Developing tuberculosis vaccines for people with HIV: consensus statements from an international expert panel.

New tuberculosis vaccine candidates that are in the development pipeline need to be studied in people with HIV, who are at high risk of acquiring Mycobacterium tuberculosis infection and tuberculosis disease and tend to develop less robust vaccine-induced immune responses. To address the gaps in developing tuberculosis vaccines for people with HIV, a series of symposia was held that posed six framing questions to a panel of international experts: What is the use case or rationale for developing tuberculosis vaccines? What is the landscape of tuberculosis vaccines? Which vaccine candidates should be prioritised? What are the tuberculosis vaccine trial design considerations? What is the role of immunological correlates of protection? What are the gaps in preclinical models for studying tuberculosis vaccines? The international expert panel formulated consensus statements to each of the framing questions, with the intention of informing tuberculosis vaccine development and the prioritisation of clinical trials for inclusion of people with HIV.

Atypical Lemierre's Syndrome. A Case Report and Review of Literature.

Lemierre's syndrome (LS) is a rare disease entity, which can be catastrophic if organism-directed treatment is not initiated early. Lemierre's syndrome is frequently caused by Fusobacterium infection which is frequently susceptible to clindamycin. Evidence suggests there is an increase in the incidence of cases of drug resistant Fusobacterium species. Through this case we present a unique case of a 45-year-old Caucasian female with Lemierre's Syndrome due to polymicrobial organisms that were resistant to clindamycin thus developing recurrent infections despite being on antibiotics.

Ethical issues in therapeutic use and research in pregnant and breastfeeding women.

Pregnant or potentially pregnant women have historically been excluded from clinical trials of new medications. However, it is increasingly recognised that it is imperative to generate evidence from the population in whom the drugs are likely to be used to inform safe, evidence-based shared clinical decision making. Reluctance by researchers and regulators to perform such studies often relates to concerns about risk, particularly to the foetus. However, this must be offset against the risk of untreated disease or using a drug in pregnancy where safety, efficacy and dosing information are not known. This review summarises the historical perspective, and the ethical and legal frameworks that inform the conduct of such research, then highlights examples of innovative practice that have enabled high quality, ethical research to proceed to inform the evidence-based use of medication in pregnancy.

Research with Pregnant Women: New Insights on Legal Decision-Making.

U.S. researchers and scholars often point to two legal factors as significant obstacles to the inclusion of pregnant women in clinical research: the Department of Health and Human Services' regulatory limitations specific to pregnant women's research participation and the fear of liability for potential harm to children born following a pregnant woman's research participation. This article offers a more nuanced view of the potential legal complexities that can impede research with pregnant women than has previously been reflected in the literature. It reveals new insights into the role of legal professionals throughout the research pathway, from product conception to market, and it highlights a variety of legal factors influencing decision-making that may slow or halt research involving pregnant women. Our conclusion is that closing the evidence gap created by the underrepresentation and exclusion of pregnant women in research will require targeted attention to the role of legal professionals and the legal factors that influence their decisions.

Investing in justice: ethics, evidence, and the eradication investment cases for lymphatic filariasis and onchocerciasis.

It has been suggested that initiatives to eradicate specific communicable diseases need to be informed by eradication investment cases to assess the feasibility, costs, and consequences of eradication compared with elimination or control. A methodological challenge of eradication investment cases is how to account for the ethical importance of the benefits, burdens, and distributions thereof that are salient in people's experiences of the diseases and related interventions but are not assessed in traditional approaches to health and economic evaluation. We have offered a method of ethical analysis grounded in theories of social justice. We have described the method and its philosophical rationale and illustrated its use in application to eradication investment cases for lymphatic filariasis and onchocerciasis, 2 neglected tropical diseases that are candidates for eradication.

Genomics and infectious disease: a call to identify the ethical, legal and social implications for public health and clinical practice.

Advances in genomics are contributing to the development of more effective, personalized approaches to the prevention and treatment of infectious diseases. Genetic sequencing technologies are furthering our understanding of how human and pathogen genomic factors - and their interactions - contribute to individual differences in immunologic responses to vaccines, infections and drug therapies. Such understanding will influence future policies and procedures for infectious disease management. With the potential for tailored interventions for particular individuals, populations or subpopulations, ethical, legal and social implications (ELSIs) may arise for public health and clinical practice. Potential considerations include balancing health-related benefits and harms between individuals and the larger community, minimizing threats to individual privacy and autonomy, and ensuring just distribution of scarce resources. In this Opinion, we consider the potential application of pathogen and host genomic information to particular viral infections that have large-scale public health consequences but differ in ELSI-relevant characteristics such as ease of transmission, chronicity, severity, preventability and treatability. We argue for the importance of anticipating these ELSI issues in advance of new scientific discoveries, and call for the development of strategies for identifying and exploring ethical questions that should be considered as clinical, public health and policy decisions are made.

