventricular metastatic brain tumors account for a small, but challenging, fraction of metastatic brain tumors (0.9%-4.5%). Metastases from renal cell carcinoma (RCC) account for a large portion of these intraventricular tumors. Although patient outcomes have been assumed to be poor, these have not been reported in a modern series with a multimodality treatment paradigm of radiotherapy (RT), resection, and cerebrospinal fluid (CSF) diversion. We have presented the first case series of patients with intraventricular metastatic tumors from RCC. We performed a single-institution retrospective review of patients with intraventricular RCC metastases treated from January 2003 to January 2019. Volumetric analysis was used to delineate the tumor size and the Kaplan-Meier method to evaluate the survival data. A total of 22 intraventricular RCC metastases were identified in 19 patients with 61.3 patient-years of follow-up. The median patient age was 64 years, and the median tumor volume was 2.2 cm3. Overall, 19 metastases had been treated initially with RT. Of these, 16 had received stereotactic body RT and 3 had received whole brain RT. Three tumors were surgically excised and had received adjuvant stereotactic body RT in the upfront setting. Although 5 patients had presented with obstructive hydrocephalus, none had required CSF diversion. After treatment, 5 metastases had progressed, resulting in 1- and 3-year progression-free survival rates of 81.6% and 68%, respectively. The median overall survival was 2.8 years, with 1- and 5-year overall survival rates of 76.7% and 28.3%, respectively. Leptomeningeal carcinomatosis was not observed. Despite the relatively limited overall survival for this population with metastatic cancer, comparable to contemporary parenchymal brain metastasis cohorts, reasonable local central nervous system control was achieved in most patients using a paradigm of focal RT and resection, where indicated. Finally, CSF diversion wasnot required even in patients presenting with hydrocephalus.

No Longer Underappreciated: The Emerging Concept of Astrocyte Heterogeneity in Neuroscience.

Astrocytes are ubiquitous in the central nervous system (CNS). These cells possess thousands of individual processes, which extend out into the neuropil, interacting with neurons, other glia and blood vessels. Paralleling the wide diversity of their interactions, astrocytes have been reported to play key roles in supporting CNS structure, metabolism, blood-brain-barrier formation and control of vascular blood flow, axon guidance, synapse formation and modulation of synaptic transmission. Traditionally, astrocytes have been studied as a homogenous group of cells. However, recent studies have uncovered a surprising degree of heterogeneity in their development and function, in both the healthy and diseased brain. A better understanding of astrocyte heterogeneity is urgently needed to understand normal brain function, as well as the role of astrocytes in response to injury and disease.

Selective peripheral neurotomy (SPN) as a treatment strategy for spasticity

Spasticity can be caused by central nervous system dysfunction, such as cerebral palsy and stroke. The accepted pathogenesis of spasticity is that the muscles are in the state of uninhibited stretch reflex without enough control of central nervous system. So far, there is no ideal way about how to repair central nervous system. However, the uninhibited stretch reflex can be reduced, targeting the posterior root of the spinal cord and peripheral nerves innervating the limbs, which are called selective posterior rhizotomy (SPR) and selective peripheral neurotomy (SPN), respectively. SPN is indicated for focal or multifocal spasticity, which is well accepted due to its low invasiveness and ease of use. How does the operation work? What do we do before and during this operation? Is there any risk to the patients? Our review summarizes the mechanism, indications, preoperative assessments, techniques, and complications of SPN. We hope that the spastic patients, such as pediatric cerebral palsy patients and older stroke patients, will benefit from this surgery.

Traumatic-Induced Coagulopathy as a Systems Failure: A New Window into Hemostasis.

