Intraoperative blood transfusions in highly alloimmunized patients undergoing orthotopic liver transplantation.

Intraoperative blood requirements were analyzed in patients undergoing primary orthotopic liver transplantation and divided into two groups on the basis of panel reactive antibody of pretransplant serum measured by lymphocytotoxicity testing. One group of highly sensitized patients (n = 25) had PRA values of over 70% and the second group of patients (n = 26) had 0% PRA values and were considered nonsensitized. During the transplant procedure, the 70% PRA group received considerably greater quantities of blood products than the 0% PRA group--namely, red blood cells: 21.1 +/- 3.7 vs. 9.8 +/- 0.8 units (P = 0.002), and platelets: 17.7 +/- 3.2 vs. 7.5 +/- 1.5 units (P = 0.003). Similar differences were observed for fresh frozen plasma and cryoprecipitate. Despite the larger infusion of platelets, the blood platelet counts in the 70% PRA group were lower postoperatively than preoperatively. Twenty patients in the 70% PRA group received platelet transfusions, and their mean platelet count dropped from 95,050 +/- 11,537 preoperatively to 67,750 +/- 8,228 postoperatively (P = 0.028). In contrast, nearly identical preoperative (84,058 +/- 17,297) and postoperative (85,647 +/- 12,445) platelet counts were observed in the 17 0% PRA patients who were transfused intraoperatively with platelets. Prothrombin time, activated partial thromboplastin time, and fibrinogen levels showed no significant differences between both groups. These data demonstrate that lymphocytotoxic antibody screening of liver transplant candidates is useful in identifying patients with increased risk of bleeding problems and who will require large quantities of blood during the transplant operation

Intraoperative blood transfusion requirements and deficient hemostasis in highly alloimmunized patients undergoing liver transplantation

During orthopic liver transplantation (OLT) a large transfusion of different blood components is frequently necessary. From 1981 to 1985 at the University Health Center in Pittsburgh, 4,318 units of RBCs and 4,788 units of platelets were administered during 366 OLT performed in adults. This results in a mean of 25 units of RBCs and 30 units of platelets per operation. The majority of adult liver transplant patients receive multiple transfusions of whole blood and/or blood components during their pretransplant course because of complications relating to their original disease. The exposure of these patients to different antigens from random donors facilitates the development of alloimmunization. The heightened alloimmune state can be identified by preoperative values of panel reacting antibodies (PRA). Since platelets possess the HLA antigens of donor specificity, platelets may function as the target of host antibodies, resulting in platelet alteration and subsequent dysfunction. Thus, the effect of alloimmunization on platelet function may be one of the factors responsible for significant blood loss after large transfusions of different blood components. In this retrospective study we compared blood loss and platelet transfusion during OLT with preoperative alloimmunization against random donor antigens, indicated by PRA values

Kidney transplantation in Pittsburgh: experience and innovations.

1. The introduction of combined CsA and steroid treatment as the baseline immunosuppressive medication significantly enhanced the results of kidney transplantation in our series. But various other preexisting recipient or donor conditions may still have an important effect on kidney transplant survival and should not go unrecognized. 2. Living-related kidney transplants were almost totally abandoned at our institution. Reasons for this approach are the increased availability of cadaveric donor organs, the improved results with cadaveric transplants under CsA and the possible risks to the living donors. 3. Combined liver/kidney transplants have been shown to offer a favorable treatment modality for patients with endstage liver and renal failure. 4. A newly developed center-oriented Transplant Information Management System (TIMY) significantly facilitates the clinical and research tasks in our department. 5. An integrated, computerized scoring system for equitable allocation of donor organs has proven to be highly effective during routine clinical use

A radiological visual scale to predict the potentially recruitable lung in ALI/ARDS patients

Introduction In ALI/ARDS patients the amount of potentially recruitable lung is extremely variable and it is poorly predictable by the changes of oxygenation, carbon dioxide or compliance during a PEEP trial [1]. At the present time the gold standard to compute the lung recruitability is the quantitative lung CT scan, in which each lung image, after being manually drawn, is analyzed by dedicated software. However, this is both a laborious and time-consuming technique. The aim of this study was to evaluate the ability of a visual radiological scale compared with lung CT scan analysis to predict the lung recruitability in ALI/ARDS patients. Methods A whole lung CT scan was performed at 5 and 45 cmH2O airway pressure. For CT scan analysis each lung image was manually outlined and analyzed by a dedicated software. The potentially recruitable lung was defi ned as the proportion of the nonaerated lung tissue in which aeration was restored [1]. For radiological visual scale analysis, two radiologists performed a blinded evaluation of the consolidation/collapsed areas in each lobe by visual inspection [2]. The overall lung change in consolidation/collapsed was obtained by the sum of each lobe and computed as the diff erence between the two conditions. Results Twenty-four ALI/ARDS patients (age 59 \ub1 15 years, BMI 26 \ub1 4 kg/m2, PaO2/FiO2 170 \ub1 60, PEEP 10 \ub1 2 cmH2O) were enrolled. The percentage of potentially recruitable lung was 16.2 \ub1 7.1% and 14.7 \ub1 7.0%, computed by CT scan and by the visual radiological scale, respectively. The mean diff erence between CT scan analysis and visual radiological analysis was 3.3 \ub1 4.6% (median: 2.91, interquartile range: 0.38 to 6.56). The error of the visual method was lower than 5% in 14 patients (58.3%), between 5% and 10% in eight patients (33.3%) and between 10% and 15% in two patients (8.3%). Conclusions The application of a radiological visual scale is able to predict the amount of potentially recruitable lung similarly to those obtained by a dedicated software avoiding the need of manually drawing each lung image. References 1. Gattinoni L, et al.: N Engl J Med 2006, 354:1775-1786. 2. Pierce RJ, et al.: Thorax 1980, 35:773-780

