Factors that affect proliferation of Salmonella in tomatoes post-harvest: the roles of seasonal effects, irrigation regime, crop and pathogen genotype

MAIN OBJECTIVES: Fresh fruits and vegetables become increasingly recognized as vehicles of human salmonellosis. Physiological, ecological, and environmental factors are all thought to contribute to the ability of Salmonella to colonize fruits and vegetables pre- and post-harvest. The goal of this study was to test how irrigation levels, fruit water congestion, crop and pathogen genotypes affect the ability of Salmonella to multiply in tomatoes post-harvest. EXPERIMENTAL DESIGN: Fruits from three tomato varieties, grown over three production seasons in two Florida locations, were infected with seven strains of Salmonella and their ability to multiply post-harvest in field-grown tomatoes was tested. The field experiments were set up as a two-factor factorial split plot experiment, with the whole-plot treatments arranged in a randomized complete-block design. The irrigation treatment (at three levels) was the whole-plot factor, and the split-plot factor was tomato variety, with three levels. The significance of the main, two-way, and three-way interaction effects was tested using the (type III) F-tests for fixed effects. Mean separation for each significant fixed effect in the model was performed using Tukey's multiple comparison testing procedure. MOST IMPORTANT DISCOVERIES AND SIGNIFICANCE: The irrigation regime per se did not affect susceptibility of the crop to post-harvest proliferation of Salmonella. However, Salmonella grew significantly better in water-congested tissues of green tomatoes. Tomato maturity and genotype, Salmonella genotype, and inter-seasonal differences were the strongest factors affecting proliferation. Red ripe tomatoes were significantly and consistently more conducive to proliferation of Salmonella. Tomatoes harvested in the driest, sunniest season were the most conducive to post-harvest proliferation of the pathogen. Statistically significant interactions between production conditions affected post-harvest susceptibility of the crop to the pathogen. UV irradiation of tomatoes post-harvest promoted Salmonella growth

Understanding the implementation of evidence-based care: A structural network approach

<p>Abstract</p> <p>Background</p> <p>Recent study of complex networks has yielded many new insights into phenomenon such as social networks, the internet, and sexually transmitted infections. The purpose of this analysis is to examine the properties of a network created by the 'co-care' of patients within one region of the Veterans Health Affairs.</p> <p>Methods</p> <p>Data were obtained for all outpatient visits from 1 October 2006 to 30 September 2008 within one large Veterans Integrated Service Network. Types of physician within each clinic were nodes connected by shared patients, with a weighted link representing the number of shared patients between each connected pair. Network metrics calculated included edge weights, node degree, node strength, node coreness, and node betweenness. Log-log plots were used to examine the distribution of these metrics. Sizes of k-core networks were also computed under multiple conditions of node removal.</p> <p>Results</p> <p>There were 4,310,465 encounters by 266,710 shared patients between 722 provider types (nodes) across 41 stations or clinics resulting in 34,390 edges. The number of other nodes to which primary care provider nodes have a connection (172.7) is 42% greater than that of general surgeons and two and one-half times as high as cardiology. The log-log plot of the edge weight distribution appears to be linear in nature, revealing a 'scale-free' characteristic of the network, while the distributions of node degree and node strength are less so. The analysis of the k-core network sizes under increasing removal of primary care nodes shows that about 10 most connected primary care nodes play a critical role in keeping the <it>k</it>-core networks connected, because their removal disintegrates the highest <it>k</it>-core network.</p> <p>Conclusions</p> <p>Delivery of healthcare in a large healthcare system such as that of the US Department of Veterans Affairs (VA) can be represented as a complex network. This network consists of highly connected provider nodes that serve as 'hubs' within the network, and demonstrates some 'scale-free' properties. By using currently available tools to explore its topology, we can explore how the underlying connectivity of such a system affects the behavior of providers, and perhaps leverage that understanding to improve quality and outcomes of care.</p

Obesity as Assessed by Body Adiposity Index and Multivariable Cardiovascular Disease Risk

To assess the role of body adiposity index (BAI) in predicting cardiovascular disease (CVD) and coronary heart disease (CHD) mortality, in comparison with body mass index (BMI), waist circumference (WC), and the waist circumference to hip circumference ratio (WHR). This study was a prospective 15 year mortality follow-up of 4175 Australian males, free of heart disease, diabetes and stroke. The Framingham Risk Scores (FRS) for CHD and CVD death were calculated at baseline for all subjects. Multivariable logistic regression was used to assess the effects of the measures of obesity on CVD and CHD mortality, before adjustment and after adjustment for FRS. The predictive ability of BAI, though present in the unadjusted analyses, was generally not significant after adjustment for age and FRS for both CVD and CHD mortality. BMI behaved similarly to BAI in that its predictive ability was generally not significant after adjustments. Both WC and WHR were significant predictors of CVD and CHD mortality and remained significant after adjustment for covariates. BAI appeared to be of potential interest as a measure of % body fat and of obesity, but was ineffective in predicting CVD and CHD

