bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of gene expression signatures of diamide, H2O2 and menadione exposed Aspergillus nidulans cultures – linking genome-wide transcriptional changes to cellular physiology
Authors: Pócsi István , Miskei Márton , Karányi Zsolt , Emri Tamás , Ayoubi Patricia , Pusztahelyi Tünde , Balla György , Prade Rolf A
Published: December 2005

Background

In addition to their cytotoxic nature, reactive oxygen species (ROS) are also signal molecules in diverse cellular processes in eukaryotic organisms. Linking genome-wide transcriptional changes to cellular physiology in oxidative stress-exposed Aspergillus nidulans cultures provides the opportunity to estimate the sizes of peroxide (O2
2-), superoxide (O2
•-) and glutathione/glutathione disulphide (GSH/GSSG) redox imbalance responses.

Results

Genome-wide transcriptional changes triggered by diamide, H2O2 and menadione in A. nidulans vegetative tissues were recorded using DNA microarrays containing 3533 unique PCR-amplified probes. Evaluation of LOESS-normalized data indicated that 2499 gene probes were affected by at least one stress-inducing agent. The stress induced by diamide and H2O2 were pulse-like, with recovery after 1 h exposure time while no recovery was observed with menadione. The distribution of stress-responsive gene probes among major physiological functional categories was approximately the same for each agent. The gene group sizes solely responsive to changes in intracellular O2
2-, O2
•- concentrations or to GSH/GSSG redox imbalance were estimated at 7.7, 32.6 and 13.0 %, respectively. Gene groups responsive to diamide, H2O2 and menadione treatments and gene groups influenced by GSH/GSSG, O2
2- and O2
•- were only partly overlapping with distinct enrichment profiles within functional categories. Changes in the GSH/GSSG redox state influenced expression of genes coding for PBS2 like MAPK kinase homologue, PSK2 kinase homologue, AtfA transcription factor, and many elements of ubiquitin tagging, cell division cycle regulators, translation machinery proteins, defense and stress proteins, transport proteins as well as many enzymes of the primary and secondary metabolisms. Meanwhile, a separate set of genes encoding transport proteins, CpcA and JlbA amino acid starvation-responsive transcription factors, and some elements of sexual development and sporulation was ROS responsive.

Conclusion

The existence of separate O2
2-, O2
•- and GSH/GSSG responsive gene groups in a eukaryotic genome has been demonstrated. Oxidant-triggered, genome-wide transcriptional changes should be analyzed considering changes in oxidative stress-responsive physiological conditions and not correlating them directly to the chemistry and concentrations of the oxidative stress-inducing agent.
Balance of IL-10 and Interferon-γ plasma levels in human visceral leishmaniasis: Implications in the pathogenesis
Authors: Caldas Arlene , Favali Cecília , Aquino Dorlene , Vinhas Vera , van Weyenbergh Johan , Brodskyn Cláudia , Costa Jackson , Barral-Netto Manoel , Barral Aldina
Published: December 2005

Background

Leishmaniasis remains a serious public health problem in several parts of the developing world. Effective prophylactic measurements are hampered by imprecise comprehension of different aspects of the disease, including its immunoregulation. A better comprehension of immunoregulation in human VL may be useful both for designing and evaluating immunoprophylaxis.

Methods

To explore immunoregulatory mechanisms, 20 visceral leishmaniasis (VL) patients were evaluated during active disease and at different periods up to one year after treatment determining their plasma cytokine levels, clinical parameters (palpable spleen and liver) and antibody levels.

Results

Elevated plasma levels of IFN-γ and of IL-12 p40 were observed during active disease, significantly decreasing after treatment whereas in vitro Leishmania antigen-stimulated IFN-γ production by PBMC exhibited an inverse pattern being low during disease and increasing steadily thereafter. Absence of IFN-γ activity is a hallmark of VL. The main candidate for blunting IFN-γ activity is IL-10, a cytokine highly elevated in plasma with sharp decrease after treatment. Activity of IL-10 is inferred by high levels of anti-Leishmania specific IgG1 and IgG3. TGF-β had elevated total, but not of active, levels lessening the likelihood of being the IFN-γ counterpart. Spleen or liver size presented a steady decrease but return to normal values at only 120 days after treatment. Anti-Leishmania IgG (total and subclasses) levels and DTH or Leishmania-stimulated lymphocyte proliferation conversion to positive also present a slow decrease after treatment. IL-6 plasma levels were elevated in only a few patients.

