Search

The Executive Council of the International Society of Biomechanics has initiated and overseen the commemorations of the Society's 50th Anniversary in 2023. This included multiple series of lectures at the ninth World Congress of Biomechanics in 2022 and XXIXth Congress of the International Society of Biomechanics in 2023, all linked to special issues of International Society of Biomechanics' affiliated journals. This special issue of the Journal of Applied Biomechanics is dedicated to the biomechanics of the neuromusculoskeletal system. The reader is encouraged to explore this special issue which comprises 6 papers exploring the current state-of the-art, and future directions and roles for neuromusculoskeletal biomechanics. This editorial presents a very brief history of the science of the neuromusculoskeletal system's 4 main components: the central nervous system, musculotendon units, the musculoskeletal system, and joints, and how they biomechanically integrate to enable an understanding of the generation and control of human movement. This also entails a quick exploration of contemporary neuromusculoskeletal biomechanics and its future with new fields of application. [ABSTRACT FROM AUTHOR]

Omega-3 (n3) is a polyunsaturated fatty acid well known for its anti-inflammatory and neuroprotective properties. Obesity is linked to chronic inflammation that disrupts metabolism, the intestine physiology and the central nervous system functioning. This study aims to determine if n3 supplementation can interfere with the effects of obesity on the mitochondrial activity, intestinal barrier, and neurotransmitter levels in the brain of Wistar rats that received cafeteria diet (CAF). We examined adipose tissue, skeletal muscle, plasma, intestine, and the cerebral cortex of four groups: CT (control diet), CTn3 (control diet with n3 supplementation), CAF, and CAFn3 (CAF and n3). Diets were offered for 13 weeks, with n3 supplementation in the final 5 weeks. Adipose tissue Electron Transport Chain complexes I, II, and III showed higher activity in CAF groups, as did complexes III and IV in skeletal muscle. Acetate levels in plasma were reduced in CAF groups, and Lipopolysaccharide (LPS) was higher in the CAF group but reduced in CAFn3 group. Claudin-5 in the intestine was lower in CAF groups, with no n3 supplementation effect. In the cerebral cortex, dopamine levels were decreased with CAF, which was reversed by n3. DOPAC, a dopamine metabolite, also showed a supplementation effect, and HVA, a diet effect. Serotonin levels increased in the CAF group that received supplementation. Therefore, we demonstrate disturbances in mitochondria, plasma, intestine and brain of rats submitted to CAF and the potential benefit of n3 supplementation in endotoxemia and neurotransmitter levels. [ABSTRACT FROM AUTHOR]

This article discusses the work of Charles Edouard Brown-Séquard, a prominent figure in the field of neurophysiology and spinal cord anatomy. Brown-Séquard's research focused on spinal cord injuries and spinal shock, as well as the pathways of motor and sensory fibers within the cord. He made significant contributions to the understanding of these topics, including the concept of spinal shock and the eponymous Brown-Séquard lesion. Despite facing criticism and controversy during his career, Brown-Séquard's observations and ideas have had a lasting impact on the field of medicine. [Extracted from the article]

Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFNI's effects on brain aging, Alzheimer's disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STINGIFN- I axis, which extensively participates in brain aging and various forms of neurodegeneration. Understanding the intricate role of IFN-I and its associated pathways in the CNS not only advances our comprehension of brain health and disease but also presents opportunities for developing interventions to modify the process of neurodegeneration and prevent age-related cognitive decline. [ABSTRACT FROM AUTHOR]

The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress—a relationship that is continually being defined. Many studies investigating the effects of chronic stress on neuroinflammation in rodent models have identified significant changes in inflammatory modulators, including nuclear factor-κB (NF-κB) and toll-like receptors (TLRs), and cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6. This suggests that these are key inflammatory factors in the chronic stress response, which may contribute to the establishment of anxiety and depression-like symptoms. The behavioral and neurological effects of modulating inflammatory factors through gene knockdown (KD) and knockout (KO), and conventional and alternative medicine approaches, are discussed. [ABSTRACT FROM AUTHOR]

Reelin, a large extracellular glycoprotein, plays critical roles in neuronal development and synaptic plasticity in the central nervous system (CNS). Recent studies have revealed non-neuronal functions of plasma Reelin in inflammation by promoting endothelial–leukocyte adhesion through its canonical pathway in endothelial cells (via ApoER2 acting on NF-κB), as well as in vascular tone regulation and thrombosis. In this study, we have investigated the safety and efficacy of selectively depleting plasma Reelin as a potential therapeutic strategy for chronic inflammatory diseases. We found that Reelin expression remains stable throughout adulthood and that peripheral anti-Reelin antibody treatment with CR-50 efficiently depletes plasma Reelin without affecting its levels or functionality within the CNS. Notably, this approach preserves essential neuronal functions and synaptic plasticity. Furthermore, in mice induced with experimental autoimmune encephalomyelitis (EAE), selective modulation of endothelial responses by anti-Reelin antibodies reduces pathological leukocyte infiltration without completely abolishing diapedesis. Finally, long-term Reelin depletion under metabolic stress induced by a Western diet did not negatively impact the heart, kidney, or liver, suggesting a favorable safety profile. These findings underscore the promising role of peripheral anti-Reelin therapeutic strategies for autoimmune diseases and conditions where endothelial function is compromised, offering a novel approach that may avoid the immunosuppressive side effects associated with conventional anti-inflammatory therapies. [ABSTRACT FROM AUTHOR]

In the Posner cueing paradigm, the early attentional capture and subsequent inhibition of return (IOR) of attention to the same location, although they are microscale phenomena measured in milliseconds, seem to encapsulate the interaction between two fundamental dimensions of behavior - engaging in and sustaining activity versus withdrawing from and inhibiting activity. In the field of differential psychology, the dynamics of reciprocal relations between these behavioral dimensions have been thought to be determined by central nervous system properties that constitute an individual's temperament. Yet the research on any differential effects of temperament on visuospatial orienting is rather sparse and has produced ambiguous results. Here, we used saccadic responses to measure whether individual differences in reactivity as a temperamental trait might affect orienting of visuospatial attention on discrimination cueing tasks. Our results suggested that, in individuals with lower reactivity, attentional capture took place at a short stimulus onset asynchrony (SOA), producing a facilitatory cueing effect, which was not the case in those who were higher in reactivity. We explain and discuss these results with the Regulative Theory of Temperament. [ABSTRACT FROM AUTHOR]

A recent study published in the Proceedings of the National Academy of Sciences of the United States of America has found a genetic defect that connects congenital hydrocephalus (CH) and autism spectrum disorder (ASD) at a molecular and cellular level. The study focused on KATNAL2 mutations, which disrupt the development of cilia, important structures in human development and genetic disorders. The findings suggest that KATNAL2 is necessary for normal cilia function and that its impairment may contribute to the development of CH and ASD. Further research is needed to fully understand these conditions and develop potential interventions. [Extracted from the article]