On the Tropical Atlantic SST warm bias in the Kiel Climate Model

Most of the current coupled general circulation models show a strong warm bias in the eastern Tropical Atlantic. In this paper, various sensitivity experiments with the Kiel Climate Model (KCM) are described. A largely reduced warm bias and an improved seasonal cycle in the eastern Tropical Atlantic are simulated in one particular version of KCM. By comparing the stable and well-tested standard version with the sensitivity experiments and the modified version, mechanisms contributing to the reduction of the eastern Atlantic warm bias are identified and compared to what has been proposed in literature. The error in the spring and early summer zonal winds associated with erroneous zonal precipitation seems to be the key mechanism, and large-scale coupled ocean-atmosphere feedbacks play an important role in reducing the warm bias. Improved winds in boreal spring cause the summer cooling in the eastern Tropical Atlantic (ETA) via shoaling of the thermocline and increased upwelling, and hence reduced sea surface temperature (SST). Reduced SSTs in the summer suppress convection and favor the development of low-level cloud cover in the ETA region. Subsurface ocean structure is shown to be improved, and potentially influences the development of the bias. The strong warm bias along the southeastern coastline is related to underestimation of low-level cloud cover and the associated overestimation of surface shortwave radiation in the same region. Therefore, in addition to the primarily wind forced response at the equator both changes in surface shortwave radiation and outgoing longwave radiation contribute significantly to reduction of the warm bias from summer to fall

Airway and Esophageal Stenting in Patients with Advanced Esophageal Cancer and Pulmonary Involvement

BACKGROUND: Most inoperable patients with esophageal-advanced cancer (EGC) have a poor prognosis. Esophageal stenting, as part of a palliative therapy management has dramatically improved the quality of live of EGC patients. Airway stenting is generally proposed in case of esophageal stent complication, with a high failure rate. The study was conducted to assess the efficacy and safety of scheduled and non-scheduled airway stenting in case of indicated esophageal stenting for EGC. METHODS AND FINDINGS: The study is an observational study conducted in pulmonary and gastroenterology endoscopy units. Consecutive patients with EGC were referred to endoscopy units. We analyzed the outcome of airway stenting in patients with esophageal stent indication admitted in emergency or with a scheduled intervention. Forty-four patients (58+/-\-8 years of age) with esophageal stenting indication were investigated. Seven patients (group 1) were admitted in emergency due to esophageal stent complication in the airway (4 fistulas, 3 cases with malignant infiltration and compression). Airway stenting failed for 5 patients. Thirty-seven remaining patients had a scheduled stenting procedure (group 2): stent was inserted for 13 patients with tracheal or bronchial malignant infiltration, 12 patients with fistulas, and 12 patients with airway extrinsic compression (preventive indication). Stenting the airway was well tolerated. Life-threatening complications were related to group 1. Overall mean survival was 26+/-10 weeks and was significantly shorter in group 1 (6+/-7.6 weeks) than in group 2 (28+/-11 weeks), p<0.001). Scheduled double stenting significantly improved symptoms (95% at day 7) with a low complication rate (13%), and achieved a specific cancer treatment (84%) in most cases. CONCLUSION: Stenting the airway should always be considered in case of esophageal stent indication. A multidisciplinary approach with initial airway evaluation improved prognosis and decreased airways complications related to esophageal stent. Emergency procedures were rarely efficient in our experience

H5N1 Whole-Virus Vaccine Induces Neutralizing Antibodies in Humans Which Are Protective in a Mouse Passive Transfer Model

BACKGROUND: Vero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; however, clinical efficacy is difficult to evaluate in the absence of wide-spread human disease. A lethal mouse model has been utilized which allows investigation of the protective efficacy of active vaccination or passive transfer of vaccine induced sera following lethal H5N1 challenge. METHODS: We used passive transfer of immune sera to investigate antibody-mediated protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole-virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced rodent or human immune sera and subsequently challenged with a lethal dose of wild-type H5N1 virus. RESULTS: Passive transfer of H5N1 vaccine-induced mouse, guinea pig and human immune sera provided dose-dependent protection of recipient mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty values for serum H5N1 neutralizing antibody titers were calculated to be ≤1∶11 for all immune sera, independently of source species. CONCLUSIONS: These data underpin the confidence that the Vero cell culture-derived, whole-virus H5N1 vaccine will be effective in a pandemic situation and support the use of neutralizing serum antibody titers as a correlate of protection for H5N1 vaccines

A randomized controlled trial investigation of a non-stimulant in attention deficit hyperactivity disorder (ACTION): Rationale and design

<p>Abstract</p> <p>Background</p> <p>The ACTION study (<it>Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant) </it>is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD). The primary aims are to examine the efficacy of atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study.</p> <p>Methods</p> <p>Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment), Session 2 (six weeks, atomoxetine or placebo), and Session 3 (13 weeks, cross-over after one-week washout period). The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo.</p> <p>Results</p> <p>The methodology for the ACTION study has been detailed.</p> <p>Conclusions</p> <p>The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD with and without comorbid anxiety. First enrollment was in March 2008. The outcomes of this study will be a significant step towards a 'personalized medicine' (and therefore a more efficient) approach to ADHD treatment.</p> <p>Trial registration</p> <p>Australian and New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ANZCTRN12607000535471.aspx">ANZCTRN12607000535471</a>.</p

Targeting poly(ADP-ribose) polymerase activity for cancer therapy

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD+. The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD+ at the enzyme’s activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated