Detection of Interstitial Lung Disease in Rheumatoid Arthritis by Thoracic Ultrasound: A Diagnostic Test Accuracy Study.

OBJECTIVE: To determine the diagnostic accuracy of thoracic ultrasound (TUS) for detecting interstitial lung disease (ILD) in rheumatoid arthritis (RA) with respiratory symptoms. METHODS: Individuals with RA visiting rheumatologic outpatient clinics in the Region of Southern Denmark were systematically screened for dyspnea, cough, recurrent pneumonia, prior severe pneumonia, or a chest x-ray indicating interstitial abnormalities. Eighty participants with a positive screening were consecutively included. Individuals were not eligible if they had a chest high-resolution computed tomography (HRCT) less than 12 months ago or were already diagnosed with ILD. A blinded TUS expert evaluated TUS, and TUS was registered as positive for ILD if at least 10 B-lines or bilateral thickened and fragmented pleura were present. The primary outcomes were TUS's sensitivity, specificity, and positive predictive value and negative predictive value. An ILD-specialized thoracic radiologist assessed HRCT, followed by a multidisciplinary team discussion, which was the reference standard. The accepted window of HRCT was less than 30 days after TUS was performed. RESULTS: A total of 77 participants received HRCT less than 30 days after TUS, and 23 (30%) were diagnosed with ILD. TUS had a sensitivity of 82.6% (95% confidence interval [CI] 61.2%-95.0%) and a specificity of 51.9% (95% CI 37.8%-65.7%), corresponding to a positive predictive value of 42.2% (95% CI 27.7%-57.8%) and a negative predictive value of 87.5% (95% CI 71.0%-96.5%). CONCLUSION: To our knowledge, this prospective study is the first to use respiratory symptoms in RA as inclusion criteria. Systematic screening for respiratory symptoms combined with TUS can reduce the diagnostic delay of ILD in RA.

Experimental determination of concentration factors of Ni, Ru and Sb in the model diatom Phaeodactylum tricornutum.

This paper describes the experimental determination of concentration factors (CF) for nickel, ruthenium and antimony in the model diatom Phaeodactylum tricornutum Bohlin (Bacillariophyceae), which was chosen as a representative of marine phytoplankton. Better determinations of these CF are needed to improve the modelling of marine ecosystems at release points, where radioactive pollutants enter the ecosystem, for more accurate predictions of radiation dose to humans caused by these pollutants. A literature study revealed that the currently implemented values of these CF are based on very scarce data, and a computational sensitivity study showed that the radiation dose caused by radioisotopes of these elements depend strongly on the phytoplankton CF. Nutrient-enriched water samples from Swedish coastal waters were used as a medium for growing of the diatom species P. tricornutum and radioactive isotopes of the studied elements were added to the cultures during the exponential growth phase. The radioactivity in the P. tricornutum and in the culture medium were measured separately and used for determination of CF. Conservative estimates of the CF based on this phytoplankton proxy on the present data are 6400 L/kg for nickel, 20,000 L/kg for ruthenium and 890 L/kg for antimony, with P. tricornutum biomass masses referring to dry weight. The estimates for nickel and ruthenium are similar to previously published values, which underpins the credibility of radiation dose calculations based on these values. The estimate for antimony is uncertain, but also, to our knowledge, represents the first published experimentally based data on this CF.

Experimental determination of concentration factors of Mn, Zn and I in the phytoplankton species Phaeodactylum Tricornutum.

Anthropogenic radionuclides released into the environment cause a radiation dose to wildlife and humans which must be quantified, both to assess the effect of normal releases, and to predict the consequences of a larger, unplanned release. To estimate the spread of the radioactive elements, the ecosystem around release points is modelled, and element uptake is usually quantified by concentration factors (CF), which relates the concentration of an element in an organism to the concentration of the same element in a medium under equilibrium conditions. In this work, we experimentally determine some phytoplankton CF that are needed for improved modelling of the marine ecosystems around nuclear facilities and release points. CFs that require better determination have been identified through literature search. Sensitivity studies, using the currently used ecosystem modelling software PREDO, show that for most studied groups, the dose committed by the respective radionuclides is almost proportional to the corresponding phytoplankton CFs. In the present work, CFs are determined through laboratory experiments with cultured phytoplankton and radionuclides of the concerned elements, assessing the element uptake by the phytoplankton through detection of the emitted radiation. The three CF assessed in this work were those for manganese, zinc and iodine in phytoplankton. Conservative estimates of these CF based on the present data are 40 000 L/kg for manganese, 50 000 L/kg for zinc and 180 L/kg for iodine with the phytoplankton masses referring to their dry weight.

