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Objective: Neuropeptide Y (NPY) is a 36 amino acid peptide widely considered to provide neuroprotection in a range of neurodegenerative diseases. In the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), recent evidence supports a link between NPY and ALS disease processes. The goal of this study was to determine the therapeutic potential and role of NPY in ALS, harnessing the brain-targeted intranasal delivery of the peptide, previously utilised to correct motor and cognitive phenotypes in other neurological conditions., Methods: To confirm the association with clinical disease characteristics, NPY expression was quantified in post-mortem motor cortex tissue of ALS patients and age-matched controls. The effect of NPY on ALS cortical pathophysiology was investigated using slice electrophysiology and multi-electrode array recordings of SOD1 G93A cortical cultures in vitro. The impact of NPY on ALS disease trajectory was investigated by treating SOD1 G93A mice intranasally with NPY and selective NPY receptor agonists and antagonists from pre-symptomatic and symptomatic phases of disease., Results: In the human post-mortem ALS motor cortex, we observe a significant increase in NPY expression, which is not present in the somatosensory cortex. In vitro, we demonstrate that NPY can ameliorate ALS hyperexcitability, while brain-targeted nasal delivery of NPY and a selective NPY Y1 receptor antagonist modified survival and motor deficits specifically within the symptomatic phase of the disease in the ALS SOD1 G93A mouse., Interpretation: Taken together, these findings highlight the capacity for non-invasive brain-targeted interventions in ALS and support antagonism of NPY Y1Rs as a novel strategy to improve ALS motor function., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Destabilization of faciliatory and inhibitory circuits is an important feature of corticomotor pathology in amyotrophic lateral sclerosis (ALS). While GABAergic inputs to upper motor neurons are reduced in models of the disease, less understood is the involvement of peptidergic inputs to upper motor neurons in ALS. The neuropeptide Y (NPY) system has been shown to confer neuroprotection against numerous pathogenic mechanisms implicated in ALS. However, little is known about how the NPY system functions in the motor system. Herein, we investigate post-synaptic NPY signaling on upper motor neurons in the rodent and human motor cortex, and on cortical neuron populations in vitro. Using immunohistochemistry, we show the increased density of NPY-Y1 receptors on the soma of SMI32-positive upper motor neurons in post-mortem ALS cases and SOD1 G93A excitatory cortical neurons in vitro. Analysis of receptor density on Thy1-YFP-H -positive upper motor neurons in wild-type and SOD1 G93A mouse tissue revealed that the distribution of NPY-Y1 receptors was changed on the apical processes at early-symptomatic and late-symptomatic disease stages. Together, our data demonstrate the differential density of NPY-Y1 receptors on upper motor neurons in a familial model of ALS and in ALS cases, indicating a novel pathway that may be targeted to modulate upper motor neuron activity.

Neuropeptide Y (NPY) is an endogenous peptide of the central and enteric nervous systems which has gained significant interest as a potential neuroprotective agent for treatment of neurodegenerative disease. Amyotrophic lateral sclerosis (ALS) is an aggressive and fatal neurodegenerative disease characterized by motor deficits and motor neuron loss. In ALS, recent evidence from ALS patients and animal models has indicated that NPY may have a role in the disease pathogenesis. Increased NPY levels were found to correlate with disease progression in ALS patients. Similarly, NPY expression is increased in the motor cortex of ALS mice by end stages of the disease. Although the functional consequence of increased NPY levels in ALS is currently unknown, NPY has been shown to exert a diverse range of neuroprotective roles in other neurodegenerative diseases; through modulation of potassium channel activity, increased production of neurotrophins, inhibition of endoplasmic reticulum stress and autophagy, reduction of excitotoxicity, oxidative stress, neuroinflammation and hyperexcitability. Several of these mechanisms and signalling pathways are heavily implicated in the pathogenesis of ALS. Therefore, in this review, we discuss possible effects of NPY and NPY-receptor signalling in the ALS disease context, as determining NPY's contribution to, or impact on, ALS disease mechanisms will be essential for future studies investigating the NPY system as a therapeutic strategy in this devastating disease., (© 2020 International Society for Neurochemistry.)

