Δευτέρα, 27 Νοεμβρίου 2017

Breast MRI as a Problem-solving Study in the Evaluation of BI-RADS Categories 3 and 4 Microcalcifications

Publication date: Available online 27 November 2017
Author(s): Akiko Shimauchi, Youichi Machida, Ichiro Maeda, Eisuke Fukuma, Kazuei Hoshi, Mitsuhiro Tozaki
Rationale and ObjectivesWe aimed to investigate the utility of problem-solving breast magnetic resonance imaging (MRI) for mammographic Breast Imaging Reporting and Data System (BI-RADS) categories 3 and 4 microcalcifications.Materials and MethodsBetween January 1, 2010 and December 31, 2011, 138 women with 146 areas of categories 3 and 4 microcalcifications without sonographic correlates underwent breast MRI and had a stereotactic core biopsy using an 11-gauge needle or follow-up at least for 24 months. Positive predictive value (PPV), negative predictive value, sensitivity, and specificity were calculated on the basis of BI-RADS category, with categories 1–3 being considered benign and categories 4 and 5 being considered malignant.ResultsTwenty-four cases (16.4%) were malignant (18 ductal carcinoma in situ, 6 invasive). MRI increased PPV and specificity from 43% to 68% and from 80% to 93% (P = .054 and .005) compared to mammography. Within 102 category 3 microcalcifications, 5 carcinomas were assessed correctly as category 4 by MRI. Within 44 category 4 microcalcifications, a correct diagnosis was made by MRI in 77% (34 of 44) as opposed to 43% (19 of 44) by mammography, and 80% (20 of 25) of unnecessary biopsies could have been avoided. Within the 24 carcinomas, 5 were negative at MRI. MRI-negative carcinomas have a significantly higher possibility of being low grade (ductal carcinoma in situ or invasive) (P = .0362).ConclusionsBreast MRI has the potential to improve the diagnosis of category 3 or 4 microcalcifications and could alter indications for biopsy. Breast MRI could help predict the presence or absence of higher-grade carcinoma for category 3 or 4 microcalcifications.

Model-based Iterative Reconstruction in Low-radiation-dose Computed Tomography Colonography

Publication date: Available online 27 November 2017
Author(s): Narumi Taguchi, Seitaro Oda, Masanori Imuta, Sadahiro Yamamura, Takeshi Nakaura, Daisuke Utsunomiya, Masafumi Kidoh, Yasunori Nagayama, Hideaki Yuki, Kenichiro Hirata, Yuji Iyama, Yoshinori Funama, Hideo Baba, Yasuyuki Yamashita
Rationale and ObjectivesTo assess the effect of model-based iterative reconstruction (MBIR) on image quality and diagnostic performance of low-radiation-dose computed tomography colonography (CTC) in the preoperative assessment of colorectal cancer.Materials and MethodsThis study included 30 patients with colorectal cancer referred for surgical treatment. All patients underwent CTC with a standard dose (SD) protocol in the supine position and a low-dose (LD; radiation dose reduction of approximately 85%) protocol in the prone position. The SD protocol images were post-processed using filtered back projection (FBP), whereas the LD protocol images were post-processed using FBP and MBIR. Objective and subjective image quality parameters were compared among the three different methods. Preoperative evaluations, including site, length, and tumor and node staging were performed, and the findings were compared to the postsurgical findings.ResultsThe mean image noise of SD-FBP, LD-FBP, and LD-MBIR images was 17.3 ± 3.2, 40.5 ± 10.9, and 11.2 ± 2.0 Hounsfield units, respectively. There were significant differences for all comparison combinations among the three methods (P < .01). For image noise, the mean visual scores were significantly higher for SD-FBP and LD-MBIR than for LD-FBP, and the scores for SD-FBP and LD-MBIR were equivalent (3.9 ± 0.3 [SD-FBP], 2.0 ± 0.5 [LD-FBP], and 3.7 ± 0.3 [LD-MBIR]). Preoperative information was more accurate under SD-FBP and LD-MBIR than under LD-FBP, and the information was comparable between SD-FBP and LD-MBIR.ConclusionMBIR can yield significantly improved image quality on low-radiation-dose CTC and provide preoperative information equivalent to that of standard-radiation-dose protocol.

CT Features of Hepatic Veno-occlusive Disease

Publication date: Available online 27 November 2017
Author(s): Song Yang, Jing Wu, Si Lei
Rationale and ObjectiveThe computed tomography (CT) features of hepatic veno-occlusive disease (HVOD) could play a role in its diagnosis. We aimed to perform a meta-analysis of studies examining the CT features of HVOD.MethodsRelevant studies published up to May 3, 2017 were searched in major electronic databases. The extracted data included the proportion of various CT features in patients with HVOD. The meta-analysis was conducted using R 3.3.3 with the "meta" package.ResultsEleven studies were included. The studies involved 326 patients with a mean age range of 50.2–58.9 years, and the proportion of female patients ranged from 20% to 57.5%. The meta-analysis showed the pooled proportion of CT features: hepatic parenchyma with heterogeneous hypoattenuation (81.05%, 95% confidence interval [CI]: 56.97%–93.25%), patchy enhancement in the portal venous phase (87.09%, 95% CI: 75.15%–93.77%) with or without a narrow or invisible hepatic vein (71.02% 95% CI: 42.09%–89.20%), gallbladder wall edema (65.51%, 95% CI: 28.98%–89.84%), and patchy heterogeneous enhancement in the arterial phase (44.36%, 95% CI: 29.98%–59.76%) with or without slightly enlarged hepatic artery (56.61%, 95% CI: 40.62%–71.33%).ConclusionHepatic parenchyma with heterogeneous hypoattenuation and patchy enhancement with or without narrowing or an invisible hepatic vein in the portal venous or equilibrium phase may be the most important CT feature for diagnosing HVOD.

The Benefits of Maintaining a Diagnostic and Interventional Co-sponsored Radiology Interest Group

Publication date: Available online 27 November 2017
Author(s): Michael V. Friedman, Jennifer E. Gould, Gretchen M. Foltz

To describe the radiological findings of radiation-induced lung damage (RILD) present on CT imaging of lung cancer patients 12 months after radical chemoradiation.

The physics of small megavoltage photon beam dosimetry

The increased interest during recent years in the use of small megavoltage photon beams in advanced radiotherapy techniques has led to the development of dosimetry recommendations by different national and international organizations. Their requirement of data suitable for the different clinical options available, regarding treatment units and dosimetry equipment, has generated a considerable amount of research by the scientific community during the last decade. The multiple publications in the field have led not only to the availability of new invaluable data, but have also contributed substantially to an improved understanding of the physics of their dosimetry.

High Radon Areas and lung cancer prevalence: Evidence from Ireland

Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): Seraphim Dempsey, Seán Lyons, Anne Nolan
This paper examined the relationship between radon risk and lung cancer prevalence using a novel dataset combining spatially-coded survey data with a radon risk map. A logit model was employed to test for significant associations between a high risk of indoor radon and lung cancer prevalence using data on 5590 people aged 50+ from The Irish Longitudinal Study on Ageing (TILDA) and radon risk data from Ireland's Environmental Protection Agency (EPA). The use of data at the individual level allowed a wide range of potentially confounding factors (such as smoking) to be included. Results indicate that those who lived in an area in which 10%–20% of households were above the national reference level (200 Bq/m3) were 2.9–3.1 times more likely to report a lung cancer diagnosis relative to those who lived in areas in which less than 1% of households were above the national reference level.

Population sensitivities of animals to chronic ionizing radiation-model predictions from mice to elephant

Publication date: Available online 20 November 2017
Author(s): Tatiana G. Sazykina

Natural radioactivity in soils of the state of Rio de Janeiro (Brazil): Radiological characterization and relationships to geological formation, soil types and soil properties

Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): F.C.A. Ribeiro, J.I.R. Silva, E.S.A. Lima, N.M.B. do Amaral Sobrinho, D.V. Perez, D.C. Lauria
Located in the south-western part of Brazil, the state of Rio de Janeiro is geotectonically contained within a complex structural province that resulted in the amalgamation of the Western Gondwana Paleocontinent. To undertake an extensive radiological characterization of this complex geological province and investigate the influence of bedrock, soil type and soil chemical-physical characteristics on natural radionuclide levels in soils, 259 surface soil samples were collected that encompassed the main soil types and geological formations throughout the state. Gamma spectrometry analysis of the samples resulted in median values of 114 Bq.kg−1for 40K, 32 Bq.kg−1 for 226Ra and 74 Bq.kg−1 for 228Ra. The median value for 226Ra was similar to the world median value for soils, the 40K value was well below the worldwide value, and that for 228Ra exceeded the world median value. The intense weathering caused by the high rainfall rates and high temperatures may be responsible for the low levels of 40K in the soils, of which the strongly acidic and clayey soils are markedly K-depleted. A soil from a high-grade metamorphic rock (granulite) presented the lowest 226Ra (18 Bq.kg−1) content, whereas the highest levels for 226Ra (92 Bq.kg−1) and 228Ra (139 Bq.kg-1) were observed in a young soil enriched in primary minerals (Leptsol). A lowland soil (Gleysol) showed the highest median of 40K (301 Bq.kg−1). Strongly acidic soils tended to present high amounts of 226Ra, and sandy soils tended to contain low levels of 228Ra. The external radiation dose indicates that the state has a background radiation level within the natural range.

