Majority of artificially lit Earth surface associated with the non-urban population.

Key to understanding the negative impacts of artificial light at night (ALAN) on human health and the natural environment is its relationship with human density. ALAN has often primarily been considered an urban issue, however although over half of the population is urbanized, the 46 % that are not inhabit a dispersed array of smaller settlements. Here, we determine the global relationships between two dimensions of ALAN, namely direct emissions (radiance) and skyglow, and human density, and how these relationships vary across continents. We correct the Visible Infrared Imaging Radiometer Suite Day/Night Band (VIIRS DNB) product for albedo, skyglow, airglow, the aurora and permanent snow and ice to represent upward radiance overland at 1.61 ∗ 2.12 km resolution from artificial sources only. For skyglow we use the World Atlas of Artificial Sky Brightness. Globally (between 59°N and 55°S), direct emissions were detected over 26.5 % and skyglow over 46.9 % of land area. Over half of all cumulative direct emissions (54.9 %) were emitted at low levels by the non-urban population, whilst these populations experienced the negative impacts of over two-thirds of all cumulative skyglow (69.8 %). This emphasises the extent of ALAN outside of urban areas, and its similarity in this regard to a number of other forms of pollution. Although powerful sources of rural direct emissions (e.g., industry, recreation) are important contributors of light pollution, cumulatively they only contributed 10 % to total direct emissions. The relationship between each dimension of ALAN and population density varied across continents, driven by powerful rural emissions, non-urban populations and urban design. These relationships reflect the unique socio-economic and geographical make-up of each region and inform on where best to target light pollution mitigation strategies, not only in urban areas but also in rural ones.

Aerobic plate count, Salmonella and Campylobacter loads of whole bird carcass rinses from pre-chillers with different water management strategies in a commercial poultry processing plant.

Salmonella and Campylobacter are significant issues for poultry processors because of increasing regulatory standards as well as public health concerns. The goal of this study is to report the effects of two different pre-chiller systems that utilize different temperatures and water recirculation systems on whole bird carcass rinsates. Both pre-chiller tanks were contained within a single poultry processing facility and operated at different temperatures and water systems. The incidence of Campylobacter spp. and Salmonella spp., as well as the aerobic plate counts on whole bird carcass rinses are reported in this study from each pre-chiller system. The results from this study reveal that there are significant differences in how microbial populations and pathogens change over time in each pre-chiller system. Furthermore, we identify that these patterns are different per system. Such data are impactful as it indicates that measuring carcasses within a plant must consider both temperature and water recirculation as it may prevent comparability of different lines within a single processing facility.

Australian fitness professionals' level of interest in engaging with high health-risk population subgroups: findings from a national survey.

OBJECTIVES: Fitness industry professionals (personal trainers, group instructors) may have a role in health promotion, particularly when working with subgroups with known health risks (e.g. older adults, obese). The aim of this study is to examine fitness professionals' level of interest in engaging with high-risk populations. STUDY DESIGN: Cross-sectional evaluation of a national survey. METHODS: In 2014, 9100 Australian registered exercise professionals were invited to complete an online survey. Respondents reported their level of interest in engaging with nine health-risk population subgroups. A multivariable logistic regression analysis assessed the odds of being classified as having a 'low level' of interest in training high health-risk subgroups, adjusting for demographic and fitness industry-related factors. RESULTS: Of 1185 respondents (aged 17-72 years), 31.1% reported having a 'high level' of interest in training high health-risk subgroups. The highest level of interest was among 'obese clients' and 'adults (18-64 years) with chronic health conditions'. In the adjusted analysis, males (odds ratio [OR], 1.55, 95% confidence interval [CI]: 1.06-2.25) and those in urban settings (OR, 2.26, 95% CI: 1.54-3.37) were more likely to have a 'low level' of interest. CONCLUSIONS: Fitness professionals have a modest level of interest in training high health-risk subgroups. In addition to the development of strategies to increase interest, research should examine whether fitness professionals are able to safely prescribe exercise to high health-risk subgroups.

Lipofuscin Formation Catalyzed by the Milk Protein ß-Lactoglobulin: Lysine Residues in Cycloretinal Synthesis.

Lipofuscins are toxic autofluorescent byproducts of the visual cycle. The accumulation of lipofuscins such as cycloretinal in the retina is thought to play a role in the progression of age-related macular degeneration (AMD). Intriguingly, the milk protein ß-lactoglobulin (BLG) can promote the cyclodimerization of all-trans-retinal to cycloretinal both in vitro and in vivo. Here, site-directed mutagenesis of BLG and mass spectrometric analysis with substrate analogues demonstrate that lysine residues play a key role in catalysis. It is also shown that catalytic activity necessitates the presence of a physical binding site and cannot be mediated by a peptide chain. These studies provide insight into the mechanism of the cyclodimerization process and provide a model system for biocatalysis and biosynthesis of cycloretinal in vivo. In the long term, these studies may pave the way for drug development and inhibitor design as an early treatment regimen for AMD.

Self-reported health-enhancing physical activity recommendation adherence among 64,380 finnish adults.

The Finnish recommendations for health-enhancing physical activity (PA) for adults (≥18 years) recommend: (i) ≥150 minutes of moderate-to-vigorous-intensity physical activity (MVPA) and (ii) activities that develop muscle strength and balance ≥2 days/week. However, adherence to these recommendations among the Finnish adults is currently unknown. This study reports on the self-reported adherence to the PA recommendations and associations with sociodemographic factors among Finnish adults. Data were used from the Finnish "Regional Health and Well-being Study." In 2013-2014, postal questionnaires were sent to 132,560 persons, with 69,032 responding (response rate =52.1%). The weighted proportions adhering to the: (i) MVPA recommendation, (ii) sufficient muscle-strengthening activity (≥2 days/week), (iii) sufficient balance training (≥2 days/week), and (iv) Finnish health-enhancing PA recommendations (Finnish recommendations) were calculated. Associations with sociodemographic variables (eg, age, education level, self-rated health) were assessed using multiple logistic regression analyses. Of 69,032 respondents, 92.6% (n=64,380, response rate =48.6%, 18-98 years) reported on their physical activity levels. A total of 31.2% (95% CI: 30.8%-31.6%) met the aerobic MVPA recommendation, 17.2% (95% CI: 16.9%-17.6%) reported sufficient muscle-strengthening activity, 6.7% (95% CI: 6.4%-6.9%) reported sufficient balance training, and 10.8% (95% CI: 10.5%-11.1%) met the Finnish recommendations. In the adjusted analysis, those with poorer self-rated health, older age, lower education levels, and those classified overweight or obese were independently associated with lower odds of meeting the Finnish recommendations. The vast majority of Finnish adults do not meet the full PA recommendations. Public health action is needed to increase PA in Finland.

A large-scale genetic screen in Arabidopsis to identify genes involved in pollen exine production.

Exine, the outer plant pollen wall, has elaborate species-specific patterns, provides a protective barrier for male gametophytes, and serves as a mediator of strong and species-specific pollen-stigma adhesion. Exine is made of sporopollenin, a material remarkable for its strength, elasticity, and chemical durability. The chemical nature of sporopollenin, as well as the developmental mechanisms that govern its assembly into diverse patterns in different species, are poorly understood. Here, we describe a simple yet effective genetic screen in Arabidopsis (Arabidopsis thaliana) that was undertaken to advance our understanding of sporopollenin synthesis and exine assembly. This screen led to the recovery of mutants with a variety of defects in exine structure, including multiple mutants with novel phenotypes. Fifty-six mutants were selected for further characterization and are reported here. In 14 cases, we have mapped defects to specific genes, including four with previously demonstrated or suggested roles in exine development (MALE STERILITY2, CYP703A2, ANTHER-SPECIFIC PROTEIN6, TETRAKETIDE α-PYRONE REDUCTASE/DIHYDROFLAVONOL-4-REDUCTASE-LIKE1), and a number of genes that have not been implicated in exine production prior to this screen (among them, fatty acid ω-hydroxylase CYP704B1, putative glycosyl transferases At1g27600 and At1g33430, 4-coumarate-coenzyme A ligase 4CL3, polygalacturonase QUARTET3, novel gene At5g58100, and nucleotide-sugar transporter At5g65000). Our study illustrates that morphological screens of pollen can be extremely fruitful in identifying previously unknown exine genes and lays the foundation for biochemical, developmental, and evolutionary studies of exine production.

