Apparent Tolerance Of Turkey Vultures (\u3ci\u3eCathartes Aura\u3c/i\u3e) To The Non-Steroidal Anti-Inflammatory Drug Diclofenac

The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose ~0.1–0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted

Apparent Tolerance Of Turkey Vultures (\u3ci\u3eCathartes Aura\u3c/i\u3e) To The Non-Steroidal Anti-Inflammatory Drug Diclofenac

The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose ~0.1–0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted

HIV-Related Sexual Risk among African American Men Preceding Incarceration: Associations with Support from Significant Others, Family, and Friends

We evaluated the association between social support received from significant others, family, and friends and HIV-related sexual risk behaviors among African American men involved in the criminal justice system. Project DISRUPT is a cohort study among African American men released from prison in North Carolina (N = 189). During the baseline (in-prison) survey, we assessed the amount of support men perceived they had received from significant others, family, and friends. We measured associations between low support from each source (<median value) and participants' sex risk in the 6 months before incarceration. Low levels of social support from significant others, family, or friends were associated with poverty and homelessness, mental disorders, and substance use. Adjusting for age, poverty, and other sources of support, perceiving low support from significant others was strongly associated with multiple partnerships (fully adjusted odds ratio (OR) 2.64, 95% confidence interval (CI) 1.29-5.42). Low significant other support also was strongly associated with sex trade involvement when adjusting for age and poverty status (adjusted OR 3.51, 95% CI 1.25-9.85) but further adjustment for low family and friend support weakened the association (fully adjusted OR 2.81, 95% CI 0.92-8.55). Significant other support was not associated with other sex risk outcomes including concurrent partnerships, anal sex, or sex with an STI/HIV-infected partner. Low family support was associated with multiple partnerships in analyses adjusting for age and poverty (adjusted OR 1.98, 95% CI 1.05-3.76) but the association weakened and was no longer significant after adjusting for other sources of support (fully adjusted OR 1.40, 95% CI 0.65-3.00); family support was not correlated with other risk behaviors. Friend support was not significantly associated with sex risk outcomes. Indicators of overall support from any source were not associated with sex risk outcomes. Helping inmates maintain ties may improve economic security and well-being during community re-entry, while supporting and strengthening relationships with a significant other in particular may help reduce sex risk. Studies should evaluate the protective effects of distinct support sources to avoid masking effects of support and to best understand the influence of social support on health

MICL controls inflammation in rheumatoid arthritis

Acknowledgments We thank G Milne, D MacCallum, S Hardison, G Wilson, C Wallace, S Hadebe and A Richmond for assistance; H. El-Gabalawy for tissues and the animal facility staff for the care of our animals. Flow cytometry was undertaken in the Iain Fraser Cytometry Centre, University of Aberdeen. Funding: GDB was funded by the Wellcome Trust and MRC (UK). AA and CDB are supported by the Arthritis Research UK Tissue Engineering Centre (grant 19429). This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk, and was funded by the Wellcome Trust (076113). MJGF was funded by The Arthritis Society and the Canadian Arthritis Network and J-ML by a scholarship from the Canadian Arthritis Network.Peer reviewedPublisher PD

Land Use Change to Reduce Freshwater Nitrogen and Phosphorus will Be Effective Even with Projected Climate Change

Recent studies have demonstrated that projected climate change will likely enhance nitrogen (N) and phosphorus (P) loss from farms and farmland, with the potential to worsen freshwater eutrophication. Here, we investigate the relative importance of the climate and land use drivers of nutrient loss in nine study catchments in Europe and a neighboring country (Turkey), ranging in area from 50 to 12,000 km2. The aim was to quantify whether planned large-scale, land use change aimed at N and P loss reduction would be effective given projected climate change. To this end, catchment-scale biophysical models were applied within a common framework to quantify the integrated effects of projected changes in climate, land use (including wastewater inputs), N deposition, and water use on river and lake water quantity and quality for the mid-21st century. The proposed land use changes were derived from catchment stakeholder workshops, and the assessment quantified changes in mean annual N and P concentrations and loads. At most of the sites, the projected effects of climate change alone on nutrient concentrations and loads were small, whilst land use changes had a larger effect and were of sufficient magnitude that, overall, a move to more environmentally focused farming achieved a reduction in N and P concentrations and loads despite projected climate change. However, at Beyşehir lake in Turkey, increased temperatures and lower precipitation reduced water flows considerably, making climate change, rather than more intensive nutrient usage, the greatest threat to the freshwater ecosystem. Individual site responses did however vary and were dependent on the balance of diffuse and point source inputs. Simulated lake chlorophyll-a changes were not generally proportional to changes in nutrient loading. Further work is required to accurately simulate the flow and water quality extremes and determine how reductions in freshwater N and P translate into an aquatic ecosystem response

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P &lt; 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P &lt; 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Isoform-selective induction of human p110δ PI3K expression by TNFα: identification of a new and inducible PIK3CD promoter

PI3Ks (phosphoinositide 3-kinases) are signalling molecules and drug targets with important biological functions, yet the regulation of PI3K gene expression is poorly understood. Key PI3Ks are the class IA PI3Ks that consist of a catalytic subunit (p110α, p110β and p110δ) in complex with a p85 regulatory subunit. Whereas p110α and p110β are ubiquitously expressed, high levels of p110δ are mainly found in white blood cells, with most non-leucocytes expressing low levels of p110δ. In the present paper we report that TNFα (tumour necrosis factor α) stimulation induces p110δ expression in human ECs (endothelial cells) and synovial fibroblasts, but not in leucocytes, through transcription start sites located in a novel promoter region in the p110δ gene (PIK3CD). This promoter is used in all cell types, including solid tumour cell lines that express p110δ, and is activated by TNFα in ECs and synovial fibroblasts. We further present a detailed biochemical and bioinformatic characterization of p110δ gene regulation, demonstrating that PIK3CD has distinct promoters, some of which can be dynamically activated by pro-inflammatory mediators. This is the first molecular identification of a PI3K promoter under the control of acute extracellular stimulation

Quantum numbers of the X(3872)X(3872) state and orbital angular momentum in its ρ0Jψ\rho^0 J\psi decay

Angular correlations in $B^+\to X(3872) K^+$ decays, with $X(3872)\to \rho^0 J/\psi$, $\rho^0\to\pi^+\pi^-$ and $J/\psi \to\mu^+\mu^-$, are used to measure orbital angular momentum contributions and to determine the $J^{PC}$ value of the $X(3872)$ meson. The data correspond to an integrated luminosity of 3.0 fb$^{-1}$ of proton-proton collisions collected with the LHCb detector. This determination, for the first time performed without assuming a value for the orbital angular momentum, confirms the quantum numbers to be $J^{PC}=1^{++}$. The $X(3872)$ is found to decay predominantly through S wave and an upper limit of $4\%$ at $95\%$ C.L. is set on the fraction of D wave.Comment: 16 pages, 4 figure