Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF.

The cardiovascular system is under the control of the circadian clock, and disturbed circadian rhythms can induce cardiovascular pathologies. This cyclic regulation is probably brought about by the circadian expression of genes encoding enzymes and regulators involved in cardiovascular functions. We have previously shown that the rhythmic transcription of output genes is, in part, regulated by the clock-controlled PAR bZip transcription factors DBP (albumin D-element Binding Protein), HLF (Hepatic Leukemia Factor), and TEF (Thyrotroph Embryonic Factor). The simultaneous deletion of all three PAR bZip transcription factors leads to increased morbidity and shortened life span. Here, we demonstrate that Dbp/Tef/Hlf triple knockout mice develop cardiac hypertrophy and left ventricular dysfunction associated with a low blood pressure. These dysfunctions are exacerbated by an abnormal response to this low blood pressure characterized by low aldosterone levels. The phenotype of PAR bZip knockout mice highlights the importance of circadian regulators in the modulation of cardiovascular functions.

Soil carbon and nitrogen mineralization caused by pig slurry application under different soil tillage systems

The objective of this work was to evaluate the change in soil C and N mineralization due to successive pig slurry application under conventional tillage (CT) and no tillage (NT) systems. The experiment was carried out in a clayey Latossolo Vermelho eutrófico (Rhodic Eutrudox) in Palotina, PR, Brazil. Increasing doses of pig slurry (0, 30, 60 and 120 m³ ha-1 per year) were applied in both tillage systems, with three replicates. Half of the pig slurry was applied before summer soil preparation, and the other half before the winter crop season. The areas were cultivated with soybean (Glycine max L.) and maize (Zea mays L.) in the summers of 1998 and 1999, respectively, and with wheat (Triticum sativum Lam.) in the winters of both years. Soil samples were collected at 0-5, 5-10, and 10-20 cm depths. Under both CT and NT systems, pig slurry application increased C and N mineralization. However, increasing pig slurry additions decreased the C to N mineralization ratio. Under the NT system, C and N mineralization was greater than in CT system.

Large D gravity and low D strings

We show that in the limit of a large number of dimensions a wide class of nonextremal neutral black holes has a universal near-horizon limit. The limiting geometry is the two-dimensional black hole of string theory with a two-dimensional target space. Its conformal symmetry explains the properties of massless scalars found recently in the large-D limit. For black branes with string charges, the near-horizon geometry is that of the three-dimensional black strings of Horne and Horowitz. The analogies between the α′ expansion in string theory and the large-D expansion in gravity suggest a possible effective string description of the large-D limit of black holes. We comment on applications to several subjects, in particular to the problem of critical collapse.

Carbon and nitrogen cycling in an integrated soybean-beef cattle production system under different grazing intensities

Abstract:The objective of this work was to evaluate the effect of grazing intensity on the decomposition of cover crop pasture, dung, and soybean residues, as well as the C and N release rates from these residues in a long-term integrated soybean-beef cattle system under no-tillage. The experiment was initiated in 2001, with soybean cultivated in summer and black oat + Italian ryegrass in winter. The treatments consisted of four sward heights (10, 20, 30, and 40 cm), plus an ungrazed area, as the control. In 2009-2011, residues from pasture, dung, and soybean stems and leaves were placed in nylon-mesh litter bags and allowed to decompose for up to 258 days. With increasing grazing intensity, residual dry matter of the pasture decreased and that of dung increased. Pasture and dung lignin concentrations and C release rates were lower with moderate grazing intensity. C and N release rates from soybean residues are not affected by grazing intensity. The moderate grazing intensity produces higher quality residues, both for pasture and dung. Total C and N release is influenced by the greater residual dry matter produced when pastures were either lightly grazed or ungrazed.

Adverse drug reactions following nonresponse in a depressed patient with CYP2D6 deficiency and low CYP 3A4/5 activity

A 47-year-old male taxi driver experienced multiple adverse drug reactions during therapy with clomipramine (CMI) and quetiapine for major depressive disorder, after having been unsuccessfully treated with adequate doses of mirtazapine and venlafaxine. Drug serum concentrations of CMI and quetiapine were significantly increased and pharmacogenetic testing showed a poor metabolizer status for CYP2D6, low CYP3A4/5 activity and normal CYP2C19 genotype. After reduction of the CMI dose and discontinuation of quetiapine, all ADR subsided except for the increase in liver enzymes. The latter improved but did not normalize completely, even months later, possibly due to concomitant cholelithiasis.

