In a separate group of 11 matched plasma and CSF cerebral malaria

In a separate group of 11 matched plasma and CSF cerebral malaria patient samples, the ratio of plasma to CSF PfHRP-2 was 175. The CSF PfHRP-2 reflects elevated plasma PfHRP-2 rather than elevated CM-specific CSF ratios, falling short of a validated biomarker.”
“Endothelial cells (ECs) are a critical

target of viruses, and infection of the endothelium represents a defining point in viral pathogenesis. Human cytomegalovirus (HCMV), the prototypical betaherpesvirus, encodes proteins specialized for entry into ECs and delivery of the genome to the nuclei of ECs. Virus strains competent to enter ECs replicate with differing efficiencies, selleck kinase inhibitor suggesting that the virus encodes genes for postentry tropism in ECs. We previously reported a specific requirement for the UL133/8 locus of HCMV for replication in ECs. The UL133/8 locus harbors four genes: UL133, UL135, UL136, and UL138. In this study, we find that while UL133 and UL138 are dispensable for replication in ECs, both UL135 and UL136 are important. These genes are not required for virus entry or the expression of viral genes. The phenotypes associated with disruption of either gene reflect phenotypes observed for the UL133/8NULL virus, which lacks the entire UL133/8 locus, but are largely distinct from one another. Viruses

lacking UL135 fail to properly envelop capsids Angiogenesis inhibitor in the cytoplasm, produce fewer dense bodies (DB) than the wild-type (WT) virus, and are unable to incorporate viral products into multivesicular bodies (MVB). Viruses lacking UL136 also fail to properly envelop virions and produce larger dense bodies than the WT virus. Our results indicate roles for the UL135 and UL136 proteins in commandeering host membrane-trafficking pathways for virus maturation. UL135 and UL136 Small molecule library represent

the first HCMV genes crucial for early-to late-stage tropism in ECs. IMPORTANCE Human cytomegalovirus (HCMV) persists in the majority of the world’s population. While typically asymptomatic in healthy hosts, HCMV can cause significant morbidity and mortality in immunocompromised or naive individuals, particularly transplant patients and patients with congenital infections, respectively. Lifelong persistence of the virus may also contribute to agerelated pathologies, such as vascular disease. One aspect of HCMV infection contributing to complex and varied pathogenesis is the diverse array of cell types that this virus infects in the host. The vascular endothelium is a particularly important target of infection, contributing to viral dissemination and likely leading to CMV complications following transplantation. In this work, we identify two viral gene products required for postentry tropism in endothelial cells. Identifying tropism factors required for replication in critical cell targets of infection is important for the development of strategies to restrict virus replication.”
“Skeletal muscle has been identified as a secretory organ.

5% were infected with more than one pathogen M pneumoniae

5% were infected with more than one pathogen. M pneumoniae

infection strongly correlated with mean temperature. Children with a single M pneumoniae infection had significantly higher neutrophil percentages and CRP levels than children with co-infections.\n\nConclusions: M pneumoniae is one of the most commonly held pathogens, according to the 5-year surveillance. M pneumoniae infection has its own epidemic season, especially in the summer. Mean temperature is the main meteorological factor affecting the epidemiology of M pneumoniae infections.”
“Background: The clinical relevance of observations of serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor -kappa B ligand (RANKL) in juvenile idiopathic Ion Channel Ligand Library purchase arthritis (JIA) is not clear. To elucidate the potential role of OPG and RANKL in JIA we determined serum levels of OPG and RANKL in patients with early JIA compared to healthy children, and prospectively explored changes in relation to radiographic score, bone and lean mass, severity of the disease, and treatment.\n\nMethods: Ninety children with early oligoarticular or polyarticular JIA (ages 6-18 years; mean disease duration 19.4 months) and 90 healthy children individually matched for age, sex, race, and county of residence, were examined at baseline and 2-year follow-up. OPG and RANKL were quantified by enzyme-immunoassay. Data were analyzed with the use of t-tests, ANOVA, and multiple regression

analyses.\n\nResults: Serum OPG was significantly lower in patients than controls at Veliparib order baseline, and there was a trend towards higher RANKL and a lower OPG/RANKL ratio. Patients with polyarthritis had significantly higher increments in RANKL from baseline to follow-up, compared to patients with oligoarthritis. RANKL was a significant negative predictor for increments in total body lean

