How polluted is the Yangtze river? Water quality downstream from the Three Gorges Dam.
The concentrations of major anions and cations, nitrogen and phosphorus, dissolved and particulate trace elements, and organic pollutants were determined for the middle and lower reaches of the Yangtze River (Changjiang) from below the Three Gorges Dam (TGD) to the mouth at Shanghai in November 2006. The concentration of dissolved inorganic phosphate (DIP) was constant at a low level of 6-8 microgP/L, but the concentration of nitrate (NO(3)(-)) approximately doubled downstream and was closely correlated with K(+). This translated to a daily load of well over 1000 t of dissolved inorganic nitrogen (DIN) at Datong. The average concentrations of dissolved Pb (0.078+/-0.023 microg/L), Cd (0.024+/-0.009 microg/L), Cr (0.57+/-0.09 microg/L), Cu (1.9+/-0.7 microg/L), and Ni (0.50+/-0.49 microg/L) were comparable with those in other major world rivers, while As (3.3+/-1.3 microg/L) and Zn (1.5+/-0.6 microg/L) were higher by factors of 5.5 and 2.5, respectively. The trace element contents of suspended particles of As (31+/-28 microg/g), Pb (83+/-34 microg/g), and Ni (52+/-16 microg/g) were close to maximum concentrations recommended for rivers by the European Community (EC). The average concentrations of Cd (2.6+/-1.6 microg/g), Cr (185+/-102 microg/g), Cu (115+/-106 microg/g), and Zn (500+/-300 microg/g) exceeded the EC standards by a factor of two, and Hg (4.4+/-4.7 microg/g) by a factor of 4 to 5. Locally occurring peak concentrations exceed these values up to fourfold, among them the notorious elements As, Hg, and Tl. All dissolved and particulate trace element concentrations were higher than estimates made twenty years ago [Zhang, J., Geochemistry of trace metals from Chinese river/estuary systems: an overview. Estuar Coast Shelf Sci 1995; 41: 631-658.]. The enormous loads of anthropogenic pollutants disposed to the river were diluted by the large water discharge of the Yangtze even during the lowest flow resulting in the relatively low concentration levels of trace elements and organic pollutants observed. We estimated loads of e.g. As, Pb and Ni to the East China Sea to be about 4600 kg As d(-1), 3000 kg Pb d(-1), and 2000 kg Ni d(-1). About 6000 t d(-1) of dissolved organic carbon (DOC) was delivered into the sea at the time of our cruise. We tested for 236 organic pollutants, and only the most infamous were found to be barely above detection limits. We estimated that the load of chlorinated compounds, aromatic hydrocarbons, phenols, and PAHs were between 500 and 3500 kg d(-1). We also detected eight herbicides entering the estuary with loads of 5-350 kg d(-1). The pollutant load, even when at low concentrations, are considerable and pose an increasing threat to the health of the East China Sea ecosystem.


Quality Improvement in Surgery Combining Lean Improvement Methods with Teamwork Training: A Controlled Before-After Study.
To investigate the effectiveness of combining teamwork training and lean process improvement, two distinct approaches to improving surgical safety. We conducted a controlled interrupted time series study in a specialist UK Orthopaedic hospital incorporating a plastic surgery team (which received the intervention) and an Orthopaedic theatre team acting as a control. We used a 3 month intervention with 3 months data collection period before and after it. A combined teamwork training and lean process improvement intervention was delivered by an experienced specialist team. Before and after the intervention we evaluated team non-technical skills using NOTECHS II, technical performance using the glitch rate and WHO checklist compliance using a simple 3 point scale. We recorded complication rate, readmission rate and length of hospital stay data for 6 months before and after the intervention. In the active group, but not the control group, full compliance with WHO Time Out (T/O) increased from 14 to 71% (p = 0.032), Sign Out attempt rate (S/O) increased from 0% to 50% (p<0.001) and Oxford NOTECHS II scores increased after the intervention (P = 0.058). Glitch rate decreased in the active group and increased in the control group (p = 0.001). Complications and length of stay appeared to rise in the control group and fall in the active group. Combining teamwork training and systems improvement enhanced both technical and non-technical operating team process measures, and were associated with a trend to better safety outcome measures in a controlled study comparison. We suggest that approaches which address both system and culture dimensions of safety may prove valuable in reducing risks to patients.


Going, going, still there: using the WebCite service to permanently archive cited web pages.
Scholars are increasingly citing electronic "web references" which are not preserved in libraries or full text archives. WebCite is a new standard for citing web references. To "webcite" a document involves archiving the cited Web page through www.webcitation.org and citing the WebCite permalink instead of (or in addition to) the unstable live Web page. This journal has amended its "instructions for authors" accordingly, asking authors to archive cited Web pages before submitting a manuscript. Almost 200 other journals are already using the system. We discuss the rationale for WebCite, its technology, and how scholars, editors, and publishers can benefit from the service. Citing scholars initiate an archiving process of all cited Web references, ideally before they submit a manuscript. Authors of online documents and websites which are expected to be cited by others can ensure that their work is permanently available by creating an archived copy using WebCite and providing the citation information including the WebCite link on their Web document(s). Editors should ask their authors to cache all cited Web addresses (Uniform Resource Locators, or URLs) "prospectively" before submitting their manuscripts to their journal. Editors and publishers should also instruct their copyeditors to cache cited Web material if the author has not done so already. Finally, WebCite can process publisher submitted "citing articles" (submitted for example as eXtensible Markup Language [XML] documents) to automatically archive all cited Web pages shortly before or on publication. Finally, WebCite can act as a focussed crawler, caching retrospectively references of already published articles. Copyright issues are addressed by honouring respective Internet standards (robot exclusion files, no-cache and no-archive tags). Long-term preservation is ensured by agreements with libraries and digital preservation organizations. The resulting WebCite Index may also have applications for research assessment exercises, being able to measure the impact of Web services and published Web documents through access and Web citation metrics.


[Molecular characteristics of the full-length genome of two new Japanese encephalitis virus isolated from mosquitoes in Hubei province].
To sequence and analyze the complete genome of two new Japanese encephalitis virus (JEV) strains isolated from mosquitoes collected in Hubei province in 2008, and to understand the molecular biological characteristics of JEV in this area. RT-PCR was used to amplify the fragments of HBZG08-09 strain and HBZG08-55 strain with 16 pairs overlapping primers after they had been recovered and identified, then the full-length genome was obtained by sequencing and splicing. Biological sequence alignment, nucleotide and amino acid sequence analysis, phylogenetic analysis and analysis of amino acid differences were performed by the software of Clustal X (1.83), MegAlign, Mega (4.0) and Genedoc (3.2). The genome of two new strains were both 10 965 nucleotides in length with a single open reading frame from 96 to 10 392 coding for a 3432 amino acid poly-protein, the homology of nucleotide and amino acid sequence between two isolates were 98.2% and 99.7% respectively. Further study showed that the new strains were both belonging to genotype I. Two new strains were most closely related to isolates obtained from Henan and Zhejiang province in recent years. Compared with the live attenuated vaccine strain SA-14-14-2 in China, HBZG08-09 strain had 82 amino acid divergence; HBZG08-55 had 84 amino acid divergences. But the amino acid difference occurred in sites were not the key ones affecting the toxicity or antigenic of JEV. Two new JEV isolates were both belonging to genotype I, and the key sites of amino acid were not changed.


[NEURODEGENERATIVE DISEASES; NUTRITIONAL ASPECTS].
neurodegenerative diseases cause changes in the level of consciousness or swallowing mechanisms that often necessitate a specialized nutritional support. review the risk of malnutrition and its treatment in patients with cerebral vascular disease, Parkinson's disease, dementia and amyotrophic lateral sclerosis. degenerative neurological diseases are one of the main indications for nutritional support in our country. In acute processes (cerebral vascular disease), proper nutritional management is related to better outcomes and reduced complications. In chronic neurodegenerative processes (amyotrophic lateral sclerosis and dementia), malnutrition is a major problem that worsens the prognosis of these patients, the proper management of dysphagia and its complications, as well as the use of different stages of support being necessary nutritional. A correct nutritional evaluation of these patients and a right nutrition intervention is essential in monitoring their disease. Finally, in advanced Parkinson's disease, nutritional support, as in previous neurodegenerative diseases, is of huge importance. Protein dietary load and its distribution in the diet of these patients are important, too. Finally, American Society for Parenteral and Enteral Nutrition ASPEN recommend, with a degree of evidence B, performing a screening of malnutrition in patients with neurological diseases. a correct nutritional evaluation and adequate nutritional support should be part of diagnostic and therapeutic process of these diseases.


Post-fire forest regeneration shows limited climate tracking and potential for drought-induced type conversion.
Disturbance such as wildfire may create opportunities for plant communities to reorganize in response to climate change. The interaction between climate change and disturbance may be particularly important in forests, where many of the foundational plant species (trees) are long-lived and where poor initial tree establishment can result in conversion to shrub- or graminoid-dominated systems. The response of post-disturbance vegetation establishment to post-disturbance weather conditions, particularly to extreme weather, could therefore provide useful information about how forest communities will respond to climate change. We examined the effect of post-fire weather conditions on post-fire tree, shrub, and graminoid recruitment in fire-adapted forests in northern California, USA, by surveying regenerating vegetation in severely burned areas 4-5 yr after 14 different wildfires that burned between 2004 and 2012. This time period (2004-2016) encompassed a wide range of post-fire weather conditions, including a period of extreme drought. For the most common tree species, we observed little evidence of disturbance-mediated community reorganization or range shifts but instead either (1) low sensitivity of recruitment to post-fire weather or (2) weak but widespread decreases in recruitment under unusually dry post-fire conditions, depending on the species. The occurrence of a single strong drought year following fire was more important than a series of moderately dry years in explaining tree recruitment declines. Overall, however, post-fire tree recruitment patterns were explained more strongly by long-term climate and topography and local adult tree species abundance than by post-fire weather conditions. This observation suggests that surviving adult trees can contribute to a "biological inertia" that restricts the extent to which tree community composition will track changes in climate through post-disturbance recruitment. In contrast to our observations in trees, we observed substantial increases in shrub and graminoid establishment under post-fire drought, suggesting that shifts in dominance between functional groups may become more likely in a future with more frequent and intense drought.