Traumatic-induced coagulopathy (TIC) is often associated with significant bleeding, transfusion requirements, inflammation, morbidity, and mortality. This review considers TIC as a systems failure, not as a single-event manifestation of trauma. After briefly reviewing the meaning of TIC and the bewildering array of fibrinolysis phenotypes, we will discuss the role of platelets and fibrinogen in coagulopathy. Next, we will review the different TIC hypotheses and drill down to a single mechanistic domain comprising (1) thrombin's differential binding to thrombomodulin, (2) the expression of annexin II-S100A10 complex, and (3) the functional integrity of the endothelial glycocalyx. This triad forms the basis of the "switch" hypothesis of TIC. We will next address the potential limitations of current practice in treating a coagulation or fibrinolytic defect, and the next defect, and so on down the line, which often leads to what U.S. surgeon William C. Shoemaker considered "an uncoordinated and sometimes contradictory therapeutic outcome." The treat-as-you-go approach using sequential, single-target treatments appears to be a by-product of decades of highly reductionist thinking and research. Lastly, we will present a unified systems hypothesis of TIC involving three pillars of physiology: the central nervous system (CNS)-cardiovascular system, the endothelial glycocalyx, and mitochondrial integrity. If CNS control of ventriculoarterial coupling is maintained close to unity following trauma, we hypothesize that the endothelium will be protected, mitochondrial energetics will be maintained, and TIC (and inflammation) will be minimized. The Systems Hypothesis of Trauma (SHOT) also helps to answer why certain groups of severely bleeding trauma patients are still dying despite receiving the best care. Currently, no drug therapy exists that targets the whole system.

How does the CNS control arm reaching movements?Introducing a hierarchical nonlinear predictive control organization based on the idea of muscle synergies.

In this study, we introduce a hierarchical and modular computational model to explain how the CNS (Central Nervous System) controls arm reaching movement (ARM) in the frontal plane and under different conditions. The proposed hierarchical organization was established at three levels: 1) motor planning, 2) command production, and 3) motor execution. Since in this work we are not discussing motion learning, no learning procedure was considered in the model. Previous models mainly assume that the motor planning level produces the desired trajectories of the joints and feeds it to the next level to be tracked. In the proposed model, the motion control is described based on a regulatory control policy, that is, the output of the motor planning level is a step function defining the initial and final desired position of the hand. For the command production level, a nonlinear predictive model was developed to explain how the time-invariant muscle synergies (MSs) are recruited. We used the same computational model to explain the arm reaching motion for a combined ARM task. The combined ARM is defined as two successive ARM such that it starts from point A and reaches to point C via point B. To develop the model, kinematic and kinetic data from six subjects were recorded and analyzed during ARM task performance. The subjects used a robotic manipulator while moving their hand in the frontal plane. The EMG data of 15 muscles were also recorded. The MSs used in the model were extracted from the recorded EMG data. The proposed model explains two aspects of the motor control system by a novel computational approach: 1) the CNS reduces the dimension of the control space using the notion of MSs and thereby, avoids immense computational loads; 2) at the level of motor planning, the CNS generates the desired position of the hand at the starting, via and the final points, and this amounts to a regulatory and non-tracking structure.

Long-term treatment with elosulfase alfa has an acceptable safety profile for patients with Morquio syndrome type A: Real-world results from the Morquio A Registry Study (MARS)

Childhood central nervous system (CNS) tumour registration and control programs in Southern and Eastern Europe remain thin, despite the lethal nature of the disease. Mortality/survival data were assembled to estimate the burden of malignant CNS tumours, as well as the potential role of sociodemographic survival determinants across 14 cancer registries of this region.Average age-adjusted mortality rates were calculated, whereas time trends were quantified through Poisson and Joinpoint regressions. Kaplan–Meier curves were derived for the maximum and the more recent (10 and 5 year) registration periods. Multivariate Cox regression models were used to assess demographic and disease-related determinants.Variations in mortality (8–16 per million) and survival (5-year: 35–69%) were substantial among the participating registries; in most registries mortality trend was stable, whereas Bulgaria, having the highest starting rate, experienced decreasing annual mortality (−2.4%, p = 0.001). A steep decrease in survival rates was evident before the second year of follow-up. After controlling for diagnostic subgroup, age, gender and diagnostic year, Greece seemed to present higher survival compared with the other contributing registries, although the follow-up period was short. Irrespective of country, however, rural residence was found to impose substantial adverse repercussions on survival (hazard ratio (HR): 1.2, 95% confidence interval (CI): 1.1–1.4).Cross-country mortality and survival variations possibly reflect suboptimal levels of health care delivery and cancer control in some regions of Southern and Eastern Europe, notwithstanding questionable death certification patterns or follow-up procedures. Continuous childhood cancer registration and linkage with clinical data are prerequisite for the reduction of survival inequalities across Europe.