Conclusion

Taken together our results suggest that IFN-γ and IL-10 are the molecules most likely involved in determining fate of disease. After treatment, there is a long delay before the immune profile returns to normal what precludes using plasma cytokine levels as criteria of cure as simpler clinical evaluations, as a palpable spleen or liver, can be used.
Takifugu obscurus is a euryhaline fugu species very close to Takifugu rubripes and suitable for studying osmoregulation
Authors: Kato Akira , Doi Hiroyuki , Nakada Tsutomu , Sakai Harumi , Hirose Shigehisa
Published: December 2005

Background

The genome sequence of the pufferfishTakifugu rubripesis an enormously useful tool in the molecular physiology of fish. Euryhaline fish that can survive both in freshwater (FW) and seawater (SW) are also very useful for studying fish physiology, especially osmoregulation. Recently we learned that there is a pufferfish,Takifugu obscurus, common name "mefugu" that migrates into FW to spawn. IfT. obscurusis indeed a euryhaline fish and shares a high sequence homology withT. rubripes, it will become a superior animal model for studying the mechanism of osmoregulation. We have therefore determined its euryhalinity and phylogenetic relationship to the members of theTakifugufamily.

Results

The following sixTakifuguspecies were used for the analyses:T. obscurus,T. rubripes,T. niphobles,T. pardalis,T. poecilonotus, andT. porphyreus. When transferred to FW, onlyT. obscuruscould survive while the others could not survive more than ten days in FW. During this course of FW adaptation, serum Na+concentration ofT. obscurusdecreased only slightly, but a rapid and large decrease occurred even in the case ofT. niphobles, a peripheral fresh water species that is often seen in brackish river mouths. Phylogenetic analysis using nucleotide sequences of the mitochondrial 16S ribosomal RNA gene of each species indicated that the sixTakifuguspecies are very closely related with each other.

Conclusion

T. obscurusis capable of adapting to both FW and SW. Its genomic sequence shares a very high homology with those of the otherTakifuguspecies such that the existingTakifugugenomic information resources can be utilized. These properties make "mefugu", which has drawn little attention from animal physiologists until this study, a useful model animal for studying the molecular mechanism of maintaining body fluid homeostasis.
The influence of objectives, learning experiences and examination blueprint on medical students' examination preparation
Authors: McLaughlin K , Coderre S , Woloschuk W , Lim T , Muruve D , Mandin H
Published: December 2005

Background

The influence of intended and informal curricula on examination preparation has not been extensively studied. This study aims to firstly describe how students utilized components of intended and informal curricula to guide examination preparation, and secondly to study the relationship between examination preparation and performance.

Methods

Students received a pre-examination questionnaire to identify components from the intended curriculum (objectives and examination blueprint), and informal curriculum (content emphasised during lectures and small groups), used during examination preparation. Multiple logistic regression was used to study the relationship between these variables and student performance (above versus at or below average).

Results

Eighty-one students participated. There was no difference in the proportions using the examination blueprint, content emphasised during lectures, and content emphasised during small groups (87 – 93%) but fewer students used objectives (35%, p < 0.001). Objectives use was associated with reduced odds of above average examination performance (adjusted odds ratio 0.27 [0.07, 0.97], p = 0.04).

Conclusion

When preparing for the renal course examination, students were influenced at least as much by the informal as the intended curriculum. Of the two intended curriculum components, the examination blueprint appeared to be more widely used than the course objectives. This decreased use of objectives on examination preparation did not appear to have a detrimental effect on student performance.
Providing education on evidence-based practice improved knowledge but did not change behaviour: a before and after study
Authors: McCluskey Annie , Lovarini Meryl
Published: December 2005

Background

Many health professionals lack the skills to find and appraise published research. This lack of skills and associated knowledge needs to be addressed, and practice habits need to change, for evidence-based practice to occur. The aim of this before and after study was to evaluate the effect of a multifaceted intervention on the knowledge, skills, attitudes and behaviour of allied health professionals.

Methods

114 self-selected occupational therapists were recruited. The intervention included a 2-day workshop combined with outreach support for eight months. Support involved email and telephone contact and a workplace visit. Measures were collected at baseline, post-workshop, and eight months later. The primary outcome was knowledge, measured using the Adapted Fresno Test of Evidence-Based Practice (total score 0 to 156). Secondary outcomes were attitude to evidence-based practice (% reporting improved skills and confidence; % reporting barriers), and behaviour measured using an activity diary (% engaging/not engaging in search and appraisal activities), and assignment completion.

Results

Post-workshop, there were significant gains in knowledge which were maintained at follow-up. The mean difference in the Adapted Fresno Test total score was 20.6 points (95% CI, 15.6 to 25.5). The change from post-workshop to follow-up was small and non-significant (mean difference 1.2 points, 95% CI, -6.0 to 8.5). Fewer participants reported lack of searching and appraisal skills as barriers to evidence-based practice over time (searching = 61%, 53%, 24%; appraisal 60%, 65%, 41%). These differences were statistically significant (p = 0.0001 and 0.010 respectively). Behaviour changed little. Pre-workshop, 6% engaged in critical appraisal increasing to 18% post-workshop and 18% at follow-up. Nearly two thirds (60%) were not reading any research literature at follow-up. Twenty-three participants (20.2%) completed their assignment.

