Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Molecular Modeling and Simulation: Force Field Development, Evaporation Processes and Thermophysical Properties of Mixtures

To gain physical insight into the behavior of fluids on a microscopic level as well as to broaden the data base for thermophysical properties especially for mixtures, molecular modeling and simulation is utilized in this work. Various methods and applications are discussed, including a procedure for the development of new force field models. The evaporation of liquid nitrogen into a supercritical hydrogen atmosphere is presented as an example for large scale molecular dynamics simulation. System-size dependence and scaling behavior are discussed in the context of Kirkwood-Buff integration. Further, results for thermophysical mixture properties are presented, i.e. the Henry’s law constant of aqueous systems and diffusion coefficients of a ternary mixture

Non-aqueous electrolyte solutions in chemistry and modern technology

In this paper a brief survey is given of the properties of non-aqueous electrolyte solutions and their applications in chemistry and technology without going into the details of theory. Specific solvent-solute interactions and the role of the solvent beyond its function as a homogenous isotropic medium are stressed. Taking into account Parker's statement1) ldquoScientists nowadays are under increasing pressure to consider the relevance of their research, and rightly sordquo we have included examples showing the increasing industrial interest in non-aqueous electrolyte solutions. The concepts and results are arranged in two parts. Part A concerns the fundamentals of thermodynamics, transport processes, spectroscopy and chemical kinetics of non-aqueous solutions and some applications in these fields. Part B describes their use in various technologies such as high-energy batteries, non-emissive electro-optic displays, photoelectrochemical cells, electrodeposition, electrolytic capacitors, electro-organic synthesis, metallurgic processes and others. Four Appendices are added. Appendix A gives a survey on the most important non-aqueous solvents, their physical properties and correlation parameters, and the commonly used abbreviations. Appendices B and C show the mathematical background of the general chemical model. The Symbols and abbreviations of the text are listed and explained in Appendix D

Assay of GTP\u3b3S binding in autoradiography

Autoradiography of radiolabeled GTP\u3b3S ([35S]GTP\u3b3S) binding is a relevant method to study the function of G protein-coupled receptors (GPCRs), in tissue sections. Here, we describe the protocol for such a binding autoradiography, suitable to investigate the functionality of CB1receptor in tissue slices from rodent brain