654 research outputs found

    Rate of Decline of the Oriental White-Backed Vulture Population in India Estimated from a Survey of Diclofenac Residues in Carcasses of Ungulates

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    The non-steroidal anti-inflammatory drug diclofenac is a major cause of the rapid declines in the Indian subcontinent of three species of vultures endemic to South Asia. The drug causes kidney failure and death in vultures. Exposure probably arises through vultures feeding on carcasses of domesticated ungulates treated with the drug. However, before the study reported here, it had not been established from field surveys of ungulate carcasses that a sufficient proportion was contaminated to cause the observed declines. We surveyed diclofenac concentrations in samples of liver from carcasses of domesticated ungulates in India in 2004–2005. We estimated the concentration of diclofenac in tissues available to vultures, relative to that in liver, and the proportion of vultures killed after feeding on a carcass with a known level of contamination. We assessed the impact of this mortality on vulture population trend with a population model. We expected levels of diclofenac found in ungulate carcasses in 2004–2005 to cause oriental white-backed vulture population declines of 80–99% per year, depending upon the assumptions used in the model. This compares with an observed rate of decline, from road transect counts, of 48% per year in 2000–2003. The precision of the estimate based upon carcass surveys is low and the two types of estimate were not significantly different. Our analyses indicate that the level of diclofenac contamination found in carcasses of domesticated ungulates in 2004–2005 was sufficient to account for the observed rapid decline of the oriental white-backed vulture in India. The methods we describe could be used again to assess changes in the effect on vulture population trend of diclofenac and similar drugs. In this way, the effectiveness of the recent ban in India on the manufacture and importation of diclofenac for veterinary use could be monitored

    An Eight-Week Trial Investigating the Efficacy and Tolerability of Atorvastatin for Children and Adolescents With Heterozygous Familial Hypercholesterolemia

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    This study aimed to assess the efficacy and tolerability of atorvastatin in Tanner stage (TS) 1 patients ages 6 to 10 years and TS ≥2 patients ages 10 to <18 years with genetically confirmed heterozygous familial hypercholesterolemia (HeFH) and a low density lipoprotein cholesterol (LDL-C) level of 4 mmol/l (155 mg/dl) or higher. In this open-label, 8-week study, 15 TS 1 children were treated initially with atorvastatin 5 mg/day and 24 TS ≥2 children with 10 mg/day. Doses were doubled at week 4 if the LDL-C target (<3.35 mmol/l [130 mg/dl]) was not achieved. The efficacy variables were the percentage change from baseline in LDL-C, total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), and apolipoprotein (Apo) A-I and Apo B. Safety evaluations included clinical monitoring, subject-reported adverse events (AEs), vital signs, and clinical laboratory tests. The mean values for LDL-C, TC, VLDL-C, and Apo B decreased by week 2 among all TS 1 and TS ≥2 patients, whereas TG, HDL-C, and Apo A-I varied considerably from week to week. After 8 weeks, the mean reduction in LDL-C was −40.7% ± 8.4 for the TS 1 children and −39.7% ± 10.3 for the TS ≥2 children. For the TS 1 patients, the mean reductions were −34.1% ± 6.9 for TC and −6.0% ± 32.1 for TG. The corresponding changes for the TS ≥2 patients were −35.6% ± 9.5 for TC and −21.1% ± 29.7 for TG. Four patients experienced mild to moderate treatment-related AEs. No serious AEs or discontinuations were reported. Overall, no difference in safety or tolerability was observed between the younger and older cohorts. Across the range of exposures after atorvastatin 5 to 10 mg (TS 1) or atorvastatin 10 to 20 mg (TS ≥2) doses for 8 weeks, clinically meaningful reductions in LDL-C, TC, VLDL-C, and Apo were observed with atorvastatin in pediatric patients who had HeFH. Atorvastatin also was well tolerated in this population

    Lignin biomarkers as tracers of mercury sources in lakes water column

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    This study presents the role of specific terrigenous organic compounds as important vectors of mercury (Hg) transported from watersheds to lakes of the Canadian boreal forest. In order to differentiate the autochthonous from the allochthonous organic matter (OM), lignin derived biomarker signatures [Lambda, S/V, C/V, P/(V ? S), 3,5-Bd/V and (Ad/Al)v] were used. Since lignin is exclusively produced by terrigenous plants, this approach can give a non equivocal picture of the watershed inputs to the lakes. Moreover, it allows a characterization of the source of OM and its state of degradation. The water column of six lakes from the Canadian Shield was sampled monthly between June and September 2005. Lake total dissolved Hg concentrations and Lambda were positively correlated, meaning that Hg and ligneous inputs are linked (dissolved OM r2 = 0.62, p\0.0001; particulate OM r2 = 0.76, p\0.0001). Ratios of P/(V ? S) and 3,5-Bd/V from both dissolved OM and particulate OM of the water column suggest an inverse relationship between the progressive state of pedogenesis and maturation of the OM in soil before entering the lake, and the Hg concentrations in the water column. No relation was found between Hg levels in the lakes and the watershed flora composition—angiosperm versus gymnosperm or woody versus non-woody compounds. This study has significant implications for watershed management of ecosystems since limiting fresh terrestrial OM inputs should reduce Hg inputs to the aquatic systems. This is particularly the case for largescale land-use impacts, such as deforestation, agriculture and urbanization, associated to large quantities of soil OM being transferred to aquatic systems