mass. Patients who were receiving corticosteroids (CS) or disease-modifying antirheumatic drugs (DMARDs) at follow-up had higher OPG/RANKL ratio compared with patients who did not receive this medication.\n\nConclusions: The data supports that levels of OPG are lower in patients with JIA compared to healthy children, and higher levels of RANKL is associated with more serious disease. RANKL was a significant negative predictor of lean mass in patients AZD9291 price with JIA. The OPG/RANKL ratio was higher in patients on DMARDs or CS treatment.”
“Myocardin is an important transcriptional regulator in smooth and cardiac muscle development. We noticed that the expression of myocardin was markedly downregulated in human uterine leiomyosarcoma cells. Restoration of myocardin expression induced the reexpression of smooth muscle marker proteins and the formation of well-developed actin fibers. A concomitant increase in the expression of a cyclin-dependent kinase inhibitor, p21, led to significantly reduced cell proliferation, via p21′s inhibition of the G(1)-S transition.

Based on the geometric organization of the Mn4CaO5 cluster reveal

Based on the geometric organization of the Mn4CaO5 cluster revealed by the crystallographic analysis, in combination with the results of a vast number of experimental studies involving spectroscopic and other techniques as well as various theoretical studies, the article also discusses possible mechanisms for water splitting that are currently under consideration.”
“We report here, for the first time, the case of a 41-year-old man with both Machado-Joseph disease (MJD)/spinocerebellar selleck chemicals ataxia type 3 (SCA3) and myotonic dystrophy type 1. The patient noted dysarthria at 14 years of age and unsteady gait at 30 years of age. Similar sized

expansions of the CAG trinucleotide repeats in one allele of the ataxin-3 (ATXN3) gene were found in both the patient and his father, although in the other allele the length of the CAG repeats was shorter in the father compared with the patient. In the dystrophia myotonica protein kinase (DMPK) gene the CTG repeats were much more expanded in the patient compared with his father. Thus it is possible that, in the farther, the short CTG repeat in the non-expanded ATXN3 allele delayed the onset of cerebellar symptoms, and/or that the expanded CMG repeat in the DMPK gene in the patient

accelerated the pathogenesis of MJD/SCA3. (C) 2009 Published by Elsevier B.V.”
“Several reports have shown liquid nitrogen containers as not being sterile. Microorganism transmission has been observed in different cells and tissues stored under this condition, but there is no data on contamination of stored human valves. We performed a survey on heart valve banking in Spain. Regarding the questionnaire, we have a complete drug discovery microbiological analysis of 304 thawed tissues prior to implant. this website In six cases positive culture results were observed. Patient follow-up did not reveal any adverse effects. Although some other possibilities should be stated, contamination of heart valves during storage in liquid nitrogen should be considered as a risk element in tissue banking. Strategies to asses and prevent microbial

transmission from liquid nitrogen to heart valve banking ought to be further developed.”
“Spectroscopic investigations of individual single-crystalline GaN nanowires with a lateral dimensions of similar to 30-90 nm were performed using the spatially resolved technique of electron energy-loss spectroscopy in conjunction with scanning transmission electron microscope showing a 2-angstrom electron probe. Positioning the electron probe upon transmission impact and at aloof setup with respect to the nanomaterials, we explored two types of surface modes intrinsic to GaN, surface exciton polaritons at similar to 8.3 eV (similar to 150 nm) and surface guided modes at 3.88 eV (similar to 320 nm), which are in visible/ultra-violet spectral regime above GaN bandgap of similar to 3.3 eV (similar to 375 nm) and difficult to access by conventional optical spectroscopies.

One of the mutations was present in 7 unrelated Korean patients

One of the mutations was present in 7 unrelated Korean patients. Reduced expression of VPS33B

and cellular phenotype was detected in fibroblasts from patients clinically DZNeP diagnosed with ARC with and without known VPS33B mutations. One mutation-negative patient was found to have normal mRNA and protein levels. This patient’s clinical condition improved and he is alive at the age of 2.5 years. Thus we show that all patients with a classical clinical course of ARC had decreased expression of VPS33B whereas normal VPS33B expression was associated with good prognosis despite initial diagnosis of ARC. (C) 2008 Wiley-Liss, Inc.”
“Transplantation of human umbilical cord blood cells (HUCBC) produces reliable behavioral and morphological improvements in animal models of stroke. However, the mechanisms find more of action still have not been fully elucidated. The aim of the present study is the evaluation of potential neuroprotective effects produced by HUCBC in terms of reduced infarct volume and caspase-3-dependent cell death. Permanent middle cerebral

artery occlusion was induced in 90 spontaneously hypertensive rats. The animals were randomly assigned to the control group (n = 49) or the verum group (n = 41). The cell suspension (8 x 10(6) HUCBC per kilogram bodyweight) or vehicle solution was intravenously administered 24 h after stroke onset. Fifty subjects (n = 25/25) were sacrificed after 25, 48, 72 and 96 h, and brain specimens were removed for immunohistochemistry for MAP2, cleaved caspase-3 (casp3) and GFAP. Another 42 animals (n = 26/16) were sacrificed after 0, 6, 24, 36 and

48 h and their brains processed for quantitative PCR for casp3 and survivin. The infarct volume remained stable over the entire experimental period. However, cleaved casp3 activity increased significantly in the infarct border zone within the same time frame. Numerous cleaved casp3-positive cells were colocalized with the astrocytic marker GFAP, whereas cleavage of neuronal casp3 was observed rarely. Neither the infarct volume nor casp3 activity was significantly affected Dinaciclib by cell transplantation. Delayed systemic transplantation of HUCBC failed to produce neuroprotective effects in a permanent stroke model using premorbid subjects. (C) 2010 Elsevier Inc. All rights reserved.”
“Background: Current American Heart Association guidelines recommend against the performance of elective or primary percutaneous coronary intervention (PCI) without on-site surgical backup (i.e. a class III and IIb recommendation respectively). Despite this, numerous centers have already implemented PCI programs with no on-site surgery backup (NSOS).\n\nMethods: To evaluate the necessity for on-site surgical backup (SOS) when performing PCI we performed a systematic review and meta-analysis. English-language articles published from 1966 through December 2010 were retrieved using keyword searches of Medline and Scopus, supplemented by letters to authors and reviews of all bibliographies.

This finding suggests that the neural organisation underlying the

This finding suggests that the neural organisation underlying the exploitation of bifunctional muscle properties, in the natural context, constrains the system to maintain the “natural” coordination pattern in an altered dynamic environment, even at the cost of reduced biomechanical efficiency. We suggest an important role for afference from the imposed movement in promoting the “natural” pattern. Practical implications for the emerging field of robot-assisted therapy and rehabilitation are briefly mentioned.”
“DNA methylation of coding

regions, known as gene body methylation, is conserved across eukaryotic lineages. The function of body methylation is not known, but it may this website either prevent aberrant expression from intragenic promoters

or enhance the accuracy of splicing. Given these putative functions, we hypothesized that body-methylated genes would be both longer and more functionally important than unmethylated genes. To test these hypotheses, we reanalyzed single-base resolution bisulfite sequence data from Arabidopsis thaliana to differentiate body-methylated genes from unmethylated genes using a probabilistic approach. Contrasting genic characteristics between the two groups, we found that body-methylated genes tend to be longer and to be more functionally important, as measured by phenotypic effects of insertional mutants and by gene expression, than unmethylated genes. We also found that methylated genes HSP990 cell line evolve more slowly than unmethylated genes, despite the potential for increased mutation rates in methylated CpG dinucleotides. We propose that slower rates in body-methylated genes are a function

of higher selective constraint, lower nucleosome occupancy, and a lower proportion of CpG dinucleotides.”
“Current study determined, in sows, the accuracy of ultrasonography for in vivo (n = 8) and ex vivo (n = 7) evaluation of corpora lutea (CLs) and follicles >= 1.5 mm in size, by comparison with macroscopic findings in sliced ovaries. The accuracy for ex vivo detection AZD4547 molecular weight of follicles increased with follicle size (P < 0.05), being low for 1.5-1.9 mm follicles (65.9%) and higher for >= 6 mm follicles (93.3%); differences between ultrasonographic and macroscopic observations were significant only for follicles smaller than 3.9 mm (P < 0.05), due to underestimation. Ex vivo observation succeeded to detect presence or absence of CLs in all the ovaries; the efficiency for determining the exact number of CLs being 94.4%. The accuracy for in vivo detection of follicles also increased with follicle size (P < 0.05), dropping to values lower than 40% for 1.5-1.9 mm follicles; therefore, there were significant differences between ultrasonographic and macroscopic observations (P < 0.05). On the other hand, accuracy remained around 92% for >= 6 mm follicles.