Conclusion

Evidence-based practice skills and knowledge improved markedly with a targetted education intervention and outreach support. However, changes in behaviour were small, based on the frequency of searching and appraisal activities. Allied health educators should focus more on post-workshop skill development, particularly appraisal, and help learners to establish new routines and priorities around evidence-based practice. Learners also need to know that behaviour change of this nature may take months, even years.
Mechanomyographic amplitude and frequency responses during dynamic muscle actions: a comprehensive review
Authors: Beck Travis W , Housh Terry J , Cramer Joel T , Weir Joseph P , Johnson Glen O , Coburn Jared W , Malek Moh H , Mielke Michelle
Published: December 2005

The purpose of this review is to examine the literature that has investigated mechanomyographic (MMG) amplitude and frequency responses during dynamic muscle actions. To date, the majority of MMG research has focused on isometric muscle actions. Recent studies, however, have examined the MMG time and/or frequency domain responses during various types of dynamic activities, including dynamic constant external resistance (DCER) and isokinetic muscle actions, as well as cycle ergometry. Despite the potential influences of factors such as changes in muscle length and the thickness of the tissue between the muscle and the MMG sensor, there is convincing evidence that during dynamic muscle actions, the MMG signal provides valid information regarding muscle function. This argument is supported by consistencies in the MMG literature, such as the close relationship between MMG amplitude and power output and a linear increase in MMG amplitude with concentric torque production. There are still many issues, however, that have yet to be resolved, and the literature base for MMG during both dynamic and isometric muscle actions is far from complete. Thus, it is important to investigate the unique applications of MMG amplitude and frequency responses with different experimental designs/methodologies to continually reassess the uses/limitations of MMG.
Hemangiopericytoma of the spleen: Unusual presentation as multiple abscess
Authors: Kumar Mukesh , Tripathi Kamlakar , Khanna Rahul , Kumar Mohan , Khanna Ajay K
Published: December 2005

Background

Hemangiopericytoma is a soft tissue vascular neoplasm arising from capillary pericytes and is found throughout the body in soft tissues and bone. It was first described in 1942. Primary vascular neoplasm of the spleen constitutes the majority of nonhaematolymphoid splenic tumors like haemangioma, lymphangioma, hemangioendothelioma, hemangiopericytoma etc. Splenic hemangiopericytoma is a rare tumor and probably first case was described in 1989. Uptill now only eight cases are reported in the English literature.

Case presentation

A-35-year old male presented with fever and dull aching pain in left hypochondriac region. Radiological evaluation showed presence of multiple abscesses in spleen. Investigations were done to rule out common causes of abscess in spleen. After failure of medical management, he was subjected to elective splenectomy. There were dense adhesions between the spleen and the adjacent structures and the diaphragm. The histopathology of the resected specimen showed hemangiopericytoma of spleen.

Conclusion

The present case illustrate that the hemangiopericytoma of spleen can mimic as multiple abscess. Splenectomy is the treatment of choice.
Involvement of claudin-7 in HIV infection of CD4(-) cells
Authors: Zheng Junying , Xie Yiming , Campbell Richard , Song Jun , Massachi Samira , Razi Miriam , Chiu Robert , Berenson James , Yang Otto O , Chen Irvin SY , Pang Shen
Published: December 2005

Background

Human immunodeficiency virus (HIV) infection of CD4(-) cells has been demonstrated, and this may be an important mechanism for HIV transmission.

Results

We demonstrated that a membrane protein, claudin-7 (CLDN-7), is involved in HIV infection of CD4(-) cells. A significant increase in HIV susceptibility (2- to 100-fold) was demonstrated when CLDN-7 was transfected into a CD4(-) cell line, 293T. In addition, antibodies against CLDN-7 significantly decreased HIV infection of CD4(-) cells. Furthermore, HIV virions expressing CLDN-7 on their envelopes had a much higher infectivity for 293T CD4(-) cells than the parental HIV with no CLDN-7. RT-PCR results demonstrated that CLDN-7 is expressed in both macrophages and stimulated peripheral blood leukocytes, suggesting that most HIV virions generated in infected individuals have CLDN-7 on their envelopes. We also found that CLDN-7 is highly expressed in urogenital and gastrointestinal tissues.

Conclusion

Together these results suggest that CLDN-7 may play an important role in HIV infection of CD4(-) cells.
Scutellaria baicalensis decreases ritonavir-induced nausea
Authors: Aung Han , Mehendale Sangeeta , Chang Wei-Tien , Wang Chong-Zhi , Xie Jing-Tian , Yuan Chun-Su
Published: December 2005

Background

Protease inhibitors, particularly ritonavir, causes significant gastrointestinal disturbances such as nausea, even at low doses. This ritonavir-induced nausea could be related to its oxidative stress in the gut. Alleviation of drug-induced nausea is important in effectively increasing patients' compliance and improving their quality of life. Conventional anti-emetic drugs can only partially abate the symptoms in these patients, and their cost has also been a concern. Rats respond to nausea-producing emetic stimuli by increasing consumption of non-nutritive substances like kaolin or clay, a phenomenon known as pica. In this study, we used this rat pica model to evaluate the effects ofScutellaria baicalensis, a commonly used oriental herbal medicine, on ritonavir-induced nausea.