Effect of water velocity on the uptake of polychlorinatedd biphenyls (PCBs) by silicone rubber (SR) and low-density polyethylene (LDPE) passive samplers: an assessment of the efficiency of performance reference compounds (PRCs) in river-like flow conditions

One aim of this study is to determine the impact of water velocity on the uptake of indicator polychlorinated biphenyls (iPCBs) by silicone rubber (SR) and low-density polyethylene (LDPE) passive samplers. A second aim is to assess the efficiency of performance reference compounds (PRCs) to correct for the impact of water velocity. SR and LDPE samplers were spiked with 11 or 12 PRCs and exposed for 6 weeks to four different velocities (in the range of 1.6 to 37.7 cm s−1) in river-like flow conditions using a channel system supplied with river water. A relationship between velocity and the uptakewas found for each iPCB and enables to determine expected changes in the uptake due to velocity variations. For both samplers, velocity increases from 2 to 10 cm s−1, 30 cm s−1 (interpolated data) and 100 cm s−1 (extrapolated data) lead to increases of the uptake which do not exceed a factor of 2, 3 and 4.5, respectively. Results also showed that the influence of velocity decreased with increasing the octanol-water coefficient partition (log Kow) of iPCBs when SR is used whereas the opposite effect was observed for LDPE. Time-weighted average (TWA) concentrations of iPCBs in water were calculated from iPCB uptake and PRC release. These calculations were performed using either a single PRC or all the PRCs. The efficiency of PRCs to correct the impact of velocity was assessed by comparing the TWA concentrations obtained at the four tested velocities. For SR, a good agreement was found among the four TWA concentrations with both methods (average RSD b 10%). Also for LDPE, PRCs offered a good correction of the impact of water velocity (average RSD of about 10 to 20%). These results contribute to the process of acceptance of passive sampling in routine regulatory monitoring programs.

Effects of a post-weaning cafeteria diet in young rats: metabolic syndrome, reduced activity and low anxiety-like behaviour.

Among adolescents, overweight, obesity and metabolic syndrome are rapidly increasing in recent years as a consequence of unhealthy palatable diets. Animal models of diet-induced obesity have been developed, but little is known about the behavioural patterns produced by the consumption of such diets. The aim of the present study was to determine the behavioural and biochemical effects of a cafeteria diet fed to juvenile male and female rats, as well as to evaluate the possible recovery from these effects by administering standard feeding during the last week of the study. Two groups of male and female rats were fed with either a standard chow diet (ST) or a cafeteria (CAF) diet from weaning and for 8 weeks. A third group of males (CAF withdrawal) was fed with the CAF diet for 7 weeks and the ST in the 8th week. Both males and females developed metabolic syndrome as a consequence of the CAF feeding, showing overweight, higher adiposity and liver weight, increased plasma levels of glucose, insulin and triglycerides, as well as insulin resistance, in comparison with their respective controls. The CAF diet reduced motor activity in all behavioural tests, enhanced exploration, reduced anxiety-like behaviour and increased social interaction; this last effect was more pronounced in females than in males. When compared to animals only fed with a CAF diet, CAF withdrawal increased anxiety in the open field, slightly decreased body weight, and completely recovered the liver weight, insulin sensitivity and the standard levels of glucose, insulin and triglycerides in plasma. In conclusion, a CAF diet fed to young animals for 8 weeks induced obesity and metabolic syndrome, and produced robust behavioural changes in young adult rats, whereas CAF withdrawal in the last week modestly increased anxiety, reversed the metabolic alterations and partially reduced overweight.

Drought tolerance and light requirements of high and low sublittoral species of Mediterranean macroalgae of the genus Cystoseira C. Agardh (Fucales, Phaeophyceae)

Article sobre la tolerància a la sequera i les necessitats de llum d'espècies de l'alt i baix sublitoral de macroalgues de la Mediterrània del gènere Cystoseira C. Agardh (Fucales, Phaeophyceae)

Soil carbon and nitrogen mineralization under different tillage systems and Permanent Groundcover cultivation between Orange trees

