Computational hemodynamic optimization predicts dominant aortic arch selection is driven by embryonic outflow tract orientation in the chick embryo

In the early embryo, a series of symmetric, paired vessels, the aortic arches, surround the foregut and distribute cardiac output to the growing embryo and fetus. During embryonic development, the arch vessels undergo large-scale asymmetric morphogenesis to form species-specific adult great vessel patterns. These transformations occur within a dynamic biomechanical environment, which can play an important role in the development of normal arch configurations or the aberrant arch morphologies associated with congenital cardiac defects. Arrested migration and rotation of the embryonic outflow tract during late stages of cardiac looping has been shown to produce both outflow tract and several arch abnormalities. Here, we investigate how changes in flow distribution due to a perturbation in the angular orientation of the embryonic outflow tract impact the morphogenesis and growth of the aortic arches. Using a combination of in vivo arch morphometry with fluorescent dye injection and hemodynamics-driven bioengineering optimization-based vascular growth modeling, we demonstrate that outflow tract orientation significantly changes during development and that the associated changes in hemodynamic load can dramatically influence downstream aortic arch patterning. Optimization reveals that balancing energy expenditure with diffusive capacity leads to multiple arch vessel patterns as seen in the embryo, while minimizing energy alone led to the single arch configuration seen in the mature arch of aorta. Our model further shows the critical importance of the orientation of the outflow tract in dictating morphogenesis to the adult single arch and accurately predicts arch IV as the dominant mature arch of aorta. These results support the hypothesis that abnormal positioning of the outflow tract during early cardiac morphogenesis may lead to congenital defects of the great vessels due to altered hemodynamic loading.     

Cranial morphology of the Early Permian mesosaurid Mesosaurus tenuidens and the evolution of the lower temporal fenestration reassessed

The Early Permian mesosaurids are the oldest known aquatic amniotes with an exclusively Gondwanan distribution. Although several hundred of complete skeletons have been discovered and intensively studied, the anatomy and taxonomic composition of the group, as well as its phylogenetic relationships remain controversial. Several well-preserved mesosaurid specimens found in Uruguay justify a new anatomical reconstruction of the skull of Mesosaurus tenuidens, differing from earlier ones especially in the presence of a lower temporal fenestra. The significance of this structure for the evolution of temporal fenestration in amniotes is evaluated according to the two most recent phylogenetic hypotheses, in which mesosaurids are basalmost sauropsids or basalmost parareptiles. A synapsid-like fenestration may be the primitive condition for Amniota, and it may be also a basal condition for parareptiles, because recent phylogenies suggest a basal position for mesosaurids and lanthanosuchoids within that group, and both possess a lower temporal fenestra. Our results also give a moderately strengthened support for diapsid affinities of turtles.     

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10⁻⁸–1.2×10⁻⁴³). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10⁻⁴). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10⁻³, n = 22,044), increased triglycerides (p = 2.6×10⁻¹⁴, n = 93,440), increased waist-to-hip ratio (p = 1.8×10⁻⁵, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10⁻³, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10⁻¹³, n = 96,748) and decreased BMI (p = 1.4×10⁻⁴, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.     

CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial

Background

Single-limb knee extension exercises have been found to be effective at improving lower extremity exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Since the positive local physiological effects of exercise training only occur in the engaged muscle(s), should upper extremity muscles also be included to determine the effect of single limb exercises in COPD patients.

Methods/design

Trial design: a prospective, assessor-blind, block randomized controlled, parallel-group multicenter trial. Participants: stage II-IV COPD patients, > 40?years of age, ex-smokers, with stable medical treatment will be included starting May 2011. Recruitment at three locations in Sweden. Interventions: 1) high-repetitive single limb exercise (HRSLE) training with elastic bands, 60 minutes, three times/week for 8?weeks combined with four sessions of 60 minutes patient education, or 2) the same patient education alone. Outcomes: Primary: determine the effects of HRSLE on local muscle endurance capacity (measured as meters walked during 6-minute walk test and rings moved on 6-minute ring and pegboard test) and quality of life (measured as change on the Swedish version of the Chronic Respiratory Disease Questionnaire). Secondary: effects on maximal strength, muscular endurance, dyspnea, self-efficacy, anxiety and depression. The relationship between changes in health-related variables and changes in exercise capacity, sex-related differences in training effects, feasibility of the program, strategies to determine adequate starting resistance and provide accurate resistance for each involved movement and the relationship between muscle fatigue and dyspnea in the different exercise tests will also be analyzed. Randomization: performed by a person independent of the recruitment process and using a computer random number generator. Stratification by center and gender with a 1:1 allocation to the intervention or control using random block sizes. Blinding: all outcome assessors will be blinded to group assignment.

Discussion

The results of this project will contribute to increase the body of knowledge regarding COPD and HRSLE.

