Despite the prevalence of neck pain, evidence is lacking regarding the relationship of pathophysiology to function in people with neck conditions. Although movement-based diagnoses based on directional preference (DP) are described for lumbar spinal conditions, how these diagnoses guide interventions is not supported in the Cervical Spine Clinical Practice Guidelines. To date, there are no case studies in the literature that demonstrate the efficacy of cervical spine management based on a rotation DP.
View Article and Find Full Text PDFThe modulation of dopamine release from midbrain projections to the striatum has long been demonstrated in reward-based learning, but the synaptic basis of aversive learning is far less characterized. The cerebellum receives axonal projections from the locus coeruleus, and norepinephrine release is implicated in states of arousal and stress, but whether aversive learning relies on plastic changes in norepinephrine release in the cerebellum is unknown. Here we report that in mice, norepinephrine is released in the cerebellum following an unpredicted noxious event (a foot-shock) and that this norepinephrine release is potentiated powerfully with fear acquisition as animals learn that a previously neutral stimulus (tone) predicts the aversive event.
View Article and Find Full Text PDFMyriad neuropsychiatric disorders are due to dopamine dysfunction. However, understanding these disorders is limited by our ability to measure dopamine storage and release. Fluorescent false neurotransmitters (FFNs), small-molecule dyes that co-transit through the synaptic vesicle cycle, have allowed us to image dopamine in cell culture and acute brain slice, but microscopy is constrained by the biopenetrance of light.
View Article and Find Full Text PDFDopamine is a modulatory neurotransmitter involved in learning, motor functions, and reward. Many neuropsychiatric disorders, including Parkinson's disease, autism, and schizophrenia, are associated with imbalances or dysfunction in the dopaminergic system. Yet, our understanding of these pervasive public health issues is limited by our ability to effectively image dopamine in humans, which has long been a goal for chemists and neuroscientists.
View Article and Find Full Text PDFDynamic changes in motor abilities and motivated behaviors occur during the juvenile and adolescent periods. The striatum is a subcortical nucleus critical to action selection, motor learning, and reward processing. Its tonically active cholinergic interneuron (ChI) is an integral regulator of the synaptic activity of other striatal neurons, as well as afferent axonal projections of midbrain dopamine (DA) neurons; however, little is known about its development.
View Article and Find Full Text PDFMacroautophagy (hereafter referred to as autophagy) plays a critical role in neuronal function related to development and degeneration. Here, we investigated whether autophagy is developmentally regulated in the striatum, a brain region implicated in neurodevelopmental disease. We demonstrate that autophagic flux is suppressed during striatal postnatal development, reaching adult levels around postnatal day 28 (P28).
View Article and Find Full Text PDFJ Man Manip Ther
February 2020
: Morton's neuroma (MN) is a neuralgia involving the common plantar digital nerves of the metatarsal region. Evidence-based treatment options for MN are sparse, and utility of physical therapy (PT) is unknown. Mechanical Diagnosis and Therapy (MDT) is a classification system utilizing direction-specific treatment for orthopedic conditions based on mechanical and symptomatic response to repeated end range movements.
View Article and Find Full Text PDFMorton's neuroma (MN) is a neuralgia involving the common plantar digital nerves of the metatarsal region. Evidence-based treatment options for this condition are sparse, and physiotherapy's usefulness is limited. A woman aged 44 years was referred to physiotherapy for left forefoot pain lasting 3 months.
View Article and Find Full Text PDFSeveral lines of evidence place alpha-synuclein (aSyn) at the center of Parkinson's disease (PD) etiology, but it is still unclear why overexpression or mutated forms of this protein affect some neuronal populations more than others. Susceptible neuronal populations in PD, dopaminergic neurons of the substantia nigra pars compacta (SNpc) and the locus coeruleus (LC), are distinguished by relatively high cytoplasmic concentrations of dopamine and calcium ions. Here we review the evidence for the multi-hit hypothesis of neurodegeneration, including recent papers that demonstrate synergistic interactions between aSyn, calcium ions and dopamine that may lead to imbalanced protein turnover and selective susceptibility of these neurons.
