Prevalence and factors associated with thriving in older adulthood: a 10-year population-based study.
Interest in the determinants of "successful aging" is growing. Nonetheless, successful aging remains ill defined, and its appropriate measurement is hotly contested. Most studies have focused on the absence of disability or deficits in physical performance as outcomes. The present study extends this research by using the Health Utilities Index Mark 3 (HUI3), a multidimensional measure of health status, to examine the maintenance of exceptionally good health among older participants in the Canadian National Population Health Survey (1994--2004). The maintenance of exceptionally good health in old age was examined prospectively among 2432 individuals (65-85 years old at baseline) who met the inclusion criteria. The participants were classified into one of four health trajectories: thrivers (who maintained exceptional health with no or only mild disability), nonthrivers (who experienced a moderate or severe disability), the deceased, and the institutionalized. In 10 years of follow-up, 190 (8%) were thrivers (HUI3 score > or = 0.89 at all interviews), 1076 (47%) were nonthrivers, 893 (36%) died, and 273 (9%) were institutionalized. The maintenance of exceptionally good health among the elderly participants was related to younger age at baseline, socioeconomic status (higher income), psychosocial factors (including lower psychological distress), and behavioral factors (never smoked and moderate alcohol use). The maintenance of exceptionally good health in old age is related, at least in part, to modifiable lifestyle factors. However, elevated socioeconomic status also distinguishes those who are able to maintain exceptionally good health.


Biocontrol traits of Pseudomonas spp. are regulated by phase variation.
Of 214 Pseudomonas strains isolated from maize rhizosphere, 46 turned out to be antagonistic, of which 43 displayed clear colony phase variation. The latter strains formed both opaque and translucent colonies, designated as phase I and phase II, respectively. It appeared that important biocontrol traits, such as motility and the production of antifungal metabolites, proteases, lipases, chitinases, and biosurfactants, are correlated with phase I morphology and are absent in bacteria with phase II morphology. From a Tn5luxAB transposon library of Pseudomonas sp. strain PCL1171 phase I cells, two mutants exhibiting stable expression of phase II had insertions in gacS. A third mutant, which showed an increased colony phase variation frequency was mutated in mutS. Inoculation of wheat seeds with PCL1171 bacteria of phase I morphology resulted in efficient suppression of take-all disease, whereas disease suppression was absent with phase II bacteria. Neither the gacS nor the mutS mutant was able to suppress take-all, but biocontrol activity was restored after genetic complementation of these mutants. Furthermore, in a number of cases, complementation by gacS of wild-type phase II sectors to phase I phenotype could be shown. A PCL1171 phase I mutant defective in antagonistic activity appeared to have a mutation in a gene encoding a lipopeptide synthetase homologue and had lost its biocontrol activity, suggesting that biocontrol by strain PCL1171 is dependent on the production of a lipopeptide. Our results show that colony phase variation plays a regulatory role in biocontrol by Pseudomonas bacteria by influencing the expression of major biocontrol traits and that the gacS and mutS genes play a role in the colony phase variation process. Therefore phase variation not only plays a role in escaping animal defense but it also appears to play a much broader and vital role in the ecology of bacteria producing exoenzymes, antibiotics, and other secondary metabolites.


Materials and microfluidics: enabling the efficient isolation and analysis of circulating tumour cells.
We present a critical review of microfluidic technologies and material effects on the analyses of circulating tumour cells (CTCs) selected from the peripheral blood of cancer patients. CTCs are a minimally invasive source of clinical information that can be used to prognose patient outcome, monitor minimal residual disease, assess tumour resistance to therapeutic agents, and potentially screen individuals for the early diagnosis of cancer. The performance of CTC isolation technologies depends on microfluidic architectures, the underlying principles of isolation, and the choice of materials. We present a critical review of the fundamental principles used in these technologies and discuss their performance. We also give context to how CTC isolation technologies enable downstream analysis of selected CTCs in terms of detecting genetic mutations and gene expression that could be used to gain information that may affect patient outcome.


Biodegradable PEG-dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA.
One important drawback of most of the currently used dendrimers for biomedical applications is their high stability under physiological conditions that can result in cytotoxicity or complications induced by the accumulation of non-degradable synthetic materials in the organism. Particularly in the gene therapy field, vector stability can further hinder the intracellular release of the nucleic acid from the dendriplex, consequently leading to low transfection efficiencies. Therefore, biodegradable cationic dendritic structures have been eagerly awaited. However, the development of these dendritic nanocarriers is challenging because of the undesired and/or premature degradation observed during their synthesis and/or application. Here, we report new hybrid-biodegradable, biocompatible, non-toxic, and water-soluble azide-terminated PEG-GATGE dendritic block copolymers, based on a gallic acid (GA) core and triethylene glycol (TG) butanoate arms, incorporating ester bonds (E) at the dendritic arms/shell. Their successful functionalization by "click" chemistry with unprotected alkynated amines allowed complexation and delivery of siRNA. The hydrophobic character of the GATGE building unit confers to these hydrolyzable dendritic bionanomaterials a great ability to complex, protect and mediate the cellular internalization of siRNA. Moreover, the localization of the degradation points at the dendritic periphery, close to the complexed siRNA, was found to be important for nucleic acid release from the nanoparticles, rendering a significant improvement of the transfection efficiency compared to their hydrolytically stable PEG-GATG copolymer counterparts. The present study puts forward these biodegradable PEG-dendritic block copolymers not only as suitable vectors for nucleic acids, but also as new avenues for further developments exploring their use in theranostics.


Chronic intermittent hypoxia increases blood pressure and expression of FosB/DeltaFosB in central autonomic regions.
Chronic intermittent hypoxia (CIH) models repetitive bouts of arterial hypoxemia that occur in humans suffering from obstructive sleep apnea. CIH has been linked to persistent activation of arterial chemoreceptors and the renin-angiotensin system, which have been linked to chronic elevations of sympathetic nerve activity (SNA) and mean arterial pressure (MAP). Because Fos and FosB are transcription factors involved in activator protein (AP)-1 driven central nervous system neuronal adaptations, this study determined if CIH causes increased Fos or FosB staining in brain regions that regulate SNA and autonomic function. Male Sprague Dawley rats were instrumented with telemetry transmitters for continuous recording of MAP and heart rate (HR). Rats were exposed to continuous normoxia (CON) or to CIH for 8 h/day for 7 days. CIH increased MAP by 7-10 mmHg without persistently affecting HR. A separate group of rats was killed 1 day after 7 days of CIH for immunohistochemistry. CIH did not increase Fos staining in any brain region examined. Staining for FosB/ΔFosB was increased in the organum vasculosum of the lamina terminalis (CON: 9 ± 1; CIH: 34 ± 3 cells/section), subfornical organ (CON: 7 ± 2; CIH: 31 ± 3), median preoptic nucleus (CON 15 ± 1; CIH: 38 ± 3), nucleus of the solitary tract (CON: 9 ± 2; CIH: 28 ± 4), A5 (CON: 3 ± 1; CIH: 10 ± 1), and rostral ventrolateral medulla (CON: 5 ± 1; CIH: 17 ± 2). In the paraventricular nucleus, FosB/ΔFosB staining was located mainly in the dorsal and medial parvocellular subnuclei. CIH did not increase FosB/ΔFosB staining in caudal ventrolateral medulla or supraoptic nucleus. These data indicate that CIH induces an increase in FosB/ΔFosB in autonomic nuclei and suggest that AP-1 transcriptional regulation may contribute to stable adaptive changes that support chronically elevated SNA.


Genetic and Molecular Basis of Botrydial Biosynthesis: Connecting Cytochrome P450-Encoding Genes to Biosynthetic Intermediates.
Over two hundred species of plants can be infected by the phytopathogenic fungus Botrytis cinerea under a range of different environmental conditions. In response to these, the fungus produces unique terpenoid and polyketide metabolites. Parts of the plants may be killed by the phytotoxin botrydial, enabling the fungus to feed on the dead cells. In this paper, we describe the genetic and molecular basis of botrydial biosynthesis and the function of the five genes of the genome of B. cinerea that together constitute the botrydial biosynthetic gene cluster. Genes BcBOT3 and BcBOT4, encoding two cytochrome P450 monooxygenases, were inactivated by homologous recombination and were shown to catalyze regio- and stereospecific hydroxylations at the carbons C-10 and C-4, respectively, of the presilphiperfolan-8β-ol skeleton. The null mutants, bcbot3Δ and bcbot4Δ, accumulated key intermediates in the botrydial biosynthesis enabling the complete genetic and molecular basis of the botrydial biosynthetic pathway to be established. Furthermore, the bcbot4Δ mutant overproduced a significant number of polyketides, which included, in addition to known botcinins, botrylactones and cinbotolide A, two new botrylactones and two new cinbotolides, cinbotolides B and C.


The use of indomethacin, sulindac, and tamoxifen for the treatment of desmoid tumors associated with familial polyposis.
Seven familial polyposis patients with desmoid tumors were treated with indomethacin, sulindac, or tamoxifen either as single agents or in combination. Serial computed tomographic (CT) scan examination was employed for objective measurement of tumor size since physical examination alone was an inaccurate means to evaluate intraabdominal and retroperitoneal desmoids. Only one patient with minimal tumor burden demonstrated a favorable response with complete resolution of an abdominal wall desmoid.


A Pre-Exercise Dose of Muscle Sentry® has no Effect on Performing Repeated Leg Press Sets to Failure.
This study compared the number of bilateral leg presses done at 150% of body mass while on either Muscle Sentry® (MS) or placebo (PL). Participants (16 women, 14 men, college students 19-26 years) performed 2 sets of leg press to failure using 150% of their body mass with 5 min rest separating the 2 sets. Each exercise was performed twice (1× MS, 1× PL) at the same time of day with 48 h separating each exercise. Both MS and PL were ingested 30 min prior to performing the exercise. Just prior to starting the exercise and at the end of each set, heart rate, and blood pressure were obtained and the rate pressure product was calculated to determine myocardial workload. Two-way repeated measures ANOVA for lift number showed no significant main effects for either MS vs. PL, or for Set1 vs. Set2 (p > 0.05). The interaction was also not statistically different (mean repetitions ± std. dev.: MS1= 28±20, MS2= 26±18, PL1 = 30±24, PL2 = 29±20). Two-way repeated measures ANOVA for rate pressure product showed no significance for either the main effect for MS vs. PL, or supplement × pre-post interaction (p > 0.05). The main effect for pre-lift vs. post lift was significant (p<0.001) with post being higher than pre. Ingestion of Muscle Sentry® 30 min prior to leg pressing 150% of body mass to failure had no effect upon either total work performance or myocardial workload.