Trial registration

ClinicalTrials.gov Identifier: NCT01354067. Registration date: 2011-05-11. First participant randomized: 2011-09-02     

Guiametabolica.org: empowerment through internet tools in inherited metabolic diseases

ABSTRACT: Web-based interventions are effective on the patient empowerment. Guiametabolica.org constitutes an interface for people involved in inherited metabolic diseases, trying to facilitate access to information and contact with professionals and other patients, offering a platform to develop support groups. Guiametabolica.org is widely considered for Spanish-speaking patients and caregivers with inherited metabolic diseases. Preliminary evaluations show changes in their habits, decrease in their senses of isolation and improvement regarding self-efficacy. Specific inherited metabolic diseases websites, especially participative websites, should be considered as a complement to more traditional clinical approaches. Their contribution lies in patient's general well-being, without interfering with traditional care.     

Methane production by treating vinasses from hydrous ethanol using a modified UASB reactor

Background

A modified laboratory-scale upflow anaerobic sludge blanket (UASB) reactor was used to obtain methane by treating hydrous ethanol vinasse. Vinasses or stillage are waste materials with high organic loads, and a complex composition resulting from the process of alcohol distillation. They must initially be treated with anaerobic processes due to their high organic loads. Vinasses can be considered multipurpose waste for energy recovery and once treated they can be used in agriculture without the risk of polluting soil, underground water or crops. In this sense, treatment of vinasse combines the elimination of organic waste with the formation of methane. Biogas is considered as a promising renewable energy source. The aim of this study was to determine the optimum organic loading rate for operating a modified UASB reactor to treat vinasse generated in the production of hydrous ethanol from sugar cane molasses.

Results

The study showed that chemical oxygen demand (COD) removal efficiency was 69% at an optimum organic loading rate (OLR) of 17.05 kg COD/m³-day, achieving a methane yield of 0.263 m³/kg COD_added and a biogas methane content of 84%. During this stage, effluent characterization presented lower values than the vinasse, except for potassium, sulfide and ammonia nitrogen. On the other hand, primers used to amplify the 16S-rDNA genes for the domains Archaea and Bacteria showed the presence of microorganisms which favor methane production at the optimum organic loading rate.

Conclusions

The modified UASB reactor proposed in this study provided a successful treatment of the vinasse obtained from hydrous ethanol production.Methanogen groups (Methanobacteriales and Methanosarcinales) detected by PCR during operational optimum OLR of the modified UASB reactor, favored methane production.

     

A new species of Heteromyoxyuris (Nematoda: Oxyuridae), parasite of Perognathus flavus (Rodentia: Heteromyidae) from Mexico

Heteromyoxyuris otomii n. sp., which inhabits the intestinal caecum of Perognathus flavus (Heteromyidae), in Zaragoza, Hidalgo, Mexico, is described. This new species differs from the 2 other congeneric species in the morphology and length of lateral alae in males. Heteromyoxyuris deserti has simple lateral alae located at both sides of the body, whereas in the new species, these structures are double at both sides; in contrast, lateral alae of Heteromyoxyuris longejector begin at the posterior half of the body, whereas they arise in the first third in the new species. Heteromyoxyuris longejector was found in 2 new host species, i.e., Perognathus amplus and Chaetodipus hispidus. This record represents the first record for the species in Mexico, increasing its geographic distribution.     

Genetic and molecular characterization of three novel S-haplotypes in sour cherry (Prunus cerasus L.)

Tetraploid sour cherry (Prunus cerasus L.) exhibits gametophytic self-incompatibility (GSI) whereby the specificity of self-pollen rejection is controlled by alleles of the stylar and pollen specificity genes, S-RNase and SFB (S haplotype-specific F-box protein gene), respectively. As sour cherry selections can be either self-compatible (SC) or self-incompatible (SI), polyploidy per se does not result in SC. Instead the genotype-dependent loss of SI in sour cherry is due to the accumulation of non-functional S-haplotypes. The presence of two or more non-functional S-haplotypes within sour cherry 2x pollen renders that pollen SC. Two new S-haplotypes from sour cherry, S(33) and S(34), that are presumed to be contributed by the P. fruticosa species parent, the complete S-RNase and SFB sequences of a third S-haplotype, S(35), plus the presence of two previously identified sweet cherry S-haplotypes, S(14) and S(16) are described here. Genetic segregation data demonstrated that the S(16)-, S(33)-, S(34)-, and S(35)-haplotypes present in sour cherry are fully functional. This result is consistent with our previous finding that 'hetero-allelic' pollen is incompatible in sour cherry. Phylogenetic analyses of the SFB and S-RNase sequences from available Prunus species reveal that the relationships among S-haplotypes show no correspondence to known organismal relationships at any taxonomic level within Prunus, indicating that polymorphisms at the S-locus have been maintained throughout the evolution of the genus. Furthermore, the phylogenetic relationships among SFB sequences are generally incongruent with those among S-RNase sequences for the same S-haplotypes. Hypotheses compatible with these results are discussed.