Detection of Bacillus anthracis in animal tissues using InBios active anthrax detect rapid test lateral flow immunoassay.

The Active Anthrax Detect (AAD) Rapid Test lateral flow immunoassay is a point-of-care assay that was under investigational use for detecting Bacillus anthracis capsular polypeptide (polyglutamic acid) in human blood, serum and plasma. Small sample volumes, rapid results and no refrigeration required allow for easy use in either the field or laboratory. Although the test was developed for use in suspect cases of human inhalation anthrax, its features also make it a potentially powerful tool for testing suspect animal cases. We tested animal tissue samples that were confirmed or ruled out for B. anthracis. The AAD Rapid Tests were also deployed in the field, testing animal carcasses during an anthrax outbreak in hippopotami (Hippopotamus amphibius) and Cape buffalo (Syncerus caffer) in Namibia. Evaluation of all samples showed a specificity of 82% and sensitivity of 98%. However, when the assay was used on specimens from only fresh carcasses (dead for <24 h), the specificity increased to 96%. The AAD Rapid Test is a rapid and simple screening assay, but confirmatory testing needs to be done, especially when the age of the sample (days animal has been deceased) is unknown. SIGNIFICANCE AND IMPACT OF THE STUDY: In countries where anthrax is endemic, many human outbreaks are often caused by epizootics. Earlier detection of infected animals may allow for identification of exposed people, early implementation of prevention and control methods, and ultimately lessen the number of people and animals affected. Detection of Bacillus anthracis in animal tissues using a simple, rapid and field-deployable method would allow for faster outbreak response. We evaluated a simple sample collection and processing method for use with the Active Anthrax Detect Rapid Test lateral flow immunoassay to screen dead animals for anthrax.

Risk and protective factors for thrombosis in systemic lupus erythematosus: results from a large, multi-ethnic cohort.

OBJECTIVES: Few studies have examined thrombosis in systemic lupus erythematosus (SLE), none have included Asian-Americans, and most have had small sample sizes. We analysed risk factors for thrombosis in a large, multi-ethnic SLE cohort. METHODS: We studied 1930 SLE subjects, including Caucasians, African-Americans, Asian-Americans and Hispanics. Data were derived from questionnaires and medical records. Documented history of thrombosis was the primary outcome. Explanatory variables included age at SLE diagnosis, gender, ethnicity, disease duration, smoking, antiphospholipid antibody (aPL) status, nephritis and specific medications. RESULTS: Smoking (OR 1.26, p = 0.011), longer disease duration (OR 1.26 per 5 years p = 0.027 x 10(-7)), nephritis (OR 1.35, p = 0.036), aPL positivity (OR 3.22, p<10(-9)) and immunomodulating medication use (OR 1.40, p = 0.011) were statistically significant risk factors for thrombosis. Younger age at SLE onset was protective (OR 0.52 for age

Biogeochemical consequences of rapid microbial turnover and seasonal succession in soil.

Soil microbial communities have the metabolic and genetic capability to adapt to changing environmental conditions on very short time scales. In this paper we combine biogeochemical and molecular approaches to reveal this potential, showing that microbial biomass can turn over on time scales of days to months in soil, resulting in a succession of microbial communities over the course of a year. This new understanding of the year-round turnover and succession of microbial communities allows us for the first time to propose a temporally explicit N cycle that provides mechanistic hypotheses to explain both the loss and retention of dissolved organic N (DON) and inorganic N (DIN) throughout the year in terrestrial ecosystems. In addition, our results strongly support the hypothesis that turnover of the microbial community is the largest source of DON and DIN for plant uptake during the plant growing season. While this model of microbial biogeochemistry is derived from observed dynamics in the alpine, we present several examples from other ecosystems to indicate that the general ideas of biogeochemical fluxes being linked to turnover and succession of microbial communities are applicable to a wide range of terrestrial ecosystems.

Meta-analysis of genome-wide linkage studies of systemic lupus erythematosus.