Inside Front Cover - Editorial Board Page

Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181

Predicted cumulative dose to firefighters and the offsite public from natural and anthropogenic radionuclides in smoke from wildland fires at the Savannah River Site, South Carolina USA

Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): Brian J. Viner, Tim Jannik, Allan Hepworth, Olorunfemi Adetona, Luke Naeher, Teresa Eddy, Eric Doman, John Blake
The contaminated ground surface at Savannah River Site (SRS) is a result of the decades of work that has been performed maintaining the country's nuclear stockpile and performing research and development on nuclear materials. The volatilization of radionuclides during wildfire results in airborne particles that are dispersed within the smoke plume and may result in doses to downwind firefighters and the public. To better understand the risk that these smoke plumes present, we have characterized four regions at SRS in terms of their fuel characteristics and radiological contamination on the ground. Combined with general meteorological conditions describing typical and extreme burn conditions, we have simulated potential fires in these regions and predicted the potential radiological dose that could be received by firefighting personnel and the public surrounding the SRS. In all cases, the predicted cumulative dose was a small percent of the US Department of Energy regulatory limit (0.25 mSv). These predictions were conservative and assumed that firefighters would be exposed for the duration of their shift and the public would be exposed for the entire day over the duration of the burn. Realistically, firefighters routinely rotate off the firefront during their shift and the public would likely remain indoors much of the day. However, we show that even under worst-case conditions the regulatory limits are not exceeded. We can infer that the risks associated with wildfires would not be expected to cause cumulative doses above the level of concern to either responding personnel or the offsite public.

Topsoil radiological characterisation of L-54M reactor surroundings preliminary to decommissioning operations

Publication date: Available online 27 November 2017
Author(s): E. Mossini, L. Codispoti, M. Giola, L. Castelli, E. Macerata, A. Porta, F. Campi, M. Mariani
The radiological characterization of the topsoil of the L-54M reactor surroundings carried out in this work aims at obtaining the reference blank point for the forthcoming decommissioning operations and ascertain if unexpected radionuclide release occurred during the operational life of the plant. Standardised methods have been employed in order to collect representative samples and reliable results. Suitable sample pre-treatment procedures were applied. Gamma and beta spectrometric analyses were carried out to measure the activity concentrations of 60Co 137Cs, 152Eu, 241Am and 90Sr. These have been considered as representative radionuclides that could have been originated from reactor operations and that could still be present at four decades post reactor shutdown.

Analysis of air mass trajectories to explain observed variability of tritium in precipitation at the Southern Sierra Critical Zone Observatory, California, USA

Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181
Author(s): Ate Visser, Melissa Thaw, Brad Esser
Understanding the behavior of tritium, a radioactive isotope of hydrogen, in the environment is important to evaluate the exposure risk of anthropogenic releases, and for its application as a tracer in hydrology and oceanography. To understand and predict the variability of tritium in precipitation, HYSPLIT air mass trajectories were analyzed for 16 aggregate precipitation samples collected over a 2 year period at irregular intervals at a research site located at 2000 m elevation in the southern Sierra Nevada (California, USA). Attributing the variation in tritium to specific source areas confirms the hypothesis that higher latitude or inland sources bring higher tritium levels in precipitation than precipitation originating in the lower latitude Pacific Ocean. In this case, the source of precipitation accounts for 79% of the variation observed in tritium concentrations. Air mass trajectory analysis is a promising tool to improve the predictions of tritium in precipitation at unmonitored locations and thoroughly understand the processes controlling transport of tritium in the environment.

Feedback of the third interlaboratory exercise organised on wheat in the framework of the OBT working group

Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181
Author(s): N. Baglan, C. Cossonnet, E. Roche, S.B. Kim, I. Croudace, P. Warwick
Organically bound tritium (OBT) has become of increasing interest within the last decade, with a focus on its behaviour and also its analysis, which are both important to assess tritium distribution in the environment and dose consequences. After the first OBT International Workshop which was held in France in May 2012, an international working group was created. The expected benefits are the following: remove or reduce uncertainty in OBT analysis results, provide better OBT model validation data and better public dose results, increase the number of potential measuring OBT laboratories, validate all of the stages of the procedures based on a larger population and more statistically significant results, and investigate the feasibility of CRM's and RM's production. In this framework, three OBT exercises were organised; the 1st one on potatoes was conducted in 2013 by the Canadian National Laboratories (former AECL) with about 20 participating labs from around the world, the 2nd one on a sediment was organised in 2014 by GAU Radioanalytical (University of Southampton) on a sediment with again about 20 participating labs and the third one on wheat was organised in 2015 by the Commissariat à l'énergie atomique (CEA) with about 25 participating labs.

Impact of ventilation systems and energy savings in a building on the mechanisms governing the indoor radon activity concentration

Publication date: Available online 24 November 2017
Author(s): Bernard Collignan, Emilie Powaga
For a given radon potential in the ground and a given building, the parameters affecting the indoor radon activity concentration (IRnAC) are indoor depressurization of a building and its air change rate. These parameters depend mainly on the building characteristics, such as airtightness, and on the nature and performances of the ventilation system. This study involves a numerical sensitivity assessment of the indoor environmental conditions on the IRnAC in buildings. A numerical ventilation model has been adapted to take into account the effects of variations in the indoor environmental conditions (depressurization and air change rate) on the radon entry rate and on the IRnAC. In the context of the development of a policy to reduce energy consumption in a building, the results obtained showed that IRnAC could be strongly affected by variations in the air permeability of the building associated with the ventilation regime.

Assessment of uranium release to the environment from a disabled uranium mine in Brazil

Publication date: Available online 16 November 2017
Author(s): Wagner de Souza Pereira, Alphonse Germaine Albert Charles Kelecom, Ademir Xavier da Silva, Alessander Sá do Carmo, Delcy de Azavedo Py Júnior
The Ore Treatment Unit (in Portuguese Unidade de Tratamento de Minérios - UTM) located in Caldas, MG, Brazil is a disabled uranium mine. Environmental conditions generate acid drainage leaching metals and radionuclides from the waste rock pile. This drainage is treated to remove the heavy metals and radionuclides, before allowing the release of the effluent to the environment. To validate the treatment, samples of the released effluents were collected at the interface of the installation with the environment. Sampling was carried out from 2010 to 2015, and the activity concentration (AC, in Bq·l−1) of uranium in the liquid effluent was analyzed by arzenazo UV-Vis spectrophotometry of the soluble and particulate fractions, and of the sum of both fractions. Descriptive statistics, Z test and Pearson R2 correlation among the fractions were performed. Then, the data were organized by year and both ANOVA and Tukey test were carried out to group the means by magnitude of AC. The annual mean ranged from 0.02 Bq·l−1 in 2015 to 0.11 Bq·l−1 in 2010. The soluble fraction showed a higher AC mean when compared to the mean of the particulate fraction and no correlation of the data could be observed. Concerning the magnitude of the release, the ANOVA associated with the Tukey test, identified three groups of annual means (AC2010> AC2011 = AC2012 = AC2013 = AC2014 > AC2015). The mean values of uranium release at the interface installation-environment checking point (point 014) were within the Authorized Annual Limit (AAL) set by the regulator (0.2 Bq·l−1) indicating compliance of treatment with the licensing established for the unit. Finally, the data showed a decreasing tendency of U release.

Indoor radon measurements in south west England explained by topsoil and stream sediment geochemistry, airborne gamma-ray spectroscopy and geology

Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181
Author(s): Antonio Ferreira, Zornitza Daraktchieva, David Beamish, Charles Kirkwood, T. Robert Lister, Mark Cave, Joanna Wragg, Kathryn Lee

Efficacy of hydrocortisone in preventing posttraumatic stress disorder following critical illness and major surgery

Like other humans exposed to extreme trauma, patients who have been treated in an intensive care unit (ICU) often report traumatic memories. Extremely traumatic memories from the ICU in some of these patients are associated with the development of posttraumatic stress disorder (PTSD), which results in significant impairments in health-related quality of life (HRQL) outcomes of ICU therapy. Severely ill patients in the ICU often show insufficient endogenous glucocorticoid signaling, which has recently been termed critical illness-related corticosteroid insufficiency (CIRCI). We performed several controlled trials in ICU patients with suspected CIRCI from septic shock or cardiac surgery, which indicated that the administration of glucocorticoids (stress doses of hydrocortisone) during ICU treatment results in a significant reduction of PTSD symptoms in long-term survivors as well as improvements in HRQL outcomes. Stress doses of hydrocortisone could help to surmount impaired glucocorticoid signaling from CIRCI during critical illness resulting in a downregulation of the stress response as well as inhibition of traumatic memory retrieval and facilitated extinction of aversive information.

