Evaluation of the use of sludge containing plutonium as a soil conditioner for food crops

An experiment was conducted to assess the potential hazard associated with the use of sludge containing plutonium as a soil conditioner for food crops. Conditions were chosen that would maximize exposure to the $sup 239$Pu in the sludge through resuspension and in plant content and thus approximated the maximum potential hazards due to the inhalation and ingestion pathways. The estimated 50-year radiation doses to the pulmonary region of the lung, bone, and liver based on the results of the inhalation experiment are 6 x 10$sup -4$ rem, 1.2 x 10$sup -3$ rem, and 0.55 x 10$sup -4$ rem, respectively. Similarly, the 50- year radiation doses attributable to ingestion of the sludge-grown vegetables were 2.2 x 10$sup -5$ rem to the bone and 1.5 x 10$sup -5$ rem to the liver. Thus, the inhalation pathway is the more critical of the two. The maximum permissible annual doses to the lungs, bone, and the liver for a member of the general public are 1.5, 3.0, and 1.5 rem, respectively. Thus, the maximum credible 50-year lung, bone, and liver dose commitments associated with the use of the $sup 239$Pu-contaminated sludge as a soil conditioner are approximately 4.0 x 10$sup -2$ percent of the annual maximum permissible dose. Under more realistic exposure circumstances, one might expect less drying of the sludge, less resuspension of dust and flying dirt before and during rototilling, and a much smaller sludge vegetable consumption rate. The conservative assumptions made in this analysis tend to assure that actual radiation doses would be even less than those calculated. (auth

Novel Human Rhinoviruses and Exacerbation of Asthma in Children1

To determine links between human rhinoviruses (HRV) and asthma, we used data from a case–control study, March 2003–February 2004, among children with asthma. Molecular characterization identified several likely new HRVs and showed that association with asthma exacerbations was largely driven by HRV-A and a phylogenetically distinct clade of 8 strains, genogroup C

Longitudinal molecular microbial analysis of influenza-like illness in New York City, may 2009 through may 2010

<p>Abstract</p> <p>Background</p> <p>We performed a longitudinal study of viral etiology in samples collected in New York City during May 2009 to May 2010 from outpatients with fever or respiratory disease symptoms in the context of a pilot respiratory virus surveillance system.</p> <p>Methods</p> <p>Samples were assessed for the presence of 13 viruses, including influenza A virus, by MassTag PCR.</p> <p>Results</p> <p>At least one virus was detected in 52% of 940 samples analyzed, with 3% showing co-infections. The most frequently detected agents were rhinoviruses and influenza A, all representing the 2009 pandemic H1N1 strain. The incidence of influenza H1N1-positive samples was highest in late spring 2009, followed by a decline in summer and early fall, when rhinovirus infections became predominant before H1N1 reemerged in winter. Our study also identified a focal outbreak of enterovirus 68 in the early fall of 2009.</p> <p>Conclusion</p> <p>MassTag multiplex PCR affords opportunities to track the epidemiology of infectious diseases and may guide clinicians and public health practitioners in influenza-like illness and outbreak management. Nonetheless, a substantial proportion of influenza-like illness remains unexplained underscoring the need for additional platforms.</p

Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza

Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease.We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0.0004). In subjects 6 to 55 years of age, the adjusted odds ratio (OR) of severe disease in the presence of S. pneumoniae was 125.5 (95% confidence interval [CI], 16.95, 928.72; p<0.0001).The association of S. pneumoniae with morbidity and mortality is established in the current and previous influenza pandemics. However, this study is the first to demonstrate the prognostic significance of non-invasive antemortem diagnosis of S. pneumoniae infection and may provide insights into clinical management

The use of a physiologically based pharmacokinetic model to evaluate deconvolution measurements of systemic absorption

BACKGROUND: An unknown input function can be determined by deconvolution using the systemic bolus input function (r) determined using an experimental input of duration ranging from a few seconds to many minutes. The quantitative relation between the duration of the input and the accuracy of r is unknown. Although a large number of deconvolution procedures have been described, these routines are not available in a convenient software package. METHODS: Four deconvolution methods are implemented in a new, user-friendly software program (PKQuest, ). Three of these methods are characterized by input parameters that are adjusted by the user to provide the "best" fit. A new approach is used to determine these parameters, based on the assumption that the input can be approximated by a gamma distribution. Deconvolution methodologies are evaluated using data generated from a physiologically based pharmacokinetic model (PBPK). RESULTS AND CONCLUSIONS: The 11-compartment PBPK model is accurately described by either a 2 or 3-exponential function, depending on whether or not there is significant tissue binding. For an accurate estimate of r the first venous sample should be at or before the end of the constant infusion and a long (10 minute) constant infusion is preferable to a bolus injection. For noisy data, a gamma distribution deconvolution provides the best result if the input has the form of a gamma distribution. For other input functions, good results are obtained using deconvolution methods based on modeling the input with either a B-spline or uniform dense set of time points

Distinguishing Molecular Features and Clinical Characteristics of a Putative New Rhinovirus Species, Human Rhinovirus C (HRV C)

Background: Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected

Influence of non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine) on the pharmacodynamic activity of gliclazide in animal models

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes may occur as a result of HIV infection and/or its treatment. Gliclazide is a widely used drug for the treatment of type 2 diabetes. Efavirenz and nevirapine are widely used non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection. The role of Efavirenz and nevirapine on the pharmacodynamic activity of gliclazide is not currently known. The objective of this study was to examine the effect of oral administration of efavirenz and nevirapine on blood glucose and investigate their effect on the activity of gliclazide in rats (normal and diabetic) and rabbits to evaluate the safety and effectiveness of the combination.</p> <p>Methods</p> <p>Studies in normal and alloxan induced diabetic rats were conducted with oral doses of 2 mg/kg bd. wt. of gliclazide, 54 mg/kg bd. wt. of efavirenz or 18 mg/kg bd. wt. of nevirapine and their combination with adequate washout periods in between treatments. Studies in normal rabbits were conducted with 5.6 mg/1.5 kg bd. wt. of gliclazide, 42 mg/1.5 kg bd. wt. of efavirenz or 14 mg/1.5 kg bd. wt. of nevirapine and their combination given orally. Blood samples were collected at regular time intervals in rats from retro orbital puncture and by marginal ear vein puncture in rabbits. All the blood samples were analysed for blood glucose by GOD/POD method.</p> <p>Results</p> <p>Efavirenz and nevirapine alone have no significant effect on the blood glucose level in rats and rabbits. Gliclazide produced hypoglycaemic/antidiabetic activity in normal and diabetic rats with peak activity at 2 h and 8 h and hypoglycaemic activity in normal rabbits at 3 h. In combination, efavirenz reduced the effect of gliclazide in rats and rabbits, and the reduction was more significant with the single dose administration of efavirenz than multiple dose administration. In combination, nevirapine has no effect on the activity of gliclazide in rats and rabbits.</p> <p>Conclusion</p> <p>Thus, it can be concluded that the combination of efavirenz and gliclazide may need dose adjustment and care should be taken when the combination is prescribed for their clinical benefit in diabetic patients. The combination of nevirapine and gliclazide was safe. However, further studies are warranted.</p

Rac1 Is Required for Pathogenicity and Chm1-Dependent Conidiogenesis in Rice Fungal Pathogen Magnaporthe grisea

Rac1 is a small GTPase involved in actin cytoskeleton organization and polarized cell growth in many organisms. In this study, we investigate the biological function of MgRac1, a Rac1 homolog in Magnaporthe grisea. The Mgrac1 deletion mutants are defective in conidial production. Among the few conidia generated, they are malformed and defective in appressorial formation and consequently lose pathogenicity. Genetic complementation with native MgRac1 fully recovers all these defective phenotypes. Consistently, expression of a dominant negative allele of MgRac1 exhibits the same defect as the deletion mutants, while expression of a constitutively active allele of MgRac1 can induce abnormally large conidia with defects in infection-related growth. Furthermore, we show the interactions between MgRac1 and its effectors, including the PAK kinase Chm1 and NADPH oxidases (Nox1 and Nox2), by the yeast two-hybrid assay. While the Nox proteins are important for pathogenicity, the MgRac1-Chm1 interaction is responsible for conidiogenesis. A constitutively active chm1 mutant, in which the Rac1-binding PBD domain is removed, fully restores conidiation of the Mgrac1 deletion mutants, but these conidia do not develop appressoria normally and are not pathogenic to rice plants. Our data suggest that the MgRac1-Chm1 pathway is responsible for conidiogenesis, but additional pathways, including the Nox pathway, are necessary for appressorial formation and pathogenicity

Apple phytochemicals and their health benefits

Evidence suggests that a diet high in fruits and vegetables may decrease the risk of chronic diseases, such as cardiovascular disease and cancer, and phytochemicals including phenolics, flavonoids and carotenoids from fruits and vegetables may play a key role in reducing chronic disease risk. Apples are a widely consumed, rich source of phytochemicals, and epidemiological studies have linked the consumption of apples with reduced risk of some cancers, cardiovascular disease, asthma, and diabetes. In the laboratory, apples have been found to have very strong antioxidant activity, inhibit cancer cell proliferation, decrease lipid oxidation, and lower cholesterol. Apples contain a variety of phytochemicals, including quercetin, catechin, phloridzin and chlorogenic acid, all of which are strong antioxidants. The phytochemical composition of apples varies greatly between different varieties of apples, and there are also small changes in phytochemicals during the maturation and ripening of the fruit. Storage has little to no effect on apple phytochemicals, but processing can greatly affect apple phytochemicals. While extensive research exists, a literature review of the health benefits of apples and their phytochemicals has not been compiled to summarize this work. The purpose of this paper is to review the most recent literature regarding the health benefits of apples and their phytochemicals, phytochemical bioavailability and antioxidant behavior, and the effects of variety, ripening, storage and processing on apple phytochemicals

Checkpoints in a Yeast Differentiation Pathway Coordinate Signaling during Hyperosmotic Stress

All eukaryotes have the ability to detect and respond to environmental and hormonal signals. In many cases these signals evoke cellular changes that are incompatible and must therefore be orchestrated by the responding cell. In the yeast Saccharomyces cerevisiae, hyperosmotic stress and mating pheromones initiate signaling cascades that each terminate with a MAP kinase, Hog1 and Fus3, respectively. Despite sharing components, these pathways are initiated by distinct inputs and produce distinct cellular behaviors. To understand how these responses are coordinated, we monitored the pheromone response during hyperosmotic conditions. We show that hyperosmotic stress limits pheromone signaling in at least three ways. First, stress delays the expression of pheromone-induced genes. Second, stress promotes the phosphorylation of a protein kinase, Rck2, and thereby inhibits pheromone-induced protein translation. Third, stress promotes the phosphorylation of a shared pathway component, Ste50, and thereby dampens pheromone-induced MAPK activation. Whereas all three mechanisms are dependent on an increase in osmolarity, only the phosphorylation events require Hog1. These findings reveal how an environmental stress signal is able to postpone responsiveness to a competing differentiation signal, by acting on multiple pathway components, in a coordinated manner