Cardiac Surgery in Jehovah's Witnesses Patients and Association With Peri-Operative Outcomes: A Systematic Review and Meta-Analysis

Background: Strategies for blood conservation, coupled with a careful preoperative assessment, may be applied to Jehovah's Witnesses (JW) patients who are candidates for cardiac surgery interventions. There is a need to assess clinical outcomes and safety of bloodless surgery in JW patients undergoing cardiac surgery. Methods: We performed a systematic review and meta-analysis of studies comparing JW patients with controls undergoing cardiac surgery. The primary endpoint was short-term mortality (in-hospital or 30-day mortality). Peri-procedural myocardial infarction, re-exploration for bleeding, pre-and postoperative Hb levels and cardiopulmonary bypass (CPB) time were also analyzed. Results: A total of 10 studies including 2,302 patients were included. The pooled analysis showed no substantial differences in terms of short-term mortality among the two groups (OR 1.13, 95% CI 0.74-1.73, I2=0%). There were no differences in peri-operative outcomes among JW patients and controls (OR 0.97, 95% CI 0.39-2.41, I2=18% for myocardial infarction; OR 0.80, 95% CI 0.51-1.25, I2=0% for re-exploration for bleeding). JW patients had a higher level of preoperative Hb (Standardized Mean Difference [SMD] 0.32, 95% CI 0.06-0.57) and a trend toward a higher level of postoperative Hb (SMD 0.44, 95% CI -0.01-0.90). A slightly lower CPB time emerged in JWs compared with controls (SMD -0.11, 95% CI -0.30-0.07). Conclusions: JW patients undergoing cardiac surgery, with avoidance of blood transfusions, did not have substantially different peri-operative outcomes compared with controls, with specific reference to mortality, myocardial infarction, and re-exploration for bleeding. Our results support the safety and feasibility of bloodless cardiac surgery, applying patient blood management strategies

Dynamic Distribution of Histone H4 Arginine 3 Methylation Marks in the Developing Murine Cortex

Epigenetic modifications regulate key transitions in cell fate during development of the central nervous system (CNS). During cortical development the initial population of proliferative neuroepithelial precursor cells give rise to neurons and then glia in a strict temporal order. Neurogenesis and gliogenesis are accompanied by a switch from symmetric to asymmetric divisions of the neural precursor cells generating another precursor and a differentiated progeny. To investigate whether specific post-translational histone modifications define specific stages of neural precursor differentiation during cortical development I focussed on the appearance of two different types of histone arginine methylation, the dimethyl symmetric H4R3 (H4R3me2s) and dimethyl asymmetric H4R3 (H4R3me2a) in the developing mouse cortex.An immunohistochemical study of the developing cortex at different developmental stages was performed to detect the distribution of H4R3me2s and H4R3me2a modifications. I analysed the distribution of these modifications in: 1) undifferentiated neural precursors, 2) post-mitotic neurons and 3) developing oligodendrocyte precursors (OLPs) using lineage-specific and histone modification-specific antibodies to co-label the cells. I found that the proliferative neuroepithelium during the stage of mainly symmetric expansive divisions is characterised by the prevalence of H4R3me2s modification and almost no detectable H4R3me2a modification. However, at a later stage, when the cortical layers with post-mitotic neurons have begun forming, both H4R3me2a and H4R3me2s modifications are detected in the post-mitotic neurons and in the developing OLPs.I propose that the H4R3me2s modification forms part of the "histone code" of undifferentiated neural precursors. The later appearance of the H4R3me2a modifications specifies the onset of neurogenesis and gliogenesis and the commitment of the NSCs to differentiate. Thus, the sequential appearance of the two different H4R3 methylation marks may define a particular cellular state of the NSCs during their development and differentiation demonstrating the role of histone arginine methylation in cortical development

