Dynamic risk control by human nucleus accumbens

Real-world decisions about reward often involve a complex counterbalance of risk and value. Although the nucleus accumbens has been implicated in the underlying neural substrate, its criticality to human behaviour remains an open question, best addressed with interventional methodology that probes the behavioural consequences of focal neural modulation. Combining a psychometric index of risky decision-making with transient electrical modulation of the nucleus accumbens, here we reveal profound, highly dynamic alteration of the relation between probability of reward and choice during therapeutic deep brain stimulation in four patients with treatment-resistant psychiatric disease. Short-lived phasic electrical stimulation of the region of the nucleus accumbens dynamically altered risk behaviour, transiently shifting the psychometric function towards more risky decisions only for the duration of stimulation. A critical, on-line role of human nucleus accumbens in dynamic risk control is thereby established

Validation in clinical population of the Problematic Internet Entertainment Use Scale for Adults (PIEUSAd)

Addiction to technologies has been a widely debated scientific and clinically, being a condition for further study as potential psychiatric disorder. Some Spanish scales measure Internet addiction, but no one has been validated clinically. The aims were to describe a clinical sample of patients in treatment for a technology addiction, and to validate clinically the “Problematic Internet Entertainment Use Scale for Adults” (PIEUSAd). Little-scale clinical adult sample (N=31; 71 % men, and an age mean of 33.31) was selected, collecting socio-demographic and clinical data, technological usages, and the PIEUSAd and Compulsive Internet Use Scale in a survey. The setting was a public health center in Barcelona (Spain). The patients in treatment for a technological addiction as primary diagnosis were usually young males, which suffer from a genuine e-addiction (above all, internet addiction, gaming and cybersex); only the middle seems to have a dual pathology (usually another addiction). They are usually referred by other clinician and the majority don’t have previous psychiatric care. The PIEUSAd showed large variability in item scored, and high factor and construct validity, and excellent reliability (a=0.98). In conclusion, the heterogeneity in the characteristics of patients is evidenced. Moreover, the PIEUSAd has been clinical validated to do a better screen in technological addictions, where “loss of control” and “evasion” seems to be the prevalent addictive symptoms in these types of patients. Spanish abstract: La adicción a las tecnologías ha sido debatida ampliamente tanto científica como clínicamente, siendo una condición a estudiar como potencial trastorno psiquiátrico. Algunas escalas españolas miden la adicción al internet, pero ninguna ha sido validada clínicamente. Los objetivos son describir la muestra clínica de pacientes en tratamiento por una adicción tecnológica, así como validar clínicamente la “Problematic Internet Entertainment Use Scale for Adults” (PIEUSAd). Una muestra clínica a pequeña escala (N=31; 71 % hombres, con una edad media de 33,31) fue seleccionada, se recogieron datos socio-demográficos, clínicos y de uso de tecnologías, así como la PIEUSAd y la “Compulsive Internet Use Scale” a través de una encuesta. El contexto fue un centro de salud pública de Barcelona (España). Los pacientes en tratamiento por una adicción tecnológica como primer diagnóstico eran usualmente hombres jóvenes que sufrían de una e-adicción genuina (sobre todo, adicción a internet, videojuegos o cibersexo); solo la mitad parecía sufrir una patología dual (normalmente otra adicción). Eran normalmente derivados por otros profesionales de la salud y la mayor parte no habían sido tratados psiquiá- tricamente con anterioridad. La PIEUSAd mostró gran variabilidad en sus puntuaciones, alta validez factorial y de constructo, y excelente fiabilidad (a=0,98). En conclusión, la heterogeneidad de las características de los pacientes fue evidenciada. Además, la PIEUSAd ha sido validada clínicamente para poder hacer un mejor cribado en las adicciones tecnológicas, donde la “pérdida de control” y la “evasión” parecen ser los síntomas prevalentes en estos tipos de pacientes

Leaf-applied sodium chloride promotes cadmium accumulation in durum wheat grain

Cadmium (Cd) accumulation in durum wheat grain is a growing concern. Among the factors affecting Cd accumulation in plants, soil chloride (Cl) concentration plays a critical role. The effect of leaf NaCl application on grain Cd was studied in greenhouse-grown durum wheat (Triticum turgidum L. durum, cv. Balcali-2000) by immersing (10 s) intact flag leaves into Cd and/or NaCl-containing solutions for 14 times during heading and dough stages. Immersing flag leaves in solutions containing increasing amount of Cd resulted in substantial increases in grain Cd concentration. Adding NaCl alone or in combination with the Cd-containing immersion solution promoted accumulation of Cd in the grains, by up to 41%. In contrast, Zn concentrations of grains were not affected or even decreased by the NaCl treatments. This is likely due to the effect of Cl complexing Cd and reducing positive charge on the metal ion, an effect that is much smaller for Zn. Charge reduction or removal (CdCl2 0 species) would increase the diffusivity/lipophilicity of Cd and enhance its capability to penetrate the leaf epidermis and across membranes. Of even more significance to human health was the ability of Cl alone to penetrate leaf tissue and mobilize and enhance shoot Cd transfer to grains, yet reducing or not affecting Zn transfer

How and why DNA barcodes underestimate the diversity of microbial eukaryotes

Background: Because many picoplanktonic eukaryotic species cannot currently be maintained in culture, direct sequencing of PCR-amplified 18S ribosomal gene DNA fragments from filtered sea-water has been successfully used to investigate the astounding diversity of these organisms. The recognition of many novel planktonic organisms is thus based solely on their 18S rDNA sequence. However, a species delimited by its 18S rDNA sequence might contain many cryptic species, which are highly differentiated in their protein coding sequences. Principal Findings: Here, we investigate the issue of species identification from one gene to the whole genome sequence. Using 52 whole genome DNA sequences, we estimated the global genetic divergence in protein coding genes between organisms from different lineages and compared this to their ribosomal gene sequence divergences. We show that this relationship between proteome divergence and 18S divergence is lineage dependant. Unicellular lineages have especially low 18S divergences relative to their protein sequence divergences, suggesting that 18S ribosomal genes are too conservative to assess planktonic eukaryotic diversity. We provide an explanation for this lineage dependency, which suggests that most species with large effective population sizes will show far less divergence in 18S than protein coding sequences. Conclusions: There is therefore a trade-off between using genes that are easy to amplify in all species, but which by their nature are highly conserved and underestimate the true number of species, and using genes that give a better description of the number of species, but which are more difficult to amplify. We have shown that this trade-off differs between unicellular and multicellular organisms as a likely consequence of differences in effective population sizes. We anticipate that biodiversity of microbial eukaryotic species is underestimated and that numerous ''cryptic species'' will become discernable with the future acquisition of genomic and metagenomic sequences

Large-scale latitudinal and vertical distributions of NMHCs and selected halocarbons in the troposphere over the Pacific Ocean during the March-April 1999 Pacific Exploratory Mission (PEM-Tropics B)

Nonmethane hydrocarbons (NMHCs) and selected halocarbons were measured in whole air samples collected over the remote Pacific Ocean during NASA's Global Tropospheric Experiment (GTE) Pacific Exploratory Mission-Tropics B (PEM-Tropics B) in March and early April 1999. The large-scale spatial distributions of NMHCs and C2Cl4 reveal a much more pronounced north-south interhemispheric gradient, with higher concentrations in the north and lower levels in the south, than for the late August to early October 1996 PEM-Tropics A experiment. Strong continental outflow and winter-long accumulation of pollutants led to seasonally high Northern Hemisphere trace gas levels during PEM-Tropics B. Observations of enhanced levels of Halon 1211 (from developing Asian nations such as the PRC) and CH3Cl (from SE Asian biomass burning) support a significant southern Asian influence at altitudes above 1 km and north of 10° N. By contrast, at low altitude over the North Pacific the dominance of urban/industrial tracers, combined with low levels of Halon 1211 and CH3Cl, indicate a greater influence from developed nations such as Japan, Europe, and North America. Penetration of air exhibiting aged northern hemisphere characteristics was frequently observed at low altitudes over the equatorial central and western Pacific south to ∼5° S. The relative lack of southern hemisphere biomass burning sources and the westerly position of the South Pacific convergence zone contributed to significantly lower PEM-Tropics B mixing ratios of the NMHCs and CH3Cl south of 10° S compared to PEM-Tropics A. Therefore the trace gas composition of the South Pacific troposphere was considerably more representative of minimally polluted tropospheric conditions during PEM-Tropics B. Copyright 2001 by the American Geophysical Union