The objective of this work was to evaluate the alterations in carbon and nitrogen mineralization due to different soil tillage systems and groundcover species for intercropped orange trees. The experiment was established in an Ultisol soil (Typic Paleudults) originated from Caiuá sandstone in northwestern of the state of Paraná, Brazil, in an area previously cultivated with pasture (Brachiaria humidicola). Two soil tillage systems were evaluated: conventional tillage (CT) in the entire area and strip tillage (ST) with a 2-m width, each with different groundcover vegetation management systems. The citrus cultivar utilized was the 'Pera' orange (Citrus sinensis) grafted onto a 'Rangpur' lime rootstock. The soil samples were collected at a 0-15-cm depth after five years of experiment development. Samples were collected from under the tree canopy and from the inter-row space after the following treatments: (1) CT and annual cover crop with the leguminous Calopogonium mucunoides; (2) CT and perennial cover crop with the leguminous peanut Arachis pintoi; (3) CT and evergreen cover crop with Bahiagrass Paspalum notatum; (4) CT and cover crop with spontaneous B. humidicola grass vegetation; and (5) ST and maintenance of the remaining grass (pasture) of B. humidicola. The soil tillage systems and different groundcover vegetation influenced the C and N mineralization, both under the tree canopy and in the inter-row space. The cultivation of B. humidicola under strip tillage provided higher potential mineralization than the other treatments in the inter-row space. Strip tillage increased the C and N mineralization compared to conventional tillage. The grass cultivation increased the C and N mineralization when compared to the others treatments cultivated in the inter-row space.

Assessment of subjective and hemodynamic tolerance of different high- and low-flux dialysis membranes in patients undergoing chronic intermittent hemodialysis: a randomized controlled trial.

Clinical experience and experimental data suggest that intradialytic hemodynamic profiles could be influenced by the characteristics of the dialysis membranes. Even within the worldwide used polysulfone family, intolerance to specific membranes was occasionally evoked. The aim of this study was to compare hemodynamically some of the commonly used polysulfone dialyzers in Switzerland. We performed an open-label, randomized, cross-over trial, including 25 hemodialysis patients. Four polysulfone dialyzers, A (Revaclear high-flux, Gambro, Stockholm, Sweden), B (Helixone high-flux, Fresenius), C (Xevonta high-flux, BBraun, Melsungen, Germany), and D (Helixone low-flux, Fresenius, Bad Homburg vor der Höhe, Germany), were compared. The hemodynamic profile was assessed and patients were asked to provide tolerance feedback. The mean score (±SD) subjectively assigned to dialysis quality on a 1-10 scale was A 8.4 ± 1.3, B 8.6 ± 1.3, C 8.5 ± 1.6, D 8.5 ± 1.5. Kt/V was A 1.58 ± 0.30, B 1.67 ± 0.33, C 1.62 ± 0.32, D 1.45 ± 0.31. The low- compared with the high-flux membranes, correlated to higher systolic (128.1 ± 13.1 vs. 125.6 ± 12.1 mmHg, P < 0.01) and diastolic (76.8 ± 8.7 vs. 75.3 ± 9.0 mmHg; P < 0.05) pressures, higher peripheral resistance (1.44 ± 0.19 vs. 1.40 ± 0.18 s × mmHg/mL; P < 0.05) and lower cardiac output (3.76 ± 0.62 vs. 3.82 ± 0.59 L/min; P < 0.05). Hypotension events (decrease in systolic blood pressure by >20 mmHg) were 70 with A, 87 with B, 73 with C, and 75 with D (P < 0.01 B vs. A, 0.05 B vs. C and 0.07 B vs. D). The low-flux membrane correlated to higher blood pressure levels compared with the high-flux ones. The Helixone high-flux membrane ensured the best efficiency. Unfortunately, the very same dialyzer correlated to a higher incidence of hypotensive episodes.

High hepatic and extrahepatic mortality and low treatment uptake in HCV-coinfected persons in the Swiss HIV cohort study between 2001 and 2013.

BACKGROUND & AIMS: The landscape of HCV treatments is changing dramatically. At the beginning of this new era, we highlight the challenges for HCV therapy by assessing the long-term epidemiological trends in treatment uptake, efficacy and mortality among HIV/HCV-coinfected people since the availability of HCV therapy. METHODS: We included all SHCS participants with detectable HCV RNA between 2001 and 2013. To identify predictors for treatment uptake uni- and multivariable Poisson regression models were applied. We further used survival analyses with Kaplan-Meier curves and Cox regression with drop-out as competing risk. RESULTS: Of 12,401 participants 2107 (17%) were HCV RNA positive. Of those, 636 (30%) started treatment with an incidence of 5.8/100 person years (PY) (95% CI 5.3-6.2). Sustained virological response (SVR) with pegylated interferon/ribavirin was achieved in 50% of treated patients, representing 15% of all participants with replicating HCV-infection. 344 of 2107 (16%) HCV RNA positive persons died, 59% from extrahepatic causes. Mortality/100 PY was 2.9 (95% CI 2.6-3.2) in untreated patients, 1.3 (1.0-1.8) in those treated with failure, and 0.6 (0.4-1.0) in patients with SVR. In 2013, 869/2107 (41%) participants remained HCV RNA positive. CONCLUSIONS: Over the last 13years HCV treatment uptake was low and by the end of 2013, a large number of persons remain to be treated. Mortality was high, particularly in untreated patients, and mainly due to non-liver-related causes. Accordingly, in HIV/HCV-coinfected patients, integrative care including the diagnosis and therapy of somatic and psychiatric disorders is important to achieve mortality rates similar to HIV-monoinfected patients.