Astrocytes, the most abundant glial cells in the central nervous system, respond to a wide variety of neurotransmitters binding to metabotropic receptors. Here, we investigated the intracellular calcium responses of spinal cord astrocytes to dopamine and noradrenaline, two catecholamines released by specific descending pathways. In a slice preparation from the spinal cord of neonatal mice, puff application of dopamine resulted in intracellular calcium responses that remained in the endfeet. Noradrenaline induced stronger responses that also started in the endfeet but spread to neighbouring compartments. The intracellular calcium responses were unaffected by blocking neuronal activity or inhibiting various neurotransmitter receptors, suggesting a direct effect of dopamine and noradrenaline on astrocytes. The intracellular calcium responses induced by noradrenaline and dopamine were inhibited by the D1 receptor antagonist SCH 23390. We assessed the functional consequences of these astrocytic responses by examining changes in arteriole diameter. Puff application of dopamine or noradrenaline resulted in vasoconstriction of spinal arterioles. However, blocking D1 receptors or manipulating astrocytic intracellular calcium levels did not abolish the vasoconstrictions, indicating that the observed intracellular calcium responses in astrocyte endfeet were not responsible for the vascular changes. Our findings demonstrate a compartmentalized response of spinal cord astrocytes to catecholamines and expand our understanding of astrocyte–neurotransmitter interactions and their potential roles in the physiology of the central nervous system. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is increasingly affecting pediatric and adult populations. Neuropsychiatric manifestations (ie, cognitive dysfunction and mood disorders) appear to occur with greater severity and poorer prognosis in childhood‐onset SLE (cSLE) versus adult‐onset SLE, negatively impacting school function, self‐management, and psychosocial health, as well as lifelong health‐related quality of life. In this review, we describe pathogenic mechanisms active in cSLE, such as maladaptive inflammatory processes and ischemia, which are hypothesized to underpin central phenotypes in patients with cSLE, and the role of alterations in protective central nervous system (CNS) barriers (ie, the blood–brain barrier) are also discussed. Recent findings derived from novel neuroimaging approaches are highlighted because the methods employed in these studies hold potential for identifying CNS abnormalities that would otherwise remain undetected with conventional multiple resonance imaging studies (eg, T2‐weighted or fluid‐attenuated inversion recovery sequences). Furthermore, we propose that a more robust presentation of neuropsychiatric symptoms in cSLE is in part due to the harmful impact of a chronic inflammatory insult on a developing CNS. Although the immature status of the CNS may leave patients with cSLE more vulnerable to harboring neuropsychiatric manifestations, the same property may represent a greater urgency to reverse the maladaptive effects associated with a proneuroinflammatory state, provided that effective diagnostic tools and treatment strategies are available. Finally, considering the crosstalk among the CNS and other organ systems affected in cSLE, we postulate that a finer understanding of this interconnectivity and its role in the clinical presentation in cSLE is warranted. [ABSTRACT FROM AUTHOR]

Fibroblasts are typically described as cells that produce extracellular matrix, contribute to the formation of connective tissue, and maintain the structural framework of tissues. Fibroblasts are the first cell type to be transdifferentiated into inducible pluripotent stem cells (iPSCs), demonstrating their versatility and reprogrammability. Currently, there is relatively extensive characterization of the anatomical, molecular, and functional diversity of fibroblasts in different peripheral organs and tissues. With recent advances in single cell RNA sequencing, heterogeneity and diversity of fibroblasts in the central nervous system (CNS) have also begun to emerge. Based on their distinct anatomical locations in the meninges, perivascular space, and choroid plexus, as well as their molecular diversity, important roles for fibroblasts in the CNS have been proposed. Here, we draw inspirations from what is known about fibroblasts in peripheral tissues, in combination with their currently identified CNS locations and molecular characterizations, to propose potential functions of CNS fibroblasts in health and disease. Future studies, using a combination of technologies, will be needed to determine the bona fide in vivo functions of fibroblasts in the CNS. [ABSTRACT FROM AUTHOR]

The pancreas exerts endocrine and exocrine functions in energy balance. The neural innervation and immune milieu are both crucial in supporting pancreatic homeostasis. The neuronal network connects the pancreas with the central nervous system (CNS) and the enteric nervous system (ENS) and sustains metabolic activities. The nerves in the pancreas are categorized as spinal sensory afferent fibers, vagal sensory afferent nerves, autonomic fibers of both sympathetic and parasympathetic divisions, and fibers from the ENS and intrapancreatic ganglia. They innervate different regions and various cell types, which collectively determine physiological functions. Studies have established that the diverse pathological conditions, including pancreatitis, diabetes, and pancreatic tumor, are attributed to aberrant immune reactions; however, it is largely not clear how the neuronal network may influence the disease conditions. Enlightened by the recent advances illuminating the organ-wide neuronal architecture and the dysfunctions in pancreatic disorders, this review will highlight emerging opportunities to explore the cellular interrelationship, particularly the neuroimmune components in pancreatic health and diseases. [ABSTRACT FROM AUTHOR]

Central sensitization (CS) involves amplified central nervous system (CNS) signaling and several biochemical changes which lead to pain hypersensitivity. Data on the effects of CS are limited in orthopaedics and has been associated with reported levels of postoperative pain after hip arthroscopy. Patients over the age of 18 who underwent hip arthroscopy with preoperative as well as 2-year postoperative functional outcome scores were identified through the Multicenter Arthroscopic Study of the Hip (MASH) database. Patient demographics, procedure information, as well as patient reported outcome measures (PROMs) were collected along with CS index scores. 34 patients met inclusion criteria for our study. Preop MCS and iHOT as well as Postop MCS, showed moderate to strong negative correlations with CSI scores (−0.607, −0.573, and −0.756, respectively). VAS, PCS and MSC scores were significantly different preoperatively to postoperatively, ensuring alleviation of pain after hip arthroscopy. Subgroup analysis by stratifying CSI scores into 1 SD below the mean, within 1 SD of the mean, and above 1 SD showed significant differences across all 3 groups for preoperative MCS (p < 0.001), postoperative MCS (p = 0.001), and PSEQ2 (p = 0.015). Postoperative VAS pain approached significance but did not meet criteria of p < 0.05 (p = 0.062). Increased postoperative CSI scores directly correlated with decreased preoperative and postoperative MCS scores and worse preoperative resilience. Recognizing the influence of CS on pain perception and resilience on coping with adversity in the recovery period may guide orthopaedic surgeons in developing comprehensive treatment plans to continue to improve surgical outcomes in hip arthroscopy. IV. [ABSTRACT FROM AUTHOR]

Disorders of the nervous system, encompassing the brain, spinal cord and peripheral nerves, have emerged as a significant public health issue, with profound implications for individuals worldwide. These conditions result in significant morbidity and mortality. Many patients with neurological disorders often have comorbidities, further complicating their clinical presentation. Therefore, nurses must possess a comprehensive understanding of the nervous system and its associated disorders to formulate detailed care plans that address the unique needs of each patient. This article aims to explore the underlying pathophysiology of some of the most prevalent neurological disorders and how this informs effective patient assessment and diagnostic strategies. A further article will build on this to consider patient assessment and formulating a care plan in more detail. [ABSTRACT FROM AUTHOR]

