Climate change: Comparing "green" and "polluting" nation-states.

Some nation-states, i.e., Norway, Sweden, and Denmark, repeatedly score the highest in environmental indicators such as the Environmental Performance Index (EPI) and the Climate Change Performance Index (CCPI). Their cities win environmental awards; they have well-developed recycling systems; they perform well with biodegradable waste; and their citizens show awareness of environmental problems, protesting publicly and even sueing their governing bodies if they don't do the same. For these and other reasons, recent scholarship defined these countries as "exemplary" green nation-states. The question is, which factors pushed them toward the green transition faster than others? And overall, what stops top polluting countries such as China, the United States and Russia from walking the same path? This article attempts to answer these questions by looking at climate change through a theoretical framework based on theories of nationalism and case studies of green nation-states. It compares three of said top polluting countries, China, the United States, and Russia, with "exemplary" green nation-states, and argues that the pace of greener nation-states rests on (1) a tradition of ecologism and environmentalism rooted in the long run, (2) the lock in of "green nationalism," a form of nationalism grounded on sustainability, (3) free and effective environmental movements, (4) inclusivity and welfare, and (5) a sense of national pride in environmental achievements. The available evidence seems to suggest that top polluting nation-states lack one or more of these factors.

Arthrospira (Spirulina) platensis Attenuates Dextran Sulfate Sodium-induced Colitis in Mice by Suppressing Key Pro-inflammatory Cytokines.

Background/Aims: Therapies aimed at modulating cytokines have been used to treat inflammatory illnesses, such as inflammatory bowel disease. On the other hand, patients may become intolerant, refractory, or present with several side effects. Arthrospira (Spirulina) platensis (SPI) is a blue-green microalga with bioactive molecules that have been evaluated to treat inflammatory diseases. On the other hand, few studies have examined their effects on the production of specific cytokines and the intestinal architecture in dextran sulfate sodium (DSS)-induced colitis. Therefore, this study examined the effects of a treatment using SPI in a murine model of intestinal inflammation. Methods: All mice (C57BL/6 male) were evaluated daily for their food and water intake, bodyweight variations, and clinical signs of disease. Colon inflammation was induced by exposure to DSS for 6 consecutive days. SPI was given orally at 50, 100, and 250 mg/kg/day. ELISA was performed to assess the production of cytokines. Myeloperoxidase and nitric oxide were also investigated. The level of microscopic damage was assessed by staining colon sections with hematoxylin and eosin. Results: SPI attenuated the DSS-induced inflammation, with improvements in the clinical signs and a decrease in the production of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ. In addition, particularly at 250 mg/kg, SPI attenuated the severity of colitis by modulating the level of mucosal and submucosal cell infiltration, which preserved the epithelial barrier. Conclusions: SPI may be an alternative source of bioactive molecules with immunomodulatory properties, and has great potential to be used in the treatment of inflammatory diseases.

The Excitatory Effects of GABA within the Suprachiasmatic Nucleus: Regulation of Na-K-2Cl Cotransporters (NKCCs) by Environmental Lighting Conditions.

The suprachiasmatic nucleus (SCN) contains a pacemaker that generates circadian rhythms and entrains them with the 24-h light-dark cycle (LD). The SCN is composed of 16,000 to 20,000 heterogeneous neurons in bilaterally paired nuclei. γ-amino butyric acid (GABA) is the primary neurochemical signal within the SCN and plays a key role in regulating circadian function. While GABA is the primary inhibitory neurotransmitter in the brain, there is now evidence that GABA can also exert excitatory effects in the adult brain. Cation chloride cotransporters determine the effects of GABA on chloride equilibrium, thereby determining whether GABA produces hyperpolarizing or depolarizing actions following activation of GABAA receptors. The activity of Na-K-2Cl cotransporter1 (NKCC1), the most prevalent chloride influx cotransporter isoform in the brain, plays a critical role in determining whether GABA has depolarizing effects. In the present study, we tested the hypothesis that NKCC1 protein expression in the SCN is regulated by environmental lighting and displays daily and circadian changes in the intact circadian system of the Syrian hamster. In hamsters housed in constant light (LL), the overall NKCC1 immunoreactivity (NKCC1-ir) in the SCN was significantly greater than in hamsters housed in LD or constant darkness (DD), although NKCC1 protein levels in the SCN were not different between hamsters housed in LD and DD. In hamsters housed in LD cycles, no differences in NKCC1-ir within the SCN were observed over the 24-h cycle. NKCC1 protein in the SCN was found to vary significantly over the circadian cycle in hamsters housed in free-running conditions. Overall, NKCC1 protein was greater in the ventral SCN than in the dorsal SCN, although no significant differences were observed across lighting conditions or time of day in either subregion. These data support the hypothesis that NKCC1 protein expression can be regulated by environmental lighting and circadian mechanisms within the SCN.

Correlation of bioimpedance changes after compressive loading of murine tissues in vivo.

OBJECTIVE: Rises in the incidence of pressure ulcers are increasingly prevalent in an aging population. Pressure ulcers are painful, are associated with increased morbidity and mortality, increase the risk for secondary infections and inpatient stay, and adds $26.8 billion annually to the healthcare costs of the USA. Evidence suggests that a change in the bioimpedance of living tissue in response to continuous local contact pressure can be a useful indicator for the onset of pressure injuries. APPROACH: Thirty-five Sprague Dawley rats were subjected to various skin pressures for differing periods of time via a surgically inserted steel disk and an externally applied magnet. Contact pressure and bioimpedance were measured and correlated with tissue loading intensity and compared to clinical ulcer grading. MAIN RESULTS: Moderate relationships between bioimpedance changes and tissue loading intensity were found. Stronger correlations were found by utilizing a combination of bioimpedance and phase angle. Thresholds were applied to the bioimpedance parameters and the usefulness of bioimpedance in classifying different ulcer stages is demonstrated. SIGNIFICANCE: These results indicate that bioimpedance may be useful as an early indicator of pressure ulcer formation and has practical significance in the development of early pressure injury detection devices.

Wireless Pressure Ulcer Sensor: Validation in an Animal Model.

Pressure ulcers are increasingly prevalent in an aging population. The most commonly used method of pressure ulcer prevention is pressure off-loading achieved by physically turning bedbound patients or by using expensive, single application devices such as wheelchair cushions. Our aim is to approach the problem of pressure ulcer prevention in a new way: a wireless sensor worn by the patient at locations susceptible to pressure injury. The sensor will monitor local pressure over time and transmits the data wirelessly to a base station (in a hospital setting) or smartphone (for home care). When a condition that would be harmful to tissue is reached, an alert would enable immediate direct intervention to prevent development of a pressure ulcer. The goal of this study was to validate the sensor's use in a live animal model and to lay the foundation for building time-pressure curves to predict the probability of pressure injury. Sprague-Dawley rats underwent surgical implantation of bilateral steel discs deep to the latissimus dorsi muscles. After the animals recovered from the surgical procedure, pressure was applied to the overlying tissue using magnets of varying strengths (30-150 mm Hg) for between 1 and 8 hours. Our sensor was placed on the skin prior to magnet application to wirelessly collect data regarding pressure and time. Three days after pressure application, animals were killed, injuries were graded clinically, and biopsies were collected for histological analysis. Results reveal that all animals with magnet application for more than 2 hours had clinical evidence of ulceration. Similarly, histological findings of hemorrhage were associated with increased time of pressure application. However, at high pressures (120-150 mm Hg), there were ischemic changes within the muscular layer without corresponding skin ulceration. We have developed a wireless sensor that can be placed on any at-risk area of the body and has the potential to alert caregivers when patients are at risk of developing a pressure injury. Our sensor successfully transmitted pressure readings wirelessly in a live, mobile animal. Future studies will focus on safety and efficacy with human use and development of algorithms to predict the probability of pressure ulcer formation.

Experimental Spinal Cord Injury Causes Left-Ventricular Atrophy and Is Associated with an Upregulation of Proteolytic Pathways.

Spinal cord injury (SCI) causes autonomic dysfunction, altered neurohumoral control, profound hemodynamic changes, and an increased risk of heart disease. In this prospective study, we investigated the cardiac consequences of chronic experimental SCI in rats by combining cutting edge in vivo techniques (magnetic resonance imaging [MRI] and left-ventricular [LV] pressure-volume catheterization) with histological and molecular assessments. Twelve weeks post-SCI, MRI-derived structural indices and in vivo LV catheterization-derived functional indices indicated the presence of LV atrophy (LV mass in Control vs. SCI = 525 ± 38.8 vs. 413 ± 28.6 mg, respectively; p = 0.0009), reduced ventricular volumes (left-ventricular end-diastolic volume in Control vs. SCI = 364 ± 44 vs. 221 ± 35 µL, respectively; p = 0.0004), and contractile dysfunction (end-systolic pressure-volume relationship in Control vs. SCI = 1.31 ± 0.31 vs. 0.76 ± 0.11 mm Hg/µL, respectively; p = 0.0045). Cardiac atrophy and contractile dysfunction in SCI were accompanied by significantly lower blood pressure, reduced circulatory norepinephrine, and increased angiotensin II. At the cellular level, we found the presence of reduced cardiomyocyte size and increased expression of angiotensin II type 1 receptors and transforming growth factor-beta receptors (TGF-ß receptor 1 and 2) post-SCI. Importantly, we found more than a two-fold increase in muscle ring finger-1 and Beclin-1 protein level following SCI, indicating the upregulation of the ubiquitin-proteasome system and autophagy-lysosomal machinery. Our data provide novel evidence that SCI-induced cardiomyocyte atrophy and systolic cardiac dysfunction are accompanied by an upregulation of proteolytic pathways, the activation of which is likely due to loss of trophic support from the sympathetic nervous system, neuromechanical unloading, and altered neurohumoral pathways.

A New Vision for Preventing Pressure Ulcers: Wearable Wireless Devices Could Help Solve a Common-and Serious-Problem.

With an aging population, the incidence and prevalence of wound problems is on the rise. Bedsores (also known as pressure ulcers or decubitus ulcers) are painful, take months to heal, and, for many patients, never do, leading to other health problems. The condition has become so acute that treating bedsores is now a significant burden on the healthcare system. An estimated 2.5 million pressure ulcers are treated in U.S. hospitals each year, adding US$11 billion annually to health care costs.

Overview of the SAMPL6 host-guest binding affinity prediction challenge.

Accurately predicting the binding affinities of small organic molecules to biological macromolecules can greatly accelerate drug discovery by reducing the number of compounds that must be synthesized to realize desired potency and selectivity goals. Unfortunately, the process of assessing the accuracy of current computational approaches to affinity prediction against binding data to biological macromolecules is frustrated by several challenges, such as slow conformational dynamics, multiple titratable groups, and the lack of high-quality blinded datasets. Over the last several SAMPL blind challenge exercises, host-guest systems have emerged as a practical and effective way to circumvent these challenges in assessing the predictive performance of current-generation quantitative modeling tools, while still providing systems capable of possessing tight binding affinities. Here, we present an overview of the SAMPL6 host-guest binding affinity prediction challenge, which featured three supramolecular hosts: octa-acid (OA), the closely related tetra-endo-methyl-octa-acid (TEMOA), and cucurbit[8]uril (CB8), along with 21 small organic guest molecules. A total of 119 entries were received from ten participating groups employing a variety of methods that spanned from electronic structure and movable type calculations in implicit solvent to alchemical and potential of mean force strategies using empirical force fields with explicit solvent models. While empirical models tended to obtain better performance than first-principle methods, it was not possible to identify a single approach that consistently provided superior results across all host-guest systems and statistical metrics. Moreover, the accuracy of the methodologies generally displayed a substantial dependence on the system considered, emphasizing the need for host diversity in blind evaluations. Several entries exploited previous experimental measurements of similar host-guest systems in an effort to improve their physical-based predictions via some manner of rudimentary machine learning; while this strategy succeeded in reducing systematic errors, it did not correspond to an improvement in statistical correlation. Comparison to previous rounds of the host-guest binding free energy challenge highlights an overall improvement in the correlation obtained by the affinity predictions for OA and TEMOA systems, but a surprising lack of improvement regarding root mean square error over the past several challenge rounds. The data suggests that further refinement of force field parameters, as well as improved treatment of chemical effects (e.g., buffer salt conditions, protonation states), may be required to further enhance predictive accuracy.

High drug related mortality rates following prison release: Assessing the acceptance likelihood of a naltrexone injection and related concerns.

BACKGROUND AND AIMS: High drug related mortality amongst former prisoners in the 4 weeks following release is an internationally recognised problem. Naltrexone injections at release could diminish this by blockading opioid receptors, but naltrexone is not licensed for injection for treating opiate misuse in the United Kingdom and some other countries. This study examined the likelihood of accepting a naltrexone injection at release, and the relationship of this likelihood to other relevant variables. METHOD: Sixty-one male prisoners with a history of heroin use, who were approaching release from two prisons in the north-west of England, provided likelihood ratings for accepting a naltrexone injection if it were to have been available. Additional data was gathered regarding demographic and drug use histories, and also from psychometric instruments relevant to drug misuse and treatment preparedness. RESULTS: Maximum likelihood ratings for accepting a naltrexone injection were recorded by 55.7% of the sample with only 9.8% indicating no likelihood of accepting an injection. Likelihood ratings were positively related to serving a current sentence for an acquisitive offence compared to drug related or violence offences, and negatively related to peak methadone dosages during the current sentence. CONCLUSIONS: Although naltrexone injections were not available to participants in this study, the findings suggest that the potential uptake for this intervention is sufficient to warrant a clinical trial with this population of British prisoners, with a view to potential changes to its current licencing status. However, the importance of individual patient readiness for such an abstinence orientated intervention is emphasised by the negative correlation between the likelihood ratings and recent methadone doses.

Functional Significance of the Excitatory Effects of GABA in the Suprachiasmatic Nucleus.

Over 90% of neurons within the suprachiasmatic nucleus (SCN) express γ-aminobutyric acid (GABA). Although GABA is primarily an inhibitory neurotransmitter, in vitro studies suggest that the activation of GABAA receptors (GABAAR) elicits excitation in the adult SCN. The ratio of excitatory to inhibitory responses to GABA depends on the balance of chloride influx by Na+-K+-Cl- cotransporter 1 (NKCC1) and chloride efflux by K+-Cl- cotransporters (KCCs). Excitatory responses to GABA can be blocked by inhibition of the inward chloride cotransporter, NKCC1, with the loop diuretic bumetanide. Here we investigated the role of NKCC1 activity in phase shifting the circadian pacemaker in response to photic and nonphotic signals in male Syrian hamsters housed in constant darkness. In the early subjective night (CT 13.5), injection of bumetanide into the SCN reduced light-induced phase delays. However, during the late subjective night (CT 19), bumetanide administration did not alter light-induced phase advances. Injection of bumetanide during the subjective day (CT 6) did not alter the phase of free-running circadian rhythms but attenuated phase advances induced by injection of the GABAAR agonist muscimol into the SCN. These data support the hypothesis that the excitatory effects of endogenously released GABA contribute to the ability of light to induce phase delays, thereby contributing to the most important function of the circadian system, its entrainment with the day-night cycle. Further, the finding that bumetanide inhibits the phase-advancing effects of muscimol during the subjective day supports the hypothesis that the excitatory responses to GABA also contribute to the ability of nonphotic stimuli to phase shift the circadian pacemaker.

