Infectious gastroenterocolitides in children: an update on emerging pathogens

The recognition that bacterial infections induce signal transduction responses in infected epithelial cells also provides new avenues to consider as novel forms of therapy. For example, the chemokine interleukin-8, which attracts neutrophils to sites of mucosal infection, is produced by epithelial cells of gastric and intestinal origin in response to bacterial infection. Inhibitors of chemokine production or inhibition of the biologic effects of neutrophil chemoattractants have the potential to reduce both mucosal inflammatory responses and the attendant clinical sequelae. Eukaryotic cells also respond to infection with elevations in cytosolic second messengers, including inositol triphosphate (IP3) and calcium ([Ca2+]i). In intestinal epithelium, these second messengers can mediate the diarrheal response to infection. Calcium/calmodulin inhibitors may have a beneficial effect in treating those gastrointestinal infections mediated through changes in the level of cytosolic free calcium. DuPont and colleagues showed, for example, that oral therapy with zaldaride maleate relieves symptoms of disease and shortens the duration of diarrhea in travelers with ETEC-induced diarrhea. Evaluation of additional signal transduction responses to microbial infections should provide both new insights into the pathogenesis of gastrointestinal infectious diseases and novel approaches to consider for the prevention and therapy for these human illnesses.     

Positron emission tomographic imaging of the cardiovascular system: an emerging clinical tool

Cyclic GMP-dependent protein kinase (cGMP kinase) is the major receptor protein for cGMP in vascular smooth muscle. Vascular smooth muscle cells (VSMC) isolated from the rat aorta express type I cGMP kinase at high levels, but expression decreases markedly upon passage of the cells. In primary or early passage, the expression of cGMP kinase is lowest when cells are plated at low density as assessed by immunological and Northern analyses. Expression increases at confluence and is maintained in postconfluent cultures. With repeated passaging, however, the levels of cGMP kinase decrease even in confluent and postconfluent cultures so that after several passages enzyme levels are undetectable. The decrease in expression in passaged cells is not due to exposure to serum-derived growth factors, but rather on the repeated exposure of cells to conditions in which cell density is reduced (i.e., subculturing). These results indicate that aortic VSMC grown at low density or those repetitively passaged have reduced expression of cGMP kinase, and thus may not represent appropriate cultures with which to investigate the role of nitric oxide and cGMP in VSMC function.     

Quantitative risk assessment for Escherichia coli O157:H7 in ground beef hamburgers

Quantitative Risk Assessment (QRA) is a methodology used to organize and analyze scientific information to estimate the probability and severity of an adverse event. Applied to microbial food safety, the methodology can also help to identify those stages in the manufacture, distribution, handling, and consumption of foods that contribute to an increased risk of foodborne illness, and help focus resources and efforts to most effectively reduce the risk of foodborne pathogens. The term Process Risk Model (PRM) is introduced in this paper to describe the integration and application of QRA methodology with scenario analysis and predictive microbiology to provide an objective assessment of the hygienic characteristics of a manufacturing process. The methodology was applied to model the human health risk associated with Escherichia coli O157:H7 in ground beef hamburgers. The PRM incorporated two mathematical submodels; the first was intended to described the behaviour of the pathogen from the production of the food through processing, handling, and consumption to predict human exposure. The exposure estimate was then used as input to a dose-response model to estimate the health risk associated with consuming food from the process. Monte Carlo simulation was used to assess the effect of the uncertainty and variability in the model parameters on the predicted human health risk. The model predicted a probability of Hemolytic Uremic Syndrome of 3.7 x 10(-6) and a probability of mortality of 1.9 x 10(-7) per meal for the very young. These estimates are likely high for all hamburger meals, but may be reasonable for the home-prepared hamburgers described by this model. The efficacy of three risk mitigation strategies were evaluated by modifying the values of the predictive factors and comparing the new predicted risk. The average probability of illness was predicted to be reduced by 80% under a hypothetical mitigation strategy directed at reducing microbial growth during retail storage through a reduction in storage temperature. This strategy was predicted to be more effective than a hypothetical intervention which estimated a plausible reduction in the concentration of E. coli O157:H7 in the feces of cattle shedding the pathogen and one aimed at convincing consumers to cook hamburgers more thoroughly. The conclusions of this approach are only accurate to the extent that the model accurately represents the process. Currently, uncertainty and ignorance about the hygienic effects of the individual operations during production, processing, and handling limit the applicability of a PRM to specify HACCP criteria in a quantitative manner. However, with continuous improvement through stimulated research, a PRM should encompass all available information about the process, food, and pathogen and should be the most appropriate decision-support tool since it represents current knowledge.     

