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Biophysical Reviews Aug 2023Diabetes mellitus (DM) leads to medical complications, the epidemiologically most important of which is diabetic peripheral neuropathy (DPN). Electrophysiology is a... (Review)
Review
Diabetes mellitus (DM) leads to medical complications, the epidemiologically most important of which is diabetic peripheral neuropathy (DPN). Electrophysiology is a major component of neural functioning and several studies have been undertaken to elucidate the neural electrophysiological alterations caused by DM and their mechanisms of action. Due to the importance of electrophysiology for neuronal function, the review of the studies dealing predominantly with electrophysiological parameters and mechanisms in the neuronal somata of peripheral neural ganglia of diabetic animals during the last 45 years is here undertaken. These studies, using predominantly techniques of electrophysiology, most frequently patch clamp for voltage clamp studies of transmembrane currents through ionic channels, have investigated the experimental DPN. They also have demonstrated that various cellular and molecular mechanisms of action of diabetic physiopathology at the level of biophysical electrical parameters are affected in DPN. Thus, they have demonstrated that several passive and active transmembrane voltage parameters, related to neuronal excitability and neuronal functions, are altered in diabetes. The majority of the studies agreed that DM produces depolarization of the resting membrane potential; alters excitability, increasing and decreasing it in dorsal root ganglia (DRG) and in nodose ganglion, respectively. They have tried to relate these changes to sensorial alterations of DPN. Concerning ionic currents, predominantly studied in DRG, the most frequent finding was increases in Na, Ca, and TRPV1 cation current, and decreases in K current. This review concluded that additional studies are needed before an understanding of the hierarchized, time-dependent, and integrated picture of the contribution of neural electrophysiological alterations to the DPN could be reached. DM-induced electrophysiological neuronal alterations that so far have been demonstrated, most of them likely important, are either consistent with the DPN symptomatology or suggest important directions for improvement of the elucidation of DPN physiopathology, which the continuation seems to us very relevant.
PubMed: 37681090
DOI: 10.1007/s12551-023-01094-1 -
Cortex; a Journal Devoted To the Study... Jan 2015The most widely accepted model of obsessive-compulsive disorder (OCD) assumes brain abnormalities in the "affective circuit", mainly consisting of volume reduction in... (Review)
Review
The most widely accepted model of obsessive-compulsive disorder (OCD) assumes brain abnormalities in the "affective circuit", mainly consisting of volume reduction in the medial orbitofrontal, anterior cingulate and temporolimbic cortices, and tissue expansion in the striatum and thalamus. The advent of whole-brain, voxel-based morphometry (VBM) has provided increasing evidence that regions outside the "affective" orbitofronto-striatal circuit are involved in OCD. Nevertheless, potential confounds from the different image analysis methods, as well as other factors, such as patients' medication and comorbidity status, may limit generalization of results. In the present paper, we systematically reviewed the whole-brain VBM literature on OCD by focussing specifically on degree of consistency between studies, extent to which findings have been replicated and interrelation between clinical variables and OCD anatomy, a potentially crucial factor that has been systematically examined only in a limited number of studies. The PubMed database was searched through February 2012. A total of 156 studies were identified; 18 of them fulfilled the inclusion/exclusion criteria and included 511 patients and 504 controls. Results support the notion that the brain alterations responsible for OCD are represented at the network level, and that widespread structural abnormalities may contribute to neurobiological vulnerability to OCD. Apart from defects in regions within the classic "affective" circuit, volume reduction of the cortical source of the dorsolateral (DL) prefronto-striatal "executive" circuit (dorsomedial, DL, ventrolateral and frontopolar prefrontal cortices), and of reciprocally connected regions (temporo-parieto-occipital associative areas) is consistently described in OCD patients. Moreover, increased volume of the internal capsule and reduced frontal and parietal white matter volumes may account for altered anatomical connectivity in fronto-subcortical circuitry. Morphometric changes in both "affective" and "executive" parallel the disease clinical course, being at the same time responsible for variation in symptom severity. Thus, OCD mechanisms involve a more widespread network of cerebral dysfunctions than previously thought, which may explain the heterogeneity in clinical manifestations and symptom severity.