Results

Rats treated with 20 mg/kg ritonavir significant caused increases of kaolin consumption at 24 to 48 hr (P< 0.01). Pretreatment with 0.3 and 3 mg/kgScutellaria baicalensisextract significantly decreased ritonavir-induced kaolin intake in a dose-related manner (P< 0.01). Compared to vehicle treatment, the extract completely prevented ritonavir-induced kaolin consumption at dose 3 mg/kg. The area under the curves (AUC) for kaolin intake from time 0 to 120 hr for vehicle only, ritonavir only, SbE 0.3 mg/kg plus ritonavir, and SbE 3 mg/kg plus ritonavir were 27.3 g•hr, 146.7 g•hr, 123.2 g•hr, and 32.7 g•hr, respectively. The reduction in area under the curves of kaolin intake from time 0 to 120 hr between ritonavir only and SbE 0.3 mg/kg plus ritonavir, ritonavir only and SbE 3 mg/kg plus ritonavir were 16.0% and 77.7%, respectively.

Conclusion

Scutellaria baicalensissignificantly attenuated ritonavir-induced pica, and demonstrated a potential in treating ritonavir-induced nausea.
The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: A pilot study
Authors: Mavropoulos John C , Yancy William S , Hepburn Juanita , Westman Eric C
Published: December 2005

Background

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age and is associated with obesity, hyperinsulinemia, and insulin resistance. Because low carbohydrate diets have been shown to reduce insulin resistance, this pilot study investigated the six-month metabolic and endocrine effects of a low-carbohydrate, ketogenic diet (LCKD) on overweight and obese women with PCOS.

Results

Eleven women with a body mass index >27 kg/m2 and a clinical diagnosis of PCOS were recruited from the community. They were instructed to limit their carbohydrate intake to 20 grams or less per day for 24 weeks. Participants returned every two weeks to an outpatient research clinic for measurements and reinforcement of dietary instruction. In the 5 women who completed the study, there were significant reductions from baseline to 24 weeks in body weight (-12%), percent free testosterone (-22%), LH/FSH ratio (-36%), and fasting insulin (-54%). There were non-significant decreases in insulin, glucose, testosterone, HgbA1c, triglyceride, and perceived body hair. Two women became pregnant despite previous infertility problems.

Conclusion

In this pilot study, a LCKD led to significant improvement in weight, percent free testosterone, LH/FSH ratio, and fasting insulin in women with obesity and PCOS over a 24 week period.
Thickness of the human cranial diploe in relation to age, sex and general body build
Authors: Lynnerup Niels , Astrup Jacob G , Sejrsen Birgitte
Published: December 2005

Background

Earlier studies have addressed the human total cranial vault thickness and generally found no correlation with sex, age or body weight. However, the thickness of the diploe has not been investigated. Our study has determined the diploeic thickness of the human cranial vault using modern autopsy material.

Methods

The diploeic bone thickness was measured in 64 individuals (43 males, 21 females) autopsied at our institute. The thickness was measured by X-raying biopsies trephined at four specific locations on the skull. Complete medical records and pathologic autopsy results were available.

Results

There was a statistically significant difference in diploeic thickness between males and females in the frontal region only. Diploeic thickness was highly correlated with total cranial vault bone thickness, except for the left euryon in females. Subsequent analyses failed to reveal any correlations between the diploeic thickness and age and height and weight of the individual.

Conclusion

Males overall have a thicker diploe, albeit this difference is statistically significant only in the frontal region. We could not discern any trends as pertains to diploeic thickness versus age, height or weight. Since the thickness of the diploe may be an important parameter in biomechanical modelling of the cranial vault, this means that the diploe can be built into such models based on the total cranial thickness, except for the frontal region where the sexual dimorphism must be taken into account. Our findings are consistent with previous studies relating the total cranial thickness to the same parameters, in that we found a high correlation between diploeic and total cranial thickness (except at the left euryon for females). Finally, we recommend that future studies try to incorporate CT or MR scan imaging, rather than point sampling, in order to achieve a total assessment of the dimensionalities of the diploe.
A procedure for localisation and electrophysiological characterisation of ion channels heterologously expressed in a plant context
Authors: Hosy E , Duby G , Véry A-A , Costa A , Sentenac H , Thibaud J-B
Published: December 2005

Background

In silico analyses based on sequence similarities with animal channels have identified a large number of plant genes likely to encode ion channels. The attempts made to characterise such putative plant channels at the functional level have most often relied on electrophysiological analyses in classical expression systems, such as Xenopus oocytes or mammalian cells. In a number of cases, these expression systems have failed so far to provide functional data and one can speculate that using a plant expression system instead of an animal one might provide a more efficient way towards functional characterisation of plant channels, and a more realistic context to investigate regulation of plant channels.

Results

With the aim of developing a plant expression system readily amenable to electrophysiological analyses, we optimised experimental conditions for preparation and transformation of tobacco mesophyll protoplasts and engineered expression plasmids, that were designed to allow subcellular localisation and functional characterisation of ion channels eventually in presence of their putative (possibly over-expressed) regulatory partners. Two inward K+ channels from the Shaker family were functionally expressed in this system: not only the compliant KAT1 but also the recalcitrant AKT1 channel, which remains electrically silent when expressed in Xenopus oocytes or in mammalian cells.

