Use of passive samplers to detect Organochlorine Pesticides in air and water at Wetland Mountain region sites (S-SE Brazil)

Low-density polyethylene (LDPE) passive samplers were deployed in upland surface waters and the overlying atmosphere during May and June 2012, to determine the transport and trends of freely dissolved and gaseous organochlorine pesticides (OCPs) along altitudinal gradients in mountain regions in south and southeast Brazil. Gaseous OCP concentrations were dominated by hexachlorobenzene (3.0 to 29 pg.m-3) and endosulfans (Ʃ= α-endosulfan + β-endosulfan + endosulfan sulphate, 170 to 260 pg.m-3), whereas freely dissolved endosulfans were significantly higher than all other OCPs (p \u3c 0.001). The presence of some target pesticides at the highest elevation sites indicated their efficient high-altitude transport from regional sources. Air-water exchange gradients indicated net deposition of most volatile and recently banned OCPs (e.g., HCB, endosulfan) over Brazilian mountains. Moreover, the exposure of these sites to large-scale continental airflows with varying source contributions may partly explain the atmospheric deposition of selected OCPs over upland freshwaters at tropical and subtropical mountains sites in Brazil. These findings, couple with LDPE passive air and water sampling measurements, point out the potential inputs from distant sources of semi-volatile chemicals to the two high-altitude sites

Calcium and phosphorus metabolism in peripartal dogs

Recommended allowances for calcium and phosphorus are mostly based on factorial calculations partly set at the level determined adequate for giant breeds (Nutrient requirements of dogs and cats. Washington, DC, USA: The National Academies Press. 2006). Information about appropriateness of supply with both minerals during the peripartal phase is limited. From other species is known that bone mineral stores are used in addition to oral intake of calcium and phosphorus in periods of higher needs such as gestation and lactation. The aim of this study was to determine parameters of calcium and phosphorus homeostasis in female dogs receiving the recommended amount of these minerals according to NRC (Nutrient requirements of dogs and cats. Washington, DC, USA: The National Academies Press. 2006) during the peripartal phase. In five Beagles and four Foxhound crossbreds, all primiparous with a litter size of 1–8 puppies, apparent digestibility of calcium and phosphorus as well as serum parameters of mineral metabolism (total and ionised calcium, phosphorus, parathyroid hormone, bone specific alkaline phosphatase, crosslaps) was determined in the period of 12–9 days before and 4–9 days after parturition. The apparent digestibility of calcium was relatively low and did not differ significantly between both peripartal phases, whereas the apparent digestibility of phosphorus increased during lactation. Serum concentrations of calcium (total as well as ionised), phosphorus and parathyroid hormone did not differ between gestation and lactation. The bone resorption marker serum crosslaps increased in lactating dogs but most individual values were within the reference range for adult female dogs at maintenance. On the other hand, the bone formation marker bone specific alkaline phosphatase decreased from prepartal to postpartal phase with values clearly above reference range in both phases. Based on the results especially of the bone markers, which stayed within the reference range during the peripartal phase without indicating predominant bone resorption, we hypothesise that the applied recommended daily allowances defined for peripartal dogs are appropriate

Response of the bacterial communities associated with maize rhizosphere to poultry litter as an organomineral fertilizer.

Maize is an important food source worldwide and is of considerable industrial importance. Low maize yields are mostly due to low soil fertility, so expensive mineral fertilizers are often used to offset the lack of nutrients. Poultry litter (PL) is one of the most valuable and phosphorous-rich animal wastes. However, PL usually contains veterinary antibiotic residues, particularly fluoroquinolones (FQs), which may alter soil microorganism diversity and resistance patterns. In this study, we aimed to understand the impact of applying mineral (triple superphosphate?STP) or organomineral (STP with PL and reactive Bayovar phosphate with PL) fertilizers (130 or 260 kg/ha of total P2O5) on the structure and composition of the soil bacteriome and on phosphate-mineralizing bacteria associated with the maize rhizosphere. Maize plants were sampled at 60 and 90 days after sowing and a clear rhizosphere effect was observed in all samples. No specific groups of bacterial genera predominated (>3% relative abundance) according to the different fertilizer treatments and most of the genera were shared among samples. Multivariate analyses of 16S rRNA sequences revealed clear clustering based on sampling time and distinct separation from bulk soil samples. Abundances of phosphate-mineralizing bacteria varied depending on the sampling time.We observed a positive effect on phytase activity under the 260 kg STP with PL treatment. Although the FQ enrofloxacin and its main metabolite ciprofloxacin were detected in PL, their concentrations in fertilized soils were below quantification thresholds. Quinolone resistance genes were not detected in the maize rhizosphere or bulk soil. Together, these results suggest that the rhizosphere effect, plant age and applied amounts of fertilizer are more influential on bacterial communities than the type of fertilizer used. Thus, application of PL as an organomineral fertilizer does not appear to have extensive impacts on the bacterial diversity of maize rhizosphere, so it could be an excellent option for enhancing maize production

HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, prevents ischemia-induced neuronal damage

Ischemic stroke is amongst the leading causes of death and disabilities. The available treatments are suitable for only a fraction of patients and thus novel therapies are urgently needed. Blockage of one of the cerebral arteries leads to massive and persisting inflammatory reaction contributing to the nearby neuronal damage. Targeting the detrimental pathways of neuroinflammation has been suggested to be beneficial in conditions of ischemic stroke. Nuclear receptor 4A-family (NR4A) member Nurr1 has been shown to be a potent modulator of harmful inflammatory reactions, yet the role of Nurr1 in cerebral stroke remains unknown. Here we show for the first time that an agonist for the dimeric transcription factor Nurr1/retinoid X receptor (RXR), HX600, reduces microglia expressed proinflammatory mediators and prevents inflammation induced neuronal death in in vitro co-culture model of neurons and microglia. Importantly, HX600 was protective in a mouse model of permanent middle cerebral artery occlusion and alleviated the stroke induced motor deficits. Along with the anti-inflammatory capacity of HX600 in vitro, treatment of ischemic mice with HX600 reduced ischemia induced Iba-1, p38 and TREM2 immunoreactivities, protected endogenous microglia from ischemia induced death and prevented leukocyte infiltration. These anti-inflammatory functions were associated with reduced levels of brain lysophosphatidylcholines (lysoPCs) and acylcarnitines, metabolites related to proinflammatory events. These data demonstrate that HX600 driven Nurr1 activation is beneficial in ischemic stroke and propose that targeting Nurr1 is a novel candidate for conditions involving neuroinflammatory component.Peer reviewe

Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis : effects of exercise training (CROSSYS). Exercise training intervention in monozygotic twins discordant for body weight

Background: Obesity and physical inactivity are major global public health concerns, both of which increase the risk of insulin resistance and type 2 diabetes. Regulation of glucose homeostasis involves cross-talk between the central nervous system, peripheral tissues, and gut microbiota, and is affected by genetics. Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS) aims to gain new systems-level understanding of the central metabolism in human body, and how exercise training affects this cross-talk. Methods: CROSSYS is an exercise training intervention, in which participants are monozygotic twins from pairs discordant for body mass index (BMI) and within a pair at least the other is overweight. Twins are recruited from three population-based longitudinal Finnish twin studies, including twins born in 1983-1987, 1975-1979, and 1945-1958. The participants undergo 6-month-long exercise intervention period, exercising four times a week (including endurance, strength, and high-intensity training). Before and after the exercise intervention, comprehensive measurements are performed in Turku PET Centre, Turku, Finland. The measurements include: two positron emission tomography studies (insulin-stimulated whole-body and tissue-specific glucose uptake and neuroinflammation), magnetic resonance imaging (brain morphology and function, quantification of body fat masses and organ volumes), magnetic resonance spectroscopy (quantification of fat within heart, pancreas, liver and tibialis anterior muscle), echocardiography, skeletal muscle and adipose tissue biopsies, a neuropsychological test battery as well as biosamples from blood, urine and stool. The participants also perform a maximal exercise capacity test and tests of muscular strength. Discussion: This study addresses the major public health problems related to modern lifestyle, obesity, and physical inactivity. An eminent strength of this project is the possibility to study monozygotic twin pairs that share the genome at the sequence level but are discordant for BMI that is a risk factor for metabolic impairments such as insulin resistance. Thus, this exercise training intervention elucidates the effects of obesity on metabolism and whether regular exercise training is able to reverse obesity-related impairments in metabolism in the absence of the confounding effects of genetic factors.Peer reviewe

Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design

OBJECTIVETo assess whether use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy is associated with an increased risk of birth defects, with emphasis on cardiovascular birth defects even when accounting for lifestyle or other familial confounding.DESIGNMulticountry population based cohort study, including sibling controlled design.SETTINGNordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers at different periods in 1996-2010.POPULATIONThe full study cohort included women giving birth to 2.3 million live singletons. The sibling cohort included 2288 singleton live births. The sibling controlled analyses included sibling pairs who were discordant for exposure to SSRIs or venlafaxine and birth defects.MAIN OUTCOME MEASUREPrevalence of birth defects, including subtypes of cardiac defects. Odds ratio of birth defects from logistic and conditional logistic regression.RESULTSAmong 36 772 infants exposed to any SSRI in early pregnancy, 3.7% (n=1357) had a birth defect compared with 3.1% of 2 266 875 unexposed infants, yielding a covariate adjusted odds ratio of 1.13 (95% confidence interval 1.06 to 1.20). In the sibling controlled analysis the adjusted odds ratio decreased to 1.06 (0.91 to 1.24). The odds ratios for any cardiac birth defect with use of any SSRI or venlafaxine were 1.15 (95% confidence interval 1.05 to 1.26) in the covariate adjusted analysis and 0.92 (0.72 to 1.17) in the sibling controlled analysis. For atrial and ventricular septal defects the covariate adjusted odds ratio was 1.17 (1.05 to 1.31). Exposure to any SSRI or venlafaxine increased the prevalence of right ventricular outflow tract obstruction defects, with a covariate adjusted odds ratio of 1.48 (1.15 to 1.89). In the sibling controlled analysis the adjusted odds ratio decreased to 0.56 (0.21 to 1.49) for any exposure to SSRIs or venlafaxine and right ventricular outflow tract obstruction defects.CONCLUSIONSIn this large Nordic study no substantial increase was found in prevalence of overall cardiac birth defects among infants exposed to SSRIs or venlafaxine in utero. Although the prevalence of septal defects and right ventricular outflow tract defects was higher in exposed infants, the lack of an association in the sibling controlled analyses points against a teratogenic effect of these drugs.</p

MRI assessment of the effects of acetazolamide and external lumbar drainage in idiopathic Normal Pressure Hydrocephalus

BACKGROUND: The objective was to identify changes in quantitative MRI measures in patients with idiopathic normal pressure hydrocephalus (iNPH) occurring in common after oral acetazolamide (ACZ) and external lumbar drainage (ELD) interventions. METHODS: A total of 25 iNPH patients from two clinical sites underwent serial MRIs and clinical assessments. Eight received ACZ (125-375 mg/day) over 3 months and 12 underwent ELD for up to 72 hours. Five clinically-stable iNPH patients who were scanned serially without interventions served as controls for the MRI component of the study. Subjects were divided into responders and non-responders to the intervention based on gait and cognition assessments made by clinicians blinded to MRI results. The MRI modalities analyzed included T1-weighted images, diffusion tensor Imaging (DTI) and arterial spin labelling (ASL) perfusion studies. Automated threshold techniques were used to define regions of T1 hypo-intensities. RESULTS: Decreased volume of T1-hypointensities and decreased mean diffusivity (MD) within remaining hypointensities was observed after ACZ and ELD but not in controls. Patients responding positively to these interventions had more extensive decreases in T1-hypointensites than non-responders: ACZ-responders (4,651 ± 2,909 mm(3)), ELD responders (2,338 ± 1,140 mm(3)), ELD non-responders (44 ± 1,188 mm(3)). Changes in DTI MD within T1-hypointensities were greater in ACZ-responders (7.9% ± 2%) and ELD-responders (8.2% ± 3.1%) compared to ELD non-responders (2.1% ± 3%). All the acetazolamide-responders showed increases in whole-brain-average cerebral blood flow (wbCBF) estimated by ASL (18.8% ± 8.7%). The only observed decrease in wbCBF (9.6%) occurred in an acetazolamide-non-responder. A possible association between cerebral atrophy and response was observed, with subjects having the least cortical atrophy (as indicated by a positive z-score on cortical thickness measurements) showing greater clinical improvement after ACZ and ELD. CONCLUSIONS: T1-hypointensity volume and DTI MD measures decreased in the brains of iNPH patients following oral ACZ and ELD. The magnitude of the decrease was greater in treatment responders than non-responders. Despite having different mechanisms of action, both ELD and ACZ may decrease interstitial brain water and increase cerebral blood flow in patients with iNPH. Quantitative MRI measurements appear useful for objectively monitoring response to acetazolamide, ELD and potentially other therapeutic interventions in patients with iNPH