Milk, revealed "silent" chemistry: new mode of cycloretinal synthesis.

Bovine milk is by far the most commonly consumed milk in the western world. The protein composition in milk consists of casein and whey proteins, of which ß-lactoglobulin (BLG) is the principal constituent of the latter. Here we provide biochemical evidence that this milk protein, in purified form and in pasteurized store-bought milk, promotes the formation of cycloretinal (all-trans retinal dimer), and a variety of other cycloterpenals of biological relevance [Fishkin et al., Proc. Natl. Acad. Sci. U. S. A., 2005, 102, 7091-7096; Fishkin et al., Chirality, 2004, 16, 637-641; Kim et al., Proc. Natl. Acad. Sci. U. S. A., 2007, 104, 19273-19278]. Cycloretinal is an eye metabolite and among several toxic byproducts of the visual cycle firmly established to cause age-related macular degeneration. Experiments in rabbits further demonstrate that BLG/milk can survive the digestive system and promote this reaction in vivo [Caillard et al., Am. J. Physiol., 1994, 266(6), G1053-G1059]. Proteomic studies on age-related macular degeneration patients have detected BLG in the eye of these patients further suggesting that this milk protein could contribute to disease progression [Crabb et al., Proc. Natl. Acad. Sci. U. S. A., 2002, 99(23), 14682-14687].

Combining LiDAR and IKONOS data for eco-hydrological classification of an ombrotrophic peatland.

Remote sensing techniques have potential for peatland monitoring, but most previous work has focused on spectral approaches that often result in poor discrimination of cover types and neglect structural information. Peatlands contain structural "microtopes" (e.g., hummocks and hollows) which are linked to hydrology, biodiversity and carbon sequestration, and information on surface structure is thus a useful proxy for peatland condition. The objective of this work was to develop and test a new eco-hydrological mapping technique for ombrotrophic (rain-fed) peatlands using a combined spectral-structural remote sensing approach. The study site was Wedholme Flow, Cumbria, UK. Airborne light dectection and ranging (LiDAR) data were used with IKONOS data in a combined multispectral-structural approach for mapping peatland condition classes. LiDAR data were preprocessed so that spatial estimates of minimum and maximum land surface height, variance and semi-variance (from semi-variogram analysis) were extracted. These were assimilated alongside IKONOS data into a maximum likelihood classification procedure, and thematic outputs were compared. Ecological survey data were used to validate the results. Considerable improvements in thematic separation of peatland classes were achieved when spatially-distributed measurements of LiDAR variance or semi-variance were included. Specifically, the classification accuracy improved from 71.8% (IKONOS data only) to 88.0% when a LiDAR semi-variance product was used. Of note was the improved delineation of management classes (including Eriophorum bog, active raised bog and degraded raised bog). The application of a combined textural-optical approach can improve land cover mapping in areas where reliance on purely spectral discrimination approaches would otherwise result in considerable thematic uncertainty.

Synthesis and cellular effects of cycloterpenals: cyclohexadienal-based activators of neurite outgrowth.

