Showing papers by "University of Iowa published in 2007"

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

Abstract: Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline. Candida albicans remains the predominant cause of IC, accounting for over half of all cases, but Candida glabrata has emerged as the second most common cause of IC in the United States, and several less common Candida species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.

Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology

Abstract: Chelsea Kidwell, Patrick D. Lyden, Lewis B. Morgenstern, Adnan I. Qureshi, Robert Brass, Anthony Furlan, Robert L. Grubb, Randall T. Higashida, Edward C. Jauch, Harold P. Adams, Jr, Gregory del Zoppo, Mark J. Alberts, Deepak L. Bhatt, Lawrence Guidelines for the Early Management of Adults With Ischemic Stroke : ISSN: 1524-4628 Copyright © 2007 American Heart Association. All rights reserved. Print ISSN: 0039-2499. Online Stroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514 doi: 10.1161/STROKEAHA.107.181486 2007, 38:1655-1711: originally published online April 12, 2007 Stroke http://stroke.ahajournals.org/content/38/5/1655 located on the World Wide Web at: The online version of this article, along with updated information and services, is http://stroke.ahajournals.org/ http://stroke.ahajournals.org/ An erratum has been published regarding this article. Please see the attached page for:

Evolution of genes and genomes on the Drosophila phylogeny.

Abstract: Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Prevalence of dementia in the United States: the aging, demographics, and memory study.

Abstract: Aim: To estimate the prevalence of Alzheimer’s disease (AD) and other dementias in the USA using a nationally representative sample. Methods: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender. Results: The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71–79 years to 37.4% of those aged 90 and older. Conclusions: Dementia prevalence estimates from this first nation

Rankings and Reactivity: How Public Measures Recreate Social Worlds

Abstract: Recently, there has been a proliferation of measures responding to demands for accountability and transparency. Using the example of media rankings of law schools, this article argues that the methodological concept of reactivity—the idea that people change their behavior in reaction to being evaluated, observed, or measured—offers a useful lens for disclosing how these measures effect change. A framework is proposed for investigating the consequences, both intended and unintended, of public measures. The article first identifies two mechanisms, self‐fulfilling prophecy and commensuration, that induce reactivity and then distinguishes patterns of effects produced by reactivity. This approach demonstrates how these increasingly fateful public measures change expectations and permeate institutions, suggesting why it is important for scholars to investigate the impact of these measures more systematically.

Challenges for semiconductor spintronics

Abstract: High-volume information-processing and communications devices are at present based on semiconductor devices, whereas information-storage devices rely on multilayers of magnetic metals and insulators. Switching within information-processing devices is performed by the controlled motion of small pools of charge, whereas in the magnetic storage devices information storage and retrieval is performed by reorienting magnetic domains (although charge motion is often used for the final stage of readout). Semiconductor spintronics offers a possible direction towards the development of hybrid devices that could perform all three of these operations, logic, communications and storage, within the same materials technology. By taking advantage of spin coherence it also may sidestep some limitations on information manipulation previously thought to be fundamental. This article focuses on advances towards these goals in the past decade, during which experimental progress has been extraordinary.

Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Abstract: Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Use of Positron Emission Tomography for Response Assessment of Lymphoma: Consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma

Abstract: Purpose To develop guidelines for performing and interpreting positron emission tomography (PET) imaging for treatment assessment in patients with lymphoma both in clinical practice and in clinical trials. Methods An International Harmonization Project (IHP) was convened to discuss standardization of clinical trial parameters in lymphoma. An imaging subcommittee developed consensus recommendations based on published PET literature and the collective expertise of its members in the use of PET in lymphoma. Only recommendations subsequently endorsed by all IHP subcommittees were adopted.

CMS physics technical design report, volume II: Physics performance

Abstract: CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider (LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking--through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start-up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb−1 or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z' and supersymmetric particles, Bs production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb−1 to 30 fb−1. The Standard Model processes include QCD, B-physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z0 boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2-6 describe examples of full analyses, with photons, electrons, muons, jets, missing ET, B-mesons and τ's, and for quarkonia in heavy ion collisions. Chapters 7-15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model

Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Abstract: The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed.

Folic acid for the prevention of colorectal adenomas: a randomized clinical trial.