Topics: Brain; Humans; Magnetic Resonance Imaging; Neural Pathways; Obsessive-Compulsive Disorder; Organ Size
PubMed: 23582297
DOI: 10.1016/j.cortex.2013.01.016 -
Frontiers in Synaptic Neuroscience 2023The synapse has consistently been considered a vulnerable and critical target within Alzheimer's disease, and synapse loss is, to date, one of the main biological... (Review)
Review
The synapse has consistently been considered a vulnerable and critical target within Alzheimer's disease, and synapse loss is, to date, one of the main biological correlates of cognitive decline within Alzheimer's disease. This occurs prior to neuronal loss with ample evidence that synaptic dysfunction precedes this, in support of the idea that synaptic failure is a crucial stage within disease pathogenesis. The two main pathological hallmarks of Alzheimer's disease, abnormal aggregates of amyloid or tau proteins, have had demonstrable effects on synaptic physiology in animal and cellular models of Alzheimer's disease. There is also growing evidence that these two proteins may have a synergistic effect on neurophysiological dysfunction. Here, we review some of the main findings of synaptic alterations in Alzheimer's disease, and what we know from Alzheimer's disease animal and cellular models. First, we briefly summarize some of the human evidence to suggest that synapses are altered, including how this relates to network activity. Subsequently, animal and cellular models of Alzheimer's disease are considered, highlighting mouse models of amyloid and tau pathology and the role these proteins may play in synaptic dysfunction, either in isolation or examining how the two pathologies may interact in dysfunction. This specifically focuses on neurophysiological function and dysfunction observed within these animal models, typically measured using electrophysiology or calcium imaging. Following synaptic dysfunction and loss, it would be impossible to imagine that this would not alter oscillatory activity within the brain. Therefore, this review also discusses how this may underpin some of the aberrant oscillatory patterns seen in animal models of Alzheimer's disease and human patients. Finally, an overview of some key directions and considerations in the field of synaptic dysfunction in Alzheimer's disease is covered. This includes current therapeutics that are targeted specifically at synaptic dysfunction, but also methods that modulate activity to rescue aberrant oscillatory patterns. Other important future avenues of note in this field include the role of non-neuronal cell types such as astrocytes and microglia, and mechanisms of dysfunction independent of amyloid and tau in Alzheimer's disease. The synapse will certainly continue to be an important target within Alzheimer's disease for the foreseeable future.
PubMed: 36970154
DOI: 10.3389/fnsyn.2023.1129036 -
Pharmacological Reports : PR Oct 2022Insulin resistance and impaired lipoprotein metabolism contribute to a plethora of metabolic and cardiovascular disorders. These alterations have been extensively linked... (Review)
Review
Insulin resistance and impaired lipoprotein metabolism contribute to a plethora of metabolic and cardiovascular disorders. These alterations have been extensively linked with poor lifestyle choices, such as consumption of a high-fat diet, smoking, stress, and a redundant lifestyle. Moreover, these are also known to increase the co-morbidity of diseases like Type 2 diabetes mellitus and atherosclerosis. Under normal physiological conditions, insulin and lipoproteins exert a neuroprotective role in the central nervous system. However, the tripping of balance between the periphery and center may alter the normal functioning of the brain and lead to neurological disorders such as Alzheimer's disease, Parkinson's disease, stroke, depression, and multiple sclerosis. These neurological disorders are further characterized by certain behavioral and molecular changes that show consistent overlap with alteration in insulin and lipoprotein signaling pathways. Therefore, targeting these two mechanisms not only reveals a way to manage the co-morbidities associated with the circle of the metabolic, central nervous system, and cardiovascular disorders but also exclusively work as a disease-modifying therapy for neurological disorders. In this review, we summarize the role of insulin resistance and lipoproteins in the progression of various neurological conditions and discuss the therapeutic options currently in the clinical pipeline targeting these two mechanisms; in addition, challenges faced in designing these therapeutic approaches have also been touched upon briefly.
Topics: Humans; Insulin; Insulin Resistance; Diabetes Mellitus, Type 2; Lipoproteins; Nervous System Diseases; Cardiovascular Diseases
PubMed: 36149598
DOI: 10.1007/s43440-022-00417-5 -
Journal of Animal Science May 2019In vitro embryo production (IVP) in cattle has gained worldwide interest in recent years, but the efficiency of using IVP embryos for calf production is far from... (Review)
Review
In vitro embryo production (IVP) in cattle has gained worldwide interest in recent years, but the efficiency of using IVP embryos for calf production is far from optimal. This review will examine the pregnancy retention rates of IVP embryos and explore causes for pregnancy failures. Based on work completed over the past 25 yr, only 27% of cattle receiving IVP embryos will produce a live calf. Approximately 60% of these pregnancies fail during the first 6 wk of gestation. When compared with embryos generated by superovulation, pregnancy rates are 10% to 40% lower for cattle carrying IVP embryos, exemplifying that IVP embryos are consistently less competent than in vivo-generated embryos. Several abnormalities have been observed in the morphology of IVP conceptuses. After transfer, IVP embryos are less likely to undergo conceptus elongation, have reduced embryonic disk diameter, and have compromised yolk sac development. Marginal binucleate cell development, cotyledon development, and placental vascularization have also been documented, and these abnormalities are associated with altered fetal growth trajectories. Additionally, in vitro culture conditions increase the risk of large offspring syndrome. Further work is needed to decipher how the embryo culture environment alters post-transfer embryo development and survival. The risk of these neonatal disorders has been reduced by the use of serum-free synthetic oviductal fluid media formations and culture in low oxygen tension. However, alterations are still evident in IVP oocyte and embryo transcript abundances, timing of embryonic cleavage events and blastulation, incidence of aneuploidy, and embryonic methylation status. The inclusion of oviductal and uterine-derived embryokines in culture media is being examined as one way to improve the competency of IVP embryos. To conclude, the evidence presented herein clearly shows that bovine IVP systems still must be refined to make it an economical technology in cattle production systems. However, the current shortcomings do not negate its current value for certain embryo production needs and for investigating early embryonic development in cattle.