To perform a 'trustworthy' systematic review (SR) with meta-analysis on the potential mechanisms of manual therapy used to treat spinal impairments. SR with meta-analysis Articles published between January 2010 and October 2022 from CENTRAL, CINAHL, MEDLINE, PubMed, ProQuest, and PEDro. This SR included English-language randomized clinical trials (RCTs) involving manual therapy to treat spinal impairments in adults. The primary outcome was pressure pain thresholds (PPTs). To synthesize RCTs with high confidence in estimated effects using the GRADE, RCTs with questionable prospective, external, and internal validity, and high risk of bias (RoB) were excluded. Following title and abstract screening, 89 full-text RCTs were reviewed. Twenty-two studies included the criteria of interest. Sixteen were not prospectively registered, two contained discussion/conclusions judged to be inconsistent with the registry, and one was rated as having a high RoB. Three studies met the inclusion criteria; heterogeneous interventions and locations for PPT testing prevented synthesis into practice recommendations. The two studies with high confidence in estimated effects had small effect sizes, and one study had confidence intervals that crossed zero for the outcome measures of interest. Standardized PPT testing, as a potential measure of centrally mediated pain, could provide clues regarding the mechanisms of manual therapy or help identify/refine research questions. High-quality RCTs could not be synthesized into strong conclusions secondary to the dissimilarity in research designs. Future research regarding quantitative sensory testing should develop RCTs with high confidence in estimated effects that can be translated into strong recommendations. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of chronic primary pain (CPP), according to the recently released International Classification of Disease (ICD‐11) criteria, refers to conditions with complex aetiologies. CPP is characterized by specific clinical features such as generalized sensory hypersensitivity and widespread pain, and is associated with functional disability and emotional distress. Objective: This study investigated clinical features of CPP in individuals with painful temporomandibular disorders (TMD) and comorbidities (fibromyalgia, migraine and/or tension‐type headache). Methods: This cross‐sectional study was conducted with a sample of 129 individuals. Painful TMD, fibromyalgia and primary headaches were evaluated based on well‐established international criteria. Generalized sensory hypersensitivity was assessed using psychophysical tests. Symptoms of anxiety and depression were assessed by the Generalized Anxiety Disorder‐7 and Patient Health Questionnaire‐9. The Central Sensitization Inventory was applied to assess central sensitization‐related symptoms and the Pittsburg Sleep Quality Index to evaluate the quality of sleep. The presence of widespread pain was assessed using a body map. The sample was stratified into three groups: control (n = 25), TMD—painful TMD only (n = 35) and TMD + Cm—painful TMD and comorbidities (n = 69). Statistical analysis was performed using one‐way ANOVA, chi‐squared test and ANCOVA, considering gender as a covariate (α =.05). Results: Compared to controls, individuals presenting painful TMD and comorbidities showed lower pressure pain thresholds in all evaluated areas (p ≤.012) and a higher number of painful areas in the body (p =.001). They presented more symptoms of anxiety (p =.040) and depression (p =.018), and a higher score in the Central Sensitization Inventory (p ≤.006) than the other groups. Conclusion: Individuals with painful TMD and comorbidities presented more clinical features of CPP compared to those affected by TMD only. [ABSTRACT FROM AUTHOR]

Cortex glia in Drosophila central nervous system form a niche around neural cells for necessary signals to establish cross talk with their surroundings. These cells grow and expand their thin processes around neural cell bodies. Although essential for the development and function of the nervous system, how these cells make extensive and intricate connected networks remains largely unknown. In this study, we show that Cut, a homeodomain transcription factor, directly regulates the fate of the cortex glia, impacting neural stem cell (NSC) homeostasis. Focusing on the thoracic ventral nerve cord, we found that Cut is required for the normal growth and development of cortex glia and timely increase in DNA content through endocycle to later divide via acytokinetic mitosis. Knockdown of Cut in cortex glia significantly reduces the growth of cellular processes, the network around NSCs, and their progeny's cell bodies. Conversely, overexpression of Cut induces overall growth of the main processes at the expense of side ones. Whereas the Cut knockdown slows down the timely increase of DNA, the Cut overexpression results in a significant increase in nuclear size and volume and a 3-fold increase in DNA content of cortex glia. Further, we note that constitutively high Cut also interfered with nuclei separation during acytokinetic mitosis. Since the cortex glia form syncytial networks around neural cells, the finding identifies Cut as a novel regulator of glial growth and variant cell cycles to support a functional nervous system. [ABSTRACT FROM AUTHOR]

This document is a collection of abstracts from the 44th Annual Meeting of the American College of Toxicology, covering a range of topics related to toxicology research. The abstracts discuss various studies, including the protective effect of an antioxidant on kidney fibrosis in mice, sex differences in the lung-brain axis transcriptome in response to exposure to indoor fungi, and the evaluation of respiratory sensitizers using an in vitro model. Other studies explore the role of asparagine synthetase in colorectal cancer tumor metabolism, the induction of platinum resistance in ovarian cancer by certain substances, and the modulation of lung injury and inflammation by an RNA-binding protein. Additionally, the frequency of potential drug interactions in pediatric patients and the rescue role of myricetin in testicular oxidative stress, inflammation, and apoptosis in a rat model of Parkinson's disease are examined. The document also includes studies on the effects of nicotine products on gingival tissue, the safety evaluation of a novel sweetener alternative, the cardiovascular effects of a specific drug in monkeys, the use of an in silico system for drug development assessments, the release of cardiac troponin I from cardiomyocytes, the Membrane Proteome Array platform for assessing biotherapeutics, the translational and in silico assessment of liver injury for a specific compound, a modified method for collecting cerebrospinal fluid in rodents and monkeys, and different methods of delivering gene therapies to the central nervous system in non-human primates. These abstracts provide [Extracted from the article]

BACKGROUND: Sleep quality in patients with chronic low back pain (CLBP) may affect quality of life (QoL), possibly due to worsening pain, central sensitization (CS), and cognitive factors. However, causal relationship among the factors has not been confirmed yet. OBJECTIVE: The purpose of this study was to test the hypothesis that sleep quality in patients with CLBP is attributable to pain, cognitive factors, and CS, and influences QoL, by structural covariance analysis. METHODS: This is a cross-sectional study. Participants were recruited from six health care facilities and 101 patients with CLBP were included. Structural covariance analysis assessed the fit of data to the model using goodness of fit index (GFI), adjusted goodness of fit index (AGFI), comparative fit index (CFI), and mean squared approximation error (RMSEA). RESULTS: The structural covariance analysis showed that the goodness-of-fit indices were high (GFI = 0.993, AGFI = 0.964, CFI = 1.00, RMSEA < 0.01). Sleep quality was not directly influenced by QoL but rather by CS and cognitive factors. CONCLUSION: This study suggests that sleep quality in patients with CLBP is indirectly mediated through multiple pathways, including cognitive factors and CS, which may influence QoL. [ABSTRACT FROM AUTHOR]

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia. [ABSTRACT FROM AUTHOR]

Interest in interstitial fluid dynamics has increased since the proposal of the glymphatic system hypothesis. Abnormal dynamics of the interstitial fluid have been pointed out to be an important factor in various pathological statuses. In this article, we propose the concept of central nervous system interstitial fluidopathy as a disease or condition in which abnormal interstitial fluid dynamics is one of the important factors for the development of a pathological condition. We discuss the aspects of interstitial fluidopathy in various diseases, including Alzheimer's disease, Parkinson's disease, normal pressure hydrocephalus, and cerebral small vessel disease. We also discuss a method called "diffusion tensor image analysis along the perivascular space" using MR diffusion images, which is used to evaluate the degree of interstitial fluidopathy or the activity of the glymphatic system. [ABSTRACT FROM AUTHOR]

This article explores the role of the extracellular matrix (ECM) in the central nervous system (CNS). The ECM is a network of biomolecules that is crucial for various brain processes, including neuronal migration and synaptic maturation. Abnormal ECM and remodeling have been linked to CNS pathologies. The article emphasizes the need for more research to understand the molecular mechanisms of ECM and its role in CNS diseases. It also discusses the regulatory roles of ECM in learning and memory processes, the impact of aging on ECM, and the role of collagen XIX in the mammalian cerebral cortex. The study provides evidence that collagen XIX is involved in pheromone recognition and synapse formation in the olfactory bulb. The findings highlight the importance of collagen XIX in brain function and expand our understanding of ECM molecules in different brain regions. [Extracted from the article]