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Glucocorticoid-induced inhibition of memory retrieval: implications for posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is characterized by traumatic memories that can manifest as daytime recollections, traumatic nightmares, or flashbacks in which components of the event are relieved. These symptoms reflect excessive retrieval of traumatic memories that often retain their vividness and power to evoke distress for decades or even a lifetime. We have reported previously that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy human subjects. We therefore hypothesized that the administration of cortisol might also inhibit the retrieval of traumatic memories in patients with PTSD. In a recent pilot study, we found the first evidence to support this hypothesis. During a 3-month observation period, low-dose cortisol (10 mg/day) was administered orally for 1 month to three patients with chronic PTSD using a double-blind, placebo-controlled, crossover design. In each patient investigated, there was a significant treatment effect with cortisol-related reductions in one of the daily rated symptoms of traumatic memories without causing adverse side effects. Future studies with more patients and longer treatment periods are required to evaluate the efficacy of cortisol treatment for PTSD.

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Encoding difficulty promotes postlearning changes in sleep spindle activity during napping

Learning-dependent increases in sleep spindle density have been reported during nocturnal sleep immediately after the learning session. Here, we investigated experience-dependent changes in daytime sleep EEG activity after declarative learning of unrelated word pairs. At weekly intervals, 13 young male volunteers spent three 24 h sessions in the laboratory under carefully controlled homeostatic and circadian conditions. At approximately midday, subjects performed either one of two word-pair learning tasks or a matched nonlearning control task, in a counterbalanced order. The two learning lists differed in the level of concreteness of the words used, resulting in an easier and a more difficult associative encoding condition, as confirmed by performance at immediate cued recall. Subjects were then allowed to sleep for 4 h; afterward, delayed cued recall was tested. Compared with the control condition, sleep EEG spectral activity in the low spindle frequency range and the density of low-frequency sleep spindles (11.25-13.75 Hz) were both significantly increased in the left frontal cortex after the difficult but not after the easy encoding condition. Furthermore, we found positive correlations between these EEG changes during sleep and changes in memory performance between pre-nap and post-nap recall sessions. These results indicate that, like during nocturnal sleep, daytime sleep EEG oscillations including spindle activity are modified after declarative learning of word pairs. Furthermore, we demonstrate here that the nature of the learning material is a determinant factor for sleep-related alterations after declarative learning.

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Gene therapy works in animal models of rheumatoid arthritis...so what!

Rheumatoid arthritis (RA) is a systemic disease with polyarticular manifestation of chronic inflammation in the knees and small joints of hand and feet. The current systemic anti-tumor necrosis factor (TNF)-alpha therapies with biologics ameliorate disease in 60% to 70% of RA patients. However, biologics must be given systemically in relatively high dosages to achieve constant therapeutic levels in the joints, and side effects have been reported. To this end, local gene delivery can provide an alternative approach to achieve high, long-term expression of biologics, optimizing the therapeutic efficacy and minimizing systemic exposure. Evidence from animal models convincingly supports the application of local gene therapy in rheumatoid arthritis, but preclinical studies remain necessary to evaluate the merge of cell-specific targeting, viral vector development, and disease-regulated transgene expression to optimize efficacy and safety.

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Analysis of patient flows for orthopedic procedures using small area analysis in Switzerland

In general cantons regulate and control the Swiss health service system; patient flows within and between cantons are thereby partially disregarded. This paper develops an alternative spatial model, based upon the construction of orthopedic hospital service areas (HSAOs), and introduces indices for the analysis of patient streams in order to identify areas, irrespective of canton, with diverse characteristics, importance, needs, or demands.; HSAOs were constructed using orthopedic discharge data. Patient streams between the HSAOs were analysed by calculating three indices: the localization index (% local residents discharged locally), the netindex (the ratio of discharges of nonlocal incoming residents to outgoing local residents), and the market share index (% of local resident discharges of all discharges in local hospitals).; The 85 orthopedic HSAOs show a median localization index of 60.8%, a market share index of 75.1%, and 30% of HSAOs have a positive netindex. Insurance class of bed, admission type, and patient age are partially but significantly associated with those indicators. A trend to more centrally provided health services can be observed not only in large urban HSAOs such as Geneva, Bern, Basel, and Zurich, but also in HSAOs in mountain sport areas such as Sion, Davos, or St.Moritz. Furthermore, elderly and emergency patients are more frequently treated locally than younger people or those having elective procedures.; The division of Switzerland into HSAOs provides an alternative spatial model for analysing and describing patient streams for health service utilization. Because this small area model allows more in-depth analysis of patient streams both within and between cantons, it may improve support and planning of resource allocation of in-patient care in the Swiss healthcare system.

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Diagnostic value of signs, symptoms and laboratory values in lower respiratory tract infection

BACKGROUND: Lower respiratory tract infections (LRTI) account for the majority of all antibiotics prescribed in the clinical practice, irrespective of the fact that most cases are self-limiting. Using the outcome and microbiology findings as gold standard, we determined sensitivity, specificity, positive and negative predictive values of common used signs and symptoms of bacterial LRTI requiring antibiotic therapy. PATIENTS: 243 consecutive patients with suspected LRTI admitted to a tertiary care hospital. RESULTS: Bacterial LRTI requiring antibiotic therapy and self-limiting LRTI were diagnosed in 32 and 86 patients, respectively. Assessing these two groups, sputum, dyspnea, crackles, fever and leukocytes (WBC) were insensitive and unspecific parameters for the diagnosis of bacterial LRTI requiring antibiotic therapy. Cough was sensitive (93.8%) but unspecific (5.8%). The sensitivity of infiltrates, C-reactive protein (CRP) <50 mg/L and procalcitonin (PCT) <0.1 ng/mL was 96.9%, 93.8% and 93.8%, respectively. PCT <0.25 ng/mL showed the highest specificity (97.7%), followed by WBC <16 x 109/L (94.2%) and CRP <100 mg/L (91.9%). The sensitivity of WBC <16 x 109/L was low (37.5%). CONCLUSION: The overall sensitivity and specificity of signs and symptoms for bacterial LRTI requiring antibiotic therapy was poor. Obtaining a chest-X-ray with infiltrates and determining CRP at a cut-off value of 50 mg/L or PCT at a cutoff value of 0.1 ng/mL was required to ascertain the need for antibiotics in LRTI.

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Diminishing reciprocal fairness by disrupting the right prefrontal cortex

Humans restrain self-interest with moral and social values. They are the only species known to exhibit reciprocal fairness, which implies the punishment of other individuals' unfair behaviors, even if it hurts the punisher's economic self-interest. Reciprocal fairness has been demonstrated in the Ultimatum Game, where players often reject their bargaining partner's unfair offers. Despite progress in recent years, however, little is known about how the human brain limits the impact of selfish motives and implements fair behavior. Here we show that disruption of the right, but not the left, dorsolateral prefrontal cortex (DLPFC) by low-frequency repetitive transcranial magnetic stimulation substantially reduces subjects' willingness to reject their partners' intentionally unfair offers, which suggests that subjects are less able to resist the economic temptation to accept these offers. Importantly, however, subjects still judge such offers as very unfair, which indicates that the right DLPFC plays a key role in the implementation of fairness-related behaviors.

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Agranulozytose bei einem mit Metamizol und Clopidogrel behandelten Patienten

Wir berichten über einen 75-jährigen Patienten, der drei Wochen nach einem ischämischen zerebrovaskulären Insult eine Agranulozytose entwickelte und anschliessend an einer Pneumonie erkrankte. Als mögliche Ursachen für die Agranulozytose konnten am ehesten Metamizol oder Clopidogrel identifiziert werden. Die Agranulozytose ist eine seltene, aber ernst zu nehmende unerwünschte Arzneimittelwirkung. Seit 1997 wurden den Schweizer Arzneimittelbehörden sechs Fälle von Agranulozytose unter Metamizol und zwei unter Clopidogrel gemeldet. Die Therapie besteht in der Injektion von hämatopoietischem Wachstumsfaktor (G-CSF, granulocyte colony stimulating factor) sowie der Gabe von breit wirksamen Antibiotika im Falle einer bakteriellen Infektion. Bei adäquater Therapie ist die Prognose gut. Wir diskutieren den Einsatz des Analgetikums und Antipyretikums Metamizol in der Akut- und Langzeittherapie.

