Strain Energy Absorption Corresponds to Decreased Incidence of Ventricular Fibrillation in a Commotio Cordis Model

A healthy teenage boy is playing high school baseball, when he is struck in the chest by the ball; minutes later, his heart is experiencing ventricular fibrillation (VF) and the only way to resuscitate him is to use a defibrillator. This phenomenon, is known as Commotio Cordis (CC), and occurs as many as 20 times each year in the United States. CC most frequently occurs in sports with small balls (e.g. baseball or lacrosse) and requires a specific set of circumstances–a projectile with a certain amount of energy that impacts directly over the left ventricle of the heart during a ~15ms window during the upstroke of the heartbeat’s T-wave. While it might seem that commercially available chest protectors would prevent CC, the sad reality is that they don’t – 20% of recorded cases have been wearing chest protectors, and studies using a porcine animal model have shown that none of the protectors tested significantly reduced the incidence of VF [1]. There is a need to determine protector materials that might prevent CC from occurring. The goal of this study is to determine whether the energy absorption of potential protector materials correlates with the occurrence of VF in a porcine model

Using productivity and susceptibility indices to assess the vulnerability of United States fish stocks to overfishing

Assessing the vulnerability of stocks to fishing practices in U.S. federal waters was recently highlighted by the National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric Administration, as an important factor to consider when 1) identifying stocks that should be managed and protected under a fishery management plan; 2) grouping data-poor stocks into relevant management complexes; and 3) developing precautionary harvest control rules. To assist the regional fishery management councils in determining vulnerability, NMFS elected to use a modified version of a productivity and susceptibility analysis (PSA) because it can be based on qualitative data, has a history of use in other fisheries, and is recommended by several organizations as a reasonable approach for evaluating risk. A number of productivity and susceptibility attributes for a stock are used in a PSA and from these attributes, index scores and measures of uncertainty are computed and graphically displayed. To demonstrate the utility of the resulting vulnerability evaluation, we evaluated six U.S. fisheries targeting 162 stocks that exhibited varying degrees of productivity and susceptibility, and for which data quality varied. Overall, the PSA was capable of differentiating the vulnerability of stocks along the gradient of susceptibility and productivity indices, although fixed thresholds separating low-, moderate-, and highly vulnerable species were not observed. The PSA can be used as a flexible tool that can incorporate regional-specific information on fishery and management activity

Active single cell encapsulation using SAW overcoming the limitations of Poisson distribution

We demonstrate the use of an acoustic device to actively encapsulate single red blood cells into individual droplets in a T-junction. We compare the active encapsulation with the passive encapsulation depending on the number of loaded cells as well as the created droplet volumes. This method overcomes the Poisson limitation statistic loading of cells for the passive encapsulation. In our experiments we reach a single cell encapsulation efficiency of 97.9 ± 2.1 % at droplet formation rates exceeding 15 Hz

Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.

ObjectiveTo determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples.MethodsFor this study, 371 genome-wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells.ResultsOf 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single-nucleotide polymorphisms from a genome-wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA-DRB1 shared epitope risk allele and with a validated RA genetic risk score.ConclusionFLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status

Characterization of an electron conduit between bacteria and the extracellular environment

A number of species of Gram-negative bacteria can use insoluble minerals of Fe(III) and Mn(IV) as extracellular respiratory electron acceptors. In some species of Shewanella, deca-heme electron transfer proteins lie at the extracellular face of the outer membrane (OM), where they can interact with insoluble substrates. To reduce extracellular substrates, these redox proteins must be charged by the inner membrane/periplasmic electron transfer system. Here, we present a spectro-potentiometric characterization of a trans-OM icosa-heme complex, MtrCAB, and demonstrate its capacity to move electrons across a lipid bilayer after incorporation into proteoliposomes. We also show that a stable MtrAB subcomplex can assemble in the absence of MtrC; an MtrBC subcomplex is not assembled in the absence of MtrA; and MtrA is only associated to the membrane in cells when MtrB is present. We propose a model for the modular organization of the MtrCAB complex in which MtrC is an extracellular element that mediates electron transfer to extracellular substrates and MtrB is a trans-OM spanning ß-barrel protein that serves as a sheath, within which MtrA and MtrC exchange electrons. We have identified the MtrAB module in a range of bacterial phyla, suggesting that it is widely used in electron exchange with the extracellular environment