Molecular tweezers for lysine and arginine - powerful inhibitors of pathologic protein aggregation.
Molecular tweezers represent the first class of artificial receptor molecules that have made the way from a supramolecular host to a drug candidate with promising results in animal tests. Due to their unique structure, only lysine and arginine are well complexed with exquisite selectivity by a threading mechanism, which unites electrostatic, hydrophobic and dispersive attraction. However, tweezer design must avoid self-dimerization, self-inclusion and external guest binding. Moderate affinities of molecular tweezers towards sterically well accessible basic amino acids with fast on and off rates protect normal proteins from potential interference with their biological function. However, the early stages of abnormal Aβ, α-synuclein, and TTR assembly are redirected upon tweezer binding towards the generation of amorphous non-toxic materials that can be degraded by the intracellular and extracellular clearance mechanisms. Thus, specific host-guest chemistry between aggregation-prone proteins and lysine/arginine binders rescues cell viability and restores animal health in models of AD, PD, and TTR amyloidosis.


The interaction of C6H6 and C6H12 with noble metal surfaces: electronic level alignment and the origin of the interface dipole.
The electronic interaction of two molecules, the aromatic benzene (C6H6) and the saturated hydrocarbon cyclohexane (C6H12) with a Cu(111) surface, have been determined using precise, ab initio electronic structure calculations. For the interaction of these adsorbates with the substrate, we present a detailed analysis and decomposition of various individual chemical mechanisms that contribute. A novel aspect of this analysis is the use of charge-density difference contour plots to graphically display the chemistry. A wave-function-based approach was used in order to avoid problems when the presently most commonly employed approach, density-functional theory, is applied to weakly chemisorbed molecules, where the interaction is dominated by van der Waals forces. The present information are not only relevant with regard to understanding the chemistry going on when molecules are adsorbed on a Cu surface but also have important consequences with regard to charge injection in molecular electronic devices, e.g., organic field-effect transistors and organic light-emitting diodes.


Assessing the functional performance of post-call hospital doctors using a Nintendo Wii.
Sleep deprivation is an established part of the working life for Non-Consultant Hospital Doctors (NCHDs) in Ireland. Concern exists about the effect of extended NCHD work hours. We utilised a Nintendo Wii to evaluate motor function of NCHDs both prior to their on-call shift and the day afterwards. Data was exported to SPSS ver. 15 for statistical analysis with p < 0.05 considered significant. A total of 72 NCHDs were invited to participate in this study. There was a 62.5% (45) rate of follow-up. Overall 27 (60%) NCHDs were on medical call, with 18 (40%) on surgical call. There was no statistically significant difference between NCHDs pre-and post-call motor assessment scores. The majority of study participants (75.5%, n = 34) had four or more hours sleep. On-call duty allows for a greater than anticipated amount of sleep per on-call shift and therefore has a negligible effect on the motor skills of medical staff.


Labor-Force Participation, Policies & Practices in an Aging America: Adaptation Essential for a Healthy & Resilient Population.
Population aging in the United States poses challenges to societal institutions while simultaneously creating opportunities to build a more resilient, successful, and cohesive society. Work organization and labor-force participation are central to both the opportunities and challenges posed by our aging society. We argue that expectations about old age have not sufficiently adapted to the reality of aging today. Our institutions need more adaptation in order to successfully face the consequences of demographic change. Although this adaptation needs to focus especially on work patterns among the "younger elderly," our society has to change its general attitudes toward work organization and labor-force participation, which will have implications for education and health care. We also show that work's beneficial effects on well-being in older ages are often neglected, while the idea that older workers displace younger workers is a misconception emerging from the "lump of labor" fallacy. We conclude, therefore, that working at older ages can lead to better quality of life for older people and to a more productive and resilient society overall.


Urinary metabolites of prostanoids and risk of recurrent colorectal adenomas in the Aspirin/Folate Polyp Prevention Study (AFPPS).
Aspirin has been shown to protect against colorectal neoplasms; however, the optimal chemopreventive dose and underlying mechanisms are unclear. We aimed to study the relationship between prostanoid metabolites and aspirin's effect on adenoma occurrence. We used data from the Aspirin/Folate Polyp Prevention Study, in which 1,121 participants with a recent adenoma were randomized to placebo or two doses of aspirin (81 or 325 mg/d) to be taken until the next surveillance colonoscopy, anticipated about 3 years later. Urinary metabolites of prostanoids (PGE-M, PGI-M, and dTxB2) were measured using liquid chromatography/mass spectrometry or GC/NICI-MS in 876 participants near the end of treatment follow-up. Poisson regression with a robust error variance was used to calculate relative risks and 95% confidence intervals. PGE-M, PGI-M, and dTxB2 levels were 28%, 37%, and 60% proportionately lower, respectively, in individuals who took 325 mg of aspirin compared with individuals who took placebo (all P < 0.001). Similarly, among individuals who took 81 mg of aspirin, PGE-M, PGI-M, and dTxB2 were, respectively, 18%, 30%, and 57% proportionally lower compared with placebo (all P < 0.005). None of the metabolites or their ratios were statistically significantly associated with the risk of adenoma occurrence. The effect of aspirin in reducing adenoma risk was independent of prostanoid levels. Aspirin use is associated with lower levels of urinary prostanoid metabolites. However, our findings do not support the hypothesis that these metabolites are associated with adenoma occurrence, suggesting that COX-dependent mechanisms may not completely explain the chemopreventive effect of aspirin on colorectal neoplasms.


Speckle reducing bilateral filter for cattle follicle segmentation.
Ultrasound imaging technology has wide applications in cattle reproduction and has been used to monitor individual follicles and determine the patterns of follicular development. However, the speckles in ultrasound images affect the post-processing, such as follicle segmentation and finally affect the measurement of the follicles. In order to reduce the effect of speckles, a bilateral filter is developed in this paper. We develop a new bilateral filter for speckle reduction in ultrasound images for follicle segmentation and measurement. Different from the previous bilateral filters, the proposed bilateral filter uses normalized difference in the computation of the Gaussian intensity difference. We also present the results of follicle segmentation after speckle reduction. Experimental results on both synthetic images and real ultrasound images demonstrate the effectiveness of the proposed filter. Compared with the previous bilateral filters, the proposed bilateral filter can reduce speckles in both high-intensity regions and low intensity regions in ultrasound images. The segmentation of the follicles in the speckle reduced images by the proposed method has higher performance than the segmentation in the original ultrasound image, and the images filtered by Gaussian filter, the conventional bilateral filter respectively.


Quality assurance in military medical research and medical radiation accident management.
The provision of quality radiation-related medical diagnostic and therapeutic treatments cannot occur without the presence of robust quality assurance and standardization programs. Medical laboratory services are essential in patient treatment and must be able to meet the needs of all patients and the clinical personnel responsible for the medical care of these patients. Clinical personnel involved in patient care must embody the quality assurance process in daily work to ensure program sustainability. In conformance with the German Federal Government's concept for modern departmental research, the international standard ISO 9001, one of the relevant standards of the International Organization for Standardization (ISO), is applied in quality assurance in military medical research. By its holistic approach, this internationally accepted standard provides an excellent basis for establishing a modern quality management system in line with international standards. Furthermore, this standard can serve as a sound basis for the further development of an already established quality management system when additional standards shall apply, as for instance in reference laboratories or medical laboratories. Besides quality assurance, a military medical facility must manage additional risk events in the context of early recognition/detection of health risks of military personnel on deployment in order to be able to take appropriate preventive and protective measures; for instance, with medical radiation accident management. The international standard ISO 31000:2009 can serve as a guideline for establishing risk management. Clear organizational structures and defined work processes are required when individual laboratory units seek accreditation according to specific laboratory standards. Furthermore, international efforts to develop health laboratory standards must be reinforced that support sustainable quality assurance, as in the exchange and comparison of test results within the scope of external quality assurance, but also in the exchange of special diagnosis data among international research networks. In summary, the acknowledged standard for a quality management system to ensure quality assurance is the very generic standard ISO 9001.Health Phys. 103(2):221-225; 2012.


Quantitative digital assessment of MGMT immunohistochemical expression in glioblastoma tissue.
Recent reports have suggested an important clinical role for hypermethylation of the O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter in patients with glioblastomas. Whether MGMT protein expression is correlated with promoter hypermethylation and patient outcomes, however, has not been elucidated. Here we describe a quantitative digital method for assessment of MGMT-specific immunostaining, and analyze the relationship between expression levels and methylation status of the MGMT promoter. We investigated 46 tumors from patients who received a diagnosis of glioblastoma or gliosarcoma. Immunohistochemistry with anti-MGMT antibody and methylation-specific PCR using bisulfite-modified tumor DNA were performed. The digital assessment method used image-analysis software to determine a digital MGMT staining index, and the results were compared with those obtained via conventional visual assessments. The digital staining index clearly correlated with the methylation status of MGMT promoter. In addition, the index correlated with our observational results when nuclear and cytoplasmic staining were assessed in three different fields. Our digital assessment method enabled us to assess uncertain immunopositive samples objectively and quantitatively, which is an important consideration when examining heterogeneous cellular staining. We expect that this method will be useful for assessment of heterogeneous staining with any antibodies.


