0001 in risk allele cases and P < 0.0001 in non-risk allele cases; TNIP3: P = 0.050 in risk allele cases and P = 0.026 in non-risk allele cases). Table 4 shows the average expression level of genes in each SNP genotype. Of the Selleckchem Dabrafenib 10 genes, IGF2R was the only gene with an expression level that was significantly lower in the non-risk allele cases than in the risk allele cases (P = 0.012). In this study, the expression of IGF2R varied with the genotype of the SNP, rs6983267, at 8q24, which suggested that the carcinogenesis of CRC associated with diabetes mellitus or metabolic syndrome occurs via loss of IGF2R expression in the non-risk allele of 8q24. Additionally,

we analyzed the association between IGF2R downregulation and diabetes mellitus in 8q24 non-risk allele CRC cases by gene set enrichment analysis.12 First, we divided 85 non-risk allele cases into nine cases with diabetes and 76 cases without diabetes. Although positive correlation was not found in any gene set, negative correlation was observed in nine gene sets including IGF2R related to cancer in diabetic cases. Table 5 shows the nine gene sets. In this study, we investigated the association between the SNP at 8q24 and important genes of environmental risk factors of CRC (diabetes mellitus, hyperlipidemia, and metabolic syndrome) using array-CGH and cDNA microarray. IGF2R

was the only molecule associated with CRC in non-risk allele cases with diabetes in this study. Torin 1 datasheet With respect to the mechanism of colorectal carcinogenesis from diabetes or metabolic syndrome, hyperglycemia, hyperinsulinemia, and insulin

resistance are causal factors of CRC.5 Although it is widely known that IGF1R mediates carcinogenesis of various cancers, including CRC, IGF2R, which encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and cytotoxic T cell-induced apoptosis, has also proven to be associated with cancer. IGF2R is considered a tumor suppressor, and the loss of IGF2R has been described in many human malignancies, including CRC.13 Moreover, selleck compound IGF2R is located at chromosome 6q26, a region that has been shown to be related to insulin resistance and obesity-related metabolic phenotypes.14 In principle, IGF2R downregulation should be validated, but Western blotting could not be performed because of the difficulty of sample collection. However, our data and gene set enrichment analysis indicated a correlation between the genotype of rs6983267 at 8q24 and IGF2R expression level, which is associated with carcinogenesis and diabetes, not in risk allele but non-risk allele cases with diabetes mellitus. This result suggests that the SNP at 8q24 makes diabetes a risk factor for colorectal carcinogenesis via IGF2R especially in non-risk allele cases, even though the way the SNP at 8q24 works on diabetes or the relation of IGF2R to CRC carcinogenesis is not clear.

To test this hypothesis, we designed a series of experiments generating LDPCs from two different species. First, we obtained an extremely pure population of hepatocytes from rat liver. Then, by fluorescently labeling and documenting the evolution of LDPC cultures set up with these hepatocytes, we were able to show that the LDPCs were also fluorescently labeled, strongly suggesting that they were directly derived from hepatocytes. The quantitative flow cytometric analysis of the initial and resultant cell populations indicated that hepatocytes were the only logical source for LDPCs. Next, we wanted

to show the origin of LDPCs in a transgenic mouse model, which would allow us to track the fate of hepatocytes. To accomplish this, we generated a double-transgenic AlbCreXRosa26 mouse strain, www.selleckchem.com/products/LBH-589.html which was previously generated and published by others.32 Again, using several different techniques, we showed that these animals activated and expressed β-galactosidase only in hepatocytes. Using purified hepatocytes from these animals, we found that the LDPCs

were also β-galactosidase positive, supporting the conclusion that they were derived directly from hepatocytes. These studies also showed two potentially unique mechanisms by which hepatocytes dedifferentiate into hepatic progenitors. One is by cell condensation or shrinkage, which is morphologically similar to cells undergoing apoptosis; the other is budding off from multinucleated learn more cell clusters reminiscent of cell division in yeast.33, 34 It will be important to confirm these observations by future studies. Another interesting finding was the up-regulation of mesenchymal markers CD44 and vimentin during this dedifferentiation process, suggesting an epithelial-mesenchymal transition.