    Increased Membrane Cholesterol in Lymphocytes Diverts T-Cells toward an Inflammatory Response

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    Cell signaling for T-cell growth, differentiation, and apoptosis is initiated in the cholesterol-rich microdomains of the plasma membrane known as lipid rafts. Herein, we investigated whether enrichment of membrane cholesterol in lipid rafts affects antigen-specific CD4 T-helper cell functions. Enrichment of membrane cholesterol by 40–50% following squalene administration in mice was paralleled by an increased number of resting CD4 T helper cells in periphery. We also observed sensitization of the Th1 differentiation machinery through co-localization of IL-2Rα, IL-4Rα, and IL-12Rβ2 subunits with GM1 positive lipid rafts, and increased STAT-4 and STAT-5 phosphorylation following membrane cholesterol enrichment. Antigen stimulation or CD3/CD28 polyclonal stimulation of membrane cholesterol-enriched, resting CD4 T-cells followed a path of Th1 differentiation, which was more vigorous in the presence of increased IL-12 secretion by APCs enriched in membrane cholesterol. Enrichment of membrane cholesterol in antigen-specific, autoimmune Th1 cells fostered their organ-specific reactivity, as confirmed in an autoimmune mouse model for diabetes. However, membrane cholesterol enrichment in CD4+ Foxp3+ T-reg cells did not alter their suppressogenic function. These findings revealed a differential regulatory effect of membrane cholesterol on the function of CD4 T-cell subsets. This first suggests that membrane cholesterol could be a new therapeutic target to modulate the immune functions, and second that increased membrane cholesterol in various physiopathological conditions may bias the immune system toward an inflammatory Th1 type response

    Energy expenditure, intake and availability in female soccer players via doubly labelled water: Are we misrepresenting low energy availability?

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    Female soccer players have been identified as presenting with low energy availability (LEA), though the prevalence of LEA may be overestimated given inaccuracies associated with self-reporting dietary intakes. Accordingly, we aimed to quantify total daily energy expenditure (TDEE) via the doubly labelled water (DLW) method, energy intake (EI) and energy availability (EA). Adolescent female soccer players (n = 45; 16 ± 1 years) completed a 9–10 day ‘training camp’ representing their national team. Absolute and relative TDEE was 2683 ± 324 and 60 ± 7 kcal kg−1 fat free mass (FFM), respectively. Mean daily EI was lower (P < 0.01) when players self-reported using the remote food photography method (RFPM) (2047 ± 383 kcal day−1) over a 3-day period versus DLW derived EI estimates accounting for body mass (BM) changes (2545 ± 518 kcal day−1) over 7–8 days, representing a mean daily Δ of 499 ± 526 kcal day−1 and 22% error when using the RFPM. Estimated EA was different (P < 0.01) between methods (DLW: 48 ± 14 kcal kg−1 FFM, range: 22–82; RFPM: 37 ± 8 kcal kg−1 FFM, range: 22–54), such that prevalence of LEA (<30 kcal kg−1 FFM) was lower in DLW compared with RFPM (5% vs. 15%, respectively). Data demonstrate the potential to significantly underestimate EI when using self-report methods. This approach can therefore cause a misrepresentation and an over-prevalence of LEA, which is the underlying aetiology of ‘relative energy deficiency in sport’ (REDs)

    The emotional movie database (EMDB): a self-report and psychophysiological study

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    Film clips are an important tool for evoking emotional responses in the laboratory. When compared with other emotionally potent visual stimuli (e.g., pictures), film clips seem to be more effective in eliciting emotions for longer periods of time at both the subjective and physiological levels. The main objective of the present study was to develop a new database of affective film clips without auditory content, based on a dimensional approach to emotional stimuli (valence, arousal and dominance). The study had three different phases: (1) the pre-selection and editing of 52 film clips (2) the self-report rating of these film clips by a sample of 113 participants and (3) psychophysiological assessment [skin conductance level (SCL) and the heart rate (HR)] on 32 volunteers. Film clips from different categories were selected to elicit emotional states from different quadrants of affective space. The results also showed that sustained exposure to the affective film clips resulted in a pattern of a SCL increase and HR deceleration in high arousal conditions (i.e., horror and erotic conditions). The resulting emotional movie database can reliably be used in research requiring the presentation of non-auditory film clips with different ratings of valence, arousal and dominance.Portuguese Foundation for Science and Technology with individual grants (SFRH/BD/41484/2007 and SFRH/BD/64355/2009

    A novel mutation (Cys308Phe) of the LDL receptor gene in families from the South-Eastern part of Poland

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    The purpose of this investigation was to characterize a new mutation in the LDL-receptor (LDLR) gene in three families with clinically diagnosed familial hypercholesterolemia (FH) from the South-Eastern part of Poland. Mutational screening with exon by exon sequencing analysis was performed in all probands. The novel mutation c986G>T (Cys308Phe) in the exon 7 of LDLR gene was found in three apparently unrelated probands with FH. Analysis of the receptor activity of peripheral blood lymphocytes by binding and uptake of DiL-LDL showed a significant reduction (by 24% versus healthy control) of the fluorescent label in the lymphocytes of patients heterozygous for this mutation. Concentrations of serum LDL-C in probands before treatment were between 9.5 and 10.5 mmol/l. All patients had corneal arcus and tendon xanthoma. Clinically, families were characterized by premature coronary artery disease. This mutation occurred relatively frequently in our group of patients with FH, but this could be explained by a founder effect since we demonstrated their common ancestors
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