Abstract: ContextLaboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine.ObjectiveTo assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas.Design, Setting, and ParticipantsA double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma.InterventionParticipants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later).Main Outcome MeasuresThe primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (≥25% villous features, high-grade dysplasia, size ≥1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or ≥3 adenomas).Results During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation. ConclusionsFolic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.Trial Registration clinicaltrials.gov Identifier: NCT00272324

Alcohol Drinking in Never Users of Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Abstract: Background At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor. Methods We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case – control studies that included 10 244 head and neck cancer case subjects and 15 227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided. Results Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose – response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx. Conclusions Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology. J Natl Cancer Inst 2007;99: 777 – 89

An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations

Abstract: Aging is an inherently complex process that is manifested within an organism at genetic, molecular, cellular, organ, and system levels. Although the fundamental mechanisms are still poorly understo...

Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus

Abstract: The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies.

The Effect of SOX Internal Control Deficiencies and Their Remediation on Accrual Quality

Abstract: This paper investigates the effect of internal control deficiencies and their remediation on accrual quality. We first document that firms reporting internal control deficiencies have lower quality accruals as measured by accrual noise and absolute abnormal accruals relative to firms not reporting internal control problems. Second, we find that firms that report internal control deficiencies have significantly larger positive and larger negative abnormal accruals relative to control firms. This finding suggests internal control weaknesses are more likely to lead to unintentional errors that add noise to accruals than intentional misstatements that bias earnings upward. Third, we document that firms whose auditors confirm remediation of previously reported internal control deficiencies exhibit an increase in accrual quality relative to firms that do not remediate their control problems. Finally, we find firms that receive different internal control audit opinions in successive years exhibit changes in accrual quality consistent with changes in internal control quality. Collectively, our cross-sectional and inter-temporal change tests provide strong evidence that the quality of internal control affects the quality of accruals.

Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis

Abstract: We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the similar to 160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.

Evaluation and treatment of chagas disease in the United States : A systematic review

Abstract: ContextBecause of population migration from endemic areas and newly instituted blood bank screening, US clinicians are likely to see an increasing number of patients with suspected or confirmed chronic Trypanosoma cruzi infection (Chagas disease).ObjectiveTo examine the evidence base and provide practical recommendations for evaluation, counseling, and etiologic treatment of patients with chronic T cruzi infection.Evidence AcquisitionLiterature review conducted based on a systematic MEDLINE search for all available years through 2007; review of additional articles, reports, and book chapters; and input from experts in the field.Evidence SynthesisThe patient newly diagnosed with Chagas disease should undergo a medical history, physical examination, and resting 12-lead electrocardiogram (ECG) with a 30-second lead II rhythm strip. If this evaluation is normal, no further testing is indicated; history, physical examination, and ECG should be repeated annually. If findings suggest Chagas heart disease, a comprehensive cardiac evaluation, including 24-hour ambulatory ECG monitoring, echocardiography, and exercise testing, is recommended. If gastrointestinal tract symptoms are present, barium contrast studies should be performed. Antitrypanosomal treatment is recommended for all cases of acute and congenital Chagas disease, reactivated infection, and chronic T cruzi infection in individuals 18 years or younger. In adults aged 19 to 50 years without advanced heart disease, etiologic treatment may slow development and progression of cardiomyopathy and should generally be offered; treatment is considered optional for those older than 50 years. Individualized treatment decisions for adults should balance the potential benefit, prolonged course, and frequent adverse effects of the drugs. Strong consideration should be given to treatment of previously untreated patients with human immunodeficiency virus infection or those expecting to undergo organ transplantation.ConclusionsChagas disease presents an increasing challenge for clinicians in the United States. Despite gaps in the evidence base, current knowledge is sufficient to make practical recommendations to guide appropriate evaluation, management, and etiologic treatment of Chagas disease.

Assessment and Diagnosis of Personality Disorder: Perennial Issues and an Emerging Reconceptualization

Abstract: This chapter reviews recent (2000–2005) personality disorder (PD) research, focusing on three major domains: assessment, comorbidity, and stability. (a) Substantial evidence has accrued favoring dimensional over categorical conceptualization of PD, and the five-factor model of personality is prominent as an integrating framework. Future directions include assessing dysfunction separately from traits and learning to utilize collateral information. (b) To address the pervasiveness and extent of comorbidity, researchers have begun to move beyond studying overlapping pairs or small sets of disorders and are developing broader, more integrated common-factor models that cross the Axis I–Axis II boundary. (c) Studies of PD stability have converged on the finding that PD features include both more acute, dysfunctional behaviors that resolve in relatively short periods, and maladaptive temperamental traits that are relatively more stable—similar to normal-range personality traits—with increasing stability ...