This is particularly intriguing, given the known role of EMT in liver development and regeneration.35-37 However, the confirmation of EMT in the generation of LDPCs requires further studies. The other somewhat unexpected finding was the click here transient expression of some oval cell markers as hepatocytes dedifferentiated into LDPC. Based on the coexpression of OV-6 and LDPC markers by the majority of cells in culture, we believe that there is a single population of hepatic progenitors that are generated through a transient oval cell-like stage from hepatocytes. Having shown the ability of mature hepatocytes to dedifferentiate into LDPCs in vitro, we tested the potential biological relevance by demonstrating their ability to regenerate hepatocytes in an animal model. Therefore, we proceeded with a well-established transplant protocol consisting of retrorsine pretreatment and partial hepatectomy in rats. The presence of both PKH-labeled and Y-chromosome-positive hepatocytes in the recipient animals convincingly showed that transplanted LDPCs were able to engraft and redifferentiate into hepatocytes in vivo.

The cluster fragments are denatured, annealed with a sequencing primer and subjected to DNA synthesis with four differentially reversible labeled fluorescent nucleotides that have their 3′-end chemical termination to ensure that only a single base is extended. Everolimus manufacturer After a single base is incorporated into the DNA strand, the terminator nucleotide is detected via its labeled fluorescent dye by the CCD camera. Then, the labeled fluorescent dye and 3′-end chemical terminations are removed and the next DNA synthesis cycle

is repeated. The Genome Analyzer IIx can obtain 30–100 nucleotide read lengths and data output per paired-end run from 1–3 Gb.[16-18] Moreover, Illumina released a HiSeq sequencer series which enabled higher throughput and a desktop MiSeq sequencer type which could sequence more rapidly in 2013. THE ABI SOLID sequencer was introduced in October 2007. SOLiD is an abbreviation for “sequencing by oligo ligation AZD6244 cost and detection”. It uses a unique sequencing method catalyzed by DNA ligase. The universal P1 adaptor-linked DNA fragments are attached to magnetic beads. Emulsion PCR is conducted in microreactors containing the reagents of the PCR reaction. The magnetic beads are covalently attached to the surface of a specially treated glass slide that is placed into a fluidic cassette within the sequencer. The universal sequence primers

hybridize to the P1 adapter within the library template.

The set of four fluorescent-labeled di-base 8-mer probes are annealed to the sequencing primer and library template. Identification of the nucleotide sequence by the 8-mer probe is achieved by interrogating every first and second base in each ligation reaction. When there is a matching of the 8-mer probe to the library template adjacent to the universal primer of the 3′-end, DNA ligase seals the phosphate backbone. After the ligation, the probe is enzymatically removed together with the last three bases attaching the linkage between base 5 and 6. Then, the same probe hybridizing process is conducted and the sequence data of each library template can be obtained at five nucleotide selleck chemical intervals. Following a series of ligation cycles, the library template is reset with five rounds of universal primers complementary to the n to n-4 position for a multistep round of ligation cycles. Through the primer reset process, each base is interrogated in two independent ligation reactions by two different primers and the nucleotide sequence is defined by this repetition. The ABI SOLiD 2.0 platform, produced in 2008, can obtain data output from 3–10 Gb per run.[16-18] HOWEVER, MUCH IMPROVED the NGS systems have already become, the competition in technology development is intensifying. The demand for low cost, high speed and highly accurate systems has spurred development beyond third-generation NGS systems (Table 1).

The cluster fragments are denatured, annealed with a sequencing primer and subjected to DNA synthesis with four differentially reversible labeled fluorescent nucleotides that have their 3′-end chemical termination to ensure that only a single base is extended. Selleckchem Nutlin 3a After a single base is incorporated into the DNA strand, the terminator nucleotide is detected via its labeled fluorescent dye by the CCD camera. Then, the labeled fluorescent dye and 3′-end chemical terminations are removed and the next DNA synthesis cycle

is repeated. The Genome Analyzer IIx can obtain 30–100 nucleotide read lengths and data output per paired-end run from 1–3 Gb.[16-18] Moreover, Illumina released a HiSeq sequencer series which enabled higher throughput and a desktop MiSeq sequencer type which could sequence more rapidly in 2013. THE ABI SOLID sequencer was introduced in October 2007. SOLiD is an abbreviation for “sequencing by oligo ligation CP-868596 and detection”. It uses a unique sequencing method catalyzed by DNA ligase. The universal P1 adaptor-linked DNA fragments are attached to magnetic beads. Emulsion PCR is conducted in microreactors containing the reagents of the PCR reaction. The magnetic beads are covalently attached to the surface of a specially treated glass slide that is placed into a fluidic cassette within the sequencer. The universal sequence primers

hybridize to the P1 adapter within the library template.