Temporal Regulation of GABAA Receptor Subunit Expression: Role in Synaptic and Extrasynaptic Communication in the Suprachiasmatic Nucleus.

Recent molecular studies suggest that the expression levels of δ and γ2 GABAA receptor (GABAAR) subunits regulate the balance between synaptic and extrasynaptic GABA neurotransmission in multiple brain regions. We investigated the expression of GABAAδ and GABAAγ2 and the functional significance of a change in balance between these subunits in a robust local GABA network contained within the suprachiasmatic nucleus of the hypothalamus (SCN). Muscimol, which can activate both synaptic and extrasynaptic GABAARs, injected into the SCN during the day phase advanced the circadian pacemaker, whereas injection of the extrasynaptic GABAA superagonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) had no effect on circadian phase. In contrast, injection of either THIP or muscimol during the night was sufficient to block the phase shifting effects of light. Gene expression analysis of the whole SCN revealed different temporal patterns in GABAAδ and GABAAγ2 mRNA expression. When examined across all subregions of the SCN, quantitative immunohistochemical analysis found no significant variations in GABAAδ protein immunoreactivity (IR) but did find significant variations in GABAAγ2 protein-IR in hamsters housed in either LD cycles or in constant darkness. Remarkably, significant interactions in the ratio of GABAAδ:GABAAγ2 subunits between lighting condition and circadian phase occurred only within one highly discrete anatomical area of the SCN; a region that functions as the input for lighting information from the retina. Taken together, these data support the hypothesis that the balance between synaptic and extrasynaptic GABAARs determines the functional response to GABA, and that this balance is differentially regulated in a region-specific manner.

The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus.

Virtually every neuron within the suprachiasmatic nucleus (SCN) communicates via GABAergic signaling. The extracellular levels of GABA within the SCN are determined by a complex interaction of synthesis and transport, as well as synaptic and non-synaptic release. The response to GABA is mediated by GABAA receptors that respond to both phasic and tonic GABA release and that can produce excitatory as well as inhibitory cellular responses. GABA also influences circadian control through the exclusively inhibitory effects of GABAB receptors. Both GABA and neuropeptide signaling occur within the SCN, although the functional consequences of the interactions of these signals are not well understood. This review considers the role of GABA in the circadian pacemaker, in the mechanisms responsible for the generation of circadian rhythms, in the ability of non-photic stimuli to reset the phase of the pacemaker, and in the ability of the day-night cycle to entrain the pacemaker.

Cardiac Consequences of Autonomic Dysreflexia in Spinal Cord Injury.

Autonomic dysreflexia (AD), which describes episodic hypertension, is highly prevalent in people with spinal cord injury (SCI). In non-SCI, primary hypertension depresses cardiac contractile reserve via ß-adrenergic mechanisms. In this study, we investigated whether AD contributes to the impairment in cardiac contractile function that accompanies SCI. We induced SCI in rodents and stratified them into sham, SCI, or SCI plus repetitive induction of AD. At 6-week post-SCI, we assessed cardiac function using in vivo (speckle-tracking echocardiography), ex vivo (working heart), and molecular approaches (Western blot). We also provide unique translational insight by comparing the relationship between the number of daily AD events and cardiac function in 14 individuals with cervical SCI. We found SCI and SCI plus repetitive induction of AD exhibited a reduction in left ventricular dimensions at 6-week post-SCI versus preinjury (P<0.049). Compared with sham, SCI exhibited a reduction in peak radial strain along with a down and rightward shift in the Starling curve (P<0.037), both of which were further depressed in SCI plus repetitive induction of AD (P<0.042). In response to ß-adrenergic stimulation, SCI plus repetitive induction of AD exhibited an attenuated increase in contractile indices (P<0.001), despite no differences in ß-receptor expression within the left ventricle. Our clinical data confirm our experimental findings by demonstrating significant associations between the number of daily AD events and markers of systolic and diastolic function along with left ventricular mechanics. Here, we provide the first evidence from a translational perspective that AD exerts insidious effects on cardiac function in rodents and humans with SCI.