One Health and antimicrobial resistance, a United States perspective.

Antimicrobial drugs are a precious resource, responsible for saving millions of lives since their discovery. Unfortunately, some antimicrobials are rapidly losing their effectiveness due to the development and spread of antimicrobial resistance (AMR), a multi-faceted and complex problem affecting humans, animals, plants and the environment. While AMR is a global problem, in this paper, the authors briefly highlight some ongoing efforts in the United States of America aimed at integrating a One Health approach into policies and programmes that address this important health threat.

Les antibiotiques sont des ressources de grande valeur qui ont sauvé des millions de vies depuis leur découverte. Malheureusement, certains agents antimicrobiens perdent rapidement leur efficacité en raison de l'apparition et propagation des résistances à ces agents, phénomène complexe et multidimensionnel qui affecte l'homme, les animaux, les plantes et l'environnement. La résistance aux agents antimicrobiens est un problème mondial ; dans cet article, les auteurs décrivent certaines initiatives actuellement mises en oeuvre aux États-Unis d'Amérique pour intégrer l'approche Une seule santé dans les politiques et les programmes conçus pour lutter contre cette menace sanitaire majeure.

Los fármacos antimicrobianos son un recurso valiosísimo, cuyo uso ha salvado millones de vidas desde que fueron descubiertos. Lamentablemente, algunos de ellos están perdiendo rápidamente eficacia debido a la aparición y propagación de resistencias, lo que plantea un problema tan complejo como poliédrico, que afecta a personas, animales, plantas y ecosistemas. Aunque la dimensión del problema es planetaria, los autores destacan aquí brevemente algunas de las iniciativas en curso en los Estados Unidos de América que tienen por objetivo integrar los planteamientos de Una sola salud en el conjunto de políticas y programas desde los cuales se aborda esta importante amenaza sanitaria.

Comparison of mixed effects models of antimicrobial resistance metrics of livestock and poultry Salmonella isolates from a national monitoring system.

Antimicrobial use in agriculture is considered a pathway for the selection and dissemination of resistance determinants among animal and human populations. From 1997 through 2003 the U.S. National Antimicrobial Resistance Monitoring System (NARMS) tested clinical Salmonella isolates from multiple animal and environmental sources throughout the United States for resistance to panels of 16-19 antimicrobials. In this study we applied two mixed effects models, the generalized linear mixed model (GLMM) and accelerated failure time frailty (AFT-frailty) model, to susceptible/resistant and interval-censored minimum inhibitory concentration (MIC) metrics, respectively, from Salmonella enterica subspecies enterica serovar Typhimurium isolates from livestock and poultry. Objectives were to compare characteristics of the two models and to examine the effects of time, species, and multidrug resistance (MDR) on the resistance of isolates to individual antimicrobials, as revealed by the models. Fixed effects were year of sample collection, isolate source species and MDR indicators; laboratory study site was included as a random effect. MDR indicators were significant for every antimicrobial and were dominant effects in multivariable models. Temporal trends and source species influences varied by antimicrobial. In GLMMs, the intra-class correlation coefficient ranged up to 0.8, indicating that the proportion of variance accounted for by laboratory study site could be high. AFT models tended to be more sensitive, detecting more curvilinear temporal trends and species differences; however, high levels of left- or right-censoring made some models unstable and results uninterpretable. Results from GLMMs may be biased by cutoff criteria used to collapse MIC data into binary categories, and may miss signaling important trends or shifts if the series of antibiotic dilutions tested does not span a resistance threshold. Our findings demonstrate the challenges of measuring the AMR ecosystem and the complexity of interacting factors, and have implications for future monitoring. We include suggestions for future data collection and analyses, including alternative modeling approaches.

