Do Soluble Phosphates Direct the Formose Reaction towards Pentose Sugars?

The formose reaction has been a leading hypothesis for the prebiotic synthesis of sugars such as ribose for many decades but tends to produce complex mixtures of sugars and often tars. Channeling the formose reaction towards the synthesis of biologically useful sugars such as ribose has been a holy grail of origins-of-life research. Here, we tested the hypothesis that a simple, prebiotically plausible phosphorylating agent, acetyl phosphate, could direct the formose reaction towards ribose through phosphorylation of intermediates in a manner resembling gluconeogenesis and the pentose phosphate pathway. We did indeed find that addition of acetyl phosphate to a developing formose reaction stabilized pentoses, including ribose, such that after 5 h of reaction about 10-fold more ribose remained compared with control runs. But mechanistic analyses using liquid chromatography-mass spectrometry showed that, far from being directed towards ribose by phosphorylation, the formose reaction was halted by the precipitation of Ca2+ ions as phosphate minerals such as apatite and hydroxyapatite. Adding orthophosphate had the same effect. Phosphorylated sugars were only detected below the limit of quantification when adding acetyl phosphate. Nonetheless, our findings are not strictly negative. The sensitivity of the formose reaction to geochemically reasonable conditions, combined with the apparent stability of ribose under these conditions, serves as a valuable constraint on possible pathways of sugar synthesis at the origin of life.

Randomised clinical study: GR-MD-02, a galectin-3 inhibitor, vs. placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis. AIM: To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR-MD-02 in subjects having NASH with bridging fibrosis. METHODS: The GT-020 study was a first-in-human, sequential dose-ranging, placebo controlled, double-blinded study with the primary objective to assess the safety, tolerability and dose limiting toxicity of GR-MD-02, in subjects with biopsy-proven NASH with advanced fibrosis (Brunt stage 3). The secondary objectives were to characterise first-dose and multiple-dose pharmacokinetic profiles and to evaluate changes in potential serum biomarkers and liver stiffness as assessed by FibroScan. RESULTS: GR-MD-02 single and three weekly repeated of 2, 4 and 8 mg/kg revealed no meaningful clinical differences in treatment emergent adverse events, vital signs, electrocardiographic findings or laboratory tests. Pharmokinetic parameters showed a dose-dependent relationship with evidence of drug accumulation following 8 mg/kg (~twofold). CONCLUSIONS: GR-MD-02 doses were in the upper range of the targeted therapeutic dose determined from pre-clinical data and were safe and well tolerated with evidence of a pharmacodynamic effect. These results provide support for a Phase 2 development programme in advanced fibrosis due to NASH.

The prevalence of NAFLD and NASH among patients with psoriasis in a tertiary care dermatology and rheumatology clinic.

BACKGROUND: Psoriasis has been linked to metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Data suggest that the prevalence of NAFLD is increased in patients with psoriasis. The aim of this study was to determine the prevalence and severity of NAFLD in this patient population. AIM: To determine the prevalence of both NAFLD and non-alcoholic steatohepatitis (NASH) in patients with psoriasis. METHODS: Patients between the ages of 18 and 70 years with a diagnosis of psoriasis or psoriatic arthritis and followed by either the Dermatology or Rheumatology Division within the Department of Medicine at San Antonio Military Medical Center were considered for enrollment. Each patient completed a questionnaire, underwent a thorough skin evaluation, and had a right upper quadrant ultrasound and fasting blood work. If the liver enzymes were elevated or fatty liver detected on imaging, percutaneous liver biopsy was recommended. RESULTS: One hundred and twenty-nine patients were enrolled and 103 completed all necessary studies. The participants were predominantly middle aged (52.7 ± 12) and overweight or obese (average BMI 30.1 ± 5.9, range: 19.8-52.5 kg/m(2)). 53% (n = 54) were male while 15% (n = 15) of participants identified themselves as being a diabetic. The overall prevalence of NAFLD was 47%. The overall prevalence of NASH was 22% in those who underwent biopsy. CONCLUSIONS: Non-alcoholic fatty liver disease is very common among our cohort of patients with psoriasis, occurring in roughly 47% of patients. The more progressive form of the disease, NASH, is found in approximately one in five patients. Health care providers should be mindful of this association given the high prevalence of both NAFLD and NASH in this cohort of patients.