Ethylene glycol ethers: an environmental risk assessment

Ethylene glycol ethers and acetates are used as intermediates, solvents, and plasticizers. They primarily enter the environment from manufacturing effluents and emissions and during their use in commercial products. Therefore, an examination of their ultimate fate and toxicity, as well as their potential for exposure, was performed. Overall, these data show that ethylene glycol ethers and acetates are not persistent in the environment, are not bioaccumulative, are generally classified by U.S. Environmental Protection Agency (EPA) procedures as "practically non-toxic" to aquatic organisms based on acute toxicity, and that conservatively calculated exposures are mostly below concentrations of concern for chronic risks to aquatic life.     

Quantitative microbiological risk assessment: principles applied to determining the comparative risk of salmonellosis from chicken products

Ensuring microbiological safety requires identification of realistic hazards and the means of controlling them. The risk assessment framework proposed by Codex Alimentarius allows the impact of raw materials and processes to be appreciated, and the output can be used for risk management and communication. Mathematical models allow numerical information to be processed by a computer and interpreted to give quantitative or comparative risk assessments. In this example, models have been put together according to the Codex. Alimentarius principles, providing a quantitative risk assessment (QRA) of salmonellosis from frozen poultry products. This model-based QRA takes into account three types of information: occurrence and distribution of the agent, sensitivity of populations to infection (e.g., normal or susceptible), and the effect of cooking (in the factory or home) on concentration of the agent and hence risks of infection after product consumption. It only demonstrates the impact of a single-process step (heating) and the effect of changes in population sensitivity, raw material quality, and cooking regime on the final risk. The effects of growth and recontamination are not considered. To aid risk communication, the models have been visualized by means of displays and slider controls on a computer screen because effective communication is essential to encourage manufacturers and their product designers to assess the effect of changes in processing or materials on risk.     

An emerging cancer risk: organ transplantation

Advancements in surgical techniques, procurement, and immunosuppressant therapy have made organ transplantation a major treatment modality with increasing survival posttransplantation. However, this longevity has placed individuals with transplanted organs at an increased risk for developing cancer. This article examines the following pertinent issues. First, what is the prevalence of malignancies among transplant recipients? Second, are organ recipients told that they may be at risk for developing cancer? Third, is the medical community trading one lethal disease for another? And finally, are oncology nurses properly trained to handle the maintenance of a transplanted organ while caring for a person with cancer? This article looks at several ethical issues, including the ethical principle of autonomy, which examines the respect for a patient's right to choose or refuse treatment. Within this text, autonomy will be the basis for informed consent and the need for cancer risk disclosure. The ethical principle of beneficence is also examined, in regards to the health-care community trading one illness for another. The final ethical principle of nonmaleficence is considered and the need for future oncology nurses to examine their practice to determine if they are ready to care for these posttransplant cancer patients.     

An assessment tool for older patients

A full and detailed assessment of older patients should include social circumstances. An assessment should identify problems of functional activity and use screening tools to aid referral to specialist multidisciplinary staff.     