Changes in the pollen seasons of the early flowering trees Alnus spp. and Corylus spp. in Worcester, United Kingdom, 1996-2005.
Previous work on Betula spp. (birch) in the UK and at five sites in Europe has shown that pollen seasons for this taxon have tended to become earlier by about 5-10 days per decade in most regions investigated over the last 30 years. This pattern has been linked to the trend to warmer winters and springs in recent years. However, little work has been done to investigate the changes in the pollen seasons for the early flowering trees. Several of these, such as Alnus spp. and Corylus spp., have allergens, which cross-react with those of Betula spp., and so have a priming effect on allergic people. This paper investigates pollen seasons for Alnus spp. and Corylus spp. for the years 1996-2005 at Worcester, in the West Midlands, United Kingdom. Pollen data for daily average counts were collected using a Burkard volumetric trap sited on the exposed roof of a three-story building. The climate is western maritime. Meteorological data for daily temperatures (maximum and minimum) and rainfall were obtained from the local monitoring sites. The local area up to approximately 10 km surrounding the site is mostly level terrain with some undulating hills and valleys. The local vegetation is mixed farmland and deciduous woodland. The pollen seasons for the two taxa investigated are typically late December or early January to late March. Various ways of defining the start and end of the pollen seasons were considered for these taxa, but the most useful was the 1% method whereby the season is deemed to have started when 1% of the total catch is achieved and to have ended when 99% is reached. The cumulative catches (in grains/m(3)) for Alnus spp. varied from 698 (2001) to 3,467 (2004). For Corylus spp., they varied from 65 (2001) to 4,933 (2004). The start dates for Alnus spp. showed 39 days difference in the 10 years (earliest 2000 day 21, latest 1996 day 60). The end dates differed by 26 days and the length of season differed by 15 days. The last 4 years in the set had notably higher cumulative counts than the first 2, but there was no trend towards earlier starts. For Corylus spp. start days also differed by 39 days (earliest 1999 day 5, latest 1996 day 44). The end date differed by 35 days and length of season by 26 days. Cumulative counts and lengths of season showed a distinct pattern of alternative high (long) and low (short) years. There is some evidence of a synchronous pattern for Alnus spp.. These patterns show some significant correlations with temperature and rainfall through the autumn, winter and early spring, and some relationships with growth degree 4s and chill units, but the series is too short to discern trends. The analysis has provided insight to the variation in the seasons for these early flowering trees and will form a basis for future work on building predictive models for these taxa.


Tea leaf-derived exosome-like nanotherapeutics retard breast tumor growth by pro-apoptosis and microbiota modulation.
While several artificial nanodrugs have been approved for clinical treatment of breast tumor, their long-term applications are restricted by unsatisfactory therapeutic outcomes, side reactions and high costs. Conversely, edible plant-derived natural nanotherapeutics (NTs) are source-widespread and cost-effective, which have been shown remarkably effective in disease treatment. Herein, we extracted and purified exosome-like NTs from tea leaves (TLNTs), which had an average diameter of 166.9 nm and a negative-charged surface of - 28.8 mV. These TLNTs contained an adequate slew of functional components such as lipids, proteins and pharmacologically active molecules. In vitro studies indicated that TLNTs were effectively internalized by breast tumor cells (4T1 cells) and caused a 2.5-fold increase in the amount of intracellular reactive oxygen species (ROS) after incubation for 8 h. The high levels of ROS triggered mitochondrial damages and arrested cell cycles, resulting in the apoptosis of tumor cells. The mouse experiments revealed that TLNTs achieved good therapeutic effects against breast tumors regardless of intravenous injection and oral administration through direct pro-apoptosis and microbiota modulation. Strikingly, the intravenous injection of TLNTs, not oral administration, yielded obvious hepatorenal toxicity and immune activation. These findings collectively demonstrate that TLNTs can be developed as a promising oral therapeutic platform for the treatment of breast cancer.


Thyroid vascularity and blood flow are not dependent on serum thyroid hormone levels: studies in vivo by color flow doppler sonography.
Thyroid blood flow is greatly enhanced in untreated Graves' disease, but it is not known whether it is due to thyroid hormone excess or to thyroid hyperstimulation by TSH-receptor antibody. To address this issue in vivo patients with different thyroid disorders were submitted to color flow doppler sonography (CFDS). We investigated 24 normal subjects, and 78 patients with untreated hyperthyroidism (49 with Graves' hyperthyroidism, 24 with toxic adenoma, and 5 patients with TSH-secreting pituitary adenoma (TSHoma)), 19 patients with thyrotoxicosis (7 with thyrotoxicosis factitia, and 12 with subacute thyroiditis), 37 euthyroid patients with goitrous Hashimoto's thyroiditis, and 21 untreated hypothyroid patients with Hashimoto's thyroiditis. Normal subjects had CFDS pattern 0 (absent or minimal intraparenchimal spots) and mean intraparenchimal peak systolic velocity (PSV) of 4.8+/-1.2cm/s. Patients with spontaneous hyperthyroidism due to Graves' disease, TSHoma, and toxic adenoma had significantly increased PSV (P<0.0001, P=0.0004, P<0.0001 respectively vs controls) and CFDS pattern. Patients with Graves' disease had CFDS pattern II (mild increase of color flow doppler signal) in 10 (20%) and pattern III (marked increase) in 39 cases (80%). Mean PSV was 15+/-3cm/s. Patients with toxic adenoma had CFDS pattern I (presence of parenchymal blood flow with patchy uneven distribution) in 2 (8%), pattern II in 16 (70%) and pattern III in 5 (22%). Mean PSV was 11+/-2.4cm/s. Patients with TSHoma showed CFDS pattern I in one case (20%) and pattern II in 4 (80%). Mean PSV was 14.8+/-4.2cm/s. Patients with thyrotoxicosis had normal PSV (4.2+/-1. 1cm/s in subacute thyroiditis, 4+/-0.8cm/s in thyrotoxicosis factitia, P=not significant vs controls) and CFDS pattern 0. Untreated euthyroid patients with goitrous Hashimoto's thyroiditis had CFDS pattern 0, and mean PSV (4.3+/-0.9cm/s; P=not significant vs controls). Untreated hypothyroid patients with goitrous Hashimoto's thyroiditis had CFDS pattern I in 14 cases (67%), pattern II in 4 (19%) and pattern 0 in 3 (14%) and mean PSV (5.6+/-1. 4cm/s) was higher than that of controls (P=0.026). An increase in both intrathyroidal vascularity and blood velocity was observed in patients with spontaneous hyperthyroidism but not in thyrotoxicosis due to either ingestion of thyroid hormones or to a thyroidal destructive process. The slightly increased vascularity and blood velocity observed in patients with hypothyroid Hashimoto's thyroiditis suggests that thyroid stimulation by either TSH-receptor antibody or TSH is responsible for the increased thyroid blood flow.


The Dose-Response Relationship Between Tobacco Education Advertising and Calls to Quitlines in the United States, March-June, 2012.
We estimated changes in call volume in the United States in response to increases in advertising doses of the Tips From Former Smokers (Tips) campaign, the first federal national tobacco education campaign, which aired for 12 weeks from March 19 to June 10, 2012. We also measured the effectiveness of ad taglines that promoted calls directly with a quitline number (1-800-QUIT-NOW) and indirectly with a cessation help website (Smokefree.gov). Multivariate regressions estimated the weekly number of calls to 1-800-QUIT-NOW by area code as a function of weekly market-level gross rating points (GRPs) from CDC's Tips campaign in 2012. The number of quitline calls attributable solely to Tips was predicted. For quitline-tagged ads, an additional 100 television GRPs per week was associated with an increase of 89 calls per week in a typical area code in the United States (P < .001). The same unit increase in advertising GRPs for ads tagged with Smokefree.gov was associated with an increase of 29 calls per week in any given area code (P < .001). We estimated that the Tips campaign was responsible for more than 170,000 additional calls to 1-800-QUIT-NOW during the campaign and that it would have generated approximately 140,000 additional calls if all ads were tagged with 1-800-QUIT-NOW. For campaign planners, these results make it possible to estimate 1) the likely impact of tobacco prevention media buys and 2) the additional quitline capacity needed at the national level should future campaigns of similar scale use 1-800-QUIT-NOW taglines exclusively.


Rasch Analysis of the Norwegian Version of the Occupational Balance Questionnaire in a Sample of Occupational Therapy Students.
Recently, the Occupational Balance Questionnaire developed in Sweden was translated into Norwegian. No studies to date have examined the measurement properties of the Norwegian version of this questionnaire. The study is aimed at examining the psychometric properties of the Norwegian version of the Occupational Balance Questionnaire, the OBQ11-N. Along with sociodemographic data, 180 occupational therapy students enrolled at two Norwegian universities completed the OBQ11-N as well as one question each related to health and quality of life and some sociodemographic variables. Rasch analysis was employed for examining rating scale functioning, item and person validity, dimensionality, and differential item functioning. Item categories were ordered, but there were potential gaps in the measurement of the construct. Person reliability was fair, whereas item reliability was low. Point biserial correlations were positive, indicating that all items contributed to the construct. Factor loadings were low for two items, and there were indices of a second underlying dimension and item redundancy. Many people were not aligned with the items, and some items functioned differently across various demographic variables. Conclusion and Significance. The OBQ11-N did not function as an adequate measure of occupational balance in a sample of students. Potentially, the detected measurement problems may be solved by adding more relevant items to a larger item pool, from which the best fitting items should be selected.


Human immunodeficiency virus type 1 drug susceptibility determination by using recombinant viruses generated from patient sera tested in a cell-killing assay.
A simple approach for the determination of drug susceptibilities by using human immunodeficiency virus type 1 (HIV-1) RNA from the sera of patients is described. HIV-1 RNA was extracted from patient sera, and the 5' part of the reverse transcriptase (RT) gene was transcribed into DNA and amplified in a nested PCR. The amplified fragment covers the 3' part of the protease gene and amino acids 1 to 304 of the RT gene. This fragment can be introduced through homologous recombination, as described previously, into a novel HIV-1 reference strain (pHXB2 delta 2-261RT) from which amino acids 2 to 261 of RT have been deleted. The resulting recombinant virus expresses all properties of the HXB2 reference strain except for those encoded by the introduced part of the patient RT gene. Recombinant viruses were subsequently tested for drug susceptibility in a microtiter format killing assay [3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay] as well as in the standard HeLa CD4+ plaque reduction assay. Similar susceptibility profiles were obtained by each assay with recombinant viruses derived from patients receiving alternating nevirapine and zidovudine treatment or lamivudine-zidovudine combination therapy. In conclusion, this approach enables high-through-put determination of the drug susceptibilities of serum RNA-derived RT genes, independent of the patient's viral background, and generates the possibility of relating changes in susceptibility to changes in viral genotypes.