Aldose reductase inhibition counteracts oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation in tissue sites for diabetes complications.
This study evaluated the effects of aldose reductase inhibition on diabetes-induced oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation. In animal experiments, control and streptozotocin-induced diabetic rats were treated with or without the aldose reductase inhibitor (ARI) fidarestat (16 mg . kg(-1) . day(-1)) for 6 weeks starting from induction of diabetes. Sorbitol pathway intermediate, but not glucose, accumulation in sciatic nerve and retina was completely prevented in diabetic rats treated with fidarestat. Sciatic motor nerve conduction velocity, hindlimb digital sensory nerve conduction velocity, and sciatic nerve concentrations of two major nonenzymatic antioxidants, glutathione and ascorbate, were reduced in diabetic versus control rats, and these changes were prevented in diabetic rats treated with fidarestat. Fidarestat prevented the diabetes-induced increase in nitrotyrosine (a marker of peroxynitrite-induced injury) and poly(ADP-ribose) immunoreactivities in sciatic nerve and retina. Fidarestat counteracted increased superoxide formation in aorta and epineurial vessels and in in vitro studies using hyperglycemia-exposed endothelial cells, and the DCF test/flow cytometry confirmed the endothelial origin of this phenomenon. Fidarestat did not cause direct inhibition of PARP activity in a cell-free system containing PARP and NAD(+) but did counteract high-glucose-induced PARP activation in Schwann cells. In conclusion, aldose reductase inhibition counteracts diabetes-induced nitrosative stress and PARP activation in sciatic nerve and retina. These findings reveal the new beneficial properties of fidarestat, thus further justifying the ongoing clinical trials of this specific, potent, and low-toxic ARI.


Clinical Ultrasound Is Safe and Highly Specific for Acute Appendicitis in Moderate to High Pre-test Probability Patients.
Clinical ultrasound (CUS) is highly specific for the diagnosis of acute appendicitis but is operator-dependent. The goal of this study was to determine if a heterogeneous group of emergency physicians (EP) could diagnose acute appendicitis on CUS in patients with a moderate to high pre-test probability. This was a prospective, observational study of a convenience sample of adult and pediatric patients with suspected appendicitis. Sonographers received a structured, 20-minute CUS training on appendicitis prior to patient enrollment. The presence of a dilated (>6 mm diameter), non-compressible, blind-ending tubular structure was considered a positive study. Non-visualization or indeterminate studies were considered negative. We collected pre-test probability of acute appendicitis based on a 10-point visual analog scale (moderate to high was defined as >3), and confidence in CUS interpretation. The primary objective was measured by comparing CUS findings to surgical pathology and one week follow-up. We enrolled 105 patients; 76 had moderate to high pre-test probability. Of these, 24 were children. The rate of appendicitis was 36.8% in those with moderate to high pre-test probability. CUS were recorded by 33 different EPs. The sensitivity, specificity, and positive and negative likelihood ratios of EP-performed CUS in patients with moderate to high pre-test probability were 42.8% (95% confidence interval [CI] [25-62.5%]), 97.9% (95% CI [87.5-99.8%]), 20.7 (95% CI [2.8-149.9]) and 0.58 (95% CI [0.42-0.8]), respectively. The 16 false negative scans were all interpreted as indeterminate. There was one false positive CUS diagnosis; however, the sonographer reported low confidence of 2/10. A heterogeneous group of EP sonographers can safely identify acute appendicitis with high specificity in patients with moderate to high pre-test probability. This data adds support for surgical consultation without further imaging beyond CUS in the appropriate clinical setting.


Delayed bilateral vocal cord paresis after a continuous interscalene brachial plexus block and endotracheal intubation: A lesson why we should use low concentrated local anesthetics for continuous blocks.
Recurrent laryngeal nerve block is an uncommon complication that can occur after an interscalene brachial plexus block (ISB), which may lead to vocal cord palsy or paresis. However, if the recurrent laryngeal nerve is blocked in patients with a preexisting contralateral vocal cord palsy following neck surgery, this may lead to devastating acute respiratory failure. Thus, ISB is contraindicated in patients with contralateral vocal cord lesion. To the best of our knowledge, there are no reports of bilateral vocal cord paresis, which occurred after a continuous ISB and endotracheal intubation in a patient with no history of vocal cord injury or surgery of the neck. A 59 year old woman was planned for open acromioplasty and rotator cuff repair under general anesthesia. General anesthesia was induced following an ISB using 0.2% ropivacaine and catheter insertion for postoperative pain control. While recovering in the postanesthesia care unit (PACU), however, the patient complained of a sore throat and hoarseness without respiratory insufficiency. On the morning of the first postoperative day, she still complained of mild dyspnea, dysphonia, and slight aspiration. She was subsequently diagnosed with bilateral vocal cord paresis following an endoscopic laryngoscopy examination. The continuous ISB catheter was immediately removed and the dyspnea and hoarseness symptoms improved, although mild aspiration during drinking water was still present. On the 4th postoperative day, a laryngoscopy examination revealed that the right vocal cord movement had returned to normal but that the left vocal cord paresis still remained. When ISB is planned, a detailed history-taking and examination of the airway are essential for patient safety and we recommend that any local anesthetics be carefully injected under ultrasound guidance. We also recommend the use of low concentration of local anesthetics to avoid possible paralysis of the vocal cord.


Whole body donation for medical science: a population-based study.
Although cadaveric whole-body donation for the purposes of medical science is extremely important for medical education, the number of persons who choose to donate remains low. We assessed persons' willingness to consider whole body donation in a standardized telephone survey of Maryland households, identified using random digit dialing. In multivariable analyses, we assessed the independent relation of sociodemographics and attitudinal factors to willingness to consider donation, and we determined the amount of variation in willingness to consider donation among the study population that could be explained by these factors. Of 385 participants (84% of randomized homes), 49% reported they would consider whole body donation. In bivariate analysis, younger age, African-American race/ethnicity, less education and income, greater number of dependents, marital status, and attitudes about religion/spirituality, trust in hospitals, and income, gender, and racial/ethnic discrimination in hospitals were statistically significantly associated with 40-70% less odds of willingness to consider donation. After adjustment, persons of African-American race/ethnicity, less education, and those agreeing with the statements, "Rich patients receive better care at hospitals than poor patients," and "White patients receive better care at hospitals than other racial or ethnic groups," had 40-60% less odds of willingness to consider donation when compared to their counterparts. Respondents' race/ethnicity and education contributed most to willingness to consider donation. We conclude that demographic and attitudinal factors are strongly related to willingness to consider whole body donation. Efforts to enhance donation should seek to identify ways in which potential barriers to donation can be addressed by health professionals.


Cardiac afferent activity modulates early neural signature of error detection during skilled performance.
Behavioral adaptations during performance rely on predicting and evaluating the consequences of our actions through action monitoring. Previous studies revealed that proprioceptive and exteroceptive signals contribute to error-monitoring processes, which are implemented in the posterior medial frontal cortex. Interestingly, errors also trigger changes in autonomic nervous system activity such as pupil dilation or heartbeat deceleration. Yet, the contribution of implicit interoceptive signals of bodily states to error-monitoring during ongoing performance has been overlooked. This study investigated whether cardiovascular interoceptive signals influence the neural correlates of error processing during performance, with an emphasis on the early stages of error processing. We recorded musicians' electroencephalography and electrocardiogram signals during the performance of highly-trained music pieces. Previous event-related potential (ERP) studies revealed that pitch errors during skilled musical performance are preceded by an error detection signal, the pre-error-negativity (preERN), and followed by a later error positivity (PE). In this study, by combining ERP, source localization and multivariate pattern classification analysis, we found that the error-minus-correct ERP waveform had an enhanced amplitude within 40-100 ms following errors in the systolic period of the cardiac cycle. This component could be decoded from single-trials, was dissociated from the preERN and PE, and stemmed from the inferior parietal cortex, which is a region implicated in cardiac autonomic regulation. In addition, the phase of the cardiac cycle influenced behavioral alterations resulting from errors, with a smaller post-error slowing and less perturbed velocity in keystrokes following pitch errors in the systole relative to the diastole phase of the cardiac cycle. Lastly, changes in the heart rate anticipated the upcoming occurrence of errors. This study provides the first evidence of preconscious visceral information modulating neural and behavioral responses related to early error monitoring during skilled performance.


Occupational mortality and morbidity in relation to selective turnover.
Because of the "healthy worker effect" most occupational cohorts, especially those of persons doing physically heavy work, are selected groups with regard to life expectancy. Health selection is also involved in turnover. Mortality and morbidity were studied on three different exposure levels, defined primarily according to physical demands: heavy level (iron foundries), medium level (manufacture of metal products), and light level (manufacture of electrical devices). The population comprised about 15,700 men who were employed in 1950-1976 in the three branches of the metal industry representing the different levels. The number of person-years of follow-up became about 215,800. During the period 1950-1978, there had occurred 1,407 deaths. Data for the mortality and disability analyses were obtained from the national death and disability registers. Occupational history, morbidity, and reasons for turnover were studied in a sample by means of questionnaire sent to 400 current and 600 former workers from each branch. In addition, a questionnaire concerning occupational history was sent to the next of kin of 450 dead persons. When the three cohorts were compared to the general male population of Finland, the standardized mortality ratio was 124 for the foundry workers, 92 for the metal product workers, and 107 for the electrical workers. The survival curves showed no great differences between the three exposure levels. However, the heavy level had the highest degree of mortality, and the medium level the lowest. Foundry workers showed less social selection than the two other cohorts. Metal product workers seemed to be socially and health selected. Economic fluctuations clearly regulated entries of new employees into the industries and thus introduced additional selective features.


Community-based hepatitis B screening programs in the United States in 2008.
The Centers for Disease Control and Prevention (CDC) recommends hepatitis B surface antigen (HBsAg) testing to identify hepatitis B virus (HBV) infection for foreign-born persons from areas with HBsAg prevalence of > or = 2%. Currently, most HBsAg screening in the United States is performed by independent community organizations. For these HBsAg screening programs, we collected information about the location, number of people screened, other services beyond screening provided, the population/ethnicity groups targeted for screening, and the prevalence of HBsAg among those screened. We identified programs offering screening by contacting programs known to us, from interviews with identified programs, and from structured Internet searches, and collected information using a simple e-mail survey with follow-up phone calls. We identified 55 possible community HBsAg screening programs, of which we successfully contacted 31 programs. In the past year, contacted programs screened an estimated 21 817 patients with an 8.1% average HBsAg prevalence. The majority of programs screened persons born in Asia and their children, and a small number of programs screened persons from Africa or Eastern Europe; very few programs screened U.S.-born persons at risk of HBV infection due to behavioural factors. We identified few or no programs in the American Southeast, the Midwest, and the Southwest outside of California and the Houston area. The HBsAg screening programs that we contacted were effective in identifying and screening patients at risk of HBV as evidenced by the high prevalence observed among those screened. However, their efforts alone are likely insufficient to meet the need for screening recommended by CDC.


Self-assembly based plasmonic arrays tuned by atomic layer deposition for extreme visible light absorption.
Achieving complete absorption of visible light with a minimal amount of material is highly desirable for many applications, including solar energy conversion to fuel and electricity, where benefits in conversion efficiency and economy can be obtained. On a fundamental level, it is of great interest to explore whether the ultimate limits in light absorption per unit volume can be achieved by capitalizing on the advances in metamaterial science and nanosynthesis. Here, we combine block copolymer lithography and atomic layer deposition to tune the effective optical properties of a plasmonic array at the atomic scale. Critical coupling to the resulting nanocomposite layer is accomplished through guidance by a simple analytical model and measurements by spectroscopic ellipsometry. Thereby, a maximized absorption of light exceeding 99% is accomplished, of which up to about 93% occurs in a volume-equivalent thickness of gold of only 1.6 nm. This corresponds to a record effective absorption coefficient of 1.7 × 10(7) cm(-1) in the visible region, far exceeding those of solid metals, graphene, dye monolayers, and thin film solar cell materials. It is more than a factor of 2 higher than that previously obtained using a critically coupled dye J-aggregate, with a peak width exceeding the latter by 1 order of magnitude. These results thereby substantially push the limits for light harvesting in ultrathin, nanoengineered systems.


Induced superficial chondrocyte death reduces catabolic cartilage damage in murine posttraumatic osteoarthritis.
Joints that have degenerated as a result of aging or injury contain dead chondrocytes and damaged cartilage. Some studies have suggested that chondrocyte death precedes cartilage damage, but how the loss of chondrocytes affects cartilage integrity is not clear. In this study, we examined whether chondrocyte death undermines cartilage integrity in aging and injury using a rapid 3D confocal cartilage imaging technique coupled with standard histology. We induced autonomous expression of diphtheria toxin to kill articular surface chondrocytes in mice and determined that chondrocyte death did not lead to cartilage damage. Moreover, cartilage damage after surgical destabilization of the medial meniscus of the knee was increased in mice with intact chondrocytes compared with animals whose chondrocytes had been killed, suggesting that chondrocyte death does not drive cartilage damage in response to injury. These data imply that chondrocyte catabolism, not death, contributes to articular cartilage damage following injury. Therefore, therapies targeted at reducing the catabolic phenotype may protect against degenerative joint disease.


Temperature and sperm incorporation in polyploid salamanders.
Although most animals reproduce sexually, a number of all-female groups exist. Triploid hybrid salamanders appear to maintain themselves by using a male's sperm to activate their eggs, after which the sperm nucleus is eliminated (gynogenesis). The incidence of sperm nuclear incorporation in eggs of these salamanders depends on temperature. Triploid offspring derived gynogenetically are more frequent at lower temperature, whereas tetraploid offspring derived sexually are far more frequent at higher temperatures. Temperature-dependent variability in sperm nuclear incorporation helps explain the variability in reproductive modes reported for hybrid salamanders.


Low dose aspirin is associated with plasma chemerin levels and may reduce adipose tissue inflammation.
Chemerin is a peptide chemoattractant for macrophages and an adipokine regulating adipocyte differentiation and metabolism. Plasma chemerin is increased in chronic inflammatory diseases and in obesity. As inflammation and obesity are risk factors for coronary artery disease (CAD), we investigated possible associations of plasma chemerin with inflammatory markers and atherosclerosis in a CAD case-control study (n=470). Chemerin levels were associated with C-reactive protein, BMI and LDL levels, and negatively associated with HDL levels. Mean plasma chemerin levels were similar in controls and CAD patients but significantly higher in CAD patients not taking low dose aspirin. To investigate the mechanism of chemerin reduction by aspirin, we analyzed chemerin expression in hepatocytes and adipocytes treated with aspirin in the presence and absence of inflammatory cytokines. Chemerin expression was upregulated by pro-inflammatory stimuli in adipocytes but not in hepatocytes. Treatment of stimulated hepatocytes and adipocytes with aspirin did not affect chemerin expression. However, treatment of inflammatory M1 macrophages with aspirin reduced secretion of the pro-inflammatory cytokines IL-1β and IL-6, and increased secretion of the anti-inflammatory IL-10. In summary, we show that plasma chemerin levels are associated with markers of inflammation and that they are significantly higher in CAD patients not treated with low dose aspirin. In addition, we show that low dose aspirin treatment reduces pro-inflammatory cytokine secretion by macrophages, which may lead to reduced chemerin secretion by adipocytes and may be a reason for the lower chemerin levels in the circulation of CAD patients on low dose aspirin.


Experimental evidence of neutrinos produced in the CNO fusion cycle in the Sun.
For most of their existence, stars are fuelled by the fusion of hydrogen into helium. Fusion proceeds via two processes that are well understood theoretically: the proton-proton (pp) chain and the carbon-nitrogen-oxygen (CNO) cycle1,2. Neutrinos that are emitted along such fusion processes in the solar core are the only direct probe of the deep interior of the Sun. A complete spectroscopic study of neutrinos from the pp chain, which produces about 99 per cent of the solar energy, has been performed previously3; however, there has been no reported experimental evidence of the CNO cycle. Here we report the direct observation, with a high statistical significance, of neutrinos produced in the CNO cycle in the Sun. This experimental evidence was obtained using the highly radiopure, large-volume, liquid-scintillator detector of Borexino, an experiment located at the underground Laboratori Nazionali del Gran Sasso in Italy. The main experimental challenge was to identify the excess signal-only a few counts per day above the background per 100 tonnes of target-that is attributed to interactions of the CNO neutrinos. Advances in the thermal stabilization of the detector over the last five years enabled us to develop a method to constrain the rate of bismuth-210 contaminating the scintillator. In the CNO cycle, the fusion of hydrogen is catalysed by carbon, nitrogen and oxygen, and so its rate-as well as the flux of emitted CNO neutrinos-depends directly on the abundance of these elements in the solar core. This result therefore paves the way towards a direct measurement of the solar metallicity using CNO neutrinos. Our findings quantify the relative contribution of CNO fusion in the Sun to be of the order of 1 per cent; however, in massive stars, this is the dominant process of energy production. This work provides experimental evidence of the primary mechanism for the stellar conversion of hydrogen into helium in the Universe.


Antisense regulation of atrial natriuretic peptide expression.
The cardiac hormone atrial natriuretic peptide (ANP) is a central regulator of blood volume and a therapeutic target in hypertension and heart failure. Enhanced ANP activity in such conditions through inhibition of the degradative enzyme neprilysin has shown clinical efficacy but is complicated by consequences of simultaneous accumulation of a heterogeneous array of other hormones. Targets for specific ANP enhancement have not been available. Here, we describe a cis-acting antisense transcript (NPPA-AS1), which negatively regulates ANP expression in human cardiomyocytes. We show that NPPA-AS1 regulates ANP expression via facilitating NPPA repressor RE1-silencing transcription factor (REST) binding to its promoter, rather than forming an RNA duplex with ANP mRNA. Expression of ANP mRNA and NPPA-AS1 was increased and correlated in isolated strained human cardiomyocytes and in hearts from patients with advanced heart failure. Further, inhibition of NPPA-AS1 in vitro and in vivo resulted in increased myocardial expression of ANP, increased circulating ANP, increased renal cGMP, and lower blood pressure. The effects of NPPA-AS1 inhibition on NPPA expression in human cardiomyocytes were further marked under cell-strain conditions. Collectively, these results implicate the antisense transcript NPPA-AS1 as part of a physiologic self-regulatory ANP circuit and a viable target for specific ANP augmentation.


Toddlers show sensorimotor activity during auditory verb processing.
Language that describes actions, for instance verbs, can help to predict future actions of conspecifics in social interactions. Language and action are therefore interrelated. This interrelation has been described on a behavioral level for adults and toddlers. Furthermore, in adults, the sensorimotor system is involved in this interrelation. However, little is known about the early interrelation on the neural level at the onset of verb acquisition. In the present study, we examined the role of the sensorimotor system during the processing of acoustically presented verbs that describe dynamic actions and visually presented actions in toddlers, who are in the earliest stage of expressive language development. The activity of the sensorimotor system, in particular the suppression of the mu rhythm, was measured by means of electroencephalography (EEG). Results showed a significant suppression of the mu rhythm during both the processing of action verbs and observed actions, but not during the processing of pseudoverbs. This suggests that the sensorimotor system is already involved in the processing of action and language early in life.


