Evidence that badnavirus infection in Musa can originate from integrated pararetroviral sequences

When some virus- and disease-free Musa spp. (banana and plantain) are propagated by tissue culture, the resulting plants develop infections with banana streak badnavirus (BSV), a pararetrovirus. In sharp contrast to the virion DNA recovered from natural infections, the virion DNA from tissue culture-associated infections of different Musa spp. was highly similar if not identical. Although BSV does not employ integration during the infection cycle, BSV DNA was found to be integrated into the Musa genome. While one integration consisted of a partial BSV genome, a second contained more than one complete genome that was almost identical to BSV recovered from tissue culture-derived plants. The arrangement of this integrated BSV DNA suggests that it can yield an infectious episomal genome via homologous recombination. This report documents the first instance of integrated DNA of a nonintegrating virus giving rise to an episomal viral infection and identifies tissue culture as a possible trigger for the infection, raising the question of whether similar activatable viral sequences exist in the genomes of other plants and animals.     

Varicella-Zoster virus-specific cell-mediated immunity in HIV-infected children receiving highly active antiretroviral therapy

Herpes zoster (HZ) is a frequent complication of advanced human immunodeficiency virus (HIV) infection. We determined the effect of highly active antiretroviral therapy (HAART) on reconstitution of varicella-zoster virus (VZV)-specific cell-mediated immunity (VZV-CMI) in 56 VZV- and HIV-infected children. VZV-CMI did not change over the course of >/=3 years of observation, despite a reduction in HIV load. VZV-CMI correlated with lower HIV load but not with CD4 cell percentage. The incidence of HZ was unaffected by HAART. None of 5 patients who developed HZ during the study had VZV-CMI before developing HZ. After developing HZ, only the 2 HAART-compliant patients developed VZV-CMI. Thus, VZV-specific immune reconstitution in HIV infection may require antigenic reexposure, in addition to control of HIV replication.     

Effects of EDTA- and sulfite-containing formulations of propofol on respiratory system resistance after tracheal intubation in smokers

BACKGROUND: The formulation of sulfite-containing propofol (SCP) has not been thoroughly investigated in patients with the extensive smoking history for the effects on the total respiratory system resistance after tracheal intubation. However adverse effects, including acute asthma and bronchospasm, have been reported with several other parenteral formulations of drugs containing sulfite as preservative. Therefore, the aim of this prospective randomized and double blind study was to investigate the effects of EDTA-containing propofol (ECP) and SCP on total respiratory system resistance (Rrs) in patients with the prolonged smoking history and undergoing propofol-based total intravenous anesthesia with tracheal intubation. METHODS: 40 patients scheduled for general anesthesia were enrolled into the study. Anesthesia was induced with either 2 mg/kg ECP, or 2 mg/kg SCP followed by vecuronium (0.1 mg/kg) to ensure complete neuromuscular relaxation for the time of the study. Maintenance anesthesia was continued with propofol infusion at 0.15 mg/kg/min for the first 15 min after intubation. Total respiratory system resistance (Rrs), was measured continuously for 10 min postintubation. RESULTS: The analysis of repeated Rrs measurements taken every minute for 10 min postintubation revealed trend consisting of higher Rrs in the SCP group when compared to the ECP group. The statistical analysis of the data performed using repeated measures analysis of covariance demonstrated statistically significant effect (P < 0.05) of the treatment group factor (SCP vs. ECP) and the time factor (time after intubation) on the postintubation Rrs. CONCLUSION: The total respiratory system resistance measured repeatedly for 10 min after tracheal intubation in patients with smoking history is significantly elevated after induction with SCP than after induction with ECP. The preservative used for propofol formulation may alter the effects of propofol on the total respiratory system resistance in smokers.     

In vivo inhibition of Fas ligand-mediated killing by TR6, a Fas ligand decoy receptor.

TR6, a member of the tumor necrosis factor (TNF) receptor superfamily, has recently been shown to bind to Fas ligand (FasL) and inhibit FasL-mediated cell killing in vitro. In the current study, we demonstrate that TR6 can block the lethal activity of FasL in multiple in vitro systems, and extend this finding to an in vivo model of hepatitis. The binding of human TR6 to human FasL was verified with BIAcore chip technology. Human primary hepatocytes, HT-29 cells and Jurkat cells were assayed for viability to demonstrate TR6 inhibition of FasL-mediated cytotoxicity in vitro. Human TR6 was also shown to cross-react with membrane-bound mouse FasL, since the in vitro cytotoxic activity of L929 cells transfected with murine FasL was inhibited in the presence of human TR6. In vivo, FasL-induced acute, lethal, fulminant hepatic apoptosis resulting in death within 2 h of intravenous injection into Fas+ mice, but not Fas- MRL/lpr mice. Pretreatment of mice with TR6 blocked FasL-induced mortality, presumably by attenuating FasL-induced hepatic apoptosis. Thus, in both in vitro and in vivo systems, TR6 acts as a functional FasL decoy receptor and may be clinically useful in the treatment of hepatitis and other diseases associated with FasL-mediated tissue injury.     

