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Reviews an Internet site called The Virtual Hospital, from the Electric Differential Multimedia Laboratory of the Department of Radiology, University of Iowa College of Medicine.

Reviews the videotex system `Online Images From the History of Medicine Division, National Library of Medicine.'

Reviews the computer software Medical Matrix by the American Medical Informatics Association.

Objectives: Ineffective communication between healthcare clinicians and Aboriginal and Torres Strait Islander patients with persistent pain is a significant barrier to optimal pain management. This manuscript is a study protocol and describes the development and evaluation methods of a tailored, culturally-informed training program, to improve clinicians' communication with patients., Study Design: This is a single-arm, multicentre (2 metropolitan and 1 regional persistent pain service) intervention feasibility study that will be evaluated using mixed methods., Methods: A communication training program will be developed informed by qualitative interviews with key stakeholders, and adapt the patient-centred 'clinical yarning' framework for the Queensland context. Evaluation of the effectiveness of the training will involve the analysis of quantitative data collected at three study sites over a 12-month period. At the patient level, communication experience will be rated at differing times of the training rollout to reflect participants' experience of communication either prior to or following the treating clinician attending the communication training. At the clinician level, evaluation of the training program will be based on changes of ratings in the importance of training, knowledge, ability and confidence to communicate with Aboriginal and Torres Strait Islander patients; satisfaction, acceptance and relevance to their clinical practice. This study will be grounded in the needs and preferences of communication of Aboriginal and Torres Strait Islander people living with pain., Conclusion: It is hypothesized that the patient-centred intervention will have immediate benefits for patients, improving patient experience of care. This research will focus on an area of unmet need in addressing persistent pain., (© 2021 The Authors.)

Background: The use of rasburicase has been evaluated extensively in children, but not in adults. We review the current literature to evaluate its effect on adults., Study Design: Systematic review and meta-analysis., Setting & Population: Adults receiving rasburicase for tumor lysis syndrome (TLS)., Selection Criteria for Studies: Electronic databases, regulatory documents, and websites were searched up to August 7, 2012. Reference lists of published articles were examined for additional relevant references. Any controlled trial or observational studies (controlled before and after) were included. Studies considering children only or mixing data for children and adults were excluded., Intervention: Rasburicase for TLS., Outcomes: The primary outcome was TLS development. Secondary outcomes included percentage of patients improving, total adverse events, acute kidney failure, deaths, and serum uric acid and creatinine levels., Results: 21 studies (24 publications) reported data for 1,261 adult patients, 768 receiving rasburicase for either the treatment or prophylaxis of TLS; these comprised 4 controlled trials and 17 observational studies. No statistically significant differences in clinical TLS development were observed in the controlled trials between the rasburicase and control groups. For the observational studies, 7.4% of patients developed clinical TLS after rasburicase (95% CI, 1.7%-16.7%), 93.4% of patients achieved normalized serum uric acid levels after rasburicase treatment (95% CI, 91.7%-94.6%), 4.4% developed acute kidney injury (95% CI, 3.0%-6.0%), and 2.6% died (95% CI, 0.95%-5.0%). The mean reduction in serum uric acid levels ranged from 5.3-12.8 mg/dL, and for serum creatinine levels, from 0.10-2.1 mg/dL., Limitations: Controlled trials differed in outcomes reported; meta-analysis was not performed., Conclusions: Rasburicase is effective in reducing serum uric acid levels in adults with TLS but at a significant cost, and evidence currently is lacking in adults to report whether rasburicase use improves clinical outcomes compared with other alternatives. Until new evidence is available, use of rasburicase may be limited to adult patients with a high risk of TLS., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Three modeling systems were used to estimate human health risks from air pollution: two versions of MNRiskS (for Minnesota Risk Screening), and the USEPA National Air Toxics Assessment (NATA). MNRiskS is a unique cumulative risk modeling system used to assess risks from multiple air toxics, sources, and pathways on a local to a state-wide scale. In addition, ambient outdoor air monitoring data were available for estimation of risks and comparison with the modeled estimates of air concentrations. Highest air concentrations and estimated risks were generally found in the Minneapolis-St. Paul metropolitan area and lowest risks in undeveloped rural areas. Emissions from mobile and area (nonpoint) sources created greater estimated risks than emissions from point sources. Highest cancer risks were via ingestion pathway exposures to dioxins and related compounds. Diesel particles, acrolein, and formaldehyde created the highest estimated inhalation health impacts. Model-estimated air concentrations were generally highest for NATA and lowest for the AERMOD version of MNRiskS. This validation study showed reasonable agreement between available measurements and model predictions, although results varied among pollutants, and predictions were often lower than measurements. The results increased confidence in identifying pollutants, pathways, geographic areas, sources, and receptors of potential concern, and thus provide a basis for informing pollution reduction strategies and focusing efforts on specific pollutants (diesel particles, acrolein, and formaldehyde), geographic areas (urban centers), and source categories (nonpoint sources). The results heighten concerns about risks from food chain exposures to dioxins and PAHs. Risk estimates were sensitive to variations in methodologies for treating emissions, dispersion, deposition, exposure, and toxicity., (© 2011 Society for Risk Analysis.)