The set of four fluorescent-labeled di-base 8-mer probes are annealed to the sequencing primer and library template. Identification of the nucleotide sequence by the 8-mer probe is achieved by interrogating every first and second base in each ligation reaction. When there is a matching of the 8-mer probe to the library template adjacent to the universal primer of the 3′-end, DNA ligase seals the phosphate backbone. After the ligation, the probe is enzymatically removed together with the last three bases attaching the linkage between base 5 and 6. Then, the same probe hybridizing process is conducted and the sequence data of each library template can be obtained at five nucleotide click here intervals. Following a series of ligation cycles, the library template is reset with five rounds of universal primers complementary to the n to n-4 position for a multistep round of ligation cycles. Through the primer reset process, each base is interrogated in two independent ligation reactions by two different primers and the nucleotide sequence is defined by this repetition. The ABI SOLiD 2.0 platform, produced in 2008, can obtain data output from 3–10 Gb per run.[16-18] HOWEVER, MUCH IMPROVED the NGS systems have already become, the competition in technology development is intensifying. The demand for low cost, high speed and highly accurate systems has spurred development beyond third-generation NGS systems (Table 1).

Patients receiving lamivudine prophylaxis should be monitored with serial HBV DNA assays, and formal testing for lamivudine resistance should be performed if there is a 1 log increase in HBV DNA.86 Once resistance is confirmed, patients should be given adefovir in addition to lamivudine

or changed to tenofovir if this is available. Patients receiving intensive chemotherapy who are positive for HBcAb but HBsAg negative should have a sensitive HBV DNA assay performed to determine whether they have occult HBV infection. If HBV DNA is detected, these patients should be treated as for positive-HBsAg patients. Patients with undetectable Rapamycin clinical trial HBV DNA should be monitored regularly during chemotherapy for evidence of HBV reactivation.

The optimal monitoring schedule for these patients has not yet been ascertained. However it seems logical to perform regular measurement of HBsAb, HBsAg titers and HBV DNA after each cycle of chemotherapy since changes in these parameters are likely to precede changes in ALT and the development of clinically important hepatitis; this would allow antiviral treatment to be commenced in a timely fashion. Recipients of hematopoietic stem cell transplants R428 clinical trial positive for HBcAb are likely to undergo seroreversion; they are then at risk of HBV reactivation. These patients should probably be treated with prophylactic lamivudine, as for the HBsAg-positive patients. Chemotherapy-induced reactivation of hepatitis B may result in severe liver injury and prevent completion of life-saving treatment of the underlying malignancy. This potentially fatal complication can be effectively prevented by the use of oral antiviral medication prior to commencing

chemotherapy. It is therefore paramount that all patients receiving intensive chemotherapy be screened for HBV. Most of the experience with antivirals in this setting has centered on lamivudine. Although drug resistance is a problem with long-term use of this drug, it has proven to see more be safe, well tolerated and highly effective in preventing HBV reactivation. All those involved in the use of immunosuppressive chemotherapy should be aware of the risk of HBV reactivation and understand the principles of prevention or management of this condition. Finally, it is very likely that alternative antiviral agents such as entecavir and tenofovir, will prove at least as effective as lamivudine however, they are currently more expensive and there is a need for further research to confirm their cost-efficacy in this setting. “
“The hemodynamics of patients with portal hypertension within 4 h after a single injection of terlipressin has been studied. However, the hemodynamics in a longer phase under different infusion styles is unknown.

Medians and non-parametric statistics, with odds ratios (OR) to depict bivariate associations, were used. Results: 200 IBD patients who had received MTX were identified. Nausea was seen in

50/200 (25%); of these, 13 (26 %) had anticipatory nausea, 28 (56%) were female, median age 44 y, (38) 76% had Crohn’s disease. Median duration of MTX prior nausea onset was 4 months despite all concurrently receiving folate supplementation at median weekly dose 5 mg (range 5, 35). Nausea (all types) resulted in MTX cessation in 16 (32%), whereas 6/13 (46%) specifically with AN ceased MTX, despite the latter receiving higher weekly folate doses (median 5 vs 15 mg, p = 0.003). Nausea was most commonly treated with MTX dose reduction (68%), followed by increase to daily folate (26%), switch from CCI-779 parenteral to oral (20%), and anti-emetic (16%). Factors (bivariate analyses) associated with MTX cessation due to nausea included CD as diagnosis (OR 7.2, p = 0.06), concurrent 5ASA therapy (OR