An unusual class of diterpenoid natural products, 'cycloterpenals' (with a central cyclohexadienal core), that arise in nature by condensation of retinoids and other isoprenes, have been isolated from a variety of organisms including marine sponges as well as from the human eye. A milk whey protein has also demonstrated the formation of a cycloterpenal derived from beta-ionylidineacetaldehyde. Here, we generate a synthetic library of these molecules where we detail reaction conditions required to effect cross condensation of alpha,beta-unsaturated aldehydes as opposed to homodimerization. The ability of this class of molecules to activate neurite outgrowth activity is reported.

An efficient one-pot synthesis of tethered cyclohexadiene enaminonitriles from methyl-ketones: an effective route to quinazolines.

The quinazolines represent a useful natural product scaffold with demonstrated activities against disorders such as high blood pressure and benign prostatic hyperplasia. Here we report on the synthesis and biological activity of a series of quinazolines that were prepared by a one-pot synthesis of substituted cyclohexadiene enaminonitriles from methyl-ketones. The approach, which employs NaH, complements published procedures where LDA is utilized. While the NaH catalyzed reaction generates the cyclohexadiene enaminonitriles in high yields with heterocyclic substrates, the reaction fails to promote product formation of aliphatic alkyl substrates. On the contrary, the LDA mediated synthesis favors the long chain alkyl substituents while reactions involving the aromatic substrates result in low yields. The final conversion to the quinazolines is also a modification on literature protocols. In cellular assays, the quinazolines showed the most promising activity against Jurkat with CC(50) values in the low micromolar range. Weak activity was observed against microbial strains (Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae). The substituted enaminonitrile intermediates also exhibited weak anti-microbial activity and cytotoxicity against human T-cell leukemia.

A double-blind, placebo-controlled, dose-response pilot study evaluating intradiscal etanercept in patients with chronic discogenic low back pain or lumbosacral radiculopathy.

BACKGROUND: In recent years, convincing evidence has emerged implicating tumor necrosis factor alpha as a causative factor in radiculopathy and discogenic back pain. But although preliminary open-label studies demonstrated promising results for the treatment of low back pain with tumor necrosis factor-alpha inhibitors, early optimism has been tainted by a controlled study showing no significant benefit in sciatica. To determine whether outcomes might be improved by a more direct route of administration, the authors evaluated escalating doses of intradiscal etanercept in 36 patients with chronic lumbosacral radiculopathy or discogenic low back pain. METHODS: A double-blind, placebo-controlled pilot study was conducted whereby six patients received 0.1, 0.25, 0.5, 0.75, 1.0, or 1.5 mg etanercept intradiscally in each pain-generating disc. In each escalating dose group of six patients, one received placebo. A neurologic examination and postprocedure leukocyte counts were performed in all patients at 1-month follow-up visits. In patients who experienced significant improvement in pain scores and function, follow-up visits were conducted 3 and 6 months after the procedure. RESULTS: At 1-month follow-up, no differences were found for pain scores or disability scores between or within groups for any dose range or subgroup of patients. Only eight patients remained in the study after 1 month and elected to forego further treatment. No complications were reported, and no differences were noted between preprocedure and postprocedure leukocyte counts. CONCLUSIONS: Although no serious side effects were observed in this small study, a single low dose of intradiscal etanercept does not seem to be an effective treatment for chronic radicular or discogenic low back pain.

Proline promoted synthesis of ring-fused homodimers: self-condensation of alpha,beta-unsaturated aldehydes.

1,2,4-Trisubstituted cyclohexadienals can be prepared synthetically by self-condensation of beta-methyl substituted alpha, beta-unsaturated aldehydes. While molecules with this structural scaffold have been observed in nature, the biological roles of these compounds have yet to be thoroughly investigated. Here we investigate the use of L-proline and its derivatives to effect synthesis of these ring-fused homodimers. The scope of this reaction is investigated with different substrates and proline derivatives. Mechanistic hypotheses are put forth supported by NMR and mass spectrometry studies. The method will enable diversification of this scaffold in sufficient quantities for biological investigations.

Pyocyanin isolated from a marine microbial population: synergistic production between two distinct bacterial species and mode of action.