Contaminated vermiculite ore from Libby, Montana was processed in northeast Minneapolis from 1936 to 1989 in a densely populated urban residential neighborhood, resulting in non-occupational exposure scenarios from plant stack and fugitive emissions as well as from activity-based scenarios associated with use of the waste rock in the surrounding community. The objective of this analysis was to estimate potential cumulative asbestos exposure for all non-occupationally exposed members of this community. Questionnaire data from a neighborhood-exposure assessment ascertained frequency of potential contact with vermiculite processing waste. Monte Carlo simulation was used to develop exposure estimates based on activity-based concentration estimates and contact durations for four scenarios: S1, moved asbestos-contaminated waste; S2, used waste at home, on lawn or garden; S3, installed/removed vermiculite insulation; S4, played in or around waste piles at the plant. The simulation outputs were combined with air-dispersion model results to provide total cumulative asbestos exposure estimates for the cohort. Fiber emissions from the plant were the largest source of exposure for the majority of the cohort, with geometric mean cumulative exposures of 0.02 fibers/cc × month. The addition of S1, S2 and S3 did not significantly increase total cumulative exposure above background exposure estimates obtained from dispersion modeling. Activity-based exposures were a substantial contributor to the upper end of the exposure distribution: 90th percentile S4 exposure estimates are ∼10 times higher than exposures from plant emissions. Pile playing is the strongest source of asbestos exposure in this cohort, with other activity scenarios contributing less than from plant emissions.

Regulatory agencies are frequently called upon to assess the potential for significant environmental impacts from air pollution emissions. These assessments often entail air dispersion modeling to estimate air concentrations that can be compared with standards or health benchmarks. Some air pollutants can also impact human health through pathways in media besides air. Risk assessment models are available that consider pollutant deposition, movement, uptake, and other processes on land and water and in biota, but they are typically effort-intensive. A screening-level assessment of potential multipathway effects would be useful. We developed multipathway screening factors (MPSFs) that can be applied to inhalation risk estimates to give screening estimates of risks via ingestion pathways. The MPSFs were generated using a generic multipathway risk assessment, consisting of air dispersion and deposition modeling followed by risk modeling for 42 persistent, bioaccumulative air pollutants. MPSFs are defined as the ratio of ingestion risks to inhalation risks. We report here the results of a sensitivity analysis that evaluates the effects on the MPSF ratio of varying inputs to the air dispersion and deposition modeling analysis. Model input parameters were systematically varied and multipathway risks recalculated. From the sensitivity analysis results, reasonable upper-bound values for the ratio of ingestion risks to inhalation risks for each pollutant were selected. The particle size distribution and the method of calculating particle deposition had the most disproportionate effect on inhalation versus ingestion risks and the greatest effect on MPSFs. Risk calculations are often done at the points of maximum air concentration and maximum deposition. In this study, the MPSFs were usually highest at the location of the maximum inhalation risk.

Ethanol fuel production is growing rapidly in the rural Midwest, and this growth presents potential environmental impacts. In 2002, the U.S. Environmental Protection Agency (EPA) and the Minnesota Pollution Control Agency (MPCA) entered into enforcement actions with 12 fuel ethanol plants in Minnesota. The enforcement actions uncovered underreported emissions and resulted in consent decrees that required pollution control equipment be installed. A key component of the consent decrees was a requirement to conduct emissions tests for volatile organic compounds (VOCs) with the goal of improving the characterization and control of emissions. The conventional VOC stack test method was thought to underquantify total VOC emissions from ethanol plants. A hybrid test method was also developed that involved quantification of individual VOC species. The resulting database of total and speciated VOC emissions from 10 fuel ethanol plants is relatively small, but it is the most extensive to date and has been used to develop and gauge compliance with permit limits and to estimate health risks in Minnesota. Emissions were highly variable among facilities and emissions units. In addition to the variability, the small number of samples and the presence of many values below detection limits complicate the analysis of the data. To account for these issues, a nested bootstrap procedure on the Kaplan-Meier method was used to calculate means and upper confidence limits. In general, the fermentation scrubbers and fluid bed coolers emitted the largest mass of VOC emissions. Across most facilities and emissions units ethanol was the pollutant emitted at the highest rate. Acetaldehyde, acetic acid, and ethyl acetate were also important emissions from some units. Emissions of total VOCs, ethanol, and some other species appeared to be a function of the beer feed rate, although the relationship was not reliable enough to develop a production rate-based emissions factor.