(C) 2014 The Authors Published by Elsevier Inc “
“Introduct

(C) 2014 The Authors. Published by Elsevier Inc.”
“Introduction Many studies have demonstrated a rise in troponin and brain natriuretic peptide (BNP) levels following prolonged and/or strenuous exercise. Only one study looked at athletes who collapse and this showed no difference in cardiac biomarkers between those who collapsed and selleck chemicals llc those who completed without requiring medical attention. We set out to describe and quantify the changes in troponin and BNP in three groups of non-elite runners at the 2009 London marathon: those with and without

known structural heart disease (SHD) and those who collapsed on completion. Methods The first group (recruited group, RG) was recruited at the prerace exhibition. This group had

two subsets, runners with SHD and without (non-SHD). A second group was recruited from those who collapsed (collapsed group, CG). Blood was taken for troponin I (TnI), troponin T (TnT), high sensitivity TnT (HSTnT) and BNP. Results Cardiac biomarker levels increased in all groups following the marathon. No statistically significant difference was seen between the SHD and non-SHD subgroups. When comparing the RG and CG the number and degree of rise was greater in those who collapsed. A trend for the degree of rise of HSTnT was demonstrated. Discussion We identified runners beta-catenin cancer with troponin levels that, in other circumstances, would raise concern for myocardial necrosis. However

absence of adverse clinical sequelae would suggest this rise is physiological. The cause and clinical significance of the increased HSTnT levels seen in those that collapsed is yet to be fully elucidated.”
“Sandfly-borne phleboviruses may cause a transient febrile illness (sandfly ML323 fever) or more severe neuroinvasive disease. In the Old World, they are vectored by phlebotomine flies, which are widely distributed in the Mediterranean basin, North Africa, the Indian subcontinent, the Middle East and central Asia. High seroprevalence rates have been recorded in humans and domestic animals in areas where sandflies are present. Most published studies have focused on phlebovirus infections of travelers and of soldiers stationed in endemic areas, but the health impact on local populations should not be underestimated, as seroprevalence studies indicate massive circulation of these viruses, even if disease is seldom documented. Except for Toscana virus, which shows a marked neurotropism and is a leading cause of aseptic meningitis in endemic regions, phlebovirus infections are inadequately considered by physicians and are generally underestimated. However, several properties of these viruses suggest that they will extend their geographic range. First, changes in the areas occupied by sandflies as a result of climate change have a direct impact on the epidemiology of associated human and animal diseases.

This estimator is unbiased in case of i i d data In an NSL conf

This estimator is unbiased in case of i.i.d. data. In an NSL configuration, the clutter power spectrum is range dependent and the data are consequently not i.i.d. We here present a solution to mitigate this range

dependency of the data: the range recursive subspace-based algorithms. They are used in two architectures: a fully and a partially adaptive ones. Then a new range-recursive algorithm using Taylor series expansion is investigated. The performance of these algorithms are compared with that of the conventional STAP algorithms in term of SINR loss. (C) 2009 Elsevier B.V. All rights reserved.”
“Bone resorption and peri-implantitis are some of the most important problems of dental implantology. The PXD101 implant macrodesign might decrease initial bone loss. The aim of this longitudinal study was to investigate crestal bone loss around screw type, tapered implants showing a fine threaded neck and platform switching design. In 32 patients of a dental practice, 147 maxillary

implants with a diameter of 3.7 mm and 4.2 mm were placed and loaded according to clinical criteria. Immediate loading was exclusively performed in 3.7 mm diameter implants when adequate splinting and implant stability could be guaranteed (n=50). The remaining implants were loaded delayed. The bone level change was measured mesially and distally of the implant shoulder using follow-up X-rays and calculated per year in a linear mixed model. Bone resorption was low in all groups (3.7 immediate: -0.06 mm/year; 3.7 delayed: -0.16 mm/year; 4.2 delayed:

