The objectives of this study are (1) to review and critique the clinical studies

reporting an association between joint hypermobility, CTDs and headache and (2) to postulate mechanisms though which CTDs might predispose to headache disorders. PubMed was searched for relevant articles with search terms that included joint hypermobility, Ehlers–Danlos syndrome, Marfan syndrome, and specific headache disorders. A narrative review was performed of these articles as well as those identified from the bibliography of these articles. Case reports and case control studies confirm an association between CTDs and migraine, coat-hanger headaches, carotid arterial dissections, intracranial hypotension, Arnold Chiari malformations-type 1, cervical spine disorders, and temporomandibular joint disorders. Observational cross-sectional studies selleck chemicals suggest that the prevalence of CTDs is increased in patients with specific types of headache disorders. It is unknown if the CTDs directly cause these headaches disorders or are associated with them through other mechanisms. “
“To repair and refine a previously proposed method for statistical analysis of association between migraine and menstruation. Menstrually related migraine (MRM) affects about 20% of female migraineurs in the general population. The exact pathophysiological link from menstruation

to migraine find protocol is hypothesized to be through fluctuations in female reproductive hormones, but the exact mechanisms remain unknown. Therefore, the main diagnostic criterion today is concurrency of migraine attacks with menstruation. Methods aiming to exclude spurious associations are wanted, so that further research into these mechanisms can be performed on a population with a true association. The statistical method is based on a simple two-parameter null model of MRM (which

allows for simulation modeling), 3-mercaptopyruvate sulfurtransferase and Fisher’s exact test (with mid-p correction) applied to standard 2 × 2 contingency tables derived from the patients’ headache diaries. Our method is a corrected version of a previously published flawed framework. To our best knowledge, no other published methods for establishing a menstruation–migraine association by statistical means exist today. The probabilistic methodology shows good performance when subjected to receiver operator characteristic curve analysis. Quick reference cutoff values for the clinical setting were tabulated for assessing association given a patient’s headache history. In this paper, we correct a proposed method for establishing association between menstruation and migraine by statistical methods. We conclude that the proposed standard of 3-cycle observations prior to setting an MRM diagnosis should be extended with at least one perimenstrual window to obtain sufficient information for statistical processing.

There was a strong disequilibrium of sex between the two disease states: thus, the male/female sex ratio was 3.4 in HCC and 1.3 in LC. We found that the value of SNP rs2880301 was associated with sex rather than with disease status (Fig. 1). We thus believe that the data from this genome-wide association study does not encourage further study of TPTE2 in these diseases. Pierre Galichon M.D.* † ‡, Alexandre Hertig M.D., Ph.D.* † ‡, Eric Rondeau M.D., Ph.D.* † ‡, Laurent

Mesnard* † ‡, * Institut National de la Santé et de la Recherche Médicale, Unité 702, Paris, France, † Université Pierre et Marie Curie, Universite de Paris 6, Paris, France, ‡ Emergency Nephrology and Renal Transplantation, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Paris, France. “
“Background and Aims:  We previously Dasatinib nmr demonstrated that antibiotic combination therapy is effective for induction and maintenance of ulcerative colitis (UC) remission. Herein, we assessed whether antibiotic combination therapy is effective for active UC, including selleck compound cases with steroid refractory or dependent disease. Methods:  We enrolled 25 patients with active UC including 17 steroid-dependent or refractory cases. These patients received amoxicillin 500 mg t.i.d., tetracycline 500 mg t.i.d. and metronidazole 250 mg t.i.d. for 2 weeks

as well as conventional treatment. Seven colonic segments from the appendiceal region to the rectum were scored for endoscopic activity and histology. Clinical activity indexes (CAI) were also determined. Results:  At 3 and 12 months after antibiotic treatment, CAI and endoscopic score were significantly decreased as compared to those before treatment

(P < 0.001 and P < 0.05, P < 0.01, respectively). Histological scores were also significantly decreased at 12 months as compared to before treatment (P < 0.01). The clinical response rates in steroid-dependent patients were 60% and 73.3% at 3 and 12 months, respectively, while being 50% at 12 months in steroid-refractory next patients. Among the 17 steroid-dependent or refractory patients, 12 (70.6%) were able to discontinue steroid therapy at 12 months. No serious drug-related toxicities were observed during the trial. Conclusion:  This long-term follow-up study suggests 2-week antibiotic combination therapy to be effective and safe in patients with active UC including those with steroid-refractory or dependent disease. “
“Microparticles (MPs), membrane fragments of 0.1-1.0 μm, are derived from many cell types in response to systemic inflammation. Acute liver failure (ALF) is a prototypical syndrome of systemic inflammatory response syndrome (SIRS) associated with a procoagulant state. We hypothesized that patients with ALF develop increased procoagulant MPs in proportion to the severity of systemic complications and adverse outcome.

Still today, young PWH in Romania are not yet evaluated for musculoskeletal complications and for functional limitations ever in their lives and they never were included in a rehabilitation programme. From this perspective, there is a big learn more discrepancy between the patients from rural areas and those living in larger cities, giving access to university hospitals with rehabilitation departments. The main goal of rehabilitation in developing countries is to restore joint and muscle function, which is different from developed countries where the goal is to prevent musculoskeletal complications. Following the detailed musculoskeletal

and functional assessment, physical therapists, together with patient (and family) decide the goals of rehabilitation and develop a customized treatment. The first objective is often to decrease pain. Physiotherapists use ice cube massage, hydrotherapy, or electrotherapy suitable for children with haemophilia (pulsed ultrasound, phonophoresis with a hydrocortisone or Lidocaine) [31,32,33]. The use of kinesiotaping (elastic and adhesive tapes developed for re-educating the neuromuscular system, reduce pain, prevent injuries and to promote circulation

and healing) shows good results in controlling pain and inflammation. To prevent check details or to correct joint deformities, physiotherapists use custom-made splints or orthotics. This is cheaper than the high-tech imported ones. As soon as acute bleeding has stopped and the pain subsides, the click here goal is to restore the muscle strength and joint range of motion (ROM). Patients start with isometric exercises at different joint angles, followed by isotonic and resistive exercises. In the Rehabilitation unit of the Elias Hospital, Bucharest, good results are seen in muscle training supervised by use of EMG-biofeedback. If ROM

does not improve accordingly with strength, self-stretching exercise, then pool therapy or continuous passive motion (CPM) could be efficient [34]. As gait is the major determinant of functional independence, gait training becomes a key goal of rehabilitation. Physical therapists of the above mentioned unit start the gait training with body-weight support [35], in order to decrease the risk of re-bleeding and to re-learn a better gait pattern in young PWH. Last but not least, an important role of the physiotherapist is to teach patients a safe home exercise programme, how to manage an acute bleed and to help patients understand that without regular physical activity, adolescents with haemophilia are often overweight and at greater risk of recurrent haemarthroses. The articular problems of PWH begin early in infancy; the immature skeleton is very sensitive and severe structural deficiencies may develop quickly [36]. Untreated, this will result in handicaps in early life, while proper treatment is expensive, inadequate treatment is even more so, both to the individual and to the community [37].

The IL28B polymorphism did predict for short duration in the RGT arm, with 90% of good-responder patients qualifying for 28 weeks of therapy. Poor-response IL28B patients GSK-3 phosphorylation gained the most from the addition of BOC, with SVR rates increasing approximately twofold.74 The RESPOND-2 trial included only patients with prior relapse and partial response, that is, primary non-responders with a < 2log10 drop in HCV—RNA at week 12 were excluded.73 In this more difficult-to-treat population with a well-documented treatment

history, major improvements were seen in SVR rates irrespective of IL28B genotype. The IL28B genotype was not an independent predictor of SVR. Despite not predicting for SVR, the IL28B genotype did identify patients who were more likely to be eligible for short-duration therapy (36 weeks in total). The ADVANCE trial assessed TVR and peg-IFN/RBV in comparison with peg-IFN/RBV control.77 Patients were randomized to receive either standard of care, or 24 or 48 weeks of peg-IFN or RBV in combination with either 8 or 12 weeks of TVR. A total of 454 Caucasian patients or 42% of the overall trial cohort were genotyped, with improvements compared to control across all IL28B genotypes, but greater than twofold in poor-response genotypes.76 Again, the association between the IL28B genotype and treatment response was attenuated with TVR regimens, and the major SVR increment was noted in patients

who carried the poor-response IL28B genotypes. In contrast to SPRINT-2, SVR rates did increase compared to control Ridaforolimus in patients with the good-response IL28B genotype. The IL28B genotype identified patients more likely to be eligible for short-duration therapy. The REALIZE study included patients who failed to achieve SVR from prior treatment (i.e. patients with prior primary non-response were included), with patients receiving either 48 weeks of peg-IFN/RBV (control) or 12 weeks of combination triple therapy with TVR, and then another 36 weeks of peg-IFN/RBV.78 Absolute increases in SVR rate of 40–50% were seen with TVR, irrespective of IL28B genotype.75