Hospital care, physician and clinical services, and prescription drugs continue to drive healthcare expenditures across healthcare systems and nations. The critical-care setting, owing to the complexity and intensity of care, is a high user of the resources that drive healthcare spending. Information regarding the cost and effectiveness of critical-care therapies is necessary to properly guide care and policies for this unique population. Many challenges exist for conducting and comparing economic evaluation in critical care. Recently, recommendations on cost and cost-effectiveness analysis in critical care have been developed that will guide future research. A focus area, severe sepsis in oncology, is reviewed to highlight the challenges and opportunities of economic evaluation in this setting.

Huntington's disease (HD) is one of a group of neurodegenerative disorders caused by the pathological expansion of a glutamine tract. A hallmark of these so-called polyglutamine diseases is the presence of ubiquitylated inclusion bodies, which sequester various components of the 19S and 20S proteasomes. In addition, the ubiquitin-proteasome system (UPS) has been shown to be severely impaired in vitro in cells overexpressing mutant huntingtin. Thus, because of its fundamental housekeeping function, impairment of the UPS in neurons could contribute to neurotoxicity. We have recently proposed that the proteasome activator REGgamma could contribute to UPS impairment in polyglutamine diseases by suppressing the proteasomal catalytic sites responsible for cleaving Gln-Gln bonds. Capping of proteasomes with REGgamma could therefore contribute to a potential 'clogging' of the proteasome by pathogenic polyglutamines. We show here that genetic reduction of REGgamma has no effect on the well-defined neurological phenotype of R6/2 HD mice and does not affect inclusion body formation in the R6/2 brain. Surprisingly, we observe increased proteasomal 'chymotrypsin-like' activity in 13-week-old R6/2 brains relative to non-R6/2, irrespective of REGgamma levels. However, assays of 26S proteasome activity in mouse brain extracts reveal no difference in proteolytic activity regardless of R6/2 or REGgamma genotype. These findings suggest that REGgamma is not a viable therapeutic target in polyglutamine disease and that overall proteasome function is not impaired by trapped mutant polyglutamine in R6/2 mice.

PA200, the most recently discovered activator of the 20S proteasome, is a nuclear protein thought to play a role in DNA repair. Homologs of PA200 have been found in rat, frog, birds, worms, and budding yeast, where it is called Blm3p (now known as Blm10p), but not in Drosophila or fission yeast. Western blots of SDS-PAGE transfers reveal 160 and 200K forms of mammalian PA200, and organ surveys demonstrate that the 200K species is highest in testis. PA200 purified from bovine testis binds the ends of the cylindrical 20S proteasome, forming volcano-shaped structures in negatively stained EM images. In vitro assays demonstrate that binding of PA200 activates peptide hydrolysis by the 20S proteasome. This chapter describes the purification and assay of bovine testis PA200.

Proteasomes perform the bulk of nonlysosomal degradation of aberrant, damaged, misfolded, and naturally short-lived regulatory proteins in eukaryotic cells. They are approximately 700-kDa assemblies whose hollow architecture sequesters the proteolytic sites inside a central chamber, thereby ensuring that the activity of isolated proteasomes is repressed. In vivo, proteasomes are activated by protein complexes, including the 11S activators (PA28 and PA26), which bind to one or both ends of the barrel-shaped structure. This chapter describes protocols for the purification of recombinant 11S regulators, characterization of their ability to stimulate proteasome activity, and crystallization of proteasome complexes.

The proteasome activation properties of recombinant REG gamma molecules depend on purification procedures. Prior to ammonium sulfate precipitation recombinant REG gamma activates the trypsin-like catalytic subunit of the proteasome; afterwards it activates all three catalytic subunits. The expanded activation specificity is accompanied by reduced stability of the REG gamma heptamer providing support for the idea that a "tight" REG gamma heptamer suppresses the proteasome's chymotrypsin-like and postglutamyl-preferring active sites. In an attempt to determine whether REG gamma synthesized in mammalian cells also exhibits restricted activation properties, extracts were prepared from several mammalian organs and cell lines. Surprisingly, endogenous REG gamma was found to be largely monomeric. In an alternate approach, COS7 cells were cotransfected with plasmids expressing FLAG-REG gamma and REG gamma. The expressed FLAG-REG gamma molecules were shown to form oligomers with untagged REG gamma subunits, and the mixed oligomers preferentially activated the proteasome's trypsin-like subunit. Thus, REG gamma molecules synthesized in mammalian cells also exhibit restricted activation properties.

We have identified a novel 200 kDa nuclear protein that activates the proteasome. The protein, which we call PA200, has been purified to homogeneity from bovine testis and has been shown to activate proteasomal hydrolysis of peptides, but not proteins. Following gamma-irradiation of HeLa cells the uniform nuclear distribution of PA200 changes to a strikingly punctate pattern, a behavior characteristic of many DNA repair proteins. Homologs of PA200 are present in worms, plants and yeast. Others have shown that mutation of yeast PA200 results in hypersensitivity to bleomycin, and exposure of yeast to DNA damaging agents induces the PA200 message. Taken together, these findings implicate PA200 in DNA repair, possibly by recruiting proteasomes to double strand breaks.