Case-control study of a multistate equine herpesvirus myeloencephalopathy outbreak.

BACKGROUND: A large multistate outbreak of equine herpesvirus myeloencephalopathy (EHM) occurred in May 2011 among horses that participated in a competitive event. OBJECTIVE: To identify EHM risk factors among horses with a common exposure venue. ANIMALS: A total of 123 horses: 19 horses with EHM, 14 equine herpesvirus-1 cases with no reported neurologic signs, and 90 control horses. METHODS: EHM case survey data were compared with data from EHV-1 cases with no neurologic signs and healthy controls using univariable and multivariable methods. RESULTS: Significant factors associated with higher risk for EHM compared with EHV-1 cases with no neurologic signs were (1) greater number of biosecurity risks at the event, (2) female sex, (3) increasing number of classes competed in at the event, and (4) an interaction between sex and number of classes competed in. In the EHM versus controls comparison, in addition to sex and biosecurity risks, factors associated with higher EHM risk included EHV-1 vaccination in the 5 weeks before the event and increasing number of events attended in April 2011; zinc dietary supplementation was associated with decreased risk. An interaction between sex and the number of events attended in April 2011 also was significant. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings from this study suggest that dietary zinc supplementation may be associated with decreased risk of EHM. Several factors were associated with increased risk of EHM. Additional investigations of factors associated with risk of EHM are warranted to evaluate the importance of these factors in this complex disease of horses.

Interaction vs. observation: distinctive modes of social cognition in human brain and behavior? A combined fMRI and eye-tracking study.

Human cognition has usually been approached on the level of individual minds and brains, but social interaction is a challenging case. Is it best thought of as a self-contained individual cognitive process aiming at an "understanding of the other," or should it rather be approached as an collective, inter-personal process where individual cognitive components interact on a moment-to-moment basis to form coupled dynamics? In a combined fMRI and eye-tracking study we directly contrasted these models of social cognition. We found that the perception of situations affording social contingent responsiveness (e.g., someone offering or showing you an object) elicited activations in regions of the right posterior temporal sulcus and yielded greater pupil dilation corresponding to a model of coupled dynamics (joint action). In contrast, the social-cognitive perception of someone "privately" manipulating an object elicited activation in medial prefrontal cortex, the right inferior frontal gyrus and right inferior parietal lobus, regions normally associated with Theory of Mind and with the mirror neuron system. Our findings support a distinction in social cognition between social observation and social interaction, and demonstrate that simple ostensive cues may shift participants' experience, behavior, and brain activity between these modes. The identification of a distinct, interactive mode has implications for research on social cognition, both in everyday life and in clinical conditions.

In vivo dosimetry with a linear MOSFET array to evaluate the urethra dose during permanent implant brachytherapy using iodine-125.

PURPOSE: To develop a technique to monitor the dose rate in the urethra during permanent implant brachytherapy using a linear MOSFET array, with sufficient accuracy and without significantly extending the implantation time. METHODS AND MATERIALS: Phantom measurements were performed to determine the optimal conditions for clinical measurements. In vivo measurements were performed in 5 patients during the (125)I brachytherapy implant procedure. To evaluate if the urethra dose obtained in the operating room with the ultrasound transducer in the rectum and the patient in treatment position is a reference for the total accumulated dose; additional measurements were performed after the implantation procedure, in the recovery room. RESULTS: In vivo measurements during and after the implantation procedure agree very well, illustrating that the ultrasound transducer in the rectum and patient positioning do not influence the measured dose in the urethra. In vivo dose values obtained during the implantation are therefore representative for the total accumulated dose in the urethra. In 5 patients, the dose rates during and after the implantation were below the maximum dose rate of the urethra, using the planned seed distribution. CONCLUSION: In vivo dosimetry during the implantation, using a MOSFET array, is a feasible technique to evaluate the dose in the urethra during the implantation of (125)I seeds for prostate brachytherapy.

In vivo dosimetry using a linear Mosfet-array dosimeter to determine the urethra dose in 125I permanent prostate implants.