Social justice and HIV vaccine research in the age of pre-exposure prophylaxis and treatment as prevention.

The advent of pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) as means of HIV prevention raises issues of justice concerning how most fairly and equitably to apportion resources in support of the burgeoning variety of established HIV treatment and prevention measures and further HIV research, including HIV vaccine research. We apply contemporary approaches to social justice to assess the ethical justification for allocating resources in support of HIV vaccine research given competing priorities to support broad implementation of HIV treatment and prevention measures, including TasP and PrEP. We argue that there is prima facie reason to believe that a safe and effective preventive HIV vaccine would offer a distinct set of ethically significant benefits not provided by current HIV treatment or prevention methods. It is thereby possible to justify continued support for HIV vaccine research despite tension with priorities for treatment, prevention, and other research. We then consider a counter-argument to such a justification based on the uncertainty of successfully developing a safe and effective preventive HIV vaccine. Finally, we discuss how HIV vaccine research might now be ethically designed and conducted given the new preventive options of TasP and PrEP, focusing on the ethically appropriate standard of prevention for HIV vaccine trials.

Changes in endogenous gene transcript and protein levels in maize plants expressing the soybean ferritin transgene.

Transgenic agricultural crops with increased nutritive value present prospects for contributing to public health. However, their acceptance is poor in many countries due to the perception that genetic modification may cause unintended effects on expression of native genes in the host plant. Here, we tested effects of soybean ferritin transgene (SoyFer1, M64337) on transcript and protein levels of endogenous genes in maize. Results showed that the transgene was successfully introduced and expressed in the maize seed endosperm. mRNA abundance of seven tested iron homeostasis genes and seed storage protein genes differed significantly between seed samples positive and negative for the transgene. The PCR negative samples had higher zein and total protein content compared to the positive samples. However, PCR positive samples had significantly higher concentrations of calcium, magnesium, and iron. We have shown that the soybean ferritin transgene affected the expression of native iron homeostasis genes in the maize plant. These results underscore the importance of taking a holistic approach to the evaluation of transgenic events in target plants, comparing the transgenic plant to the untransformed controls.

Effect of a mitochondria-targeted vitamin E derivative on mitochondrial alteration and systemic oxidative stress in mice.

The objective of the present study was to determine whether a mitochondria-targeted vitamin E derivative (MitoVit E) would affect certain mitochondrial parameters, as well as systemic oxidative stress. A total of sixty-four mice were fed a high-fat (HF) diet for 5 weeks. They were then switched to either a low-fat (LF) or a medium-fat (MF) diet, and administered orally with MitoVit E (40 mg MitoVit E/kg body weight) or drug vehicle (10 % (v/v) ethanol in 0·9 % (w/v) NaCl solution), every other day for 5 weeks. Mitochondrial ATP and H(2)O(2) production rates in both the liver and the gastrocnemius were not affected by MitoVit E administration in either LF or MF diet-fed mice. However, the number and average size of the subsarcolemmal mitochondria, but not the intermyofibrillar mitochondria, from the soleus muscle were significantly higher in the MF group receiving MitoVit E (MF-E) than in the MF group receiving vehicle only (MF-C). After the mice were switched from the HF diet to the four dietary treatments (LF-C, LF-E, MF-C and MF-E), the decrease in urinary isoprostane concentration was significantly greater in the LF-E group than in the other three groups during the whole study (weeks 6-10). In addition, MitoVit E significantly increased plasma superoxide dismutase (SOD) activity in the MF diet-fed group without affecting plasma glutathione peroxidase activity or H(2)O(2) levels. Overall, these data suggest that MitoVit E affects subsarcolemmal mitochondrial density and systemic oxidative stress parameters such as plasma SOD activity and urinary isoprostane concentration.

A mitochondria-targeted vitamin E derivative decreases hepatic oxidative stress and inhibits fat deposition in mice.

