Elevated bile acids are associated with left ventricular structural changes in biliary atresia.

BACKGROUND: In children with biliary atresia (BA), pathologic structural changes within the heart, which define cirrhotic cardiomyopathy, are associated with adverse perioperative outcomes. Despite their clinical relevance, little is known about the pathogenesis and triggers of pathologic remodeling. Bile acid excess causes cardiomyopathy in experimental cirrhosis, but its role in BA is poorly understood. METHODS: Echocardiographic parameters of left ventricular (LV) geometry [LV mass (LVM), LVM indexed to height, left atrial volume indexed to BSA (LAVI), and LV internal diameter (LVID)] were correlated with circulating serum bile acid concentrations in 40 children (52% female) with BA listed for transplantation. A receiver-operating characteristic curve was generated to determine optimal threshold values of bile acids to detect pathologic changes in LV geometry using Youden index. Paraffin-embedded human heart tissue was separately analyzed by immunohistochemistry for the presence of bile acid-sensing Takeda G-protein-coupled membrane receptor type 5. RESULTS: In the cohort, 52% (21/40) of children had abnormal LV geometry; the optimal bile acid concentration to detect this abnormality with 70% sensitivity and 64% specificity was 152 µmol/L (C-statistics=0.68). Children with bile acid concentrations >152 µmol/L had ∼8-fold increased odds of detecting abnormalities in LVM, LVM index, left atrial volume index, and LV internal diameter. Serum bile acids positively correlated with LVM, LVM index, and LV internal diameter. Separately, Takeda G-protein-coupled membrane receptor type 5 protein was detected in myocardial vasculature and cardiomyocytes on immunohistochemistry. CONCLUSION: This association highlights the unique role of bile acids as one of the targetable potential triggers for myocardial structural changes in BA.

Improving culture of care through maximising learning from observations and events: Addressing what is at fault.

The term 'culture of care' in the context of using animals for scientific purpose describes the culture in organisations that provides support to staff to strive for continuous improvement in:• animal care and welfare;• support and recognition of staff involved in the animal care and use programme;• scientific quality;• openness and transparency.We developed a systematic process for reporting observations and events that have the potential to help with continuous learning, improving animal welfare and supporting staff. The process took learning from the safety, health and environment arena on accident prevention. The two key aspects were (a) the systematic logging of observations and events; and (b) the learning approach to following up on observations. Underpinning our systematic process is the 'Learning from Observations and Events Log'. Reported observations and events can relate to positive practices, general observations as well as near misses.We created an environment to promote continuous improvement for both animals and staff by recognising, rewarding and sharing good practice, as well as where near misses are openly reported and learnt from. Supporting animal welfare, staff welfare, improving scientific quality and transparency are the four key pillars of a positive culture of care.We recognised early on that using a system and learning approach to follow up on observations and events rather than a people and blame approach was key to developing open reporting and a positive culture. In the systems approach, errors are consequences rather than causes, having their origins in systemic factors.

Single-pot extraction-analysis of dyed wool fibers with ionic liquids.

Analytical capabilities to identify dyes associated with structurally robust wool fibers would critically assist crime-scene and explosion-scene forensics. Nondestructive separation of dyes from wool, removal of contaminants, and dye analysis by MALDI- or ESI-MS, were achieved in a single-pot, ionic liquid-based method. Ionic liquids (ILs) that readily denature the wool α-keratin structure have been identified and are conducive to small volume, high-throughput analysis for accelerated threat-response times. Wool dyed with commercial or natural, plant-based dyes have unique signatures that allow classification and matching of samples and identification of dyestuffs. Wool released 0.005 mg of dye per mg of dyed wool into the IL, allowing for analysis of single-thread sample sizes. The IL + dye mixture promotes sufficient ionization in MALDI-MS: addition of common MALDI matrices does not improve analysis of anionic wool dyes. An inexpensive, commercially available tetrabutylphosponium chloride IL was discovered to be capable of denaturing wool and was determined to be the most effective for this readily fieldable method.

Structure and magnetic behavior of transition metal based ionic liquids.

A series of ionic liquids containing different paramagnetic anions have been prepared and all show paramagnetic behavior with potential applications for magnetic and electrochromic switching as well as novel magnetic transport; also, the tetraalkylphosphonium-based ionic liquids reveal anomalous magnetic behavior.

Combustible ionic liquids by design: is laboratory safety another ionic liquid myth?

The non-flammability of ionic liquids (ILs) is often highlighted as a safety advantage of ILs over volatile organic compounds (VOCs), but the fact that many ILs are not flammable themselves does not mean that they are safe to use near fire and/or heat sources; a large group of ILs (including commercially available ILs) are combustible due to the nature of their positive heats of formation, oxygen content, and decomposition products.

13C NMR relaxation rates in the ionic liquid 1-ethyl-3-methylimidazolium butanesulfonate.

A new method of obtaining molecular reorientational dynamics from 13C spin-lattice relaxation data of aromatic carbons in viscous solutions is applied to 13C relaxation data of both the cation and anion in the ionic liquid, 1-ethyl-3-methylimidazolium butanesulfonate ([EMIM]BSO3). 13C pseudorotational correlation times are used to calculate corrected maximum NOE factors from a combined isotropic dipolar and nuclear Overhauser effect (NOE) equation. These corrected maximum NOE factors are then used to determine the dipolar relaxation rate part of the total relaxation rate for each aromatic 13C nucleus in the imidazolium ring. Rotational correlation times are compared with viscosity data and indicate several [EMIM]BSO3 phase changes over the temperature range from 278 to 328 K. Modifications of the Stokes-Einstein-Debye (SED) model are used to determine molecular radii for the 1-ethyl-3-methylimidazolium cation. The Hu-Zwanzig correction yields a cationic radius that compares favorably with a DFT gas-phase calculation, B3LYP/(6-311+G(2d,p)). Chemical shift anisotropy values, Deltasigma, are obtained for the ring and immediately adjacent methylene and methyl carbons in the imidazolium cation and for the three carbon atoms nearest to the sulfonate group in the anion.

Development of MEDLINE in Brazil

Meeting of the Advisory Committee on Medical Research, 15. Pan American Health Organization; Jun. 13-17, 1976

Strengthening of the Brazilian biomedical information network

Meeting of the Advisory Committe on Medical Research, 13. Pan American Health Organization; 24-28 Jun. 1974