Glucose lowering effect of montbretin A in Zucker Diabetic Fatty rats.

Diabetes is an increasingly prevalent disease state with a global impact. It is important that effective and cost-efficient methods be developed to treat this disease state. Zucker diabetic fatty rats, an animal model of type 2 diabetes, were treated with montbretin A (MbA), a selective human pancreatic α-amylase inhibitor, isolated from the corms of the Crocosmia crocosmiiflora plant that may have potential as a glucose-lowering agent. The study purpose was to determine if MbA was an orally effective treatment for diabetes. The effect of MbA was compared to a current clinical treatment modality, acarbose that is associated with gastrointestinal side effects known to affect patient compliance. MbA and acarbose were administered daily in the drinking water. Body weight and fluid intake were measured daily to calculate dose consumption. Plasma glucose levels were determined twice weekly in both the fed and fasted state. At termination samples were collected to assess increased risk of secondary complications related to diabetes and oxidative stress. There was no effect of either MbA or acarbose treatment on insulin levels. Plasma glucose levels were significantly lower following MbA treatment in the ZT group which persisted throughout the study period (day 49: 12.1 ± 1.2 mM). However, while there was an initial decrease in plasma glucose levels in the acarbose-treated fatty group, this effect was not sustained (day 49: 20.6 ± 1.3 mM) through to termination. MbA improved the oxidative status of the fatty diabetic animals as well as attenuated markers for increased risk of cardiovascular complications associated with diabetes. This study demonstrated that, at a lower dose as compared to acarbose (10 mg/kg/day), chronic oral administration of MbA (7.5 mg/kg/day) was an effective glucose-lowering agent in the treatment of type 2 diabetes.

Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome.

PURPOSE: Benzodiazepines (BDZs) are the drugs of choice to prevent the symptoms of alcohol withdrawal syndrome (AWS). Various treatment protocols are published and have been shown to be effective in both office-managed and facility-managed treatment of AWS. The aim of this scientific commentary is to demonstrate the differences in the expected exposure to BDZs during AWS treatment using different treatment regimens available in the literature, in patients with or without alcoholic liver cirrhosis. METHODS: Diazepam and lorazepam AWS protocols were examined and reviewed in the literature, and blood plasma levels were examined and compared, respectively. RESULTS: Considerable variation in the blood levels with the different dosing schedules was found. Because the drugs are metabolized differently, we have also shown that liver disease affects the blood levels of diazepam, but not of lorazepam. CONCLUSIONS: Differences in treatment regimens, the choice of BDZ, as well as the presence of liver cirrhosis can substantially alter the exposure of patients to drugs used for AWS treatment. Outpatient treatment of AWS has been shown to be relatively safe and effective for the treatment of AWS but patients should be carefully monitored.

Highly saline fluids from a subducting slab as the source for fluid-rich diamonds.

The infiltration of fluids into continental lithospheric mantle is a key mechanism for controlling abrupt changes in the chemical and physical properties of the lithospheric root, as well as diamond formation, yet the origin and composition of the fluids involved are still poorly constrained. Such fluids are trapped within diamonds when they form and so diamonds provide a unique means of directly characterizing the fluids that percolate through the deep continental lithospheric mantle. Here we show a clear chemical evolutionary trend, identifying saline fluids as parental to silicic and carbonatitic deep mantle melts, in diamonds from the Northwest Territories, Canada. Fluid-rock interaction along with in situ melting cause compositional transitions, as the saline fluids traverse mixed peridotite-eclogite lithosphere. Moreover, the chemistry of the parental saline fluids--especially their strontium isotopic compositions--and the timing of host diamond formation suggest that a subducting Mesozoic plate under western North America is the source of the fluids. Our results imply a strong association between subduction, mantle metasomatism and fluid-rich diamond formation, emphasizing the importance of subduction-derived fluids in affecting the composition of the deep lithospheric mantle.