Control of the lumbar neutral zone decreases low back pain and improves self-evaluated work ability: a 12-month randomized controlled study.
A randomized controlled study with 12 months intervention. To study the effectiveness of a training intervention with emphases on the control of lumbar neutral zone (NZ) and behavior modeling as secondary prevention of low back pain (LBP) and disability. Improving the control of lumbar NZ and enhancing muscle activation patterns ensuring spinal stability have been proposed as means for secondary prevention of LBP and disability. In addition, cognitive behavior interventions have been shown to lower the risk of recurrence of LBP and long-term disability. Middle-aged working men with recent LBP but without severe disability were randomly allocated to either a training (TG, n = 52) or control group (CG, n = 54). The aim was to exercise twice a week for 12 months, once guided and once independently. The outcome measures were the changes in intensity of LBP, disability, self-evaluated future work ability, and neuromuscular fitness. The intensity of LBP decreased significantly more (39%) in the TG than in CG at 12 months. The proportion of subjects with negative expectations about their future work ability decreased in both groups at 6 and 12 months; however, the proportion was significantly bigger in TG compared with CG (P = 0.028). There effects on disability indexes and fitness were not statistically significant. Controlling lumbar NZ is a specific form of exercise and daily self-care with potential for prevention of recurrent nonspecific LBP and disability among middle aged working men.


Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring.
Prenatal cannabis exposure has been linked to addiction vulnerability, but the neurobiology underlying this risk is unknown. Striatal dopamine and opioid-related genes were studied in human fetal subjects exposed to cannabis (as well as cigarettes and alcohol). Cannabis-related gene disturbances observed in the human fetus were subsequently characterized with an animal model of prenatal Δ-9-tetrahydrocannabinol (THC) (.15 mg/kg) exposure. Prenatal cannabis exposure decreased dopamine receptor D2 (DRD2) messenger RNA expression in the human ventral striatum (nucleus accumbens [NAc]), a key brain reward region. No significant alterations were observed for the other genes in cannabis-exposed subjects. Maternal cigarette use was associated with reduced NAc prodynorphin messenger RNA expression, and alcohol exposure induced broad alterations primarily in the dorsal striatum of most genes. To explore the mechanisms underlying the cannabis-associated disturbances, we exposed pregnant rats to THC and examined the epigenetic regulation of the NAc Drd2 gene in their offspring at postnatal day 2, comparable to the human fetal period studied, and in adulthood. Chromatin immunoprecipitation of the adult NAc revealed increased 2meH3K9 repressive mark and decreased 3meH3K4 and RNA polymerase II at the Drd2 gene locus in the THC-exposed offspring. Decreased Drd2 expression was accompanied by reduced dopamine D2 receptor (D(2)R) binding sites and increased sensitivity to opiate reward in adulthood. These data suggest that maternal cannabis use alters developmental regulation of mesolimbic D(2)R in offspring through epigenetic mechanisms that regulate histone lysine methylation, and the ensuing reduction of D(2)R might contribute to addiction vulnerability later in life.


IRIDIUM exposure increases c-fos expression in the mouse brain only at levels which likely result in tissue heating.
With the rapid development of wireless communication technology over the last 20 years, there has been some public concern over possible health effects of long-term, low-level radiofrequency exposure from cellular telephones. As an initial step in compiling a database for risk analysis by government agencies, the effects of 1-h exposure of mice to a 1.6-GHz radiofrequency signal, given as either a continuous wave or pulse modulated at 11 Hz with a duty cycle of 4:1 and a pulse duration of 9.2 ms IRIDIUM), on c-fos gene expression in the brain was investigated. The IRIDIUM signal is the operating frequency for a ground-to-satellite-to-ground cellular communications web which has recently become fully operational, and was named as such due to the original designed employment of the same number of low orbiting satellites as there are electrons orbiting the nucleus of an iridium atom. The expression of c-fos was not significantly elevated in the brains of mice until exposure levels exceeded six times the peak dose and 30 times the whole body average dose as maximal cellular telephone exposure limits in humans. Higher level exposure using either continuous wave (analog) or IRIDIUM signals elevated c-fos to a similar extent, suggesting no obvious pulsed modulation-specific effects. The pattern of c-fos elevation in limbic cortex and subcortex areas at higher exposure levels is most consistent with a stress response due to thermal perception coupled with restraint and/or neuron activity near thermoregulatory regions, and not consistent with any direct interaction of IRIDIUM energy with brain tissue.


[Services for the early recognition of psychoses and bipolar disorders in Germany: inventory survey study].
In order to successfully implement early recognition and intervention services in psychiatry, it is crucial to improve the attention to and recognition of severe mental disorders and to establish low threshold services that are available at short notice for diagnostic and treatment procedures. For this inventory survey study, questionnaires regarding the presence and type of early recognition services for psychoses and bipolar disorders were sent separately to German psychiatric hospitals by mail in September and October 2012. Additionally, an internet search and telephone inquiries as well as an alignment of responses from the two surveys and with network lists from published and ongoing early recognition studies were performed. Response rates in the psychosis and bipolar disorder surveys were 21 % (51/246) and 36 % (91/255), respectively. Three quarters of participating institutions reported at least an interest in creating an early recognition service for psychoses and one half for bipolar disorders. Overall, 26 institutions were identified that already offer early recognition of psychoses and 18 of bipolar disorders. Of these 16 are low threshold early recognition centres with direct access at short notice for first-episode patients and person from at-risk groups and separate specific public relations work. Of these early recognition centres five have a separate and easy to find homepage available; in an additional 15 institutions the specific websites are part of the institutions homepage. Despite widespread interest and the increasingly recognized importance of early recognition and intervention services in psychiatry, there is currently no nationwide coverage with early recognition services for severe mental disorders in Germany. Public relations and information activities are not (yet) sufficiently provided to reach affected persons and their environment. Common standards are (still) missing and interdisciplinary models are sparse. To correct these shortcomings, amongst other factors, acquisition of sufficient funding for such services is required.


Fluxviz - Cytoscape plug-in for visualization of flux distributions in networks.
Methods like FBA and kinetic modeling are widely used to calculate fluxes in metabolic networks. For the analysis and understanding of simulation results and experimentally measured fluxes visualization software within the network context is indispensable. We present Flux Viz, an open-source Cytoscape plug-in for the visualization of flux distributions in molecular interaction networks. FluxViz supports (i) import of networks in a variety of formats (SBML, GML, XGMML, SIF, BioPAX, PSI-MI) (ii) import of flux distributions as CSV, Cytoscape attributes or VAL files (iii) limitation of views to flux carrying reactions (flux subnetwork) or network attributes like localization (iv) export of generated views (SVG, EPS, PDF, BMP, PNG). Though FluxViz was primarily developed as tool for the visualization of fluxes in metabolic networks and the analysis of simulation results from FASIMU, a flexible software for batch flux-balance computation in large metabolic networks, it is not limited to biochemical reaction networks and FBA but can be applied to the visualization of arbitrary fluxes in arbitrary graphs. The platform-independent program is an open-source project, freely available at http://sourceforge.net/projects/fluxvizplugin/ under GNU public license, including manual, tutorial and examples.


What methods are used to promote patient and family involvement in healthcare regulation? A multiple case study across four countries.
In the regulation of healthcare, the subject of patient and family involvement figures increasingly prominently on the agenda. However, the literature on involving patients and families in regulation is still in its infancy. A systematic analysis of how patient and family involvement in regulation is accomplished across different health systems is lacking. We provide such an overview by mapping and classifying methods of patient and family involvement in regulatory practice in four countries; Norway, England, the Netherlands, and Australia. We thus provide a knowledge base that enables discussions about possible types of involvement, and advantages and difficulties of involvement encountered in practice. The research design was a multiple case study of patient and family involvement in regulation in four countries. The authors collected 1) academic literature if available and 2) documents of regulators that describe user involvement. Based on the data collected, the authors from each country completed a pre-agreed template to describe the involvement methods. The following information was extracted and included where available: 1) Method of involvement, 2) Type of regulatory activity, 3) Purpose of involvement, 4) Who is involved and 5) Lessons learnt. Our mapping of involvement strategies showed a range of methods being used in regulation, which we classified into four categories: individual proactive, individual reactive, collective proactive, and collective reactive methods. Reported advantages included: increased quality of regulation, increased legitimacy, perceived justice for those affected, and empowerment. Difficulties were also reported concerning: how to incorporate the input of users in decisions, the fact that not all users want to be involved, time and costs required, organizational procedures standing in the way of involvement, and dealing with emotions. Our mapping of user involvement strategies establishes a broad variety of ways to involve patients and families. The four categories can serve as inspiration to regulators in healthcare. The paper shows that stimulating involvement in regulation is a challenging and complex task. The fact that regulators are experimenting with different methods can be viewed positively in this regard.


Oxytocin signaling in mouse taste buds.
The neuropeptide, oxytocin (OXT), acts on brain circuits to inhibit food intake. Mutant mice lacking OXT (OXT knockout) overconsume salty and sweet (i.e. sucrose, saccharin) solutions. We asked if OXT might also act on taste buds via its receptor, OXTR. Using RT-PCR, we detected the expression of OXTR in taste buds throughout the oral cavity, but not in adjacent non-taste lingual epithelium. By immunostaining tissues from OXTR-YFP knock-in mice, we found that OXTR is expressed in a subset of Glial-like (Type I) taste cells, and also in cells on the periphery of taste buds. Single-cell RT-PCR confirmed this cell-type assignment. Using Ca2+ imaging, we observed that physiologically appropriate concentrations of OXT evoked [Ca2+]i mobilization in a subset of taste cells (EC50 approximately 33 nM). OXT-evoked responses were significantly inhibited by the OXTR antagonist, L-371,257. Isolated OXT-responsive taste cells were neither Receptor (Type II) nor Presynaptic (Type III) cells, consistent with our immunofluorescence observations. We also investigated the source of OXT peptide that may act on taste cells. Both RT-PCR and immunostaining suggest that the OXT peptide is not produced in taste buds or in their associated nerves. Finally, we also examined the morphology of taste buds from mice that lack OXTR. Taste buds and their constituent cell types appeared very similar in mice with two, one or no copies of the OXTR gene. We conclude that OXT elicits Ca2+ signals via OXTR in murine taste buds. OXT-responsive cells are most likely a subset of Glial-like (Type I) taste cells. OXT itself is not produced locally in taste tissue and is likely delivered through the circulation. Loss of OXTR does not grossly alter the morphology of any of the cell types contained in taste buds. Instead, we speculate that OXT-responsive Glial-like (Type I) taste bud cells modulate taste signaling and afferent sensory output. Such modulation would complement central pathways of appetite regulation that employ circulating homeostatic and satiety signals.


