Quantitative risk assessment: an emerging tool for emerging foodborne pathogens

New challenges to the safety of the food supply require new strategies for evaluating and managing food safety risks. Changes in pathogens, food preparation, distribution, and consumption, and population immunity have the potential to adversely affect human health. Risk assessment offers a framework for predicting the impact of changes and trends on the provision of safe food. Risk assessment models facilitate the evaluation of active or passive changes in how foods are produced, processed, distributed, and consumed.     

Qualitative and quantitative assessment of exposure to geomagnetic field variations on the functional status of the human brain

The comparison of functional dynamics of human brain with reference to qualitative and quantitative characteristics of local geomagnetic field (GMF) variations was conducted. It was showed that just local GMF variations can be a principal reason of modulation the human brain's functional state. The steady and unsteady states of human brain can be determined: by geomagnetic disturbances before the observation period; by structure and doses of GMF variations; by different combinations of qualitative and quantitative characteristics of GMF variations. The optimal level of GMF activity, manifested in periodic oscillations in certain amplitude-frequency range is demanded for steady brain's functional state. The decrease of optimal GMF activity level and the appearance of aperiodic disturbances of GMF can be a reason of unsteady brain's state.     

Serious traumatic brain injury: an evaluation of functional outcomes

OBJECTIVES: Evaluate independent living, productivity, and social outcomes of patients with serious traumatic brain injury (TBI) after inpatient rehabilitation. METHODS: Fifty-five adults with serious TBI (Abbreviated Injury Scale score > or = 3) were admitted to a Level I trauma center and subsequently transferred to a comprehensive inpatient rehabilitation hospital (Walton Rehabilitation Hospital). Functional Independence Measures were obtained at admission (Adm), discharge (D/C), and at 3- (n = 52) and 1-year (n = 51) follow-up. RESULTS: At 1 year, 90% of the patients were living at home. Eight (16%) required full-time supervision, while 41 (82%) were independent of supervision throughout most of the day. Thirteen (25%) patients had returned to work, eight full time and five with reduced responsibility and fewer hours than before injury. Nineteen shared household duties, while eight (16%) had primary responsibility. Fourteen (27%) patients demonstrated socially inappropriate or disruptive behavior at least weekly. [table: see text] CONCLUSION: Although cognitive skills were diminished for the majority of patients, many achieved a substantial reduction in disability within 18 months after TBI.     

Selective brain dopamine depletion in developing rats: an experimental model of minimal brain dysfunction

Administration of 6-hydroxydopamine to neonatal rats produces a rapid and profound depletion of brain dopamine. Total activity of treated animals is significantly greater than that of controls between 12 and 22 days of age, but then declines, an activity pattern similar to that seen in affected children. This suggests a functional deficiency of brain dopamine in the pathogenesis of minimal brain dysfunction.     

Glycosylation is essential for functional expression of a human brain ecto-apyrase

The importance of N-linked glycosylation for the function and oligomerization of an E-type ATPase was examined by using tunicamycin and peptide N-glycosidase F, two agents used to prevent and remove glycosylations, respectively. The cDNA encoding a human ecto-apyrase (HB6), predicted to have seven N-linked glycosylation sites, was transiently expressed in mammalian COS cells and the resulting membrane preparations were treated with peptide N-glycosidase F (PNGase-F). PNGase-F caused a decrease in the apparent molecular weight of the protein (consistent with glycan removal) and a decrease in enzymatic activity over time. The ecto-apyrase was also expressed in the presence of tunicamycin, which completely prevented N-linked glycosylation, resulting in a nonglycosylated core protein devoid of ATP and ADP hydrolyzing activity. However, control and tunicamycin-treated cells expressed the enzyme to similar levels and localization. Interestingly, the quaternary structure of this E-type ATPase appears to be dependent upon the presence of glycan chains. The glycosylated ecto-apyrase exists as a homodimer in situ as assessed by both size-exclusion chromatography of detergent-solubilized ecto-apyrase and cross-linking of membrane-bound ecto-apyrase, in contrast to the enzymatically deglycosylated ecto-apyrase and the tunicamycin-treated ecto-apyrase. These results suggest that glycosylation is necessary for homooligomerization and nucleotide hydrolyzing activity, but not for expression and plasma membrane localization of the E-type ATPase. Similar results were obtained with another human ecto-apyrase, CD39, suggesting that the importance of glycosylation may be generalized to all membrane-bound E-type ATPases.     