Musculoskeletal complaint rates are high among those performing low-level static exertions (LLSEs), such as computer users. However, our understanding of the causal mechanisms is lacking. It was hypothesized that myofascial trigger point (MTrP) development might be one causal mechanism to help explain these complaints and that static postural and visual demands may be contributing factors. Therefore, the purpose of this experiment was to examine MTrP development and the behavior of multiple parts of the trapezius muscle under postural and mental stress (represented by visual stress) conditions during computer work. Twelve subjects (six male and six female) were monitored for MTrP development via expert opinion, subject self-report, and cyclic changes in EMG median frequency across fourteen spatial locations. Results showed that MTrPs developed after one hour of continuous typing, despite the stress condition. Interestingly, both the high postural and high visual stress conditions resulted in significantly fewer median frequency cycles (3.76 and 5.35 cycles, respectively), compared to the baseline low stress condition (6.26 cycles). Lastly, the MTrP location as well as locations more medial to the spine showed significantly fewer cycles than other locations. Findings suggest that MTrPs may be one causal pathway for pain during LLSEs and both postural and visual demands may play a role in muscle activation patterns, perhaps attributing to MTrP development and resultant discomfort., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Stooped, restricted, kneeling, and other awkward postures adopted during manual materials handling have frequently been associated with LBP onset. However, lift assessment tools have focused on materials handling performed in an upright, or nearly upright standing posture. Unfortunately, many of the tools designed to analyze standing postures are not easily adapted to jobs requiring restricted postures. Therefore, the objective of this study was to evaluate spinal loading during manual materials handing in kneeling postures and determine if those loads can be predicted using simple regression. An EMG-driven biomechanical model, previously validated for upright lifting, was adapted for use in kneeling tasks. Subjects knelt under a 1.07m ceiling and lifted luggage of six weights (6.8, 10.9, 15.0, 19.1, 23.1 and, 27.2kgf) to one of four destination heights (0, 25.4, 53.3, 78.7cm). Spine loading was significantly affected by both destination height and load weight. Destination height increased compression, AP shear and lateral shear by an average of 14.5, 3.7 and 6.6N respectively per cm height increase. Load weight increased compression, AP shear and lateral shear by an average of 83.8, 27.0 and 13.1N respectively per kgf lifted. Regression equations were developed to predict peak spine loading using subject height, load weight and destination height with R(2) values of 0.62, 0.51 and 0.57 for compression, AP and lateral shear respectively.

We designed a polymerase chain reaction (PCR) for amplifying the Helicobacter pylori gene encoding 16S rRNA. Primers for the specific detection of H. pylori were designed for areas of the 16S rRNA gene in which there is the least sequence homology between H. pylori and its closest relatives. The specificity of detection was confirmed by ensuring that the primers did not amplify DNA extracts from the campylobacters H. cinaedi, H. mustelae, and Wolinella succinogenes, which are the closest relatives of H. pylori, as determined by 16S rRNA sequencing. Serial dilution experiments revealed the detection of as little as 0.1 pg of DNA by PCR and 0.01 pg by nested PCR. H. pylori DNA was detected successfully in clinical paraffin-embedded and fresh gastric biopsy specimens from patients positive for the bacterium and also in fecal suspensions seeded with the organism. The DNA from the nonculturable coccoid form of H. pylori was also identified by the primers. Universal primers designed for highly conserved areas on the 16S rRNA gene enabled large amplification products to be produced for direct sequencing analysis. Gastric bacteria resembling H. pylori have been isolated from animals. DNA of these animal gastric bacteria amplified with H. pylori-specific primers yielded PCR products identical to those from human isolates of H. pylori, as confirmed by the use of a 20-base radiolabelled probe complementary to an internal sequence flanked by the H. pylori-specific primers. The results of PCR amplification and partial 16S rRNA gene sequence analysis strongly support the contention that the gastric organisms previously recovered from a pig, a baboon, and rhesus monkeys are H. pylori.

Infection of the lungs of immunodeficient mice with the paramyxovirus simian virus 5 (SV5) was prolonged compared with the time course of infection in immunocompetent mice. Although there was a significant increase in both viral RNA and proteins, little infectious virus was produced. Adoptive transfer of immune lymphocytes (isolated from the spleens of mice previously infected with SV5) but not of nonimmune lymphocytes increased the speed of clearance of virus from the lungs of immunodeficient mice. In contrast, passive transfer of a pool of neutralizing monoclonal antibodies specific for the HN and F glycoproteins of SV5 did not have a significant effect on the speed of clearance of virus. Furthermore, no significant increase in the rate of virus clearance was observed upon adoptive transfer of purified immune B lymphocytes to SV5-infected immunodeficient mice despite production by the mice of high titers of neutralizing antibodies. Evidence is presented that CD8+ effector cells are primarily responsible for the clearance observed. The general significance of these results with respect to immune clearance of persistent virus infections is discussed.