Transcriptome analysis of genetically matched human induced pluripotent stem cells disomic or trisomic for chromosome 21.
Trisomy of chromosome 21, the genetic cause of Down syndrome, has the potential to alter expression of genes on chromosome 21, as well as other locations throughout the genome. These transcriptome changes are likely to underlie the Down syndrome clinical phenotypes. We have employed RNA-seq to undertake an in-depth analysis of transcriptome changes resulting from trisomy of chromosome 21, using induced pluripotent stem cells (iPSCs) derived from a single individual with Down syndrome. These cells were originally derived by Li et al, who genetically targeted chromosome 21 in trisomic iPSCs, allowing selection of disomic sibling iPSC clones. Analyses were conducted on trisomic/disomic cell pairs maintained as iPSCs or differentiated into cortical neuronal cultures. In addition to characterization of gene expression levels, we have also investigated patterns of RNA adenosine-to-inosine editing, alternative splicing, and repetitive element expression, aspects of the transcriptome that have not been significantly characterized in the context of Down syndrome. We identified significant changes in transcript accumulation associated with chromosome 21 trisomy, as well as changes in alternative splicing and repetitive element transcripts. Unexpectedly, the trisomic iPSCs we characterized expressed higher levels of neuronal transcripts than control disomic iPSCs, and readily differentiated into cortical neurons, in contrast to another reported study. Comparison of our transcriptome data with similar studies of trisomic iPSCs suggests that trisomy of chromosome 21 may not intrinsically limit neuronal differentiation, but instead may interfere with the maintenance of pluripotency.


Identification of plant glutaredoxin targets.
Glutaredoxins (Grxs) are small ubiquitous proteins of the thioredoxin (Trx) family, which catalyze dithiol-disulfide exchange reactions or reduce protein-mixed glutathione disulfides. In plants, several Trx-interacting proteins have been isolated from different compartments, whereas very few Grx-interacting proteins are known. We describe here the determination of Grx target proteins using a mutated poplar Grx, various tissular and subcellular plant extracts, and liquid chromatography coupled to tandem mass spectrometry detection. We have identified 94 putative targets, involved in many processes, including oxidative stress response [peroxiredoxins (Prxs), ascorbate peroxidase, catalase], nitrogen, sulfur, and carbon metabolisms (methionine synthase, alanine aminotransferase, phosphoglycerate kinase), translation (elongation factors E and Tu), or protein folding (heat shock protein 70). Some of these proteins were previously found to interact with Trx or to be glutathiolated in other organisms, but others could be more specific partners of Grx. To substantiate further these data, Grx was shown to support catalysis of the stroma beta-type carbonic anhydrase and Prx IIF of Arabidopsis thaliana, but not of poplar 2-Cys Prx. Overall, these data suggest that the interaction could occur randomly either with exposed cysteinyl disulfide bonds formed within or between target proteins or with mixed disulfides between a protein thiol and glutathione.


Time-sensitive prefrontal involvement in associating confidence with task performance illustrates metacognitive introspection in monkeys.
Metacognition refers to the ability to be aware of one's own cognition. Ample evidence indicates that metacognition in the human primate is highly dissociable from cognition, specialized across domains, and subserved by distinct neural substrates. However, these aspects remain relatively understudied in macaque monkeys. In the present study, we investigated the functionality of macaque metacognition by combining a confidence proxy, hierarchical Bayesian meta-d' computational modelling, and a single-pulse transcranial magnetic stimulation technique. We found that Brodmann area 46d (BA46d) played a critical role in supporting metacognition independent of task performance; we also found that the critical role of this region in meta-calculation was time-sensitive. Additionally, we report that macaque metacognition is highly domain-specific with respect to memory and perception decisions. These findings carry implications for our understanding of metacognitive introspection within the primate lineage.


Pore stability and gating in voltage-activated calcium channels.
Calcium channel family members activate at different membrane potentials, which enables tissue specific calcium entry. Pore mutations affecting this voltage dependence are associated with channelopathies. In this review we analyze the link between voltage sensitivity and corresponding kinetic phenotypes of calcium channel activation. Systematic changes in hydrophobicity in the lower third of S6 segments gradually shift the activation curve thereby determining the voltage sensitivity. Homology modeling suggests that hydrophobic residues that are located in all four S6 segments close to the inner channel mouth might form adhesion points stabilizing the closed gate. Simulation studies support a scenario where voltage sensors and the pore are essentially independent structural units. We speculate that evolution designed the voltage sensing machinery as robust "all-or-non" device while the varietys of voltage sensitivities of different channel types was accomplished by shaping pore stability.


Combining common genetic variants and non-genetic risk factors to predict risk of cutaneous melanoma.
Melanoma heritability is among the highest for cancer and single nucleotide polymorphisms (SNPs) contribute to it. To date, only SNPs that reached statistical significance in genome-wide association studies or few candidate SNPs have been included in melanoma risk prediction models. We compared four approaches for building polygenic risk scores (PRS) using 12 874 melanoma cases and 23 203 controls from Melanoma Meta-Analysis Consortium as a training set, and newly genotyped 3102 cases and 2301 controls from the MelaNostrum consortium for validation. We estimated adjusted odds ratios (ORs) for melanoma risk using traditional melanoma risk factors and the PRS with the largest area under the receiver operator characteristics curve (AUC). We estimated absolute risks combining the PRS and other risk factors, with age- and sex-specific melanoma incidence and competing mortality rates from Italy as an example. The best PRS, including 204 SNPs (AUC = 64.4%; 95% confidence interval (CI) = 63-65.8%), developed using winner's curse estimate corrections, had a per-quintile OR = 1.35 (95% CI = 1.30-1.41), corresponding to a 3.33-fold increase comparing the 5th to the 1st PRS quintile. The AUC improvement by adding the PRS was up to 7%, depending on adjusted factors and country. The 20-year absolute risk estimates based on the PRS, nevus count and pigmentation characteristics for a 60-year-old Italian man ranged from 0.5 to 11.8% (relative risk = 26.34), indicating good separation.


High-resolution, large-scale laboratory measurements of a sandy beach and dynamic cobble berm revetment.
High quality laboratory measurements of nearshore waves and morphology change at, or near prototype-scale are essential to support new understanding of coastal processes and enable the development and validation of predictive models. The DynaRev experiment was completed at the GWK large wave flume over 8 weeks during 2017 to investigate the response of a sandy beach to water level rise and varying wave conditions with and without a dynamic cobble berm revetment, as well as the resilience of the revetment itself. A large array of instrumentation was used throughout the experiment to capture: (1) wave transformation from intermediate water depths to the runup limit at high spatio-temporal resolution, (2) beach profile change including wave-by-wave changes in the swash zone, (3) detailed hydro and morphodynamic measurements around a developing and a translating sandbar.


The role of diffusion weighted magnetic resonance imaging in oncologic settings.
There is growing interest in the applications of diffusion-weighted-imaging (DWI) in oncologic area for last ten years. DWI has important advantages as do not require contrast medium, very quick technique and it provides qualitative and quantitative information that can be helpful for tumor assessment. In this article, we present oncologic applications of DWI in the parts of the body. DWI has been applied to the evaluation of central nervous system (CNS) pathologies. Some technologic advances lead to using of DWI in the extracranial sites such as abdomen and pelvis. As well as tumor detection and characterization, DWI has been widely used for predicting and monitoring response to therapy. One of the most prominent contributions of DWI is differentiation of between malignant and benign tumoral process. Apparent-diffusion-coefficient (ADC) value is quantitative parameter of DWI which reflects diffusion movements of water molecules in various tissues. Most of the studies suggested that malignant tumors had lower ADC values than benign ones. DWI may be a routine sequence in oncologic settings and it provides much useful information about tumoral tissue. We think it can be added to conventional magnetic resonance imaging (MRI) sequences.


When the heart rules the head: ischaemic stroke and intracerebral haemorrhage complicating infective endocarditis.
Sir William Osler meticulously described the clinical manifestations of infective endocarditis in 1885, concluding that: 'few diseases present greater difficulties in the way of diagnosis … which in many cases are practically insurmountable'. Even with modern investigation techniques, diagnosing infective endocarditis can be hugely challenging, yet is critically important in patients presenting with stroke (both cerebral infarction and intracranial haemorrhage), its commonest neurological complication. In ischaemic stroke, intravenous thrombolysis carries an unacceptably high risk of intracranial haemorrhage, while in intracerebral haemorrhage, mycotic aneurysms require urgent treatment to avoid rebleeding, and in all cases, prompt treatment with antibiotics and valve surgery may be life-saving. Here, we describe typical presentations of ischaemic stroke and intracerebral haemorrhage caused by infective endocarditis. We review the diagnostic challenges, the importance of rapid diagnosis, treatment options and controversies.