Electroconvulsive Therapy (ECT) is an effective treatment for mood disorders, particularly treatment-resistant depression, and several psychiatric illnesses. Anesthetic management of patients undergoing ECT requires an understanding of ECT, the physiologic changes induced by electrical stimulus, the anesthetic agents used, and the potential complications associated with the procedure. Numerous medical and surgical conditions can impact procedural approach and anesthetic management. ECT is challenging due to its typically off-site location, fast-paced general anesthesia with bag-mask ventilation, selection of anesthetic agents that minimally affect the seizure, patient's comorbidities, and unique physiologic responses. This comprehensive review aims to update anesthetists on the periprocedural management of patients undergoing ECT. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to explore the neural correlates of pain sensitization in patients with chronic low back pain (cLBP). While the association between cLBP and pain sensitization has been widely reported, the underlying brain mechanism responsible for this relationship requires further investigation. Methods: Our study included 56 cLBP patients and 56 healthy controls (HC). Functional magnetic resonance imaging data were obtained, and the voxel-wise amplitude of low-frequency fluctuation (ALFF) was calculated to identify brain alterations in cLBP patients compared to HC groups. Pearson correlation coefficients were computed to explore the association between clinical data and brain alterations. Furthermore, mediation analyses were performed to investigate the path association between brain alterations and pain-related behaviors. Results: Our findings revealed that patients with cLBP exhibited higher sensitivity, attention, and catastrophizing tendencies towards pain compared to HC. Furthermore, cLBP patients displayed significantly higher ALFF in various brain regions within the "pain matrix" and the default mode network when compared to HC. The altered precuneus ALFF was positively correlated with pain intensity (R = 0.51, P<0.001) and was negatively correlated with pain sensitivity (R = −0.43, P<0.001) in cLBP patients. Importantly, the effect of altered precuneus ALFF on pain intensity was mediated by pain threshold in these patients. Conclusion: Our study suggests that altered neural activity in the precuneus may contribute to pain hypersensitivity, which further exacerbating pain in cLBP patients. [ABSTRACT FROM AUTHOR]

Introduction: Transcranial Magnetic Stimulation (TMS) is a noninvasive technique that uses pulsed magnetic fields to affect the physiology of the brain and central nervous system. Repetitive TMS (rTMS) has been used to study and treat several neurological conditions, but its complex molecular basis is largely unexplored. Methods: Utilizing three experimental rat models (in vitro, ex vivo, and in vivo) and employing genome-wide microarray analysis, our study reveals the extensive impact of rTMS treatment on gene expression patterns. Results: These effects are observed across various stimulation protocols, in diverse tissues, and are influenced by time and age. Notably, rTMS-induced alterations in gene expression span a wide range of biological pathways, such as glutamatergic, GABAergic, and anti-inflammatory pathways, ion channels, myelination, mitochondrial energetics, multiple neuron-and synapse-specific genes. Discussion: This comprehensive transcriptional analysis induced by rTMS stimulation serves as a foundational characterization for subsequent experimental investigations and the exploration of potential clinical applications. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Trauma & Emergency Surgery / Ulusal Travma ve Acil Cerrahi Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: The aim of this umbrella review with meta-meta-analysis was to assess the effectiveness of orthopedic manual therapy in isolation on pain sensitization in patients with chronic musculoskeletal pain. Design: A systematic search was performed in different databases including systematic reviews with or without meta-analysis. The outcome measures included were pressure pain threshold, temporal summation, and conditioned pain modulation. The results of the different reviews were statistically synthesized through a random-effect meta-analysis, of all standardized mean differences and the corresponding 95% confidence interval reported by each study. Results: For mechanical hyperalgesia, the meta-meta-analysis of three meta-analyses revealed a statistically significant small-moderate effect of orthopedic manual therapy, with no evidence of heterogeneity and moderate-quality evidence. In terms of temporal summation, one meta-analysis revealed a statistically significant small effect of orthopedic manual therapy intervention, with moderate heterogeneity and low quality of evidence. Finally, one review without meta-analysis found that orthopedic manual therapy improved endogenous analgesia with low-quality evidence. Conclusion: Orthopedic manual therapy in isolation improved mechanical hyperalgesia with moderate-quality evidence, as well as temporal summation and conditioned pain modulation with low-quality evidence. However, its effects are limited only to immediate and short-term. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of dementia, accounting for approximately 38.5 million cases of all-cause dementia. Over 60% of these individuals live in low- and middle-income countries and are the worst affected, especially by its deleterious effects on the productivity of both patients and caregivers. Numerous risk factors for the disease have been identified and our understanding of gene–environment interactions have shed light on several gene variants that contribute to the most common, sporadic form of AD. Microglial cells, the innate immune cells of the central nervous system (CNS), have long been established as guardians of the brain by providing neuroprotection and maintaining cellular homeostasis. A protein with a myriad of effects on various important signaling pathways that is expressed in microglia is the Src Homology 2 (SH2) domain-containing Inositol 5′ Phosphatase 1 (SHIP1) protein. Encoded by the INPP5D (Inositol Polyphosphate-5-Phosphatase D) gene, SHIP1 has diminutive effects on most microglia signaling processes. Polymorphisms of the INPP5D gene have been found to be associated with a significantly increased risk of AD. Several studies have elucidated mechanistic processes by which SHIP1 exerts its perturbations on signaling processes in peripheral immune cells. However, current knowledge of the controllers of INPP5D/SHIP1 expression and the idiosyncrasies of its influences on signaling processes in microglia and their relevance to AD pathophysiology is limited. In this review, we summarize these discoveries and discuss the potential of leveraging INPP5D/SHIP1 as a therapeutic target for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism (PHPT) is rare in children. The most common cause of PHPT is parathyroid adenoma, which occurs either sporadically or as part of the syndrome (the most common being multiple endocrine neoplasia syndrome). The clinical presentation is often vague with nonspecific symptoms involving the gastrointestinal, renal, musculoskeletal, and central nervous systems making the diagnosis challenging. Biochemical profiles and modern imaging techniques are the mainstay for diagnosing the condition, planning the right treatment, and for perioperative management. Herein, we present a case of PHPT who presented to us with all the classical symptoms of hypercalcemia described as "Bones, Stones, Groans, and Moans." [ABSTRACT FROM AUTHOR]

Individuals with peripheral vestibulopathy are known to have difficulty with volitional head turns. This leads to differences in head and body turning kinematics, compared to those without vestibular dysfunction. Multiple sclerosis (MS), a neuro-inflammatory disease affecting the central nervous system, can cause vestibular dysfunction (dizziness, unsteadiness, gaze instability). However, head and trunk turning kinematics in people with MS (PwMS) have not been assessed. Will PwMS, demonstrate head and body kinematics alterations similar to individuals with a peripheral dysfunction compared to vestibular healthy individuals? Eleven individuals with a recent vestibular schwannoma resection (VSR), fourteen PwMS, and 10 healthy control (HC) participants were fitted with head and trunk worn inertial measurement units (IMUs) and performed walking and turning tasks. Head and trunk peak turning speed and amplitude were extracted. Regression models controlling for gait speed were fit per outcome with post hoc corrections applied to significant models. Yaw plane head turn speed and amplitude were significantly less in the VSR group compared to HC. Pitch plane head turn amplitude was significantly smaller in PwMS compared to HC (p = 0.04), however pitch plane speed did not differ between the groups. There was no difference between PwMS and the VSR group in yaw or pitch plane speed and amplitude. Both PwMS and the VSR group turned significantly slower than HC during the 180d body turn as measured at the head and trunk (head speed model p = 0.009 and <0.001; trunk speed model p < 0.001 for both groups) however the MS and VSR groups did not differ from each other. Turning kinematics while walking in PwMS are altered compared to HC and are similar to individuals with unilateral vestibular hypofunction. Centrally mediated vestibular dysfunction in PwMS may alter movement kinematics and should be considered during examination and treatment. • People with MS have turning kinematics similar to people with vestibular loss (78). • Turning kinematics differ in people with multiple sclerosis compared to controls (81). • Centrally mediated vestibular dysfunction may alter movement kinematics (71). [ABSTRACT FROM AUTHOR]