PURPOSE: In vivo dosimetry during brachytherapy of the prostate with (125)I seeds is challenging because of the high dose gradients and low photon energies involved. We present the results of a study using metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a permanent prostate implantation procedure. METHODS AND MATERIALS: Phantom measurements were made to validate the measurement technique, determine the measurement accuracy, and define action levels for clinical measurements. Patient measurements were performed with a MOSFET array in the urinary catheter immediately after the implantation procedure. A CT scan was performed, and dose values, calculated by the treatment planning system, were compared to in vivo dose values measured with MOSFET dosimeters. RESULTS: Corrections for temperature dependence of the MOSFET array response and photon attenuation in the catheter on the in vivo dose values are necessary. The overall uncertainty in the measurement procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose values were obtained for 17 patients. In the high-dose region (> 100 Gy), calculated and measured dose values agreed within 1.7% +/- 10.7% (1 SD). In the low-dose region outside the prostate (< 100 Gy), larger deviations occurred. CONCLUSIONS: MOSFET detectors are suitable for in vivo dosimetry during (125)I brachytherapy of prostate cancer. An action level of +/- 16% (2 SD) for detection of errors in the implantation procedure is achievable after validation of the detector system and measurement conditions.

Modulation of voluntary ethanol consumption by beta-arrestin 2.

Beta-arrestin 2 is a multifunctional key component of the G protein-coupled receptor complex and is involved in mu-opiate and dopamine D2 receptor signaling, both of which are thought to mediate the rewarding effects of ethanol consumption. We identified elevated expression of the beta-arrestin 2 gene (Arrb2) in the striatum and the hippocampus of ethanol-preferring AA rats compared to their nonpreferring counterpart ANA line. Differential mRNA expression was accompanied by different levels of Arrb2 protein. The elevated expression was associated with a 7-marker haplotype in complete linkage disequilibrium, which segregated fully between the lines, and was unique to the preferring line. Furthermore, a single, distinct, and highly significant quantitative trait locus for Arrb2 expression in hippocampus and striatum was identified at the locus of this gene, providing evidence that genetic variation may affect a cis-regulatory mechanism for expression and regional control of Arrb2. These findings were functionally validated using mice lacking Arrb2, which displayed both reduced voluntary ethanol consumption and ethanol-induced psychomotor stimulation. Our results demonstrate that beta-arrestin 2 modulates acute responses to ethanol and is an important mediator of ethanol reward.

Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress.

Alcoholism is a chronic relapsing disorder with substantial heritability. Uncovering gene-environment interactions underlying this disease process can aid identification of novel treatment targets. Here, we found a lowered threshold for stress-induced reinstatement of alcohol seeking in Marchigian-Sardinian Preferring (msP) rats genetically selected for high alcohol preference. In situ hybridization for a panel of 20 stress-related genes in 16 brain regions was used to screen for differential gene expression that may underlie this behavioral phenotype. An innate up-regulation of the Crhr1 transcript, encoding the corticotropin-releasing hormone receptor 1 (CRH-R1), was found in several limbic brain areas of msP rats genetically selected for high alcohol preference, was associated with genetic polymorphism of the Crhr1 promoter, and was accompanied by increased CRH-R1 density. A selective CRH-R1 antagonist (antalarmin, 10-20 mg/kg) was devoid of effects on operant alcohol self-administration in unselected Wistar rats but significantly suppressed this behavior in the msP line. Stress-induced reinstatement of alcohol seeking was not significantly affected by antalarmin in Wistar rats but was fully blocked in msP animals. These data demonstrate that Crhr1 genotype and expression interact with environmental stress to reinstate alcohol-seeking behavior.

Glutathione-S-transferase expression in the brain: possible role in ethanol preference and longevity.

