Ageing and gastrointestinal sensory function : altered colonic mechanosensory and chemosensory function in the aged mouse

Proceedings of the British Pharmacological Society at http://www.pA2online.org/abstracts/Vol12Issue3abst258P.pdf © 2016 pA2 Online ISSN 1741-1157Ageing has a profound effect upon gastrointestinal function through mechanisms that are poorly understood (1). A feature of ageing is impaired sensory perception, including a diminished sensory response to inflammatory evoked gastrointestinal injury (2). Since nociception is a key consequence of disease or tissue injury, triggering neurogenic inflammation and pain behaviour, its attenuation with age has consequences for disease progression and seeking medical advice (3). However, surprisingly little is known about the mechanisms contributing towards the age-associated blunting of sensory perception. In this current study we investigated the effect of ageing upon colonic sensory signalling pathways in order to address this question.Peer reviewe

A Set of Computationally Designed Orthogonal Antiparallel Homodimers that Expands the Synthetic Coiled-Coil Toolkit

Molecular engineering of protein assemblies, including the fabrication of nanostructures and synthetic signaling pathways, relies on the availability of modular parts that can be combined to give different structures and functions. Currently, a limited number of well-characterized protein interaction components are available. Coiled-coil interaction modules have been demonstrated to be useful for biomolecular design, and many parallel homodimers and heterodimers are available in the coiled-coil toolkit. In this work, we sought to design a set of orthogonal antiparallel homodimeric coiled coils using a computational approach. There are very few antiparallel homodimers described in the literature, and none have been measured for cross-reactivity. We tested the ability of the distance-dependent statistical potential DFIRE to predict orientation preferences for coiled-coil dimers of known structure. The DFIRE model was then combined with the CLASSY multistate protein design framework to engineer sets of three orthogonal antiparallel homodimeric coiled coils. Experimental measurements confirmed the successful design of three peptides that preferentially formed antiparallel homodimers that, furthermore, did not interact with one additional previously reported antiparallel homodimer. Two designed peptides that formed higher-order structures suggest how future design protocols could be improved. The successful designs represent a significant expansion of the existing protein-interaction toolbox for molecular engineers.National Science Foundation (U.S.) (MCB-0950233)United States. National Institutes of Health (GM67681)National Science Foundation (U.S.) (DBI-0821391

Filling the Gaps with Public Policy: The Application of the Hague Convention Protocol in US Courts in the Absence of a Co-Signing State

This article will consider a possible avenue for filling \u27gaps\u27 when the 1980 Hague Abduction Convention or the 1996 Child Protection Convention do not apply in child custody/abduction cases. Specifically, it will explore utilizing internal US domestic relations law to facilitate the return of a child who has been abducted to the USA from a non-signatory country. To better illustrate the potential effects, the article will explore this \u27gap filler\u27 through the lens of a case study involving Japan, the most prominent first world country that is not yet a signatory to the Convention. The article also considers the implications for the international community

POLAR: Instrument and Results

We describe the design, performance, and results of a polarimeter used to make precision measurements of the 2.7 K cosmic microwave background. In the Spring of 2000 the instrument searched for polarized emission in three microwave frequency bands spanning 26–36 GHz. The instrument achieved high sensitivity and long-term stability, and has produced the most stringent limits to date on the amplitude of the large angular scale polarization of the cosmic microwave background radiation

Manual Therapy and Exercise for the Management of Chronic Neck Pain With Multiple Neurovascular Comorbidities: A Case Report

This case describes the clinical decision-making behind the conservative clinical management of an individual presenting with chronic neck pain with myriad neuromuscular comorbidities. The focus of this case report is to support the safe utilization of manual therapy and describe the tolerable prescription of strength and endurance exercise in a patient with numerous complications to improve self-efficacy. A 22-year-old female college student presented with a chief complaint of chronic, non-specific neck pain with comorbid Chiari malformation, migraines, upper cervical spinal fusion, Ehlers-Danlos syndrome (EDS), and postural orthostatic tachycardia syndrome (POTS) to an outpatient physical therapy clinic for evaluation and treatment. Following four sessions of physical therapy treatment, no clinically significant improvement in the individual\u27s symptoms and daily function was achieved. Despite the lack of measurable change, the patient reported the program\u27s value on her ability to self-manage her complex condition. The patient responded well to manual therapy, specifically thrust manipulations. In addition, both endurance and strengthening exercises were well tolerated and provided a measure of self-management that may not have been achieved before physical therapy management. This case report highlights the need for exercise and pain-modulating interventions in highly complex individuals to reduce medical intervention by advancing the patient\u27s self-efficacy. There is a need for further research about the utility of standardized outcome measures, joint manipulations, and the addition of cervico-ocular exercises for those who present with neck pain and pertinent neuromuscular comorbidities