Marine microbial populations collected from the Hawaiian Islands were screened for antimicrobial activity. A blue metabolite was identified from mixed cell cultures, but production was not evident in pure cultures. Experiments designed to probe the synergistic role of the microorganisms are presented. Full characterization of the blue natural product, pyocyanin, is provided including corrections made to 1H and 13C-NMR assignments of the molecule misreported in the chemical literature and yeast transcriptome analysis. The transcriptional effects were consistent with the compound's purported role as an inducer of oxidative stress and damage and illustrates the overall potential of the method to reveal the primary biological/cellular effects of a natural product. The experiments outlined here might serve as a general paradigm for identification of natural products arising from microbial communities and investigation of their respective interactions.

The intravenous ketamine test predicts subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients.

UNLABELLED: Fibromyalgia (FM) is a challenging pain syndrome for which no reliable pharmacologic treatment exists. Recent clinical studies suggest that N-methyl-D-aspartate receptors might play a role in the pathogenesis of this disorder. To determine whether an intravenous (IV) ketamine test predicts the response to a therapeutic trial with an oral N-methyl-D-aspartate receptor antagonist, we performed a low-dose (0.1 mg/kg) IV ketamine infusion on 34 consecutive patients with FM, which was subsequently followed by an oral dextromethorphan (DX) treatment regimen. As per previous guidelines, the cutoff value for a positive response to the IV ketamine test was designated to be 67% pain relief, and a positive response to DX treatment was 50% pain reduction at 4- to 6-week follow-up visits. The degree of correlation between pain relief with ketamine and DX was highly significant (Pearson correlation coefficient, 0.66; P < .001). Ten patients responded positively to both ketamine and DX, 19 responded to neither drug, 3 had a positive response to ketamine but not DX, and 2 obtained good pain relief with DX but not ketamine. The sensitivity of the IV ketamine test was 83%, the specificity was 86%, the positive predictive value was 77%, and the negative predictive value was 91%. An association was also found between the development of side effects to the two treatments. PERSPECTIVE: The response to an IV ketamine infusion was found to predict the subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients, with an observed agreement of 83%. Considering the refractory nature of fibromyalgia to conventional pain treatments, the IV ketamine test might enhance patient care by saving time and reducing unnecessary treatment trials.

Avidin self-associates with boric acid gel suspensions: an affinity boron carrier that might be developed for boron neutron-capture therapy.

It has been shown in preliminary studies that the antibacterial protein avidin self-associates with the boric acid gel polymer, and avidin-coated gel particles in the micrometer and submicrometer size ranges are of interest for boron neutron-capture therapy (BNCT), which is neutron-induced fission of boron-10 to produce intense alpha radiation for tumor destruction. The gel particles carry large amounts of boron-10 and are theoretically able effect a meaningful tissue dosing through BNCT. A gross precipitation of gel particles occurs within 46 min of mixing when the avidin/colloid ratio is about 0.34 g avidin/g colloid. This is a minimum time if gel and avidin concentrations are in the low microgram/milliliter range, but at higher proportions of avidin the time delay to precipitation increases significantly; i.e., the colloid surface becomes blocked, inhibiting lattice formation. The avidin-coated gel particles eventually cross-link, forming a solid matrix and precipitating on a timescale measured on the order of an hour. At shorter exposure times rapid agglutination-like reactions were observed with biotinylated bovine albumin, suggesting that two-stage pretargeting of specific tissues should be possible with biotinylated antitumor antibodies. However, for BNCT to be practical, avidin's interaction with the gel needs to be strengthened, and all aryl-B(OH)(2) groups on the particle surfaces must be blocked, or else the particles will interact strongly and nonspecifically with each other and with the carbohydrate groups present on most cell surfaces. Glyceric acid delays the precipitation of the particle suspensions while most simple and complex carbohydrates accelerate it.

Serotonergic 5-HT2A receptors important for the oestradiol-induced surge of luteinising hormone-releasing hormone in the rat.