Effect of Ankle Angles on the Soleus H-Reflex Excitability During Standing.

This study investigated effects of ankle joint angle on the Hoffman's reflex (H-reflex) excitability during loaded (weight borne with both legs) and unloaded (full body weight borne with the contralateral leg) standing in people without neurological injuries. Soleus H-reflex/M-wave recruitment curves were examined during upright standing on three different slopes that imposed plantar flexion (-15°), dorsiflexion (+15°), and neutral (0°) angles at the ankle, with the test leg loaded and unloaded. With the leg loaded and unloaded, maximum H-reflex/maximum M-wave ratio of -15° was significantly larger than those of 0° and +15° conditions. The maximum H-reflex/maximum M-wave ratios were 51%, 43%, and 41% with loaded and 56%, 46%, and 44% with unloaded for -15°, 0°, and +15° slope conditions, respectively. Thus, limb loading/unloading had limited impact on the extent of influence that ankle angles exert on the H-reflex excitability. This suggests that task-dependent central nervous system control of reflex excitability may regulate the influence of sensory input on the spinal reflex during standing.

The Influence of Energy Drinks on Lower Limb Neuromuscular Timing and Postural Sway in Healthy Young Adults

Energy drinks have become popular during the last few years. Many researchers explain the benefits the beverage has on sports or college settings. Other studies focused on the negative position of these drinks, such as reducing blood flow and balance alterations. Various modifications related to energy drink intake might be at a more system and physiological level, like the central nervous system and neuromuscular control. Purpose: This study aims to ascertain the influence of a standard 16-ounce energy drink on neuromuscular timing and standing postural compensation of young, healthy adults while performing a series of complex dual-motor tasks. Methods: Nine females and four males were recruited, screened, and signed the informed consent to be studied for this work. All participants were apparently healthy young adults with no underlying conditions that could potentially impact muscle activation and balance. The Tibialis anterior and Gastrocnemius neuromuscular timing data were collected with surface EMG electrodes. Accelerometers and gyroscopes were used to collect postural sway data. Subjects were asked to execute four balance tasks pre-energy drink consumption, and the same tasks were repeated post energy drink consumption to equate data points. Results: Postural Sway was comparable before and after energy drink intake. Neuromuscular timing data indicates modifications of nerve conduction on the Tibialis anterior and Gastrocnemius musculature. Conclusion: We infer that the ingredients in energy drinks, including guarana and B-vitamins, are altering nerve conduction velocity in postural muscles. Future studies should research the influence of energy drinks in different scenarios and different populations.

Central nervous system control of micturition reflex

Central nervous system control of micturition reflex

CMET-21. A PHASE IB STUDY OF PROTON CRANIOSPINAL IRRADIATION FOR THE TREATMENT OF SOLID TUMOR LEPTOMENINGEAL METASTASES

Abstract Leptomeningeal metastases (LM) is associated with limited survival and treatment options for patients with solid tumor malignancies. While focal radiotherapy is effective for local palliation, it lacks durability due to cerebrospinal fluid (CSF) tumor cells reseeding. Craniospinal irradiation (CSI) in contrast treats the entire central nervous system (CNS) compartment thus potentially improves disease control. We performed a phase IB study of proton CSI using 30CGE in 10 fractions for treating solid tumor LM (NCT03520504). The primary end point is dose-liming toxicity (DLT) within 1 month of treatment. Clinical outcomes and CSF circulating tumor cells (CTCs) by CellSearch® were evaluated. Overall (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimates. Of the 24 patients enrolled, 4 were excluded from analysis: 3 did not complete treatment due to CNS or systemic disease progression (PD), and 1 completed treatment outside study window. The majority of patients had metastatic lung (55%) and breast (30%) malignancies. At this submission, the median follow-up was 2.8 months (0.5–9.4 months). No DLT was observed. Treatment-related grade 2+ toxicities were: fatigue (G2=43%), anorexia (G2=5%), anemia (G2=10%), thrombocytopenia (G3=5%, G2=10%), and leukopenia (G3=14%, G2=14%). Median survival is not reached with 17 patients (85%) alive with stable/improved LM including 2 with durable CNS control for &gt;9 months, 1 patient alive with CNS and systemic PD at 3.7 months, 2 patients died at 3.6 and 5.1 months with CNS and systemic PD. At 3-month, OS and PFS were 100% and 90% (95% CI 100–72%), respectively. In the 13 patients with CSF CTCs evaluation, decreased quantifiable CTCs at 1-month after proton CSI correlated significantly with improved CNS PFS (log-rank p=0.014). These early findings suggest that proton CSI is a safe and potentially effective treatment for patients with solid tumor LM. CSF biomarkers assessment is needed to better elucidate predictors of response.