Primary Prevention of Sudden Cardiac Death: Implications of Recent Trials

Based on the results of randomized multicenter studies, such as the MADIT I, MADIT II, DINAMIT, and SCD-HeFT and DEFINITE trials, patients can be identified who are at high risk for sudden cardiac death (SCD) who demonstrate a reduction in arrhythmic mortality and total mortality with the implantation of an implantable cardioverter defibrillator (ICD). These are patients with coronary artery disease, impaired left ventricular function, spontaneous nonsustained ventricular tachycardia and inducible ventricular tachycardia not suppressed by procainamide. Also patients with coronary artery disease and left ventricular ejection fraction < 30% benefit from ICD placement.  Based on the SCD-HeFT results, patients with ischemic or nonischemic cardiomyopathy and class II or III congestive heart failure also benefit from the ICD.  At the same time, based on the results of the DINAMIT study, it has become apparent that the ICD does not play a role in patients within 45 days of myocardial infarction. The implications of these trials are further analyzed in this overview

Contemporary Natural History and Management of Nonobstructive Hypertrophic Cardiomyopathy

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Country differences in the diagnosis and management of coronary heart disease : a comparison between the US, the UK and Germany

Background The way patients with coronary heart disease (CHD) are treated is partly determined by non-medical factors. There is a solid body of evidence that patient and physician characteristics influence doctors' management decisions. Relatively little is known about the role of structural issues in the decision making process. This study focuses on the question whether doctors' diagnostic and therapeutic decisions are influenced by the health care system in which they take place. This non-medical determinant of medical decision-making was investigated in an international research project in the US, the UK and Germany. Methods Videotaped patients within an experimental study design were used. Experienced actors played the role of patients with symptoms of CHD. Several alternative versions were taped featuring the same script with patients of different sex, age and social status. The videotapes were shown to 384 randomly selected primary care physicians in the three countries under study. The sample was stratified on gender and duration of professional experience. Physicians were asked how they would diagnose and manage the patient after watching the video vignette using a questionnaire with standardised and open-ended questions. Results Results show only small differences in decision making between British and American physicians in essential aspects of care. About 90% of the UK and US doctors identified CHD as one of the possible diagnoses. Further similarities were found in test ordering and lifestyle advice. Some differences between the US and UK were found in the certainty of the diagnoses, prescribed medications and referral behaviour. There are numerous significant differences between Germany and the other two countries. German physicians would ask fewer questions, they would order fewer tests, prescribe fewer medications and give less lifestyle advice. Conclusion Although all physicians in the three countries under study were presented exactly the same patient, some disparities in the diagnostic and patient management decisions were evident. Since other possible influences on doctors treatment decisions are controlled within the experimental design, characteristics of the health care system seem to be a crucial factor within the decision making process

Recurrent transcriptional responses in AML and MDS patients treated with decitabine

The molecular events responsible for decitabine responses in myelodysplastic syndrome and acute myeloid leukemia patients are poorly understood. Decitabine has a short serum half-life and limited stability in tissue culture. Therefore, theoretical pharmacologic differences may exist between patient molecular changes in vitro and the consequences of in vivo treatment. To systematically identify the global genomic and transcriptomic alterations induced by decitabine in vivo, we evaluated primary bone marrow samples that were collected during patient treatment and applied whole-genome bisulfite sequencing, RNA-sequencing, and single-cell RNA sequencing. Decitabine induced global, reversible hypomethylation after 10 days of therapy in all patients, which was associated with induction of interferon-induced pathways, the expression of endogenous retroviral elements, and inhibition of erythroid-related transcripts, recapitulating many effects seen previously in in vitro studies. However, at relapse after decitabine treatment, interferon-induced transcripts remained elevated relative to day 0, but erythroid-related transcripts now were more highly expressed than at day 0. Clinical responses were not correlated with epigenetic or transcriptional signatures, although sample size and interpatient variance restricted the statistical power required for capturing smaller effects. Collectively, these data define global hypomethylation by decitabine and find that erythroid-related pathways may be relevant because they are inhibited by therapy and reverse at relapse