The Effect of Transposable Element Insertions on Gene Expression Evolution in Rodents

Background:Many genomes contain a substantial number of transposable elements (TEs), a few of which are known to be involved in regulating gene expression. However, recent observations suggest that TEs may have played a very important role in the evolution of gene expression because many conserved non-genic sequences, some of which are know to be involved in gene regulation, resemble TEs. Results:Here we investigate whether new TE insertions affect gene expression profiles by testing whether gene expression divergence between mouse and rat is correlated to the numbers of new transposable elements inserted near genes. We show that expression divergence is significantly correlated to the number of new LTR and SINE elements, but not to the numbers of LINEs. We also show that expression divergence is not significantly correlated to the numbers of ancestral TEs in most cases, which suggests that the correlations between expression divergence and the numbers of new TEs are causal in nature. We quantify the effect and estimate that TE insertion has accounted for ~20% (95% confidence interval: 12% to 26%) of all expression profile divergence in rodents. Conclusions:We conclude that TE insertions may have had a major impact on the evolution of gene expression levels in rodents

ALMA observations of the multiplanet system 61 Vir: What lies outside super-Earth systems?

A decade of surveys has hinted at a possible higher occurrence rate of debris discs in systems hosting low mass planets. This could be due to common favourable forming conditions for rocky planets close in and planetesimals at large radii. In this paper we present the first resolved millimetre study of the debris disc in the 4.6 Gyr old multiplanet system 61 Vir, combining ALMA and JCMT data at 0.86 mm. We fit the data using a parametric disc model, finding that the disc of planetesimals extends from 30 AU to at least 150 AU, with a surface density distribution of millimetre sized grains with a power law slope of 0.1$^{+1.1}_{-0.8}$. We also present a numerical collisional model that can predict the evolution of the surface density of millimetre grains for a given primordial disc, finding that it does not necessarily have the same radial profile as the total mass surface density (as previous studies suggested for the optical depth), with the former being flatter. Finally, we find that if the planetesimal disc was stirred at 150 AU by an additional unseen planet, that planet should be more massive than 10 M$_{\oplus}$ and lie between 10-20 AU. Lower planet masses and semi-major axes down to 4 AU are possible for eccentricities $\gg$ 0.1.This paper makes use of the following ALMA data: ADS/JAO.ALMA#2013.1.00359.S. ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada) and NSC and ASIAA (Taiwan) and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO and NAOJ. MCW, LM and AS acknowledge the support of the European Union through ERC grant number 279973. GMK is supported by the Royal Society as a Royal Society University Research Fellow. AS is partially supported by funding from the Center for Exoplanets and Habitable Worlds. The Center for Exoplanets and Habitable Worlds is supported by the Pennsylvania State University, the Eberly College of Science and the Pennsylvania Space Grant Consortium

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Effectiveness, cost-effectiveness and cost-benefit of a single annual professional intervention for the prevention of childhood dental caries in a remote rural Indigenous community

Background The aim of the study is to reduce the high prevalence of tooth decay in children in a remote, rural Indigenous community in Australia, by application of a single annual dental preventive intervention. The study seeks to (1) assess the effectiveness of an annual oral health preventive intervention in slowing the incidence of dental caries in children in this community, (2) identify the mediating role of known risk factors for dental caries and (3) assess the cost-effectiveness and cost-benefit of the intervention. Methods/design The intervention is novel in that most dental preventive interventions require regular re-application, which is not possible in resource constrained communities. While tooth decay is preventable, self-care and healthy habits are lacking in these communities, placing more emphasis on health services to deliver an effective dental preventive intervention. Importantly, the study will assess cost-benefit and cost-effectiveness for broader implementation across similar communities in Australia and internationally. Discussion There is an urgent need to reduce the burden of dental decay in these communities, by implementing effective, cost-effective, feasible and sustainable dental prevention programs. Expected outcomes of this study include improved oral and general health of children within the community; an understanding of the costs associated with the intervention provided, and its comparison with the costs of allowing new lesions to develop, with associated treatment costs. Findings should be generalisable to similar communities around the world. The research is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12615000693527; date of registration: 3rd July 2015

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Specificity of the E. coli LysR-Type Transcriptional Regulators

Families of paralogous oligomeric proteins are common in biology. How the specificity of assembly evolves is a fundamental question of biology. The LysR-Type Transcriptional Regulators (LTTR) form perhaps the largest family of transcriptional regulators in bacteria. Because genomes often encode many LTTR family members, it is assumed that many distinct homooligomers are formed simultaneously in the same cell without interfering with each other's activities, suggesting specificity in the interactions. However, this assumption has not been systematically tested.A negative-dominant assay with λcI repressor fusions was used to evaluate the assembly of the LTTRs in E. coli K-12. Thioredoxin (Trx)-LTTR fusions were used to challenge the homooligomeric interactions of λcI-LTTR fusions. Eight cI-LTTR fusions were challenged with twenty-eight Trx fusions. LTTRs could be divided into three classes based on their interactions with other LTTRs.Multimerization of LTTRs in E. coli K-12 is mostly specific. However, under the conditions of the assay, many LTTRs interact with more than one noncognate partner. The physiological significance and physical basis for these interactions are not known