Gastric vagal afferent neuropathy following experimental spinal cord injury

Dramatic impairment of gastrointestinal (GI) function accompanies high-thoracic spinal cord injury (T3-SCI). The vagus nerve contains mechano- and chemosensory fibers as well as the motor fibers necessary for the central nervous system (CNS) control of GI reflexes. Cell bodies for the vagal afferent fibers are located within the nodose gangla (NG) and the majority of vagal afferent axons are unmyelinated C fibers that are sensitive to capsaicin through activation of transient receptor potential vanilloid-1 (TRPV1) channels. Vagal afferent fibers also express receptors for GI hormones, including cholecystokinin (CCK). Previously, T3-SCI provokes a transient GI inflammatory response as well as a reduction of both gastric emptying and centrally-mediated vagal responses to GI peptides, including CCK. TRPV1 channels and CCK-A receptors (CCKar) expressed in vagal afferents are upregulated in models of visceral inflammation. The present study investigated whether T3-SCI attenuates peripheral vagal afferent sensitivity through plasticity of TRPV1 and CCK receptors.Vagal afferent response to graded mechanical stimulation of the stomach was significantly attenuated by T3-SCI at 3-day and 3-week recovery. Immunocytochemical labeling for CCKar and TRPV1 demonstrated expression on dissociated gastric-projecting NG neurons. Quantitative assessment of mRNA expression by qRT-PCR revealed significant elevation of CCKar and TRPV1 in the whole NG following T3-SCI in 3-day recovery, but levels returned to normal after 3-weeks. Three days after injury, systemic administration of CCK-8 s showed a significantly diminished gastric vagal afferent response in T3-SCI rats compared to control rats while systemic capsaicin infusion revealed a significant elevation of vagal response in T3-SCI vs control rats.These findings demonstrate that T3-SCI provokes peripheral remodeling and prolonged alterations in the response of vagal afferent fibers to the physiological signals associated with digestion.

Measurement of Neutrophil Gelatinase-Associated Lipocalin Concentration in Canine Cerebrospinal Fluid and Serum and Its Involvement in Neuroinflammation.

Neutrophil gelatinase-associated Lipocalin (NGAL) is a glycoprotein involved in inflammation acting as an acute phase protein and chemokine as well as a regulator of iron homeostasis. NGAL has been shown to be upregulated in experimental autoimmune encephalomyelitis (EAE) in mice. Increased NGAL concentration in cerebrospinal fluid (CSF) and expression in central nervous system (CNS) has been described in human neuroinflammatory disease such as multiple sclerosis and neuropsychiatric lupus as well as in bacterial meningitis. We aimed to investigate involvement of NGAL in spontaneous canine neuroinflammation as a potential large animal model for immune- mediated neurological disorders. A commercially available Enzyme-linked Immunosorbent Assay (ELISA) for detection of canine NGAL was validated for use in canine CSF. Concentration in CSF and serum of canine patients suffering from steroid- responsive meningitis- arteriitis (SRMA), Meningoencephalitis of unknown origin (MUO), different non- inflammatory CNS disease and control dogs were compared. Relationship between NGAL concentration in CSF and serum and inflammatory parameters in CSF and blood (IgA concentration, total nucleated cell count (TNCC), protein content) as well as association with erythrocytes in CSF, duration of illness, plasma creatinine and urinary leucocytes were evaluated. In dogs with SRMA and MUO, CSF concentration of NGAL was significantly higher than in dogs with idiopathic epilepsy, compressive myelopathy, intracranial neoplasia and SRMA in remission (p < 0.0001). Patients with acute SRMA had significantly higher levels of NGAL in CSF than neurologically normal controls (p < 0.0001). Serum NGAL concentrations were significantly higher in dogs with SRMA than in patients with myelopathy and intracranial neoplasia (p < 0.0001). NGAL levels in CSF were strongly positively associated with IgA concentration (rSpear= 0.60116, p < 0.0001), TNCC (rSpear= 0.65746, p < 0.0001) and protein content (rSpear= 0.73353, p < 0.0001) in CSF. It can be measured in CSF of healthy and diseased dogs. Higher concentrations in canine patients with SRMA as well as positive association with TNCC in CSF suggest an involvement in pro-inflammatory pathways and chemotaxis in SRMA. High serum levels of NGAL in serum of SRMA patients in different stages of disease might reflect the systemic character of the disease.