Multicenter study to investigate factors associated with change in rectal temperature during anesthesia in dogs.
To determine factors associated with change in rectal temperature (RT) of dogs undergoing anesthesia. 507 dogs. In a prospective observational study, the RT of dogs undergoing anesthesia at 5 veterinary hospitals was recorded at the time of induction of anesthesia and at the time of recovery from anesthesia (ie, at the time of extubation). Demographic data, body condition score, American Society of Anesthesiologists (ASA) physical status classification, types of procedure performed and medications administered, duration of anesthesia, and use of heat support were also recorded. Multiple regression analysis was performed to determine factors that were significantly associated with a decrease or an increase (or no change) in RT. Odds ratios were calculated for factors significantly associated with a decrease in RT. Among the 507 dogs undergoing anesthesia, RT decreased in 89% (median decrease, -1.2°C [-2.2°F]; range, -0.1°C to -5.7°C [-0.2°F to -10.3°F]), increased in 9% (median increase, 0.65°C [1.2°F]; range, 0.1°C to 2.1°C [3.8°F]), and did not change in 2%. Factors that significantly predicted and increased the odds of a decrease in RT included lower weight, ASA classification > 2, surgery for orthopedic or neurologic disease, MRI procedures, use of an α2-adrenergic or μ-opioid receptor agonist, longer duration of anesthesia, and higher heat loss rate. Lack of μ-opioid receptor agonist use, shorter duration of anesthesia, and lower heat loss rate were significantly associated with an increase in RT. Multiple factors that were associated with a decrease in RT in dogs undergoing anesthesia were identified. Knowledge of these factors may help identify dogs at greater risk of developing inadvertent perianesthetic hypothermia.


Measurement of energy expenditure.
Measurement of energy expenditure in humans is required to assess metabolic needs, fuel utilisation, and the relative thermic effect of different food, drink, drug and emotional components. Indirect and direct calorimetric and non-calorimetric methods for measuring energy expenditure are reviewed, and their relative value for measurement in the laboratory and field settings is assessed. Where high accuracy is required and sufficient resources are available, an open-circuit indirect calorimeter can be used. Open-circuit indirect calorimeters can employ a mask, hood, canopy or room/chamber for collection of expired air. For short-term measurements, mask, hood or canopy systems suffice. Chamber-based systems are more accurate for the long-term measurement of specified activity patterns but behaviour constraints mean they do not reflect real life. Where resources are limited and/or optimum precision can be sacrificed, flexible total collection systems and non-calorimetric methods are potentially useful if the limitations of these methods are appreciated. The use of the stable isotope technique, doubly labelled water, enables total daily energy expenditure to be measured accurately in free-living subjects. The factorial method for combining activity logs and data on the energy costs of activities can also provide detailed information on free-living subjects.


Interactions of Opioids and HIV Infection in the Pathogenesis of Chronic Pain.
Over 50% of HIV-1/AIDS patients suffer chronic pain. Currently, opioids are the cornerstone medications for treating severe pain in these patients. Ironically, emerging clinical data indicates that repeated use of opiate pain medicines might in fact heighten the chronic pain states in HIV patients. Both laboratory-based and clinical studies strongly suggest that opioids exacerbate the detrimental effects of HIV-1 infection on the nervous system, both on neurons and glia. The combination of opioids and HIV-1infection may promote the damage of neurons, including those in the pain sensory and transmission pathway, by activating both caspase-dependent and caspase-independent pro-apoptotic pathways. In addition, the opiate-HIV-1 interaction may also cause widespread disturbance of glial function and elicit glial-derived pro-inflammatory responses that dysregulate neuronal function. The deregulation of neuron-glia cross-talk that occurs with the combination of HIV-1 and opioids appears to play an important role in the development of the pathological pain state. In this article, we wish to provide an overview of the potential molecular and cellular mechanisms by which opioids may interact with HIV-1 to cause neurological problems, especially in the context of HIV-associated pathological pain. Elucidating the underlying mechanisms will help researchers and clinicians to understand how chronic use of opioids for analgesia enhances HIV-associated pain. It will also assist in optimizing therapeutic approaches to prevent or minimize this significant side effect of opiate analgesics in pain management for HIV patients.


Organic compounds in fluid inclusions of Archean quartz-Analogues of prebiotic chemistry on early Earth.
The origin of life is still an unsolved mystery in science. Hypothetically, prebiotic chemistry and the formation of protocells may have evolved in the hydrothermal environment of tectonic fault zones in the upper continental crust, an environment where sensitive molecules are protected against degradation induced e.g. by UV radiation. The composition of fluid inclusions in minerals such as quartz crystals which have grown in this environment during the Archean period might provide important information about the first organic molecules formed by hydrothermal synthesis. Here we present evidence for organic compounds which were preserved in fluid inclusions of Archean quartz minerals from Western Australia. We found a variety of organic compounds such as alkanes, halocarbons, alcohols and aldehydes which unambiguously show that simple and even more complex prebiotic organic molecules have been formed by hydrothermal processes. Stable-isotope analysis confirms that the methane found in the inclusions has most likely been formed from abiotic sources by hydrothermal chemistry. Obviously, the liquid phase in the continental Archean crust provided an interesting choice of functional organic molecules. We conclude that organic substances such as these could have made an important contribution to prebiotic chemistry which might eventually have led to the formation of living cells.


Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients.
Diabetic nephropathy leading to kidney failure is a major complication of both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes mellitus, and glomerular structural lesions (especially expansion of the mesangium) may constitute the principal cause of decline in kidney function experienced by a significant fraction of diabetic patients. Although the biochemical bases of these mesangial abnormalities remain unknown, an understanding of the natural history of diabetic nephropathy from a combined structural and functional approach can lead to greater pathophysiological insight. Work in animals has supported the concept that the metabolic disturbances of diabetes mellitus cause diabetic nephropathy, with structural and functional lesions prevented or reversed with improved or normalized glycemic control. Additional research must address this fundamental issue in humans, especially the response of advancing mesangial lesions to improved glycemic control. Factors not directly related to the metabolic perturbations of diabetes may serve to accelerate or diminish the pathophysiological processes of diabetic nephropathy. The elucidation and management of these factors, when coupled with improved glycemic control, may moderate the development or progression of diabetic kidney lesions in humans.


Deletions in GRID2 lead to a recessive syndrome of cerebellar ataxia and tonic upgaze in humans.
To identify the genetic cause of a syndrome causing cerebellar ataxia and eye movement abnormalities. We identified 2 families with cerebellar ataxia, eye movement abnormalities, and global developmental delay. We performed genetic analyses including single nucleotide polymorphism genotyping, linkage analysis, array comparative genomic hybridization, quantitative PCR, and Sanger sequencing. We obtained eye movement recordings of mutant mice deficient for the ortholog of the identified candidate gene, and performed immunohistochemistry using human and mouse brain specimens. All affected individuals had ataxia, eye movement abnormalities, most notably tonic upgaze, and delayed speech and cognitive development. Homozygosity mapping identified the disease locus on chromosome 4q. Within this region, a homozygous deletion of GRID2 exon 4 in the index family and compound heterozygous deletions involving GRID2 exon 2 in the second family were identified. Grid2-deficient mice showed larger spontaneous and random eye movements compared to wild-type mice. In developing mouse and human cerebella, GRID2 localized to the Purkinje cell dendritic spines. Brain MRI in 2 affected children showed progressive cerebellar atrophy, which was more severe than that of Grid2-deficient mice. Biallelic deletions of GRID2 lead to a syndrome of cerebellar ataxia and tonic upgaze in humans. The phenotypic resemblance and similarity in protein expression pattern between humans and mice suggest a conserved role for GRID2 in the synapse organization between parallel fibers and Purkinje cells. However, the progressive and severe cerebellar atrophy seen in the affected individuals could indicate an evolutionarily unique role for GRID2 in the human cerebellum.


Habitual diets rich in dark-green vegetables are associated with an increased response to ω-3 fatty acid supplementation in Americans of African ancestry.
Although substantial variation exists in individual responses to omega-3 (ω-3) (n-3) fatty acid supplementation, the causes for differences in response are largely unknown. Here we investigated the associations between the efficacy of ω-3 fatty acid supplementation and a broad range of nutritional and clinical factors collected during a double-blind, placebo-controlled trial in participants of African ancestry, randomly assigned to receive either 2 g eicosapentaenoic acid (EPA) + 1 g docosahexaenoic acid (n = 41) or corn/soybean oil placebo (n = 42) supplements for 6 wk. Food-frequency questionnaires were administered, and changes in erythrocyte lipids, lipoproteins, and monocyte 5-lipoxygenase-dependent metabolism were measured before and after supplementation. Mixed-mode linear regression modeling identified high (n = 28) and low (n = 13) ω-3 fatty acid response groups on the basis of changes in erythrocyte EPA abundance (P < 0.001). Compliance was equivalent (∼88%), whereas decreases in plasma triglycerides and VLDL particle sizes and reductions in stimulated monocyte leukotriene B4 production were larger in the high-response group. Although total diet quality scores were similar, the low-response group showed lower estimated 2005 Healthy Eating Index subscores for dark-green and orange vegetables and legumes (P = 0.01) and a lower intake of vegetables (P = 0.02), particularly dark-green vegetables (P = 0.002). Because the findings reported here are associative in nature, prospective studies are needed to determine if dietary dark-green vegetables or nutrients contained in these foods can enhance the efficacy of ω-3 fatty acid supplements. This trial was registered at clinicaltrials.gov as NCT00536185.


Nutritional effects on reproductive performance of captive adult female coyotes (Canis latrans).
Interactions between animals and their environment are fundamental to ecological research. Field studies of coyote (Canis latrans) reproductive performance suggest mean litter size changes in response to prey abundance. However, this relationship has been assessed primarily by using carcasses collected from trappers. The objective of this study was to assess whether nutritional manipulation prior to mating affected reproduction in adult female coyotes. We examined the effects of caloric restriction during the 7 months prior to estrus on the reproductive rates of 11 captive female coyotes and the subsequent initial survival of pups through two reproductive cycles. This was a 2-year study with a cross-over design so each female was monitored for reproductive performance on each of the two diet treatments. We assessed the number of implantation scars, number of pups born, sex ratios of pups, average pup weight at birth and 2- and 6-weeks of age, and the survival rates between implantation and 2-weeks of age for two diet treatments. We found the mean number of implantation sites and pups whelped during a reproductive cycle was influenced by food-intake prior to conception. Additionally, we found evidence suggesting the effects of nutritional stress may persist for additional breeding cycles. We also provided evidence suggesting well-fed females tended to have more male pups. Understanding how environmental factors influence reproductive output may improve model predictions of coyote population dynamics.


Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial.
To provide paclitaxel, an investigational drug at the inception of this study, to women with chemotherapy-refractory metastatic breast cancer and to evaluate response and toxicity in these patients. Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastatic breast cancer and a contraindication to further doxorubicin treatment received paclitaxel either at 175 mg/m2 intravenously (IV) over 24 hours or at 135 mg/m2 if they had prior irradiation to 30% of marrow-bearing bone or a cumulative dose of mitomycin > or = 20 mg/m2. In a subgroup of patients (n = 172) with measurable disease, four complete responses (CRs) and 36 partial responses (PRs) occurred, for an overall response rate of 23% (95% confidence interval [CI], 17% to 30%). No differences in response rates were noted according either to the number of prior chemotherapy regimens received or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutropenia in 45% of patients and a hospitalization rate of 49%. Paclitaxel's activity in this multiinstitutional trial in heavily pretreated patients confirms the encouraging results attained in single-institution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative care, supportive measures such as colony-stimulating factors and antibiotics were not used prophylactically. Current research efforts are focusing on whether paclitaxel's activity against breast cancer is dose- and/or schedule-dependent, and on what role it has in patients with less advanced disease.


Multi-omics studies in cellular models of methylmalonic acidemia and propionic acidemia reveal dysregulation of serine metabolism.
Methylmalonic acidemia (MMA) and propionic acidemia (PA) are related disorders of mitochondrial propionate metabolism, caused by defects in methylmalonyl-CoA mutase (MUT) and propionyl-CoA carboxylase (PCC), respectively. These biochemical defects lead to a complex cascade of downstream metabolic abnormalities, and identification of these abnormal pathways has important implications for understanding disease pathophysiology. Using a multi-omics approach in cellular models of MMA and PA, we identified serine and thiol metabolism as important areas of metabolic dysregulation. We performed global proteomic analysis of fibroblasts and untargeted metabolomics analysis of plasma from individuals with MMA to identify novel pathways of dysfunction. We probed these novel pathways in CRISPR-edited, MUT and PCCA null HEK293 cell lines via targeted metabolomics, gene expression analysis, and flux metabolomics tracing utilization of 13C-glucose. Proteomic analysis of fibroblasts identified upregulation of multiple proteins involved in serine synthesis and thiol metabolism including: phosphoserine amino transferase (PSAT1), cystathionine beta synthase (CBS), and mercaptopyruvate sulfurtransferase (MPST). Metabolomics analysis of plasma revealed significantly increased levels of cystathionine and glutathione, central metabolites in thiol metabolism. CRISPR-edited MUT and PCCA HEK293 cells recapitulate primary defects of MMA and PA and have upregulation of transcripts associated with serine and thiol metabolism including PSAT1. 13C-glucose flux metabolomics in MUT and PCCA null HEK293 cells identified increases in serine de novo biosynthesis, serine transport, and abnormal downstream TCA cycle utilization. We identified abnormal serine metabolism as a novel area of cellular dysfunction in MMA and PA, thus introducing a potential new target for therapeutic investigation.


Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling.
The generation of excessive amounts of reactive oxygen species (ROS) leads to cellular oxidative stress that underlies a variety of forms of hepatocyte injury and death including that from alcohol. Although ROS can induce cell damage through direct effects on cellular macromolecules, the injurious effects of ROS are mediated largely through changes in signal transduction pathways such as the mitogen-activated protein kinase c-Jun N-terminal kinase (JNK). In response to alcohol, hepatocytes have increased levels of the enzyme cytochrome P450 2E1 (CYP2E1) which generates an oxidant stress that promotes the development of alcoholic steatosis and liver injury. These effects are mediated in large part through overactivation of JNK that alters cell death pathways. Targeting the JNK pathway or its downstream effectors may be a useful therapeutic approach to the oxidative stress generated by CYP2E1 in alcoholic liver disease.


Teaching resources. Ligand-gated ion channels.
This Teaching Resource provides a summary and slides derived from a lecture covering ligand-gated ion channels (LGICs), and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture focuses on two families of LGICs: the Cys-loop receptors and the ionotropic glutamate receptors. For Cys-loop receptors, much of the material is based on studies of the nicotinic acetylcholine receptor, including overall receptor topology, the basis for ionic selectivity, the identity of the gate, and the coupling of agonist binding to the opening of the gate. In the glutamate receptors, the conserved topology, and the differential kinetics and ion selectivities, among the AMPA-type and NMDA-type glutamate receptors are covered. The unique voltage-dependence of NMDA-type receptors is addressed, with special reference to the role of these receptors in synaptic plasticity.


The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span.
The highly conserved target-of-rapamycin (TOR) protein kinases control cell growth in response to nutrients and growth factors. In mammals, TOR has been shown to interact with raptor to relay nutrient signals to downstream translation machinery. We report that in C. elegans, mutations in the genes encoding CeTOR and raptor result in dauer-like larval arrest, implying that CeTOR regulates dauer diapause. The daf-15 (raptor) and let-363 (CeTOR) mutants shift metabolism to accumulate fat, and raptor mutations extend adult life span. daf-15 transcription is regulated by DAF-16, a FOXO transcription factor that is in turn regulated by daf-2 insulin/IGF signaling. This is a new mechanism that regulates the TOR pathway. Thus, DAF-2 insulin/IGF signaling and nutrient signaling converge on DAF-15 (raptor) to regulate C. elegans larval development, metabolism and life span.


Reassessment of psychological distress and post-traumatic stress disorder in United States Air Force Distributed Common Ground System operators.
The goal of this study was to assess for the main sources of occupational stress, as well as self-reported symptoms of distress and post-traumatic stress disorder among U.S. Air Force (USAF) Distributed Common Ground System (DCGS) intelligence exploitation and support personnel. DCGS intelligence operators (n=1091) and nonintelligence personnel (n = 447) assigned to a USAF Intelligence, Surveillance, and Reconnaissance Wing responded to the web-based survey. The overall survey response rate was 31%. Study results revealed the most problematic stressors among DCGS intelligence personnel included high workload, low manning, as well as organizational leadership and shift work issues. Results also revealed 14.35% of DCGS intelligence operators' self-reported high levels of psychological distress (twice the rate of DCGS nonintelligence support personnel). Furthermore, 2.0% to 2.5% self-reported high levels of post-traumatic stress disorder symptoms, with no significant difference between groups. The implications of these findings are discussed along with recommendations for USAF medical and mental health providers, as well as operational leadership.


Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration.
The signaling adapter p62 plays a coordinating role in mediating phosphorylation and ubiquitin-dependent trafficking of interacting proteins. However, there is little known about the physiologic role of this protein in brain. Here, we report age-dependent constitutive activation of glycogen synthase kinase 3beta, protein kinase B, mitogen-activated protein kinase, and c-Jun-N-terminal kinase in adult p62(-/-) mice resulting in hyperphosphorylated tau, neurofibrillary tangles, and neurodegeneration. Biochemical fractionation of p62(-/-) brain led to recovery of aggregated K63-ubiquitinated tau. Loss of p62 was manifested by increased anxiety, depression, loss of working memory, and reduced serum brain-derived neurotrophic factor levels. Our findings reveal a novel role for p62 as a chaperone that regulates tau solubility thereby preventing tau aggregation. This study provides a clear demonstration of an Alzheimer-like phenotype in a mouse model in the absence of expression of human genes carrying mutations in amyloid-beta protein precursor, presenilin, or tau. Thus, these findings provide new insight into manifestation of sporadic Alzheimer disease and the impact of obesity.


Analyzing protein topology based on Laguerre tessellation of a pore-traversing water network.
Given the tight relation between protein structure and function, we present a set of methods to analyze protein topology, implemented in the VLDP program, relying on Laguerre space partitions built from series of molecular dynamics snapshots. The Laguerre partition specifies inter-atomic contacts, formalized in graphs. The deduced properties are the existence and count of water aggregates, possible passage ways and constrictions, the structure, connectivity, stability and depth of the water network. As a test-case, the membrane protein FepA is investigated in its full environment, yielding a more precise description of the protein surface. Inside FepA, the solvent splits into isolated clusters and an intricate network connecting both sides of the lipid bilayer. The network is dynamic, connections set on and off, occasionally substantially relocating traversing paths. Subtle differences are detected between two forms of FepA, ligand-free and complexed with its natural iron carrier, the enterobactin. The complexed form has more constricted and more centered openings in the upper part whereas, in the lower part, constriction is released: two main channels between the plug and barrel lead directly to the periplasm. Reliability, precision and the variety of topological features are the main interest of the method.


Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy.
Interleukin-7 (IL-7) has critical and nonredundant roles in T-cell development, hematopoiesis, and postdevelopmental immune functions as a prototypic homeostatic cytokine. Based on a large body of preclinical evidence, it may have multiple therapeutic applications in immunodeficiency states, either physiologic (immunosenescence), pathologic (HIV), or iatrogenic (postchemotherapy and posthematopoietic stem cell transplant), and may have roles in immune reconstitution or enhancement of immunotherapy. We report here on the toxicity and biological activity of recombinant human IL-7 (rhIL-7) in humans. Subjects with incurable malignancy received rhIL-7 subcutaneously every other day for 2 weeks in a phase I interpatient dose escalation study (3, 10, 30, and 60 microg/kg/dose). The objectives were safety and dose-limiting toxicity determination, identification of a range of biologically active doses, and characterization of biological and, possibly, antitumor effects. Mild to moderate constitutional symptoms, reversible spleen and lymph node enlargement, and marked increase in peripheral CD3(+), CD4(+), and CD8(+) lymphocytes were seen in a dose-dependent and age-independent manner in all subjects receiving >or=10 microg/kg/dose, resulting in a rejuvenated circulating T-cell profile, resembling that seen earlier in life. In some subjects, rhIL-7 induced in the bone marrow a marked, transient polyclonal proliferation of pre-B cells showing a spectrum of maturation as well as an increase in circulating transitional B cells. This study shows the potent biological activity of rhIL-7 in humans over a well-tolerated dose range and allows further exploration of its possible therapeutic applications.


