Sham-operated animals (sham group) received equal amounts of saline. The rats were killed at the end of the reperfusion period. Serum levels of AP24534 concentration aspartate aminotransferase and alanine aminotransferase were determined, and histological examination and oxidative stress were evaluated in liver tissues. In addition, antimycin A-stimulated RAW264.7 cells (murine macrophage-like cells) were treated with DHLHZn to estimate its antioxidant effect. Results:  Serum aspartate aminotransferase and alanine aminotransferase levels were increased

in the I/R group, but these increases were significantly inhibited in the I/R + DHLHZn group. Similarly, liver tissue damage observed in the I/R group was attenuated in the I/R + DHLHZn group. Cells treated in vitro with both DHLHZn and antimycin A showed reduced reactive oxygen species activity compared to cells treated with antimycin A alone. Conclusion:  The new antioxidant DHLHZn may have potential for therapeutic application in liver I/R injury, although this is a limited animal study. “
“Acute Talazoparib concentration liver failure (ALF) is associated with massive hepatocyte

cell death and high mortality rates. Therapeutic approaches targeting hepatocyte injury in ALF are hampered by the activation of distinct stimulus-dependent pathways, mechanism of cell death, and a limited therapeutic window. The apoptosis repressor with caspase recruitment domain (ARC) is a recently discovered death repressor that inhibits both death receptor and mitochondrial apoptotic signaling. Here, we investigated the in vivo effects of ARC fused with the transduction domain of human immunodeficiency virus 1 (HIV-1) (TAT-ARC) on Fas- and tumor necrosis factor (TNF)-mediated murine models of fulminant liver failure. Treatment with TAT-ARC protein completely abrogated otherwise lethal liver

failure induced by Fas-agonistic antibody (Jo2), concanavalin A (ConA), or D-galactosamine/lipopolysaccharide (GalN/LPS) administration. Importantly, survival of mice was even preserved when TAT-ARC therapy was initiated in a delayed manner after stimulation with Jo2, ConA, or GalN/LPS. ARC blocked hepatocyte apoptosis by directly interacting with members of the death-inducing signaling complex. TNF-mediated liver damage was inhibited by two independent mechanisms: inhibition of jun kinase (JNK)-mediated why TNF-α expression and prevention of hepatocyte apoptosis by inhibition of both death receptor and mitochondrial death signaling. We identified JNK as a novel target of ARC. ARC’s caspase recruitment domain (CARD) directly interacts with JNK1 and JNK2, which correlates with decreased JNK activation and JNK-dependent TNF-α production. Conclusion: This work suggests that ARC confers hepatoprotection upstream and at the hepatocyte level. The efficacy of TAT-ARC protein transduction in multiple murine models of ALF demonstrates its therapeutic potential for reversing liver failure.

tamiyavanichi/tropicale/fraterculus (Balech) Balech clade (including species from the formerly termed tropical Asian [TROP] clade) may be

considered as a sister group of the Alexandrium tamarense species complex. “
“Oxylipins are oxygenated derivatives of polyunsaturated fatty acids (PUFAs) that act as chemical mediators in many ecological and physiological processes in marine and freshwater diatoms. The occurrence and distribution of these Selleckchem GPCR Compound Library molecules are relatively widespread within the lineage with considerable species-specific differences due to the variability of both the fatty acids recognized as substrates and the enzymatic transformations. The present review provides a general introduction to recent studies on diatom oxylipins and describes an analytical method for the detection and assessment of these elusive molecules in laboratory and field samples. This methodology is based on selective enrichment of the oxylipin fraction by solvent extraction, followed by parallel acquisition of full-scan UV and tandem mass spectra on reverse phase liquid chromatography (LC) peaks.