Complexities in cardiovascular rhythmicity: perspectives on circadian normality, ageing and disease.

Biological rhythms exist in organisms at all levels of complexity, in most organs and at myriad time scales. Our own biological rhythms are driven by energy emitted by the sun, interacting via our retinas with brain stem centres, which then send out complex messages designed to synchronize the behaviour of peripheral non-light sensing organs, to ensure optimal physiological responsiveness and performance of the organism based on the time of day. Peripheral organs themselves have autonomous rhythmic behaviours that can act independently from central nervous system control but is entrainable. Dysregulation of biological rhythms either through environment or disease has far-reaching consequences on health that we are only now beginning to appreciate. In this review, we focus on cardiovascular rhythms in health, with ageing and under disease conditions.

Autism risk genes are evolutionarily ancient and maintain a unique feature landscape that echoes their function.

Previous research on autism risk (ASD), developmental regulatory (DevReg), and central nervous system (CNS) genes suggests they tend to be large in size, enriched in nested repeats, and mutation intolerant. The relevance of these genomic features is intriguing yet poorly understood. In this study, we investigated the feature landscape of these gene groups to discover structural themes useful in interpreting their function, developmental patterns, and evolutionary history. ASD, DevReg, CNS, housekeeping, and whole genome control (WGC) groups were compiled using various resources. Multiple gene features of interest were extracted from NCBI/UCSC Bioinformatics. Residual variation intolerance scores, Exome Aggregation Consortium pLI scores, and copy number variation data from Decipher were used to estimate variation intolerance. Gene age and protein-protein interactions (PPI) were estimated using Ensembl and EBI Intact databases, respectively. Compared to WGC: ASD, DevReg, and CNS genes are longer, produce larger proteins, maintain greater numbers/density of conserved noncoding elements and transposable elements, produce more transcript variants, and are comparatively variation intolerant. After controlling for gene size, mutation tolerance, and clinical association, ASD genes still retain many of these same features. In addition, we also found that ASD genes that are extremely mutation intolerant have larger PPI networks. These data support many of the recent findings within the field of autism genetics but also expand our understanding of the evolution of these broad gene groups, their potential regulatory complexity, and the extent to which they interact with the cellular network. Autism Res 2019, 12: 860-869. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism risk genes are more ancient compared to other genes in the genome. As such, they exhibit physical features related to their age, including long gene and protein size and regulatory sequences that help to control gene expression. They share many of these same features with other genes that are expressed in the brain and/or are associated with prenatal development.

Risk-Based Data Monitoring: Quality Control in Central Nervous System (CNS) Clinical Trials.