Topics: Animals; Cattle; Embryo Transfer; Embryo, Mammalian; Embryonic Development; Female; Oocytes; Placenta; Pregnancy; Pregnancy Rate; Uterus
PubMed: 30968113
DOI: 10.1093/jas/skz116 -
Frontiers in Microbiology 2023The alpine grassland ecosystem is a biodiversity hotspot of plants on the Qinghai-Tibetan Plateau, where rapid climate change is altering the patterns of plant...
The alpine grassland ecosystem is a biodiversity hotspot of plants on the Qinghai-Tibetan Plateau, where rapid climate change is altering the patterns of plant biodiversity along elevational and seasonal gradients of environments. However, how belowground microbial biodiversity changes along elevational gradient during the growing season is not well understood yet. Here, we investigated the elevational distribution of soil prokaryotic communities by using 16S rRNA amplicon sequencing along an elevational gradient between 3,200 and 4,200 m, and a seasonal gradient between June and September in the Qinghai-Tibetan alpine grasslands. First, we found soil prokaryotic diversity and community composition significantly shifted along the elevational gradient, mainly driven by soil temperature and moisture. Species richness did not show consistent elevational trends, while those of evenness declined with elevation. Copiotrophs and symbiotic diazotrophs declined with elevation, while oligotrophs and AOB increased, affected by temperature. Anaerobic or facultatively anaerobic bacteria and AOA were hump-shaped, mainly influenced by moisture. Second, seasonal patterns of community composition were mainly driven by aboveground biomass, precipitation, and soil temperature. The seasonal dynamics of community composition indicated that soil prokaryotic community, particularly Actinobacteria, was sensitive to short-term climate change, such as the monthly precipitation variation. At last, dispersal limitation consistently dominated the assembly process of soil prokaryotic communities along both elevational and seasonal gradients, especially for those of rare species, while the deterministic process of abundant species was relatively higher at drier sites and in drier July. The balance between deterministic and stochastic processes in abundant subcommunities might be strongly influenced by water conditions (precipitation/moisture). Our findings suggest that both elevation and season can alter the patterns of soil prokaryotic biodiversity in alpine grassland ecosystem of Qinghai-Tibetan Plateau, which is a biodiversity hotspot and is experiencing rapid climate change. This work provides new insights into the response of soil prokaryotic communities to changes in elevation and season, and helps us understand the temporal and spatial variations in such climate change-sensitive regions.
PubMed: 37808282
DOI: 10.3389/fmicb.2023.1280011 -
Urology Practice Nov 2023We evaluated germline and somatic testing practices and compared results from tissue and liquid biopsy specimens in a large community urology setting.
INTRODUCTION
We evaluated germline and somatic testing practices and compared results from tissue and liquid biopsy specimens in a large community urology setting.
METHODS
A retrospective analysis was performed on advanced prostate cancer patients from a single community practice between June 2016 and September 2021. Clinical data and sequencing results from tissue and liquid biopsy specimens were available for 389 patients. Genomic data were available for 81 tissues and 74 liquid biopsy specimens. Comparison of genomic findings included 81 tissues and 27 liquid biopsy specimens. The number of actionable biomarkers and patients screened and enrolled in clinical trials was assessed from germline and somatic testing. Frequency of pathogenically altered genes, alteration types, and biomarkers were assessed from tissue and liquid specimens. Alteration frequency was compared between specimen types for the top 25 altered genes.
RESULTS
Clinically relevant alterations were found from germline and somatic testing in both tissue and liquid biopsy specimens. The frequency of microsatellite instability-high, tumor mutational burden-high, or alterations in homologous recombination repair genes was consistent with published findings. Concordance between tissue and liquid findings varied with low circulating tumor DNA.
CONCLUSIONS
Germline and somatic testing is critical for treatment decisions and should be standard of care for community practices. Liquid biopsy is a viable alternative when circulating tumor DNA is high.
PubMed: 37647173
DOI: 10.1097/UPJ.0000000000000454 -
Journal of Sport and Health Science May 2024B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins. Exercise...