A genetic contribution to the development of systemic lupus erythematosus (SLE) is well established. Several genome-wide linkage scans have identified a number of putative susceptibility loci for SLE, some of which have been replicated in independent samples. This study aimed to identify the regions showing the most consistent evidence for linkage by applying the genome scan meta-analysis (GSMA) method. The study identified two genome-wide suggestive regions on 6p21.1-q15 and 20p11-q13.13 (P-value=0.0056 and P-value=0.0044, respectively) and a region with P-value<0.01 on 16p13-q12.2. The region on chromosome 6 contains the human leukocyte antigen cluster, and the chromosome 16 and 20 regions have been replicated in several cohorts. The potential importance of the identified genomic regions are also highlighted. These results, in conjunction with data emerging from dense single nucleotide polymorphism typing of specific regions or future genome-wide association studies will help guide efforts to identify the actual predisposing genetic variation contributing to this complex genetic disease.

Surgical applications of organ preconditioning.

In 1986, Murry et al. reported that brief periods of antecedent ischemia in dogs paradoxically reduced (rather than exacerbated) the size of myocardial infarcts created by subsequent prolonged ischemia. This fortuitous discovery, now termed "preconditioning", stimulated further investigation of the inherent adaptive mechanisms present in a variety of tissues and organs. In addition to ischemia, it is now recognized that a protective response can be initiated by multiple means including lipopolysaccharide, heat stress, exercise, adrenergic drugs and even noise. Furthermore, preconditioning protects not only against cell death but also against postischemic contractile dysfunction, stunning and arrhythmias. Despite the preponderance of animal studies demonstrating the benefits of preconditioning, its clinical application has been hampered by clinicians' hesitancy to intentionally subject patients to a noxious stress prior to a planned intervention. However, many of the intracellular signals responsible for the protective effect of preconditioning have been delineated, and pharmacologic manipulation of these signals can accomplish the same benefits. The existence of preconditioning in humans has been demonstrated in vitro and in small clinical trials, and targeted strategies that exploit this endogenous protective mechanism promise to broaden the therapeutic potential of organ preconditioning.

Charge migration in DNA: ion-gated transport.

Electron hole (radical cation) migration in DNA, where the quantum transport of an injected charge is gated in a correlated manner by the thermal motions of the hydrated counterions, is described here. Classical molecular dynamics simulations in conjunction with large-scale first-principles electronic structure calculations reveal that different counterion configurations lead to formation of states characterized by varying spatial distributions and degrees of charge localization. Stochastic dynamic fluctuations between such ionic configurations can induce correlated changes in the spatial distribution of the hole, with concomitant transport along the DNA double helix. Comparative ultraviolet light-induced cleavage experiments on native B DNA oligomers and on ones modified to contain counterion (Na(+))-starved bridges between damage-susceptible hole-trapping sites called GG steps show in the latter a reduction in damage at the distal step. This reduction indicates a reduced mobility of the hole across the modified bridge as predicted theoretically.

Biodegradation kinetics for pesticide exposure assessment.

Understanding pesticide risks requires characterizing pesticide exposure within the environment in a manner that can be broadly generalized across widely varied conditions of use. The coupled processes of sorption and soil degradation are especially important for understanding the potential environmental exposure of pesticides. The data obtained from degradation studies are inherently variable and, when limited in extent, lend uncertainty to exposure characterization and risk assessment. Pesticide decline in soils reflects dynamically coupled processes of sorption and degradation that add complexity to the treatment of soil biodegradation data from a kinetic perspective. Additional complexity arises from study design limitations that may not fully account for the decline in microbial activity of test systems, or that may be inadequate for considerations of all potential dissipation routes for a given pesticide. Accordingly, kinetic treatment of data must accommodate a variety of differing approaches starting with very simple assumptions as to reaction dynamics and extending to more involved treatments if warranted by the available experimental data. Selection of the appropriate kinetic model to describe pesticide degradation should rely on statistical evaluation of the data fit to ensure that the models used are not overparameterized. Recognizing the effects of experimental conditions and methods for kinetic treatment of degradation data is critical for making appropriate comparisons among pesticide biodegradation data sets. Assessment of variability in soil half-life among soils is uncertain because for many pesticides the data on soil degradation rate are limited to one or two soils. Reasonable upper-bound estimates of soil half-life are necessary in risk assessment so that estimated environmental concentrations can be developed from exposure models. Thus, an understanding of the variable and uncertain distribution of soil half-lives in the environment is necessary to estimate bounding values. Statistical evaluation of measures of central tendency for multisoil kinetic studies shows that geometric means better represent the distribution in soil half-lives than do the arithmetic or harmonic means. Estimates of upper-bound soil half-life values based on the upper 90% confidence bound on the geometric mean tend to accurately represent the upper bound when pesticide degradation rate is biologically driven but appear to overestimate the upper bound when there is extensive coupling of biodegradation with sorptive processes. The limited data available comparing distribution in pesticide soil half-lives between multisoil laboratory studies and multilocation field studies suggest that the probability density functions are similar. Thus, upper-bound estimates of pesticide half-life determined from laboratory studies conservatively represent pesticide biodegradation in the field environment for the purposes of exposure and risk assessment. International guidelines and approaches used for interpretations of soil biodegradation reflect many common elements, but differ in how the source and nature of variability in soil kinetic data are considered. Harmonization of approaches for the use of soil biodegradation data will improve the interpretative power of these data for the purposes of exposure and risk assessment.