Monitoring the quality of clinical trial efficacy outcome data has received increased attention in the past decade, with regulatory guidance encouraging it to be conducted proactively, and remotely. However, the methods utilized to develop and implement risk-based data monitoring (RBDM) programs vary, and there is a dearth of published material to guide these processes in the context of central nervous system (CNS) trials. We reviewed regulatory guidance published within the past 6 years, generic white papers, and studies applying RBDM to data from CNS clinical trials. Methodologic considerations and system requirements necessary to establish an effective, real-time risk-based monitoring platform in CNS trials are presented. Key RBDM terms are defined in the context of CNS trial data, such as "critical data," "risk indicators," "noninformative data," and "mitigation of risk." Additionally, potential benefits of, and challenges associated with implementation of data quality monitoring are highlighted. Application of methodological and system requirement considerations to real-time monitoring of clinical ratings in CNS trials has the potential to minimize risk and enhance the quality of clinical trial data.

REAL-TIME BIOFEEDBACK INTEGRATED INTO NEUROMUSCULAR TRAINING INCREASES BRAIN FUNCTIONAL CONNECTIVITY AND REDUCES HIGH-RISK KNEE BIOMECHANICS

Background: Anterior cruciate ligament (ACL) injury is associated with alterations in the central nervous system and resultant sensorimotor control (Courtney et al., 2005; Grooms et al., 2017). Our prospective data indicates that altered knee-motor functional brain connectivity is associated with increased risk for ACL injury (Diekfuss et al., revisions invited), revealing novel neural targets for neuromuscular training interventions. Specifically, interventions that integrate concomitant sensorimotor feedback with injury prevention techniques have the potential to enhance brain functional connectivity to optimize ACL injury risk reduction strategies. To deliver concomitant sensorimotor feedback, we have developed an augmented neuromuscular training (aNMT) system that utilizes interactive, real-time biofeedback to simultaneously target multiple biomechanical variables associated with ACL injury risk (Bonnette et al., in press; Figure 1A). aNMT calculates and maps key biomechanical parameters to an interactive graphical shape that responds in real time as a function of participants’ movements. Participants are instructed to perform exercises to achieve a goal shape, which equates to producing biomechanical parameters associated with ACL injury risk reduction, while deviations toward injury risk factors result in specific shape distortions. We hypothesized that aNMT would significantly improve biomechanics associated with ACL injury risk and also increase knee-motor functional connectivity. We further predicted that the identified connectivity changes would be associated with the hypothesized changes in biomechanics. Methods: Over six weeks of training, participants (n = 25) performed a series of aNMT-based progressive exercises (e.g., squat, overhead squat, squat jump, tuck jump, single-leg Romanian dead lift, pistol squat) and completed a drop vertical jump (DVJ) task while fully instrumented for 3D motion analysis pre- and post-training. Peak knee abduction moment (pKAM; bilateral average) from the DVJ was used as the biomechanical outcome variable. Resting-state functional magnetic resonance imaging (fMRI) scans were also collected pre- and post-training on a subset of the cohort (n = 17). Thirteen additional participants were recruited to serve as untrained controls and completed the DVJ and resting-state fMRI on two testing sessions separated by approximately 6 weeks. Twenty-five knee-motor regions of interest (ROIs) were created based on the areas of brain activation derived from previously published data (Grooms et al., 2015; Kapreli et al., 2007). Paired-samples t tests with a false discovery rate correction for multiple comparisons determined differences in functional connectivity among these 25 ROIs (post &gt; pre). Fisher-transformed Pearson correlation coefficients between the average residual blood oxygen level dependent (BOLD) signal time series extracted from ROIs that demonstrated significant group level changes were associated with pKAM in DVJ task at pre- and post-training. The pre- and post-training Pearson correlation coefficients were subsequently compared using the cocor package (Diedenhofen &amp; Musch, 2015) to determine if the two relationships were significantly different. Results: Results showed that pKAM in the aNMT group was significantly lower following aNMT (p &lt; .05), while no significant changes were found between the two time points for controls (p &gt; .05). Results also revealed significantly greater functional connectivity between the right supplementary motor area (SMA) and the left thalamus at post-training relative to pre-training for the aNMT group, t(16) = 3.37, p = .04 (Figure 1B). No significant differences between the two time points were observed for the controls (all p &gt; .05). The association between pKAM and the right SMA and left thalamus at pre-training (r = -.22; Figure 1C) was significantly different compared to that at post-training (r = .26; Figure 1D), p &lt; .05, with a positive relationship between pKAM and SMA and thalamus activation following aNMT biofeedback. No similar changes in pKAM and right SMA and left thalamus connectivity were observed for the untrained controls, p &gt; .05. Conclusions/Significance: The right SMA is involved in the planning and coordination of movement, and the left thalamus is associated with neuromotor control. The increased functional connectivity between these regions, combined with the reduction in pKAM, which is associated with reduced risk of ACL injury, indicate a possible neural mechanism for improved motor adaption associated with aNMT biofeedback. These findings have distinct implications for ACL injury prevention strategies. Biofeedback tools such as aNMT can be designed to target specifically the neural drivers of aberrant movement biomechanics underlying increased ACL injury risk. [Figure: see text]