Identification of genes that are differentially expressed in rats bidirectionally selected for alcohol preference might reveal biological mechanisms underlying alcoholism or related phenotypes. Microarray analysis from medial prefrontal cortex (mPFC), a key brain region for drug reward, indicated increased expression of glutathione-S-transferases of the alpha (Gsta4) and mu (Gstm1-5) classes in ethanol-preferring AA rats compared with nonpreferring ANA rats. Real-time RT polymerase chain reaction (RT-PCR) analysis demonstrated approximately 2-fold higher Gsta4 transcript levels in several brain regions of ethanol-naive AA compared with ANA rats. Differences in mRNA levels were accompanied by differential levels of GSTA4 protein. We identified a novel haplotype variant in the rat Gsta4 gene, defined here as var3. Allele frequencies of var3 were markedly different between AA and ANA rats, 52% and 100%, respectively. Gsta4 expression was strongly correlated with the gene dose of var3, with approximately 60% of the variance in expression accounted for by genotype at this locus. The contribution of glutathione S-transferase expression to the ethanol-preferring phenotype is presently unclear. It could, however, underlie observed differences in life span between AA and ANA lines, prompting a utility of this animal model in aging research.

A cluster of differentially expressed signal transduction genes identified by microarray analysis in a rat genetic model of alcoholism.

Analyzing gene expression patterns in genetic models of alcoholism may uncover previously unknown susceptibility genes, and point to novel targets for drug development. Here, we compared expression profiles in alcohol-preferring AA rats with the alcohol-avoiding counterpart ANA line, and unselected Wistar rats. Cingulate cortex, Nc. accumbens, amygdala and hippocampus of each line were analyzed using the Afymetrix RN U34 arrays and dChip 1.1 software. Analysis of line-specific expression revealed 48 differentially expressed genes between AA and ANA rats. Elevated hippocampal neuropeptide Y (NPY) was found in ANA rats in agreement with previous studies. A cluster of MAP-kinases indicating altered signal transduction was upregulated within the Nc. Accumbens of the AA line, and is of particular functional interest. Within the amygdala, a more loosely inter-related cluster of cytoskeleton-associated genes may point to structural abnormalities. The observed dysregulations may contribute to the alcohol-preferring phenotype.

Insulin(GIK) improves myocardial metabolism in patients during blood cardioplegia.

The aim of this study was to test the hypothesis that abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and early reperfusion are attenuated further by insulin(GIK) than by alpha-ketoglutarate enrichment of blood cardioplegia alone. Twenty-eight males (47 to 78 years) undergoing coronary artery bypass grafting (CABG) participated in a prospective, controlled, randomized study. All patients had alpha-ketoglutarate-enriched blood cardioplegia. Insulin(GIK) was infused in 13 patients during aortic cross-clamping. Insulin(GIK) prevented lactate release during cardioplegia (1.5+/-15 vs -44+/-14 micromol/min, p = 0.04), and a significant extraction of lactate was induced shortly after declamping the aorta (15+/-3 vs 2+/-1%, p = 0.001). Free fatty acid uptake was reduced after cardioplegic cross-clamping (5.7+/-1.6 vs 16.0+/-3.8 micromol/min, p = 0.02). More positive/less negative levels of alanine, aspartate, glutamine, glycine, ornithine, taurine and tyrosine were found in all the insulin-treated patients. We conclude that insulin(GIK) attenuates abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and early reperfusion further than is obtained with alpha-ketoglutarate enrichment of blood cardioplegia alone.

Parasites and parasite stages of free-ranging wild lions (Panthera leo) of northern Tanzania.

Fecal samples from 33 lions (Panthera leo) in Serengeti National Park and Ngorongoro Crater Conservation Area in northern Tanzania contained 19 different parasites, 12 of which, including Aelurostrongylus sp., a species of Acanthocephala, a species of Anoplocephalidae, Capillaria sp., Demodex sp., Eimeria sp., Habronema sp., Isospora felis, Isospora rivolta, one species of Isospora that was previously undescribed from lions, one species of Trematoda that was previously undescribed from lions, and Trichuris sp., were new reports for lions. Seven other species had been previously reported from lions.

Addition of alpha-ketoglutarate to blood cardioplegia improves cardioprotection.

