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Background Persons with Parkinson’s disease exhibit gait deficits during comfortable-pace overground walking and data from pressure sensitive mats have been used to quantify gait performance. The Primary Gait Screen is a new assessment which includes gait initiation, overground walking, turning, and gait termination. Although overground assessments are useful, the Primary Gait Screen offers a more complex evaluation than traditional gait assessments. Research question Is the overground walking portion of the Primary Gait Screen comparable to traditional gait assessments? Methods Persons with Parkinson’s disease (N = 175; 47 F, 128 M; 67 ± 9 yrs) prospectively completed 4 passes at a self-selected speed and two trials of the Primary Gait Screen on an 8 m long pressure-sensing mat. Spatiotemporal gait variables were computed and a repeated-measures MANOVA with a Bonferroni correction compared the spatiotemporal variables from the Primary Gait Screen to the self-selected trials: gait velocity, cadence, step length, step time, and stride length. Results The analyses failed to detect differences between the Primary Gait Screen and self-selected trials for gait velocity, step length, or stride length (p > .01). Post-hoc tests revealed decreased cadence and increased step time were the only differences between the Primary Gait Screen trials and the self-selected trial (p Significance Differences seen in cadence and step time during the Primary Gait Screen may be attributed to patients’ strategy, but are likely not clinically meaningful. The Primary Gait Screen appears to be a comparable assessment of overground walking in persons with Parkinson’s disease, and may be a useful and accurate clinical assessment of walking.

Children with sickle cell disease are at increased risk of developing bacteremia and other serious bacterial infections. Fever is a common symptom in sickle cell disease and can also occur with sickle cell crises and viral infections. We aimed to evaluate the incidence and predictors of bacteremia and bacterial infection in children with sickle cell disease presenting with fever to a district hospital and sickle cell center in London. A retrospective analysis was performed on all attendances of children (aged under 16 years) with sickle cell disease presenting with a fever of 38.5 °C or higher over a 1-year period. Confirmed bacterial infection was defined as bacteremia, bacterial meningitis, urinary tract infection (UTI), pneumonia, osteomyelitis or other bacterial infection with positive identification of organism. Children were defined as having a suspected bacterial infection if a bacterial infection was suspected clinically, but no organism was identified. Over a 1-year period there were 88 episodes analyzed in 59 children. Bacteremia occurred in 3.4% of episodes and confirmed bacterial infection in 7.0%. Suspected bacterial infection occurred in 33.0%. One death occurred from Salmonella typhirium septicemia. C-reactive protein (CRP) level and white blood cell (WBC) count were both significantly associated with bacterial infection (p = 0.004 and 0.02, respectively.) In conclusion, bacterial infections continue to be a significant problem in children with sickle cell disease. C-reactive protein was significantly associated with bacterial infections, and could be included in clinical risk criteria for febrile children with sickle cell disease.

Listeria monocytogenes is a food-borne pathogen that must cross the intestinal epithelial barrier to reach its target organs. We have investigated the importance of M cells in translocation using an experimental mouse model and a novel, recently described in vitro co-culture system that mimics the follicle-associated epithelium (FAE). Our data demonstrate that L. monocytogenes does not require, nor specifically use, M cells of the FAE to cross the gut. We also show that bacterial translocation is rapid and L. monocytogenes can attach very efficiently to exposed basal lamina of the small intestine indicating an important role for extracellular matrix proteins.

Two different plasmid-vector systems were developed which allow the efficient production and presentation of protein antigens in antigen-presenting cells (APC) by means of virulence-attenuated bacteria. The first antigen-delivery system is based on the secretion machinery of the Escherichia coli hemolysin (HlyA-type I secretion system), which transports proteins, possessing the specific HlyA secretion signal (HlyAs) at the C-terminus, across both membranes of gram-negative bacteria. This system functions in all gram-negative bacteria that possess the TolC-analogous protein in the outer membrane. This outer membrane protein is necessary for the stable anchoring of the type I secretion apparatus in the cell envelope. Suitable HlyAs-fused antigens are secreted with high efficiency by E. coli and by virulence-attenuated strains of Salmonella, Shigella, Vibrio cholerae and Yersinia enterocolitica. The other vector system expresses the heterologous antigen under the control of an eukaryotic promoter in a similar fashion as in plasmids commonly used for vaccination with naked DNA. This plasmid DNA is introduced into APCs with the help of virulence-attenuated self-destructing Listeria monocytogenes mutants. After synthesis of the heterologous protein, epitopes of the antigen are presented by the APC together with MHC class I molecules. This system functions in macrophages and dendritic cells in vitro and can also be used in a modified form in animal models. © 2000 Elsevier Science B.V. All rights reserved.

Einige der grosten Geiseln der Menschheit wie die Pest, die Tuberkulose und die Bakterienruhr werden von Bakterien verursacht, die sich in Wirtszellen vermehren.Doch erst seit den letzten zehn Jahren beginnen wir die zellularen und molekularen Grundlagen dieser Krankheiten zu verstehen.