The analytical procedure enables identification of potential genetic differences, enzymatic regulation, and ecophysiological AT9283 in vivo conditions that result in different oxylipin signatures, thus providing an effective tool for probing the functional relevance of this class of lipids in plankton communities. Examples of oxylipin measurements in field samples are also provided as a demonstration

of the analytical potential of the methodology. “
“We quantified the effects of initial macroalgal tissue nitrogen (N) status (depleted and enriched) and varying pulses of nitrate (NO3−) concentration MTMR9 on uptake and storage of nitrogen in Ulva intestinalis L. and Ulva expansa (Setch.) Setch. et N. L. Gardner using mesocosms modeling shallow coastal estuaries in Mediterranean climates. Uptake of NO3− (μmol · g dry weight [dwt]−1 · h−1) was measured as loss from the water after 1, 2, 4, 8, 12, and 24 h and storage as total tissue nitrogen (% dwt) and nitrate (ppm). Both species of algae exhibited a high affinity for NO3− across all N pulses and initial tissue contents. There was greater NO3− removal from the water for depleted than enriched algae across all time intervals. In the low-N-pulse treatment, U. intestinalis and U. expansa removed all measurable NO3− within 8 and 12 h, respectively, and in the medium and high treatments, removal was high and then decreased over time. Maximum mean uptake rates of nitrate were greater for U. expansa (∼300 μmol · g dwt−1 · h−1) than U. intestinalis (∼100 μmol · g dwt−1 · h−1); however, uptake rates were highly variable over time. Overall, U. expansa uptake rates were double those of U. intestinalis. Maximum tissue NO3− for U. expansa was >1,000 ppm, five times that of U. intestinalis, suggesting that U. expansa has a greater storage capacity in this cellular pool.

We also establish a web-based tool, HNF4 Motif Finder, that can be used to identify potential HNF4α-binding sites in any sequence. (HEPATOLOGY 2009.) Hepatocyte nuclear factor 4α, HNF4α (HNF4A), is a member of the nuclear receptor superfamily of ligand-dependent transcription factors (NR2A1) and a liver-enriched transcription factor (TF) that is also expressed in the kidney, pancreas, intestine, colon, and

stomach.1 Originally identified based on its ability to bind DNA response elements in the human apolipoprotein C3 (APOC3) and mouse transthyretin (Ttr) promoters,2 Androgen Receptor antagonist HNF4α has since been shown to play a critical role in both the development of the embryo and the adult liver.3, 4 Mutations in the HNF4A coding sequence and promoter regions are linked to Maturity Onset Diabetes of the Young 1 (MODY1),5 and mutations in HNF4α response elements have been directly linked to disease, most notably in genes encoding blood coagulation factors in hemophilia and in HNF1α in MODY3.6–8 Through classical promoter analysis, functional HNF4α-binding sites have been identified in >140 genes, including those involved in the metabolism of glucose, lipids, and amino acids, as well as xenobiotics and drugs1, 4, 9 (see Supporting Table 1A for a listing of those genes). Recent genome-wide location analyses suggest

that the number of HNF4α targets may be much greater (>1000) based on widespread binding of HNF4α to promoter regions,10–12 although it is not known how many of those are functional targets. A more comprehensive Rucaparib chemical structure list of direct HNF4α targets was recently made even more critical with our finding that HNF4α binds an exchangeable ligand and hence may be a potential drug target.13 HNF4α binds DNA exclusively Ergoloid as a homodimer.14, 15 The canonical HNF4α consensus sequence consists of the half site AGGTCA with one nucleotide spacer (referred to as a DR1, AGGTCAxAGGTCA).16 Whereas the number of experimentally verified HNF4α binding sequences is sizable (>217) (Supporting Tables 1A and 1B), they were derived in a biased

fashion building on the first HNF4α-binding sites,2 and subsequently on the direct repeat rules for nuclear receptor DNA binding.16 Furthermore, the total number of 13-base oligomer (13-mer) permutations is much greater than 217 (413 ∼ 67 million), and whereas HNF4α will certainly not bind all potential 13-mers, the total number of DNA sequences that will bind HNF4α is anticipated to be in the tens of thousands. Because the presence of one or more HNF4α response elements in the promoter region of a gene is a prerequisite for classification as a direct HNF4α target, it is desirable to accurately predict all the HNF4α-binding sites throughout the genome in an unbiased fashion. Recent genome-wide technologies, most notably genome-wide location analysis (i.e.