Our objective in this study was to determine whether a mitochondria-targeted vitamin E derivative (MitoVit E) would decrease oxidative stress and associated obesity by preventing a previously proposed aconitase inhibition cascade. Sixty-four mice were fed a high-fat (HF) diet for 5 wk. They were then switched to either a low-fat (LF) or a medium-fat (MF) diet and gavaged with MitoVit E (40 mg MitoVit E x kg body weight(-1)) or drug vehicle (10% ethanol in 0.9% NaCl solution) every other day for 5 wk. Epididymal fat weight, as well as liver lipid and remaining carcass lipid, were significantly lower in the MF group receiving MitoVit E (MF-E) than in the MF group receiving vehicle only (MF-C). Liver mitochondrial H(2)O(2) production and the protein carbonyl level were also significantly lower in MF-E than in MF-C mice. In contrast, none of the biochemical variables (aconitase activity, ATP and H(2)O(2) production, and protein carbonyl level) in the muscle mitochondria were modified by MitoVit E in either MF or LF groups. Expression of acetyl-CoA carboxylase and fatty acid synthase in both liver and adipose tissue of MF groups was not affected by MitoVit E. However, expression of carnitine palmitoyltransferase 1a in the liver and uncoupling protein 2 in adipose tissue were significantly enhanced by MitoVit E in both LF and MF groups. In conclusion, MitoVit E attenuates hepatic oxidative stress and inhibits fat deposition in mice but not through alleviation of the aconitase inhibition cascade.

Individual and interactional effects of ß-glucan, starch, and protein on pasting properties of oat flours.

Seven experimental oat lines with high (6.2-7.2%), medium (5.5-5.9%), and low (4.4-5.3%) ß-glucan concentrations were evaluated for contributions of ß-glucan, starch, protein, and their interactions, to pasting properties of oat flours by using a Rapid Visco Analyser (RVA, Newport Scientific, Warriewood, NSW, Australia). Significant correlations (P < 0.05) between ß-glucan concentration and pasting parameters of oat slurries were obtained under autolysis without 1 h of incubation, inhibition, and amylolysis. The relative decrease of viscosity after enzymatic hydrolysis of ß-glucan correlated with ß-glucan concentration (P < 0.05). These data demonstrated the important contribution of ß-glucan to pasting. The relative decrease of viscosity after either amylolysis or enzymatic removal of protein correlated with ß-glucan concentration (P < 0.1), which might be explained by the considerable contribution of the interaction of ß-glucan with starch and protein, to pasting. The viscosity decrease by hydrolysis of protein was much greater than the actual viscosity remaining after hydrolysis of both ß-glucan and starch, reconfirming the importance of interactions between protein and other oat components to pasting. Optimal multiple linear regression (MLR) models were generated to predict key pasting parameters in both buffer without 1 h of incubation and silver nitrate solution by using a stepwise procedure. The ß-glucan concentration alone or together with the concentration of starch, rather than protein, was selected as the predictor under certain conditions. These results illustrated the major unit contribution of ß-glucan, secondary unit contribution of starch, and minimal unit contribution of protein to pasting.

Application of predictive models to estimate Listeria monocytogenes growth on frankfurters treated with organic acid salts.

Organic acid salts including sodium lactate, sodium diacetate, potassium benzoate, potassium sorbate, and their combinations were assessed as potential inhibitors of Listeria monocytogenes growth on frankfurters. Predictive models for L. monocytogenes growth on frankfurters treated with these salts were compared to select a proper L. monocytogenes growth curve model under these conditions. Sigmoidal equations, including logistic and Gompertz equations, are widely used to describe bacterial growth. In this study, the reparameterized Gompertz model provided a better fit to the L. monocytogenes growth data compared with the other models that were included in this study. Rather than a fixed value for the maximum number of organisms, the reparameterized Gompertz model allows this quantity to be estimated from the data to determine the effect, if any, of the treatments on maximum population density. This information is expected to improve practical methodology for hazard characterization of microbial pathogens on ready-to-eat meat products.

Oxalate and phytate concentrations in seeds of soybean cultivars [Glycine max (L.) Merr.].