-0.09 selleck inhibitor mm/year) after a mean follow-up period of 1.6 years (0.5-3.2 years). Based on the results of this study, it can be concluded that this implant macrodesign showed negligible bone resorption for all selleck chemicals llc loading times. Immediate loading seems to be a reliable treatment option in the maxilla when clinical criteria are considered.”
“Terpenoids are natural products of great interest due to their widespread use in agrochemicals, drugs, fragrances, flavouring and pigments. Biocatalysts are increasingly being used in the search for new derivatives with improved properties especially to obtain structurally novel leads for new drugs which are difficult to obtain using conventional organic chemical methods. This review, covering up to the end of 2012, reports on the application of Mucor species as catalysts in terpenoid biotransformation to obtain new drug targets, enhance pharmacological activity or decrease the unwanted effects of starting material.”
“The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo.

These experiments indicated that T alpha 3-T alpha 4 collaborates

These experiments indicated that T alpha 3-T alpha 4 collaborates with factors bound to T alpha 1-T alpha 2 for the strict developmental regulation of Tcra rearrangement. The compact enhanceosome created on T alpha 1-T alpha 2 explained the molecular basis for requirement of intact T alpha 2 TCF/LEF and ets

sites for enhancer function. We have created a mutant version of E alpha, E alpha MC, in which E delta myb and runx sites have been substituted for T alpha 2 runx and ets sites, that argues against the notion of a requirement for strict E alpha enhanceosome structure for function. E alpha MC resulted GW786034 chemical structure in a very potent enhancer indicating that stereospecific interactions among proteins that form learn more an E alpha enhanceosome are rather flexible. Activation of V(D)J recombination by E alpha MC during thymocyte development resulted, however, to be premature and indistinguishable from that of T alpha 1-T alpha 4. These results indicate that T alpha 3-T alpha 4 itself is not sufficient to impart a developmental delay to a chimeric “early” enhancer, and indicate the need for functional collaboration between T

alpha 2 runx/ets sites binding proteins and proteins bound to T alpha 3-T alpha 4 for proper developmental activation. The possibility of assembly of distinct sets of proteins on E alpha might represent a more flexible form of information processing during thymocyte development. The Journal of Immunology, 2009, 183: 1871-1883.”
“Bottjer SW, Alderete TL, Chang D. Conjunction of vocal production and perception regulates expression of the immediate early gene (IEG) ZENK in a novel cortical region of songbirds. J Neurophysiol 103: 1833-1842, 2010. First published January 27, 2010; doi: 10.1152/jn.00869.2009. The cortical nucleus LMAN (lateral magnocellular nucleus of the anterior nidopallium) provides the output of a basal ganglia pathway

that is necessary for acquisition of learned vocal behavior during development in songbirds. LMAN is composed of two subregions, a core and a surrounding shell, that give rise to independent pathways that traverse the forebrain in parallel. The LMAN(shell) pathway forms a recurrent loop that includes a cortical region, the dorsal region of Birinapant mouse the caudolateral nidopallium (dNCL), hitherto unknown to be involved with learned vocal behavior. Here we show that vocal production strongly induces the IEG product ZENK in dNCL of zebra finches. Hearing tutor song while singing is more effective at inducing expression in dNCL of juvenile birds during the auditory-motor integration stage of vocal learning than is hearing conspecific song. In contrast, hearing conspecific song is relatively more effective at inducing expression in adult birds, regardless of whether they are producing song.

Purpose The purpose of this in vitro study was to

evalua

Purpose. The purpose of this in vitro study was to

evaluate the influence of digitizing techniques on the fit of implant-retained crowns with 2 antirotational features. Material and Methods. An experimental working cast housing a tissue-level dental implant was created. Resin-retained abutments with different antirotational features were connected to the implant. Optical impressions of 2 abutment types were obtained separately with 1 chairside and 2 laboratory approaches. Alumina silicate restorations were milled from chairside optical impressions, and ceramic oxide cores were milled from laboratory optical impressions. Restoration fit was evaluated from axial sections of restorations with silicone materials representing the PD-1/PD-L1 Inhibitor 3 ic50 marginal and axial gaps. Rabusertib inhibitor Axial and marginal fits were measured on digital photographs of the sectioned specimens with a computer program. Two-way ANOVA was used to compare differences between abutments with 2 different antirotational features and digitizing techniques separately for the marginal and axial fits of single implant-retained crowns. A post hoc least significant difference test was used to compare digitizing techniques

