Use of ex vivo and in vitro cultures of the human respiratory tract to study the tropism and host responses of highly pathogenic avian influenza A (H5N1) and other influenza viruses

The tropism of influenza viruses for the human respiratory tract is a key determinant of host-range, and consequently, of pathogenesis and transmission. Insights can be obtained from clinical and autopsy studies of human disease and relevant animal models. Ex vivo cultures of the human respiratory tract and in vitro cultures of primary human cells can provide complementary information provided they are physiologically comparable in relevant characteristics to human tissues in vivo, e.g. virus receptor distribution, state of differentiation. We review different experimental models for their physiological relevance and summarize available data using these cultures in relation to highly pathogenic avian influenza H5N1, in comparison where relevant, with other influenza viruses. Transformed continuous cell-lines often differ in important ways to the corresponding tissues in vivo.     

High-Dose Omega-3 Fatty Acids in Cardiovascular Prevention: Finally Living Up to Their Potential?

American Journal of Cardiovascular Drugs - Despite the widespread use of statins in the setting of high cardiovascular risk, many patients continue to experience clinical events. This highlights...     

Balance and Strength—Estimating the Maximum Prey‐Lifting Potential of the Large Predatory Dinosaur Carcharodontosaurus saharicus

Motivated by the work of palaeo‐art “Double Death (2011),” a biomechanical analysis using three‐dimensional digital models was conducted to assess the potential of a pair of the large, Late Cretaceous theropod dinosaur Carcharodontosaurus saharicus to successfully lift a medium‐sized sauropod and not lose balance. Limaysaurus tessonei from the Late Cretaceous of South America was chosen as the sauropod as it is more completely known, but closely related to the rebbachisaurid sauropods found in the same deposits with C. saharicus. The body models incorporate the details of the low‐density regions associated with lungs, systems of air sacs, and pneumatized axial skeletal regions. These details, along with the surface meshes of the models, were used to estimate the body masses and centers of mass of the two animals. It was found that a 6 t C. saharicus could successfully lift a mass of 2.5 t and not lose balance as the combined center of mass of the body and the load in the jaws would still be over the feet. However, the neck muscles were found to only be capable of producing enough force to hold up the head with an added mass of 424 kg held at the midpoint of the maxillary tooth row. The jaw adductor muscles were more powerful, and could have held a load of 512 kg. The more limiting neck constraint leads to the conclusion that two, adult C. saharicus could successfully lift a L. tessonei with a maximum body mass of 850 kg and a body length of 8.3 m. Anat Rec, 298:1367–1375, 2015. © 2015 Wiley Periodicals, Inc.     

ApoA-I Induction as a Potential Cardioprotective Strategy: Rationale for the SUSTAIN and ASSURE Studies

Background  

Considerable interest has focused on the development of therapies that target the functionality of high-density lipoproteins (HDL). Upregulation of endogenous synthesis of the major protein on HDL particles, apolipoprotein A-I (apoA-I), represents a novel approach to generation of new HDL particles. The Study of Quantitative Serial Trends in Lipids with Apolipoprotein A-I Stimulation (SUSTAIN, NCT01423188) study aims to evaluate the lipid efficacy, safety and tolerability of an apoA-I inducer (RVX-208). The ApoA-I Synthesis Stimulation and Intravascular Ultrasound for Coronary Atheroma Regression Evaluation (ASSURE, NCT01067820) study aims to evaluate the effect of RVX-208 on plaque burden.     

Nutritional intake and oxidative stress in chronic heart failure

Background and aimsPatients with chronic heart failure (CHF) are known to be at risk of malnutrition, and cardiac cachexia is an adverse prognostic indicator. The aim of this study was to determine the dietary adequacy of CHF patients compared with Dietary Reference Values, to compare the nutritional intake and status of CHF patients to a healthy comparison group, and finally to determine whether nutritional intake and status depended on New York Heart Association (NYHA) functional class.Methods and ResultsPatients with CHF (n = 39) and a comparison group of 27 healthy participants, who did not have CHF, were asked to complete a four-day food diary, and energy and nutrient intakes were calculated. F_2α-isoprostanes were measured in urine as an indicator of oxidative stress and antioxidants were measured in serum or plasma. Overall 73% of the CHF patients were consuming less than recommended energy intakes, and more than 50% of these patients were also consuming less than recommended vitamin D, selenium and zinc intakes. Nutrient intake (energy, vitamin B6, D, E, iron, folate and riboflavin) was lower in CHF patients than in the comparison group, with vitamin B6 and folate intake and antioxidant status decreasing, and isoprostane status increasing as NYHA functional class increased.ConclusionThe majority of CHF patients do not meet dietary reference values for energy and a range of nutrients, and nutrient intake is lower in CHF patients than in healthy individuals. Dietary inadequacy tends to be increased in those with more severe disease.