Hepatitis C and lipid metabolism, hepatic steatosis, and NAFLD: still important in the era of direct acting antiviral therapy?

Chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) have an individual prevalence of 1.8-3% and at least 30%, respectively, in the United States. It is therefore not surprising that there is overlap between these two common chronic liver diseases, although the relationship appears to go beyond isolated co-existence. Hepatic steatosis is a common feature of CHC infection and can be related to both metabolic and viral specific factors. Steatosis in the setting of nongenotype 3 CHC has been predictive of response to therapy prior to the advent of the direct acting antiviral medications (DAAs). Similarly, lipid metabolism appears important in response to CHC treatment. The pathways for both lipid homeostasis and NAFLD as it pertains to CHC infection as well as the utilization of statin therapy in CHC infection will be reviewed with a focus on the relevance of these topics in the era of DAA therapy.

Unconjugated hyperbilirubinemia is inversely associated with non-alcoholic steatohepatitis (NASH).

BACKGROUND: It has been recognised that unconjugated bilirubin contains hepatic anti-fibrogenic and anti-inflammatory properties and is a potent physiological antioxidant cytoprotectant. We believe that unconjugated hyperbilirubinemia may protect against development of non-alcoholic steatohepatitis (NASH). AIM: This study was conducted to assess the association of serum unconjugated bilirubin levels and histological liver damage in non-alcoholic fatty liver disease (NAFLD). METHODS: This was a retrospective analysis involving adult patients from a tertiary medical centre undergoing liver biopsy to evaluate suspected NAFLD or NASH and a control group without NAFLD based on normal liver ultrasound, labs and history. Identification of unconjugated hyperbilirubinemia was based on the presence of predominantly unconjugated bilirubin ≥1.0 mg/dL (17.1 µmol/L) while fasting, in the absence of haemolytic disease or other hepatic function alteration. RESULTS: Six-hundred and forty-one patients were included. Unconjugated hyperbilirubinemia was inversely associated with NASH (OR 16.1, 95% CI 3.7-70.8 P < 0.001). Of the patients without NAFLD (133 patients), 13 (9.8%) had unconjugated hyperbilirubinemia (range 1.0-1.8, mean 1.4). Of the patients with NAFLD without NASH (285 patients), 32 (11.2%) had unconjugated hyperbilirubinemia (range 1.0-3.0, mean 1.4). Of the patients with NASH (223 patients), three (1.3%) had unconjugated hyperbilirubinemia (1.0, 1.1, 1.4). CONCLUSIONS: Unconjugated hyperbilirubinemia is inversely associated with the histopathological severity of liver damage in non-alcoholic fatty liver disease.

Interleukin 28B polymorphisms are the only common genetic variants associated with low-density lipoprotein cholesterol (LDL-C) in genotype-1 chronic hepatitis C and determine the association between LDL-C and treatment response.

Low-density lipoprotein cholesterol (LDL-C) levels and interleukin 28B (IL28B) polymorphism are associated with sustained viral response (SVR) to peginterferon/ribavirin (pegIFN/RBV) for chronic hepatitis C (CHC) infection. IL28B has been linked with LDL-C levels using a candidate gene approach, but it is not known whether other genetic variants are associated with LDL-C, nor how these factors definitively affect SVR. We assessed genetic predictors of serum lipid and triglyceride levels in 1604 patients with genotype 1 (G1) chronic hepatitis C virus (HCV) infection by genome-wide association study and developed multivariable predictive models of SVR. IL28B polymorphisms were the only common genetic variants associated with pretreatment LDL-C level in Caucasians (rs12980275, P = 4.7 × 10(-17), poor response IL28B variants associated with lower LDL-C). The association was dependent on HCV infection, IL28B genotype was no longer associated with LDL-C in SVR patients after treatment, while the association remained significant in non-SVR patients (P < 0.001). LDL-C was significantly associated with SVR for heterozygous IL28B genotype patients (P < 0.001) but not for homozygous genotypes. SVR modelling suggested that IL28B heterozygotes with LDL-C > 130 mg/dL and HCV RNA ≤600 000 IU/mL may anticipate cure rates >80%, while the absence of these two criteria was associated with an SVR rate of <35%. IL28B polymorphisms are the only common genetic variants associated with pretreatment LDL-C in G1-HCV. LDL-C remains significantly associated with SVR for heterozygous IL28B genotype patients, where LDL-C and HCV RNA burden may identify those patients with high or low likelihood of cure with pegIFN/RBV therapy.