(alpha=.05). Results. Significant differences in the marginal fit of single-implant-retained crowns were found among digitizing techniques (P=.011) and between antirotational features (P smaller than .001). No significant difference in the axial fit of single-implant-retained crowns was found among digitizing techniques (P=.905) or between antirotational features (P=.075). Conclusions. Within the limitations of this in vitro study,

the marginal fit of single-implant-retained crowns was affected by antirotational abutment features. Furthermore, digitizing techniques were found to play an important role in the marginal fit of single-implant-retained restorations.”
“Recently, nanomaterials have been utilized in various fields. In particular, amorphous nanosilica particles are increasingly being used in a range of applications, including cosmetics, Selleck Panobinostat food technology, and medical diagnostics. However, there is concern that the unique characteristics of nanomaterials might induce undesirable effects. The roles played by the physical characteristics of nanomaterials in cellular responses have not yet been elucidated precisely. Here, by using nanosilica particles (nSPs) with a diameter of 70 nm whose surface was either unmodified (nSP70) or modified with amine (nSP70-N) or carboxyl groups (nSP70-C), we examined the relationship between the surface properties of nSPs and cellular responses such as cytotoxicity, reactive oxygen species (ROS) generation, and DNA damage. To compare the cytotoxicity of nSP70, nSP70-N, or nSP70-N, we examined in vitro cell viability after nSP treatment.

A strictly transverse screw trajectory is needed for central or b

A strictly transverse screw trajectory is needed for central or bilateral fracture patterns up to a complete iliosacroiliac fixation. However, secure screw insertion is aggravated by a narrow sacroiliac bone

stock. This study investigates the influence of a highly variable sacral morphology to the existence of S1 and S2 transverse corridors.\n\nThe analysis contained in this study is based on 125 CT datasets of intact human pelvises. First, sacral dysplasia was identified using the “lateral sacral triangle” method in a lateral 3-D semi-transparent pelvic view. Second, 3-D corridors click here for a 7.3 mm screw in the upper two sacral levels were visualised using a proprietary IT workflow of custom-made programme scripts based on the Amira (R)-software. Shape-describing measurement variables were calculated as output variables.\n\nThe results show a significant linear correlation between ratio(T)

and the screw-limiting S1 isthmus height (Pearson coefficient of 0.84). A boundary ratio of 1.5 represented a positive predictive value of 96% for the existence of a transverse S1-corridor for at least one 7.3 mm screw. In 100 out of 125 pelvises (80%), a sufficient S1 corridor existed, whereas in 124 specimens (99%), an S2 corridor was found. Statistics revealed significantly larger S1 and S2 corridors in males compared to females (p < 0.05). However, no gender-related differences were observed for clinically relevant numbers of up to 3 screws in S1 and 1 screw in S2.\n\nThe expanse of the S1 corridor is highly influenced by the dimensions of the dysplastic elevated upper sacrum, whereas the S2 corridor is not affected. Hence, in dysplastic pelvises, sacroiliac www.selleckchem.com/products/nu7441.html screw insertion should selleck chemicals be recommended into the 2nd sacral segment. Our IT workflow for the automatic computation of 3-D corridors may assist in surgical pre-operative planning. Furthermore, the workflow could be implemented in computer-assisted surgery applications involving pelvic trauma. (C) 2013 Elsevier Ltd. All rights reserved.”
“The

X-ray single crystal structure determination of Lu2O3 sesquioxide and of polycrystalline transparent ceramic fabricated by the unconventional spark plasma sintering (SPS) method is presented for the first time. High quality single crystals of Lu2O3 samples were obtained by using both the micropulling-down (mu-PD) method and the laser heated pedestal growth (LHPG) technique. The SPS method is promising for obtaining high-density ceramics with fine grains at a relatively low temperature within a short holding time. The structural characterizations helped to complete information about the cubic structure of Lu2O3 sesquioxide, not clear until now in the literature from only polycrystalline samples and has raised doubts among many researchers.”
“Purpose of review\n\nContinued hemorrhage remains a major contributor of mortality in massively transfused patients and controversy regarding their optimal management exists.