Objective This study aims to compare trunk control, manual dexterity, and reaction time according to different balance states in people with Parkinson's Disease (PwPD). Material and Method A total of 25 PwPD, 6 of whom were women, were included in the study. Individuals were divided into the Moderate-risk group (n=11) and the Low-risk group (n=14) according to the Berg Balance Scale (BBS) cut-off scores. To evaluate trunk control and functions, static and dynamic sitting balance were evaluated with the Trunk Impairment Scale (TIS), which consists of trunk coordination sub-parameters. Hand grip strength was measured with the Jamar hand dynamometer, manual dexterity was measured bilaterally with the Purdue Pegboard Test, and hand reaction time was measured bilaterally with the the Ruler Drop Test. Results When the groups were compared for trunk control, there was a significant difference in the dynamic sitting subparameter and the total score of the trunk impairment scale in favor of the low-risk group (p=0.030, p=0.005). However, there was no difference between the groups in static sitting and coordination sub-parameters (p=0.181, p=0.558). There was no difference between the groups in the grip strength, dexterity, and reaction time of both hands (p>0.05). Conclusion While the dynamic sitting balance and trunk impairment of the moderate-risk balance group was worse than the low-risk group, manual dexterity and reaction time were similar. Further studies are needed to examine manual dexterity for trunk and distal mobility, which play a key role in proximal stabilization and balance in PwPD. [ABSTRACT FROM AUTHOR]

Purpose: The effectiveness of a neuromuscular electrical stimulation (NMES) program is proportional to the level of evoked torque, which can be achieved with either conventional or wide‐pulse stimulations. The aim of this study was to compare evoked torque, objective fatigability, and related peripheral and central alterations, as well as changes in central nervous system (CNS) excitability induced by an acute session of conventional versus wide‐pulse NMES. Methods: Seventeen young men underwent three 20‐min NMES sessions: conventional (0.2 ms/50 Hz), wide‐pulse at 50 Hz (1 ms/50 Hz), and wide‐pulse at 100 Hz (1 ms/100 Hz). Neuromuscular measurements (i.e., maximal voluntary contraction, voluntary activation, evoked responses to femoral nerve stimulation, and CNS excitability) were performed on the right quadriceps femoris muscle before and after each NMES session. CNS excitability was measured using transcranial magnetic, thoracic, and transcutaneous spinal cord stimulations. Results: The level of evoked torque was not significantly different between conventional and wide‐pulse protocols applied at the maximal tolerable current intensity. All NMES protocols induced objective fatigability (~14% decrease in maximal voluntary contraction torque, p < 0.001) associated with peripheral (decrease in doublet torque and potentiated M‐wave amplitude, p = 0.002 and p < 0.001, respectively) but not central (unchanged voluntary activation, p = 0.79) alterations. However, these acute changes did not differ between NMES protocols and none of the NMES protocols modified markers of CNS excitability. Conclusion: These results may allow to conjecture that chronic effects and treatment effectiveness could be comparable between conventional and wide‐pulse NMES. [ABSTRACT FROM AUTHOR]

Objective Widespread pain hypersensitivity and enhanced temporal summation of pain (TSP) are commonly reported in patients with complex regional pain syndrome (CRPS) and discussed as proxies for central sensitization. This study aimed to directly relate such signs of neuronal hyperexcitability to the pain phenotype of CRPS patients. Methods Twenty-one CRPS patients and 20 healthy controls (HC) were recruited. The pain phenotype including spatial pain extent (assessed in % body surface) and intensity were assessed and related to widespread pain hypersensitivity, TSP, and psychological factors. Quantitative sensory testing (QST) was performed in the affected, the contralateral and a remote (control) area. Results CRPS patients showed decreased pressure pain thresholds in all tested areas (affected: t(34)  = 4.98, P  < .001, contralateral: t(35) = 3.19, P  = .005, control: t(31) = 2.65, P  = .012). Additionally, patients showed increased TSP in the affected area (F(3,111) = 4.57, P  = .009) compared to HC. TSP was even more enhanced in patients with a high compared to a low spatial pain extent (F(3,51) = 5.67, P  = .008), suggesting pronounced spinal sensitization in patients with extended pain patterns. Furthermore, the spatial pain extent positively correlated with the Bath Body Perception Disturbance Scale (ρ = 0.491; P  = .048). Conclusions Overall, we provide evidence that the pain phenotype in CRPS, that is, spatial pain extent, might be related to sensitization mechanism within the central nociceptive system. This study points towards central neuronal excitability as a potential therapeutic target in patients with more widespread CRPS. [ABSTRACT FROM AUTHOR]

Cellular redox status has a crucial role in brain physiology, as well as in pathologic conditions. Physiologic senescence, by dysregulating cellular redox homeostasis and decreasing antioxidant defenses, enhances the central nervous system's susceptibility to diseases. The reduction of free radical accumulation through lifestyle changes, and the supplementation of antioxidants as a prophylactic and therapeutic approach to increase brain health, are strongly suggested. Bilirubin is a powerful endogenous antioxidant, with more and more recognized roles as a biomarker of disease resistance, a predictor of all-cause mortality, and a molecule that may promote health in adults. The alteration of the expression and activity of the enzymes involved in bilirubin production, as well as an altered blood bilirubin level, are often reported in neurologic conditions and neurodegenerative diseases (together denoted NCDs) in aging. These changes may predict or contribute both positively and negatively to the diseases. Understanding the role of bilirubin in the onset and progression of NCDs will be functional to consider the benefits vs. the drawbacks and to hypothesize the best strategies for its manipulation for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Obesity is a common health condition that is increasing worldwide. Obesity is also a multifactorial condition that affects many physiological systems in the human body. Some include the following: central nervous system (CNS) effects, metabolic effects such as type 2 diabetes (T2D), various effects on the cardiovascular system (CVS), haematological effects and infertility in females. Treatment is suggested to be initiated by first making lifestyle changes such as increasing physical activity, decreasing caloric intake of foods, inclusion and accessibility to healthy foods (e.g. fruits, fibre, vegetables) and consuming foods of a lower glycaemic content. In addition to these interventions, pharmacological management strategies can also be considered adjuncts to managing obesity. These medicines (monotherapies/combined products) include amfepramone, cathine (syn D-norpseudoepherine), phendimetrazine, phentermine, orlistat, liraglutide, semaglutide, bupropion and the bupropion-naltrexone combination, and phentermine-topiramate combination. The pharmacist plays an essential role in identifying obese individuals, making suggestions for losing excess weight, suggesting lifestyle modifications, providing information about anti-obesity medicines and dispensing these medicines. [ABSTRACT FROM AUTHOR]

Purpose: In recent years, research has yielded new information regarding the impact of intense, long-term alcohol consumption on the development of permanent changes in the central nervous system. The present study examines the mechanisms related to the existence of addiction memory, sensitization and allostasis. A dual-process model was also created, which analyses the role of conscious and automatic mechanisms in the functioning of addicts. The aim of the article is to present these mechanisms and to consider the implications of their existence for the course of therapy. Views: The mechanisms analysed shed new light on some of the negative phenomena occurring during and after therapy, such as frequent abstinence after treatment, switching addictions, and returning to drinking after a long period of abstinence. The existence of these mechanisms should also change the character of addiction therapy, which has so far focused mainly on conscious aspects and ignored the existence of automatic ones. Attempts are already being made to implement the dual-process model in addiction therapy. Conclusions: A better understanding of the mechanisms resulting from the dual-process model can significantly influence perspectives regarding functioning in addiction and the course of therapy. These processes merit further research, as do possible therapeutic interventions based on them. [ABSTRACT FROM AUTHOR]