5.5, p = 0.03), MTX dose not reduced (OR 4.6, p = 0.02), not switched to oral (OR 4.0, p = 0.07). The only significant factor associated with development of AN included presence of psychological comorbidity (OR 5.0, p = 0.03). Age, sex, folate dose, antiemetic use and other disease characteristics had no significant effect on either cessation of MTX or presence of AN (all p > 0.10). Conclusion: MTX-induced nausea is common occurring in 25 % of IBD patients, a quarter of these had AN. Dose reduction and possibly a switch to oral route appear most effective buy Inhibitor Library in avoiding MTX cessation, but may increase risk of IBD relapse. Avoiding use of MTX in those with psychological comorbidity may be advisable due to the

apparent link with AN, plus the risk of non-adherence. D PATRICK,1 DR VAN LANGENBERG1,2 1Department of Gastroenterology, Eastern health, Melbourne, Victoria, Australia, 2Eastern health clinical school, Monash University, selleck products Melbourne, Victoria, Australia Background: Clostridium difficile infection (CDI) prevalence is thought to be higher in the adult IBD population compared with adult non-IBD patients and has been shown elsewhere to have a higher morbidity and mortality. Aim: We aimed to evaluate the prevalence of CDI in our adult IBD patient cohort and compare outcomes of IBD CDI patients with a cohort of age and sex matched non-IBD patients with CDI. Methods: Retrospective evaluation of medical records of patients with confirmed IBD attending Eastern Health between January 2005 and May 2014 was conducted. 14 patients met the inclusion criteria of documented toxin positive, symptomatic CDI with at least 1 month follow-up post infection. Baseline demographics and relevant clinical data were recorded. A control cohort of patients with CDI was matched to the IBD cohort by sex, age and Charlson comorbidity score in a 3:1 ratio (controls: IBD cases).

Strong annual variation in cyst production characterizes the region. Cyst production of generally all investigated OSI-906 nmr species, including Alexandrium pseudogonyaulax (Biecheler) T. Horig. ex T. Kita et Fukuyo (cyst genus Impagidinium) and Gonyaulax spinifera (Clap. et J. Lachm.) Diesing (cyst genus Nematosphaeropsis)

was enhanced with increasing upper water nutrient and trace-element concentrations. Cyst production of Lingulodinium polyedrum (F. Stein) J. D. Dodge was the highest at the transition between upwelling and upwelling-relaxation. Cyst production of Protoperidinium americanum (Gran et Braarud) Balech, Protoperidinium monospinum (Paulsen) K. A. F. Zonn. et B. Dale, and Protoperidinium stellatum (D. Wall) Balech, and heterotrophic dinoflagellates forming Brigantedinium Palbociclib order spp. and Echinidinium aculeatum Zonn., increased most pronouncedly during upwelling

episodes. Production of Protoperidinium conicum (Gran) Balech and Protoperidinium pentagonum (Gran) Balech cysts and total diatom valves were related, providing evidence of a predator–prey relationship. The export cyst-flux of E. aculeatum, P. americanum, P. monospinum, and P. stellatum was strongly linked to the flux of total diatom valves and CaCO3, whereas the export production of Echinidinium granulatum Zonn. and Protoperidinium subinerme (Paulsen) A. R. Loebl. correlated with total organic carbon, suggesting potential consumption of diatoms, prymnesiophytes, and organic matter, respectively. selleck chemicals Sinking velocities were at least 274 m · d−1, which is in range of the diatom- and coccolith-based phytoplankton aggregates and “slower” fecal pellets. Species-selective degradation did not occur in the water column, but on the ocean floor. “
“Microalgae are major primary producers of organic matter in aquatic environments through their photosynthetic activities. Fermented microalga (Pavlova lutheri Butcher) preparation (FMP) is the product of yeast fermentation by Hansenula polymorpha. It was tested for the antioxidant activities including lipid peroxidation

inhibitory activity, free-radical-scavenging activity, inhibition of reactive oxygen species (ROS) on mouse macrophages (RAW264.7 cell), and inhibited myeloperoxidase (MPO) activity in human myeloid cells (HL60). FMP exhibited the highest antioxidant activity on free-radical scavenging, inhibitory intracellular ROS, and inhibited MPO activity. MTT [3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide] assay showed no cytotoxicity in mouse macrophages (RAW264.7 cell), human myeloid cells (HL60), and human fetal lung fibroblast cell line (MRC-5). Furthermore, the antioxidative mechanism of FMP was evaluated by protein expression levels of antioxidant enzyme (superoxide dismutase [SOD] and glutathione [GSH]) using Western blot.