Again, however, there remained a 18–19% difference in SVR rates observed between the good- and poor-response genotypes, even with the addition of TVR (SVR by IL28B genotype for TVR12/PR48: CC 79% vs CT 61% Amylase vs TT 60%). The IL28B genotype remains relevant to treatment outcomes in the setting of TVR/BOC therapy for treatment-naïve patients, but the strength of the association is attenuated. The major benefit of DAA is in poor-response IL28B genotype patients, where SVR rates are dramatically increased. In good-responder IL28B patients, the SVR benefit of DAA therapy is less clear. We feel that DAA therapy is likely to be associated with a small increase in SVR rate, but that the major benefit of DAA therapy in these patients will be to allow short-duration therapy. SVR rates were not increased in good-responder IL28B patients in SPRINT-2 (BOC), but were in ADVANCE (TVR).

Associations from sensitivity analyze that segregated women according to probable migraine (ICHD-2 category 1.6.1) and migraine (ICHD-2 category 1.1) diagnoses were of similar magnitudes as those reported here for women with any migraine diagnoses. IPV, particularly sexual violence, appears to be a risk factor for migraine. Conclusion.— Our findings suggest the potential R788 research buy importance of considering a history of violence among migraineurs. “
“To determine if baseline/interictal saliva calcitonin gene-related peptide (CGRP) levels would be lower in subjects with

chronic migraine receiving onabotulinumtoxinA compared with those receiving saline. CGRP is considered central to the pathogenesis of episodic migraine, but its relationship to chronic migraine is less understood. OnabotulinumtoxinA is an effective treatment for chronic migraine and has been demonstrated to inhibit the vesicular release of CGRP. This was an exploratory, randomized, placebo-controlled, crossover pilot study of 20 subjects that received onabotulinumtoxinA and saline injection (placebo). The amount of CGRP in saliva samples collected on a nonheadache or low headache day, and prior to JAK inhibitor and after treatment of a headache exacerbation was measured. Daily headache records, medications, and response to treatment were recorded

in a diary. A decrease in baseline/interictal saliva CGRP levels for subjects receiving onabotulinumtoxinA Carbohydrate from 39.4 ± 7.5 pg CGRP/mg total protein after the first month to 25.5 ± 4.1 pg after the third month was observed. However, this difference did not reach significance nor was it significant when compared to the saline treatment. There was a reduction in the number of headache days for both onabotulinumtoxinA and saline over baseline throughout the active phases of the study. However, there was no statistical difference in headache days between groups. Subjects with a greater than 50% response to onabotulinumtoxinA had better 2-hour pain relief with acute treatment than non-responders to onabotulinumtoxinA

or saline. While CGRP levels were not elevated during a migraine attack in chronic migraine subjects as has been reported in episodic migraine, there was an overall decrease in the baseline/interictal levels in response to onabotulinumtoxinA. “
“(Headache 2010;50:965-972) Objective.— To evaluate relative telomere length of female migraine patients. Background.— Migraine is a debilitating disorder affecting 6-28% of the population. Studies on the mechanisms of migraine have demonstrated genetic causes but the pathophysiology and subcellular effects of the disease remain poorly understood. Shortened telomere length is associated with age-related or chronic diseases, and induced stresses. Migraine attacks may impart significant stress on cellular function, thus this study investigates a correlation between shortening of telomeres and migraine. Methods.