Peroxisome proliferator-activated receptors and hepatitis C virus.

The prevalence of type 2 diabetes mellitus and insulin resistance are higher among people chronically infected with hepatitis C (CHC) when compared with the general population and people with other causes of chronic liver disease. Both insulin resistance and diabetes are associated with adverse outcomes across all stages of CHC, including the liver transplant population. CHC is also associated with the development of hepatic steatosis, a common histological feature present in approximately 55% (32-81%) of cases. There is a complex interrelationship between insulin resistance and hepatic steatosis and both are postulated to aggravate each other. The peroxisome proliferator-activated receptors (PPARs) are nuclear factors involved in the regulation of glucose, lipid homeostasis, inflammatory response, cell differentiation, and cell cycle. The relationship between hepatitis C virus replication and PPARs has been the focus of recent study. Given the availability of potent agonists, PPARs may represent a novel pharmacological target in the treatment of CHC.

Validation of the non-alcoholic fatty liver disease activity score.

BACKGROUND: The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) is a scoring system designed by the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) to encompass the spectrum of NAFLD and evaluate histological changes. However, the NAS and the correlation between the NAS and a diagnosis of NASH have not been validated outside the NASH CRN. AIM: To validate the NAS outside the NASH CRN. METHODS: This study retrospectively examined liver biopsies from adults with NAFLD or steatohepatitis obtained from January 2003 to May 2010. Biopsy specimens were evaluated twice in a blinded manner by a single hepatopathologist, once to determine a diagnosis (steatohepatitis or steatosis/not-steatohepatitis), and a second time to determine the NAS. RESULTS: A total of 386 liver biopsies were evaluated. Mean age of patients at time of biopsy was 49.9±10.2years. NASH was found in 51% of the patients. For NAS ≥5 as a diagnosis of steatohepatitis and NAS <5 for not-steatohepatitis, the sensitivity was 57%, specificity: 95%, negative predictive value (NPV): 68% and positive predictive value (PPV): 93%. Lowering the NAS to ≥4 as a diagnosis of steatohepatitis increased the sensitivity to 85% with a decrease in specificity to 81%; NPV: 84%, PPV: 82% and Cohen's kappa 0.658. CONCLUSIONS: The NAFLD activity score is a valid scoring system encompassing the spectrum of NAFLD with an excellent level of agreement between the histological diagnosis and the NAFLD activity score. A NAFLD activity score ≥4 has optimal sensitivity and specificity for predicting steatohepatitis, and is the recommended value for admission into an interventional trial for NASH.

Quantitative trait loci in the Ogle/TAM O-301 oat mapping population controlling resistance to Puccinia coronata in the field.

Crown rust is the most damaging disease of cultivated oat (Avena sativa) and genetic resistance is the primary means of controlling the disease. Quantitative trait loci (QTL) with major and minor effects have been identified in Ogle1040 and TAM O-301 (most notably, Pc58 and PcNQMG/LGCG from TAM O-301 and OT-27 from Ogle1040) through single-isolate greenhouse and field tests. To map loci and determine the effectiveness of previously identified QTL against naturally occurring pathogen populations in highly disease-conducive environments, the Ogle/TAM O-301 (OT) recombinant inbred line (RIL) population was grown in Texas and Louisiana over 2 years and in Manitoba, Canada. The genetic region characterized by the Pc58 resistance gene complex, particularly Pc58a, accounted for most of the diseased leaf area (DLA) and infection type (IT) variance in all five experiments. Additionally, the genetic region characterized by PcNQMG/LGCG accounted for a portion of the IT variance in three experiments. Although no QTL was detected on OT-27 in this study, all the markers on this linkage group were associated (P < 0.0001) with reducing both IT and DLA using single-marker analysis. Screening with 25 Puccinia coronata isolates from six different states indicated that Pc58abc and Pc58a were highly effective, while characterization using F(2) populations derived from OT RILs containing the two main genetic regions responsible for crown rust resistance in TAM O-301 (Pc58 and PcNQMG/LGCG) and a minor QTL in Ogle (OT-27) indicated that Pc58a, in combination with a locus in Ogle1040, provided high levels of resistance to natural races in Texas. This study provides new information and key loci in OT mapping population and may be useful for effective control of crown rust in North America.