However, the underlying mechanisms of obesity-related metabolic disorders still remain elusive. Interferon (IFN) regulatory factors (IRFs) are a family of nine transcription

factors (IRF1-IRF9) in mammals.[11] IRFs are involved in cytosolic pattern-recognition receptor- and Toll-like receptor-mediated signal transduction and regulate type I IFN expression.[12] IRFs play central roles in gene-expression regulation in innate immunity and immune cell differentiation.[13] IRFs were also involved in malignant transformation through regulation MK0683 of cell growth and apoptosis.[14] Moreover, we newly observed that cardiovascular diseases, such as cardiac hypertrophic, can be regulated by IRF family members.[15] Besides the above-mentioned factors, metabolic roles of IRFs have also emerged. IRF3 was reported to regulate metabolism-related NRs, such as liver X receptor and retinoid X receptor alpha.[16, 17] Another group found that IRFs regulate adipogenesis and adipocyte lipid metabolism.[18, 19] However, the roles of IRFs in hepatic and whole-body metabolism are unclear. IRF9, an IRF family member, has

previously been characterized as mediating innate immunity by activating IFN-mediated transcription.[20-22] In the present study, we discovered a protective role for IRF9 against metabolic disorders. IRF9 knockout (KO) mice fed a high-fat diet (HFD) had higher levels of obesity-induced inflammation, lower insulin sensitivity, and more severe hepatic steatosis than did wild-type (WT) controls, whereas

liver-specific IRF9 overexpression Selleckchem Antiinfection Compound Library ameliorated these phenotypes in both diet-induced and genetically (ob/ob) obese mice. Furthermore, we determined that IRF9 up-regulated the expression of PPAR-α target genes. These results suggest that IRF9 improves hepatic lipid metabolism and insulin sensitivity. All protocols were approved by the animal care and use committee of Renmin Hospital of Wuhan University (Wuhan, China). IRF9 KO mice were kindly provided by Dr. Tadatsugu Taniguchi (Department see more of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan). Ob/ob mice were purchased from The Jackson Laboratory (stock no.: 000632; The Jackson Laboratory, Bar Harbor, ME). Nine-week-old female and 8-week-old male ob/ob mice were used. Eight-week-old male C57BL/6 mice and IRF9 KO mice were fed with either normal chow (NC; protein, 18.3%; fat, 10.2%; carbohydrates, 71.5%; D12450B; Research Diets, Inc., New Brunswick, NJ) or an HFD (protein, 18.1%; fat, 61.6%; carbohydrates, 20.3%; D12492; Research Diets) ad libitum for up to 26 weeks. Detailed protocols for animal experiments were described in the Supporting Materials. To overexpress IRF9 and PPAR-α, we used replication-defective adenoviral vectors encompassing the entire coding region of Flag-tagged IRF9 (obtained from OriGene Technologies, Inc.

15 Dietary fructose is absorbed into the intestine by way of a saturable, facultative glucose transporter

(GLUT5). Healthy persons are able to absorb up to 25 g. Malabsorption can lead to increased fructose fermentation by gut bacteria.48 Findings regarding endotoxin (lipopolysaccharide [LPS]) NVP-AUY922 levels in portal blood in human NAFLD have been mixed, in part because portal blood is difficult to sample in human subjects and circulating levels are inconsistent. Normally, endotoxin released from the gut is cleared rapidly on first pass by Kupffer cells. However, a growing body of evidence supports a role for increased gut permeability and endotoxin in human NAFLD. In type II diabetes, endotoxin contributes to the development of the subclinical inflammatory state and insulin resistance by stimulating the innate immune system and inducing release of proinflammatory cytokines from adipose tissue. While HDL is known to neutralize LPS, this antiinflammatory function has been shown to be less effective in patients