Elevation Apitolisib ic50 of CO2 concentration increased the

value of K1/2(Ci) (the half-saturation constant) for photosynthesis, whereas high N supply lowered it. Neither short-term nor long-term CO2 enrichment had inhibitory effects on respiration rate, irrespective of the N supply, under which the algae were grown. Under high-N growth, the Q10 value of respiration was higher in the elevated-CO2-grown algae than the ambient-CO2-grown algae. Either short- or long-term exposure to CO2 enrichment decreased respiration as a proportion of gross photosynthesis (Pg) in low-N-grown H. fusiformis. It was proposed that in a future world of higher atmospheric CO2 concentration and simultaneous coastal eutrophication, the respiratory carbon flux would be more sensitive to changing temperature. “
“This study assessed the implication of oxidative stress in the mortality of cells of Microcystis aeruginosa Kütz. Cultures grown at 25°C were exposed to 32°C, darkness, and hydrogen peroxide (0.5 mM) for 96 h. The cellular abundance, chl a concentration and content, maximum photochemical see more efficiency of PSII (Fv/Fm ratio), intracellular oxidative stress (determined with dihydrorhodamine 123 [DHR]), cell mortality (revealed by SYTOX-labeling of DNA), and activation of caspase 3–like proteins were assessed every 24 h. The presence of DNA degradation in cells of M. aeruginosa was also assessed using

a terminal deoxynucletidyl transferase-mediated dUTP nick end labeling (TUNEL) assay at 96 h. Transferring cultures from 25°C to 32°C was generally beneficial to the cells. The cellular abundance and chl a concentration increased, and the mortality remained low (except for a transient burst at 72 h) as did the oxidative stress. In darkness, cells did

not divide, and the Fv/Fm continuously decreased with time. The slow increase in intracellular oxidative stress mafosfamide coincided with the activation of caspase 3–like proteins and a 15% and 17% increase in mortality and TUNEL-positive cells, respectively. Exposure to hydrogen peroxide had the most detrimental effect on cells as growth ceased and the Fv/Fm declined to near zero in less than 24 h. The 2-fold increase in oxidative stress matched the activation of caspase 3–like proteins and a 40% and 37% increase in mortality and TUNEL-positive cells, respectively. These results demonstrate the implication of oxidative stress in the stress response and mortality of M. aeruginosa. “
“The genus Mallomonas, a common and often abundant member of the planktic community in many freshwater habitats worldwide, consists of 180 species divided into 19 sections and 23 series. Classification of species is based largely on ultrastructural characteristics of the siliceous scales and bristles that collectively form a highly organized covering over the cell.

26 Age-group of peak prevalence varies by region, and is expected to also vary by country depending on local epidemiology of HCV transmission. For example, in the U.S. cohort effects were seen that were specific to infection stemming from injection drug use in the 1970s.27 Areas with type 1 transmission such as North mTOR inhibitor America exhibit signs of the aging cohort in prevalence, i.e., a shift in age group with highest risk of HCV-sequelae between 1990 and 2005. Regions such as East Asia and Southern Latin America, without previously hypothesized cohort effects, also show signs of type 1 transmission; this suggests that these regions

may have their own cohort effects that are not as well understood or characterized. Further attention should be given to documenting the transmission patterns in different countries, particularly those that have high prevalence (such as Pakistan in South Asia), in order to inform future estimation efforts. The total prevalence estimates in this study are higher compared to those of previous anti-HCV estimates2 and some prominent findings in prevalence patterns of some regions require further discussion. In Australasia,

the estimated peak prevalence at ages 20-24 years may reflect the high incidence of HCV among PWID reported recently.28, 29 Contrary to the literature describing Australia as having very low prevalence and type 1 transmission, our findings may be due to fewer datapoints beyond age 40, resulting in borrowing of strength Miconazole and more influence from younger ages with higher prevalence for the Australasian region. Mother-to-infant Torin 1 research buy transmission is the commonest route of HCV infection in children, with a vertical transmission rate of 5%.30 In West sub-Saharan Africa, the relatively high prevalence in young children may reflect the overlapping human immunodeficiency virus (HIV) epidemic and HIV-HCV coinfection in sub-Saharan Africa, which is known to increase the risk of vertical transmission of HCV and requires further investigation.31 Finally, despite the fact that Central Asia is estimated

to have the highest total prevalence based on very limited data, the high prevalence of immigrants from Uzbekistan (31%) in a study of former Soviet Union immigrants in New York suggests the plausibility of these estimates.32 In conclusion, this analysis highlights the age group with the highest probability for sequelae, i.e., the group with peak prevalence that deserves attention for screening and treatment in each region. Further, it sets the stage for modeling the current and future global burden of HCV-related disease based on seroprevalence and natural history that 5%-20% will go on to develop cirrhosis over a period of 20-30 years and 1%-5% will die from the consequences of chronic infection.33-35 This study also identifies challenges in producing useful “global” and even “regional” estimates for hepatitis C.