Structural and functional characterization of the human brain D-aspartate oxidase

The most common commercially available test measuring activated protein C (APC) resistance relies on the the anticoagulant response to added APC in an activated partial thromboplastin time (APTT) based method. Another method is a Russell Viper venom time (RVVT) based system. To improve the specificity for factor V Leiden of the APTT based method, pre-dilution of test plasma in FV-deficient plasma has recently been recommended. In this study we tested the relative suitabilities of the APTT-based system, the RVVT-based system and their corresponding assays modified by pre-dilution in FV-deficient plasma, for screening asymptomatic subjects, a group of thrombophilic patients (in particular those with low APC ratios), patients on oral anticoagulants, and patients with lupus anticoagulant (LAC). We found the RVVT-based assay to be superior to the APTT-based method in the separation of normals from those with FV Leiden mutation both in asymptomatic subjects and in the thrombophilic patient group. Both modified assays demonstrated a sensitivity and specificity of 100% for FV Leiden, as verified by genotyping in asymptomatic subjects, thrombophilic patients and patients on oral anticoagulants, with the modified RVVT-based assay giving better separation between normals and FV Leiden. Inhibition of phospholipid-dependent coagulation by LAC antibodies rendered the APTT-based system less suitable than the phospholipid-rich RVVT-based one, and as nine of the 20 LAC-positive patients were on warfarin, we showed only the modified RVVT assay to be a reliable predictor of factor V Leiden in this patient group.     

Arginine vasopressin receptor antagonists for treatment of vasogenic brain edema: an experimental study

Recent studies indicate that centrally released arginine vasopressin (AVP) facilitates brain water permeability in normal and pathological conditions. The effects of central administration of arginine vasopressin (AVP) receptor antagonists on vasogenic brain edema were studied in rats. V1 or V2 receptor antagonists were stereotactically injected into the lateral ventricle 10 min prior to or 1 h after cold brain injury. The injury resulted in significant increases in the mean water content of the lesion and the contralateral hemispheres by 1.15 and 0.38%, respectively. Twenty-four hours after injury, the brain water and sodium contents, the brain swelling, and plasma osmolality were measured. V1 receptor antagonist of 50 ng significantly decreased the brain water and sodium contents and the brain swelling in the adjacent cortex of the lesion without changes in serum osmolality. On the other hand, 5 ng of V1 receptor antagonist and V2 receptor antagonist had no effect on edema. The V1 receptor of AVP is thought to act predominantly on water permeability of the brain. Peptide therapy may become an additional tool for brain edema treatment.     

A computerized method for assessment of musculoskeletal discomfort in the workforce: a tool for surveillance

A musculoskeletal discomfort survey was conducted to assess musculoskeletal discomforts among rural mail carriers in two post offices. Perceived musculoskeletal discomfort was collected directly from the workforce by means of a computerized discomfort assessment system (DAS). This investigation aimed at: (1) assessing the rural mail carrier's perception of DAS; and (2) assessing the rural mail carrier's musculoskeletal discomforts resulting from work. Most participants in the study found the computer tool easy to learn and easy to use. The information collected by DAS was used: (1) to determine the number of participating employees who were experiencing some kind of musculoskeletal problem; (2) to determine subtasks associated with discomfort; (3) to determine the body areas most affected by different subtasks; and (4) to investigate the patterns of discomfort that occurred with time.     

Interhemispheric transmission of information and functional asymmetry of the human brain

Culturally informed social work health and mental health interventions directed toward American Indian clients must be harmonious with their environment and acculturation. This article discusses American Indian beliefs about health and illness and degrees of acculturation. Guidelines are offered to help non-Indian social workers design culturally appropriate interventions.     