Androgens and Psychosocial Factors Related to Sexual Dysfunctions in Premenopausal Women∗: ∗2016 ISSM Female Sexual Dysfunction Prize.
The female sexual response is complex and influenced by several biological, psychological, and social factors. Testosterone is believed to modulate a woman's sexual response and desire, because low levels are considered a risk factor for impaired sexual function, but previous studies have been inconclusive. To investigate how androgen levels and psychosocial factors are associated with female sexual dysfunction (FSD), including hypoactive sexual desire disorder (HSDD). The cross-sectional study included 428 premenopausal women 19 to 58 years old who completed a questionnaire on psychosocial factors and had blood sampled at days 6 to 10 in their menstrual cycle. Logistic regression models were built to test the association among hormone levels, psychosocial factors, and sexual end points. Five different sexual end points were measured using the Female Sexual Function Index and the Female Sexual Distress Scale: impaired sexual function, sexual distress, FSD, low sexual desire, and HSDD. Serum levels of total and free testosterone, androstenedione, dehydroepiandrosterone sulfate, and androsterone glucuronide were analyzed using mass spectrometry. After adjusting for psychosocial factors, women with low sexual desire had significantly lower mean levels of free testosterone and androstenedione compared with women without low sexual desire. None of the androgens were associated with FSD in general or with HSDD in particular. Relationship duration longer than 2 years and mild depressive symptoms increased the risk of having all the sexual end points, including FSD in general and HSDD in particular in multivariate analyses. In this large cross-sectional study, low sexual desire was significantly associated with levels of free testosterone and androstenedione, but FSD in general and HSDD in particular were not associated with androgen levels. Length of relationship and depression were associated with FSD including HSDD. Wåhlin-Jacobsen S, Kristensen E, Tønnes Pedersen A, et al. Androgens and Psychosocial Factors Related to Sexual Dysfunctions in Premenopausal Women. J Sex Med 2017;14:366-379.


Herbacetin Is a Novel Allosteric Inhibitor of Ornithine Decarboxylase with Antitumor Activity.
Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the first step of polyamine biosynthesis that is associated with cell growth and tumor formation. Existing catalytic inhibitors of ODC have lacked efficacy in clinical testing or displayed unacceptable toxicity. In this study, we report the identification of an effective and nontoxic allosteric inhibitor of ODC. Using computer docking simulation and an in vitro ODC enzyme assay, we identified herbacetin, a natural compound found in flax and other plants, as a novel ODC inhibitor. Mechanistic investigations defined aspartate 44 in ODC as critical for binding. Herbacetin exhibited potent anticancer activity in colon cancer cell lines expressing high levels of ODC. Intraperitoneal or oral administration of herbacetin effectively suppressed HCT116 xenograft tumor growth and also reduced the number and size of polyps in a mouse model of APC-driven colon cancer (ApcMin/+). Unlike the well-established ODC inhibitor DFMO, herbacetin treatment was not associated with hearing loss. Taken together, our findings defined the natural product herbacetin as an allosteric inhibitor of ODC with chemopreventive and antitumor activity in preclinical models of colon cancer, prompting its further investigation in clinical trials.


HIV testing experiences of Aboriginal youth in Canada: service implications.
The objective of this study was to explore HIV testing experiences and service views of Canadian Aboriginal youth in order to provide information for HIV testing services. An exploratory, mixed-method, community-based research design was used for this study. Findings reported here are from 210 survey participants who had experienced an HIV test. Youth were recruited through 11 Aboriginal organizations across Canada, including AIDS service organizations, health centers, community organizations, and friendship centers. Youth who had tested for HIV ranged in age from 15 to 30 years of age (20% were <20), and came from First Nations (75%), Metis (14%), and Inuit (9%) backgrounds. Participants lived in all provinces and one territory. Over half (62%) were female. While the majority of survey respondents indicated at their last HIV test they had been treated with care (80%), respect (77%), or kindness (76%), some reported being treated with hostility (19%), fear (12%), discrimination (11%), avoidance (10%), or being treated in a bored way (15%). When asked about information they had received, 28% of survey respondents could not remember; 23% said they were not given any information, and 24% said their questions were not answered. Emotional reactions to testing ranged from anxiety/apprehension (64% of survey respondents) to being "calm" (19%). When asked for suggestions to improve testing services, participants indicated emotional support, compassion, professional yet personable services, and personalized HIV information were important. Study results suggest that to facilitate HIV testing for Aboriginal youth, testing services and counseling must be respectful, compassionate, non-judgmental, and culturally responsive in order to provide emotional support and HIV information that is meaningful and memorable.


Impact of metabolic syndrome on the development of cardiovascular disease in a general Japanese population: the Hisayama study.
The metabolic syndrome (MetS) is associated with an increased risk of cardiovascular disease (CVD) events in general populations. However, well-designed prospective studies in Asian populations are very limited. We prospectively evaluated a total of 2452 community-dwelling Japanese individuals aged 40 years or older from 1988 to 2002 and examined the effects of MetS defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria on incident CVD. The prevalence of the MetS was 21% in men and 30% in women at baseline. During the follow up, 307 CVD events occurred. Compared with those without MetS, the age-adjusted incidence of CVD (per 1000 person-years) was significantly higher in subjects with the MetS in both men (21.8 versus 11.6, P<0.01) and women (12.9 versus 6.5, P<0.01). The risk of CVD events was significantly higher even after adjusting for the following confounding factors: age, proteinuria, electrocardiographic abnormalities, serum total cholesterol, smoking habits, alcohol intake, and regular exercise (hazard ratio, 1.86; 95% CI, 1.32 to 2.62 in men and hazard ratio, 1.70; 95% CI, 1.22 to 2.36 in women). The risk of incident CVD was found to increase with the number of components of MetS and became significantly predictive when the number of components reached 3. Similar associations were also observed when CVD was divided into coronary heart disease and stroke. Our findings suggest that MetS is a significant risk factor for the development of CVD in the Japanese middle-aged population.


The home environment and childhood obesity in low-income households: indirect effects via sleep duration and screen time.
Childhood obesity disproportionally affects children from low-income households. With the aim of informing interventions, this study examined pathways through which the physical and social home environment may promote childhood overweight/obesity in low-income households. Data on health behaviors and the home environment were collected at home visits in low-income, urban households with either only normal weight (n = 48) or predominantly overweight/obese (n = 55) children aged 6-13 years. Research staff conducted comprehensive, in-person audits of the foods, media, and sports equipment in each household. Anthropometric measurements were collected, and children's physical activity was assessed through accelerometry. Caregivers and children jointly reported on child sleep duration, screen time, and dietary intake of foods previously implicated in childhood obesity risk. Path analysis was used to test direct and indirect associations between the home environment and child weight status via the health behaviors assessed. Sleep duration was the only health behavior associated with child weight status (OR = 0.45, 95% CI: 0.27, 0.77), with normal weight children sleeping 33.3 minutes/day longer on average than overweight/obese children. The best-fitting path model explained 26% of variance in child weight status, and included paths linking chaos in the home environment, lower caregiver screen time monitoring, inconsistent implementation of bedtime routines, and the presence of a television in children's bedrooms to childhood overweight/obesity through effects on screen time and sleep duration. This study adds to the existing literature by identifying aspects of the home environment that influence childhood weight status via indirect effects on screen time and sleep duration in children from low-income households. Pediatric weight management interventions for low-income households may be improved by targeting aspects of the physical and social home environment associated with sleep.


NAADP-regulated two-pore channels drive phagocytosis through endo-lysosomal Ca2+ nanodomains, calcineurin and dynamin.
Macrophages clear pathogens by phagocytosis and lysosomes that fuse with phagosomes are traditionally regarded as to a source of membranes and luminal degradative enzymes. Here, we reveal that endo-lysosomes act as platforms for a new phagocytic signalling pathway in which FcγR activation recruits the second messenger NAADP and thereby promotes the opening of Ca2+ -permeable two-pore channels (TPCs). Remarkably, phagocytosis is driven by these local endo-lysosomal Ca2+ nanodomains rather than global cytoplasmic or ER Ca2+ signals. Motile endolysosomes contact nascent phagosomes to promote phagocytosis, whereas endo-lysosome immobilization prevents it. We show that TPC-released Ca2+ rapidly activates calcineurin, which in turn dephosphorylates and activates the GTPase dynamin-2. Finally, we find that different endo-lysosomal Ca2+ channels play diverse roles, with TPCs providing a universal phagocytic signal for a wide range of particles and TRPML1 being only required for phagocytosis of large targets.


Effects of a deep-sea mining experiment on seafloor microbial communities and functions after 26 years.
Future supplies of rare minerals for global industries with high-tech products may depend on deep-sea mining. However, environmental standards for seafloor integrity and recovery from environmental impacts are missing. We revisited the only midsize deep-sea disturbance and recolonization experiment carried out in 1989 in the Peru Basin nodule field to compare habitat integrity, remineralization rates, and carbon flow with undisturbed sites. Plough tracks were still visible, indicating sites where sediment was either removed or compacted. Locally, microbial activity was reduced up to fourfold in the affected areas. Microbial cell numbers were reduced by ~50% in fresh "tracks" and by <30% in the old tracks. Growth estimates suggest that microbially mediated biogeochemical functions need over 50 years to return to undisturbed levels. This study contributes to developing environmental standards for deep-sea mining while addressing limits to maintaining and recovering ecological integrity during large-scale nodule mining.


A new strategy to synthesize anisotropic SmCo5 nanomagnets.
We report a simple strategy to synthesize anisotropic SmCo5 nanoplates. The strategy involves the pre-synthesis of 125 × 12 nm Sm(OH)3 nanorods and 10 nm Co nanoparticles followed by the self-assembly of these nanorods and nanoparticles into Sm(OH)3-Co nanocomposites. Once embedded in a CaO matrix, the nanocomposite is subjected to high temperature (850 °C) annealing in the presence of Ca, leading to the formation of 125 × 10 nm SmCo5 nanoplates, which are dispersible in ethanol, allowing the alignment in epoxy resin under a 20 kOe magnetic field. The aligned SmCo5 nanoplates show a square hysteresis behavior with room temperature coercivity reaching 30.1 kOe, which is among the highest values ever reported for SmCo5 made from chemical methods. This work provides a new approach to high-performance anisotropic SmCo5 for permanent magnetic applications.