BACKGROUND: We hypothesized that myocardial content of alpha-ketoglutarate (alpha-KG), an intermediate of the Krebs cycle, can be critically low during heart operations, and that provision of alpha-KG could reduce metabolic abnormalities and lead to improved myocardial protection. METHODS: Twenty-four men aged 46 to 78 years who were undergoing heart operations participated in a prospective, controlled, randomized study. In 13 patients, an average of 28 g of alpha-KG was added to blood cardioplegia. Plasma creatine kinase isoenzyme MB and troponin T, and myocardial extraction of oxygen, substrates, and amino acids were measured. RESULTS: alpha-Ketoglutarate treatment was associated with lower creatine kinase isoenzyme MB (F = 39.6, df = 1.172, p < 0.001) and lower troponin (F = 12.9, df = 1.172, p < 0.001). The values at 4 hours were 31 +/- 2.4 microg/L versus 49 +/- 4.9 microg/L (creatine kinase isoenzyme MB) and 1.1 +/- 0.05 microg/L versus 2.0 +/- 0.34 microg/L (troponin T). Myocardial oxygen extraction was higher during alpha-KG cardioplegia (p < 0.01), but there were no significant differences in myocardial uptake or release of substrates or amino acids. Lactate release was observed in both groups during cardioplegia. Myocardial lactate release had ceased after 30 minutes of reperfusion in nearly half the alpha-KG-treated patients (6 of 13) but remained in all the control patients (11 of 11, p = 0.016). There were no other differences after 30 minutes of reperfusion. CONCLUSION: Provision of alpha-KG during blood cardioplegia improves myocardial protection in patients undergoing coronary operations. This may be linked to enhanced oxidation.

Alpha-ketoglutarate for myocardial protection in heart surgery.

A low myocardial content of alpha-ketoglutarate during heart surgery might aggravate ischaemic injury. 24 men undergoing coronary surgery participated in a randomised controlled study. 28 g alpha-ketoglutarate was added to blood cardioplegia for intermittent antegrade intracoronary perfusion in 13 cases. alpha-ketoglutarate reduced the appearance in blood of the ischaemic markers creatine kinase MB and troponin T (at 4 h after release of aortic cross-clamp; median [95% CI] 49 [37-60] micrograms/L in controls vs 32 [27-37] micrograms/L for creatine kinase MB, 2.0 [1.2-2.8] vs 1.1 [0.8-1.4] micrograms/L for troponin T). These findings signify attenuated ischaemic injury, possibly secondary to enhanced myocardial oxidative capacity.

A new sampling technique that allows quantitative fit testing by using the employee's own respirator.

A new, in-mask sampling technique has been developed that enhances current quantitative respirator fit test methods. This new sampling technique eliminates the need for a permanently modified (probed) respirator for conducting fit tests. With this new technique, a sample was drawn from the breathing zone inside the respirator by means of a sampling adapter, which was temporarily attached between one of the air-purifying filters and the facepiece before a fit test was performed. To ensure that the performance of the respirator was not altered, the sampling adapter was designed so that all major functional aspects of the respirator were unchanged. This new sampling technique was evaluated on human test subjects by simultaneous sampling from a probed respirator by using two quantitative respirator fit test instruments. One instrument sampled through a conventional respirator probe; the other used the new method. Test results show that equivalent fit test data were obtained with both sampling techniques.

Duodenal villous tumors.

The treatment of 36 patients with duodenal villous tumors was reviewed to determine the long-term outcome of various surgical treatment options for specific adenoma histopathology. Duodenal villous tumors were typically solitary and periampullary in location. Villous adenomas contained epithelial atypia in 30% of patients, in situ carcinoma in 14%, and invasive carcinoma in 33%. Treatment consisted of transduodenal submucosal excision in 19 patients and radical pancreaticoduodenectomy in 15. There was no perioperative mortality. Perioperative morbidity for transduodenal excision and pancreaticoduodenectomy was 16% and 47%, respectively. Benign adenomas recurred more than 5 years postoperatively in 17% of patients undergoing transduodenal excision. Five-year survival following radical resection for invasive cancers was 45%. Overall median follow-up was 5.8 years. We conclude that duodenal villous tumors without invasive cancer can be managed successfully by local submucosal excision, but invasive carcinoma requires radical resection.