Conclusion

The level of endogenous currents in control protoplasts seems compatible with the use of the described experimental procedures for the characterisation of plant ion channels, by studying for instance their subcellular localisation, functional properties, structure-function relationships, interacting partners and regulation, very likely in a more realistic context than the classically used animal systems.
Cell surface expression of intermediate filament proteins vimentin and lamin B1 in human neutrophil spontaneous apoptosis
Authors: Moisan Eliane , Girard Denis
Published: December 2005

Neutrophils represent an important source of autoantigens for antineutrophil cytoplasmic antibody associated with vasculitis. To date, two cytoskeletal proteins, vinculin and vimentin, have been reported to be expressed on the cell surfaces of activated macrophages, platelets, and apoptotic T lymphocytes. However, such cell surface expression has never been studied in human neutrophils. As we recently demonstrated that different cytoskeletal proteins were cleaved in apoptotic neutrophils, we hypothesized that some of these were expressed on the cell surface of apoptotic neutrophils. Herein, we found that among vinculin, paxillin, gelsolin, vimentin, lamin B1, α-tubulin, and β-tubulin, only the two intermediate filament (INFIL) proteins, vimentin and lamin B1, are expressed on the cell surface of 24-h aged neutrophils [spontaneous apoptosis (SA)]. By monitoring intracellular expression of vimentin and lamin B1 during SA, we found that these two proteins were cleaved and that such cleavage was reversed by the pan caspase inhibitor N-benzyloxy-carbonyl-V-A-D-O-methylfluoromethyl ketone (z-VAD-fmk). When neutrophil apoptosis was delayed or suppressed by lipopolysaccharide or the cytokines granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage (GM)-CSF, or interleukin-4, the loss of intracellular expression of vimentin and lamin B1 was prevented. The INFIL proteins were absent from the cell surface when neutrophil apoptosis was delayed. Addition of z-VAD-fmk significantly decreased the cell surface expression of vimentin and lamin B1 during SA. This study provides the first evidence that apoptotic neutrophils express cytoskeletal proteins on their surface, opening the possibility that these cells may participate in the development of autoantibodies directed against cytoskeletal proteins, a condition frequently reported in several inflammatory diseases.
Neutrophil chemorepulsion in defined interleukin-8 gradients in vitro and in vivo
Authors: Tharp William G , Yadav R , Irimia D , Upadhyaya A , Samadani A , Hurtado O , Liu S Y , Munisamy S , Brainard D M , Mahon M J , Nourshargh S , van Oudenaarden A , Toner M G , Poznansky Mark C
Published: December 2005

We report for the first time that primary human neutrophils can undergo persistent, directionally biased movement away from a chemokine in vitro and in vivo, termed chemorepulsion or fugetaxis. Robust neutrophil chemorepulsion in microfluidic gradients of interleukin-8 (IL-8; CXC chemokine ligand 8) was dependent on the absolute concentration of chemokine, CXC chemokine receptor 2 (CXCR2), and was associated with polarization of cytoskeletal elements and signaling molecules involved in chemotaxis and leading edge formation. Like chemoattraction, chemorepulsion was pertussis toxin-sensitive and dependent on phosphoinositide-3 kinase, RhoGTPases, and associated proteins. Perturbation of neutrophil intracytoplasmic cyclic adenosine monophosphate concentrations and the activity of protein kinase C isoforms modulated directional bias and persistence of motility and could convert a chemorepellent to a chemoattractant response. Neutrophil chemorepulsion to an IL-8 ortholog was also demonstrated and quantified in a rat model of inflammation. The finding that neutrophils undergo chemorepulsion in response to continuous chemokine gradients expands the paradigm by which neutrophil migration is understood and may reveal a novel approach to our understanding of the homeostatic regulation of inflammation.
An evaluation of the US Environmental Protection Agency definition of a risk assessment
Authors: Beck B D
Published: December 2005

A full presentation of relevant information, including both non–adverse and beneficial effects, of chemicals is important to developing sound and balanced risk assessments. Such considerations are not new. For example, the American Thoracic Society has developed criteria for defining adverse and non–adverse pulmonary effects. Failing to allow risk assessors to even consider non–adverse and beneficial effects will discourage the use of information from developing technologies, such as genomics, and from new understandings of dose–response relationships, as reflected in the hormetic model. Failing to provide such information to risk managers potentially provides a biased perspective on risk
The case for integrating low dose, beneficial responses into US EPA risk assessments
Authors: DeSesso J M , Watson R E
Published: December 2005

When conducting risk assessments, the US Environmental Protection Agency (EPA) does not currently consider the beneficial effects from exposure to concentrations of agents below the no observed adverse effect level (NOAEL). If such benefits were observed, and if the beneficial and toxicological mechanisms of action were identical, this would probably be represented as a ‘j–shaped’ hormetic dose–response curve. If such data are available, they should be considered when assigning uncertainty factors for safe exposure calculations. However, when such data are not readily available, as is likely the case when the mechanism of action of the benefit differs from that of toxicity, current US EPA methods appear adequate.
The issue of risk in complex adaptive systems: the case of low-dose radiation induced cancer
Authors: Feinendegen L E , Neumann R D
Published: December 2005

Living systems exist in hierarchical levels of biological organization, ascending from the basic atomic-molecular level, to the cellular level, the tissue-organ level, and the whole organism. All levels and elements at each level communicate with each other though intricate intra-and intercellular signaling through many specified molecular interactions. These regulate homeostasis between the system levels and their individual elements.