An Economic Analysis of the Association Among Secondary Health Conditions, Health Care Costs, and Quality of Life for Persons With Spinal Cord Injury.
A previous analysis using the Canadian Spinal Cord Injury (SCI) Community Survey data identified that there were individuals with a high number of secondary health conditions, high health care utilization, poor health outcomes, and unmet health care needs. The objectives of this study were to estimate the annual health care costs of persons with SCI who report secondary health conditions, and to determine the association between these secondary health conditions with health care utilization and self-reported life satisfaction and quality of life. The survey respondents were divided into four groups: traumatic SCI (tSCI; those who said they received needed care and those who said they did not) and nontraumatic SCI (ntSCI; those who said they received needed care and those who said they did not). The average annual health care costs per respondent were estimated for each group. Using regression analysis, we estimated the change in average annual health care costs that were associated with an additional secondary health condition for respondents in each group. Participants who reported not receiving needed care had on average 23% more secondary health conditions than those receiving needed care. The increase in average annual health care costs associated with one additional secondary health conditions was between $428 ($37-$820) (ntSCI, receiving needed care) and $1240 ($739-$1741) (tSCI, not receiving needed care). This study provides insight into potential cost savings associated with a reduction of secondary health conditions as well as an estimate of the reduction in health care costs associated with moving from not receiving all needed care to receiving needed care.


Inhibition of diacylglycerol-sensitive TRPC channels by synthetic and natural steroids.
TRPC channels are a family of nonselective cation channels that regulate ion homeostasis and intracellular Ca(2+) signaling in numerous cell types. Important physiological functions such as vasoregulation, neuronal growth, and pheromone recognition have been assigned to this class of ion channels. Despite their physiological relevance, few selective pharmacological tools are available to study TRPC channel function. We, therefore, screened a selection of pharmacologically active compounds for TRPC modulating activity. We found that the synthetic gestagen norgestimate inhibited diacylglycerol-sensitive TRPC3 and TRPC6 with IC(50)s of 3-5 µM, while half-maximal inhibition of TRPC5 required significantly higher compound concentrations (>10 µM). Norgestimate blocked TRPC-mediated vasopressin-induced cation currents in A7r5 smooth muscle cells and caused vasorelaxation of isolated rat aorta, indicating that norgestimate could be an interesting tool for the investigation of TRP channel function in native cells and tissues. The steroid hormone progesterone, which is structurally related to norgestimate, also inhibited TRPC channel activity with IC(50)s ranging from 6 to 18 µM but showed little subtype selectivity. Thus, TRPC channel inhibition by high gestational levels of progesterone may contribute to the physiological decrease of uterine contractility and immunosuppression during pregnancy.


Contributions of the cerebellum and the motor cortex to acquisition and retention of motor memories.
We investigated the contributions of the cerebellum and the motor cortex (M1) to acquisition and retention of human motor memories in a force field reaching task. We found that anodal transcranial direct current stimulation (tDCS) of the cerebellum, a technique that is thought to increase neuronal excitability, increased the ability to learn from error and form an internal model of the field, while cathodal cerebellar stimulation reduced this error-dependent learning. In addition, cathodal cerebellar stimulation disrupted the ability to respond to error within a reaching movement, reducing the gain of the sensory-motor feedback loop. By contrast, anodal M1 stimulation had no significant effects on these variables. During sham stimulation, early in training the acquired motor memory exhibited rapid decay in error-clamp trials. With further training the rate of decay decreased, suggesting that with training the motor memory was transformed from a labile to a more stable state. Surprisingly, neither cerebellar nor M1 stimulation altered these decay patterns. Participants returned 24hours later and were re-tested in error-clamp trials without stimulation. The cerebellar group that had learned the task with cathodal stimulation exhibited significantly impaired retention, and retention was not improved by M1 anodal stimulation. In summary, non-invasive cerebellar stimulation resulted in polarity-dependent up- or down-regulation of error-dependent motor learning. In addition, cathodal cerebellar stimulation during acquisition impaired the ability to retain the motor memory overnight. Thus, in the force field task we found a critical role for the cerebellum in both formation of motor memory and its retention.


Neurotoxicity among pesticide applicators exposed to organophosphates.
An epidemiological study of 90 male pesticide applicators licensed in New York was conducted to investigate the effect of exposure to organophosphate pesticides on the peripheral nervous system. A cohort of farmers and pesticide applicators from New York State were questioned off season (November 1988-February 1989) and again during the spraying season (April 1989-August 1989) about the presence of several acute signs and symptoms. Short term exposure was validated by measuring the concentration of dimethylthiophosphate (DMTP), a metabolite of guthion, in urine. Chronic signs of subtle peripheral nerve damage were determined by vibration threshold sensitivity of the farmers and applicators tested during November 1988-February 1989 and compared with controls drawn from the general population who were tested during the same time period the next year (November 1989-February 1990). Vibration threshold sensitivity was determined for both the hands and feet. Long term exposure to pesticides was determined by questionnaire. Paired t tests show that mean vibration threshold scores were significantly higher for the dominant (P < 0.00) and non-dominant (P < 0.04) hands among pesticide applicators when compared with scores for population based controls individually matched on age, sex, and county of residence. A significant increase in mean vibration threshold sensitivity for the dominant and non-dominant hand suggests previous organophosphate exposure among pesticide applicators was associated with a loss of peripheral nerve function.


Evidence for the effectiveness of electrophysical modalities for treatment of medial and lateral epicondylitis: a systematic review.
Several treatments are available to treat epicondylitis. Among these are instrumental electrophysical modalities, ranging from ultrasound, extracorporeal shock wave therapy (ESWT), transcutaneous electrical nerve stimulation (TENS) to laser therapy, commonly used to treat epicondylitis. To present an evidence-based overview of the effectiveness of electrophysical modality treatments for both medial and lateral epicondylitis (LE). Searches in PubMed, EMBASE, CINAHL and Pedro were performed to identify relevant randomised clinical trials (RCTs) and systematic reviews. Two reviewers independently extracted data and assessed the methodological quality. A best-evidence synthesis was used to summarise the results. A total of 2 reviews and 20 RCTs were included, all of which concerned LE. Different electrophysical regimes were evaluated: ultrasound, laser, electrotherapy, ESWT, TENS and pulsed electromagnetic field therapy. Moderate evidence was found for the effectiveness of ultrasound versus placebo on mid-term follow-up. Ultrasound plus friction massage showed moderate evidence of effectiveness versus laser therapy on short-term follow-up. On the contrary, moderate evidence was found in favour of laser therapy over plyometric exercises on short-term follow-up. For all other modalities only limited/conflicting evidence for effectiveness or evidence of no difference in effect was found. Potential effectiveness of ultrasound and laser for the management of LE was found. To draw more definite conclusions high-quality RCTs examining different intensities are needed as well as studies focusing on long-term follow-up results.


The evolution of basal mantle structure in response to supercontinent aggregation and dispersal.
Seismic studies have revealed two Large Low-Shear Velocity Provinces (LLSVPs) in the lowermost mantle. Whether these structures remain stable over time or evolve through supercontinent cycles is debated. Here we analyze a recently published mantle flow model constrained by a synthetic plate motion model extending back to one billion years ago, to investigate how the mantle evolves in response to changing plate configurations. Our model predicts that sinking slabs segment the basal thermochemical structure below an assembling supercontinent, and that this structure eventually becomes unified due to slab push from circum-supercontinental subduction. In contrast, the basal thermochemical structure below the superocean is generally coherent due to the persistence of a superocean in our imposed plate reconstruction. The two antipodal basal thermochemical structures exchange material several times when part of one of the structures is carved out and merged with the other one, similarly to "exotic" tectonic terranes. Plumes mostly rise from thick basal thermochemical structures and in some instances migrate from the edges towards the interior of basal thermochemical structures due to slab push. Our results suggest that the topography of basal structures and distribution of plumes change over time due to the changing subduction network over supercontinent cycles.


Rationale, design, and methods for a Coreg (carvedilol) Heart Failure Registry (COHERE). COHERE Participant Physicians.
The success of beta-blocking agents in clinical trials of heart failure (HF) has led to a widespread call for their increased use, which assumes these agents will perform as well in the usual care setting. Given the traditional contraindication of the use of beta-blocking agents in HF, and their perception as difficult to use in HF, observing how they perform in the usual care setting could be critical in accelerating their widespread application. Carvedilol is the only beta-blocking agent currently approved in the United States for use in HF. The Coreg (brand of carvedilol; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) Heart Failure Registry (COHERE) is intended to collect data on outcomes and other clinical variables in a typical HF population and to observe experience with carvedilol in the hands of community practitioners. COHERE does not include any specific patient selection or exclusion criteria. The decision to use carvedilol is entirely at the discretion of the participant physician, based on evidence of HF as judged by assessments the practitioner usually uses. All patients will be followed for 1 year, with information on outcomes and other clinical variables collected and analyzed at baseline, the end of titration, and at 6 and 12 months after reaching the maximum tolerated dose. About 600 participant physicians selected to be as representative as possible of the community practice setting will enroll approximately 6,000 patients. COHERE will be the first and largest prospective observational experience with a new treatment, ie, carvedilol, in patients with HF managed in the usual care setting and should provide valuable information about this new treatment in this environment compared with the more rigid clinical trials setting.


An Information-Theoretic Approach to the Cost-benefit Analysis of Visualization in Virtual Environments.
Visualization and virtual environments (VEs) have been two interconnected parallel strands in visual computing for decades. Some VEs have been purposely developed for visualization applications, while many visualization applications are exemplary showcases in general-purpose VEs. Because of the development and operation costs of VEs, the majority of visualization applications in practice have yet to benefit from the capacity of VEs. In this paper, we examine this status quo from an information-theoretic perspective. Our objectives are to conduct cost-benefit analysis on typical VE systems (including augmented and mixed reality, theater-based systems, and large powerwalls), to explain why some visualization applications benefit more from VEs than others, and to sketch out pathways for the future development of visualization applications in VEs. We support our theoretical propositions and analysis using theories and discoveries in the literature of cognitive sciences and the practical evidence reported in the literatures of visualization and VEs.


Neuromuscular training and muscle strengthening in patients with patellofemoral pain syndrome: a protocol of randomized controlled trial.
Patellofemoral pain syndrome (PFPS) is a common musculoskeletal condition, particularly among women. Patients with PFPS usually experience weakness in the gluteal muscles, as well as pain and impaired motor control during activities of daily living. Strengthening the hip muscles is an effective way of treating this disorder. Neuromuscular training has also been identified as a therapeutic tool, although the benefits of this intervention in patients with PFPS patients remain inconclusive. This is a protocol of randomized controlled trial with a blind assessor. Thirty-four women with a clinical diagnosis of PFPS participated. These participants were allocated into two groups (experimental and control). The experimental group performed twelve sessions to strengthen the knee extensors, hip abductor and lateral rotator muscles in association with neuromuscular training of the trunk and lower extremities. The control group performed the same number of sessions to strengthen the muscles of the hip and knee. The primary outcome was functional capacity (Anterior Knee Pain Scale - AKPS) at 4 weeks. Pain intensity, muscle strength and kinematic changes were also measured during the step down test after four weeks of intervention. Follow up assessments were conducted after three and six months to assess functional capacity and pain. The effects of the treatment (i.e. between-group differences) were calculated using mixed linear models. The present study was initiated on the 1st of April 2013 and is currently in progress. The results of this study may introduce another effective technique of conservative treatment and could guide physical therapists in the clinical decision-making process for women with PFPS. Current Controlled Trials NCT01804608.


Aqueous corrosion of phosphide minerals from iron meteorites: a highly reactive source of prebiotic phosphorus on the surface of the early Earth.
We present the results of an experimental study of aqueous corrosion of Fe-phosphide under conditions relevant to the early Earth. The results strongly suggest that iron meteorites were an important source of reactive phosphorus (P), a requirement for the formation of P-based life. We further demonstrate that iron meteorites were an abundant source of phosphide minerals early in Earth history. Phosphide corrosion was studied in five different solutions: deionized water, deionized water buffered with sodium bicarbonate, deionized water with dissolved magnesium and calcium chlorides, deionized water containing ethanol and acetic acid, and deionized water containing the chlorides, ethanol, and acetic acid. Experiments were performed in the presence of both air and pure Ar gas to evaluate the effect of atmospheric chemistry. Phosphide corrosion in deionized water results in a metastable mixture of mixed-valence, P-bearing ions including pyrophosphate and triphosphate, key components for metabolism in modern life. In a pH-buffered solution of NaHCO(3), the condensed and reduced species diphosphonate is an abundant corrosion product. Corrosion in ethanol- and acetic acid-containing solutions yields additional P-bearing organic molecules, including acetyl phosphonate and a cyclic triphosphorus molecule. Phosphonate is a major corrosion product of all experiments and is the only P-bearing molecule that persists in solutions with high concentrations of magnesium and calcium chlorides, which suggests that phosphonate may have been a primitive oceanic source of P. The stability and reactivity of phosphonate and hypophosphite in solution were investigated to elucidate reaction mechanisms and the role of mineral catalysts on P-solution chemistry. Phosphonate oxidation is rapid in the presence of Fe metal but negligible in the presence of magnetite and in the control sample. The rate of hypophosphite oxidation is independent of reaction substrate.


Impact of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine use in wound management on health care costs and pertussis cases.
The Advisory Committee on Immunization Practices (ACIP) recommends the use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine for routine wound management in adolescents and adults who require a tetanus toxoid-containing vaccine who were vaccinated ≥ 5 years earlier with tetanus toxoid, reduced diphtheria toxoid (Td) vaccine, and who have not previously received Tdap. To estimate the overall budget and health impact of vaccinating individuals presenting for wound management with Tdap instead of Td vaccine, the current standard of care in practices that do not use Tdap for purposes of wound management. A decision-analytic economic model was developed to estimate the expected increase in direct medical costs and the expected number of cases of pertussis avoided associated with the use of Tdap instead of Td vaccine in the wound management setting. Patients eligible for Tdap were aged 10+ years and required a tetanus-containing vaccine. Age-specific wound incidence data and Td and Tdap vaccination rates were taken from the National Health Interview Survey and the National Immunization Survey for the most recent available year. Age-specific pertussis incidence used in this analysis (151 per 100,000 for adolescents, 366 per 100,000 for those aged 20-64 years, and 176 per 100,000 for those aged 65+ years) used reported incidence rates adjusted by a factor of 10 for adolescents and by a factor of 100 for adults, based on assumptions previously made by ACIP to account for underreporting. Vaccine wholesale acquisition costs without federal excise tax were assumed in the base case. Efficacy of vaccination with Tdap in preventing pertussis was based on clinical trial data. Possible herd immunity effects of vaccination were not included in the model. Costs associated with vaccination and treatment of pertussis cases were reported as total annual costs and per-member-per-month (PMPM) costs for hypothetical health plans and for the U.S. population. Aggregate and incremental costs and pertussis cases avoided were presented undiscounted (as recommended for budget-impact analyses) annually and cumulatively over a 3-year time horizon in 2012 U.S. dollars. Scenario analyses were conducted on key parameters, including wound incidence, pertussis incidence, vaccine efficacy and waning protection against pertussis, uptake rates for Tdap, and vaccine prices using alternative data sources or alternative clinically relevant assumptions. For a health plan with 1 million covered lives aged < 65 years, vaccination with Tdap instead of Td was estimated to cost an additional $132,364 ($0.01 PMPM) in the first year and an additional $368,640 ($0.01 PMPM) cumulatively over 3 years. For a health plan with 1 million covered lives aged 65+ years, vaccination with Tdap instead of Td was estimated to cost an additional $201,165 ($0.02 PMPM) in the first year and an additional $549,568 ($0.02 PMPM) cumulatively over 3 years. For the U.S. population aged 10+ years, vaccination with Tdap instead of Td was estimated to result in protection against pertussis for an additional 2.7 million patients with wounds annually and was estimated to cost an additional $121,101,671 to avoid 42,104 cases of pertussis over the 3-year time horizon. Results were sensitive to input parameter values, particularly parameters associated with the number of patients with wounds vaccinated with Tdap (range 2.7 to 5.1 million patients). However, for all of the alternative scenarios tested, the expected increase in PMPM costs ranged from < $0.01 to $0.03. Vaccination of adolescents and adults with Tdap for wound management may result in an increase in PMPM costs for health plans of < $0.01 to $0.03. Given the potential reduction in pertussis cases at the population level, vaccination with Tdap for routine wound management could be considered as another strategy to help address the pertussis public health concern in the United States.


Deleterious mutation accumulation and the long-term fate of chromosomal inversions.
Chromosomal inversions contribute widely to adaptation and speciation, yet they present a unique evolutionary puzzle as both their allelic content and frequency evolve in a feedback loop. In this simulation study, we quantified the role of the allelic content in determining the long-term fate of the inversion. Recessive deleterious mutations accumulated on both arrangements with most of them being private to a given arrangement. This led to increasing overdominance, allowing for the maintenance of the inversion polymorphism and generating strong non-adaptive divergence between arrangements. The accumulation of mutations was mitigated by gene conversion but nevertheless led to the fitness decline of at least one homokaryotype under all considered conditions. Surprisingly, this fitness degradation could be permanently halted by the branching of an arrangement into multiple highly divergent haplotypes. Our results highlight the dynamic features of inversions by showing how the non-adaptive evolution of allelic content can play a major role in the fate of the inversion.


Regulation of EGF receptor signaling establishes pattern across the developing Drosophila retina.
Developing epithelia use a variety of patterning mechanisms to place individual cells into their correct positions. However, the means by which pattern elements are established are poorly understood. Here, we report evidence that regulation of Drosophila EGF receptor (DER) activity plays a central role in propagating the evenly spaced array of ommatidia across the developing Drosophila retina. DER activity is essential for establishing the first ommatidial cell fate, the R8 photoreceptor neuron. R8s in turn appear to signal through Rhomboid and Vein to create a patterned array of 'proneural clusters' which contain high levels of phosphorylated ERKA and the bHLH protein Atonal. Finally, secretion by the proneural clusters of Argos represses DER activity in less mature regions to create a new pattern of R8s. Propagation of this process anteriorly results in a retina with a precise array of maturing ommatidia.


Comparative evaluation of mineral trioxide aggregate and bioaggregate as apical barrier material in traumatized nonvital, immature teeth: A clinical pilot study.
Clinical research examining the use of mineral trioxide aggregate (MTA) as an apical barrier material are limited, and no studies have so far examined the clinical performance of BioAggregate as apical barrier material in nonvital immature teeth. This study was aimed to provide a comparative evaluation of the clinical and radiographic success of MTA and BioAggregate as an apical barrier material in children with traumatized nonvital, immature permanent maxillary incisors. A total of 26 maxillary incisor teeth in 20 children aged 7-11 were chosen for this study. Teeth were randomly divided into two groups according to the material to be applied, and the apical barrier was performed. Following treatment, for 24-month, teeth were clinically and radiographically evaluated once every 3- and 6-month, respectively. All teeth treated with MTA and BioAggregate were clinically and radiographically successful throughout the 24-month follow-up period. Similar success was achieved in the apical barrier that using BioAggregate and MTA. BioAggregate would be considered suitable materials for apical barrier technique and can be used as an alternative to MTA.


Environmental conflicts and defenders: A global overview.
Recent research and policies recognize the importance of environmental defenders for global sustainability and emphasize their need for protection against violence and repression. However, effective support may benefit from a more systematic understanding of the underlying environmental conflicts, as well as from better knowledge on the factors that enable environmental defenders to mobilize successfully. We have created the global Environmental Justice Atlas to address this knowledge gap. Here we present a large-n analysis of 2743 cases that sheds light on the characteristics of environmental conflicts and the environmental defenders involved, as well as on successful mobilization strategies. We find that bottom-up mobilizations for more sustainable and socially just uses of the environment occur worldwide across all income groups, testifying to the global existence of various forms of grassroots environmentalism as a promising force for sustainability. Environmental defenders are frequently members of vulnerable groups who employ largely non-violent protest forms. In 11% of cases globally, they contributed to halt environmentally destructive and socially conflictive projects, defending the environment and livelihoods. Combining strategies of preventive mobilization, protest diversification and litigation can increase this success rate significantly to up to 27%. However, defenders face globally also high rates of criminalization (20% of cases), physical violence (18%), and assassinations (13%), which significantly increase when Indigenous people are involved. Our results call for targeted actions to enhance the conditions enabling successful mobilizations, and for specific support for Indigenous environmental defenders.


Effect of lipids from Erabu sea snake, Laticauda semifasciata, on plasma glucose, insulin, and adipocytokine concentrations of normal and streptozotocin-diabetic mice.
To clarify the influence of Erabu sea snake lipid on levels of plasma insulin and adipocyte-derived hormones. Normal male mice (6 months) and streptozotocin-diabetic mice (a single administration, 150 mg/kg i.p.) were fed diets containing 10% fat as either lard or a mixture of 5% lard and 5% sea snake lipid for 4 months. The normal mice on the sea snake lipid diet had a significantly lower plasma glucose concentration (198 +/- 16 mg/dl; 148 +/- 11 mg/dl) than those mice on the lard diet. Although plasma insulin concentrations were not influenced by the dietary fat type, leptin (10 +/- 1 ng/ml; 16 +/- 2 ng/ml) and adiponectin (18 +/- 1 mug/ml; 21 +/- 1 mug/ml) concentrations were significantly higher in the sea snake lipid group than in the lard group. However, these effects of a sea snake lipid intake were not evident in the streptozotocin-diabetic mice. The results suggest that the decrease in plasma glucose following the intake of sea snake lipids could be related to a corresponding increase in leptin and adiponectin level.


Non-invasive prenatal testing.
Non-invasive prenatal testing (NIPT), also known as cell-free DNA testing and non-invasive prenatal screening (NIPS), is an important addition to the range of screening tests for fetal chromosomal abnormalities. For trisomy 21 in particular, NIPT is superior to other screening modalities. However, NIPT has limitations and complexities that requesting clinicians and their patients should understand. This review article will briefly describe the technical basis of NIPT assays and compare the performance characteristics of NIPT with existing screening tests. The clinical use of NIPT will also be discussed. NIPT is now an established option for antenatal screening for trisomy 21, 18, 13 and other selected chromosomal abnormalities. If used appropriately, it increases the detection rate for fetal chromosomal abnormalities, while decreasing the number of invasive tests required. An understanding of the scientific basis of NIPT, and the appropriate clinical use and limitations, will enable medical practitioners to provide optimal antenatal screening.


At the Bench: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer.
Helicobacter pylori infection is the strongest known risk factor for the development of gastric cancer. Given that ∼50% of the global population is infected with this pathogen, there is great impetus to elucidate underlying causes that mediate progression from infection to cancer. Recent evidence suggests that H. pylori-induced chronic inflammation and oxidative stress create an environment conducive to DNA damage and tissue injury. DNA damage leads to genetic instability and eventually, neoplastic transformation. Pathogen-encoded virulence factors induce a robust but futile immune response and alter host pathways that lower the threshold for carcinogenesis, including DNA damage repair, polyamine synthesis and catabolism, antioxidant responses, and cytokine production. Collectively, such dysregulation creates a protumorigenic microenvironment within the stomach. This review seeks to address each of these aspects of H. pylori infection and to call attention to areas of particular interest within this field of research. This review also seeks to prioritize areas of translational research related to H. pylori-induced gastric cancer based on insights garnered from basic research in this field. See related review by Dalal and Moss, At the Bedside: H. pylori, dysregulated host responses, DNA damage, and gastric cancer.


[From PICO to search terms on the Internet: how to find relevant information? New coxibs: do they have a better gastrointestinal safety?].
In the first article of this series, we have shown how to translate a clinical problem into a well built question, by creating a PICO (Patient--Intervention--Comparison--Outcome). In this second article, we will explain how to transform the PICO in English search terms for use on the internet. We use these terms in the different databases to find the answer to the following clinical problem: "In patients aged 65 or over with hip osteoarthritis, and a history of peptic ulcer, is the risk of a new peptic ulcer less using a cox-2 inhibitor than with a classic nonsteroidal anti-inflammatory drug?"


Formulating a health quality improvement strategy for a developing country.
The purpose of this paper is to present the idea of a national health quality plan as a way of mobilising and organising effort towards quality improvement, and stimulate debate and interes in the West in the subject, showing how quality improvement can be developed and invigorated by engaging in issues arising from quality strategies in developing countries. Considers why developing countries are concerned to improve the quality of health care and the different methods which can be used. Stresses the importance of recognising the starting-point and what can help and hinder this work. Concentrates on improving the quality of health care, rather than the wider and important question of improving health. Concludes that developing countries do have the exerptise and that extra resources are needed, mostly for training and supervision. Opines that if implementation is not managed then the investment will be wasted.


A guide to understanding social science research for natural scientists.
Natural scientists are increasingly interested in social research because they recognize that conservation problems are commonly social problems. Interpreting social research, however, requires at least a basic understanding of the philosophical principles and theoretical assumptions of the discipline, which are embedded in the design of social research. Natural scientists who engage in social science but are unfamiliar with these principles and assumptions can misinterpret their results. We developed a guide to assist natural scientists in understanding the philosophical basis of social science to support the meaningful interpretation of social research outcomes. The 3 fundamental elements of research are ontology, what exists in the human world that researchers can acquire knowledge about; epistemology, how knowledge is created; and philosophical perspective, the philosophical orientation of the researcher that guides her or his action. Many elements of the guide also apply to the natural sciences. Natural scientists can use the guide to assist them in interpreting social science research to determine how the ontological position of the researcher can influence the nature of the research; how the epistemological position can be used to support the legitimacy of different types of knowledge; and how philosophical perspective can shape the researcher's choice of methods and affect interpretation, communication, and application of results. The use of this guide can also support and promote the effective integration of the natural and social sciences to generate more insightful and relevant conservation research outcomes.


Rubella.
Experience with the vaccine can be summarized as follows: There were minimal problems with neuralgia and neuropathy as a result of the vaccine; vaccinated children were not a significant source of infection to the pregnant woman; the duration of immunity is similar to that obtained with natural rubella virus, but with lower antibody levels; and reinfection is more common with vaccination, but apparently no viremia develops. Several studies were reported regarding inadvertent vaccination in women who were pregnant at the time of vaccination. In one series [7], 19 pregnant women who were vaccinated were studied. Ten went to term and delivered normal babies and 9 aborted, 8 induced and 1 spontaneously. In one induced abortion, virus was demonstrable in fetal tissue including, notably, in the eye. Another case of CRS was diagnosed in utero amniocentesis [12], and the fetus was aborted at 12 weeks' gestation. Another evaluation of reinfection during pregnancy [1] confirmed that this was of little risk to the fetus, as there was no apparent viremia. In summary, then, in one ophthalmological generation, from Gregg until the present time, we have experienced the recognition, the observation, and, essentially, the conquest of the congenital rubella syndrome. However, if vaccination programs are not assiduously continued, we can expect a renewed upsurge of this difficult problem.


Natriuretic Propeptides as Markers of Atrial Fibrillation Burden and Recurrence (from the AMIO-CAT Trial).
Natriuretic peptides are established plasma markers of systolic heart failure, but their usefulness for the evaluation of atrial fibrillation (AF) is unknown. We examined mid-regional pro-atrial natriuretic peptide (MR-proANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients undergoing ablation for AF. A subpopulation of 102 patients (median age 60 [52;65], 82% male) from the AMIO-CAT trial (Recurrence of arrhythmia following short-term oral AMIOdarone after CATheter ablation for atrial fibrillation: a double-blind, randomized, placebo-controlled study) undergoing ablation for paroxysmal (n = 55) or persistent (n = 47) AF was studied. MR-proANP and NT-proBNP were measured before ablation and at 1, 3, and 6 months' follow-up. Three-day Holter monitoring was performed before ablation, and 6 to 8 weeks and 6 months after ablation. Plasma MR-proANP and NT-proBNP concentrations were higher during AF than during sinus rhythm before ablation (188 pmol/L [131;260] vs 94 pmol/L [64;125], p <0.001; 78 pmol/L [43;121] vs 10.3 pmol/L [5.9;121], p <0.001) and at 1, 3, and 6 months' follow-up. Categories of AF burden on 3-day Holter monitoring (0%, 0% to 99%, and 99% to 100%) were associated with plasma concentrations of both MR-proANP (94 pmol/L [55;127] vs 117 pmol/L [88;185] vs 192 pmol/L [127;261], p <0.001) and NT-proBNP (10 pmol/L [5.9;22] vs 22 pmol/L [8.9;53] vs 81 pmol/L [45;116], p <0.001). In a multivariate regression analysis, however, there was no significant association between baseline propeptide concentrations and recurrence of AF at 6 months' follow-up. In conclusion, AF was associated with higher plasma concentrations of MR-proANP and NT-proBNP than sinus rhythm. Moreover, AF burden was associated with subsequent concentrations of both MR-proANP and NT-proBNP. The results suggest that natriuretic propeptide measurement reflects functional cardiac dysfunction during AF, and that AF burden should be included in biochemical assessment of left ventricular dysfunction.