Evaluation of universal preenrichment broth for the recovery of foodborne pathogens from milk and cheese

The use of universal preenrichment broth for the recovery of verotoxigenic Escherichia coli, Salmonella spp., and Listeria monocytogenes from milk and cheese was examined. Universal preenrichment broth supported the growth of low inoculum levels (10 cfu/ml) of these organisms in pure cultures and in mixed cultures containing higher levels of other pathogens or bacterial flora from raw milk. This medium also supported the recovery and growth of heat-injured Salmonella spp., L. monocytogenes, and verotoxigenic E. coli at inoculum levels of 10(2) cfu/ml to yield cell levels of 10(8) cfu/ml in pure cultures and at least 10(5) cfu/ml in the presence of high levels of known competitive pathogens or microflora of cheese samples after 24 h of incubation. Universal preenrichment broth performed better than Listeria enrichment broth in supporting the recovery and growth of heat-injured L. monocytogenes and equally as well as buffered peptone water or trypticase soy broth in supporting the growth of uninjured L. monocytogenes, Salmonella spp., and verotoxigenic E. coli. Coenrichment of these pathogens in universal preenrichment broth reduced the quantity of milk or cheese samples that were required for analysis and also reduced the cost and labor involved in preparing and processing separate preenrichment media.     

Imaging motor-to-sensory discharges in the human brain: an experimental tool for the assessment of functional connectivity

We present a new approach to studying functional connectivity in the human brain. This approach is based on the observation that when we engage in motor activity, a discharge corollary to the motor command is sent from motor to sensory structures. Thus, as long as movement-related sensory input is either prevented or masked, modulation of neuronal activity in sensory structures would indicate the presence of functional connectivity between the motor and the sensory regions. Using positron emission tomography, such a central interaction between motor and sensory regions can be assessed by measuring regional changes in cerebral blood flow (CBF) in sensory regions. In this paper, we describe the experimental design and the results of two studies of corollary discharges, namely those generated during eye movements and speech. In these studies, a graded approach was used to establish the relationship between the number of eye movements or utterances and CBF in visual or auditory regions, respectively. Significant covariations between the number of movements and CBF in sensory regions were found, thus indicating the presence of functional connectivity between motor and sensory regions. In addition, interregional CBF covariations were computed and the effect of removing the intersubject variance on these covariations was evaluated. The corollary-discharge-based approach to studying functional connectivity is discussed in the context of more traditional computational approaches to network analysis in functional brain imaging.     

Quantitative complete tooth variation among east Asians and Native Americans: developmental biology as a tool for the assessment of human divergence

The quantification of total tooth structure derived from X-rays of Vietnamese, Southern Chinese, Mongolians, Western Eskimos, and Peruvian pre-Inca (Huari Empire) populations was used to examine dental divergence and the morphogenetics of change. Multivariate derived distances between the samples helped identify a quasicontinuous web of ethnic groups with two binary clusters ensconced within the web. One cluster was composed of Mongolians, Western Eskimos, and pre-Inca, and the other group consisted of the Southern Chinese and Vietnamese. Mongolians entered the quasicontinuum from a divergent angle (externally influenced) from that of the Southeast Asians. The Chinese and pre-Inca formed the polar samples of the distance superstructure. The pre-Inca sample was the most isolated, its closest neighbor being the Western Eskimos. Univariate and multivariate analyses suggested that the pre-Inca, whose ancestors arrived in America perhaps approximately 30,000 years ago, was the least derived sample. Clearly, microevolutionary change occurred among the samples, but the dental phenotype was resistant to environmental developmental perturbations. An assessment of dental divergence and developmental biology suggested that the overall dental phenotype is a complex multigenic morphological character, and that the observed variation evolved through total genomic drift. The quantified dental phenotype is greater than its highly multigenic algorithm and its development homeostasis is tightly controlled, or canalized, by the deterministic organization of a complex nonlinear epigenetic milieu. The overall dental phenotype quantified here was selectively neutral and a good character to help reconstruct the sequence of human evolution, but if the outlying homeostatic threshold was or will be exceeded in antecedents and descendants, respectively, evolutionary saltation occurs.     

Construction of composite scales for risk assessment in epidemiology: an application to ectopic pregnancy

Composite scoring systems that combine information contained in a number of risk factors are being used increasingly in clinical practice, planning, and health risk appraisal. The authors propose a methodological framework for the construction and validation of a composite measurement scale to assess the risk, considered as a continuous phenomenon, of developing a particular disease or outcome. This framework integrates several statistical methods, especially those concerning model fitting, coefficient rounding, and validation strategy. It also uses psychometric methods, addressing important measurement properties such as measurement level, content and construct validity, and reliability of the constructed scale. The proposed framework is illustrated by application to the construction of a composite scale for measurement of the risk of ectopic pregnancy.     

A self-care assessment tool (SCAT) for persons with a spinal cord injury: an expanded abstract

The purpose of this study was to develop a reliable and valid tool that assesses the cognitive and functional skills needed for self-care in persons with spinal cord injury (SCI). The Self-Care Assessment Tool (SCAT) assesses cognitive and functional skills in eight self-care areas: bathing/grooming, nutritional management, medications, mobility/transfers/safety, skin management, bladder management, bowel management and dressing. The tool was carefully developed and has demonstrated content validity. Using two samples of veterans seen in the SCI clinics of two Southern Veterans Affairs Medical Centers, n = 13 and n = 15, interrater reliabilities computed by Pearson product moment correlations for the cognitive, functional and total scores ranged from .69 to .94. Test-retest reliabilities using Pearson product moment correlations for the cognitive, functional and total scores of two groups (n = 14 and n = 15) ranged from -.06 to .86. Regarding predictive validity, R2 was found to be .61 to .90 for the cognitive, functional and total scores. Although continued reliability and validity studies are needed, the SCAT has potential to measure patient rehabilitation outcomes, to evaluate nursing care approaches and to serve as a quality assurance indicator for nursing care.     

The validity and reliability of the Violence Risk Scale: A treatment-friendly violence risk assessment tool.

The development of risk assessment tools that use dynamic variables to predict recidivism and to inform and facilitate violence reduction interventions is the next major challenge in the field of risk assessment and management. This study is the first in a 2-step process to validate the Violence Risk Scale (VRS), a risk assessment tool that integrates violence assessment, prediction, and treatment. Ratings of the 6 static and 20 dynamic VRS variables assess the client's level of risk. Ratings of the dynamic variables identify treatment targets linked to violence, and ratings of the stages of change of the treatment targets assess the client's treatment readiness and change. The VRS scores of 918 male offenders showed good interrater reliability and internal consistency and could predict violent and nonviolent recidivism over both short- and longer term (4.4-year) follow-up. The probability of violent and nonviolent recidivism varied linearly with VRS scores. Dynamic and static variables performed equally well. The results support the contention that the VRS can be used to assess violent risk and to guide violence reduction treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inorganic arsenic: a need and an opportunity to improve risk assessment

This paper presents views on the current status of (inorganic) arsenic risk assessment in the United States and recommends research needed to set standards for drinking water. The opinions are those of the Arsenic Task Force of the Society for Environmental Geochemistry and Health, which has met periodically since 1991 to study issues related to arsenic risk assessment and has held workshops and international conferences on arsenic. The topic of this paper is made timely by current scientific interest in exposure to and adverse health effects of arsenic in the United States and passage of the Safe Drinking Water Act Amendment of 1996, which has provisions for a research program on arsenic and a schedule mandating the EPA to revise the maximum contaminant level of arsenic in drinking water by the year 2001. Our central premise and recommendations are straightforward: the risk of adverse health effects associated with arsenic in drinking water is unknown for low arsenic concentrations found in the United States, such as at the current interim maximum contaminant level of 50 microg/l and below. Arsenic-related research should be directed at answering that question. New epidemiological studies are needed to provide data for reliable dose-response assessments of arsenic and for skin cancer, bladder cancer, or other endpoints to be used by the EPA for regulation. Further toxicological research, along with the observational data from epidemiology, is needed to determine if the dose-response relationship at low levels is more consistent with the current assumption of low-dose linearity or the existence of a practical threshold. Other recommendations include adding foodborne arsenic to the calculation of total arsenic intake, calculation of total arsenic intake, and encouraging cooperative research within the United States and between the United States and affected countries.