Serotonin (5-HT) plays a role in mediating the oestradiol-induced surge of luteinising hormone (LH), but so far the 5-HT receptor subtype involved has not been identified. Our previous in-situ hybridization and pharmacological studies suggest that the action of 5-HT involves the 5-HT2A receptor. The aim of the present study was to investigate this possibility by the direct approach of determining whether 5-HT2A receptor antagonists block the oestradiol-induced surge of luteinising hormone releasing hormone (LHRH). Adult female Wistar rats, which had shown at least two consecutive 4-day oestrous cycles, were ovariectomised under halothane anaesthesia in the morning of dioestrus and injected with vehicle (arachis oil) alone or oestradiol benzoate (OB). At 12.00 h of the next day, presumptive pro-oestrus, the animals were injected intraperitoneally with one of three 5-HT2A antagonists, a selective 5-HT reuptake inhibitor (fluoxetine), or the appropriate vehicles; hypophysial portal blood was then collected under alphaxalone anaesthesia between 15.00 and 19.00 h. The amount of LHRH released into hypophysial portal blood during consecutive 30-min periods was determined by radioimmunoassay. As expected, oestradiol, but not oil, triggered a surge of LHRH in hypophysial portal blood with a peak at about 16.00 h of presumptive pro-oestrus. This oestradiol-induced surge of LHRH was blocked by ketanserin, ritanserin and the highly selective 5-HT2A receptor antagonist, RP62203, but not by fluoxetine. These results provide the first direct evidence that the 5-HT2A receptor plays an important role in the oestradiol-induced surge of LHRH.

Diurnal variation of adrenocortical activity in chronic fatigue syndrome.

Baseline morning and evening serum cortisol and ACTH concentrations, and diurnal changes in hormone levels, were measured in 30 patients with chronic fatigue syndrome (CFS) but without concurrent depressive disorder and a control group of 15 weight-, age- and sex-matched healthy volunteers. Morning cortisol levels were non-significantly lower in CFS patients, while evening levels were non-significantly higher. ACTH concentrations were non-significantly higher in both the morning and evening. The diurnal change in cortisol levels was significantly less in CFS than in controls (p < 0.05). In CFS subjects, evening levels of cortisol correlated significantly with measures of general health and physical functioning, while diurnal change in cortisol was positively correlated with measures of functional improvement over the past year and current social functioning. These results suggest that there is a relationship between adrenocortical function and disability in CFS, but do not reveal the causal connection.

Diurnal variation of mood and neuropsychological function in major depression with melancholia.

20 DSM-III-R melancholics with clinically evident diurnal symptoms and 20 controls were assessed with a battery of neuropsychological tests, a test of maximum voluntary hand-grip, and neuroendocrine measures of hypothalamic-pituitary-adrenal axis function morning and evening in a 24-h period, using a balanced design. The morning pattern of neuropsychological impairment in the melancholics was comprehensive, affecting attention and concentration/working memory, episodic memory, reaction time and, strikingly, the speed of simultaneous match to sample, which was performed more slowly than the version of the task delayed to 0 or 4 s. The melancholics were significantly weaker than controls, on a measure of maximal voluntary contraction. Significantly improved neuropsychological function was seen in the melancholic patients in the evening, in line with diurnal improvement in mood; there was also a large increase in strength. Slowing on the digit symbol substitution test, the simultaneous match to sample task, total errors on the match to sample and hand-grip remained impaired in the evening compared to controls; other neuropsychological measures were no longer statistically different from control values which were often worsened. Neuroendocrine measures showed significantly raised levels of cortisol and ACTH morning and evening in the melancholics. Morning cortisol in the melancholics correlated with the diurnal improvement in neuropsychological functioning. The results have implications for the timing of neuropsychological assessment in major depression. Indices of neuropsychological and motor function may be as reliable quantitative estimates of illness severity as subjective estimates of mood.