Long-term treatment with kefir probiotics ameliorates cardiac function in spontaneously hypertensive rats

This work evaluated the effects of long-term kefir treatment in cardiac function (cardiac contractility and calcium-handling proteins) and the central nervous system (CNS) control of the sympathetic signaling in spontaneously hypertensive rats (SHR). Male normotensive rats [Wistar Kyoto rats (WKYs)] and SHRs were divided into three groups: WKYs and SHRs treated with vehicle, and SHRs treated with milk fermented by the grains of kefir (5%; SHR-Kefir; oral gavage, 0.3 ml/100 g daily/9 weeks). At the end of treatment, mean arterial pressure (MAP) and heart rate (HR) were measured by direct arterial catheterization. Hemodynamic parameters (left ventricular systolic pressure, left ventricular isovolumetric relaxation time constant, maximal and minimal pressure decay) were acquired through a left ventricular catheter implantation. Left ventricle protein expressions of phospholamban (PLB), its phosphorylated form (p-PLB) and sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) were determined by Western blot. Tyrosine hydroxylase (TH) protein expression was evaluated via immunofluorescence within the paraventricular nucleus (PVN) of the hypothalamus and the rostral ventrolateral medulla (RVLM). SHR-Kefir group presented lower MAP and HR compared to SHRs. Kefir treatment ameliorated cardiac hypertrophy and promoted reduced expression of PLB, p-PLB and SERCA2a contractile proteins. Within the PVN and RVML, TH protein overexpression observed in SHRs was reduced by probiotic treatment. In addition, kefir improved cardiac hemodynamic parameters in SHR-treated animals. Altogether, the data show that long-term kefir treatment reduced blood pressure by mechanisms involving reduction of cardiac hypertrophy, improvement of cardiac contractility and calcium-handling proteins, and reduction in the CNS regulation of the sympathetic activity.

EMG-CHARACTERISTIC OF MASTICATORY MUSCLES IN PATIENTS WITH CLASS II MALOCCLUSION AND TEMPOROMANDIBULAR DISORDERS

Introduction: A stable state of musculoskeletal system is provided by harmony of occlusion, the anatomy of temporomandibular joints, and the activity of the masticatory muscles under the control of peripheral and central nervous system. Surface electromyography (EMG) is a well-used modality and is used in dentistry to access the status of the muscles of mastication. The aim of the research was to evaluate the EMG-characteristic of masticatory muscles in patients with TMD and Angle Class II malocclusion. Materials and methods: The study comprised 23 patients with Angle Class II malocclusion and TMD. The average age of the subjects was 26,5 ± 2,3 years. Malocclusion was evaluated according to Angle classification, TMD - according to the Research Diagnostic Criteria (RDC/TMD). Registration of EMG-activity of masseter and anterior temporalis muscles was performed during maximum voluntary clenching, clenching on the right and left sides. Results: EMG-activity of masticatory muscles are characterized by: 1) increased values of EMG-activity of temporal and masseter muscles - peak and average amplitude in tests of unilateral clenching and maximum clenching (values are greater than 2000 μV); 2) in unilateral clenching of jaws (on the left or right) the increased EMG-activity was detected on the balancing side; 3) in unilateral clenching of jaws (on the left or right) the increased muscle activity on the working side with disproportional (asymmetric) load distribution between masseter and temporal muscles has been found. Conclusions: Patients with Angle Class II malocclusion and TMD were found features of EMG-activity of masticatory muscles.