Spinal pain syndromes: nociceptive, neuropathic, and psychologic mechanisms.

BACKGROUND: Pain continues to be the main symptom reported by patients. Frequently, clinicians incorrectly diagnose patients and resulting treatments are ineffective, which may promote the development of chronic pain. This situation may arise as a result of a lack of clarity in the literature regarding pain syndromes. OBJECTIVE: To discuss the differences between nociceptive, neuropathic, and psychologic induction of pain and provide important clinical correlates to aid in diagnosis and treatment. DATA SOURCES: The data were accumulated over a period of years by reviewing contemporary articles and books and subsequently retrieving relevant papers. Articles also were selected from MEDLINE searches and from manual library searches. DATA SYNTHESIS: Nociceptive pain syndromes are responsible for the majority of pain complaints in clinical practice. Care must be taken to avoid the common mistake of the diagnosis of neuropathic pain, which can lead to inappropriate treatments. CONCLUSION: Although the treatment of neuropathic pain is difficult, sufficient evidence in the literature demonstrates that the treatment of nociceptive pain should be multimodal and involve spinal manipulation, muscle lengthening/stretching, trigger point therapy, rehabilitation exercises, electrical modalities, a variety of nutritional factors, and mental/emotional support.

Microbial consumption of atmospheric isoprene in a temperate forest soil.

Isoprene (2-methyl-1,3 butadiene) is a low-molecular-weight hydrocarbon emitted in large quantities to the atmosphere by vegetation and plays a large role in regulating atmospheric chemistry. Until now, the atmosphere has been considered the only significant sink for isoprene. However, in this study we performed both in situ and in vitro experiments with soil from a temperate forest near Ithaca, N.Y., that indicate that the soil provides a sink for atmospheric isoprene and that the consumption of isoprene is carried out by microorganisms. Consumption occurred rapidly in field chambers (672.60 +/- 30.12 to 2,718.36 +/- 86.40 pmol gdw day) (gdw is grams [dry weight] of soil; values are means +/- standard deviations). Subsequent laboratory experiments confirmed that isoprene loss was due to biological processes: consumption was stopped by autoclaving the soil; consumption rates increased with repeated exposure to isoprene; and consumption showed a temperature response consistent with biological activity (with an optimum temperature of 30 degrees C). Isoprene consumption was diminished under low oxygen conditions (120 +/- 7.44 versus 528.36 +/- 7.68 pmol gdw day under ambient O(2) concentrations) and showed a strong relationship with soil moisture. Isoprene-degrading microorganisms were isolated from the site, and abundance was calculated as 5.8 x 10 +/- 3.2 x 10 cells gdw. Our results indicate that soil may provide a significant biological sink for atmospheric isoprene.

Determination of monensin in high-moisture cattle rations by liquid chromatography with postcolumn derivatization.

An existing liquid chromatographic method using postcolumn derivatization has been used extensively to quantitate monensin in animal feeds. Because of the relatively high moisture content of many cattle feed rations, some modifications were made to this method. Several sample-processing steps were evaluated to determine optimum sample-processing procedure. The sample weight/sample diluent ratio was modified, and method linearity was validated for the lower monensin concentrations anticipated in high-moisture cattle rations. The accuracy and precision of data generated at these lower concentrations were also determined. Because of the high moisture content of these rations, data analysis for this method required correction of feed potency for loss on drying. With these modifications, monensin can be accurately determined in high-moisture cattle rations.

Cleveland chiropractic: the early years, 1917-1933.

Although the Cleveland family is well known in the profession for the two colleges that carry its name, relatively few of the details of the early activities of these chiropractic pioneers are recalled. This paper traces the early lives and careers of Ruth Ashworth and Carl S. Cleveland, Sr. from their education and marriage at the Palmer School in 1917 through their college operations and national professional activities before the start of the National Chiropractic Association's educational reform initiatives in the mid-1930s. The pair was active in Missouri chiropractors' struggles for licensure in the 1920s and fought to prevent the enactment of basic science legislation later on. The Clevelands remained allied to B. J. Palmer and the Chiropractic Health Bureau (today's International Chiropractors' Association) after the introduction of the neurocalometer (NCM) in 1924. However, they followed a less strident and less extreme course within straight chiropractic than did their Davenport mentor. The Cleveland College perpetuated a full-spine approach to chiropractic technique and always included diagnostic instruction. In the late 1920s and early 1930s, Carl Cleveland's more moderate stance found favor within the unification efforts centered in the International Chiropractic Congress, and he served during 1931-1933 as president of the Congress' division of school leaders. The Cleveland Chiropractic College's battle for economic survival during the lean days of the nation's economic depression is a testimony to its founders' vision and commitment to chiropractic education.

Rhinolaryngoscopic examination of patients with the multiple chemical sensitivity syndrome.

Ten patients who met the Cullen case definition for the multiple chemical sensitivity syndrome were evaluated; a history was taken, and physical examination and fiberoptic rhinolaryngoscopy were performed. All patients had an initial chemical exposure, which was followed by multiple physical and mental complaints in response to subsequent exposure to a variety of odorous organic chemicals. Rhinitis was a prominent complaint in nine patients, but one patient denied any nasal symptoms. Rhinolaryngoscopic findings were abnormal in all patients; edema, excessive mucus, a cobblestone appearance of the posterior pharynx and base of the tongue, and mucosal injection were observed frequently. A particularly striking finding was focal areas of blanched mucosa that surrounded a prominent vessel. These results suggest that nasal pathology may be a prominent feature of this disorder.

Chronic rhinitis: an underrecognized association with fibromyalgia.

We prospectively studied 47 consecutive patients with either seasonal or perennial allergic rhinitis or nonallergic rhinitis in a general allergy clinic. A diagnostic questionnaire was administered for symptoms of rhinitis and fibromyalgia, and patients were examined for tender points. A history of congestion was present in 91%, rhinorrhea in 87%, and postnasal drip in 83%. Forty-nine percent had a history of diffuse, aching pain, or tiredness for at least 3 months; 49% percent had 11 or more tender points; and 38% had both a history of widespread pain plus 11 or more tender points (the 1990 criteria of the American College of Rheumatology for fibromyalgia). This frequency is much higher than the expected 4 to 5% prevalence of fibromyalgia in a general population. Seventy-nine percent of all subjects were skin-test positive to inhalant allergens, but positive skin tests alone did not correlate with the number of tender points or criteria for fibromyalgia. Rhinitis, rather than atopy, is associated with fibromyalgia and may be an underdiagnosed, but important causative factor.

Dynamics of cluster-surface collisions.

The structure, energetics, and dynamics of shock conditions generated in a nano-cluster upon impact on a crystalline surface are investigated with molecular-dynamics simulations for a 561-atom argon cluster incident with a velocity of 3 kilometers per second onto a sodium chloride surface. The "piling-up" shock phenomenon occurring upon impact, coupled with cascades of energy and momentum transfer processes and inertial confinement of material in the interior of the cluster, creates a transient medium lasting for about a picosecond and characterized by extreme local density, pressure, and kinetic temperature. The nano-shock conditions and impulsive nature of interactions in the newly formed compressed nonequilibrium environment open avenues for studying chemical reactivity and dynamics catalysed via cluster impact.

