Most indole-3-acetic acid (IAA) in higher plants is conjugated to amino acids, sugars, or peptides, and these conjugates are implicated in regulating the concentration of the free hormone. We identified iar1 as an Arabidopsis mutant that is resistant to the inhibitory effects of several IAA-amino acid conjugates but remains sensitive to free IAA. iar1 partially suppresses phenotypes of a mutant that overproduces IAA, suggesting that IAR1 participates in auxin metabolism or response. We used positional information to clone IAR1, which encodes a novel protein with seven predicted transmembrane domains and several His-rich regions. IAR1 has homologs in other multicellular organisms, including Drosophila, nematodes, and mammals; in addition, the mouse homolog KE4 can functionally substitute for IAR1 in vivo. IAR1 also structurally resembles and has detectable sequence similarity to a family of metal transporters. We discuss several possible roles for IAR1 in auxin homeostasis.

This study was conducted to examine factors affecting health insurance and employment status in long-term liver transplant (OLT) recipients. All adult primary OLT recipients surviving at least 1 year were surveyed using existing questionnaires. Out of 217 eligible recipients, 186 (86%) responded. The median age of respondents was 55 years with a median survival after OLT of 3.4 years. The majority (98%) of respondents had health insurance coverage. Thirty-four (18%) reported having lost and/or having been denied health insurance since OLT, and 63 (34%) switched health insurance since OLT. Of the 179 that reported employment status, 98 (55%) were employed, including homemakers and students, while 39 (22%) were retired and 42 (24%) unemployed. The majority (76%) of those unemployed cited poor health as the reason for unemployment, followed by 5 (12%) who feared loss of disability or Medicaid benefits. Fourteen reported to have been denied or terminated from employment because of their transplant. In the regression analysis, employment prior to transplantation (odds ratio (OR) = 5.1), age less than 57 (OR = 5.1), physical function score >52.4 (OR = 3.6) and general health score >33.3 (OR = 7.6) were significantly associated with employment. These data may help identify high-risk pre-OLT patients for intervention measures such as work rehabilitation.

Most indole-3-acetic acid (IAA) in higher plants is conjugated to amino acids, sugars, or peptides, and these conjugates are implicated in regulating the concentration of the free hormone. We identified iar1 as an Arabidopsis mutant that is resistant to the inhibitory effects of several IAA-amino acid conjugates but remains sensitive to free IAA. iar1 partially suppresses phenotypes of a mutant that overproduces IAA, suggesting that IAR1 participates in auxin metabolism or response. We used positional information to clone IAR1 , which encodes a novel protein with seven predicted transmembrane domains and several His-rich regions. IAR1 has homologs in other multicellular organisms, including Drosophila, nematodes, and mammals; in addition, the mouse homolog KE4 can functionally substitute for IAR1 in vivo. IAR1 also structurally resembles and has detectable sequence similarity to a family of metal transporters. We discuss several possible roles for IAR1 in auxin homeostasis. INTRODUCTIONIndole-3-acetic acid (IAA) is the major endogenous auxin and participates in many plant developmental processes, including cell enlargement and division, differentiation of vascular tissue, initiation of lateral roots, apical dominance, and responses to environmental stimuli such as gravity and light (reviewed by Estelle and Klee, 1994; Bennett et al., 1998). Plants contain little free IAA; most IAA is found conjugated to amino acids, peptides, sugars, or high molecular weight glycans. These conjugates have been implicated in such processes as storage, transport, and protection from oxidative degradation (reviewed in Cohen and Bandurski, 1982; Bandurski et al., 1995). Plants apparently also permanently inactivate excess IAA by conjugation (reviewed in Normanly, 1997). For example, many plants form IAA-Asp as an intermediate in IAA catabolism (Tsurumi and Wada, 1986;Monteiro et al., 1988;Tuominen et al., 1994;Östin et al., 1998).Conjugation and hydrolysis of conjugates are probable mechanisms used to regulate the concentrations of free IAA (reviewed in Normanly and Bartel, 1999), and characterization of the genes involved in these processes is a prerequisite to understanding this regulation. Although diverse land plants conjugate IAA to glucose and other molecules (Sztein et al., 1995(Sztein et al., , 1999, the only plant gene so involved that has been identified is the maize iaglu gene, which encodes an enzyme esterifying IAA to glucose (Szerszen et al., 1994). Various plants hydrolyze IAA conjugates, and IAA-glucose hydrolases have been identified in maize, potato, oat, and bean (Kowalczyk and Bandurski, 1990; Jakubowska et al., 1993). IAA-Ala hydrolases have been partially purified from bean and carrot (Cohen et al., 1988; Kuleck and Cohen, 1993), and Chinese cabbage extracts contain isoenzymes that hydrolyze IAA-Ala, IAA-Asp, and IAA-Phe (LudwigMüller et al., 1996).The ability of several IAA conjugates to mimic the effects of free IAA on plant growth (reviewed by Bartel, 1997) has been exploited to identify Arabidopsis mutan...