Proper functioning of the nervous system relies not only on the generation of a vast repertoire of distinct neural cell types but also on the precise neural circuitry within them. How the generation of highly diverse neural populations is regulated during development remains a topic of interest. Landmark studies in Drosophila have identified the genetic and temporal cues regulating neural diversity and thus have provided valuable insights into our understanding of temporal patterning of the central nervous system. The development of the Drosophila central complex, which is mostly derived from type II neural stem cell (NSC) lineages, showcases how a small pool of NSCs can give rise to vast and distinct progeny. Similar to the human outer subventricular zone (OSVZ) neural progenitors, type II NSCs generate intermediate neural progenitors (INPs) to expand and diversify lineages that populate higher brain centers. Each type II NSC has a distinct spatial identity and timely regulated expression of many transcription factors and mRNA binding proteins. Additionally, INPs derived from them show differential expression of genes depending on their birth order. Together type II NSCs and INPs display a combinatorial temporal patterning that expands neural diversity of the central brain lineages. We cover advances in current understanding of type II NSC temporal patterning and discuss similarities and differences in temporal patterning mechanisms of various NSCs with a focus on how cell-intrinsic and extrinsic hormonal cues regulate temporal transitions in NSCs during larval development. Cell extrinsic ligands activate conserved signaling pathways and extrinsic hormonal cues act as a temporal switch that regulate temporal progression of the NSCs. We conclude by elaborating on how a progenitor's temporal code regulates the fate specification and identity of distinct neural types. At the end, we also discuss open questions in linking developmental cues to neural identity, circuits, and underlying behaviors in the adult fly. [ABSTRACT FROM AUTHOR]

The laboratory mouse has provided tremendous insight to the underpinnings of mammalian central nervous system physiology. In recent years, it has become possible to image single neurons, glia and vascular cells in vivo by using head-fixed preparations combined with cranial windows to study local networks of activity in the living brain. Such approaches have also succeeded without the use of general anesthesia providing insights to the natural behaviors of the central nervous system. However, the same has not yet been developed for the eye, which is constantly in motion. Here we characterize a novel head-fixed preparation that enables high-resolution adaptive optics retinal imaging at the single-cell level in awake-behaving mice. We reveal three new functional attributes of the normal eye that are overlooked by anesthesia: 1) High-frequency, low-amplitude eye motion of the mouse that is only present in the awake state 2) Single-cell blood flow in the mouse retina is reduced under anesthesia and 3) Mouse retinae thicken in response to ketamine/xylazine anesthesia. Here we show key benefits of the awake-behaving preparation that enables study of retinal physiology without anesthesia to study the normal retinal physiology in the mouse. A high-resolution imaging apparatus that allows functional retinal imaging in awake and free moving mice was developed, allowing the study of the effect of anaesthesia on eye motion, blood flow and retinal thickness. [ABSTRACT FROM AUTHOR]

Unrestrained excessive inflammatory responses exacerbate ischemic brain injury and impede post-stroke brain recovery. CD4+CD25+Foxp3+ regulatory T (Treg) cells play important immunosuppressive roles to curtail inflammatory responses and regain immune homeostasis after stroke. Accumulating evidence confirms that Treg cells are neuroprotective at the acute stage after stroke and promote brain repair at the chronic phases. The beneficial effects of Treg cells are mediated by diverse mechanisms involving cell–cell interactions and soluble factor release. Multiple types of cells, including both immune cells and non-immune CNS cells, have been identified to be cellular targets of Treg cells. In this review, we summarize recent findings regarding the function of Treg cells in ischemic stroke and the underlying cellular and molecular mechanisms. The protective and reparative properties of Treg cells endorse them as good candidates for immune therapy. Strategies that boost the numbers and functions of Treg cells have been actively developing in the fields of transplantation and autoimmune diseases. We discuss the approaches for Treg cell expansion that have been tested in stroke models. The application of these approaches to stroke patients may bring new hope for stroke treatments. [ABSTRACT FROM AUTHOR]

Hypogonadism in males confers elevated cardiovascular disease (CVD) risk by unknown mechanisms. Recent radiological evidence suggests that low testosterone (T) is associated with mediobasal hypothalamic (MBH) gliosis, a central nervous system (CNS) cellular response linked to metabolic dysfunction. To address mechanisms linking CNS androgen action to CVD risk, we generated a hypogonadal, hyperlipidemic mouse model with orchiectomy (ORX) combined with hepatic PCSK9 overexpression. After 4 wk of high-fat, high-sucrose diet (HFHS) consumption, despite equal body weights and glucose tolerance, androgen-deficient ORX mice had a more atherogenic lipid profile and increased liver and leukocyte inflammatory signaling compared with sham-operated control mice. Along with these early CVD risk indicators, ORX markedly amplified HFHS-induced astrogliosis in the MBH. Transcriptomic analysis further revealed that ORX and high-fat diet feeding induced upregulation of inflammatory pathways and downregulation of metabolic pathways in hypothalamic astrocytes. To interrogate the role of sex steroid signaling in the CNS in cardiometabolic risk and MBH inflammation, central infusion of T and dihydrotestosterone (DHT) was performed on ORX mice. Central DHT prevented MBH astrogliosis and reduced the liver inflammatory signaling and monocytosis induced by HFHS and ORX; T had a partial protective effect. Finally, a cross-sectional study in 41 adult men demonstrated a positive correlation between radiological evidence of MBH gliosis and plasma lipids. These findings demonstrate that T deficiency in combination with a Western-style diet promotes hypothalamic gliosis concomitant with increased atherogenic risk factors and provide supportive evidence for regulation of lipid metabolism and cardiometabolic risk determinants by the CNS action of sex steroids. NEW & NOTEWORTHY This study provides evidence that hypothalamic gliosis is a key early event through which androgen deficiency in combination with a Western-style diet might lead to cardiometabolic dysregulation in males. Furthermore, this work provides the first evidence in humans of a positive association between hypothalamic gliosis and LDL-cholesterol, advancing our knowledge of CNS influences on CVD risk progression. [ABSTRACT FROM AUTHOR]

Background & Aims: Nerve stem cell transplantation is one of the effective strategies for repairing nerve lesions. Oligodendrocytes are myelinated cells located in the central nervous system and are involved in the formation of myelin axons (8). Oligodendrocytes express O-A proteins, especially O4, which is a marker for the cell body and oligodendrocyte processes, during differentiation and maturation in the central nervous system (29). The results of some studies have shown that glial cells that express only O4 protein have the potential to become precursors of astrocytes and oligodendrocytes and can increase the growth stages in stem cells (29). Glial fibrillary acid protein (GFAP) is known as a specific marker for the identification of astrocytes in the central nervous system. This protein is the main cytoskeleton constituent of astrocytes (27) and plays an important role in maintaining, repairing and maintaining the white matter integrity of the central nervous system as well as the blood-brain barrier (35). The aim of this study was to compare the effect of High intensity interval training with hind limb suspension on the level of GFAP and O4 in glial and neuronal stem cell of male rats. Methods: Twenty-four male wistar rats (body weight = 189.25 ± 5.71g.) were randomly divided into four groups: HIIT+HLS (n= 6), HIIT (n= 6), HLS (n= 6) or CON (n= 6). The exercise protocol was performed on a rodent treadmill for 6 weeks, 5 sessions per week. The rats were sampled and studied 24 h after last training session. Glial fibrillary acidic protein (GFAP) and monoclonal antibody O4 (O4) were analyzed before and after the training interventions. To suspend the lower limb, the animal's tail was first cleaned and dried using cotton and alcohol. Then two-thirds of the mouse tail was taped longitudinally from the beginning to the end third. Next, three pieces of kinesio-tape were placed transversely on the mouse tail, so that normal blood flow was not disturbed. We attached the upper end of the kinesio-tape to the suspension hook and then has been attached the hook to the cage movable bar chain so that the angle between the animal's chest and the floor of the cage is 30 degrees and the mouse legs do not come into contact with the floor of the cage. The suspension system, including a movable bar, pulley and hook, was mounted on top and on both parallel sides of the cage, allowing the animal to have full access to all parts of the cage by moving freely around a 360-degree axis. Data analysis was used using Shapiro-Wilk and Levine tests to investigate the natural distribution of data and homogeneity of variances and one-way and post-hoc Bonferroni statistics to test research hypotheses. Results: The results suggested that the percentage of changes in the amounts of fibrillary acidic protein of the cerebral hippocampus of the brain in the intense interval training group + group under the conditions of the hind legs compared to the control group showed a significant decrease (p≥0.001). Also, the percentage of changes in cerebral hippocampal glial fibrillary acid protein in the lower extremity suspension group increased significantly more than the control group (p≥0.001), but the percentage of changes in this protein in the intense interval training group compared to the group There was no significant difference in control (p≥1,000). The results of the data obtained from the percentage of changes in the O4 protein of the cerebral hippocampus of the groups showed that this change was significantly lower in the group of intense interval training with the conditions of the hind limb suspended than the control group (p≥0.001). Also, the percentage of O4 changes in the cerebral hippocampus in the lower extremity suspension group was significantly higher than the control (p≥0.001). In addition, the percentage of changes in the intense interval training group was not significantly different from the control group (p≥0.465). Conclusion: The results of this study revealed that HIIT+HLS was being able to prevent damage to the cells of the central nervous system and direct the neural stem cells towards the production of neurons, astrocyte and oligodendrocyte. Mesenchymal stem cells are currently the main choice for cellular treatment of neuropsychiatric diseases. Mechanical stimuli have been reported to play a decisive role in the final fate of stem cells and their cell differentiation pathways, so that the path and flow of induced signals and activated factors determine cellular fate in time, position, and mediate an appropriate number (36). Studies have shown that the proliferation, differentiation, and cytoskeleton organization of stem cells are affected by microgravity and tend to produce neurons or nerve cells (31). Astroglia cells also act as neuronal stem cells and participate in neurogenesis. Evidence suggests a very important role for these cells during plasticity. These cells are involved in the neurogenesis of the adult mammalian brain in the ventricular region, and in the sub-granular region and the olfactory bulb. On the other hand, previous research has shown that lactate production during intense interval trainings and suspension of hind legs can play an important role in the development of oligodendrocytes and myelination, so that increasing lactate production as a substrate in myelination, and used by the nervous system. Considering this issue, it is possible to use this exercise mode in the condition of lower limb suspension as a treatment method or non-pharmacological supplement effective in neuromuscular disorders and other related diseases, to enhance fitness in athletes, improve injury and also prevention of adverse effects of being in weightlessness, especially on space missions. In general, the results show that intense interval training with hind leg suspension conditions had a greater effect on health and no damage to the hippocampus of the brain of a healthy male rat than other groups (intense interval, suspension or control group). Since no research has been done on the effect of intense interval training under the conditions of hind limb suspension on cellular changes in the hippocampus and human brain, judgment in this regard needs further study. Findings of this study may help in the rehabilitation process of people with neuromotor disorders, injured athletes, the elderly, sedentary people, as well as the conditioning program of athletes in various sports to adapt to the use of such exercises. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the glymphatic function in patients with new daily persistent headache (NDPH) using the diffusion tensor image analysis along the perivascular space (DTI‐ALPS) method. Background: NDPH, a rare and treatment‐refractory primary headache disorder, is poorly understood. There is limited evidence to suggest that headaches are associated with glymphatic dysfunction. Thus far, no studies have evaluated glymphatic function in patients with NDPH. Methods: In this cross‐sectional study conducted in the Headache Center of Beijing Tiantan Hospital, patients with NDPH and healthy controls were enrolled. All participants underwent brain magnetic resonance imaging examinations. Clinical characteristics and neuropsychological evaluation were examined in patients with NDPH. ALPS indexes for both hemispheres were measured to determine the glymphatic system function in patients with NDPH and healthy controls. Results: In total, 27 patients with NDPH (14 males, 13 females; age [mean ± standard deviation (SD)]: 36.6 ± 20.6) and 33 healthy controls (15 males, 18 females; age [mean ± SD]: 36.0 ± 10.8) were included in the analysis. No significant differences between groups were observed in the left ALPS index (1.583 ± 0.182 vs. 1.586 ± 0.175, mean difference = 0.003, 95% confidence interval [CI] of difference = −0.089 to 0.096, p = 0.942), or right ALPS index (1.578 ± 0.230 vs. 1.559 ± 0.206, mean difference = −0.027, 95% CI of difference = −0.132 to 0.094, p = 0.738). Additionally, ALPS indexes were not correlated with clinical characteristics or neuropsychiatric scores. Conclusion: No glymphatic dysfunction was detected in patients with NDPH by means of the ALPS method. Additional studies with larger samples are needed to confirm these preliminary findings and improve the understanding of glymphatic function in NDPH. [ABSTRACT FROM AUTHOR]

Secreted amyloid precursor protein alpha (sAPPα), processed from a parent mammalian brain protein, amyloid precursor protein, can modulate learning and memory. Recently it has been shown to modulate the transcriptome and proteome of human neurons, including proteins with neurological functions. Here, we analysed whether the acute administration of sAPPα facilitated changes in the proteome and secretome of mouse primary astrocytes in culture. Astrocytes contribute to the neuronal processes of neurogenesis, synaptogenesis and synaptic plasticity. Cortical mouse astrocytes in culture were exposed to 1 nM sAPPα, and changes in both the whole-cell proteome (2 h) and the secretome (6 h) were identified with Sequential Window Acquisition of All Theoretical Fragment Ion Spectra–Mass Spectrometry (SWATH-MS). Differentially regulated proteins were identified in both the cellular proteome and secretome that are involved with neurologically related functions of the normal physiology of the brain and central nervous system. Groups of proteins have a relationship to APP and have roles in the modulation of cell morphology, vesicle dynamics and the myelin sheath. Some are related to pathways containing proteins whose genes have been previously implicated in Alzheimer's disease (AD). The secretome is also enriched in proteins related to Insulin Growth Factor 2 (IGF2) signaling and the extracellular matrix (ECM). There is the promise that a more specific investigation of these proteins will help to understand the mechanisms of how sAPPα signaling affects memory formation. [ABSTRACT FROM AUTHOR]

Recent research integrates novel technologies and methods from the interface of RNA biology and neuroscience. This advancing integration of both fields creates new opportunities in neuroscience to deepen the understanding of gene expression programs and their regulation that underlies the cellular heterogeneity and physiology of the central nervous system. Currently, transcriptional heterogeneity can be studied in individual neural cell types in health and disease. Furthermore, there is an increasing interest in RNA technologies and their application in neurology. These aspects were discussed at an online conference that was shortly named NeuroRNA. [ABSTRACT FROM AUTHOR]