BACKGROUND
B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins. Exercise alters B cell counts and immunoglobulin levels, but evidence-based conclusions on potential benefits for adaptive immunity are lacking. This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells, immunoglobulins, and markers of secretory immunity in human biofluids.
METHODS
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, MEDLINE, Web of Science, and Embase were searched on March 8, 2023. Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions, immunoglobulin levels, salivary flow rate, or secretory immunoglobulin A secretion rate were included. Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise. Study characteristics, outcome measures, and statistically significant changes were summarized tabularly.
RESULTS
Of the 67 eligible studies, 22 applied acute exercise and 45 applied exercise training. All included outcomes revealed significant alterations over time in acute exercise and exercise training context, but only a few investigations showed significant differences compared to control conditions. Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.
CONCLUSION
B cell-related outcomes are altered by acute exercise and exercise training, but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities. Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.
Topics: Humans; Adaptive Immunity; B-Lymphocytes; Biomarkers; Exercise; Immunoglobulin A, Secretory; Saliva
PubMed: 37832643
DOI: 10.1016/j.jshs.2023.10.002 -
Medicine and Science in Sports and... Jan 2020The influence of interdependency between competitors on pacing decision-making and information-seeking behavior has been explored. This has been done by only altering... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The influence of interdependency between competitors on pacing decision-making and information-seeking behavior has been explored. This has been done by only altering instructions, and thereby action possibilities, while controlling environment (i.e., competitor behavior) and exercise task.
METHODS
Twelve participants performed a 4-km time trial on a Velotron cycle ergometer in a randomized, counterbalanced order alone with no virtual opponent (NO), against a virtual opponent with no restrictions (low athlete-opponent interdependency [OP-IND]), or against a virtual opponent who the participant was permitted to overtake only once during the trial (high athlete-opponent interdependency [OP-DEP]). Information-seeking behavior was evaluated using an SMI eye tracker. Differences in pacing, performance, and information-seeking behavior were examined using repeated-measures ANOVA (P < 0.05).
RESULTS
Neither mean power output (NO, 298 ± 35 W; OP-IND, 297 ± 38 W; OP-DEP, 296 ± 37 W) nor finishing time (NO, 377.7 ± 17.4 s; OP-IND, 379.3 ± 19.5 s; OP-DEP, 378.5 ± 17.7 s) differed between experimental conditions. However, power output was lower in the first kilometer of OP-DEP compared with the other experimental conditions (NO, 332 ± 59 W; OP-IND, 325 ± 62 W; OP-DEP, 316 ± 58 W; both P < 0.05), and participants decided to wait longer before they overtook their opponent (OP-IND, 137 ± 130 s; OP-DEP, 255 ± 107 s; P = 0.040). Moreover, total fixation time spent on the avatar of the virtual opponent increased when participants were only allowed to overtake once (OP-IND, 23.3 ± 16.6 s; OP-DEP, 55.8 ± 32.7 s; P = 0.002).
CONCLUSION
A higher interdependency between athlete and opponent altered pacing behavior in terms of in-race adaptations based on opponent's behavior, and it induced an increased attentional focus on the virtual opponent. Thus, in the context of exercise regulation, attentional cues are likely to be used in an adaptive way according to their availability and situational relevance, consistent with a decision-making framework based on the interdependence of perception and action.
Topics: Adult; Athletic Performance; Attention; Bicycling; Competitive Behavior; Cues; Decision Making; Exercise Test; Humans; Information Seeking Behavior; Middle Aged
PubMed: 31343518
DOI: 10.1249/MSS.0000000000002101 -
Quarterly Journal of Experimental... Oct 2019Previous research on the effect of perturbed auditory feedback in speech production has focused on two types of responses. In the short term, speakers generate...
Previous research on the effect of perturbed auditory feedback in speech production has focused on two types of responses. In the short term, speakers generate compensatory motor commands in response to unexpected perturbations. In the longer term, speakers adapt feedforward motor programmes in response to feedback perturbations, to avoid future errors. The current study investigated the relation between these two types of responses to altered auditory feedback. Specifically, it was hypothesised that consistency in previous feedback perturbations would influence whether speakers adapt their feedforward motor programmes. In an altered auditory feedback paradigm, formant perturbations were applied either across all trials (the consistent condition) or only to some trials, whereas the others remained unperturbed (the inconsistent condition). The results showed that speakers' responses were affected by feedback consistency, with stronger speech changes in the consistent condition compared with the inconsistent condition. Current models of speech-motor control can explain this consistency effect. However, the data also suggest that compensation and adaptation are distinct processes, which are not in line with all current models.
Topics: Adult; Feedback, Sensory; Female; Humans; Male; Motor Activity; Speech; Speech Perception; Young Adult
PubMed: 30836818
DOI: 10.1177/1747021819838939