Recruitment of aged donor heart with pharmacological stress echo. A case report

BACKGROUND: The heart transplant is a treatment of the heart failure, which is not responding to medications, and its efficiency is already proved: unfortunately, organ donation is a limiting step of this life-saving procedure. To counteract heart donor shortage, we should screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease. Donors with a history of cardiac disease are generally excluded. Coronary angiography is recommended for most male donors older than 45 years and female donors older than 50 years to evaluate coronary artery stenoses. A simpler way to screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease should be stress echocardiography. CASE REPORT: A marginal donor (A 57 year old woman meeting legal requirements for brain death) underwent a transesophageal (TE) Dipyridamole stress echo (6 minutes accelerated protocol) to rule out moderate or severe heart and coronary artery disease. Wall motion was normal at baseline and at peak stress (WMSI = 1 at baseline and peak stress, without signs of stress inducible ischemia). The pressure/volume ratio was 9.6 mmHg/ml/m(2 )at baseline, increasing to 14 mmHg/ml/m(2 )at peak stress, demonstrating absence of latent myocardial dysfunction. The marginal donor heart was transplanted to a recipient "marginal" for co-morbidity ( a 63 year old man with multiple myeloma and cardiac amyloidosis , chronic severe heart failure, NYHA class IV). Postoperative treatment and early immunosuppressant regimen were performed according to standard protocols. The transplanted heart was assessed normal for dimensions and ventricular function at transthoracic (TT) echocardiography on post-transplant day 7. Coronary artery disease was ruled out at coronary angiography one month after transplant; left ventriculography showed normal global and segmental LV function of the transplanted heart. CONCLUSION: For the first time stress echo was successfully used in the critical theater of screening potential donor hearts. This method is enormously more feasible, less expensive, and more environmentally sustainable than any possible alternative strategy based on stress scintigraphy perfusion imaging or coronary angiography. The selection of hearts "too good to die" on the basis of bedside resting and stress echo can be a critical way to solve the mismatch between donor need and supply

Statins Enhance Clonal Growth of Late Outgrowth Endothelial Progenitors and Increase Myocardial Capillary Density in the Chronically Ischemic Heart

Coronary artery disease and ischemic heart disease are leading causes of heart failure and death. Reduced blood flow to heart tissue leads to decreased heart function and symptoms of heart failure. Therapies to improve heart function in chronic coronary artery disease are important to identify. HMG-CoA reductase inhibitors (statins) are an important therapy for prevention of coronary artery disease, but also have non-cholesterol lowering effects. Our prior work showed that pravastatin improves contractile function in the chronically ischemic heart in pigs. Endothelial progenitor cells are a potential source of new blood vessels in ischemic tissues. While statins are known to increase the number of early outgrowth endothelial progenitor cells, their effects on late outgrowth endothelial progenitor cells (LOEPCs) and capillary density in ischemic heart tissue are not known. We hypothesized that statins exert positive effects on the mobilization and growth of late outgrowth EPCs, and capillary density in ischemic heart tissue.We determined the effects of statins on the mobilization and growth of late outgrowth endothelial progenitor cells from pigs. We also determined the density of capillaries in myocardial tissue in pigs with chronic myocardial ischemia with or without treatment with pravastatin. Pravastatin therapy resulted in greater than two-fold increase in CD31+ LOEPCs versus untreated animals. Addition of pravastatin or simvastatin to blood mononuclear cells increased the number of LOEPCs greater than three fold in culture. Finally, in animals with chronic myocardial ischemia, pravastatin increased capillary density 46%.Statins promote the derivation, mobilization, and clonal growth of LOEPCs. Pravastatin therapy in vivo increases myocardial capillary density in chronically ischemic myocardium, providing an in vivo correlate for the effects of statins on LOEPC growth in vitro. Our findings provide evidence that statin therapy can increase the density of capillaries in the chronically ischemic heart

New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype

Macrophage-derived lymphatic endothelial cell progenitors (M-LECPs) contribute to new lymphatic vessel formation, but the mechanisms regulating their differentiation, recruitment, and function are poorly understood. Detailed characterization of M-LECPs is limited by low frequency in vivo and lack of model systems allowing in-depth molecular analyses in vitro. Our goal was to establish a cell culture model to characterize inflammation-induced macrophage-to-LECP differentiation under controlled conditions.Time-course analysis of diaphragms from lipopolysaccharide (LPS)-treated mice revealed rapid mobilization of bone marrow-derived and peritoneal macrophages to the proximity of lymphatic vessels followed by widespread (∼50%) incorporation of M-LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the lymphatic phenotype was found in three LPS-induced subsets of activated macrophages that were positive for VEGFR-3 and many other lymphatic-specific markers. VEGFR-3 was strongly elevated in the early stage of macrophage transition to LECPs but undetectable in M-LECPs prior to vascular integration. Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages activated by LPS in vitro. Activated RAW264.7 cells co-expressed VEGF-C that induced an autocrine signaling loop as indicated by VEGFR-3 phosphorylation inhibited by a soluble receptor. LPS-activated RAW264.7 macrophages also showed a 68% overlap with endogenous CD11b(+)/VEGFR-3(+) LECPs in the expression of lymphatic-specific genes. Moreover, when injected into LPS- but not saline-treated mice, GFP-tagged RAW264.7 cells massively infiltrated the inflamed diaphragm followed by integration into 18% of lymphatic vessels.We present a new model for macrophage-LECP differentiation based on LPS activation of cultured RAW264.7 cells. This system designated here as the "RAW model" mimics fundamental features of endogenous M-LECPs. Unlike native LECPs, this model is unrestricted by cell numbers, heterogeneity of population, and ability to change genetic composition for experimental purposes. As such, this model can provide a valuable tool for understanding the LECP and lymphatic biology

The Formin-Homology Protein SmDia Interacts with the Src Kinase SmTK and the GTPase SmRho1 in the Gonads of Schistosoma mansoni

BACKGROUND:Schistosomiasis (bilharzia) is a parasitic disease of worldwide significance affecting human and animals. As schistosome eggs are responsible for pathogenesis, the understanding of processes controlling gonad development might open new perspectives for intervention. The Src-like tyrosine-kinase SmTK3 of Schistosoma mansoni is expressed in the gonads, and its pharmacological inhibition reduces mitogenic activity and egg production in paired females in vitro. Since Src kinases are important signal transduction proteins it is of interest to unravel the signaling cascades SmTK3 is involved in to understand its cellular role in the gonads. METHODOLOGY AND RESULTS:Towards this end we established and screened a yeast two-hybrid (Y2H) cDNA library of adult S. mansoni with a bait construct encoding the SH3 (src homology) domain and unique site of SmTK3. Among the binding partners found was a diaphanous homolog (SmDia), which was characterized further. SmDia is a single-copy gene transcribed throughout development with a bias towards male transcription. Its deduced amino acid sequence reveals all diaphanous-characteristic functional domains. Binding studies with truncated SmDia clones identified SmTK3 interaction sites demonstrating that maximal binding efficiency depends on the N-terminal part of the FH1 (formin homology) domain and the inter-domain region of SmDia located upstream of FH1 in combination with the unique site and the SH3 domain of SmTK3, respectively. SmDia also directly interacted with the GTPase SmRho1 of S. mansoni. In situ hybridization experiments finally demonstrated that SmDia, SmRho1, and SmTK3 are transcribed in the gonads of both genders. CONCLUSION:These data provide first evidence for the existence of two cooperating pathways involving Rho and Src that bridge at SmDia probably organizing cytoskeletal events in the reproductive organs of a parasite, and beyond that in gonads of eukaryotes. Furthermore, the FH1 and inter domain region of SmDia have been discovered as binding sites for the SH3 and unique site domains of SmTK3, respectively

Radial bone size and strength indices in male road cyclists, mountain bikers and controls

Mountain biking (MB), unlike road cycling (RC) involves exposure to ground impact bone strain and requires upper-body muscle forces to maintain stability over uneven terrain and therefore may have differential effects on radial bone structure and strength. This study aimed to compare serum bone turnover marker concentration, 1-repetition maximum muscle strength and the radial proximal (diaphysis) and distal (metaphysis) bone structure [bone mineral content, total and cortical area (CoA), density and thickness, diameter and circumference], strength strain indices and muscle cross-sectional area (MCSA) using peripheral quantitative computed tomography (pQCT) between 30 male cyclists (18–34 years) MB (n = 10), RC (n = 10) and non-athletes controls (CON, n = 10). Differences were assessed by ANOVA and an ANCOVA (adjusting for body mass and height) where appropriate. MB radii were characterised by significantly stronger (14–16%), denser (9–27%) and larger (10%) metaphyses and stronger (22–23%) and larger (11–13%) diaphyses compared to RC and CON. RC had significantly 7% higher strength indices and 4% greater CoA and thickness than CON at the diaphysis, with no differences for other bone measurements. Serum C-terminal telopeptides of type-1 collagen concentration (bone resorption marker) was higher in RC than MB (p < 0.05) and above the age-reference range. MCSA and strength were greater in MB than RC (p < 0.05). Muscle forces generated during RC appear to produce an osteogenic stimulus to increase radial bone strength indices with minimal improvement in bone structure. However greater resorptive activity in RC suggests inadequate loading to support bone maintenance. In conclusion, bone loading, muscle size and strength of MB are superior to RC

Paying with a selfie: a hybrid micro-payment framework based on visual cryptography

In developing countries, the mobile revolution is happening in these days, and technology is now improving life conditions and providing new opportunities for the developing of the economies. In this paper, we provide a micro-payment framework that can be used to conclude everyday financial transactions. The novelty of the approach relies on the usage of techniques of easy understanding and application, even for uncultured people. The security of the system is also ensured by exploiting visual cryptography schemes, whose reconstruction phase requires no particular technical skills and relies only on human activities. The description of usage scenarios and the prototypal architecture of the framework are provided together with the initial plan for the experimental deployment