DNAView: a quality assessment tool for the visualization of large sequenced regions

This communication describes DNAView, a graphical tool for the visualization and printing of large nucleic acid sequences. DNAView uses color coding to compactly display genomic segments of up to 100 kb on a single printed page. The specific color schemes integrated into DNAView can highlight 'local aggregate' properties of large segments of DNA. We have also incorporated a confidence expression for the assigned sequence. This is represented by base color intensity that is proportional to the number of times that base was sequenced. Areas of interest, such as exons, introns, repetitive elements and splice sites, can be emphasized using overlays. The colored image can be saved in a standard TIFF image file format that may be imported and annotated by other application software.     

The organized brain (an essay on the structure of functional brain organization). II

This communication is dedicated to the main postulates of the author's conception about systematic-structural organization of the cerebral functions--the principles of the space and temporal dispersion of the external and internal signals, the division of connections on the mono- and oligoprojections as well as hierarchic stage of fashion and modulation of entering information, the functional multifactory of the sensory stimuli as well as principles of overlapping both afferent and efferent influences and their mutual regulation. The principle of the change of dominant participation of one brain system to another within the behavioral act's formation is one of the main postulate of our conception. These data testify to very complicate dynamic character of the function's correlation with the brain structures. This correlation depends on the self cerebral organization as well as the role in its acting the diverse afferent messages and effector reactions.     

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.     

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.     

Environmental endocrine modulators and human health: an assessment of the biological evidence

Recently, a great deal of attention and interest has been directed toward the hypothesis that exposure, particularly in utero exposure, to certain environmental chemicals might be capable of causing a spectrum of adverse effects as a result of endocrine modulation. In particular, the hypothesis has focused on the idea that certain organochlorine and other compounds acting as weak estrogens have the capability, either alone or in combination, to produce a variety of adverse effects, including breast, testicular and prostate cancer, adverse effects on male reproductive tract, endometriosis, fertility problems, alterations of sexual behavior, learning disability or delay, and adverse effects on immune and thyroid function. While hormones are potent modulators of biochemical and physiological function, the implication that exposure to environmental hormones (e.g., xenoestrogens) has this capability is uncertain. While it is reasonable to hypothesize that exposure to estrogen-like compounds, whatever their source, could adversely affect human health, biological plausibility alone is an insufficient basis for concluding that environmental endocrine modulators have adversely affected humans. Diethylstilbestrol (DES) is a potent, synthetic estrogen administered under a variety of dosing protocols to millions of women in the belief (now known to be mistaken) that it would prevent miscarriage. As a result of this use, substantial in utero exposure to large numbers of male and female offspring occurred. Numerous studies have been conducted on the health consequences of in utero DES exposure among the adult offspring of these women. There are also extensive animal data on the effects of DES and there is a high degree of concordance between effects observed in animals and humans. The extensive human data in DES-exposed cohorts provide a useful basis for assessing the biological plausibility that potential adverse effects might occur following in utero exposure to compounds identified as environmental estrogens. The effects observed in both animals and humans following in utero exposure to sufficient doses of DES are consistent with basic principles of dose response as well as the possibility of maternal dose levels below which potential non-cancer effects may not occur. Significant differences in estrogenic potency between DES and chemicals identified to date as environmental estrogens, as well as an even larger number of naturally occurring dietary phytoestrogens, must be taken into account when inferring potential effects from in utero exposure to any of these substances. The antiestrogenic properties of many of these same exogenous compounds might also diminish net estrogenic effects. Based on the extensive data on DES-exposed cohorts, it appears unlikely that in utero exposure to usual levels of environmental estrogenic substances, from whatever source, would be sufficient to produce many of the effects (i.e., endometriosis, adverse effects on the male reproductive tract, male and female fertility problems, alterations of sexual behavior, learning problems, immune system effects or thyroid effects) hypothesized as potentially resulting from exposure to chemicals identified to date as environmental estrogens.     

Elucidating dynamic brain interactions with across-subjects correlational analyses of positron emission tomographic data: the functional connectivity of the amygdala and orbitofrontal cortex during olfactory tasks

Covariance analyses of positron emission tomography (PET) data are used increasingly to elucidate the functional connectivity between brain regions during different cognitive tasks. Functional connectivity may be estimated by examining the covariance between regions over time or across subjects. In functional brain-mapping studies, across-subjects covariance matrices derived from within-task (nonsubtracted) and between-task (subtracted) data characterize different, complementary aspects of functional interactions. The authors study amygdala-orbitofrontal interactions during three task conditions (aversive olfaction, odor detection, and resting with eyes closed) to illustrate the strengths and limitations of across-subjects covariance analyses based on subtracted and nonsubtracted data. This example underscores the dynamic nature of connectivity between the amygdalae and orbitofrontal cortices and highlights the importance of including data from resting conditions in covariance analyses.     

Radiolabelled monoclonal antibodies (McAb): an alternate approach to the conventional methods for the assessment of cardiomyocyte damage in an experimental brain-death pig model

BACKGROUND: According to the Ministry of Health and Welfare AIDS Surveillance Committee's report on vertically transmitted human immunodeficiency virus (HIV) infection, there have been eight children with acquired immune deficiency syndrome (AIDS) and 18 children with HIV infection in Japan, totalling 26 in all as of February 1997. A search of the literature fails to reveal any report that deals with many cases of vertically transmitted HIV infection in Japan. METHODS: A primary questionnaire survey was taken of the main medical institutions across the country, followed by a secondary questionnaire survey of physicians and pediatricians who treated the disease. A clinical review was made of 19 children with vertically transmitted HIV infection (including eight AIDS children) according to the 1994 Revised Classification System for HIV Infection in Children. RESULTS: The mean age at diagnosis was 14.5 months and the diagnosis was made at less than 18 months of life in approximately 70% of infected children. In the mean observation period of 16 months, six of eight AIDS children (75%), and one child of group B died. The mean period of observation for the seven dead children was 7 months, and six of seven children died by 36 months of life. The survival period after the diagnosis of AIDS was 15 months. The diagnosis of HIV infection was made based on the clinical symptoms of all children with AIDS. Of 11 children, six (45%) presented with symptoms of HIV infection by 6 months of life, and 10 of 11 children (91%) presented with symptoms by 26 months of life. The noteworthy clinical findings included hepatomegaly, splenomegaly, recurrent respiratory tract infection, lymph node swelling, oral candidiasis, hepatitis, wasting syndrome, HIV encephalopathy and severe pneumonia. The favored age for the start of complications and the magnitude of decrease in the HIV helper cell count varied with each case of complications of HIV infection (wasting syndrome, HIV encephalopathy) or opportunistic infections (cytomegalovirus infection, Mycobacterium avium complex infection). Anti-HIV drugs (mainly zidovudine) had been used in five of eight children with AIDS and were effective in two long survivors alone. CONCLUSIONS: Children who are diagnosed with HIV infection, based on their clinical symptoms, carry a poor prognosis. In this respect, early diagnosis and progress in anti-HIV therapy are necessary.     

Expression of genes for human globin in the cell line K-562: an experimental model for the study of fetal erythropoiesis

Human leukemia K-562(S) cells are a useful model system to study the relationship between cell proliferation and induced erythroid differentiation. In these studies K-562(S) cells were cultured in alpha -medium, 10% fetal calf serum and induced to express erythroid genes by 75 microM hemin, 1.2 mM butyric acid or 1.5 ng/ml actinomycin D. Cell number was determined using a ZF Coulter Counter and the increase in the proportion of hemoglobin-containing cells was detected by a specific colorimetric reaction with benzidine. The characterization of the synthesized hemoglobins was performed by cellulose-acetate gel electrophoresis of post-mitochondrial supernatants. By cloning K-562(S) cells in semi-solid medium (O,33% agar) containing 75 microM hemin a variant cell line, denominated K-562(S6), have been isolated which does not undergo terminal cell division but does express human globin genes and accumulates on the average 12 pg of Hb/cell. K-562(S6) cells accumulate, upon exposure to 75 microM hemin, mostly Hb Gower 1 (zeta 2 epsilon 2) and low amounts of Hb X (epsilon 2 gamma 2) and Hb Portland (zeta 2 gamma 2), being suitable for studies focused on the expression of embryonic globin genes and on the molecular mechanisms controlling the switching from embryonic-type to fetal-type hemoglobin accumulation, when in the human embryo zeta and epsilon globin genes become less active, being sharply increased accumulation of alpha and gamma globin chains.