Recent studies have shown that Salmonella typhimurium invades the M cells of Peyer's patches (PP) of the murine ileum. The slyA gene of S. typhimurium has also recently been reported to affect virulence of this pathogen in mice and survival in macrophages. We therefore compared the effect on PP tissue of four strains of S. typhimurium: a wild-type strain, two slyA insertion mutants, and a recombinant S. typhimurium derivative carrying multiple copies of slyA. Invasion assays performed 2 and 7 days after orogastric infection revealed significantly lower numbers of bacteria of the slyA mutants and of the SlyA-overproducing strain in PP than of the wild type. However, similar numbers of bacteria of all strains were still present in the lumen of the small intestine after these times. Invasion assays of PP tissue after 90-min ileal loop infection yielded comparable numbers of bacteria of all strains in PP. Transmission and scanning electron microscopy of PP tissue after ileal loop infection demonstrated that the two slyA mutants and the SlyA-overproducing strain were able to attach to, induce membrane ruffling of, and invade M cells in a way morphologically and quantitatively similar to that of the wild type. In contrast to the wild type, both slyA mutants and, to a lesser extent, the SlyA-overproducing strain were significantly impaired in their ability to destroy M cells and adjacent enterocytes. Taken together, these data suggest that slyA is involved in intracellular survival and M-cell cytotoxicity but not in the invasion process and that the amount of SlyA needs to be precisely balanced for virulence.

The Alexander Project is a global surveillance study conducted from 1992 to 2001. Minimum inhibitory concentrations and percent resistance to a panel of antimicrobial agents were determined according to National Committee for Clinical Laboratory Standards methodology. Resistance to penicillin (PEN-R) and erythromycin (ERY-R) have increased in the period 1992-2001 by 3.9 and 4.5 times to 20.7% and 27.9%, respectively. Joint PEN-ERY-R has increased 4.9 times, up to 15.3%. In 1992, 57.1% of all PEN-R isolates were also ERY-R, whereas in 2001, 75.8% were ERY-R. Resistance to only 1 antibiotic increased slightly, from 8% in 1992 to 12% in 2001, whereas resistance to more than 1 antibiotic increased 4.3 times, from 6.4% in 1992 to 27.8% of all strains in 2001. Multidrug-resistant pneumococci are an increasingly common finding in the United States. Three of four PEN-R isolates are also multiresistant. The rate of growth of multidrug resistance is higher than that of single antibiotic resistance.

Internalization of Listeria monocytogenes into human brain microvascular endothelial cells (HBMEC) has recently been demonstrated to be dependent upon the inlB gene. In the present scanning electron microscopic study we show that L. monocytogenes efficiently interacts with the surface of HBMEC in an inlB -independent manner which is also different from invasion. The inlB -dependent invasion of HBMEC by L. monocytogenes is accompanied by intracellular multiplication, movement, and production of bacterium-containing protrusions. These protrusions extend from the cell surface without perturbation of any adjacent cellular membrane.

Several large, cell wall-associated internalins and one small, secreted internalin (InlC) have been described previously in Listeria monocytogenes. Using degenerate primers derived from sequenced peptides of an L. ivanovii major secreted protein, we identified a new 4.25 kb internalin locus of L. ivanovii, termed i-inlFE. The two proteins encoded by this locus, i-InlE and i-InlF, belong to the group of small, secreted internalins. Southern blot analyses show that the i-inlFE locus does not occur in L. monocytogenes. These data also indicate that six genes encoding small, secreted internalins are present in L. ivanovii, in contrast to L. monocytogenes, in which inlC encodes the only small internalin. The mature i-InlE protein (198 amino acids) is secreted in large amounts into the brain-heart infusion (BHI) culture medium in the stationary growth phase. In minimum essential medium (MEM), which has been used previously to induce PrfA-dependent gene transcription, i-inlE mRNA and i-InlE protein are expressed at high levels. As shown by Northern blot analysis and primer extension, transcription of the tandemly arranged i-inlF and i-inlE genes is dependent on the virulence regulator PrfA, and characteristic palindromic sequences ('PrfA-boxes') were identified in the promoter regions of i-inlF and i-inlE. Non-polar i-inlE and i-inlF deletion mutants and an i-inlFE double deletion mutant were constructed and tested in the mouse infection model. After intravenous infection, all three mutants entirely failed to kill C57BL/6 mice even at high infectious doses of 109 bacteria per mouse, whereas the LD50 for the parental strain was determined as 4 x 107 bacteria per mouse. These data suggest an important role for i-InlE and i-InlF in L. ivanovii virulence.