We have shown that phosphorylation of C/EBPb-Thr21/ by Ribosomal-S6 Kinase (RSK) induces injury and inflammation but the molecular mechanisms remain unknown. Hypothesis: Phosphorylation of C/EBPb-Thr217 induces

activation of the Inflammasome in liver macrophages and the consequent liver injury. Methods: Liver macrophages were isolated from control G/EBPb-wf, and from transgenic mice expressing either a phosphorylation mimic C/EBPb-Glu2l7, or a non-phosphorylatable G/EBPb-Ala217. The inactive Inflammasome complex was identified by the presence of procaspase-1, pro-IL-1b and proIL-18, inactive NF-қB, non-signaling MyD-88 and Interferon-Regulatory Factor (IRF)−4 while the active Inflammasome complex was identified by the presence of caspase-1, IL-1b, IL-18, ITF2357 cost nuclear NF-қB, signaling MyD-88, adaptor aSg, IfR-5 and NALP-3 (Nat lmmunol. 10: 241,2009) Results: Treatment of learn more G/EBPb-wt mice with GGl4, Fas or dimethyl-nitrosamine induced C/EBPb-Thr21/ phosphorylation, which was physically associated with the activated Inflammasome complex (caspase-1, IRF-5 ASG and NALP-3) in liver macrophages. In contrast, both the G/EBPb-Ala217 mice and G/EBPb-wt mice treated with G/EBPb-Ala217 peptides were refractory to the assembly and activation of the

Inflammasome. The C/EBPbGlu217 mice were highly susceptible to hepatotoxin-induced activation of the Inflammasome, which assembled with C/EBPbGlu217. Cultured liver macrophages from G/EBPb-wt, G/EBPbAla217 and C/EBPb-Glu217 had a response to TGFa-induced C/EBPb-Thr2 17 phosphorylation and its assembly within the activated Inflammasome essentially identical to their respective in vivo animal models. Further, Fas-L induced liver macrophage activation and severe liver injury in C/EBPb-Glu21/ mice (ALT: 1//0 丨し/ml) compared to mice expressing the G/EBPb-Ala217 transgene (ALT: 182 Iし/ml; P < 0.0001). In addition, the G/EBPb-Ala21/ peptide stimulates the switch to non-inflammatory liver macrophages after acute dimethyl-nitrosamine or GGl4 administration to G/EBPb-wt mice. The peptide or transfer of myeloid cells from G/EBPb-Ala217

(but not from G/EBPbGlu2 17) mice normalized the increased Inflammasome activation and prevented liver injury (P < 0.001 for both). Conclusion: Phosphorylation PJ34 HCl of C/EBPb-Thr2 17 is required for the Inflammasome Complex assembly and activation in liver macrophages and for the consequent liver injury. The RSKG/EBPb phosphorylation pathway is a potential therapeutic target for liver injury. Disclosures: The following people have nothing to disclose: Martina Buck, Mario Chojkier Introduction: The inflammasome is a cytosolic protein complex that is central to the production of IL-1 p, and has important roles in chronic liver inflammation and fibrosis. Activation requires two signals but it is not known how inflammasome activity is sustained.

The adoption of the roadmap concept, with testing of HBV DNA at week 24, might further minimize resistance. In summary, the study by

selleckchem Liu and colleagues has provided further evidence that off-treatment virological response is not durable, even with adherence to strict cessation criteria. For both HBeAg-positive and -negative patients, the ideal treatment end-points in the era of potent antiviral therapy with low resistance should be the seroclearance of HBsAg. “
“Pancreatic ductal adenocarcinoma represents the commonest type of pancreatic exocrine neoplasm.[1] Early diagnosis of pancreatic cancer is desirable but challenging. Despite improvement in imaging technology, most cases of pancreatic cancers are diagnosed at a late stage, which often precludes surgical resection.[1, 2] Prognosis of advanced pancreatic cancer remains poor, with a 5-year survival rate being less than 10%.[2] Epidemiologically, pancreatic cancer has been thought to affect more people in the Western countries. Although traditionally low incidence rates of pancreatic cancer have been reported in most Asian countries, recent epidemiological