The probability of a defined effect at the basic atomic-molecular level per impact increment of a toxic agent, such as ionizing radiation, at that level appears constant at low doses, even if the probability constant may change as a consequence of a previous exposure. Thus, at a given state of the system, the incidence of effect at the atomic-molecular level increases linearly with the number of impact increments in terms of energy deposition events. Primary effects may amplify to damage and there are immediate attempts at repairing the damage from an effect.

Amplification and propagation of damage at, and from, the basic to higher levels of biological organization meets resistance, the degree of which per impact increment is not constant. It changes with the number of impact increments. This resistance encompasses both physicochemical and biochemical reactions. The corresponding biochemical reactions express the physiological system's capacity to respond to perturbations of homeostasis at and between the various levels. Types and degrees of these responses depend on the system and the degree of homeostatic perturbation. At relatively mild to moderate degrees of perturbation, protective responses appear with a delay of hours and may last for months, shield also against endogenous non-radiogenic damage, and in doing so may prevail over radiogenic damage. With increasing degrees of homeostatic perturbation, damage eventually overwhelms adaptive protection. Thus, systems do not respond in a linear function of impact increments at the lowest level of biological organization.

For assessing the probability of radiation damage per absorbed dose, i.e., risk, in complex adaptive systems, both damaging and protecting responses need attention, and to exclude one for the other is scientifically unjustified and misleading.
An examination of the Environmental Protection Agency risk assessment principles and practices: a brief commentary on section 4.1.3 of the EPA March 2004 Staff Paper
Authors: Mundt K A
Published: December 2005

The US Environmental Protection Agency (EPA) recently issued a Staff Paper that articulates current risk assessment practices. In section 4.1.3, EPA states,“...effects that appear to be adaptive, non–adverse, or beneficial may not be mentioned.” This statement may be perceived as precluding risk assessments based on non–default risk models, including the hormetic–or biphasicdose–response model. This commentary examines several potential interpretations of this statement and the anticipated impact of ignoring hormesis, if present, in light of necessary conservatism for protecting human and environmental health, and the potential for employing alternative risk assessment approaches.
Examining the risks and benefits of considering both the traditional dose–response and hormesis in arriving at an acceptable exposure level
Authors: Pickrell J A , Oehme F W
Published: December 2005

In examining traditional dose–response and hormesis, we have considered the case examples of pulmonary hyperplasia following inhalation of carbon black and pulmonary hyperplasia after methyleneindolenine (3MEIN) exposures, development of irreversible pulmonary fibrosis, effect of continuous exercise and low–level lead exposures, and colorectal cancer. Adaptation can be used to estimate conventional dose responses. All cases discussed provided increased information about the reactions if hormetic features were included. In only the shigatoxin case was there clear irrefutable evidence that beneficial hormetic properties exist and must be considered; however, the one–in–six advantage is too great to ignore the potential benefits of hormesis. We recommend such hormetic properties be considered together with conventional dose responses to improve estimates of chemical risk.
Science-policy in environmental and health risk assessment: if we cannot do without, can we do better?
Authors: Ricci P F , Cox L A , MacDonald T R
Published: December 2005

How can empirical evidence of adverse effects from exposure to noxious agents, which is often incomplete and uncertain, be used most appropriately to protect human health? We examine several important questions on the best uses of empirical evidence in regulatory risk management decision–making raised by the US Environmental Protection Agency (EPA)'s science–policy concerning uncertainty and variability in human health risk assessment. In our view, the US EPA (and other agencies that have adopted similar views of risk management) can often improve decision–making by decreasing reliance on default values and assumptions, particularly when causation is uncertain. This can be achieved by more fully exploiting decision–theoretic methods and criteria that explicitly account for uncertain, possibly conflicting scientific beliefs and that can be fully studied by advocates and adversaries of a policy choice, in administrative decision–making involving risk assessment. The substitution of decision–theoretic frameworks for default assumption–driven policies also allows stakeholder attitudes toward risk to be incorporated into policy debates, so that the public and risk managers can more explicitly identify the roles of risk–aversion or other attitudes toward risk and uncertainty in policy recommendations. Decision theory provides a sound scientific way explicitly to account for new knowledge and its effects on eventual policy choices. Although these improvements can complicate regulatory analyses, simplifying default assumptions can create substantial costs to society and can prematurely cut off consideration of new scientific insights (e.g., possible beneficial health effects from exposure to sufficiently low ‘hormetic’ doses of some agents). In many cases, the administrative burden of applying decision–analytic methods is likely to be more than offset by improved effectiveness of regulations in achieving desired goals. Because many foreign jurisdictions adopt US EPA reasoning and methods of risk analysis, it may be especially valuable to incorporate decision–theoretic principles that transcend local differences among jurisdictions.
Comments on the Environmental Protection Agency's definition of risk assessment
Authors: Doull J
Published: December 2005