In recent years, rapid spread of toxic metals has occurred in all environmental matrices. The phenomenon started since many decades. Due to their bioaccumulation and toxicity, these contaminants are very dangerous pollutants for human health. The hazardousness of toxic metals is not lower than pesticides. Indeed, toxic metals are perhaps the most important reason of the pollution load in environmental ecosystems; certainly they are among the greatest. They come from almost all human activities: industries, agriculture, vehicular traffic, urban heating and so on. Pollution of an ecosystem can be caused in many ways, such as direct input through watercourses; for example, the case of aquatic ecosystems. But in general all ecosystems are subjected to pollution caused by atmospheric transport such as particulate or fumes. In order to evaluate the pollution load of ecosystems, two paths can be followed: 1) determination of pollutant concentrations by timely and repeated sampling in well-defined ecosystem sites; 2) determination of the same pollutants in species that live and are continually present in the same ecosystem (bio-monitoring). Evidently, punctual determinations cannot provide information to evaluate the long-term trend of the pollution load. This information can only be provided through bio-monitoring campaigns. Several Authors have given this suggestion, but the scientific community did not firmly support it. For each toxic-metal determination, the present work reports various species employed in bio-monitoring campaigns: mussels, oysters and clams, algae, vegetables, lichens, mosses. For each bio-monitor and for all metals or group of metals, the various analytical techniques and procedures employed are critically discussed. Particular attention is paid to the analytical performance, in terms of accuracy and detectability. A separate section is dedicated to the analytical procedure for the determination in bio-monitors of new emerging anthropic polluting traffic-related pollutants, i.e., the platinum group metals (platinum, palladium, rhodium, osmium, ruthenium and iridium)

Recently, the problem relevant to the increasing presence in the environment of platinum group metals (PGMs) have been a topical subject of great interest, even if the scientific attention has been generally addressed to platinum(II), palladium(II) and rhodium(III), and in few cases to iridium(III), osmium(VIII) and ruthenium(III). This is because the PGMs concentration is significantly growing as a consequence of their increasing use in the production of industrial catalysts, anticancer drugs, jewels, and especially autocatalytic converters. In the case of the last tools, their continuous incorrect use “stop and go” with consequent deterioration implies a considerable release of these metals in the environment. Even if initially the metals used in autocatalytic converters were platinum, palladium and rhodium, in recent years such PGMs were gradually replaced in part, or alloyed with osmium, ruthenium and, especially, iridium. In particular, in the last decade, and always more frequently, iridium is employed as alloying (10-20 % w/w) with platinum, palladium and rhodium in the manufacture of autocatalytic converters in order to withstand high temperature and high wear. Finally, it is also important to highlight that iridium is one of the least abundant elements in the environment, and, probably for this reason, very few data are available. Thus, this work intends to propose voltammetric methods for the determination of ultra-trace iridium in environmental samples: airborne particulate matter, superficial waters, soils/sediments, vegetables, mussels, clams and algae. To better validate the proposed analytical procedures, a critical comparison with spectroscopic measurements — electro-thermal atomic absorption spectroscopy (ET–AAS) because of its well established and tested robustness — has been also carried out and discussed here, taking into account all the parameters of interest to set-up an analytical method, such as precision, trueness, limit of detection and quantification, selectivity and, especially, sensitivity.

The presence of sources of pollution which release chemicals of concern into environmental media designate a major threat for human health and ecosystems. In general regulations prescribe the observance of emission threshold values for single sources and quality limit values and alert thresholds for separate environmental media, nevertheless the complete impact evaluation of industrial, agricultural and civil activities on environment requires a detailed and global analysis, in which manifold aspects of a specific area of interest are taken into account. A complete Environmental and Human Health Risk Assessment (EHHRA) procedure to quantify the adverse effects of exposure to carcinogenic or toxic substances is a fundamental focus both in order to control and monitor the environmental impact of existing plants and infrastructures and to prevent adverse effects (especially on human beings) by means of good manages of new installations and land use planning. The analysis is a well-consolidated procedure, and requires the integration of information on environmental and chemicals database, inter and intra media dispersion models output, site description maps, exposure patterns and demographic database. In addition, to include uncertainties and variability, probabilistic risk assessment and sensitivity analysis of calculation input parameters form an integral part of the analysis. As a result, the designing and conducting analysis of the effects of contaminants on human health is a complex and time expensive procedure, which call for the support of Decision Support Systems (DSS). A useful assistance in managing a large amount of spatial and non-spatial data is represented in particular by the GIS Decision Support Systems, explicitly designed to assist decision research process for complex spatial problems such as EHHRA. An examination of the existing literature on human health risk assessment tools is presented. Among these, the description of the EHHRA-GIS tool is detailed, pointing out the open architecture of the methodology approach, the implemented models, the performance and the potential developments of the tool. The upper-bound excess lifetime cancer risk and non-carcinogenic hazards are evaluated as risk measures, the spatial distribution of which is calculated and mapped on the involved territory.