Objectives To describe the prevalence, distribution and risk factors for hepatitis C virus (HCV) infection among homeless adults using eight Health Care for the Homeless (HCH) clinics nationally. Methods Data were collected for 387 participants through blood draws, structured interviews, chart reviews. Results Overall prevalence of HCV-antibody positivity was 31.0%, including 70.0% among injection drug users and 15.5% among reported non-injectors. Much HCV infection was “hidden” as the majority (53.3%) of HCV-antibody positive participants was unaware of their status. Independent risk factors for HCV among the total sample included injection drug use, prison and tattoos; among injectors, risk factors included prison and ≥ 3 years of injection drug use; and among reported non-injectors, risk factors included tattoos and prison. Conclusion These HCH clinics serve high concentrations of HCV-infected injectors, making these and similar clinics priority intervention sites for aggressive screening, education, testing, and treatment for HCV and other blood-borne diseases.

BackgroundSpecialist physician concentration in urban areas can affect access and quality of care for rural patients. As effective drug treatment for hepatitis C (HCV) becomes increasingly available, the extent to which rural patients needing HCV specialists face access or quality deficits is unknown. We sought to determine the influence of rural residency on access to HCV specialists and quality of liver care.MethodsThe study used a national cohort of 151,965 Veterans Health Administration (VHA) patients with HCV starting in 2005 and followed to 2009. The VHA’s constant national benefit structure reduces the impact of insurance as an explanation for observed disparities. Multivariate cox proportion regression models for each quality indicator were performed.ResultsThirty percent of VHA patients with HCV reside in rural and highly rural areas. Compared to urban residents, highly rural (HR 0.70, CI 0.65-0.75) and rural (HR 0.96, CI 0.94-0.97) residents were significantly less likely to access HCV specialty care. The quality indicators were more mixed. While rural residents were less likely to receive HIV screening, there were no significant differences in hepatitis vaccinations, endoscopic variceal and hepatocellular carcinoma screening between the geographic subgroups. Of note, highly rural (HR 1.31, CI 1.14-1.50) and rural residents (HR 1.06, CI 1.02-1.10) were more likely to receive HCV therapy. Of those treated for HCV, a third received therapy from a non-specialist provider. ConclusionRural patients have less access to HCV specialists, but this does not necessarily translate to quality deficits. The VHA's efforts to improve specialty care access, rural patient behavior and decentralization of HCV therapy beyond specialty providers may explain this contradiction. Lessons learned within the VHA are critical for US healthcare systems restructuring into accountable care organizations that acquire features of integrated systems.

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The treatment of alcoholic hepatitis remains one of the most debated topics in medicine and a field of continued research. In this review, we discuss the evolution of scoring systems, including the recent development of the Glasgow alcoholic hepatitis score, role of liver biopsy and current treatment interventions. Studies of treatment interventions with glucocorticoids, pentoxifylline, infliximab, s-adenosyl-methionine, and colchicine are reviewed with discussion on quality. Glucocorticoids currently remain the mainstay of treatment for severe alcoholic hepatitis.

Background and Aim The American Association for the Study of Liver Disease (AASLD) recommends screening for esophageal varices (EV) by esophagoduodenoscopy (EGD) in patients with cirrhosis to guide decisions regarding primary prophylaxis for EV hemorrhage. We aimed to identify patient and facility factors associated with EV screening in veterans with hepatitis C (HCV)-associated cirrhosis. Methods This was a population-based cohort study. Veterans with HCV and newly diagnosed cirrhosis between 1/1/2004 and 12/31/2005 and followed until 12/31/2011 were included. The primary outcome was receipt of EGD within 1 year of cirrhosis diagnosis. Patient- and facility-level factors associated with EV screening were determined. Results A total of 4230 patients with HCV cirrhosis were identified. During median follow-up of 6.1 years (IQR: 4.0–8.0), 21.5 % developed a decompensating event, and 38.3 % died. Fifty-four percent received an EGD, and 33.8 % had an EGD within guidelines. Median time from cirrhosis diagnosis to EGD was 72 days (IQR: 12–176). Factors independently associated with receipt of EV screening were a decompensation event (OR 1.16, CI 1.01–1.32) and gastroenterology/hepatology clinic access (OR 2.1, CI 1.73–2.46), whereas cardiovascular (OR 0.81, CI 0.69–0.95), mental health (OR 0.79, CI 0.68–0.91), and respiratory (OR 0.85, CI 0.72–0.99) comorbidities were associated with reduced likelihood of EV screening. Conclusion EV screening per AASLD guidelines occurs in only one-third of patients. This missed opportunity was strongly associated with access to gastroenterology/hepatology specialty care. Additionally, providers may be relying on clinical cues (i.e., decompensation) to prompt referral for endoscopy suggesting education to improve compliance with guidelines is needed.