Common sense requires that regulation to prevent the adverse effects of exposure to chemicals should when possible preserve the desirable or beneficial effects of exposure to the chemical. Excluding such effects by definition is contrary to good science and common sense.
Profiles in Patient Safety: Confirmation Bias in Emergency Medicine
Authors: Pines Jesse M.
Published: December 2005

Confirmation bias is a pitfall in emergency care and may lead to inaccurate diagnoses and inappropriate treatments and care plans. Because of the increasing severity and volume of emergency care, emergency physicians often must rely on heuristics, such as rule‐out protocols, as a guide to diagnosing and treating patients. The use of heuristics or protocols can be potentially misleading if the initial diagnostic impression is incorrect. To minimize cognitive dissonance, clinicians may accentuate confirmatory data and ignore nonconfirmatory data. Clinicians should recognize confirmation bias as a potential pitfall in medical decision making in the emergency department. Reliance on the scientific method, Bayesian reasoning, metacognition, and cognitive forcing strategies may serve to improve diagnostic accuracy and improve patient care.
Predicting Smoking Stage of Change among Emergency Department Patients and Visitors
Authors: Boudreaux Edwin D. , Hunter Gabrielle C. , Bos Karen , Clark Sunday , Camargo Carlos A.
Published: December 2005

Objectives:

Little is known about whether emergency department (ED) patients or those who accompany them (visitors) are interested in smoking cessation. The authors hypothesized that several variables would be associated with stage of change, including nicotine dependence, self‐efficacy, presence of a smoking‐related illness, and anticipated cessation‐related health improvement.

Methods:

For two 24‐hour periods, consecutive patients and visitors aged 18 years and older presenting to four Boston EDs were interviewed. The authors assessed a range of smoking‐related constructs. Exclusion criteria included severe illness, cognitive insufficiency, and acute distress.

Results:

One thousand ten subjects were screened (56% patients, 44% visitors). Two hundred thirty‐seven (23%) subjects were current smokers, with 57% being in precontemplation, 31% in contemplation, and 12% in preparation stages. When ordinal regression was used, the variables most strongly associated with stage of change were as follows: self‐efficacy (odds ratio [OR] = 5.1; p < 0.001), anticipated cessation‐related health improvement (OR = 2.7; p = 0.02), and having a smoking‐related health problem (OR = 1.9; p = 0.08).

Conclusions:

Because many disenfranchised Americans use the ED as a regular source of health care, increased attention to smoking in the ED setting holds tremendous public health potential. This study's results reinforce the validity of the stage‐of‐change model within the ED setting. Developers of ED‐initiated interventions will have to consider the heterogeneity in stage of change when designing their treatments.
Susceptibility of Recent Bacterial Isolates to Cefdinir and Selected Antibiotics among Children with Urinary Tract Infections
Authors: Bonsu Bema K. , Shuler Lori , Sawicki Laura , Dorst Pam , Cohen Daniel M.
Published: December 2005

Background: Cefdinir, an extended‐spectrum cephalosporin administered orally, is approved by the U.S. Federal Drug Administration for treatment of skin and respiratory tract infections. During the last two years at the authors' institution, this agent has been used as an off‐label treatment for urinary tract infections in children.

Objectives: To evaluate antimicrobial susceptibility testing data in children to determine whether there is support for this prescribing practice.

Methods: In this retrospective study (2003–2004), the authors compared the susceptibility patterns of urinary pathogens to cefdinir and selected antibiotics in children who were evaluated for urinary tract infections in an urban tertiary academic pediatric emergency department. Pathogens (community acquired vs. opportunistic or nosocomial) were categorized as susceptible, indeterminate, or resistant on the basis of antibiotic susceptibility breakpoints. The frequency of these categorizations for individual drugs was determined.

Results: Seven hundred five isolates were recovered from urine during the study period. Pathogens isolated most frequently were Escherichia coli, Klebsiella spp, and Proteus spp. Of 431 isolates retained in the data set, 412 (95.6%) were susceptible to cefdinir. This rate was comparable or superior to rates observed for other antibiotics: 49.4% for ampicillin, 84.9% for trimethoprim–sulfamethoxazole, 88.4% for cefazolin, 93.3% for nitrofurantoin, 94.2% for ticarcillin–clavulanate potassium, 97.5% for gentamicin, and 97.7% for ceftriaxone. Cefdinir, however, had lower activity (64.7%) against 17 bacterial isolates categorized as opportunistic or nosocomial pathogens.