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Anticipatory cognitive stress appraisal and the acute procoagulant stress response in men

Acute mental stress elicits blood hypercoagulability. Following a transactional stress model, we investigated whether individuals who anticipate stress as more threatening, challenging, and as exceeding their coping skills show greater stress reactivity of the coagulation activation marker D-dimer, indicating fibrin generation in plasma.; Forty-seven men (mean age 44 +/- 14 years; mean blood pressure [MBP] 101 +/- 12 mm Hg; mean body mass index [BMI] 26 +/- 3 kg/m(2)) completed the Primary Appraisal Secondary Appraisal (PASA) scale before undergoing the Trier Social Stress Test (combination of mock job interview and mental arithmetic task). Heart rate, blood pressure, plasma catecholamines, and D-dimer levels were measured before and after stress, and during recovery up to 60 minutes poststress.; Hemodynamic measures, catecholamines, and D-dimer changed across all time points (p values <.001). The PASA "Stress Index" (integrated measure of transactional stress perception) correlated with total D-dimer area under the curve (AUC) between rest and 60 minutes poststress (r = 0.30, p = .050) and with D-dimer change from rest to immediately poststress (r = 0.29, p = .046). Primary appraisal (combined "threat" and "challenge") correlated with total D-dimer AUC (r = 0.37, p = .017), D-dimer stress change (r = 0.41, p = .004), and D-dimer recovery (r = 0.32, p = .042). "Challenge" correlated more strongly with D-dimer stress change than "threat" (p = .020). Primary appraisal (DeltaR(2) = 0.098, beta = 0.37, p = .019), and particularly its subscale "challenge" (DeltaR(2) = 0.138, beta = 0.40, p = .005), predicted D-dimer stress change independently of age, BP, BMI, and catecholamine change.; Anticipatory cognitive appraisal determined the extent of coagulation activation to and recovery from stress in men. Particularly individuals who anticipated the stressor as more challenging and also more threatening had a greater fibrin stress response.

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Markers of acute inflammation in assessing and managing lower respiratory tract infections: focus on procalcitonin

This review describes the pathophysiological basis for using procalcitonin to help diagnose infections, and the strengths and weaknesses of implementing the test rationally in a routine clinical setting. Meta-analyses of observational studies and intervention studies both suggest that as a surrogate marker, procalcitonin allows an improved diagnostic assessment of a variety of infections, e.g., respiratory tract infections, meningitis, acute infectious endocarditis and pancreatitis. Measuring procalcitonin is not a substitute for careful clinical assessment and obtaining appropriate cultures in all patients. However, used appropriately, procalcitonin allows an earlier diagnosis of infection and can inform physicians about the course and prognosis of the disease better than more commonly used clinical and laboratory markers. With use of a sensitive assay, a procalcitonin-based therapeutic strategy can safely and markedly reduce antibiotic usage in those respiratory tract infections that are mostly viral, and in viral meningitis. More sensitive procalcitonin assays, with a functional sensitivity within the normal reference range of >0.03 microg/L, should be available soon. There is a need for more intervention studies in other sites of infection to tackle the existing vicious cycle of antibiotic overuse and emerging multiresistance. Furthermore, as procalcitonin is a hormokine mediator, its immunoneutralisation might open new treatment options for sepsis.

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Abstract

A novel Gram-negative, capnophilic, fusiform bacterium, designated strain ChDC OS43T, was isolated from a human refractory periapical abscess in the left mandibular second molar and was characterized by polyphasic taxonomic analysis. The 16S rRNA gene sequence revealed that the strain belongs to the genus Capnocytophaga, as it showed sequence similarities to Capnocytophaga ochracea ATCC 27872T (96.30%) and C. sputigena ATCC 33612T (96.16%). The prevalent fatty acids of strain ChDC OS43T were isoC15:0 (57.54%), C16:0 (5.93%), C16:0 3OH (5.72%), and C18:1cis 9 (4.41%). The complete genome of strain ChDC OS43T was 3,412,686 bp, and the G+C content was 38.2 mol%. The average nucleotide identity (ANI) value between strain ChDC OS43T and C. ochracea ATCC 27872T or C. sputigena ATCC 33612T was >92.01%. The genome-to-genome distance (GGD) value between strain ChDC OS43T and C. ochracea ATCC 27872T or C. sputigena ATCC 33612T was 32.0 and 45.7%, respectively. Based on the results of phenotypic, chemotaxonomic, and phylogenetic analysis, strain ChDC OS43T (= KCOM 1579T = KCTC 5562T = KCCM 42841T = JCM 32133T) should be classified as the type strain of a novel species of genus Capnocytophaga, for which the name Capnocytophaga endodontalis sp. nov. is proposed.

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Objectives

The objective of these recommendations is to highlight the importance of infection prevention and control in ultrasound (US), including diagnostic and interventional settings.

Methods

Review of available publications and discussion within a multidisciplinary group consistent of radiologists and microbiologists, in consultation with European patient and industry representatives.

Recommendations

Good basic hygiene standards are essential. All US equipment must be approved prior to first use, including hand held devices. Any equipment in direct patient contact must be cleaned and disinfected prior to first use and after every examination. Regular deep cleaning of the entire US machine and environment should be undertaken. Faulty transducers should not be used. As outlined in presented flowcharts, low level disinfection is sufficient for standard US on intact skin. For all other minor and major interventional procedures as well as all endo-cavity US, high level disinfection is mandatory. Dedicated transducer covers must be used when transducers are in contact with mucous membranes or body fluids and sterile gel should be used inside and outside covers.

Conclusions

Good standards of basic hygiene and thorough decontamination of all US equipment as well as appropriate use of US gel and transducer covers are essential to keep patients safe.

Main messages

• Transducers must be cleaned/disinfected before first use and after every examination.

• Low level disinfection is sufficient for standard US on intact skin.

• High level disinfection is mandatory for endo-cavity US and all interventions.

• Dedicated transducer covers must be used for endo-cavity US and all interventions.

• Sterile gel should be used for all endo-cavity US and all interventions.

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Objectives

The objective of these recommendations is to highlight the importance of infection prevention and control in ultrasound (US), including diagnostic and interventional settings.

Methods

Review of available publications and discussion within a multidisciplinary group consistent of radiologists and microbiologists, in consultation with European patient and industry representatives.

Recommendations

Good basic hygiene standards are essential. All US equipment must be approved prior to first use, including hand held devices. Any equipment in direct patient contact must be cleaned and disinfected prior to first use and after every examination. Regular deep cleaning of the entire US machine and environment should be undertaken. Faulty transducers should not be used. As outlined in presented flowcharts, low level disinfection is sufficient for standard US on intact skin. For all other minor and major interventional procedures as well as all endo-cavity US, high level disinfection is mandatory. Dedicated transducer covers must be used when transducers are in contact with mucous membranes or body fluids and sterile gel should be used inside and outside covers.

Conclusions

Good standards of basic hygiene and thorough decontamination of all US equipment as well as appropriate use of US gel and transducer covers are essential to keep patients safe.

Main messages

• Transducers must be cleaned/disinfected before first use and after every examination.

• Low level disinfection is sufficient for standard US on intact skin.

• High level disinfection is mandatory for endo-cavity US and all interventions.

• Dedicated transducer covers must be used for endo-cavity US and all interventions.

• Sterile gel should be used for all endo-cavity US and all interventions.

Objectives

The objective of these recommendations is to highlight the importance of infection prevention and control in ultrasound (US), including diagnostic and interventional settings.

Methods

Review of available publications and discussion within a multidisciplinary group consistent of radiologists and microbiologists, in consultation with European patient and industry representatives.

Recommendations

Good basic hygiene standards are essential. All US equipment must be approved prior to first use, including hand held devices. Any equipment in direct patient contact must be cleaned and disinfected prior to first use and after every examination. Regular deep cleaning of the entire US machine and environment should be undertaken. Faulty transducers should not be used. As outlined in presented flowcharts, low level disinfection is sufficient for standard US on intact skin. For all other minor and major interventional procedures as well as all endo-cavity US, high level disinfection is mandatory. Dedicated transducer covers must be used when transducers are in contact with mucous membranes or body fluids and sterile gel should be used inside and outside covers.

Conclusions

Good standards of basic hygiene and thorough decontamination of all US equipment as well as appropriate use of US gel and transducer covers are essential to keep patients safe.

Main messages

• Transducers must be cleaned/disinfected before first use and after every examination.

• Low level disinfection is sufficient for standard US on intact skin.

• High level disinfection is mandatory for endo-cavity US and all interventions.

• Dedicated transducer covers must be used for endo-cavity US and all interventions.

• Sterile gel should be used for all endo-cavity US and all interventions.

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Image Restoration for Fluorescence Planar Imaging with Diffusion Model

Fluorescence planar imaging (FPI) is failure to capture high resolution images of deep fluorochromes due to photon diffusion. This paper presents an image restoration method to deal with this kind of blurring. The scheme of this method is conceived based on a reconstruction method in fluorescence molecular tomography (FMT) with diffusion model. A new unknown parameter is defined through introducing the first mean value theorem for definite integrals. System matrix converting this unknown parameter to the blurry image is constructed with the elements of depth conversion matrices related to a chosen plane named focal plane. Results of phantom and mouse experiments show that the proposed method is capable of reducing the blurring of FPI image caused by photon diffusion when the depth of focal plane is chosen within a proper interval around the true depth of fluorochrome. This method will be helpful to the estimation of the size of deep fluorochrome.