The Effect of Metformin and Standard Therapy versus Standard Therapy alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial.

Nonalcoholic steatohepatitis (NASH) is increasing in prevalence and is related to underlying insulin resistance. The aim of this study was to assess the efficacy of metformin on the characteristic histopathologic lesions of NASH. This was a 12-month prospective, randomized, placebo-controlled trial comparing diet and exercise alone to diet, exercise and metformin in nondiabetic patients with insulin resistance and NASH. Patients were randomized to either group A or B. Group A received placebo, dietary counseling, recommendations for weight loss and exercise four times per week. Group B received long-acting metformin 500 mg daily (titrated to 1000 mg daily) plus dietary counseling, recommendations for weight loss and exercise four times per week. Histopathology was assessed at 12 months and biopsies were scored by two pathologists who were blinded to all data. Twenty-three subjects were screened and 19 were randomized to either group A (n »10) or group B (n» 9). Seven of the 10 subjects in group A completed the study including repeat liver biopsy while all patients in group B completed the study. Body mass index improved in both groups decreasing by 1.7 kg/m(2) in group A and 0.9 kg/m(2) in group B (not significant, control versus treatment). Homeostasis model assessment of insulin resistance scores improved in both groups decreasing by 1.14 in group A and 1.58 in group B (not significant, control versus treatment). No significant difference in histopathology was seen between groups on follow-up liver biopsy. Metformin appeared to have little effect in improvement in liver function tests or liver histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA-IR scores, serum aminotransferases and liver histology.

Nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common chronic liver condition in many parts of the world. It is a heterogeneous disease encompassing a broad spectrum of histologic states characterized universally by macrovesicular hepatic steatosis. NAFLD is now recognized as the hepatic manifestation of the metabolic syndrome and is a major cause of liver-related morbidity and mortality. The prevalence of the disease is increasing, tied closely to the increased prevalence of insulin resistance in industrialized countries. Risk factors for NAFLD include obesity, diabetes, insulin resistance, and hypertriglyceridemia. The clinical course of NAFLD depends upon the histologic subtype. Patients with simple hepatic steatosis generally are thought to have a benign long-term prognosis. However, nonalcoholic steatohepatitis can progress to cirrhosis and may have a similar prognosis as cirrhosis from other liver disease with progression to end stage liver disease and hepatocellular carcinoma. The decision to obtain a biopsy is determined by weighing the risks of the biopsy against the information obtained from the biopsy. No standardized therapeutic approach exists although many promising modalities are under investigation. This paper presents an overview of the incidence and prevalence of disease, diagnosis, histologic spectrum, natural history, pathogenesis, clinical course, and current treatment of nonalcoholic fatty liver disease.

Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease.

BACKGROUND: Clinical predictors of advanced non-alcoholic liver disease (NAFLD) are needed to guide diagnostic evaluation and treatment. METHODS: To better understand the demographics of NAFLD and risk factors for advanced disease, this study analysed 827 patients with NAFLD at two geographically separate tertiary medical centres. RESULTS: The cohort was 51% female and had a median body mass index (BMI) of 33 kg/m(2); 3% had a normal BMI. Common co-morbidities included hypertension (60%) and diabetes (35%); insulin resistance was present in 91% and advanced fibrosis in 24% of patients. When comparing patients with no fibrosis or mild fibrosis to those with advanced fibrosis, BMI > or = 28 kg/m(2), age > 50 years, and aspartate transaminase/alanine aminotransferase (AST/ALT) ratio > or = 0.8, a quantitative assessment check index (QUICKI) score < 0.294 (equivalent to homeostasis model assessment (HOMA) > 6.2) and the presence of diabetes mellitus (DM) were individually associated by univariate analysis with odds ratios (ORs) of > or = 2.4 for advanced fibrosis. Based on the results of forced entry logistic regression analysis, three variables were combined in a weighted sum (BMI > or = 28 = 1 point, AAR of > or = 0.8 = 2 points, DM = 1 point) to form an easily calculated composite score for predicting advanced fibrosis called the BARD score. A score of 2-4 was associated with an OR for advanced fibrosis of 17 (confidence interval 9.2 to 31.9) and a negative predictive value of 96%. CONCLUSIONS: Insulin resistance and its co-morbidities are often present in patients with NAFLD. An easily calculated score based on readily available clinical data can reliably exclude the presence of advanced fibrosis in these patients, particularly among non-diabetics.