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures.

Transiliac bone biopsies, while widely considered to be the standard for the analysis of bone microstructure, are typically restricted to specialized centers. The benefit of Trabecular Bone Score (TBS) in addition to areal bone mineral density (aBMD) for fracture risk assessment has been documented in cross-sectional and prospective studies. The aim of this study was to test if TBS may be useful as a surrogate to histomorphometric trabecular parameters of transiliac bone biopsies. Transiliac bone biopsies from 80 female patients (median age 39.9years-interquartile range, IQR 34.7; 44.3) and 43 male patients (median age 42.7years-IQR 38.9; 49.0) with idiopathic osteoporosis and low traumatic fractures were included. Micro-computed tomography values of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structural model index (SMI) as well as serum bone turnover markers (BTMs) sclerostin, intact N-terminal type 1 procollagen propeptide (P1NP) and cross-linked C-telopeptide (CTX) were investigated. TBS values were higher in females (1.282 vs 1.169, p< 0.0001) with no differences in spine aBMD, whereas sclerostin levels (45.5 vs 33.4pmol/L) and aBMD values at the total hip (0.989 vs 0.971g/cm(2), p<0.001 for all) were higher in males. Multiple regression models including: gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R(2) values of 69.1% for SMI, 79.5% for Tb.N, 68.4% for Tb.Sp, and 83.3% for BV/TV. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for Tb.N. TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture and should be implemented as an additional tool for the determination of trabecular bone properties.

High rates of smoking especially in female Crohn's disease patients and low use of supportive measures to achieve smoking cessation : Data from the SwissIBD cohort study

BACKGROUND AND AIMS: Smoking is a crucial environmental factor in inflammatory bowel disease (IBD). However, knowledge on patient characteristics associated with smoking, time trends of smoking rates, gender differences and supportive measures to cease smoking provided by physicians is scarce. We aimed to address these questions in Swiss IBD patients. METHODS: Prospectively obtained data from patients participating in the Swiss IBD cohort study was analysed and compared to the general Swiss population (GSP) matched by age, sex and year. RESULTS: Among a total of 1770 IBD patients analysed (49.1% male), 29% are current smokers. More than twice as many patients with Crohn's disease (CD) are active smokers compared to ulcerative colitis (UC, 39.6% vs. 15.3%, p<0.001). In striking contrast to the GSP, significantly more women than men with CD smoke (42.8% vs. 35.8%, p=0.025), with also an overall significantly increased smoking rate compared to the GSP in women but not men. The vast majority of smoking IBD patients (90.5%) claim to never have received any support to achieve smoking cessation, significantly more in UC compared to CD. We identify a significantly negative association of smoking and primary sclerosing cholangitis, indicative of a protective effect. Psychological distress in CD is significantly higher in smokers compared to non-smokers, but does not differ in UC CONCLUSIONS: Despite well-established detrimental effects, smoking rates in CD are alarmingly high with persistent and stagnating elevations compared to the GSP, especially in female patients. Importantly, there appears to be an unacceptable underuse of supportive measures to achieve smoking cessation.

High mass microquasars and low latitude gamma-ray sources

Population studies of unidentified EGRET sources suggest that there exist at least three different populations of galactic gamma-ray sources. One of these populations is formed by young objects distributed along the galactic plane with a strong concentration toward the inner spiral arms of the Galaxy. Variability, spectral and correlation analysis indicate that this population is not homogeneous. In particular, there is a subgroup of sources that display clear variability in their gamma-ray fluxes on timescales from days to months. Following the proposal by Kaufman Bernad\'o et al. (2002), we suggest that this group of sources might be high-mass microquasars, i.e. accreting black holes or neutron stars with relativistic jets and early-type stellar companions. We present detailed inhomogeneous models for the gamma-ray emission of these systems that include both external and synchrotron self-Compton interactions. We have included effects of interactions between the jet and all external photon fields to which it is exposed: companion star, accretion disk, and hot corona. We make broadband calculations to predict the spectral energy distribution of these objects from radio up to GeV energies. The results and predictions can be tested by present and future gamma-ray instruments like INTEGRAL, AGILE, and GLAST.