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System Dynamic Model for Simulating Demand-Supply Interaction of Railway Express Freight System

Express freight transportation is a rich seam of profit for China railway, and railway express freight system is a complex system with multiple variables and nonlinear feedback loops. This paper presents a System Dynamic Model for simulating the interaction between demand and supply of railway express freight system in China. The model consists of three submodels including economic environment, demand, supply, and investment, and its validity is verified by running in Vensim DDS software using historical data. In the simulation of period 2000–2025, the three variables are taken as control variables including growth rate of the national economy, railway express freight rate, and investment in fixed railway assets. Three scenarios for each control variable are simulated, and their effects are analyzed to provide beneficial reference for regulating the demand-supply gap of railway express freight. The simulation demonstrated that raising freight rate, adding investment in fixed railway assets, and decelerating economic growth rate are all effective ways to shrink the demand-supply gap of railway express freight. The model can be used to forecast the transport demand of railway express freight and test the outcomes of demand-supply regulating measures.

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The Expression of AQP5 and UTs in the Sweat Glands of Uremic Patients

Purpose. To research the distribution and quantitative changes of UT-A1, UT-B1, and AQP5 in uremic skin tissue. Methods. 34 cases of uremic patients (UP) and 11 controls were recruited. Immunohistochemistry, immunofluorescence, RT-PCR, and Western Blot were used to identify the proteins in sweat glands. Results. AQP5, UT-A1, and UT-B1 were expressed and localized in human skin basal lines, skin sweat glands, and sweat ducts, both in UP and controls. Compared to controls, AQP5 mRNA abundance was significantly decreased in UP (), and, with the decrease of eGFR, the AQP5 expression was significantly decreased (). By contrast, UT-A1 and UT-B1 mRNA abundance was significantly increased in the skin of UP compared with the control (), and, with the decrease of eGFR, the AQP5 expression was significantly increased (). We found that the gene changes were coincident with the corresponding target proteins. The urea transporter subtypes, UT-A1 and UT-B1, were expressed in the skin basal cell layer and exocrine sweat glands. The abundance of UT-A1 and UT-B1 in uremic sweat glands was significantly increased in UP, while the expression of AQP5 was decreased. Conclusion. Elimination of urea through the skin by producing sweat is a potential therapeutic strategy for renal failure patients.

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Endovascular Repair of Aortobronchial Fistula due to Saccular Aneurysm of Thoracic Aorta

Aortobronchial fistula (ABF) is a rare condition which can be lethal if left untreated. Open surgical treatment carries high morbidity and mortality. Recent advances in endovascular technology have made thoracic endovascular aortic repair (TEVAR) the treatment of choice. We present a successful endovascular repair of aortobronchial fistula due to a saccular aneurysm of descending thoracic aorta.

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Subspace Method Aided Data-Driven Fault Detection Based on Principal Component Analysis

The model-based fault detection technique, which needs to identify the system models, has been well established. The objective of this paper is to develop an alternative procedure instead of identifying the system models. In this paper, subspace method aided data-driven fault detection based on principal component analysis (PCA) is proposed. The basic idea is to use PCA to identify the system observability matrices from input and output data and construct residual generators. The advantage of the proposed method is that we just need to identify the parameterized matrices related to residuals rather than the system models, which reduces the computational steps of the system. The proposed approach is illustrated by a simulation study on the Tennessee Eastman process.

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Preeruptive Intracoronal Radiolucencies: Detection and Nine Years Monitoring with a Series of Dental Radiographs

Preeruptive intracoronal radiolucencies (PEIRs) are mostly incidentally found by routine radiographic examination of unerupted teeth. PEIRs are classified into two types according to the nature of the lesion: progressive and nonprogressive. A case report of a 17-year-old boy with a nonprogressive PEIR on the permanent mandibular left second molar is presented. The lesion was initially detected on an unerupted tooth at age eight years, eight months. It was clinically and radiographically assessed yearly. Cone beam computed tomography (CBCT) was used to evaluate the lesion’s size and location when the patient was 11 and 14 years old. The assessments confirmed that the lesion was nonprogressive and had no connection to the pulp or oral cavity. Due to the static nature of the detected PEIR during the nine-year follow-up period, the patient’s low caries-risk status, and high patient and parental cooperation in periodic dental care, it was decided to place resin sealant on the affected tooth and monitor the lesion without any operative treatment.

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Studies on Chemical Composition and Antioxidant Activity of Rudbeckia triloba

The paper describes the physicochemical studies made on the decorative plant, Rudbeckia triloba (Asteraceae). For this purpose, essential oil, infusion, decoction, and hydroalcoholic macerate obtained from different aerial parts of Rudbeckia triloba were analyzed. The main phytochemical constituents identified by GC-MS analysis were found to be α-pinene (in dried leaves (46.0%) and flowers (40.1%)) and β-phellandrene (in essential oil of dried inflorescences (26.09%)). The Folin–Ciocalteu and quercetin assays revealed different values of total phenolic and flavonoid contents of petals, leaves, and seeds as a function of the solvent used and extraction procedure. The hydroalcoholic macerate of petals was found to present the maximum phenolic and flavonoid contents (130.29 ± 5.58 mg gallic acid equivalent/g dry vegetable material and 30.72 ± 1.35 mg quercetin equivalent/g dry vegetable material, resp.) and also exhibits the lower value of EC50 (0.32% (v/v)), obtained by applying the DPPH⋅ assay. Comparing the extraction methods applied, the maceration was found to be the most effective for phenolic compounds, most likely due to the solvent (70% ethanol). The use of water-alcohol mixture leads to an improvement of the extraction yield of phenolic compounds (including those with higher molecular weights) than by using water as extractive solvent, in the case of infusions and decocts.

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Aberrant Long Noncoding RNAs Expression Profiles Affect Cisplatin Resistance in Lung Adenocarcinoma

Background. Long noncoding RNAs (lncRNAs) have been shown to be involved in the mechanism of cisplatin resistance in lung adenocarcinoma (LAD). However, the roles of lncRNAs in cisplatin resistance in LAD are not well understood. Methods. We used a high-throughput microarray to compare the lncRNA and mRNA expression profiles in cisplatin resistance cell A549/DDP and cisplatin sensitive cell A549. Several candidate cisplatin resistance-associated lncRNAs were verified by real-time quantitative reverse transcription polymerase chain reaction (PCR) analysis. Results. We found that 1,543 lncRNAs and 1,713 mRNAs were differentially expressed in A549/DDP cell and A549 cell, hinting that many lncRNAs were irregular from cisplatin resistance in LAD. We also obtain the fact that 12 lncRNAs were aberrantly expressed in A549/DDP cell compared with A549 cell by quantitative PCR. Among these, UCA1 was the aberrantly expressed lncRNA and can significantly reduce the IC50 of cisplatin in A549/DDP cell after knockdown, while it can increase the IC50 of cisplatin after UCA1 was overexpressed in NCI-H1299. Conclusions. We obtained patterns of irregular lncRNAs and they may play a key role in cisplatin resistance of LAD.

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No advantage of Sodium Bicarbonate and Acetyl cysteine in Preventing Contrast Nephropathy

Steven D. Weisbord et al in NEJM published the results of Prevention of Serious Adverse Events Following Angiography (PRESERVE) trial which was done compare intravenous sodium bicarbonate with intravenous sodium chloride and oral acetylcysteine with oral placebo for the prevention of major adverse outcomes and acute kidney injury in a large population of high-risk patients undergoing coronary or noncoronary angiography.

Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury.

Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease

The influence of thyroid failure on haemostasis is controversial, both hypocoagulable and hypercoagulable states have been reported. Since both subclinical and overt hypothyroidism have been associated with atherosclerosis, a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. We investigated various haemostatic variables in 42 women with subclinical hypothyroidism and compared them to 66 euthyroid controls. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VII activity (FVII:C), factor VII antigen (FVII:Ag), factor VIII activity, von Willebrand factor (vWF), antithrombin III, heparin cofactor II, protein C, protein S, plasminogen, antiplasmin, plasminogen activator inhibitor and tissue plasminogen activator, as well as common lipid variables, were measured. Factor VII:C (P > 0.02) and the ratio FVII:C/FVII:Ag (P > 0.01) were significantly increased in subclinical hypothyroid patients compared to the control group. Both parameters remained higher in hypothyroid patients after exclusion of 18 women on oestrogen replacement therapy. No differences were found between the groups with respect to vWF or the other haemostatic and lipid variables tested. Patients with subclinical hypothyroidism had significantly higher levels of FVII:C. The greater increase in FVII:C compared to that of FVII:Ag, as shown by the increase in their ratio, might reflect the presence of activated FVIIa. This might mean a hypercoagulable state, which could contribute to the increased prevalence of coronary heart disease reported in such patients. A hypercoagulable state might be another argument in favour of thyroxine replacement treatment in subclinical hypothyroidism, especially in patients with additional risk factors for vascular disease.