Improved breast cancer survival among hormone replacement therapy users is durable after 5 years of additional follow-up

BACKGROUND: We previously reported that breast cancer patients who used hormone replacement therapy (HRT) had significantly lower stage tumors and higher survival than never-users. We present an update with longer follow-up, HRT use data, and in vitro research. METHODS: Our database of 292 postmenopausal breast cancer patients was updated to include HRT type, duration, and disease status. In vitro effects of estrogen (E) and/or medroxyprogesterone (MPA) on breast cancer cell growth were measured. RESULTS: Tumor prognostic factors were better and survival rates higher for both E and combination HRT users of any duration. Use greater than 10 years correlated with node-negative disease, mammographically detected tumors, and 100% survival. E supported minimal proliferation; MPA induced cell death; E+MPA results were similar to E alone. CONCLUSIONS: HRT users, regardless of type or duration of HRT use, continued to have higher survival rates. In vitro results supported the clinical finding that outcomes for users of E and E+MPA were similar.     

Sawtooth wave density analysis during REM sleep in normal volunteers

OBJECTIVE: Sawtooth waves (STW) are a characteristic EEG feature of REM sleep but their source and function are unknown. We previously reported stereotypical properties of STW at stage REM onset, and alterations in bulbar postpolio syndrome. This study analyzes STW features throughout REM, in order to test the hypothesis that sawtooth wave activity may be predictable and have a consistent relationship across REM periods. METHODS: Twenty polysomnographic recordings were scored for occurrence, duration, and frequency of STWs. STW density was calculated based on the number of bursts/min REM and duration of STW activity/min REM. The density measurements were statistically analyzed to assess for differences across REM periods. RESULTS: STW density mean was 0.97 bursts/min REM (95% CI [0.85, 1.09]); 6.85 s/min REM (95% CI [5.95, 7.76]). STW frequency range was 1.5-5 Hz, mean 2.5 Hz. STWs occurred in bursts with a mean duration of 7 s (range 2-26 s). There was a lower density of bursts of STW activity per minute in the first REM period compared to the second, third, and fifth cycles. CONCLUSIONS: This study reports STW density characteristics throughout REM sleep in normal subjects. Our density measurements suggest a difference in STW activity between the first REM period and later periods. Analysis of STW and related phenomena may increase the understanding of REM sleep mechanisms and may be useful to evaluate brainstem function during normal and pathological sleep.     

Cost-effectiveness of training rural providers to identify and treat patients at risk for fragility fractures

Summary

This is a cost-effectiveness analysis of training rural providers to identify and treat osteoporosis. Results showed a slight cost savings, increase in life years, increase in treatment rates, and decrease in fracture incidence. However, the results were sensitive to small differences in effectiveness, being cost-effective in 70 % of simulations during probabilistic sensitivity analysis.

Introduction

We evaluated the cost-effectiveness of training rural providers to identify and treat veterans at risk for fragility fractures relative to referring these patients to an urban medical center for specialist care. The model evaluated the impact of training on patient life years, quality-adjusted life years (QALYs), treatment rates, fracture incidence, and costs from the perspective of the Department of Veterans Affairs.

Methods

We constructed a Markov microsimulation model to compare costs and outcomes of a hypothetical cohort of veterans seen by rural providers. Parameter estimates were derived from previously published studies, and we conducted one-way and probabilistic sensitivity analyses on the parameter inputs.

Results

Base-case analysis showed that training resulted in no additional costs and an extra 0.083 life years (0.054 QALYs). Our model projected that as a result of training, more patients with osteoporosis would receive treatment (81.3 vs. 12.2 %), and all patients would have a lower incidence of fractures per 1,000 patient years (hip, 1.628 vs. 1.913; clinical vertebral, 0.566 vs. 1.037) when seen by a trained provider compared to an untrained provider. Results remained consistent in one-way sensitivity analysis and in probabilistic sensitivity analyses, training rural providers was cost-effective (less than $50,000/QALY) in 70 % of the simulations.

Conclusions

Training rural providers to identify and treat veterans at risk for fragility fractures has a potential to be cost-effective, but the results are sensitive to small differences in effectiveness. It appears that provider education alone is not enough to make a significant difference in fragility fracture rates among veterans.