Review article: nonalcoholic fatty liver disease and hepatitis C virus--partners in crime.

BACKGROUND: Both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) are frequent causes of chronic liver disease. In recent years, there have been significant revelations as regards the relationship between NAFLD and CHC. AIM: To conduct a systematic, evidence-based review of the epidemiology, pathophysiology and potential treatments of coexistent NAFLD and CHC. METHODS: The terms such as hepatitis C, fatty liver, NAFLD, nonalcoholic steatohepatitis and steatosis were searched on PubMed up to January 2008. References from selected articles and pertinent abstracts were also included. RESULTS: Hepatic steatosis affects up to 80% of patients with CHC and is dependent on both viral and host factors. While insulin resistance (IR) is associated with hepatic steatosis and hepatitis C virus, genotype-specific pathogenic mechanisms have been identified and are currently the focus of intense investigation in the literature. Clinical implications of concurrent NAFLD, CHC and IR include increased disease progression, elevated risk of hepatocellular carcinoma, and decreased response to antiviral therapy. CONCLUSIONS: NAFLD and IR are common in patients with CHC virus infection. IR is a driving force in the development of hepatic steatosis. Because of the clinical implications of hepatic steatosis and IR in the setting of CHC, further studies evaluating treatments, which may increase response to antiviral therapy, are needed.

Evaluation of Components of Fusarium Head Blight Resistance in Soft Red Winter Wheat Germ Plasm Using a Detached Leaf Assay.

A large environmental influence on phenotypic estimates of disease resistance and the complex polygenic nature of Fusarium head blight (FHB) resistance in wheat (Triticum aestivum) are impediments to developing resistant cultivars. The objective of this research was to investigate the utility of a detached leaf assay, inoculated using inoculum from isolates of Microdochium nivale var. majus, to identify components of FHB resistance among 30 entries of U.S. soft red winter wheat in the 2002 Uniform Southern FHB Nursery (USFHBN). Whole plant FHB resistance of the USFHBN entries was evaluated in replicated, mist-irrigated field trials at 10 locations in eight states during the 2001-2002 season. Incubation period (days from inoculation to the first appearance of a dull gray-green water-soaked lesion) was the only detached leaf variable significantly correlated across all FHB resistance parameters accounting for 45% of the variation in FHB incidence, 27% of FHB severity, 30% of Fusarium damaged kernels, and 26% of the variation in grain deoxynivalenol (DON) concentration. The results for incubation period contrasted with previous studies of moderately resistant European cultivars, in that longer incubation period was correlated with greater FHB susceptibility, but agreed with previous findings for the Chinese cultivar Sumai 3 and CIMMYT germ plasm containing diverse sources of FHB resistance. The results support the view that the detached leaf assay method has potential for use to distinguish between specific sources of FHB resistance when combined with data on FHB reaction and pedigree information. For example, entry 28, a di-haploid line from the cross between the moderately resistant U.S. cultivar Roane and the resistant Chinese line W14, exhibited detached leaf parameters that suggested a combination of both sources of FHB resistance. The USFHBN represents the combination of adapted and exotic germ plasm, but four moderately resistant U.S. commercial cultivars (Roane, McCormick, NC-Neuse, and Pat) had long incubation and latent periods and short lesion lengths in the detached leaf assay as observed in moderately FHB resistant European cultivars. The dichotomy in the relationship between incubation period and FHB resistance indicates that this may need to be considered to effectively combine exotic and existing/adapted sources of FHB resistance.

A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients.