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Cutting edge: human gamma delta T cells are activated by intermediates of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis

Activation of V gamma 9/V delta 2 T cells by small nonprotein Ags is frequently observed after infection with various viruses, bacteria, and eukaryotic parasites. We suggested earlier that compounds synthesized by the 2-C:-methyl-D-erythritol 4-phosphate (MEP) pathway of isopentenyl pyrophosphate synthesis are responsible for the V gamma 9/V delta 2 T cell reactivity of many pathogens. Using genetically engineered Escherichia coli knockout strains, we now demonstrate that the ability of E. coli extracts to stimulate gamma delta T cell proliferation is abrogated when genes coding for essential enzymes of the MEP pathway, dxr or gcpE, are disrupted or deleted from the bacterial genome.

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Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes

The endocrine cells of the rat pancreatic islets of Langerhans, including insulin-producing beta-cells, turn over every 40-50 days by processes of apoptosis and the proliferation and differentiation of new islet cells (neogenesis) from progenitor epithelial cells located in the pancreatic ducts. However, the administration to rats of islet trophic factors such as glucose or glucagon-like peptide 1 for 48 h results in a doubling of islet cell mass, suggesting that islet progenitor cells may reside within the islets themselves. Here we show that rat and human pancreatic islets contain a heretofore unrecognized distinct population of cells that express the neural stem cell-specific marker nestin. Nestin-positive cells within pancreatic islets express neither the hormones insulin, glucagon, somatostatin, or pancreatic polypeptide nor the markers of vascular endothelium or neurons, such as collagen IV and galanin. Focal regions of nestin-positive cells are also identified in large, small, and centrolobular ducts of the rat pancreas. Nestin-positive cells in the islets and in pancreatic ducts are distinct from ductal epithelium because they do not express the ductal marker cytokeratin 19 (CK19). After their isolation, these nestin-positive cells have an unusually extended proliferative capacity when cultured in vitro (approximately 8 months), can be cloned repeatedly, and appear to be multipotential. Upon confluence, they are able to differentiate into cells that express liver and exocrine pancreas markers, such as alpha-fetoprotein and pancreatic amylase, and display a ductal/endocrine phenotype with expression of CK19, neural- specific cell adhesion molecule, insulin, glucagon, and the pancreas/duodenum specific homeodomain transcription factor, IDX-1. We propose that these nestin-positive islet-derived progenitor (NIP) cells are a distinct population of cells that reside within pancreatic islets and may participate in the neogenesis of islet endocrine cells. The NIP cells that also reside in the pancreatic ducts may be contributors to the established location of islet progenitor cells. The identification of NIP cells within the pancreatic islets themselves suggest possibilities for treatment of diabetes, whereby NIP cells isolated from pancreas biopsies could be expanded ex vivo and transplanted into the donor/recipient.

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Basolateral amygdala-nucleus accumbens interactions in mediating glucocorticoid enhancement of memory consolidation

Systemic or intracerebral administration of glucocorticoids enhances memory consolidation in several tasks. Previously, we reported that these effects depend on an intact basolateral nucleus of the amygdala (BLA) and efferents from the BLA that run through the stria terminalis (ST). The BLA projects directly to the nucleus accumbens (NAc) via this ST pathway. The NAc also receives direct projections from the hippocampus and, therefore, may be a site of convergence of BLA and hippocampal influences in modulating memory consolidation. In support of this view, we found previously that lesions of either the NAc or the ST also block the memory-modulatory effect of systemically administered glucocorticoids. The present experiments examined the effects of lesions of the NAc or the ST on the memory-modulatory effects of intracerebral glucocorticoids on inhibitory avoidance training. Microinfusions of the specific glucocorticoid receptor agonist 11beta,17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362; 1.0 or 3.0 ng) into either the BLA or the hippocampus of male Sprague Dawley rats administered immediately after training enhanced the 48 hr retention performance in a dose-dependent manner. Bilateral lesions of the NAc or the ST alone did not affect retention performance but blocked the memory enhancement induced by intra-BLA or intrahippocampal glucocorticoid receptor agonist administration. These findings indicate that the BLA-NAc pathway plays an essential role in mediating glucocorticoid effects on memory consolidation and suggest that the BLA interacts with hippocampal effects on memory consolidation via this pathway.

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Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion

Feedback is a ubiquitous control mechanism of gene networks. Here, we have used positive feedback to construct a synthetic eukaryotic gene switch in Saccharomyces cerevisiae. Within this system, a continuous gradient of constitutively expressed transcriptional activator is translated into a cell phenotype switch when the activator is expressed autocatalytically. This finding is consistent with a mathematical model whose analysis shows that continuous input parameters are converted into a bimodal probability distribution by positive feedback, and that this resembles analog-digital conversion. The autocatalytic switch is a robust property in eukaryotic gene expression. Although the behavior of individual cells within a population is random, the proportion of the cell population displaying either low or high expression states can be regulated. These results have implications for understanding the graded and probabilistic mechanisms of enhancer action and cell differentiation.

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Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients

OBJECTIVE: To evaluate the recently discovered long pentraxin PTX3 in plasma of critically ill patients and to compare it with the classic short pentraxin C-reactive protein and with other indicators of inflammation. DESIGN: A cohort study on plasma samples. SETTING: Medical intensive care unit (ICU) of the University Hospital of Basel. PATIENTS: A total of 101 consecutive critically ill patients admitted to the medical ICU. INTERVENTIONS: Venous blood samples were routinely obtained at entry, on day 2, and at discharge or before death. MEASUREMENTS AND MAIN RESULTS: Plasma samples were obtained from 101 consecutive critically ill patients admitted to the ICU with systemic inflammatory response syndrome, sepsis, or septic shock. PTX3 plasma levels were measured by enzyme-linked immunosorbent assay. PTX3 was elevated in critically ill patients, with a gradient from systemic inflammatory response syndrome to septic shock. PTX3 levels correlated with clinical scores reflecting severity of disease (e.g., Acute Physiology and Chronic Health Evaluation II: p =.00097). In addition, high levels of PTX3 were associated with unfavorable outcome. CONCLUSIONS: The long pentraxin PTX3 is elevated in critically ill patients and correlates with severity of disease and infection. Compared with the short pentraxin C-reactive protein, PTX3 may be a more direct indicator of tissue involvement by inflammatory and infectious processes.

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Psychoneuroendocrinological contributions to the etiology of depression, posttraumatic stress disorder, and stress-related bodily disorders: the role of the hypothalamus-pituitary-adrenal axis

Following the assumption that stressors play an important part in the etiology and maintenance of psychiatric disorders, it is necessary to evaluate parameters reflecting stress-related physiological reactions. Results from these examinations may help to deepen the insight into the etiology of psychiatric disorders and to elucidate diagnostic uncertainties. One of the best-known stress-related endocrine reactions is the hormonal release of the hypothalamic-pituitary-adrenal (HPA) axis. Dysregulations of this axis are associated with several psychiatric disorders. Profound hyperactivity of the HPA-axis has been found in melancholic depression, alcoholism, and eating disorders. In contrast, posttraumatic stress disorder, stress-related bodily disorders like idiopathic pain syndromes, and chronic fatigue syndrome seem to be associated with diminished HPA activity (lowered activity of the adrenal gland). Hypotheses referring to (a) the psychophysiological meaning and (b) the development of these alterations are discussed.

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Listening through different ears alters spatial response fields in ferret primary auditory cortex

The localization of sounds in space is based on spatial cues that arise from the acoustical properties of the head and external ears. Individual differences in localization cue values result from variability in the shape and dimensions of these structures. We have mapped spatial response fields of high-frequency neurons in ferret primary auditory cortex using virtual sound sources based either on the animal's own ears or on the ears of other subjects. For 73% of units, the response fields measured using the animals' own ears differed significantly in shape and/or position from those obtained using spatial cues from another ferret. The observed changes correlated with individual differences in the acoustics. These data are consistent with previous reports showing that humans localize less accurately when listening to virtual sounds from other individuals. Together these findings support the notion that neural mechanisms underlying auditory space perception are calibrated by experience to the properties of the individual.

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TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study)

This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 +/- 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk. Individual L-thyroxine replacement (mean dose, 85.5 +/- 4.3 microg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 +/- 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the L-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [-0.24 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02). This is the first double blind study to show that physiological L-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9-31% can be estimated from the observed improvement in low density lipoprotein cholesterol.

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Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents

The lateral walls of the forebrain lateral ventricles are the richest source of stem cells in the adult mammalian brain. These stem cells give rise to new olfactory neurons that are renewed throughout life. The neurons originate in the subventricular zone (SVZ), migrate within the rostral extension (RE) of the SVZ along the rostral migratory stream (RMS) within tube-like structures formed of glial cells, to eventually reach the olfactory bulb (OB). We demonstrate that, contrary to the current view, multipotential (neuronal-astroglial-oligodendroglial) precursors with stem cell features can be isolated not only from the SVZ but also from the entire RE, including the distal portion within the OB. Specifically, these stem cells do not derive from the migratory neuroblasts coming from the SVZ. Interestingly, stem cells isolated from the proximal RE generate significantly more oligodendrocytes, and those from the distal RE proliferate significantly more slowly than stem cells derived from the SVZ and other RE regions. These findings demonstrate that stem cells are not confined to the forebrain periventricular region and indicate that stem cells endowed with different functional characteristics occur at different levels of the SVZ-RE pathway.