Diferencias psicopatológicas en mujeres con Dependencia Emocional con y sin uso de sustancias ilegales comórbido

En este artículo se presenta un análisis clínico de las diferencias psicopatológicas entre dos grupos de pacientes, mujeres, con problemas de Dependencia Emocional con y sin consumo de sustancias ilegales comórbido. Las pacientes fueron evaluadas mediante los cuestionarios TDS100, SCL-90-R, BIS-11 y una entrevista semiestructurada adaptada de la entrevista SCID-I. Los grupos se formaron en función de si existía consumo de drogas o no en el momento de la evaluación. A través de los resultados hallados, se puede concluir que el grupo de mujeres con un consumo ocasional de drogas presenta una mayor gravedad en la escala de Acomodación medida a través del TDS-100, así como puntuaciones más altas en psicopatología comórbida (Sensibilidad Interpersonal, Ansiedad, Hostilidad, Ideación paranoide, Psicoticismo y GSI) medida por el SCL-90-R. Finalmente, el grupo con uso de drogas obtuvo puntuaciones significativamente más altas en la subescala Impulsividad Motora medida por el BIS-11. English abstract: In this article we present a clinical analysis of the psychopathological differences between women patients with Affective Dependence problems with and without comorbid substance use. The patients were assessed trough the TDS-100, SCL-90-R, BIS-11 questionnaires and a semi-structured interview adapted from the SCID-I interview. The groups were created based on the substance use at the moment of the assessment. The results reveal that the group of women with occasional use of drugs shows higher severity in the Accommodation scale measured trough the TDS-100 and in the comorbid psychopathology measured by the SCL-90R (Interpersonal Sensitivity, Anxiety, Hostility, Paranoid ideation, Psychoticism y GSI). Finally, the group with drug use obtained significantly higher scores in the Motor Impulsiveness subscale measured by the BIS-11

Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves

HAT-P-26b: A Neptune-mass exoplanet with a well-constrained heavy element abundance

This is the author accepted manuscript. The final version is available from American Association for the Advancement of Science via the DOI in this record.A correlation between giant-planet mass and atmospheric heavy elemental abundance was first noted in the past century from observations of planets in our own Solar System and has served as a cornerstone of planet-formation theory. Using data from the Hubble and Spitzer Space Telescopes from 0.5 to 5 micrometers, we conducted a detailed atmospheric study of the transiting Neptune-mass exoplanet HAT-P-26b. We detected prominent H2O absorption bands with a maximum base-to-peak amplitude of 525 parts per million in the transmission spectrum. Using the water abundance as a proxy for metallicity, we measured HAT-P-26b’s atmospheric heavy element content (Embedded Image times solar). This likely indicates that HAT-P-26b’s atmosphere is primordial and obtained its gaseous envelope late in its disk lifetime, with little contamination from metal-rich planetesimals.Support for this work was provided by NASA through grants under the HST-GO-14260 program from the STSci. H.R.W. acknowledges support from the NASA Postdoctoral Program, administered by Universities Space Research Association through a contract with NASA. Several authors acknowledge funding from the European Research Council under the European Union Seventh Framework Program: D.K.S., T.K., N.N., and T.M.E. under grant 336792; E.D.L. under grant 313014; and P.T. and D.S.A. under grant 247060-PEPS

Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania.

To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection. A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI. Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians