A computer-based simulation of childbirth using the partial Dirichlet–Neumann contact method with total Lagrangian explicit dynamics on the GPU

During physiological or ‘natural’ childbirth, the fetal head follows a distinct motion pattern—often referred to as the cardinal movements or ‘mechanisms’ of childbirth—due to the biomechanical interaction between the fetus and maternal pelvic anatomy. The research presented in this paper introduces a virtual reality-based simulation of physiological childbirth. The underpinning science is based on two numerical algorithms including the total Lagrangian explicit dynamics method to calculate soft tissue deformation and the partial Dirichlet–Neumann contact method to calculate the mechanical contact interaction between the fetal head and maternal pelvic anatomy. The paper describes the underlying mathematics and algorithms of the solution and their combination into a computer-based implementation. The experimental section covers first a number of validation experiments on simple contact mechanical problems which is followed by the main experiment of running a virtual reality childbirth. Realistic mesh models of the fetus, bony pelvis and pelvic floor muscles were subjected to the intra-uterine expulsion forces which aim to propel the virtual fetus through the virtual birth canal. Following a series of simulations, taking variations in the shape and size of the geometric models into account, we consistently observed the cardinal movements in the simulator just as they happen in physiological childbirth. The results confirm the potential of the simulator as a predictive tool for problematic childbirths subject to patient-specific adaptations.

     

Computational and biological inference of gene regulatory networks of the LINE-1 retrotransposon

Computational approaches were used to define structural and functional determinants of a putative genetic regulatory network of murine LINE-1 (long interspersed nuclear element-1), an active mammalian retrotransposon that uses RNA intermediates to populate new sites throughout the genome. Polymerase (RNA) II polypeptide E AI845735 and mouse DNA homologous to Drosophila per fragment M12039 were identified as primary attractors. siRNA knockdown of the aryl hydrocarbon receptor NM_013464 modulated gene expression within the network, including LINE-1, Sgpl1, Sdcbp, and Mgst1. Genes within the network did not exhibit physical proximity and instead were dispersed throughout the genome. The potential impact of individual members of the network on the global dynamical behavior of LINE-1 was examined from a theoretical and empirical framework.     

Construction of a novel lipolytic fusion biocatalyst GDEst-lip for industrial application

The gene encoding esterase (GDEst-95) from Geobacillus sp. 95 was cloned and sequenced. The resulting open reading frame of 1497 nucleotides encoded a protein with calculated molecular weight of 54.7 kDa, which was classified as a carboxylesterase with an identity of 93–97% to carboxylesterases from Geobacillus bacteria. This esterase can be grouped into family VII of bacterial lipolytic enzymes, was active at broad pH (7–12) and temperature (5–85 °C) range and displayed maximum activity toward short acyl chain p-nitrophenyl (p-NP) esters. Together with GD-95 lipase from Geobacillus sp. strain 95, GDEst-95 esterase was used for construction of fused chimeric biocatalyst GDEst-lip. GDEst-lip esterase/lipase possessed high lipolytic activity (600 U/mg), a broad pH range of 6–12, thermoactivity (5–85 °C), thermostability and resistance to various organic solvents or detergents. For these features GDEst-lip biocatalyst has high potential for applications in various industrial areas. In this work the effect of additional homodomains on monomeric GDEst-95 esterase and GD-95 lipase activity, thermostability, substrate specificity and catalytic properties was also investigated. Altogether, this article shows that domain fusing strategies can modulate the activity and physicochemical characteristics of target enzymes for industrial applications.     

Heart rate variability after radiofrequency ablation of epicardial ganglionated plexuses on the ovine left atrium

Background

Ganglionated plexuses (GP) are terminal parts of cardiac autonomous nervous system (ANS). Radiofrequency ablation (RFA) for atrial fibrillation (AF) possibly affects GP. Changes in heart rate variability (HRV) after RFA can reflect ANS modulation.

Methods

Epicardial RFA of GP on the left atrium (LA) was performed under the general anesthesia in 15 mature Romanov sheep. HRV was used to assess the alterations in autonomic regulation of the heart. A 24???hour ECG monitoring was performed before the ablation, 2 days after it and at each of the 12 following months. Ablation sites were evaluated histologically.