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Use of pro-atrial natriuretic peptide in the detection of myocardial ischaemia

BACKGROUND: Because of its unique storage and release mechanisms allowing a very rapid response to haemodynamic changes, pro-atrial natriuretic peptide (proANP) may be a helpful cardiac marker in the detection of myocardial ischaemia. MATERIALS AND METHODS: A total of 260 consecutive patients with suspected myocardial ischaemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography (SPECT) were enrolled. Levels of plasma proANP were determined before and 1 min after maximal exercise. RESULTS: Baseline proANP and peak exercise proANP were significantly higher in patients with myocardial ischaemia as compared to those without ischaemia (median, 82 [IQR, 57-112] vs. 67 [IQR, 50-106] pmol L(-1), P = 0.007; and 89 [IQR, 65-121] vs. 78 [IQR, 57-116] pmol L(-1), P = 0.033). The area under the ROC curve for baseline proANP was 0.597 (95% CI, 0.527-0.667), as compared to 0.577 (95% CI, 0.507-0.648) for peak exercise proANP. Exercise-induced changes in proANP were similar in patients with and without myocardial ischaemia, and showed no correlation with the extent of myocardial ischaemia. CONCLUSIONS: Baseline proANP and peak exercise proANP are significantly higher in patients with myocardial ischaemia. However, because of considerable overlap in proANP levels between patients with and without myocardial ischaemia, neither measurement seems helpful in the detection of myocardial ischaemia in clinical practice.

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Radioiodine therapy in hyperthyroidism: inverse correlation of pretherapeutic iodine uptake level and post-therapeutic outcome

BACKGROUND: High iodine uptake levels are widely accepted as a condition for successful treatment with radioiodine (RAI). However, the existing data are controversial and the correlation of pretherapeutic RAI uptake level and outcome of RAI therapy has not yet been quantified. The aim of this study was to analyze the influence of RAI uptake on the outcome after RAI treatment and to estimate uptake-dependent success rates. MATERIALS AND METHODS: We retrospectively analyzed 229 patients (m = 53, f = 176; age 64 +/- 14 years) suffering from toxic adenoma, multinodular goitre or Graves' disease, respectively. Clinical status and T3, fT4 and TSH levels were assessed 3, 6, 12 and 18 months after treatment. Successful treatment was defined as loss of hyperthyroidism 18 months after radioiodine therapy. Logistic regression was used to assess the relation between the maximum iodine uptake and the rate of success and hypothyroidism, respectively, after RAI treatment. RESULTS: Overall, patients presented with pretherapeutic RAI uptake values between 17% and 100%. Eighteen months after RAI treatment, an euthyroid state was achieved in 136 patients (60%), hypothyroidism occurred in 47 patients (20%) and 46 patients (20%) remained hyperthyroid. The patients with the lowest pretherapeutic RAI uptakes showed the highest success rates. The overall success rate significantly decreased from 92% at low RAI uptakes to 57% at high uptakes (P = 0.002). This effect was found in the patients suffering from multinodular goitre as well as in the patients with Graves' disease. CONCLUSION: In contrast to the current opinion, our results provide evidence that the pretherapeutic iodine uptake level and post-therapeutic outcome are inversely correlated.

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Is there a clinical relevance of partial androgen deficiency of the aging male?

PURPOSE: Aging in men is characterized by a progressive, generally moderate decrease in plasma testosterone (T) levels and T substitution is increasingly prescribed. However, the association of partial androgen deficiency of the aging male with clinical symptoms and the ideal screening test are controversial. We investigate the association between various T measures and clinical and biochemical parameters of the aging male. MATERIALS AND METHODS: We investigated the association between total (TT), calculated free (FTcalc) and bioavailable (BT) testosterone, and various clinical and biochemical parameters in 51 healthy community living male volunteers, 55 and 75 years old. The parameters included serum levels of sex hormone-binding globulin, estradiol and lipid profile after an overnight fast; questionnaires assessing clinical symptoms, erectile function and mood; bone mineral density and body composition. RESULTS: TT correlated with FTcalc (r2 = 0.71, p >0.001) but not with BT (r2 = 0.04, p not significant) and FTcalc correlated moderately with BT (r2 = 0.23, p >0.001). Testicular volume correlated with TT levels (r2 = 0.17, p >0.001) and FTcalc (r2 = 0.17, p >0.001) but not with BT. There was neither a correlation of TT, FTcalc nor BT values with clinical symptoms nor with biochemical and radiological parameters, ie affective symptoms and sexual interest, circulating estradiol, lipid levels, bone mineral density or lean body mass. CONCLUSIONS: T values in our study sample did not correlate with clinical signs and symptoms of hypogonadism. Thus, according to our data, symptoms of the aging male could be rather multifactorial and should not be indiscriminately assigned to the age associated decrease in T levels.

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Late immunoneutralization of procalcitonin arrests the progression of lethal porcine sepsis

BACKGROUND: Procalcitonin (ProCT) is becoming increasingly recognized as a mediator as well as a marker of sepsis. Serum ProCT concentrations rise soon after induction of sepsis and remain elevated over a prolonged period of time. In contrast, many pro-inflammatory cytokines, e.g., tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), rise and decline early in the course of sepsis. Researchers have improved survival in animal models of sepsis by prophylactically blocking IL-1beta and TNF-alpha with immunotherapy, but therapeutic treatment has been less successful in clinical trials. We hypothesized that the sustained elevation of ProCT in the serum would allow for effective therapeutic immunoneutralization of this peptide late in the course of sepsis. METHODS: Lethal polymicrobial sepsis was induced in 10 castrated, male Yorkshire pigs by intraabdominal spillage of cecal contents (1 gm/kg) and intraabdominal instillation of 2 x 10(11) cfu of a toxigenic strain of E. coli (O18:K1:H7). The treated group (n = 5) received an intravenous infusion of purified rabbit antiserum to the aminoterminus of porcine ProCT. The control group (n = 5) received nonreactive, purified rabbit IgG. The purified antiserum was infused to all animals 3 h after the induction of sepsis, at which time very severe physiologic dysfunction was manifest, and many of the animals appeared to be preterminal. Physiologic and metabolic parameters were measured until death or for 15 h after induction of sepsis, at which time all surviving animals were euthanized. RESULTS: Therapeutic immunoneutralization of serum ProCT improved most measured physiologic and metabolic parameters in septic pigs. Specifically, there was a significant increase in mean arterial pressure, urine output and cardiac index in all animals treated with ProCT antibody. Serum creatinine was significantly lower in treated animals. Although acidosis was not as severe in treated animals, as indicated by higher pH values and lower lactate concentrations, these results did not achieve statistical significance. Significantly, 11 h after the induction of sepsis there was 100% mortality in the control group while only one animal in the treated group expired. CONCLUSION: The prolonged elevation of ProCT concentrations in sepsis allows neutralization of this peptide to be effective during the course of this disorder. These findings suggest that immunoneutralization of ProCT may be a useful treatment in clinical situations where sepsis is already fully established.

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Prolactin dysregulation in women with subclinical hypothyroidism: effect of levothyroxine replacement therapy

This study investigated the effect of levothyroxine treatment on serum prolactin (PRL) levels in women with subclinical hypothyroidism. Sixty-six women (mean age, 58.5 +/- 1.3 years) with confirmed subclinical hypothyroidism (mean thyrotropin [TSH], 11.7 +/- 0.8 mIU/L) were randomly assigned to receive levothyroxine or placebo for 48 weeks. Based on blinded TSH monitoring, physiologic levothyroxine replacement (85.5 +/- 4.3 microg/d; TSH, 3.1 +/- 0.3 mIU/L) was ascertained throughout the study. PRL levels were measured before and after administration of thyrotropin-releasing hormone (TRH) at baseline, after 24 and 48 weeks. Sixty-three of the 66 women completed the study. At baseline, basal PRL levels were elevated in 19% of the patients. None of the patients reported menstrual disturbances, infertility, or galactorrhea. In the levothyroxine group (n = 31) basal and peak PRL levels were significantly reduced after 24 and 48 weeks (p = 0.03 and p = 0.001). Mean changes in PRL levels differed significantly between the two treatment groups after 24 weeks (p = 0.03 and p = 0.01). The treatment effect was more pronounced in patients with PRL and TSH levels above the median at baseline (i.e., PRL < 16 ng/mL; TSH < 11 mIU/L). Based on this double-blinded, placebo-controlled study we demonstrate that in subclinical hypothyroidism PRL regulation is altered with elevated basal and stimulated PRL levels, and that physiologic levothyroxine treatment restores PRL concentrations.