This study analyzed soybean seeds from 116 cultivars for total, insoluble, and soluble oxalate (Ox), phytate (InsP6), calcium (Ca), and magnesium (Mg) because of their potential beneficial or harmful effects on human nutrition. These cultivars were divided into four groups (A-D) on the basis of the year and geographic location where they were grown. Oxalate concentration ranged from about 82 to 285 mg/100 g of dry seed. The InsP6 concentration ranged from 0.22 to 2.22 g/100 g of dry seed. There was no correlation between Ox and InsP6 within or among the four groups of cultivars. There was a significant correlation between total Ox and Ca, but not Mg, in group D cultivars (r = 0.3705; p < 0.0005). No significant relationship was found in the group A-C cultivars. Eleven group D cultivars had InsP6 less than 500 mg/100 g, but all had total Ox of 130 mg/100 g or greater. Five cultivars from groups A-C had relatively low InsP6 (group B; < or =1.01 g/100 g) and low Ox (<140 mg/100 g). These cultivars could be useful for producing soy foods beneficial to populations at risk for kidney stones and for improved mineral bioavailability. The Ox and InsP6 concentrations of the cultivars indicate that choosing specific parents could generate seeds in succeeding generations with desirable Ox and InsP6 concentrations.

Inhibitory effects of organic acid salts for control of Listeria monocytogenes on frankfurters.

Sodium diacetate (SD), sodium diacetate plus potassium benzoate (SD-PB), and sodium lactate plus sodium diacetate plus potassium benzoate (SL-SD-PB) were selected for initial effectiveness against Listeria monocytogenes on frankfurters. Treatments were evaluated at -2.2, 1.1, 4.4, 10.0, and 12.8 degrees C for up to 90 days. The compounds were applied as 3 or 6% (total concentration) dipping solutions for surface treatment of the frankfurters. The treated frankfurters were inoculated with a five-strain cocktail of L. monocytogenes (Scott A 4b, H7764 1/2a, H7962 4b, H7762 4b, and H7969 4b) using 1 ml of 10(4) cells for each 90.8-g package of two frankfurters. The maximum population of L. monocytogenes was decreased and generation time and lag phase were increased after surface treatments with 6% SD, 6% SL-SD-PB, 3% SD-PB, and 6% SD-PB solutions at 1.1 degrees C. Surface treatment of frankfurters with SD at 6% was more effective for inhibiting L. monocytogenes growth than were the other treatments. Under the conditions of this study, L. monocytogenes survived in refrigerated storage even in the presence of the additives tested.

Cytokine effects on maturation of the phagosomes containing Mycobacteria avium subspecies paratuberculosis in J774 cells.

Mycobacterium avium subspecies paratuberculosis (M. a. ptb) is an intracellular pathogen of macrophages. Intracellular survival of several species of pathogenic mycobacteria is dependent on inhibition of maturation of the phagosomes containing these pathogens into functional phagolysosomes. In activated macrophages, however, this capacity is reduced, leading to increased bacterial killing. It is the hypothesis of this study that there is increased acidification and maturation of the phagosome containing M. a. ptb in interferon gamma and lipopolysaccharide (IFN-gamma/LPS) activated macrophages. In activated macrophages colocalization of M. a. ptb with either a marker of acidic compartments (Lysotracker Red) or compartments containing a late phagosome maturation marker lysosome-associated membrane protein-1 (Lamp-1) were evaluated by laser confocal microscopy. Intracellular survival of M. a. ptb in activated macrophages was evaluated directly using differential fluorescent live/dead staining. The results of this study demonstrated increased colocalization of both Lysotracker Red and Lamp-1 with FITC labeled M. a. ptb, which correlated with decreased survival of M. a. ptb within activated macrophages.

Effects of row spacing and plant density on corn rootworm (Coleoptera: Chrysomelidae) emergence and damage potential to corn.

Planting corn, Zea mays L., in row spacings less than the conventional width of 76 cm has been shown to increase grain yields. This study was conducted to determine if row spacing and plant density affected corn rootworm, Diabrotica virgifera virgifera LeConte and D. barberi Smith & Lawrence, adult emergence, larval injury to the roots, and plant tolerance to injury. Field experiments were conducted at Ames and Nashua, IA, in 1998, 1999, and 2000. Treatments were row spacings of 38 and 76 cm, and plant populations of 64,500 and 79,600 plants per hectare. Adult emergence was 31% greater in 38 cm compared with 76-cm rows. However, root injury was not significantly different between row spacings or plant populations. Row spacing alone did not significantly influence tolerance to injury, measured as root size and the amount of root regrowth. However, at one environment where precipitation was low, plants in 38-cm rows produced 25% more regrowth compared with plants in 76-cm rows. Root dry weight and regrowth were suppressed by 16 and 32%, respectively, at the high plant population. Although lodging was 51% lower in the 38-cm rows compared with the 76-cm rows, grain yields were not significantly different between row spacings. Reducing the row spacing of field corn from 76-38 cm should not increase the potential for injury from corn rootworm larvae.