Continuous flow electrophoretic separation of proteins and cells from mammalian tissues.

A new continuous flow electrophoretic separator for cells and macromolecules was built and tested in laboratory experiments and in the microgravity environment of space flight. Buffer flows upward in a 120-cm long flow chamber, which is 6 cm wide X 1.5 mm thick in the laboratory version and 16 cm wide X 3.0 mm thick in the microgravity version. Electrophoretic subpopulations are collected in 197 fractions spanning 16 cm at the upper end of the chamber. The electrode buffer is recirculated through front and back cooling chambers, which are also electrode chambers. Ovalbumin and rat serum albumin were used as test proteins in resolution and throughout tests; resolution of these two proteins at 25% total w/v concentration in microgravity was the same as that found at 0.2% w/v concentration in the laboratory. Band spreading caused by Poiseuille flow and conductance gaps was evaluated using polystyrene microspheres in microgravity, and these phenomena were quantitatively the same in microgravity as in the laboratory. Rat anterior pituitary cells were separated into subpopulations enriched with cells that secrete specific hormones; growth-hormone-secreting cells were found to have high electrophoretic mobility, whereas prolactin-secreting cells were found to have low electrophoretic mobility. Cultured human embryonic kidney cells were separated into several electrophoretic subfractions that produced different plasminogen activators; a medium-high-mobility subpopulation and a medium-low-mobility subpopulation each produced a different molecular form of urokinase, whereas a high- and an intermediate-mobility subpopulation produced tissue plasminogen activator. Canine pancreatic islets of Langerhans cells were separated into subpopulations, which, after reaggregation into pseudoislets, were found to be enriched with cells that secrete specific hormones; insulin-secreting beta cells were found in lowest mobility fractions, whereas glucagon-secreting alpha cells were found in the highest mobility fractions. Results of particle electrophoresis experiments were comparable in microgravity and in the laboratory, since cell densities that overloaded the carrier buffer (resulting in zone sedimentation) were avoided, and a 500-fold increase in protein throughput was achieved without compromising resolution in microgravity.

Relationship among function, phenotype, and specificity in primary allospecific T cell populations: identification of phenotypically identical but functionally distinct primary T cell subsets that differ in their recognition of MHC class I and class II allodeterminants.

The goal of the present study was to evaluate the relationship among function, Lyt phenotype, and MHC recognition specificity in primary allospecific T cell populations. By using Lyt-2+ and L3T4+ T cells obtained from the same responder populations, we assessed the ability of T cells of each phenotype to generate cytotoxic effector cells (CTL) and IL 2-secreting helper T cells in response to either class I or class II MHC allodeterminants. It was found that a discordance between Lyt phenotype and MHC recognition specificity does exist in primary allospecific T cells, but only in one T cell subpopulation with limited functional potential: namely, Lyt-2+ T cells with cytotoxic, but not helper, function that recognize class II MHC alloantigens. Target cell lysis by these Lyt-2+ class II-allospecific CTL was inhibited by anti-Ia monoclonal antibodies (mAb), but not anti-Lyt-2 mAb, indicating that they recognized class II MHC determinants as their "restriction" specificity and not as their "nominal" specificity even though they were Lyt-2+. A second allospecific T cell subset with limited functional potential was also identified but whose Lyt phenotype and MHC restriction specificity were not discordant: namely, an L3T4+ T cell subset with helper, but not cytotoxic, function specific for class I MHC allodeterminants presented in the context of self-Ia. Thus, the present study demonstrates that primary allospecific T cell populations contain phenotypically identical subpopulations of helper and effector cells that express fundamentally different MHC recognition specificities. Because the recognition specificities expressed by mature T cells reflect the selection pressures they encountered during their differentiation into functional competence, these findings suggest that functionally distinct but phenotypically identical T cell subsets may be selected independently of one another during ontogeny. Thus, the existence of Lyt-2+ CTL specific for class II allodeterminants can be explained by the hypothesis that the association of Lyt phenotype with MHC recognition specificity results from the process of thymic selection that these Lyt-2+ effector cells avoid.