Diagnosis of cirrhosis was

established by histology or by clinical, analytical, and ultrasonographic findings. Inclusion criteria were age between 18 and 80 years and hospitalization due to clinical decompensation of cirrhosis. Exclusion criteria were: human immunodeficiency virus (HIV) infection, previous transplantation or any other type of immunodeficiency, steroid treatment, pituitary or adrenal disease, advanced hepatocellular carcinoma (Barcelona-Clinic Liver Cancer [BCLC] stage B, C, or D), severe chronic heart (New York Heart Association [NYHA] class III or IV) or pulmonary disease (global initiative for chronic obstructive lung disease [GOLD] III or IV), chronic hemodialysis, time between hospital admission and baseline evaluation >24 hours, severe sepsis, hypovolemic or septic shock, acute respiratory distress syndrome, and refusal selleck chemicals of patient to participate. Patients or their relatives, in cases of hepatic encephalopathy, gave written informed LY2606368 research buy consent to participate in the study. It was approved by the Clinical Investigation and Ethics Committee of the Hospital Clinic of Barcelona. On resolution of hepatic encephalopathy, informed consent was requested from the patients for continuation in the study. Inclusion and the baseline clinical evaluation was performed within 24 hours of hospitalization and

included history and physical examination, liver and renal tests, ascitic fluid analysis and culture, fresh urine sediment, chest x-ray,

and abdominal ultrasonography. Heart and respiratory rates and body temperature were recorded to estimate systemic inflammatory response syndrome (SIRS). Mean arterial pressure, calculated as the median of three values, was measured noninvasively with the patient in supine position with a 5-minute interval (DINAMAP Vital Signs Monitor, Critikon, Tampa, FL). Severity of liver failure was estimated by the Child-Pugh and the model for endstage liver disease (MELD) scores. Fasting blood samples were also obtained within this first 24 hours after hospital admission for assessment L-NAME HCl of vasoactive mediators, proinflammatory cytokines, and lipid profile. Samples were obtained in all patients through an intravenous catheter inserted at least 6 hours before sampling. A short Synacthen test (SST) was performed between 8:00 and 9:00 am within the first 24 hours of admission. Synthetic adrenocorticotropic hormone (250 μg, Synacthen, Novartis Pharma, Basel, Switzerland) was given intravenously. Blood samples to measure serum total cortisol levels (competitive immunoassay using direct chemiluminescent technology; Advia-Centaur, Bayer, Pittsburgh, PA) were obtained prior and 60 minutes following Synacthen administration. The coefficient of variation for this test is 7%.

Stock

solutions of esterase (E3019; Sigma Inc., St. Louis, MO, USA), horseradish peroxidase (Sigma P8125), and catalase were prepared in DI water daily. The reaction mixture was inverted to mix and incubated for 3 min at room temperature before reading on a Fluoromax 2 fluorometer (HORIBA Ixazomib cost Jobin Yvon Inc., Edison, NJ, USA). Excitation and emission were 488 and 525 nm, respectively. The experiment was conducted under low light conditions to avoid photooxidation of DCFH during sample incubation. Fluorescence readings in counts per min were converted to concentration of strong oxidants by comparison to a standard curve generated daily using H2O2. The concentration of strong oxidants was converted to the number of moles of oxidants released per gram of algal fresh weight (nm oxidants · g−1 FW) and strong oxidant release immediately upon wounding was determined by subtracting the amount of oxidants measured in

the seawater medium before wounding from those measured in the medium 1 min after wounding. The ability of 500 U catalase to decompose 1 M H2O2 in ice-cold seawater selleck products was verified each day by measuring DCFH fluorescence of a dilution of 30% H2O2 (Sigma 216763) made in ice-cold SFSW as above with and without the addition of 500 U catalase from the fresh catalase stock solution. In order to look at the relative timeline of the oxidative burst, we sampled oxidant release in the seawater medium over the course of 65 min after the wounding of three species (A. mirabilis, P. decipiens, and T. antarcticus). Samples were wounded at t = 5 min and oxidants were measured as above, with and without the addition of 500 U catalase, in the medium of each species (n = 3) at times 0, 20, 40, and 70 min. To determine whether RNS were a component of the wound-induced oxidative burst, paired samples of A. mirabilis, D. anceps, P. decipiens, and T. antarcticus were flash frozen in liquid nitrogen 30–60 s after punching with a sterile pipette tip. Protein was extracted from each

sample using a plant total protein extraction kit (Sigma PE0230) and quantified using a Bradford-based check details protein microassay (Bio-Rad protein assay kit II #500-0002), both according to the manufacturer’s protocol. For comparison, protein was also extracted from samples of Saccharina latissima (Linnaeus) C.E. Lane, C. Mayes, Druehl et G.W. Saunders collected from the dock at Friday Harbor Laboratories (University of Washington, Friday Harbor, WA 98250, USA) in August 2012 and exposed to peroxynitrite (ONOO−, Cayman Chemical 81565, Ann Arbor, MI, USA), an RNS and a strong nitrating agent. Protein samples were stored at −80°C until use. Nitrated proteins were detected using 1-D 10% SDS polyacrylamide gel electrophoresis (PAGE) with subsequent transfer to PVDF membrane and immunoblotting. 20–40 μg of protein were loaded for 1-D PAGE depending on the species, with equal amounts loaded for each replicate within a species (n = 6 for P.