Mutations in smooth muscle α-actin ( ACTA2 ) lead to thoracic aortic aneurysms and dissections

Abstract: Mutations in smooth muscle α-actin ( ACTA2 ) lead to thoracic aortic aneurysms and dissections

How human neutrophils kill and degrade microbes: an integrated view.

Abstract: Neutrophils constitute the dominant cell in the circulation that mediates the earliest innate immune human responses to infection. The morbidity and mortality from infection rise dramatically in patients with quantitative or qualitative neutrophil defects, providing clinical confirmation of the important role of normal neutrophils for human health. Neutrophil-dependent anti-microbial activity against ingested microbes represents the collaboration of multiple agents, including those prefabricated during granulocyte development in the bone marrow and those generated de novo following neutrophil activation. Furthermore, neutrophils cooperate with extracellular agents as well as other immune cells to optimally kill and degrade invading microbes. This brief review focuses attention on two examples of the integrated nature of neutrophil-mediated anti-microbial action within the phagosome. The importance and complexity of myeloperoxidase-mediated events illustrate a collaboration of anti-microbial responses that are endogenous to the neutrophil, whereas the synergy between the phagocyte NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and plasma-derived group IIA phospholipase A(2) exemplifies the collective effects of the neutrophil with an exogenous factor to achieve degradation of ingested staphylococci.

Biogenesis and Function of Multivesicular Bodies

Abstract: The two major cellular sites for membrane protein degradation are the proteasome and the lysosome. Ubiquitin attachment is a sorting signal for both degradation routes. For lysosomal degradation, ubiquitination triggers the sorting of cargo proteins into the lumen of late endosomal multivesicular bodies (MVBs)/endosomes. MVB formation occurs when a portion of the limiting membrane of an endosome invaginates and buds into its own lumen. Intralumenal vesicles are degraded when MVBs fuse to lysosomes. The proper delivery of proteins to the MVB interior relies on specific ubiquitination of cargo, recognition and sorting of ubiquitinated cargo to endosomal subdomains, and the formation and scission of cargo-filled intralumenal vesicles. Over the past five years, a number of proteins that may directly participate in these aspects of MVB function and biogenesis have been identified. However, major questions remain as to exactly what these proteins do at the molecular level and how they may accomplish these tasks.

Development and validation of the Inventory of Depression and Anxiety Symptoms (IDAS).

Abstract: The authors describe a new self-report instrument, the Inventory of Depression and Anxiety Symptoms (IDAS), which was designed to assess specific symptom dimensions of major depression and related anxiety disorders. They created the IDAS by conducting principal factor analyses in 3 large samples (college students, psychiatric patients, community adults); the authors also examined the robustness of its psychometric properties in 5 additional samples (high school students, college students, young adults, postpartum women, psychiatric patients) who were not involved in the scale development process. The IDAS contains 10 specific symptom scales: Suicidality, Lassitude, Insomnia, Appetite Loss, Appetite Gain, Ill Temper, Well-Being, Panic, Social Anxiety, and Traumatic Intrusions. It also includes 2 broader scales: General Depression (which contains items overlapping with several other IDAS scales) and Dysphoria (which does not). The scales (a) are internally consistent, (b) capture the target dimensions well, and (c) define a single underlying factor. They show strong short-term stability and display excellent convergent validity and good discriminant validity in relation to other self-report and interview-based measures of depression and anxiety.

The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity

Abstract: A novel antiinfective approach is to exploit stresses already imposed on invading organisms by the in vivo environment. Fe metabolism is a key vulnerability of infecting bacteria because organisms require Fe for growth, and it is critical in the pathogenesis of infections. Furthermore, humans have evolved potent Fe-withholding mechanisms that can block acute infection, prevent biofilm formation leading to chronic infection, and starve bacteria that succeed in infecting the host. Here we investigate a "Trojan horse" strategy that uses the transition metal gallium to disrupt bacterial Fe metabolism and exploit the Fe stress of in vivo environments. Due to its chemical similarity to Fe, Ga can substitute for Fe in many biologic systems and inhibit Fe-dependent processes. We found that Ga inhibits Pseudomonas aeruginosa growth and biofilm formation and kills planktonic and biofilm bacteria in vitro. Ga works in part by decreasing bacterial Fe uptake and by interfering with Fe signaling by the transcriptional regulator pvdS. We also show that Ga is effective in 2 murine lung infection models. These data, along with the fact that Ga is FDA approved (for i.v. administration) and there is the dearth of new antibiotics in development, make Ga a potentially promising new therapeutic for P. aeruginosa infections.

Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial

Abstract: Object The authors report the results of a prospective randomized multicenter study in which the results of cervical disc arthroplasty were compared with anterior cervical discectomy and fusion (ACDF) in patients treated for symptomatic single-level cervical degenerative disc disease (DDD). Methods Five hundred forty-one patients with single-level cervical DDD and radiculopathy were enrolled at 32 sites and randomly assigned to one of two treatment groups: 276 patients in the investigational group underwent anterior cervical discectomy and decompression and arthroplasty with the PRESTIGE ST Cervical Disc System (Medtronic Sofamor Danek); 265 patients in the control group underwent decompressive ACDF. Eighty percent of the arthroplasty-treated patients (223 of 276) and 75% of the control patients (198 of 265) completed clinical and radiographic follow-up examinations at routine intervals for 2 years after surgery. Analysis of all currently available postoperative 12- and 24-month data indicated a two-point...

An interdisciplinary expert consensus statement on assessment of pain in older persons

Abstract: This paper represents an expert-based consensus statement on pain assessment among older adults. It is intended to provide recommendations that will be useful for both researchers and clinicians. Contributors were identified based on literature prominence and with the aim of achieving a broad representation of disciplines. Recommendations are provided regarding the physical examination and the assessment of pain using self-report and observational methods (suitable for seniors with dementia). In addition, recommendations are provided regarding the assessment of the physical and emotional functioning of older adults experiencing pain. The literature underlying the consensus recommendations is reviewed. Multiple revisions led to final reviews of 2 complete drafts before consensus was reached.

Irrational Economic Decision-Making after Ventromedial Prefrontal Damage: Evidence from the Ultimatum Game

Abstract: Emotion regulation is often critical for adaptive decision making. Here, we investigate whether emotion regulation defects following focal prefrontal brain damage are associated with exceptionally irrational economic decision making in situations of unfair treatment. In the Ultimatum Game, two players are given one opportunity to split a sum of money. One player (the proposer) offers a portion of the money to the second player (the responder) and keeps the rest. The responder can either accept the offer (in which case both players split the money as proposed) or reject the offer (in which case both players get nothing). Relatively low Ultimatum offers are often rejected, and this “irrational” behavior has been attributed to an emotional reaction to unfair treatment. Using the lesion method, we tested the hypothesis that damage to ventromedial prefrontal cortex (VMPC), an area critical for the modulation of emotional reactions, would result in exaggerated irrational economic decisions. Subjects acted as the responder to 22 different proposers who offered various splits of $10. Offers ranged from fair (give $5, keep $5) to extremely unfair (give $1, keep $9). The rejection rate of the VMPC group was higher than the rejection rates of the comparison groups for each of the most unfair offers ($7/$3, $8/$2, $9/$1). These results suggest that emotion regulation processes subserved by VMPC are a critical component of normal economic decision making.

In vivo Preservation of the Hybrid Layer by Chlorhexidine

Abstract: Host-derived proteases have been reported to degrade the collagen matrix of incompletely-resin-infiltrated dentin. This study tested the hypothesis that interfacial degradation of resin-dentin bonds may be prevented or delayed by the application of chlorhexidine (CHX), a matrix metalloproteinase inhibitor, to dentin after phosphoric acid-etching. Contralateral pairs of resin-bonded Class I restorations in non-carious third molars were kept under intra-oral function for 14 months. Preservation of resin-dentin bonds was assessed by microtensile bond strength tests and TEM examination. In vivo bond strength remained stable in the CHX-treated specimens, while bond strength decreased significantly in control teeth. Resin-infiltrated dentin in CHX-treated specimens exhibited normal structural integrity of the collagen network. Conversely, progressive disintegration of the fibrillar network was identified in control specimens. Auto-degradation of collagen matrices can occur in resin-infiltrated dentin, but may be prevented by the application of a synthetic protease inhibitor, such as chlorhexidine.