data have shown that the pancreatic cancer incidence has increased over the years in Japan and South Korea, with rates approaching https://www.selleckchem.com/products/abc294640.html that of the Western world.[3] In addition, the pancreatic cancer related mortality in these two Asian countries also approximates that in the United States and Europe.[3] In this issue of the Journal, Kongkam et al. reviewed the epidemiology of pancreatic cancer in Asia and the use of endoscopic ultrasound (EUS) in the evaluation of pancreatic cancer.[4] While the incidence of pancreatic cancer varies in different Asian countries, the authors hope to achieve early detection

of this dreaded malignancy by the use of EUS. In this article, the authors reviewed the fundamental roles of EUS in detection, staging, and tissue acquisition by fine needle aspiration (FNA) of suspected pancreatic cancer. The potential benefits of newer technologies such as contrast harmonic EUS (CH-EUS) and EUS elastography in differentiating pancreatic cancer from other pancreatic neoplasms Immune system were also discussed. Although noninvasive cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are often the first step in the evaluation of suspected pancreatic neoplasm, small pancreatic lesions that are not observed initially on CT or MRI but are eventually picked up by EUS are not uncommon. In studies comparing EUS with multi-detector CT, EUS is shown to have a higher detection rate for small pancreatic masses.[5-7] Accurate preoperative imaging and staging are vital to identifying potentially resectable pancreatic cancers. However, these lesions are often more difficult to detect due to their relatively smaller size.

AAV vectors have been shown to be able to introduce specific mutations, including insertions,

into homologous chromosomal sequences of many cell types and species.13, 14 In addition, AAV-mediated gene targeting has been shown to be more efficient than conventional techniques based on transfection or electroporation of plasmid constructs.15-17 The goal of this study was to develop a more efficient method to create pig knockout models of human diseases and to create Fah-null heterozygote pigs to PLX3397 manufacturer be used to generate homozygote Fah-null animals for future studies related to metabolic liver disease, cirrhosis, HCC, and cell and gene therapy. We used for the first time the novel chimeric AAV-DJ serotype to disrupt the porcine Fah gene by targeted gene knockout by homologous recombination. We report here on the successful and efficient generation of targeted Fah-null heterozygote fibroblasts and their use by SCNT to generate Fah-null heterozygote pigs. AAV, adeno-associated virus; CF, cystic fibrosis; FAH, fumarylacetoacetate hydrolase; HCC, hepatocellular carcinoma; HT1, hereditary type I tyrosinemia; Dabrafenib supplier SCNT, somatic cell nuclear transfer. Genomic DNA was isolated and purified (Qiamp; Qiagen) from pig fetal liver. Two fragments of DNA, adjacent to exon 5 of the Fah locus of chromosome 7, were amplified

using primers MG2616 and MG2678 (left homologous recombination arm; 1479 basepairs [bp]) and MG2619 and MG2680 (right homologous recombination arm; 1523 bp) and a high-fidelity polymerase (Phusion; Finnzymes). Primers were designed based on the domestic pig working draft genomic sequence (GenBank accession numbers CU468492 and CU467891).

These polymerase chain reaction (PCR) products were subcloned into pCR-Blunt II-TOPO (Invitrogen) and confirmed by restriction digest and sequencing. The overall strategy to knockout the Fah gene was to insert an in-frame stop codon and a neomycin-resistance cassette (PGK-neo) into exon 5 of the porcine Fah gene. To generate a PGK-neo expression cassette, with an additional in-frame Glutamate dehydrogenase TGA stop codon at the 5′ end, a 1681 bp fragment was amplified using primers MG2622 and MG2679, subcloned into pCR-Blunt II-TOPO, and confirmed by restriction digest and sequencing. To generate the complete targeting vector, each fragment was sequentially subcloned into pcDNA3.1- (Invitrogen) and orientation confirmed by restriction digest and sequencing. Once the full-sized 4683 bp-targeting construct was generated, it was cloned into an AAV2 plasmid backbone, thus providing it with the inverted terminal repeat (ITR) sequences required for viral packaging. Plasmids containing the AAV-DJ shuffle capsid sequences were generously provided by Dr. Mark Kay at Stanford. AAV-DJ virus containing the Fah-null construct was produced using a standard triple plasmid transfection protocol, as described.