View Article and Find Full Text PDFA cation-π interaction between the ammonium group of an agonist and a conserved tryptophan termed TrpB is a near universal feature of agonist binding to nicotinic acetylcholine receptors (nAChRs). TrpB is one of five residues that form the aromatic box of the agonist binding site, and for the prototype agonists ACh and nicotine, only TrpB makes a functional cation-π interaction. We report that, in addition to TrpB, a significant cation-π interaction is made to a second aromatic, TyrC2, by the agonists metanicotine, TC299423, varenicline, and nornicotine.
View Article and Find Full Text PDFDesigning subtype-selective agonists for neuronal nicotinic acetylcholine receptors is a challenging and significant goal aided by intricate knowledge of each subtype's binding patterns. We previously reported that in α6β2 receptors, acetylcholine makes a functional cation-π interaction with Trp149, but nicotine and TC299423 do not, suggesting a distinctive binding site. This work explores hydrogen binding at the backbone carbonyl associated with α6β2 Trp149.
View Article and Find Full Text PDFChronic pain is a highly prevalent and poorly managed human health problem. We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia, a prominent symptom of chronic pain. We identified expression levels of Chrna6, which encodes the α6 subunit of the nicotinic acetylcholine receptor (nAChR), as highly associated with allodynia.
View Article and Find Full Text PDFThe α6-containing subtypes of the nicotinic acetylcholine receptor (nAChR) are localized to presynaptic terminals of the dopaminergic pathways of the central nervous system. Selective ligands for these nAChRs are potentially useful in both Parkinson's disease and addiction. For these and other goals, it is important to distinguish the binding behavior of agonists at the α6-β2 binding site versus other subtypes.
View Article and Find Full Text PDFThrough use of word association as detailed in McCarthy (1990) this paper will explore pedagogic implications derived from the following three points in relation to the lexical development of Japanese learners of English: 1) the ability of word association tests to examine the mental links between words in learners' developing mental lexicon, 2) the importance of phonological similarities for lower level students and 3) the correlation between the results from a word association test with the characteristic types of word association patterns discussed in McCarthy (1990). It will be argued that while lexical development within the mental lexicon is difficult to delineate due to overlap of organizational categories, the patterns of syntactic, semantic and conceptual relations between learned words is apparent within the retrieval process for word association and that additionally, context may play a vital role in how words are construed along the links within the mental lexicon. Pedagogic ideas and future research ideas are detailed.
View Article and Find Full Text PDFBackground: Public access defibrillation (PAD) programs are a major goal of the American Heart Association (AHA) to ensure that automated external defibrillators and trained lay rescuers are available in public areas where sudden cardiac arrest (SCA) is likely to occur. The Johnson County Early Defibrillation Task Force (JCEDTF) is a volunteer organization which distributed AEDs throughout Johnson County, Iowa. JCEDTF was responsible for initial training but ongoing support was the responsibility of each site.
View Article and Find Full Text PDFCancer Genomics Proteomics
January 2006
This review explores the recent chemotherapeutic work on drug delivery using nanoparticles as carriers for the targeted treatment of cancer. Compared to direct drug delivery, delivery through a carrier can increase the efficacy of a drug, but decrease the side-effects by utilizing the enhanced permeability and retention (EPR) effect and tumor-specific targeting. The search for efficient and safe transport vehicles (carriers) to achieve better drug availability at the target site has been a challenging yet exciting area of research.
View Article and Find Full Text PDFA method for homogenizing heterogeneous catalyst is described. The method is based on growing polyaminoamido (PAMAM) dendrons on silica-coated magnetic nanoparticles. After the dendronizing process, the silica-coated magnetic nanoparticles are more stable and more soluble in organic solvents.
View Article and Find Full Text PDFA novel method combining wet chemistry for synthesis of an Fe core, 532 nm laser irradiation of Fe nanoparticles and Au powder in liquid medium for deposition of an Au shell, and sequential magnetic extraction/acid washing for purification has been developed to fabricate oxidation-resistant Fe@Au magnetic core-shell nanoparticles. The nanoparticles have been extensively characterized at various stages during and up to several months after completion of the synthesis by a suite of electron microscopy techniques (HRTEM, HAADF STEM, EDX), X-ray diffraction (XRD), UV-vis spectroscopy, inductively coupled plasma atomic emission spectroscopy, and magnetometry. The surface plasmon resonance of the Fe@Au nanoparticles is red shifted and much broadened as compared with that of pure colloidal nano-gold, which is explained to be predominantly a shell-thickness effect.
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