7. Of interest, the patients who were able to permanently discontinue prophylaxis appeared to have a milder bleeding phenotype as evidenced by having a later start

of prophylaxis, requiring a lower weekly dose of factor replacement and experiencing a lower joint bleed frequency on prophylaxis [38]. In Denmark, 10 of 22 cases (45%) studied at a median age of 26.2 years were able to permanently discontinue prophylaxis [39]. Long-term studies are now required to determine the musculoskeletal consequences of discontinuing long-term factor prophylaxis in early adulthood. Use of secondary prophylaxis in adults with severe haemophilia is increasing in countries with access to safe FVIII and FIX concentrates. This practice is supported by results from prospective studies. In a longitudinal MAPK Inhibitor Library study of RO4929097 mw 477 patients under 25 years of age with severe haemophilia A, prophylaxis for >45 weeks year−1 significantly reduced the rate at which joints deteriorated both on physical and X-ray examinations [8]. Patients on long-term prophylaxis had significantly fewer days lost from work or school as well as fewer days spent in hospital. The investigators concluded that ‘a haemophiliac may well be better served with prophylaxis as the treatment regimen’ [8]. Recently, Collins and colleagues have reported

the results of a cross-over study comparing on-demand treatment with full-dose prophylaxis in 20 adults ages 30–45 years of age with severe haemophilia A

and Amino acid an average of two bleeds per month [40]. Subjects received on-demand treatment for 6 months and were then switched to a high-dose prophylaxis regimen for 7 months. The first month of prophylaxis was considered a run-in period to allow stabilization on the prophylaxis regimen. Compared to on-demand treatment, prophylaxis was associated with a significant reduction in the frequency of joint bleeds (median 0 vs. a median of 15 for on-demand treatment). Of note, postinfusion FVIII trough levels were >5% at 48 h in 75% of cases and ≥2% at 72 h for 57% of patients. These studies provide a foundation in support of secondary prophylaxis in adults, and suggest that, in general, adults will require lower total doses of FVIII or FIX compared with children to maintain equivalent trough FVIII/FIX levels. The lower dose requirement in adults is predictable from the fact that FVIII half-life tends to be longer in adults than in small children 41, 42). Stabilization of clotting factor consumption in adulthood for subjects who receive early intensive prophylaxis has been reported by Dutch investigators [43]. The beneficial role of primary prophylaxis in young boys with severe haemophilia can no longer be questioned.

Notably, administration of Myrcludex-B, an entry inhibitor derived from the pre-S1 domain of the HBV envelope, provoked a comparable murine CYP7A1 induction in uninfected mice, thus designating the pre-S1 domain as the viral component triggering such metabolic selective HDAC inhibitors alterations. Conclusion: Binding of HBV to NTCP limits its function, thus promoting compensatory BA synthesis and cholesterol provision. The intimate link determined between HBV and liver metabolism underlines the importance to exploit further metabolic pathways, as well as possible NTCP-related

viral-drug interactions. (Hepatology 2014;60:1483–1493) “
“The development of metabolic abnormalities after liver transplantation (LTx) contributes to cardiovascular events and mortality. We analyzed the prevalence and risk factors of obesity, hypertension, dyslipidemia and diabetes mellitus (DM) after adult living donor liver transplantation. Fifty-four adult recipients with a minimum follow up of 6 months receiving living

donor liver transplantation between 2001 and 2012 at the Tohoku University Hospital were retrospectively analyzed. The prevalence of hypertension increased from 18.5% before transplantation to 35.2% post-transplantation, and new-onset hypertension after transplantation was 57.9% of post-transplant hypertension. Univariate analysis showed that risk factors of post-transplant hypertension were age (>50 years, P = 0.0023), pretransplant body mass index (BMI)