Solution structure of the first three zinc fingers of TFIIIA bound to the cognate DNA sequence: determinants of affinity and sequence specificity.
The high resolution solution structure of a protein containing the three amino-terminal zinc fingers of Xenopus laevis transcription factor IIIA (TFIIIA) bound to its cognate DNA duplex was determined by nuclear magnetic resonance spectroscopy. The protein, which is designated zf1-3, binds with all three fingers in the DNA major groove, with a number of amino acids making base-specific contacts. The DNA structure is close to B-form. Although the mode of interaction of zf1-3 with DNA is similar to that of zif268 and other structurally characterized zinc finger complexes, the TFIIIA complex exhibits several novel features. Each zinc finger contacts four to five base-pairs and the repertoire of known base contact residues is extended to include a tryptophan at position +2 of the helix (finger 1) and arginine at position +10 (finger 3). Sequence-specific base contacts are made over virtually the entire length of the finger 3 helix. Lysine and histidine side-chains involved in base recognition are dynamically disordered in the solution structure; in the case of lysine, in particular, this could significantly decrease the entropic cost of DNA binding. The TGEKP(N) linker sequences, which are highly flexible in the unbound protein, adopt ordered conformations on DNA binding. The linkers appear to play an active structural role in stabilization of the protein-DNA complex. Substantial protein-protein contact surfaces are formed between adjacent fingers. As a consequence of these protein-protein interactions, the orientation of finger 1 in the major groove differs from that of the other fingers. Contributions to high affinity binding by zf1-3 come from both direct protein-DNA contacts and from indirect protein-protein interactions associated with structural organization of the linkers and formation of well-packed interfaces between adjacent zinc fingers in the DNA complex. The structures provide a molecular level explanation for the large body of footprinting and mutagenesis data available for the TFIIIA-DNA complex.


Mannan Mucin-1 Peptide Immunization: Influence of Cyclophosphamide and the Route of Injection.
SUMMARY: The mucin MUC1 is greatly increased in breast cancer and is a potential target for immunotherapy. In mice, MUC1 conjugated to oxidized mannan (MUC1-mannan fusion protein [M-FP]) targets the mannose receptor and induces a high frequency of cytotoxic T lymphocytes and anti-tumor responses. On this basis, three phase I trials were performed in patients with adenocarcinoma to evaluate the tnxicity and the immunologic responses to mannan MUC1. Forty-one patients with metastatic or locally advanced carcinoma of the breast (trial 1), colon (trial 2), and various adenocarcinomas (trial 3) received increasing doses of M-FP (1 to 300 &mgr;g). The immunizations were given at weekly intervals (weeks 1 to 3) and repeated in weeks 7 to 9. Cyclophosphamide (to increase cellular immunity) was given on weeks 1 and 4. M-FP was given intramuscularly in trial 1 and intraperitoneally in trial 2. No toxic effects occurred, and delayed-type hypersensitivity responses were present only as a microscopic lymphocytic infiltration. Overall, approximately 60% of the patients had high-titer MUC1 immunoglobulin G1 antibody responses, with the intraperitoneal route yielding approximately 10-fold higher responses. Cellular responses (proliferation, cytotoxic T cells, or CD8 T cells secreting tumor necrosis factor-alpha alphand interferon-gamma in response to MUC1 stimulation in vitro) were found in 28% of the patients, which was similar to that seen without cyclophosphamide. In most patients, disease progressed, but in five it remained stable. In addition, there were no objective responses. M-FP is not toxic and induces immune responses that were amplified by the intraperitoneal route of immunization. Cyclophosphamide was of no benefit.


The role of intraspecific competition between plants in a nursery pollination system-Comments on Villacañas de Castro and Hoffmeister 2020.
We present comments on an article published by Villacañas de Castro and Hoffmeister (Ecology and Evolution, 10, 4220; 2020). The authors studied a tritrophic system composed of a plant, its pollinating seed predator, and a parasitoid of the latter. Their concern was whether the parasitoid modifies the interaction between the plant and its pollinator-herbivore along the mutualism-antagonism gradient, but they reduced their question to how the parasitoid impacts plant fitness. After showing that the parasitoid increases seed output of the plant by decreasing the amount of seeds consumed by the pollinating seed predator, they tested whether seed output is a good proxy for plant fitness. They argue that it is not by showing that the increased seed density has a negative impact on survival probability and flower production, likely due to plant intraspecific competition. The work presented shows careful experimentation and interesting results, but we do not share some of their conclusions. Most importantly, we believe that the net effect of the parasitoid on the plant-herbivore interaction cannot be adequately investigated by focusing on individual plant fitness. Thus, we first suggest considering the number of surviving plants up to adulthood as a proxy for population performance to address this question. Using this proxy, we show that the increase in seed output due to the parasitoid is beneficial to the plant population until its carrying capacity is achieved. Next, using a population dynamics model, we show under which particular conditions the negative effect of intraspecific competition outweighs the positive effect of seed density increase (due to parasitoid's defense). When these conditions do not hold, the role of plant intraspecific competition is basically limited to the prevention of unbounded population growth, while the parasitoid increases the plant's equilibrium density above its carrying capacity as measured when interacting only with the pollinating seed predator, thus making the system more stable.


Identification and evaluation of agents isolated from traditionally used herbs against Ophiophagus hannah venom.
The aim of this study was firstly to identify active molecules in herbs, that are traditionally used for the treatment of snake bite, such as Curcuma antinaia, Curcuma contravenenum, Andrographis paniculata, and Tanacetum parthenium; secondly to test similar structurally related molecules and finally to prepare and evaluate an efficient formulation against Ophiophagus hannah venom intoxification. Three labdane based compounds, including labdane dialdehyde, labdane lactone, and labdane trialdehyde and two lactones including 14-deoxy-11,12-didehydroandrographolide and parthenolide were isolated by column chromatography and characterised. Using the isolated rat phrenic nerve-hemidiaphragm preparation, the antagonistic effect of crude extracts, isolated compounds and prepared formulations were measured in vitro on the inhibition of the neuromuscular transmission. Inhibition on muscle contraction, produced by the 5 μg/mL venom, was reversed by test agents in organ bath preparations. A labdane trialdehyde, isolated from C. contravenenum, was identified as the best antagonising agent in the low micromolar range. Tests on formulations of the most potent C. contravenenum extract showed, that the suppository with witepsol H15 was an effective medicine against O. hannah venom. This study elucidated the active compounds, accounting for the antivenin activity of traditionally used herbs and suggested the most suitable formulation, which may help to develop potent medicines for the treatment of snake bite in the future.


Alexithymia and psychological distress in fibromyalgia: prevalence and relation with quality of life.
Fibromyalgia (FM) is a chronic syndrome characterised by widespread musculoskeletal pain associated with other symptoms like fatigue, stiffness, non-restorative sleep and psychological distress that strongly affects the quality of life in FM patients. While the psychological distress has been widely explored in FM, only a few studies investigated alexithymia, an emotional dysregulation trait. Evaluate the prevalence of alexithymia and psychological distress and their impact on patients quality of life. A battery of tests assessing alexithymia, depression, anxiety, emotional distress symptoms and the health related quality of life (HRQoL) was filled out by 55 female FM patients. After having analysed their prevalence, two regression analyses were performed in order to evaluate the role that alexithymia, depression, anxiety, emotional distress and pain characteristics have on quality of life of FM patients. Results showed that a clinically relevant level of psychological distress was present in more than half of our sample, whereas alexithymic traits were present in 20% of the patients. Regression analyses showed that pain intensity, depression and current pain were the variables that best contribute to explain the physical component of the HRQoL while anxiety, depression and pain intensity were the variables that mainly contributed to explain the mental component of quality of life. These results underline the high prevalence of alexithymia in FM patients and the great impact of psychological symptoms on FM patients HRQoL. Wholistic care of FM patients which addresses both physical and psychological symptoms is needed.


Cognitive effects of transcranial direct current stimulation in depression: Results from the SELECT-TDCS trial and insights for further clinical trials.
Cognitive dysfunction treatment remains an unmet clinical need in major depressive disorder (MDD). Transcranial direct current stimulation (tDCS) may improve cognitive symptoms in MDD. Our aim was to investigate the cognitive effects of tDCS in the Sertraline vs. Electric Current Therapy for Treating Depression Clinical Study (SELECT-TDCS). We also explored whether tDCS could have mood-independent cognitive effects. One hundred twenty MDD patients aged from 18 to 65 years received 12 sessions of active/sham tDCS (2mA for 30min) and real/placebo 50mg/d sertraline over 6 weeks in a factorial trial. We analyzed whether changes in performance of neuropsychological tests (Trail Making, Digit Span, Stroop Task, Mini-Mental Status Exam and Montreal Cognitive Assessment) occurred over time, according to treatment group and depression improvement. Exploratory analyses were carried out to verify the influence of clinical and demographic variables on the outcomes. Cognitive improvement was showed in most tests used, although they occurred regardless of intervention type and depression improvement. Further exploratory analyses revealed that clinical response and education level could have mediated pro-cognitive tDCS effects on some of the tests used. The neuropsychological battery used might not have been sensitive to detect tDCS-induced effects on cognition. Lack of simultaneous cognitive training during application may have also limited its cognitive effects. We found no evidence of beneficial or deleterious cognitive effects of tDCS as a treatment for depression. We discussed clinical trial design considerations for further tDCS studies assessing cognitive effects, including sample and outcomes considerations.


Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. III. Responses To translation.
The three-dimensional (3-D) properties of the translational vestibulo-ocular reflexes (translational VORs) during lateral and fore-aft oscillations in complete darkness were studied in rhesus monkeys at frequencies between 0.16 and 25 Hz. In addition, constant velocity off-vertical axis rotations extended the frequency range to 0.02 Hz. During lateral motion, horizontal responses were in phase with linear velocity in the frequency range of 2-10 Hz. At both lower and higher frequencies, phase lags were introduced. Torsional response phase changed more than 180 degrees in the tested frequency range such that torsional eye movements, which could be regarded as compensatory to "an apparent roll tilt" at the lowest frequencies, became anticompensatory at all frequencies above approximately 1 Hz. These results suggest two functionally different frequency bandwidths for the translational VORs. In the low-frequency spectrum (<<0.5 Hz), horizontal responses compensatory to translation are small and high-pass-filtered whereas torsional response sensitivity is relatively frequency independent. At higher frequencies however, both horizontal and torsional response sensitivity and phase exhibit a similar frequency dependence, suggesting a common role during head translation. During up-down motion, vertical responses were in phase with translational velocity at 3-5 Hz but phase leads progressively increased for lower frequencies (>90 degrees at frequencies <0.2 Hz). No consistent dependence on static head orientation was observed for the vertical response components during up-down motion and the horizontal and torsional response components during lateral translation. The frequency response characteristics of the translational VORs were fitted by "periphery/brain stem" functions that related the linear acceleration input, transduced by primary otolith afferents, to the velocity signals providing the input to the velocity-to-position neural integrator and the oculomotor plant. The lowest-order, best-fit periphery/brain stem model that approximated the frequency dependence of the data consisted of a second order transfer function with two alternating poles (at 0.4 and 7.2 Hz) and zeros (at 0.035 and 3.4 Hz). In addition to clearly differentiator dynamics at low frequencies (less than approximately 0.5 Hz), there was no frequency bandwidth where the periphery/brain stem function could be approximated by an integrator, as previously suggested. In this scheme, the oculomotor plant dynamics are assumed to perform the necessary high-frequency integration as required by the reflex. The detailed frequency dependence of the data could only be precisely described by higher order functions with nonminimum phase characteristics that preclude simple filtering of afferent inputs and might be suggestive of distributed spatiotemporal processing of otolith signals in the translational VORs.


Neuroanatomical distribution of the enkephalinergic and tachykininergic systems in the alpaca brainstem: an immunohistochemical study.
A recent study has shown a close neuroanatomical relationship between the enkephalinergic (methionine-enkephalin) and tachykininergic (substance P) systems in the alpaca diencephalon. In this study, our aim is to show this relationship in the alpaca brainstem. Using an immunohistochemical technique, the distribution of immunoreactive (Ir) fibers and cell bodies containing substance P (SP) or methionine-enkephalin (MET) has been studied in the alpaca brainstem. Five adult males were used; brain tissue was fixed and processed by standard methods. SP- and MET-Ir fibers showed a widespread and similar distribution in the mesencephalon, pons and medulla oblongata. The co-localization of fibers containing SP or MET was found in most of the nuclei/tracts of the alpaca brainstem. This close neuroanatomical relationship suggests multiple physiological interactions between both neuropeptides. The distribution of the cell bodies containing SP was very restricted (cell bodies were only observed in a few nuclei located in the mesencephalon and medulla oblongata), whereas MET-Ir perikarya showed a moderately widespread distribution in the mesencephalon, pons and medulla oblongata. This study increases the knowledge on the neuroanatomical distribution/relationship of the tachykininergic (SP) and enkephalinergic (MET) systems in the alpaca central nervous system.


A Bayesian model for gene family evolution.
A birth and death process is frequently used for modeling the size of a gene family that may vary along the branches of a phylogenetic tree. Under the birth and death model, maximum likelihood methods have been developed to estimate the birth and death rate and the sizes of ancient gene families (numbers of gene copies at the internodes of the phylogenetic tree). This paper aims to provide a Bayesian approach for estimating parameters in the birth and death model. We develop a Bayesian approach for estimating the birth and death rate and other parameters in the birth and death model. In addition, a Bayesian hypothesis test is developed to identify the gene families that are unlikely under the birth and death process. Simulation results suggest that the Bayesian estimate is more accurate than the maximum likelihood estimate of the birth and death rate. The Bayesian approach was applied to a real dataset of 3517 gene families across genomes of five yeast species. The results indicate that the Bayesian model assuming a constant birth and death rate among branches of the phylogenetic tree cannot adequately explain the observed pattern of the sizes of gene families across species. The yeast dataset was thus analyzed with a Bayesian heterogeneous rate model that allows the birth and death rate to vary among the branches of the tree. The unlikely gene families identified by the Bayesian heterogeneous rate model are different from those given by the maximum likelihood method. Compared to the maximum likelihood method, the Bayesian approach can produce more accurate estimates of the parameters in the birth and death model. In addition, the Bayesian hypothesis test is able to identify unlikely gene families based on Bayesian posterior p-values. As a powerful statistical technique, the Bayesian approach can effectively extract information from gene family data and thereby provide useful information regarding the evolutionary process of gene families across genomes.


DRD2/ANKK1 TaqI A genotype moderates the relationship between alexithymia and the relative value of alcohol among male college binge drinkers.
Binge drinking remains prevalent on college campuses (particularly among males), and a behavioral economic conceptualization of alcohol use provides novel insight into this problem. Further understanding also comes from identifying personality and genetic vulnerabilities associated with problem drinking among male college students. The present study hypothesized that DRD2/ANKK1 TaqI A (rs1800497) genotype would moderate the relationship between alexithymia and an alcohol purchase task (APT) among male college binge drinkers. Specifically, among individuals with at least 1 A1 allele (A1+), greater alexithymia would be related to higher breakpoint (the point at which consumption is 0), O(max) (maximum expenditure on consumption), P(max) (price at which maximum expenditure occurs), intensity (consumption at the lowest price), and lesser elasticity (sensitivity to increasing price). Secondary analyses aimed to replicate APT associations with problematic drinking (AUDIT) and alcohol-related problems (RAPI). Participants were 120 male European-American college student binge drinkers ( M=10.33, SD=4.41). Five Bonferroni-corrected moderation models were tested using APT indices as the criteria, alexithymia as the predictor, and DRD2/ANKK1 TaqI A1 allele presence as the moderator. Results indicated that, in A1+ individuals, greater alexithymia predicted lesser elasticity. Findings were not significant in A1- individuals. APT intensity was positively correlated with AUDIT total; however, no other significant relationships were found. This suggests that possession of the A1 allele interacts with hypoemotionality to predict a novel index of problem drinking. Results support the notion that college campuses would benefit from behavioral economic approaches to reduce binge drinking.


Dietary Intake Is Related to Multifactor Cardiovascular Risk Score in Obese Boys.
Cardiovascular disease (CVD) originates in childhood and early identification of risk factors provides an early intervention opportunity. The aim was to identify children at higher risk using a CVD risk score, developed from factors known to cluster in childhood. Risk was scored as very high (≥97.5th centile), high (≥95th), moderate (≥90th) or threshold (<90th) using normal pediatric reference ranges for 10 common biomedical risk factors. These were summed in a multifactor CVD risk score and applied to a sample of 285 observations from 136 overweight Australian children (41% male, aged 7-12 years). Strength of associations between CVD risk score and individual biomedical and dietary variables were assessed using univariate logistic regression. High waist circumference (Odds Ratio: 5.48 [95% CI: 2.60-11.55]), body mass index (OR: 3.22 [1.98-5.26]), serum insulin (OR: 3.37 [2.56-4.42]) and triglycerides (OR: 3.02 [2.22-4.12]) were all significantly related to CVD risk score. High intakes of total fat (OR: 4.44 [1.19-16.60]), sugar (OR: 2.82 [1.54-5.15]) and carbohydrate (OR 1.75 [1.11-2.77]) were significantly related to CVD risk score in boys only. This multifactor CVD risk score could be a useful tool for researchers to identify elevated risk in children. Further research is warranted to examine sex-specific dietary factors related to CVD risk in children.


Combining agent-based modeling and life cycle assessment for the evaluation of mobility policies.
This article presents agent-based modeling (ABM) as a novel approach for consequential life cycle assessment (C-LCA) of large scale policies, more specifically mobility-related policies. The approach is validated at the Luxembourgish level (as a first case study). The agent-based model simulates the car market (sales, use, and dismantling) of the population of users in the period 2013-2020, following the implementation of different mobility policies and available electric vehicles. The resulting changes in the car fleet composition as well as the hourly uses of the vehicles are then used to derive consistent LCA results, representing the consequences of the policies. Policies will have significant environmental consequences: when using ReCiPe2008, we observe a decrease of global warming, fossil depletion, acidification, ozone depletion, and photochemical ozone formation and an increase of metal depletion, ionizing radiations, marine eutrophication, and particulate matter formation. The study clearly shows that the extrapolation of LCA results for the circulating fleet at national scale following the introduction of the policies from the LCAs of single vehicles by simple up-scaling (using hypothetical deployment scenarios) would be flawed. The inventory has to be directly conducted at full scale and to this aim, ABM is indeed a promising approach, as it allows identifying and quantifying emerging effects while modeling the Life Cycle Inventory of vehicles at microscale through the concept of agents.


First Report of the East-Central South African Genotype of Chikungunya Virus in Rio de Janeiro, Brazil.
Chikungunya virus (CHIKV) is an arbovirus that causes an acute febrile syndrome with a severe and debilitating arthralgia. In Brazil, the Asian and East-Central South African (ECSA) genotypes are circulating in the north and northeast of the country, respectively. In 2015, the first autochthonous cases in Rio de Janeiro, Brazil were reported but until now the circulating strains have not been characterized. Therefore, we aimed here to perform the molecular characterization and phylogenetic analysis of CHIKV strains circulating in the 2016 outbreak occurred in the municipality of Rio de Janeiro. The cases analyzed in this study were collected at a private Hospital, from April 2016 to May 2016, during the chikungunya outbreak in Rio de Janeiro, Brazil. All cases were submitted to the Real Time RT-PCR for CHIKV genome detection and to anti-CHIKV IgM ELISA. Chikungunya infection was laboratorially confirmed by at least one diagnostic method and, randomly selected positive cases (n=10), were partially sequenced (CHIKV E1 gene) and analyzed. The results showed that all the samples grouped in ECSA genotype branch and the molecular characterization of the fragment did not reveal the A226V mutation in the Rio de Janeiro strains analyzed, but a K211T amino acid substitution was observed for the first time in all samples and a V156A substitution in two of ten samples. Phylogenetic analysis and molecular characterization reveals the circulation of the ECSA genotype of CHIKV in the city of Rio de Janeiro, Brazil and two amino acids substitutions (K211T and V156A) exclusive to the CHIKV strains obtained during the 2016 epidemic, were reported.