with NAFLD.49 If HDL protection of LDL is decreased, that could lead to greater levels of oxidized LDL in NAFLD, which has previously been demonstrated.50, 51 Supporting this, in a small study of children with NAFLD, a low fructose diet resulted in diminished oxidized LDL.51 The relationship of fructose-induced endotoxin to disease in humans is even less well understood than the role of endotoxin find more in NAFLD; the direct relationships require further exploration. Limited studies suggest an association between fructose consumption and NAFLD. A pediatric study demonstrated increased carbohydrate intake in children with NAFLD identified by ultrasound compared to obese non-NAFLD counterparts.52 Small see more case-control studies of adults demonstrate higher

fructose and/or soft drink consumption in those with NAFLD.53-55 A study demonstrating excess soft drink consumption predicted NAFLD in a cohort of adults without typical risk factors for NAFLD lends support for a fructose effect independent of obesity.56 Abdelmalek et al.57 evaluated histologic features of a large cohort of adults with NAFLD and correlated this to estimated fructose intake. Although steatosis grade was lower in those with increased fructose intake, the degree of fibrosis was increased. In this same study, serum uric acid was substantially higher in those with increased fructose intake. Uric acid has been proposed as a biologic marker of fructose intake because uric acid levels increase with fructose intake.58, 59 In a large cohort of children with NAFLD, histopathology did not correlate with self-reported sugar consumption; however, uric acid was significantly increased in those with NASH compared to those with steatosis alone.60 It has been proposed that uric acid may mediate some of the abnormalities seen with fructose consumption through induction of retinol binding protein-4 (RBP-4), an adipokine linked to hepatic insulin resistance.

These results suggest Atezolizumab supplier that in Japanese haemophilia patients, the type of clotting factor preparations used for therapy has not influenced the incidence of inhibitor formation. “
“This chapter contains sections titled:

Introduction Structure and function of the factor VIII gene (F8) and protein F8 gene defects found in hemophilia A Conclusion Public databases Mutation nomenclature Acknowledgment References “
“Summary.  The most common severe hereditary bleeding disorder phenotype in humans, the coagulation factor VIII (F8) deficiency haemophilia A (HEMA), maps on Xq28 band, a region that comprises 11.7% of genes and 14.2% of phenotypes on X chromosome. Information about the distribution and extent of gametic disequilibrium (GD) covering the F8 gene is scarce, despite its relevance for linkage and association studies. The aim of this study was to determine the patterns, by frequency and strength, of non-random multiallelic interallelic associations between two-locus combinations of seven microsatellite loci (REN90833, F8Int25.2, F8Int22, F8Int13.2, HEMA154311.3, TMLHEInt5 and HEMA154507.3, in that

physical order) spanning 0.813 Mb on distalmost Xq28. We measured sign-based interallelic D′ coefficients in 106 men and in 100 women drawn from a single unrelated Brazilian population. Significance and patterns of GD using haploid and phased diploid sample probabilities were close to conformity. Only 9.18% of the variance of D′ could be accounted for by changes in length, indicating that GD is not a monotonically decreasing function of length. We defined Tanespimycin order two regions of overlapping long-range GD extending 698 735 base pairs (bp) (REN90833/TMLHEInt5

block) and 689 900 bp (F8Int13.2/HEMA154507.3 block) The extent of GD overlap is 575 637 bp (F8Int13.2/TMLHEInt5 interstice). Extended haplotype homozygosity analysis centred at the F8 intronic loci revealed that the most frequent core haplotypes decay the least in the flanking GD. The F8 intronic loci attend distinct non-random association forces; F8Int13.2 serves at maintenance of the long-range overlapping pattern of GD, whereas F8Int25.2 and F8Int22 serve at lessening it in force or effect. “
“Children’s Hospital of Philadelphia, Philadelphia, PA, USA Department of Pediatrics and Medicine, Division of Hematology, Johns Hopkins School of click here Medicine, Baltimore, MD, USA All Children’s Research Institute, All Children’s Hospital – Johns Hopkins Medicine (ACH-JHM), St. Petersburg, FL, USA Department of Pediatrics, Section of Pediatric Hematology/Oncology, Rush University Medical Center, Chicago, IL, USA Division of Blood Diseases and Resources at the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA Congenital factor VII (FVII) deficiency is characterized by genotypic variability and phenotypic heterogeneity. Traditional screening and factor assays are unable to reliably predict clinical bleeding phenotype and guide haemorrhage prevention strategy.