BACKGROUND: Treatment options for non-alcoholic steatohepatitis (NASH) are limited. Weight loss remains the most recommended therapy. Orlistat is an effective adjunct to dietary weight loss therapy. AIM: To evaluate the efficacy of orlistat, given for 6 months to patients with obesity and biopsy confirmed NASH. METHODS: Ten obese patients with biopsy proven NASH were enrolled. Orlistat was given with meals for 6 months. Body Mass Index (BMI), liver enzymes, haemoglobin A1c, fasting lipids and glucose were assessed at baseline and at completion of the study. Paired liver histology was obtained. RESULTS: Six women and four men were enrolled. The mean weight loss was 22.7 lb and ranged from 0 to 24.3%. The following clinical values significantly improved: mean BMI: 43.4-39.8 (P = 0.007); mean haemoglobin A1c (%): 7.14-5.95 (P = 0.021); mean alanine aminotransferase (ALT) (U/L): 93 -54 (P = 0.009); and mean aspartate aminotransferase (AST) (U/L): 79-48 (P = 0.008). Steatosis improved in six patients, and fibrosis improved in three patients. CONCLUSIONS: Orlistat therapy and dietary counselling were associated with significant decreases in body weight, haemoglobin A1c, ALT and AST. A 10% or greater reduction in weight improved steatosis and fibrosis as well as haemoglobin A1c levels in the majority of patients treated for 6 months. Controlled trials of longer duration are warranted to assess for histopathologic improvement as well as cost-efficacy in comparison to diet and exercise alone.

Clustering of Environments of Southern Soft Red Winter Wheat Region for Milling and Baking Quality Attributes.

Division of regional nursery test sites into homogenous subregions contributes to more efficient evaluation and better differentiation of cultivars. Data from the Uniform Southern Soft Red Winter Wheat Nursery (USSRWWN) were analyzed to group testing sites into relatively homogenous subregions for milling and baking quality (MBQ) attributes. Environmental effects due to years accounted for over 50% of the total variation for protein content (P) and 42% for alkaline water retention capacity (AWRC). Genotype effect accounted for 63% of the total variation for softness equivalence (SE), and 37% for flour yield (FLY). A significant genotype x location (GxL) interaction occurred for FLY and P. However, the GxL variance component accounted for a small proportion of the total phenotypic variance, suggesting that clustering would be more beneficial for resource efficiency than for increasing differentiation of genotypes. A hierarchical cluster analysis was used to group locations on the basis of GxL interaction effects for FLY, P, AWRC, and SE. Cluster analysis divided the USSRWWN into two main subregions within which the GxL interaction was reduced by over 90% for FLY and by 60% for P. Although this classification is not entirely consistent with the geographic distribution of locations, clusters do follow general geographic-climatic-disease regions. Our results suggest that the USSR-WWN can be divided into subregions to reduce the resources expended on evaluation of MBQ attributes. This classification of locations could be useful in breeding for specific adaptability within subregions.

Telemedical evaluation and management of retinopathy of prematurity using a fiberoptic digital fundus camera.

OBJECTIVE: We sought to determine whether retinopathy of prematurity (ROP) can be evaluated and managed telemedically. DESIGN: Multicenter noncomparative case series. PARTICIPANTS: Ten patients (19 eyes) with ROP were evaluated and treated per standard of care and imaged with the RetCam 120 digital fundus camera (Massie Research Laboratories, Inc., Dublin, CA). INTERVENTION: Images were transmitted to a remote site for evaluation and management recommendations. MAIN OUTCOME MEASURES: Telemedical evaluations and management recommendations were compared with traditional on-site standard of care evaluations and treatments. RESULTS: The identification of Plus disease at the remote site was accurately identified in 95% of eyes. Prethreshold, threshold, and stage 4 or 5 ROP were correctly detected in 17 of 19 (89%) eyes. CONCLUSIONS: Results indicate ROP can be evaluated and treatment recommendations made at remote sites with telemedicine strategies.

Clinical evaluation of a vaccinia-vectored Hantaan virus vaccine.