Making the Environmental Justice Grade: The Relative Burden of Air Pollution Exposure in the United States

This paper assesses whether the Clean Air Act and its Amendments have been equally successful in ensuring the right to healthful air quality in both advantaged and disadvantaged communities in the United States. Using a method to rank air quality established by the American Lung Association in its 2009 State of the Air report along with EPA air quality data, we assess the environmental justice dimensions of air pollution exposure and access to air quality information in the United States. We focus on the race, age, and poverty demographics of communities with differing levels of ozone and particulate matter exposure, as well as communities with and without air quality information. Focusing on PM2.5 and ozone, we find that within areas covered by the monitoring networks, non-Hispanic blacks are consistently overrepresented in communities with the poorest air quality. The results for older and younger age as well as poverty vary by the pollution metric under consideration. Rural areas are typically outside the bounds of air quality monitoring networks leaving large segments of the population without information about their ambient air quality. These results suggest that substantial areas of the United States lack monitoring data, and among areas where monitoring data are available, low income and minority communities tend to experience higher ambient pollution levels

The H I Environment Of The M101 Group

We present a wide (8. Degree-Sign 5 Multiplication-Sign 6. Degree-Sign 7, 1050 Multiplication-Sign 825 kpc), deep ({sigma}{sub N{sub H{sub {sub {sub i}}}}}10{sup 16.8}-10{sup 17.5} cm{sup -2}) neutral hydrogen (H I) map of the M101 galaxy group. We identify two new H I sources in the group environment, one an extremely low surface brightness (and hitherto unknown) dwarf galaxy, and the other a starless H I cloud, possibly primordial in origin. Our data show that M101\u27s extended H I envelope takes the form of a {approx}100 kpc long tidal loop or plume of H I extending to the southwest of the galaxy. The plume has an H I mass of {approx}10{sup 8} M{sub Sun} and a peak column density of N{sub H{sub i}}= 5 Multiplication-Sign 10{sup 17} cm{sup -2}, and while it rotates with the main body of M101, it shows kinematic peculiarities suggestive of a warp or flaring out of the rotation plane of the galaxy. We also find two new H I clouds near the plume with masses {approx}10{sup 7} M{sub Sun }, similar to H I clouds seen in the M81/M82 group, and likely also tidal in nature. Comparing to deep optical imaging of the M101 group, neithermore » the plume nor the clouds have any extended optical counterparts down to a limiting surface brightness of {mu}{sub B} = 29.5. We also trace H I at intermediate velocities between M101 and NGC 5474, strengthening the case for a recent interaction between the two galaxies. The kinematically complex H I structure in the M101 group, coupled with the optical morphology of M101 and its companions, suggests that the group is in a dynamically active state that is likely common for galaxies in group environments.« les

Protocol for DRAUP: A deimplementation programme to decrease routine chest radiographs after central venous catheter insertion

INTRODUCTION: Avoiding low value medical practices is an important focus in current healthcare utilisation. Despite advantages of point-of-care ultrasound (POCUS) over chest X-ray including improved workflow and timeliness of results, POCUS-guided central venous catheter (CVC) position confirmation has slow rate of adoption. This demonstrates a gap that is ripe for the development of an intervention. METHODS: The intervention is a deimplementation programme called DRAUP ( ETHICS AND DISSEMINATION: Approval of the study by the Human Research Protection Office has been obtained. This work will be disseminated by publication of peer-reviewed manuscripts, presentation in abstract form at scientific meetings and data sharing with other investigators through academically established means. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier, NCT04324762, registered on 27 March 2020