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Protein stoichiometry of a multiprotein complex, the human spliceosomal U1 small nuclear ribonucleoprotein: absolute quantification using isotope-coded tags and mass spectrometry

The human U1 snRNP (small nuclear ribonucleoprotein), which is a part of the spliceosome, consists of U1 snRNA and ten different proteins: seven Sm proteins B/B`, D1, D2, D3, E, F, and G and the three U1-specific proteins U1-70 K, U1-A, U1-C. To determine the stoichiometry of all ten proteins, the complex was denatured, digested completely with an endoproteinase and labeled with an amine-specific tag. Corresponding peptides were synthesized and labeled with the same tag containing heavier isotopes. The digest was then spiked with defined amounts of the synthetic peptides, and the resulting isotopic peptide pairs were analyzed quantitatively by mass spectrometry. The mass spectra provided information about the absolute amount of each component in the starting protein mixture. The use of the isotope-coded, amine-specific reagents propionyl-N-oxysuccinimide and nicotinoyl-N-oxysuccinimide was evaluated for stoichiometry determination; the nicotinoyl reagent was found to be advantageous because of its greater mass spectrometric sensitivity. Absolute quantities of all ten proteins were measured, showing equal numbers of all ten proteins in the U1 spliceosomal snRNP. These data demonstrate that quantitative mass spectrometry has great potential for the determination of the stoichiometry of multiprotein complexes.

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Rapid amyloid fiber formation from the fast-folding WW domain FBP28

The WW domains are small proteins that contain a three-stranded, antiparallel beta-sheet. The 40-residue murine FBP28 WW domain rapidly formed twirling ribbon-like fibrils at physiological temperature and pH, with morphology typical of amyloid fibrils. These ribbons were unusually wide and well ordered, making them highly suitable for structural studies. Their x-ray and electron-diffraction patterns displayed the characteristic amyloid fiber 0.47-nm reflection of the cross-beta diffraction signature. Both conventional and electron cryomicroscopy showed clearly that the ribbons were composed of many 2.5-nm-wide subfilaments that ran parallel to the long axis of the fiber. There was a region of lower density along the center of each filament. Lateral association of these filaments generated twisted, often interlinked, sheets up to 40 nm wide and many microns in length. The pitch of the helix varied from 60 to 320 nm, depending on the width of the ribbon. The wild-type FBP28 fibers were formed under conditions in which multiexponential folding kinetics is observed in other studies and which was attributed to a change in the mechanism of folding. It is more likely that those phases result from initial events in the off-pathway aggregation observed here.

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Linear processing of spatial cues in primary auditory cortex

To determine the direction of a sound source in space, animals must process a variety of auditory spatial cues, including interaural level and time differences, as well as changes in the sound spectrum caused by the direction-dependent filtering of sound by the outer ear. Behavioural deficits observed when primary auditory cortex (A1) is damaged have led to the widespread view that A1 may have an essential role in this complex computational task. Here we show, however, that the spatial selectivity exhibited by the large majority of A1 neurons is well predicted by a simple linear model, which assumes that neurons additively integrate sound levels in each frequency band and ear. The success of this linear model is surprising, given that computing sound source direction is a necessarily nonlinear operation. However, because linear operations preserve information, our results are consistent with the hypothesis that A1 may also form a gateway to higher, more specialized cortical areas.

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IJMS, Vol. 18, Pages 2537: Thermodynamic Aspects and Reprogramming Cellular Energy Metabolism during the Fibrosis Process

IJMS, Vol. 18, Pages 2537: Thermodynamic Aspects and Reprogramming Cellular Energy Metabolism during the Fibrosis Process

International Journal of Molecular Sciences doi: 10.3390/ijms18122537

Authors: Alexandre Vallée Yves Lecarpentier Jean-Noël Vallée

Fibrosis is characterized by fibroblast proliferation and fibroblast differentiation into myofibroblasts, which generate a relaxation-free contraction mechanism associated with excessive collagen synthesis in the extracellular matrix, which promotes irreversible tissue retraction evolving towards fibrosis. From a thermodynamic point of view, the mechanisms leading to fibrosis are irreversible processes that can occur through changing the entropy production rate. The thermodynamic behaviors of metabolic enzymes involved in fibrosis are modified by the dysregulation of both transforming growth factor β (TGF-β) signaling and the canonical WNT/β-catenin pathway, leading to aerobic glycolysis, called the Warburg effect. Molecular signaling pathways leading to fibrosis are considered dissipative structures that exchange energy or matter with their environment far from the thermodynamic equilibrium. The myofibroblastic cells arise from exergonic processes by switching the core metabolism from oxidative phosphorylation to glycolysis, which generates energy and reprograms cellular energy metabolism to induce the process of myofibroblast differentiation. Circadian rhythms are far-from-equilibrium thermodynamic processes. They directly participate in regulating the TGF-β and WNT/β-catenin pathways involved in energetic dysregulation and enabling fibrosis. The present review focusses on the thermodynamic implications of the reprogramming of cellular energy metabolism, leading to fibroblast differentiation into myofibroblasts through the positive interplay between TGF-β and WNT/β-catenin pathways underlying in fibrosis.

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Abstract

The original version of this article unfortunately contained an incorrect assignment of affiliations of Linwei Zhang and Tetsuo Ashizawa.

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Abstract

The adsorption of $$\mathrm{N}{\mathrm{H}}_4^{+}$$ and $${\mathrm{PO}}_4^{3-}$$ by sesame straw biochars (C-300, C-500, and C-700) prepared under different temperatures (300, 500, and 700 °C) was investigated in this study. The physicochemical properties of the biochars were characterized using Brunauer–Emmett–Teller method, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectrometry. In batch experiments, C-300 showed the best $$\mathrm{N}{\mathrm{H}}_4^{+}$$ adsorption capacity of 3.45 mg/g because of its abundant surface functional groups at low pyrolysis temperature. C-700 achieved the optimal $${\mathrm{PO}}_4^{3-}$$ adsorption capacity of 34.17 mg/g because of its high Ca, Mg, and Al contents and high surface area at high pyrolysis temperature. The isothermal study showed that the Langmuir–Freundlich model could sufficiently describe the $$\mathrm{N}{\mathrm{H}}_4^{+}$$ and $${\mathrm{PO}}_4^{3-}$$ adsorption values, indicating the multiple adsorption processes of nutrients on biochars. The maximum $$\mathrm{N}{\mathrm{H}}_4^{+}$$ adsorption capacity was 93.61 mg/g on C-300, whereas the maximum $${\mathrm{PO}}_4^{3-}$$ adsorption capacity was as high as 116.58 mg/g on C-700. Kinetic study showed that $$\mathrm{N}{\mathrm{H}}_4^{+}$$ adsorption on C-300 was mainly controlled by intraparticle diffusion, and the pseudo-second-order model could well describe $${\mathrm{PO}}_4^{3-}$$ adsorption on C-700.

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Abstract

The increase in the frequency of exposure to gasoline fumes and the growing incidence of infertility among humans has been a major concern and subject of discussion over the years in Nigeria. We therefore present the reproductive effect of gasoline fumes on inhalation exposure in 40 male albino rats. The rats were randomized into five experimental treatments (T) with eight rats per treatment. T1 (control) was exposed to distilled water while T2, T3, T4, and T5 were exposed to gasoline fumes in exposure chambers for 1, 3, 5, and 9 h daily respectively for 12 weeks. Serum level of testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, oxidative stress markers in the testicular tissue, epididymal sperm health assessment, and testicular histopathology of the rats were used as a diagnostic marker of reproductive dysfunction. Significant (p < 0.05) alterations in the levels of all the reproductive hormones and oxidative stress markers assayed were observed in rats exposed to gasoline fume. Significant reductions (p < 0.05) in sperm count and percentage motility in the exposed rats were observed. Significant (p < 0.05) increased in abnormal sperm cells characterized by damaged head, bent tail, damaged tail, and without head were also observed in the exposed rats. Histopathologically, severe degenerative testicular architectural lesions characterized by alterations in all the generations of sperm cells and reduction of interstitial cells were seen in the exposed rats. Gasoline fume is thus said to interfere with spermatogenesis and impair fertility in male gonad.

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Abstract

The present work submits an investigation about the effect of urea injection parameters on NOx emissions from a four-stroke four-cylinder diesel engine fueled with B20 blended biodiesel. An L9(34) Taguchi orthogonal array was used to design the test plan. The results reveal that increasing urea concentration leads to lower NOx emissions. Urea flow rate increment has the same influence on NOx emission. The same result is obtained by an increase in spray angle. Also, according to the analysis of variance (ANOVA), urea concentration and then urea flow rate are the most effective design parameters on NOx emissions, while spray angle and mixing length have less influence on this pollutant emission. Finally, since the result of confirmation test is in good agreement with the predicted value based on the Taguchi technique, the predictive capability of this method in the present study could be deduced.

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