Conclusions: Cefdinir provides good coverage against common pathogens responsible for urinary tract infections in children and compares favorably with other oral and parenteral antibiotics that are used in the empiric treatment of this infection.
Using Queueing Theory to Increase the Effectiveness of Emergency Department Provider Staffing
Authors: Green Linda V. , Soares João , Giglio James F. , Green Robert A.
Published: December 2005

Objectives:
Significant variation in emergency department (ED) patient arrival rates necessitates the adjustment of staffing patterns to optimize the timely care of patients. This study evaluated the effectiveness of a queueing model in identifying provider staffing patterns to reduce the fraction of patients who leave without being seen.

Methods:
The authors collected detailed ED arrival data from an urban hospital and used a Lag SIPP queueing analysis to gain insights on how to change provider staffing to decrease the proportion of patients who leave without being seen. The authors then compared this proportion for the same 39‐week period before and after the resulting changes.

Results:
Despite an increase in arrival volume of 1,078 patients (6.3%), an average increase in provider hours of 12 hours per week (3.1%) resulted in 258 fewer patients who left without being seen. This represents a decrease in the proportion of patients who left without being seen by 22.9%. Restricting attention to a four‐day subset of the week during which there was no increase in total provider hours, a reallocation of providers based on the queueing model resulted in 161 fewer patients who left without being seen (21.7%), despite an additional 548 patients (5.5%) arriving in the second half of the study.

Conclusions:
Timely access to a provider is a critical dimension of ED quality performance. In an environment in which EDs are often understaffed, analyses of arrival patterns and the use of queueing models can be extremely useful in identifying the most effective allocation of staff.
Publication Bias of Randomized Controlled Trials in Emergency Medicine
Authors: Ospina Maria B. , Kelly Karen , Klassen Terry P. , Rowe Brian H.
Published: December 2005

Objectives:To determine the publication status and time to publication of randomized controlled trials (RCTs) that were presented at the Society for Academic Emergency Medicine (SAEM) meetings from 1995 to 2003. The impact of positive‐outcome bias, time‐lag bias, and gray literature bias also was assessed.

Methods:Retrospective cohort study of RCT abstracts presented at nine SAEM scientific meetings. Electronic searches identified publications from the abstracts.

Results:Of 4,399 abstracts, 383 (8.7%; 95% confidence interval [CI] = 7.8% to 9.5%) were identified as RCTs. One hundred ninety‐four (50.7%; 95% CI = 45.7% to 55.7%) were subsequently published up to May 2004. The median time to publication was 32 months (95% CI = 23 to 41), with 59% of RCT abstracts published within five years of presentation. No evidence of positive‐outcome bias or time‐lag bias was identified; however, changes from abstract to manuscript were found. Manuscripts were less likely to endorse the experimental intervention than were abstracts (OR, 0.2; 95% CI = 0.0 to 0.6).

Conclusions:The proportion of emergency medicine RCT abstracts published is slightly lower than that for other biomedical specialties; however, biases reported by investigators in other biomedical areas do not appear to be as problematic in emergency medicine research. Differences between conclusions from abstracts and manuscripts must be considered when employing meeting abstracts as a source of evidence for future research or for systematic reviews in emergency medicine.
Funding and Publishing Trends of Original Research by Emergency Medicine Investigators over the Past Decade
Authors: Birkhahn Robert H. , Van Deusen Shawn K. , Okpara Okemefuna I. , Datillo Paris A. , Briggs William M. , Gaeta Theodore J.
Published: December 2005

Objectives: To update the profile of author‐reported funding of reports of original research published since 1994 in the four U.S. peer‐reviewed general emergency medicine (EM) journals.

Methods: For the primary analysis, articles published in Academic Emergency Medicine, American Journal of Emergency Medicine, Annals of Emergency Medicine, and Journal of Emergency Medicine between 1994 and 2003 were reviewed by two emergency physicians trained in abstracting from the literature. Original research was identified; case reports, case series, abstracts, and meta‐analysis were excluded. Articles were classified by author report of extramural funding as government (public), private nonprofit (foundation), for profit (industry), or multiple. Data are reported as percent per year per journal. A secondary analysis of MEDLINE was performed to identify publishing trends by EM investigators outside of these four journals over the same period.

Results: The primary analysis identified 5,728 articles; 3,278 (57%) were considered original research, with 32% of these reporting extramural funding. In 1994, there were 292 articles with 28% funded (28% public, 43% foundation, 17% industry, and 12% multiple). By 2003, there were 358 articles with 36% funded (42% public, 30% foundation, 18% industry, and 10% multiple). There was a trend toward increased extramural funding in all four journals (p = 0.007), with an estimated growth of 3.6% (95% confidence interval = 1.0% to 6.3%) per year over the past decade. The primary review identified 48% of all articles published by EM investigators.

Conclusions: Author‐reported extramural funding rates for original research have increased in the EM literature over the past decade. Foundations have funded the largest number of studies, with public (government) sources increasing in 2003.