After an injury, the limited regenerative capacity of the central nervous system makes the reconnection and functional recovery of the affected nervous tissue almost impossible. To address this problem, biomaterials appear as a promising option for the design of scaffolds that promote and guide this regenerative process. Based on previous seminal works on the ability of regenerated silk fibroin fibers spun through the straining flow spinning (SFS) technique, this study is intended to show that the usage of functionalized SFS fibers allows an enhancement of the guidance ability of the material when compared with the control (nonfunctionalized) fibers. It is shown that the axons of the neurons not only tend to follow the path marked by the fibers, in contrast to the isotropic growth observed on conventional culture plates, but also that this guidance can be further modulated through the biofunctionalization of the material with adhesion peptides. Establishing the guidance ability of these fibers opens the possibility of their use as implants for spinal cord injuries, so that they may represent the core of a therapy that would allow the reconnection of the injured ends of the spinal cord. [ABSTRACT FROM AUTHOR]

The function of the protein-coupled receptor 35 (GPR35) in the central nervous system (CNS) remains largely unknown. Due to its expression in the ventral striatum, a key area in the brain reward system, the function of GPR35 in reinforcing actions is questioning. To analyze if activation of GPR35 in the ventral striatum is related to reinforcing actions, male Wistar rats (250-300 g) received stereotaxic surgery to place guide cannulae in the ventral striatum. Lodoxamide (a full rat-GPR35 agonist) or vehicle (DMSO 10%) were injected (intra-ventral-striatum) in the absence and during the pretreatment with ML-194 (a selective GPR35 antagonist). Lodoxamide (100 pmol) induced a significant increment in preference for the drug-conditioning chamber (p < 0.05), but not vehicle or ML-194 per se (p > 0.05). On the other hand, the pretreatment with ML-194 did not prevent lodoxamide's reinforcing effects. Thus, the reinforcing actions of lodoxamide (intra-ventral-striatum) involve mechanisms likely independent of GPR35 which remains to be identified; and a role for GPR35 in the brain reward systems (at least in ventral striatum) seems improbable. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether sensitivity to movement‐evoked pain (SMEP), central sensitivity symptom burden, and quantitative sensory testing (QST) outcomes differ between healthy controls and people with chronic shoulder pain. Methods: People with chronic shoulder pain (n = 39) and healthy controls (n = 26) completed validated questionnaires measuring demographic, pain characteristics, psychological factors, social support, sleep quality, central sensitivity inventory (CSI), and physical activity levels. A blinded assessor administered QST measuring pressure pain threshold, temporal summation, conditioned pain modulation, and cold hyperalgesia. All participants performed repeated lifting of weighted canisters and reported severity of pain over successive lifts of the weighted canisters. Between‐group differences in the QST, SMEP and CSI scores were investigated. Demographic and psychosocial variables were adjusted in the analyses. Results: Dynamic mechanical allodynia, mechanical temporal summation, movement‐evoked pain scores, SMEP index, and CSI scores were significantly (p ≤ 0.05) higher in the chronic shoulder pain group than in healthy controls. A significant proportion of people with chronic shoulder pain presented with pro‐nociceptive profiles and experienced higher pain severity, interference, and disability. Conclusions: People with chronic shoulder pain displayed symptoms and signs of central sensitization. Future research should investigate the predictive role of central sensitization on clinical outcomes in shoulder pain. [ABSTRACT FROM AUTHOR]

Vitamin D has come up as a pluripotent biochemical modulator of several systemic functions including its wellestablished musculoskeletal effects functioning as well as other key roles in nervous, cardiac, immune, vascular, and endocrinological systems. It undergoes metabolic activation in the skin, liver, and kidneys to exert its systemic actions primarily through Vitamin D receptor-mediated gene expression. In recent times, the involvement of Vitamin D has been documented in the regulation of neurotrophins, neural differentiation, and maturation, and the synthesis of neuromodulators including acetylcholine, dopamine, and gamma-aminobutyric acid. Clinical studies have also highlighted the involvement of Vitamin D in neurological disorders, thereby underscoring its potential in the clinical management of such disorders. Further, research is required to determine the multipronged roles of Vitamin D and its molecular pathways in neurophysiology for the potential prevention and treatment of neurological dysfunction. [ABSTRACT FROM AUTHOR]

Mounting evidence shows that the complex gut microbial ecosystem in the human gastrointestinal (GI) tract regulates the physiology of the central nervous system (CNS) via microbiota and the gut–brain (MGB) axis. The GI microbial ecosystem communicates with the brain through the neuroendocrine, immune, and autonomic nervous systems. Recent studies have bolstered the involvement of dysfunctional MGB axis signaling in the pathophysiology of several neurodegenerative, neurodevelopmental, and neuropsychiatric disorders (NPDs). Several investigations on the dynamic microbial system and genetic–environmental interactions with the gut microbiota (GM) have shown that changes in the composition, diversity and/or functions of gut microbes (termed "gut dysbiosis" (GD)) affect neuropsychiatric health by inducing alterations in the signaling pathways of the MGB axis. Interestingly, both preclinical and clinical evidence shows a positive correlation between GD and the pathogenesis and progression of NPDs. Long-term GD leads to overstimulation of hypothalamic–pituitary–adrenal (HPA) axis and the neuroimmune system, along with altered neurotransmitter levels, resulting in dysfunctional signal transduction, inflammation, increased oxidative stress (OS), mitochondrial dysfunction, and neuronal death. Further studies on the MGB axis have highlighted the significance of GM in the development of brain regions specific to stress-related behaviors, including depression and anxiety, and the immune system in the early life. GD-mediated deregulation of the MGB axis imbalances host homeostasis significantly by disrupting the integrity of the intestinal and blood–brain barrier (BBB), mucus secretion, and gut immune and brain immune functions. This review collates evidence on the potential interaction between GD and NPDs from preclinical and clinical data. Additionally, we summarize the use of non-therapeutic modulators such as pro-, pre-, syn- and post-biotics, and specific diets or fecal microbiota transplantation (FMT), which are promising targets for the management of NPDs. [ABSTRACT FROM AUTHOR]

Background Central nervous system (CNS) function after ACLR, quantified by the blood oxygen level dependent (BOLD) response, is altered in regions of sensory function during knee movement after ACLR. However, it is unknown how this altered neural response may manifest in knee loading and response to sensory perturbations during sport specific movements. Purpose To investigate the relationship among CNS function and lower extremity kinetics, under multiple visual conditions, during 180° change of direction task in individuals with a history of ACLR. Methods Eight participants, 39.3 ± 37.1 months after primary, left ACLR performed repetitive active knee flexion and extension of their involved knee during fMRI scanning. Participants separately performed 3D motion capture analysis of a 180° change of direction task under full vision (FV) and stroboscopic vision (SV) conditions. A neural correlate analysis was performed to associate BOLD signal to knee loading of the left lower extremity. Results Involved limb peak internal knee extension moment (pKEM) was significantly lower in the SV condition (1.89 ± 0.37 N*m/Kg) compared to the FV condition (2.0 ± 0.34 N*m/Kg) (p = .018). Involved limb pKEM during the SV condition was positively correlated with BOLD signal in the contralateral precuneus and superior parietal lobe (Voxels: 53; p = .017; z-stat max: 6.47; MNI peak: 6, -50, 66). Conclusion There is a positive association between involved limb pKEM in the SV condition and BOLD response in areas of visual-sensory integration. Activation of contralateral precuneus and superior parietal lobe brain regions may be a strategy to maintain joint loading when vision is perturbed. Level of Evidence Level 3 [ABSTRACT FROM AUTHOR]