Results

There was an instant change in HRV parameters after the ablation. A standard deviation of all intervals between normal QRS (SDNN), a square root of the mean of the squared differences between successive normal QRS intervals (RMSSD) along with HRV triangular index (TI), low frequency (LF) power and high frequency (HF) power decreased, while LF/HF ratio increased. Both the SDNN, LF power and the HF power changes persisted throughout the 12???month follow???up. Significant decrease in RMSSD persisted only for 3 months, HRV TI for 6 months and increase in LF/HF ratio for 7 months of the follow???up. Afterwards these three parameters were not different from the preprocedural values.

Conclusions

Epicardial RFA of GP’s on the ovine left atrium has lasting effect on the main HRV parameters (SDNN, HF power and LF power). The normalization of RMSSD, HRV TI and LF/HF suggests that HRV after epicardial RFA of GPs on the left atrium might restore over time.

     

Twenty years of human research ethics committees in the Baltic States

Two decades have passed since the first attempts were made to establish systematic ethical review of human research in the Baltic States. Legally and institutionally much has changed. In this paper we provide an historical and structural overview of ethical review of human research and identify some problems related to the role of ethical review in establishing quality research environment in these countries. Problems connected to (a) public availability of information, (b) management of conflicts of interest, (c) REC composition and motivation of REC members, and (d) differing levels of stringency of ethical review for different types of studies, are identified. Recommendations are made to strengthen cooperation among the Baltic RECs.     

The Prognostic Value of Family History for the Estimation of Cardiovascular Mortality Risk in Men: Results from a Long-Term Cohort Study in Lithuania

Aim

To evaluate the additional prognostic value of family history for the estimation of cardiovascular (CVD) mortality risk in middle-aged urban Lithuanian men.

Methods

The association between family history of CVD and the risk of CVD mortality was examined in a population-based cohort of 6,098 men enrolled during 1972–1974 and 1976–1980 in Kaunas, Lithuania. After up to 40 years of follow-up, 2,272 deaths from CVD and 1,482 deaths from coronary heart disease (CHD) were identified. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) for CVD and CHD mortality.

Results

After adjustment for traditional CVD risk factors, the HR for CVD mortality was 1.24 (95% CI 1.09–1.42) and for CHD mortality 1.20 (1.02–1.42) in men with first-degree relatives having a history of myocardial infarction (MI), compared to men without positive family history. A significant effect on the risk of CVD and CHD mortality was also observed for the family history of sudden cardiac death and any CVD. Addition of family history of MI, sudden death, and any CVD to traditional CVD risk factors demonstrated modest improvement in the performance of Cox models for CVD and CHD mortality.

Conclusions

Family history of CVD is associated with a risk of CVD and CHD mortality significantly and independently of other risk factors in a middle-aged male population. Addition of family history to traditional CVD risk factors improves the prediction of CVD mortality and could be used for identification of high-risk individuals.     

Lenticular chaperones suppress the aggregation of the cataract-causing mutant T5P gamma C-crystallin

The T5P mutation in human gamma C-crystallin produces a lens cataract. Here, we have investigated the effects of the T5P mutation upon the aggregation of gamma C-crystallin in vitro and in transfected cells. By sedimentation assay and sucrose gradient centrifugation, the mutation significantly increased the aggregation of the protein and reduced dramatically its solubility in vitro. Similar effects were seen when T5P gamma C-crystallin was transfected into tissue culture cells, resulting in the formation of cytoplasmic aggregates of T5P gamma C-crystallin. Interestingly, the major lenticular protein chaperones, alpha A- and alpha B-crystallin, increased the solubility of the T5P gamma C-crystallin both in vitro and in transfected cells. More importantly, the size of the T5P gamma C-crystallin aggregates were also significantly reduced in the presence of the lenticular chaperones. These data therefore suggest a dual role for these chaperones in maintaining transparency in the lens. The first is that these protein chaperones increase the proportion of the soluble T5P gamma C-crystallin and the second is that they also reduce light scatter by reducing the aggregate size of T5P gamma C-crystallin. Both activities could modify the cataract phenotype and help explain the observed variability reported for identical gamma-crystallin mutations, which identify cataract as a polygenic disease.