We evaluated a vaccinia-vectored vaccine for hemorrhagic fever with renal syndrome in clinical trials. A Phase I dose-escalation study in 16 volunteers divided into four groups demonstrated that subcutaneous inoculation of approximately 10(7) plaque-forming units of the recombinant virus was safe and immunogenic. Vaccination of a fifth group of 12 volunteers indicated that neutralizing antibody titers to both vaccinia virus and Hantaan virus were enhanced after a second inoculation. Comparing two routes of vaccination showed that scarification effectively induced neutralizing antibodies in vaccinia virus-naive volunteers but that subcutaneous inoculation was superior to scarification in vaccinia virus-immune individuals. A Phase II, double-blinded, placebo-controlled clinical trial was conducted among 142 volunteers. Two subcutaneous vaccinations were administered at 4-week intervals. Neutralizing antibodies to Hantaan virus or to vaccinia virus were detected in 72% or 98% of vaccinia virus-naive volunteers, respectively. In contrast, only 26% of the vaccinia virus-immune volunteers developed neutralizing antibody responses to Hantaan virus. J. Med. Virol. 60:77-85, 2000. Published 2000 Wiley-Liss, Inc.

Yield Loss Caused by Bacterial Streak in Winter Wheat.

The relationship between severity of bacterial streak and yield in winter wheat was studied in field plots and using a single-tiller method. Regression analysis from single-tiller studies showed that the grain weight per spike decreased as bacterial streak severity increased in cvs. Florida 304 and Savannah. The number of kernels per spike decreased as bacterial streak severity increased in Savannah but not in Florida 304. There was no difference in slope of the regression line between different years, locations, or cultivars for grain weight per spike. However, grain weight per spike at 0% bacterial streak (intercept) was different for different years, locations, and cultivars. The average reduction in grain weight per spike was 0.012 g for every 1% increase in bacterial streak severity. Using this relationship for cv. Savannah, average bacterial streak severity of 10% would result in about a 9% reduction in the grain weight per spike. In Florida 304, bacterial streak severity of 10% would result in about a 7% reduction in the grain weight per spike. During 1993-94, the largest difference in bacterial streak severity between inoculated and noninoculated plots was 4% in cv. Pioneer 2548, and the smallest difference was less than 1% in cvs. Terral 101 and Florida 304. There were no yield differences between inoculated and noninoculated treatments for any genotype. In field plot studies at two locations during 1989-90, bacterial streak severity did not differ between inoculated and noninoculated plots in Alexandria, Louisiana; but in Winnsboro, Louisiana, bacterial streak severity was 18 to 40% in inoculated plots and less than 5% in noninoculated plots. Differences in yield between inoculated and noninoculated plots ranged from 1,370 kg/ha (24% loss) to -121 kg/ha in Winns-boro. During the three seasons in which these studies were conducted, bacterial streak severity averaged about 10% or less in susceptible cultivars in all experiments except one. Based on the relationships derived from single-tiller studies, this suggests that yield loss is likely to be low most years. As indicated by the experiment in Winnsboro, however, more severe yield reductions could occur in a susceptible cultivar if weather conditions are favorable for disease development.

Analysis of Bacterial Leaf Streak Epidemics on Winter Wheat in Louisiana.

Studies were conducted to characterize spatial and temporal progress of bacterial leaf streak disease (Xanthomonas translucens pv. translucens) on susceptible (Florida 304) and moderately resistant (Terral 101) winter wheat cultivars. Epidemics were initiated with rifampicin-resistant strain 88-14rif of X. translucens pv. translucens by establishing point sources of inoculum in plot centers. Incidence of bacterial leaf streak was assessed five times in 1995 and three times in 1996, starting from the first observation of leaf streak symptoms. Rainfall, temperature, and wind speed were significantly related to disease incidence, but relative humidity was not. The Gompertz model gave the best statistical fit for the progression of disease incidence over time. Average rates of disease progress (k) obtained from the regression of bacterial leaf streak incidence against time provided a good method of comparing the cultivars Florida 304 and Terral 101 and were consistent across locations. Bacterial leaf streak disease gradients were best described by the negative exponential model. Bacterial leaf streak incidence decreased with distance from inoculum source for both cultivars. Disease incidence on Terral 101 was near 0% at 2 m from the source, and disease incidence close to the source was consistently lower on Terral 101 than on Florida 304 at all growth stages sampled. This was not unexpected because the two cultivars differed in susceptibility. Disease incidence data were more useful than severity data in providing a good estimate of disease spread away from the source.