of 25 or more (P = 0.0123), pretransplant hypertension (P = 0.0012) Selumetinib solubility dmso and cyclosporin A (61.5% vs tacrolimus 25.0%, P = 0.0248). The incidence of obesity, dyslipidemia and DM did not change from before to after transplantation. LTx was curative in 77.8% of cases of pretransplant dyslipidemia and 20% of cases of pretransplant DM. Primary biliary cirrhosis cases comprised 85.7% of cases of pretransplant dyslipidemia that were cured by LTx. In univariate analysis, pretransplant BMI of 25 or more was the only risk factor of post-transplant dyslipidemia (P = 0.0098). The incidence of new-onset DM after transplantation was 20%. Risk factors of post-transplant DM were male sex (P = 0.0156), pretransplant DM (P < 0.0001), alcohol abuse (P = 0.0248) and mycophenolate mofetil (P = 0.0181) by univariate analysis. The prevalence of hypertension Methocarbamol increased after LTx and pretransplant obesity was associated with several post-transplant metabolic abnormalities. “
“Vitamin D supplementation was reported to improve the probability of achieving a sustained virological response when combined with antiviral treatment against hepatitis C virus (HCV). Our aim was to determine the in vitro potential of vitamin D to inhibit HCV infectious virus production and explore the mechanism(s) of inhibition. Here we show that vitamin D3 remarkably inhibits HCV production in Huh7.5 hepatoma cells.

6A). It is noteworthy that in the three woodchucks that received IL-12 only, a decrease of wIL-10 and wPD-L1 was observed, and in two of these animals this was associated with an increase in IFN-γ expression (Fig. 6A). This result suggests learn more that the combination of IL-12 treatment and block of Treg activity may cause/induce/have a detrimental effect. The expression

of Class I, β2-m, CD3, and CD8 molecules, however, remained unchanged in all animals (Supporting Fig. 3A). Untreated control woodchucks had no changes in the expression of these molecules (Supporting Fig. 3B), indicating that the increase in the immunosuppressive environment of the liver was due to the applied treatment. In chronic hepatitis B the failure to mount an efficient immune response against viral antigens allows continuing viral replication and progression of liver damage. T-cell function is particularly affected in this condition. The mechanism underlying impaired T-cell reactivity is not fully understood. Immunotherapy of chronic HBV infection aims at activating antiviral

T-cell immunity to promote seroconversion and long-lasting control of viral replication. In a previous study we treated woodchucks with chronic WHV infection with a gene transfer vector to express intrahepatically the immunostimulatory cytokine IL-12 under the control of an inducible promoter.18 Baf-A1 We observed that the induction of IL-12 expression resulted in a significant reduction of viral load and Sorafenib mw stimulation of specific anti-WHV immune response. More important, the activation of antiviral immunity was associated with a reduction of WHV covalently closed circular DNA (cccDNA) forms from the liver that are mainly responsible for the maintenance of persistent viral infection. However, the decrease in viral load was only observed in woodchucks with viremias lower than 1010 vg/mL. Woodchucks with higher viremia did not respond to treatment, and surprisingly, at the end of IL-12 administration hepatic expression of FoxP3 was significantly increased, whereas in the responder

animals FoxP3 expression was clearly reduced. Further analysis showed that peripheral blood lymphocytes obtained from woodchucks with high viral load failed to respond to IL-12 stimulation. In the present study we found that the frequency of Treg in liver of WHV chronically infected woodchucks was higher than that observed in uninfected animals. The increase in hepatic Treg was accompanied by significantly higher expression of antiinflammatory cytokines such as TGF-β1 and IL-10, and immunosuppressive molecules such as PD-1 and PD-L1. Thus, similar to chronic HBV infection, persistent infection in WHV infection is associated with a strong immunosuppressive environment within the liver.

Symptomatic treatment should attempt to lower intracranial pressure, reduce pain, and protect the optic nerves. Consideration for lumbar puncture and draining fluid as an option for reducing pressure may be helpful; however, repeated treatment is not usually favored by patients. Traditional prophylactic medications used in migraine may help reduce the primary headache often

induced by raised intracranial pressure. We suggested surgical intervention see more for patients experiencing visual loss or impending visual loss and not responding to medication therapy. In this review, we discuss headache associated with IIH and spontaneous intracranial hypotension. Much needs to be learned about treatment options for patients with cerebrospinal fluid leaks including methods to strengthen the dura. “
“To describe the GSK1120212 mouse relationship between mood/anxiety disorders and migraine headaches emphasizing the frequency of episodes based in a cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health. It has been suggested that frequency of migraine headaches can be directly associated with the presence of psychiatric disorders. Migraine headaches (International Headache Society

criteria) was classified as <1×/month, 1×/month-1×/week, 2-6×/week, and daily. Psychiatric disorders using the Clinical Interview Schedule – Revised were classified in 6 categories: common mental (CMD), major depressive (MDD), generalized anxiety (GAD), panic, obsessive-compulsive (OCD),

and mixed anxiety and depressive (MADD) disorders. We performed multivariate logistic models adjusted for age, race, education, marital status, income, and use of selective serotonin reuptake inhibitors. In our sample, 1261 presented definite migraine and 10,531 without migraine headaches (reference). Our main result was an increase in the strength of association between migraine and MDD as frequency of migraine increased for all sample: odds ratio of 2.14 (95% confidence interval [CI] 1.33-3.43) for <1 episode of migraine/month to 6.94 (95% CI 4.20-11.49) for daily headaches for all sample. Significant associations with migraine were also found for GAD, OCD, MADD, and CMD for total sample: MDD, GAD, OCD, MADD, and CMD for women, and MADD and CMD for men. Among men with daily migraine complaint, we found a significant association between migraine and OCD after correction CYTH4 for multiple comparisons (odds ratio 29.86 [95% CI 4.66-191.43]). Analyzing probable and definite migraine cases together, we replicated the findings in a lower magnitude. The increase in migraine frequency was associated with progressively higher frequencies of having mood/anxiety disorders in all samples suggesting for some psychiatric disorders a likely dose-response effect especially for women. “
“Objective.— To determine whether extended-cycle dosing of an ultralow dose vaginal ring contraceptive decreases frequency of migraine aura and prevents menstrual related migraine (MRM).

Over time, these data have also allowed WFH to track programme progress, target resources and identify development needs [14]. Historically, WFH country development programmes focused on one or two elements of the WFH Model. To advance care further and faster, O’Mahony had an idea for a new intensive programme that would work on all five development elements at once to close the gap

in diagnosis, access to treatment products and mortality that existed between developed and developing countries. On World Hemophilia Day (April 17) in 2003, the WFH launched the Global Alliance for Progress (GAP) Program, which was a culmination of all that the WFH had learned about building sustainable care. This 10-year health care development initiative aimed to greatly increase the diagnosis selleck kinase inhibitor and treatment of people with haemophilia in 20 developing BIBW2992 datasheet countries. An overarching goal was to identify 50 000 people with haemophilia globally. In 2013, GAP celebrated its tenth anniversary and a decade of success in achieving

demonstrable change in each of the 20 participating countries (Algeria, Armenia, Azerbaijan, Belarus, China, Ecuador, Egypt, Georgia, Jordan, Lebanon, Mexico, Moldova, Morocco, Peru, Philippines, Syria, Thailand, Tunisia, Russia and South Africa). In these countries, to date 26 381 patients with haemophilia were identified and national care programmes were established in 16 countries. Globally, the number people diagnosed with haemophilia increased from 105 971 in 2003 [15] to 167 110 in 2011 [16]. Although the success of health care development projects like GAP depend on a winning coalition it is often the patient leaders, those who have the most to gain or lose, who are the local drivers for change. To better prepare the WFH NMOs in the late 1990s, the WFH began developing workshops to help patient leaders develop the skills to lobby their government for improved care. This grew into a global advocacy in action training programme launched in 2006. So far, over 1000 patient organization leaders have been trained and gone on to improve care

MRIP in their own countries. Soon after being elected WFH president in 2004, Mark Skinner (US) led the WFH to adopt the vision of Treatment for All, which is the foundation upon which the WFH’s global development strategy is built today [17]. Treatment for All means that one day treatment will be available for all patients with inherited bleeding disorders regardless of where they live. It also means more than simply access to treatment products. It means: Proper diagnosis, management and care by a multidisciplinary team of trained specialists; Safe, effective treatment products are available for all people with inherited bleeding disorders; Expansion of services beyond haemophilia, to those with von Willebrand’s disease (VWD), rare factor deficiencies and inherited platelet disorders.